Steroids最新文献

{"title":"Kuwanon C inhibits proliferation and induction of apoptosis via the intrinsic pathway in MDA-MB231 and T47D breast cancer cells","authors":"Peng Qian,&nbsp;Gangxiang Yuan,&nbsp;Chao Yang,&nbsp;Qi Zhang,&nbsp;Lin Chen,&nbsp;Ningjia He","doi":"10.1016/j.steroids.2024.109450","DOIUrl":"10.1016/j.steroids.2024.109450","url":null,"abstract":"<div><p>Breast cancer ranks as the most prevalent malignancy, presenting persistent therapeutic challenges encompassing issues such as drug resistance, recurrent occurrences, and metastatic progression. Therefore, there is a need for targeted drugs that are less toxic and more effective against breast cancer. Kuwanon C, an isoamylated flavonoid derived from mulberry resources, has shown promise as a potential candidate due to its strong cytotoxicity against cancer cells. The present study focused on investigating the anticancer activity of kuwanon C in two human breast cancer cell lines, MDA-MB231 and T47D cells. MTS assay results indicated a decrease in cell proliferation with increasing concentrations of kuwanon C. Furthermore, kuwanon C upregulated the expression levels of the cyclin-dependent kinase inhibitor p21 and effectively inhibited cell DNA replication and induced DNA damage. Flow cytometry confirmed that kuwanon C induced cell apoptosis and upregulated the expression levels of pro-apoptotic proteins (Bax and c-caspase3). Additionally, it stimulated the production of reactive oxygen species (ROS) in the cells. Transmission electron microscopy and Fluo-4 AM-calcium ion staining experiments provided insights into the endoplasmic reticulum (ER), revealing that kuwanon C induced ER stress. Kuwanon C upregulated the expression levels of unfolded protein response-related proteins (ATF4, GADD34, HSPA5, and DDIT3). Overall, the present findings suggested that kuwanon C exerts a potent inhibitory effect on breast cancer cell proliferation through modulating of the p21, induction of mitochondrial-mediated apoptosis, activation of ER stress and induction of DNA damage. These results position kuwanon C as a potential targeted therapeutic agent for breast cancer.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"208 ","pages":"Article 109450"},"PeriodicalIF":2.7,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative analysis of 34 sex (pro)hormones, conjugates and bioactive oxidation products thereof in human plasma by GC- and LC-MS/MS and systematic investigation of overestimations of analyte concentrations not accounted for by method validation","authors":"Miriam Raps,&nbsp;Carolin Kleider,&nbsp;Leane Lehmann","doi":"10.1016/j.steroids.2024.109441","DOIUrl":"10.1016/j.steroids.2024.109441","url":null,"abstract":"<div><p>When investigating endocrine disorders, it is essential to assess a comprehensive quantitative profile of sex (pro)hormones in plasma including conjugates. Thus, the present study aimed to develop and validate a comprehensive mass spectrometry-based multimethod combining the direct analysis of unconjugated sex (pro)hormones and oxidation products thereof (by GC), as well as their sulfates and glucuronides present in higher concentrations (by LC) with the indirect quantification of glucuronides present in lower concentrations after selective glucuronide hydrolysis (by GC) and its application to plasma derived from ten pre- and postmenopausal women and men each. Even guideline-compliant validation experiments cannot completely reflect overestimation of analyte concentrations due to effects depending on the individual ratio of analytes (i.e. chemical formation of analytes or incomplete removal of interfering analytes). Thus, the extent of processes not accounted for by the calibration strategy were investigated and maximum over- or underestimations of analyte concentrations were assessed for each plasma sample individually. 34 analytes were successfully calibrated, validated (median accuracy 101.1 %, median inter-day precision 8.1 %) and 31 were detected above the detection limit in plasma samples. The sporadic maximum individual over- or underestimation of analyte concentrations amounted to less than 20 %.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"208 ","pages":"Article 109441"},"PeriodicalIF":2.1,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0039128X24000795/pdfft?md5=17289ae7ec60ab7509dc3a8dcfbbe225&pid=1-s2.0-S0039128X24000795-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review on glucocorticoids induced osteoporosis: A medication caused disease","authors":"Asim Rahman,&nbsp;Md Faheem Haider","doi":"10.1016/j.steroids.2024.109440","DOIUrl":"10.1016/j.steroids.2024.109440","url":null,"abstract":"<div><p>Glucocorticoids (GCs) are steroid hormones that are extensively used in the treatment of autoimmune diseases, inflammation, and cancer. The major ill effect of administering GCs is that it has a deleterious effect on bone, which leads to GC-induced osteoporosis. GC therapy induces bone loss and is associated with the risk of nonvertebral and vertebral fractures, as it works in combination by increasing bone reabsorption and suppressing bone formation during the initial phase of therapy. It is seen and established that GC in excess or in low dose for 3 months or more can be a risk factor for fracture, and the risk increases with an increase in dose and duration of usage. The most common cause of secondary osteoporosis is the administration of GC inside the body to treat various diseases. The degree of bone loss is directly proportional to the GC dose and the exposure duration. The first step is to evaluate the patients' risk factors for the development of glucocorticoids that induce osteoporosis, which include the dose, duration of use, patient age, sex, previous fractures, and other medical conditions.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"207 ","pages":"Article 109440"},"PeriodicalIF":2.7,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141039795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Withania frutescens (L.) Pauquy, a valuable Mediterranean shrub containing bioactive withanolides","authors":"Latifa Bouissane ,&nbsp;Christian Bailly","doi":"10.1016/j.steroids.2024.109439","DOIUrl":"10.1016/j.steroids.2024.109439","url":null,"abstract":"<div><p>The bushy plant <em>Withania frutescens</em> (L<em>.</em>) Pauquy is well distributed in the West-Mediterranean area, notably in the south of Spain, Algeria and Morocco where is it is used traditionally for the treatment of various human diseases, including diabetes. Unlike the two major species <em>W. somnifera</em> and <em>W. coagulans</em> extensively studied, the genomically close species <em>W. frutescens</em> has been much less investigated. Nevertheless, this shrub species displays a comparable phytochemical profile and marked antioxidant and anti-inflammatory properties, at the origin of reported pharmacological effects and its traditional uses. Here we have analyzed the diversity of biological effects reported with leaves and root extracts of <em>W. frutescens</em>. Hydroalcoholic extracts prepared from the aerial parts of the plant have revealed antihyperglycemic and cell-protective activities along with antimicrobial and anticorrosive effects. The extracts contained diverse polyphenolic compounds and a few alkaloids (calystegines) but most of the observed effects have been attributed to the presence of withanolides which are modified C28 ergostane-type steroids. Our analysis focused in part on specific withanolides found in <em>W. frutescens</em>, in particular an unusual 3-O-sulfated withanolide considered as a potential pro-drug of the major active compound withaferin A (WA) and a lead compound for the development of a potential drug candidate. The mechanism of action of this sulfated WA analogue is discussed. Altogether, our unprecedented extensive analysis of <em>W. frutescens</em> highlighted the pharmacological potential of this atypical medicinal plant. By analogy with the major cultivated <em>Withania</em> species, the market potential of little-known plant is underlined.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"207 ","pages":"Article 109439"},"PeriodicalIF":2.7,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0039128X24000771/pdfft?md5=c3e00e179a5ba8eaff4d8025f46eb7b3&pid=1-s2.0-S0039128X24000771-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significance of vitamin D responsiveness on the etiology of vitamin D-related diseases","authors":"Ulla M. Järvelin ,&nbsp;Juho M. Järvelin","doi":"10.1016/j.steroids.2024.109437","DOIUrl":"10.1016/j.steroids.2024.109437","url":null,"abstract":"<div><p>Vitamin D resistance (VDRES) explains the necessity for higher doses of Vitamin D (VD) than those recommended for treatment success. VD receptor (VDR) signaling blockade, such as that caused by infections and poisons, is one basis for VDRES etiology. Mutations within genes affecting the VD system cause susceptibility to developing low VD responsiveness and autoimmunity. In contrast, VD hypersensitivity (VDHY) occurs if there is extra VD in the body; for example, as a result of an overdose of a VD supplement. Excess 1,25(OH)2D3 is produced in lymphomas and granulomatous diseases. The placenta produces excess 1,25(OH)₂D₃. Gene mutations regulating the production or degradation of 1,25(OH)₂D₃ enhance the effects of 1,25(OH)₂D₃. Increased 1,25(OH)₂D₃ levels stimulate calcium absorption in the gut, leading to hypercalcemia. Hypercalcemia can result in the calcification of the kidneys, circulatory system, or placenta, leading to kidney failure, cardiovascular disease, and pregnancy complications. The primary treatment involves avoiding exposure to the sun and VD supplements. The prevalence rates of VDRES and VDHY remain unclear. One estimate was that 25%, 51%, and 24% of the patients had strong, medium, and poor responses, respectively. Heavy-dose VD therapy may be a promising method for the treatment of autoimmune diseases; however, assessing its potential side effects is essential. To avoid VD-mediated hypercalcemia, responsiveness must be considered when treating pregnancies or cardiovascular diseases associated with VD. Furthermore, how VD is associated with the related disorders remains unclear. Investigating responsiveness to VD may provide more accurate results.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"207 ","pages":"Article 109437"},"PeriodicalIF":2.7,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0039128X24000758/pdfft?md5=eac1c052596a77de0de1336e880e7b55&pid=1-s2.0-S0039128X24000758-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-dependent dual mode of action of COX-2 inhibition on mouse serum corticosterone levels","authors":"Patrycja Pańczyszyn-Trzewik ,&nbsp;Magdalena Sowa-Kućma ,&nbsp;Paulina Misztak ,&nbsp;Anna Tabecka-Lonczynska ,&nbsp;Katarzyna Stachowicz","doi":"10.1016/j.steroids.2024.109438","DOIUrl":"10.1016/j.steroids.2024.109438","url":null,"abstract":"<div><p>To elucidate the effect of cyclooxygenase-2 (COX-2) inhibition on corticosterone release, mice were divided into a group receiving NS398, a selective COX-2 inhibitor at a dose of 3 mg/kg for seven days, and a group receiving NS398 for fourteen days. After this time, the mice were sacrificed, and blood serum was collected. An ELISA protocol was used to analyze serum corticosterone levels. Short-term COX-2 inhibition increased corticosterone levels, while long-term inhibition lowered them. The exact schedule of experiments was repeated after the lipopolysaccharide (LPS) <em>Escherichia coli</em> challenge in mice to check the influence of stress stimuli on the tested parameters. In this case, we observed increases in corticosterone levels, significant in a seven-day pattern. These results indicate that corticosterone levels are regulated through a COX-2-dependent mechanism in mice.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"207 ","pages":"Article 109438"},"PeriodicalIF":2.7,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle ultrasound to identify prednisone-induced muscle damage in adults with nephrotic syndrome","authors":"Mengmeng Wu ,&nbsp;Jinnuo Yu ,&nbsp;Ao Zhong ,&nbsp;Yifan Tang ,&nbsp;Manzhi Li ,&nbsp;Caixia Liu ,&nbsp;Dong Sun","doi":"10.1016/j.steroids.2024.109434","DOIUrl":"10.1016/j.steroids.2024.109434","url":null,"abstract":"<div><p>Steroid myopathy is a non-inflammatory toxic myopathy that primarily affects the proximal muscles of the lower limbs. Due to its non-specific symptoms, it is often overshadowed by patients’ underlying conditions. Prolonged or high-dosage use of glucocorticoids leads to a gradual decline in muscle mass. There are no tools available to identify the course of steroid myopathy before the patient displays substantial clinical symptoms. In this study, we investigated individuals with nephrotic syndrome receiving prednisone who underwent muscle ultrasound to obtain cross-sectional and longitudinal pictures of three major proximal muscles in the lower limbs: the vastus lateralis, tibialis anterior, and medial gastrocnemius muscles. Our findings revealed that grip strength was impaired in the prednisolone group, creatine kinase levels were reduced within the normal range; echo intensity of the vastus lateralis and medial gastrocnemius muscles was enhanced, the pennation angle was reduced, and the tibialis anterior muscle exhibited increased echo intensity and decreased thickness. The total dose of prednisone and the total duration of treatment impacted the degree of muscle damage. Our findings indicate that muscle ultrasound effectively monitors muscle structure changes in steroid myopathy. Combining clinical symptoms, serum creatine kinase levels, and grip strength improves the accuracy of muscle injury evaluation.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"207 ","pages":"Article 109434"},"PeriodicalIF":2.7,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The beneficial roles and mechanisms of estrogens in immune health and infection disease","authors":"Lan Chen ,&nbsp;Ting Xu ,&nbsp;Jun Lou ,&nbsp;Ting Zhang ,&nbsp;Sheng Wu ,&nbsp;Rui Xie ,&nbsp;Jingyu Xu","doi":"10.1016/j.steroids.2024.109426","DOIUrl":"10.1016/j.steroids.2024.109426","url":null,"abstract":"<div><p>Multiple epidemiologic studies have revealed that gender is considered one of the important factors in the frequency and severity of certain infectious diseases, in which estrogens may play a vital role. There is growing evidence that estrogens as female sex hormone can modulate multiple biological functions outside of the reproductive system, such as in brain and cardiovascular system. However, it is largely unknown about the roles and mechanisms of estrogens/estrogen receptors in immune health and infection disease. Thence, by reading a lot of literature, we summarized the regulatory mechanisms of estrogens/estrogen receptors in immune cells and their roles in certain infectious diseases with gender differences. Therefore, estrogens may have therapeutic potentials to prevent and treat these infectious diseases, which needs further clinical investigation.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"207 ","pages":"Article 109426"},"PeriodicalIF":2.7,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism of progestogens used for contraception and menopausal hormone therapy","authors":"Frank Z. Stanczyk ,&nbsp;Alexandra McGough ,&nbsp;Laura Chagam ,&nbsp;Regine Sitruk-Ware","doi":"10.1016/j.steroids.2024.109427","DOIUrl":"10.1016/j.steroids.2024.109427","url":null,"abstract":"<div><p>A variety of progestogens are widely used by women for contraception and menopausal hormone therapy. The progestogens undergo extensive metabolism by oral and parenteral routes of administration to form many metabolites. Although a small number of metabolites have been shown to be biologically active, most have not been tested for biologic activity. The present review shows that we know most about progesterone metabolism, followed by the metabolism of levonorgestrel and norethindrone. Very few studies have been carried out on metabolism of most of the progestogens. The clinical significance of this deficiency is that those progestogen metabolites that bind to the progesterone receptors may also bind to other steroid receptors and be responsible for some of the well-documented side effects of administered progestogens. We also discuss how obesity and genetic polymorphisms alter progestogen metabolism, and how development of oral progestogen formulations that are targeted to the colon, where the concentration of steroid-metabolizing enzymes is much lower than in the proximal gut, may have a beneficial effect on progestogen metabolism.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"207 ","pages":"Article 109427"},"PeriodicalIF":2.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140758174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dehydroepiandrosterone with a high-fat diet treatment at inducing polycystic ovary syndrome in rat model","authors":"Ying He ,&nbsp;Xiaoyan Li ,&nbsp;Yueying Li ,&nbsp;Dan Kuai ,&nbsp;Huiying Zhang ,&nbsp;Yingmei Wang ,&nbsp;Wenyan Tian","doi":"10.1016/j.steroids.2024.109424","DOIUrl":"https://doi.org/10.1016/j.steroids.2024.109424","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to evaluate the effects of dehydroepiandrosterone (DHEA) and DHEA combined with a high-fat diet (HFD) treatment of reproductive and endocrine metabolism in rats and then identify an ideal model of polycystic ovary syndrome (PCOS).</p></div><div><h3>Methods</h3><p>Three-week-old female Sprague–Dawley rats were injected subcutaneously with DHEA or oil, fed with or without a HFD, for 21 days, during which body weight, feed intake, and estrous cycle monitoring were carried out. Fasting blood glucose was measured, and serum fasting insulin, testosterone, dihydrotestosterone (DHT), estradiol, progesterone, luteinizing hormone (LH), anti-Müllerian hormone (AMH), and follicle-stimulating hormone (FSH) were estimated by ELISA. Serum total cholesterol (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by colorimetric assay. Whereas, histologic changes in rat ovaries were evaluated by H&amp;E staining. Ovarian steroid hormone synthases and their protein levels (StAR, 3β-HSD2, 17β-HSD1, CYP11A1, CYP17A1, and CYP19A1) were examined by Western blotting.</p></div><div><h3>Results</h3><p>Both DHEA and DHEA + HFD-treated rats lost a regular estrous cycle; had polycystic ovarian changes, significantly higher serum fasting insulin and testosterone levels; and increased ovarian StAR, 3β-HSD2, and CYP11A1 protein levels. Additionally, rats in the DHEA + HFD-treated group were obese; had elevated fasting blood glucose, TG, DHT, AMH levels and LH:FSH ratios; increased ovarian 17β-HSD1 protein levels.</p></div><div><h3>Conclusion</h3><p>DHEA combined with HFD treatment is more effective at inducing PCOS than DHEA alone. The reproductive and endocrine metabolic aspects of this method are more consistent with the clinical characteristics of PCOS patients.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"206 ","pages":"Article 109424"},"PeriodicalIF":2.7,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0039128X2400062X/pdfft?md5=d8522dfb4e5ee3c074838c24b6be5c78&pid=1-s2.0-S0039128X2400062X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140645414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}