Mulberry fruit polysaccharides have demonstrated excellent anti-inflammatory, antioxidant, hypolipidemic, and hypoglycemic properties. This study tested the effect of white mulberry fruit polysaccharides (WMFPs) on bl...
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Mulberry fruit polysaccharides have demonstrated excellent anti-inflammatory, antioxidant, hypolipidemic, and hypoglycemic properties. This study tested the effect of white mulberry fruit polysaccharides (WMFPs) on blood pressure. WMFPs induced endothelium-dependent relaxation in rat mesenteric arteries and NO production in endothelial cells, both of which were reversed by the NO synthase inhibitor N omega-nitro-L-arginine methyl ester hydrochloride, a phosphoinositide 3-kinase inhibitor LY294002, a cell-permeable Ca2+ chelator (1,2-bis (oaminophenoxy) ethane-N,N,N',N'-tetraacetic acid (acetoxymethyl ester)), and inhibitors of molecules downstream of NO, including the soluble guanylyl cyclase inhibitor 1H- [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, the potassium channel inhibitor tetraethylammonium chloride, the large conductance calcium-activated potassium channel-specific inhibitor iberiotoxin, and the K-ATP channel inhibitor glibenclamide. Intravenous injection of WMFPs reduced mean arterial blood pressure in both normotensive Sprague-Dawley and spontaneously hypertensive rats through enhanced endothelial NO production. This study demonstrated that WMFPs induce endothelium-dependent relaxation in rat mesenteric arteries to regulate blood pressure, suggesting that development of WMFPs as a novel antihypertensive agent is warranted.
Metastasis is the hallmark of failed tumor treatment and is typically associated with death due to cancer. Transient receptor potential (TRP) channels affect changes in intracellular calcium concentrations and partici...
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Metastasis is the hallmark of failed tumor treatment and is typically associated with death due to cancer. Transient receptor potential (TRP) channels affect changes in intracellular calcium concentrations and participate at every stage of metastasis. Further, they increase the migratory ability of tumor cells, promote angiogenesis, regulate immune function, and promote the growth of tumor cells through changes in gene expression and function. In this review, we explore the potential mechanisms of action of TRP channels, summarize their role in tumor metastasis, compile inhibitors of TRP channels relevant in tumors, and discuss current challenges in research on TRP channels involved in tumor metastasis.
Scope: Tropomyosin (TPM), an actin-binding protein widely expressed across different cell types, is primarily involved in cellular contractile processes. We investigated whether TPM3 physically and functionally intera...
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Scope: Tropomyosin (TPM), an actin-binding protein widely expressed across different cell types, is primarily involved in cellular contractile processes. We investigated whether TPM3 physically and functionally interacts with stromal interaction molecule 1 (STIM1) to contribute to vascular smooth muscle cell (VSMC) contraction, store-operated calcium entry (SOCE), and high-salt intake-induced hypertension in rats. Methods and results: Analysis of a rat RNA-seq data set of 80 samples showed that the STIM1 and Tpm3 transcriptome expression pattern is highly correlated, and co-immunoprecipitation results indicated that TPM3 and STIM1 proteins physically interacted in rat VSMCs. Immunohistochemical data displayed obvious co-localization of TPM3 and STIM1 in rat VSMCs. Knockdown of TPM3 or STIM1 in VSMCs with specific small interfering RNA significantly suppressed contractions in tension measurement assays and decreased SOCE in calcium assays. Rats fed a high-salt diet for 4 weeks had significantly higher systolic blood pressure than controls, with significantly increased contractility and markedly increased TPM3 and STIM1 expression levels in the mesenteric resistance artery (shown by tension measurements and immunoblotting, respectively). Additionally, high salt environment in vitro induced significant enhancement of TPM3 and STIM1 expression levels in VSMCs. Conclusions: We showed for the first time that TPM3 and STIM1 physically and functionally interact to contribute to VSMC contraction, SOCE, and high-salt intake-induced hypertension. Our findings provide mechanistic insights and offer a potential therapeutic target for high-salt intake-induced hypertension.
HLEpiCs were cultured with normal glucose (5.5 mM) or high glucose (25.6 mM) for 1, 3, 7, and 14 days and found that compared with the cells in normal glucose, the Ca2+ influx via SOCE was significantly increased in t...
HLEpiCs were cultured with normal glucose (5.5 mM) or high glucose (25.6 mM) for 1, 3, 7, and 14 days and found that compared with the cells in normal glucose, the Ca2+ influx via SOCE was significantly increased in the high glucose group after either thapsigargin (TG) or ATP treatment, and the increase in SOCE was greater when the high glucose treatment lasted longer (Figure 1).
[...]compared with those in the cells in normal glucose, the expression levels of Orai3 and STIM1 proteins were significantly enhanced in the cells in high glucose on each day (Figure S2A, B, and E).
The fasting blood glucose levels were significantly higher both in streptozotocin-injected Orai3–/– and wild-type rats compared to control Orai3–/– and wild-type rats (Figure 2D–G).
[...]the lens turbidity levels were markedly higher both in diabetic Orai3–/– and wild-type rats compared to control Orai3–/– and wild-type rats (Figure 2H–I), but interestingly, the lens turbidity levels were significantly lower in Orai3–/– diabetic rats compared with wild-type diabetic rats (Figure 2H–I).
[...]the results in animal models strongly suggest that Orai3 may be importantly involved in the development of DC.
In our study, we provided evidence that a high glucose environment increased the apoptotic ratio of the lens epithelial cells, which would contribute to lens opacities.
BackgroundFamilial nonmedullary thyroid cancer (FNMTC) accounts for approximately 3%-9% of all thyroid cancers;however, the mechanisms underlying FNMTC remain unclear. Environmental and genetic (especially genetic mut...
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BackgroundFamilial nonmedullary thyroid cancer (FNMTC) accounts for approximately 3%-9% of all thyroid cancers;however, the mechanisms underlying FNMTC remain unclear. Environmental and genetic (especially genetic mutation) factors may play important roles in FNMTC etiology, development, and pathogenesis. MethodsThree affected members, including two first-degree relatives, and three healthy members of a family with FNMTC were studied. We performed whole-exome and targeted gene sequencing to identify gene mutations that may be associated with FNMTC pathogenesis. The results were analyzed using Exome Aggregation Consortium data and the Genome Aggregation Database and further validated using Sanger sequencing. ResultsOf 28 pivotal genes with rare nonsynonymous mutations found, 7 were identified as novel candidate FNMTC pathogenic genes (ANO7, CAV2, KANK1, PIK3CB, PKD1L1, PTPRF, and RHBDD2). Among them, three genes (PIK3CB, CAV2, and KANK1) are reportedly involved in tumorigenesis through the PI3K/Akt signaling pathway. ConclusionWe identified seven pathogenic genes in affected members of a family with FNMTC. The PI3K/Akt signaling pathway is thought to be closely related to the development of FNMTC, and three of the susceptibility genes identified herein are associated with this pathway. These findings expand our understanding of FNMTC pathogenesis and underscore PI3K/Akt pathology as a potential therapy target.
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