Medicine Pharmacology

Healthcare and Venom Research

Description

This cluster of papers explores the therapeutic potential of bee venom and its constituent compounds, particularly melittin, in various medical applications. The research covers anti-cancer effects, pain relief, anti-inflammatory properties, apoptosis induction, and potential use in conditions such as rheumatoid arthritis and neurodegenerative diseases. Additionally, it investigates the use of bee venom in acupuncture and its immunomodulatory effects.

Keywords

Bee Venom; Melittin; Anti-cancer; Pain Relief; Anti-inflammatory; Apoptosis Induction; Rheumatoid Arthritis; Neuroprotective Effects; Acupuncture; Immunomodulation

Mastoparan, a peptide toxin from wasp venom, is a nonspecific secretagogue. We show here that mastoparan increases the GTPase activity and the rate of nucleotide binding of several purified GTP-binding … Mastoparan, a peptide toxin from wasp venom, is a nonspecific secretagogue. We show here that mastoparan increases the GTPase activity and the rate of nucleotide binding of several purified GTP-binding regulatory proteins (G proteins) whose function is to couple cell-surface receptors to intracellular mediators. Mastoparan accelerated guanosine-5'-(3-O-thiotriphosphate binding and consequent G protein activation in part by promoting the dissociation of bound GDP, the mechanism by which receptors regulate G proteins. ADP-ribosylation by pertussis toxin, which uncouples receptors from G proteins, selectively inhibited mastoparan-stimulated activation. Like receptors, mastoparan was more potent if the G protein was reconstituted in phospholipid vesicles and was active at micromolar concentrations of Mg2+. The structure of mastoparan in a lipid bilayer is similar to that predicted for a cationic intracellular loop of G protein-coupled receptors. Mastoparan thus displays a novel mode of toxicity by acting directly on G proteins to mimic the role normally played by agonist-liganded receptors.
Melittin is the principal protein component of bee venom and is thought to function as a lytic agent. Despite its predominantly hydrophobic character, melittin is soluble as a tetramer in … Melittin is the principal protein component of bee venom and is thought to function as a lytic agent. Despite its predominantly hydrophobic character, melittin is soluble as a tetramer in aqueous salt solutions. We report here on the determination of the crystal structure of tetrameric melittin at 2.8-A resolution by the method of multiple isomorphous replacement, followed by partial atomic refinement at 2.0-A resolution. The melittin tetramer contains a noncrystallographic 2-fold axis of symmetry in addition to a crystallographic 2-fold axis, so that the four polypeptide chains have nearly identical structures. The noncrystallographic 2-fold axis was utilized twice during the determination of the structure. The multiple isomorphous replacement electron density map was averaged over this 2-fold axis before model building and strict noncrystallographic symmetry was assumed during the initial stages of atomic refinement. The 2.8-A resolution electron density map suggests that the melittin monomer contains two alpha-helical regions separated by a non-alpha-helical segment at residues 11 and 12. Difference maps at 2.0-A resolution tend to confirm this structure and reveal that at least six solvent molecules are bound to the melittin tetramer in the crystal. The relatively high occupancies of four of these suggest that they are ions of crystallization rather than water molecules.
Abstract To study mechanisms whereby lytic proteins disrupt biomembranes, artificial phospholipid spherules (liposomes) were exposed to melittin, a cationic peptide in which sequences of hydrophobic (Positions 1 to 20) and … Abstract To study mechanisms whereby lytic proteins disrupt biomembranes, artificial phospholipid spherules (liposomes) were exposed to melittin, a cationic peptide in which sequences of hydrophobic (Positions 1 to 20) and hydrophilic (Positions 21 to 26) amino acids are unequally distributed. At concentrations above 10-6 m, melittin, which is the major toxin of bee venom, released marker anions (CrO4=) or glucose from the model structures. Release of marker ions was equivalent whether liposomes were prepared with a net negative (dicetyl phosphate) or net positive (stearylamine) charge. Nor was the presence of cholesterol in the model membranes necessary for the action of melittin. Spherules with net negative charges competed approximately 10 times more effectively for melittin's lytic activity on erythrocytes than did spherules with positive charges. Studies with lipid monolayers indicated that melittin had a remarkable affinity for the air-water and more so for the lipid-water interface, for it spread as a film readily from water and penetrated lipid monolayers avidly, irrespective of the surface charge of the lipid film. Negatively stained preparations of liposomes in the electron microscope showed that melittin-treated spherules lost the integrity of their concentric lamellae, which became beaded, frayed, and finally fragmented. These studies indicate that the lytic effects of melittin upon biological membranes may be due to a similar reaction with structural phospholipids. Since ionic interactions between the cationic peptide and charged lamellae were not crucial for lysis, and since melittin has an extraordinary affinity for lipid membranes, it is suggested that the surface activity of melittin and convenient apolar associations between hydrophobic portions of melittin and the acyl chains of phospholipid could account for disruption of the spherules.
Duplicate determinations of secretion rate and buffer effect of resting and stimulated whole saliva were made in 629 adults (286 males and 343 females) within an interval of 1-2 weeks. … Duplicate determinations of secretion rate and buffer effect of resting and stimulated whole saliva were made in 629 adults (286 males and 343 females) within an interval of 1-2 weeks. The subjects were arbitrarily classified into four separate age-groups. For all variables studied, a highly significant correlation was obtained between the duplicate tests. The secretion rate of resting as well as stimulated saliva was significantly lower for females than for males. For females, the resting secretion rate was negatively correlated with age. The buffer effect was also significantly lower in the females for both resting and stimulated saliva. For the females, the buffer effect was positively correlated with age and therefore, with advancing age, the females tended to catch up with the males. Irrespective of sex, the secretion rate of resting saliva was highly correlated to that of stimulated saliva. This relationship was established also for the buffer effect. However, between secretion rate and buffer effect a correlation was observed only for stimulated saliva.
The mechanisms of bee venom immunotherapy (VIT) are largely unknown. The aim of this study was to follow the changes of T cell cytokine secretion during the course of VIT. … The mechanisms of bee venom immunotherapy (VIT) are largely unknown. The aim of this study was to follow the changes of T cell cytokine secretion during the course of VIT. Ten bee venom-allergic patients with a history of severe systemic reactions, positive skin tests, and bee venom (BV)-specific serum IgE Abs were treated as follows: on the first day, a cumulative dose of 111 micrograms, starting with 0.1 microgram, was administered s.c. under intensive care conditions. Further injections of 100 micrograms BV were given on day 7, day 21, and thereafter at intervals of 4 wk. Blood samples were obtained just before the initiation of VIT, after the last injection on the same day, and before the subsequent BV injections on days 7, 21, and 50 of VIT. Peripheral blood mononuclear cells (PBMC) were stimulated with phospholipase A (PLA), the major BV allergen, or with a control Ag tetanus toxoid (TT). Cytokine secretion was measured 24 h after restimulation of the cultures with solid-phase bound OKT3 F(ab')2 mAbs after 7 days of culture. In PLA-stimulated cultures, VIT resulted in decreased IL-4 and IL-5 and increased IFN-gamma secretion. In TT-stimulated cultures, we observed similar levels of cytokines before and during VIT. We conclude that ultra-rush VIT changes allergen-specific T cell reactivity.
1. K-sensitive electrodes placed in the extracellular fluid have been used to show that ATP and noradrenaline cause a rapid loss of up to 10% of the K content of … 1. K-sensitive electrodes placed in the extracellular fluid have been used to show that ATP and noradrenaline cause a rapid loss of up to 10% of the K content of isolated guinea-pig hepatocytes. 2. The hypothesis tha this response is a consequence of a rise in the K permeability of the hepatocyte membrane triggered by an increase in cytosolic Ca is supported by the finding that the divalent cation ionophore A23187 also initiated K loss, in this instance of up to 20-25% of the amount in the cells. 3. Under similar conditions A23187 caused a transient increase, followed by a larger decrease, in the 45Ca content of guinea-pig hepatocytes equilibrated with this isotope. The decrease alone was seen with ATP and noradrenaline. 4. Quinine (1 mM) and the bee venom neurotoxin apamin (10 nM) greatly reduced the effect of ATP, noradrenaline and A23187 on K content without affecting the changes in 45Ca movement. 5. Apamin (10 nM) also abolished the increase in 42K efflux which follows the application of the alpha-adrenoceptor agonist amidephrine to rabbit liver slices; the concurrent rises in 45Ca efflux and glucose release were unaffected. 6. It was concluded that quinine and apamin are able to block either the Ca-dependent K channels present in guinea-pig and rabbit liver cell membranes or the mechanism that controls them. 7. Surprisingly, rat hepatocytes took up rather than lost K when treated with the concentrations of ATP, noradrenaline or A23187 that initiated K loss from guinea-pig cells. This response was greatly reduced by ouabain. 8. Application of large concentrations of A23187 to rat hepatocytes caused K loss associated with cell death. 9. The influence of apamin (10-1000 nM) and quinine (200-1000 micro M) on the Ca-dependent K permeability of red blood cells and ghosts was also studied. Apamin was without effect even when applied to both sides of the ghost membrane, whereas quinine caused inhibition, as reported by others. 10. The results suggest that Ca-dependent K channels or carriers are present in the membranes of liver cells of the guinea-pig and rabbit, but are either lacking or inactive in rat liver. The finding that apamin blocks this mechanism in hepatocytes but not in erythrocytes may mean that the channels differ in these cells.
This paper describes the interaction of apamin, a bee venom neurotoxin, with the mouse neuroblastoma cell membrane. Voltage-clamp analyses have shown that apamin at low concentrations specifically blocks the Ca2+-dependent … This paper describes the interaction of apamin, a bee venom neurotoxin, with the mouse neuroblastoma cell membrane. Voltage-clamp analyses have shown that apamin at low concentrations specifically blocks the Ca2+-dependent K+ channel in differentiated neuroblastoma cells. Binding experiments with highly radiolabeled toxin indicate that the dissociation constant of the apamin-receptor complex in differentiated neuroblastoma cells is 15-22 pM and the maximal binding capacity is 12 fmol/mg of protein. The receptor is destroyed by proteases, suggesting that it is a protein. The binding capacity of neuroblastoma cells for radiolabeled apamin dramatically increases during the transition from the nondifferentiated to the differentiated state. The number of Ca2+-dependent K+ channels appears to be at most 1/5th the number of fast Na+ channels in differentiated neuroblastoma. The binding of radiolabeled apamin to its receptor is antagonized by monovalent and divalent cations. Na+ inhibition of the binding of 125I-labeled apamin is of the competitive type (Kd(Na+) = 44 mM). Guanidinium and guanidinated compounds such as amiloride or neurotensin prevent binding of 125I-labeled apamin, the best antagonist being neurotensin.
Many peptides and proteins that act at lipid--water interfaces assume a unique amphiphilic secondary structure which is induced by the anisotropy of the interface. By using synthetic peptides in which … Many peptides and proteins that act at lipid--water interfaces assume a unique amphiphilic secondary structure which is induced by the anisotropy of the interface. By using synthetic peptides in which these inducible amphiphilic structures have been optimized, one can show that the amphiphilic alpha helix is a functional determinant of representative apolipoproteins, peptide toxins, and peptide hormones. By increasing the amphiphilicity of the structurally important regions of the molecule, one can enhance the biological activity of the peptide even beyond that of the naturally occurring polypeptide. It is proposed that rigid amphiphilic secondary structures such as alpha helix, beta sheet, or pi helix will be found in most medium-sized peptides acting at membranes and lipid--water interfaces.
The prevalence of insect sting reaction and of venom sensitization in adults is unknown. We report the results of intake evaluation of a stratified random sample of a large adult … The prevalence of insect sting reaction and of venom sensitization in adults is unknown. We report the results of intake evaluation of a stratified random sample of a large adult population previously studied for the determinants of atopic disease. In 269 subjects, the prevalence of systemic allergic sting reactions was 3.3% and 26.5% had IgE antibodies to venom demonstrated by skin test or radioallergosorbent test. Asymptomatic sensitization (positive venom skin test) was observed in 15% of subjects with no history of an allergic sting reaction. Positive venom skin tests were more frequent in men, in those with positive skin tests to inhalant allergens, and in subjects aged 20 through 29 years. A positive venom skin test or radioallergosorbent test was more frequent in subjects who had been stung within the previous 3 years (35%) than in those stung more than 3 years before (20%). We conclude that both systemic allergic reactions to insect stings and asymptomatic sensitivity to venom are common and that most affected persons never seek medical advice. The significance of asymptomatic venom sensitization is unknown. (<i>JAMA</i>1989;262:240-244)
While knowledge of the composition and mode of action of bee and wasp venoms dates back 50 years, the therapeutic value of these toxins remains relatively unexploded. The properties of … While knowledge of the composition and mode of action of bee and wasp venoms dates back 50 years, the therapeutic value of these toxins remains relatively unexploded. The properties of these venoms are now being studied with the aim to design and develop new therapeutic drugs. Far from evaluating the extensive number of monographs, journals and books related to bee and wasp venoms and the therapeutic effect of these toxins in numerous diseases, the following review focuses on the three most characterized peptides, namely melittin, apamin, and mastoparan. Here, we update information related to these compounds from the perspective of applied science and discuss their potential therapeutic and biotechnological applications in biomedicine.
Measurement of thresholds for heat-induced pain was performed on 106 normal subjects, at thenar eminence and foot dorsum, using the reaction time-inclusive method of limits. Tests were repeated 2 weeks … Measurement of thresholds for heat-induced pain was performed on 106 normal subjects, at thenar eminence and foot dorsum, using the reaction time-inclusive method of limits. Tests were repeated 2 weeks following the first test for most of the subjects. After determination that there were no outlying data points and that there was no systematic relationship between magnitude and variability of test scores, data from between 72 and 76 subjects were used to define normal upper and lower ranges by age, as well as repeatability coefficients. This was done through ANOVA-based procedures that extend standard repeatability assessment methods. Normative data tables are presented, with measures of repeatability for the various sites and modalities. For the conventional test range, reaching 55 degrees C, measurement of heat pain thresholds can define both hyper- and hypoalgesia. Application of repeatability coefficients allows for intra-individual inter-session comparison in longitudinal studies.
Bee venom phospholipase A2 (PLA) is the major allergen in bee sting allergy. It displays three peptide and a glycopeptide T cell epitopes, which are recognized by both allergic and … Bee venom phospholipase A2 (PLA) is the major allergen in bee sting allergy. It displays three peptide and a glycopeptide T cell epitopes, which are recognized by both allergic and non-allergic bee venom sensitized subjects. In this study PLA- and PLA epitope-specific T cell and cytokine responses in PBMC of bee sting allergic patients were investigated before and after 2 mo of rush immunotherapy with whole bee venom. After successful immunotherapy, PLA and T cell epitope peptide-specific T cell proliferation was suppressed. In addition the PLA- and peptide-induced secretion of type 2 (IL-4, IL-5, and IL-13), as well as type 1 (IL-2 and IFN-gamma) cytokines were abolished, whereas tetanus toxoid-induced cytokine production and proliferation remained unchanged. By culturing PBMC with Ag in the presence of IL-2 or IL-15 the specifically tolerized T cell response could be restored with respect to specific proliferation and secretion of the type 1 T cell cytokines, IL-2 and IFN-gamma. In contrast, IL-4, IL-5, and IL-13 remained suppressed. Treatment of tolerized T cells with IL-4 only partially restored proliferation and induced formation of distinct type 2 cytokine pattern. In spite of the allergen-specific tolerance in T cells, in vitro produced anti-PLA IgE and IgG4 Ab and their corresponding serum levels slightly increased during immunotherapy, while the PLA-specific IgE/IgG4 ratio changed in favor of IgG4. These findings indicate that bee venom immunotherapy induces a state of peripheral tolerance in allergen-specific T cells, but not in specific B cells. The state of T cell tolerance and cytokine pattern can be in vitro modulated by the cytokines IL-2, IL-4, and IL-15, suggesting the importance of microenvironmental cytokines leading to success or failure in immunotherapy.
The induction of allergen-specific anergy in peripheral T cells represents a key step in specific immunotherapy (SIT). Here we demonstrate that the anergic state results from increased IL-10 production. In … The induction of allergen-specific anergy in peripheral T cells represents a key step in specific immunotherapy (SIT). Here we demonstrate that the anergic state results from increased IL-10 production. In bee venom (BV)-SIT the specific proliferative and cytokine responses against the main allergen, the phospholipase A2 (PLA), and T cell epitope-containing PLA peptides were significantly suppressed after 7 d of treatment. Simultaneously, the production of IL-10 increased during BV-SIT. After 28 d of BV-SIT the anergic state was established. Intracytoplasmic cytokine staining of PBMC combined with surface marker detection revealed that IL-10 was produced initially by activated CD4(+)CD25(+), allergen-specific T cells, and followed by B cells and monocytes. Neutralization of IL-10 in PBMC fully reconstituted the specific proliferative and cytokine responses. A similar state of IL-10-associated T cell anergy, as induced in BV-SIT, was found in hyperimmune individuals who recently had received multiple bee stings. The addition of IL-10 to soluble CD40 ligand IL-4-stimulated PBMC or purified B cells inhibited the PLA-specific and total IgE and enhanced the IgG4 formation. Accordingly, increased IL-10 production by SIT causes specific anergy in peripheral T cells, and regulates specific IgE and IgG4 production toward normal IgG4-related immunity.
Background: Evidence on the efficacy of acupuncture for reducing the pain and dysfunction of osteoarthritis is equivocal. Objective: To determine whether acupuncture provides greater pain relief and improved function compared … Background: Evidence on the efficacy of acupuncture for reducing the pain and dysfunction of osteoarthritis is equivocal. Objective: To determine whether acupuncture provides greater pain relief and improved function compared with sham acupuncture or education in patients with osteoarthritis of the knee. Design: Randomized, controlled trial. Setting: Two outpatient clinics (an integrative medicine facility and a rheumatology facility) located in academic teaching hospitals and 1 clinical trials facility. Patients: 570 patients with osteoarthritis of the knee (mean age [±SD], 65.5 ± 8.4 years). Intervention: 23 true acupuncture sessions over 26 weeks. Controls received 6 two-hour sessions over 12 weeks or 23 sham acupuncture sessions over 26 weeks. Measurements: Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores at 8 and 26 weeks. Secondary outcomes were patient global assessment, 6-minute walk distance, and physical health scores of the 36-Item Short-Form Health Survey (SF-36). Results: Participants in the true acupuncture group experienced greater improvement in WOMAC function scores than the sham acupuncture group at 8 weeks (mean difference, −2.9 [95% CI, −5.0 to −0.8]; P = 0.01) but not in WOMAC pain score (mean difference, −0.5 [CI, −1.2 to 0.2]; P = 0.18) or the patient global assessment (mean difference, 0.16 [CI, −0.02 to 0.34]; P > 0.2). At 26 weeks, the true acupuncture group experienced significantly greater improvement than the sham group in the WOMAC function score (mean difference, −2.5 [CI, −4.7 to −0.4]; P = 0.01), WOMAC pain score (mean difference, −0.87 [CI, −1.58 to −0.16];P = 0.003), and patient global assessment (mean difference, 0.26 [CI, 0.07 to 0.45]; P = 0.02). Limitations: At 26 weeks, 43% of the participants in the education group and 25% in each of the true and sham acupuncture groups were not available for analysis. Conclusions: Acupuncture seems to provide improvement in function and pain relief as an adjunctive therapy for osteoarthritis of the knee when compared with credible sham acupuncture and education control groups.
Study Design The current prospective longtudinal study examined the predictive value of psychological, somatic and social variables for the prediction of the short- and long-term follow-up in 111 consecutively selected … Study Design The current prospective longtudinal study examined the predictive value of psychological, somatic and social variables for the prediction of the short- and long-term follow-up in 111 consecutively selected patients with acute radicular pain and a lumbar disc prolapse or protrusion. Objectives The criteria for the therapy outcome were the intensity of persistent pain at the time of the discharge from the hospital and 6 months later and the application for early retirement at the 6 month follow-up. Methods As for the psychological predictors, we examined depression (Beck Depression Inventory BDI), daily hassles (kiel Interview of the Subjective Situation KISS), pain coping strategies (Kiel Pain Inventory KSI), and Health locus of control (GKÜ). As somatic predictors, we assessed the duration of pain before treatment, previous operations, paresis, disc displacement, scoliosis, adipositas, treatment, and age. As social predictors, we assessed the social status, occupational characteristics, and the duration of inability to work. Results The results indicated that persistent pain was best predicted by combination of somatic (degree of disc displacement), psychological (depression and the pain coping strategies avoidance behavior, endurance strategies, nonverbal pain behavior and search for social support), and social parameters (social status and sitting position) with a correct prediction in 86%. The application for early retirement at the 6 month follow-up was best predicted by depression and stress at work. Conclusions The results lead to several hypotheses about biopsychosocial interrelations within the chronification of radicular pain and provide the clinician with a short screening instrument for early diagnosis of chronification.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHemolytic and antimicrobial activities of the twenty-four individual omission analogs of melittinSylvie E. Blondelle and Richard A. HoughtenCite this: Biochemistry 1991, 30, 19, 4671–4678Publication Date (Print):May 1, … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHemolytic and antimicrobial activities of the twenty-four individual omission analogs of melittinSylvie E. Blondelle and Richard A. HoughtenCite this: Biochemistry 1991, 30, 19, 4671–4678Publication Date (Print):May 1, 1991Publication History Published online1 May 2002Published inissue 1 May 1991https://doi.org/10.1021/bi00233a006RIGHTS & PERMISSIONSArticle Views746Altmetric-Citations221LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1014 KB) Get e-Alerts Get e-Alerts
To examine the effect of progressive resistance training on muscle function, functional performance, balance, body composition, and muscle thickness in men receiving androgen deprivation for prostate cancer.Ten men aged 59-82 … To examine the effect of progressive resistance training on muscle function, functional performance, balance, body composition, and muscle thickness in men receiving androgen deprivation for prostate cancer.Ten men aged 59-82 yr on androgen deprivation for localized prostate cancer undertook progressive resistance training for 20 wk at 6- to 12-repetition maximum (RM) for 12 upper- and lower-body exercises in a university exercise rehabilitation clinic. Outcome measures included muscle strength and muscle endurance for the upper and lower body, functional performance (repeated chair rise, usual and fast 6-m walk, 6-m backwards walk, stair climb, and 400-m walk time), and balance by sensory organization test. Body composition was measured by dual-energy x-ray absorptiometry and muscle thickness at four anatomical sites by B-mode ultrasound. Blood samples were assessed for prostate specific antigen (PSA), testosterone, growth hormone (GH), cortisol, and hemoglobin.Muscle strength (chest press, 40.5%; seated row, 41.9%; leg press, 96.3%; P < 0.001) and muscle endurance (chest press, 114.9%; leg press, 167.1%; P < 0.001) increased significantly after training. Significant improvement (P < 0.05) occurred in the 6-m usual walk (14.1%), 6-m backwards walk (22.3%), chair rise (26.8%), stair climbing (10.4%), 400-m walk (7.4%), and balance (7.8%). Muscle thickness increased (P < 0.05) by 15.7% at the quadriceps site. Whole-body lean mass was preserved with no change in fat mass. There were no significant changes in PSA, testosterone, GH, cortisol, or hemoglobin.Progressive resistance exercise has beneficial effects on muscle strength, functional performance and balance in older men receiving androgen deprivation for prostate cancer and should be considered to preserve body composition and reduce treatment side effects.
The crystal structure of a complex between a phosphonate transition-state analogue and the phospholipase A2 (PLA2) from Naja naja atra venom has been solved and refined to a resolution of … The crystal structure of a complex between a phosphonate transition-state analogue and the phospholipase A2 (PLA2) from Naja naja atra venom has been solved and refined to a resolution of 2.0 angstroms. The identical stereochemistry of the two complexes that comprise the crystal's asymmetric unit indicates both the manner in which the transition state is stabilized and how the hydrophobic fatty acyl chains of the substrate are accommodated by the enzyme during interfacial catalysis. The critical features that suggest the chemistry of binding and catalysis are the same as those seen in the crystal structure of a similar complex formed with the evolutionarily distant bee-venom PLA2.
Bee venom (BV) has traditionally been used in Oriental medicine to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis (RA). While several investigators have evaluated the anti-inflammatory … Bee venom (BV) has traditionally been used in Oriental medicine to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis (RA). While several investigators have evaluated the anti-inflammatory effect of BV treatment, the anti-nociceptive effect of BV treatment on inflammatory pain has not been examined. Previous studies in experimental animals suggest that the therapeutic effect of BV on arthritis is dependent on the site of administration. Because of this potential site specificity, the present study was designed to evaluate the anti-nociceptive effect of BV injections into a specific acupoint (Zusanli) compared to a non-acupoint in an animal model of chronic arthritis. Subcutaneous BV treatment (1 mg/kg per day) was found to dramatically inhibit paw edema caused by Freund's adjuvant injection. Furthermore, BV therapy significantly reduced arthritis-induced nociceptive behaviors (i.e. the nociceptive scores for mechanical hyperalgesia and thermal hyperalgesia). These anti-nociceptive/anti-inflammatory effects of BV were observed from 12 days through 21 days post-BV treatment. In addition, BV treatment significantly suppressed adjuvant-induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. Finally, injection of BV into the Zusanli acupoint resulted in a significantly greater analgesic effect on arthritic pain as compared to BV injection in to a more distant non-acupoint. The present study demonstrates that BV injection into the Zusanli acupoint has both anti-inflammatory and anti-nociceptive effects on Freund's adjuvant-induced arthritis in rats. These findings raise the possibility that BV acupuncture may be a promising alternative medicine therapy for the long-term treatment of rheumatoid arthritis.
Temporal summation of sensory intensity was investigated in normal subjects using novel methods of thermal stimulation. A Peltier thermode was heated and then applied in a series of brief (700 … Temporal summation of sensory intensity was investigated in normal subjects using novel methods of thermal stimulation. A Peltier thermode was heated and then applied in a series of brief (700 ms) contacts to different sites on the glabrous skin of either hand. Repetitive contacts on the thenar or hypothenar eminence, at interstimulus intervals (ISIs) of 3 s, progressively increased the perceived intensity of a thermal sensation that followed each contact at an onset latency > 2 s. Temporal summation of these delayed (late) sensations was proportional to thermode temperature over a range of 45-53 degrees C, progressing from a nonpainful level (warmth) to painful sensations that could be rated as very strong after 10 contacts. Short-latency pain sensations rarely were evoked by such stimuli and never attained levels substantially above pain threshold for the sequences and temperatures presented. Temporal summation produced by brief contacts was greater in rate and amount than increases in sensory intensity resulting from repetitive ramping to the same temperature by a thermode in constant contact with the skin. Variation of the interval between contacts revealed a dependence of sensory intensity on interstimulus interval that is similar to physiological demonstrations of windup, where increasing frequencies of spike train activity are evoked from spinal neurons by repetitive activation of unmyelinated nociceptors. However, substantial summation at repetition rates of > or = 0.33 Hz was observed for temperatures that produced only late sensations of warmth when presented at frequencies < 0.16 Hz. Measurements of subepidermal skin temperature from anesthetized monkeys revealed different time courses for storage and dissipation of heat by the skin than for temporal summation and decay of sensory intensity for the human subjects. For example, negligible heat loss occurred during a 6-s interval between two trials of 10 contacts at 0.33 Hz, but ratings of sensory magnitude decreased from very strong levels of pain to sensations of warmth during the same interval. Evidence that temporal summation of sensory intensity during series of brief contacts relies on central integration, rather than a sensitization of peripheral receptors, was obtained using two approaches. In the first, a moderate degree of temporal summation was observed during alternating stimulation of adjacent but nonoverlapping skin sites at 0.33 Hz. Second, temporal summation was significantly attenuated by prior administration of dextromethorphan, a N-methyl-D-aspartate receptor antagonist.
Insect hypersensitivity is currently treated by immunization using whole-body extracts. We compared this regimen with immunotherapy using insect venoms or placebo in groups of 20 patients matched for history and … Insect hypersensitivity is currently treated by immunization using whole-body extracts. We compared this regimen with immunotherapy using insect venoms or placebo in groups of 20 patients matched for history and sensitivity, as judged by venom skin test, histamine release and IgE antibody to venom. After six to 10 weeks of immunization, systemic reactions to stings occurred in seven of 12, seven of 11, and one of 18 patients treated with placebo, whole-body extract, and venom, respectively. Placebo and whole-body extract gave similar results and were significantly less effective than venom immunotherapy (P less than 0.01). The 14 patients with failure of treatment with whole-body extract and placebo were subsequently provided with venom immunotherapy; one reacted to a subsequent sting. We conclude that venom immunotherapy is clinically superior to therapy on whole-body extract or placebo.
Apitherapy is an alternate therapy that relies on the usage of honeybee products, most importantly bee venom for the treatment of many human diseases. The venom can be introduced into … Apitherapy is an alternate therapy that relies on the usage of honeybee products, most importantly bee venom for the treatment of many human diseases. The venom can be introduced into the human body by manual injection or by direct bee stings. Bee venom contains several active molecules such as peptides and enzymes that have advantageous potential in treating inflammation and central nervous system diseases, such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. Moreover, bee venom has shown promising benefits against different types of cancer as well as anti-viral activity, even against the challenging human immunodeficiency virus (HIV). Many studies described biological activities of bee venom components and launched preclinical trials to improve the potential use of apitoxin and its constituents as the next generation of drugs. The aim of this review is to summarize the main compounds of bee venom, their primary biological properties, mechanisms of action, and their therapeutic values in alternative therapy strategies.
In a crossover study conducted over a six-month period in eight patients with well-characterized premenstrual syndrome, physical and behavioral symptoms were relieved by daily administration of an agonist of gonadotropin-releasing … In a crossover study conducted over a six-month period in eight patients with well-characterized premenstrual syndrome, physical and behavioral symptoms were relieved by daily administration of an agonist of gonadotropin-releasing hormone. The reversible "medical ovariectomy" attained with this agonist suggests that it may be an effective and rational treatment for this distressing syndrome in the short term. Whether prolonged therapy would be safe and effective, or even necessary, remains to be determined.
<h3>Abstract</h3> <h3>Objective</h3> Electroencephalography (EEG) interpretations through visual (by human raters) and automated (by computer technology) analysis are still not reliable for the diagnosis of non-convulsive status epilepticus (NCSE). This study … <h3>Abstract</h3> <h3>Objective</h3> Electroencephalography (EEG) interpretations through visual (by human raters) and automated (by computer technology) analysis are still not reliable for the diagnosis of non-convulsive status epilepticus (NCSE). This study aimed to identify typical pitfalls in the EEG analysis and make suggestions as to how those pitfalls might be avoided. <h3>Methods</h3> We analyzed the EEG recordings of individuals who had clinically confirmed or suspected NCSE. Epileptiform EEG activity during seizures (ictal discharges) were visually analyzed by two independent raters. We investigated whether unreliable EEG visual interpretations quantified by low inter-rater agreement can be predicted by the characteristics of ictal discharges and individuals’ clinical data. In addition, the EEG recordings were automatically analyzed by in-house algorithms. To further explore the causes of unreliable EEG interpretations, two epileptologists analyzed EEG patterns most likely misinterpreted as ictal discharges based on the differences between the EEG interpretations through the visual and automated analysis. <h3>Results</h3> Short ictal discharges with a gradual onset (developing over 3 seconds in length) were liable to be misinterpreted. An extra 2 minutes of ictal discharges contributed to an increase in the kappa statistics of &gt; 0.1. Other problems were the misinterpretation of abnormal background activity (slow wave activities, other abnormal brain activity, and the ictal-like movement artifacts), continuous interictal discharges, and continuous short ictal discharges. <h3>Conclusion</h3> A longer duration criterion for NCSE-EEGs than 10 seconds that commonly used in NCSE working criteria is needed. Using knowledge of historical EEGs, individualized algorithms, and context-dependent alarm thresholds may also avoid the pitfalls.
The pathological mechanism of Parkinson's disease (PD) is complex and affected by multi-system and multi-level factors including mitochondrial dysfunction (MD). It has been demonstrated that all patients with PD have … The pathological mechanism of Parkinson's disease (PD) is complex and affected by multi-system and multi-level factors including mitochondrial dysfunction (MD). It has been demonstrated that all patients with PD have a marked loss of dopaminergic neurons in the substantial nigra pars compacta, and MD is an important initial factor causing dopaminergic neuron degeneration. Clinical practice has shown that acupuncture has a positive role in the treatment of PD. In the present article, we summed up recent research results about the mechanisms of acupuncture underlying improvement of PD from the standpoint of mitochondrial function. Acupuncture has been shown to be able in improving mitochondrial function, and restoring mitochondrial homeostasis, and protecting the normal morphological structure of mitochondria. It can also regulate the expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), and Sirtuins (SIRT) to take part in mitochondrial biogenesis; decrease the levels of dynamin-related protein 1 (Drp1), mitochondrial fission factor (MFF), and mitochondrial fission protein 1 (Fis1) protein to preserve mitochondrial dynamic stability; and modulate the expression of PTEN-induced putative kinase 1 (PINK1), Parkin, P62, microtubule-associated protein light chain 3Ⅱ (LC3Ⅱ), and Beclin1 to promote autophagy. In addition, through controlling mitochondrial energy metabolism, preserving calcium homeostasis, reducing oxidative stress, and preventing neuronal apoptosis, acupuncture can also help improve mitochondrial dysfunction and prevent the onset and progression of PD. However, more researches are warranted to fully unravel the underlying mechanisms of acupuncture intervention before it can be popularized in clinical settings.
This study examined the effects of circuit weight training (CWT) and traditional weight training on changes in blood lactate levels and stress indices and determined their impact on performance enhancement … This study examined the effects of circuit weight training (CWT) and traditional weight training on changes in blood lactate levels and stress indices and determined their impact on performance enhancement in sports climbing athletes specializing in speed and lead events. Thirty male sports climbing athletes were randomly assigned to the circuit weight-training group (n=15) or traditional weight-training group (n=15). Each training program was conducted for 60 min per session, 3 times/wk, for 30 sessions over 10 weeks. CWT was performed at an intensity of 40%–55% of one-repetition maximum (1RM) with maximum repeti-tions for 30 sec. Traditional weight training was performed at an intensi-ty of 70%–80% of 1RM with 8–10 repetitions. Both training protocols consisted of 3 sets, with rest intervals of 60 and 120 sec between sets for CWT and traditional weight training, respectively. Blood lactate and adrenocorticotropic hormone levels significantly decreased in the cir-cuit weight-training group. Norepinephrine and α-amylase levels de-creased in both groups, without significant differences between groups regarding the degree of change posttraining. Regarding performance changes posttraining, unlike speed records, lead records significantly differed between groups, with greater improvements in the circuit weight-training group. Changes in blood lactate affected lead records, whereas changes in stress indices influenced both speed and lead re-cords. However, effects of these changes did not significantly differ be-tween groups. Applying exercise programs tailored to sports climbing athletes according to specific events may contribute to improved per-formance by reducing blood lactate levels and stress indices, ultimately achieving better competition outcomes.
Introduction: Gout pain is a common issue among the elderly, caused by the accumulation of uric acid crystals in the joints, leading to discomfort and limited mobility. Clove (Syzygium aromaticum), … Introduction: Gout pain is a common issue among the elderly, caused by the accumulation of uric acid crystals in the joints, leading to discomfort and limited mobility. Clove (Syzygium aromaticum), known for its anti-inflammatory and analgesic properties, has been studied as a potential natural treatment for alleviating gout pain. Objective: This study aims to analyze the effectiveness of clove (Syzygium aromaticum) decoction in reducing gout pain among the elderly. Method: A systematic review search was conducted across four journal databases: PubMed, ProQuest, Garuda, and JSTOR, covering the period from 2019 to 2024. The population involved in the studies consisted of elderly individuals diagnosed with gout. The intervention analyzed in this review was the administration of clove decoction, while pain as the primary outcome was measured using the Numerical Rating Scale (NRS). The uric acid levels, as a secondary outcome, were assessed using a GCU meter. Two to three independent reviewers conducted the search, selection, extraction, and quality assessment of the identified articles. The selection process followed the PRISMA flowchart standards, while the quality of the articles was evaluated using the CASP checklist. The extracted data included key aspects such as author, intervention, facilitators, setting, number of sessions, duration, methods or media used, as well as the topics discussed in each study. Result: Of the five articles identified, a total of 95 participants were involved. The administration of clove decoction significantly reduced pain intensity due to its higher eugenol content, which was given orally (consumed) and via warm compress. The intervention was administered for 5-7 days, while the warm compress was applied for 15-20 minutes. The duration of this intervention allowed sufficient time for the eugenol content in cloves to act as an anti-inflammatory and analgesic, resulting in a more optimal therapeutic effect. Conclusion: The administration of clove decoction is a non-pharmacological therapy that demonstrates a significant impact in reducing gout pain. It may serve as a supportive alternative in pain management, reducing the use of analgesics, and improving the quality of life with minimal side effects.
Aishwarya Navarkhele | International Journal for Research in Applied Science and Engineering Technology
In this research, we formulated and evaluated herbal shampoo and done comparative assessment on marketed product name of product ‘clinic plus as it is cheap and commomly used product all … In this research, we formulated and evaluated herbal shampoo and done comparative assessment on marketed product name of product ‘clinic plus as it is cheap and commomly used product all around. People are now more conscious of the negative impacts of every component used in shampoo formulations and other cosmetic preparations. As a result, there is a rise in demand for formulations that contain natural ingredients. To evaluate its physiochemical function, which places a focus on efficacy, safety, removing dangerous substances, and replacing them with natural, safe alternatives. Hibiscus powder, henna powder, neem leaf powder, shikakai powder, reetha powder, aloe vera, lemon, orange peel powder, and other components collected to create the herbal shampoo. Additionally, distilled water, sodium chloride, and sodium lauryl sulphate were used to create a chemical shampoo. Wet duration, foam amount and stability, pH, skin sensitisation test, surface tension, detergency, soil dispersion after washing, antimicrobial test, and other experiments were performed to ascertain the physical characteristics of shampoos. The purpose of these studies was to evaluate the chemical and formulated shampoos' physicochemical properties.
Background Knee osteoarthritis is the most prevalent chronic joint disease affecting persons &amp;gt;50 years, which significantly impairs the patients’ lives. Although acupuncture can treat knee osteoarthritis; none of the studies … Background Knee osteoarthritis is the most prevalent chronic joint disease affecting persons &amp;gt;50 years, which significantly impairs the patients’ lives. Although acupuncture can treat knee osteoarthritis; none of the studies have compared the effectiveness of four common acupuncture techniques (electroacupuncture, filiform acupuncture, warming acupuncture, and fire acupuncture) in knee osteoarthritis. Methods The Web of Science, EMBASE, PubMed, Scopus, and CNKI databases were searched for the clinical randomized controlled trials of electroacupuncture, filiform acupuncture, warming acupuncture, and fire acupuncture in the treatment of knee osteoarthritis published before September 1, 2024. We collected 52 studies and used R software to analyze data. Results The results of meta-analysis showed that the efficacy rates for electroacupuncture, filiform acupuncture, warming acupuncture, and fire acupuncture were 91.5, 83.4, 84.9, and 83.5%, respectively. The respective visual analog scale (VAS) scores were 2.1, 3.2, 2.9, and 4.1, respectively. Moreover, the patient’s age and body mass index (BMI) can negatively affect the efficacy rate of acupuncture therapies, whereas age and BMI positively impacts the VAS scores. Conclusion Thus, our study suggests that electroacupuncture has the best clinical efficacy for knee osteoarthritis; however, patients’ age and BMI should be considered in future acupuncture therapies.
Background: Shoulder pain affects 20–40% of the global population and is associated with substantial healthcare costs. This study aimed to investigate the current clinical practice for shoulder pain in Korean … Background: Shoulder pain affects 20–40% of the global population and is associated with substantial healthcare costs. This study aimed to investigate the current clinical practice for shoulder pain in Korean medicine (KM) clinics and collate the insights to suggest updates to the Korean Clinical Practice Guidelines (KCPGs) for shoulder pain. Methods: A web-based survey was conducted among Korean Medicine Doctors (KMDs) from 6 March 2023 to 27 March 2023. The survey comprised 28 questions related to clinical practice, diagnosis, treatment, progress, prognosis, perception of KM on shoulder pain, and demographic characteristics. Some questions accepted multiple responses, whereas some were scaled response questions. Statistical analyses were performed on the collected data. Results: In total, 788 KMDs participated in the survey. More than 40% reported treating over 20 shoulder pain patients monthly. Diagnosis primarily relied on pain pattern, range of motion (ROM), activities of daily living (ADL), and social history. Prognostic valuation also relied on these parameters. Most KMDs used multiple treatment methods, including acupuncture, pharmacopuncture, cupping therapy, Chuna therapy, and herbal medicine. Conclusions: KMDs adopted a comprehensive multifactorial approach toward shoulder pain treatment. Insights from this survey will help update the previous KCPG for shoulder pain.
In South Korea, bee venom pharmacopuncture (BVP) is used for various conditions, such as pain, neurodegenerative diseases, and cancer. However, there is a risk of side effects. To determine whether … In South Korea, bee venom pharmacopuncture (BVP) is used for various conditions, such as pain, neurodegenerative diseases, and cancer. However, there is a risk of side effects. To determine whether there are systemic allergic side effects of BVP, we compared the total IgE level before and after BVP injection with skin test results as a fundamental study for the safe use of BVP. Thirty volunteers, who were informed about the study, agreed to participate; one had an adverse reaction to the skin test. Blood was collected before and after injecting 0.3 cc of 10% (1 mg/mL) bee venom (melittin) for joint pain, and the corresponding total IgE levels were measured for comparison. The total IgE level did not significantly change one hour after BVP injection. Ten subjects had an IgE level greater than the threshold of 100 kU/L, while 19 had an IgE level < 100 kU/L. Total IgE and wheal size were partially correlated. Moreover, the correlation coefficients between total IgE and the Mada Total IgE kit were as high as r = 0.99 in plasma, and r = 0.98 in blood. To develop a Venom Allergy Diagnostic Kit for the safe use of BVP therapy, we compared the wheal size and redness size from a skin test, before and after BVP injection. In addition, the correlations between total IgE level and the Mada total IgE kit level in plasma and blood were significantly high, indicating that measuring the total IgE level in blood might be clinically valid. In the future, it is necessary to develop a diagnostic device that can detect melittin antibodies to determine the presence of systemic allergic reactions.
Objective: This case report describes the clinical course of a male patient in his 20s with unexplained chronic fatigue who showed marked clinical improvement following traditional Korean medicine treatment.Methods: The … Objective: This case report describes the clinical course of a male patient in his 20s with unexplained chronic fatigue who showed marked clinical improvement following traditional Korean medicine treatment.Methods: The patient presented with severe fatigue, chronic constipation, and bradycardia. Based on a diagnosis of Kidney Yang deficiency, he was treated with a modified &lt;i&gt;Palmiijihwang-tang&lt;/i&gt; decoction, acupuncture, and moxibustion. Clinical progress was evaluated through subjective symptom reports, physical examinations, the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Health Questionnaire, pulse rate tracking via wearable devices, and pulse wave analysis (3D-MAC).Results: Following treatment, the patient experienced substantial improvements in fatigue and sleep quality and his constipation resolved. Bradycardia improved, with a minimum heart rate increasing from 40 bpm to 50-60 bpm. Pulse wave analysis indicated improved energy distribution patterns. EQ-5D-5L index scores increased from 0.662 to 0.920 and Visual Analogue Scale (VAS) scores from 30 to 80, reflecting a substantial improvement in quality of life.Conclusion: This case suggests that individualized traditional Korean medicine therapy may effectively improve systemic function, even in young patients with unexplained fatigue. Both subjective reports and objective physiological indicators support its potential as a holistic therapeutic option.
Objective: This case report presents a patient with idiopathic abdominal pain who experienced symptomatic improvement after receiving a complex Korean medicine treatment centered on &lt;i&gt;Cheongyeolseogeun-tang&lt;/i&gt;.Methods: A 67-year-old male presented with … Objective: This case report presents a patient with idiopathic abdominal pain who experienced symptomatic improvement after receiving a complex Korean medicine treatment centered on &lt;i&gt;Cheongyeolseogeun-tang&lt;/i&gt;.Methods: A 67-year-old male presented with idiopathic abdominal pain. Despite undergoing conventional medical examinations, no abnormalities were found, and previous treatments with Western medicine had minimal effects. Based on a Korean medical diagnosis, &lt;i&gt;Cheongyeolseogeun-tang&lt;/i&gt; was prescribed and taken three times daily. In addition, acupuncture, moxibustion, and cupping therapy were concurrently administered during a 31-day hospitalization period. Symptom changes and therapeutic effects were then evaluated.Results: After treatment, the intensity of the patient’s abdominal pain, assessed using the Numeric Rating Scale (NRS), and the frequency of pain episodes, recorded during the treatment period, significantly decreased. Digestive function and overall quality of life also improved. Objective assessments using the EQ-5D-5L and VAS scales showed significant improvements in both quality of life and pain intensity.Conclusion: This case report suggests that complex Korean medicine treatments, including &lt;i&gt;Cheongyeolseogeun-tang&lt;/i&gt;, may be effective in alleviating idiopathic abdominal pain. Further studies involving diverse clinical cases and large-scale clinical research are necessary to elucidate treatment mechanisms and evaluate efficacy.
Objective, This study aims to investigate the long-term therapeutic effects of conventional medical techniques—muscle release therapy and Pilates exercise, as well as their combination, on lumbar muscle strain in middle-aged … Objective, This study aims to investigate the long-term therapeutic effects of conventional medical techniques—muscle release therapy and Pilates exercise, as well as their combination, on lumbar muscle strain in middle-aged and young patients. Methods: A total of 100 patients aged 20–50 years who visited six hospitals in Nanjing for lumbar muscle strain were randomly assigned to four groups: muscle release therapy group (Group A), Pilates exercise group (Group B), combined muscle release therapy and Pilates exercise group (Group C), and conventional acupuncture and massage therapy group (Group D), with 25 cases in each group. Each intervention session lasted 60 minutes and was conducted three times per week. The intensity of lumbar pain and lumbar spine mobility were assessed before the intervention and at 3, 6, and 12months post-intervention. Results: After three months of treatment, patients in the combined muscle release therapy and Pilates exercise group (Group C) showed significant improvements in all indicators compared to before treatment (P&lt;0.05). At six months, this group continued to show significantly better outcomes than the other groups. The muscle release group (Group A) and the conventional acupuncture and massage group (Group D) had similar results, which were better than those in the Pilates exercise group (Group B). At 12 months, the combined treatment group (Group C) still had significantly better outcomes than the other groups. The Pilates exercise group (Group B) had better outcomes than the muscle release group (Group A) and the conventional acupuncture and massage group (Group D), but the differences between Group B and the other groups were not significant. The indicators of the muscle release group (Group A) and the conventional acupuncture and massage group (Group D) were similar. Conclusion: The combination of muscle release therapy and Pilates exercise is the most effective treatment for lumbar muscle strain in middle-aged and young patients.
Background: The diagnostic accuracy of the exercise treadmill test (ETT) remains suboptimal in premenopausal women. Menstrual cycle phases display hormonal variations and biological effects in premenopausal women. The early and … Background: The diagnostic accuracy of the exercise treadmill test (ETT) remains suboptimal in premenopausal women. Menstrual cycle phases display hormonal variations and biological effects in premenopausal women. The early and late follicular phases of the menstrual cycle demonstrate nearly four-fold differences in estrogen levels. Methods: This study assessed the variability in ETT results between the early and late follicular phases in premenopausal women. This study included premenopausal females with regular menstrual cycles and chest pain. As per the study protocol, patients underwent two separate ETTs at the early and late follicular phases of the menstrual cycle. Hormones and high-sensitivity cardiac troponin T (hs-cTnT) were measured. The primary endpoint was the ST segment/heart rate (HR) index. The secondary endpoints were maximum ST/HR slope, ST segment depression, HR and blood pressure (BP) response, exercise capacity, and hs-cTnT change after ETT. Results: False-positive ETT results were common in premenopausal women. The early follicular phase displayed significantly higher hs-cTnT and BP responses to ETT compared to the late follicular phase. This study reports that ETT results are similar between the early and late follicular phases of the menstrual cycle in premenopausal women. Biological variability is observed in the BP and hs-cTnT response to ETT between the two phases. Conclusions: The menstrual cycle phase (early versus late follicular phase) did not affect the ETT results. The consideration of estrogen and hormonal status when evaluating the diagnostic test results can improve our understanding of cardiovascular disease in women.
Background and Objectives: There have been a limited number of randomized controlled trials (RCTs) comparing pharmacopuncture therapy (PPT) and physical therapy (PT) for chronic knee pain. In this study, we … Background and Objectives: There have been a limited number of randomized controlled trials (RCTs) comparing pharmacopuncture therapy (PPT) and physical therapy (PT) for chronic knee pain. In this study, we assess the feasibility, safety, and preliminary effectiveness of PPT compared to PT in patients with chronic knee pain. Materials and Methods: This pilot study was designed as a two-arm, parallel RCT. Patients were recruited through in-hospital advertisements. Forty patients aged 19 to 70 with knee pain with a numeric rating scale (NRS) score of 5, persisting for >3 months, were randomized into the PPT or PT group. The type of PT solution or PT method was not determined in advance, leaving it to the clinician's judgment. Treatment was administered twice weekly for 3 weeks with a 6-week follow-up. The primary outcome was the NRS score for knee pain, whereas the secondary outcomes were the visual analog scale (VAS), knee range of motion, Korean Western Ontario and McMaster (K-WOMAC), Patient Global Impression of Change, and five-level EuroQol five-dimension scores. Additionally, adherence, acceptability, dropout rate, and adverse events were measured to assess the feasibility of a follow-up main study. The protocol was registered at ClinicalTrials.gov (NCT06505681). Results: The PPT group showed significantly superior improvement compared with the PT group in the NRS (difference = -2.05, 95% confidence interval [CI]: -2.76 to -1.34), VAS (difference = -21.58, 95% CI: -29.42 to -13.74), and K-WOMAC scores (difference = -13.17, 95% CI: -21.67 to -4.67). Of the 55 patients who initially expressed interest in participation, 8 declined after receiving detailed information about this study. Among the forty enrolled participants, one patient in the PPT group dropped out, and one missed a single treatment session. Apart from these cases, all participants completed the assigned treatments and follow-up assessments, demonstrating high adherence. No serious adverse events were reported. Conclusions: PPT demonstrated excellent effectiveness in pain relief and functional improvement in these patients.
Cleome genus is commonly known as spider flower plant or cats whiskers, and is the largest genus of the family Cleomaceae, with around 200 species containing a range of remedial … Cleome genus is commonly known as spider flower plant or cats whiskers, and is the largest genus of the family Cleomaceae, with around 200 species containing a range of remedial applications. Several species of Cleome genus show anti-cancer properties, however, nothing has been reported with genus spinosa, an anti-inflammatory and immunomodulatory plant. Thus, the present study examined the likely anti-cancer property of ethanolic leaf extract of Cleome spinosa (CSE) in Ehrlich ascites carcinoma (EAC) cells in vitro and in vivo. CSE treatment in vitro significantly caused higher percentage of death in EAC in a dose dependent manner compared to control groups (untreated and ethanol treated). Bright field, fluorescence and electron microscopies revealed apoptotic changes such as surface blebbings, nuclear fragmentation, chromatin condensation and apoptotic body formation, which probably could be the cause of death in EAC cells with CSE treatment. Apoptosis of CSE-treated EAC cells appeared to be mediated through upregulation of pro-apoptotic protein p53 and downregulation of anti-apoptotic protein, Bcl-xL expression, as ascertained through western blot both in vitro and in vivo. CSE was protective toward murine splenocytes by scavenging free radicals; it also reduced the ascitic tumor burden and increased the survival of the tumor-bearing mice compared to the control. Gas Chromatography-Mass Spectrometry (GCMS) analysis identified 43 phytocompounds in CSE. In silico molecular docking analysis indicated that a number of bioactive compounds, such as cycloartenol, stigmasterol, clionasterol, beta-sitosterol, lupenone, and sitostenone that were abundant in the CSE extract, exhibited strong binding affinities for the key apoptosis- regulating proteins, p53 and Bcl-xL. Thus, CSE derived-compounds appear to act as natural antioxidants, and have anti-cancer properties via induction of apoptosis in EAC possibly through upregulation of p53 and downregulation of Bcl-xL proteins in murine model. Hence, CSE could be considered as a promising natural compound for future cancer therapies.
| Indian Journal of Traditional Knowledge
Limited research has addressed safety concerns related to vaccination against the human papillomavirus (HPV). To investigate the association between receipt of HPV vaccination and autonomic dysfunction and menstrual irregularities in … Limited research has addressed safety concerns related to vaccination against the human papillomavirus (HPV). To investigate the association between receipt of HPV vaccination and autonomic dysfunction and menstrual irregularities in girls and young women. Using a 25% random sample of IQVIA PharMetrics® Plus for Academics claims database from 2016 to 2020, we conducted a self-controlled case series study in commercially insured girls and young women receiving their first HPV vaccine dose (analyses conducted between March 2024 and April 2025). Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated for two outcomes-autonomic dysfunction and menstrual irregularities. We conducted further analyses stratified by number of HPV vaccine doses received per beneficiary and by age (9-17 years vs. 18-26 years), as well as adjusted for age as a time-varying covariate. The IRRs were estimated over a maximum risk case post-vaccination period of 36 months compared to a 6-month within-person control pre-vaccination period. There were 1654 individuals in the autonomic dysfunction cohort and 3140 individuals in the menstrual irregularities cohort. When adjusted for age, HPV vaccination was associated with elevated IRRs for autonomic dysfunction (IRR 1.23; 95% CI 1.08-1.41) and menstrual irregularities (IRR 1.30; 95% CI 1.18-1.43). IRRs for individual outcomes varied by age group, with the younger cohort showing a significantly higher age-adjusted IRR than the older cohort for menstrual irregularities (IRR 1.51; 95% CI 1.33-1.72 vs. IRR 1.15; 95% CI 0.99-1.33, respectively). Although the risk of experiencing autonomic dysfunction was not significant in the adjusted younger cohort, young women aged 18-26 years had a heightened age-adjusted risk (IRR 1.40; 95% CI 1.12-1.75). Findings from the dose-response analysis were inconclusive. HPV vaccination is associated with elevated risks of autonomic dysfunction and menstrual irregularities, which vary by age. Further research is needed to identify additional risk factors associated with HPV vaccination safety.
“Thuốc viên khớp Abipha” là chế phẩm gồm nhiều dược liệu đã được chứng minh có tác dụng giảm đau chống viêm và ức chế phá hủy sụn khớp. Nghiên … “Thuốc viên khớp Abipha” là chế phẩm gồm nhiều dược liệu đã được chứng minh có tác dụng giảm đau chống viêm và ức chế phá hủy sụn khớp. Nghiên cứu được thực hiện trên chuột cống trắng chủng Wistar được gây mô hình thoái hóa khớp gối bằng MIA (monosodium-iodoacetate) liều 3 mg/khớp, nhằm khảo sát tác dụng chống thoái hóa khớp của chế phẩm trên thực nghiệm. Các thuốc nghiên cứu gồm có: diclofenac 3 mg/kg và “Thuốc viên khớp Abipha” ở các mức liều 216 mg/kg, 648 mg/kg. Sau 6 tuần uống thuốc liên tục, diclofenac 3 mg/kg, “Thuốc viên khớp Abipha” cả 2 liều có tác dụng chống thoái hóa khớp gối của chuột thông qua giảm đau khớp gối, ức chế phá hủy sụn khớp và làm giảm chỉ số cytokin (IL-1β, TNF-α).
Nghiên cứu nhằm đánh giá độc tính cấp và bán trường diễn của viên nang cứng “Kiện vị bổ trung HĐ” trên thực nghiệm. Nghiên cứu độc tính cấp của … Nghiên cứu nhằm đánh giá độc tính cấp và bán trường diễn của viên nang cứng “Kiện vị bổ trung HĐ” trên thực nghiệm. Nghiên cứu độc tính cấp của viên nang cứng trên chuột nhắt trắng theo đường uống, nghiên cứu độc tính bán trường diễn của viên nang cứng trên chuột cống trắng theo hướng dẫn của WHO. Kết quả nghiên cứu cho thấy với liều cao nhất (liều 25 g/kg thể trọng chuột - gấp 34,7 lần liều dự kiến dùng trên lâm sàng) không xác định được liều gây chết 50% số động vật thí nghiệm (LD50) của viên nang cứng. Viên nang cứng “Kiện vị bổ trung HĐ” không gây độc tính bán trường diễn trên chuột cống trắng với liều tương đương lâm sàng (0,36 g/kg thể trọng chuột/ngày) và liều gấp 3 liều lâm sàng (1,08 g/kg thể trọng chuột/ngày) trong 90 ngày liên tục uống thuốc. Tất cả các chỉ số theo dõi về tình trạng chung, cân nặng, chức năng tạo máu, chức năng gan, chức năng thận, mô học gan và thận đều nằm trong giới hạn bình thường.
Ji-Yong Joo | Korean Association For Learner-Centered Curriculum And Instruction
Objectives The purpose of this study was to provide foundational data on whether the application of myofascial release therapy during pull-up exercises can enhance muscle activation. Methods For this purpose, … Objectives The purpose of this study was to provide foundational data on whether the application of myofascial release therapy during pull-up exercises can enhance muscle activation. Methods For this purpose, the participants were students from the Department of Physical Education at C University who had no musculoskeletal issues in the past year and could perform at least 10 pull-ups without assistance. After performing standard pull-ups, participants rested sufficiently before performing pull-ups with myofascial release therapy applied. Results First, when comparing the time taken for the pull-up exercise, the pull-up with myofascial release therapy was statistically faster than the standard pull-up (p&lt;.05). Second, the number of repetitions for the pull-up exercise was statistically higher for the pull-up with myofascial release therapy than for the standard pull-up (p&lt;.05). Third, regarding muscle activation during the pull-up exercise, the activation of the posterior deltoid and upper trapezius was statistically lower in the pull-up with myofascial release therapy compared to the standard pull-up (p&lt;.05). Fourth, when analyzing muscle activation in 1% increments through time series, there were no statistically significant differences in the activation of the forearm muscles, biceps brachii, middle trapezius, and lower trapezius. However, the activation of the latissimus dorsi, pectoralis major, posterior deltoid, and upper trapezius was significantly higher in the pull-up with myofascial release therapy compared to the standard pull-up (p&lt;.05). Additionally, the activation of the anterior deltoid was significantly lower in the pull-up with myofascial release therapy than in the standard pull-up (p&lt;.05). Conclusions The myofascial release therapy applied to the pull-up exercise increased the initial activation of the latissimus dorsi, which led to a compensatory increase in the activation of the back muscles.
This study aims to perform a comprehensive multi-strategy screening of quality markers (Q-markers) by integrating serum pharmacochemistry, chromatographic fingerprinting, and network pharmacology. The objective is to apply these methodologies for … This study aims to perform a comprehensive multi-strategy screening of quality markers (Q-markers) by integrating serum pharmacochemistry, chromatographic fingerprinting, and network pharmacology. The objective is to apply these methodologies for the quality control of traditional Chinese medicine (TCM) compound preparations. Firstly, the UPLC-Q-Exactive Orbitrap-MS was used to conduct a comparative analysis of the aqueous extract of Di Huang Yin Zi (DHYZ), the blank group, and the dosing group. Through the Xcalibur software, 10 blood components and 17 metabolites absorbed by DHYZ were identified. Then, the HPLC acetonitrile-formic acid water gradient elution system was used for detection at 330 nm. HPLC analysis was conducted on 16 batches of samples, and 22 common peaks with a similarity greater than 0.9 were established. 8 qualitative chemical components were quantitatively analyzed. Including morroniside, loganin, echinacoside, 5-hydroxymethylfurfural, acteoside, cinnamaldehyde, polygalaxanthone III and 3,6'-disinapoyl sucrose. The sample quality was comprehensively evaluated by using cluster analysis (HCA), Principal component analysis (PCA), and Orthogonal partial least squares discriminant Analysis (OPLS-DA). The results show that the 16 batches can be divided into 4 categories, and the results of PCA and HCA are consistent. The OPLS-DA model is stable and reliable, identifying morroniside (peak 4), echinacoside (peak 9), acteoside (peak 11), and 3,6'-disinapoyl sucrose (peak 13) as key discrimination markers. Finally, using network pharmacology methods, we constructed a component-target-disease-pathway network, thereby identifying 27 components associated with the efficacy of DHYZ. By integrating the above results, 3 active ingredients, morroniside, echinacoside, and 3,6'-disinapoyl sucrose, were identified as Q-markers that can be used for the quality control of DHYZ, providing a reference for establishing a robust quality control system for DHYZ.
Objective: To examine the efficacy and safety of pestle needle therapy (PNT) across several prevalent conditions, including insomnia, cervical spondylosis, lumbar disc herniation and other systemic diseases. Methods: We searched … Objective: To examine the efficacy and safety of pestle needle therapy (PNT) across several prevalent conditions, including insomnia, cervical spondylosis, lumbar disc herniation and other systemic diseases. Methods: We searched eight databases (SinoMed, China National Knowledge Infrastructure, Wanfang Data, VIP Database, Google Scholar, PubMed, Embase and Web of Science) from inception to 31 December 2023, using both subject terms and free-text terms related to ‘pestle needle’ and ‘randomised controlled trial’. Eligible randomised controlled trials (RCTs) that investigated PNT alone or in combination with other therapies were included. Primary outcomes included the overall response rate (ORR) and incidence of adverse events. Results: A total of 29 RCTs involving 2,614 patients were included. Meta-analysis results showed that, compared with controls, PNT significantly improved ORR in insomnia (odds ratio [OR] = 4.07, 95% confidence interval [CI]: 2.33, 7.09), cervical spondylosis (OR = 4.38, 95% CI: 2.41, 7.97), lumbago and leg pain (OR = 3.32, 95% CI: 1.86, 5.91) and lumbar disc herniation (OR = 1.92, 95% CI: 1.12, 3.29). Regarding cervical spondylosis, the intervention of the observation group was significantly better than that of the control group (Z = 4.84, P &lt; 0.001). In terms of low back pain and leg pain, the intervention of the observation group was significantly better than that of the control group (Z = 4.07, P &lt; 0.001). The intervention of the observation group was significantly better than in the control group in improving the total effective rate of the treatment of lumbar disc herniation (Z = 2.37, P = 0.02). Conclusion: Pestle needle therapy is a safe and effective treatment modality that can complement or substitute conventional interventions. This systematic review and meta-analysis contributes to the evidence base for acupuncture-related therapies, highlighting the potential of PNT to address both musculoskeletal and neurological conditions, thus offering new clinical options and underscoring the need for large-scale, high-quality RCTs to refine treatment protocols.
Objective To study the pattern reversal visual evoked potential (PRVEP) in patients with post stroke cognitive impairment (PSCI) and to provide an objective and accurate basis for the neurophysiological assessment … Objective To study the pattern reversal visual evoked potential (PRVEP) in patients with post stroke cognitive impairment (PSCI) and to provide an objective and accurate basis for the neurophysiological assessment of cognitive function in stroke patients. Methods First stroke patients admitted to the department of Rehabilitation Medicine of the Second Hospital of Jilin University between October 2022 and October 2023 were enrolled as subjects according to the inclusion criteria, exclusion criteria, shedding and exclusion criteria. They were screened for whole cognitive function using the Montreal Cognitive Assessment (MoCA), and were divided into a post-stroke cognitive impairment (PSCI) group (n=44) and a control group (post-stroke patients with normal cognitive function, n=25). The PSCI group was divided into three group including mild, moderate and severe PSCI patients according to the severity of their cognitive impairment. Clinical data of the above patients were collected, PRVEP examination was performed and index of P100 waves were calculated for both eyes. SPSS 25.0 statistical analysis was used to analyze data of patients. Results 69 first-stroke patients completed the whole experiment, including 25 cases in control group, 14 cases in mild PSCI group, 14 cases in moderate PSCI group, and 16 cases in severe PSCI group. In patients with detectable VEP, the difference in latent period of P100 in both eyes of the PSCI group (n=20) was greater than that of the control group (n=19) (P&lt;0.01), and the amplitude ratio of P100 waves on both sides in PSCI group was higher than that of the control group (P&lt;0.05). Compared with PSCI patients with left-sided hemiplegia, PSCI patients with right-sided hemiplegia had a longer P100 latency in the right eye (P&lt;0.05); Compared with PSCI patients without brainstem involvement, PSCI patients with brainstem involvement had an increased P100 latency in both eyes (P&lt;0.01); Pearson correlation analysis showed that the binocular amplitude ratio in the VEP parameters in the PSCI group was correlated with the MoCA score (r=-0.624, P&lt;0.01). The ROC curve showed that the difference in the latent period of P100 in both eyes and the ratio of P100 amplitude in both eyes had certain predictive value for the diagnosis of PSCI (AUC=0.875, 0.842; P&lt;0.05). Conclusion PRVEP examination and VEP parameters can help to distinguish stroke patients with or without cognitive impairment. In first-stroke patients with detectable VEP, the difference in binocular P100 latency and the ratio of binocular P100 amplitude have certain predictive value for diagnosis of PSCI, which is worthy of further study and application.
Abstract Glioblastoma (GBM), a highly aggressive brain tumor, thrives in hypoxic environments. Tumor-derived exosomes are key drivers of glioma progression, facilitating tumor growth, immune evasion, angiogenesis, and therapy resistance. Acrolein, … Abstract Glioblastoma (GBM), a highly aggressive brain tumor, thrives in hypoxic environments. Tumor-derived exosomes are key drivers of glioma progression, facilitating tumor growth, immune evasion, angiogenesis, and therapy resistance. Acrolein, a toxic byproduct produced under hypoxic conditions, causes DNA damage, inflammation, mitochondrial dysfunction, and potentiates oxidative stress. Elevated acrolein levels and associated DNA damage are linked to poor GBM prognosis. This study aims to uncover the role of acrolein in GBM progression through exosome-mediated pathways and the associated molecular mechanisms. We found that acrolein production under hypoxia promotes GBM cell malignant behavior, such as migration and spheroid formation, by downregulating neural cell adhesion molecule 1 (NCAM1) via autocrine and paracrine signaling of miR-30a-5p. Inhibiting the miR-30a-5p/NCAM1 axis reverses the tumor-promoting effects of acrolein treatment. Analysis of tumor samples from GL261 tumor-bearing mice and glioma patients showed that decreased NCAM1 levels in glioma tissues correlate with elevated acrolein expression. In patient GBM samples, lower NCAM1 levels are associated with a worse prognosis. This study suggests that targeting the miR-30a-5p/NCAM1 axis could be a potential therapeutic strategy for GBM.
Abstract Background: Breast cancer associates a broad variety of psychological and physical symptoms with a significant impact on quality of life. Mindfulness therapies (MBIs), such as MBSR (Mindfulness-Based Stress Reduction) … Abstract Background: Breast cancer associates a broad variety of psychological and physical symptoms with a significant impact on quality of life. Mindfulness therapies (MBIs), such as MBSR (Mindfulness-Based Stress Reduction) and MBCT (Mindfulness-Based Cognitive Therapy) have been related with better control of this daily routine signs, achieving better emotional regulation, decreasing internal dialogue, increasing awareness of body sensations (posture, breathing...) and slowing down of mental processes. Mindfulness is a psychological technique that tries to reach a state of full consciousness. It is useful on the treatment and prevention of several diseases by different mechanisms. The brain areas linked to MBIs are: the insular cortex, related to body and emotional awareness; the hippocampus, involved in memory organization; the secondary somatosensory cortex and anterior cingulate, related to pain and the bilateral superior parietal lobe and left superior frontal gyrus, involved in attention. MBI is also related with an increase in telomeric length, increased expression of the hTERT (human telomerase reverse transcriptase) and HTR (human telomerase RNA) genes and a decrease in the level of methylation of the hTERT promoter regions (implying increased gene expression). These changes have potential effect to delay cellular aging. There is a relationship between long-term meditation practice and a loss of methylation of CpG nucleotides and epigenetic changes in the tumor necrosis factor (TNF) and beta neurotrophic factor (NF-κß) signaling pathway. PURPOSE: The aim of this study is to compile the effects of different mindfulness therapies on the symptoms associated with breast cancer, both in women with active disease and in survivors. Methods: a systematic review was conducted using PubMed, PsycINFO, Cochrane library and Web of Science. Thirteen studies, published in the last seven years (between January 1st, 2017 and December 31st, 2023), were included: 10 on patients with “active disease” and 3 on “survivors”. Results: MBIs produce statistically and significant benefits in the short and medium term, on depressive symptoms, anxiety and stress. Among physical symptoms, a significant effect is seen about the reduction of fatigue with MBSR therapies. Other symptoms such as cognitive function and sleep quality also improve with these therapies. Regarding quality of life, only short-term improvements are been observed. MBCT protocols are included in few works. Its role in BC survivors is limited because the low number of researches and the lack of a homogeneous definition of “survivor”. Conclusion: Because of the benefit that mindfulness therapies (MBIs) (specially MBSR and MBCT) have on anxiety, stress, depressive symptoms, fatigue and other symptoms associated with breast cancer, it is proposed to use it as a complementary therapy in the management of these patients. Citation Format: Maria-Eva Perez-Lopez, Iria Fernandez-Somme, Cristina Reboredo, Beatriz Alonso, Silvia Antolin, Patricia Cordeiro, Lourdes Calvo. Mindfulness as effective complementary therapy in the management of Breast Cancer (BC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-05-09.
Background: Cardiorespiratory endurance is vital to athletic performance, particularly in sports requiring sustained physical exertion such as martial arts. Objectives: This study examined the predictive roles of body composition (BMI), … Background: Cardiorespiratory endurance is vital to athletic performance, particularly in sports requiring sustained physical exertion such as martial arts. Objectives: This study examined the predictive roles of body composition (BMI), hemoglobin concentration, and motivation on cardiorespiratory endurance among university-level martial arts athletes. Methods: Using a quantitative path analysis design, data were collected from 20 purposively selected martial arts athletes who regularly trained. Cardiorespiratory endurance was assessed via the multistage fitness test, BMI was calculated using standard anthropometric measures, hemoglobin was measured using the Harenz scale, and motivation was evaluated with a validated Likert-scale questionnaire. Results: The analysis showed that BMI (ρ = 0.705, t = 3.071, p = 0.007) and hemoglobin concentration (ρ = 0.946, t = 4.672, p &lt; 0.001) had significant positive effects on cardiorespiratory endurance. Motivation, however, did not have a significant direct effect (ρ = 0.087, t = 0.853, p = 0.203). Additionally, BMI correlated positively with both hemoglobin (ρ = 0.923, p &lt; 0.001) and motivation (ρ = 0.670, p = 0.034), suggesting indirect effects through physiological mechanisms. Conclusions: The findings underscore that physiological indicators, specifically BMI and hemoglobin, are more critical predictors of aerobic capacity than psychological factors like motivation in this athletic population. Due to sport-specific demands, these results may not be generalizable to non-martial arts athletes. Future studies should incorporate additional mediators such as training intensity and account for potential self-report bias in motivation assessments.
Martial arts exercise causes significant wear and tear on the knee joint. The existing anti-collision knee pads are insufficient to meet the requirements of wearing comfort and mechanical performance. Therefore, … Martial arts exercise causes significant wear and tear on the knee joint. The existing anti-collision knee pads are insufficient to meet the requirements of wearing comfort and mechanical performance. Therefore, a composite material based on shear thickening gel (STG) is proposed. The preparation process of this material is doped with polyester short fibers and multi-walled carbon nanotubes (MWNT). The composite is filled into naturally structured Kevlar flat weave fabric (Kevlar) to enhance the mechanical properties of the pure fabric. The results indicated that the MWNT/STG/Kevlar composite material prepared by the proposed method effectively enhanced the dynamic properties of the shear thickening agent. The worst fracture strength and displacement were 600 N and 38 mm, respectively, both of which complied with national standards. The bending performance was 10.2 % and 14.2 % higher than the other two composite materials. The average air permeability was 190 mm/s, which was 60 % and 78 % higher than the other two materials, respectively. The impact resistance performance decreased by 42 %, 54 %, 57 %, and 68 % compared with the other three knee pads, respectively. Therefore, the MWNT/STG/Kevlar composite material prepared by the proposed method can be applied in the knee pad preparation process, effectively increasing the mechanical properties of the knee pad, preventing impact during martial arts exercise, and improving the wear comfort.