Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently a pressing public health issue associated with adverse outcomes such as cirrhosis, malignancy, transplantation, and mortality. Lifestyle modifications constitute the most effective and fundamental management approach, but they often pose challenges in sustaining long-term clinical benefits. Hence, there is a critical need to enhance our understanding through pharmacological management, which unfortunately remains limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a leading treatment in the fields of diabetes and obesity, with recent preclinical and clinical studies indicating significant benefits in the management and treatment of MASLD. Our article begins by reviewing the beneficial therapeutic components of GLP-1RAs in MASLD. Subsequently, from a clinical research perspective, we concluded with the liver outcomes of current primary GLP-1RAs and co-agonists. Finally, we presented our insights on clinical concerns such as appropriate trial endpoints, management of comorbidities, and future developments. In conclusion, the benefits of GLP-1RAs in MASLD are promising, and background therapy involving metabolic modulation may represent one of the future therapeutic paradigms.

Gut dysbiosis and abnormal cytokine profiles are common in cirrhosis. This study aimed to evaluate the correlations between them.

In the blood plasma of cirrhosis patients and controls, 27 cytokines were examined using a multiplex assay. The plasma levels of nitrites (stable metabolites of the endothelial dysfunction biomarker nitric oxide) and lipopolysaccharide (LPS) were examined. The fecal microbiota was assessed by 16S rRNA gene sequencing.

Levels of IL-1b, IL-2, IL-6, IL-13, IP-10, IFN-g, TNF-a, LPS, and nitrites were higher in cirrhosis patients than in controls, while levels of IL-4, IL-7, and PDGF-BB were lower. The LPS level was directly correlated with the levels of IL-1b, IL1-Ra, IL-9, IL-17, PDGF-BB, IL-6, TNF-a, and nitrites. The nitrite level was significantly directly correlated with the levels of TNF-a, GM-CSF, IL-17, and IL-12, and inversely correlated with the IL-7 level. TNF-a levels were directly correlated with ascites severity and the abundance of Negativicutes, Enterobacteriaceae, Veillonellaceae, and Klebsiella, while inversely correlated with the abundance of Firmicutes, Clostridia, and Subdoligranulum. IFN-g levels were directly correlated with the abundance of Bacteroidaceae, Lactobacillaceae, Bacteroides, and Megasphaera, and inversely correlated with the abundance of Verrucomicrobiota, Akkermansiaceae, Coriobacteriaceae, Akkermansia, Collinsella, and Gemella. IL-1b levels were directly correlated with the abundance of Comamonadaceae and Enterobacteriaceae and inversely correlated with the abundance of Marinifilaceae and Dialister. IL-6 levels were directly correlated with the abundance of Enterobacteriaceae, hepatic encephalopathy, and ascites severity, and inversely correlated with the abundance of Peptostreptococcaceae, Streptococcaceae, and Streptococcus.

The abundance of harmful gut microbiota taxa and endotoxinemia directly correlates with the levels of proinflammatory cytokines.

The overwhelming majority of genes in the human genome encode RNA molecules that are not translated into proteins. These RNA molecules are named non-coding RNAs (ncRNAs). ncRNAs play a crucial role in the regulation of gene expression and abnormalities in ncRNAs can cause disease progression, including atherosclerosis. ncRNAs regulate different stages of atherosclerosis progression, such as foam cell formation and lipid metabolism. Diverse types of ncRNAs have been studied, but the best known and widely used are small non-coding (sncRNAs), specifically microRNAs and small interfering RNAs, which are ∼22 nucleotides long. The majority of drugs based on ncRNAs are composed of sncRNAs. There is strong evidence that besides sncRNAs, other types of ncRNAs, such as long ncRNAs and circular RNAs, take part in the regulation of gene expression. This review summarized recent advances in ncRNAs and atherosclerosis.

Fuzi, the processed product of daughter roots of Aconitum carmichaelii Debx., is a well-known Chinese medicine for the treatment of heart failure (HF) and related cardiac diseases. This study aimed to investigate the molecular mechanism of the cardioprotective effects of Fuzi water decoction (FWD) and Fuzi water-soluble alkaloids (FWA) on the model of HF.

The HF model of rats was prepared through intravenous injection of propafenone hydrochloride. The normal group, model group, FWD-treated groups (1.25 g/kg, 2.5 g/kg, 5 g/kg) and positive group (Shenfu Injection, 3.3 mL/kg) were set up. Heart rate, LV+dp/dtmax, and LV-dp/dtmax were recorded at 5 m, 10 m, 20 m, 30 m, and 60 m after drug administration, respectively. The contents of atrial natriuretic peptide, brain natriuretic peptide (BNP), angiotensin II, and aldosterone in serum were determined 20 m post-administration. An in vitro cardiomyocyte hypertrophy model with HDAC2 overexpression was constructed and verified by lentivirus transfection. The experiment included a blank group, FWD-treated groups (3 mg/mL, 1.5 mg/mL), and FWA-treated groups (4 mg/mL, 2 mg/mL). For transcriptome analysis, the model group, blank group, and FWD-treated group (2.5 g/kg) at 20 m and 60 m in vivo, and different dose groups in vitro, were selected to analyze the therapeutic mechanisms of FWD and FWA.

All FWD treatment groups showed an increased heart rate, among which the groups with 2.5 g/kg and 5 g/kg FWD showed better effects, significantly increasing LV+dp/dtmax and LV-dp/dtmax after 20 m of administration and significantly reducing BNP and aldosterone serum levels. In the constructed cardiomyocyte hypertrophy model, HDAC2 expression, atrial natriuretic peptide and BNP protein levels, and cell surface area increased. Transcriptome data from both in vivo and in vitro showed that FWD and FWA could exert cardioprotective effects through pathways such as the PI3K-Akt signaling pathway, NF-κB signaling pathway, and ATP-binding cassette (ABC) transporters, involving key genes such as ITGB1, TLR2, and CDKN1A. Fuzi inhibited the hypertrophic gene HDAC2. Additionally, based on weighted gene co-expression network analysis, ABC transporters may be an important molecular pathway for FWA in treating HF.

Both FWD and FWA can ameliorate HF by regulating apoptosis, proliferation, and anti-fibrosis, with ABC transporters potentially being the main pathway for the action of FWA.

Huaier (Trametes robiniophila Murr) is a traditional Chinese medicine with a clinical application history of over 1,000 years. Its chemical components mainly include polysaccharides, sterols, and alkaloids. Huaier has been shown to demonstrate potent antitumor effects in a variety of cancer types, including breast cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, and others. In recent years, multiple in-vitro experiments have confirmed the good antitumor effect of Huaier and its mechanism of action, such as inhibiting proliferation, inducing apoptosis and oxidative stress, interfering with cell cycle arrest, inhibiting tumor metastasis and angiogenesis, inducing autophagy, and regulating immune function. In addition, multiple in-vivo studies and clinical trials have demonstrated the multidimensional antitumor potential of Huaier, such as slowing tumor progression, reversing drug resistance, improving chemotherapy drug sensitivity, and extending the survival time of cancer patients. In this article, the extraction methods of Huaier and its properties for the treatment of many cancers are reviewed. Moreover, the current molecular mechanisms of Huaier are summarized, revealing that it has great potential as an anticancer drug and providing strong theoretical support for related research. Furthermore, this review also provides suggestions for further research on the anticancer effects of Huaier, hoping to offer fresh perspectives for researchers in the realm of anticancer medicine.

A mental disorder, also referred to as a psychiatric disorder or mental illness, is characterized by significant disturbances in an individual’s thinking, emotions, or behavior. In Ayurveda, herbal plants are used as alternative therapies for various ailments, including mental disorders. This review aims to provide a comprehensive overview of herbal medicines used in treating mental disorders in Sri Lanka. It relies on foundational books as primary sources to systematically identify and analyze the therapeutic potential of 24 traditional medicinal plants for treating mental disorders. Each plant was evaluated based on its scientific name, plant parts used, distribution in Sri Lanka, mechanisms of action, and identified phytochemicals. Furthermore, additional research was conducted using keywords such as mental disorders, herbal plants, plant distribution, phytochemicals, side effects, and mechanism of action through scientific databases. The phytochemicals present in these herbal plants possess antioxidant, anti-inflammatory, and neuroprotective properties, contributing to their potential antipsychotic activities. Trigonelline (from Abrus precatorius), bacosides (from Bacopa monnieri), asiaticoside and asiatic acid (from Centella asiatica), quercetin (from Ginkgo biloba), alliin and allicin (from Allium sativum), luteolin-7-O-glucoside (from Eclipta alba), and shogaol (from Zingiber officinale) demonstrate significant potential in modulating neurotransmitter levels, reducing oxidative stress, and alleviating symptoms associated with mental disorders such as depression, anxiety, and neurodegenerative diseases. The suggested therapeutic value of these identified herbal plants and their bioactive phytochemicals indicates the need for preserving and extensively investigating these remedies to establish their clinical effectiveness.

Environmental factors such as heavy metals can influence the gene expression profiles that can lead to diseases. MicroRNAs (miRNAs) are primary regulatory molecules related to health and disease that are sensitive to environmental factors. Several studies have shown an association between environmental exposure to toxic metals such as cadmium (Cd) and disease risk. Growing knowledge has shown that heavy metal toxicity can manifest through miRNAs. Therefore, dysregulated miRNAs are proposed as potential biomarkers for monitoring chronic metal exposure. This review aimed to evaluate the effect of Cd on changes in miRNA expression. The databases of PubMed, Web of Science (ISI), Scopus, and Google Scholar were systematically searched for all previous relevant articles from 2000 up to 2022. The following medical subject headings were used: (microRNAs OR miRs) AND (Heavy Metals OR Cadmium OR Cd) AND (miRs profile OR miRs Expression). Searched articles were divided into the categories of in vitro, in vivo, and human studies. MiRNAs, widely used for biomarker discovery in Cd-induced diseases, are still being researched to use these genes for reliable biomarker discovery in addition to current diagnostic and prognostic approaches. As the functional effects of miRNAs are by their target proteins, it is important to analyze the expression levels of multiple potential target proteins to fully understand the role and mechanism of miRNAs in Cd-induced diseases. Therefore, further investigations are required to understand the regulatory mechanisms of miRNAs and to obtain novel biomarkers, and these findings will be used to develop early diagnostic approaches as well as new preventive methods and treatment options for Cd-induced diseases.

The liver plays a crucial role in maintaining whole-body homeostasis in both health and disease, engaging in important communication with other organs. The coordination of multiple signaling pathways is essential for facilitating such interorgan communication. Among these pathways, the transforming growth factor-β (TGF-β) and HIPPO signaling pathways serve critical functions as tumor suppressors, exerting pivotal control over liver development, size, and tissue regeneration. In the normal hepatic context, these pathways exhibit significant crosstalk through various molecular mechanisms. This interaction is context-dependent within the hepatic microenvironment, regulating diverse cellular processes from development to adulthood. Disruptions in the regulation of these pathways and their crosstalk contribute to the onset of liver diseases. This review delves into the intricate interplay between the canonical pathways of TGF-β and HIPPO, exploring their involvement in liver development and various pathologies such as fibrosis, cirrhosis, and tumorigenesis. Special attention is given to their impact on the epithelial-to-mesenchymal transition process, a crucial element associated with liver wound healing and cancer metastasis. By addressing these molecular interactions, the review aimed to provide insights into the underlying mechanisms that influence liver physiology and pathology, offering potential avenues for therapeutic interventions.

Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease caused by autoimmune reactions, with an unknown etiology. If left untreated, it can progress to cirrhosis, liver failure, or even death. While most patients respond well to first-line treatments, a significant number experience poor responses or intolerance, requiring the use of second- or third-line therapies. Ongoing research into the pathogenesis of AIH is leading to the development of novel therapeutic approaches. This review summarized recent advancements in the treatment of AIH both domestically and internationally.