Endogenous n-3 PUFAs Improve Non-Alcoholic Fatty Liver Disease through FFAR4-Mediated Gut-Liver Crosstalk.

The gut-liver axis plays a key role in the development and progression of non-alcoholic fatty liver disease (NAFLD). Due to the complexity and incomplete understanding of the cross-talk between the gut and liver, effective therapeutic targets are largely unknown. Free fatty acid receptors (FFARs) may bridge the cross-talk between the gut and liver. FFAR4 has received considerable attention due to its important role in lipid metabolism. However, the role of FFAR4 in this cross talk in NAFLD remains unclear. In this study, mice with high endogenous n-3 PUFAs but FFAR4 deficiency were generated by crossbreeding Fat-1 and FFAR4 knockout mice. FFAR4 deficiency blocked the protective effects of high endogenous n-3 PUFAs on intestinal barrier dysfunction and hepatic steatosis. In addition, FFAR4 deficiency decreased gut microbiota diversity and enriched Rikenella, Anaerotruncus, and Enterococcus, and reduced Dubosiella, Ruminococcaceae UCG-010, Ruminococcaceae UCG-014, Coriobacteriaceae UCG-002, Faecalibaculum, Ruminococcaceae UCG-009, and Akkermansia. Notably, FFAR4 deficiency co-regulated pantothenic acid and CoA biosynthesis, ß-alanine metabolism, and sphingolipid metabolism pathways in the gut and liver, potentially associated with the aggravation of NAFLD. Together, the beneficial effects of n-3 PUFAs on the gut and liver were mediated by FFAR4, providing insights on the role of FFAR4 in the treatment of NAFLD through the gut-liver axis.

Properties of plant-derived soluble dietary fibers for fiber-enriched foods: A comparative evaluation.

Plant-derived soluble dietary fibers (SDF) have many important physiological functions and the applications of SDF vary based on their properties, which are worth further investigating for fiber-enriched food production. In this study, SDF derived from konjac, apple, chicory, flaxseed, orange, psyllium seed, soybean and oat were purified, and their structural, physicochemical and functional properties were systematically evaluated. Monosaccharide composition analysis showed that these SDF belonged to heteropolysaccharides, of which konjac, psyllium seed, apple, soybean and oat SDF were glucomannan, arabinoxylan, pectin, arabinogalactan and glucan, respectively. The molecular weight of konjac glucomannan (KGM, 5.22 × 106 Da) was the highest, and inulin, soybean arabinogalactan (SA) and oat glucan (OG) had higher water solubility. Moreover, KGM, apple pectin (AP), flaxseed SDF (FS) and psyllium seed arabinoxylan (PA) exhibited better water-holding capacity, swelling capacity, emulsifying activity and stability. Rheological studies and texture profile analysis suggested that KGM had the best viscosity and gelation ability. In addition, AP and orange SDF (OS) showed better α-amylase inhibitory activity, while OS and KGM had higher pancreatic lipase inhibitory activity. Also, KGM and FS displayed fine cholesterol absorption capacity. To summary, these functional properties illustrated the feasibility of SDF to regulate blood sugar and blood lipid levels.

Deep Learning-Based Surface Nerve Electromyography Data of E-Health Electroacupuncture in Treatment of Peripheral Facial Paralysis.

This study was aimed at exploring the application value of electroacupuncture in the treatment of peripheral facial palsy using surface nerve electromyogram (EMG) image data based on deep learning. The surface nerve EMG recognition model was constructed based on multiview convolutional neural network, and the differences between it and the traditional single-view convolutional neural network were analyzed. Meanwhile, the influence of the multiview aggregation method based on pooling of view and decision fusion on facial recognition accuracy was compared and analyzed. 150 patients with peripheral facial paralysis were randomly divided into the control group (n = 70, basic treatment) and treatment group (n = 80, basic treatment + electroacupuncture). After 4 weeks of treatment, the therapeutic effect was evaluated by surface EMG parameters based on Horsfall-Barratt (H-B) scale and multiview convolutional neural network. The results showed that the face recognition accuracy of multiview convolutional neural networks was significantly higher than that of all single-view convolutional neural networks. The multiview aggregation network proposed in this research had a higher accuracy in facial recognition than the pooling of the view method and decision fusion-based multiview aggregation method. According to the evaluation results of H-B scale, the number of patients who recovered, significantly effective, effective, and ineffective in the control group was 39, 17, 3, and 11, respectively. The number of patients in the treatment group who recovered, significantly effective, effective, and ineffective was 51, 15, 9, and 5, respectively. Total effective rate of patients in the control group was 84.29%, and that of the treatment group was 93.75%, which was significantly higher than the control group (P < 0.05). According to surface EMG assessment results, compared with the control group, the mean root mean square (RMS), median frequency (MF), and mean power frequency (MPF) of the buccal and frontalis muscles in the treatment group increased significantly (P < 0.05). Compared with that before treatment, the mean buccal and frontalis RMS of patients in the control and treatment groups increased significantly after treatment (P < 0.05). In conclusion, electroacupuncture treatment could significantly improve the muscle strength of patients with peripheral facial paralysis.

Influencing factors of holistic nursing intervention under a social medical model on the psychology and quality of life of patients with advanced gastric cancer.

OBJECTIVE: This research was designed to probe into the influencing factors of holistic nursing intervention under a social medical model on psychology and quality of life in advanced gastric cancer (GC) patients. METHODS: Altogether 194 patients with advanced GC treated in our hospital from May 2017 to July 2018 were divided into two groups according to different nursing intervention methods. Where from, 86 were given routine nursing intervention and 108 were given holistic nursing intervention under a social medical model. The psychology, pain relief, sleep quality and self-nursing ability of patients were compared before and after intervention. The quality of life before and after intervention and the nursing satisfaction score after nursing were recorded. The factors affecting their quality of life were assessed by Logistic regression analysis. RESULTS: The SAS, SDS, NRS and PSQI scores in the intervention group (IG) were obviously lower than those in the control group (CG) after nursing. The ESCA and EORTC QLQ-C30 scores after nursing in the IG were markedly higher than those in the CG. The total nursing satisfaction of patients in the IG after nursing was obviously higher than that in the CG. Logistic regression analysis revealed that age, lymph node metastasis, TNM stage, unimproved negative emotion, lack of self-nursing ability and routine nursing intervention all increased the risk of reduced quality of life. CONCLUSION: The decline in the quality of life of patients with advanced GC results from a comprehensive action of various risk factors, and holistic nursing under a social medical model can improve the psychology of patients, improve their self-nursing ability and quality of life.

Triptolide decreases tumor-associated macrophages infiltration and M2 polarization to remodel colon cancer immune microenvironment via inhibiting tumor-derived CXCL12.

Colon cancer is a common and deadly human digestive tract malignant tumor with poor prognosis. Immunotherapy has elicited tremendous success as a treatment modality for multiple solid tumors. Triptolide is extracted from the traditional Chinese medicine Tripterygium wilfordii Hook. F which shows various pharmacological actions including antitumor, anti-inflammatory, antimicrobial, antifibrosis, and antirheumatic. However, the influence of triptolide treatment on remodeling tumor immune microenvironment is still unknown in colon cancer. This study was aimed to investigate the therapeutic effect of triptolide treatment on colon cancer and the impact on tumor immune microenvironment and its underlying mechanism. We used CT26 subcutaneous tumors to conduct in vivo experiments and HT29, CT16, and Raw264.7 cells to perform in vitro assays. Triptolide had a therapeutic effect against colon cancer in vivo. Triptolide treatment distinctly inhibited the proliferation of colon cancer cells and induced apoptosis in vitro. In colon cancer immune microenvironment, triptolide treatment decreased the infiltration of tumor-associated macrophages through downregulating tumor-derived CXCL12 expression via nuclear factor kappa B and extracellular signal-regulated protein kinases 1 and 2 axis to remodel the immune microenvironment. Triptolide-educated colon cancers retarded the macrophages polarize to anti-inflammatory M2 status by decreasing the expression of Arg-1, CD206, and interleukin-10. Moreover, triptolide inhibited the migration of colon cancer cells via decreasing vascular endothelial growth factor expression. Our results identified the role of triptolide treatment in remodeling colon cancer immune microenvironment along with the distinct cytotoxicity function against colon cancer cells, which may provide the evidence for triptolide treatment in clinical.

Discovery of potentially biased agonists of mu-opioid receptor (MOR) through molecular docking, pharmacophore modeling, and MD simulation.

Opioids are well known for their potent analgesic efficacy and severe side effects. Studies have shown that analgesic effects are mediated by the downstream G-protein-dependent pathway of the µ-opioid receptor (MOR), and another ß-arrestin-dependent pathway mediates side effects such as respiratory depression, constipation and tolerance etc. TRV130 is a biased ligand for G-protein-dependent pathway, which has high analgesia and has fewer side effects than morphine. In this study, the structure similarity search was performed on the IBSSC database using Oliceridine (TRV130) and PZM21 as templates. The 3D structure-based pharmacophore model was built and combined molecular docking prediction mode was selected to filter out small molecules, Finally, based on affinity prediction, four candidate molecules were obtained. Molecular dynamics simulations explored the detailed interaction mechanism of proteins with small molecules under dynamics. These results suggest that these candidate molecules are potential MOR agonists.

Metabolic Alterations Induced by Kudingcha Lead to Cancer Cell Apoptosis and Metastasis Inhibition.

Kudingcha is implicated in alleviating metabolic disorders in traditional Chinese medicine. However, the role of Kudingcha, one of the Ligustrum robustum species, in metabolic regulations and its antitumor activity in triple-negative breast cancer (TNBC) remains to be determined. Two breast cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Kudingcha treatment. The production of reactive oxygen species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift was examined by metabonomics and western blot analysis. In this study, we found that aqueous extract of Kudingcha dose dependently inhibited cell growth and induced apoptosis in vitro and in vivo. Moreover, Kudingcha supplementation significantly reduced cancer metastasis. Kudingcha significantly inhibited glycolysis and glutamine metabolism. In addition, we demonstrated that the antitumor effects of Kudingcha were dependent on ROS production, which was increased by ß-oxidation and oxidative phosphorylation. These findings provide a novel potential benefit of Kudingcha from targeting the cancer metabolism.

Metabolic Shift Induced by ω -3 PUFAs and Rapamycin Lead to Cancer Cell Death.

BACKGROUND/AIMS: Rapamycin (Rp), the main mammalian target of rapamycin complex inhibitor, is a promising therapeutic agent for breast cancer. However, metabolic disorders and drug resistance reduce its efficacy. Epidemiological, clinical, and experimental studies have demonstrated that omega-3 polyunsaturated fatty acids (ω-3 PUFAs) significantly reduce the incidence and mortality of breast cancer and improve metabolic disorders. METHODS: Three breast cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Rp plus ω-3 PUFA treatment. The production of reactive oxygen species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift was examined by metabonomics, seahorse experiments, and western blot analysis. RESULTS: We found that ω-3 PUFAs and Rp synergistically induced cell cycle arrest and apoptosis in vitro and in vivo, accompanied by autophagy blockage. In addition, Rp-induced hypertriglyceridemia and hypercholesterolemia were completely abolished by ω-3 PUFA supplementation. Moreover, the combined treatment of ω-3 PUFA and Rp significantly inhibited glycolysis and glutamine metabolism. The anti-tumor effects of this combination treatment were dependent on ROS production, which was increased by ß-oxidation and oxidative phosphorylation. CONCLUSION: Our study revealed that ω-3 PUFA enhanced the anti-tumor activity of Rp while minimizing its side effects in vitro and in vivo. These results provide novel insights into the mechanisms underlying the potential beneficial effects of Rp combined with ω-3 PUFAs on the prevention of breast cancer.

Regulation of three isoforms of SOD gene by environmental stresses in citrus red mite, Panonychus citri.

Superoxide dismutase (SOD) is a family of enzymes with multiple isoforms that possess antioxidative abilities in response to environmental stresses. Panonychus citri is one of the most important pest mites and has a global distribution. In this study, three distinct isoforms of SOD were cloned from P. citri and identified as cytoplasmic Cu-ZnSOD (PcSOD1), extracellular Cu-ZnSOD (PcSOD2), and mitochondrial MnSOD (PcSOD3). mRNA expression level analysis showed that all three isoforms were up-regulated significantly after exposure to the acaricide abamectin and to UV-B ultraviolet irradiation. In particular, PcSOD3 was up-regulated under almost all environmental stresses tested. The fold change of PcSOD3 expression was significantly higher than those of the two Cu-ZnSOD isoforms. Taken together, the results indicate that abamectin and UV-B can induce transcripts of all three SOD isoforms in P. citri. Furthermore, PcSOD3 seems to play a more important role in P. citri tolerance to oxidative stress.

Molecular characteristics, mRNA expression, and alternative splicing of a ryanodine receptor gene in the oriental fruit fly, Bactrocera dorsalis (Hendel).

Ryanodine receptors (RyRs) are a distinct class of ligand-gated channels controlling the release of calcium from intracellular stores. The emergence of diamide insecticides, which selectively target insect RyRs, has promoted the study of insect RyRs. In the present study, the full-length RyR cDNA (BdRyR) was cloned and characterized from the oriental fruit fly, Bactrocera dorsalis (Hendel), a serious pest of fruits and vegetables throughout East Asia and the Pacific Rim. The cDNA of BdRyR contains a 15,420-bp open reading frame encoding 5,140 amino acids with a predicted molecular weight of 582.4 kDa and an isoelectric point of 5.38. BdRyR shows a high level of amino acid sequence identity (78 to 97%) to other insect RyR isoforms. All common structural features of the RyRs are present in the BdRyR, including a well-conserved C-terminal domain containing consensus calcium-binding EF-hands and six transmembrane domains, and a large N-terminal domain. Quantitative real-time PCR analyses revealed that BdRyR was expressed at the lowest and highest levels in egg and adult, respectively, and that the BdRyR expression levels in the third instar larva, pupa and adult were 166.99-, 157.56- and 808.56-fold higher, respectively, than that in the egg. Among different adult body parts, the highest expression level was observed in the thorax compared with the head and abdomen. In addition, four alternative splice sites were identified in the BdRyR gene, with the first, ASI, being located in the central part of the predicted second spore lysis A/RyR domain. Diagnostic PCR analyses revealed that alternative splice variants were generated not only in a tissue-specific manner but also in a developmentally regulated manner. These results lay the foundation for further understanding the structural and functional properties of BdRyR, and the molecular mechanisms for target site resistance in B. dorsalis.

[Effect of Tribulus terrestris extract on melanocyte-stimulating hormone expression in mouse hair follicles].

OBJECTIVE: To observe the effect of Tribulus terrestris extract on melanocyte stimulating hormone (MSH) expression in C57BL/6J mouse hair follicles, and investigate the role of Tribulus terrestris extract in activation, proliferation, epidermal migration of dormant hair follicle melanocytes. METHODS: The aqueous extract of Tribulus terrestris was administered orally in specific pathogen-free C57BL/6J mouse at the daily dose equivalent to 1 g/1 kg in adult human, and the expression and distribution of MSH in the mouse hair follicles was observed with immunohistochemistry. RESULTS: The positivity rate of MSH expression in the hair follicle melanocytes was 75% in mice treated with the extract, significantly higher than the rate of only 18.75% in the control group (P<0.01). CONCLUSION: The aqueous extract of Tribulus terrestris can significantly increase MSH expression in the hair follicle melanocytes by activating tyrosinase activity and promoting melanocyte proliferation, melanine synthesis, and epidermal migration of dormant melanocytes.