Synergistic impact of Gui Zhi Shao Yao Zhi Mu Decoction and leflunomide on gut microbiota in rheumatoid arthritis: insights from 16S rDNA sequencing.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex pathogenesis, including alterations in the gut microbiota. Gui Zhi Shao Yao Zhi Mu Decoction (GSZD), a traditional Chinese herbal formula, has shown efficacy in RA treatment, but its impact on intestinal microflora remains unclear. This study aimed to investigate the effects of GSZD combined with leflunomide on the gut microbiota of RA patients. METHODS: The study enrolled 48 RA patients who were randomly assigned to either a control group receiving leflunomide or a treatment group receiving GSZD combined with leflunomide for 12 weeks. Gut microbiota composition was analyzed pre- and post-intervention using 16S rDNA sequencing. Changes in microbial diversity, abundance, and metabolic functions were assessed. RESULTS: Post-treatment, both groups exhibited significant alterations in gut microbiota composition. GSZD combined with leflunomide led to an increased Bacteroidetes/Firmicutes ratio and a reduction in Actinobacteria compared to leflunomide alone. This was associated with beneficial shifts in microbial genera and metabolic pathways, suggesting improved gut health and systemic immune modulation. CONCLUSION: GSZD combined with leflunomide significantly modulates the gut microbiota in RA patients. This study provides insights into the mechanisms underlying the therapeutic effects of GSZD and highlights the potential of integrating traditional Chinese medicine with conventional treatments in managing RA.

Exploring the potential mechanism of Taohong Siwu decoction in the treatment of avascular necrosis of the femoral head based on network pharmacology and molecular docking.

Based on network pharmacology and molecular docking, this study seeks to investigate the mechanism of Taohong Siwu decoction (THSWD) in the treatment of avascular necrosis of the femoral head (AVNFH). The Traditional Chinese Medicine Systems Pharmacology database was used in this investigation to obtain the active ingredients and related targets for each pharmaceutical constituent in THSWD. To find disease-related targets, the terms "avascular necrosis of the femoral head," "necrosis of the femoral head," "steroid-induced necrosis of the femoral head," "osteonecrosis," and "avascular necrosis of the bone" were searched in the databases DisGeNET, GeneCards, Comparative Toxicogenomics Database, and MalaCards. Following the identification of the overlap targets of THSWD and AVNFH, enrichment analysis using gene ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and WikiPathways was conducted. The "THSWD-drug-active compound-intersection gene-hub gene-AVNFH" network and protein-protein interaction network were built using Cytoscape 3.9.1 and string, and CytoHubba was used to screen hub genes. The binding activities of hub gene targets and key components were confirmed by molecular docking. 152 prospective therapeutic gene targets were found in the bioinformatics study of ONFH treated with THSWD, including 38 major gene targets and 10 hub gene targets. The enrichment analysis of 38 key therapeutic targets showed that the biological process of gene ontology analysis mainly involved cytokine-mediated signaling pathway, angiogenesis, cellular response to reactive oxygen species, death-inducing signaling complex. The Kyoto Encyclopedia of Genes and Genomes signaling pathway mainly involves TNF signaling pathway, IL-17 signaling pathway, and the Recactome pathway mainly involves Signaling by Interleukins, Apoptosis, and Intrinsic Pathway for Apoptosis. WikiPathways signaling pathway mainly involves TNF-related weak inducer of apoptosis signaling pathway, IL-18 signaling pathway. According to the findings of enrichment analysis, THSWD cured AVNFH by regulating angiogenesis, cellular hypoxia, inflammation, senescence, apoptosis, cytokines, and cellular proliferation through the aforementioned targets and signaling pathways. The primary component of THSWD exhibits a strong binding force with the key protein of AVNFH. This study sheds new light on the biological mechanism of THSWD in treating AVNFH by revealing the multi-component, multi-target, and multi-pathway features and molecular docking mechanism of THSWD.

Effect of transvaginal Lactobacillus supplementation on reversing lower genital tract dysbiosis and improving perinatal outcomes in PCOS patients after IVF-FET: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization-frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET. METHODS/DESIGN: This is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography-mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited. DISCUSSION: This is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET. ETHICS AND DISSEMINATION: Ethical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed. TRIAL REGISTRATION: ChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549 .

Network pharmacological analysis on the mechanism of Coix seed decoction for osteoarthritis of the knee.

Based on network pharmacology methods, we explored the mechanism of the classic Chinese medicine formula Coix seed decoction (CSD) in treating knee osteoarthritis (KOA). We searched each single drug in the CSD in the traditional Chinese medicine systematic pharmacology database in turn to obtain information on the active ingredients and target proteins of the CSD, and obtain the name of the genes corresponding to the target proteins through the UniProt database. We collected KOA-related genes from DisGeNET, GeneCards, comparative toxicogenomics database, and MalaCards database. The Venny online tool identified potential therapeutic targets by intersecting CSD and KOA target genes, while gene ontology and Kyoto encyclopedia of genes and genomes analysis was performed using the Oebiotech Cloud Platform. A protein-protein interaction network was established using the String database; a "CSD-active ingredient-target gene-KOA" network plot was constructed using Cytoscape 3.9.1 software and screened for key targets and hub targets. Finally, molecular docking was performed for hub genes with high Degree values. A total of 227 effective target genes for CSD and 8816 KOA-related target genes were obtained, as well as 191 cross-target genes for CSD and KOA. We screened 37 key gene targets and identified the top 10 hub target genes in descending order of Degree value using protein-protein interaction and Cytoscape 3.9.1 software (TNF, IL-6, MMP-9, IL-1ß, AKT-1, VEGFα, STAT-3, PTGS-2, IL-4, TP53). Gene ontology analysis showed that the biological process of CSD treatment of KOA mainly involves cytokine-mediated signaling pathway, negative regulation of apoptotic process, cellular response to hypoxia, cellular response to cadmium ion, response to estradiol, and extrinsic apoptotic signaling pathway in absence of ligand. Kyoto encyclopedia of genes and genomes analysis revealed major signaling pathways including Cellular senescence, TNF signaling pathway, and PI3K-Akt signaling pathway. The molecular docking results show that the core components bind well to the core targets. In conclusion, CSD may exert therapeutic effects on KOA by inhibiting pathological processes such as inflammatory response, apoptosis, cellular senescence, and oxidative stress.

An innovative virtual reality training tool for the pre-hospital treatment of cranialmaxillofacial trauma.

Virtual reality (VR) surgery using the High Technology Computer Corporation Very Immersive Virtual Experience professional 2(HTC VIVE Pro2) suite is a multi-sensory, holistic surgical training experience. A multimedia combination including videos and three-dimensional interaction in VR has been developed to enable trainees to experience a realistic battlefield environment. The innovation allows trainees to interact with the individual components of the cranialmaxillofacial(CMF) anatomy and apply surgical instruments while watching close-up stereoscopic three-dimensional videos of the surgery. In this study, a novel training tool for the pre-hospital treatment of CMF trauma based on immersive virtual reality (iVR) was developed and validated. Twenty-five CMF surgeons evaluated the application for face and content validity. Using a structured assessment process, the surgeons commented on the content of the developed training tool, its realism and usability and the applicability of VR surgery for CMF trauma rescue simulation training. The results confirmed the applicability of VR for delivering training in the pre-hospital treatment of CMF trauma. Modifications were suggested to improve the user experience and interactions with the surgical instruments. This training tool is ready for testing with surgical trainees.

Defect Surface Engineering of Hollow NiCo2S4 Nanoprisms towards Performance-Enhanced Non-Enzymatic Glucose Oxidation.

Transition metal sulfides have been explored as electrode materials for non-enzymatic detection. In this work, we investigated the effects of phosphorus doping on the electrochemical performances of NiCo2S4 electrodes (P-NiCo2S4) towards glucose oxidation. The fabricated non-enzymatic biosensor displayed better sensing performances than pristine NiCo2S4, with a good sensitivity of 250 µA mM-1 cm-2, a low detection limit (LOD) of 0.46 µM (S/N = 3), a wide linear range of 0.001 to 5.2 mM, and high selectivity. Moreover, P-NiCo2S4 demonstrated its feasibility for glucose determination for practical sample testing. This is due to the fact that the synergetic effects between Ni and Co species, and the partial substitution of S vacancies with P can help to increase electronic conductivity, enrich binary electroactive sites, and facilitate surface electroactivity. Thus, it is found that the incorporation of dopants into NiCo2S4 is an effective strategy to improve the electrochemical activity of host materials.

Lu3+-based nanoprobe for virtual non-contrast CT imaging of hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE), the mainstream treatment for hepatocellular carcinoma (HCC), is a method of blocking tumor blood vessels with a mixture of lipiodol and chemotherapeutics. And the contrast-enhanced computed tomography (CT) is the commonly used way for follow-up of HCC after TACE. However, it is noteworthy that when lipiodol deposition plays an embolic effect, it also produces high-density artifacts in CT images. These artifacts usually conceal the enhancement effect of iodine contrast agents. As a result, the residual region is difficult to be visualized. To overcome this obstacle, we developed one kind of Lu3+/Gd3+ doped fluoride nanoprobe modified with Dp-PEG2000 to realize CT/MRI dual-modality imaging of HCC. Compared with lipiodol or ioversol, the obtained PEGylated product LG-PEG demonstrated a greater density value in high keV CT images. In vitro experiments showed the lipiodol artifacts can be removed in virtual non-contrast (VNC) imaging, but the density of ioversol was also removed at the same time. However, the LG-PEG synthesized in this work can still maintain a high density in VNC imaging, which indicates that LG-PEG can exploit its advantages to the full in VNC imaging. Furthermore, LG-PEG successfully exerted tumor enhancement effects in the in vivo VNC images of HCC with lipiodol deposition. In addition, LG-PEG exhibited a strong T2 enhancement effect with low biological toxicity and less side-effect on the main organ and blood. Thus, the LG-PEG reported in this research can serve as an effective and safe VNC contrast agent for HCC imaging after TACE.

Sex differences in the pharmacokinetics and tissue residues of Macleaya cordata extracts in rats.

Macleaya cordata extracts (MCE) are listed as feed additives in animal production by the European Food Authority. The core components of MCE are mainly sanguinarine (SA) and chelerythrine (CHE). This study aims to investigate sex differences in the pharmacokinetics and tissue residues of MCE in rats.Male and female rates were intragastrically administered MCE (1.25 mg·kg-1 body weight and 12.5 mg·kg-1 body weight dose for 28 days). SA and CHE concentrations were determined using high-performance liquid chromatography/tandem mass spectrometry.The peak plasma concentration (Cmax) and area under the curve (AUC) of both CHE and SA were higher in female than in male rats (12.5 mg·kg-1 body weight group), whereas their half-life (T1/2) and apparent volume of distribution (Vd) was lower (p < 0.05). Tissue rfesidue analysis indicated that SA and CHE were more distributed in male than in female rats and were highly distributed in the caecum and liver. SA and CHE were completely eliminated from the liver, kidney, lung, heart, spleen, leg muscle, and caecum after 120 h, indicating they did not accumulate in rats for a long time.Overall, we found that the pharmacokinetics and tissue residues of SA and CHE of male and female rats showed sex differences.

Current Status and Evaluation of Randomized Clinical Trials of Traditional Chinese Medicine in the Treatment of Cardiovascular Diseases.

Traditional Chinese medicine has long been applied to various diseases in China for a few thousand years. In recent years, its market has gradually developed from Asian countries to Western countries. At present, due to the lack of evidence-based medicine research, the effect of traditional Chinese medicine on the prevention and treatment of cardiovascular disease remains unclear. In evaluating the efficacy and safety of drugs, randomized controlled clinical trials (RCTs) are recognized as the gold standard for testing the effectiveness and safety of treatments and could offer the best evidence for the formulation of clinical treatment guidelines. Although traditional Chinese medicine has long been used to treat cardiovascular diseases, the research on the application of RCT to test the combination of traditional Chinese and Western medicine therapy or single traditional Chinese medicine therapy started late, and the number is comparably small. In order to summarize and objectively evaluate the research results of integrated traditional Chinese and Western medicine in intervention of cardiovascular diseases, we reviewed the literature of RCTs in this field by searching some Chinese and English databases and put forward some suggestions for the future development and research of traditional Chinese medicine.

Treatment of subclinical varicocele with acupuncture: A case report.

Varicocele is a vascular lesion characterized by abnormal dilatation and/or tortuosity of the veins of the pampiniform plexus, which sometimes manifests as chronic, dull pain in the scrotum, testicle or inguinal area. Subclinical varicocele (SCV) is as an early phase in the progression of its clinical analog. Given the lack of relevant studies on treatment strategies, no conclusive answer exists regarding how SCV should be managed. In this case report, a 40-year-old male patient visited our acupuncture outpatient clinic for left-sided scrotal pain and heaviness caused by SCV. After ten sessions of acupuncture treatments (acupuncture was performed at Zhongji (CV3), Guanyuan (CV4), qihai (CV6) and bilateral Guilai (ST29), Hegu (LI4), Taichong (LR3), Zusanli (ST36), Sanyinjiao (SP6), with electroacupuncture (EA) stimulation at Qihai (CV6) and Zhongji (CV3) as well as Guilai (ST29) on both sides), the patient was symptom-free. More unexpectedly, ultrasound reexamination showed no obvious abnormalities in bilateral spermatic veins. From this case, we conclude that acupuncture may be an effective alternative therapy for SCV treatment.

Kaempferol attenuates streptozotocin-induced diabetic nephropathy by downregulating TRAF6 expression: The role of TRAF6 in diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia rhizome is a famous traditional herbal medical in tropical and subtropical areas. Kaempferol (KPF) is one of the main bioactive compounds in Kaempferia rhizome, with anti-oxidant/anti-inflammatory effects demonstrated in various disease models, including cancers, obesity and diabetes. AIM OF THE STUDY: Inflammation plays an important role in the pathogenesis of diabetic nephropathy (DN). TRAF6 functions as a signal transducer in toll-like receptor 4 and NF-κB pro-inflammatory signaling pathway. We aimed at investigate whether KPF is able to mitigate inflammatory responses by regulating TRAF6 in DN. MATERIAL AND METHODS: C57BL/6 mice were injected with streptozotocin to induce type 1 DN. NRK-52E, a tubular epithelial cell line, was used for in vitro analysis. TRAF6 was knockdown using siRNA in vitro and AAV2/2-shRNA in vivo. The anti-DN and inflammatory effects of KPF or knockdown of TRAF6 were evaluated by investigating renal filtration index, pathological changes of kidney tissue. Proinflammatory cytokine levels were detected using ELISA. NF-κB pathway and protein levels of related pathways were detected through Western blot. RESULTS: KPF significantly reduced renal inflammation, fibrosis, and kidney dysfunction in diabetic mice. These effects were associated with a downregulation of TRAF6 in diabetic mouse kidneys, indicating the potential role of TRAF6. Knockdown of TRAF6 in mice through AAV2-shTRAF6 confirmed the importance of TRAF6 in DN. In vitro, treatment of KPF in NRK-52E cells attenuated high glucose (HG)-induced inflammatory and fibrogenic responses, associated with downregulated TRAF6 expression. The conclusion was further confirmed in NRK-52E cells by knocking down the expression and by overexpression of TRAF6. CONCLUSION: Our findings provide direct evidence that TRAF6 mediates diabetes-induced inflammation leading to renal dysfunction. We also show that KPF is a potential therapeutic agent to reduce inflammatory responses in DN. Also, TRAF6 may represent an interesting target to combat DN.

Isoliquiritigenin attenuates diabetic cardiomyopathy via inhibition of hyperglycemia-induced inflammatory response and oxidative stress.

BACKGROUND: Inflammation and oxidative stress play essential roles in the occurrence and progression of diabetic cardiomyopathy (DCM). Isoliquiritigenin (ISL), a natural chalcone, exhibits strong anti-inflammatory and antioxidant activities. HYPOTHESIS/PURPOSE: In this study, we aimed to investigate the protective effects of ISL on DCM using high glucose (HG)-challenged cultured cardiomyocytes and streptozotocin (STZ)-induced diabetic mice. STUDY DESIGN AND METHODS: Embryonic rat heart-derived H9c2 cells challenged with a high concentration of glucose were used to evaluate the anti-inflammatory and antioxidant effects of ISL. STZ-induced diabetic mice were used to study the effects of ISL in DCM in vivo. Furthermore, cardiac fibrosis, hypertrophy, and apoptosis were explored both in vitro and in vivo. RESULTS: ISL effectively inhibited HG-induced hypertrophy, fibrosis, and apoptosis probably by alleviating the inflammatory response and oxidative stress in H9c2 cells. Results from in vivo experiments showed that ISL exhibited anti-inflammatory and antioxidant stress activities that were characterized by the attenuation of cardiac hypertrophy, fibrosis, and apoptosis, which resulted in the maintenance of cardiac function. The protective effects of ISL against inflammation and oxidative stress were mediated by the inhibition of mitogen-activated protein kinases (MAPKs) and induction of nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway, respectively. CONCLUSION: Our results provided compelling evidence that ISL, by virtue of neutralizing excessive inflammatory response and oxidative stress, could be a promising agent in the treatment of DCM. Targeting the MAPKs and Nrf2 signaling pathway might be an effective therapeutic strategy for the prevention and treatment of DCM.

Efficacy of Curcumin on Aortic Atherosclerosis: A Systematic Review and Meta-Analysis in Mouse Studies and Insights into Possible Mechanisms.

Since the first report in 2005, accumulating interests have been focused on the effect of curcumin in atherosclerosis with discrepancies. Therefore, we conducted a systematic review and meta-analysis to comprehensively estimate its effect against atherosclerosis. Literature search was performed on the database of PubMed, EMBASE, and Cochrane Library to identify relevant studies which estimated the effect of curcumin in atherosclerosis. Reporting effects on aortic lesion area was the primary outcome while effects on serum lipid profiles and circulating inflammatory markers were the secondary outcome. A total of 10 studies including 14 independent pairwise experiments were included in our analysis. We clarified that curcumin could significantly reduce aortic atherosclerotic lesion area (SMD = -0.89, 95% CI: -1.36 to -0.41, P = 0.0003), decrease serum lipid profiles (Tc, MD = -1.005, 95% CI: -1.885 to -0.124, P = 0.025; TG, MD = -0.045, 95% CI: -0.088 to -0.002, P = 0.042; LDL-c, MD = -0.523, 95% CI: -0.896 to -0.149, P = 0.006) as well as plasma inflammatory indicators (TNF-α, MD = -56.641, 95% CI: -86.848 to -26.433, P < 0.001; IL-1ß, MD = -5.089, 95% CI: -8.559 to -1.619, P = 0.004). Dose-response meta-analysis predicted effective dosage of curcumin between 0 and 347 mg/kg BW per day, which was safe and nontoxic according to the existing publications. The underlying mechanisms were also discussed and might be associated with the modulation of lipid transport and inflammation in cells within artery walls as well as indirect modulations in other tissues. Clinical evidence from nonatherosclerosis populations revealed that curcumin would lower the lipid profiles and inflammatory responses as it has in a mouse model. However, standard preclinical animal trial designs are still needed; further studies focusing on the optimal dose of curcumin against atherosclerosis and RCTs directly in atherosclerosis patients are also warranted.

Dynamic urinary metabolomics analysis based on UHPLC-Q-TOF/MS to investigate the potential biomarkers of blood stasis syndrome and the effects of Danggui Sini decoction.

Blood stasis syndrome (BSS) is one of the common syndromes in traditional Chinese medicine (TCM). It involves abnormal blood circulation, which can progress to produce many severe diseases. Danggui Sini decoction (DSD) is a classical TCM prescription frequently used to treat BSS by decreasing blood stasis and improving blood circulation. However, understanding of the therapeutic mechanism of DSD during the development of BSS is still limited, as the development of BSS is a slow dynamic process. Therefore, a dynamic urinary metabolomics analysis based on ultra-high-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UHPLC-Q-TOF/MS) combined with multivariate statistical analysis was used to explore the distinctive metabolic patterns of BSS development and the efficacy of DSD. The dynamic changes of endogenous metabolites over time revealed the progression of BSS and allowed the overall efficacy of DSD in rats with BSS to be evaluated. The effects of the DSD compatibilities were also explored. A total of 21 metabolites were identified during the development of BSS. They are involved in the metabolic pathways of tryptophan metabolism, phenylalanine metabolism, riboflavin metabolism, nicotinate and nicotinamide metabolism, pentose and glucuronate interconversions, histidine metabolism, steroid hormone biosynthesis, and starch and sucrose metabolism. A receiver operating characteristic (ROC) curve analysis showed that 10 metabolites with an area under the curve (AUC) value >0.9, which can be used as potential biomarkers for the diagnosis of BSS. In conclusion, a dynamic urinary metabolomics approach was applied to identify potential biomarkers of the development of BSS and to clarify the therapeutic mechanism of DSD in BSS. The results could provide a theoretical basis for further research on the therapeutic mechanism of DSD.

IL-8 is involved in radiation therapy resistance of esophageal squamous cell carcinoma via regulation of PCNA.

Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. Our present study revealed that the expression of IL-8 was increased in radiation therapy resistance of ESCC cells. Targeted inhibition of IL-8 by its neutralization antibody (anti-IL-8) can re-sensitize ESCC cells to radiation therapy and suppress the expression of proliferating cell nuclear antigen (PCNA). IL-8 can regulate the expression of PCNA via modulating its mRNA stability and promoter activity. Mechanistically, IL-8 can regulate the expression of miR-27b-5p, which can directly bind with 3'UTR of PCNA to decrease its mRNA stability. Further, anti-IL-8 can decrease the expression of transcription factor YY1, which can bind with the promoter of PCNA to increase its transcription. Taken together, our data revealed that IL8 can regulate the radiation resistance of ESCC cells and expression of PCNA. It suggested that targeted inhibition of IL-8 may improve the clinical treatment efficiency of radio therapy.

Transcriptome-wide association study and eQTL analysis to assess the genetic basis of bulb-yield traits in garlic (Allium sativum).

BACKGROUND: Garlic bulbs are abnormal expanding axillary buds that are rarely found among vascular plants. Bulb-yield is one of the valuable agronomic traits of garlic. However, due to the large genome size and a strictly asexual life cycle in the cultivars, the genetic basis of the yield traits are poorly understood in garlic. RESULTS: In the present study, we carried out an association mapping for three yield traits of garlic bulbs: bulb weight (BW), diameter (BD), and the number of garlic cloves (CN), using the recently proposed transcriptome-referenced association study. In total 25, 2, and 30 single nucleotide polymorphisms (SNPs), were identified in the transcripts to be associated with BW, BD, and CN traits, respectively. Of the transcripts with associated SNPs, the expression of 17 of them showed a significant correlation with the corresponding traits in the population, suggesting their relation to bulbs yield traits. Six transcripts were long non-coding RNAs (lncRNAs), and the others encode proteins involved mainly in carbohydrate metabolism, transcription regulation, cytokinin activity, protein degradation, etc. In addition, expression quantitative trait locus (eQTL) and expression correlation analysis have revealed that seven CN-related transcripts displayed interrelation, constituting two potential pathways. CONCLUSION: This study provides novel insights into the genetic basis of the yield traits in garlic bulbs, and the identification of trait-associated SNPs/transcripts provides a basis for improving the bulb yield in garlic breeding.

Polydatin promotes the osteogenic differentiation of human bone mesenchymal stem cells by activating the BMP2-Wnt/ß-catenin signaling pathway.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory disease induced by glucocorticoids. Marrow mesenchymal stem cells (MSCs) differentiate into multiple bone matrix cells and have been used as cell-based therapies to treat ONFH. However, the osteogenesis of MSCs isolated from patients with SONFH is significantly decreased. Polydatin has been widely used in traditional Chinese remedies due to its multiple pharmacological actions. As shown in our previous study, Polydatin protects from oxidative stress and promotes BMSC migration. However, little is known about its role in BMSC (Bone marrow mesenchymal stem cells) osteogenesis; therefore, we further investigated the effect and mechanism of Polydatin in hBMSC osteogenesis. The ability of Polydatin to promote the proliferation and osteogenic differentiation of hBMSCs was determined using the MTT assay, ALP staining and the ALP activity assay. Next, qPCR and western blotting were performed to measure the levels of genes and proteins related to the osteogenesis of hBMSCs. Then, the effect of Polydatin on the nuclear translocation of ß-catenin was determined using immunofluorescence staining. Polydatin (30 µM) markedly enhanced the proliferation of hBMSCs and alkaline phosphatase (ALP) activity. Additionally, it also significantly upregulated the expression of osteogenic genes (Runx2, osteopontin, DLX5, osteocalcin, collagen type I and BMP2) and components of the Wnt signaling pathway (ß-catenin, Lef1, TCF7, c-jun, c-myc and cyclin D). These osteogenesis-potentiating effects of Polydatin were blocked by Noggin, an inhibitor of the BMP pathway, and DKK1, an inhibitor of the Wnt/ß-catenin pathway. However, DKK1 did not affect Polydatin-induced BMP2 expression. Based on our results, Polydatin promotes the proliferation and osteogenic differentiation of hBMSCs through the BMP2-Wnt/ß-catenin signaling pathway.

Asian Society of Gynecologic Oncology International Workshop 2018.

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.

Protective Effect of Koumine, an Alkaloid from Gelsemium Sempervirens, on Injury Induced by H2O2 in IPEC-J2 Cells.

Medicinal herbal plants have been commonly used for intervention in different diseases and improvement of health worldwide. Koumine, an alkaloid monomer found abundantly in Gelsemium plants, can be effectively used as an antioxidant. The purpose of this study was to evaluate the potential protective effect of koumine against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in porcine intestinal epithelial cell line (IPEC-J2 cells). MTT assays showed that koumine significantly increased cell viability in H2O2-mediated IPEC-J2 cells. Preincubation with koumine ameliorated H2O2-medicated apoptosis by decreasing reactive oxygen species (ROS) production, and efficiently suppressed the lactate dehydrogenase (LDH) release and malondialdehyde (MDA) production. Moreover, a loss of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) activities was restored to normal level in H2O2-induced IPEC-J2 cells upon koumine exposure. Furthermore, pretreatment with koumine suppressed H2O2-mediated loss of mitochondrial membrane potential, caspase-9 and caspase-3 activation, decrease of Bcl-2 expression and elevation of Bax expressions. Collectively, the results of this study indicated that koumine possesses the cytoprotective effects in IPEC-J2 cells during exposure to H2O2 by suppressing production of ROS, inhibiting the caspase-3 activity and influencing the expression of Bax and Bcl-2. Koumine could potentially serve as a protective effect against H2O2-induced apoptosis.

Anti-inflammatory effects of Eucommia ulmoides Oliv. male flower extract on lipopolysaccharide-induced inflammation.

BACKGROUND: Eucommia ulmoides Oliv. is a medicinal plant native to China, with its bark (Eucommiae Cortex) traditionally being used for medicinal purposes. Previous research has shown that Eucommia male flowers can exert anti-inflammatory, analgesic, antibacterial, and other pharmacological effects, including immune regulation. This study explored the anti-inflammatory effects of the 70% ethanol extract of male flowers (EF) of E. ulmoides in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-administered mice. METHODS: Cytotoxicity of EF for RAW 264.7 cells was investigated using Cell Counting Kit-8. The production of proinflammatory mediators, nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 was determined using enzyme-linked immunosorbent assays. IL-17, IL-23, and IL-10 mRNA levels were determined using quantitative real-time polymerase chain reaction. Activation of the nuclear factor (NF)-κB pathway in RAW 264.7 cells was investigated via Western blotting. In vivo anti-inflammatory effects of EF were studied in an LPS-induced acute inflammation mouse model by analyzing lung tissue histopathology, serum TNF-α and IL-6 levels, and myeloperoxidase (MPO) activity in lung tissue. RESULTS: EF showed no significant cytotoxicity at concentrations from 10 to 60 µg/mL (cell viability > 80%) in the CCK-8 cell viability assay. EF inhibited the RAW 264.7 cell proliferation (EF 60 µg/mL, 120 µg/mL, and 250 µg/mL vs. negative control: 87.31 ±â€Š2.39% vs. 100.00 ±â€Š2.50%, P = 0.001; 79.01 ±â€Š2.56 vs. 100.00 ±â€Š2.50%, P < 0.001; and 64.83 ±â€Š2.50 vs. 100.00 ±â€Š2.50%, P < 0.001), suppressed NO (EF 20 µg/mL and 30 µg/mL vs. LPS only, 288.81 ±â€Š38.01 vs. 447.68 ±â€Š19.07 µmol/L, P = 0.004; and 158.80 ±â€Š45.14 vs. 447.68 ±â€Š19.07 µmol/L, P < 0.001), TNF-α (LPS+EF vs. LPS only, 210.20 ±â€Š13.85 vs. 577.70 ±â€Š5.35 pg/mL, P < 0.001), IL-1ß (LPS+EF vs. LPS only, 193.30 ±â€Š10.80 vs. 411.03 ±â€Š42.28 pg/mL, P < 0.001), and IL-6 (LPS+EF vs. LPS only, 149.67 ±â€Š11.60 vs. 524.80 ±â€Š6.24 pg/mL, P < 0.001) secretion, and downregulated the mRNA expression of IL-17 (LPS+EF vs. LPS only, 0.23 ±â€Š0.02 vs. 0.43 ±â€Š0.12, P < 0.001), IL-23 (LPS+EF vs. LPS only, 0.29 ±â€Š0.01 vs. 0.42 ±â€Š0.06, P=0.002), and IL-10 (LPS+EF vs. LPS only, 0.30 ±â€Š0.01 vs. 0.47 ±â€Š0.01, P=0.008) in LPS-stimulated RAW 264.7 cells. EF inhibited the LPS-induced NF-κB p65 (LPS+EF 20 µg/mL and 30 µg/mL vs. LPS only: 0.78 ±â€Š0.06 vs. 1.17 ±â€Š0.08, P < 0.001; and 0.90 ±â€Š0.06 vs. 1.17 ±â€Š0.08, P =0.002) and inhibitor of kappa B (IκBα) phosphorylation (LPS+EF 20 µg/mL and 30 µg/mL vs. LPS only: 0.25 ±â€Š0.01 vs. 0.63 ±â€Š0.03, P < 0.001; and 0.31 ±â€Š0.01 vs. 0.63 ±â€Š0.03, P < 0.001), LPS+EF 30 µg/mL inhibited IκB kinase (IKKα/ß) phosphorylation (LPS+EF 30 µg/mL vs. LPS only, 1.12 ±â€Š0.14 vs. 1.71 ±â€Š0.25, P = 0.002) in RAW 264.7 cells. Furthermore, EF 10 mg/kg and EF 20 mg/kg inhibited lung tissue inflammation in vivo and suppressed the serum TNF-α (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 199.99 ±â€Š186.49 vs. 527.90 ±â€Š263.93 pg/mL, P=0.001; and 260.56 ±â€Š175.83 vs. 527.90 ±â€Š263.93 pg/mL, P = 0.005), and IL-6 (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 41.26 ±â€Š30.42 vs. 79.45 ±â€Š14.16 pg/ ml, P = 0.011; and 42.01 ±â€Š26.26 vs. 79.45 ±â€Š14.16 pg/mL, P = 0.012) levels and MPO (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 3.19 ±â€Š1.78 vs. 5.39 ±â€Š1.51 U/g, P = 0.004; and 3.32 ±â€Š1.57 vs. 5.39 ±â€Š1.51 U/g, P = 0.006) activity in lung tissue. CONCLUSIONS: EF could effectively inhibit the expression of inflammatory factors and overactivation of neutrophils. Further investigation is needed to evaluate its potential for anti-inflammation therapy.