ZDHXB-101 (3',5-Diallyl-2, 4'-dihydroxy-[1,1'-biphen-yl]-3,5'-dicarbaldehyde) protects against airway remodeling and hyperresponsiveness via inhibiting both the activation of the mitogen-activated protein kinase and the signal transducer and activator of transcription-3 signaling pathways.

Airway remodeling consists of the structural changes of airway walls, which is often considered the result of longstanding airway inflammation, but it may be present to an equivalent degree in the airways of children with asthma, raising the need for early and specific therapeutic interventions. The arachidonic acid cytochrome P-450 (CYP) pathway has thus far received relatively little attention in its relation to asthma. In this study, we studied the inhibition of soluble epoxide hydrolase (sEH) on airway remodeling and hyperresponsiveness (AHR) in a chronic asthmatic model which long-term exposure to antigen over a period of 12 weeks. The expression of sEH and CYP2J2, the level of 14, 15-epoxyeicosatrienoic acids (EETs), airway remodeling, hyperresponsiveness and inflammation were analyzed to determine the inhibition of sEH. The intragastric administration of 3 or 10 mg/kg ZDHXB-101, which is a structural derivative of natural product honokiol and a novel soluble epoxide hydrolase (sEH) inhibitor, daily for 9 weeks significantly increased the level of 14, 15-EETs by inhibiting the expression of sEH and increasing the expression of CYP2J2 in lung tissues. ZDHXB-101 reduced the expression of remodeling-related markers such as interleukin (IL)-13, IL-17, MMP-9 N-cadherin, α-smooth muscle actin, S100A4, Twist, goblet cell metaplasia, and collagen deposition in the lung tissue or in bronchoalveolar lavage fluid. Moreover, ZDHXB-101 alleviated AHR, which is an indicator that is used to evaluate the airway remodeling function. The inhibitory effects of ZDHXB-101 were demonstrated to be related to its direct inhibition of the extracellular signal-regulated kinase (Erk1/2) phosphorylation, as well as inhibition of c-Jun N-terminal kinases (JNK) and the signal transducer and activator of transcription-3 (STAT3) signal transduction. These findings first revealed the anti-remodeling potential of ZDHXB-101 lead in chronic airway disease.

Shp2 positively regulates cigarette smoke-induced epithelial mesenchymal transition by mediating MMP-9 production.

Cigarette smoke (CS) is a major risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) commonly coexists in lung cancer and COPD. CS triggers many factors including matrix metalloproteinases (MMPs) production, contributing to EMT progression in the lungs. Here, how Shp2 signaling regulates the CS-induced MMP-9 production and EMT progression were investigated in mouse lungs and in pulmonary epithelial cell cultures (NCI-H292) found CS induced MMP-9 production, EMT progression (increased vimentin and α-SMA; decreased E-cadherin) and collagen deposition in lung tissues; cigarette smoke extract (CSE) induced MMP-9 production and EMT-related phenotypes in NCI-H292 cells, which were partially prevented by Shp2 KO/KD or Shp2 inhibition. The CSE exposure induced EMT phenotypes were suppressed by MMP-9 inhibition. Recombinant MMP-9 induced EMT, which was prevented by MMP-9 inhibition or Shp2 KD/inhibition. Mechanistically, CS and CSE exposure resulted in ERK1/2, JNK and Smad2/3 phosphorylation, which were suppressed by Shp2 KO/KD/inhibition. Consequentially, the CSE exposure-induced MMP-9 production and EMT progression were suppressed by ERK1/2, JNK and Smad2/3 inhibitors. Thus, CS induced MMP-9 production and EMT resulted from activation of Shp2/ERK1/2/JNK/Smad2/3 signaling pathways. Our study contributes to the underlying mechanisms of pulmonary epithelial structural changes in response to CS, which may provide novel therapeutic solutions for treating associated diseases, such as COPD and lung cancer.

Rac1 signaling regulates cigarette smoke-induced inflammation in the lung via the Erk1/2 MAPK and STAT3 pathways.

Cigarette smoke (CS) is a major risk factor for the development of chronic obstructive pulmonary disease (COPD). Our previous studies have indicated that Rac1 is involved in lipopolysaccharide-induced pulmonary injury and CS-mediated epithelial-mesenchymal transition. However, the contribution of Rac1 activity to CS-induced lung inflammation remains not fully clear. In this study, we investigated the regulation of Rac1 in CS-induced pulmonary inflammation. Mice or 16HBE cells were exposed to CS or cigarette smoke extract (CSE) to induce acute inflammation. The lungs of mice exposed to CS showed an increase in the release of interleukin-6 (IL-6) and keratinocyte-derived chemokine (KC), as well as an accumulation of inflammatory cells, indicating high Rac1 activity. The exposure of 16HBE cells to CSE resulted in elevated Rac1 levels, as well as increased release of IL-6 and interleukin-8 (IL-8). Selective inhibition of Rac1 ameliorated the release of IL-6 and KC as well as inflammation in the lungs of CS-exposed mice. Histological assessment showed that treatment with a Rac1 inhibitor, NSC23766, led to a decrease in CD68 and CD11b positive cells and the infiltration of neutrophils and macrophages into the alveolar spaces. Selective inhibition or knockdown of Rac1 decreased IL-6 and IL-8 release in 16HBE cells induced by CSE, which correlated with CSE-induced Rac1-regulated Erk1/2 mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3) signaling. Our data suggest an important role for Rac1 in the pathological alterations associated with CS-mediated inflammation. Rac1 may be a promising therapeutic target for the treatment of CS-induced pulmonary inflammation.

Cigarette smoke-induced alveolar epithelial-mesenchymal transition is mediated by Rac1 activation.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is the major pathophysiological process in lung fibrosis observed in chronic obstructive pulmonary disease (COPD) and lung cancer. Smoking is a risk factor for developing EMT, yet the mechanism remains largely unknown. In this study, we investigated the role of Rac1 in cigarette smoke (CS) induced EMT. METHODS: EMT was induced in mice and pulmonary epithelial cells by exposure of CS and cigarette smoke extract (CSE) respectively. RESULTS: Treatment of pulmonary epithelial cells with CSE elevated Rac1 expression associated with increased TGF-ß1 release. Blocking TGF-ß pathway restrained CSE-induced changes in EMT-related markers. Pharmacological inhibition or knockdown of Rac1 decreased the CSE exposure induced TGF-ß1 release and ameliorated CSE-induced EMT. In CS-exposed mice, pharmacological inhibition of Rac1 reduced TGF-ß1 release and prevented aberrations in expression of EMT markers, suggesting that Rac1 is a critical signaling molecule for induction of CS-stimulated EMT. Furthermore, Rac1 inhibition or knockdown abrogated CSE-induced Smad2 and Akt (PKB, protein kinase B) activation in pulmonary epithelial cells. Inhibition of Smad2, PI3K (phosphatidylinositol 3-kinase) or Akt suppressed CSE-induced changes in epithelial and mesenchymal marker expression. CONCLUSIONS AND GENERAL SIGNIFICANCE: Altogether, these data suggest that CS initiates EMT through Rac1/Smad2 and Rac1/PI3K/Akt signaling pathway. Our data provide new insights into the fundamental basis of EMT and suggest a possible new course of therapy for COPD and lung cancer.

AD-1, a novel ginsenoside derivative, shows anti-lung cancer activity via activation of p38 MAPK pathway and generation of reactive oxygen species.

BACKGROUND: Ginseng is a traditional Chinese herb that has been used for thousands of years. In the present study, effects and mechanisms of AD-1 were evaluated for its development as a novel anti-lung cancer drug. METHODS: The cytotoxic activity was evaluated by MTT assay. Flow cytometry was employed to detect cell cycle, apoptosis and ROS. Western blot and immunohistochemistry were used to analyze signaling pathways. Lung cancer xenograft models were established by subcutaneous implantation of A549 or H292 cells into nude mice. RESULTS: AD-1 concentration-dependently reduces lung cancer cell viability without affecting normal human lung epithelial cell viability. In A549 and H292 lung cancer cells, AD-1 induces G0/G1 cell cycle arrest, apoptosis and ROS production. The apoptosis can be attenuated by a ROS scavenger - N-acetylcysteine (NAC). In addition, AD-1 up-regulates the expression of p38 and ERK phosphorylation. Addition of a p38 inhibitor SB203580, suppresses the AD-1-induced decrease in cell viability. Furthermore, genetic silencing of p38 attenuates the expression of p38 and decreases the AD-1-induced apoptosis. Treatment with NAC reduces AD-1-induced p38 phosphorylation, which indicates that ROS generation is involved in the AD-1-induced p38 activation. In mice, oral administration of AD-1 (10-40mg/kg) dose-dependently inhibited the growth of xenograft tumors without affecting body weight and decreases the expression of VEGF, MMP-9 and CD34 in tumor tissue. TUNEL staining confirms that the tumors from AD-1 treated mice exhibit a markedly higher apoptotic index. CONCLUSIONS AND GENERAL SIGNIFICANCE: These data support development of AD-1 as a potential agent for lung cancer therapy.

Shp2 plays an important role in acute cigarette smoke-mediated lung inflammation.

Cigarette smoke (CS), the major cause of chronic obstructive pulmonary disease, contains a variety of oxidative components that were implicated in the regulation of Src homology domain 2-containing protein tyrosine phosphatase 2 (Shp2) activity. However, the contribution of Shp2 enzyme to chronic obstructive pulmonary disease pathogenesis remains unclear. We investigated the role of Shp2 enzyme in blockading CS-induced pulmonary inflammation. Shp2 levels were assessed in vivo and in vitro. Mice (C57BL/6) or pulmonary epithelial cells (NCI-H292) were exposed to CS or cigarette smoke extract (CSE) to induce acute injury and inflammation. Lungs of smoking mice showed increased levels of Shp2, compared with those of controls. Treatment of lung epithelial cells with CSE showed elevated levels of Shp2 associated with the increased release of IL-8. Selective inhibition or knockdown of Shp2 resulted in decreased IL-8 release in response to CSE treatment in pulmonary epithelial cells. In comparison with CS-exposed wild-type mice, selective inhibition or conditional knockout of Shp2 in lung epithelia reduced IL-8 release and pulmonary inflammation in CS-exposed mice. In vitro biochemical data correlate CSE-mediated IL-8 release with Shp2-regulated epidermal growth factor receptor/Grb-2-associated binders/MAPK signaling. Our data suggest an important role for Shp2 in the pathological alteration associated with CS-mediated inflammation. Shp2 may be a potential target for therapeutic intervention for inflammation in CS-induced pulmonary diseases.

The efficacy of Chinese herbal drugs for adults with angina pectoris: Bayesian network meta-analysis of 331 RCTs involving 36,467 individuals.

ETHNOPHARMACOLOGICAL RELEVANCE: Hundreds of randomized controlled trials (RCT) on Chinese herbal drugs (CHDs) including Shexiang baoxin pill (BXP), compound Danshen dripping pill (DSP), compound Danshen tablet (DST), Suxiao jiuxin pill (JXP), Naoxintong capsule (NXT), Tongxinluo capsule (TXL), and Di'ao xinxuekang capsule (XXK) and conventional chemical drugs, such as isosorbide dinitrate (ISDN), for angina pectoris are available but have not been evaluated by a PRISMA-compliant network meta-analysis (NMA). AIM OF THE STUDY: This study aimed to compare the efficacy of nine anti-anginal drugs through NMA on RCTs. METHODS: RCTs of drug treatment for adult patients with angina pectoris for improvements in symptoms and electrocardiography were retrieved. Odds ratios and 95% credible intervals were computed to measure effect sizes. RCT quality was evaluated with the Cochrane risk of bias tool. Evidence synthesis was performed with Bayesian NMA. Essential analyses including subgroup analysis, sensitivity analysis, meta-regression analysis, publication bias analysis, and ranking analysis were conducted to assess the robustness of efficacies. Evidence strength was assessed with the GRADE approach. RESULTS: A total of 331 RCTs with 36,467 participants were eligible. The overall quality of all included RCTs was low. Overall efficacy estimates from different approaches of evidential synthesis found that BXP, TXL, and DSP were more efficacious than DST and ISDN. Essential analyses indicated consistent efficacy estimates, insignificant publication bias, and corroborative ranking results. The overall GRADE evidence strength was low. CONCLUSION: This comprehensive Bayesian NMA found BXP, TXL, and DSP to be the top three candidates among the seven tested CHDs for treating adults suffering from angina pectoris. However, the quality and the evidence strength of eligible RCTs were low. Further high-quality RCTs with more outcome measures and their NMAs are warranted. REGISTRATION: PROSPERO CRD42014007035.

Citations of microRNA Biomarker Articles That Were Retracted: A Systematic Review.

Importance: Retraction is a tool that journals can use to deter research misconduct and alert their audience to erroneous content published in the journals. However, retracted articles may continue to damage science if they are still cited as legitimate articles. Objective: To characterize patterns of postretraction citations, particularly in microRNA biomarker research, a field with one of the highest rates of retraction. Evidence Review: Retracted scientific articles on microRNAs were retrieved from PubMed, Web of Science, and Retraction Watch between database inception and July 17, 2021, according to preestablished search strategies. Control articles with characteristics in common with retracted articles (ie, published in the same journals in the same years and months and with the same number of authors) were matched and retrieved from PubMed. Citation metrics of retractions and control articles were collected from Web of Science. PubPeer was referenced to examine the public response or comments on included retractions. Data were analyzed from September 2021 through March 2023. Findings: A total of 10 461 articles were analyzed, with 887 retractions and 9574 articles as controls. Among retracted articles, which were published from 1999 to 2021, there were 756 articles (85.23%) written by researchers affiliated with Chinese institutions. Retracted articles were cited 6327 times after retraction. Of 792 retracted articles that were cited, 621 articles (78.41%) were cited at least once after retraction and 238 articles (30.05%) were cited more often after retraction than before retraction. Overall citations (comprising citations before and after retraction) and postretraction citations accumulated over time (eg, the median [IQR] number of postretraction citations was 1 [1-2] and 23 [9-44] citations at the first 6 and 66 months, respectively, between retraction and citation retrieval). A random sample of 87 retracted articles (9.81%) recorded 478 citations after retraction, with 208 citations (43.51%) in articles published 12 months or longer after retraction. Of these citing articles, 19 articles (3.97%) mentioned the retractions. Compared with the control group of 1620 nonretracted articles, no significant differences were found in overall number of citations or citations after retraction. Among 478 articles citing retracted articles, 414 articles were found on PubMed and had matched control articles; these articles had higher odds of being subsequently retracted than 7954 matched control articles (odds ratio, 6.57; 95% CI, 3.39-12.72). Conclusions and Relevance: In this study, retraction was not associated with a reduction in citations of retracted articles, but articles that cited retracted publications had higher odds of later retraction. These findings suggest that journals may need to implement mechanisms for detection of postretraction citations.

The efficacy and safety of compound kushen injection for adults with esophageal cancer: A meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Kushen injection (CKI), derived from the traditional Chinese medicine Sophora flavescens, has been widely prescribed to treat a variety of cancers including esophageal cancer (ESCA) in China. AIM OF THE STUDY: This study aimed to evaluate the efficacy and safety of CKI for ESCA systematically. METHODS: The protocol was registered in the PROSPERO database with No. CRD42022320503. PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang Database, Clinicaltrials, and Chi-CTR were searched to select RCTs that compared CKI with other interventions for ESCA with outcome measures including clinical efficacy, complete response, quality of life (QoL), adverse events (AEs), and serious AEs (SAEs). The Cochrane Risk of Bias 2 (RoB2) tool was used to assess the quality of RCT. The overall effect sizes were estimated with odds ratios (ORs) and 95% confidence intervals (CIs) on binary outcome data. Meta-analyses were conducted to estimate effect sizes. Subgroup and sensitivity analyses on characteristics of RCTs were performed to test the robustness. Publication bias was also detected with different methods. The evidence strength was assessed with the Grading of Recommendation, Assessment, Development, and Evaluation method. RESULTS: This study finally included 35 RCTs with 2491 ESCA patients. The RoB of RCTs was some concern. The effect size of OR was 2.92 (95% CI [2.39, 3.57]) on clinical efficacy, 2.27 (95% CI [1.84, 2.81]) on complete response, 3.71 (95% CI [2.86, 4.80]) on QoL, 0.39 (95% CI [0.30, 0.50]) on AEs, and 0.13 (95% CI [0.07, 0.27]) on SAEs where the statistical significances (P < 0.00001) were found for all outcome measures. These overall effect sizes showed that CKI was more efficacious and safety for ESCA. Moreover, subgroup and sensitivity analyses found consistent results. Most publication bias analyses showed insignificant differences. The evidence strengths were moderate. CONCLUSION: The moderate evidence from this comprehensive PRISMA-compliant meta-analysis suggested that CKI may be a valuable alternative for adult patients with ESCA on its significant efficacy and safety. However, more RCTs of high quality with low RoB, large sample sizes, and long follow-up periods are still warranted to update the ESCA clinical guideline for physicians and policymakers in further study.

Molecular mechanisms of HER2-targeted therapy and strategies to overcome the drug resistance in colorectal cancer.

HER2 amplification is one of the mechanisms that induce drug resistance to anti-EGFR therapy in colorectal cancer. In recent years, data from several randomized clinical trials show that anti-HER2 therapies improved the prognosis of patients with HER2-positive colorectal cancer. These results indicate that HER2 is a promising therapeutic target in advanced colorectal cancer. Despite the anti-HER2 therapies including monoclonal antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates improving the outcomes, less than 30 % of the patients achieve objective response and eventually have drug resistance. It is necessary to explore the primary and secondary mechanisms for the resistance to anti-HER2 therapies, which will pave the way to overcome the drug resistance. Several studies have reported the potential mechanisms for the resistance to anti-HER2 therapies. In this review, we present a comprehensive overview of the recent advances in clinical research, mechanisms of treatment resistance, and strategies for reversing resistance in HER2-positive colorectal cancer patients.

B-cell targeted therapies in autoimmune encephalitis: mechanisms, clinical applications, and therapeutic potential.

Autoimmune encephalitis (AE) broadly refers to inflammation of the brain parenchyma mediated by autoimmune mechanisms. In most patients with AE, autoantibodies against neuronal cell surface antigens are produced by B-cells and induce neuronal dysfunction through various mechanisms, ultimately leading to disease progression. In recent years, B-cell targeted therapies, including monoclonal antibody (mAb) therapy and chimeric antigen receptor T-cell (CAR-T) therapy, have been widely used in autoimmune diseases. These therapies decrease autoantibody levels in patients and have shown favorable results. This review summarizes the mechanisms underlying these two B-cell targeted therapies and discusses their clinical applications and therapeutic potential in AE. Our research provides clinicians with more treatment options for AE patients whose conventional treatments are not effective.

Cardiovascular protection and antioxidant activity of the extracts from the mycelia of Cordyceps sinensis act partially via adenosine receptors.

Mycelia of cultured Cordyceps sinensis (CS) is one of the most common substitutes for natural CS and was approved for arrhythmia in China. However, the role of CS in ameliorating injury during ischemia-reperfusion (I/R) is still unclear. We examined effects of extracts from CS on I/R and investigated the possible mechanisms. Post-ischemic coronary perfusion pressure, ventricular function, and coronary flow were measured using the Langendorff mouse heart model. Oxidative stress of cardiac homogenates was performed using an ELISA. Our results indicate that CS affords cardioprotection possibly through enhanced adenosine receptor activation. Cardioprotection was demonstrated by reduced post-ischemic diastolic dysfunction and improved recovery of pressure development and coronary flow. Treatment with CS largely abrogates oxidative stress and damage in glucose- or pyruvate-perfused hearts. Importantly, observed reductions in oxidative stress [glutathione disulfide (GSSG)]/[GSSG + glutathione] and [malondialdehyde (MDA)]/[superoxide dismutase + MDA] ratios as well as the resultant damage upon CS treatment correlate with functional markers of post-ischemic myocardial outcome. These effects of CS were partially blocked by 8-ρ-sulfophenyltheophylline, an adenosine receptor antagonist. Our results demonstrate a suppressive role of CS in ischemic contracture. Meanwhile, the results also suggest pre-ischemic adenosine receptor activation may be involved in reducing contracture in hearts pretreated with CS.

Critical quality appraisal of randomized controlled trials with traditional Chinese medicines for the coronavirus disease 2019.

OBJECTIVE: Traditional Chinese medicines (TCM) play an indispensable role during the pandemic of coronavirus disease 2019 (COVID-19), with an increasing number of randomized controlled trials (RCTs) designed and performed to evaluate the efficacy and safety of TCM for COVID-19. This study aimed to critically appraise the quality of currently available RCTs of TCM for COVID-19. METHODS: RCTs of TCM for COVID-19 were searched from three databases by two investigators and selected according to pre-established inclusion and exclusion criteria. General information of included studies was presented by applying descriptive statistics. The methodological and reporting quality of eligible RCTs was critically evaluated based on the risk of bias assessment tool 2 (RoB2) and CONSORT Extension for TCM (CONSORT-CHM Formulas 2017), respectively. The differences of risks and main general information were compared between RCTs published in English and Chinese journals. Microsoft Excel 2019 and SPSS were used for the statistical analysis. A result with p < 0.05 was considered statistically significant. RESULTS: This study finally included 64 RCTs with a total of 10858 participants investigating TCM for COVID-19. All 64 RCTs were evaluated as moderate-to-low RoB including 27 RCTs with high bias, 26 RCTs with some concerns, and 11 with low bias. Results of reporting quality appraisal by CONSORT-CHM Formulas 2017 showed that 61 (95%) RCTs reported more than 18 (50%) items, and 14 (22%) RCTs reported more than 26 (70%) items among all 38 items. Forty-two RCTs were approved by ethics committees and 47 RCTs reported the informed consent information. Twenty-five RCTs and 39 RCTs provided information on trial registration and funding resources, respectively. The quality of 44 RCTs published in Chinese was significantly worse than that of 20 RCTs published in English, especially in the following considerations including the overall RoB, ethics approved, informed consent, trial register, and reporting quality with CONSORT-CHM Formulas 2017. CONCLUSION: The overall quality of RCTs investigating TCM for COVID-19 was appraised as moderate-to-high that was substandard and needs to be continuously improved, especially for RCTs published in Chinese, in the future.

How efficacious are traditional Chinese medicine injections in treating angina pectoris? A network meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Over 50 million adults in China suffer from angina pectoris, which are often treated with traditional Chinese medicine injections (TCMIs). However, the efficacies of TCMIs and conventional drugs as determined by randomized controlled trials (RCTs) were not rigorously compared with one another by network meta-analysis (NMA). This PRISMA-compliant NMA aimed to compare the efficacy and assess the evidence strengths of 24 TCMIs in treating adults with angina pectoris of RCTs. MATERIALS AND METHODS: Following the protocol (PROSPERO registration number CRD42018117720), the RCTs that compared any TCMI with another TCMI or conventional drug on outcome measures including symptomatic and electrocardiography improvements were included. The quality of included RCTs was assessed with the Cochrane's risk of bias 2 tool. Frequentist statistical analyses were performed, including NMA, pairwise meta-analysis (PMA), subgroup analysis, sensitivity analysis, meta-regression, and publication bias analysis. The certainty of evidence was assessed with the GRADE approach. RESULTS: Totally, 556 eligible RCTs with 57015 participants were identified while the quality of all but five included RCTs was poor. The significant efficacy estimates and insignificant heterogeneity assessment from PMA and NMA indicated that nearly all TCMIs were more efficacious than conventional treatments for angina pectoris. Adequate subgroup and sensitivity analyses found the robust and consistent results. However, the evidence strengths of meta-analyses were assessed as very low to low due to the high risk of RCTs. The comprehensive efficacy estimates suggested that 4 TCMIs (HH, Honghua injection; HHH, Honghua Huangsesu injection; GLP, Gualoupi injection; and SM, Shenmai injection) was the best anti-anginal drugs for adults with angina pectoris. CONCLUSION: TCMIs appear to be efficacious for angina pectoris, although evidence evaluation of high-quality RCTs of TCMIs would be necessary. In particular, randomization and blinding procedures of the RCTs should be explicated to meet the CONSORT requirements.

Effects of 101BHG-D01, a novel M receptor antagonism, on allergic rhinitis in animal models and its mechanism.

Allergic rhinitis (AR) is a nasal mucosal disease with sneezing and nasal itching as the main symptoms. Although AR treatment continues to improve, there remains a lack of effective drugs. There are still controversies regarding whether anticholinergic drugs can effectively and safely relieve the symptoms of AR and reduce inflammation in the nasal mucosa. Here, we synthesized 101BHG-D01, which is a novel anticholinergic drug that mainly targets the M3 receptor and may reduce the adverse effects of other anticholinergic drugs on the heart. We evaluated the effects of 101BHG-D01 on AR and investigated the potential molecular mechanism of anticholinergic therapy for AR. We found that 101BHG-D01 effectively alleviated AR symptoms, reduced the infiltration of inflammatory cells and attenuated the expression of inflammatory factors (IL-4, IL-5, IL-13, etc.) in various AR animal models. In addition, 101BHG-D01 reduced the activation of mast cells and the release of histamine from rat peritoneal mesothelial cells (RPMCs) challenged by IgE. Moreover, 101BHG-D01 reduced the expression of MUC5AC in IL-13-challenged rat nasal epithelial cells (RNECs) and human nasal epithelial cells (HNEpCs). Furthermore, IL-13 stimulation significantly increased JAK1 and STAT6 phosphorylation, which was suppressed by 101BHG-D01. We demonstrated that 101BHG-D01 reduced mucus secretion and inflammatory cell infiltration in the nasal mucosa, which may occur through a reduction in activation of the JAK1-STAT6 signaling pathway, indicating that 101BHG-D01 is a potent and safe anticholinergic therapy for AR.

Preparation and characterization of a biocompatible glucose-sensitive electrospun nanofibers scaffolds containing dexamethasone with enhanced osteogenic propertiesin vitrohigh glucose environment.

Diabetes has made it challenging to repair alveolar bone defects. A successful method for bone repair utilizes a glucose-sensitive osteogenic drug delivery. This study created a new glucose-sensitive nanofiber scaffold with controlled dexamethasone (DEX) release. DEX-loaded polycaprolactone/chitosan nanofibers scaffolds were created using electrospinning. The nanofibers had high porosity (>90%) and proper drug loading efficiency (85.51 ± 1.21%). Then, glucose oxidase (GOD) was immobilized on the obtained scaffolds by a natural biological cross-linking agent, genipin (GnP), after soaking in the mixture solution containing GOD and GnP. The enzyme properties and glucose sensitivity of the nanofibers were investigated. The results showed that GOD was immobilized on the nanofibers and exhibited good enzyme activity and stability. Meanwhile, the nanofibers expanded gradually in response to the increase in glucose concentration, followed by the release of DEX increased. The phenomena indicated that the nanofibers could sense glucose fluctuation and possess favorable glucose sensitivity. In addition, the GnP nanofibers group showed lower cytotoxicity in the biocompatibility test compared with a traditional chemical cross-linking agent. Lastly, the associated osteogenesis evaluation found that the scaffolds effectively promoted MC3T3-E1 cells' osteogenic differentiation in high-glucose environments. As a result, the glucose-sensitive nanofibers scaffolds offer a viable treatment option for people with diabetes with alveolar bone defects.

Meta-Analysis of Randomized Controlled Trials on the Efficacy of Di'ao Xinxuekang Capsule and Isosorbide Dinitrate in Treating Angina Pectoris.

Objective. Randomized controlled trials (RCTs) on di'ao xinxuekang capsule (XXK) in treating angina pectoris were published only in Chinese and have not been systematically reviewed particularly for comparing XXK with isosorbide dinitrate (ISDN). This study aims to provide a comprehensive PRISMA compliant and internationally accessible systematic review and meta-analysis to evaluate the efficacies of XXK and ISDN in treating angina pectoris. Methods. The RCTs published between 1989 and 2011 on XXK and ISDN in treating angina pectoris were selected according to specific criteria. Meta-analysis was performed to evaluate the symptomatic (SYMPTOMS) and electrocardiographic (ECG) improvements after treatment. Odds ratios (OR) were used to measure effect sizes. Subgroup analysis, sensitivity analysis, and metaregression were conducted to evaluate the robustness of the results. Results. Seven RCTs with 550 participants were eligible. Overall ORs for comparing XXK with ISDN were 4.11 (95% CI : 2.57, 6.55) in SYMPTOMS and 2.37 (95% CI : 1.46, 3.84) in ECG. Subgroup analysis, sensitivity analysis, and metaregression found no significant dependence of overall ORs upon specific study characteristics. Conclusion. The meta-analysis of eligible but limited RCTs demonstrates that XXK seems to be more effective than ISDN in treating angina pectoris. Further RCTs of high quality are warranted to be conducted for update of the results of this meta-analysis.