NAD+ supplementation prevents STING-induced senescence in CD8+ T cells by improving mitochondrial homeostasis.

Understanding the connection between senescence phenotypes and mitochondrial dysfunction is crucial in aging and premature aging diseases. Loss of mitochondrial function leads to a decline in T cell function, which plays a significant role in this process. However, more research is required to determine if improving mitochondrial homeostasis alleviates senescence phenotypes. Our research has shown an association between NAD+ and senescent T cells through the cGAS-STING pathway, which can lead to an inflammatory phenotype. Further research is needed to fully understand the role of NAD+ in T-cell aging and how it can be utilized to improve mitochondrial homeostasis and alleviate senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence-associated secretory phenotype (SASP) occur in senescent T cells and tumor-bearing mice. Senescence is mediated by a stimulator of interferon genes (STING) and involves ectopic cytoplasmic DNA. We further show that boosting intracellular NAD+ levels with nicotinamide mononucleotide (NMN) prevents senescence and SASP by promoting mitophagy. NMN treatment also suppresses senescence and neuroinflammation and improves the survival cycle of mice. Encouraging mitophagy may be a useful strategy to prevent CD8+ T cells from senescence due to mitochondrial dysfunction. Additionally, supplementing with NMN to increase NAD+ levels could enhance survival rates in mice while also reducing senescence and inflammation, and enhancing mitophagy as a potential therapeutic intervention.

Effect of dietary koumine on the immune and antioxidant status of carp (Cyprinus carpio) after Aeromonas hydrophila infection.

Koumine (KM) has anxiolytic, anti-inflammatory and growth-promoting effects in pigs and sheep. Based on the growth-promoting and immunological effects of koumine, the present study was conducted on Cyprinus carpio (C. carpio) with four KM concentrations: 0 mg/kg, 0.2 mg/kg, 2 mg/kg, and 20 mg/kg for 10 weeks, followed by a 1-week Aeromonas hydrophila (A. hydrophila) infection experiment. The effect of KM on the immunity of A. hydrophila infected carp was analyzed by histopathology, biochemical assay, and qRT-PCR to assess the feasibility of KM in aquaculture. The results showed that the presence of KM alleviated pathogen damage to carp tissues. At 2 mg/kg and 20 mg/kg concentrations of KM successively and significantly elevated (p < 0.05) the SOD activities in the intestinal tract, hepatopancreas and kidney of carp. The expression levels of hepatopancreatic antioxidant genes Nrf2 and IGF-1 were significantly up-regulated in the same group (p < 0.05), while the expression levels of immune genes IL-8 and IL-10 were down-regulated. In summary, KM at concentrations of 2 mg/kg and 20 mg/kg could regulate the expression of antioxidant and immune genes in various tissues in an orderly and rapid manner, and significantly improve the antioxidant and immune abilities of carp, which is conducive to the improvement of the resilience of carp.

Using Hyperbaric Oxygen to Improve the Radiosensitivity of Human U251 Glioma Cells.

The aim of this study was to explore the use of hyperbaric oxygen to enhance the radiosensitivity of human glioma cells. Sub-cultured U251 human glioma cells were randomly divided into four groups: an untreated control group, cells treated with hyperbaric oxygen (HBO) only, cells treated with X-ray irradiation (X-ray) only, and cells treated with both HBO and X-ray. Cell morphology, cell proliferation activity, cell cycle distribution, and apoptosis were observed in these groups to evaluate the role of HBO in improving the radiosensitivity of glioma cells. With the increase in X-ray doses (0 Gy, 2 Gy, 4 Gy, 6 Gy, 8 Gy), the survival fraction (SF) of glioma cells gradually decreased. Significantly lower SF was observed for the cells treated with the HBO and X-ray together than in the X-ray group for each dose (all P < 0.05). The proliferation inhibition was significantly higher in the HBO combined with X-ray group than in the X-ray group for each dose (all P < 0.05) for the U251 cell line. The percentage of G2/M phase cells was significantly higher in the HBO combined with X-ray (2 Gy) group (26.70% ± 2.46%) and the HBO group (22.36% ± 0.91%) than in the control group (11.56% ± 2.01%) and X-ray (2 Gy) group (10.35% ± 2.69%) (all P < 0.05). U251 cell apoptosis was significantly higher in the HBO combined with X-ray (2 Gy) group than in the HBO group, the X-ray (2 Gy) group, and the control group (all P < 0.05). We conclude that HBO can enhance the proliferation inhibition and apoptosis of glioma U251 cells by blocking glioma cells in the G2/M phase and improve the radiosensitivity of U251 glioma cells.

Effects of Dietary Koumine on Growth Performance, Intestinal Morphology, Microbiota, and Intestinal Transcriptional Responses of Cyprinus carpio.

Gelsemium elegans Benth. (GEB) is a traditional medicinal plant in China, and acts as a growth promoter in pigs and goats. Koumine (KM) is the most abundant alkaloid in GEB and produces analgesic, anti-cancer, and immunomodulatory effects. KM can be used as an aquatic immune stimulant, but its growth-promoting effects and transcriptional mechanisms have not been investigated. Diets containing KM at 0, 0.2, 2, and 20 mg/kg were fed to Cyprinus carpio for 71 days to investigate its effects on growth performance, intestinal morphology, microflora, biochemical indicators, and transcriptional mechanisms. Cyprinus carpio fed with KM as the growth promoter, and the number of intestinal crypts and intestinal microbial populations were influenced by KM concentration. KM increased the abundance of colonies of Afipia, Phyllobacterium, Mesorhizobium, and Labrys, which were associated with compound decomposition and proliferation, and decreased the abundance of colonies of pathogenic bacteria Methylobacterium-Methylorubrum. A total of 376 differentially-expressed genes (DEGs) among the four experimental groups were enriched for transforming growth factor-ß1 and small mother against decapentaplegic (TGF-ß1/Smad), mitogen-activated protein kinase (MAPK), and janus kinases and signal transducers and activators of transcription (Jak/Stat) signaling pathways. In particular, tgfbr1, acvr1l, rreb-1, stat5b, smad4, cbp, and c-fos were up-regulated and positively correlated with KM dose. KM had a growth-promoting effect that was related to cell proliferation driven by the TGF-ß1/Smad, MAPK, and Jak/Stat signaling pathways. KM at 0.2 mg/kg optimized the growth performance of C. carpio, while higher concentrations of KM (2 and 20 mg/kg) may induce apoptosis without significantly damaging the fish intestinal structure. Therefore, KM at low concentration has great potential for development as an aquatic growth promotion additive.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Dietary Antimicrobial Peptides Improve Intestinal Function, Microbial Composition and Oxidative Stress Induced by Aeromonas hydrophila in Pengze Crucian Carp (Carassius auratus var. Pengze).

There is increasing evidence for the potential use of antimicrobial peptides as dietary supplements and antibiotic substitutes. In this study, we analyzed the differential effects of varying levels of antimicrobial peptides on the intestinal function and intestinal microbial and disease resistance of Pengze crucian carp. Approximately 630 experimental fishes were randomized in the control group (G0: 0 mg/kg) and in five groups supplemented with different doses of AMPs (G1: 100 mg/kg, G2: 200 mg/kg, G3: 400 mg/kg, G4: 800 mg/kg, and G5: 1600 mg/kg) and were fed for ten weeks. Three replicates per group of 35 fish were performed. The results showed that AMPs promoted intestinal villus development and increased intestinal muscular thickness (p < 0.05) and goblet cell abundance. The enzymatic activities of all groups supplemented with AMPs were effectively improved. AMP supplementation significantly enhanced the activities of antioxidant enzymes and digestive enzymes in the intestines of G3 animals (p < 0.05). Compared with G0 animals, AMP-supplemented animals regulated the expression of intestinal immune-related genes and exhibited significant differences in the G3 animal group (p < 0.05). The abundance of intestinal Firmicutes and Bacteroidetes increased in the AMP-supplemented groups, but the Firmicutes/Bacteroidetes ratio was lower than that in the G0 group. AMP supplementation also decreased the abundance of Fusobacterium while increasing the proportion of Actinobacteria (p < 0.05). After Aeromonas hydrophila infection, the expression levels of anti-inflammatory factors in the intestinal tract of G3 animals were significantly upregulated, and the level of the proinflammatory factor was decreased (p < 0.05). The intestinal Cetobacterium levels of G3 animals were significantly increased (p < 0.01), while the Proteobacteria levels were decreased, and the intestinal goblet cell proliferation was significantly lower than that of G0 animals (p < 0.05). This indicates that groups supplemented with AMPs have better disease resistance than the G0 group and can rapidly reduce the adverse effects caused by inflammatory response. Taken together, the present results suggest that AMP supplementation can improve intestinal function and intestinal microbial and pathogen resistance in Pengze crucian carp.

Analysis of the Anti-Tumour Effect of Xuefu Zhuyu Decoction Based on Network Pharmacology and Experimental Verification in Drosophila.

Background: Tumours are among the most lethal diseases that heavily endanger human health globally. Xuefu Zhuyu Decoction (XFZYD) is a prescription used to treat blood-activating stasis. Although XFZYD has been shown to suppress migration and invasion of tumour cells, the active ingredients, potential targets, and underlying mechanism remain largely elusive. Purpose: To identify the prospective ingredients and major targets of XFZYD against tumours, and evaluate the efficacy and potential molecular mechanisms of XFZYD extract on tumour growth and invasion. Methods: We predicted that XFZYD might act on 80 targets through 128 active components using the network pharmacology analysis method. In addition, we prepared an XFZYD aqueous extract and employed the RasV12/lgl -/- -induced Drosophila tumour model to carry out experimental verification. Results: XFZYD did not exhibit any side effects on development, viability, and fertility. Furthermore, XFZYD significantly impeded tumour size and invasion at moderate concentrations and suppressed the increased phosphorylation of JNK but strongly enhanced the expression of Caspase 3 in the RasV12/lgl -/- model. Finally, the mRNA level of the transcription complex AP-1 component c-FOS was remarkably reduced. In contrast, the transcription of three pro-apoptotic genes was significantly increased when XFZYD was used to treat the tumour model. Conclusion: The study findings suggest that XFZYD may promote tumour cell apoptosis by activating caspase signalling to control primary growth and hinder tumour cell invasion by suppressing JNK/AP-1 signalling activity, thus providing a potential therapeutic strategy for XFZYD in the clinical treatment of cancer and other related diseases.

Yu Shi An Chang Fang Ameliorates TNBS-Induced Colitis in Mice by Reducing Inflammatory Response and Protecting the Intestinal Mucosal Barrier.

Ulcerative colitis (UC) is an inflammatory bowel disease that is related to the occurrence of colon cancer. This study aimed to investigate the underlying mechanism by which Yu Shi An Chang Fang (YST) treated UC. 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) was used to construct the UC model. The body weight, fecal viscosity, and fecal bleeding of all mice were recorded every day to calculate the DAI value. The pathological changes in colon tissues were observed by hematoxylin-eosin (H&E) staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and myeloperoxidase (MPO) reflecting inflammation and the levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) reflecting oxidative stress in colon tissues were all measured by their assay kits. The mRNA expression of TNF-α, IL-1ß, and IL-6 in colon tissues was detected by quantitative reverse transcription-PCR (qRT-PCR). The expression of proteins related to pyroptosis and the colonic mucosal barrier was analyzed by Western blot. As a result, TNBS caused decreases in body weight and colon lengths, triggered serious histological damage, promoted inflammation, oxidative stress, and pyroptosis, and destroyed the colonic mucosal barrier. The above changes caused by TNBS in colitis mice could be partially reversed by YST. In conclusion, YST ameliorates TNBS-induced UC in mice by reducing the inflammatory response and protecting the intestinal mucosal barrier.

Weakened Effective Connectivity Related to Electroacupuncture in Stroke Patients with Prolonged Flaccid Paralysis: An EEG Pilot Study.

Flaccid paralysis in the upper extremity is a severe motor impairment after stroke, which exists for weeks, months, or even years. Electroacupuncture treatment is one of the most widely used TCM therapeutic interventions for poststroke flaccid paralysis. However, the response to electroacupuncture in different durations of flaccid stage poststroke as well as in the topological configuration of the cortical network remains unclear. The objectives of this study are to explore the disruption of the cortical network in patients in different durations of flaccid stage and observe dynamic network reorganization during and after electroacupuncture. Resting-state networks were constructed from 18 subjects with flaccid upper extremity by partial directed coherence (PDC) analysis of multichannel EEG. They were allocated to three groups according to time after flaccid paralysis: the short-duration group (those with flaccidity for less than two months), the medium-duration group (those with flaccidity between two months and six months), and the long-duration group (those with flaccidity over six months). Compared with short-duration flaccid subjects, weakened effective connectivity was presented in medium-duration and long-duration groups before electroacupuncture. The long-duration group has no response in the cortical network during electroacupuncture. The global network measures of EEG data (sPDC, mPDC, and N) indicated that there was no significant difference among the three groups. These results suggested that the network connectivity reduced and weakly responded to electroacupuncture in patients with flaccid paralysis for over six months. These findings may help us to modulate the formulation of electroacupuncture treatment according to different durations of the flaccid upper extremity.

Tuina for lumbar disc herniation: A protocol for systematic review and meta analysis.

BACKGROUND: Lumbar disc herniation (LDH) is an important factor of causing leg pain and numbness. As a secondary discipline of Traditional Chinese Medicine, tuina is widely used for the treatment of LDH in China even in other nations while its clinical value is not acknowledged universally. So, we focus on this article aims to evaluate its efficacy and safety of LDH. METHODS: Electronic databases involving Cochrane Library, PubMed, Web of Science, EMBASE, China Science and Technology Journal, China National Knowledge Infrastructure, Wanfang and Chinese Biomedical Literature Database will be pertained with appropriate search strategy. And RevMan V.5.3.5 software will be conducted as the assessment tool for bias risk, data synthesis, subgroup analysis as well as meta-analyses. RESULTS: This systematic review will provide a high-quality synthesis of current evidence of tuina for LDH. CONCLUSION: This protocol will determine whether Tuina is an effective and safe treatment method for LDH.

Evodiamine inhibits high-fat diet-induced colitis-associated cancer in mice through regulating the gut microbiota.

OBJECTIVE: High-fat diet is one of the main risk factors that disrupt the balance of gut microbiota, which eventually will induce colorectal cancer (CRC). Evodiamine (EVO) is a wildly used multifunctional traditional Chinese medicine extract. In this study, we investigated the role of gut microbiota in high-fat diet-propelled CRC and the potential of EVO for CRC chemoprevention. METHODS: Gut microbiota, serum d-lactic acid and endotoxin from 38 patients with colon cancer and 18 healthy subjects were detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). In addition, body mass index, phospho-signal transducer and activator of transcription 3 (p-STAT3) expression in cancer tissues and paracancerous tissues were detected by immunohistochemistry. A mouse intestinal inflammatory tumor model was established by azomethane/sodium dextran sulfate, followed by treatment with EVO and 5-aminosalicylic acid (ASA). Gut microbiota and inflammatory factors were detected by quantitative polymerase chain reaction, while serum d-lactic acid and endotoxin were detected by ELISA. Furthermore, cell proliferation, cell apoptosis, and interleukin (IL)-6/STAT3/P65 pathway were evaluated by 5-ethynyl-2'-deoxyuridine, terminal-deoxynucleotidyl transferase-mediated nick-end labeling, and Western blot assays. RESULTS: In patients with colon cancer, the numbers of Enterococcus faecalis and Escherichia coli were increased, while those of Bifidobacterium, Campylobacter and Lactobacillus were decreased. Serum endotoxin and d-lactic acid levels and p-STAT3 levels were significantly increased. In the mouse model, both EVO and ASA inhibited tumor formation, decreased the proliferation of tumor cells, and induced apoptosis of tumor cells. Compared with the control group, the numbers of E. faecalis and E. coli were decreased, while Bifidobacterium, Campylobacter and Lactobacillus numbers were increased. In the EVO group, serum endotoxin and d-lactic acid levels and inflammatory factors were significantly decreased. Further, the IL6/STAT3/P65 signaling pathway was inhibited in the EVO group. CONCLUSION: EVO may inhibit the occurrence of colon cancer by regulating gut microbiota and inhibiting intestinal inflammation. The potential mechanism involves inhibition of the IL6/STAT3/P65 signaling pathway, revealing its potential therapeutic significance in clinical applications.

The Impact of Electroacupuncture at Hegu, Shousanli, and Quchi Based on the Theory "Treating Flaccid Paralysis by Yangming Alone" on Stroke Patients' EEG: A Pilot Study.

BACKGROUND: In China, electroacupuncture based on meridians theory "treating flaccid paralysis by Yangming alone" has been widely used for stroke rehabilitation in clinical practice. The aim of this study was to explore the electroencephalography change of electroacupuncture intervention on strokes patients with flaccid paralysis. METHODS: Twenty-three stroke patients with flaccid paralysis and six stroke patients with spasticity accepted electroacupuncture with the acupoints Hegu [LI4], Shousanli [LI10], and Quchi [LI11] for 20 minutes and their EEG data were recorded before, during, and after the electroacupuncture intervention. RESULTS: Compared with the baseline EEG signals before electroacupuncture, the ipsilesional and contralesional beta-band average power of patients with flaccid paralysis and spasticity were significantly increased during the needles retention stage and decreased slightly after removing the needles. The significant decrease of the ipsilesional and contralesional delta band average power in patients with flaccid paralysis occurred during the electroacupuncture stimulation, and they increased after the removal of the needles. The ipsilesional delta band average power of patients with spasticity significantly decreased during the electroacupuncture stimulation. CONCLUSION: From this pilot electrophysiological study, we provided a possible electrophysiological mechanism of the curative effect of electroacupuncture for stroke rehabilitation.

[Regulatory effect of Qianliexiao Decoction on TGF-ß1, Smad4 and Smad 7 signaling pathways and the proliferation and apoptosis of prostate fibroblasts in mice with experimental autoimmune prostatitis].

OBJECTIVE: To study the effect of intervening in the signal transduction pathways of TGF-ß1, Smad4 and Smad7 with Qianliexiao Decoction (QLX) on the proliferation and apoptosis of prostate fibroblasts (PrF) in mice with experimental autoimmune prostatitis (EAP). METHODS: A model of EAP with damp-heat syndrome was established in C57BL/6 mice by immunization induction combined with the TCM modeling method. The prostate tissue of the mice was harvested for isolation, culturing and purification of PrFs and detection of their purity. After modeling by stimulation with a medium containing >90%-purity or 5 ng/ml TGF-ß1, the PrFs in the logarithmic growth phase were obtained and randomly divided into a blank control (serum-free medium), a model control, a positive control (medium containing 5 ng/ml TGF-ß1), a low-dose QLX (serum containing 5% QLX), a medium-dose QLX (serum containing 10% QLX), and a high-dose QLX group (serum containing 20% QLX). After 24 hours of intervention, the proliferation of the PrFs was measured, the protein expressions of TGF-ß1, Smad4, Smad7, p-Smad4 and p-Smad7 detected by Western blot, their mRNA expressions determined by qPCR, and the apoptosis of the PrFs examined by flow cytometry. RESULTS: After induction with TGF-ß1, the proliferation of the PrFs was significantly increased in the positive control (P < 0.05), but inhibited in the medium- and low-dose QLX groups (P < 0.05) and even more significantly in the high-dose QLX group as compared with that in the model control (P < 0.01). The expressions of Smad4, p-Samd7 and TGF-ß1 proteins in the PrFs were remarkably higher in the positive control than in the model control group (P < 0.05), while those of p-Smad4 and TGF-ß1 markedly lower (P < 0.01) and that of p-Smad7 dramatically higher in the QLX intervention groups than in the positive control (P < 0.01), in an evident dose-dependent manner. In comparison with the model control group, the high-dose QLX group exhibited a significant decrease in the mRNA expression of Smad4 (P < 0.05) but all the three QLX groups showed a dramatic increase in those of Smad7 (P < 0.05) and TGF-ß1 (P < 0.01). The mRNA expression of Smad4 was markedly down-regulated in the high-dose QLX group compared with that in the positive control (P < 0.05), that of Smad7 up-regulated in the model control and QLX groups (P < 0.01), and that of TGF-ß1 down-regulated in the three QLX groups (P < 0.01). The apoptosis rate of the PrFs was significantly higher in the QLX groups than in the model control (P < 0.05) in a dose-dependent manner, but showed no statistically significant difference between the model control and the positive control groups (P > 0.05). CONCLUSIONS: TGF-ß1 can stimulate the proliferation of PrFs, up-regulate the expressions of TGF-ß1 and p-Smad4, and down-regulate that of p-Smad7, while QLX can inhibit the proliferation of PrFs in a dose-dependent manner by decreasing the expressions of TGF-ß1 and p-Smad4, increasing that of p-Smad7, and thereby suppressing TGF-ß1-induced proliferation of PrFs.

[Literature research and discussion of Chinese medicinal properties of Morinda citrifolia].

Noni is a dry and mature fruit of Morinda citrifolia, which is widely distributed in the islands in the southern Pacific Ocean and the Indochina Peninsula in Asia. It is edible and has been used as a natural medicine for thousands of years. At present, Noni has been legally introduced into China, but there is no clear standard of traditional Chinese medicine properties and clinical application of traditional Chinese medicine, which greatly limits the application of compatibility with traditional Chinese medicine in China. This article appllied our pioneering modern research technology of new herbal medicine outside of China, theoretically studied the traditional Chinese medicine properties of Noni, and scientifically guided the reasonable compatibility and application of Noni with traditional Chinese medicine. The Web of Science and PubMed databases were selected to access the literatures on Noni. The retrieval time was August 1, 2018, with Noni or Morinda citrifolia as the search term. A total of 862 articles were retrieved. By reading the titles and abstracts of the articles, in addition to repetitive and irrelevant literature, 251 scientific research literatures with reasonable design and high credibility were selected, including 25 clinical trials, 94 pharmacological experiments, and 51 chemical composition literatures. Through analysis of scientific research literatures, led by clinical experiments, supported by pharmacological experiments, combined with the research progress of chemical components, the medicinal properties were studied under the guidance of traditional Chinese medicine theory. The Chinese medicine property of Noni is flat, with acid and sweet flavor.The channel tropisms of Noni included kidney, liver and spleen. The function of Noni included tonifying kindey and liver, strengthening tendon and bone, yiqi yangyin. The clinical application of Noni is used for liver and kidney deficiency, waist and knee weakness, weak muscles and bones; Qi and Yin deficiency, tiredness and thirst. Taken as fruit pulp or dry powder, the equivalent of dried product is 1-4 g. Noni is also distributed in Taiwan, Hainan in China. Hainan, Yunnan have been cultivated and introduced. Give Noni a clear Chinese medicine property, and lay a theoretical foundation for the compatibility of Noni with traditional Chinese medicine, which can enrich the Chinese medicine resources and promote the development of Chinese medicine.

miR-138 mediates sorafenib-induced cell survival and is associated with poor prognosis in cholangiocarcinoma cells.

Cholangiocarcinoma is an aggressive malignancy with rapid invasion, metastasis and poor prognosis, however, the mechanism mediating its cholangiocarcinoma development needs further investigation. Here, we demonstrate that decreased miR-138 in tumor tissues is related to the poor prognosis in patients, and that miR-138 mediates sorafenib-induced cell survival in cholangiocarcinoma cells. Moreover, miR-138 negatively regulates SOX4 expression by specifically targeting its 3' untranslated region (3' UTR). As per our results, overexpression of SOX4 reversed sorafenib-induced changes in cell viability and apoptosis. Furthermore, the elevated levels of SOX4 in the tumor tissues that correlated with poor prognosis. Overall, the present study reveals that miR-138/SOX4 is involved in sorafinib-mediated cell survival in cholangiocarcinoma cells, and is associated with poor prognosis.

Traditional Chinese Medicine-Guided Dietary Intervention for Male Youth Undergoing Drug Detoxification: A Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of traditional Chinese medicine- (TCM-) guided dietary interventions in improving yang-qi deficiency and yin-blood deficiency TCM syndromes according to the principles of TCM syndrome differentiation theory in male youths undergoing drug detoxification during the rehabilitation period who stayed in a compulsory isolation detoxification center. METHODS: Male youths undergoing drug detoxification who met the criteria to be included in the study were randomly divided into the intervention group (n = 62) and the control group (n = 61) according to a random number table in a 1 : 1 ratio. The intervention group received a TCM-guided diet, and the control group received routine food support. Over an intervention period of 3 months, we observed changes in the TCM syndrome element scores in the two groups before and after intervention. RESULTS: After 3 months, the qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndrome in the intervention group improved significantly (P values 0.009, 0.000, 0.005, and 0.001, respectively). In the control group, yang deficiency, qi deficiency, and yang-qi deficiency syndromes worsened significantly (P values 0.003, 0.032, and 0.009, respectively). The differences (post-pre) in yang deficiency, qi deficiency, yang-qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndromes between the two groups were statistically significant (P values 0.003, 0.003, 0.003, 0.001, 0.005, and 0.002, respectively). CONCLUSION: A TCM-guided diet can delay the worsening of yang-qi deficiency syndrome symptoms and improve yin-blood deficiency syndrome and the prognosis of male youth undergoing drug detoxification during the rehabilitation period.

RNASET2 impairs the sperm motility via PKA/PI3K/calcium signal pathways.

Asthenozoospermia is one of the leading causes of male infertility owing to a decline in sperm motility. Herein, we determined if there is a correlation between RNASET2 content on human spermatozoa and sperm motility in 205 semen samples from both asthenozoospermia patients and normozoospermia individuals. RNASET2 content was higher in sperm from asthenozoospermia patients than in normozoospermia individuals. On the other hand, its content was inversely correlated with sperm motility as well as progressive motility. Moreover, the inhibitory effect of RNASET2 on sperm motility was induced by incubating normozoospermic sperm with RNase T2 protein. Such treatment caused significant declines in intracellular spermatozoa PKA activity, PI3K activity and calcium level, which resulted in severely impaired sperm motility, and the sperm motility was largely rescued by cAMP supplementation. Finally, protein immunoprecipitation and mass spectrometry identified proteins whose interactions with RNASET2 were associated with declines in human spermatozoa motility. AKAP4, a protein regulating PKA activity, coimmunoprecipated with RNASET2 and they colocalized with one another in the sperm tail, which might contribute to reduced sperm motility. Thus, RNASET2 may be a novel biomarker of asthenozoospermia. Increases in RNASET2 can interact with AKAP4 in human sperm tail and subsequently reduce sperm motility by suppressing PKA/PI3K/calcium signaling pathways.

Proliferation of Bilateral Nerve Fibers Following Thalamic Infarction Contributes to Neurological Function Recovery: A Diffusion Tensor Imaging (DTI) Study.

BACKGROUND The aim of this study was to investigate the reorganization in ipsilesional and contralesional thalamic radiation fibers after unilateral focal thalamic stroke in sensory disturbance patients. MATERIAL AND METHODS We recruited 12 patients with acute unilateral thalamic infarction and sensory disturbance and 12 healthy age- and sex-matched controls. All patients underwent diffusion tensor imaging (DTI) and were assessed with National Institutes of Health stroke scale (NIHSS), Barthel index (BI), and paragraph 8 of NIHSS (NIHSS8) at 1 week (W1), 4 weeks (W4), 3 months (M3), and 6 months (M6) after thalamic infraction. The relationship between FA changes and the clinical scores changes were then examined. RESULTS NIHSS and NIHSS8 scores decreased while BI scores increased gradually from W1 to M6 in patients, but not in controls. FA values of the patients gradually increased in ipsilesional and contralesional thalamic radiation fibers from W1 to M6. In addition, the FA values in patients were significantly higher at M3 and M6 compared to W1. No significant changes were observed in the controls. Regarding the relationship between FA changes and the clinical scores changes, the FA increases were negatively correlated with NIHSS and NIHSS8 decrease while FA increases were positively correlated with BI increases. CONCLUSIONS Our results indicate that reorganization occurred after unilateral focal thalamic infarct not only in ipsilesional, but also in contralesional thalamic radiation fibers in patients with sensory disturbance. In addition, the results suggested that the reorganization can support and promote stroke restoration.

Ginkgo May Sensitize Ovarian Cancer Cells to Cisplatin: Antiproliferative and Apoptosis-Inducing Effects of Ginkgolide B on Ovarian Cancer Cells.

Ginkgolide B (GB), the primary active component ofGinkgo bilobaextracts, may have antitumor properties. The objective of this study was to determine the effects and possible mechanisms of GB in ovarian cancer cells. In this study, human ovarian cancer cell lines (SKOV3 and CAOV3) were treated with different concentrations of GB alone or in combination with Cis-diaminodichloroplatinum (CDDP). An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to determine cell viability. The apoptosis rates of cells were measured by flow cytometric analysis. The expression of apoptosis-associated and proliferation-associated proteins was detected by Western blot. The cytotoxicity of GB was analyzed using a lactate dehydrogenase assay. Treatment with 100 µM GB for 3 days significantly inhibited SKOV3 and CAOV3 cell proliferation by 57.3% and 63.1% compared with control cells, respectively, as determined by MTT assay. Similarly, the apoptotic cell population was increased when treated with GB in a dose-dependent manner both in SKOV3 and CAOV3 cells. These effects were characterized by the upregulation of p21, p27, cleaved capase-3, and cleaved caspase-8 and downregulation of cyclin D1. In addition, a combined treatment of low concentrations of GB and CDDP showed an additive effect on the inhibition of SKOV3 cell proliferation. Furthermore, GB had significantly less cytotoxicity than CDDP in normal human ovarian surface epithelial cells. This study suggests that GB can be proposed as an effective antiproliferative and apoptosis-inducing agent with interesting translational application in ovarian cancers, used in addition to conventional chemotherapy.

Optimization of biodiesel production process from soybean oil using the sodium potassium tartrate doped zirconia catalyst under Microwave Chemical Reactor.

A solid base catalyst was prepared by the sodium potassium tartrate doped zirconia and microwave assisted transesterification of soybean oil was carried out for the production of biodiesel. It was found that the catalyst of 2.0(n(Na)/n(Zr)) and calcined at 600°C showed the optimum activity. The base strength of the catalysts was tested by the Hammett indicator method, and the results showed that the fatty acid methyl ester (FAME) yield was related to their total basicity. The catalyst was also characterized by FTIR, TGA, XRD and TEM. The experimental results showed that a 2.0:1 volume ratio of methanol to oil, 65°C reaction temperature, 30 min reaction time and 10 wt.% catalyst amount gave the highest the yield of biodiesel. Compared to conventional method, the reaction time of the way of microwave assisted transesterification was shorter. The catalyst had longer lifetime and maintained sustained activity after being used for four cycles.