Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Search for other papers by Sonu Khanka in
Google Scholar
PubMed
Search for other papers by Charul Somani in
Google Scholar
PubMed
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Search for other papers by Kriti Sharma in
Google Scholar
PubMed
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Search for other papers by Shivani Sharma in
Google Scholar
PubMed
Sophisticated Analytical Instrument Facility & Research, Division, CSIR-Central Drug Research Institute, Lucknow, India
Search for other papers by Akhilesh Kumar in
Google Scholar
PubMed
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Search for other papers by Naibedya Chattopadhyay in
Google Scholar
PubMed
Sophisticated Analytical Instrument Facility & Research, Division, CSIR-Central Drug Research Institute, Lucknow, India
Search for other papers by Sanjeev K Kanojiya in
Google Scholar
PubMed
Search for other papers by Dinesh Kumar Yadav in
Google Scholar
PubMed
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Search for other papers by Divya Singh in
Google Scholar
PubMed
Estrogen deficiency is one of the main causes for postmenopausal osteoporosis. Current osteoporotic therapies are of high cost and associated with serious side effects. So there is an urgent need for cost-effective anti-osteoporotic agents. Anti-osteoporotic activity of Litsea glutinosa extract (LGE) is less explored. Moreover, its role in fracture healing and mechanism of action is still unknown. In the present study we explore the osteoprotective potential of LGE in osteoblast cells and fractured and ovariectomized (Ovx) mice models. Alkaline phosphatase (ALP), MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and mineralization assays revealed that LGE treatment increased osteoblast cell differentiation, viability and mineralization. LGE treatment at 0.01 μg increased the expression of BMP2, PSMAD, RUNX2 and type 1 col. LGE also mitigated RANKL-induced osteoclastogenesis. Next, drill hole injury Balb/C mice model was treated with LGE for 12 days. Micro-CT analysis and Calcein labeling at the fracture site showed that LGE (20 mg/kg) enhanced new bone formation and bone regeneration, also increased expression of BMP2/SMAD1 signaling genes at fracture site. Ovx mice were treated with LGE for 1 month. μCT analysis indicated that the treatment of LGE at 20 mg/kg dose prevented the alteration in bone microarchitecture and maintained bone mineral density and bone mineral content. Treatment also increased bone strength and restored the bone turnover markers. Furthermore, in bone samples, LGE increased osteogenesis by enhancing the expression of BMP2/SMAD1 signaling components and decreased osteoclast number and surface. We conclude that LGE promotes osteogenesis via modulating the BMP2/SMAD1 signaling pathway. The study advocates the therapeutic potential of LGE in osteoporosis treatment.
Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan Hubei Province, PR China
Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan Hubei Province, PR China
Department of Gynaecology and Obstetrics, Sinopharm Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei Province, PR China
Search for other papers by Yaxiong Huang in
Google Scholar
PubMed
Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan Hubei Province, PR China
Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan Hubei Province, PR China
Search for other papers by Zihan Wang in
Google Scholar
PubMed
Search for other papers by Bin Li in
Google Scholar
PubMed
Search for other papers by Lina Ke in
Google Scholar
PubMed
Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan Hubei Province, PR China
Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan Hubei Province, PR China
Search for other papers by Yao Xiong in
Google Scholar
PubMed
Hubei Clinical Research Center for Prenatal Diagnosis and Birth Health, Wuhan Hubei Province, PR China
Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan Hubei Province, PR China
Search for other papers by Yuanzhen Zhang in
Google Scholar
PubMed
The impaired endometrial receptivity is a major factor contributing to infertility in patients with endometriosis (EM), but the underlying mechanism remains unclear. Our study aimed to investigate the role of Kruppel-like factor 15 (KLF15) in endometrial receptivity and its regulation in EM. We observed a significant decrease in KLF15 expression in the mid-secretory epithelial endometrial cells of EM patients compared to normal females without EM. To confirm the role of KLF15 in endometrial receptivity, we found a significantly reduced KLF15 expression and a significant decrease in embryo implantation number in the rat model via uterine horn infection with siRNA. This highlights the importance of KLF15 as a regulator receptivity. Furthermore, through ChIP-qPCR, we discovered that the progesterone receptor (PR) directly binds to KLF15 promoter regions, indicating that progesterone resistance may mediate the decrease in KLF15 expression in EM patients. Additionally, we found that the mid-secretory endometrium of EM patients exhibited impaired epithelial–mesenchymal transition (EMT). Knockdown of KLF15 upregulated E-cadherin and downregulated vimentin expression, leading to inhibited invasiveness and migration of Ishikawa cells. Overexpression KLF15 promotes EMT, invasiveness, and migration ability, and increases the attachment rate of JAR cells to Ishikawa cells. Through RNA-seq analysis, we identified TWIST2 as a downstream gene of KLF15. We confirmed that KLF15 directly binds to the promoter region of TWIST2 via ChIP-qPCR, promoting epithelial cell EMT during the establishment of endometrial receptivity. Our study reveals the involvement of KLF15 in the regulation of endometrial receptivity and its downstream effects on EMT. These findings provide valuable insights into potential therapeutic approaches for treating non-receptive endometrium in patients with EM.
Search for other papers by Qin Yin in
Google Scholar
PubMed
Search for other papers by Jun Gu in
Google Scholar
PubMed
Search for other papers by Pengju Ren in
Google Scholar
PubMed
Search for other papers by Zhiqiang Guan in
Google Scholar
PubMed
Department of Orthopedics, Northern Jiangsu People’s Hospital, Yangzhou, China
Search for other papers by Yongxiang Wang in
Google Scholar
PubMed
Search for other papers by Ruijun Bai in
Google Scholar
PubMed
Search for other papers by Yu Liu in
Google Scholar
PubMed
The role of this study was to evaluate the impact of gut microbiota depletion on the progression of osteoarthritis (OA) and osteoporosis (OP). We conducted an experimental mouse model of OA and OP over an 8-week period. The model involved destabilization of the medial meniscus and bilateral ovariectomy (OVX). To deplete the gut microbiota, we administered a course of antibiotics for 8 weeks. The severity of OA was assessed through micro-CT scanning, X-rays, and immunohistochemical staining. Microbiome analysis was performed using PCR of 16S DNA on fecal samples, and the levels of serum lipopolysaccharide, interleukin 6, tumor necrosis factor-α (TNF-α), osteocalcin, and estrogen were measured using enzyme-linked immunosorbent assay. We found that in comparison to the OVX+OA group, the OVX+OA+ABT group exhibited increased bone mineral density (P < 0.0001), bone volume fraction (P = 0.0051), and trabecular number (P = 0.0023) in the metaphyseal bone. Additionally, cartilage injury and levels of matrix metalloproteinase 13 were reduced in the OVX+OA+ABT group compared to the OVX+OA group. Moreover, the OVX+OA+ABT group demonstrated decreased relative abundance of Bacteroidetes, serum lipopolysaccharide (P = 0.0005), TNF-α (P < 0.0001), CTX-1 (P = 0.0002), and increased expression of bone formation markers. These findings were further supported by correlation network analyses. Depletion of gut microbiota was shown to protect against bone loss and cartilage degradation by modulating the composition of the gut microbiota in osteoporosis and osteoarthritis.
Search for other papers by Thomas Willmott in
Google Scholar
PubMed
Search for other papers by Elizabeth C Cottrell in
Google Scholar
PubMed
During pregnancy, all major physiological systems undergo remarkable changes, driven largely by alterations in the maternal hormonal milieu. In healthy pregnancies, maternal cardiovascular and metabolic adaptation to pregnancy occurs to support fetal growth and maternal well-being. Impaired maternal adaptation to pregnancy is associated with a range of pregnancy complications, including gestational diabetes and preeclampsia. There is growing recognition of the importance of different maternal microbiota, including in the gut, vagina and oral cavity, in supporting normal maternal adaptations to pregnancy as well as evidence for microbial disturbances associating with pregnancy pathologies. Here, we aim to summarise emerging evidence demonstrating that differences in maternal microbiota associate with pregnancy outcomes and discuss potential therapeutic approaches under development that might restore an ‘optimal’ microbiome. In particular, we highlight recent work by ourselves and others exploring the role of the oral microbiome in pregnancy, given established links between poor oral health (e.g. periodontitis) and adverse pregnancy outcomes. Our research has focussed on specific nitrate-reducing oral bacteria which play a role in the generation of nitric oxide (NO) and other bioactive nitrogen oxides associated with cardiovascular health and maternal cardiovascular adaption to pregnancy. Ongoing research aims to define whether altered microbial profiles have clinical utility in the prediction of pregnancy pathologies, and whether interventions designed to optimise specific maternal microbiota could help prevent future complications.
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
Search for other papers by Ana Fernanda Castillo in
Google Scholar
PubMed
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
Search for other papers by Cecilia Poderoso in
Google Scholar
PubMed
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
Search for other papers by Paula Mariana Maloberti in
Google Scholar
PubMed
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
Search for other papers by Fabiana Cornejo Maciel in
Google Scholar
PubMed
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
Search for other papers by María Mercedes Mori Sequeiros Garcia in
Google Scholar
PubMed
Search for other papers by Ulises Daniel Orlando in
Google Scholar
PubMed
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
Search for other papers by Pablo Mele in
Google Scholar
PubMed
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
Search for other papers by Yanina Benzo in
Google Scholar
PubMed
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
Search for other papers by Melina Andrea Dattilo in
Google Scholar
PubMed
Search for other papers by Jesica Prada in
Google Scholar
PubMed
Search for other papers by Luciano Quevedo in
Google Scholar
PubMed
Search for other papers by Matías Belluno in
Google Scholar
PubMed
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
Search for other papers by Cristina Paz in
Google Scholar
PubMed
CONICET – Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas (INBIOMED), Buenos Aires, Argentina
Search for other papers by Ernesto Jorge Podesta in
Google Scholar
PubMed
For many years, research in the field of steroid synthesis has aimed to understand the regulation of the rate-limiting step of steroid synthesis, i.e. the transport of cholesterol from the outer to the inner mitochondrial membrane, and identify the protein involved in the conversion of cholesterol into pregnenolone. The extraordinary work by B Clark, J Wells, S R King, and D M Stocco eventually identified this protein and named it steroidogenic acute regulatory protein (StAR). The group’s finding was also one of the milestones in understanding the mechanism of nonvesicular lipid transport between organelles. A notable feature of StAR is its high degree of phosphorylation. In fact, StAR phosphorylation in the acute phase is required for full steroid biosynthesis. As a contribution to this subject, our work has led to the characterization of StAR as a substrate of kinases and phosphatases and as an integral part of a mitochondrion-associated multiprotein complex, essential for StAR function and cholesterol binding and mitochondrial transport to yield maximum steroid production. Results allow us to postulate the existence of a specific cellular microenvironment where StAR protein synthesis and activation, along with steroid synthesis and secretion, are performed in a compartmentalized manner, at the site of hormone receptor stimulation, and involving the compartmentalized formation of the steroid molecule-synthesizing complex.
Endocrinology, SBMS, Faculty of Medicine, The University of Queensland, St Lucia, Qld, Australia
Search for other papers by Jianmei Yang in
Google Scholar
PubMed
Search for other papers by Chen Chen in
Google Scholar
PubMed
Polycystic ovary syndrome (PCOS) is a common endocrinopathy occurring in reproductive-age women. Hyperandrogenism, polycystic ovaries, chronic anovulation, and metabolic aberrations are the common features in PCOS. Hormonal changes are causing pathological symptoms in women with PCOS. The various hormone alterations in PCOS have been demonstrated. Hormones, such as insulin, growth hormones (GH), ghrelin, LEAP-2, gonadotropin-releasing hormone (GnRH), insulin, the luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, androgens, and estrogens, are all abnormal in PCOS women. These hormones are related to metabolic disorders, such as diabetes and insulin resistance, overweight and obesity, infertility, and disturbed menstrual cycle in PCOS patients. The pathological changes of these hormones, such as increased insulin, reduced GH, increased ghrelin, and leptin resistance, result in an increased prevalence of diabetes and obesity in PCOS women. A reduced GH, increased LEAP-2 levels, high LH basal, increased LH/FSH ratio, high androgens, and low estrogen are demonstrated in PCOS and linked to infertility. This narrative review aims to clarify the changes of hormone profiles, such as insulin, GH, LH, FSH, androgens, estrogen, progesterone, ghrelin, LEAP-2, asprosin, and subfatin, in PCOS, which may reveal novel targets for better diagnosis and treatment of PCOS.
Search for other papers by Christine A Beamish in
Google Scholar
PubMed
Search for other papers by Yoon K Lee in
Google Scholar
PubMed
Search for other papers by A Osama Gaber in
Google Scholar
PubMed
Search for other papers by Priyanka Chanana in
Google Scholar
PubMed
Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, Texas, USA
Search for other papers by Edward A Graviss in
Google Scholar
PubMed
Department of Cell and Microbiology, Weill Cornell Medical College, New York, New York, USA
Department of Genetics, The University of Texas Anderson Cancer Center, Houston, Texas, USA
Search for other papers by Malgorzata Kloc in
Google Scholar
PubMed
Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, Texas, USA
Search for other papers by M Waleed Gaber in
Google Scholar
PubMed
Search for other papers by Willa A Hsueh in
Google Scholar
PubMed
Department of Cell and Microbiology, Weill Cornell Medical College, New York, New York, USA
Search for other papers by Omaima M Sabek in
Google Scholar
PubMed
Metabolic syndrome (MetS) is an increasing global health threat and strong risk factor for type 2 diabetes (T2D). MetS causes both hyperinsulinemia and islet size overexpansion, and pancreatic β-cell failure impacts insulin and proinsulin secretion, mitochondrial density, and cellular identity loss. The low-density lipoprotein receptor knockout (LDLr −/−) model combined with high-fat diet (HFD) has been used to study alterations in multiple organs, but little is known about the changes to β-cell identity resulting from MetS. Osteocalcin (OC), an insulin-sensitizing protein secreted by bone, shows promising impact on β-cell identity and function. LDLr −/− mice at 12 months were fed chow or HFD for 3 months ± 4.5 ng/h OC. Islets were examined by immunofluorescence for alterations in nuclear Nkx6.1 and PDX1 presence, insulin–glucagon colocalization, islet size and %β-cell and islet area by insulin and synaptophysin, and mitochondria fluorescence intensity by Tomm20. Bone mineral density (BMD) and %fat changes were examined by Piximus Dexa scanning. HFD-fed mice showed fasting hyperglycemia by 15 months, increased weight gain, %fat, and fasting serum insulin and proinsulin; concurrent OC treatment mitigated weight increase and showed lower proinsulin-to-insulin ratio, and higher BMD. HFD increased %β and %islet area, while simultaneous OC-treatment with HFD was comparable to chow-fed mice. Significant reductions in nuclear PDX1 and Nkx6.1 expression, increased insulin–glucagon colocalization, and reduction in β-cell mitochondria fluorescence intensity were noted with HFD, but largely prevented with OC administration. OC supplementation here suggests a benefit to β-cell identity in LDLr −/− mice and offers intriguing clinical implications for countering metabolic syndrome.
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
Search for other papers by Manuel Gado in
Google Scholar
PubMed
Search for other papers by Eva Tsaousidou in
Google Scholar
PubMed
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
Diabetes and Nutritional Sciences, King's College London, London, UK
Search for other papers by Stefan R Bornstein in
Google Scholar
PubMed
Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
Search for other papers by Nikolaos Perakakis in
Google Scholar
PubMed
Sexual dimorphism in energy metabolism is now established and suggested to affect many aspects of metabolic diseases and in particular diabetes and obesity. This is strongly related to sex-based differences in whole-body insulin resistance. Women are more insulin sensitive compared to men, but this metabolic advantage gradually disappears after menopause or when insulin resistance progresses to hyperglycemia and diabetes. In this narrative review, first, we describe the pathophysiology related to insulin resistance and then we present the epidemiological evidence as well as the important biological factors that play a crucial role in sexual dimorphism in insulin sensitivity. We focus particularly on the differences in body fat and muscle mass distribution and function, in inflammation and in sex hormones between males and females. Most importantly, we describe the significant mechanistic differences in insulin sensitivity as well as glucose and lipid metabolism in key metabolic organs: liver, white adipose tissue, and skeletal muscle. Finally, we present the sex-based differences in response to different interventions and discuss important open research questions.
Search for other papers by Matthew W S Lim in
Google Scholar
PubMed
Department of Paediatric Endocrinology, Royal Hospital for Children, Glasgow, UK
Search for other papers by Angela K Lucas-Herald in
Google Scholar
PubMed
Search for other papers by Avril Mason in
Google Scholar
PubMed
Search for other papers by Christian Delles in
Google Scholar
PubMed
Search for other papers by Paul J Connelly in
Google Scholar
PubMed
The integral role of the hypothalamic–pituitary–gonadal axis in reproductive processes makes it a prime therapeutic target. By inhibiting sex steroid synthesis, gonadotropin-releasing hormone (GnRH) analogues are used in the management of cancers, benign neoplasms, infertility and gender dysphoria. However, the wide application of these therapeutics raises concerns regarding the unintended effects upon the cardiovascular system. In males with prostate cancer, GnRH analogues when used as an androgen deprivation therapy appear to increase the risk of cardiovascular disease, which is the leading cause of death in this population. Therefore, due to the utilisation of GnRH analogues across the lifespan and gender spectrum, this relationship merits discussion. Existing data suggest an association between GnRH analogues and major adverse cardiovascular events in males. Conversely, females receiving GnRH analogues for breast cancer treatment appear to be at an increased risk of developing hypertension. In this narrative review, we describe the uses of GnRH analogues in adults, adolescents and children. We discuss whether sex plays a role in the cardiovascular effects of GnRH analogues and explore the significance of sex hormone receptors in the vasculature. We also consider confounding factors such as malignancy, advanced age and infertility.
Search for other papers by Zhongqin Gong in
Google Scholar
PubMed
Search for other papers by Minghui Wei in
Google Scholar
PubMed
Search for other papers by Alexander C Vlantis in
Google Scholar
PubMed
Search for other papers by Jason Y K Chan in
Google Scholar
PubMed
Search for other papers by C Andrew Van Hasselt in
Google Scholar
PubMed
Search for other papers by Dongcai Li in
Google Scholar
PubMed
Search for other papers by Xianhai Zeng in
Google Scholar
PubMed
Search for other papers by Lingbin Xue in
Google Scholar
PubMed
Search for other papers by Michael C F Tong in
Google Scholar
PubMed
Search for other papers by George G Chen in
Google Scholar
PubMed
The solute carrier (SLC) family is a large group of membrane transport proteins. Their dysfunction plays an important role in the pathogenesis of thyroid cancer. The most well-known SLC is the sodium-iodide symporter (NIS), also known as sodium/iodide co-transporter or solute carrier family 5 member 5 (SLC5A5) in thyroid cancer. The dysregulation of NIS in thyroid cancer is well documented. The role of NIS in the uptake of iodide is critical in the treatment of thyroid cancer, radioactive iodide (RAI) therapy in particular. In addition to NIS, other SLC members may affect the autophagy, proliferation, and apoptosis of thyroid cancer cells, indicating that an alteration in SLC members may affect different cellular events in the evolution of thyroid cancer. The expression of the SLC members may impact the uptake of chemicals by the thyroid, suggesting that targeting SLC members may be a promising therapeutic strategy in thyroid cancer.
