Global burden of non-alcoholic fatty liver disease in 204 countries and territories from 1990 to 2019.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic linked to metabolic disease and is the most prevalent cause of chronic liver disease. We, therefore, designed the study to analyze the global and regional burden of NAFLD from 1990 to 2019. METHODS: We collected data on NAFLD from the Global Burden of Disease study 2019, aiming to conduct a systematic assessment of the changes and trends in NAFLD in 204 countries. Secondary analysis of NAFLD was conducted using age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) to show the changing trends and development characteristics. Data statistics and visualization were executed with the R program. RESULTS: Globally, incidence, deaths and disability-adjusted life years (DALYs) of NAFLD all showed an upward trend. Between 1990 and 2019, the incidence of NAFLD increased by 95.4%, from 88,177 to 172,330 cases. Meanwhile, the ASIR of the middle SDI region had the highest increase, followed by the low-middle SDI region. Of all countries, the most incident cases were in China, which accounted for approximately 23.6% of NAFLD. China was also the country with the largest cases of deaths and DALYs. And behavioral risk, metabolic factors, smoking and high fasting plasma glucose were the critical risk factors associated with the mortality and DALYs of NAFLD. CONCLUSION: NAFLD has become a considerable health burden in many countries. Therefore, we should control the risk factors of NAFLD and take corresponding measures to achieve its early prevention and treatment.

The Therapeutic Potential of Mesenchymal Stem Cells in the Treatment of Diabetes Mellitus.

Mesenchymal stem cells (MSCs) exist in many tissues and can differentiate into cells of multiple lineages, such as adipocytes, osteoblasts, or chondrocytes. MSC administration has demonstrated therapeutic potential in various degenerative and inflammatory diseases (e.g., graft-vs.-host disease, multiple sclerosis, Crohn's disease, organ fibrosis, and diabetes mellitus [DM]). The mechanisms involved in the therapeutic effects of MSCs are multifaceted. Generally, implanted MSCs can migrate to sites of injury, where they establish an anti-inflammatory and regenerative microenvironment in damaged tissues. In addition, MSCs can modulate innate and adaptive immune responses through immunosuppressive mechanisms that involve immune cells, inflammatory cytokines, chemokines, and immunomodulatory factors. DM has a high prevalence worldwide; it also contributes to a high rate of mortality worldwide. MSCs offer a promising therapeutic agent to prevent or repair damage from DM and diabetic complications through properties such as multilineage differentiation, homing, promotion of angiogenesis, and immunomodulation (e.g., prevention of oxidative stress, fibrosis, and cell death). In this study, we review current findings regarding the immunomodulatory and regenerative mechanisms of MSCs, as well as their therapeutic applications in DM and DM-related complications.

Thyroid Cancer and COVID-19: Prospects for Therapeutic Approaches and Drug Development.

Thyroid cancer is the most prevalent endocrine malignancy and the reported incidence of thyroid cancer has continued to increase in recent years. Since 2019, coronavirus disease 2019 (COVID-19) has been spreading worldwide in a global pandemic. COVID-19 aggravates primary illnesses and affects disease management; relevant changes include delayed diagnosis and treatment. The thyroid is an endocrine organ that is susceptible to autoimmune attack; thus, thyroid cancer after COVID-19 has gradually attracted attention. Whether COVID-19 affects the diagnosis and treatment of thyroid cancer has also attracted the attention of many researchers. This review examines the literature regarding the influence of COVID-19 on the pathogenesis, diagnosis, and treatment of thyroid cancer; it also focuses on drug therapies to promote research into strategies for improving therapy and management in thyroid cancer patients with COVID-19.

The impact of exposure to environmental contaminant on hepatocellular lipid metabolism.

Increasing evidences show that ubiquitous perfluorooctanoic acid (PFOA), a representative environmental pollutant, is found to be linked to lipid dysmetabolism. However, the biological mechanism behind this outcome remains uninvestigated. In the present study, we established the PFOA-injured liver in mice to explore the underlying mechanism associated with PFOA-induced lipid disturbance in the liver via a group of biochemical and molecular assays. As results, PFOA-exposed mice showed increased transaminase (ALT), reduced triglyceride and free fatty acid contents in serum, as well as elevated level of hepatic triglyceride. Morphologically, PFOA-exposed mice displayed visible vacuolation in cytoplasm and abnormal cytoarchitecture in liver. In addition, PFOA-exposed liver showed up-regulated expressions of lipid-uptake associated mRNA of hepatic lipoprotein lipase (LPL) and fatty acid translocase (CD36) and down-regulated expression of lipid-uptake associated mRNA of apolipoprotein-B100 (APOB). Moreover, validated data from immunohistochemistry and immunoblotting found that hepatocellular LPL and CD36 proteins were increased dose-dependently, and lowered expression of hepatic APOB was observed. In conclusion, our current findings reveal that PFOA-induced lipid dysmetabolism in the liver is involved to dysregulation of fatty acid trafficking.

Induction of haemeoxygenase-1 improves FFA-induced endothelial dysfunction in rat aorta.

BACKGROUND: The induction of haemeoxygenase-1 (HO-1) exerts beneficial effects in the setting of endothelial dysfunction in obesity. High free fatty acid (FFA) levels are a common feature of obesity and are the primary cause of endothelial dysfunction. The objective of our study was to explore the effects of HO-1 induction on FFA-induced endothelial dysfunction in rats. METHODS: Rats received FFA treatment with either cobalt protoporphyrin (CoPP) to induce HO-1 or stannous protoporphyrin (SnPP) to inhibit HO-1. Endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV). Nitric oxide (NO) production, superoxide production and nuclear factor (NF)-κB expression in the aorta were each determined. The levels of adenosine monophosphate (AMP)-activated kinase (AMPK) and endothelial nitric oxide synthase (eNOS) expression in endothelial cells were determined via Western blotting. RESULTS: Induction of HO-1 by CoPP decreased circulating FFA, high-sensitivity C-reactive protein and malondialdehyde levels and increased serum adiponectin and glutathione levels compared with the FFA group (P<0.05). High FFA levels resulted in EDV impairment, which was improved by HO-1 induction (P<0.05). Induction of HO-1 increased NO levels and reduced aortic superoxide production and NF-κB expression compared with the FFA group. The FFA group exhibited decreased AMPK expression and eNOS phosphorylation, both of which were enhanced via HO-1 induction (P<0.05). The beneficial effects of CoPP on EDV were partially attenuated in vitro in the presence of inhibitors of AMPK, phosphatidylinositol 3-kinase (PI3K), and eNOS. CONCLUSIONS: HO-1 induction with CoPP improves FFA-induced endothelial dysfunction in the rat aorta. The protective mechanism appears to be related to the activation of the AMPK-PI3K-eNOS pathway as a result of increased adiponectin levels as well as decreased inflammation and oxidative stress.

Effect of 3,4-dihydroxyacetophenone on endothelial dysfunction in obese rats.

CONTEXT: 3,4-Dihydroxyacetophenone (DHAP) has been reported to possess cardiovascular pharmacological effects. OBJECTIVE: This study was designed to determine whether DHAP could improve endothelial function in obese rats. MATERIALS AND METHODS: Wistar rats were randomly divided into control, obesity, and DHAP groups and fed a normal, high-fat, and high-fat plus DHAP (10 mg kg(-1) d(-1)) diet, respectively, for 8 weeks. Endothelial-dependent vasodilatation was assessed. Endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production in endothelial cells were determined. Nuclear transcription factor kappa B (NF-κB) expression and superoxide production in aorta were evaluated. RESULTS: DHAP treatment significantly decreased plasma triglycerides (0.94 ± 0.31 mmol/l versus 1.36 ± 0.29 mmol/l, p < 0.05) and free fatty acids (0.53 ± 0.15 mmol/l versus 0.99 ± 0.24 mmol/l, p < 0.05), reduced serum tumor necrosis factor α (35.56 ± 9.28 pg/ml versus 68.3 ± 10.24 pg/ml, p < 0.05) and malondialdehyde (2.94 ± 0.58 pg/ml versus 6.45 ± 0.70 pg/ml, p < 0.05), and increased serum adiponectin levels (164.5 ± 34.5 µg/l versus 84.5 ± 20.4 µg/l, p < 0.05). DHAP enhanced endothelial-dependent vasodilatation and improved endothelial function in obese rats (p < 0.05). eNOS activity and NO production in endothelial cells significantly decreased and NF-κB activation and superoxide production in aorta significantly increased in obese rats compared with the control group (p < 0.05). However, DHAP treatment significantly up-regulated the eNOS-NO pathway and decreased NF-κB activation and superoxide production (p < 0.05). CONCLUSION: DHAP improved endothelial function in obese rats. This beneficial effect may be associated with up-regulation of the eNOS-NO pathway by improving lipid metabolism and reducing oxidative stress and inflammation activity.

Effect of high free fatty acids on the anti-contractile response of perivascular adipose tissue in rat aorta.

To determine whether high free fatty acids (FFA) could affect the anti-contractile properties of perivascular adipose tissue (PVAT) in rat aortas. Wistar rats were divided into normal, obesity and fenofibrate groups and fed a normal, high-fat, and high-fat plus fenofibrate diet, respectively. Thoracic aortas with or without PVAT (PVAT+ and PVAT-) were prepared with either intact endothelium (E+) or with endothelium removed (E-). Aortas pre-treated with either 500µmol/L of palmitic acid (PA) or physiological salt solution (PSS), as a control, were used for in vitro study. Concentration-dependent responses of aortas to norepinephrine were measured. The anti-contractile effects of PVAT were attenuated in both obese rats with high FFA levels and in the PA group in the presence of endothelium, but not in the absence of endothelium. The attenuation of the anti-contractile effect was restored by reducing FFA levels in the fenofibrate group (P<0.05). Incubation of aortas (PVAT+ E+) with nitric oxide (NO) synthase inhibitor and tumor necrosis factor-alpha (TNF-α) in the normal group caused attenuation of the anti-contractile effect of PVAT (P<0.05). Incubation of aortas (PVAT+ E+) in the obese and PA groups with a NO donor, anti-TNF-α antibodies or free radical scavengers partially restored the anti-contractile effect of PVAT (P<0.05). Under both acute and chronic conditions, high FFA levels could attenuate the anti-contractile properties of PVAT by an endothelium-dependent rather than an endothelium-independent mechanism, in which inflammation and oxidative stress may play important roles.