The aims of this study were to investigate the combined effects of a natural compound 1'S-1'-acetoxychavicol acetate (ACA) with cisplatin (CDDP) on HPV-positive human cervical carcinoma cell lines (Ca Ski-low cisplatin sensitivity and HeLa-high cisplatin sensitivity), and to identify microRNAs (miRNAs) modulated in response toward ACA and/or CDDP. It was revealed that both ACA and CDDP induced dose- and time-dependent cytotoxicity when used as a stand-alone agent, while synergistic effects were observed when used in combination with a combination index (CI) value of 0.74 ± 0.01 and 0.85 ± 0.01 in Ca Ski and HeLa cells, respectively. A total of 25 miRNAs were found to be significantly differentially expressed in response to ACA and/or CDDP. These include hsa-miR-138, hsa-miR-210, and hsa-miR-744 with predicted gene targets involved in signaling pathways regulating apoptosis and cell cycle progression. In conclusion, ACA acts as a chemosensitizer which synergistically potentiates the cytotoxic effect of CDDP in cervical cancer cells. The altered miRNA expression upon administration of ACA and/or CDDP suggests that miRNAs play an important role in anticancer drug responses, which can be manipulated for therapeutic purposes.
Immunological infertility contributes significantly to the etiology of idiopathic male infertility. Shielding the spermatogenic cells from systemic immune responses is fundamental to secure normal production of spermatozoa. The body's immune system is tuned with the host self-components since the early postnatal period, while sperm first develops during puberty, thus rendering spermatogenic proteins as 'non-self' or 'antigenic.' Development of antibodies to these antigens elicits autoimmune responses affecting sperm motility, functions, and fertility. Therefore, the testes need to establish a specialized immune-privileged microenvironment to protect the allogenic germ cells by orchestration of various testicular cells and resident immune cells. This is achieved through sequestration of antigenic germ cells by blood-testis barrier and actions of various endocrine, paracrine, immune-suppressive, and immunomodulatory mechanisms. The various mechanisms are very complex and need conceptual integration to disclose the exact physiological scenario, and to facilitate detection and management of immunogenic infertility caused by disruption of testicular immune regulation. The present review aims to (a) discuss the components of testicular immune privilege; (b) explain testicular somatic and immune cell interactions in establishing and maintaining the testicular immune micro-environment; and (c) illustrate the integration of multiple mechanisms involved in the control of immune privilege of the testis.
Several clinical trials in women with endometriosis demonstrated that dienogest reduces endometrial lesions and improves health-related quality of life (HRQoL). To assess HRQoL in dienogest-treated patients in real-world setting, we conducted a prospective, non-interventional study in 6 Asian countries. Women aged ≥18 years with clinical or surgical diagnosis of endometriosis, presence of endometriosis-associated pelvic pain (EAPP) and initiating dienogest therapy were enrolled. The primary objective was to evaluate HRQoL using the Endometriosis Health Profile-30 (EHP-30) questionnaire. The secondary objectives included analysis of EAPP, satisfaction with dienogest, endometriosis symptoms and bleeding patterns. 887 patients started dienogest therapy. Scores for all EHP-30 scales improved with the largest mean changes at month 6 and 24 in scale pain (-28.9 ± 27.5 and - 34 ± 28.4) and control and powerlessness (-23.7 ± 28.2 and - 28.5 ± 26.2). Mean EAPP score change was -4.6 ± 3.0 for both month 6 and 24 assessments. EAPP decrease was similar in surgically and only clinically diagnosed patients. From baseline to month 24, rates of normal bleeding decreased (from 85.8% to 17.5%) while rates of amenorrhea increased (from 3.5% to 70.8%). Majority of patients and physicians were satisfied with dienogest. Over 80% of patients reported symptoms improvement. 39.9% of patients had drug-related treatment-emergent adverse events, including vaginal hemorrhage (10.4%), metrorrhagia (7.3%) and amenorrhea (6.4%). In conclusion, dienogest improves HRQoL and EAPP in the real-world setting in women with either clinical or surgical diagnosis of endometriosis. Dienogest might be a promising first-line treatment option for the long-term management of debilitating endometriosis-associated symptoms.NCT02425462, 24 April 2015.
Uterine fibroid is a common gynecological disorder that affects women of reproductive age and has emerged as a major public health concern. The symptoms have a negative influence on both their physical health and quality of life. The cost of treatment has a significant impact on the disease's burden. Even though its origin is uncertain, estrogen is thought to be a key player in fibroid pathophysiology. Many theories, including those based on genetic and environmental factors, explain what causes hyper-estrogenic condition in fibroid patients. One such possibility that is currently being explored is the hypothesis that an altered gut microbiome can contribute to the development of diseases characterized by estrogen dominance. Gut dysbiosis is often a "hot area" in the health sciences. According to a recent study, uterine fibroid patients have altered gut microbiome. A variety of risk factors influence both fibroid development and gut homeostasis. Diet, lifestyle, physical activity, and environmental contaminants have an impact on estrogen and the gut flora. A better understanding of uterine fibroids' pathophysiology is required to develop effective preventative and treatment options. A few ways by which the gut microbiota contributes to UF include estrogen, impaired immune function, inflammation, and altered gut metabolites. Therefore, in the future, while treating fibroid patients, various strategies to deal with changes in the gut flora may be advantageous. For developing suggestions for clinical diagnosis and therapy, we reviewed the literature on the relationship between uterine fibroids and the gut microbiota.
Endometrial injury is one of the leading causes of female infertility and is caused by intrauterine surgery, endometrial infection, repeated abortion, or genital tuberculosis. Currently, there is little effective treatment to restore the fertility of patients with severe intrauterine adhesions and thin endometrium. Recent studies have confirmed the promising therapeutic effects of mesenchymal stem cell transplantation on various diseases with definite tissue injury. The aim of this study is to investigate the improvements of menstrual blood-derived endometrial stem cells (MenSCs) transplantation on functional restoration in the endometrium of mouse model. Therefore, ethanol-induced endometrial injury mouse models were randomly divided into two groups: the PBS-treated group, and the MenSCs-treated group. As expected, the endometrial thickness and gland number in the endometrium of MenSCs-treated mice were significantly improved compared to those of PBS-treated mice (P
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization (WHO) on 11th March 2020. Bulk of research on this virus are carried out to unveil its multivariate pathology. Surprisingly, men are reportedly more vulnerable to COVID-19 even with higher fatality rate compared to women. Thus, it is crucial to determine whether SARS-CoV-2 infection can even affect male fertility as an immediate or long-term consequence of the disease. Among the discrete data available, an important finding is that angiotensin converting enzymes 2 (ACE2) receptor, that aids the SARS-CoV-2 entry into host cells, is profoundly expressed in testicular cells. In addition, the endogenous androgen milieu and its receptors are associated with ACE2 activation reflecting that enhanced testosterone levels may trigger the pathogenesis of COVID-19. In contrary, hypogonadism has also been reported in the acute phase of some COVID-19 cases. Moreover, SARS-CoV-2 infection-induced uncontrolled inflammatory responses may lead to systemic oxidative stress (OS), whose severe disruptive effects on testicular functions are well-documented. This article aims to precisely present the possible impact of COVID-19 on male reproductive functions, and to highlight the speculations that need in-depth research for the exact underlying mechanisms how COVID-19 is associated with men's health and fertility.