Colorectal Cancer: Pathogenesis and Targeted Therapy.

Colorectal cancer (CRC) ranks among the most prevalent malignant neoplasms globally. A growing body of evidence underscores the pivotal roles of genetic alterations and dysregulated epigenetic modifications in the pathogenesis of CRC. In recent years, the reprogramming of tumor cell metabolism has been increasingly acknowledged as a hallmark of cancer.

Regulation of histone H3K27 methylation in inflammation and cancer.

Inflammation is a multifaceted defense mechanism of the immune system against infection. Chronic inflammation is intricately linked to all stages of tumorigenesis and is therefore associated with an elevated risk of developing serious cancers. Epigenetic mechanisms have the capacity to trigger inflammation as well as facilitate tumor development and transformation within an inflammatory context.

Cholesterol overload in macrophages drives metabolic dysfunction-associated steatohepatitis via inhibiting 7-dehydrocholesterol reductase in mice.

Background: Dietary cholesterol promotes metabolic dysfunction-associated steatohepatitis (MASH), with hepatic macrophages central to disease pathology. However, the mechanisms by which cholesterol-loaded macrophages influence MASH remain unclear.

Methods: In this study, mice were fed a cholesterol-rich choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD).

Gan-Jiang-Ling-Zhu decoction improves steatohepatitis induced by choline-deficient-high-fat-diet through the METTL14/N6-methyladenosine-mediated Ugt2a3 expression.

Ethnopharmacological Relevance: Gan-Jiang-Ling-Zhu (GJLZ) decoction, a classical Chinese herbal prescription, can be applied for the treatment of metabolic diseases including liver steatosis. Although GJLZ decoction has been widely applied clinically for thousands of years, the mechanism of GJLZ decoction behind treatment of nonalcoholic steatohepatitis (NASH) remains relatively unelucidated.

Aim Of The Study: To elucidate the efficacy of GJLZ decoction in the treatment of NASH and to investigate its underlying mechanisms from an epigenetic perspective.

Protein posttranslational modifications in metabolic diseases: basic concepts and targeted therapies.

Metabolism-related diseases, including diabetes mellitus, obesity, hyperlipidemia, and nonalcoholic fatty liver disease, are becoming increasingly prevalent, thereby posing significant threats to human health and longevity. Proteins, as the primary mediators of biological activities, undergo various posttranslational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, methylation, and SUMOylation, among others, which substantially diversify their functions. These modifications are crucial in the physiological and pathological processes associated with metabolic disorders.

Copper homeostasis and cuproptosis in health and disease.

Copper is a vital trace element in human physiology, essential for the synthesis of numerous crucial metabolic enzymes and facilitation of various biological processes. Regulation of copper levels within a narrow range is imperative for maintaining metabolic homeostasis. Numerous studies have demonstrated the significant roles of copper homeostasis and cuproptosis in health and disease pathogenesis.

decoction improves steatohepatitis by regulating gut microbiota-mediated 12-tridecenoic acid inhibition.

(GJLZ) decoction is a classical traditional Chinese medicine prescription. Through invigorating , activating and dissipating , GJLZ decoction is widely applied for the treatment of chronic digestive disease, including nonalcoholic fatty liver disease. However, efficacy and mechanism of GJLZ decoction behind nonalcoholic steatohepatitis (NASH) treatment remains unelucidated.

Evaluating the efficacy of immunotherapy in gastric cancer: Insights from immune checkpoint inhibitors.

The emergence of immunotherapy, particularly immune checkpoint inhibitors (ICIs), represents a groundbreaking approach to treating gastric cancer (GC). However, the prognosis of GC patients receiving ICI treatment is influenced by various factors. This manuscript identified sarcopenia and myosteatosis as inde-pendent prognostic factors impacting the outcomes of GC patients treated with ICIs.

The role of N6-methyladenosine in macrophage polarization: A novel treatment strategy for non-alcoholic steatohepatitis.

RNA methylation modifications, as a widespread type of modification in eukaryotic cells, especially N6-methyladenosine (mA), are associated with many activities in organisms, including macrophage polarization and progression of non-alcoholic steatohepatitis (NASH). Macrophages in the liver are of diverse origin and complex phenotype, exhibiting different functions in development of NASH. In the review, we discuss the functions of mA and mA-related enzymes in macrophage polarization.

Targeted metabolomics revealed the mechanisms underlying the role of Liansu capsule in ameliorating functional dyspepsia.

Ethnopharmacological Relevance: Liansu capsule could alleviate dyspeptic symptoms; however, the mechanisms underlying its role in treating functional dyspepsia (FD) remain unclear.

Aim Of The Study: To elucidate the mechanism underlying the efficacy of Liansu capsule in alleviating FD symptoms.

Materials And Methods: Thirty-six male mice were randomly divided into the following six groups: control, model, low-strength Liansu, moderate-strength Liansu, high-strength Liansu, and domperidone groups.

Impact of smoking cessation on non-alcoholic fatty liver disease prevalence: a systematic review and meta-analysis.

Objectives: The negative effects of smoking on numerous cardiovascular and metabolic diseases have been widely acknowledged. However, the potential effect of smoking cessation is relatively unelucidated. The objective of this study is to explore whether the prevalence of non-alcoholic fatty liver disease (NAFLD) in former smokers differs from the prevalence in current smokers.

Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites.

Background: Lingguizhugan decoction is a traditional Chinese medicine prescription that has been used to improve non-alcoholic fatty liver disease and its progressive form, non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and underlying mechanisms of Lingguizhugan decoction remain unclear.

Methods: Male Sprague-Dawley rats were fed a methionine- and choline-deficient (MCD) diet to induce NASH, and then given Lingguizhugan decoction orally for four weeks.

Roles of gut microbiota and metabolites in overweight and obesity of children.

The prevalence of overweight and obesity in children and adolescents is an increasing public health problem. Pediatric overweight and obesity result from multiple factors, including genetic background, diet, and lifestyle. In addition, the gut microbiota and their metabolites play crucial roles in the progression of overweight and obesity of children.

The methyltransferase METTL3-mediated fatty acid metabolism revealed the mechanism of cinnamaldehyde on alleviating steatosis.

Background: As a primarily N6-methyladenosine methyltransferase, methyltransferase 3 (METTL3) plays a crucial role in nonalcoholic fatty liver disease. However, its regulatory mechanism in steatosis remains unknown.

Methods: Alpha mouse liver 12 (AML12) cells were induced by free fatty acids (FFA).

Recent advances in lean NAFLD.

As the predominant type of chronic liver disease, the growing prevalence of nonalcoholic fatty liver disease (NAFLD) has become a concern worldwide. Although obesity plays the most pivotal role in NAFLD, approximately 10-20% of individuals with NAFLD who are not overweight or obese (BMI < 25 kg/m2, or BMI < 23 kg/m2 in Asians) have "lean NAFLD." Lean individuals with NAFLD have a lower prevalence of diabetes, hypertension, hypertriglyceridemia, central obesity, and metabolic syndrome than nonlean individuals with NAFLD, but higher fibrosis scores and rates of cardiovascular morbidity and all-cause mortality in advanced stages.

Natural PPARs agonists for the treatment of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a general term for a series of liver diseases including simple steatosis, non-alcoholic steatohepatitis, liver fibrosis, which is closely related to metabolic syndrome. The pathogenesis of NAFLD is relatively complex, which has gradually changed from the previous 'two-hit' hypothesis to the current "multiple hits" hypothesis. However, there is currently no approved treatment for NAFLD in clinic, highlighting the urgent need for drug development.

Lingguizhugan Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects with non-alcoholic fatty liver disease: a translational approach.

Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed.

METTL3 promotes colorectal carcinoma progression by regulating the m6A-CRB3-Hippo axis.

Background: Colorectal carcinoma (CRC) is the third most common cancer and second most common cause of cancer-related deaths worldwide. Ribonucleic acid (RNA) N6-methyladnosine (m6A) and methyltransferase-like 3 (METTL3) play key roles in cancer progression. However, the roles of m6A and METTL3 in CRC progression require further clarification.

Jiangzhi Granule attenuates non-alcoholic steatohepatitis by suppressing TNF/NFκB signaling pathway-a study based on network pharmacology.

Jiangzhi Granule is a commonly used traditional Chinese medicine for treating non-alcoholic fatty liver disease. However, its key ingredients and underlying mechanisms for attenuating nonalcoholic steatohepatitis (NASH) remain unclear. To address this issue, UPLC-TOF-MS based chemical profiling, network pharmacology and animal experimental validation were employed.

CircRNA_0084927 promotes colorectal cancer progression by regulating miRNA-20b-3p/glutathione S-transferase mu 5 axis.

Background: Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related death worldwide. The 5-year survival rate of patients with early-stage CRC could reach 90%, but it is very low in patients with advanced-stage CRC. Recent studies have shown that circular RNAs play important roles in regulating the migration and invasion of CRC cells.

Quantitative Profiling of Oxylipin Reveals the Mechanism of Pien-Tze-Huang on Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is a liver disease caused by long-term alcohol consumption. ROS-mediated oxidative stress is the leading cause of ALD. Pien-Tze-Huang (PZH), a traditional formula, is famous in China.

Gut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment.

Mesalamine has been well used in the improvement of ulcerative colitis (UC) in clinics, however, the underlying mechanisms were not well illustrated. To explore its efficacy from the perspective of gut microbiota and related metabolites, we employed 16S rRNA sequencing and metabolomics approaches in stool samples across 14 normal healthy controls (NC group), 10 treatment-naïve UC patients (UC group) and 14 UC patients responded to mesalamine treatment (mesalamine group). We noted that the gut microbiota diversity and community composition were remarkably perturbed in UC group and partially restored by mesalamine treatment.