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Localised scleroderma predominantly affects the skin with an unknown aetiology. Despite its clinical importance, no comprehensive bibliometric analysis has been conducted to assess the existing research landscape and future prospects for localised scleroderma. The articles related to localised scleroderma were retrieved from the WoSCC database and analysed by VOSviewer 1.6.10.0 (Leiden University, Netherlands), CiteSpace 6.1.R1 (Dreiser University, USA), and HistCite 2.1 (New York, United States). 2049 research papers pertaining to localised scleroderma spanning the years from 1993 to 2022 were extracted from the WoSCC database. The United States exhibited the highest productivity with 644 papers, accounting for 31.43% of the total output, followed by Germany with 206 papers (10.05%) and Italy with 200 papers (9.76%). Regarding academic institutions and journals, the University of Texas System and Dermatology published the most significant number of papers, and Professor Ihn, H emerged as the most prolific contributor among scholars. The top 10 cited references primarily concentrated on the diagnosis and treatment of localised scleroderma. "Phototherapy" and "methotrexate (MTX)" surfaced as the most recent and noteworthy keywords, representing the research hotspots in the domain of localised scleroderma. This bibliometric analysis furnishes valuable insights into the contemporary research landscape of localised scleroderma.
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Esclerodermia Localizada , Humanos , Esclerodermia Localizada/terapia , Pele , Bibliometria , Bases de Dados Factuais , AlemanhaRESUMO
AIMS: We aimed to assess the comparative efficiency and safety of the use of glyburide, metformin, and insulin in gestational diabetes mellitus (GDM). METHODS: We searched for randomized controlled trials that compared glyburide, metformin, and insulin in GDM. Data regarding glycemic control and neonatal safety were collected and analyzed in pairwise and network meta-analyses. RESULTS: A total of 4533 individuals from 23 trials were included. Compared with glyburide, metformin reduced 2-h postprandial blood glucose (2HPG) to a greater extent (standard mean difference (SMD) 0.18; 95% credible interval (CI) 0.01, 0.34). There were significantly lower prevalence of neonatal hypoglycemia (risk difference (RD) - 0.07; 95%CI - 0.11, - 0.02) and preeclampsia (RD - 0.03; 95%CI - 0.06, 0) in the metformin group than in the insulin group. The metformin group had significantly lower birth weight (SMD - 0.17; 95%CI - 0.25, - 0.08) and maternal weight gain (SMD - 0.61; 95%CI - 0.86,- 0.35) compared with the insulin group. Network meta-analysis suggested that metformin had the highest probability of successfully controlling glycemia and preventing neonatal complications. CONCLUSIONS: The present meta-analysis suggests that metformin may be as effective as insulin for glycemic control and is the most promising drug for the prevention of neonatal and maternal complications.
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Diabetes Gestacional/tratamento farmacológico , Controle Glicêmico , Hipoglicemiantes/uso terapêutico , Resultado da Gravidez/epidemiologia , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Gestacional/epidemiologia , Feminino , Glibureto/uso terapêutico , Controle Glicêmico/métodos , Controle Glicêmico/estatística & dados numéricos , Humanos , Hipoglicemiantes/classificação , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/etiologia , Insulina/uso terapêutico , Masculino , Análise por Pareamento , Metformina/uso terapêutico , Metanálise em Rede , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricosRESUMO
BACKGROUND: Anti-Müllerian hormone (AMH) is now considered the best serum biomarker of ovarian reserve, while basal sex hormones are classic markers used for assessing ovarian reserve. The interaction between AMH and sex hormones are complicated and not sufficiently addressed. In this study, we took diminished ovarian reserve (DOR) and polycystic ovarian syndrome (PCOS) as two extremes of ovarian reserve (deficient and excessive respectively) to investigate the role of AMH and sex hormones in follicular growth. METHODS: A retrospective cross-sectional survey was performed. The patients assessed AMH and basal sex hormones in the Second Hospital of Zhejiang University from April 2016 to March 2019 were involved in this study. Serum AMH and sex hormone concentrations were tested with electrochemiluminescence method. Stepwise linear regression and binary logistic regression was used to determine the predictors of AMH level and to explore the involved factors determining DOR and PCOS. RESULTS: In the present study, we found that age and follicle-stimulating hormone (FSH) were main negative correlation factors, and luteinizing hormone (LH) and testosterone (T) were main positive factors of AMH. In DOR group, age, FSH and estradiol (E2) increased and T decreased, while in PCOS group, LH and T increased. Binary logistic regression found that age, weight, FSH, E2, and T were the significant factors which independently predicted the likelihood of DOR, and that age, body mass index (BMI), AMH, LH, and T predicted the likelihood of PCOS. CONCLUSIONS: Our study demonstrated that age, FSH, and T were factors that most closely correlated with AMH level, and T was involved in both DOR and PCOS. Since DOR and PCOS are manifested with insufficient AMH and excessive AMH respectively, it is suggested that total testosterone correlated with AMH closely and plays an important role in follicular growth. More attention should be given to testosterone level during controlled ovarian hyperstimulation (COH) process.
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Hormônio Antimülleriano/sangue , Folículo Ovariano/citologia , Reserva Ovariana , Síndrome do Ovário Policístico/patologia , Testosterona/sangue , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Folículo Ovariano/metabolismo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/epidemiologia , Estudos RetrospectivosRESUMO
AIMS: To investigate the potential risk factors for haemorrhage during suction curettage after uterine artery embolization (UAE) in the treatment of caesarean scar pregnancy (CSP). METHODS: A case-control study was executed including 35 patients with CSP and haemorrhage during suction curettage after UAE and 140 controls without haemorrhage. The data collected included gestational age, the distance between the gestational mass and the bladder, and the volume of vaginal bleeding. RESULTS: Six patients with UAE needed blood transfusions and two had a hysterectomy, while no patient in the control group needed these interventions. Multivariate analysis showed that both gestational age and the distance between the gestational mass and the bladder were associated with haemorrhage in the CSP group. The odds ratio (OR) of gestational age between cases and controls was 1.579 (95% confidence interval [CI] 1.291-1.933), and the OR of the distance between the gestational mass and the bladder was 0.208 (95% CI 0.082-0.531). CONCLUSION: Increased gestational age might be an important risk factor for haemorrhage during suction curettage after UAE in the treatment of patients with CSP, and a distance of >0.2 cm between the gestational mass and the bladder was protective against haemorrhage.
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Cesárea/efeitos adversos , Cicatriz/complicações , Curetagem/efeitos adversos , Complicações na Gravidez/cirurgia , Embolização da Artéria Uterina/métodos , Adulto , Perda Sanguínea Cirúrgica , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Fatores de Risco , Sucção/efeitos adversosRESUMO
This was a single dose mass balance and metabolite characterization study of the antimalarial agent pyronaridine. Six healthy male adults were administered a single oral dose of 720 mg pyronaridine tetraphosphate with 800 nCi of radiolabeled (14)C-pyronaridine. Urine and feces were continuously collected through 168 h post-dose, with intermittent 48 h collection periods thereafter through 2064 h post-dose. Drug recovery was computed for analyzed samples and interpolated for intervening time periods in which collection did not occur. Blood samples were obtained to evaluate the pharmacokinetics of total radioactivity and of the parent compound. Total radioactivity in urine, feces, and blood samples was determined by accelerator mass spectrometry (AMS); parent concentrations in blood were determined with LC/MS. Metabolite identification based on blood, urine, and feces samples was conducted using a combination of LC + AMS for identifying radiopeaks, followed by LC/MS/MS for identity confirmation/elucidation. The mean cumulative drug recovery in the urine and feces was 23.7 and 47.8 %, respectively, with an average total recovery of 71.5 %. Total radioactivity was slowly eliminated from blood, with a mean half-life of 33.5 days, substantially longer than the mean parent compound half-life of 5.03 days. Total radioactivity remained detectable in urine and feces collected in the final sampling period, suggesting ongoing elimination. Nine primary and four secondary metabolites of pyronaridine were identified. This study revealed that pyronaridine and its metabolites are eliminated by both the urinary and fecal routes over an extended period of time, and that multiple, varied pathways characterize pyronaridine metabolism.
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Antimaláricos/farmacocinética , Naftiridinas/farmacocinética , Administração Oral , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/sangue , Antimaláricos/urina , Biotransformação , Cromatografia Líquida , Fezes/química , Meia-Vida , Voluntários Saudáveis , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Naftiridinas/administração & dosagem , Naftiridinas/sangue , Naftiridinas/urina , Suíça , Espectrometria de Massas em Tandem/métodosRESUMO
1. The metabolism, pharmacokinetics, excretion and tissue distribution of a hepatitis C NS3/NS4 protease inhibitor, faldaprevir, were studied in rats following a single 2 mg/kg intravenous or 10 mg/kg oral administration of [(14)C]-faldaprevir. 2. Following intravenous dosing, the terminal elimination t1/2 of plasma radioactivity was 1.75 h (males) and 1.74 h (females). Corresponding AUC0-∞, CL and Vss were 1920 and 1900 ngEq · h/mL, 18.3 and 17.7 mL/min/kg and 2.32 and 2.12 mL/kg for males and females, respectively. 3. After oral dosing, t1/2 and AUC0-∞ for plasma radioactivity were 1.67 and 1.77 h and 11 300 and 17 900 ngEq · h/mL for males and females, respectively. 4. In intact rats, ≥90.17% dose was recovered in feces and only ≤1.08% dose was recovered in urine for both iv and oral doses. In bile cannulated rats, 54.95, 34.32 and 0.27% dose was recovered in feces, bile and urine, respectively. 5. Glucuronidation plays a major role in the metabolism of faldaprevir with minimal Phase I metabolism. 6. Radioactivity was rapidly distributed into tissues after the oral dose with peak concentrations of radioactivity in most tissues at 6 h post-dose. The highest levels of radioactivity were observed in liver, lung, kidney, small intestine and adrenal gland.
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Oligopeptídeos/farmacocinética , Inibidores de Proteases/farmacocinética , Tiazóis/farmacocinética , Administração Oral , Ácidos Aminoisobutíricos , Animais , Bile , Biotransformação , Radioisótopos de Carbono/análise , Fezes , Feminino , Injeções Intravenosas , Leucina/análogos & derivados , Masculino , Prolina/análogos & derivados , Quinolinas , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , UrinaRESUMO
Diabetic foot ulcers (DFUs) pose a critical medical challenge, significantly im-pairing the quality of life of patients. Adipose-derived stem cells (ADSCs) have been identified as a promising therapeutic approach for improving wound healing in DFUs. Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU, its clinical applications remain elusive. In this review, we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs. The review begins with a discussion of the classification and clinical management of diabetic foot conditions. It then discusses the current landscape of clinical trials, focusing on their geographic distribution, reported efficacy, safety profiles, treatment timing, administration techniques, and dosing considerations. Finally, the review discusses the preclinical strategies to enhance ADSC efficacy. This review shows that many trials exhibit biases in study design, unclear inclusion criteria, and intervention protocols. In conclusion, this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches, with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.
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Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.
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Background: Armadillo repeat-containing 10 (ARMC10) is involved in the progression of multiple types of tumors. Pancreatic adenocarcinoma (PAAD) is a lethal disease with poor survival and prognosis. Methods: We acquired the data of ARMC10 in PAAD patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets and compared the expression level with normal pancreatic tissues. We evaluated the relevance between ARMC10 expression and clinicopathological factors, immune infiltration degree and prognosis in PAAD. Results: High expression of ARMC10 was relevant to T stage, M stage, pathologic stage, histologic grade, residual tumor, primary therapy outcome (P < 0.05) and related to lower Overall-Survival (OS), Disease-Specific Survival (DSS), and Progression-Free Interval (PFI). Gene set enrichment analysis showed that ARMC10 was related to methylation in neural precursor cells (NPC), G alpha (i) signaling events, APC targets, energy metabolism, potassium channels and IL10 synthesis. The expression level of ARMC10 was positively related to the abundance of T helper cells and negatively to that of plasmacytoid dendritic cells (pDCs). Knocking down of ARMC10 could lead to lower proliferation, invasion, migration ability and colony formation rate of PAAD cells in vitro. Conclusions: Our research firstly discovered ARMC10 as a novel prognostic biomarker for PAAD patients and played a crucial role in immune regulation in PAAD.
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PSI-352938 is a novel cyclic phosphate prodrug of ß-D-2'-deoxy-2'-α-fluoro-2'-ß-C-methylguanosine-5'-monophosphate with potent anti-HCV activity. In order to inhibit the NS5B RNA-dependent RNA polymerase, PSI-352938 must be metabolized to the active triphosphate form, PSI-352666. During in vitro incubations with PSI-352938, significantly larger amounts of PSI-352666 were formed in primary hepatocytes than in clone A hepatitis C virus (HCV) replicon cells. Metabolism and biochemical assays were performed to define the molecular mechanism of PSI-352938 activation. The first step, removal of the isopropyl group on the 3',5'-cyclic phosphate moiety, was found to be cytochrome P450 (CYP) 3A4 dependent, with other CYP isoforms unable to catalyze the reaction. The second step, opening of the cyclic phosphate ring, was catalyzed by phosphodiesterases (PDEs) 2A1, 5A, 9A, and 11A4, all known to be expressed in the liver. The role of these enzymes in the activation of PSI-352938 was confirmed in primary human hepatocytes, where prodrug activation was reduced by inhibitors of CYP3A4 and PDEs. The third step, removal of the O(6)-ethyl group on the nucleobase, was shown to be catalyzed by adenosine deaminase-like protein 1. The resulting monophosphate was consecutively phosphorylated to the diphosphate and to the triphosphate PSI-352666 by guanylate kinase 1 and nucleoside diphosphate kinase, respectively. In addition, formation of nucleoside metabolites was observed in primary hepatocytes, and ecto-5'-nucleotidase was able to dephosphorylate the monophosphate metabolites. Since CYP3A4 is highly expressed in the liver, the CYP3A4-dependent metabolism of PSI-352938 makes it an effective liver-targeted prodrug, in part accounting for the potent antiviral activity observed clinically.
Assuntos
Antivirais/metabolismo , Óxidos P-Cíclicos/metabolismo , Hepacivirus/efeitos dos fármacos , Nucleosídeos/metabolismo , Células Cultivadas , Citocromo P-450 CYP3A/metabolismo , Guanilato Quinases/metabolismo , Hepatócitos/metabolismo , Humanos , Núcleosídeo-Difosfato Quinase/metabolismo , Diester Fosfórico Hidrolases/metabolismoRESUMO
OBJECTIVE: To investigate the feasibility and safety of early dressing removal of clean wounds following thoracotomy. SUBJECTS AND METHODS: A total of 230 patients (127 males, mean age 55.6 ± 16.7 years) were randomly divided into study and control groups. In the study group the cotton gauze dressing was removed 48 h after the surgery, whereas in the control group the dressing was kept on for 7-8 days until the removal of skin sutures. The infection and healing of the wounds were examined, and patients were followed up for 30 days. RESULTS: There was no statistically significant difference in age, sex, smoking rates, concurrent illnesses and operational characteristics between the study and control groups (p > 0.05). The wound infection rate in the study and control groups was 6 (5.2%) and 7 patients (6.1%), respectively (p = 0.775). Two patients (1.7%) from the study group and 1 (0.9%, p = 0.561) from the control group had partial wound approximation by day 7. Surrounding skin integrity was normal in 106 (92.2%) of the study group and 107 (93.0%) of the control group patients by postoperative day 7 (p = 0.801). CONCLUSION: Removal of wound dressing 48 h after thoracic surgery was not associated with an increased risk of surgical site infection. Hence the early removal of wound dressing did not appear to have an adverse impact on wound healing.
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Bandagens , Toracotomia/métodos , Cicatrização , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/epidemiologia , Fatores de TempoRESUMO
Fibrosis is the hyperactivation of fibroblasts that results in excessive accumulation of extracellular matrix, which is involved in numerous pathological changes and diseases. Adipose-derived stem cells (ASCs) are promising seed cells for regenerative medicine due to their bountiful source, low immunogenicity and lack of ethical issues. Their anti-fibrosis, immunomodulation, angiogenesis and other therapeutic effects have made them suitable for treating fibrosis-related diseases. Here, we review the literature on ASCs treating fibrosis, elaborate and discuss their mechanisms of action, changes in disease environment, ways to enhance therapeutic effects, as well as current preclinical and clinical studies, in order to provide a general picture of ASCs treating fibrotic diseases.
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We report that an intrauterine contraceptive device (IUCD) embedded within intrauterine tumour (submucous myoma) in a postmenopausal woman was misdiagnosed, definitively diagnosed and successfully removed with hysteroscopic resection. Hysteroscopy and hysteroscopic resection of the submucous myoma with IUCD should be reserved as a minimally invasive, safe and reliable treatment method, and can avoid a laparotomy and hysterotomy. This is believed to be the first reported case of such an occurrence.
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Dispositivos Intrauterinos/efeitos adversos , Mioma/diagnóstico , Mioma/cirurgia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgia , Remoção de Dispositivo , Feminino , Humanos , Histeroscopia , Pessoa de Meia-IdadeRESUMO
Digestive tract cancer is one of the main diseases that endanger human health. At present, the early diagnosis of digestive tract tumors mainly depends on serology, imaging, endoscopy, and so on. Although tissue specimens are the gold standard for cancer diagnosis, with the rapid development of precision medicine in cancer, the demand for dynamic monitoring of tumor molecular characteristics has increased. Liquid biopsy involves the collection of body fluids via non-invasive approaches, and analyzes biological markers such as circulating tumor cells, circulating tumor DNA, circulating cell-free DNA, microRNAs, and exosomes. In recent years, liquid biopsy has become more and more important in the diagnosis and prognosis of cancer in clinical practice due to its convenience, non-invasiveness, high specificity and it overcomes temporal-spatial heterogeneity. Therefore, this review summarizes the current evidence on liquid biopsies in digestive tract cancers in relation to diagnosis and prognosis.
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The aim of the study is to investigate chemical constituents of the leaves of Pieris japonica. The isolation and purification of the constituents were performed by various chromatography and spectral analysis. Three new phenolic glucosides, erythro-syringoylglycerol 4-O-beta-D-glucoside (1), 1-(2-beta-D-glucopyranoxyl-4-methoxyl-6-hydroxyphenyl)-3-hydroxyl-l-propanone (3), erythro-l-(4-hydroxyl-3-methoxyphenyl)-2-[4-(3-beta-D-glucopyranoxypropyl)-2 ,6-dimethoxyphenoxy]-1, 3-propanediol (4), along with five known phenolic glucosides, syringoylglycerol 8-O-beta-D-glucoside (2), magnolenin C (5), syringaresinol mono-beta-D-glucoside (6), 3-(4-hydroxyl-3-methyphenyl)-1 -propanol-l-O-beta-D-glucoside (7) and 3, 5-dimethoxyl-4-hydroxybenzyl alcohol 4-O-beta-D-glucoside (8) were isolated and identified from the plant leaves. Compounds 1 and 2 inhibited significantly (P <0.01) the proliferation of murine T and B cells at concentration of 1 x 10(-6) mol L(-1), in vitro.
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Ericaceae/química , Glucosídeos/isolamento & purificação , Lignanas/isolamento & purificação , Glucosídeos/química , Imunossupressores/química , Imunossupressores/isolamento & purificação , Lignanas/química , Fenóis/química , Fenóis/isolamento & purificação , Folhas de Planta/química , Plantas Medicinais/químicaRESUMO
Twin pregnancies have a higher prevalence of intrahepatic cholestasis of pregnancy (ICP) than single pregnancies. It is unknown whether in vitro fertilization-embryo transfer (IVF-ET) influences the fetal outcomes in twin pregnancies complicated by ICP. This study aimed to explore the impact of IVF-ET on the perinatal outcomes of ICP in twin pregnancy. Clinical data from 142 twin pregnant women complicated with ICP were retrospectively analyzed, including 51 patients who conceived through IVF-ET (IVF group) and 91 patients with spontaneous conception (SC group). Several biochemical indicators and perinatal outcomes were analyzed. Compared to the SC group, the IVF group had a higher incidence of early-onset ICP (P = 0.015) and more frequent clinical symptoms (P = 0.020), including skin pruritus, skin scratch, and jaundice. Furthermore, the IVF group had higher rates of neonatal asphyxia (IVF vs. SC, 9.80% vs. 1.10%, P = 0.023) and premature delivery (IVF vs. SC, 96.08% vs. 83.52%, P = 0.027) compared to the SC group. The IVF-conceived twin pregnancy group had a higher risk of early-onset ICP and suffered from clinical symptoms and poor perinatal outcomes.
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Colestase Intra-Hepática/complicações , Transferência Embrionária , Fertilização in vitro , Gravidez de Gêmeos , Adulto , Transferência Embrionária/métodos , Feminino , Fertilização , Fertilização in vitro/métodos , Humanos , Gravidez , Complicações na Gravidez , Resultado da Gravidez , Estudos RetrospectivosRESUMO
Insufficient endometrial receptivity is a major factor leading to implantation failure (IF), and the traditional way of morphological observation of endometrium cannot determine the condition of receptivity sufficiently. Considering that long-noncoding RNAs (lncRNAs) regulate endometrial receptivity and competing endogenous RNA (ceRNA) mechanism works in plenty of biological processes, ceRNA is likely to function in the pathology of IF. In the present study, we aim to construct an implantation failure related lncRNA-mRNA network (IFLMN), and to identify the key lncRNAs as the candidates for predicting endometrial receptivity. The global background network was constructed based on the presumed lncRNA-miRNA and miRNA-mRNA pairs obtained from lncRNASNP and miRTarBase. Differentially expressed genes (DEGs) of IF were calculated using the data of GSE26787, and then re-annotated as differentially expressed mRNAs (DEMs) and lncRNAs (DELs). IFLMN was constructed by hypergeometric test, including 255 lncRNA-mRNA pairs, 10 lncRNAs, and 212 mRNAs. Topological analysis determined the key lncRNAs with the highest centroid. Functional enrichment analyses were performed by unsupervised clustering, GO classification, KEGG pathway, and co-expression module analyses, achieving six key lncRNAs and their ceRNA sub-networks, which were involved in immunological activity, growth factor binding, vascular proliferation, apoptosis, and steroid biosynthesis in uterus and prepared endometrium for embryo implantation. Sixteen endometrial samples were collected during mid-luteal phase, including 8 recurrent implantation failure (RIF) or recurrent miscarriage (RM) women and 8 controls who conceived successfully. Quantitative real-time PCR was performed to compare the expression of the above six lncRNAs, which validated that the expression of all these lncRNAs was significantly elevated in endometrium of RIF/RM patients. Further studies are needed to investigate the underlying mechanism, and the lncRNAs may be developed into predictive biomarkers for endometrial receptivity.
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Endométrio/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Biomarcadores/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/fisiologia , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The sulfonation of 17beta-estradiol (E2) by human liver and recombinant sulfotransferases is influenced by environmental contaminants such as hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs), which are potent inhibitors, and the therapeutic drug, celecoxib, which affects positional sulfonation of E2. In some locations, the aquatic environment is contaminated by PCBs, OH-PCBs and widely used therapeutic drugs. The objectives of this study were to investigate the sulfonation kinetics of E2 in liver cytosol from channel catfish (Ictalurus punctatus); to examine the effect of OH-PCBs on E2 sulfonation; and to determine if celecoxib altered the position of E2 sulfonation, as it does with human liver cytosol. E2 was converted to both 3- and 17-sulfates by catfish liver cytosol. At E2 concentrations below 1 microM, formation of E2-3-sulfate (E2-3-S) predominated, but substrate inhibition was observed at higher concentrations. Rates of E2-3-S formation at different E2 concentrations were fit to a substrate inhibition model, with K'm and V'max values of 0.40 +/- 0.10 microM and 91.0 +/- 4.7 pmol/min/mg protein, respectively and K(i) of 1.08 +/- 0.09 microM. The formation of E2-17-S fit Michaelis-Menten kinetics over the concentration range 25 nM to 2.5 microM, with K(m) and V(max) values of 1.07 +/- 0.23 microM and 25.7 +/- 4.43 pmol/min/mg protein, respectively. The efficiency (V(max)/K(m)) of formation of E2-3-S was 9.8-fold higher than that of E2-17-S. Several OH-PCBs inhibited E2 3-sulfonation, measured at an E2 concentration of 1 nM. Of those tested, the most potent inhibitor was 4'-OH-CB79, with two chlorine atoms flanking the OH group (IC(50): 94 nM). The inhibition of estrogen sulfonation by OH-PCBs may disrupt the endocrine system and thus contribute to the known toxic effects of these compounds. Celecoxib did not stimulate E2-17-S formation, as is the case with human liver cytosol, but did inhibit the formation of E2-3-S (IC(50): 44 microM) and to a lesser extent, E2-17-S (IC(50): > 160 microM), suggesting the previously found effect of celecoxib on E2-17-S formation may be specific to human SULT2A1.
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Estradiol/metabolismo , Ictaluridae/metabolismo , Bifenilos Policlorados/toxicidade , Pirazóis/toxicidade , Sulfonamidas/toxicidade , Sulfotransferases/efeitos dos fármacos , Animais , Celecoxib , Citosol/química , Inibidores Enzimáticos/toxicidade , Estradiol/análise , Feminino , Concentração Inibidora 50 , Cinética , Fígado/efeitos dos fármacos , Masculino , Bifenilos Policlorados/química , Pirazóis/química , Sulfonamidas/química , Sulfotransferases/antagonistas & inibidoresRESUMO
The sulfotransferase (SULT) family comprises important phase II conjugation enzymes for the detoxification of xenobiotics and modulation of the activity of physiologically important endobiotics such as thyroid hormones, steroids, and neurotransmitters. SULT enzymes catalyze the transfer of a sulfuryl group, donated by 3'-phosphoadenosine-5'-phosphosulfate (PAPS), to an acceptor substrate that may be a hydroxy group or an amine group in a process originally called sulfation, but more correctly referred to as sulfonation or sulfurylation. SULT activity may be inhibited when humans are exposed to certain xenobiotics including drugs (mefenamic acid, salicylic acid, clomiphene, danazol etc.), dietary chemicals (catechins, food colorants, flavonoids and phytoestrogens etc.), and environmental chemicals (hydroxylated polychlorinated biphenyls, hydroxylated polyhalogenated aromatic hydrocarbons, pentachlorophenol, triclosan and bisphenol A, etc.). Inhibition of individual SULT isoforms may cause adverse effects on human health. For example, hydroxylated polychlorinated biphenyls have been shown to interfere with the transport of thyroid hormones, inhibit estradiol sulfonation, and inhibit thyroid hormone sulfonation, thereby potentially disrupting the thyroid hormone system. Formation of sulfate conjugates of toxic xenobiotics usually decreases their toxicity, so inhibition of this pathway may lead to prolonged exposure to the compounds. Conversely, some sulfate conjugates are chemically reactive, inhibition of their formation may protect from toxicity. This manuscript will review the literature concerning the inhibition of SULTs by xenobiotics including isoform-selective effects, inhibition kinetics and health effects resulting from the inhibition.