Female Genital Research Articles

The cGAS-STING pathway and female reproductive system diseases.

The cGAS-STING pathway has become a crucial role in the detection of cytosolic DNA and the initiation of immune responses. The cGAS-STING pathway not only mediates protective immune defense against various DNA-containing pathogens but also detects tumor-derived DNA to generate intrinsic anti-tumor immunity. However, abnormal activation of the cGAS-STING pathway by self-DNA can also lead to autoimmune diseases and inflammatory disorders. This article reviews the mechanisms and functions of the cGAS-STING pathway, as well as the latest research progress in female reproductive-related diseases. We focus on the regulatory mechanisms and roles of this pathway in common female reproductive disorders, discuss the clinical potential of the cGAS-STING pathway as biomarkers and therapeutic agents for female reproductive diseases, as well as the research controversies, technical issues, and biological knowledge gaps that need to be resolved. Furthermore, we provide new ideas for the treatment and prevention of these diseases.

Targeting KRAS in gynecological malignancies.

Cervical, endometrial, and ovarian cancers stand prominently as the leading gynecological malignancies of the female reproductive system. The conventional therapeutic modalities for gynecological malignancies have predominantly encompassed surgery, chemotherapy, and radiotherapy. However, efficacy of these approaches remains limited in cases of relapse or drug resistance. KRAS is one of the most frequently mutated oncogenes in human cancers. The KRAS gene encodes a small guanosine triphosphatase protein that acts as a molecular switch for crucial intracellular signaling pathways. KRAS mutations are deeply involved in the occurrence and development of gynecological malignancies. The present review aims to expound upon the role of oncogenic KRAS as a biomarker, elucidating various therapeutic approaches under investigation targeting the KRAS pathway in gynecological tumors.

8795 Impact of Retinoic Acid Receptor Alpha Conditional Knockout on Ovarian Follicle Development in the Mouse

Abstract Disclosure: Z. Bogin: None. A. Keisker: None. A. Urbanowski: None. C. White: None. J.L. Kipp: None. The ovaries are the primary endocrine and reproductive organs in females. The ovarian follicle is the basic structural and functional unit of the ovary. When there is abnormal development in ovarian follicles, infertility and reproductive diseases such as polycystic ovarian syndrome (PCOS), premature ovarian failure (POF), and ovarian cancers may occur. Retinoic acid (RA), a biologically active derivative of vitamin A, is a signaling molecule that plays a vital role in various physiological processes, including embryonic development, tissue differentiation, and reproduction. We have shown that RA stimulates granulosa cell proliferation through a cell signaling cascade involving Retinoic Acid Receptors (RARs), which have three isoforms alpha, beta, and gamma. In this study, we characterized a new retinoic acid receptor alpha conditional knockout (RARA cKO) mouse model with RARA deleted in granulosa cells during embryonic development. The body weight and uterus weight of the RARA cKO mice were decreased at week 7 but returned to normal at week 15 and 12 months. The animals were either sub-fertile or infertile with phenotypic evidence of POF. In addition, a variety of ovarian pathologies were observed, including the presence of hemosiderin, increased cyst formation, and abnormal follicle counts. Overall, this study provides evidence of the involvement of retinoic acid signaling, mediated by RARA, in ovarian development and fertility. This study will help to better understand the prevention and treatment of ovarian diseases. Presentation: 6/2/2024

8795 Impact of Retinoic Acid Receptor Alpha Conditional Knockout on Ovarian Follicle Development in the Mouse

Abstract Disclosure: Z. Bogin: None. A. Keisker: None. A. Urbanowski: None. C. White: None. J.L. Kipp: None. The ovaries are the primary endocrine and reproductive organs in females. The ovarian follicle is the basic structural and functional unit of the ovary. When there is abnormal development in ovarian follicles, infertility and reproductive diseases such as polycystic ovarian syndrome (PCOS), premature ovarian failure (POF), and ovarian cancers may occur. Retinoic acid (RA), a biologically active derivative of vitamin A, is a signaling molecule that plays a vital role in various physiological processes, including embryonic development, tissue differentiation, and reproduction. We have shown that RA stimulates granulosa cell proliferation through a cell signaling cascade involving Retinoic Acid Receptors (RARs), which have three isoforms alpha, beta, and gamma. In this study, we characterized a new retinoic acid receptor alpha conditional knockout (RARA cKO) mouse model with RARA deleted in granulosa cells during embryonic development. The body weight and uterus weight of the RARA cKO mice were decreased at week 7 but returned to normal at week 15 and 12 months. The animals were either sub-fertile or infertile with phenotypic evidence of POF. In addition, a variety of ovarian pathologies were observed, including the presence of hemosiderin, increased cyst formation, and abnormal follicle counts. Overall, this study provides evidence of the involvement of retinoic acid signaling, mediated by RARA, in ovarian development and fertility. This study will help to better understand the prevention and treatment of ovarian diseases. Presentation: 6/2/2024

6694 A Case of an Extraneous Organ: A Uterus Found in a Genotypic and Phenotypic Male

Abstract Disclosure: R.A. Zielinski: None. S. Shteyman: None. A.G. Samat: None. Background: Persistent Mullerian Duct Syndrome (PMDS) is a rare entity that occurs when a phenotypic male is found to have female reproductive organs. In our case we describe an XY male who was found to have an abdominal mass consistent with a uterus on pathology. Clinical Case: Our patient is a 58-year-old male with hypertension, obesity, and obstructive sleep apnea who presented to the ED with 3 weeks of left upper quadrant pain. Abdominal CT showed two homogeneous enhancing oval lesions in the pelvis superior to the urinary bladder; 8.3 x 4.6 cm on the right and 3.6 x 3 cm on the left. Exploratory laparotomy was performed, and intraoperatively the mass was firm with a left satellite lesion and two fibrous bands that appeared similar in structure to round ligaments. Microscopically the tissue contained mullerian-type epithelium and smooth muscle with cystic degeneration. It was CK7 positive, estrogen receptor variable positive, and CK20 negative. Genetic testing confirmed the patient’s karyotype to be XY without genetic mosaicism. Our patient had two children spontaneously, regular spontaneous erections, and occasional hot flashes. Physical exam revealed an obese male (BMI 51) with bilateral gynecomastia and normal testicular size. He had no history of intra-abdominal or undescended testes requiring surgery. Labs showed increased total estrogen (283.7 pg/mL, n 60-190 pg/mL) and estradiol (39 pg/mL, n <= 29 pg/mL), decreased total testosterone (86 ng/dL, n 250-1,100 ng/dL), and normal free testosterone when corrected for SHBG (140 ng/dL, n 110-574 ng/dL). Testicular ultrasound was unrevealing. 3 years postoperatively his estradiol level normalized (34 pg/mL) and his total testosterone improved from 86 ng/dL to 223 ng/dL after losing 40 pounds on semaglutide. Discussion and Conclusion: Although the exact incidence of PMDS is unknown, it is a rare phenomenon. Only 200 cases between 1964 and 2000 and 34 cases between 2013 and 2017 have been reported. Mullerian ducts are embryologic structures present in both XY and XX fetuses until week 8 of life, when XY fetuses produce anti-mullerian hormone (AMH). In PMDS, the XY fetus either fails to produce AMH, or there is a defect in the AMH receptors, leading to the persistence of mullerian ducts. These ducts can then differentiate into a uterus, fallopian tubes, and/or the upper vagina. Our patient is a genotypical and phenotypical male with a uterus-like organ. The mild elevation in his estrogen level is likely secondary to his obesity. The estrogen could have increased the size of the uterus, causing the patient’s initial symptoms of abdominal pain which prompted his presentation to the hospital.

ALOG/LSHs, a novel class of transcription factors: Evolutionarily conserved regulators of plant growth and development.

The ALOG/LSH group of proteins is highly conserved across plant lineage, starting from moss to higher flowering plants, suggesting their crucial role in the evolution and adaptation of land plants. The role of ALOG proteins is highly conserved in various developmental responses, such as vegetative and reproductive developmental programs. Their role in meristem identity, cotyledon development, seedling photomorphogenesis and leaf and shoot development has been relatively well established. Moreover, several key pieces of evidence suggest their role in inflorescence architecture and flower development, including male and female reproductive organs and flower colouration. Recent research has started to explore their role in stress response. Functionally, ALOG proteins have been demonstrated to act as transcriptional regulators and are considered a newly emerging class of transcription factors in plants that regulate diverse developmental and physiological processes. This review aims to stimulate discussion about their role in plant development and their role as transcription factors. It also aims to further unravel the underlying molecular mechanism by which they regulate growth and development throughout the plant lineage.

Exploring the Protective Effect of Silver Croton tiglium Nano-Extract against Azoxymethane Induced Toxicity in Female Reproductive Organs in Rats

Reproductive toxicity from food and environmental contaminants has greatly affected human life. Plants are a fundamental source of bioactive components for relieving the harmful effects of pollutants. Hydrazine metabolites pose health threats when they enter the food chain. Croton tiglium (C. tiglium) exhibits anti-inflammatory and anti-tumor properties. Silver nanoparticles enhance the chemical stability of C. tiglium. Reproductive toxicity of Azoxymethane (AOM) and anticancer effects of silver C. tiglium were evaluated. Thirty-six adult female rats were divided into six groups (n=6) and treated with AOM with or without silver C. tiglium nano-extract as pre- and post-treatment. Sexual hormones and proteins were assessed under silver C. tiglium nano-extract and AOM. Histopathologically, AOM caused metaplastic myometrial endometriotic cysts and endometrial metaplasia. Silver C. tiglium in pre- and post-treated rats mitigated the carcinogenic effects of AOM. Immunohistochemically, AOM carcinogenicity was evident through moderate detection of the CK-7 tumor marker in the ovaries and uterus of the AOM-, simultaneous-, and post-treated groups. C. tiglium ameliorated this, with CK-7 slightly expressed in the pre-treated group. Furthermore, C. tiglium alleviated the negative impact on FSH, LH, and 17-β estradiol hormones. In conclusion, Silver C. tiglium nano-extract successfully prevented tumors in the ovaries and uterus of AOM-treated rats.

Toxicopathological and Biochemical Effects of Acrylonitrile on albino female mice reproductive system

Toxicopathological and Biochemical Effects of Acrylonitrile on albino female mice reproductive system

An Eleven-Year Retrospective Survey of Anaerobic Bloodstream Infection in Adults in a General Hospital.

During conditions accompanied by the disruption of normal mucosal barriers, anaerobic bacteria, which a part of normal human mucosal microflora, may cause various infections. In this study, clinical features of anaerobic bloodstream infections (BSI) in a general hospital in China were investigated. Patients with anaerobic BSI were retrospectively enrolled between 2012 and 2022. Demographic data, clinical manifestations, antibiotic treatments, and disease outcomes were analyzed. In total, 391 anaerobic bacterial strains were isolated from 381 patients aged older than 11 years of age. Given that medical records of 47 patients were missing, 334 patients were included in the clinical investigation. Patients with anaerobic BSI included in the study were predominantly older than 50 years of age. Intra-abdominal infections were the most common source of anaerobic BSI (59%), followed by those of the female genital tract (10.2%) and lower respiratory tract (7.2%). Among the isolates, Bacteroides and Clostridium spp. were the most frequently isolated anaerobes. Most of the patients received antibiotic therapy. The crude mortality was 4.5%. The detection rate of anaerobic BSI in Ningxia, China, remained relatively stable from 2012 to 2022. These results provide a reference for the diagnosis and empirical treatment of anaerobic BSI in this region of China. Continuous mul-ticenter studies should be conducted to monitor the incidence of anaerobic BSI and drug resistance of anaerobic isolates to improve the treatment outcomes of patients.

Antifungal susceptibility and biofilm production of Candida species- causative agents of female genital tract infections.

Recurrent vulvovaginal candidosis (RVVC) is a chronic infection affecting 8-10% of women worldwide. Biofilm production of the infecting species and reduced sensitivity to antimycotics could contribute to the recurrence of this infection. This study aimed to examine the biofilm production ability and antifungal susceptibility of genital yeast isolates to determine their virulence potential. Matrix-assisted laser desorption in ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to identify 300 Candida species. Using crystal violet method, strains were categorized into non-producers, weak, moderate, and strong biofilm producers (BFP). Antifungal susceptibility testing was performed using commercial Integral System YEASTS Plus test (ISYPT) and broth microdilution method (BMM). MALDI-TOF MS identified 150 Candida albicans, 124 non-albicans Candida (NAC), and 26 Saccharomyces cerevisiae strains. Within 138 (46.0%) BFP, 23 (16.7%) were strong, 44 (31.9%) moderate, and 71 (51.4%) weak. BMM was done for 43 BFP selected isolates with nystatin MIC ˃1.25 μl, fluconazole MIC ˃64 μl, and clotrimazole MIC ˃1.0 μl determined by ISYPT. Compared to all examined isolates, BMM confirmed that: i) C. albicans and NAC BFP showed low sensitivity to fluconazole (12% and 4%, respectively); ii) all BFP showed low sensitivity to nystatin (12.7% C. albicans, 14.5% NAC, and 23.1% S. cerevisiae); iii) clotrimazole in vitro was the most efficient regarding C. albicans and S. cerevisiae strains, but in 4.0% NAC BFP for this antimycotic higher MIC was established. Novel antimycotics or possible combinations of antifungal agents and natural products could be a new treatment option for RVVC.

Characterization of decellularized porcine oviduct- and uterine-derived scaffolds evaluated by spermatozoa-based biocompatibility and biotoxicity

Extracellular matrix-derived scaffolds (dECM) are widely utilized in regenerative medicine and tissue engineering due to their ability to promote cell growth, proliferation, and differentiation. In reproduction, research is focused on using these scaffolds to treat pathologies causing reproductive dysfunction or to improve assisted reproduction technologies (ARTs). We developed an efficient protocol employing the immersion-agitation technique to decellularize porcine oviductal and uterine sections, comparing the efficacy of fresh versus frozen treatments. Both methods successfully generated acellular matrices with less than 3% residual DNA, effectively preserving structural and protein integrity. Scanning and transmission electron microscopy confirmed the ultrastructural integrity, whereas Masson's Trichrome staining highlighted better collagen preservation in frozen treatments. Proteomic analysis of decellularized scaffolds revealed collagen and key macromolecules such as laminin, filamin, dermatopontin, and fibronectin, which are essential for extracellular matrix structure and cell functions such as adhesion and migration. Innovatively, we assessed the biocompatibility and cytotoxicity of the scaffolds using spermatozoa, demonstrating that thorough washing ensures the scaffold biocompatibility without compromising sperm viability or motility. Our findings not only contribute to the standardization of decellularization protocols for female reproductive organs but also emphasize the importance of evaluating sperm biocompatibility to ensure the safety of dECM scaffolds.

Endometrial Cancer - Long-Term Survival in Certified Cancer Centers and Non-Certified Hospitals: Comparative Analysis Based on a Large German Retrospective Cohort Study (WiZen).

Introduction Endometrial cancer is the most common malignant tumor of the female genital organs. In Germany, treatment is provided in both cancer centers certified by the German Cancer Society (Deutsche Krebsgesellschaft, DKG) and in non-certified hospitals. This study investigated whether treatment in DKG-certified centers leads to improved overall survival of patients with endometrial cancer. Materials and Methods Data from 11 legally independent German statutory health insurance (SHI) funds of the AOK were analyzed as well as data from four clinical cancer registries (CCR), resulting in inclusion of 30 102 AOK patients and 8190 registry patients with a diagnosis (incidental cases) of ICD-10-GM code C54 (malignant neoplasm of corpus uteri). For comparative survival analyses, multivariable Cox regressions and Kaplan-Meier analyses were used. Results The Kaplan-Meier estimator for 5-year overall survival was 66.7% for patients from certified centers and 65.0% for patients from non-certified hospitals (using SHI data; CCR data: 63.4% vs. 60.7%). Cox regression adjusted for relevant confounders showed a hazard ratio (HR) of 0.93 (SHI data; 95%CI 0.86 - 1.00; p = 0.050) and 0.935 (CCR data; 95% CI 0.827 - 1.057; p = 0.281) for all-cause mortality. In a subgroup analysis (CCR), patients with International Union against Cancer Control (UICC) stage I had a significant survival benefit if treated in a certified center (HR 0.783; 95% CI 0.620 - 0.987; p = 0.038). Conclusion The study presented herein shows that patients with endometrial cancer treated in a certified cancer center tend to have better survival rates. This should be considered when selecting the treating hospital.

Microbe-binding Antibodies in the Female Genital Tract: Associations with the Vaginal Microbiome and Genital Immunology.

Bacteria-Ig interactions maintain homeostasis in the gut through the clearance of pathogenic bacteria and the development of immune tolerance to inflammatory bacteria; whether similar interactions modulate inflammation and bacterial colonization in the female genital tract is uncertain. In this study, we used a flow cytometry-based assay to quantify microbe-binding IgA and IgG in the cervicovaginal secretions of 200 HIV-uninfected women from Nairobi, Kenya that were enriched for bacterial vaginosis. Total IgA and IgG were abundant and frequently demonstrated ex vivo binding to the key vaginal bacteria species Gardnerella vaginalis, Prevotella bivia, Lactobacillus iners, and Lactobacillus crispatus, which are largely microbe-specific. Microbe-binding Abs were generally not associated with the presence or abundance of their corresponding bacteria. Total and microbe-binding IgA and IgG were inversely correlated with total bacterial abundance and positively correlated with several proinflammatory cytokines (IL-6, TNF) and chemotactic chemokines (IP-10, MIG, MIP-1α, MIP-1β, MIP-3α, MCP-1, IL-8), independent of total bacterial abundance. Flow cytometry-based quantification of microbe-binding Abs provides a platform to investigate host-microbiota interactions in the female genital tract of human observational and interventional studies. In contrast to the gut, cervicovaginal microbe-binding IgA and IgG do not appear to be immunoregulatory but may indirectly mitigate bacteria-induced inflammation by reducing total bacterial abundance.

Expression of thyroid antigens in the female reproductive system.

Thyroid autoimmunity (TAI) has been linked to fertility disorders and pregnancy complications, even in euthyroid women. However, the exact pathophysiological mechanism underlying this association is not fully understood. This study seeks to investigate the expression of thyroid antigens within the human female reproductive system, potentially identifying targets for thyroid antibodies. Human biopsies of endometrium and follicular granulosa cells were collected and thyroperoxidase (TPO) and thyroglobulin (TG) expression was evaluated in these tissues by immunohistochemistry. Results showed, for the first time, the expression of TG protein and confirmed the presence of thyroid TPO in human endometrium and granulosa cells. Results suggest that TPO antibodies (TPOAbs) and TG antibodies (TGAbs) could interact with TPO and TG expressed in the reproductive system in patients with positive thyroid antibodies, thereby disrupting the function of TPO and TG and generating an inflammatory response, leading to fertility disorders and pregnancy complications.

Chlamydia-driven ISG15 expression dampens the immune response of epithelial cells independently of ISGylation.

Excessive inflammation upon Chlamydia trachomatis infection can cause severe damages in the female genital tract. This obligate intracellular bacterium develops mainly in epithelial cells, whose innate response contributes to the overall inflammatory response to infection. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) stimulates interferon γ (IFNγ) production and is required for bacterial clearance in several infectious contexts. Here, we describe and investigate the consequences of the increase in ISG15 expression by epithelial cells infected with C. trachomatis. Infection of HeLa cells and primary ecto-cervical epithelial cells resulted in a transcriptional upregulation of ISG15 expression. This did not involve the canonical type I interferon (IFN-I) signaling pathway and depended instead on the activation of the STING/TBK1/IRF3 pathway. The absence or reduction of ISG15 synthesis led to increased production of several cytokines and chemokines, including interleukin (IL) 6 and IL8. This implicates that ISG15 normally dampens the immune response induced by C. trachomatis infection in epithelial cells. ISG15 exerted its control from an intracellular location, but without involving ISGylation. Finally, higher levels of inflammation and delayed bacterial clearance were observed in the genital tracts of ISG15-KO mice infected by C. trachomatis compared with wild-type animals; however, IFNγ production was unchanged. Altogether, our data show that ISG15 expression acts as a brake on the immune response to C. trachomatis infection in epithelial cells and limits bacterial burden and inflammation in mice.IMPORTANCEInfection of epithelial cells by Chlamydia trachomatis elicits an innate immune response by these cells. The signaling pathways involved, and their outcomes, are still very poorly understood. In this paper, we described how Chlamydia infection triggered the expression of ISG15, a small molecule normally associated to type I interferon (IFN-I) signaling and control of INF-γ production. ISG15 synthesis by epithelial cells attenuated their immune response to Chlamydia infection. In mice, we observed that ISG15 displayed a marginal role in modulating the production of IFN-γ, a key component of the host immune response to infection, but facilitated bacterial clearance. Overall, our study strengthens the importance of ISG15 not only in the resolution of viral but also of bacterial infection and document its role of "immune brake" in the context of Chlamydia infection.

Assessment IL-6, TGF-1, CRP, and Vit-D in Women With Uterine Fibroid

Background: Uterine fibroids, also known as UFs, are the most common type of tumor that occurs in the female reproductive system. They affect a significant majority, around 70-80%, of women during their lifetime. Various factors that increase the incidence of Uterine Fibroids (UFs) have been found, including as vitamin D deficiency, inflammation, DNA repair deficit, and exposure to endocrine-disrupting chemicals (EDCs) in the environment. Objective: The purpose of this study to evaluated the level of IL-6, TGF-1, CRP, and Vit-D in women with uterine fibroid and study the relation these parameter with different ages. Materials and methods: 90 blood samples were collected and divided into (50) blood samples from women with uterine fibroids who received a diagnosis from a qualified medical specialist, and (40) blood samples from healthy women, whose ages ranged from (20-50). Assessment level of IL-6, TGF-1, CRP, and Vit-D have been done by using ELISA technique. Result: The results showed that there was no significant difference at the probability level (P>0.05) in the level of IL-6 in women with uterine fibroids, as it reached (44.9±4.4 pg/ml) when compared with healthy women (42.5±4.1 pg/ml). The results of this study showed a significant increase in the levels of both β-TGF and CRP in women with uterine fibroids at the probability level (P<0.05), reaching (2.870±0.760ng/ml, 62.9±6.4 pg/ml), respectively, when compared with Healthy women: As for Vit.D3, it showed a significant decrease in women with uterine fibroids at the probability level (P≤0.05), as it reached (5.92±1.87 ng/ml). Conclusion: This result concluded no differences in the level of IL-6 in women with uterine fibroids, while increase in the levels of both β-TGF and CRP . Furthermore, decrease level of Vit.D3.

Survey on Uterus Cancer and Its Types

Abstract: The vital component of the female reproductive system is the uterus. Women are currently dealing with a number of issues pertaining to reproduction. Additionally, the prevalence of cancer is rising daily, with a higher risk of malignant tumors in women. To effectively detect the cancer, a variety of techniques are being utilized, including image processing, machine learning, and datamining. This study describes the various machine learning algorithms used in the diagnosis of uterine cancer.

Vaginal microbiome: modern approaches for correction and/or restoration

Today, women’s health is a separate issue for doctors of many specialties, including obstetricians and gynecologists, family doctors, etc. There is a wide range of treatment options for managing diseases of the reproductive system in women. But despite this, many of these strategies do not work for our patients. Therefore, we need the latest personalized approaches to therapy. One of the newest trends in women’s health is the correction or restoration of the vaginal microbiome. In our previous publications, we have covered the issue of the normal composition of the vaginal microbiome and its changes in various pathological conditions. Modification of the vaginal microbiome can be a useful strategy in the treatment of sexually transmitted infections, bacterial vaginosis, candidiasis, benign, precancerous and even malignant diseases of the female reproductive system, miscarriage, preterm birth and other pregnancy complications.The concept of using exogenous microorganisms as a treatment has been known for centuries. Possible mechanisms by which exogenous strains of lactobacilli can affect vaginal microbiome include vaginal recolonization, increased production or release of lactic acid and other antimicrobial compounds, and modulation of the local mucosal immune response. From a microbiome perspective, “prebiotics” are nutraceutical compounds that induce bacterial growth or the activity of probiotics or beneficial endogenous microorganisms. One of the limitations of prebiotics is their dependence on the presence of lactobacilli, which are absent or almost absent in dysbiosis. Symbiotics are combinations of prebiotics and probiotics based on the concept that the first nutraceutical can improve the bacterial growth and function of the other. This review highlights the latest views on correction and/or restoration of the vaginal microbiome using not only probiotics, prebiotics, and symbiotic, but also phage-altering agents, phage therapy, vaginal microbiome transplantation, etc. Such methods of correction and/or restoration are currently relevant in the reproductive medicine, gynecology and obstetrics all over the world. Despite the fact that these are the newest methods of correction and/or restoration, they are developing every day and require more detailed coverage of this issue.

Heat and mass transfer in tri‐layer ependymal ciliary transport with diverse viscosity

AbstractSpecialized cilia known as ependymal cilia help the cerebrospinal fluid, which is important for nutrient delivery and waste elimination, to circulate in the brain. Many species rely on cilia and flagella for fluid movement and motility. Cilia and flagella, for instance, produce propulsive forces that allow unicellular creatures like Paramecium and Euglena to move through their surroundings. Ciliary transport plays a role in the flow of egg cells, or oocytes, via the fallopian tubes in the female reproductive system. The transfer of the egg towards the uterus is facilitated by the synchronized wave‐like motion produced by the cilia lining the fallopian tubes. Like this, ciliary transport in men aids in the passage of sperm cells via the epididymis. Many scientists and researchers are studying the mechanics of cilia motion and the properties of the viscoelastic fluid layer to develop new treatments and applications in biomedical engineering and for some diseases. Motivated by a wide range of biological applications, the objective of this study is to investigate the heat and mass transfer flow of tri‐layered Newtonian fluids flowing with the help of ciliary beating in a Cartesian coordinate. The fluid is incompressible, and fluid layers are not intermixed. The fluid flow with heat and mass transfer is first modelled in wave and then transmuted into fixed. Solutions for temperature profile, velocity distribution, stresses and concentration distribution are obtained. The influence of incipient parameters is displayed with graphs and plotted with the computational software MATHEMATICA 13.0 in the results section. The key findings obtained from graphs show that the maximum magnitude for temperature and velocity is achieved in the middle layer of fluid whereas in the outer layer concentration profile is maximum. It is predicted that this approach will make an essential contribution to the progress and enhancement of various types of drug delivery systems in the biomedical industry and biomechanics.

Causal relationships between leukocyte telomere length and female reproductive system diseases: A bidirectional Mendelian randomization study

Objective: Although numerous observational studies have revealed a correlation between leukocyte telomere length (LTL) and female reproductive system diseases (RSDs), the findings of these studies have tended to be consistent. In this study, we accordingly sought to clarify the causal relationships between LTL and RSDs. Methods: We performed a bidirectional two-sample Mendelian randomization (MR) analysis using pooled statistics from genome-wide association studies of LTL and nine female RSDs. The final results were analyzed using five MR methods, with the inverse variance weighted (IVW) method used as the primary outcome. We applied MR-PRESSO to exclude outliers. Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy. Results: In the forward MR analysis, a genetic prediction of longer LTLs was found to be causally associated with higher risks of endometriosis (IVW: OR = 1.25, 95%CI: 1.06–1.46, P = 0.008), leiomyoma of the uterus (IVW: OR = 1.73, 95%: 1.52–1.98, P = 4.9E-16) and ovarian cysts (IVW: OR = 1.31, 95%:1.19–1.45, P = 1.5E-07). In the reverse MR results, female RSDs were shown to have no significant effect on LTLs (all P-values > 0.05). Sensitivity analysis confirmed the robustness of these results. Conclusions: Our findings substantiate the assumption that a genetically predicted longer LTL elevates the risk of endometriosis, leiomyoma of the uterus, and ovarian cysts, with no influence of RSDs on LTL. These findings contribute to establishing a causal link between LTL and RSDs, overcoming the constraints of earlier observational studies. They also imply that LTL could potentially serve as a biomarker for the occurrence of endometriosis, leiomyoma of the uterus, and ovarian cysts.