The Hippo signaling pathway is recognized for its significant role in cell differentiation, proliferation, survival, and tissue regeneration. Recently, the Hippo signaling pathway was also found to be associated with oxidative stress and reactive oxygen species (ROS) regulation, which are important in the regulation of cell survival. Studies indicate a correlation between components of the Hippo signaling pathway, including MST1, YAP, and TAZ, and the generation of ROS. On the other hand, ROS and oxidative stress can activate key components of the Hippo signaling pathway. For example, ROS production activates MST1, which subsequently phosphorylates FOXO3, leading to apoptotic cell death. ROS was also found to regulate YAP, in addition to MST1/2. Oxidative stress and ROS formation can impair lipids, proteins, and DNA, leading to many disorders, including aging, neurodegeneration, atherosclerosis, and diabetes. Consequently, understanding the interplay between the Hippo signaling pathway, ROS, and oxidative stress is crucial for developing future disease management strategies. This paper aimed to review the association between the Hippo signaling pathway, regulation of ROS production, and oxidative stress to provide beneficial information in understanding cell function and pathological processes.

Diabetes mellitus (DM) is one of the major causes of death in the world. There are two types of DM—type 1 DM and type 2 DM. Type 1 DM can only be treated by insulin injection whereas type 2 DM is commonly treated using anti-hyperglycemic agents. Despite its effectiveness in controlling blood glucose level, this therapeutic approach is not able to reduce the decline in the number of functional pancreatic β cells. MST1 is a strong pro-apoptotic kinase that is expressed in pancreatic β cells. It induces β cell death and impairs insulin secretion. Recently, a potent and specific inhibitor for MST1, called XMU-MP-1, was identified and characterized. We hypothesized that treatment with XMU-MP-1 would produce beneficial effects by improving the survival and function of the pancreatic β cells. We used INS-1 cells and STZ-induced diabetic mice as in vitro and in vivo models to test the effect of XMU-MP-1 treatment. We found that XMU-MP-1 inhibited MST1/2 activity in INS-1 cells. Moreover, treatment with XMU-MP-1 produced a beneficial effect in improving glucose tolerance in the STZ-induced diabetic mouse model. Histological analysis indicated that XMU-MP-1 increased the number of pancreatic β cells and enhanced Langerhans islet area in the severe diabetic mice. Overall, this study showed that MST1 could become a promising therapeutic target for diabetes mellitus.

Background: Cervical cancer is one of the deadliest diseases for women’s lives. It is estimated that almost every hour, one died because of cervical cancer and 70% of new cases are found in an advanced stage. Many factors could cause cervical cancer, one of the risk factors is the age of the early coitarche. This study aims to determine the association between the age of coitarche and cervical cancer.Methods: This study was an analysis of observational study with a case-control design. There were two groups in this study; the case group of outpatients who were diagnosed with cervical cancer and the control group of outpatients who had normal cervical cytology by Papanicolaou screening. The 39 respondents of both the control and case groups, calculated using the Lemeshow’s formula for consecutive sampling, were interviewed for their details concerning reproductive and sexual histories, socio-economic status, hygiene, and education. The independent variable in this study was the age of coitarche; the dependent variable was cervical cancer. The data were analyzed descriptively and using the bivariate analysis (Chi-square) with α=0.05.Results: It is identified that 39 respondents for each group (case and control) have almost the same percentage of the age of coitarche in One-Stop Oncology Polyclinic (POSA’s outpatient); early coitarche of 43.6% and late coitarche of 56.4%. The age of early coitarche in Obstetrics and Gynecology’s outpatients, as a control group, is rare (4 of 39 respondents; 10.3%) and most of them did their sexual debut at the age of >18 years (89.7%). The chi-square test showed there was a correlation between the age of coitarche and cervical cancer (P=.002; OR=6.76; 95% CI 2.01—22.75).Conclusions: Early coitarche has a potential effect on cervical cancer.

Ria Margiana, Widya Juwita, Khoirul Ima, Zakiyatul Faizah, Supardi Supardi. Anat Cell Biol 2023;56:421-7. https://doi.org/10.5115/acb.23.056

Highlights:1. Spermatozoa can be affected by coronavirus disease 2019 (COVID-19) due to a disruption in spermatogenesis, leading to a decline in semen quality.2. This study compared the semen quality of COVID-19 survivors and those who had not been infected with COVID-19, specifically on the first spermatogenesis cycle following the confirmation of COVID-19 infection.3. This study is distinctive since no previous research in Indonesia has examined the semen quality parameters, such as the concentration, morphology, motility, and vitality of spermatozoa, in men who had a COVID-19 infection. Abstract Semen quality in COVID-19 patients shows inconsistencies and variations. This research was conducted considering that health is the main capital for humans in Indonesia's development, as outlined in Sustainable Development Goal 3. The purpose of this study was to compare the semen quality of COVID-19 survivors with non-COVID-19 men. This study was an analytical observational study with a cross-sectional design. Subjects were selected through consecutive sampling of up to 26 men of childbearing age who met the predetermined criteria. Semen quality assessment using the WHO Semen Analysis Guide 6th edition. Quantitative data were analyzed using SPSS. The data normality test was carried out using the Saphiro-Wilk test. Then, the data were tested by t-test from two unpaired samples and by the Mann-Whitney test. Data from semen analysis based on COVID-19 severity were tested using variant analysis (One-way ANOVA) and the Kruskal Wallis test. The normal morphology of spermatozoa in COVID-19 survivors was significantly lower (p=0.011) compared to uninfected men. Other semen quality parameters did not differ significantly, although they were lower in COVID-19 survivors. The results of the analysis also showed no significant difference in semen parameters related to COVID-19 severity (p=0.488 for progressive motility; p=0.372 for non-progressive motility; p=0.325 for total motility; p=0.707 for immotility; p=0.412 for vitality; p=0.324 for concentration; and p=0.334 for normal morphology). The study provides evidence that COVID-19 survivors have a lower normal spermatozoa morphology compared to uninfected men. However, the motility, vitality, and concentration of spermatozoa did not differ significantly between the two groups.

Background/Objectives: Spermatogenesis is a key process in male reproduction that, if it does not happen correctly, can lead to infertility, with diabetes being one of the most prevalent causes of spermatogenesis disruption. Currently, there is a lack of research examining the potential benefits of targeting cell proliferation to enhance spermatogenesis in this condition. XMU-MP1 has been identified as an inhibitor of MST1, a core component of the Hippo pathway, which is anticipated to promote proliferation and regeneration. This study aims to evaluate the effects of XMU-MP1 treatment on sperm and testicular characteristics in mice. Methods: We used the STZ-induced diabetic mouse model to investigate the impact of administering XMU-MP1 on testicular tissue and sperm parameters. This study compared the seminiferous tubules, specifically focusing on the diameter of the seminiferous tubule, the thickness of the seminiferous tubule epithelium, the ratio of the thickness of the seminiferous tubule epithelium to the diameter of the seminiferous tubules, and the lumen diameter of the seminiferous tubules. We also conducted a comparison of sperm parameters, including sperm concentration, progressive motility, total motility, total motility, and morphology. Results: XMU-MP1-treated mice had a larger spermatogenesis area and better sperm motility than control mice. Diabetic mice treated with XMU-MP1 also showed a trend toward improvements in the spermatogenesis area, sperm concentration, sperm motility, and sperm morphology, although these improvements were not statistically significant. Conclusions: XMU-MP1 serves as a potential compound to improve spermatogenesis in mice.