Examining the relationship between nutritional status and wound healing in head and neck cancer treatment: A focus on malnutrition and nutrient deficiencies.

The research was conducted to examine the correlation between nutritional status and wound healing in individuals who were receiving treatment for head and neck cancer. Specifically, this study sought to identify crucial nutritional factors that influenced both the recovery process and efficacy of the treatment. From February 2022 to September 2023, this cross-sectional study was undertaken involving 300 patients diagnosed with head and neck cancer who were treated at Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. In order to evaluate nutritional status, body mass index (BMI), serum protein levels and dietary intake records were utilized. The assessment of wound healing was conducted using established oncological wound healing scales, photographic documentation and clinical examinations. After treatment, we observed a noteworthy reduction in both BMI (p < 0.05) and serum albumin levels (p < 0.05). There was slightly increased prevalence of head and neck cancer among males (61.0%, p < 0.05). Over the course of 6 months, significant enhancement in wound healing scores was noted, exhibiting overall improvement of 86% in the healing process. An inverse correlation was identified between nutritional status and wound healing efficacy through multivariate analysis. A logistic regression analysis revealed a significant positive correlation (p < 0.05) between elevated levels of serum protein and total lymphocytes and enhanced wound healing. Conversely, negative correlation (p < 0.05) was observed between larger wound size at baseline and healing. The research findings indicated noteworthy association between malnutrition and impaired wound repair among individuals diagnosed with head and neck cancer. The results underscored the significance of integrating nutritional interventions into therapeutic protocol in order to enhance clinical results. This research study provided significant contributions to the knowledge of intricate nature of head and neck cancer management by advocating for multidisciplinary approach that incorporates nutrition as the critical element of patient care and highlighted the importance of ongoing surveillance and customized dietary approaches in order to optimize wound healing and treatment efficacy.

Meta-analysis and machine learning reveal the antiobesity effects of melatonin on obese rodents.

Melatonin appears to be a promising supplement for obesity treatment. The antiobesity effects of melatonin on obese rodents are influenced by various factors, including the species, sex, the dosage of melatonin, treatment duration, administration via, daily treatment time, and initial body weight (IBW). Therefore, we conducted a meta-analysis and machine learning study to evaluate the antiobesity effect of melatonin on obese mice or rats from 31 publications. The results showed that melatonin significantly reduced body weight, serum glucose (GLU), triglycerides (TGs), low-density lipoprotein (LDL), and cholesterol (TC) levels in obese mice or rats but increased high-density lipoprotein (HDL) levels. Melatonin showed a slight positive effect on clock-related genes, although the number of studies was limited. Meta-regression analysis and machine learning indicated that the dosage of melatonin was the primary factor influencing body weight, with higher melatonin dosages leading to a stronger weight reduction effect. Together, male obese C57BL/6 mice and Sprague-Dawley rats with an IBW of 100-200 g showed better body weight reduction when supplemented with a dose of 10-30 mg/kg melatonin administered at night via injection for 5-8 weeks.

Clinical observation on inverted T-shaped herb-separated moxibustion for chronic pelvic pain in sequelae of pelvic inflammatory diseases. / 倒Tå­—å½¢éš”è¯ç¸æ²»ç–—ç›†è ”ç‚Žæ€§ç–¾ç— åŽé—ç—‡æ ¢æ€§ç›†è ”ç—›ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To compare the clinical effect between inverted T-shaped herb-separated moxibustion combined with western medication and simple western medication on chronic pelvic pain(CPP)in sequelae of pelvic inflammatory diseases. METHODS: A total of 60 patients with CPP in sequelae of pelvic inflammatory diseases were randomly divided into an observation group and a control group, 30 cases in each group. The control group was given ibuprofen tablets 10 days before menstruation, 0.2 g each time, once a day for 10 days. After menstruation, the medication was stopped, and the treatment was given for 3 menstrual cycles.On the basis of the treatment in the control group, the observation group was treated with inverted T-shaped herb-separated moxibustion at the connection between Zhongwan(CV 12)and Zhongji(CV 3), and the connection between Zigong(EX-CA 1)on both sides.The treatment was performed once a week, with an interval of 6 days. The moxibustion was stopped during the menstrual period, the treatment was given for 3 menstrual cycles.Before and after treatment, the visual analogue scale(VAS)score of lower abdominal and lumbosacral pain, local symptom (uterine tenderness, adnexal tenderness and uterosacral ligament tenderness) score and quality of life assessment (QOL) score of the two groups were observed. RESULTS: After treatment, the lower abdominal and lumbosacral pain VAS scores, the local symptom scores of uterine tenderness, adnexal tenderness, uterosacral ligament tenderness and total scores in the two groups were lower than those before treatment(P<0.01).The lower abdominal and lumbosacral pain VAS score in the observation group was lower than that in the control group(P<0.01),and the changes of local symptom scores of uterine tenderness, adnexal tenderness and uterosacral ligament tenderness and total score in the observation group were greater than those in the control group(P<0.01). After treatment, the QOL scores of the two groups were higher than those before treatment(P<0.01), and the score in the observation group was higher than that in the control group(P<0.01). CONCLUSIONS: Inverted T-shaped herb-separated moxibustion combined with western medication can effectively reduce the pain in patients with CPP in sequelae of pelvic inflammatory diseases, relieve the local symptoms, improve the quality of life, and the curative effect is better than western medication alone.

Plant-derived squalene supplementation improves growth performance and alleviates acute oxidative stress-induced growth retardation and intestinal damage in piglets.

Piglets are particularly susceptible to oxidative stress, which causes inferior growth performance and intestinal damage. Squalene (SQ), a natural bioactive substance enriched in shark liver oil, shows excellent antioxidant properties and can currently be obtained at a low cost from deodorizer distillate during the production of plant oil. This study aimed to evaluate the effects of plant-derived SQ supplementation on the growth performance of piglets and explore the beneficial roles of SQ against oxidative stress and intestinal injury in diquat-challenged piglets. Forty piglets were randomly divided into five groups and fed a basal diet supplemented with SQ at 0, 500, 1000, or 2000 mg/kg for 5 weeks. Acute oxidative stress was induced in the piglets with diquat (10 mg/kg BW) at the fourth week of the experiment, followed by a 7-d recovery period. Results showed that before the diquat challenge, SQ supplementation significantly improved growth performance (average daily gain and feed conversion ratio) and serum antioxidant status, and after the diquat challenge, SQ supplementation significantly mitigated diquat-induced growth arrest, intestinal villous atrophy, intestinal epithelial cell apoptosis, intestinal hyperpermeability, and deficiency of intestinal epithelial tight junction proteins (zonula occludens-1, occludin, and claudin-3). Under oxidative stress induced by diquat, SQ supplementation consistently improved the antioxidant status of the small intestine, liver, and muscle. In vitro, SQ was shown to alleviate hydrogen peroxide (H2O2)-induced increase of the levels of intracellular reactive oxygen species and apoptosis of porcine intestinal epithelial cells. Taken together, SQ supplementation improves growth performance and effectively alleviates acute oxidative stress-induced growth retardation and intestinal injury via improving antioxidant capacity in piglets. Our findings may provide an efficient strategy for alleviating oxidative stress-induced inferior growth performance and intestinal damage in piglets.

Effect of Ornithine α-Ketoglutarate on Intestinal Microbiota and Serum Inflammatory Cytokines in Dextran Sulfate Sodium Induced Colitis.

Ornithine α-ketoglutarate (OKG), a nutritional compound, is an amino acid salt with anti-oxidative and anti-inflammatory effects on humans and animals. Ulcerative colitis (UC), as an inflammatory bowel disease (IBD), leads to chronic intestinal inflammatory dysfunction. This study evaluated the optimal dosage of OKG in healthy mice. Then, a mouse model of acute colitis was established using dextran sodium sulfate (DSS), and the preventive effect of OKG on DSS-induced colitis in mice was explored through analysis of serum inflammatory cytokines and fecal microbiota. Initially, the mice were randomly divided into a control group, a group given a low dose of OKG (LOKG: 0.5%), a group given a medium dose of OKG (MOKG: 1%), and a group given a high dose of OKG (HOKG: 1.5%); they remained in these groups for the entire 14-day experimental period. Our results demonstrated that 1% OKG supplementation increased body weight, serum growth hormone (GH), insulin (INS), alkaline phosphatase (ALP), Tyr, and His and decreased urea nitrogen (BUN), NH3L, and Ile. Then, a 2 × 2 factor design was used for a total of 40 mice, with diet (a standard diet or a 1% OKG diet) and challenge (4% DSS or not) as the main factors. During days 14 to 21, the DSS mice were administered 4% DSS to induce colitis. The results revealed that OKG alleviated weight loss and reversed the increases in colonic histological damage induced by DSS. OKG also increased serum IL-10 secretion. Moreover, OKG enhanced the abundance of Firmicutes and decreased that of Bacteriodetes at the phylum level and particularly enhanced the abundance of Alistipes and reduced that of Parabacterioides at the genus level. Our results indicated that OKG promotes growth performance and hormone secretion and regulates serum biochemical indicators and amino acid concentrations. Furthermore, 1% OKG supplementation prevents DSS-induced colitis in mice via altering microbial compositions and reducing the secretion of inflammatory cytokines in serum.

Integrating UPLC-Q-Exactive Orbitrap/MS, network pharmacology and experimental validation to reveal the potential mechanism of Tibetan medicine Rhodiola granules in improving myocardial ischemia-reperfusion injury.

ETHNOPHARMACOLOGY RELEVANCE: Rhodiola granules (RG) is a traditional Tibetan medicine prescription that can be used to improve the symptoms of ischemia and hypoxia in cardiovascular and cerebrovascular diseases. However, there is no report on its use to improve myocardial ischemia/reperfusion (I/R) injury, and its potential active ingredients and mechanism against myocardial ischemia/reperfusion (I/R) injury remain unclear. AIM OF THE STUDY: This study aimed to reveal the potential bioactive components and underlying pharmacological mechanisms of RG in improving myocardial I/R injury through a comprehensive strategy. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap/MS technology was used to analyze the chemical components of RG, the potential bioactive components and targets were tracked and predicted by the SwissADME and SwissTargetPrediction databases, and the core targets were predicted through the PPI network, as well the functions and pathways were determined by GO and KEGG analysis. In addition, the molecular docking and ligation of the anterior descending coronary artery-induced rat I/R models were experimentally validated. RESULTS: A total of 37 ingredients were detected from RG, including nine flavones, ten flavonoid glycosides, one glycoside, eight organic acids, four amides, two nucleosides, one amino acid, and two other components. Among them, 15 chemical components, such as salidroside, morin, diosmetin, and gallic acid were identified as key active compounds. Ten core targets, including AKT1, VEGF, PTGS2, and STAT3, were discovered through the analysis of the PPI network constructed from 124 common potential targets. These possible targets were involved in the regulation of oxidative stress and HIF-1/VEGF/PI3K-Akt signaling pathways. Furthermore, molecular docking confirmed that the potential bioactive compounds in RG have good potential binding abilities to AKT1, VEGFA, PTGS2, STAT3, and HIF-1α proteins. Then, the animal experiments showed that RG could significantly improve the cardiac function of I/R rats, reduce the size of myocardial infarction, improve the myocardial structure, and reduce the degree of myocardial fibrosis, inflammatory cell infiltration, and myocardial cell apoptosis rate in I/R rats. In addition, we also found that RG could decrease the concentration of AGE, Ox-LDL, MDA, MPO, XOD, SDH, Ca2+, and ROS, and increase the concentration of Trx, TrxR1, SOD, T-AOC, NO, ATP, Na+k+-ATPase, Ca2+-ATPase, and CCO. Moreover, RG could significantly down-regulate the expressions of Bax, Cleaved-caspase3, HIF-1α, and PTGS2, as well up-regulate the expressions of Bcl-2, VEGFA, p-AKT1, and p-STAT3. CONCLUSION: In summary, we revealed for the first time the potential active ingredients and mechanisms of RG for myocardial I/R injury therapy through a comprehensive research strategy. RG may synergistically improve myocardial I/R injury through anti-inflammatory, regulating energy metabolism, and oxidative stress, improving I/R-induced myocardial apoptosis, which may be related to the HIF-1/VEGF/PI3K-Akt signaling pathway. Our study provides new insights into the clinical application of RG and also provides a reference for the development and mechanism research of other Tibetan medicine compound preparations.

Elevation of Intracellular Alpha-Ketoglutarate Levels Inhibits Osteoclastogenesis by Suppressing the NF-κB Signaling Pathway in a PHD1-Dependent Manner.

Age-related osteoporosis, a high-prevalence disease in the aged population, is generally attributed to the excessive activity of osteoclasts. Most approved drugs treat osteoporosis by inhibition of osteoclasts. Although in vivo studies have shown that alpha-ketoglutarate (AKG), an intermediate in the TCA cycle, can ameliorate age-related osteoporosis, the effects of AKG on osteoclastogenesis and the underlying mechanism of its action have not been studied yet. Here, we showed that the elevation of intracellular AKG levels by supplementing dimethyl AKG (DM-AKG, a cell-permeable derivative of AKG) inhibits the receptor activator of NF-κB ligand (RANKL)-induced osteoclasts differentiation from primary bone marrow-derived macrophages (BMMs) and RAW264.7 cells in vitro. We further found that DM-AKG treatment suppresses NF-κB signaling and oxidative phosphorylation (OXPHOS) during RANKL-induced osteoclastogenesis in RAW264.7 cells. Interestingly, dimethyl oxalylglycine (DMOG), an AKG competitive inhibitor of AKG-dependent prolyl hydroxylases (PHDs), antagonizes the suppression of the RANKL-activated NF-κB signaling pathway caused by DM-AKG treatment. Furthermore, blocked PHD1 expression (also known as EglN2), instead of PHD2 or PHD3, was confirmed to reverse the DM-AKG treatment-induced suppression of the RANKL-activated NF-κB signaling pathway. Accordingly, blocked PHD1 expression antagonized the inhibitory effects of DM-AKG on osteoclastogenesis. Together, our finding suggests that the elevation of intracellular AKG levels inhibits osteoclastogenesis by suppressing RANKL-activated NF-κB signaling in a PHD1-dependent manner, which may provide a novel nutritional strategy for osteoporosis treatment.

Dietary Alpha-Ketoglutarate Supplementation Improves Bone Growth, Phosphorus Digestion, and Growth Performance in Piglets.

Phosphorus (P) pollution from modern swine production is a major environmental problem. Dietary interventions to promote bone growth can improve the utilization of dietary P, and thereby reduce its emission. Recent in vitro studies have shown that alpha-ketoglutarate (AKG) exerts a pro-osteogenic effect on osteoblast cells. This study aimed to evaluate the effects of AKG supplementation on bone growth, P and Ca digestion, and the gut microbial profile in piglets. Thirty-two piglets were randomly assigned into two dietary groups. The piglets were fed a basic diet containing 10 g/kg AKG or 10 g/kg maize starch (control) for 28 days. On days 21-28, titanium dioxide was used as an indicator to determine the apparent digestibility of P. AKG supplementation improved the bone mineral density, length, weight, and geometrical and strength properties of the femur and tibia. Furthermore, AKG supplementation increased apparent ileal and total tract digestibility of P. Colonic microbiota analysis results showed that AKG supplementation increased α-diversity and beneficial bacteria, including Lactobacillus and Clostridium butyricum, and decreased nitrogen fixation and chemoheterotrophy. Together, AKG supplementation improves bone growth, the utilization of dietary P, and the colonic microbial profile, which may provide a nutritional strategy for diminishing P pollution originating from the pig industry.

An In Vitro Dissolution Determination of Multi-Index Components in Tibetan Medicine Rhodiola Granules.

The composition of the Tibetan medicine Rhodiola granules (RG) is complex, and the overall quality of RG is difficult to determine. Therefore, establishing a method to determine the multi-component in vitro dissolution of RG is of great significance for quality control. This study uses the second paddle method of the fourth general rule 0931 from the Chinese Pharmacopoeia (2020 edition), compliant with apparatus 2 of the United States Pharmacopeia (USP). The dissolution apparatus was set to a rotation speed of 100 rpm with ultrapure water as the dissolution medium. A sample volume of 1 mL was collected at each timepoint. Furthermore, the cumulative dissolution of gallic acid, salidroside, and ethyl gallic acid in RG at different time points was determined by high-performance liquid chromatography (HPLC). Finally, the dissolution curves were drawn, and the curves were fitted to the GompertzMod, the Gompertz, the Logistic, and the Weibull equations. The results showed that the cumulative dissolution of gallic acid in RG was over 80% at 1 min, the cumulative dissolution of salidroside and ethyl gallic acid was over 65% at 5 min, and the cumulative dissolution of each index component decreased after 30 min. The curve fitting demonstrated that the GompertzMod equation was the best-fitting model for each index component of RG. In conclusion, the dissolution test method described in this protocol is simple, accurate, and reliable. It can characterize the dissolution behavior of the index components in RG in vitro, which provides a methodological reference for quality control of RG and quality evaluation of other ethnic compounds.

Influence of Atmospheric Phosphorus and Nitrogen Sedimentation on Water Quality in the Middle Route Project of the South-to-North Water Diversion in Henan Province.

In order to understand the potential effects of atmospheric nitrogen and phosphorus deposition on the water quality of the Middle Route Project of the South-to-North Water Diversion Project, samples of dry and wet deposition of atmospheric nitrogen and phosphorus, meteorological factors, and water quality factors were analyzed out to investigate in the Middle Route Project of the South-to-North Water Diversion in Henan Province from October 2018 to October 2020. The variation characteristics of atmospheric nitrogen and phosphorus deposition with time in the Henan section of the main canal are revealed, and the influence of atmospheric dry and wet deposition on the water quality of the middle line is discussed. It was found that the total nitrogen (TN) sedimentation flux has obvious seasonal variation, which was consistent with the variation trend of rainfall, and increased with the increase of rainfall. Nitrogen and phosphorus deposition was significantly correlated with water factors. The effects of meteorological factors and nitrogen and phosphorus deposition on water quality variation reached 18%. The contribution rate and ecological impact of atmospheric nitrogen and phosphorus deposition on water pollution of main channels will be increasing, which needs to be paid enough attention to.

Dormancy-release, germination and seedling growth of Paeonia ostii 'Fengdan' seeds under measures of physical and chemical treatment and sowing.

Paeonia ostii 'Fengdan', a woody oleaginous plant native from China, is considered an oil crop with economic potential. However, a low germination rate was still a restriction for Paeonia ostii 'Fengdan' production. The present research evaluated the germination, rooting and physiological characteristics of seedlings of Paeonia ostii 'Fengdan' in response to different physical treatments and the application of exogenous chemicals. Results indicated that seeds stored in sand at room temperature, and soaked in water for 3 days prior to planting, had a beneficial effect on hypocotyl dormancy-breaking. The rate of rooting and root growth of Paeonia ostii 'Fengdan' were significantly improved with 5 cm sowing depth in 15-20℃ soils. Compared with other sowing depths, the rooting percentage was significantly increased by 1.19% (2.5 cm), 0.98% (7.5 cm) and 1.47% (10 cm), respectively. Epicotyl dormancy was relieved when taproot length reached 50 mm. Soaking seeds in 0.76 mmol/L 5-aminolevulinic acid for 48 hours had the greatest beneficial effect on seed germination and seedling growth, the germination percentage was significantly increased by 4.25% (24 h) and 5.08% (72 h) compared with other treatments. While seed soaked in 10 mmol/L sodium nitroprusside for 48 hours also exhibited enhanced seedling growth, and the germination percentage was significantly increased by 4.36% (24 h) and 7.40% (72 h). Those results benefited seed germination and seedling growth of Paeonia ostii 'Fengdan' which could suggest the promotion of its industrial values and productive potentials. The mechanism of seed breaking dormancy and germination of Paeonia ostii 'Fengdan' needs further study.

Ornithine α-Ketoglutarate Alleviates Inflammation via Regulating Ileal Mucosa Microbiota and Metabolites in Enterotoxigenic Escherichia coli-Infected Pigs.

Enterotoxigenic Escherichia coli (ETEC) is one of the main causes of diarrhea in weaned piglets, and ornithine α-ketoglutarate (OKG) as a food supplement has been shown to improve intestinal immune status in animals and humans. However, it remains unknown whether OKG alleviates inflammation through the regulation of gut microbiota and its metabolites on ETEC-infected piglets. This study was conducted to explore the impact of OKG on growth performance, immunity, and ileal mucosa microbiota and its metabolites in piglets infected with ETEC. On a total of 40 pigs, a 2 × 2 factor design was performed; the major factors were diet (basal diet or 1% OKG diet) and challenge (E. coli or LB Broth). The results showed that ETEC-infection inhibited growth performance, and OKG supplementation alleviated growth performance. Interestingly, ETEC-infection increased the serum TNF-α and IL-6, decreased the serum IL-10, downregulated the mRNA expression of IL-1ß, IL-6, MyD88, and improved the mRNA expression of IL-8, IL-18, and TLR4. OKG inhibited serum IL-6, suppressed the phosphorylation of downstream signals of NF-κB/JNK in the ileum, and enhanced serum IL-10 and ileum SIgA in ETEC-challenged piglets. OKG supplementation enhanced the mRNA expression of IL-1ß and IL-10 and reduced NF-κB and MyD88 in the ileum. Importantly, OKG reversed intestinal microbiota dysfunction, including the diversity of ileal microbiota, the relative abundances of Actinobacillus, Turicibacter, and [Acetivibrio]_ethanolgignens_group, which significantly affected arachidonic acid metabolism and primary bile acid biosynthesis. Collectively, our results suggest that OKG improves growth performance, regulates immunity, and ileal mucosa microbiota and its metabolites in ETEC-infected piglets.

Genome architecture and tetrasomic inheritance of autotetraploid potato.

Potato (Solanum tuberosum) is the most consumed non-cereal food crop. Most commercial potato cultivars are autotetraploids with highly heterozygous genomes, severely hampering genetic analyses and improvement. By leveraging the state-of-the-art sequencing technologies and polyploid graph binning, we achieved a chromosome-scale, haplotype-resolved genome assembly of a cultivated potato, Cooperation-88 (C88). Intra-haplotype comparative analyses revealed extensive sequence and expression differences in this tetraploid genome. We identified haplotype-specific pericentromeres on chromosomes, suggesting a distinct evolutionary trajectory of potato homologous centromeres. Furthermore, we detected double reduction events that are unevenly distributed on haplotypes in 1021 of 1034 selfing progeny, a feature of autopolyploid inheritance. By distinguishing maternal and paternal haplotype sets in C88, we simulated the origin of heterosis in cultivated tetraploid with a survey of 3110 tetra-allelic loci with deleterious mutations, which were masked in the heterozygous condition by two parents. This study provides insights into the genomic architecture of autopolyploids and will guide their breeding.

Autophagy Modulators From Chinese Herbal Medicines: Mechanisms and Therapeutic Potentials for Asthma.

Asthma has become a global health issue, suffering more than 300 million people in the world, which is a heterogeneous disease, usually characterized by chronic airway inflammation and airway hyperreactivity. Combination of inhaled corticosteroids (ICS) and long acting ß-agonists (LABA) can relieve asthma symptoms and reduce the frequency of exacerbations, especially for patients with refractory asthma, but there are limited treatment options for people who do not gain control on combination ICS/LABA. The increase in ICS dose generally provides little additional benefit, and there is an increased risk of side effects. Therefore, therapeutic interventions integrating the use of different agents that focus on different targets are needed to overcome this set of diseases. Some findings suggest autophagy is closely correlated with the severity of asthma through eosinophilic inflammation, and its modulation may provide novel therapeutic approaches for severe allergic asthma. The chinese herbal medicine (CHM) have been demonstrated clinically as potent therapeutic interventions for asthma. Moreover some reports have found that the bioactive components isolated from CHM could modulate autophagy, and exhibit potent Anti-inflammatory activity. These findings have implied the potential for CHMs in asthma or allergic inflammation therapy via the modulation of autophagy. In this review, we discuss the basic pathomechanisms underpinning asthma, and the potential role of CHMs in treating asthma with modulating autophagy.

Cardioprotective effect of icariin against myocardial fibrosis and its molecular mechanism in diabetic cardiomyopathy based on network pharmacology: Role of ICA in DCM.

BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the most severe symptoms of diabetes. It continues to be a major clinical problem, but our knowledge of its molecular mechanisms and effective treatments are limited. Traditional Chinese medicine has been shown to be a pool of novel drugs for diabetes. PURPOSE: Herein, we aim to define the molecular mechanism of icariin (ICA), an extract from a traditional Chinese medicine herb, in protecting cardiac structures and restoring cardiac functions of in a rat model of type 2 diabetes mellitus (T2DM). STUDY DESIGN AND METHODS: Candidate genes related to T2DM were identified through bioinformatics screening and their interactions were constructed by molecule docking technique, followed by pathway enrichment analyses of their cellular functions. A T2DM rat model was then established to evaluate the effects of ICA on cardiac structures, myocardial fibrosis, and cellular Ca2+ inflow, as reflected by HE and Masson staining, qRT-PCR and Western blot determination of related genes, and measurement of the L-type Ca2+ current. RESULTS: Four potential target genes (Jun, p65, NOS3, and PDE5A) were identified. ICA ameliorated the structural damage and myocardial fibrosis in T2DM rats. Intracellular Ca2+ hyperactivities and dysfunction in myocardium of T2DM rats were also repressed by ICA treatment. Furthermore, ICA-induced inhibition of Jun and p65 ameliorated the irregular collagen metabolism and myocardial fibrosis. NOS3, PDE5A and the related sGC-cGMP-PKG signaling pathway mediated the ICA-induced improvement of intracellular Ca2+ inflow. CONCLUSION: In conclusion, these results demonstrate the regulatory roles of potential target genes in DCM and suggest ICA as an effective treatment of DCM by targeting these genes specifically.

Design, Synthesis, Molecular Docking, and Biological Evaluation of New Emodin Anthraquinone Derivatives as Potential Antitumor Substances.

The emodin anthraquinone derivatives are generally used in traditional Chinese medicine due to their various pharmacological activities. In the present study, a series of emodin anthraquinone derivatives have been designed and synthesized, among which 1,3-dihydroxy-6,8-dimethoxyanthracene-9,10-dione is a natural compound that has been synthesized for the very first time, and 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione is a compound that has never been reported earlier. Interestingly, while total seven of these compounds showed neuraminidase inhibitory activity in influenza virus with inhibition rate more than 50 %, specific four compounds exhibited significant inhibition of tumor cell proliferation. The further results demonstrate that 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione showed the best anticancer activity among all the synthesized compounds by inducing highest apoptosis rate to HCT116 cancer cells and arresting their G0/G1 cell cycle phase, through elevation of intracellular level of reactive oxygen species (ROS). Moreover, the binding of 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione with BSA protein has thoroughly been investigated. Altogether, this study suggests the neuraminidase inhibitory activity and antitumor potential of the new emodin anthraquinone derivatives.

Skin-patch of Xin Huang Pian on relieving joint symptoms in patients with acute gouty arthritis: A Randomized, Double-Blind, Active-Controlled Trial.

AIMS: To evaluate the effectiveness and safety of Xin Huang Pian skin patches for patients with acute gouty arthritis. BACKGROUND: In China, patients with acute gouty arthritis benefit from skin patcheses with herbal medicines. But the clinical effects of skin patches with Xin Huang Pian are rarely reported. DESIGN: A Randomized, Double-Blind, Active-Controlled Trial. METHODS: The trial was performed from January 2015-December 2018 at the First Affiliated Hospital of Sun Yat-sen University in China. It was conducted with one intervention group (skin patches of Xin Huang Pian, N = 30) and one active control group (skin patches of Diclofenac Diethylamine Emulgel, N = 31). Participants and study investigators were both blinded to the treatment assignments. The primary outcomes were the improvement of joints' symptoms. The secondary outcomes were changes in white blood cells, erythrocyte sedimentation rate and C-reactive protein. RESULTS: Skin patches of Xin Huang Pian showed quick effect on decreasing joint pain at 3rd day of treatment. Wherever only at 7th day, Diclofenac Diethylamine Emulgel markedly lowered joint pain. Xin Huang Pian also showed superior effect than Diclofenac Diethylamine Emulgel on improving joint swelling and range of motion and decreasing the levels of C-reactive protein and erythrocyte sedimentation rate. No adverse reactions were observed in skin patches of Xin Huang Pian treatment. CONCLUSION: Skin patches of Xin Huang Pian appeared to be safe and efficacious for relieving joint symptoms in patients with acute gouty arthritis. The mechanism might be associated with the decreased levels of C-reactive protein and erythrocyte sedimentation rate. IMPACT: Skin-patcheses with Xin Huang Pian are more effective than Diclofenac Diethylamine Emulgel on improving joint pain, swelling and range of motion. Xin Huang Pian treatment showed superior effects compared with Diclofenac Diethylamine Emulgel on decreasing levels of C-reactive protein and erythrocyte sedimentation rate. Patients with acute gouty arthritis may benefit from skin patches of Xin Huang Pian for effective relief from joint pain and swelling. Chinese Clinical Trial Registration: ChiCTR-TRC-1300 4122.

Branched-chain amino acids, especially of leucine and valine, mediate the protein restricted response in a piglet model.

Branched-chain amino acids (BCAAs) are reduced in various protein restricted models, while the detailed role of BCAAs in protein restricted response is still obscure. Thus, the current study mainly investigated the amino acid metabolism in protein restricted piglets and the effects of BCAA balance in a low-protein diet on growth performance, amino acid metabolism, intestinal structure, and gut microbiota with focus on which BCAAs contributed to the protein restricted response. The results showed that protein restriction increased serum Ser, Thr, Ala, Lys, and Trp but reduced His, Cys, Val, and Ile levels. Intestinal amino acid transporters mainly mediated the mechanism of amino acid uptake. The BCAA balance refreshed the serum BCAA pool, which further improved growth performance in protein restricted piglets. Leu, Val, and Ile balances increased serum BCAA concentrations, respectively, and Leu and Val but not Ile enhanced the feed intake and weight gain in protein restricted piglets. In addition, protein restriction impaired the villus structure and increased the number of goblet cells in the ileum. Also, gut microbiota (Spirochaetales, Gammaproteobacteria, Lactobacillales at the order level) were altered in protein restricted pigs, while the BCAA balance markedly improved Gammaproteobacteria, Lactobacillales, and Aeromonadales proliferation, which might mediate growth promotion and amino acid metabolism. In conclusion, protein restriction markedly affected the host amino acid metabolism (i.e., Ser, Thr, Lys, His, BCAAs). The BCAA balance (especially for supplementation with Leu and Val) improved the amino acid metabolism, growth performance, and gut microbiota communities.

Effects of ornithine α-ketoglutarate on growth performance and gut microbiota in a chronic oxidative stress pig model induced by d-galactose.

The aim of this study was to evaluate the protective effects and underlying mechanisms of ornithine α-ketoglutarate (OKG) on d-galactose (d-gal)-induced chronic oxidative stress in a pig model. A total of 40 castrated young pigs were randomly separated into five groups, including a control group, a model group treated with 5 mg per kg body weight (BW) d-gal, and three d-gal + OKG groups in which the pigs received 0.5%, 1%, and 2% OKG (n = 8). The experiment lasted for 28 days. The growth performance, serum oxidative stress index, expression of relative intestinal genes, gut microbiota, and serum amino acid pool were determined. The results demonstrated that administration of d-gal significantly affected growth performance and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels including related mRNA expression suppression, malondialdehyde (MDA) levels enhancement, gut microbiota dysfunction, and serum amino acid alteration in pigs. However, treatment with 0.5% OKG markedly ameliorated the reduction in the growth performance, as evidenced by the reversed final body weight, average feed intake, and average body weight. Also, 0.5% OKG enhanced the SOD and GSH-Px levels including relative mRNA expression in the intestine and inhibited lipid oxidation subsequent to MDA generation. The intestinal abundances of Firmicutes were increased and those of Proteobacteria, Fusobacteria, Bacteriodetes, and Euryarchaeota were decreased in the pigs supplemented with 0.5% OKG. Meanwhile, 0.5% OKG increased the glutamate, proline, aspartate, threonine, valine, isoleucine and leucine levels in the serum. Collectively, these results indicate that d-gal induced chronic oxidative stress and also proved the positive effects of 0.5% OKG on altering the pig gut microbe, restoring serum amino acid and alleviating the growth-suppression induced by d-gal chronic oxidative stress.

YY1 regulates skeletal muscle regeneration through controlling metabolic reprogramming of satellite cells.

Skeletal muscle satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute or chronic injuries. The lineage progression of quiescent SC toward activation, proliferation, and differentiation during the regeneration is orchestrated by cascades of transcription factors (TFs). Here, we elucidate the function of TF Yin Yang1 (YY1) in muscle regeneration. Muscle-specific deletion of YY1 in embryonic muscle progenitors leads to severe deformity of diaphragm muscle formation, thus neonatal death. Inducible deletion of YY1 in SC almost completely blocks the acute damage-induced muscle repair and exacerbates the chronic injury-induced dystrophic phenotype. Examination of SC revealed that YY1 loss results in cell-autonomous defect in activation and proliferation. Mechanistic search revealed that YY1 binds and represses mitochondrial gene expression. Simultaneously, it also stabilizes Hif1α protein and activates Hif1α-mediated glycolytic genes to facilitate a metabolic reprogramming toward glycolysis which is needed for SC proliferation. Altogether, our findings have identified YY1 as a key regulator of SC metabolic reprogramming through its dual roles in modulating both mitochondrial and glycolytic pathways.