Int J Med Sci
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Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive impairment and memory loss, for which there is no effective cure to date. In the past several years, numerous studies have shown that increased inflammation in AD is a major cause of cognitive impairment. This study aimed to reveal 22 kinds of peripheral immune cell types and key genes associated with AD. ⋯ We also validated the key genes in an independent dataset, and found GPR174, TRAF1, ROD1, RAET1E, OR4K2, MRPL23, ARMCX5 and EDN3 were significantly different between the AD and healthy controls. Moreover, in the 5XFAD transgenic mice, the differential expression trends of Wnt7b, Gpr174, Ptbp3, Mrpl23, Armcx5 and Raet1e are consistent with them in independent dataset. Our results provided potential therapeutic targets for AD patients.
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The incidence of colorectal cancer (CRC) has increased significantly in the past decade. Early diagnosis and new therapeutics are still urgently needed for CRC in clinical practice. Human α-defensin 6 (HD6) plays a defense role against microbes in the gastrointestinal tract. ⋯ EGF treatment caused an increase of the level of serpine-1 and pEGFR levels and then increased growth activity in HD6 overexpressing cells. Together, our study shows that HD6 may compete with EGF to bind to EGFR and interrupt cancer progression in CRC. We believe these findings may give new insights for HD6 in CRC therapy.
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Wnt signaling is relevant for a wide range of biological processes, including reproductive function. The function of Wnt10a in female fertility, however, remains obscure. In the present study, we explored the structure and function of the female reproductive organs in Wnt10a knockout (KO) mice. ⋯ The expression of the ovarian cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) was significantly lower in Wnt10a KO mice. We detected no significant changes in the levels of the gonadotropins between WT and KO mice. Together, our findings indicate that deficiency of Wnt10a causes female infertility through β-catenin and Cyp19a1signaling pathways in mice.
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Postmenopausal women exhibit a higher prevalence of obesity due to decreased energy expenditure and increased food intake compared to their premenopausal counterparts. Brown adipose tissue (BAT) plays a key role in energy homeostasis, thus providing us with appealing therapeutic targets in obesity. However, how BAT proteomes are altered in response to low levels of estrogen remains unclear. ⋯ Our findings demonstrate that the proteins involved in BAT morphology, the browning of white adipose tissue, and metabolic substrates for thermogenesis were regulated by ovariectomy. The dysregulation of proteins by ovariectomy might be related to the disruption of BAT function in the postmenopausal status. Understanding how BAT proteomes are altered in response to ovariectomy may illuminate novel therapeutic strategies for the management of postmenopausal weight gain in the future.
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Background: ECM proteins are instrumental for angiogenesis, which plays momentous roles during development and repair in various organs, including post cardiac insult. After a screening based on an open access RNA-seq database, we identified Nephronectin (NPNT), an extracellular protein, might be involved in cardiac repair post myocardial infarction (MI). However, the specific impact of nephronectin during cardiac repair in MI remains elusive. ⋯ The migration and capillary-like tube formation events could be readily revoked by EGFR or STAT3 inhibition. Notably, phosphorylation of EGFR, JAK2 and STAT3 were markedly upregulated in AAV2/9-cTnT-NPNT-treated mice with MI. Conclusions: Our study thus identifies the beneficial effects of NPNT on angiogenesis and cardiac repair post MI by enhancing the EGFR/JAK2/STAT3 signaling pathway, implying the potential therapeutic application of NPNT on myocardial dysfunction post MI.