Progress in the Treatment of Metabolic-Related Fatty Liver Disease.

Context: Metabolic fatty liver disease (MAFLD) is a common chronic liver disease, and its incidence is increasing year by year. The existing treatments mainly include drugs, surgery, and lifestyle interventions. At present, no effective treatment exists for the disease. Objective: The review intended to examine the progress of research on MAFLD in recent years, to find a future research direction and focus and identify different therapeutic targets in the treatment of patients. Design: The research team performed a narrative review by searching Pubmed databases. The search used the keywords including metabolic-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), metabolic-associated steatohepatitis (MASH), metabolic syndrome, liver, fibrosis, and lipotoxicity. Results: The purpose of this article is to provide an overview of the recent research advancements in the treatment of MAFLD from three perspectives: drug therapy, surgical treatment, and non-drug/non-surgical treatment. The aim is to identify future research directions and key areas of focus in the management of MAFLD, as well as to determine various treatment targets for patients. Conclusions: Given the complexity of MAFLD's pathogenesis, drug therapy alone isn't ideal. In caring for patients with fatty liver, clinicians must emphasize a change in lifestyle to a healthier one. At the same time, clinicians, dieticians, psychological experts, and exercise physiologists should provide, in addition to clinical medication, multidisciplinary and cooperative efforts to help patients improve the quality of their lives through diet and exercise to control disease progression.

Asprosin contributes to nonalcoholic fatty liver disease through regulating lipid accumulation and inflammatory response via AMPK signaling.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a primary contributor to liver-related morbidity and mortality. Asprosin has been reported to be implicated in NAFLD. AIMS: This work is to illuminate the effects of Asprosin on NAFLD and the possible downstream mechanism. MATERIALS & METHODS: The weight of NAFLD mice induced by a high-fat diet was detected. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) examined serum Asprosin expression. RT-qPCR and western blot analysis examined Asprosin expression in mice liver tissues. Intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were implemented. Biochemical kits tested liver enzyme levels in mice serum and liver tissues. Hematoxylin and eosin staining evaluated liver histology. Liver weight was also tested and oil red O staining estimated lipid accumulation. RT-qPCR and western blot analysis analyzed the expression of gluconeogenesis-, fatty acid biosynthesis-, fatty acid oxidation-, and inflammation-associated factors. Besides, western blot analysis examined the expression of AMP-activated protein kinase (AMPK)/p38 signaling-associated factors. In palmitic acid (PA)-treated mice hepatocytes, RT-qPCR and western blot analysis examined Asprosin expression. Lipid accumulation, gluconeogenesis, fatty acid biosynthesis, fatty acid oxidation, and inflammation were appraised again. RESULTS: Asprosin was overexpressed in the serum and liver tissues of NAFLD mice and PA-treated mice hepatocytes. Asprosin interference reduced mice body and liver weight, improved glucose tolerance and diminished liver injury in vivo. Asprosin knockdown alleviated lipid accumulation and inflammatory infiltration both in vitro and in vivo. Additionally, Asprosin absence activated AMPK/p38 signaling and AMPK inhibitor Compound C reversed the impacts of Asprosin on lipid accumulation and inflammatory response. CONCLUSION: Collectively, Asprosin inhibition suppressed lipid accumulation and inflammation to obstruct NAFLD through AMPK/p38 signaling.

Reduced macula microvascular densities may be an early indicator for diabetic peripheral neuropathy.

Purpose: To assess the alteration in the macular microvascular in type 2 diabetic patients with peripheral neuropathy (DPN) and without peripheral neuropathy (NDPN) by optical coherence tomography angiography (OCTA) and explore the correlation between retinal microvascular abnormalities and DPN disease. Methods: Twenty-seven healthy controls (42 eyes), 36 NDPN patients (62 eyes), and 27 DPN patients (40 eyes) were included. OCTA was used to image the macula in the superficial vascular complex (SVC) and deep vascular complex (DVC). In addition, a state-of-the-art deep learning method was employed to quantify the microvasculature of the two capillary plexuses in all participants using vascular length density (VLD). Results: Compared with the healthy control group, the average VLD values of patients with DPN in SVC (p = 0.010) and DVC (p = 0.011) were significantly lower. Compared with NDPN, DPN patients showed significantly reduced VLD values in the SVC (p = 0.006) and DVC (p = 0.001). Also, DPN patients showed lower VLD values (p < 0.05) in the nasal, superior, temporal and inferior sectors of the inner ring of the SVC when compared with controls; VLD values in NDPN patients were lower in the nasal section of the inner ring of SVC (p < 0.05) compared with healthy controls. VLD values in the DVC (AUC = 0.736, p < 0.001) of the DPN group showed a higher ability to discriminate microvascular damage when compared with NDPN. Conclusion: OCTA based on deep learning could be potentially used in clinical practice as a new indicator in the early diagnosis of DM with and without DPN.

Silencing circANKRD36 inhibits streptozotocin-induced insulin resistance and inflammation in diabetic rats by targeting miR-145 via XBP1.

BACKGROUND: Diabetes mellitus (DM) is defined as a group of metabolic diseases characterized by hyperglycemia, which results from a deficiency in insulin secretion and/or insulin action. In diabetic patients, type 2 diabetes mellitus (T2DM) is in the majority. We explored the effects of circANKRD36 on streptozotocin (STZ)-induced insulin resistance and inflammation in diabetic rats with the aim of uncovering the underlying mechanism. METHODS: STZ was used to induce the in vivo T2DM rat model. After circANKRD36 interference, blood glucose, insulin and adiponectin were respectively detected. Hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) were conducted to examine inflammation and apoptosis in T2DM rats, and western blot was used for detecting apoptosis-related proteins. The binding relationships among circANKRD36, miR-145 and XBP1 were examined by luciferase reporter assay. RESULTS: Results showed that circANKRD36 was expressed at a high level in T2DM rats, while silencing circANKRD36 led to decreased blood glucose and insulin, accompanied by increased adiponectin level, and ameliorating insulin resistance. Silencing circANKRD36 alleviated the inflammation and suppressed cell apoptosis in the pancreatic tissues of T2DM rats, which was abated by miR-145 inhibitor. The binding of miR-145 to XBP1 was then confirmed. Additionally, miR-145 inhibitor increased the level of XBP1 in T2DM rats, which was decreased in the presence of circANKRD36 silencing. CONCLUSION: This study is the first to prove that silencing circANKRD36 inhibits STZ-induced insulin resistance and inflammation in diabetic rats by targeting miR- 145 via XBP1. The results warrant the importance of circRNAs as drug target and thereby pave way for the development of newer therapeutic measures for T2DM.

Upregulation of miR-146a increases cisplatin sensitivity of the non-small cell lung cancer A549 cell line by targeting JNK-2.

The aim of the present study was to investigate the effects of microRNA (miR-)146a on the cisplatin sensitivity of the non-small cell lung cancer (NSCLC) A549 cell line and study the underlying molecular mechanism. The differences in expression of miRNAs between A549 and A549/cisplatin (A549/DDP) cells were determined, and miR-146a was selected to study its effect on cisplatin sensitivity of A549/DDP cells. miR-146a mimic and inhibitor transient transfection systems were constructed using vectors, and A549/DDP cells were infected with miR-146a mimic and inhibitor to investigate growth, apoptosis and migration. The directed target of miR-146a was determined and the underlying molecular mechanism was validated in the present study. The results of the present study demonstrated that miR-146a was downregulated in NSCLC A549/DDP cells, compared with A549 cells. The overexpression of miR-146a induced apoptosis and inhibited the growth and invasion of A549/DDP cells, which resulted in increased cisplatin sensitivity in NSCLC cells. The JNK2 gene was determined as the direct target of miR-146a, and may be activated by the overexpression of miR-146a. Additionally, JNK2 activated the expression of p53 and inhibited B cell lymphoma 2. The upregulation of miR-146a increased cisplatin sensitivity of the A549 cell line by targeting JNK2, which may provide a novel method for treating NSCLC cisplatin resistance.