Isofraxidin attenuates dextran sulfate sodium-induced ulcerative colitis through inhibiting pyroptosis by upregulating Nrf2 and reducing reactive oxidative species.

BACKGROUND: Ulcerative colitis (UC), a non-specific gastrointestinal disease, is commonly managed with aminosalicylic acids and immunosuppressive agents to control inflammation and relieve symptoms, despite frequent relapses. Isofraxidin is a coumarin compound extracted from traditional Chinese medicine, exhibiting anti-inflammatory and antioxidant properties; however, its alleviating effect on UC remains unclear. Therefore, we investigated the mechanism of isofraxidin in lipopolysaccharide (LPS)-induced cell inflammation in human intestinal epithelial cell (HIEC) and human colorectal adenocarcinoma cells (Caco-2), as well as in dextran sulfate sodium (DSS)-induced UC in mice. METHODS: We established colitis models in HIEC and Caco-2 cells and mice with LPS and DSS, respectively. Additionally, NLRP3 knockout mice and HIEC cells transfected with NLRP3 silencing gene and ML385 illustrated the role of isofraxidin in pyroptosis and oxidative stress. Data from cells and mice analyses were subjected to one-way analysis of variance or a paired t-test. RESULTS: Isofraxidin significantly alleviated LPS-induced cell inflammation and reduced lactic dehydrogenase release. Isofraxidin also reversed DSS- or LPS-induced pyroptosis in vivo and in vitro, increasing the expression of pyroptosis-related proteins. Moreover, isofraxidin alleviated oxidative stress induced by DSS or LPS, reducing reactive oxidative species (ROS), upregulation nuclear factor erythroid 2-related factor 2 (Nrf2), and promoting its entry into the nucleus. Mechanistically, ML385 reversed the inhibitory effect of isofraxidin on ROS and increased pyroptosis. CONCLUSION: Isofraxidin can inhibit pyroptosis through upregulating Nrf2, promoting its entry into the nucleus, and reducing ROS, thereby alleviating DSS-induced UC. Our results suggest isofraxidin as a promising therapeutic strategy for UC treatment.

Establishment and validation of a callus tissue transformation system for German chamomile (Matricaria chamomilla L.).

BACKGROUND: German chamomile (Matricaria chamomilla L.) is an important medicinal plant, and the essential oils in the flowers have various biological activities. Genetic transformation systems are important for plant quality improvement and molecular research. To the best of our knowledge, a genetic transformation system has not yet been reported for German chamomile. RESULTS: In this study, we developed Agrobacterium-mediated transformation protocols for German chamomile callus tissues. This involved optimizing key parameters, such as hygromycin and cefotaxime concentrations, bacterial density, and infection and co-culture durations. We also performed gas chromatography-mass spectrometry analysis to identify volatile compounds in non-transgenic and transgenic callus and hairy root tissues. Furthermore, to compare and verify the callus transformation system of German chamomile, we transferred McFPS to the hairy roots of German chamomile. The results showed that the optimal conditions for Agrobacterium-mediated callus tissue transformation were as follows: explant, petiole; cefotaxime concentration, 300 mg/L; hygromycin concentration, 10 mg/L; and bacterial solution concentration, OD600 = 0.6; callus transformation efficiency was the highest when the co-culture time was 3 days. CONCLUSIONS: Establishment of a high-efficiency callus transformation system will lay the foundation for gene function identification in German chamomile.

Should acupuncture become a complementary therapy in the treatment of uterine fibroid: a systematic review and meta-analysis of randomized controlled trials.

Background: Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age. The most effective treatment is myomectomy, but there is no long-term or low-invasive treatment option exists. Acupuncture can be used to treat UFs in a variety of ways. However, there is no meta-analytic synthesis including valid data that explored the efficacy of acupuncture for UFs. Objective: To assess the efficacy and safety of acupuncture for treating UFs. Methods: The PRISMA 2020 checklist was used. We identified and extracted the trials through may 2023 from six databases. The quality of the trials was assessed using the risk of bias (2.0). Meta-analysis was performed using RevMan 5.4 software, and it was synthesized using the random-effects model if the included studies were in high heterogeneity. Subgroup and sensitivity analysis were used if necessary. Results: A total of 1,035 trials were identified, of which 11 were included in the review and meta-analysis. In terms of acupuncture scheme design and fibroid-related symptoms, the trials are highly heterogeneous. All 11 trials have reported acupuncture types, with traditional acupuncture and electroacupuncture being the more representative subgroups. A qualitative review of existing evidence shows that acupuncture has no serious adverse reaction on UFs. Meta-analysis shows that acupuncture can effectively reduce the volume of UFs (MD - 3.89, 95% CI - 5.23 to - 2.56, P < 0.00001) or uterine volume (MD - 16.22, 95% CI - 19.89 To - 12.55, p < 0.00001), reduce the score of fibroid symptoms (MD - 3.03, 95% CI - 3.45 to - 2.60, p < 0.00001), improve the treatment efficiency (RR: 0.19, 95% CI: 0.13 to 0.25, p < 0.00001), and likely do not affect the estrogen level.

Effects of electroacupuncture at "Jiaji" (EX-B 2) combined with neurodynamic mobilization on gastrocnemius muscle atrophy and expression of NF-κB and MuRF1 in rabbits after sciatic nerve injury. / 电针"夹脊"ç»“åˆç¥žç»æ¾åŠ¨æœ¯å¯¹åéª¨ç¥žç»æŸä¼¤å ”è “è‚ è‚ŒèŽç¼©åŠNF-κB、MuRF1表达的影响.

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1). METHODS: A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L4 to L6, stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L4 to L6 , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected. RESULTS: After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group (P<0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group (P<0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group (P<0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group (P<0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group (P<0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group (P<0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group (P<0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group (P<0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group (P<0.05). CONCLUSIONS: Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.

[Lignans from stems and leaves of Cephalotaxus fortunei (â ¡)].

The present study aimed to explore the chemical constituents from the stems and leaves of Cephalotaxus fortunei. Seven lignans were isolated from the 75% ethanol extract of C. fortunei by various chromatographic methods, including silica gel, ODS column chromatography, and HPLC. The structures of the isolated compounds were elucidated according to physicochemical properties and spectral data. Compound 1 is a new lignan named cephalignan A. The known compounds were identified as 8-hydroxy-conidendrine(2), isolariciresinol(3), leptolepisol D(4), diarctigenin(5), dihydrodehydrodiconiferyl alcohol 9'-O-ß-D-glucopyranoside(6), and dihydrodehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside(7). Compounds 2 and 5 were isolated from the Cephalotaxus plant for the first time.

Electroacupuncture for the treatment of cancer pain: a systematic review and meta-analysis of randomized clinical trials.

Objective: This paper aims to review the current evidence on electroacupuncture as an effective and safe therapy for cancer pain management. Methods: Five databases were searched from their inception through November 11, 2022. Only the randomized controlled trials that meet the eligibility criteria were finally included in the study. Literature screening and data extraction were performed independently by two reviewers, and RevMan 5.3 used for meta-analysis. Results: A total of 17 RCTs met our inclusion criteria. We used 8 indicators to estimate the meta-analysis results, most of which proved statistically significant, including VAS scores, NRS scores, and KPS scores. To be specific, VAS scores (MD = -1.41, 95% CI: -2.42 to -0.41, P = 0.006) and NRS scores (MD = -1.19, 95% CI: -1.72 to -0.66, P < 0.0001) were significantly lower in the treatment group compared to the control group. The treatment group's KPS scores (MD = 5.48, 95% CI: 3.27 to 7.69, P < 0.00001) were higher than those of the control group. Also, in the treatment group, the number of burst pain (MD = -2.66, 95% CI: -3.32 to -1.99, P < 0.00001) and side effect rates (RR = 0.51, 95% CI: 0.39 to 0.67, P < 0.00001) greatly reduced, while the response rate (RR = 1.17, 95% CI: 1.09 to 1.26, P < 0.0001) significantly increased compared to the control group. Conclusion: This study demonstrates the advantages of electroacupuncture in the treatment of cancer pain. Meanwhile, rigorous RCTs should be designed and conducted in the future to further demonstrate the exact efficacy of electroacupuncture. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022376148.

Nuclear ATR lysine-tyrosylation protects against heart failure by activating DNA damage response.

Dysregulated amino acid increases the risk for heart failure (HF) via unclear mechanisms. Here, we find that increased plasma tyrosine and phenylalanine levels are associated with HF. Increasing tyrosine or phenylalanine by high-tyrosine or high-phenylalanine chow feeding exacerbates HF phenotypes in transverse aortic constriction and isoproterenol infusion mice models. Knocking down phenylalanine dehydrogenase abolishes the effect of phenylalanine, indicating that phenylalanine functions by converting to tyrosine. Mechanistically, tyrosyl-tRNA synthetase (YARS) binds to ataxia telangiectasia and Rad3-related gene (ATR), catalyzes lysine tyrosylation (K-Tyr) of ATR, and activates the DNA damage response (DDR) in the nucleus. Increased tyrosine inhibits the nuclear localization of YARS, inhibits the ATR-mediated DDR, accumulates DNA damage, and elevates cardiomyocyte apoptosis. Enhancing ATR K-Tyr by overexpressing YARS, restricting tyrosine, or supplementing tyrosinol, a structural analog of tyrosine, promotes YARS nuclear localization and alleviates HF in mice. Our findings implicate facilitating YARS nuclear translocation as a potential preventive and/or interfering measure against HF.

Bufalin reverses ABCB1-mediated resistance to docetaxel in breast cancer.

Background: Docetaxel (DCT) is widely used in clinical practice, but the drug resistance of breast cancer patients has become an important reason to limit its clinical efficacy. Chan'su is a commonly used traditional Chinese medicine for the treatment of breast cancer. Bufalin (BUF) is a bioactive polyhydroxy steroid extracted from chan'su and has strong antitumor activity, but there are few studies on reversing drug resistance in breast cancer. The aim of this study is to determine whether BUF can reverse the drug resistance to DCT and restore efficacy in breast cancer. Methodology: The reversal index of BUF was detected by Cell Counting Kit-8 (CCK-8) assays. The effects of BUF on enhancing the apoptosis of DCT were detected by flow cytometry and Western Blot (WB), and the main differential expression levels of sensitive and resistant strains were detected by high-throughput sequencing. Rhodamine 123 assay, WB and ATP Binding Cassette Subfamily B Member 1 (ABCB1) ATPase activity experiments were used to detect the effect of BUF on ABCB1. The nude mouse orthotopic model was constructed to investigate the reversal effect of BUF on DCT resistance in vivo. Results: With BUF intervention, the sensitivity of drug-resistant cell lines to DCT was increased. BUF can inhibit the expression of ABCB1 protein, increase the drug accumulation of DCT in drug-resistant strains, and reduce the ATPase activity of ABCB1. Animal experiments show that BUF can inhibit the growth of drug-resistant tumors in an orthotopic model of breast cancer and decrease the expression of ABCB1. Conclusion: BUF can reverse ABCB1-mediated docetaxel resistance in breast cancer.

Longitudinal Electrocochleography as an Objective Measure of Serial Behavioral Audiometry in Electro-Acoustic Stimulation Patients.

OBJECTIVE: Minimally traumatic surgical techniques and advances in cochlear implant (CI) electrode array designs have allowed acoustic hearing present in a CI candidate prior to surgery to be preserved postoperatively. As a result, these patients benefit from combined electric-acoustic stimulation (EAS) postoperatively. However, 30% to 40% of EAS CI users experience a partial loss of hearing up to 30 dB after surgery. This additional hearing loss is generally not severe enough to preclude use of acoustic amplification; however, it can still impact EAS benefits. The use of electrocochleography (ECoG) measures of peripheral hair cell and neural auditory function have shed insight into the pathophysiology of postimplant loss of residual acoustic hearing. The present study aims to assess the long-term stability of ECoG measures and to establish ECoG as an objective method of monitoring residual hearing over the course of EAS CI use. We hypothesize that repeated measures of ECoG should remain stable over time for EAS CI users with stable postoperative hearing preservation. We also hypothesize that changes in behavioral audiometry for EAS CI users with loss of residual hearing should also be reflected in changes in ECoG measures. DESIGN: A pool of 40 subjects implanted under hearing preservation protocol was included in the study. Subjects were seen at postoperative visits for behavioral audiometry and ECoG recordings. Test sessions occurred 0.5, 1, 3, 6, 12 months, and annually after 12 months postoperatively. Changes in pure-tone behavioral audiometric thresholds relative to baseline were used to classify subjects into two groups: one group with stable acoustic hearing and another group with loss of acoustic hearing. At each test session, ECoG amplitude growth functions for several low-frequency stimuli were obtained. The threshold, slope, and suprathreshold amplitude at a fixed stimulation level was obtained from each growth function at each time point. Longitudinal linear mixed effects models were used to study trends in ECoG thresholds, slopes, and amplitudes for subjects with stable hearing and subjects with hearing loss. RESULTS: Preoperative, behavioral audiometry indicated that subjects had an average low-frequency pure-tone average (125 to 500 Hz) of 40.88 ± 13.12 dB HL. Postoperatively, results showed that ECoG thresholds and amplitudes were stable in EAS CI users with preserved residual hearing. ECoG thresholds increased (worsened) while ECoG amplitudes decreased (worsened) for those with delayed hearing loss. The slope did not distinguish between EAS CI users with stable hearing and subjects with delayed loss of hearing. CONCLUSIONS: These results provide a new application of postoperative ECoG as an objective tool to monitor residual hearing and understand the pathophysiology of delayed hearing loss. While our measures were conducted with custom-designed in-house equipment, CI companies are also designing and implementing hardware and software adaptations to conduct ECoG recordings. Thus, postoperative ECoG recordings can potentially be integrated into clinical practice.

Systems biology strategy and experimental validation to uncover the pharmacological mechanism of Xihuang Pill in treating non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for almost 85% of lung cancer-related deaths worldwide. Xihuang Pill (XHP) is a representative anticancer Chinese patented medicine used to treat NSCLC in China. However, to date, a systematic analysis of XHP's antitumour effects and its impact on the immune microenvironment has not been performed. PURPOSE: Based on the systems biology strategy and experimental validation, the present study aimed to investigate the pharmacological mechanisms involved in treating NSCLC with XHP. METHODS: A subcutaneous tumour model was established to evaluate XHP's tumour-inhibitory effect in BALB/c nude mice. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify differentially expressed genes (DEGs) and signalling pathways related to XHP treatment. Network analysis based on network pharmacology and protein-to-protein networks was applied to identify the compounds and genes targeted by XHP. External data from the TCGA-NSCLC cohort were used to verify the clinical significance of XHP-targeted genes in NSCLC. The expression of survival-related candidate genes after XHP treatment was verified via qPCR. The protein expression of calcium voltage-gated channel subunit alpha 1C (CACNA1C) in different NSCLC cell lines was analysed in the Human Protein Atlas database (HPA) and DepMap Portal. Using the Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm and the single-sample gene set enrichment analysis (ssGSEA) algorithm uncovered the role of CACNA1C in the NSCLC tumour microenvironment (TME). RESULTS: XHP (2 g/kg/d) significantly inhibited the growth of transplanted A549 tumours. RNA-seq identified a total of 529 DEGs (189 upregulated and 340 downregulated). In addition, 542 GO terms, 41 significant KEGG pathways, 9 upregulated hallmarks pathways, and 18 downregulated hallmark pathways were enriched. These GO terms and signalling pathways were closely related to cell proliferation, immunity, energy metabolism, and the inflammatory response of NSCLC. In addition, XHP's network pharmacology analysis identified 301 compounds and 1,432 target genes. A comprehensive strategic analysis identified CACNA1C as a promising gene by which XHP targets and regulates the TME of NSCLC, benefiting patient survival. CACNA1C expression was positively correlated with both the immune score and stromal score but negatively correlated with the tumour purity score. Additionally, CACNA1C expression was significantly correlated with the infiltration levels of 15 types of immune cells and the expression levels of 6 well-known checkpoint genes. CONCLUSIONS: Our results show that by regulating the pathways associated with cell proliferation and immunity, XHP can suppress cancer cell growth in NSCLC. Additionally, XHP may increase the expression of CACNA1C to suppress immune cell infiltration and regulate the expression of checkpoint-related genes, thereby improving the overall survival of NSCLC patients.

Exploratory study of sea buckthorn enhancing QiangGuYin efficacy by inhibiting CKIP-1 and Notum activating the Wnt/ß-catenin signaling pathway and analysis of active ingredients by molecular docking.

Background: Sea buckthorn (SBT) is a traditional Chinese medicine (TCM), rich in calcium, phosphorus, and vitamins, which can potentially prevent and treat osteoporosis. However, no research has been conducted to confirm these hypotheses. QiangGuYin (QGY) is a TCM compound used to treat osteoporosis. There is a need to investigate whether SBT enhances QGY efficacy. Objectives: The aim of this study was to explore whether SBT enhances QGY efficacy by inhibiting CKIP-1 and Notum expression through the Wnt/ß-catenin pathway. The study also aimed to explore the active components of SBT. Methods: Experimental animals were divided into control, model, QGY, SBT, SBT + Eucommia ulmoides (EU), and SBT + QGY groups. After treatment, bone morphometric parameters, such as estrogen, PINP, and S-CTX levels, and Notum, CKIP-1, and ß-catenin expression were examined. Screening of SBT active components was conducted by molecular docking to obtain small molecules that bind Notum and CKIP-1. Results: The results showed that all the drug groups could elevate the estrogen, PINP, and S-CTX levels, improve femoral bone morphometric parameters, inhibit Notum and CKIP-1 expression, and promote ß-catenin expression. The effect of SBT + EU and SBT + QGY was superior to the others. Molecular docking identified that SBT contains seven small molecules (folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and ent-epicatechin) with potential effects on CKIP-1 and Notum. Conclusion: SBT improves bone morphometric performance in PMOP rats by inhibiting CKIP-1 and Notum expression, increasing estrogen levels, and activating the Wnt/ß-catenin signaling pathway. Furthermore, SBT enhances the properties of QGY. Folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and ent-epicatechin are the most likely active ingredients of SBT. These results provide insight into the pharmacological mechanisms of SBT in treating osteoporosis.

Acupuncture and moxibustion for chronic fatigue syndrome: A systematic review and network meta-analysis.

BACKGROUND: Research into acupuncture and moxibustion and their application for chronic fatigue syndrome (CFS) has been growing, but the findings have been inconsistent. OBJECTIVE: To evaluate the existing randomized clinical trials (RCTs), compare the efficacy of acupuncture, moxibustion and other traditional Chinese medicine (TCM) treatments. DATA SOURCES: Three English-language databases (PubMed, Embase, Web of Science, and The Cochrane Library) and 4 Chinese-language biomedical databases (Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang) were searched for RCTs published from database inception through August 2021. STUDY SELECTION: RCTs include acupuncture, moxibustion, traditional Chinese herbal medicine, western medicine and no control. DATA EXTRACTION AND SYNTHESIS: Data were screened and extracted independently using predesigned forms. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. We conducted a random-effects network meta-analysis within a frequentist framework. We assessed the certainty of evidence contributing to network estimates of the main outcomes with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. MAIN OUTCOMES AND MEASURES: The primary outcomes were the overall response rate and FS-14 scale. RESULTS: A total of 51 randomized controlled trials involving 3473 patients with CFS were included in this review. Forty one studies indicate low risk or unknown risk, and the GRADE scores of the combined results show low levels. Among the main indicators, traditional Chinese medicine therapies have excellent performance. However, the overall response rate is slightly different from the results obtained from the Fatigue Scale-14 total score. Moxibustion and traditional Chinese medicine (Odds ratios 48, 95% CrI 15-150) perform better in the total effective rate, while moxibustion plus acupuncture (MD 4.5, 95% CrI 3.0-5.9) is better in the FS-14 total score. CONCLUSIONS: The effect of acupuncture and moxibustion in the treatment of CFS was significantly higher than that of other treatments. Traditional Chinese medicine should be used more widely in the treatment of CFS.

Viola yedoensis Makino formula alleviates DNCB-induced atopic dermatitis by activating JAK2/STAT3 signaling pathway and promoting M2 macrophages polarization.

BACKGROUND: Atopic dermatitis (AD), a common inflammatory skin disorder, severely affects the life quality of patients and renders heavy financial burden on patient's family. The Chinese medicine Viola yedoensis Makino formula (VYAC) has been widely used for treating various skin disorders. Previous studies have reported that VYAC is effective in relieving DNCB-induced AD and inflammation. However, the anti-inflammatory mechanism of VYAC is still ill-defined and poorly understood. This study aims to investigate the therapeutic effects of VYAC on DNCB-induced AD and to elucidate the underlying anti-inflammatory mechanisms. METHODOLOGY: VYAC were extracted with 70% ethanol and lyophilized for use. AD mice were established by DNCB. The therapeutic effects of VYAC were evaluated by oral administration VYAC (150, 300 and 600 mg/kg) daily in vivo. The histopathological and immunohistochemistry were used to analyze skin lesion and macrophages infiltration, RT-qPCR and Elisa were used to analyze the inflammatory factors in skin tissues and serum. To explore the underlying mechanism of VYAC against AD in vitro. RAW264.7 cells and bone-marrow-derived macrophages (BMDMs) were employed for macrophage polarization analysis. Flow cytometer, immunofluorescence and western blot were used to analyze M2 macrophages markers. STAT3 siRNA were transfected into both cells to validate the effects of VYAC-induced macrophages M2 polarization via JAK2/STAT3 signaling pathway. RESULTS: VYAC ameliorated skin lesion of DNCB-induced AD mice by decreased clinical scores and epidermal thickness, decreased the level of pro-inflammatory factors (IL-1ß, TNF-α and IL-18) and enhanced IL-10 anti-inflammatory factor level, inhibited macrophages infiltration and promoted M2 macrophages polarization in vivo. VYAC significantly promoted M2 macrophages polarization in vitro. It is observed that VYAC not only inhibited the phosphorylation of JAK2 and STAT3 in RAW264.7 cells and BMDMs, but also accelerated the translocation to the nucleus. What's more, VYAC reduced the polarization of M2 macrophage by activating JAK2/STAT3 signaling pathway was observed in both cells. CONCLUSIONS: Our findings demonstrate that VYAC significantly ameliorates skin lesion of DNCB-induced AD mice and reduces the levels of inflammatory factors by activating JAK2/STAT3 signaling pathway and promoting M2 macrophages polarization.

Ultrasonic thalamic stimulation modulates neural activity of thalamus and motor cortex in the mouse.

Objective.Previous studies have demonstrated that ultrasound thalamic stimulation (UTS) can treat disorders of consciousness. However, it is still unclear how UTS modulates neural activity in the thalamus and cortex.Approach.In this study, we performed UTS in mice and recorded the neural activities including spike and local field potential (LFP) of the thalamus and motor cortex (M1). We analyzed the firing rate of spikes and the power spectrum of LFPs and evaluated the coupling relationship between LFPs from the thalamus and M1 with Granger causality.Main results.Our results clearly indicate that UTS can directly induce neural activity in the thalamus and indirectly induce neural activity in the M1. We also found that there is a strong connection relationship of neural activity between thalamus and M1 under UTS.Significance.These results demonstrate that UTS can modulate the neural activity of the thalamus and M1 in mice. It has the potential to provide guidance for the ultrasound treatment of thalamus-related diseases.

Photodynamic therapy for synovial hyperplasia in patients with refractory rheumatoid arthritis: a study protocol for a randomized, double-blind, blank-controlled prospective trial.

BACKGROUND: Persistent synovial hyperplasia with inflammation in rheumatoid arthritis is one of the main pathogeneses of refractory rheumatoid arthritis (RRA). Photodynamic therapy (PDT) causes less trauma than steroid injections or arthroscopic synovectomy while providing stronger targeting and more durable curative effects. The aim of this trial was to evaluate the short-, medium-, and long-term clinical efficacy of PDT when applied as a treatment for RRA synovial hyperplasia and synovitis. METHODS AND ANALYSIS: This protocol is for a single-center, randomized, double-blind, blank-controlled prospective trial. A sample of 126 RRA patients will be randomly divided into 3 groups: the control group, the "PDT once" group, and the "PDT twice" group, with 42 participants per group. The trial will be conducted by the Rheumatology and Immunology Department of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University. The Ultrasound Compound Score of Synovitis (UCSS) has been selected as the primary outcome measure. The secondary outcome measures include knee joint clinical assessments, ratio of relapse, duration of remission, Disease Activity Score in 28 joints (DAS28), inflammation indexes, serum concentrations of specific antibodies, and changes in articular structures as detected by X-ray scans in the 48th week. The improvement ratios of the UCSS at the 8th, 24th, and 48th weeks (compared with baseline) reflect short-, medium-, and long-term time frames, respectively. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Ethics Committee of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, China (Approval No. granted by the ethics committee: NFZXYEC-2017-005) and then entered in the Chinese Clinical Trials Registry under registration number ChiCTR1800014918 (approval date: February 21, 2018). All procedures are in accordance with Chinese laws and regulations and with the Declaration of Helsinki by the World Medical Association (WMA). Any modifications of this protocol during execution will need additional approval from the Ethics Committee of our hospital. TRIAL REGISTRATION NUMBER: ChiCTR1800014918 .

Interventions for preventing influenza: An overview of Cochrane systematic reviews and a Bayesian network meta-analysis.

BACKGROUND: Influenza places a heavy public health burden in numerous countries every year. In addition to vaccines, there are some interventions that are effective in preventing influenza. OBJECTIVE: This overview of systematic reviews (SRs) aimed to evaluate the efficacy and safety of interventions for influenza prevention. SEARCH STRATEGY: We searched the Cochrane Database of Systematic Reviews, 2020, Issue 1 for relevant Cochrane SRs using the keywords "common cold," "influenza," and "flu." INCLUSION CRITERIA: Cochrane SRs that investigated the prevention of influenza were included. Participants included the general population without influenza or influenza-like symptoms, who were treated with preventative interventions and compared to individuals receiving no treatment or placebo. DATA EXTRACTION AND ANALYSIS: Two reviewers independently screened citations against pre-defined inclusion criteria and extracted data. The methodological quality of these SRs was evaluated using the Assessing the Methodological Quality of Systematic Reviews-II (AMSTAR-II) guidelines. The primary outcome of our analysis was the incidence of influenza, and the secondary outcomes were the incidence of influenza-like illness and hospitalization. In addition to the narrative summary of SR findings, we also pooled data from homogeneous trials among these SRs and produced evidence mapping. We conducted a network meta-analysis to compare the effect across interventions and used the Cochrane approach to grading of recommendations, assessment, development, and evaluation (GRADE) to assess the quality of evidence. RESULTS: Eleven Cochrane SRs were included, covering five medications, eleven vaccinations and four complementary therapies. Among these SRs, 73% scored "high" quality on AMSTAR-II rating. We found that eight interventions, including amantadine, garlic, and six different vaccines, were beneficial for reducing the incidence of influenza compared to placebo, while oseltamivir, zanamivir, Ganmao capsule, Echinacea, and another three types of vaccine were probably beneficial. Ganmao capsule ranked highest for influenza prevention in the network meta-analysis, followed by amantadine, garlic, and vaccines of all types. Monovalent inactivated parenteral vaccine was found to be beneficial in reducing the incidence of influenza-like illness. None of the interventions reduced the hospitalization rate. CONCLUSION: High-quality evidence showed that garlic or vaccine had advantages in preventing influenza, and that vitamin C is not effective. The effect of other interventions needs to be further verified with high-quality evidence.

Influence of behavioral state on the neuromodulatory effect of low-intensity transcranial ultrasound stimulation on hippocampal CA1 in mouse.

In process of brain stimulation, the influence of any external stimulus depends on the features of the stimulus and the initial state of the brain. Understanding the state-dependence of brain stimulation is very important. However, it remains unclear whether neural activity induced by ultrasound stimulation is modulated by the behavioral state. We used low-intensity focused ultrasound to stimulate the hippocampal CA1 regions of mice with different behavioral states (anesthesia, awake, and running) and recorded the neural activity in the target area before and after stimulation. We found the following: (1) there were different spike firing rates and response delays computed as the time to reach peak for all behavioral states; (2) the behavioral state significantly modulates the spike firing rate linearly increased with an increase in ultrasound intensity under different behavioral states; (3) the mean power of local field potential induced by TUS significantly increased under anesthesia and awake states; (4) ultrasound stimulation enhanced phase-locking between spike and ripple oscillation under anesthesia state. These results suggest that ultrasound stimulation-induced neural activity is modulated by the behavioral state. Our study has great potential benefits for the application of ultrasound stimulation in neuroscience.

A TCM formula VYAC ameliorates DNCB-induced atopic dermatitis via blocking mast cell degranulation and suppressing NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: A Traditional Chinese Medicine (TCM) formula (VYAC) consists of three herbs including Viola yedoensis Makino, herb (Violaceae, Viola), Sophora flavescens Aiton, root (Fabaceae, Sophora) and Dictamnus dasycarpus Turcz, root and rhizome (Rutaceae, Dictamnus), has been traditionally prescribed to treat various skin diseases in clinic. AIM OF THE STUDY: This study aims to investigate the therapeutic effects of VYAC on the 2,4-dinitrobenzene (DNCB) induced atopic dermatitis (AD)-like mice and to explore the underlying mechanisms. MATERIALS AND METHODS: VYAC was extracted with 70 % aqueous ethanol and lyophilized powder was used. AD-like mice were challenged by DNCB, VYAC (150 and 300 mg/kg) were oral administration daily from day 7 to day 28. At the end of experiment, the clinical scores were recorded, serum and skin in the dorsal were isolated to evaluate the therapeutic effects of VYAC. RBL-2H3 cells were stimulated with C48/80 for degranulation and plasmids expressing constitutively active form of Syk (Silence or overexpression) were transfected into RBL-2H3 cells to explore the underlying mechanisms in vitro. RESULTS: VYAC significantly ameliorated the cardinal symptoms in the DNCB-induced AD-like mice by repairing the skin barrier function, inhibiting mast cells infiltration, restraining the serum IgE and histamine release and decreasing TNF-α, IL-4 as well as Syk mRNA level in dorsal skin and alleviating inflammation. Besides, VYAC significantly blocked RBL-2H3 cells degranulation, reduced ß-hexosaminidase and histamine release, and suppressed NF-κB pathway. What's more, the degranulation of RBL-2H3 was reduced after Syk silence and increased after Syk overexpression. CONCLUSION: Our findings clearly suggested that VYAC treat AD through inhibiting the inflammatory mediator productions and blocking mast cell degranulation via suppressing Syk mediated NF-κB pathway.

A combined quality evaluation method that integrates chemical constituents, appearance traits and origins of raw Rehmanniae Radix pieces.

The quality control of Chinese herbal medicine is a current challenge for the internationalization of traditional Chinese medicine. Traditional quality evaluation methods lack quantitative analysis, while modern quality evaluation methods ignore the origins and appearance traits. Therefore, an integrated quality evaluation method is urgent in need. Raw Rehmanniae Radix (RRR) is commonly used in Chinese herbal medicine. At present, much attention has been drwan towards its quality control, which however is limited by the existing quality evaluation methods. The present study was designed to establish a comprehensive and practical method for the quality evaluation and control of RRR pieces based on its chemical constituents, appearance traits and origins. Thirty-three batches of RRR pieces were collected from six provinces, while high-performance liquid chromatography (HPLC) was applied to determine the following five constituents, including catalpol, rehmannioside A, rehmannioside D, leonuride and verbascoside in RRR pieces. Their appearance traits were quantitatively observed. Furthermore, correlation analysis, principal components analysis (PCA), cluster analysis and t-test were performed to evaluate the qualities of RRR pieces. These batches of RRR pieces were divided into three categories: samples from Henan province, samples from Shandong and Shanxi provinces, and those from other provinces. Furthermore, the chemical constituents and appearance traits of RRR pieces were significantly different from diverse origins. The combined method of chemical contituents, appearance traits and origins can distinguish RRR pieces with different qualities, which provides basic reference for the quality control of Chinese herbal medicine.

Pyroelectric Catalysis-Based "Nano-Lymphatic" Reduces Tumor Interstitial Pressure for Enhanced Penetration and Hydrodynamic Therapy.

Because of the deficiency of lymphatic reflux in the tumor, the retention of tumor interstitial fluid causes aggravation of the tumor interstitial pressure (TIP), which leads to unsatisfactory tumor penetration of nanomedicine. It is the main inducement of tumor recurrence and metastasis. Herein, we design a pyroelectric catalysis-based "Nano-lymphatic" to decrease the TIP for enhanced tumor penetration and treatments. It realizes photothermal therapy and decomposition of tumor interstitial fluid under NIR-II laser irradiation after reaching the tumor, which reduces the TIP for enhanced tumor penetration. Simultaneously, reactive oxygen species generated during the pyroelectric catalysis can further damage deep tumor stem cells. The results indicate that the "Nano-lymphatic" relieves 52% of TIP, leading to enhanced tumor penetration, which effectively inhibits the tumor proliferation (93.75%) and recurrence. Our finding presents a rational strategy to reduce TIP by pyroelectric catalysis for enhanced tumor penetration and improved treatments, which is of great significance for drug delivery.