Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells.

OBJECTIVE: Research has shown that celastrol can effectively treat a variety of diseases, yet when passing a certain dosage threshold, celastrol becomes toxic, causing complications such as liver and kidney damage and erythrocytopenia, among others. With this dichotomy in mind, it is extremely important to find ways to preserve celastrol's efficacy while reducing or preventing its toxicity. METHODS: In this study, insulin-resistant HepG2 (IR-HepG2) cells were prepared using palmitic acid and used for in vitro experiments. IR-HepG2 cells were treated with celastrol alone or in combination with N-acetylcysteine (NAC) or ferrostatin-1 (Fer-1) for 12, 24 or 48 h, at a range of doses. Cell counting kit-8 assay, Western blotting, quantitative reverse transcription-polymerase chain reaction, glucose consumption assessment, and flow cytometry were performed to measure celastrol's cytotoxicity and whether the cell death was linked to ferroptosis. RESULTS: Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-HepG2 cells. Celastrol downregulated glutathione peroxidase 4 (GPX4) mRNA. Molecular docking models predicted that solute carrier family 7 member 11 (SLC7A11) and GPX4 were covalently bound by celastrol. Importantly, we found for the first time that the application of ferroptosis inhibitors (especially NAC) was able to reduce celastrol's toxicity while preserving its ability to improve insulin sensitivity in IR-HepG2 cells. CONCLUSION: One potential mechanism of celastrol's cytotoxicity is the induction of ferroptosis, which can be alleviated by treatment with ferroptosis inhibitors. These findings provide a new strategy to block celastrol's toxicity while preserving its therapeutic effects. Please cite this article as: Liu JJ, Zhang X, Qi MM, Chi YB, Cai BL, Peng B, Zhang DH. Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells. J Integr Med. 2024; 22(3): 286-294.

Enhancing Diagnostic Precision with Utilizing Combined CRP and IL-6 Testing for Deep Vein Thrombosis Detection Post-Endometrial Cancer Surgery.

Background: Deep vein thrombosis is a common complication after surgery, particularly in cancer patients, necessitating efficient diagnostic methods for timely intervention. Objective: This study aimed to investigate the potential of combining C-reactive protein (CRP) and interleukin-6 (IL-6) tests in diagnosing deep vein thrombosis (DVT) following endometrial cancer surgery. Methods: A cohort of 60 patients who developed DVT post-endometrial cancer surgery and were admitted to the First Hospital of Hebei Medical University between March 2018 and March 2022 constituted the DVT group. Additionally, 60 patients who underwent endometrial cancer surgery during the same period but did not develop DVT formed the non-DVT group. Serum levels of CRP and IL-6 were quantified and compared between the two groups using reliable laboratory techniques. Subsequently, the diagnostic accuracy of single-parameter testing (CRP or IL-6 alone) versus combined testing (CRP and IL-6) for postoperative DVT was assessed. Results: Analysis revealed significantly elevated levels of CRP and IL-6 in the serum of patients in the DVT group compared to those in the non-DVT group (P < .05). Furthermore, combined testing of CRP and IL-6 exhibited heightened sensitivity (0.85%), specificity (0.917%), and area under the curve (AUC) (0.952) compared to single-parameter testing alone, indicating its superiority in diagnosing postoperative DVT. Conclusions: The combination of CRP and IL-6 testing presents a promising diagnostic strategy for identifying postoperative DVT in endometrial cancer patients. Implementing this approach in clinical practice could facilitate early detection and prompt management of DVT, thereby potentially reducing associated morbidity and mortality.

Application of Thermal Cycling Amplification Chip Method in the Detection of Respiratory Machine-Associated Pneumonia Pathogens.

Objective: Investigating the application effectiveness of using loop-mediated isothermal amplification (LAMP) on a microfluidic chip to detect the pathogens associated with ventilator-associated pneumonia (VAP). Methods: Eighty samples of bronchoalveolar lavage fluid from patients with ventilator-associated pneumonia (VAP) were collected at The First Hospital of Hebei Medical University from July 2022 to July 2023. The bacterial culture technique and the LAMP method were used to detect the nucleic acid of the pathogens in the patient samples. The positivity rates of bacterial culture and LAMP method in detecting VAP pathogens were analyzed. Results: A total of 80 specimens were examined, with 73 positive specimens detected using the LAMP method (positivity rate of 91.25%) and 60 positive specimens detected using bacterial culture (positivity rate of 75.00%). The LAMP method exhibited a higher number of positive detections compared to bacterial culture. Both methods showed a high level of concordance and were virtually identical in detecting methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterobacter aerogenes, Haemophilus influenzae, and Streptococcus pneumoniae. Conclusion: The LAMP method demonstrates significantly improved performance in the detection of pathogens for VAP, with a higher pathogen positivity rate compared to bacterial culture. This method holds promising prospects for clinical application.

Transcriptome and metabolome profiling of the medicinal plant Veratrum mengtzeanum reveal key components of the alkaloid biosynthesis.

Veratrum mengtzeanum is the main ingredient for Chinese folk medicine known as "Pimacao" due to its unique alkaloids. A diverse class of plant-specific metabolites having key pharmacological activities. There are limited studies on alkaloid synthesis and its metabolic pathways in plants. To elucidate the alkaloid pathway and identify novel biosynthetic enzymes and compounds in V. mengtzeanum, transcriptome and metabolome profiling has been conducted in leaves and roots. The transcriptome of V. mengtzeanum leaves and roots yielded 190,161 unigenes, of which 33,942 genes expressed differentially (DEGs) in both tissues. Three enriched regulatory pathways (isoquinoline alkaloid biosynthesis, indole alkaloid biosynthesis and tropane, piperidine and pyridine alkaloid biosynthesis) and a considerable number of genes such as AED3-like, A4U43, 21 kDa protein-like, 3-O-glycotransferase 2-like, AtDIR19, MST4, CASP-like protein 1D1 were discovered in association with the biosynthesis of alkaloids in leaves and roots. Some transcription factor families, i.e., AP2/ERF, GRAS, NAC, bHLH, MYB-related, C3H, FARI, WRKY, HB-HD-ZIP, C2H2, and bZIP were also found to have a prominent role in regulating the synthesis of alkaloids and steroidal alkaloids in the leaves and roots of V. mengtzeanum. The metabolome analysis revealed 74 significantly accumulated metabolites, with 55 differentially accumulated in leaves compared to root tissues. Out of 74 metabolites, 18 alkaloids were highly accumulated in the roots. A novel alkaloid compound viz; 3-Vanilloylygadenine was discovered in root samples. Conjoint analysis of transcriptome and metabolome studies has also highlighted potential genes involved in regulation and transport of alkaloid compounds. Here, we have presented a comprehensive metabolic and transcriptome profiling of V. mengtzeanum tissues. In earlier reports, only the roots were reported as a rich source of alkaloid biosynthesis, but the current findings revealed both leaves and roots as significant manufacturing factories for alkaloid biosynthesis.

Efficacy and safety of acupuncture for polycystic ovary syndrome: An overview of systematic reviews.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the primary cause of anovulatory infertility, bringing serious harm to women's physical and mental health. Acupuncture may be an effective treatment for PCOS. However, systematic reviews (SRs) on the efficacy and safety of acupuncture for PCOS have reported inconsistent results, and the quality of these studies has not been adequately assessed. OBJECTIVE: To summarize and evaluate the current evidence on the efficacy and safety of acupuncture for PCOS, as well as to assess the quality and risks of bias of the available SRs. SEARCH STRATEGY: Nine electronic databases (Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, Chinese National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Chinese Science and Technology Periodical Database, and China Biology Medicine disc) were searched from their establishment to July 27, 2022. Based on the principle of combining subject words with text words, the search strategy was constructed around search terms for "acupuncture," "polycystic ovary syndrome," and "systematic review." INCLUSION CRITERIA: SRs of randomized controlled trials that explored the efficacy and (or) safety of acupuncture for treating patients with PCOS were included. DATA EXTRACTION AND ANALYSIS: Two authors independently extracted study data according to a predesigned form. Tools for evaluating the methodological quality, risk of bias, reporting quality, and confidence in study outcomes, including A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), were used to score the included SRs. RESULTS: A total of 885 studies were retrieved, and 11 eligible SRs were finally included in this review. The methodological quality of 2 SRs (18.18%) was low, while the other 9 SRs (81.82%) were scored as extremely low. Four SRs (36.36%) were considered to be of low risk of bias. As for reporting quality, the reporting completeness of 9 SRs (81.82%) was more than 70%. Concerning the confidence in study results, 2 study results were considered to have a high quality of evidence (3.13%), 14 (21.88%) a "moderate" quality, 28 (43.75%) a "low" quality, and 20 (31.24%) considered a "very low" quality. Descriptive analyses suggested that combining acupuncture with other medicines can effectively improve the clinical pregnancy rate (CPR) and ovulation rate, and reduce luteinizing hormone/follicle-stimulating hormone ratio, homeostasis model assessment of insulin resistance, and body mass index (BMI). When compared with medicine alone, acupuncture alone also can improve CPR. Further, when compared with no intervention, acupuncture had a better effect in promoting the recovery of menstrual cycle and reducing BMI. Acupuncture was reported to cause no adverse events or some adverse events without serious harm. CONCLUSION: The efficacy and safety of acupuncture for PCOS remains uncertain due to the limitations and inconsistencies of current evidence. More high-quality studies are needed to support the use of acupuncture in PCOS.

Role of GRPR in Acupuncture Intervention in the "Itch-scratch Vicious Cycle" Spinal Circuit of Chronic Pruritus.

Many previous studies have shown the potential antipruritic effect of acupuncture. This paper reviews the antipruritic mechanisms of acupuncture according to these aspects: sample characteristics, detail of intervention, and effects evaluation. The majority of research on acupuncture's antipruritic effect has focused on primary afferents of the peripheral mechanism. Relatively few studies, however, have addressed the central mechanisms. Combination the latest research achievements of chronic itch, gastrin-releasing peptide receptor (GRPR) in the dorsal horn of the spinal cord may represent the first molecule identified that is dedicated to mediating the itch response and may provide an important therapeutic target for the treatment of chronic pruritic conditions. Therefore, GRPR may be a new target for acupuncture to relieve itch in the future and provide new ideas for acupuncture intervention in the mechanisms of the spinal level of the "itch-scratch vicious cycle" of chronic itch.

Transcutaneous electrical acupoint stimulation for pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer: A systematic review and meta-analysis.

Background: Infertility is a common health problem affecting couples of childbearing age. The proposal of in vitro fertilization-embryo transfer (IVF-ET) solves the problem of infertility to a certain extent. However, the average success rate of IVF-ET is still low. Some studies conclude that transcutaneous electrical acupoint stimulation (TEAS) could improve pregnancy outcomes in women undergoing IVF-ET, however, there is a lack of comprehensive synthesis and evaluation of existing evidence. Objective: To conduct a systematic review and meta-analysis to assess whether TEAS is effective and safe to improve the pregnancy outcomes for women undergoing IVF-ET. Methods: Eight online databases were searched from inception to 19 November 2021. In addition, four clinical trial registries were also searched, relevant references were screened, and experts were consulted for possible eligible studies. Randomized controlled trials (RCTs) that included patients with infertility who underwent IVF and used TEAS as the main adjuvant treatment vs. non-TEAS or mock intervention controls were included. The clinical pregnancy rate (CPR) was considered the primary outcome. High-quality embryo rate (HQER), live birth rate (LBR), biochemical pregnancy rate (BPR), ongoing pregnancy rate (OPR), early miscarriage rate (EMR), birth defects rate (BDR), and adverse events related to interventions were regarded as secondary outcomes. The selection, data extraction, risk of bias assessment, and data synthesis were conducted by two independent researchers using Endnote software V.9.1 and Stata 16.0 software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the evidence quality of each outcome. Results: There were 19 RCTs involving 5,330 participants included. The results of meta-analyses showed that TEAS can improve CPR [RR = 1.42, 95% CI (1.31, 1.54)], HQER [RR = 1.09, 95% CI (1.05, 1.14)], and BPR [RR = 1.45, 95% CI (1.22, 1.71)] of women underwent IVF-ET with low quality of evidence, and improve LBR [RR = 1.42, 95% CI (1.19, 1.69)] with moderate quality of evidence. There was no significant difference in EMR [RR = 1.08, 95% CI (0.80, 1.45)] and BDR [RR = 0.93, 95% CI (0.13, 6.54)] with very low and moderate quality of evidence, respectively. A cumulative meta-analysis showed that the effective value of TEAS vs. controls was relatively stable in 2018 [RR = 1.52, 95% CI (1.35, 1.71)]. In addition, no serious adverse events associated with TEAS were reported. Conclusion: Our findings suggest that TEAS may be an effective and safe adjuvant treatment for women undergoing IVF-ET to improve pregnancy outcomes. However, the current evidence quality is considered to be limited, and more high-quality RCTs are needed for further verification in the future. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42021238871, identifier: CRD42021238871.

SDF-1/CXCR4-Mediated Stem Cell Mobilization Involved in Cardioprotective Effects of Electroacupuncture on Mouse with Myocardial Infarction.

Stem cell-based therapeutic strategies have obtained a significant breakthrough in the treatment of cardiovascular diseases, particularly in myocardial infarction (MI). Nevertheless, limited retention and poor migration of stem cells are still problems for stem cell therapeutic development. Hence, there is an urgent need to develop new strategies that can mobilize stem cells to infarcted myocardial tissues effectively. Electroacupuncture (EA) intervention can improve cardiac function and alleviate myocardial injury after MI, but its molecular mechanism is still unclear. This study is aimed at observing the effects of EA treatment on the stem cell mobilization and revealing possible mechanisms in the MI model of mice. EA treatment at Neiguan (PC6) and Xinshu (BL15) acupoints was conducted on the second day after the ligation surgery. Then, the number of stem cells in peripheral blood after EA in MI mice and their cardiac function, infarct size, and collagen deposition was observed. We found that the number of CD34-, CD117-, Sca-1-, and CD90-positive cells increased at 6 h and declined at 24 h after EA intervention in the blood of MI mice. The expression of CXC chemokine receptor-4 (CXCR4) protein was upregulated at 6 h after EA treatment, while the ratio of LC3B II/I or p-ERK/ERK showed a reverse trend. In addition, there was obvious difference in EF and FS between wild-type mice and CXCR4+/- mice. The infarct size, collagen deposition, and apoptosis of the injured myocardium in CXCR4+/- mice increased but could be ameliorated by EA. In a word, our study demonstrates that EA alleviates myocardial injury via stem cell mobilization which may be regulated by the SDF-1/CXCR4 axis.

Effect of non-pharmacological interventions for overweight/obese women with polycystic ovary syndrome on ovulation and pregnancy outcomes: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Most overweight/obese women with polycystic ovary syndrome (PCOS) have infertility issues which are difficult to treat. Non-pharmacological interventions used for the management of infertility include lifestyle interventions, acupuncture therapies and nutritional supplements. These interventions have been reported to be beneficial in alleviating infertility among overweight women with PCOS. However, effect and safety of these non-pharmacological interventions vary, and there is no standard method of clinical application. Therefore, it is necessary to conduct a systematic review and network meta-analysis (NMA) to rank these non-pharmacological interventions in terms of effect and determine which one is more effective for clinical application. METHODS AND ANALYSIS: We will retrieve eight databases including Cochrane Library, Medline, Embase, PsycINFO, Chinese National Knowledge Infrastructure, WanFang Data, the Chongqing VIP Database and China Biology Medicine disc from their inceptions onwards. In addition, four clinical trial registries and the related references will be manually retrieved. The primary outcome will be clinical pregnancy. Live birth, ovulation, pregnancy loss, multiple pregnancy and adverse events related to interventions will be considered as the secondary outcomes. STATA software V.15.0 and Aggregate Data Drug Information System V.1.16.8 will be used to conduct pairwise meta-analysis and NMA. The Grading of Recommendations Assessment, Development and Evaluation system will be adopted to evaluate the certainty of evidence. ETHICS AND DISSEMINATION: Ethical approval will not be required because the study will not include the original information of participants. The results will be published in a peer-reviewed journal or disseminated in relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42021283110.

Effective solid-phase extraction of chlorophenols with covalent organic framework material as adsorbent.

In this work, a porous extended network covalent organic framework designated as TP-NDA-COF was synthesized by the reaction of 2,4,6-trihydroxy-benzene-1,3,5-tricarbaldehyde (TP) and 1,5-naphthalenediamine (NDA). The structure and morphology of the TP-NDA-COF was characterized by means of Fourier transform infrared spectra (FT-IR), thermal gravimetric analysis (TGA), X-ray diffraction (XRD) and scanning electron microscope (SEM). The TP-NDA-COF was applied as a solid-phase extraction adsorbent for the extraction of some chlorophenols from water and lemon black tea beverage samples prior to high performance liquid chromatography-UV detection. The main experimental parameters that affect the extraction efficiency including the type and volume of eluent, sample solution volume, sample loading rate and sample solution pH were investigated. Under the optimal conditions, the calibration curves were linear in the range of 0.30-60.0 ng mL-1 with the determination coefficients (R2) of 0.9996-0.9998 for water samples and in the range of 0.60-60.0 ng mL-1 with the R2 values from 0.9990 to 0.9996 for beverage samples. At the signal to noise ratio of 3 (S/N = 3), the method LODs for the analytes were 0.10-0.15 ng mL-1 for water samples and 0.20-0.50 ng mL-1 for lemon black tea beverage, respectively. Good repeatability was achieved with the relative standard deviations of less than 7%. The results showed that the SPE-HPLC method can be used for the determination of chlorophenols in environmental water and foodstuffs samples.

The complete chloroplast genome sequence of Veratrum oxysepalum and phylogenetic analysis.

Veratrum oxysepalum Turcz. is a medicinal plant belonging to Melanthiaceae occurring in Northeast China. However, there are still limited genomic resources available for genus Veratrum. The complete chloroplast (cp) genome of V. oxysepalum was determined and analyzed in this study. The complete cp genome was 153,705 bp. That contains a large single copy (LSC) region of 83,384 bp, a small single copy (SSC) region of 17,607 bp, which were separated by a pair of 26,358 bp inverted repeat regions (IRs). A total of 135 genes were annotated, including 83 protein-coding genes, 38 tRNAs, and eight rRNAs. Phylogenetic analysis using total chloroplast genome sequence of 21 species revealed that V. oxysepalum was closely relates to V. patulum of Veratrum with 100% bootstrap value.

A network-based method for mechanistic investigation and neuroprotective effect on treatment of tanshinone â against ischemic stroke in mouse.

ETHNOPHARMACOLOGICAL RELEVANCE: Tanshinone-Ⅰ (TSNⅠ), a member of the mainly active components of Salvia miltiorrhiza Bunge (Dan Shen), which is widely used for the treatment for modern clinical diseases including cardiovascular and cerebrovascular diseases, has been reported to show the properties of anti-oxidation, anti-inflammation, neuroprotection and other pharmacological actions. However, whether TSNⅠ can improve neuron survival and neurological function against transient focal cerebral ischemia (tMCAO) in mice is still a blank field. AIM OF THE STUDY: This study aims to investigate the neuroprotective effects of TSNⅠ on ischemic stroke (IS) induced by tMCAO in mice and explore the potential mechanism of TSNⅠ against IS by combining network pharmacology approach and experimental verification. MATERIALS AND METHODS: In this study, the pivotal candidate targets of TSNⅠ against IS were screened by network pharmacology firstly. Enrichment analysis and molecular docking of those targets were performed to identify the possible mechanism of TSNⅠ against IS. Afterwards, experiments were carried out to further verify the mechanism of TSNⅠ against IS. The infarct volume and neurological deficit were evaluated by 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining and Longa respectively. Immunohistochemistry was used to observe neuronal death in the hippocampus and cortical regions by detecting the change of NeuN. The predicting pathways of signaling-related proteins were assessed by Western blot in vitro and in vivo experiments. RESULTS: In vivo, TSNⅠ was found to dose-dependently decrease mice's cerebral infarct volume induced by tMCAO. In vitro, pretreatment with TSNⅠ could increase cell viability of HT-22 cell following oxygen-glucose deprivation (OGD/R). Moreover, the results showed that 125 candidate targets were identified, Protein kinase B (AKT) signaling pathway was significantly enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and mitogen-activated protein kinases 1 (MAPK1) and AKT1 could be bound to TSNⅠ more firmly by molecular docking analysis, which implies that TSNⅠ may play a role in neuroprotection through activating AKT and MAPK signaling pathways. Meanwhile, TSNⅠ was confirmed to significantly protect neurons from injury induced by IS through activating AKT and MAPK signaling pathways. CONCLUSION: In conclusion, our study clarifies that the mechanism of TSNⅠ against IS might be related to AKT and MAPK signaling pathways, which may provide the basic evidence for further development and utilization of TSNⅠ.

Integration of lncRNA and mRNA profiles to reveal the protective effects of Codonopsis pilosula extract on the gastrointestinal tract of mice subjected to D­galactose­induced aging.

Codonopsis pilosula is a type of traditional Chinese medicine that exerts an anti­aging effect and can regulate the gastrointestinal (GI) system. The aim of the present study was to investigate the underlying molecular mechanisms responsible for the anti­aging effects of Codonopsis pilosula in the GI tract of mice with D­galactose­induced aging. First, a successful mouse model of aging was established, and Codonopsis pilosula water extract was then used for treatment. The anti­aging effects of Codonopsis pilosula on the GI tract were then detected from the perspectives of tissue structure, physiological function and cell ultrastructure. Finally, in order to explore the underlying molecular mechanisms, the expression profiles of lncRNAs and mRNAs in the stomach and intestine were examined using microarray technology. A total of 117 (41 lncRNAs and 76 mRNAs) and 168 (85 lncRNA sand 83 mRNAs) differentially expressed genes associated with the anti­aging effects of Codonopsis pilosula were identified in the stomach and intestine, respectively. Through integrated analysis of the stomach and intestine, 4 hub RNAs, including 1 lncRNA (LOC105243318) and 3 mRNAs (Fam132a, Rorc and 1200016E24Rik) were identified, which may be associated with the anti­aging effects of Codonopsis pilosula in the GI tract of aging mice. The Kyoto Encyclopedia of Genes and Genomes analysis revealed that the metabolic pathway was an important pathway underlying the anti­aging effects of Codonopsis pilosula in the GI tract. On the whole, in the present study, 4 hub RNAs associated with these effects and their regulatory networks were found in the GI tract of aging mice. In addition, the metabolic pathway was found to play an important role in these anti­aging effects in the GI tract.

Phytochemicals and bioactive analysis of different sweet tea (Lithocarpus litseifolius [Hance] Chun) varieties.

This paper aims to investigate the constituent phytochemicals and biological activities of six Lithocarpus litseifolius (Hance) Chun (L. litseifolius) cultivars. Processed by UPLC-MS/MS and untargeted metabolomics analysis software (MS-DIAL and MS-FINDER), components of different L. litseifolius cultivars were analyzed qualitatively and quantitatively. By conducting a comprehensive analysis of spectra, MS/MS fragmentation, and retention time, 40 compounds (including 6 phenolic glycosides and 34 flavonoids) were identified rapidly and accurately. Moreover, the total phenolic content (TPC), total flavonoid content (TFC), antioxidant, antimicrobial effects, and pheochromocytoma (PC12) cell viability of different L. litseifolius varieties were evaluated. Purple small leaf (PSL) was found to be the most superior variety with the highest antioxidant activities (8.27, 10.09, and 10.80 mg TE/g for DPPH, ABTS, and FRAP assays, respectively), broad-spectrum antimicrobial activity, and lowest cell cytotoxicity. The results showed that these bioactivities were closely related to phytochemicals among the six cultivars. PRACTICAL APPLICATIONS: L. litseifolius is well known as an important folk drink in the Southern China folklore for its specific efficacy in preventing diabetes. However, there is still a paucity of information on L. litseifolius, as other active components and bioactivities of it remain to be investigated. The wide range of flavonoids discovered in L. litseifolius provides abundant natural health-promoting agents for further applications in medicine and functional food.

Ginsenoside Rg1 prevents vascular intimal hyperplasia involved by SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in a rat balloon injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C. A. Mey. is a traditional tonic that has been used for thousands of years, and has positive effects on vascular diseases. Ginsenoside Rg1 (GS-Rg1) is one of the active ingredients of Panax ginseng C. A. Mey. and has been shown to have beneficial effects against ischemia/reperfusion injury. Our previously study has found that GS-Rg1 can mobilize bone marrow stem cells and inhibit vascular smooth muscle proliferation and phenotype transformation. However, pharmacological effects and mechanism of GS-Rg1 in inhibiting intimal hyperplasia is still unknown. AIM OF THE STUDY: This study was aimed to investigate whether GS-Rg1 prevented vascular intimal hyperplasia, and the involvement of stromal cell-derived factor-1α (SDF-1α)/CXCR4, stem cell factor (SCF)/c-kit and fractalkine (FKN)/CX3CR1 axes. MATERIALS AND METHODS: Rats were operated with carotid artery balloon injury. The treatment groups were injected with 4, 8 and 16 mg/kg of GS-Rg1 for 14 days. The degree of intimal hyperplasia was evaluated by histopathological examination. The expression of α-SMA (α-smooth muscle actin) and CD133 were detected by double-label immunofluorescence. Serum levels of SDF-1α, SCF and soluble FKN (sFKN) were detected by enzyme linked immunosorbent assay (ELISA). The protein expressions of SCF, SDF-1α and FKN, as well as the receptors c-kit, CXC chemokine receptor type 4 (CXCR4) and CX3C chemokine receptor type 1 (CX3CR1) were detected by immunochemistry. RESULTS: GS-Rg1 reduced intimal hyperplasia by evidence of the values of NIA, the ratio of NIA/MA, and the ratio of NIA/IELA and the ratio of NIA/LA, especially in 16 mg/kg group. Furthermore, GS-Rg1 8 mg/kg group and 16 mg/kg group decreased the protein expressions of the SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in neointima, meanwhile GS-Rg1 8 mg/kg group and 16 mg/kg group also attenuated the expressions of SDF-1α, SCF and sFKN in serum. In addition, the expression of α-SMA and CD133 marked smooth muscle progenitor cells (SMPCs) was decreased after GS-Rg1 treatment. CONCLUSIONS: GS-Rg1 has a positive effect on inhibiting vascular intimal hyperplasia, and the underlying mechanism is related to inhibitory expression of SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes.

Tea Consumption Is Associated with Decreased Disease Activity of Rheumatoid Arthritis in a Real-World, Large-Scale Study.

INTRODUCTION: The role of tea consumption on rheumatoid arthritis (RA) has been studied in recent years, but no clear conclusion has been drawn as a result of small sample size of the studies or the fact that only in vitro studies have been performed. OBJECTIVES: The aim of this study was to explore the possible association of tea consumption with RA through a large-scale, real-world study. METHODS: A total of 733 RA patients were investigated from June to December, 2016. The disease activity of RA was assessed according to disease activity score 28-erythrocyte sedimentation rate. The amount and types of tea consumption were recorded by on-site self-administered questionnaires. Logistic regression models were applied to analyze the correlation between tea consumption and disease activity, adjusting for demographics, clinical and laboratory factors. RESULTS: There was an inverse association between tea consumption and disease activity in RA patients (OR 0.66, 95% CI 0.46-0.94). Compared with non-tea drinkers, a higher-intake of tea (>750 mL/day) was associated with lower disease activity of RA (OR 0.39, 95% CI 0.19-0.79), but not low-intake (≤750 mL/day; OR 0.83, 95% CI 0.42-1.63). A significant dose-response association was found between the amount of tea consumption and disease activity (p for trend <0.01). Further hierarchical regression analysis showed that such inverse associations were mainly present in female patients (p = 0.004), non-smokers (p = 0.01) or elders (≥60 years; p = 0.01). CONCLUSION: Tea consumption is associated with decreased disease activity of RA, suggesting the potential beneficial effect of tea in the disease.

Integrative Analysis of Long Non-Coding RNAs (lncRNAs), miRNAs, and mRNA-Associated ceRNA Network in Lung Tissue of Aging Mice and Changes After Treatment with Codonopsis pilosula.

BACKGROUND Codonopsis pilosula is a traditional Chinese medicine that has an anti-aging effect. However, the anti-aging effect of Codonopsis pilosula on the lungs remains largely unknown, and the molecular mechanism also needs to be further studied. Thus, we investigated the protective effect of Codonopsis pilosula on the lungs of aging mice, and explored the underlying molecular mechanism. MATERIAL AND METHODS We established an aging mouse model and then treated the mice with Codonopsis pilosula. Microarray analysis and bioinformatics methods were used to comprehensively analyze the lncRNA-miRNA-mRNA (ceRNA) network. RESULTS Our results showed that we successfully established the aging mouse model. The microarray analysis showed that 138 lncRNAs, 128 mRNAs, and 7 miRNAs were significantly changed after aging, and 282 lncRNAs, 283 mRNAs, and 19 miRNAs were dysregulated after treatment with Codonopsis pilosula. To explore the signaling pathways involved, KEGG pathway analysis was performed. Compared with the ceRNA network in aging mice and after treatment with Codonopsis pilosula, we found that 3 mRNAs (Hif3a, Zbtb16, Plxna2) and 1 lncRNA (NONMMUT063872) were associated with the anti-aging effect of Codonopsis pilosula and they were validated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. CONCLUSIONS Our results showed that Codonopsis pilosula has a protective effect on the aging lung, and the ceRNA network plays an important role in the anti-aging effect of Codonopsis pilosula.

Ophiopogonin A Alleviates Hemorrhagic Shock-Induced Renal Injury via Induction of Nrf2 Expression.

Ophiopogonin, including Ophiopogonin A, B, C, D, is an effective active component of traditional Chinese medicine Ophiopogon japonicus which has a wide range of pharmacological effects such as protecting myocardial ischemia, resisting myocardial infarction, immune regulation, lowering blood glucose, and anti-tumor. However, the functions of ophiopogonin A on hemorrhagic shock (HS)-induced renal injury remain unclear. First, this study constructed an HS rat model and hypoxia HK-2 cell model to assess the effects of ophiopogonin A in vivo and in vitro. In vivo, HE and TUNEL staining show that ophiopogonin A dose-dependently inhibits HS-induced tissue damage and apoptosis. Moreover, ophiopogonin A dose-dependently downregulates the levels of blood urea nitrogen (BUN), creatinine (Cr), KIM-1, NGAL, iNOS, TNF-α, IL-1ß, and IL-6 in HS rats kidney tissues, and decreases the number of MPO-positive cells. In vitro, we get similar results that ophiopogonin A dose-dependently improves hypoxia-induced HK-2 cell apoptosis and damage. In addition, ophiopogonin A dose-dependently increases the expression of NF E2-related factor 2 (Nrf2), while knockdown of Nrf2 reverses the functions of ophiopogonin A in vivo and in vitro. Furthermore, ophiopogonin A dose-dependently promotes the phosphorylation of ERK in HS kidney tissues and hypoxia-treated HK-2 cells, suggesting that ophiopogonin A functions via the p-ERK/ERK signaling pathway.

Inhibitory effects of shell of Camellia oleifera Abel extract on mushroom tyrosinase and human skin melanin.

BACKGROUND: As an oil production byproducts, the shell of Camellia oleifera Abel (SC) is usually discarded in the dump. However, previous investigations suggested that the SC could provide valuable bioactive materials. OBJECTIVE: The objectives of this study were to examine the ability of SC extract to inhibit in vitro tyrosinase activity and the melanin inhibition effects of cosmetic formulations containing SC 1,3-butanediol extract in human volunteers. METHODS: The cell viability was determined using a WTT assay. A mushroom tyrosinase was used to evaluate the anti-tyrosinase activity of the SC extract. The placebo (no extract) or test (SC 1,3-butanediol extract) or positive control (kojic acid) cosmetic cream was applied on face of volunteers(30 female subjects) three times a day for 8 weeks. The active compounds in SC extract were screened using liquid chromatography-high-resolution mass spectrometry (UHPLC-QTOF). RESULTS: The result showed that the cytotoxicity of SC extract is insignificant when the concentration of SC extract is below 160 µg/mL. In addition, SC extract dose dependently inhibited tyrosinase activity and SC 1,3-butanediol extract possessed a stronger inhibitory activity than methanol extract and water extract. Clinical evaluations revealed that facial melanin levels of the volunteers receiving cosmetic formulations (containing SC 1,3-butanediol extract) were decreased 59% from baseline in 6th weeks, whereas the placebo group showed no effect. SC 1,3-butanediol extract was detected to contain 12 kaempferol compounds, significantly, kaempferol 3-O-[α-rhamnopyranosyl-(1→6)-ß-glucopyranoside] and kaempferol-3,7-O-α-L-dirhamnoside are the major compounds. CONCLUSION: These results indicate that SC extract can be used as a natural skin-whitening agent in cosmetic products.

Morphological Evolution of Vertically Standing Molybdenum Disulfide Nanosheets by Chemical Vapor Deposition.

In this study, we demonstrated the chemical vapor deposition (CVD) of vertically standing molybdenum disulfide (MoS2) nanosheets, with an unconventional combination of molybdenum hexacarbonyl (Mo(CO)6) and 1,2-ethanedithiol (C2H6S2) as the novel kind of Mo and S precursors respectively. The effect of the distance between the precursor’s outlet and substrates (denoted as d) on the growth characteristics of MoS2, including surface morphology and nanosheet structure, was investigated. Meanwhile, the relationship between the structure characteristics of MoS2 nanosheets and their catalytic performance for hydrogen evolution reaction (HER) was elucidated. The formation of vertically standing nanosheets was analyzed and verified by means of an extrusion growth model. The crystallinity, average length, and average depth between peak and valley (Rz) of MoS2 nanosheets differed depending on the spatial location of the substrate. Good crystalized MoS2 nanosheets grown at d = 5.5 cm with the largest average length of 440 nm, and the highest Rz of 162 nm contributed to a better HER performance, with a respective Tafel slope and exchange current density of 138.9 mV/decade, and 22.6 μA/cm² for raw data (127.8 mV/decade and 19.3 μA/cm² for iR-corrected data).