Saidur Rahman

Endometriosis is an estrogen-dependent inflammatory disorder frequently associated with infertility and characterized by progesterone resistance and impaired endometrial receptivity. While ectopic lesions define the disease, accumulating evidence indicates that molecular abnormalities within the eutopic endometrium substantially contribute to infertility. In this study, we performed transcriptomic analysis of proliferative-phase eutopic endometrium from women with and without endometriosis and identified 44 dysregulated genes, including 13 upregulated and 31 downregulated genes, in women with endometriosis compared with controls. Among the significantly altered genes, YWHAZ (14-3-3 zeta) emerged as a prominently downregulated gene. Reduced YWHAZ expression was further validated at the protein level in both epithelial and stromal compartments of the endometrium from women with endometriosis. To investigate its physiological regulation, we examined YWHAZ expression during early pregnancy in mice and observed a dynamic, stage-specific pattern during the peri-implantation period, with strong expression at gestational days 3.5 and 4.5 and robust expression at the primary decidual zone at gestational day 5.5. Notably, YWHAZ expression was nearly abolished in uteri from progesterone receptor knockout and uterine signal transducer and activator of transcription 3 conditional knockout (Pgrcre/+Stat3f/f) mice, indicating that YWHAZ is dependent on intact progesterone receptor and STAT3 signaling. Together, these findings identify YWHAZ as a hormonally and transcriptionally regulated endometrial factor that is disrupted in endometriosis and tightly linked to implantation and decidual progression. This study highlights YWHAZ as a potential molecular node connecting progesterone resistance and STAT3 dysregulation to defective endometrial function and infertility in endometriosis.

Ovarian steroid hormones—estrogen and progesterone—play a central role in regulating epithelial‐stromal interactions in the uterus. These interactions are critical for uterine function, including endometrial receptivity, implantation, and decidualization. These interactions involve complex signaling crosstalk between the uterine epithelium and the underlying stroma, with dynamic cell population‐specific roles. Mitogen‐inducible gene 6 (MIG‐6) is a key mediator of progesterone signaling in the endometrium, and loss of MIG‐6 results in implantation failure due to a non‐receptive endometrium. To investigate whether MIG‐6 deficiency disrupts the complex and dynamic cell population‐specific roles of uterine cells, we performed single‐cell RNA sequencing to characterize the cellular composition and functional alterations in the non‐receptive endometrium of uterine‐specific Mig‐6 knockout ( Pgr ^cre/+ Mig‐6 ^f/f ; Mig‐6 ^d/d ) mice. Compared to control mice, Mig‐6 ^d/d mice exhibited distinct gene expression patterns in both endometrial epithelial and stromal cells. We identified dysregulation of Egr1 in the non‐receptive endometrium along with attenuated expression of Foxa2 and Cyp26A1 in epithelial cells of Mig‐6 ^d/d mice. Notably, LRP2 expression was diminished in epithelial cells of both Mig‐6 ^d/d mice and infertile women with endometriosis. These findings demonstrate that MIG‐6 is a critical progesterone receptor (PGR) mediator that maintains endometrial epithelial and stromal cell function essential to uterine receptivity. Our study advances the understanding of the molecular pathways underlying endometrial receptivity and provides a foundation for therapeutic strategies to improve pregnancy outcomes.

Endometriosis, characterized by the growth of uterine‐like tissue outside the uterus, causes chronic pain and infertility. Current diagnostic and therapeutic strategies have notable limitations, including delayed diagnosis and adverse effects. The transcription factor forkhead box A2 (FOXA2), which is exclusively expressed in the uterine glandular epithelium, regulates key genes involved in endometrial proliferation, differentiation, fertility, and hormone response. While FOXA2 expression is reduced in the endometrial tissue of women with endometriosis, its pathophysiological role in the disease is not well understood. In this study, we report that endometriosis significantly reduced FOXA2 expression in the eutopic endometrium of mice with endometriosis compared to sham controls, accompanied by decreased expression of its downstream gene, CXCL15. To evaluate the effect of FOXA2 loss in endometriosis, we surgically induced endometriosis by transplanting control Rosa26 ^mTmG/+ or Pgr ^cre/+ Foxa2 ^f/f Rosa26 ^mTmG/+ ( Foxa2 ^d/d Rosa26 ^mTmG/+ ) endometrial tissue into the peritoneal cavity of mice. The number and weight of ectopic lesions were significantly increased in the mice with Foxa2 ^d/d Rosa26 ^mTmG/+ ectopic lesions compared to controls. Furthermore, progesterone receptor expression was significantly reduced in the endometrial epithelium from mice with Foxa2 ^d/d Rosa26 ^mTmG/+ ectopic lesions compared to mice with control ectopic lesions. Importantly, treatment with leukemia inhibitory factor (LIF), a cytokine regulated by FOXA2, significantly reduced ectopic lesion formation in Foxa2 ^d/d Rosa26 ^mTmG/+ endometriosis mice compared to vehicle‐treated mice. This study demonstrates that FOXA2 loss results in an increase in endometriosis incidence and that treatment with LIF offers a novel promising therapeutic approach for endometriosis.

Endometriosis is a prevalent gynecological condition associated with pelvic pain and infertility. Despite more than a century of research, the etiology of endometriosis still eludes scientific consensus. This lack of clarity has resulted in suboptimal prevention, diagnosis, and treatment options. Evidence of genetic contributors to endometriosis is interesting but limited; however, significant progress has been made in recent years in identifying an epigenetic role in the pathogenesis of endometriosis through clinical studies, in vitro cell culture experiments, and in vivo animal models. The predominant findings include endometriosis-related differential expression of DNA methyltransferases and demethylases, histone deacetylases, methyltransferases, and demethylases, and regulators of chromatin architecture. There is also an emerging role for miRNAs in controlling epigenetic regulators in the endometrium and endometriosis. Changes in these epigenetic regulators result in differential chromatin organization and DNA methylation, with consequences for gene expression independent of a genetic sequence. Epigenetically altered expression of genes related to steroid hormone production and signaling, immune regulation, and endometrial cell identity and function have all been identified and appear to play into the pathophysiological mechanisms of endometriosis and resulting infertility. This review summarizes and critically discusses early seminal findings, the ever-growing recent evidence of epigenetic contributions to the pathophysiology of endometriosis, and implications for proposed epigenetically targeted therapeutics.

Tidal energy offers a great commitment to bulk power generation without drastically harming the environment by emitting GHG or depleting fossil fuels like conventional methods. This form of energy has an enormous prospect in electrical energy generation as well as the economic development of a region. The electricity crisis is a common scene in the coastal region of Bangladesh and the construction of a dam at Kutubdia channel can make the maximum use of tidal energy available to mitigate the crisis. This paper presents an energy generation scheme and financial analysis for constructing a hydroelectricity project at the Kutubdia channel. A channel of 15.32 km in length and 2.7 km in width surrounding an area of 41.364 km ² has been selected for harnessing energy from the sea tide. A probability density function (PDF) has been developed to get the proper idea about the range of monthly tidal heads available and usable energy that can be generated yearly from the proposed project. The amount of energy generation yearly by the proposed scheme tends to be 0.20% of the total generation of BPDB (2020-2021). The financial viability analysis is also performed in this paper.

Recent evidence suggests that autophagy is a governed catabolic framework enabling the recycling of nutrients from injured organelles and other cellular constituents via a lysosomal breakdown. This mechanism has been associated with the development of various pathologic conditions, including cancer and neurological disorders; however, recently updated studies have indicated that autophagy plays a dual role in cancer, acting as a cytoprotective or cytotoxic mechanism. Numerous preclinical and clinical investigations have shown that inhibiting autophagy enhances an anticancer medicine’s effectiveness in various malignancies. Autophagy antagonists, including chloroquine and hydroxychloroquine, have previously been authorized in clinical trials, encouraging the development of medication-combination therapies targeting the autophagic processes for cancer. In this review, we provide an update on the recent research examining the anticancer efficacy of combining drugs that activate cytoprotective autophagy with autophagy inhibitors. Additionally, we highlight the difficulties and progress toward using cytoprotective autophagy targeting as a cancer treatment strategy. Importantly, we must enable the use of suitable autophagy inhibitors and coadministration delivery systems in conjunction with anticancer agents. Therefore, this review briefly summarizes the general molecular process behind autophagy and its bifunctional role that is important in cancer suppression and in encouraging tumor growth and resistance to chemotherapy and metastasis regulation. We then emphasize how autophagy and cancer cells interacting with one another is a promising therapeutic target in cancer treatment.

Autophagy is an evolutionarily conserved cellular system crucial for cellular homeostasis that protects cells from a broad range of internal and extracellular stresses. Autophagy decreases metabolic load and toxicity by removing damaged cellular components. Environmental contaminants, particularly industrial substances, can influence autophagic flux by enhancing it as a protective response, preventing it, or converting its protective function into a pro-cell death mechanism. Environmental toxic materials are also notorious for their tendency to bioaccumulate and induce pathophysiological vulnerability. Many environmental pollutants have been found to influence stress which increases autophagy. Increasing autophagy was recently shown to improve stress resistance and reduce genetic damage. Moreover, suppressing autophagy or depleting its resources either increases or decreases toxicity, depending on the circumstances. The essential process of selective autophagy is utilized by mammalian cells in order to eliminate particulate matter, nanoparticles, toxic metals, and smoke exposure without inflicting damage on cytosolic components. Moreover, cigarette smoke and aging are the chief causes of chronic obstructive pulmonary disease (COPD)-emphysema; however, the disease’s molecular mechanism is poorly known. Therefore, understanding the impacts of environmental exposure via autophagy offers new approaches for risk assessment, protection, and preventative actions which will counter the harmful effects of environmental contaminants on human and animal health.

Park YJ, et al. World J Mens Health. 2022 Jul;40(3):526-535. https://doi.org/10.5534/wjmh.210180

Alzheimer’s disease (AD) is one of the most prevailing neurodegenerative diseases, characterized by memory dysfunction and the presence of hyperphosphorylated tau and amyloid β (Aβ) aggregates in multiple brain regions, including the hippocampus and cortex. The exact etiology of AD has not yet been confirmed. However, epidemiological reports suggest that populations who were exposed to environmental hazards are more likely to develop AD than those who were not. Arsenic (As) is a naturally occurring environmental risk factor abundant in the Earth’s crust, and human exposure to As predominantly occurs through drinking water. Convincing evidence suggests that As causes neurotoxicity and impairs memory and cognition, although the hypothesis and molecular mechanism of As-associated pathobiology in AD are not yet clear. However, exposure to As and its metabolites leads to various pathogenic events such as oxidative stress, inflammation, mitochondrial dysfunctions, ER stress, apoptosis, impaired protein homeostasis, and abnormal calcium signaling. Evidence has indicated that As exposure induces alterations that coincide with most of the biochemical, pathological, and clinical developments of AD. Here, we overview existing literature to gain insights into the plausible mechanisms that underlie As-induced neurotoxicity and the subsequent neurological deficits in AD. Prospective strategies for the prevention and management of arsenic exposure and neurotoxicity have also been discussed.