Palmatine attenuates hepatocyte injury by promoting autophagy via the AMPK/mTOR pathway after alcoholic liver disease.

Alcoholic liver disease is one of the diseases with the highest fatality rate worldwide. The cellular process of autophagy which recycles damaged organelles to maintain protein and organelle homeostasis is found to positively influence survival during hepatic insufficiency, although the mechanism is poorly understood. Palmatine (PLT) has a variety of biological functions, such as broad-spectrum antibacterial action, neuroprotective, antioxidant stress, and antiviral and anti-inflammatory activities. However, it is not known whether PLT has a protective effect against alcoholic liver injury. Here, we investigated the protective effect of PLT in a cellular model of alcohol-induced acute liver injury and further explored its mechanism of action. In this study, we show for the first time that PLT attenuates alcohol-induced hepatocyte injury by promoting autophagy to play an essential protective role. As PLT treatment induced a brief increase in LC3-II conversion and p62 degradation, it also upregulated the expression of ATG5 and ATG7. The expression levels of the proapoptotic proteins Bax, Caspase 3, and Caspase 9 significantly decreased, while the antiapoptotic protein levels of Bcl-2 upregulated after treatment with PLT. However, in presence of the autophagy inhibitor, 3-methyladenine, the effect of PLT in inhibiting ethanol-induced hepatocyte injury reversed significantly. Mechanistically, the protective effects of PLT may be mediated by promoting the activation of the AMP-activated protein kinase/mammalian target of rapamycin signaling pathway. Therefore, we believe that the development of alcoholic liver injuries may be controlled by PLT by inhibiting hepatocyte apoptosis through the autophagy pathway. The study lays a solid theoretical and practical basis for future animal models and clinical studies of PLT.

RGS7 silence protects palmitic acid-induced pancreatic ß-cell injury by inactivating the chemokine signaling pathway.

Impaired insulin secretion due to pancreatic ß-cell injury is an important cause of type 2 diabetes (T2D). Regulators of guanine nucleotide binding protein (G protein) signaling proteins played a key role in regulating insulin sensitivity in vivo. To explore the role of RGS7 on palmitic acid-induced pancreatic ß-cell injury, pancreatic ß-cells Beta-TC-6 and Min6 were treated with palmitic acid (PA) to similar type 2 diabetes (T2D) injury in vitro. The 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry were used to analyze cell viability, proliferation, and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) kits were used to analyze the changes of inflammation-related cytokines. The expression of gene and protein was measured by quantitative real-time PCR (qRT-PCR) and western blot. PA modeling induced apoptosis, increased levels of inflammation-related cytokines, and suppressed cell viability and proliferation of pancreatic ß-cells. RGS7 silence markedly alleviated the cell injury induced by PA. RGS7 overexpression further aggravated apoptosis and inflammatory response in PA-induced pancreatic ß-cells and inhibited cell viability and proliferation. It is worth noting that RGS7 activated the chemokine signaling pathway. Silence of the key gene of the chemokine signaling pathway could eliminate the negative effect of RGS7 on PA-induced pancreatic ß-cells. RGS7 silence protects pancreatic ß-cells from PA-induced injury by inactivating the chemokine signaling pathway.

Probiotics alleviate adipose inflammation in high-fat diet-induced obesity by restoring adipose invariant natural killer T cells.

OBJECTIVE: Invariant natural killer T (iNKT) cells, which are depleted in obese individuals, play important roles in preventing diet-induced obesity and associated disorders. Probiotic supplementation can alter the gut microbiota and immunomodulation in obesity. However, it remains unclear whether probiotics can affect visceral adipose iNKT cells. The aim of this study was to analyze the effects of probiotics on adipose iNKT cells in mice with high-fat diet (HFD)-induced obesity and to assess the immunomodulatory function of probiotics and their role in obesity, glucose tolerance, lipid metabolism, insulin resistance, and adipose inflammation. METHODS: Wildtype (WT) male C57BL/6 mice and CD1d knockout mice were fed an HFD or a normal-fat diet. Some mice received active or heat-sacrificed VSL#3 probiotics. Preventative VSL#3 therapy was also administered to HFD mice. Body weight, metabolic parameters, expression of genes encoding adipose inflammatory factors (interleukin [IL]-4, IL-10, tumor necrosis factor-α, interferon-γ, and IL-6), adipose iNKT cell frequency, and subphenotype were evaluated. RESULTS: HFD induced more severe obesity in CD1dKO mice than in WT mice. VSL#3 intervention significantly improved HFD-induced weight gain, adipose iNKT cell depletion, and metabolic and adipose inflammatory profiles in WT mice, but not in CD1dKO mice. Preventative VSL#3 treatment improved HFD-induced obesity and metabolic parameters, and elevated total adipose iNKT and IL-4+ iNKT cell frequencies. CONCLUSIONS: Probiotic intervention alleviated weight gain, improved metabolic parameters, and reduced adipose inflammation in HFD-induced obesity. These effects seem to depend on the restoration of visceral adipose iNKT cells. These findings have potential implications for the management of obesity-related diseases.

A compact two-way power divider based on five-port structure.

A novel compact five-port waveguide power divider based on the single-ridge waveguide and three-ridge waveguide structure is proposed. It is realized by the coupling of the TE10 and TE30 modes. At the central coupling section, the single-ridge and three-ridge waveguides are used to constitute the conventional rectangular waveguide to reduce the sectional sizes. It consists of one input port, two output ports, and two isolated ports. For validation, a compact five-port power divider is designed, fabricated, and measured. The measured results show that, from 8 to 9 GHz, the return loss of the input port and output ports is higher than 18 dB, the isolation between the output ports is higher than 15 dB, the insertion loss is less than 0.3 dB, and the amplitude and the phase imbalance between the output ports are less than ±0.05 dB and ±1°, respectively. The simulated results basically agree with the simulations. Its sectional sizes are 1.1 λ × 0.4 λ which are more compact than most of the two-way isolated waveguide power dividers.

A compact five-port waveguide structure and its application as a three-way power divider.

A compact five-port waveguide structure consisting of three rectangular ports, one coaxial port, and one circular waveguide port is proposed. The three rectangular waveguides are uniformly distributed in space at angles of 120°, and the coaxial and circular waveguides are located at the top and bottom, respectively, of the rectangular waveguides. The ideal scattering matrix is derived from the symmetry properties of the structure. If the circular and coaxial ports are matched, then the entire five-port waveguide structure is automatically matched. Two connected inserted coaxial probes, a frustum, and a coaxial transition are used to match the five-port waveguide structure with a relatively wide bandwidth. The theoretical and experimental results are generally consistent with each other. With the circular port connected to the load, the five-port waveguide structure becomes a reciprocal TEM mode-to-three-way TE10 mode power divider. Measurements indicate that from 8 to 9.6 GHz, the return losses at the three rectangular ports and the coaxial port are greater than 20 dB and 17 dB, respectively. The isolation among the three rectangular ports is higher than 20 dB. The amplitude and phase imbalances in the division of power are less than 0.1 dB and 2°, respectively. The volume of the five-port waveguide structure is as small as 1.5 λ × 1.5λ × λ.