Int J Med Sci
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Zuojin Pill (ZJP) is a traditional herbal preparation used to treat various gastrointestinal (GI) disorders. The purpose of this study was to elucidate the underlying cellular and molecular mechanisms by evaluating the effects of ZJP on the pacemaker activity of isolated interstitial cells of Cajal (ICCs) and on in vivo GI motility in mice. We isolated ICCs from mouse small intestine and measured pacemaker potentials by whole-cell patch clamping as well as intracellular calcium signaling by microfluorometry. ⋯ Furthermore, ZJP reversed the reduction of ITR caused by loperamide (Imodium) and normalized the ITR abnormality of two etiologically distinct GI motility disorder (GMD) mouse models. Finally, ZJP increased serum concentrations of the pro-peristalsis factors motilin and substance P. Our results suggest that ZJP depolarizes ICCs via 5-HT4 or muscarinic M3 receptor activation and G-protein dependent calcium-, PLC-, inositol triphosphate-, and MAPK signaling pathways (but not PKC-dependent pathways), leading to enhanced GI motility.
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Estradiol (E2) deficiency arising from menopause is closely related to changes in body composition and declines of muscle mass and strength in elderly women. Whole-body vibration training (WBV) is an emerging approach expected to improve muscle mass and strength of older person, but the underlying mechanisms remain unclear. ⋯ We found that (1) WBV, E2 supplementation (E) and WBV combined with E2 supplementation (WBV+E) significantly increased serum estradiol content, quadriceps muscle mass and grip strength in ovariectomized mice, accompanied with alterations of body composition (reducing fat content, increasing lean body mass and lean percent), furthermore, the altered degrees of these indicators by WBV+E were greater than WBV alone; (2) WBV, E and WBV+E remarkably increased the activities of Akt and mTOR and decreased FoxO1 activity, and the changed degrees by WBV+E were greater than WBV alone; (3) Pearson correlation coefficient revealed that serum estradiol content was positively correlated with Akt and mTOR activities, while inversely associated with FoxO1 activity. We concluded that WBV could significantly increase muscle mass and strength in ovariectomized mice, which might achieve through activating Akt-mTOR and suppressing FoxO1 signal pathways, and the improving effect of WBV on muscle mass and strength was better when in the presence of estrogen.
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Background: Sepsis is a lethal disease due to uncontrolled inflammatory responses. Macrophages play an important role in sepsis-associated inflammation. Jing Si Herbal Tea (JSHT) is a plant-based regimen with anti-inflammatory properties designed to treat respiratory diseases; however, its underlying therapeutic mechanism remains unclear. ⋯ RAW264.7 cells exhibited filopodia protruding from the cell surface in the LPS group, which were inhibited in the Pre-JSHT and Post-JSHT groups. Conclusions: LPS induced M1 polarization with elevated inflammatory signaling and cytokine levels, while JSHT not only decreased M1 polarization but also promoted M2 polarization with decreased inflammatory responses. We propose JSHT as a potential anti-inflammatory agent against LPS-induced inflammation.
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Background: Intrahepatic cholangiocarcinoma (ICC), one type of highly malignant tumor, has a poor prognosis. However, the specific role of the polycystic kidney and hepatic disease 1 (PKHD1) gene in ICC has not yet been evaluated. This study aimed to investigate the potential function and mechanism of the PKHD1 gene in ICC. ⋯ At the same time, the expressions of Notch pathway-related proteins were dramatically increased in PKHD1(-/+) ICC cells (P<0.001). Moreover, tumor proliferation, migration, and invasion were promoted in loss-of-function experiments in vitro and in vivo, which was partially reversed by DAPT. Conclusions: PKHD1 inhibits the proliferation, migration, and invasion of ICC, and the Notch pathway may be the downstream mechanism of the negative regulatory effect of PKHD1 during the progression of ICC.
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MAPKK4 has been implicated in the pathological mechanisms underlying myocardial and vascular injury, specifically influencing endothelial cell damage and programmed cell death via subcellular pathways. Nevertheless, the regulatory role of MAPKK4 in coronary microvascular injury following myocardial infarction remains unconfirmed, and the exploration of targeted mitochondrial protective therapeutic agents remains unaddressed. In light of this gap, we established a MAPKK4 gene-modified mouse model of ischemia-reperfusion injury and employed Buyang Huanwu decoction (BYHW), a traditional cardiovascular therapeutic formula, to assess its efficacy in treating coronary microvascular injury post-ischemia-reperfusion. ⋯ Therapeutically, MAPKK4 may potentiate the apoptotic pathway in microvascular endothelial cells by modulating downstream P38 expression and phosphorylation, thereby exacerbating ischemia-reperfusion-induced coronary microvascular endothelial injury. From an in vivo perspective, the transgenic overexpression of MAPKK4 and P38 inhibited the microvascular protective effects of BYHW. These findings collectively underscore the significance of the MAPKK4-P38 axis in the protection of coronary microvascular endothelial cells.