Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord ...Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking.Here,by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey,we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord.Labeled alpha motor neurons were located in lamina IX of the L6–S1 segments,which innervate both flexors and extensors.The labeled primary sensory afferents were mainly myelinated Aβfibers that terminated mostly in laminae I and II of the L4–L7 segments.Together with the labeled proprioceptive afferents,the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons.In summary,our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.展开更多
Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-li...Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.展开更多
Mycotoxins,toxic secondary metabolites produced by fungus including Aspergillus,Penicillium,and Fusarium,pose considerable threats to food safety and human health worldwide.This review analyzes the main categories of ...Mycotoxins,toxic secondary metabolites produced by fungus including Aspergillus,Penicillium,and Fusarium,pose considerable threats to food safety and human health worldwide.This review analyzes the main categories of mycotoxins—namely aflatoxins,ochratoxins,and fusarium toxins(zearalenone and fumonisins)—along with their health implications,sources of contamination,and environmental circumstances conducive to their production.The document highlights the pressing necessity for efficient management techniques and investigates the use of food polymer-based nanotechnology as an innovative solution.Biopolymeric nanoparticles produced from natural food materials exhibit notable antibacterial characteristics,biodegradability,and the ability to enhance mycotoxin detection and management.This review emphasizes the transformative capacity of nanotechnology based innovative strategies in improving mycotoxin control,providing insights into emerging research avenues and practical applications to bolster food safety systems and keyword co-occurrence analysis,limitations and future perspectives.展开更多
Botulinum toxin,a protein exotoxin secreted by Clostridium botulinum,binds to peripheral nerve terminals,inhibits acetylcholine release,and leads to flaccid muscle paralysis.[1]Botox(onabotulinum toxin A)was approved ...Botulinum toxin,a protein exotoxin secreted by Clostridium botulinum,binds to peripheral nerve terminals,inhibits acetylcholine release,and leads to flaccid muscle paralysis.[1]Botox(onabotulinum toxin A)was approved by the Food and Drug Administration(FDA)for cosmetic and therapeutic indications in 2002,and its global use has increased substantially.[2]However,some unlicensed botulinum toxin products may cause iatrogenic botulism.[3]Early diagnosis remains challenging owing to non-specific clinical features and the lack of diagnostic biomarkers,often delaying the timely administration of antitoxin.[4]This study reviewed recent cases of botulism in our center and summarized their clinical presentations,symptoms,and outcomes.展开更多
Dear Editor,We recently reviewed two important studies that investigate the use of botulinum-A toxin(BoNT-A)injections into the bulbospongiosus muscle as a treatment for lifelong premature ejaculation(PE).While both s...Dear Editor,We recently reviewed two important studies that investigate the use of botulinum-A toxin(BoNT-A)injections into the bulbospongiosus muscle as a treatment for lifelong premature ejaculation(PE).While both studies share the goal of evaluating the efficacy and safety of BoNT-A in this context,they reached very different conclusions.The study by Shaher et al.demonstrated significant improvements in ejaculatory latency,indicating that BoNT-A injections may be a helpful treatment for PE.展开更多
Introduction:When conservative treatments fail,botulinum toxin A(BoNT-A)is an option for refractory idiopathic overactive bladder(OAB).This review evaluates the efficacy,safety,and predictive factors for BoNT-A in thi...Introduction:When conservative treatments fail,botulinum toxin A(BoNT-A)is an option for refractory idiopathic overactive bladder(OAB).This review evaluates the efficacy,safety,and predictive factors for BoNT-A in this situation.Material and Methods:A literature search up to January 2025 was performed using PubMed,Google Scholar,and Embase to assess efficacy,safety,and predictors of adverse events(AE)related to BoNT-A.The risk of bias was assessed using the Risk of Bias 2(RoB 2)tool for randomized studies and the Critical Appraisal Skills Programme(CASP)checklist for cohort studies.The quality of the review was evaluated based on the Oxford criteria,following the Strengthening the Assessment of Narrative Review Articles(SANRA)guidelines,and by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines for systematic reviews.Results:31 studies were included,involving 5410 patients.BoNT-A improves OAB symptoms even after reinjections.Higher doses do not enhance efficacy but increase AE.AE includes high post-void residual(PVR),clean intermittent self-catheterization(CISC),and Urinary Tract Infection(UTI).Predictors of CISC include age,male gender,hysterectomy,≥3 vaginal deliveries,mixed incontinence,prior mid-urethral sling(MUS),high PVR,low Pressure at Pdet at First Micturition(PIP1)in women,low Bladder Compliance Index(BCI)in men,and high Bladder Outlet Obstruction Index(BOOI).Diabetes and heart failure increase PVR.UTIs are more frequent in women and men with benign prostatic hyperplasia,with CISC increasing the risk fivefold.Severe complications are rare.Predictors of poor response include male gender,high BOOI,low urinary flow,and diabetes.Discussion:BoNT-A is effective for OAB,especially for incontinence.AE is dose-dependent and limits treatment adherence.Their link with poor response remains unclear.Conclusion:BoNT-A effectively treats refractory idiopathic OAB,improving symptoms and quality of life with repeated injections.展开更多
Orofacial muscle hypertonicity,characterized by excessive muscle tension in the facial and masticatory regions,can lead to significant functional impairment and aesthetic concerns.Botulinum toxin type A(BoNT-A),widely...Orofacial muscle hypertonicity,characterized by excessive muscle tension in the facial and masticatory regions,can lead to significant functional impairment and aesthetic concerns.Botulinum toxin type A(BoNT-A),widely known for its cosmetic applications,has emerged as a valuable therapeutic tool in dentistry and maxillofacial medicine.This review explores the pharmacological mechanisms,anatomical considerations,and clinical applications of BoNT-A in the treatment of functional disorders such as bruxism,masseter hypertrophy,temporomandibular joint dysfunction,and facial asymmetry.Emphasis is placed on precision-guided injection techniques,region-specific dosing trends,and formulation-specific performance.Adverse effects,although generally mild and self-limiting,are preventable through anatomical expertise and individualized protocols.Preliminary clinical observations and recent East Asian data suggest variations in the response patterns and optimal dosing strategies.This review also highlights the current gaps,including the need for long-term safety data,standardized training for dental practitioners,and comparative evaluations with non-pharmacological therapies.BoNT-A is a minimally invasive interdisciplinary approach for restoring oral function and facial harmony,supporting its integration into modern dental practice.展开更多
Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the associat...Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the association between the alga toxinsβ-N-methylamino-L-alanine(BMAA),brevetoxin B,cyanoginosin LR,okadaic acid and neurodegenerative diseases remains inadequately investigated.Therefore,the aim of this study was to elucidate the potential associations.Four sets of differentially expressed genes related with BMAA,brevetoxin B,cyanoginosin LR and okadaic acid in Homo sapiens and genes linked to neurodegenerative disease development were respectively collected from the Comparative Toxicogenomic Database.Metascape analysis and cluster community analysis of four alga toxins highlighted protein-protein interaction enrichment and hub genes,while biological processes analysis showed that the dominant pathways involved in harmful effects triggered by four alga toxins were the apoptotic signaling pathway,regulation of amyloid protein formation,inflammatory response and endoplasmic reticulum stress.Genes related to the interactions between four alga toxins and neurodegenerative diseases were selected and analyzed,revealing that the relevant pathways and genes were those involved in apoptotic mitochondrial changes and neuroinflammatory response pathways.The adverse outcome pathway frameworks were constructed according to the analysis results for toxins and associated neurodegenerative diseases.These discoveries provide a new perspective for us to gain a deeper understanding of the neurotoxic effects of four alga toxins.展开更多
Domoic acid(DA),a biotoxin,is produced by several species of marine dinoflagellate and diatom during harmful algal bloom events.DA is a neurotoxin,in humans and non-human primates,oral exposure to DA results in gastro...Domoic acid(DA),a biotoxin,is produced by several species of marine dinoflagellate and diatom during harmful algal bloom events.DA is a neurotoxin,in humans and non-human primates,oral exposure to DA results in gastrointestinal effects,while DA at higher doses leads to neurological symptoms,seizures and memory deficiency.Exposure of humans to DA occurs mainly through consumption of contaminated seafoods containing an accumulation of the toxin.Previously,it was unclear if DA can have toxic effects on the retina.We assessed the toxicity of DA in human retinal cells(ARPE-19)and in zebrafish embryos.DA significantly lowered ARPE-19 cell viability dose-dependently,and decreased anti-oxidative capacity,increased inflammation,and promoted cell death,possibly through modulating the NRF2 and NF-κB signalling pathways.Zebrafish embryos exposed to DA for 4 days from 1 day post fertilization(dpf)had an increase in mortality and a decrease in both hatching and heartbeat rate and exhibited morphological abnormalities.DA treatment also significantly downregulated expression of antioxidant genes and upregulated expression of inflammation mediators,as well as causing photoreceptor death in zebrafish embryos.The results demonstrate that consuming seafood containing DA will have potential toxic effects in human retinas.展开更多
Background:Androgenetic alopecia(AGA)is a common hair loss disorder that significantly affects patient’s quality of life.Botulinum toxin(BoNT)has emerged as a potential treatment;however,its effectiveness and underly...Background:Androgenetic alopecia(AGA)is a common hair loss disorder that significantly affects patient’s quality of life.Botulinum toxin(BoNT)has emerged as a potential treatment;however,its effectiveness and underlying mechanisms remain unclear.This systematic review aimed to synthesize the existing evidence on BoNT for AGA,analyze its mechanisms,evaluate its efficacy,and explore its potential for precision therapy.Methods:A PubMed search was conducted for studies published between 2020 and 2025.A total of 25 studies,including 11 clinical trials and 7 reviews,were included.The studies were analyzed for BoNT mechanisms in AGA,treatment regimens,efficacy,outcomes,cost-effectiveness,and safety profiles.Results:Experimental evidence suggests that BoNT reduces transforming growth factor-βin dermal papilla cells,a key pathological pathway in AGA.Other hypothetical mechanisms,such as scalp muscle relaxation improving microcirculation or inhibiting androgen conversion require further validation.In clinical trials,most studies used 30-150 U of BoNT via intramuscular(six studies)or intradermal(three studies)injections,with 1-3 sessions and up to 6 months of follow-up.Early open-label trials reported response rates of 70%-79%,but recent high-quality randomized controlled trials(RCTs)showed no significant improvement in hair density compared to placebo.Combination therapy with finasteride or minoxidil enhanced treatment outcomes,though large-scale evidence is lacking.BoNT was less cost-effective than first-line therapies such as minoxidil,with session costs approximately 37 times higher.Intramuscular injection appeared more effective than intradermal injection,possibly due to scalp muscle relaxation and vascular decompression.BoNT generally had a mild safety profile.Conclusion:Currently,BoNT lacks robust evidence to replace traditional treatments for AGA.Future research should focus on establishing standardized dosing protocols,conducting large-scale,long-term RCTs,and integrating molecular biomarkers to improve understanding and optimize the clinical use of BoNT in AGA management.展开更多
The integration of phytochemistry into forensic science has emerged as a groundbreaking frontier,providing unprecedented insights into nature's secrets through the precise application of phytochemical fingerprinti...The integration of phytochemistry into forensic science has emerged as a groundbreaking frontier,providing unprecedented insights into nature's secrets through the precise application of phytochemical fingerprinting of phytotoxins as a cutting-edge approach.This study explores the dynamic intersection of phytochemistry and forensic science,highlighting how the unique phytochemical profiles of toxic plants and their secondary metabolites,serve as distinctive markers for forensic investigations.By utilizing advanced techniques such as Ultra-High-Performance Liquid Chromatography(UHPLC)and High-Resolution Mass Spectrometry(HRMS),the detection and quantification of plant-derived are made more accurate in forensic contexts.Real-world case studies are presented to demonstrate the critical role of plant toxins in forensic outcomes and legal proceedings.The challenges,potential,and future prospects of integrating phytochemical fingerprinting of plant toxins into forensic science were discussed.This review aims to illuminate phytochemical fingerprinting of plant toxins as a promising tool to enhance the precision and depth of forensic analyses,offering new insights into the complex stories embedded in plant toxins.展开更多
AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at Fir...AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People’s Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study.Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality.Further stratification was performed according to preoperative deviation angles[>35 prism diopters(PD)vs≤35 PD]and age(≥18 years adult group vs<18 years adolescent group).The baseline patient characteristics were collected,deviation angles at multiple timepoints before and after treatment were measured,and stereopsis test results were documented.Through comparative analysis of therapeutic outcomes across subgroups,we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included.At the final follow-up,both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001).Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05).For patients with deviations>35 PD,surgery yielded significantly better outcomes than injection therapy in postoperative angle,success rate,and stereopsis recovery(P<0.05).Similarly,in patients aged≥18 years,surgical treatment was superior to injections in reducing strabismus angle,improving success rates,and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE.Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy,particularly in patients with deviations>35 PD and those aged≥18 years.For patients with angles≤35 PD or under 18 years,BTXA injection remains a viable treatment option.展开更多
T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue ...T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.展开更多
The different resistance of cotton (Gossypium hirsutum L.) cultivars to crude toxin of Verticillium dah/iae(VD) was correlated with the activities of chitinase and β-1, 3-glucanase in callus cells. The activities of ...The different resistance of cotton (Gossypium hirsutum L.) cultivars to crude toxin of Verticillium dah/iae(VD) was correlated with the activities of chitinase and β-1, 3-glucanase in callus cells. The activities of chitinase and β-1, 3-glucanase in the callus cells treated with the VD-toxin were increased to the higher level at earlier time point in resistant cultivars than these in the susceptible cultivars. Exogenous salicylic acid (SA) induced the accumulation of chitinase and β -1,3-glucanase, which resulted in the resistance of callus cells to the VD. toxin. Western blot using a polyclonal antibody against β -1,3-glucanase identified 28 kD protein that was induced by VD-toxin, SA, or VD-toxin plus SA.展开更多
[ Objective] This study was to investigate the pathogenic mechanism of rice sheath blight pathogen ( Rhizoctonia solani) and the bioactive components of toxin. [ Method ] Rice sheath blight pathogen was cultured in ...[ Objective] This study was to investigate the pathogenic mechanism of rice sheath blight pathogen ( Rhizoctonia solani) and the bioactive components of toxin. [ Method ] Rice sheath blight pathogen was cultured in the improved Richared medium; the culture filtrate was centrifuged and sterilized, then treated by activated carbon adsorption chromatography, distilled with methanol or water, and all were next concentrated, yielding the crude extracts of culture solution, crude extracts of methanol and crude extracts of water; the activities of these three extracts were determined, [ Result] The three extracts were russet pastes; activity determination showed that they had remarkable inhibitory effects on the growth of rice radicle and plantule, as well as the growth of four-foliage-young seedlings. They could also generate toxic effects on abscisic foliages and spots similar to the symptoms of sheath blight pathogen. [ Conclusion] Bioactive components of rice sheath blight pathogen toxin may be composed of various ingredients.展开更多
基金supported by a grant from Ministry of Science and Technology China,No.2022ZD0204704(to WW)the National Natural Science Foundation of China,No.82301572(to XZ)the China Postdoctoral Science Foundation,No.2023M731202(to XZ)。
文摘Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking.Here,by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey,we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord.Labeled alpha motor neurons were located in lamina IX of the L6–S1 segments,which innervate both flexors and extensors.The labeled primary sensory afferents were mainly myelinated Aβfibers that terminated mostly in laminae I and II of the L4–L7 segments.Together with the labeled proprioceptive afferents,the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons.In summary,our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.
基金supported by the National Key R&D Program of China,No.2019YFA0110300(to ZG)the National Natural Science Foundation of China,Nos.81773302(to YF),32070862(to ZG).
文摘Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.
基金Financial support for this study is acknowledged by the University of Sri Jayewardenepura,Sri Lanka under the research grant number RC/URG/SCI/2024/12。
文摘Mycotoxins,toxic secondary metabolites produced by fungus including Aspergillus,Penicillium,and Fusarium,pose considerable threats to food safety and human health worldwide.This review analyzes the main categories of mycotoxins—namely aflatoxins,ochratoxins,and fusarium toxins(zearalenone and fumonisins)—along with their health implications,sources of contamination,and environmental circumstances conducive to their production.The document highlights the pressing necessity for efficient management techniques and investigates the use of food polymer-based nanotechnology as an innovative solution.Biopolymeric nanoparticles produced from natural food materials exhibit notable antibacterial characteristics,biodegradability,and the ability to enhance mycotoxin detection and management.This review emphasizes the transformative capacity of nanotechnology based innovative strategies in improving mycotoxin control,providing insights into emerging research avenues and practical applications to bolster food safety systems and keyword co-occurrence analysis,limitations and future perspectives.
文摘Botulinum toxin,a protein exotoxin secreted by Clostridium botulinum,binds to peripheral nerve terminals,inhibits acetylcholine release,and leads to flaccid muscle paralysis.[1]Botox(onabotulinum toxin A)was approved by the Food and Drug Administration(FDA)for cosmetic and therapeutic indications in 2002,and its global use has increased substantially.[2]However,some unlicensed botulinum toxin products may cause iatrogenic botulism.[3]Early diagnosis remains challenging owing to non-specific clinical features and the lack of diagnostic biomarkers,often delaying the timely administration of antitoxin.[4]This study reviewed recent cases of botulism in our center and summarized their clinical presentations,symptoms,and outcomes.
文摘Dear Editor,We recently reviewed two important studies that investigate the use of botulinum-A toxin(BoNT-A)injections into the bulbospongiosus muscle as a treatment for lifelong premature ejaculation(PE).While both studies share the goal of evaluating the efficacy and safety of BoNT-A in this context,they reached very different conclusions.The study by Shaher et al.demonstrated significant improvements in ejaculatory latency,indicating that BoNT-A injections may be a helpful treatment for PE.
文摘Introduction:When conservative treatments fail,botulinum toxin A(BoNT-A)is an option for refractory idiopathic overactive bladder(OAB).This review evaluates the efficacy,safety,and predictive factors for BoNT-A in this situation.Material and Methods:A literature search up to January 2025 was performed using PubMed,Google Scholar,and Embase to assess efficacy,safety,and predictors of adverse events(AE)related to BoNT-A.The risk of bias was assessed using the Risk of Bias 2(RoB 2)tool for randomized studies and the Critical Appraisal Skills Programme(CASP)checklist for cohort studies.The quality of the review was evaluated based on the Oxford criteria,following the Strengthening the Assessment of Narrative Review Articles(SANRA)guidelines,and by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines for systematic reviews.Results:31 studies were included,involving 5410 patients.BoNT-A improves OAB symptoms even after reinjections.Higher doses do not enhance efficacy but increase AE.AE includes high post-void residual(PVR),clean intermittent self-catheterization(CISC),and Urinary Tract Infection(UTI).Predictors of CISC include age,male gender,hysterectomy,≥3 vaginal deliveries,mixed incontinence,prior mid-urethral sling(MUS),high PVR,low Pressure at Pdet at First Micturition(PIP1)in women,low Bladder Compliance Index(BCI)in men,and high Bladder Outlet Obstruction Index(BOOI).Diabetes and heart failure increase PVR.UTIs are more frequent in women and men with benign prostatic hyperplasia,with CISC increasing the risk fivefold.Severe complications are rare.Predictors of poor response include male gender,high BOOI,low urinary flow,and diabetes.Discussion:BoNT-A is effective for OAB,especially for incontinence.AE is dose-dependent and limits treatment adherence.Their link with poor response remains unclear.Conclusion:BoNT-A effectively treats refractory idiopathic OAB,improving symptoms and quality of life with repeated injections.
文摘Orofacial muscle hypertonicity,characterized by excessive muscle tension in the facial and masticatory regions,can lead to significant functional impairment and aesthetic concerns.Botulinum toxin type A(BoNT-A),widely known for its cosmetic applications,has emerged as a valuable therapeutic tool in dentistry and maxillofacial medicine.This review explores the pharmacological mechanisms,anatomical considerations,and clinical applications of BoNT-A in the treatment of functional disorders such as bruxism,masseter hypertrophy,temporomandibular joint dysfunction,and facial asymmetry.Emphasis is placed on precision-guided injection techniques,region-specific dosing trends,and formulation-specific performance.Adverse effects,although generally mild and self-limiting,are preventable through anatomical expertise and individualized protocols.Preliminary clinical observations and recent East Asian data suggest variations in the response patterns and optimal dosing strategies.This review also highlights the current gaps,including the need for long-term safety data,standardized training for dental practitioners,and comparative evaluations with non-pharmacological therapies.BoNT-A is a minimally invasive interdisciplinary approach for restoring oral function and facial harmony,supporting its integration into modern dental practice.
基金supported by the Natural Science Foundation of Shandong province(Nos.ZR2019MH048 and ZR2022QC149)the Double First-class Disciplines Construction Fund Project from Harbin Institute of Technology at Weihai(No.2023SYLHY18)Weihai Science and Technology Development Program。
文摘Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the association between the alga toxinsβ-N-methylamino-L-alanine(BMAA),brevetoxin B,cyanoginosin LR,okadaic acid and neurodegenerative diseases remains inadequately investigated.Therefore,the aim of this study was to elucidate the potential associations.Four sets of differentially expressed genes related with BMAA,brevetoxin B,cyanoginosin LR and okadaic acid in Homo sapiens and genes linked to neurodegenerative disease development were respectively collected from the Comparative Toxicogenomic Database.Metascape analysis and cluster community analysis of four alga toxins highlighted protein-protein interaction enrichment and hub genes,while biological processes analysis showed that the dominant pathways involved in harmful effects triggered by four alga toxins were the apoptotic signaling pathway,regulation of amyloid protein formation,inflammatory response and endoplasmic reticulum stress.Genes related to the interactions between four alga toxins and neurodegenerative diseases were selected and analyzed,revealing that the relevant pathways and genes were those involved in apoptotic mitochondrial changes and neuroinflammatory response pathways.The adverse outcome pathway frameworks were constructed according to the analysis results for toxins and associated neurodegenerative diseases.These discoveries provide a new perspective for us to gain a deeper understanding of the neurotoxic effects of four alga toxins.
基金funded by Namibe UniversityInstituto Nacional de Gestao de Bolsas de Estudo/Angola government through a PhD studentship program+1 种基金the TENOVUS Scotland(S20-02 to Xinhua Shu,the Chief Scientist Office/the RS Macdonald Charitable Trust(SNRF2021 to Xinhua Shu)the Lotus Scholarship Program of Hunan Province,China(2019-23 to Xinhua Shu)。
文摘Domoic acid(DA),a biotoxin,is produced by several species of marine dinoflagellate and diatom during harmful algal bloom events.DA is a neurotoxin,in humans and non-human primates,oral exposure to DA results in gastrointestinal effects,while DA at higher doses leads to neurological symptoms,seizures and memory deficiency.Exposure of humans to DA occurs mainly through consumption of contaminated seafoods containing an accumulation of the toxin.Previously,it was unclear if DA can have toxic effects on the retina.We assessed the toxicity of DA in human retinal cells(ARPE-19)and in zebrafish embryos.DA significantly lowered ARPE-19 cell viability dose-dependently,and decreased anti-oxidative capacity,increased inflammation,and promoted cell death,possibly through modulating the NRF2 and NF-κB signalling pathways.Zebrafish embryos exposed to DA for 4 days from 1 day post fertilization(dpf)had an increase in mortality and a decrease in both hatching and heartbeat rate and exhibited morphological abnormalities.DA treatment also significantly downregulated expression of antioxidant genes and upregulated expression of inflammation mediators,as well as causing photoreceptor death in zebrafish embryos.The results demonstrate that consuming seafood containing DA will have potential toxic effects in human retinas.
文摘Background:Androgenetic alopecia(AGA)is a common hair loss disorder that significantly affects patient’s quality of life.Botulinum toxin(BoNT)has emerged as a potential treatment;however,its effectiveness and underlying mechanisms remain unclear.This systematic review aimed to synthesize the existing evidence on BoNT for AGA,analyze its mechanisms,evaluate its efficacy,and explore its potential for precision therapy.Methods:A PubMed search was conducted for studies published between 2020 and 2025.A total of 25 studies,including 11 clinical trials and 7 reviews,were included.The studies were analyzed for BoNT mechanisms in AGA,treatment regimens,efficacy,outcomes,cost-effectiveness,and safety profiles.Results:Experimental evidence suggests that BoNT reduces transforming growth factor-βin dermal papilla cells,a key pathological pathway in AGA.Other hypothetical mechanisms,such as scalp muscle relaxation improving microcirculation or inhibiting androgen conversion require further validation.In clinical trials,most studies used 30-150 U of BoNT via intramuscular(six studies)or intradermal(three studies)injections,with 1-3 sessions and up to 6 months of follow-up.Early open-label trials reported response rates of 70%-79%,but recent high-quality randomized controlled trials(RCTs)showed no significant improvement in hair density compared to placebo.Combination therapy with finasteride or minoxidil enhanced treatment outcomes,though large-scale evidence is lacking.BoNT was less cost-effective than first-line therapies such as minoxidil,with session costs approximately 37 times higher.Intramuscular injection appeared more effective than intradermal injection,possibly due to scalp muscle relaxation and vascular decompression.BoNT generally had a mild safety profile.Conclusion:Currently,BoNT lacks robust evidence to replace traditional treatments for AGA.Future research should focus on establishing standardized dosing protocols,conducting large-scale,long-term RCTs,and integrating molecular biomarkers to improve understanding and optimize the clinical use of BoNT in AGA management.
文摘The integration of phytochemistry into forensic science has emerged as a groundbreaking frontier,providing unprecedented insights into nature's secrets through the precise application of phytochemical fingerprinting of phytotoxins as a cutting-edge approach.This study explores the dynamic intersection of phytochemistry and forensic science,highlighting how the unique phytochemical profiles of toxic plants and their secondary metabolites,serve as distinctive markers for forensic investigations.By utilizing advanced techniques such as Ultra-High-Performance Liquid Chromatography(UHPLC)and High-Resolution Mass Spectrometry(HRMS),the detection and quantification of plant-derived are made more accurate in forensic contexts.Real-world case studies are presented to demonstrate the critical role of plant toxins in forensic outcomes and legal proceedings.The challenges,potential,and future prospects of integrating phytochemical fingerprinting of plant toxins into forensic science were discussed.This review aims to illuminate phytochemical fingerprinting of plant toxins as a promising tool to enhance the precision and depth of forensic analyses,offering new insights into the complex stories embedded in plant toxins.
文摘AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People’s Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study.Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality.Further stratification was performed according to preoperative deviation angles[>35 prism diopters(PD)vs≤35 PD]and age(≥18 years adult group vs<18 years adolescent group).The baseline patient characteristics were collected,deviation angles at multiple timepoints before and after treatment were measured,and stereopsis test results were documented.Through comparative analysis of therapeutic outcomes across subgroups,we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included.At the final follow-up,both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001).Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05).For patients with deviations>35 PD,surgery yielded significantly better outcomes than injection therapy in postoperative angle,success rate,and stereopsis recovery(P<0.05).Similarly,in patients aged≥18 years,surgical treatment was superior to injections in reducing strabismus angle,improving success rates,and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE.Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy,particularly in patients with deviations>35 PD and those aged≥18 years.For patients with angles≤35 PD or under 18 years,BTXA injection remains a viable treatment option.
基金supported by the National Natural Science Foundation of China(No.81872567).
文摘T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.
文摘The different resistance of cotton (Gossypium hirsutum L.) cultivars to crude toxin of Verticillium dah/iae(VD) was correlated with the activities of chitinase and β-1, 3-glucanase in callus cells. The activities of chitinase and β-1, 3-glucanase in the callus cells treated with the VD-toxin were increased to the higher level at earlier time point in resistant cultivars than these in the susceptible cultivars. Exogenous salicylic acid (SA) induced the accumulation of chitinase and β -1,3-glucanase, which resulted in the resistance of callus cells to the VD. toxin. Western blot using a polyclonal antibody against β -1,3-glucanase identified 28 kD protein that was induced by VD-toxin, SA, or VD-toxin plus SA.
基金Supported by National Scientific and Technological Project(30500335)Special Projects Fund of National Excellent Doctorial Dissertation of Education Ministry(2004061)~~
文摘[ Objective] This study was to investigate the pathogenic mechanism of rice sheath blight pathogen ( Rhizoctonia solani) and the bioactive components of toxin. [ Method ] Rice sheath blight pathogen was cultured in the improved Richared medium; the culture filtrate was centrifuged and sterilized, then treated by activated carbon adsorption chromatography, distilled with methanol or water, and all were next concentrated, yielding the crude extracts of culture solution, crude extracts of methanol and crude extracts of water; the activities of these three extracts were determined, [ Result] The three extracts were russet pastes; activity determination showed that they had remarkable inhibitory effects on the growth of rice radicle and plantule, as well as the growth of four-foliage-young seedlings. They could also generate toxic effects on abscisic foliages and spots similar to the symptoms of sheath blight pathogen. [ Conclusion] Bioactive components of rice sheath blight pathogen toxin may be composed of various ingredients.
基金supported by the National Basic Research Development Program of China (No. 2010CB529806)National Natural Sciences Foundation of China (No. 30772554 and 31171064)+2 种基金Key Research Program of Science and Technology Commissions of Shanghai Municipality,China (No. 11JC1404300)Leading Academic Discipline Project of Shanghai Municipal Education Commission "Molecular Physiology" (No. J50108)the Innovation Foundation for Graduate Student,Shanghai University,China