TRPC absence induces pro-inflammatory macrophage polarization to promote obesity and exacerbate colorectal cancer

During the past half-century, although numerous interventions for obesity have arisen, the condition’s prevalence has relentlessly escalated annually. Obesity represents a substantial public health challenge, especially due to its robust correlation with co-morbidities, such as colorectal cancer (CRC), which often thrives in an inflammatory tumor milieu. Of note, individuals with obesity commonly present with calcium and vitamin D insufficiencies. Transient receptor potential canonical (TRPC) channels, a subclass within the broader TRP family, function as critical calcium transporters in calcium-mediated signaling pathways. However, the exact role of TRPC channels in both obesity and CRC pathogenesis remains poorly understood. This study set out to elucidate the part played by TRPC channels in obesity and CRC development using a mouse model lacking all seven TRPC proteins (TRPC HeptaKO mice). Relative to wild-type counterparts, TRPC HeptaKO mice manifested severe obesity, evidenced by significantly heightened body weights, augmented weights of epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT), increased hepatic lipid deposition, and raised serum levels of total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C). Moreover, TRPC deficiency was accompanied by an decrease in thermogenic molecules like PGC1-α and UCP1, alongside a upsurge in inflammatory factors within adipose tissue. Mechanistically, it was revealed that pro-inflammatory factors originating from inflammatory macrophages in adipose tissue triggered lipid accumulation and exacerbated obesity-related phenotypes. Intriguingly, considering the well-established connection between obesity and disrupted gut microbiota balance, substantial changes in the gut microbiota composition were detected in TRPC HeptaKO mice, contributing to CRC development. This study provides valuable insights into the role and underlying mechanisms of TRPC deficiency in obesity and its related complication, CRC. Our findings offer a theoretical foundation for the prevention of adverse effects associated with TRPC inhibitors, potentially leading to new therapeutic strategies for obesity and CRC prevention

Effects of prescribed burning on understory Quercus species of Pinus yunnanensis forest

IntroductionPositioning studies on prescribed burning in Pinus yunnanensis forests have been conducted for several years, focusing on the effects of fire on the composition and structure, growth, regeneration, relative bark thickness, and bark density of understory oak species in Pinus yunnanensis forests.MethodsThe study was conducted on Zhaobi Mountain, Yi-Dai Autonomous County of Xinping, Yuxi City, Yunnan Province. In the prescribed burn after restoration of full 1 year of the area and did not implement the prescribed burn area were set up 10 m × 10 m sample plots 30 pairs of comparisons, and all the oak trees in the sample plots were recorded, each sample plot in the four apexes and the middle were set up five 2 m × 2 m small sample squares, the shrubs in the small sample squares for each plant survey, comparison, statistics and analysis of all data.ResultsThe study results showed that (1) prescribed burning significantly affected the species composition of the understorey of Pinus yunnanensis forests. In both tree and shrub layers, the important values of Quercus aliena, Quercus serrata, Quercus fabri, and Quercus variabilis were significantly reduced in the burned areas. In contrast, the important values of Quercus acutissima increased somewhat. (2) The under crown height of oak trees in the burned areas was significantly lower than in the burned areas, but the height of oak trees in the burned areas was not significantly different from that in the burned areas. In the shrub layer, the height and cover of oak plants in the prescribed burning areas were significantly lower than in the unprescribed burned areas, effectively reducing the vertical continuity of the forest surface combustible material and reducing the possibility of fire converting from surface to canopy fire along the “ladder fuel.” (3) The regeneration of oak plants in the burned area is mainly by sprout tillers, and very few young sprouts are regenerated by seed germination. Renewed young sprouts are difficult to survive the prescribed burn areas the following year due to their lack of fire tolerance. (4) The relative bark thickness and density of oak plants in prescribed burn areas were significantly higher than those in unprescribed burn areas due to the fire tolerance exhibited by oak plants in long-term prescribed burns.DiscussionPrescribed burning has profoundly altered the structural composition and growth of oak plants in the understory of Pinus yunnanensis forests, and oak plants have shown significant fire-adapted traits to resist fire under long-term fire disturbance. The study can provide a scientific basis for prescribed burning, forest fuels, and forest fire management

Galacto-Oligosaccharide Alleviates Alcohol-Induced Liver Injury by Inhibiting Oxidative Stress and Inflammation

Alcoholic liver disease (ALD) is a primary cause of mortality and morbidity worldwide. Oxidative stress and inflammation are important pathogenic factors contributing to ALD. We investigated the protective mechanism of galacto-oligosaccharide (GOS) against ALD through their antioxidant and anti-inflammatory activities by performing in vivo and in vitro experiments. Western blot and RT‒PCR results indicated that the expression of cytochrome P450 protein 2E1 (CYP2E1) in liver tissues and L02 cells was reduced in the GOS-treated mice compared with the model group. In addition, GOS prominently reduced the expression of Kelch-like ECH-associated protein 1 (Keap1), increased the expression of the nuclear factor erythroid-2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1) proteins, and enhanced the antioxidant capacity. In addition, GOS decreased inflammation by reducing inflammatory factor levels and inhibiting the mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. Based on these results, GOS may be a prospective functional food for the prevention and treatment of ALD

Tea (<i>Camellia sinensis</i>) Ameliorates Hyperuricemia via Uric Acid Metabolic Pathways and Gut Microbiota

Hyperuricemia (HUA) is a metabolic disease that threatens human health. Tea is a healthy beverage with an abundance of benefits. This study revealed the uric acid-lowering efficacy of six types of tea water extracts (TWEs) on HUA in mice. The results revealed that under the intervention of TWEs, the expression of XDH, a key enzyme that produces uric acid, was significantly downregulated in the liver. TWE treatment significantly upregulated the expression of uric acid secretion transporters ABCG2, OAT1, and OAT3, and downregulated the expression of uric acid reabsorption transporter URAT1 in the kidney. Furthermore, HUA-induced oxidative stress could be alleviated by upregulating the Nrf2/HO-1 pathway. The intervention of TWEs also significantly upregulated the expression of the intestinal ABCG2 protein. On the other hand, TWE intervention could significantly upregulate the expression of intestinal ABCG2 and alleviate HUA by modulating the gut microbiota. Taken together, tea can comprehensively regulate uric acid metabolism in HUA mice. Interestingly, we found that the degree of fermentation of tea was negatively correlated with the uric acid-lowering effect. The current study indicated that tea consumption may have a mitigating effect on the HUA population and provided a basis for further research on the efficacy of tea on the dosage and mechanism of uric acid-lowering effects in humans

Chinese Tea Alleviates CCl4-Induced Liver Injury through the NF-&kappa;BorNrf2Signaling Pathway in C57BL-6J Mice

Liver injury is a life-threatening condition that is usually caused by excessive alcohol consumption, improperdiet, and stressful lifestyle and can even progress to liver cancer. Tea is a popular beverage with proven health benefits and is known to exert a protective effect on the liver, intestines, and stomach. In this study, we analyzed the therapeutic effects of six kinds of tea on carbon tetrachloride (CCl4)-induced liver injury in a mouse model. The mice were injected with 10 mL/kg 5% CCl4 to induce liver injury and then given oral gavage of green tea, yellow tea, oolong tea, white tea, black tea, and dark tea, respectively. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and the expression levels of inflammation and oxidative stress-related proteins in the liver tissues were quantified. All six kinds of tea partly reduced the liver index, restored the size of the enlarged liver in the CCl4 model, and decreased the serum levels of ALT and AST. Furthermore, the highly fermented dark tea significantly reduced the expression levels of NF-&kappa;B and the downstream inflammatory factors, whereas the unfermented green tea inhibited oxidative stress by activating the antioxidant Nrf2 pathway. Taken together, tea can protect against liver inflammation, and unfermented tea can improve antioxidant levels. Further studies are needed on the bioactive components of tea to develop drugs against liver injury