Low‐level of chronic inflammation activation is characteristic of obesity. Nonalcoholic fatty liver disease (NAFLD) is closely linked to obesity and is an emerging health problem, it originates from abnormal accumulation of triglycerides in the liver, and sometimes causes inflammatory reactions that could contribute to cirrhosis and liver cancer, thus its pathogenesis needs to be clarified for more treatment options. Once NAFLD is established, it contributes to systemic inflammation, the low‐grade inflammation is continuously maintained during NAFLD causing impaired resolution of inflammation in obesity, which subsequently exacerbates its severity. This study focuses on the effects of obesity‐induced inflammations, which are the underlying causes of the disease progression and development of more severe inflammatory and fibrotic stages. Understanding the relationship between obesity and NAFLD could help in establishing attractive therapeutic targets or diagnostic markers in obesity‐induced inflammation response and provides new approaches for the prevention and treatment of NAFLD in obesity.

Senescence is a result of cellular stress and is a potential mechanism for regulating cancer. As a member of the mitogen‑activated protein kinase family, ERK1/2 (extracellular signal‑regulated protein kinase) has an important role in delivering extracellular signals to the nucleus, and these signals regulate the cell cycle, cell proliferation and cell development. Previous studies demonstrated that ERK1/2 is closely associated with cell aging; however other previous studies suggested that ERK1/2 exerts an opposite effect on aging models and target proteins, even within the same cell model. Recent studies demonstrated that the effect of ERK1/2 on aging is likely associated with its target proteins and regulators, negative feedback loops, phosphorylated ERK1/2 factors and ERK1/2 translocation from the cytoplasm to the nucleus. The present review aims to examine the mechanism of ERK1/2 and discuss its role in cellular outcomes and novel drug development.

Curcumin has been reported to have activity for prevention and therapy of CRC, yet its underlying mechanisms remain largely unknown. Recently, emerging evidence suggests that the gut microbiota and its metabolites contribute to the causation and progression of Colorectal cancer (CRC). In this study, we aimed to investigate if curcumin affects the tumorigenesis of CRC by modulating gut microbiota and its metabolites. Forty male C57BL/6JGpt mice were randomly divided into four groups: negative control (NC), curcumin control, CRC model, and curcumin treatment (CRC-Cur) groups. CRC mouse model was induced by using azoxymethane (AOM) and dextran sodium sulfate (DSS), and the mice in CRC model and curcumin treatment groups received oral PBS or curcumin (150 mg/kg/day), respectively. Additionally, fecal samples were collected. 16 S rRNA sequencing and Liquid Chromatography Mass Spectrometry (LC-MS)-based untargeted metabolomics were used to observe the changes of intestinal flora and intestinal metabolites. Curcumin treatment restored colon length and structural morphology, and significantly inhibited tumor formation in AOM/DSS-induced CRC model mice. The 16S rRNA sequencing analysis indicated that the diversity and richness of core and total species of intestinal microflora in the CRC group were significantly lower than those in the NC group, which were substantially restored in the curcumin treatment group. Curcumin reduced harmful bacteria, including Ileibacterium, Monoglobus and Desulfovibrio, which were elevated in CRC model mice. Moreover, curcumin increased the abundance of Clostridia_UCG-014, Bifidobacterium and Lactobacillus, which were decreased in CRC model mice. In addition, 13 different metabolites were identified. Compared to the NC group, ethosuximide, xanthosine, and 17-beta-estradiol 3-sulfate-17-(beta-D-glucuronide) were elevated in the CRC model group, whereas curcumin treatment significantly reduced their levels. Conversely, glutamylleucine, gamma-Glutamylleucine, liquiritin, ubenimex, 5’-deoxy-5’-fluorouridine, 7,8-Dihydropteroic acid, neobyakangelicol, libenzapril, xenognosin A, and 7,4’-dihydroxy-8-methylflavan were decreased in the CRC group but notably upregulated by curcumin. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed enrichment in seven pathways, including folate biosynthesis (P < 0.05). The gut microecological balance was disrupted in AOM/DSS-induced CRC mice, accompanied by metabolite dysbiosis. Curcumin restored the equilibrium of the microbiota and regulated metabolites, highly indicating that curcumin may alleviate the development of AOM/DSS induced colorectal cancer in mice by regulating intestinal flora homeostasis and intestinal metabolites.

Background: Inflammatory bowel disease (IBD) is an increasingly common and globally emergent immune-mediated disorder. The etiology of IBD is complex, involving multiple factors such as immune dysregulation, environmental factors, genetic mutations, and microbiota dysbiosis, exacerbated by a lack of effective clinical therapies. Recently, studies hypothesized that dysbiosis of intestinal flora might participate in the onset of IBD. Metformin is widely used to treat type 2 diabetes and has shown beneficial effects in mouse models of IBD, although its underlying mechanisms remain poorly understood. Accumulating studies found that metformin shows beneficial effects for diabetes by affecting microbiota composition. This study explores possible regulatory effects of metformin on intestinal microecology during treatment for IBD.Methods: Inflammation was induced using 3% Dextran Sulfate Sodium (DSS) solution to generate mice models of IBD. Metformin treatments were assayed by measuring body weights and colon lengths of mice and H&E staining to observe histological effects on colon tissue structures. Changes in bacterial community composition and diversity-related to IBD and metformin treatment were assessed by high-throughput metagenomic sequencing analysis.Results: Metformin administration significantly ameliorated body weight loss, inhibited colon shrinking, and contributed to preserving the integrity of colon histological structures. The gut microbiota profiles revealed that the biodiversity of intestinal flora lost during inflammation was restored under metformin treatment. Metformin administration was also associated with decreased pathogenic Escherichia shigella and increased abundance of Lactobacillus and Akkermansia.Conclusion: Metformin appears to induce anti-inflammatory effects, thus ameliorating colitis symptoms, concurrent with enrichment for beneficial taxa and restored microbial diversity, suggesting a viable strategy against IBD.

Adenine monophosphate‐activated protein kinase (AMPK) is a fuel sensing enzyme that is activated in shortage of energy and inhibited in its surplus. Cancer is a metabolic disease characteristic of aerobic glycolysis, namely Warburg effect, and possesses heterogeneity featured by spatiotemporal hypoxia and normoxia, where AMPK is deeply implicated. The present study delineates the regulation of mitochondrial functions by AMPK in cancer cells. On the one hand, AMPKα subunit binds to mitochondria independently of β subunit and targeting AMPK to mitochondria facilitates oxidative phosphorylation and fatty acid oxidation, and inhibits glycolysis. As such, mitochondrial AMPK inhibits the growth of cancer cells and tumorigenesis. On the other hand, ablation of the β subunits completely abolishes AMPK activity and simultaneously leads to decreases in mitochondria DNA and protein contents. The effect of the β deletion is rescued by overexpression of the active mutant of bulky AMPKα1 subunit. In conjunction, the transcriptional factors PGC1α and Nrf‐1 are up‐regulated by LKB1/AMPK, an event that is abolished in the absence of the β subunits. Intriguingly, the stimulation of mitochondria biogenesis is not achieved by mitochondria‐targeted AMPK. Therefore, our study suggests that AMPK inhibits cancer cell growth and tumorigenesis via regulation of mitochondria‐mediated metabolism.

Age-related macular degeneration (AMD) is one of the major causes of irreversible blindness among aging populations in developed countries and can be classified as dry or wet according to its progression. Wet AMD, which is characterized by angiogenesis on the choroidal membrane, is uncommonly seen but more severe. Controlling or completely inhibiting the factors that contribute to the progression of events that lead to angiogenesis may be an effective strategy for treating wet AMD. Emerging evidence has shown that transforming growth factor-β (TGF-β) signaling plays a significant role in the progression of wet AMD. In this review, we described the roles of and changes in TGF-β signaling in the development of AMD and discussed the mechanisms of the TGF-β superfamily in choroidal neovascularization (CNV) and wet AMD, including the modulation of angiogenesis-related factors, inflammation, vascular fibrosis, and immune responses, as well as cross-talk with other signaling pathways. These remarkable findings indicate that TGF-β signaling is a potential target for wet AMD treatment.