To determine the expressions of Tbx3, a member of subgroup belonging to T-box family, and its prognostic value in pancreatic carcinoma. We determined the expression levels of Tbx3 on both mRNA and protein levels in 30 pairs of fresh tumor tissues and paratumor tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. In addition, protein level of Tbx3 were identified using immunochemistry in 80 pairs of paraffin-embedded specimen. The correlations between Tbx3 expression and various clinicopathological parameters as well as overall survival were evaluated. Tbx3 mRNA and protein levels in tumor tissues were significantly higher than in the paratumor tissues by qRT-PCR (0.05 ±0.007 vs. 0.087±0.001, p<0.001) and western blotting (1.134±0.043 vs. 0.287±0.017, p<0.001). The statistical analysis based on immunohistochemical evaluation suggested that Tbx3 aberrant expression was significantly associated with several conventional clinicopathological variables, such as gender, age, tumor position, preoperative CA19-9 level, pathological T staging and N staging. Univariate and multivariate analyses revealed that Tbx3 expression was an independent prognostic factor for overall survival (<0.001). Our results suggest that overexpression of Tbx3 is associated with poor prognosis of pancreatic cancer patients. However, additional clinical trials are needed to accurately validate this observation.

Context: With aging, various problems in the reproductive system emerge, especially in females. However, our understanding of reproductive aging in livestock and humans is limited. Aims: We aimed to investigate reproductive changes between young and aged mice. Methods: Eight- to ten-week-old female mice were used as the young group, and 10-month-old mice were studied as the aged group. Reproductive changes were investigated from physiological, histological, cytological, and epigenetic perspectives. Key results: The estrus cycle was shortened (P < 0.0001), and the estradiol (E2) concentration was lower in aged mice (P < 0.01), whereas the progesterone (P4) concentration did not differ between young and aged mice (P > 0.05). The histological results revealed a lower number of antral follicles in the ovary and disordered epithelial tissue structures in the oviducts in aged mice. During oogenesis, the surrounded nucleolus (SN)-type oocytes in aged mice exhibited increased mitochondrial agglutination (P < 0.05) and cellular apoptosis (P < 0.01) as well as decreased H3K36 triple-methylation (P < 0.001). Although many defects existed, the oocytes from aged mice could normally support cellular reprogramming after somatic cell nuclear transfer. Conclusions: Our results indicate that the reduced levels of reproductive hormones in aged females lead to shorter estrus cycles and reduced follicular development, leading to abnormal oogenesis, particularly in SN-type immature oocytes. Implications: These results provide new insight that enhance our understanding and improve the reproductive ability of aged females.

Objectives: Postmenopausal osteoporosis is the most common form of osteoporosis in clinical practice, affecting millions of postmenopausal women worldwide. Postmenopausal osteoporosis demands safe and effective therapies. This study aimed to evaluate the potential of hederagenin (Hed) for treating osteoporosis and to elucidate its underlying mechanisms of action. Methods: The anti-osteoporotic potential of Hed was assessed by investigating its effects on ovariectomy (OVX)-induced bone loss in mice and on receptor activator of NF-kappaB ligand (RANKL)-induced osteoclast differentiation in RAW264.7 cells. Network pharmacology analysis and molecular docking were employed to identify key targets, which were subsequently validated experimentally. Results: In vitro, Hed suppressed osteoclastogenesis by inhibiting the formation of osteoclasts and F-actin rings and by down-regulating osteoclast-specific genes (Atp6v0d2 and Acp5). In vivo, Hed significantly ameliorated OVX-induced bone loss, restoring trabecular bone volume fraction (BV/TV) and trabecular number (Tb.N), while reducing trabecular separation (Tb.Sp). Network pharmacology analysis identified 142 overlapping targets linking Hed to osteoporosis, including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-1β, with enrichment in innate immune signaling and osteoclast differentiation. Molecular docking analysis indicated strong binding affinities between Hed and targets such as TNF-α, IL-6, and IL-1β. Experimentally, Hed was found to decrease RANKL, elevate osteoprotegerin (OPG), and suppress intestinal mRNA levels of pro-inflammatory cytokines such as IL-1β, IL-6, IL-17A, and TNF-α. Conclusion: Hed exerts significant anti-osteoporotic effects in OVX-induced osteoporosis through a dual mechanism involving the suppression of both osteoclastogenesis and innate immune signaling pathways. These findings highlighted Hed’s novel role in modulating immune-bone crosstalk, offering a promising strategy for treating osteolytic diseases without estrogenic side effects.