Latent associations between low serum amylase and reduced plasma insulin levels and increased adiposity have been described previously in a small study of asymptomatic middle-aged humans. In the present study, we sought to determine the nature of such changes during the longitudinal progression from metabolically normal to overt type 2 diabetes mellitus (T2DM) in nonhuman primates (NHPs), a disease that appears to be the same in both pathophysiology and underlying mechanisms as that which most commonly develops in middle-aged adult humans. Amylase and lipase levels were characterized in 157 unrelated adult rhesus monkeys (Macaca mulatta); 38% developed T2DM while under study.
View Article and Find Full Text PDFClin Exp Pharmacol Physiol
June 2024
Metformin, a well-established anti-diabetic drug, is also used in managing various other metabolic disorders including polycystic ovarian syndrome (PCOS). There are evidences to show that metformin improves endometrial functions in PCOS women. However, fewer studies have explored the direct effects of metformin on endometrium.
View Article and Find Full Text PDFObjectives: Decreased serum creatinine levels are associated with increased risk of type 2 diabetes (T2DM) in humans, however, its association with muscle mass and insulin sensitivity have not been studied in NHPs.
Methods: Retrospective data of 229 adult NHPs were studied for association of serum creatinine levels with muscle mass and onset of T2DM.
Results: Serum creatinine levels were positively correlated with lean muscle mass in nondiabetic (non-DM), male and female NHPs.
Metformin, an antidiabetic drug, has recently been repositioned in the treatment of several nondiabetic disorders, including reproductive disorders such as polycystic ovarian syndrome, where it improves endometrial functions. In vitro studies employing supratherapeutic concentrations (5-20 mmol/L) of metformin have reported antiproliferative effects on endometrial epithelial and stromal cells. However, animal and human studies have revealed that therapeutic serum concentrations of metformin range between 20 and 70 µmol/L.
View Article and Find Full Text PDFSubstantial data posit estrogen receptors (ERs) as promising targets for prostate cancer (PCa) therapeutics. However, the trials on assessing the chemo-preventive or therapeutic potential of ER targeting drugs or selective estrogen receptor modulators (SERMs) have not yet established their clinical benefits. This could be ascribed to a possible modulation in the ER expression during PCa progression.
View Article and Find Full Text PDFObjectives: To understand the development of iron deficiency in obesity and its long-term impact on the profile of anemia in spontaneously obese nonhuman primates.
Methods: The study included 69 adult male nonhuman primates, (NHPs, Macaca mulatta, rhesus monkeys), ranging from normal to obese, and type 2 diabetes (T2D) as defined for humans.
Results: Iron deficiency was present in 31.
Recent data suggest that the DNA damage response (DDR) is altered in the eutopic endometrium (EE) of women with endometriosis and this probably ensues in response to higher DNA damage encountered by the EE in endometriosis. DDR operates in a tissue-specific manner and involves different pathways depending on the type of DNA lesions. Among these pathways, the non-homologous end joining (NHEJ) pathway plays a critical role in the repair of dsDNA breaks.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of fatalities globally since its origin in November 2019. The SARS-CoV-2 shares 79 and 50 per cent genome similarity with its predecessors, severe SARS-CoV and Middle East respiratory syndrome (MERS) coronavirus, all belonging to the same genus, Betacoronavirus. This relatively new virus has stymied the effective control of COVID-19 pandemic and caused huge social and economic impact worldwide.
View Article and Find Full Text PDFStudy Question: Is the DNA damage response (DDR) dysregulated in the eutopic endometrium of women with endometriosis?
Summary Answer: Endometrial expression of genes involved in DDR is modulated in women with endometriosis, compared to those without the disease.
What Is Known Already: Ectopic endometriotic lesions are reported to harbour somatic mutations, thereby hinting at dysregulation of DDR and DNA repair pathways. However, it remains inconclusive whether the eutopic endometrium also manifests dysregulated DDR in endometriosis.
Endometriosis is a common disorder of unknown etiology, and non-surgical therapies are still a challenge. To understand the pathogenesis and preclinical testing of drugs for endometriosis, animal models are highly desirous. Herein, we carried out longitudinal characterization of a mouse model for endometriosis where uterine tissue was transplanted onto the intestinal mesentery.
View Article and Find Full Text PDFHuman endometrial epithelium (EE) is composed of a multitude of proteins, amongst which those localized on the plasma membrane [plasma membrane proteins (PMPs)] are of critical relevance in the early stages of implantation. Evidence supports the key role of few PMPs in implantation. However, many remain unidentified, as efforts have not been made till date to generate the plasma membrane proteome of human EE cells, using a gel-free approach.
View Article and Find Full Text PDFThe plasma membrane (PM) is considered as a major druggable site. More than 50% of the existing drugs target PM proteins. In the wake of emerging data indicating a key role of estrogens in prostate cancer (PCa) pathogenesis, the study was undertaken to explore whether the estrogen binding sites exist on the PM and if such sites are functionally relevant in PCa.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
April 2019
Aging is a key contributor for subclinical progression of late-onset lung diseases. Basal, club, and type II alveolar epithelial cells (AECs) are lung epithelial progenitors whose capacities of differentiation are extensively studied. The timely transition of these cells in response to environmental changes helps maintain the intricate organization of lung structure.
View Article and Find Full Text PDFTelomerase activation is one of the key mechanisms that allow cells to bypass replicative senescence. Telomerase activity is primarily regulated at the level of transcription of its catalytic unit- hTERT. Prostate cancer (PCa), akin to other cancers, is characterized by high telomerase activity.
View Article and Find Full Text PDFUltrasound is a powerful, low-cost, non-invasive medical tool used by laboratory animal veterinarians for diagnostic imaging. Sonohysterography and transvaginal ultrasound are frequently used to assess uterine anomalies in women presenting with abnormal uterine bleeding (AUB). In the present study, we have evaluated the abdominal ultrasound of bonnet monkeys ( n = 8) showing spontaneous ovulatory ( n = 5) and anovulatory ( n = 3) AUB.
View Article and Find Full Text PDFProblem: Endometrium, the innermost mucosal layer of the uterus, serves as a lodge for the embryo in eutherian mammals. The endometrium is constituted of various cell types, and each cell type executes specific functions to facilitate embryo implantation and development. It is well established that the endometrium, despite being non-permissive to the embryo for the major period of a menstrual cycle, is irreplaceable in the scheme of events essential for procreation.
View Article and Find Full Text PDFWe report embryo-induced alterations occurring in endometrial stromal cells (ESCs) during the embryo-attachment stage in bonnet monkeys (Macaca radiata). Laser micro-dissected ESCs obtained from pregnant and non-pregnant animals were compared for levels of selected proliferation and decidualization-associated factors by analysis with quantitative real-time polymerase chain reaction or immunohistochemistry. Stromal cells exhibited extensive cellular proliferation, as indicated by cellular compaction and significantly higher (P < 0.
View Article and Find Full Text PDFAdhesiveness of the endometrial epithelium to an embryo plays a critical role in the initiation of pregnancy. Loss or gain of adhesiveness also dictates the potential of endometrial epithelial cells to metastasize, an event that can result from certain genetic insults. A proteomics-based exploration of the "adhesiveness" these epithelial cells was employed that could identify targets that could disrupt embryo-endometrium interactions and/or metastasis of endometrial cancer cells.
View Article and Find Full Text PDFWe undertook the present study to investigate the echographic characteristics of the uterus and cervix of female bonnet monkeys ( Macaca radiata ) during the proliferative and secretory phases of the menstrual cycle. The cervix was tortuous in shape and measured 2.74 ± 0.
View Article and Find Full Text PDFThe present investigation reports embryo-induced modifications in the epithelial cells of the endometrium in a primate species. In vivo, epithelial cell response to the embryonic signals was assessed at the embryo attachment stage in the gestational uterus of bonnet monkeys (Macaca radiata) and in vitro response was investigated by treating human endometrial epithelial cell line (Ishikawa) with human embryo conditioned media (CM). Endometrial epithelial (EE) cells at the embryo attachment stage in bonnet monkeys revealed higher proliferation accompanied by significant up regulation (p < 0.
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