BACKGROUND Steroids remain the primary treatment for severe alcohol-associated hepatitis(AAH),though there is little available tools to predict patient response to steroids.It was hypothesized that phosphatidylethanol...BACKGROUND Steroids remain the primary treatment for severe alcohol-associated hepatitis(AAH),though there is little available tools to predict patient response to steroids.It was hypothesized that phosphatidylethanol(PEth)value will inversely corre-late with response to steroid therapy based on Lille score in AAH.AIM To assess the relationship of patient factors,focusing on pre-steroid therapy PEth value,to steroid therapy response in AAH.METHODS A retrospective case control study was performed on patients who received≥4 days of steroid therapy for AAH at our hospital between July 1,2019 and June 30,2022.A total of 2087 patients were screened for AAH and those treated with steroids were included for statistical analysis utilizing independent sample t-test and for categorical variables using the χ^(2) test.RESULTS No correlation was found between PEth value,pre-steroids abstinence length,or number of drinks per week pre-steroids and response to steroids.Non-responder status significantly correlated with older age(P=0.024),lower albumin(P=0.003),and higher bilirubin(P=0.010)pre-steroids.Our study suggests that age,pre-steroid albumin,and pre-steroid bilirubin levels may predict nonresponse to steroid therapy.Non-responders have increased incidence of death and higher medical costs.CONCLUSION Identifying non-responders through these identified factors should prompt early referral for liver transplantation.Future prospective studies with larger population size are needed to assess the efficacy of combined pre-steroid age,albumin,bilirubin and other biochemical markers as predictors of steroid response.展开更多
GAME15, a scaffold protein, orchestrates the biosynthesis of steroidal glycoalkaloids (a class of compounds with known defensive properties) and steroidal saponins (which contribute to plant defense) in Solanaceae pla...GAME15, a scaffold protein, orchestrates the biosynthesis of steroidal glycoalkaloids (a class of compounds with known defensive properties) and steroidal saponins (which contribute to plant defense) in Solanaceae plants, essential for their defense mechanisms. By assembling key enzymes at the endoplasmic reticulum, GAME15 ensures efficient metabolite production, preventing toxic intermediate diffusion. This breakthrough in plant defense biosynthesis opens opportunities for metabolic engineering, enabling the production of valuable metabolites in non-native hosts and offering potential strategies for crop protection, reducing the need for chemical pesticides.展开更多
BACKGROUND Childhood nephrotic syndrome(NS)outcomes vary widely based on steroid responsiveness and complications.AIM To evaluate steroid response,outcomes,and the use of steroid-sparing medications in children with n...BACKGROUND Childhood nephrotic syndrome(NS)outcomes vary widely based on steroid responsiveness and complications.AIM To evaluate steroid response,outcomes,and the use of steroid-sparing medications in children with nephrotic syndrome in Jordan.METHODS This retrospective study evaluated the demographics and outcomes of 122 children aged 1-18 years with NS between 2011 and 2021 across three centers in Jordan.The outcomes assessed included steroid sensitivity rates,dependence,frequent relapses,complications[chronic kidney disease(CKD),end-stage kidney disease(ESKD)],infections,and need for steroid-sparing treatment.RESULTS Of 64%were boys;median age of disease onset was 4 years.Steroid-sensitive and steroid-resistant NS(SRNS)were observed in 81.1%and 18.9%of patients,respectively;28.7%and 9%had steroid-dependent and frequently relapsing NS,respectively.Kidney biopsies were conducted in 46.7%,the most common finding was minimal change disease in 56.1%;82.6%of biopsied SRNS cases showed focal segmental glomerulosclerosis.The median time to first relapse was 9 months.41.8%of patients required steroidsparing medications,with cyclosporine and mycophenolate mofetil being the most frequently used.Despite these treatments,relapse occurred in 11.5%of cases.Infections,primarily urinary tract infections,affected 24.6%of patients,7.4%progressed to high-grade CKD,and 6.6%required dialysis.SRNS was significantly associated with hematuria,hypertension,and ESKD.CONCLUSION Most patients were steroid sensitive,with minimal change being the most common.Focal segmental glomerulosclerosis was the predominant histopathology in the steroid-resistant cases.SRNS patients had worse outcomes,with more infections,CKD,and ESKD.展开更多
Cardiac sarcoidosis(CS)is a rare but serious manifestation of sarcoidosis that can lead to significant morbidity and mortality due to arrhythmias and heart failure.The inflammatory process in CS is characterized by th...Cardiac sarcoidosis(CS)is a rare but serious manifestation of sarcoidosis that can lead to significant morbidity and mortality due to arrhythmias and heart failure.The inflammatory process in CS is characterized by the formation of noncaseating granulomas in the myocardium,which can disrupt normal cardiac function and conduction.Corticosteroids are the primary therapeutic agents used to manage CS,particularly during the acute inflammatory phase,as they help reduce inflammation and improve cardiac function.However,the long-term use of steroids poses risks,including opportunistic infections and metabolic complications.Advanced imaging techniques,such as cardiac magnetic resonance imaging and positron emission tomography,play a crucial role in diagnosing CS and assessing myocardial involvement.These imaging modalities also aid in risk stratification for arrhythmic events,guiding therapeutic decisions such as the initiation of steroid therapy and the potential placement of implantable cardioverterdefibrillators.This review synthesizes current evidence regarding the role of steroid therapy in managing CS and its implications for cardiac arrhythmias,emphasizing the need for individualized treatment strategies to optimize patient outcomes.展开更多
Background Sudden sensorineural hearing loss(SSNHL)is a rapid condition of hearing impairment,typically occurring over 72 hours and affecting the inner ear or auditory nerve pathways.The etiology of SSNHL remains larg...Background Sudden sensorineural hearing loss(SSNHL)is a rapid condition of hearing impairment,typically occurring over 72 hours and affecting the inner ear or auditory nerve pathways.The etiology of SSNHL remains largely idiopathic,with potential causes including viral infections,vascular occlusions,and autoimmune disorders.Traditional treatment primarily involves systemic corticosteroids,but their efficacy is inconsistent,leading to exploring alternative and adjunctive therapies such as intratympanic steroid(ITS)injections.Objective This Systematic Review and Meta-Analysis intends to determine the effectiveness of ITS injections as an initial treatment,combined therapy,or salvage treatment for SSNHL compared to systemic steroids alone.Methods An inclusive study was performed through the PubMed,Scopus,Web of Science,and Cochrane Library databases,encompassing publications published from 2015 to 2024.Case-control studies,cohort studies,randomized controlled trials(RCTs),and systematic reviews were included.Two separate reviewers read the studies and extracted data on steroid administration methods,study outcomes,and risk of bias(ROB)using the Cochrane Collaboration Tool and RevMan 5.4.Results The review included 12 studies with varied designs,including prospective RCTs,systematic reviews,and retrospective analyses.Combined ITS and systemic steroid therapy showed superior hearing recovery compared to systemic steroids alone in several studies.ITS alone demonstrated variable efficacy,with some studies indicating benefits,particularly as a salvage therapy.ROB assessment revealed variability in methodological rigor,with studies like those of Li&Ding et al.(2020)and Devantier et al.(2022)showing low risk,while others exhibited higher risks,particularly in random sequence generation and allocation concealment.Conclusion The findings suggest that ITS injections,particularly when combined with systemic steroids,can enhance hearing recovery in SSNHL patients.However,variability in study outcomes and methodological quality underscores the need for standardized protocols and further high-quality RCTs.This analysis underscores the prospective advantages of ITS therapy while stressing the need for stringent study designs to enhance SSNHL treatment methodologies.展开更多
A chemical investigation on the cultures extract of the basidiomycete Armillaria gallica Marxm.&Romagn.led to the isolation of eight compounds,including a new steroid armillanal D(1),a new natural product VD2-1(8)...A chemical investigation on the cultures extract of the basidiomycete Armillaria gallica Marxm.&Romagn.led to the isolation of eight compounds,including a new steroid armillanal D(1),a new natural product VD2-1(8)and six known compounds.The structure of 1 was elucidated on the basis of extensive 1D and 2D-NMR spectra analysis,HR-ESI-MS,and electronic circular dichroism(ECD)spectra.The inhibitory activity of these compounds except 8 on NLRP3 inflammasome activation in Nigericin-induced mouse macrophage(J774A.1)cells was evaluated.Chaxine C(6)exhibited potential anti-inflammatory activity in vitro with IC50 value of(4.97±0.81)μmol/L.展开更多
Azoospermia,defined as the absence of sperm in the ejaculate,is a well-documented consequence of exogenous testosterone(ET)and anabolic–androgenic steroid(AAS)use.These agents suppress the hypothalamic–pituitary–go...Azoospermia,defined as the absence of sperm in the ejaculate,is a well-documented consequence of exogenous testosterone(ET)and anabolic–androgenic steroid(AAS)use.These agents suppress the hypothalamic–pituitary–gonadal(HPG)axis,leading to reduced intratesticular testosterone levels and impaired spermatogenesis.This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery.Azoospermia is categorized into pretesticular,testicular,and post-testicular types,with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function.Key strategies include discontinuing ET and monitoring for spontaneous recovery,particularly in patients with shorter durations of ET use.For cases of persistent azoospermia,gonadotropins(human chorionic gonadotropin[hCG]and follicle-stimulating hormone[FSH])and selective estrogen receptor modulators(SERMs),such as clomiphene citrate,are recommended,either alone or in combination.The global increase in exogenous testosterone use,including testosterone replacement therapy and AAS,underscores the need for improved management of associated azoospermia,which can be temporary or permanent depending on individual factors and the type of testosterone used.Additionally,the manuscript discusses preventive strategies,such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy.While guidelines for managing testosterone-related azoospermia remain limited,emerging research indicates the potential efficacy of hormonal stimulation therapies.However,there is a notable lack of well-structured,controlled,and long-term studies addressing the management of azoospermia related to exogenous testosterone use,highlighting the need for such studies to inform evidence-based recommendations.展开更多
Unlike most plants, members of the genus Solanum produce cholesterol and use this as a precursor for steroidal glycoalkaloids. The production of the compounds begins as a branch from brassinosteroid biosynthesis, whic...Unlike most plants, members of the genus Solanum produce cholesterol and use this as a precursor for steroidal glycoalkaloids. The production of the compounds begins as a branch from brassinosteroid biosynthesis, which produces cholesterol that is further modified to produce steroidal glycoalkaloids. During the cholesterol biosynthesis pathway, genetic engineering could alter the formation of cholesterol from provitamin D3(7-dehydrocholesterol) and produce vitamin D3. Cholesterol is a precursor for many steroidal glycoalkaloids, including a-tomatine and esculeoside A. Alpha-tomatine is consumed by mammals and it can reduce cholesterol content and improve LDL:HDL ratio. When there is a high a-tomatine content, the fruit will have a bitter flavor, which together with other steroidal glycoalkaloids serving as protective and defensive compounds for tomato against insect, fungal, and bacterial pests. These compounds also affect the rhizosphere bacteria by recruiting beneficial bacteria. One of the steroidal glycoalkaloids, esculeoside A increases while fruit ripening. This review focuses on recent studies that uncovered key reactions of the production of cholesterol and steroidal glycoalkaloids in tomato connecting to human health, fruit flavor, and plant defense and the potential application for tomato crop improvement.展开更多
Microplastics and nanoplastics(MPs/NPs)are ubiquitous environmental pollutants that act as endocrine-disrupting chemicals(EDCs),raising significant concerns about their impact on human health.Research highlights the h...Microplastics and nanoplastics(MPs/NPs)are ubiquitous environmental pollutants that act as endocrine-disrupting chemicals(EDCs),raising significant concerns about their impact on human health.Research highlights the hazardous effects of MPs/NPs on both male and female reproductive systems,influencing germ cells,embryo development,and progeny.Additionally,studies show that MPs/NPs affect the gene expression of anabolic steroid hormones in vitro and in vivo,inducing reproductive toxicity through mechanisms such as oxidative stress and inflammation.Considering these adverse effects,identifying natural compounds that can mitigate the toxicity of MPs/NPs is increasingly important.Plants offer a wealth of antioxidants and anti-inflammatory compounds that can counteract these harmful effects.Among these,anthocyanins,natural colorants responsible for the vibrant hues of fruits and flowers,exhibit a wide range of biological activities,including antioxidant,anti-inflammatory,and anti-neoplastic properties.Moreover,anthocyanins can modulate sex hormone levels and alleviate reproductive toxicity.Cyanidin-3-glucoside(C3G),one of the most extensively studied anthocyanins,shows promise in reducing reproductive toxicity,particularly in females,and in protecting male reproductive organs,including the testis and epididymis.This protective effect is believed to result from its interaction with steroid receptors,specifically the androgen and estrogen receptors(ERs).These findings highlight the need to explore the mechanisms by which anthocyanins mitigate the reproductive toxicity caused by MPs/NPs.This review provides novel insights into how natural compounds can be leveraged to lessen the impact of environmental contaminants on human health,especially concerning reproductive health.展开更多
BACKGROUND Patients with inflammatory bowel disease(IBD)are at an increased risk of bacterial pneumonia,contributing to significant morbidity and mortality.While previous studies have identified various risk factors,i...BACKGROUND Patients with inflammatory bowel disease(IBD)are at an increased risk of bacterial pneumonia,contributing to significant morbidity and mortality.While previous studies have identified various risk factors,including medications and comorbidities,the independent contribution of IBD to pneumonia risk remains unclear.We hypothesized that the increased pneumonia risk is primarily driven by factors other than IBD itself.AIM To investigate the relative contributions of IBD,comorbidities,and medications to pneumonia risk in patients with IBD.METHODS We conducted a retrospective cohort study using the All of Us Research Program database(2010-2022).We matched 2810 participants with IBD 1:1 with controls using four propensity score models:(1)Demographics/Lifestyle only;(2)Plus comorbidities;(3)Plus medications;and(4)All factors combined.Then we used Cox proportional hazards models to assess pneumonia risk and logistic regression to evaluate risk factors.RESULTS In the primary analysis of 5620 matched participants,IBD was not independently associated with increased pneumonia risk[hazard ratio(HR)=1.07,95%CI:0.84-1.35]when matched for all factors.However,participants with IBD had significantly higher risk(HR=2.08,95%CI:1.56-2.78)when matched only for demographics and lifestyle factors.Within the IBD cohort,a high comorbidity burden(Charlson Comorbidity Index≥10)[odds ratio(OR)=12.20,95%CI:6.69-23.00]and systemic steroid use(OR=2.26,95%CI:1.21-4.64)were independently associated with increased pneumonia risk.CONCLUSION Comorbidities and systemic steroids,rather than IBD itself,drive pneumonia risk.Management should focus on these factors and prioritize vaccination in high-risk patients.展开更多
Highlights●Natural variations in the SGT3 promoter TATA box repeats directly modulate gene expression and SGAs content in tubers,providing a novel molecular marker for low-steroidal glycoalkaloids(SGAs)breeding.●The...Highlights●Natural variations in the SGT3 promoter TATA box repeats directly modulate gene expression and SGAs content in tubers,providing a novel molecular marker for low-steroidal glycoalkaloids(SGAs)breeding.●The SGT3 promoter haplotype with(TA)10exhibits signifcantly higher transcriptional activity,correlating with high SGAs content,while the(TA)13haplotype is linked to low SGAs in natural germplasms.展开更多
Dear Editor,We present the reported case of steroid-induced glaucoma(SIG)treated by trabeculectome tunneling trabeculoplasty(3T).The 3T procedure is a new minimally invasive glaucoma surgery designed to protect and en...Dear Editor,We present the reported case of steroid-induced glaucoma(SIG)treated by trabeculectome tunneling trabeculoplasty(3T).The 3T procedure is a new minimally invasive glaucoma surgery designed to protect and enhance the function of the trabecular meshwork(TM)while reducing resistance to outflow of atrial fluid^([1]).A 20-year-old male patient experienced an elevation in intraocular pressure(IOP)and subsequently progressed to SIG after continuously using tobramycin-dexamethasone eyedrops for one year.Trabeculotomy of the right eye was performed.展开更多
Terpenoids with quinoid structures are found as natural products. This includes steroidal quinones, quinones with a secosteroid structure and meroterpenoid quinones. Importantly, catechol estrogens as endogenous metab...Terpenoids with quinoid structures are found as natural products. This includes steroidal quinones, quinones with a secosteroid structure and meroterpenoid quinones. Importantly, catechol estrogens as endogenous metabolites of estradiol and estrone are precursors of reactive quinones and semiquinones, which are thought to contribute to estrogen-induced carcinogenesis. On the other hand, a number of quinones that include substituted naphthoquinones and anthraquinones are highly cytotoxic and have been used in cancer treatment. This makes the structures interesting synthetic targets. The following is a review of important natural and synthetic terpenoid and steroid quinone hybrids.展开更多
This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivot...This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.展开更多
The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exert...The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.展开更多
Diabetic macular edema(DME)is a common cause of visual impairment in diabetic patients.It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier.The pa...Diabetic macular edema(DME)is a common cause of visual impairment in diabetic patients.It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier.The pathogenesis of DME is multifactorial.Several therapeutic modalities have been proposed for the treatment of DME.Corticosteroid treatments have emerged as an alternative therapy for persistent DME or refractory to conventional laser photocoagulation and other modalities,due to anti-inflammatory,anti-vascular endothelial growth factor and anti-proliferative effects.Many studies have demonstrated the beneficial therapeutic effect of corticosteroids with improvement to both retinal thickness and visual acuity in short-term on the treatment of DME.Peribulbar and intravitreal injections have been used to deliver steroids for DME with frequent injections due to the chronic and recurrent nature of the disease.Steroid-related side effects include elevated intraocular pressure,cataract,and injection related complications such as endophthalmitis,vitreous hemorrhage,and retinal detachment particularly with intravitreal steroid injections.In order to reduce the risks,complications and frequent dosing of intravitreal steroids,intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated intravitreal injections for the management of DME.展开更多
Hydroxylation of steroid core is critical to the synthesis of steroid drugs.Direct sp^(3) C-H hydroxylation is challenging through chemical catalysis,alternatively,fungal biotransformation offers a possible solution t...Hydroxylation of steroid core is critical to the synthesis of steroid drugs.Direct sp^(3) C-H hydroxylation is challenging through chemical catalysis,alternatively,fungal biotransformation offers a possible solution to this problem.However,mining and metabolic engineering of cytochrome P450 monooxygenases(CYPs)is usually regarded as a more eco-friendly and efficient strategy.Herein,we report the mining and identification of a new steroid CYP(CYP68BE1)from Beauveria bassiana by transcriptomics,heterologous expression,in vivo and in vitro functional characterization.The catalytic promiscuity of CYP68BE1 was explored,and CYP68BE1 showed promiscuously and catalytically versatile,which is qualified for monohydroxylation on C11α,C1α,C6βand dihydroxylation on C1β,11αand C6β,11αof six steroids,leading to the production of key steroid intermediates required in the industrial synthesis of some indispensable steroid drugs.Molecular dynamics simulations were performed,revealing the molecular basis of different binding orientations of CYP68BE1 with different substrates.The discovery of CYP68BE1 offers a promising biocatalyst for enriching the steroid structural and functional diversity,which also can be applied to biosynthesize valuable steroid drug intermediates.展开更多
Background: Sudden sensorineural hearing loss(SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy(IST) can serve as a salvage treatm...Background: Sudden sensorineural hearing loss(SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy(IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy(SST).Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors.Methods: Totally, 74 patients who were aged 22–81 years with SSNHL were enrolled and allocated to either the control group(n = 25) or the treatment group(n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2–6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST.Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies(250-8000 Hz) compared with the control group(P < 0.05). The findings indicated the duration from the onset of SSNHL to the beginning of IST as an independent factor for pure tone average improvement after treatment(P = 0.002), whereas age, duration of SST, and time of IST were not(P > 0.05).Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL.展开更多
BACKGROUND Endoscopic submucosal dissection(ESD)is a reliable method to resect early esophageal cancer.Esophageal stricture is one of the major complications after ESD of the esophagus.Steroid prophylaxis for esophage...BACKGROUND Endoscopic submucosal dissection(ESD)is a reliable method to resect early esophageal cancer.Esophageal stricture is one of the major complications after ESD of the esophagus.Steroid prophylaxis for esophageal strictures,particularly local injection of triamcinolone acetonide(TA),is a relatively effective method to prevent esophageal strictures.However,even with steroid prophylaxis,stenosis still occurs in up to 45%of patients.Predicting the risk of stenosis formation after local TA injection would enable additional interventions in risky patients.AIM To identify the predictors of esophageal strictures after steroids application.METHODS Patients who underwent esophageal ESD and steroid prophylaxis and who were comprehensively assessed for lesion-and ESD-related factors at Southeast University Affiliated Zhongda Hospital between February 2018 and March 2023 were included in the study.The univariate and multivariate regression analyses were conducted to identify the predictors of stricture among patients undergoing steroid prophylaxis.RESULTS A total of 120 patients were included in the analysis.In the oral prednisone and oral prednisone combined with local tretinoin injection groups,the stenosis rates were 44/53(83.0%)and 56/67(83.6%),respectively.Among them,univariate analysis showed that the lesion circumference(P=0.01)and submucosal injection solution(P=0.04)showed significant correlation with the risk of stenosis formation.Logistic regression analyses were then performed using predictors that were significant in the univariate analyses and combined with known predictors from previous reports,such as additional chemoradiotherapy and tumor location.We identified a lesion circumference<5/6(OR=0.19;P=0.02)and submucosal injection of sodium hyaluronate(OR=0.15;P=0.03)as independent predictors of on esophageal stricture formation.CONCLUSION Steroid prophylaxis effectively prevents stenosis.Moreover,the lesion circumference and submucosal injection of sodium hyaluronate were independent predictors of esophageal strictures.Additional interventions should be considered in high-risk patients.展开更多
Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the ext...Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown.Results In this study,we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows.Using metagenomic sequencing data from 85 fecal samples,we identified 37 bacterial species that were significantly associated with estrus return.Normally returning sows were characterized by increased abundances of L.reuteri and P.copri and decreased abundances of B.fragilis,S.suis,and B.pseudolongum.The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome.The results were confirmed in a validation cohort.Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis.An integrated analysis of differential bacterial species,metagenome,and fecal metabolome provided evidence that normal return-associated bacterial species L.reuteri and Prevotella spp.participated in the degradation of pregnenolone,progesterone,and testosterone,thereby promoting estrogen biosynthesis.Furthermore,the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return.Conclusions An integrated analysis of differentially abundant bacterial species,metagenome,and fecal metabolome revealed the involvement of L.reuteri and Prevotella spp.in sow estrus return.These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones,suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.展开更多
文摘BACKGROUND Steroids remain the primary treatment for severe alcohol-associated hepatitis(AAH),though there is little available tools to predict patient response to steroids.It was hypothesized that phosphatidylethanol(PEth)value will inversely corre-late with response to steroid therapy based on Lille score in AAH.AIM To assess the relationship of patient factors,focusing on pre-steroid therapy PEth value,to steroid therapy response in AAH.METHODS A retrospective case control study was performed on patients who received≥4 days of steroid therapy for AAH at our hospital between July 1,2019 and June 30,2022.A total of 2087 patients were screened for AAH and those treated with steroids were included for statistical analysis utilizing independent sample t-test and for categorical variables using the χ^(2) test.RESULTS No correlation was found between PEth value,pre-steroids abstinence length,or number of drinks per week pre-steroids and response to steroids.Non-responder status significantly correlated with older age(P=0.024),lower albumin(P=0.003),and higher bilirubin(P=0.010)pre-steroids.Our study suggests that age,pre-steroid albumin,and pre-steroid bilirubin levels may predict nonresponse to steroid therapy.Non-responders have increased incidence of death and higher medical costs.CONCLUSION Identifying non-responders through these identified factors should prompt early referral for liver transplantation.Future prospective studies with larger population size are needed to assess the efficacy of combined pre-steroid age,albumin,bilirubin and other biochemical markers as predictors of steroid response.
基金supported by the National Natural Science Foundation of China(31971314)the Open Fund of State Key Laboratory of Tea Plant Biology and Utilization(SKLTOF20210122).
文摘GAME15, a scaffold protein, orchestrates the biosynthesis of steroidal glycoalkaloids (a class of compounds with known defensive properties) and steroidal saponins (which contribute to plant defense) in Solanaceae plants, essential for their defense mechanisms. By assembling key enzymes at the endoplasmic reticulum, GAME15 ensures efficient metabolite production, preventing toxic intermediate diffusion. This breakthrough in plant defense biosynthesis opens opportunities for metabolic engineering, enabling the production of valuable metabolites in non-native hosts and offering potential strategies for crop protection, reducing the need for chemical pesticides.
文摘BACKGROUND Childhood nephrotic syndrome(NS)outcomes vary widely based on steroid responsiveness and complications.AIM To evaluate steroid response,outcomes,and the use of steroid-sparing medications in children with nephrotic syndrome in Jordan.METHODS This retrospective study evaluated the demographics and outcomes of 122 children aged 1-18 years with NS between 2011 and 2021 across three centers in Jordan.The outcomes assessed included steroid sensitivity rates,dependence,frequent relapses,complications[chronic kidney disease(CKD),end-stage kidney disease(ESKD)],infections,and need for steroid-sparing treatment.RESULTS Of 64%were boys;median age of disease onset was 4 years.Steroid-sensitive and steroid-resistant NS(SRNS)were observed in 81.1%and 18.9%of patients,respectively;28.7%and 9%had steroid-dependent and frequently relapsing NS,respectively.Kidney biopsies were conducted in 46.7%,the most common finding was minimal change disease in 56.1%;82.6%of biopsied SRNS cases showed focal segmental glomerulosclerosis.The median time to first relapse was 9 months.41.8%of patients required steroidsparing medications,with cyclosporine and mycophenolate mofetil being the most frequently used.Despite these treatments,relapse occurred in 11.5%of cases.Infections,primarily urinary tract infections,affected 24.6%of patients,7.4%progressed to high-grade CKD,and 6.6%required dialysis.SRNS was significantly associated with hematuria,hypertension,and ESKD.CONCLUSION Most patients were steroid sensitive,with minimal change being the most common.Focal segmental glomerulosclerosis was the predominant histopathology in the steroid-resistant cases.SRNS patients had worse outcomes,with more infections,CKD,and ESKD.
文摘Cardiac sarcoidosis(CS)is a rare but serious manifestation of sarcoidosis that can lead to significant morbidity and mortality due to arrhythmias and heart failure.The inflammatory process in CS is characterized by the formation of noncaseating granulomas in the myocardium,which can disrupt normal cardiac function and conduction.Corticosteroids are the primary therapeutic agents used to manage CS,particularly during the acute inflammatory phase,as they help reduce inflammation and improve cardiac function.However,the long-term use of steroids poses risks,including opportunistic infections and metabolic complications.Advanced imaging techniques,such as cardiac magnetic resonance imaging and positron emission tomography,play a crucial role in diagnosing CS and assessing myocardial involvement.These imaging modalities also aid in risk stratification for arrhythmic events,guiding therapeutic decisions such as the initiation of steroid therapy and the potential placement of implantable cardioverterdefibrillators.This review synthesizes current evidence regarding the role of steroid therapy in managing CS and its implications for cardiac arrhythmias,emphasizing the need for individualized treatment strategies to optimize patient outcomes.
文摘Background Sudden sensorineural hearing loss(SSNHL)is a rapid condition of hearing impairment,typically occurring over 72 hours and affecting the inner ear or auditory nerve pathways.The etiology of SSNHL remains largely idiopathic,with potential causes including viral infections,vascular occlusions,and autoimmune disorders.Traditional treatment primarily involves systemic corticosteroids,but their efficacy is inconsistent,leading to exploring alternative and adjunctive therapies such as intratympanic steroid(ITS)injections.Objective This Systematic Review and Meta-Analysis intends to determine the effectiveness of ITS injections as an initial treatment,combined therapy,or salvage treatment for SSNHL compared to systemic steroids alone.Methods An inclusive study was performed through the PubMed,Scopus,Web of Science,and Cochrane Library databases,encompassing publications published from 2015 to 2024.Case-control studies,cohort studies,randomized controlled trials(RCTs),and systematic reviews were included.Two separate reviewers read the studies and extracted data on steroid administration methods,study outcomes,and risk of bias(ROB)using the Cochrane Collaboration Tool and RevMan 5.4.Results The review included 12 studies with varied designs,including prospective RCTs,systematic reviews,and retrospective analyses.Combined ITS and systemic steroid therapy showed superior hearing recovery compared to systemic steroids alone in several studies.ITS alone demonstrated variable efficacy,with some studies indicating benefits,particularly as a salvage therapy.ROB assessment revealed variability in methodological rigor,with studies like those of Li&Ding et al.(2020)and Devantier et al.(2022)showing low risk,while others exhibited higher risks,particularly in random sequence generation and allocation concealment.Conclusion The findings suggest that ITS injections,particularly when combined with systemic steroids,can enhance hearing recovery in SSNHL patients.However,variability in study outcomes and methodological quality underscores the need for standardized protocols and further high-quality RCTs.This analysis underscores the prospective advantages of ITS therapy while stressing the need for stringent study designs to enhance SSNHL treatment methodologies.
文摘A chemical investigation on the cultures extract of the basidiomycete Armillaria gallica Marxm.&Romagn.led to the isolation of eight compounds,including a new steroid armillanal D(1),a new natural product VD2-1(8)and six known compounds.The structure of 1 was elucidated on the basis of extensive 1D and 2D-NMR spectra analysis,HR-ESI-MS,and electronic circular dichroism(ECD)spectra.The inhibitory activity of these compounds except 8 on NLRP3 inflammasome activation in Nigericin-induced mouse macrophage(J774A.1)cells was evaluated.Chaxine C(6)exhibited potential anti-inflammatory activity in vitro with IC50 value of(4.97±0.81)μmol/L.
文摘Azoospermia,defined as the absence of sperm in the ejaculate,is a well-documented consequence of exogenous testosterone(ET)and anabolic–androgenic steroid(AAS)use.These agents suppress the hypothalamic–pituitary–gonadal(HPG)axis,leading to reduced intratesticular testosterone levels and impaired spermatogenesis.This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery.Azoospermia is categorized into pretesticular,testicular,and post-testicular types,with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function.Key strategies include discontinuing ET and monitoring for spontaneous recovery,particularly in patients with shorter durations of ET use.For cases of persistent azoospermia,gonadotropins(human chorionic gonadotropin[hCG]and follicle-stimulating hormone[FSH])and selective estrogen receptor modulators(SERMs),such as clomiphene citrate,are recommended,either alone or in combination.The global increase in exogenous testosterone use,including testosterone replacement therapy and AAS,underscores the need for improved management of associated azoospermia,which can be temporary or permanent depending on individual factors and the type of testosterone used.Additionally,the manuscript discusses preventive strategies,such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy.While guidelines for managing testosterone-related azoospermia remain limited,emerging research indicates the potential efficacy of hormonal stimulation therapies.However,there is a notable lack of well-structured,controlled,and long-term studies addressing the management of azoospermia related to exogenous testosterone use,highlighting the need for such studies to inform evidence-based recommendations.
文摘Unlike most plants, members of the genus Solanum produce cholesterol and use this as a precursor for steroidal glycoalkaloids. The production of the compounds begins as a branch from brassinosteroid biosynthesis, which produces cholesterol that is further modified to produce steroidal glycoalkaloids. During the cholesterol biosynthesis pathway, genetic engineering could alter the formation of cholesterol from provitamin D3(7-dehydrocholesterol) and produce vitamin D3. Cholesterol is a precursor for many steroidal glycoalkaloids, including a-tomatine and esculeoside A. Alpha-tomatine is consumed by mammals and it can reduce cholesterol content and improve LDL:HDL ratio. When there is a high a-tomatine content, the fruit will have a bitter flavor, which together with other steroidal glycoalkaloids serving as protective and defensive compounds for tomato against insect, fungal, and bacterial pests. These compounds also affect the rhizosphere bacteria by recruiting beneficial bacteria. One of the steroidal glycoalkaloids, esculeoside A increases while fruit ripening. This review focuses on recent studies that uncovered key reactions of the production of cholesterol and steroidal glycoalkaloids in tomato connecting to human health, fruit flavor, and plant defense and the potential application for tomato crop improvement.
基金supported by two grants:the Ministry of Education and Culture,Finland Seed Funding–Finland-China Food and Health Network(FCFH)2023,University of Eastern Finlandand the Scientific Research Foundation of Zhejiang A&F University,China(Grant No.:2023CFR008).
文摘Microplastics and nanoplastics(MPs/NPs)are ubiquitous environmental pollutants that act as endocrine-disrupting chemicals(EDCs),raising significant concerns about their impact on human health.Research highlights the hazardous effects of MPs/NPs on both male and female reproductive systems,influencing germ cells,embryo development,and progeny.Additionally,studies show that MPs/NPs affect the gene expression of anabolic steroid hormones in vitro and in vivo,inducing reproductive toxicity through mechanisms such as oxidative stress and inflammation.Considering these adverse effects,identifying natural compounds that can mitigate the toxicity of MPs/NPs is increasingly important.Plants offer a wealth of antioxidants and anti-inflammatory compounds that can counteract these harmful effects.Among these,anthocyanins,natural colorants responsible for the vibrant hues of fruits and flowers,exhibit a wide range of biological activities,including antioxidant,anti-inflammatory,and anti-neoplastic properties.Moreover,anthocyanins can modulate sex hormone levels and alleviate reproductive toxicity.Cyanidin-3-glucoside(C3G),one of the most extensively studied anthocyanins,shows promise in reducing reproductive toxicity,particularly in females,and in protecting male reproductive organs,including the testis and epididymis.This protective effect is believed to result from its interaction with steroid receptors,specifically the androgen and estrogen receptors(ERs).These findings highlight the need to explore the mechanisms by which anthocyanins mitigate the reproductive toxicity caused by MPs/NPs.This review provides novel insights into how natural compounds can be leveraged to lessen the impact of environmental contaminants on human health,especially concerning reproductive health.
基金Supported by The Interdisciplinary Guided Network for Investigation,Translation and Equity for the All of Us Research Program,No.OT2 OD031915.
文摘BACKGROUND Patients with inflammatory bowel disease(IBD)are at an increased risk of bacterial pneumonia,contributing to significant morbidity and mortality.While previous studies have identified various risk factors,including medications and comorbidities,the independent contribution of IBD to pneumonia risk remains unclear.We hypothesized that the increased pneumonia risk is primarily driven by factors other than IBD itself.AIM To investigate the relative contributions of IBD,comorbidities,and medications to pneumonia risk in patients with IBD.METHODS We conducted a retrospective cohort study using the All of Us Research Program database(2010-2022).We matched 2810 participants with IBD 1:1 with controls using four propensity score models:(1)Demographics/Lifestyle only;(2)Plus comorbidities;(3)Plus medications;and(4)All factors combined.Then we used Cox proportional hazards models to assess pneumonia risk and logistic regression to evaluate risk factors.RESULTS In the primary analysis of 5620 matched participants,IBD was not independently associated with increased pneumonia risk[hazard ratio(HR)=1.07,95%CI:0.84-1.35]when matched for all factors.However,participants with IBD had significantly higher risk(HR=2.08,95%CI:1.56-2.78)when matched only for demographics and lifestyle factors.Within the IBD cohort,a high comorbidity burden(Charlson Comorbidity Index≥10)[odds ratio(OR)=12.20,95%CI:6.69-23.00]and systemic steroid use(OR=2.26,95%CI:1.21-4.64)were independently associated with increased pneumonia risk.CONCLUSION Comorbidities and systemic steroids,rather than IBD itself,drive pneumonia risk.Management should focus on these factors and prioritize vaccination in high-risk patients.
基金financially supported by the Guangdong Major Project of Basic and Applied Basic Research,China(2021B0301030004)the National Natural Science Foundation of China(32360757,U2202206 and 32361143517)the Yunnan Fundamental Research Projects,China(202201AT070037,202501AS070012)。
文摘Highlights●Natural variations in the SGT3 promoter TATA box repeats directly modulate gene expression and SGAs content in tubers,providing a novel molecular marker for low-steroidal glycoalkaloids(SGAs)breeding.●The SGT3 promoter haplotype with(TA)10exhibits signifcantly higher transcriptional activity,correlating with high SGAs content,while the(TA)13haplotype is linked to low SGAs in natural germplasms.
基金Supported by Sichuan Provincial Administration of Traditional Chinese Medicine(No.2024MS471)。
文摘Dear Editor,We present the reported case of steroid-induced glaucoma(SIG)treated by trabeculectome tunneling trabeculoplasty(3T).The 3T procedure is a new minimally invasive glaucoma surgery designed to protect and enhance the function of the trabecular meshwork(TM)while reducing resistance to outflow of atrial fluid^([1]).A 20-year-old male patient experienced an elevation in intraocular pressure(IOP)and subsequently progressed to SIG after continuously using tobramycin-dexamethasone eyedrops for one year.Trabeculotomy of the right eye was performed.
文摘Terpenoids with quinoid structures are found as natural products. This includes steroidal quinones, quinones with a secosteroid structure and meroterpenoid quinones. Importantly, catechol estrogens as endogenous metabolites of estradiol and estrone are precursors of reactive quinones and semiquinones, which are thought to contribute to estrogen-induced carcinogenesis. On the other hand, a number of quinones that include substituted naphthoquinones and anthraquinones are highly cytotoxic and have been used in cancer treatment. This makes the structures interesting synthetic targets. The following is a review of important natural and synthetic terpenoid and steroid quinone hybrids.
文摘This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81973377,81903689,82073906 and 82273987)the Key Natural Science Foundation of Jiangsu Higher Education Institutions of China(Grant Nos.:19KJB350006 and 19KJA460008)+1 种基金Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the initializing Fund of Xuzhou Medical University(Grant No.:D2018011)Postgraduate Research Practice Innovation Program of Jiangsu Province(Grant Nos.:KYCX21-2733 and KYCX22-2966).
文摘The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
文摘Diabetic macular edema(DME)is a common cause of visual impairment in diabetic patients.It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier.The pathogenesis of DME is multifactorial.Several therapeutic modalities have been proposed for the treatment of DME.Corticosteroid treatments have emerged as an alternative therapy for persistent DME or refractory to conventional laser photocoagulation and other modalities,due to anti-inflammatory,anti-vascular endothelial growth factor and anti-proliferative effects.Many studies have demonstrated the beneficial therapeutic effect of corticosteroids with improvement to both retinal thickness and visual acuity in short-term on the treatment of DME.Peribulbar and intravitreal injections have been used to deliver steroids for DME with frequent injections due to the chronic and recurrent nature of the disease.Steroid-related side effects include elevated intraocular pressure,cataract,and injection related complications such as endophthalmitis,vitreous hemorrhage,and retinal detachment particularly with intravitreal steroid injections.In order to reduce the risks,complications and frequent dosing of intravitreal steroids,intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated intravitreal injections for the management of DME.
基金supported by the National Key Research and Development Program of China(Nos.2020YFA0908003 and 2018YFA0901900)CAMS Innovation Fund for Medical Sciences(No.CIFMS2021-I2M-1-029).
文摘Hydroxylation of steroid core is critical to the synthesis of steroid drugs.Direct sp^(3) C-H hydroxylation is challenging through chemical catalysis,alternatively,fungal biotransformation offers a possible solution to this problem.However,mining and metabolic engineering of cytochrome P450 monooxygenases(CYPs)is usually regarded as a more eco-friendly and efficient strategy.Herein,we report the mining and identification of a new steroid CYP(CYP68BE1)from Beauveria bassiana by transcriptomics,heterologous expression,in vivo and in vitro functional characterization.The catalytic promiscuity of CYP68BE1 was explored,and CYP68BE1 showed promiscuously and catalytically versatile,which is qualified for monohydroxylation on C11α,C1α,C6βand dihydroxylation on C1β,11αand C6β,11αof six steroids,leading to the production of key steroid intermediates required in the industrial synthesis of some indispensable steroid drugs.Molecular dynamics simulations were performed,revealing the molecular basis of different binding orientations of CYP68BE1 with different substrates.The discovery of CYP68BE1 offers a promising biocatalyst for enriching the steroid structural and functional diversity,which also can be applied to biosynthesize valuable steroid drug intermediates.
文摘Background: Sudden sensorineural hearing loss(SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy(IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy(SST).Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors.Methods: Totally, 74 patients who were aged 22–81 years with SSNHL were enrolled and allocated to either the control group(n = 25) or the treatment group(n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2–6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST.Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies(250-8000 Hz) compared with the control group(P < 0.05). The findings indicated the duration from the onset of SSNHL to the beginning of IST as an independent factor for pure tone average improvement after treatment(P = 0.002), whereas age, duration of SST, and time of IST were not(P > 0.05).Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL.
基金Supported by Jiangsu Province Chinese Medicine Science and Technology Development Program,No.ZT202119.
文摘BACKGROUND Endoscopic submucosal dissection(ESD)is a reliable method to resect early esophageal cancer.Esophageal stricture is one of the major complications after ESD of the esophagus.Steroid prophylaxis for esophageal strictures,particularly local injection of triamcinolone acetonide(TA),is a relatively effective method to prevent esophageal strictures.However,even with steroid prophylaxis,stenosis still occurs in up to 45%of patients.Predicting the risk of stenosis formation after local TA injection would enable additional interventions in risky patients.AIM To identify the predictors of esophageal strictures after steroids application.METHODS Patients who underwent esophageal ESD and steroid prophylaxis and who were comprehensively assessed for lesion-and ESD-related factors at Southeast University Affiliated Zhongda Hospital between February 2018 and March 2023 were included in the study.The univariate and multivariate regression analyses were conducted to identify the predictors of stricture among patients undergoing steroid prophylaxis.RESULTS A total of 120 patients were included in the analysis.In the oral prednisone and oral prednisone combined with local tretinoin injection groups,the stenosis rates were 44/53(83.0%)and 56/67(83.6%),respectively.Among them,univariate analysis showed that the lesion circumference(P=0.01)and submucosal injection solution(P=0.04)showed significant correlation with the risk of stenosis formation.Logistic regression analyses were then performed using predictors that were significant in the univariate analyses and combined with known predictors from previous reports,such as additional chemoradiotherapy and tumor location.We identified a lesion circumference<5/6(OR=0.19;P=0.02)and submucosal injection of sodium hyaluronate(OR=0.15;P=0.03)as independent predictors of on esophageal stricture formation.CONCLUSION Steroid prophylaxis effectively prevents stenosis.Moreover,the lesion circumference and submucosal injection of sodium hyaluronate were independent predictors of esophageal strictures.Additional interventions should be considered in high-risk patients.
基金supported by the National Key R&D Program of China(2022YFA1304204)National Natural Science Foundation of China(31772579).
文摘Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown.Results In this study,we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows.Using metagenomic sequencing data from 85 fecal samples,we identified 37 bacterial species that were significantly associated with estrus return.Normally returning sows were characterized by increased abundances of L.reuteri and P.copri and decreased abundances of B.fragilis,S.suis,and B.pseudolongum.The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome.The results were confirmed in a validation cohort.Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis.An integrated analysis of differential bacterial species,metagenome,and fecal metabolome provided evidence that normal return-associated bacterial species L.reuteri and Prevotella spp.participated in the degradation of pregnenolone,progesterone,and testosterone,thereby promoting estrogen biosynthesis.Furthermore,the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return.Conclusions An integrated analysis of differentially abundant bacterial species,metagenome,and fecal metabolome revealed the involvement of L.reuteri and Prevotella spp.in sow estrus return.These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones,suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.
