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
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
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
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
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
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
Androgenic-anabolic steroids （AAS） have been misused by athletes at the Olympic Games, both before and after they were prohibited in sport in 1974. Systematic doping with AAS occurred in the German Democratic Republ...Androgenic-anabolic steroids （AAS） have been misused by athletes at the Olympic Games, both before and after they were prohibited in sport in 1974. Systematic doping with AAS occurred in the German Democratic Republic （GDR） from 1965 to 1989 which assisted that country to win many medals at Olympic Games, especially in female events. Currently, AAS are the most frequent category of prohibited substances detected in the urine of athletes both globally and at the last two Summer Olympic Games. Scientific confirmation that AAS are effective in enhancing sports performance was difficult because ethical approval was difficult for research involving male subjects taking massive doses of androgens as some athletes and bodybuilders did. Methods to detect AAS have evolved gradually over the past three decades and currently, despite an impressive array of sophisticated analytical equipment and methods, anti-doping authorities and analytical scientists continue to face challenges as have occurred from the use by athletes of designer AAS during the past few years. The future development and use of selective androgen receptor modulators （SARMs） can be anticipated to pose problems in the years ahead. Endocrinologists should be aware that on occasions, replacement testosterone （T） therapy may be authorized in sport as a therapeutic use exemption （TUE） and these circumstances are discussed.展开更多
Eosinophilic esophagitis(EoE)is an emerging chronic local immune-mediated disease of the esophagus.Beside proton pump inhibitors and food-restrictiondiets swallowed topical corticosteroids(STC)can be offered as a firs...Eosinophilic esophagitis(EoE)is an emerging chronic local immune-mediated disease of the esophagus.Beside proton pump inhibitors and food-restrictiondiets swallowed topical corticosteroids(STC)can be offered as a first line therapy according to current guidelines.This review describes the background and practical management of STCs in EoE.So far,mainly asthma inhalers containing either budesonide or fluticasone have been administered to the esophagus by swallowing these medications“off label”.Recently esophagus-targeted formulations of topical steroids have been developed showing clinicopathological response rates up to 85%-an orodispersible tablet of budesonide has been approved as the first“in label”medication for EoE in Europe in June 2018.Whereas it was shown that disease remission induction of EoE by STCs is highly effective,there is still a lack of data regarding long-term and maintenance therapy.However,current studies on STC maintenance therapy add some movement into the game.展开更多
11β-Hydroxy-androst-4-en-3,17-dione(1a),androst-4,9(11)-dien-3,17- dione-(2a),androst-4-en-3,11,17-trione(3a),11α-methoxy-androst-4-en-3,17-dione (4a)and 11β-metboxy-androst-4-en-3,17-dione(Sa)were selectively redu...11β-Hydroxy-androst-4-en-3,17-dione(1a),androst-4,9(11)-dien-3,17- dione-(2a),androst-4-en-3,11,17-trione(3a),11α-methoxy-androst-4-en-3,17-dione (4a)and 11β-metboxy-androst-4-en-3,17-dione(Sa)were selectively reduced to the corresponding 17β-OH derivatives in one step without the protection of 3- oxo(and 11-oxo,in the case of 3a)group with the yields ranging from 65% to 79%.In these reactions,the ditute NaBH_4(or KBH_4)solution in methanol was added dropwise to the 3,17-dioxo-steroids solution in methanol-benzene-pyridine, while the reaction mixtures were well stirred at -5～5℃.Acid(such as gtacial acetic acid)was added to quench the reactions.The resulted testosterone derivatives(1b～5b)were purified by flash chromatography. This method appties to the reduction of other 3,17-dioxo-steroids such as△~1 -3-one,△^(1.4)-3-one,△^(4.6)-3-one,△^(1.4.6)-3-one containing compounds.展开更多
Non-traumatic osteonecrosis is a cause of joint pain and deformity, not uncommonly caused by corticosteroid use. Despite this, corticosteroid induced osteonecrosis is poorly represented in the literature. We performed...Non-traumatic osteonecrosis is a cause of joint pain and deformity, not uncommonly caused by corticosteroid use. Despite this, corticosteroid induced osteonecrosis is poorly represented in the literature. We performed a detailed review of corticosteroid induced osteonecrosis, including aetiology, prevention, screening, clinical presentation, investigations, staging systems and treatment. We present this in the context of a patient at our institution who developed bilateral hip, shoulder and knee osteonecrosis following high dose corticosteroid therapy for dermatomyositis.展开更多
It is well known that during mammalian ovarian follicular development, the majority of follicles undergo atresia at various stages of their development. However, the mechanisms controlling this selection process remai...It is well known that during mammalian ovarian follicular development, the majority of follicles undergo atresia at various stages of their development. However, the mechanisms controlling this selection process remain unknown. In this study, we investigated apoptosis in granulosa cells during goat follicular atresia by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The changes in the levels of steroids, insulin-like growth factors (IGFs) and IGF receptors were studied by radioimmunoassay (RIA) and semi-quantitative reverse transcrip-tion-PCR. We found that the percentage of apoptotic granulosa cells in the atretic (A) follicles was significantly higher than that in the slightly atretic (SA) and healthy (H) follicles. The level of estradiol and the ratio of estradiol to progesterone in H follicles were significantly higher than those in A follicles. On the other hand, the level of progesterone was not significantly different among these follicle types. We also found that the level of IGF-Ⅰ in H follicles was higher than in SA and A follicles, whereas the amount of IGF-Ⅱ did not vary significantly. The expression of IGF receptor also decreased in A follicles as compared to that in H and SA follicles. These results suggested that estradiol and IGF-Ⅰ might be involved in controlling apoptosis in granulosa cells during follicular atresia.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
Objective:To determine the chemical profile and steroids composition of the medicinally important plant Aerva lanata(A.lanata) L.Methods:Preliminary phytochemicul screening was done by the method as Harborne described...Objective:To determine the chemical profile and steroids composition of the medicinally important plant Aerva lanata(A.lanata) L.Methods:Preliminary phytochemicul screening was done by the method as Harborne described.HPTLC studies were canied out as Harborne and Wagner et al described.The Ethyl acetate-ethanol-water(8:2:1.2) was employed as mobile phase for glycosides.Results:The desired aim was achieved using Chloroform-acetone(8:2) as the mobile phase.The methanolic extract of stem,leaves,root,flower and seeds of A.lanata showed the presence of 30 different types of steroids with 30 different Rf values from 0.04 to 0.97. Maximum number(11) of steroids has been observed in leaves followed by root(10).Conclusions: HPTLC profile of steroids has been chosen here to reveal the diversity existing in A.lanata.Such finger printing is useful in differentiating the species from the adulterant and act as biochemical markers for this medicinally important plant in the pharma industry and plant systematic studies.展开更多
A correlation between metabolic alterations of neuroactive steroids and Alzheimer’s disease remains unknown. In the present study, amyloid beta （Aβ） 25-35 （Aβ25-35） injected into the bilateral campus CA1 region...A correlation between metabolic alterations of neuroactive steroids and Alzheimer’s disease remains unknown. In the present study, amyloid beta （Aβ） 25-35 （Aβ25-35） injected into the bilateral campus CA1 region significantly reduced learning and memory. At the biochemical level, hippocampal levels of pregnenolone were significantly reduced with Aβ25-35 treatment. Furthermore, progesterone was considerably decreased in the prefrontal cortex and hippocampus, and 17β-estradiol was signifi-cantly elevated. To our knowledge, this is the first report showing that Aβ25-35, a main etiological factor of Alzheimer’s disease, can alter the level and metabolism of neuroactive steroids in the prefrontal cortex and hippocampus, which are brain regions significantly involved in learning and memory. Aβ25-35 exposure also increased the expression of inflammatory mediators, tumor necrosis factor-αand interleukin-1β. However, subcutaneous injection of progesterone reversed the upregulation of tumor necrosis factor-αand interleukin-1βin a dose-dependent manner. Concomitant with improved cognitive abilities, progesterone blocked Aβ-mediated inflammation and increased the survival rate of hippocampal pyramidal cells. We thus hypothesize that Aβ-mediated cognitive deficits may occur via changes in neuroactive steroids. Moreover, our findings provide a possible therapeutic strategy for Alzheimer’s disease via neuroactive steroids, particularly progesterone.展开更多
Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus （T2DM） and also predict the onset of these adverse metabolic states. Body composition （body mass index, waist circumference...Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus （T2DM） and also predict the onset of these adverse metabolic states. Body composition （body mass index, waist circumference） is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter＇s syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/ glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.展开更多
Two new C21 steroids were isolated from the CHCl3 extract of the stem of Marsdenia tenacissima. On the basis of spectroscopic analysis and chemical methods, their structures were elucidated as 17β-tenacigenin B (2)...Two new C21 steroids were isolated from the CHCl3 extract of the stem of Marsdenia tenacissima. On the basis of spectroscopic analysis and chemical methods, their structures were elucidated as 17β-tenacigenin B (2) and 3-O-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D- oleandropyranosyl-tenacigenin C (3). The structure of the known aglycon tenacigenin C was revised as 5α, 9α, 17β-pregnane-3β, 8β, 11α, 12β, 14β-pentanol-20-one. Compound 3 is the first reported glycoside of tenacigenin C.展开更多
A gas chromatography-mass spectrometry （GC-MS） method to determine eight anabolic steroids （diethylstilbestrol, methyltestosterone, norethindrone, 17α-ethynylestradiol, estradiol, 6α-methyl-17α-hydroxy-progester...A gas chromatography-mass spectrometry （GC-MS） method to determine eight anabolic steroids （diethylstilbestrol, methyltestosterone, norethindrone, 17α-ethynylestradiol, estradiol, 6α-methyl-17α-hydroxy-progesterone, estradiol benzoate, and chlormadinone acetate） was developed. Muscle samples were extracted with liquid-liquid extraction and clean-up was performed in two steps, the extracts obtained were derivatized with heptafluorbutyric （HBF） anhydride and analyzed by GC-MS. In the above method, the linear scope was 2.5-50 μg kg^-1. The range of the recoveries was 78.5-148% for diethylstilbestrol, 70.8-109% for methyltestosterone, 69.8-87.2% for norethindrone, 67.7-120% for 17α-ethynylestradiol, 82.8-103% for estradiol, 70.3-99.2% for 6α-methyl-17α-hydroxy-progesterone, 73.0-104% for estradiol benzoate, and 72.9- 91.8% for chlormadinone acetate. The range of the coefficients of variation within batches was 0.4-12%; the range of the coefficients of variation between batches was 6.4-11%. The limit of detections and the detection capability were 0.99 and 3.30 μg kg^-1 for diethylstilbestrol, 1.05 and 3.50 μg kg^-1 for methyltestosterone, 1.19 and 3.97 μg kg^-1 for norethindrone, 0.94 and 3.13 μg kg^-1 for 17α-ethynylestradiol, 1.45 and 4.83 μg kg^-1 for estradiol, 1.56 and 5.20 μg kg^-1 for 6α-methyl-17α- hydroxy-progesterone, 1.92 and 6.40 μg kg^-1 for estradiol benzoate, and 2.41 and 8.03 μg kg^-1 for chlormadinone acetate, respectively. These results showed that the method was widely available, accurate, and sensitive.展开更多
BACKGROUND: Alcoholic hepatitis (AH) is a necrotizing inflammatory process caused by alcoholic liver injury. It carries a significant short-term mortality. The management of AH is challenging. Although corticosteroids...BACKGROUND: Alcoholic hepatitis (AH) is a necrotizing inflammatory process caused by alcoholic liver injury. It carries a significant short-term mortality. The management of AH is challenging. Although corticosteroids have been demonstrated to exert anti-inflammatory and antifibrotic effects, their efficacy for the treatment of AH remains debatable. DATA SOURCES: A literature search was performed of MEDLINE, ScienceDirect, SpringerLink and Wiley InterScience using the key words 'alcoholic hepatitis', 'alcoholic liver disease', and 'corticosteroids'. The available data reported in the relevant literature were analyzed. RESULTS: More than 17 controlled trials and at least 13 meta-analyses have reported the efficacy of corticosteroids in the treatment of AH in the past 40 years. Many were poorly designed and used different inclusion/exclusion criteria, making it difficult to reach a consensus. In this review, we summarized all the controversial data in the past decade and analyzed the potential causes for the varying therapeutic effects of corticosteroids in AH. The focus of the controversy has changed from 'whether steroids are beneficial or harmful for AH patients' to 'how to accurately identify responders to steroids early and rationalize corticosteroid treatment'. An early response to glucocorticoids, as determined by calculating the Lille score after 7 days of treatment, has been shown to be a clinically useful indicator. Moreover, down-regulation of steroid sensitivity, risk of infection, and a rational therapeutic strategy of corticosteroids in AH patients are all crucial for therapeutic effect.CONCLUSIONS: An early and accurate determination of steroid sensitivity is important. Besides, we need to overcome the down-regulation of steroid sensitivity, reduce the infection risk and rationalize the therapeutic strategy of corticosteroids. A fresh perspective is needed on the use of corticosteroids in AH patients.展开更多
Penicildiones A-D(1-4), four new steroids derivatives together with three known compounds including 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy(5), stachybotrylactone B(6) and stachybo...Penicildiones A-D(1-4), four new steroids derivatives together with three known compounds including 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy(5), stachybotrylactone B(6) and stachybotrin(7) were isolated from the soft coral-derived fungus Penicillium sp. SCSIO41201, cultured in the 1% NaCl PDB substrate. Their structures were determined through spectroscopic methods and X-ray crystallography. Biological evaluation results revealed that 6 exhibited significant cytotoxic activity against HL-60, K562, MOLT-4, ACHN, 786-O, and OS-RC-2 cell lines with IC50 values of 5.23, 4.12, 4.31, 23.55, 7.65 and 10.81 μmol·L-1, respectively, while other compounds showed weak or no cytotoxicity at 50 μmol·L-1.展开更多
Corticoesteroids are still the first-line treatment for active ulcerative colitis more than 50 years after the publication of trials assessing their beneficial effect, with about a 50% remission rate in cases of sever...Corticoesteroids are still the first-line treatment for active ulcerative colitis more than 50 years after the publication of trials assessing their beneficial effect, with about a 50% remission rate in cases of severe disease. The mortality related to severe attacks of ulcerative colitis has decreased dramatically, to less than 1%, in experienced centers, due to the appropriate use of intensive therapeutic measures (intravenous steroids, fluids and electrolytes, artificial nutritional support, antibiotics, etc), along with timely decision-making about second-line medical therapy and early identification of patients requiring colectomy. One of the most difficult decisions in the management of severe ulcerative colitis is knowing for how long corticosteroids should be administered before deciding that a patient is a non-responder. Studies assessing the outcome of acute attacks after steroid initiation have demonstrated that, in steroid-sensitive patients, the response generally occurs early on, in the first days of treatment. Different indexes to predict treatment failure, when applied on the third day of treatment, have demonstrated a high positive predictive value for colectomy. In contrast to this resolute approach, which is the most widely accepted, other authors have suggested that in some patients a completeand prolonged response to steroids may take longer. Either way, physicians taking care of these patients need to recognize that severe ulcerative colitis may be life-threatening, and they need to be careful with excessively prolonged medical treatment and delayed surgery.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.
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.
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.
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.
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.
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Androgenic-anabolic steroids （AAS） have been misused by athletes at the Olympic Games, both before and after they were prohibited in sport in 1974. Systematic doping with AAS occurred in the German Democratic Republic （GDR） from 1965 to 1989 which assisted that country to win many medals at Olympic Games, especially in female events. Currently, AAS are the most frequent category of prohibited substances detected in the urine of athletes both globally and at the last two Summer Olympic Games. Scientific confirmation that AAS are effective in enhancing sports performance was difficult because ethical approval was difficult for research involving male subjects taking massive doses of androgens as some athletes and bodybuilders did. Methods to detect AAS have evolved gradually over the past three decades and currently, despite an impressive array of sophisticated analytical equipment and methods, anti-doping authorities and analytical scientists continue to face challenges as have occurred from the use by athletes of designer AAS during the past few years. The future development and use of selective androgen receptor modulators （SARMs） can be anticipated to pose problems in the years ahead. Endocrinologists should be aware that on occasions, replacement testosterone （T） therapy may be authorized in sport as a therapeutic use exemption （TUE） and these circumstances are discussed.
文摘Eosinophilic esophagitis(EoE)is an emerging chronic local immune-mediated disease of the esophagus.Beside proton pump inhibitors and food-restrictiondiets swallowed topical corticosteroids(STC)can be offered as a first line therapy according to current guidelines.This review describes the background and practical management of STCs in EoE.So far,mainly asthma inhalers containing either budesonide or fluticasone have been administered to the esophagus by swallowing these medications“off label”.Recently esophagus-targeted formulations of topical steroids have been developed showing clinicopathological response rates up to 85%-an orodispersible tablet of budesonide has been approved as the first“in label”medication for EoE in Europe in June 2018.Whereas it was shown that disease remission induction of EoE by STCs is highly effective,there is still a lack of data regarding long-term and maintenance therapy.However,current studies on STC maintenance therapy add some movement into the game.
文摘11β-Hydroxy-androst-4-en-3,17-dione(1a),androst-4,9(11)-dien-3,17- dione-(2a),androst-4-en-3,11,17-trione(3a),11α-methoxy-androst-4-en-3,17-dione (4a)and 11β-metboxy-androst-4-en-3,17-dione(Sa)were selectively reduced to the corresponding 17β-OH derivatives in one step without the protection of 3- oxo(and 11-oxo,in the case of 3a)group with the yields ranging from 65% to 79%.In these reactions,the ditute NaBH_4(or KBH_4)solution in methanol was added dropwise to the 3,17-dioxo-steroids solution in methanol-benzene-pyridine, while the reaction mixtures were well stirred at -5～5℃.Acid(such as gtacial acetic acid)was added to quench the reactions.The resulted testosterone derivatives(1b～5b)were purified by flash chromatography. This method appties to the reduction of other 3,17-dioxo-steroids such as△~1 -3-one,△^(1.4)-3-one,△^(4.6)-3-one,△^(1.4.6)-3-one containing compounds.
文摘Non-traumatic osteonecrosis is a cause of joint pain and deformity, not uncommonly caused by corticosteroid use. Despite this, corticosteroid induced osteonecrosis is poorly represented in the literature. We performed a detailed review of corticosteroid induced osteonecrosis, including aetiology, prevention, screening, clinical presentation, investigations, staging systems and treatment. We present this in the context of a patient at our institution who developed bilateral hip, shoulder and knee osteonecrosis following high dose corticosteroid therapy for dermatomyositis.
基金supported by the National Natural Science Foundation of China(No.30070556)the Major State Basic Research Development Program of China(No.G200016107).
文摘It is well known that during mammalian ovarian follicular development, the majority of follicles undergo atresia at various stages of their development. However, the mechanisms controlling this selection process remain unknown. In this study, we investigated apoptosis in granulosa cells during goat follicular atresia by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The changes in the levels of steroids, insulin-like growth factors (IGFs) and IGF receptors were studied by radioimmunoassay (RIA) and semi-quantitative reverse transcrip-tion-PCR. We found that the percentage of apoptotic granulosa cells in the atretic (A) follicles was significantly higher than that in the slightly atretic (SA) and healthy (H) follicles. The level of estradiol and the ratio of estradiol to progesterone in H follicles were significantly higher than those in A follicles. On the other hand, the level of progesterone was not significantly different among these follicle types. We also found that the level of IGF-Ⅰ in H follicles was higher than in SA and A follicles, whereas the amount of IGF-Ⅱ did not vary significantly. The expression of IGF receptor also decreased in A follicles as compared to that in H and SA follicles. These results suggested that estradiol and IGF-Ⅰ might be involved in controlling apoptosis in granulosa cells during follicular atresia.
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.
文摘Objective:To determine the chemical profile and steroids composition of the medicinally important plant Aerva lanata(A.lanata) L.Methods:Preliminary phytochemicul screening was done by the method as Harborne described.HPTLC studies were canied out as Harborne and Wagner et al described.The Ethyl acetate-ethanol-water(8:2:1.2) was employed as mobile phase for glycosides.Results:The desired aim was achieved using Chloroform-acetone(8:2) as the mobile phase.The methanolic extract of stem,leaves,root,flower and seeds of A.lanata showed the presence of 30 different types of steroids with 30 different Rf values from 0.04 to 0.97. Maximum number(11) of steroids has been observed in leaves followed by root(10).Conclusions: HPTLC profile of steroids has been chosen here to reveal the diversity existing in A.lanata.Such finger printing is useful in differentiating the species from the adulterant and act as biochemical markers for this medicinally important plant in the pharma industry and plant systematic studies.
基金the Department of Pathophysiology of Hebei Medical University, China for their help
文摘A correlation between metabolic alterations of neuroactive steroids and Alzheimer’s disease remains unknown. In the present study, amyloid beta （Aβ） 25-35 （Aβ25-35） injected into the bilateral campus CA1 region significantly reduced learning and memory. At the biochemical level, hippocampal levels of pregnenolone were significantly reduced with Aβ25-35 treatment. Furthermore, progesterone was considerably decreased in the prefrontal cortex and hippocampus, and 17β-estradiol was signifi-cantly elevated. To our knowledge, this is the first report showing that Aβ25-35, a main etiological factor of Alzheimer’s disease, can alter the level and metabolism of neuroactive steroids in the prefrontal cortex and hippocampus, which are brain regions significantly involved in learning and memory. Aβ25-35 exposure also increased the expression of inflammatory mediators, tumor necrosis factor-αand interleukin-1β. However, subcutaneous injection of progesterone reversed the upregulation of tumor necrosis factor-αand interleukin-1βin a dose-dependent manner. Concomitant with improved cognitive abilities, progesterone blocked Aβ-mediated inflammation and increased the survival rate of hippocampal pyramidal cells. We thus hypothesize that Aβ-mediated cognitive deficits may occur via changes in neuroactive steroids. Moreover, our findings provide a possible therapeutic strategy for Alzheimer’s disease via neuroactive steroids, particularly progesterone.
文摘Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus （T2DM） and also predict the onset of these adverse metabolic states. Body composition （body mass index, waist circumference） is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter＇s syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/ glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.
文摘Two new C21 steroids were isolated from the CHCl3 extract of the stem of Marsdenia tenacissima. On the basis of spectroscopic analysis and chemical methods, their structures were elucidated as 17β-tenacigenin B (2) and 3-O-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D- oleandropyranosyl-tenacigenin C (3). The structure of the known aglycon tenacigenin C was revised as 5α, 9α, 17β-pregnane-3β, 8β, 11α, 12β, 14β-pentanol-20-one. Compound 3 is the first reported glycoside of tenacigenin C.
基金supposed by the Projects of Agricultural Standards for Veterinary Drug Residues,China
文摘A gas chromatography-mass spectrometry （GC-MS） method to determine eight anabolic steroids （diethylstilbestrol, methyltestosterone, norethindrone, 17α-ethynylestradiol, estradiol, 6α-methyl-17α-hydroxy-progesterone, estradiol benzoate, and chlormadinone acetate） was developed. Muscle samples were extracted with liquid-liquid extraction and clean-up was performed in two steps, the extracts obtained were derivatized with heptafluorbutyric （HBF） anhydride and analyzed by GC-MS. In the above method, the linear scope was 2.5-50 μg kg^-1. The range of the recoveries was 78.5-148% for diethylstilbestrol, 70.8-109% for methyltestosterone, 69.8-87.2% for norethindrone, 67.7-120% for 17α-ethynylestradiol, 82.8-103% for estradiol, 70.3-99.2% for 6α-methyl-17α-hydroxy-progesterone, 73.0-104% for estradiol benzoate, and 72.9- 91.8% for chlormadinone acetate. The range of the coefficients of variation within batches was 0.4-12%; the range of the coefficients of variation between batches was 6.4-11%. The limit of detections and the detection capability were 0.99 and 3.30 μg kg^-1 for diethylstilbestrol, 1.05 and 3.50 μg kg^-1 for methyltestosterone, 1.19 and 3.97 μg kg^-1 for norethindrone, 0.94 and 3.13 μg kg^-1 for 17α-ethynylestradiol, 1.45 and 4.83 μg kg^-1 for estradiol, 1.56 and 5.20 μg kg^-1 for 6α-methyl-17α- hydroxy-progesterone, 1.92 and 6.40 μg kg^-1 for estradiol benzoate, and 2.41 and 8.03 μg kg^-1 for chlormadinone acetate, respectively. These results showed that the method was widely available, accurate, and sensitive.
基金supported by a grant from the General Project Foundation of the Education Department of Liaoning Province (2009A809)
文摘BACKGROUND: Alcoholic hepatitis (AH) is a necrotizing inflammatory process caused by alcoholic liver injury. It carries a significant short-term mortality. The management of AH is challenging. Although corticosteroids have been demonstrated to exert anti-inflammatory and antifibrotic effects, their efficacy for the treatment of AH remains debatable. DATA SOURCES: A literature search was performed of MEDLINE, ScienceDirect, SpringerLink and Wiley InterScience using the key words 'alcoholic hepatitis', 'alcoholic liver disease', and 'corticosteroids'. The available data reported in the relevant literature were analyzed. RESULTS: More than 17 controlled trials and at least 13 meta-analyses have reported the efficacy of corticosteroids in the treatment of AH in the past 40 years. Many were poorly designed and used different inclusion/exclusion criteria, making it difficult to reach a consensus. In this review, we summarized all the controversial data in the past decade and analyzed the potential causes for the varying therapeutic effects of corticosteroids in AH. The focus of the controversy has changed from 'whether steroids are beneficial or harmful for AH patients' to 'how to accurately identify responders to steroids early and rationalize corticosteroid treatment'. An early response to glucocorticoids, as determined by calculating the Lille score after 7 days of treatment, has been shown to be a clinically useful indicator. Moreover, down-regulation of steroid sensitivity, risk of infection, and a rational therapeutic strategy of corticosteroids in AH patients are all crucial for therapeutic effect.CONCLUSIONS: An early and accurate determination of steroid sensitivity is important. Besides, we need to overcome the down-regulation of steroid sensitivity, reduce the infection risk and rationalize the therapeutic strategy of corticosteroids. A fresh perspective is needed on the use of corticosteroids in AH patients.
基金the National Natural Science Foundation of China (Nos. 21977102, 81973235,81860626, 21772210, 41776169)Guangzhou Science and Technology Project (No. 201804010462)+3 种基金the Natural Science Foundation of Guangdong Province (No. 2018A0303130219)the Special Funds for Promoting Economic Development (Marine Economic Development)of Guangdong Province (No. GDOE[2019]A28)National Major Scientific and Technological Special Project for Significant New Drugs Development (No. 2018ZX09735001-002-003)Project from Institution of South China Sea Ecology and Environmental Engineering(No. ISEE2018PY04)。
文摘Penicildiones A-D(1-4), four new steroids derivatives together with three known compounds including 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy(5), stachybotrylactone B(6) and stachybotrin(7) were isolated from the soft coral-derived fungus Penicillium sp. SCSIO41201, cultured in the 1% NaCl PDB substrate. Their structures were determined through spectroscopic methods and X-ray crystallography. Biological evaluation results revealed that 6 exhibited significant cytotoxic activity against HL-60, K562, MOLT-4, ACHN, 786-O, and OS-RC-2 cell lines with IC50 values of 5.23, 4.12, 4.31, 23.55, 7.65 and 10.81 μmol·L-1, respectively, while other compounds showed weak or no cytotoxicity at 50 μmol·L-1.
文摘Corticoesteroids are still the first-line treatment for active ulcerative colitis more than 50 years after the publication of trials assessing their beneficial effect, with about a 50% remission rate in cases of severe disease. The mortality related to severe attacks of ulcerative colitis has decreased dramatically, to less than 1%, in experienced centers, due to the appropriate use of intensive therapeutic measures (intravenous steroids, fluids and electrolytes, artificial nutritional support, antibiotics, etc), along with timely decision-making about second-line medical therapy and early identification of patients requiring colectomy. One of the most difficult decisions in the management of severe ulcerative colitis is knowing for how long corticosteroids should be administered before deciding that a patient is a non-responder. Studies assessing the outcome of acute attacks after steroid initiation have demonstrated that, in steroid-sensitive patients, the response generally occurs early on, in the first days of treatment. Different indexes to predict treatment failure, when applied on the third day of treatment, have demonstrated a high positive predictive value for colectomy. In contrast to this resolute approach, which is the most widely accepted, other authors have suggested that in some patients a completeand prolonged response to steroids may take longer. Either way, physicians taking care of these patients need to recognize that severe ulcerative colitis may be life-threatening, and they need to be careful with excessively prolonged medical treatment and delayed surgery.
