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Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition encompassing metabolic dysfunction-associated steatotic liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). The heterogeneous and complex nature of MASLD complicates optimal drug development. Ebastine, an antihistamine, exhibits antitumor activity in various types of cancer. However, its effects on MASH remain unexplored. In the present study, we identified ebastine as a potential treatment for MASH. Our results indicated that ebastine acts as a novel MKRN1 inhibitor by promoting MKRN1 destabilization through self-ubiquitination, leading to AMP-activated protein kinase (AMPK) activation. Ebastine appeared to bind to the C-terminal domain of MKRN1, particularly at residues R298 and K360. Notably, Mkrn1 knockout (KO) mice demonstrated resistance to MASH, including obesity, steatosis, inflammation, and fibrosis under high-fat-high-fructose diet (HFHFD) conditions. Additionally, liver-specific Mkrn1 knockdown using AAV8 alleviated MASH symptoms in HFHFD-fed mice, implicating MKRN1 as a potential therapeutic target. Consistent with these findings, treatment with ebastine significantly reduced the risk of MASH in HFHFD-fed mice, with a decrease in MKRN1 expression and an increase in AMPK activity. Our study suggests that ebastine binds to MKRN1, promoting its destabilization and subsequent degradation by stimulating its ubiquitination. This enhances AMPK stability and activity, suppressing lipid accumulation, inflammation, and fibrosis. Moreover, the knockout of Mkrn1 mice decreased the risk of MASH, suggesting that ebastine could be a promising therapeutic agent for the treatment of MASH. [ABSTRACT FROM AUTHOR]

Purba-Barddhaman, a newly emerged district of West Bengal was surveyed for listing its odonate diversity. The district is located in southern West Bengal, and two major rivers, Damodar and Ajay, run through it. It also has a lot of small rivers, perineal and seasonal water bodies, grasslands, marshes, and agricultural fields, making it a great place for odonates. Five different sites of the district were surveyed by direct search and opportunistic sighting methods for a period of two years (March 2021 to February 2023) and odonate diversity was listed. We have found a total of 47 species belonging to 35 genera and six families from this district. The most diverse family was Libellulidae, with 24 species. A few major findings from this study were Macrogomphus montanus, Platygomphus dolabratus, Lathrecista asiatica, Libellago indica, and Agriocnemis kalinga. This is the first systematic study of odonates from this district, and it illustrates the value of this densely populated district for further exploration due to its high agricultural fertility. [ABSTRACT FROM AUTHOR]

Trigonelline, a major alkaloid component of fenugreek, has been demonstrated to have several biological activities, including antidiabetic and anticancer effects. This study aimed to examine the possible application of trigonelline as an anti‐obesity compound based on an investigation of its enhancement of lipid catabolism and induction of browning in white adipocytes. Trigonelline induces browning of 3T3‐L1 white adipocytes by enhancing the expressions of brown‐fat signature proteins and genes as well as beige‐specific genes, including Cd137, Cited1, Tbx1, and Tmem26. Trigonelline also improves lipid metabolism in white adipocytes by decreasing adipogenesis and lipogenesis as well as promotes lipolysis and fatty acid oxidation. Moreover, trigonelline increases the expression of Cox4, Nrf1, and Tfam genes that are responsible for mitochondrial biogenesis. Mechanistic studies revealed that the browning effect of trigonelline in 3T3‐L1 white adipocytes is mediated by activating β3‐AR and inhibiting PDE4, thereby stimulating the p38 MAPK/ATF‐2 signaling pathway. Considering its high bioavailability in humans and the results of this study, trigonelline may have potential as an anti‐obesity compound. [ABSTRACT FROM AUTHOR]