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Previous studies have suggested that the effects of androgens on body weight (BW) and appetite are affected by the estrogen milieu in females; however, the mechanism underlying these effects remains unclear. We hypothesized that androgens may affect endogenous oxytocin (OT), which is a hypothalamic anorectic factor, and that these effects of androgens may be altered by the estrogen milieu in females. To investigate this hypothesis, in the present study, we examined the effects of testosterone on peripheral and central OT levels in ovariectomized female rats that did or did not receive estradiol supplementation. Ovariectomized female rats were randomly divided into non-estradiol-supplemented or estradiol-supplemented groups, and half of the rats in each group were concurrently supplemented with testosterone (i.e., rats were divided into four groups, n = 7 per each group). We also measured peripheral and central OT receptor (OTR) gene expression levels. As a result, we found that testosterone increased serum and hypothalamic OT levels and OT receptor mRNA levels in non-estradiol-supplemented rats, whereas it had no effects on these factors in estradiol-supplemented rats. In addition, testosterone reduced food intake, BW gain, and fat weight in non-estradiol-supplemented rats, whereas it did not have any effects on BW, appetite, or fat weight in estradiol-supplemented rats. These findings indicate that the effects of androgens on OT may be affected by the estrogen milieu, and elevated OT levels may be related to the blunting of appetite and prevention of obesity under estrogen-deficient conditions. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to examine the association between fertility issues and demographic characteristics of unmarried adolescent and young adult cancer survivors. Methods: We conducted a survey among cancer survivors who were 15–39 years old and unmarried at the time of cancer diagnosis and 20–45 years old at the time of the survey. Views on fertility issues, originally developed based on the results of a qualitative study conducted with the same inclusion criteria, were used to assess thoughts and feelings regarding fertility issues. Results: Through exploratory factor analysis of the 128 respondents who either had children or desired children, two factors related to fertility issues were identified: "anxiety related to the possibility of not being able to have children" and "pressure from others to have children." Multiple regression analysis was performed to examine the association between these factors and demographic characteristics. The analysis revealed that being male and having a partner were significant predictors for both factors for views on fertility issues. Additionally, younger age at the time of diagnosis was a significant predictor for the first factor. Conclusions: Greater fertility issues among unmarried cancer survivors were associated with younger age at diagnosis, having a partner, and being male. Surprisingly, contrary to previous findings, male cancer survivors experienced more significant fertility problems than women. This result may be attributed to the well-established gender roles in Japan, where men are predominantly considered the heirs and inheritors of the family. [ABSTRACT FROM AUTHOR]

In recent years, the effects of androgens on metabolic and body weight regulation systems and their underlying mechanisms have been gradually revealed in females. In women and experimental animals of reproductive age, androgen excess can adversely affect metabolic functioning, appetite, and body weight regulation. In addition, excess androgens can increase the risk of metabolic disorders, such as obesity, insulin resistance, and diabetes. These unfavorable effects of androgens are induced by alterations in the actions of hypothalamic appetite-regulatory factors, reductions in energy expenditure, insulin resistance in skeletal muscle, and β-cell dysfunction. Interestingly, these unfavorable effects of androgens on metabolic and body-weight regulation systems are neither observed nor evident in ovariectomized animals and post-menopausal women, indicating that the adverse effects of androgens might be dependent on the estrogen milieu. Recent findings may provide novel sex- and age-specific strategies for treating metabolic diseases. [ABSTRACT FROM AUTHOR]

Oxytocin (OT) affects many behavioral, psychological, and physiological functions, including appetite and body weight regulation. Central and peripheral OT levels are markedly affected by gonadal steroids, especially estrogen, and the anorectic effects of estrogen are partially mediated by OT in rodents. In this study, the relationship between the estrogen milieu and serum OT levels was evaluated in women of reproductive age under physiological (n = 9) and supraphysiological estrogenic conditions (n = 7). Consequently, it was found that serum OT levels were increased in physiological (the ovulatory phase) and supraphysiological (on the day of the human chorionic gonadotropin trigger in an ovarian stimulation cycle) estrogenic conditions, and that serum OT levels were positively correlated with serum estradiol levels. On the other hand, serum OT levels were negatively correlated with serum progesterone levels, and there was no correlation between serum and follicular OT levels. These results suggest that OT levels may be positively and negatively regulated by estrogen and progesterone, respectively, in humans. However, the physiological roles of these actions of gonadal steroids on OT remain unclear. [ABSTRACT FROM AUTHOR]

Taxanes are important chemotherapeutic agents used to manage breast cancer and gynaecological malignancies. However, ovarian toxicity induced by the taxane docetaxel (DOC) is of great concern. We investigated DOC-induced toxicity in the ovaries of female CD1 strain mice. The mice were divided into control (saline), DOC-5 (5 mg/kg DOC), and DOC-10 (10 mg/kg DOC) groups and administered saline or DOC on the first day of the study and two weeks later. Two weeks after the second dose, the ovaries were removed for analysis after inducing superovulation. Ovary weight, the number of secondary follicles, and the total number of follicles were reduced after DOC administration. Additionally, the expression levels of caspase-3 and the pro-apoptotic protein Bcl-2 interacting mediator of cell death (BIM) increased. Our findings suggest that high-dose DOC induces damage to growing follicles; however, it may not affect primordial follicles. What is already known on this subject? Docetaxel (DOC) is one of the most effective chemotherapeutic agents used to manage various cancers. Some in-vitro studies have examined paclitaxel-induced ovarian toxicity; however, limited research on DOC is available. What do the results of this study add? We investigated DOC-induced ovarian toxicity in female CD1 strain mice at 5 mg/kg and 10 mg/kg. We found that DOC reduced ovary weight, the number of secondary follicles, and the total number of follicles, with the higher dose having a higher effect. What are the implications of these findings for clinical practice and/or further research? We believe that our study makes a significant contribution to the knowledge about the effect of DOC on ovarian function. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2007.01.032 Byline: Natsuko Mizuno (a), Hiroaki Nakahara (a), Kazumasa Sekiguchi (a), Kanako Yoshida (a), Minoru Nakano (b), Kentaro Kasai (a) Keywords: DNA; STR; Japanese; Y chromosome; Population Abstract: A total of 1079 Japanese males were typed for the following 16 Y chromosomal short tandem repeat (Y-STR) markers: DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385, DYS393, DYS391, DYS439, DYS635, DYS392, Y GATA H4, DYS437, DYS438 and DYS448 using an AmpFlSTR[R] Yfileracents PCR Amplification kit (Applied Biosystems). A total of 950 haplotypes for the 16 Y-STR markers were detected and, of these, 886 haplotypes were unique. The most frequent haplotype was found in 22 Japanese males. The haplotype diversity was 0.9992, indicating a high potential for differentiating between male individuals. There were 10 haplotypes with no allele detected at the DYS448 marker. Thus, the presence of such atypical haplotypes should be noted, when DNA typing results obtained from degraded DNA samples and/or DNA mixture samples from more than one male individual are being interpreted. Author Affiliation: (a) Fourth Biology Section, Department of First Forensic Science, National Research Institute of Police Science, 6-3-1, Kashiwanoha, Kashiwa, Chiba 277-0882, Japan (b) Department of Chemistry, Faculty of Science, Chiba University, Chiba, Japan Article History: Received 10 July 2006; Revised 4 January 2007; Accepted 5 January 2007

Purpose: This study explored the impact of cancer on romantic relationships and marriage postdiagnosis among adolescents and young adults (AYAs) who had been diagnosed with cancer in Japan. Methods: Semistructured interviews were conducted with 24 AYA cancer survivors, regardless of cancer type, who were unmarried and aged 15–39 at the time of cancer diagnosis. For theme and category generation, the authors coded the interview transcripts independently through inductive thematic analysis. Results: The analysis yielded 11 themes. The most common impact on romantic partnership was "fertility and parenthood concerns" (45.8%), followed by "disclosure of cancer history" (37.5%), and finally by "recurrence, metastasis, and poor health" (25.0%). Conclusions: Although the impacts of cancer that were identified in this study were mostly consistent with earlier findings, certain impacts seem to stem from traditional family perceptions in East Asia. Because men are traditionally seen as the family successors, unlike women, they are primarily concerned about fertility and parenthood. This causes a parental influence on romantic and marital choices. The fact that there exists a parental influence in partner selection from the parents of both men and women indicates that cultural factors in East Asia/Japan influence romantic and/or marriage postdiagnosis. [ABSTRACT FROM AUTHOR]

It is well known that undernourished conditions disturb female reproductive functions in many species, including humans. These alterations are mainly caused by a reduction in gonadotrophin‐releasing hormone (GnRH) secretion from the hypothalamus. Evidence from the literature suggests that some hypothalamic factors play pivotal roles in the coordination of reproductive functions and energy homeostasis in response to environmental cues and internal nutritional status. Generally, anorexigenic/satiety‐related factors, such as leptin, alpha‐melanocyte‐stimulating hormone, and proopiomelanocortin, promote GnRH secretion, whereas orexigenic factors, such as neuropeptide Y, agouti‐related protein, orexin, and ghrelin, attenuate GnRH secretion. Conversely, gonadotrophin‐inhibitory hormone, which exerts anti‐GnRH and gonadotrophic effects, promotes feeding behavior in many species. In addition, the activity of kisspeptin, which is a potent stimulator of GnRH, is reduced by undernourished conditions. Under normal nutritional conditions, these factors are coordinated to maintain both feeding behavior and reproductive functions. However, in undernourished conditions their activity levels are markedly altered to promote feeding behavior and temporarily suppress reproductive functions, in order to prioritize the survival of the individual over that of the species. [ABSTRACT FROM AUTHOR]

During development of the vertebrate visual system, retinal ganglion cell (RGC) axons follow a precise path toward their midbrain targets. Although much is known about the cues that direct RGC axons once they have left the optic disc, less is known about the guidance of axons at earlier stages, when RGCs first send out their axons to navigate within the developing retina. Using collagen gel coculture experiments, we find that the embryonic lens produces a powerful diffusible repulsive activity for RGC axons. We also find that this activity is localized to the lens epithelium and not the lens fiber layer, while the pigmented epithelium and vitreous humour are devoid of activity. The further observation that the lens also chemorepels primary sensory axons, but does not repel olfactory bulb axons, shows that this activity is specific for subsets of axons. Our experiments have excluded two candidate repellents for RGC axons (collapsin-1/sema III and chondroitin sulfate proteoglycans). These results implicate the lens in the earliest stages of RGC axon guidance. One function of the lens repellent may be to prevent aberrant targeting toward the lens, and it may also be involved in the directional guidance of RGC axons toward the optic disc.

Background: Coronavirus disease 2019 (COVID-19) has caused a global pandemic. Higher expression of the virus receptor angiotensin-converting enzyme 2 (ACE2) in the nasal mucosa may be associated with high transmissibility and asymptomatic infection. In COVID-19, the elucidation of the determinants of ACE2 expression at nasal tissue level is crucial. The development of strategies to downregulate ACE2 expression in nasal epithelial cells might reduce transmission and be useful as a novel therapeutic approach. Objective: To verify ACE2 expression in the nasal mucosa of patients with seasonal allergic rhinitis induced by Japanese cedar pollen (SAR-JCP) and chronic rhinosinusitis with nasal polyp (CRSwNP) and to examine the effects of short-chain fatty acids (SCFAs) on ACE2 expression in airway epithelial cells. Methods: We assessed ACE2 expression in the nasal mucosa of control subjects, patients with SAR-JCP, and those with CRSwNP using real-time polymerase chain reaction. We also quantified ACE2 gene expression in cultured airway epithelial cells. Results: Although ACE2 expression was greatly increased in a few patients with SAR-JCP during the Japanese cedar pollen season, mean levels were not significantly increased. ACE2 mRNA expression was significantly decreased in nasal polyp tissue from patients with chronic rhinosinusitis compared with the expression in that from control subjects. SCFAs generated by gastrointestinal microbiota significantly reduced resting ACE2 expression in cultured airway epithelial cells. SCFAs also significantly suppressed the dsRNA-dependent upregulation of ACE2 expression in airway epithelial cells. Conclusion: Inflammatory endotype affects ACE2 expression in the nasal mucosa and influences susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In particular, type 2 inflammation could downregulate ACE2 expression in the nasal mucosa and reduces susceptibility to SARS-CoV-2 in patients with CRSwNP. Although in vivo experiments are required, administration of SCFAs to the nasal cavity might be worthy of consideration as a preventative or therapeutic strategy for the early-stage COVID-19. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) has high recurrence rates. HCC sometimes progresses from early‐stage HCC (Barcelona Clinic Liver Cancer [BCLC] stage 0/A) to advanced‐stage HCC after repeated recurrences and treatments. HCC progression deteriorates quality of life and prognosis. However, the effect of direct‐acting antiviral (DAA)‐induced sustained virologic response (SVR) on HCC progression remains uninvestigated. We conducted a retrospective cohort study of patients with hepatitis C virus‐related HCC with BCLC stage 0/A diagnosed for the first time and treated by curative resection or ablation. Using a time‐varying method, we estimated the risk of tumour progression (defined as progression to BCLC stage B‐D) and liver‐related death and the characteristics of repeated recurrence. Overall, 165 patients were enrolled. Following curative HCC treatment, 72 patients received DAA therapy (DAA‐treated group), whereas 93 did not (untreated group). Approximately 75% of the recurrences were at an early stage and expected to be disease‐free by retreatment. We recorded 56 tumour progressions, of which 60.7% were observed after second recurrence. Multivariate adjusted time‐varying Cox regression analysis showed that the DAA‐induced SVR significantly reduced the risk of tumour progression (hazard ratio [HR] 0.28; p =.001) and liver‐related death (HR 0.12; p <.001). The annual incidence of HCC treatment until tumour progression was 82.8% and 23.9% in the untreated and DAA‐treated groups, respectively (HR 0.30; p <.001). DAA‐induced SVR significantly reduced the risk for tumour progression and liver‐related death and the frequency of HCC treatment following curative treatment for HCC at BCLC stage 0/A. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic chronic sinusitis (ECRS) is a subtype of CRS with nasal polyps (CRSwNP) that is frequently comorbid with asthma. Notably, ECRS patients often show a high recurrence of NPs after surgical resection. Leptin is a hormone produced by adipocytes that has been implicated in airway inflammatory diseases. However, to date, the role of leptin in ECRS has not been investigated. Objective: To determine whether the serum levels of leptin are altered in patients with ECRS. Methods: In total, 40 patients with ECRS, 15 patients with non-eosinophilic CRS (non-ECRS), and 12 individuals without CRS (control) were included in this study. Patient's serum leptin levels were assessed, and the number of eosinophils in their NPs were measured through a histological evaluation of the three densest areas with cellular infiltrate beneath the epithelial surface. Finally, nasal fibroblast cultures established from NPs were stimulated with varying concentrations of recombinant leptin in vitro to determine whether leptin affects eotaxin-3 (Chemokine (C-C motif) ligand 26 :26: CCL26) expression. Results: The serum leptin levels in both the ECRS and non-ECRS groups were significantly higher than those in the control subjects (p < 0.0001 vs. ECRS; p < 0.05 vs. non-ECRS). Furthermore, ECRS patients displayed significantly elevated serum leptin levels compared to non-ECRS patients (p < 0.001), although there was no difference in body mass index between the groups. Notably, serum leptin levels were correlated with the proportion of eosinophils in peripheral blood (r = 0.3575, p < 0.01) and the number of eosinophils in NPs (r = 0.5109, p < 0.0001). Serum leptin levels were also correlated with eotaxin-3 mRNA expression in NPs (r = 0.5374, p < 0.01). Finally, leptin significantly augmented eotaxin-3 expression in nasal fibroblasts established in vitro from NPs in a leptin receptor-dependent manner (p < 0.05). Conclusion: Leptin levels are elevated in ECRS patients and may both promote and indicate the severity of ECRS as well as systemic type 2-biased inflammatory responses. Combined, these data indicate that circulating leptin may play a significant role in the development of eosinophilic inflammation in NPs. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The objective of this study was to determine the role of thrombin‐activatable fibrinolysis inhibitor (TAFI) as a candidate biomarker for therapeutic efficacy of sublingual immunotherapy (SLIT) and to identify the role of TAFI in the pathogenesis of allergic rhinitis (AR). Study Design: Retrospective cohort study and laboratory study. Methods: Serum was collected from patients with allergies to Japanese cedar pollen before, during, and after treatment with SLIT. We measured the levels of immunoreactive TAFI, C3a, and C5a in serum by enzyme‐linked immunosorbent assay (ELISA) and assessed their relative impact on a combined symptom‐medication score. We also examined the impact of TAFI on mast cells and fibroblasts in experiments performed in vitro. Results: Serum levels of TAFI increased significantly in response to SLIT. By contrast, serum C3a levels decreased significantly over time; we observed a significant negative correlation between serum levels of TAFI versus C3a and symptom‐medication score. Mast cell degranulation was inhibited in response to TAFI, as it was the expression of both CCL11 and CCL5 in cultured fibroblasts. Conclusions: High serum levels of TAFI may be induced by SLIT. TAFI may play a critical protective role in pathogenesis of AR by inactivating C3a and by inhibiting mast cell degranulation and chemokines expression in fibroblasts. Level of Evidence: 4 Laryngoscope, 131:2413–2420, 2021 [ABSTRACT FROM AUTHOR]