Physical therapy intervention for breast symptoms in lactating women: a randomized controlled trial.

BACKGROUND: Therapeutic ultrasound, education, and massage are the most common physical therapy interventions provided to mothers with breast symptoms. However, there is insufficient evidence on the effectiveness of the combination of these interventions. This study aimed to explore the effects of the combination of therapeutic ultrasound, education, and massage on breast symptoms in lactating women. METHODS: This study was a single-blind randomized controlled trial. Postpartum lactating women aged from 21 to 45 with breast symptoms were recruited and randomly allocated to one of three groups (ultrasound group, sham group, and usual care group). The severity of breast symptoms (pain, redness, lump, general malaise), breast engorgement, breast hardness, body temperature, breast temperature, and milk volume were assessed at baseline (T1), immediately post-intervention (T2), and at 3 months following baseline (T3). RESULTS: A total of 37 participants were included in the study (ultrasound group n = 12; sham group n = 12; usual care n = 13). The severity of breast symptoms (i.e., pain, lump, and general malaise) as well as breast engorgement, were significantly improved in the ultrasound group at T2 when compared to T1, and these improvements were sustained at T3. The severity of breast engorgement was significantly lower in the ultrasound group when compared to the usual care group at T2. However, no statistically significant differences were found between the ultrasound and sham groups for all outcomes at any assessment time points. CONCLUSIONS: Physical therapy interventions may be beneficial in relieving breast symptoms in lactating women. Larger randomized controlled trials are needed to confirm the findings of this study. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04569136); Date of registration: 29/09/2020.

Tea polyphenols coated sodium alginate-gelatin 3D edible scaffold for cultured meat.

This study aimed to use edible scaffolds as a platform for animal stem cell expansion, thus constructing block-shaped cell culture meat. The tea polyphenols (TP)-coated 3D scaffolds were constructed of sodium alginate (SA) and gelatin (Gel) with good biocompatibility and mechanical support. Initially, the physicochemical properties and mechanical properties of SA-Gel-TP scaffolds were measured, and the biocompatibility of the scaffolds was evaluated by C2C12 cells. SEM results showed that the scaffold had a porous laminar structure with TP particles attached to the surface, while FT-IR results also demonstrated the encapsulation of TP coating on the scaffold. In addition, the porosity of all scaffolds was higher than 40% and the degradation rate during the incubation cycle was less than 40% and the S2-G1-TP0.1-3 h scaffold has excellent cell adhesion and extension. Subsequently, we inoculated rabbit skeletal muscle myoblasts (RbSkMC) on the scaffold and induced differentiation. The results showed good adhesion and extension behavior of RbSkMC on S2-G1-TP0.1-3 h scaffolds with high expression of myogenic differentiation proteins and genes, and SEM results confirmed the formation of myotubes. Additionally, the adhesion rate of cells on scaffolds with TP coating was 1.5 times higher than that on scaffolds without coating, which significantly improved the cell proliferation rate and the morphology of cells with extension on the scaffolds. Furthermore, rabbit-derived cultured meat had similar appearance and textural characteristics to fresh meat. These conclusions indicate the high potential of the scaffolds with TP coating as a platform for the production of cultured meat products.

Protein acetylation and related potential therapeutic strategies in kidney disease.

Kidney disease can be caused by various internal and external factors that have led to a continual increase in global deaths. Current treatment methods can alleviate but do not markedly prevent disease development. Further research on kidney disease has revealed the crucial function of epigenetics, especially acetylation, in the pathology and physiology of the kidney. Histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyllysine readers jointly regulate acetylation, thus affecting kidney physiological homoeostasis. Recent studies have shown that acetylation improves mechanisms and pathways involved in various types of nephropathy. The discovery and application of novel inhibitors and activators have further confirmed the important role of acetylation. In this review, we provide insights into the physiological process of acetylation and summarise its specific mechanisms and potential therapeutic effects on renal pathology.

[Effect of acupuncture at "Houxi" (SI3) and"Huantiao" (GB30) on high mobility group box 1 protein in spinal nerve trunk of rats with lumbar disc herniation].

OBJECTIVE: To observe the effect of acupuncture at "Houxi"(SI3) and "Huantiao"(GB30) on high mobility group box 1(HMGB1) protein and mRNA in spinal nerve trunk(SNT) of rats with lumbar disc herniation(LDH), so as to explore the mechanisms of acupuncture at this paired points on the treatment for LDH. METHODS: SD rats were randomly divided into sham operation, model, conventional acupuncture(CA) and paired points(PP) groups (with 8 rats in each group). The LDH model was established by injection of autologous suspension made from rats' own nucleus pulsus into the epidural space. Rats in the CA group received acupuncture treatment at bilateral "Weizhong"(BL40), "Dachangshu"(BL25) and "Shenshu"(BL23), while rats in the PP group received acupuncture at bilateral SI3 and GB30, 30 min each time, once daily for 14 consecutive days. The thermal pain threshold of bilateral hind feet of rats was detected by thermal pain stimulator. The contents of serum IL-1ß, IL-6 and IL-8 of rats were detected by ELISA. Western blot and immunofluorescence were used to detect the expression of HMGB1 protein in the lumbar(L)5 SNT of rats. The relative expression of HMGB1 mRNA in L5 SNT was determined by qPCR. HE staining was used to observe the morphological changes of L5 SNT. RESULTS: Compared with the sham operation group, the thermal pain threshold of bilateral hind feet in the model group was decreased (P<0.05); compared with the model group, the thermal pain threshold of bilateral hind feet in the CA group and the PP group were increased (P<0.05). The expressions of HMGB1 protein and mRNA in L5 SNT, and the contents of serum IL-1ß, IL-6 and IL-8 of rats in the model group were significantly increased(P<0.000 1, P<0.001) in contrast to the sham operation group. The expressions of HMGB1 protein and mRNA in L5 SNT, and the levels of serum IL-1ß, IL-6 and IL-8 were significantly decreased (P<0.01, P<0.000 1, P<0.001, P<0.05) in the CA and PP group, in comparison with those of the model group. Compared with the CA group, the above indexes of rats in the PP group recovered more significantly (P<0.05,P<0.001, P<0.01,P<0.000 1). The histomorphological results showed scattered and various-sized nerve fibers, vacuolation, a large number of disintegrating myelin sheath and lysed Schwann cells in the model group. Myelin sheaths regeneration, regularly-arranged nerve fibers were seen in the CA group and the PP group, with more obvious histopathological recovery observed in the PP group than the CA group. CONCLUSION: Acupuncture intervention inhibites the expressions of HMGB1 protein and mRNA in rats with LDH, and further reduces the production of IL-1ß, IL-6 and IL-8, which is beneficial to inflammatory response inhibition and pain alleviation. The therapeutic effect of the PP group is more obvious than that of the CA group.

Characterizing the Survival-Associated Interactions Between Tumor-Infiltrating Lymphocytes and Tumors From Pathological Images and Multi-Omics Data.

The tumor-infiltrating lymphocytes (TILs) and its correlation with tumors have shown significant values in the development of cancers. Many observations indicated that the combination of the whole-slide pathological images (WSIs) and genomic data can better characterize the immunological mechanisms of TILs. However, the existing image-genomic studies evaluated the TILs by the combination of pathological image and single-type of omics data (e.g., mRNA), which is difficulty in assessing the underlying molecular processes of TILs holistically. Additionally, it is still very challenging to characterize the intersections between TILs and tumor regions in WSIs and the high dimensional genomic data also brings difficulty for the integrative analysis with WSIs. Based on the above considerations, we proposed an end-to-end deep learning framework i.e., IMO-TILs that can integrate pathological image with multi-omics data (i.e., mRNA and miRNA) to analyze TILs and explore the survival-associated interactions between TILs and tumors. Specifically, we firstly apply the graph attention network to describe the spatial interactions between TILs and tumor regions in WSIs. As to genomic data, the Concrete AutoEncoder (i.e., CAE) is adopted to select survival-associated Eigengenes from the high-dimensional multi-omics data. Finally, the deep generalized canonical correlation analysis (DGCCA) accompanied with the attention layer is implemented to fuse the image and multi-omics data for prognosis prediction of human cancers. The experimental results on three cancer cohorts derived from the Cancer Genome Atlas (TCGA) indicated that our method can both achieve higher prognosis results and identify consistent imaging and multi-omics bio-markers correlated strongly with the prognosis of human cancers.

Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study.

OBJECTIVE: To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism. METHODS: Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines. RESULTS: A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis. CONCLUSION: Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

Macleaya cordata extract improves the growth performance and intestinal health of American eels (Anguilla rostrata) farmed in intensive system.

The present study was conducted to evaluate the effects of dietary Macleaya cordata extract (MCE) supplementation on growth performance and intestinal health of American eels (Anguilla rostrata) farmed in intensive system. A total of six cement tanks of fish were randomly divided into a control group fed a commercial diet and an MCE group fed the commercial diet with 100 mg/kg MCE, respectively. There were three replicates in each group. The results suggested that 100 mg/kg MCE could improve the growth performance and intestinal health of the American eels by strengthening the barrier function and antioxidative ability in the intestine and beneficially modulating intestinal microbiota with the higher relative abundance and more species of the potential probiotics and the lower relative abundance of potentially pathogenic bacteria.

MicroRNA-143-3p Inhibits Wilms' Tumor Cell Growth By Targeting the Ras/Raf/MEK/ERK Pathway.

Background: A previous study found that microRNA-143-3p (miR-143-3p) is a tumor suppressor in various types of human cancer. However, the roles and molecular mechanisms of miR-143-3p in the progression of Wilms' tumor (WT) remain to be clarified. The aim of the present study was to determine the expression and biological functions of miR-143-3p in WT. Material and Methods: The expression levels of miR-143-3p in primary WT tissues and adjacent tissues were determined using quantitative-reverse transcription polymerase chain reaction (qRT-PCR), and the association of the miR-143-3p expression level with various clinicopathological features of WT was investigated. Western blotting was used to evaluate the protein expression of the related signaling pathway. Results: The expression of miR-143-3p was significantly downregulated in WT tissues and its expression levels were closely associated with tumor stage and lymph node metastasis. Overexpression of miR-143-3p in SK-NEP-1 and G401 cell lines inhibited cell proliferation by G0/G1 cell cycle phase arrest and induction of apoptosis. Moreover, k-Ras, a unique oncogene, was confirmed as a direct target of miR-143-3p, and k-Ras messenger RNA (mRNA) expression was increased in WT tissues and inversely correlated with miR-143-3p. Knockdown of k-Ras by si-k-Ras could inhibit, whereas overexpression of k-Ras could promote. cell proliferation in WT cells. Meanwhile, overexpression of k-Ras reversed the inhibitory effects on WT cells induced by miR-143-3p mimics. Conclusion: Our findings indicate that miR-143-3p may be a potential novel prognostic biomarker and therapeutic target for WT.

Melatonin Attenuates Vascular Smooth Muscle Contraction Through the γ-Secretase/Notch Intracellular Domain/Myocardin Pathway.

ABSTRACT: Inositol 1, 4, 5-trisphosphate (IP3) signaling-mediated calcium release drives the contraction of vascular smooth muscles and hence regulates blood vessel volume and blood pressure. Melatonin supplementation has been suggested to be beneficial for hypertension. To determine whether the blood pressure-lowering effect of melatonin was accounted for by IP3 signaling, we evaluated the vasoconstriction response and IP3 signaling in isolated mouse thoracic aortic rings during melatonin incubation. C57BL/6 mice were given intraperitoneal injections daily with melatonin, and the systolic blood pressure and contractility of aortic rings from melatonin-treated mice were decreased, and the contraction suppression effect of melatonin was attributed to the impaired expression of contractile proteins in vascular smooth muscle cells rather than IP3 signaling. Our results further showed that melatonin increased the expression of γ-secretase, which could cleave and release the notch intracellular domain, and the notch intracellular domain prevented the transcription of contractile genes by interfering with the interaction between serum response factor and myocardin, the master regulator of contractile protein. In this article, we report a novel mechanism by which melatonin regulates smooth muscle contractility that does not depend on IP3 signaling.

S2Snet: deep learning for low molecular weight RNA identification with nanopore.

Ribonucleic acid (RNA) is a pivotal nucleic acid that plays a crucial role in regulating many biological activities. Recently, one study utilized a machine learning algorithm to automatically classify RNA structural events generated by a Mycobacterium smegmatis porin A nanopore trap. Although it can achieve desirable classification results, compared with deep learning (DL) methods, this classic machine learning requires domain knowledge to manually extract features, which is sophisticated, labor-intensive and time-consuming. Meanwhile, the generated original RNA structural events are not strictly equal in length, which is incompatible with the input requirements of DL models. To alleviate this issue, we propose a sequence-to-sequence (S2S) module that transforms the unequal length sequence (UELS) to the equal length sequence. Furthermore, to automatically extract features from the RNA structural events, we propose a sequence-to-sequence neural network based on DL. In addition, we add an attention mechanism to capture vital information for classification, such as dwell time and blockage amplitude. Through quantitative and qualitative analysis, the experimental results have achieved about a 2% performance increase (accuracy) compared to the previous method. The proposed method can also be applied to other nanopore platforms, such as the famous Oxford nanopore. It is worth noting that the proposed method is not only aimed at pursuing state-of-the-art performance but also provides an overall idea to process nanopore data with UELS.

Grape seed proanthocyanidin extract regulates lipid metabolism of the American eel (Anguilla rostrata).

The current study was aimed to examine the effect of grape seed proanthocyanidin extract (GSPE) on regulating lipid metabolism of American eels. A total of six cement tanks of fish were randomly divided into a control group fed with a commercial diet and a GSPE group fed with a commercial diet supplemented 400 mg/kg GSPE. There were three replicates in each group. Results suggested that GSPE could decrease the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and increase the high-density lipoprotein cholesterol level in serum. GSPE might regulate lipid metabolism through upregulating linoleic acid metabolism and arachidonic acid metabolism along with downregulating metabolisms of phenylalanine, tyrosine, and tryptophan biosynthesis and valine, leucine, and isoleucine biosynthesis.

Metabolomics Tools Assisting Classic Screening Methods in Discovering New Antibiotics from Mangrove Actinomycetia in Leizhou Peninsula.

Mangrove actinomycetia are considered one of the promising sources for discovering novel biologically active compounds. Traditional bioactivity- and/or taxonomy-based methods are inefficient and usually result in the re-discovery of known metabolites. Thus, improving selection efficiency among strain candidates is of interest especially in the early stage of the antibiotic discovery program. In this study, an integrated strategy of combining phylogenetic data and bioactivity tests with a metabolomics-based dereplication approach was applied to fast track the selection process. A total of 521 actinomycetial strains affiliated to 40 genera in 23 families were isolated from 13 different mangrove soil samples by the culture-dependent method. A total of 179 strains affiliated to 40 different genera with a unique colony morphology were selected to evaluate antibacterial activity against 12 indicator bacteria. Of the 179 tested isolates, 47 showed activities against at least one of the tested pathogens. Analysis of 23 out of 47 active isolates using UPLC-HRMS-PCA revealed six outliers. Further analysis using the OPLS-DA model identified five compounds from two outliers contributing to the bioactivity against drug-sensitive A. baumannii. Molecular networking was used to determine the relationship of significant metabolites in six outliers and to find their potentially new congeners. Finally, two Streptomyces strains (M22, H37) producing potentially new compounds were rapidly prioritized on the basis of their distinct chemistry profiles, dereplication results, and antibacterial activities, as well as taxonomical information. Two new trioxacarcins with keto-reduced trioxacarcinose B, gutingimycin B (16) and trioxacarcin G (20), together with known gutingimycin (12), were isolated from the scale-up fermentation broth of Streptomyces sp. M22. Our study demonstrated that metabolomics tools could greatly assist classic antibiotic discovery methods in strain prioritization to improve efficiency in discovering novel antibiotics from those highly productive and rich diversity ecosystems.

[Randomized controlled trials of acupuncture and moxibustion in China in past 45-year (1975-2019): hotspots and trends].

By searching the randomized controlled trials (RCTs) of acupuncture and moxibustion from CNKI since its inception date to december 31 of 2019, the development status and hot trend of RCTs of acupuncture and moxibustion in China were summarized. The CiteSpace and VOSviewer software were used to perform keyword co-occurrence analysis, clustering analysis, time-zone analysis and citation-burst analysis, and visual map was drawn. As a result, a total of 60 995 articles were included, which were published in 1027 academic journals with 1787 keywords. The publication date was from 1975 to 2019. During the past 45 years, the publications of RCTs on acupuncture and moxibustion had shown an overall growth trend with characteristics of the times. The RCTs of manual acupuncture ranked the top, and its proportion of publications every 5 years was stable in the past 30 years. Since 1994, the hot words such as electroacupuncture, warming needling, auricular point sticking and various acupoint therapies had emerged; meanwhile, the spectrum of diseases had broadened, and an evolutionary trend corresponding to therapies and disease systems had been formed. In recent decade, the RCTs using moxibustion therapy have increased significantly, and the hot words such as "sub-health" "winter diseases being treated in summer" and "acupoint application/ moxibustion during the dog days" had indicated that acupuncture clinical research was further inclined to the field of chronic disease prevention and health services, which was in line with social development and the needs of the times.

The Impact of Global Budgeting on the Efficiency of Healthcare under a Single-Payer System in Taiwan.

Since 1995, a national health insurance (NHI) program has been in operation in Taiwan, which provides uniform comprehensive coverage. Forced by severe financial deficit, global budgeting reimbursement was adopted in the healthcare sector to control healthcare expenditures in 2002. A two-stage data envelopment analysis (DEA) approach was used to measure the efficiency of hospital resource allocation among stakeholders in Taiwan's NHI system, and to further explore the changes in resource allocation after the introduction of a global budgeting payment scheme. The dataset was collected from the annual statistical reports of Taiwan's Ministry of Health and Welfare (MOHW) and was used to estimate the efficiency of resource allocation in hospital-based healthcare services under global budgeting. In terms of efficiency during the period from 2003 to 2009, one-third of decision-making units (DMUs) improved their productivity in stage I, and seven out of the total of eighteen DMUs saw falls in financial efficiency in stage II. After global budgeting was implemented, there were significant positive impacts on the efficiency of hospital resource allocation in Taiwan. The two-stage DEA model for analyzing the effects of the global budgeting reimbursement system on productivity and financial efficiency represents a key decision-making tool for hospital administrators and policymakers.

[Chemical constituents of Cassia occidentalis].

Compounds(1-6) were isolated and identified from 90% ethanol extract of the stems and leaves of Cassia occidentalis through column chromatography with silica gel, ODS, and Sephadex LH-20. These compounds were identified as 7-hydroxy-5-(3-hydroxy-2-oxopropyl)-2-methyl-4H-chromen-4-one(1), saccharonol A(2), S-6-hydroxymullein(3), 2-methyl-5-acetonyl-7-hydroxy-chromone(4), 2-(2'-hydroxypropyl)-5-methyl-7-hydroxychromone(5) and 7,4'-dihydroxyflavone(6) based on their physicochemical and spectroscopic data. Among them, compound 1 was a new compound, and all the compounds were isolated from this plant for the first time. DPPH method was employed to determine the antioxidant activities of these compounds in vitro. Six compounds exhibited weak antioxidant activities.

Mortality associated with the use of non-vitamin K antagonist oral anticoagulants in cancer patients: Dabigatran versus rivaroxaban.

OBJECTIVE: This study assesses the mortality outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF). METHODS: Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer-related death. Secondary outcomes were all-cause mortality, major bleeding, and gastrointestinal (GI) bleeding. RESULTS: Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer-related death at one year (HR = 0.71, 95% CI = 0.54-0.93) and at the end of follow-ups (HR = 0.79, 95% CI = 0.64-0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all-cause mortality (HR = 0.81, 95% CI = 0.67-0.97), major bleeding (HR = 0.64, 95% CI = 0.47-0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39-0.84) at the end of follow-ups compared with rivaroxaban. CONCLUSION: Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer-related death and all-cause mortality.

Deep Learning Improves Speed and Accuracy of Prostate Gland Segmentations on Magnetic Resonance Imaging for Targeted Biopsy.

PURPOSE: Targeted biopsy improves prostate cancer diagnosis. Accurate prostate segmentation on magnetic resonance imaging (MRI) is critical for accurate biopsy. Manual gland segmentation is tedious and time-consuming. We sought to develop a deep learning model to rapidly and accurately segment the prostate on MRI and to implement it as part of routine magnetic resonance-ultrasound fusion biopsy in the clinic. MATERIALS AND METHODS: A total of 905 subjects underwent multiparametric MRI at 29 institutions, followed by magnetic resonance-ultrasound fusion biopsy at 1 institution. A urologic oncology expert segmented the prostate on axial T2-weighted MRI scans. We trained a deep learning model, ProGNet, on 805 cases. We retrospectively tested ProGNet on 100 independent internal and 56 external cases. We prospectively implemented ProGNet as part of the fusion biopsy procedure for 11 patients. We compared ProGNet performance to 2 deep learning networks (U-Net and holistically-nested edge detector) and radiology technicians. The Dice similarity coefficient (DSC) was used to measure overlap with expert segmentations. DSCs were compared using paired t-tests. RESULTS: ProGNet (DSC=0.92) outperformed U-Net (DSC=0.85, p <0.0001), holistically-nested edge detector (DSC=0.80, p <0.0001), and radiology technicians (DSC=0.89, p <0.0001) in the retrospective internal test set. In the prospective cohort, ProGNet (DSC=0.93) outperformed radiology technicians (DSC=0.90, p <0.0001). ProGNet took just 35 seconds per case (vs 10 minutes for radiology technicians) to yield a clinically utilizable segmentation file. CONCLUSIONS: This is the first study to employ a deep learning model for prostate gland segmentation for targeted biopsy in routine urological clinical practice, while reporting results and releasing the code online. Prospective and retrospective evaluations revealed increased speed and accuracy.

p-MEK expression predicts prognosis of patients with adenocarcinoma of esophagogastric junction (AEG) and plays a role in anti-AEG efficacy of Huaier.

The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide with poor prognosis and unclear pathogenesis. Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine has been used in the clinical treatment of a variety of solid tumors, including AEG. However, its anticancer components and molecular mechanisms are still unclear. In our previous studies, we have found that Huaier n-butanol extract (HBE) shows the most potent anticancer activity among different extracts. In the present study, we aimed to investigate the clinical relevance of p-MEK expression in AEG patients and the role of the MEK/ERK signaling pathway in the anti-AEG efficacy of HBE in vitro and in vivo. We herein demonstrate that p-MEK expression in AEG tissues was significantly higher than that in paracancerous tissues and correlated with a poor prognosis in AEG patients. We further found that HBE inhibited the colony formation, migration, and invasion in AEG cell lines in a concentration-dependent manner in vitro. HBE also suppressed the growth of AEG xenograft tumors without causing any host toxicity in vivo. Mechanistically, HBE caused the inactivation of the MEK/ERK signaling pathway by dephosphorylating MEK1 at S298, ERK1 at T202, and ERK2 at T185 and modulating the expression of EMT-related proteins. In summary, our results demonstrate that the high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG. The clinically used anticancer drug Huaier may exert its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway.

Hydrogen-rich water protects against liver injury in nonalcoholic steatohepatitis through HO-1 enhancement via IL-10 and Sirt 1 signaling.

Nonalcoholic steatohepatitis (NASH) could progress to hepatic fibrosis in the absence of effective control. The purpose of our experiment was to investigate the protective effect of drinking water with a high concentration of hydrogen, namely, hydrogen-rich water (HRW), on mice with nonalcoholic fatty liver disease to elucidate the mechanism underlying the therapeutic action of molecular hydrogen. The choline-supplemented, l-amino acid-defined (CSAA) or the choline-deficient, l-amino acid-defined (CDAA) diet for 20 wk was used to induce NASH and fibrosis in the mice model and simultaneously treated with the high-concentration 7-ppm HRW for different periods (4 wk, 8 wk, and 20 wk). Primary hepatocytes were stimulated by palmitate to mimic liver lipid metabolism during fatty liver formation. Primary hepatocytes were cultured in a closed vessel filled with 21% O2 + 5% CO2 + 3.8% H2 and N2 as the base gas to verify the response of primary hepatocytes in a high concentration of hydrogen gas in vitro. Mice in the CSAA + HRW group had lower serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and milder histological damage. The inflammatory cytokines were expressed at lower levels in the HRW group than in the CSAA group. Importantly, HRW reversed hepatocyte fatty acid oxidation and lipogenesis as well as hepatic inflammation and fibrosis in preexisting hepatic fibrosis specimens. Molecular hydrogen inhibits the lipopolysaccharide-induced production of inflammation cytokines through increasing heme oxygenase-1 (HO-1) expression. Furthermore, HRW improved hepatic steatosis in the CSAA + HRW group. Sirtuin 1 (Sirt1) induction by molecular hydrogen via the HO-1/adenosine monophosphate activated protein kinase (AMPK)/peroxisome proliferator-activated receptor α (PPARα)/peroxisome proliferator-activated receptor γ (PPAR-γ) pathway suppresses palmitate-mediated abnormal fat metabolism. Orally administered HRW suppressed steatosis induced by CSAA and attenuated fibrosis induced by CDAA, possibly by reducing oxidative stress and the inflammation response.NEW & NOTEWORTHY The mRNA expression of inflammatory cytokines in the HRW group was lower than in the CSAA group. HRW reversed hepatocyte apoptosis as well as hepatic inflammation and fibrosis in NASH specimens. Molecular hydrogen inhibits LPS-induced inflammation via an HO-1/interleukin 10 (IL-10)-independent pathway. HRW improved hepatic steatosis in the CSAA + HRW group. Sirt1 induction by molecular hydrogen via the HO-1/AMPK/PPARα/PPARγ pathway suppresses palmitate-mediated abnormal fat metabolism.

Baicalin prevents LPS-induced activation of TLR4/NF-κB p65 pathway and inflammation in mice via inhibiting the expression of CD14.

Previous studies have shown that baicalin, an active ingredient of the Chinese traditional medicine Huangqin, attenuates LPS-induced inflammation by inhibiting the activation of TLR4/NF-κBp65 pathway, but how it affects this pathway is unknown. It has been shown that CD14 binds directly to LPS and plays an important role in sensitizing the cells to minute quantities of LPS via chaperoning LPS molecules to the TLR4/MD-2 signaling complex. In the present study we investigated the role of CD14 in the anti-inflammatory effects of baicalin in vitro and in vivo. Exposure to LPS (1 µg/mL) induced inflammatory responses in RAW264.7 cells, evidenced by marked increases in the expression of MHC II molecules and the secretion of NO and IL-6, and by activation of MyD88/NF-κB p65 signaling pathway, as well as the expression of CD14 and TLR4. These changes were dose-dependently attenuated by pretreatment baicalin (12.5-50 µM), but not by baicalin post-treatment. In RAW264.7 cells without LPS stimulation, baicalin dose-dependently inhibit the protein and mRNA expression of CD14, but not TLR4. In RAW264.7 cells with CD14 knockdown, baicalin pretreatment did not prevent inflammatory responses and activation of MyD88/NF-κB p65 pathway induced by high concentrations (1000 µg/mL) of LPS. Furthermore, baicalin pretreatment also inhibited the expression of CD14 and activation of MyD88/NF-κB p65 pathway in LPS-induced hepatocyte-derived HepG2 cells and intestinal epithelial-derived HT-29 cells. In mice with intraperitoneal injection of LPS and in DSS-induced UC mice, oral administration of baicalin exerted protective effects by inhibition of CD14 expression and inflammation. Taken together, we demonstrate that baicalin pretreatment prevents LPS-induced inflammation in RAW264.7 cells in CD14-dependent manner. This study supports the therapeutic use of baicalin in preventing the progression of LPS-induced inflammatory diseases.