Publications by authors named "Dan Wang"

3,801 Publications

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Prevalence of violence to others among individuals with schizophrenia in China: A systematic review and meta-analysis.

Front Psychiatry 2022 22;13:939329. Epub 2022 Jul 22.

Department of Health Behavior and Social Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

Background: Violence to others (hereinafter referred to as "violence-TO") is common in individuals with schizophrenia. The reported prevalence of violence-TO among schizophrenics ranges widely in existing studies. Improved prevalence estimates and identification of moderators are needed to guide future management and research.

Methods: We searched EBSCO, EMBASE, Medline, PubMed, Science Direct, Web of Science, CNKI, VIP, WANFANG data, and CBM for relevant articles published before June 5, 2022. Meanwhile, violence-TO was summarized into four categories: (a) violence-TO on the reviews of official criminal or psychiatric records (type I); (b) less serious forms of violence-TO (type II); (c) physical acts causing demonstrable harm to victims (type III); (d) homicide (type IV). We did meta-analysis for the above types of violence-TO, respectively, and applied subgroup analyses and meta-regression analyses to investigate the source of heterogeneity.

Results: A total of 56 studies were eligible in this study and 34 of them were high-quality. The prevalence of type I to type IV in individuals with schizophrenia in China was 23.83% (95% CI: 18.38-29.75%), 23.16% (95% CI: 8.04-42.97%), 17.19% (95%CI: 8.52-28.04%), and 0.62% (95% CI: 0.08-1.54%) respectively. The results of the subgroup analysis showed that the prevalence of type I was higher among subjects in the inland than in the coastal non-economic zone, while the prevalence of type III was the highest in the coastal economic zone, followed by the inland region and the lowest in the coastal non-economic zone. The results of multivariate meta-regression analyses showed that: patient source in type I (β = 0.15, < 0.01), patient source (β = 0.47, < 0.01), and proportion of male (β = 0.19, < 0.01) in type II, age (β = 0.25, < 0.01), and GDP per capita (β = 0.05, = 0.01) in type III were statistically significant.

Conclusion: The prevalence of different types of violence-TO and their influencing factors varied. Therefore, the authorities should take different management measures. In addition to individual factors, regional factors may also affect violence-TO, which suggests the need for a multi-sectorial approach to prevention and treatment for subjects in different regions and adopting targeted control strategies.

Systematic Review Registration: [www.ClinicalTrials.gov], identifier [CRD42021269767].
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http://dx.doi.org/10.3389/fpsyt.2022.939329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354073PMC
July 2022

The effects of a nurse-led integrative medicine-based structured education program on self-management behaviors among individuals with newly diagnosed type 2 diabetes: a randomized controlled trial.

BMC Nurs 2022 Aug 5;21(1):217. Epub 2022 Aug 5.

The Director's Office, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710068, People's Republic of China.

Background: International guidelines advocate providing prompt structured education to individuals with diabetes at diagnosis. However, among the few eligible structured education programs, heterogeneous intervention regimens and inconsistent findings were reported. Eligible programs for Chinese individuals with diabetes are lacking. This study aimed to investigate the effects of a nurse-led integrative medicine-based structured education program on self-management behaviors, glycemic control and self-efficacy among individuals with newly diagnosed type 2 diabetes.

Methods: Employing a randomized controlled trial, 128 individuals with type 2 diabetes diagnosed in the preceding three to nine months were recruited from four university-affiliated tertiary hospitals in Xi'an City, Northwest China, and randomly allocated to the intervention or control groups after baseline assessments. Participants in the intervention group received a 4-week nurse-led integrative medicine-based structured education program, which is theoretically based on the Health Belief Model and Self-Efficacy Theory, in line with updated diabetes management guidelines, and informed by relevant systematic reviews. Participants in the control group received routine care. Self-management behaviors and self-efficacy were measured with the Summary of Diabetes Self-Care Activities and the Diabetes Management Self-Efficacy Scale at baseline, immediate post-intervention and 12 weeks following the intervention while Glycated Hemoglobin A was measured at baseline and the 12th-week follow-up. The intervention effects were estimated using the generalized estimating equation models.

Results: Participants in the intervention group exhibited significantly better self-management performance in specific diet regarding intake of fruits and vegetables at both follow-ups (β = 1.02, p = 0.011 and β = 0.98, p = 0.016, respectively), specific diet regarding intake of high-fat foods at the immediate post-intervention follow-up (β = 0.83, p = 0.023), blood glucose monitoring at the 12th-week follow-up (β = 0.64, p = 0.004), foot care at both follow-ups (β = 1.80, p <  0.001 and β = 2.02, p <  0.001, respectively), and medication management at both follow-ups (β = 0.83, p = 0.005 and β = 0.95, p = 0.003, respectively). The intervention also introduced significant improvements in Glycated Hemoglobin A (β = - 0.32%, p <  0.001), and self-efficacy at both follow-ups (β = 8.73, p <  0.001 and β = 9.71, p <  0.001, respectively).

Conclusions: The nurse-led integrative medicine-based structured education program could produce beneficial effects on multiple diabetes self-management behaviors, glycemic control and self-efficacy.

Trial Registration: This study was retrospectively registered in the ClinicalTrials.gov . on 25/08/2017; registration number: NCT03261895 .
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http://dx.doi.org/10.1186/s12912-022-00970-7DOI Listing
August 2022

Construction of a cross-species cell landscape at single-cell level.

Nucleic Acids Res 2022 Aug 5. Epub 2022 Aug 5.

Women's Hospital, and Institute of Genetics, Zhejiang University School of Medicine, Hangzhou 310058, China.

Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal-Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging.
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http://dx.doi.org/10.1093/nar/gkac633DOI Listing
August 2022

Hepatic RNA adduction derived from metabolic activation of retrorsine in vitro and in vivo.

Chem Biol Interact 2022 Jul 30;365:110047. Epub 2022 Jul 30.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, Guizhou, 550004, PR China; Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, PR China; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, PR China. Electronic address:

Pyrrolizidine alkaloids (PAs) are among the most significant hepatotoxins widely distributed in plant species. Incidence of liver injuries caused by PAs has been reported worldwide, and the reactive metabolites of PAs are known to play a critical role in causing the hepatotoxicity. To better understand the toxicity-induction mechanisms, we explored the interactions of PA metabolites with cellular RNA molecules, and examined their effects on the biochemical and metabolic properties of hepatic RNAs. After exposure to retrorsine, adduction on adenosine and guanosine were detected in mouse liver microsomal incubations, cultured mouse primary hepatocytes, and mouse liver tissues. NMR analysis showed that the exocyclic amino group participated in the adduction. We found drastically altered properties and metabolism of the adducted RNA such as reverse-transcriptability, translatability, and RNase-susceptibility. In addition, endogenous modification of N-methyladenosine (m6A) was remarkably reduced.
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http://dx.doi.org/10.1016/j.cbi.2022.110047DOI Listing
July 2022

Targeting microbiota-host interactions with resveratrol on cancer: Effects and potential mechanisms of action.

Crit Rev Food Sci Nutr 2022 Aug 2:1-23. Epub 2022 Aug 2.

Institute of Agri-food Processing and Nutrition, Beijing Academy of Agriculture and Forestry Sciences, Beijing Key Laboratory of Agricultural Products of Fruits and Vegetables Preservation and Processing, Key Laboratory of Vegetable Postharvest Processing, Ministry of Agriculture and Rural Affairs, Beijing, China.

Resveratrol (RSV) is a natural polyphenolic compound detected in grapes, berries, and red wine. The anticancer activities of RSV have been observed in vivo and in vitro studies. However, the pharmacology mechanism of RSV is confusing due to its low bioavailability. According to studies of the metabolic characteristics of RSV, the gut intestine is a crucial site of its health benefits. Dietary RSV exhibits a profound effect on the gut microbiota structure and metabolic function. In addition, emerging evidence demonstrates a protective effect of RSV metabolites against carcinogenesis. Therefore, to better understand the anticancer mechanisms of dietary RSV, it is vital to evaluate the role of RSV-microbiota-host interactions in cancer therapy. In this review, we summarized significant findings on the anticancer activities of RSV based on epidemiological, experimental and clinical studies involved in investigating the metabolic characteristics and the traditional anticancer mechanisms of RSV. Special attention is given to the putative mechanisms involving microbiota-host interactions, such as the modulation of gut microecology and the anticancer effects of RSV metabolites. The changes in microbiota-host interactions after RSV supplementation play vital roles in cancer prevention and thus offering a new perspective on nutritional interventions to treat cancer.
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http://dx.doi.org/10.1080/10408398.2022.2106180DOI Listing
August 2022

Emerging role of toll-like receptors signaling and its regulators in preterm birth: a narrative review.

Arch Gynecol Obstet 2022 Aug 2. Epub 2022 Aug 2.

Department of Gynecology and Obstetrics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Introduction: Despite intensive research, preterm birth (PTB) rates have not decreased significantly in recent years due to a lack of understanding of the underlying causes and insufficient treatment options for PTB. We are committed to finding promising biomarkers for the treatment of PTB.

Methods: An extensive search of the literature was conducted with MEDLINE/PubMed, and in total, 151 studies were included and summarized in the present review.

Results: Substantial evidence supports that the infection and/or inflammatory cascade associated with infection is an early event in PTB. Toll-like receptor (TLR) is a prominent pattern recognition receptor (PRR) found on both immune and non-immune cells, including fetal membrane cells. The activation of TLR downstream molecules, followed by TLR binding to its ligand, is critical for infection and inflammation, leading to the involvement of the TLR signaling pathway in PTB. TLR ligands are derived from microbial components and molecules released by damaged and dead cells. Particularly, TLR4 is an essential TLR because of its ability to recognize lipopolysaccharide (LPS). In this comprehensive overview, we discuss the role of TLR signaling in PTB, focus on numerous host-derived genetic and epigenetic regulators of the TLR signaling pathway, and cover ongoing research and prospective therapeutic options for treating PTB by inhibiting TLR signaling.

Conclusion: This is a critical topic because TLR-related molecules and mechanisms may enable obstetricians to better understand the physiological changes in PTB and develop new treatment and prevention strategies.
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http://dx.doi.org/10.1007/s00404-022-06701-2DOI Listing
August 2022

Context-dependent tumor-suppressive BMP signaling in diffuse intrinsic pontine glioma regulates stemness through epigenetic regulation of CXXC5.

Nat Cancer 2022 Aug 1. Epub 2022 Aug 1.

MOE Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing, China.

The most lethal subtype of diffuse intrinsic pontine glioma (DIPG) is H3K27M. Although ACVR1 mutations have been implicated in the pathogenesis of this currently incurable disease, the impacts of bone morphogenetic protein (BMP) signaling on more than 60% of H3K27M DIPG carrying ACVR1 wild-type remain unknown. Here we show that BMP ligands exert potent tumor-suppressive effects against H3.3K27M and ACVR1 WT DIPG in a SMAD-dependent manner. Specifically, clinical data revealed that many DIPG tumors have exploited the capacity of CHRDL1 to hijack BMP ligands. We discovered that activation of BMP signaling promotes the exit of DIPG tumor cells from 'prolonged stem-cell-like' state to differentiation by epigenetically regulating CXXC5, which acts as a tumor suppressor and positive regulator of BMP signaling. Beyond showing how BMP signaling impacts DIPG, our study also identified the potent antitumor efficacy of Dacinostat for DIPG. Thus, our study delineates context-dependent features of the BMP signaling pathway in a DIPG subtype.
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http://dx.doi.org/10.1038/s43018-022-00408-8DOI Listing
August 2022

Prevalence and associated factors of frailty among community dwelling older adults in Northwest China: a cross-sectional study.

BMJ Open 2022 08 1;12(8):e060089. Epub 2022 Aug 1.

The Director's Office, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China

Objectives: To investigate the prevalence of the comprehensive frailty and its associated factors among community dwelling older adults.

Design: A cross-sectional study.

Setting: Six community healthcare centres in Xi'an City, Northwest China.

Participants: A total of 2647 community dwelling older adults completed the study between March and August 2021.

Primary And Secondary Outcome Measures: The primary outcome was the prevalence of frailty, measured with the Comprehensive Frailty Assessment Instrument. The secondary outcomes were potential factors associated with frailty, measured with a social-demographic and health-related information sheet, the Short-Form Mini-Nutritional Assessment and the Pittsburgh Sleep Quality Index.

Results: The participants averaged 27.77±10.13 in the total score of the Comprehensive Frailty Assessment Instrument. According to the cut-off points defining the classification of frailty, the majority of the participants were with mild (n=1478, 55.8%) or high (n=390, 14.8%) frailty. Multivariate stepwise linear regression analysis demonstrated that older age, lower educational level, empty nesters, higher level of self-perceived medical burden, abnormal body weight, physical inactivity, medication taking, increased number of clinic visit, undernutrition and poor sleep quality are associated with higher total score in the Comprehensive Frailty Assessment Instrument, indicating higher level of frailty. Multivariate multinomial logistic regression analysis exhibited similar findings but further captured female gender as a risk factor for the presence of mild and high frailty compared with no-low frailty.

Conclusion: The prevalence of the comprehensive frailty and frailty in the physiological, psychological, social and environmental domains is high. A variety of social-demographic, health-related and behavioural factors were associated with the comprehensive frailty. Further investigations on frailty prevalence and its associated factors based on comprehensive assessments are desirable.
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http://dx.doi.org/10.1136/bmjopen-2021-060089DOI Listing
August 2022

S100a16 deficiency prevents hepatic stellate cells activation and liver fibrosis via inhibiting CXCR4 expression.

Metabolism 2022 Jul 29;135:155271. Epub 2022 Jul 29.

Department of Pharmacy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China. Electronic address:

Introduction: Liver fibrosis caused by hepatic stellate cells (HSCs) activation is implicated in the pathogenesis of liver diseases. To date, there has been no effective intervention means for this process. S100 proteins are calcium-binding proteins that regulate cell growth and differentiation. This study aimed to investigate whether S100A16 induces HSCs activation and participates in liver fibrosis progression.

Methods: HSCs were isolated, and the relationship between S100A16 expression and HSCs activation was studied. S100a16 knockdown and transgenic mice were generated and subjected to HSCs activation and liver fibrosis stimulated by different models. Clinical samples were collected for further confirmation. Alterations in gene expression in HSCs were investigated, using transcriptome sequencing to determine the underlying mechanisms.

Results: We observed increased S100A16 levels during HSCs activation. Genetic silencing of S100a16 prevented HSCs activation in vitro. Furthermore, S100a16 silencing exhibited obvious protective effects against HSCs activation and fibrosis progression in mice. In contrast, S100a16 transgenic mice exhibited spontaneous liver fibrosis. S100A16 was also upregulated in the HSCs of patients with fibrotic liver diseases. RNA sequencing revealed that C-X-C motif chemokine receptor 4 (Cxcr4) gene was a crucial regulator of S100A16 induction during HSCs activation. Mechanistically, S100A16 bound to P53 to induce its degradation; this augmented CXCR4 expression to activate ERK 1/2 and AKT signaling, which then promoted HSCs activation and liver fibrosis.

Conclusions: These data indicate that S100a16 deficiency prevents liver fibrosis by inhibiting Cxcr4 expression. Targeting S100A16 may provide insight into the pathogenesis of liver fibrosis and pave way for the design of novel clinical therapeutic strategies.
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http://dx.doi.org/10.1016/j.metabol.2022.155271DOI Listing
July 2022

Meta-Analysis of Predictive Role of Early Neurological Deterioration after Intravenous Thrombolysis.

Emerg Med Int 2022 22;2022:2894426. Epub 2022 Jul 22.

Department of Neurology, Hubei No. 3 People's Hospital of Jianghan University, Wuhan 430033, Hubei Province, China.

With the popularization of intravenous thrombolysis, more and more people use intravenous thrombolysis to treat related diseases, but problems also arise. There are still a considerable number of patients with early disease after thrombolytic therapy not only not significantly improving, but also progressing, that is, early neurological deterioration (END). In view of this problem, the prediction of END after intravenous thrombolysis becomes very important. With the development of medical technology, research on the prediction of END after intravenous thrombolysis has gradually been carried out. Effective prediction is of great significance for the prevention and treatment of END after intravenous thrombolysis. This article aimed to carry out a meta-analysis of the predictive role of END after intravenous thrombolysis. Through an informed analysis of all studies of this type in this field, this article determines a method for predicting END after intravenous thrombolysis. The actual effect of its role is revealed in this paper, and its purpose is to promote the development of this field. This article addresses the same type of study on the predictive role of neurological deterioration after intravenous thrombolysis. The article performs test and meta-analysis of its role by conditionally searching for literature studies. It is explained using the relevant theoretical formulas. The analysis results show that the prediction of END after intravenous thrombolysis in this paper can effectively help make a preliminary judgment on the possible later neurological deterioration. Although there is an error between the predicted curve and the actual curve, the difference between the two is between 1% and 5%. It can basically effectively predict the occurrence of END. Therefore, the prediction of END after intravenous thrombolysis has a very large preventive effect on the END after intravenous thrombolysis.
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http://dx.doi.org/10.1155/2022/2894426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337960PMC
July 2022

Serum Vitamin D Level and Efficacy of Vitamin D Supplementation in Children with Atopic Dermatitis: A Systematic Review and Meta-analysis.

Comput Math Methods Med 2022 20;2022:9407888. Epub 2022 Jul 20.

Department of Pediatrics, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102 Hainan, China.

Background: The relationship between vitamin D and atopic dermatitis (AD) is controversial. This meta-analysis is aimed at exploring vitamin D level and its deficiency in pediatric AD and at evaluating the efficacy of vitamin D supplementation.

Methods: PubMed, Medline, Embase, Ovid, Cochrane Library, ISI Web of Science, and ClinicalTrials were searched. Binary variables and continuous variables were measured by odds ratio (OR) and mean difference (MD) with 95% confidence intervals, respectively. The modified Jadad scale, Newcastle-Ottawa Scale (NOS), and Cochrane's bias risk tools were used to evaluate study quality and the risk of bias of eligible studies, respectively.

Results: A total of 22 literature were included in the analysis. Serum 25 (OH) D level in pediatric AD patients was significantly lower than that of the control group with a combined MD value of -8.18 (95% CI: -13.15, -3.22). Patients with AD were more prone to develop vitamin D deficiency with a combined OR value of 2.17 (95% CI: 1.15, 4.11). According to the score of SCORAD, the level of serum 25 (OH) D level in patients with severe AD was significantly lower than that in patients with mild AD (combined MD = 9.23, 95% CI: 6.92, 11.55). Both self-control studies and randomized controlled trials showed improved SCORAD score and EASI score after vitamin D supplementation.

Conclusion: This meta-analysis showed lower serum 25 (OH) D level and increased risk of vitamin D deficiency in pediatric AD patients as compared with healthy controls. The serum 25 (OH) D level in severe AD patients was significantly lower than that in the mild AD patients. The SCORAD and EASI score improved after vitamin D supplementation, suggesting its beneficial effect to AD patients. At the same time, more homogeneous studies are needed to reduce confounding factors and further evaluate the impact of vitamin D treatment on the outcome of AD patients.
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http://dx.doi.org/10.1155/2022/9407888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328962PMC
August 2022

Auditory Manifestations of Vestibular Migraine.

Front Neurol 2022 15;13:944001. Epub 2022 Jul 15.

ENT Institute and Otorhinolaryngology Department, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, China.

Objectives: To investigate the auditory features of patients with vestibular migraine (VM) and to analyze the possible relevant factors of hearing loss.

Methods: A total of 166 patients with VM were enrolled. Demographic variables, age of onset, disease course, distribution of vestibular attacks, characteristics of hearing loss, and the coexistence of related disorders, such as visual aura, familial history, motion sickness, nausea, headache, photophobia, otalgia, tinnitus, aural fullness, and phonophobia, were analyzed and compared.

Results: Patients with VM can manifest otalgia (8.4%), tinnitus (51.8%), aural fullness (41%), and phonophobia (31.9%). Of 166 patients, the prevalence of VMw was 21.1% ( = 35). Patients with VMw mainly manifested mild and easily reversible low-frequency hearing loss. The proportions of tinnitus and aural fullness were significantly larger in patients with VMw than that in patients with VMo ( < 0.05). The duration of vestibular symptoms was significantly shorter in patients with VMw ( < 0.05). However, the age of onset, disease course, gender, frequency of vestibular attacks, the coexistence of visual aura, familial history, motion sickness, nausea, headache, photophobia, otalgia, and phonophobia had no significant difference between the two groups.

Conclusion: Auditory symptoms were common in patients with VM. The hearing loss of VM was characterized by a mild and easily reversible low-frequency hearing loss, accompanied by higher proportions of tinnitus and aural fullness, and a shorter duration of vestibular symptoms compared with patients with VMo.
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http://dx.doi.org/10.3389/fneur.2022.944001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334870PMC
July 2022

Surgical Strategies for Preservation of Pulmonary Valve Function in a Radical Operation for Tetralogy of Fallot: A Systematic Review and Meta-Analysis.

Front Cardiovasc Med 2022 13;9:888258. Epub 2022 Jul 13.

Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Objective: To evaluate the efficacy and safety of different surgical strategies to preserve pulmonary valve function. Surgical procedures evaluated include intraoperative balloon pulmonary valvuloplasty (IBPV), pulmonary valve reconstruction, and commissurotomy and pulmonary cusp augmentation (PCA) in patients who underwent a radical operation for Tetralogy of Fallot (ToF).

Materials And Methods: The five databases searched in the current study included the Cochrane Library, PubMed, China National Knowledge Infrastructure, VIP, and WanFang data. A systematic search for control trials was performed in each database from the start date of each database until December 2021. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included studies.

Results: A total of 15 retrospective studies with a total number of 1,396 participants were included in this study. In subgroup 1 (IBPV vs. TAP), patients undergoing IBPV had a less degree of regurgitation at 1-2 years after the surgery. The reintervention rate increased in the IBPV group at 5 years. In subgroup 2 (pulmonary valve reconstruction vs. TAP), the degree of regurgitation decreased in the pulmonary valve reconstruction group at 1 month after the surgery. In subgroup 3 (valve-sparing operation vs. TAP), the comparison demonstrated decreased rates for surgical mortality and reintervention at 5-10 years after the surgery.

Conclusion: We proposed that pulmonary valve function in a radical operation for ToF was preserved. IBPV, pulmonary valve reconstruction, and commissurotomy and PCA can be performed during the surgical procedure based on the developmental status and anatomical characteristics of the right ventricular outflow tract (RVOT), pulmonary valve, and pulmonary artery.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022300987].
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http://dx.doi.org/10.3389/fcvm.2022.888258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326161PMC
July 2022

Tenogenic induction of human adipose-derived stem cells by soluble tendon extracellular matrix: composition and transcriptomic analyses.

Stem Cell Res Ther 2022 Jul 29;13(1):380. Epub 2022 Jul 29.

Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR, China.

Background: Tendon healing is clinically challenging largely due to its inferior regenerative capacity. We have previously prepared a soluble, DNA-free, urea-extracted bovine tendon-derived extracellular matrix (tECM) that exhibits strong pro-tenogenic bioactivity on human adipose-derived stem cells (hASCs). In this study, we aimed to elucidate the mechanism of tECM bioactivity via characterization of tECM protein composition and comparison of transcriptomic profiles of hASC cultures treated with tECM versus collagen type I (Col1) as a control ECM component.

Methods: The protein composition of tECM was characterized by SDS-PAGE, hydroxyproline assay, and proteomics analysis. To investigate tECM pro-tenogenic bioactivity and mechanism of action, differentiation of tECM-treated hASC cultures was compared to serum control medium or Col1-treated groups, as assessed via immunofluorescence for tenogenic markers and RNA Sequencing (RNA-Seq).

Results: Urea-extracted tECM yielded consistent protein composition, including collagens (20% w/w) and at least 17 non-collagenous proteins (< 100 kDa) based on MS analysis. Compared to current literature, tECM included key tendon ECM components that are functionally involved in tendon regeneration, as well as those that are involved in similar principal Gene Ontology (GO) functions (ECM-receptor interaction and collagen formation) and signaling pathways (ECM-receptor interaction and focal adhesion). When used as a cell culture supplement, tECM enhanced hASC proliferation and tenogenic differentiation compared to the Col1 and FBS treatment groups based on immunostaining of tenogenesis-associated markers. Furthermore, RNA-Seq analysis revealed a total of 584 genes differentially expressed among the three culture groups. Specifically, Col1-treated hASCs predominantly exhibited expression of genes and pathways related to ECM-associated processes, while tECM-treated hASCs expressed a mixture of ECM- and cell activity-associated processes, which may explain in part the enhanced proliferation and tenogenic differentiation of tECM-treated hASCs.

Conclusions: Our findings showed that urea-extracted tECM contained 20% w/w collagens and is significantly enriched with other non-collagenous tendon ECM components. Compared to Col1 treatment, tECM supplementation enhanced hASC proliferation and tenogenic differentiation as well as induced distinct gene expression profiles. These findings provide insights into the potential mechanism of the pro-tenogenic bioactivity of tECM and support the development of future tECM-based approaches for tendon repair.
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http://dx.doi.org/10.1186/s13287-022-03038-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338462PMC
July 2022

Pre-attack and pre-episode symptoms in cluster headache: a multicenter cross-sectional study of 327 Chinese patients.

J Headache Pain 2022 Jul 30;23(1):92. Epub 2022 Jul 30.

Department of Neurology, the First Medical Center, Chinese PLA General Hospital, 100853, Beijing, China.

Background: There have been a few studies regarding the pre-attack symptoms (PAS) and pre-episode symptoms (PES) of cluster headache (CH), but none have been conducted in the Chinese population. The purpose of this study was to identify the prevalence and features of PAS and PES in Chinese patients, as well as to investigate their relationships with pertinent factors.

Methods: The study included patients who visited a tertiary headache center and nine other headache clinics between January 2019 and September 2021. A questionnaire was used to collect general data and information about PAS and PES.

Results: Among the 327 patients who met the CH criteria (International Classification of Headache Disorders, 3rd edition), 269 (82.3%) patients experienced at least one PAS. The most common PAS were head and facial discomfort (74.4%). Multivariable logistic regression analysis depicted that the number of triggers (OR = 1.798, p = 0.001), and smoking history (OR = 2.067, p = 0.026) were correlated with increased odds of PAS. In total, 68 (20.8%) patients had PES. The most common symptoms were head and facial discomfort (23, 33.8%). Multivariable logistic regression analysis showed that the number of triggers were associated with increased odds of PES (OR = 1.372, p = 0.005).

Conclusions: PAS are quite common in CH patients, demonstrating that CH attacks are not comprised of a pain phase alone; investigations of PAS and PES could help researchers better understand the pathophysiology of CH.
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http://dx.doi.org/10.1186/s10194-022-01459-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338588PMC
July 2022

Quercetin protects rat BMSCs from oxidative stress via ferroptosis.

J Mol Endocrinol 2022 Jul 1. Epub 2022 Jul 1.

Y Wang, Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University Affliated Stomatological Hospital, Shanghai, China.

Background: Quercetin has been shown to have a wide range of beneficial effects, such as anti-inflammation, anti-oxidation and immunomodulation. The study was designed to explore the role and molecular mechanisms of Quercetin on the protective effect of bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress in vitro.

Materials And Methods: BMSCs were isolated from 4-week-old male Sprague-Dawley rats. Upon H2O2 stimulation in vitro, the effects of Quercetin on the proliferation, anti-oxidation and osteogenic differentiation of BMSCs were evaluated by Cell Counting Kit-8 (CCK-8), Reactive Oxygen Species (ROS) analysis, Western blot (WB), Real-Time PCR (RT-PCR), Alkaline Phosphatase (ALP) staining and Alizarin Red staining (ARS). Additionally, ferroptosis-related markers were examinedby Western blot, RT-PCR and Mito-FerroGreen. Finally, PI3K/AKT/mTOR signaling pathway was explored in these processes.

Results: Quercetin significantly maintained BMSCs viability upon H2O2 stimulation. Quercetin upregulated protein and mRNA levels of osteogenic markers (ALP, OPN, OCN and RUNX2), downregulated ROS levels and upregulated antioxidative gene expressions (Nrf2, Cat, Sod-1 and Sod-2) compared with theH2O2 group. The ferroptosis in BMSCs was activated after H2O2 stimulated, and the phosphorylation level of PI3K, AKT and mTOR were upregulated in H2O2 stimulated BMSCs. More importantly, Quercetin inhibited ferroptosis and the phosphorylation level of PI3K, AKT and mTOR were downregulated after Quercetin treatment.

Conclusion: Quercetin maintained the viability and the osteoblastic differentiation of BMSCs upon H2O2 stimulation, potentially via ferroptosis inhibition by PI3K/AKT/mTOR pathway.
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http://dx.doi.org/10.1530/JME-22-0086DOI Listing
July 2022

Novel read-through fusion transcript Bcl2l2-Pabpn1 in glioblastoma cells.

J Cell Mol Med 2022 Jul 27. Epub 2022 Jul 27.

Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, China.

Read-through fusion transcripts have recently been identified as chimeric RNAs and have since been linked to tumour growth in some cases. Many fusion genes generated by chromosomal rearrangements have been described in glioblastoma. However, read-through fusion transcripts between neighbouring genes in glioblastoma remain unexplored. We performed paired-end RNA-seq of rat C6 glioma cells and normal cells and discovered a read-through fusion transcript Bcl2l2-Pabpn1 in which exon 3 of Bcl-2-like protein 2 (Bcl2l2) fused to exon 2 of Polyadenylate-binding protein 1 (Pabpn1). This fusion transcript was found in both human glioblastoma and normal cells. Unlike other fusions reported in glioblastoma, Bcl2l2-Pabpn1 appeared to result from RNA processing rather than genomic rearrangement. Bcl2l2-Pabpn1 fusion transcript encoded a fusion protein with BH4, BCL and RRM domains. Functionally, Bcl2l2-Pabpn1 knockdown by targeting its fusion junction decreased its expression, and suppressed cell proliferation, migration and invasion in vitro. Mechanistically, Bcl2l2-Pabpn1 blocked Bax activity and activated PI3K/AKT pathway to promote glioblastoma progression. Together, our work characterized a glioblastoma-associated Bcl2l2-Pabpn1 fusion transcript shared by humans and rats.
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http://dx.doi.org/10.1111/jcmm.17481DOI Listing
July 2022

Interfacial Bonding Improvement through Nickel Decoration on Carbon Nanotubes in Carbon Nanotubes/Cu Composite Foams Reinforced Copper Matrix Composites.

Nanomaterials (Basel) 2022 Jul 25;12(15). Epub 2022 Jul 25.

School of Materials Science and Engineering, Kunming University of Science and Technology, Kunming 650093, China.

Inhomogeneous structures with carbon nanotubes (CNTs), reinforced with Cu composite foams as the reinforcing skeletons (CNTs/CuCu), have been designed to overcome the paradox between strength and ductility or conductivity in copper matrix composites. The interface between CNTs and the copper matrix is usually weak, due to poor wettability and interaction. In this study, nickel nanoparticles are decorated onto CNTs to improve interfacial bonding. The broader interface transition area between CNTs and copper with NiC interfacial products formed, and a combination of improved electrical conductivity (95.6% IACS), tensile strength (364.9 MPa), and elongation (40.6%) was achieved for the Ni-decorated CNTs/CuCu (Ni-CNTs/CuCu). In addition, the strengthening mechanisms are discussed in this study.
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http://dx.doi.org/10.3390/nano12152548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332182PMC
July 2022

Translation and Modification of a Mindful Eating Questionnaire for Children Assisted by Item Response Theory in Chinese Children and Adolescents.

Nutrients 2022 Jul 12;14(14). Epub 2022 Jul 12.

Endocrinology Department, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.

Mindful eating has gained attention in studies on healthy eating. However, measurement of it is scarce, particularly in pediatrics. This study aimed to translate and modify the 12-item Mindful Eating Questionnaire for Children (MEQ-C) using techniques based on both classical test theory (ICC) and item response theory (IRT) in Chinese children and adolescents. Of the 426 participants enrolled and randomly grouped, the test ( = 223) and validation ( = 203) subsamples were well-matched in age, gender, body mass index z score (BMIz), and waist to height ratio (WHtR) ( > 0.556). Three items were eliminated due to deviating from the mindful eating concept (content validity index < 0.71) and presenting as an independent dimension in parallel analysis, or yielding a poor distribution (-4.331 < b < -0.111). The final 5-item Mindless Eating and 4-item Awareness subscales were identified with sound Cronbach's α of 0.802 and 0.779, respectively. The remaining items functioned well (a > 1, -3 < b < 3), and the Mindless Eating subscale was accurate for the low-to-medium range (-2 to 0) of the mindful eating measure. The Awareness one was reliable for the relatively high range (0 to 2). Participants' mindful eating characteristics should be taken into consideration in practice.
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http://dx.doi.org/10.3390/nu14142854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318944PMC
July 2022

[Influence of electroacupuncture of"Zusanli"(ST36)on mast cells/TRPV1 signaling pathway in visceral hypersensitivity rats with functional dyspepsia].

Zhen Ci Yan Jiu 2022 Jul;47(7):592-7

School of Acupuncture-moxibustion and Tuina, Liaoning University of Traditional Chinese Medicine, Liaoning 110847, China; The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Liaoning 110032.

Objective: To explore the interventional mechanism of electroacupuncture (EA) of "Zusanli"(ST36)based on the involvement of mast cells/ transient receptor potential vanilloid type1 (TRPV1) signaling pathway in relieving visceral hypersensitivity in functional dyspepsia (FD) rats.

Methods: Sixty SD rats (half male and half female, 10 days in age) were randomly divided into normal control, model, medication (ketotifen) and EA groups, with 15 rats in each group. The FD model was established by gavage of iodoacetamide combined with tail clamping (stress stimulation). Rats of the medication group received intraperitoneal injection of ketotifen (1 mg·kg·d) for 14 d, and those of the EA group received EA of ST36 for 20 min, once a day for 14 d. An air-balloon was inserted into the rat's stomach for recording changes of the intragastric pressure (mL/mm Hg) via a pressure transducer. The visceral hypersensitivity was assessed using abdominal withdrawal reflex (AWR) score and the number and degranulation of mast cells of gastric mucosa were observed using toluidine blue staining. The expression levels of TRPV1 and proteinase activated receptor 2 (PAR2) in the stomach were observed using immunofluorescence histochemistry and Western blot, separately, and the contents of SP and CGRP in the stomach detected using ELISA.

Results: When the intragastric pressure was at 50, 60 and 70 mm Hg, the gastric compliance was significantly decreased (<0.01), and the levels of visceral sensitivity increased in the model group (<0.01)。 TRPV1 immunofluorescence tensity, expression of PAR2 and TRPV1 proteins, and contents of SP and CGRP in the stomach were considerably up-regulated in the model group compared with the normal control group (<0.01). In comparison with the model group, under intragastric pressure of 50,60 and 70 mm Hg, the gastric compliance was obviously increased, and the visceral hypersensitivity decreased in the EA group (<0.01,<0.05). TRPV1 immunofluorescence intensity, expression levels of PAR2 and TRPV1 proteins, and the contents of SP and CGRP in the stomach were considerably down-regulated in both medication and EA groups compared with the model group (<0.01, <0.05). The therapeutic effect of EA was significantly superior to that of medication in up-regulating the gastric compliance (at 70 mm Hg), and down-regulating the contents of SP and CGRP (<0.05). No significant differences were found between the EA and medication groups in up-regulating gastric compliance at intragastric pressure of 50 and 60 mm Hg, and in down-regulating the visceral sensitivity, TRPV1 fluorescence intensity, and expression of PAR2 and TRPV1 proteins (>0.05). Toluidine blue staining showed an apparent increase of mast cell number with obvious degranulation in the gastric mucosa of rats in the model group, which was milder in the EA and medication groups.

Conclusion: EA of ST36 can suppress visceral hypersensitivity and increase the gastric compliance in FD rats, which may be related with its effects in inhibiting the activation of gastric mast cells, and down-regulating the expression of gastric PAR2 and TRPV1 proteins and SP and CGRP contents.
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http://dx.doi.org/10.13702/j.1000-0607.20210937DOI Listing
July 2022

Prediction model for synergistic anti-tumor multi-compound combinations from traditional Chinese medicine based on extreme gradient boosting, targets and gene expression data.

J Bioinform Comput Biol 2022 Jun;20(3):2250016

Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang 212013, P. R. China.

Traditional Chinese medicine (TCM) is characterized by synergistic therapeutic effect involving multiple compounds and targets, which provide potential new therapy for the treatment of complex cancer conditions. However, the main contributors and the underlying mechanisms of synergistic TCM cancer therapies remain largely undetermined. Machine learning now provides a new approach to determine synergistic compound combinations from complex components of TCM. In this study, a prediction model based on extreme gradient boosting (XGBoost) algorithm was constructed by integrating gene expression data of different cancer cell lines, targets information of natural compounds and drug response data. Radix Paeoniae Rubra (RPR) was selected as a model herbal sample to evaluate the reliability of the constructed model. The optimal XGBoost prediction model achieved a good performance with Mean Square Error (MSE) of 0.66, Mean Absolute Error (MAE) of 0.61, and the Root Mean Squared Error (RMSE) of 0.81 on test dataset. The superior synergistic anti-tumor combinations of D15 (Paeonol[Formula: see text][Formula: see text][Formula: see text]Ethyl gallate) and D13 (Paeoniflorin[Formula: see text][Formula: see text][Formula: see text]Paeonol) were successfully predicted from RPR and experimentally validated on MCF-7 cells. Moreover, the combination of D13 could work as a main contributor to a synergistic anti-proliferative activity in the compatibility of RPR and Cortex Moutan (CM). Our XGBoost model could be a reliable tool for the efficient prediction of synergistic anti-tumor multi-compound combinations from TCM.
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http://dx.doi.org/10.1142/S0219720022500160DOI Listing
June 2022

Brain structure and synaptic protein expression alterations after antidepressant treatment in a Wistar-Kyoto rat model of depression.

J Affect Disord 2022 Oct 22;314:293-302. Epub 2022 Jul 22.

Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China; Shanxi Provincial Key Laboratory of Brain Science and Neuropsychiatric Diseases, First Hospital of Shanxi Medical University, Taiyuan, China; Department of Mental Health, Shanxi Medical University, Taiyuan, China.; National Key Disciplines, Key Laboratory for Cellular Physiology of Ministry of Education, Department of Neurobiology, Shanxi Medical University, Taiyuan, China.. Electronic address:

Background: Structural MRI has demonstrated brain alterations in depression pathology and antidepressants treatment. While synaptic plasticity has been previously proposed as the potential underlying mechanism of MRI findings at a cellular and molecular scale, there is still insufficient evidence to link the MRI findings and synaptic plasticity mechanisms in depression pathology.

Methods: In this study, a Wistar-Kyoto (WKY) depression rat model was treated with antidepressants (citalopram or Jie-Yu Pills) and tested in a series of behavioral tests and a 7.0 MRI scanner. We then measured dendritic spine density within altered brain regions. We also examined expression of synaptic marker proteins (PSD-95 and SYP).

Results: WKY rats exhibited depression-like behaviors in the sucrose preference test (SPT) and forced swim test (FST), and anxiety-like behaviors in the open field test (OFT). Both antidepressants reversed behavioral changes in SPT and OFT but not in FST. We found a correlation between SPT performance and brain volumes as detected by MRI. All structural changes were consistent with alterations of the corpus callosum (white matter), dendritic spine density, as well as PSD95 and SYP expression at different levels. Two antidepressants similarly reversed these macro- and micro-changes.

Limitations: The single dose of antidepressants was the major limitation of this study. Further studies should focus on the white matter microstructure changes and myelin-related protein alterations, in addition to comparing the effects of ketamine.

Conclusion: Translational evidence links structural MRI changes and synaptic plasticity alterations, which promote our understanding of SPT mechanisms and antidepressant response in WKY rats.
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http://dx.doi.org/10.1016/j.jad.2022.07.037DOI Listing
October 2022

Diosgenin and Its Analogs: Potential Protective Agents Against Atherosclerosis.

Drug Des Devel Ther 2022 17;16:2305-2323. Epub 2022 Jul 17.

Cardiovascular Research Institute of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Atherosclerosis is a chronic inflammatory disease of the artery wall associated with lipid metabolism imbalance and maladaptive immune response, which mediates most cardiovascular events. First-line drugs such as statins and antiplatelet drug aspirin have shown good effects against atherosclerosis but may lead to certain side effects. Thus, the development of new, safer, and less toxic agents for atherosclerosis is urgently needed. Diosgenin and its analogs have gained importance for their efficacy against life-threatening diseases, including cardiovascular, endocrine, nervous system diseases, and cancer. Diosgenin and its analogs are widely found in the rhizomes of , and other species and share similar chemical structures and pharmacological effects. Recent data suggested diosgenin plays an anti-atherosclerosis role through its anti-inflammatory, antioxidant, plasma cholesterol-lowering, anti-proliferation, and anti-thrombotic effects. However, a review of the effects of diosgenin and its natural structure analogs on AS is still lacking. This review summarizes the effects of diosgenin and its analogs on vascular endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, migration and calcification, lipid metabolism, and inflammation, and provides a new overview of its anti-atherosclerosis mechanism. Besides, the structures, sources, safety, pharmacokinetic characteristics, and biological availability are introduced to reveal the limitations and challenges of current studies, hoping to provide a theoretical basis for the clinical application of diosgenin and its analogs and provide a new idea for developing new agents for atherosclerosis.
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http://dx.doi.org/10.2147/DDDT.S368836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304635PMC
July 2022

Seneca Valley Virus 3C Cleaves Heterogeneous Nuclear Ribonucleoprotein K to Facilitate Viral Replication.

Front Microbiol 2022 6;13:945443. Epub 2022 Jul 6.

College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

Seneca Valley virus (SVV) has emerged as an important pathogen that is associated with idiopathic vesicular infection in pigs, causing a potential threat to the global swine industry. The heterogeneous nuclear ribonucleoprotein K (hnRNP K) that shuttles between the nucleus and cytoplasm plays an important role in viral infection. In this study, we observed that infection with SVV induced cleavage, degradation, and cytoplasmic redistribution of hnRNP K in cultured cells, which was dependent on the activity of viral 3C protease. Also, the 3C induced degradation of hnRNP K via the caspase pathway. Further studies demonstrated that SVV 3C cleaved hnRNP K at residue Q364, and the expression of the cleavage fragment hnRNP K (aa.365-464) facilitates viral replication, which is similar to full-length hnRNP K, whereas hnRNP K (aa.1-364) inhibits viral replication. Additionally, hnRNP K interacts with the viral 5' untranslated region (UTR), and small interfering RNA (siRNA)-mediated knockdown of hnRNP K results in significant inhibition of SVV replication. Overall, our results demonstrated that the hnRNP K positively regulates SVV replication in a protease activity-dependent fashion in which the cleaved C-terminal contributes crucially to the upregulation of SVV replication. This finding of the role of hnRNP K in promoting SVV propagation provides a novel antiviral strategy to utilize hnRNP K as a potential target for therapy.
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http://dx.doi.org/10.3389/fmicb.2022.945443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298500PMC
July 2022

Homoharringtonine combined with cladribine and aclarubicin (HCA) in acute myeloid leukemia: A new regimen of conventional drugs and its mechanism.

Oxid Med Cell Longev 2022 13;2022:8212286. Epub 2022 Jul 13.

Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.

Objective: The prognosis of children with refractory acute myeloid leukemia (AML) is poor. Complete remission (CR) is not always achieved with current salvage chemotherapy regimens before transplantation, and some patients have no chance of transplantation. Here, we aimed to describe a new regimen of conventional chemotherapy drugs (homoharringtonine, cladribine , and aclarubicin (HCA)) for refractory AML and its mechanism in vitro.

Methods: We retrospectively collected the clinical data of 5 children with primary refractory AML using HCA as reinduction chemotherapy, and CR rates, adverse reactions, and disease-free survival (DFS) were analyzed. The effects of homoharringtonine, cladribine, and aclarubicin alone or in combination on the proliferation of HL60 and THP1 cells were analyzed by CCK-8 assay. Furthermore, CCK-8 was used to determine the effects of HCA, alone or in combination with apoptosis inhibitors, necroptosis inhibitors, ferroptosis inhibitors, or autophagy inhibitors, on the proliferation of HL60 and THP1 cells and to screen for possible HCA-mediated death pathways in AML cells. The pathway of HCA-mediated AML cell death was further verified by Hoechst/PI staining, flow cytometry, and Western blotting.

Results: After 2 cycles of conventional chemotherapy, none of the 5 children with AML achieved CR and were then treated with the HCA regimen for two cycles, 4 of 5 achieved CR, and another child achieved CR with incomplete hematological recovery (CRi). After CR, 3 children underwent hematopoietic stem cell transplantation (HSCT), and only 2 of them received consolidation therapy. As of the last follow-up, all 5 patients had been in DFS for a range of 23 to 28 months. The inhibition rate of homoharringtonine, cladribine, and aclarubicin in combination on HL60 and THP1 cells was significantly greater than that of a single drug or a combination of two drugs. We found that inhibitors of apoptosis and necroptosis were able to inhibit HCA-mediated cell death but not ferroptosis or autophagy inhibitors. Compared with the control group, the number of apoptotic cells in the HCA group was significantly increased and could be reduced by an apoptosis inhibitor. Western blot results showed that PARP, caspase-3, and caspase-8 proteins were activated and cleaved in the HCA group, the expression of Bax was upregulated and that of Bcl-2 was downregulated. The expression of apoptosis-related proteins could be reversed by apoptosis inhibition. Compared with the control group, the expression levels of the necroptosis-related proteins RIP1, RIP3, and MLKL were downregulated in the HCA group but were not phosphorylated. The necroptosis inhibitor increased the expression of RIP1 but caused no significant changes in RIP3 and MLKL, and none were phosphorylated.

Conclusions: HCA, as a new regimen of conventional drugs, was a safe and efficacious reinduction salvage strategy in children with refractory AML before HSCT. HCA exhibits the synergistic growth inhibition of AML cells and induces cell death mainly through apoptosis.
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http://dx.doi.org/10.1155/2022/8212286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300287PMC
July 2022

A three-dimensional "turn-on" sensor array for simultaneous discrimination of multiple heavy metal ions based on bovine serum albumin hybridized fluorescent gold nanoclusters.

Anal Chim Acta 2022 Aug 9;1220:340023. Epub 2022 Jun 9.

Department of Chemistry, Beihang University, Beijing, 100191, China. Electronic address:

Traditional single sensor is designed based on the "lock-and-key" mode, which only relies on the most dominant interactions between the sensing element and the target. Although it exhibits high selectivity, there are challenges in detecting multiple analytes at the same time. Here, a sensor array with three sensing elements is developed to detect multiple heavy metal ions simultaneously and quickly. In our experiment, bovine serum albumin-encapsulated gold nanoclusters (BSA-AuNCs) were used as fluorescence probes and three different dopamine (DA) concentrations as nonspecific receptors. As we know, self-polymerized polydopamine (PDA) can quench part of the fluorescence of BSA-AuNCs. Upon the addition of the heavy metal ions, the diverse non-specific interactions between DA and heavy metal ions result in the difference in the number of the remaining PDA. Therefore it would lead to different degrees of fluorescence recovery behavior. This unique "turn-on" fluorescence response mode can be analyzed by linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA). Two-dimensional, three-dimensional and even four-dimensional mixed ions detection and quantitative detection have also been achieved. Moreover, by using this fluorescence array mode, heavy metal ions in tap water or blood samples can be detected.
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http://dx.doi.org/10.1016/j.aca.2022.340023DOI Listing
August 2022

Clinical efficacy and safety of NSCLC ancillary treatment with compound Kushen injection through immunocompetence regulation: A systematic review and meta-analysis.

Phytomedicine 2022 Sep 6;104:154315. Epub 2022 Jul 6.

Department of Physiology, Xuzhou Medical University, Xuzhou, 221009, China. Electronic address:

Background: Compound Kushen injection (CKI) is a Chinese patented medicine that improves the immunity level of cancer patients and inhibits tumor cell proliferation and metastasis. Clinically, CKI is widely used in combination with platinum-based chemotherapy (PBC) for non-small cell lung cancer (NSCLC) treatment. This study attempted to systemically evaluate the efficacy and safety of a combination of CKI and PBC for NSCLC treatment by modulating the immune function.

Purpose: To evaluate the clinical efficacy and safety of CKI in combination with PBC for NSCLC.

Materials And Methods: English and Chinese databases were retrieved for randomized controlled trials (RCTs) of NSCLC treatment using a combination of CKI and PBC, and the changes of peripheral blood T lymphocytes (such as CD3 T cells, CD4 T cells, CD8 T cells), and CD4/CD8 T cell ratio among NSCLC patients were detected before and after treatment using CKI with PBC. The search deadline was set as November 2021. The systemic evaluation was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodology and quality of each study included in the systemic evaluation were assessed. Review Manager 5.4, Stata12.0, and trial sequential analysis (TSA) were used for data analysis. The outcome indicators were qualified using GRADEprofiler software.

Results: A total of 25 RCTs involving 2460 cases of patients were included. The results showed that the combination of CKI with PBC effectively increased the objective response rate (ORR) [relative risk (RR) = 1.31, 95% confidence interval (CI) (1.19, 1.44)] and disease control rate (DCR) [RR = 1.16, 95%CI (1.09,1.23)], regulated the expression of peripheral blood T lymphocytes (such as CD3T cells, CD4T cells, CD8T cells, and CD4/CD8T cell ratio), upregulated the level of serum immunoglobulins (such as IgA, IgG, and IgM), and reduced the frequency of gastrointestinal reaction, marrow inhibition, hepatorenal toxicity, reduction of white blood cells and blood platelets, baldness, infection, neutrophilic granulocyte counts, diarrhea, or constipation. According to subgroup analysis results, chemotherapy cycles (1-2) had a more significant effect on DCR. A combination of CKI and GP regimens had better effects on improving CD3T cell levels, and there were no significant changes among other chemotherapies regiments.

Conclusion: A combination of CKI and PBC had a marked effect in improving tumor response, priming immune function, and decreasing the frequency of adverse reactions, which was safe for NSCLC treatment.
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http://dx.doi.org/10.1016/j.phymed.2022.154315DOI Listing
September 2022

Efficacy of three novel drugs in the treatment of heart failure: A network meta-analysis.

Medicine (Baltimore) 2022 Jul 22;101(29):e29415. Epub 2022 Jul 22.

Department of Cardiovascular, The First People's Hospital of Shuangliu District, Chengdu, China.

Background: Angiotensin receptor neprilysin inhibitors (ARNI), sodium-glucose cotransporter 2 inhibitors (SGLT2i), soluble guanylate cyclase stimulators (sGCs), and the traditional golden triangle standard-of-care (SOC) are effective drugs for heart failure. We aimed to assess the efficacy of 4 interventions in these patients.

Methods: PubMed, The Cochrane Library, Embase, and Web of Science databases were electronically searched to collect randomized controlled trials of 3 novel drugs in the treatment of heart failure from inception to September 1st, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk bias of included studies. Stata 16.0 software was used for network meta-analysis.

Results: A total of 17 randomized controlled trial involving 38,088 patients were included. The results of network meta-analysis: in terms of heart failure rehospitalization rate, 3 novel drugs lower than SOC [ARNI (OR = 0.77, 95% CI: 0.71-0.83), SGLT2i (OR = 0.70, 95% CI: 0.63-0.77), sGCs (OR = 0.88, 95% CI: 0.78-0.99)], and SGLT2i was also lower than sGCs (OR = 0.79, 95% CI: 0.68-0.93). In terms of all-cause mortality, ARNI was lower than SOC (OR = 0.81, 95% CI: 0.66-0.99). In terms of cardiovascular mortality, ARNI and SGLT2i was lower than SOC (ARNI [OR = 0.80, 95% CI: 0.70-0.92], SGLT2i [OR = 0.87, 95% CI: 0.76-0.99]). In terms of rates of cardiovascular death or heart failure rehospitalization, 3 novel drugs lower than SOC (ARNI [OR = 0.76, 95% CI: 0.71-0.82], SGLT2i [OR = 0.76, 95% CI: 0.70-0.82], sGCs [OR = 0.87, 95% CI: 0.78-0.97]). In terms of Kansas city cardiomyopathy questionnaire score, ARNI and SGLT2i was superior to SOC (ARNI [MD = 1.43, 95% CI: 0.43-2.42], SGLT2i [MD = 1.88, 95% CI: 1.12-2.65]). In terms of N-terminal pro-B-type natriuretic peptide outcome indexes, SGLT2i was superior to SOC (MD = -134.63, 95% CI: -237.70 to -31.56). The results of Surface under the cumulative ranking sequencing: in terms of heart failure rehospitalization rate and rates of cardiovascular death or heart failure rehospitalization, the ranking was SGLT2i>ARNI>sGCs>SOC. in terms of all-cause mortality and cardiovascular mortality, the ranking was ARN>SGLT2i>sGCs>SOC. in terms of Kansas city cardiomyopathy questionnaire score and N-terminal pro-B-type natriuretic peptide outcome indexes, the ranking was SGLT2i>ARN>SOC.

Conclusions: The available evidence suggests that all 3 novel heart failure drugs can improve the prognosis of heart failure. ARNI may be the most effective in reducing mortality, SGLT2i may be the most effective in improving quality of life, while sGCs may be inferior to ARNI and SGLT2i.
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http://dx.doi.org/10.1097/MD.0000000000029415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302283PMC
July 2022

The complete chloroplast genome of Chinese endemic species (Pinaceae) and its phylogenetic analysis.

Mitochondrial DNA B Resour 2022 12;7(7):1282-1284. Epub 2022 Jul 12.

State Key Laboratory of Tree Genetics and Breeding, Chinese Academy of Forestry, Beijing, China.

Bordères & Gaussen 1947 is endemic to China, where it is distributed at 3300-4000 meters in the mountains of Southwest Sichuan and Northwest Yunnan. In this study, the complete chloroplast genome of was reconstructed by assembly using whole-genome sequencing data. The complete chloroplast genome of was 120,049 bp in length with a GC content of 37.9%. A total of 113 genes were identified, including 4 rRNA genes, 35 tRNA genes, and 74 protein-coding genes. Among these, 14 genes contain introns. In the phylogenetic tree with 12 other species of , and W. L. Huang et al. 1984 were grouped into the same branch, with a bootstrap value of 100%. The complete chloroplast genome of provides potential genetic resources for further evolutionary and genomic studies.
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http://dx.doi.org/10.1080/23802359.2022.2097028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291656PMC
July 2022

Ataluren suppresses a premature termination codon in an MPS I-H mouse.

J Mol Med (Berl) 2022 Aug 20;100(8):1223-1235. Epub 2022 Jul 20.

Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, BBRB 444, 1720 Second Avenue South, Birmingham, AL, 35294-2170, USA.

Abstarct: Suppressing translation termination at premature termination codons (PTCs), termed readthrough, is a potential therapy for genetic diseases caused by nonsense mutations. Ataluren is a compound that has shown promise for clinical use as a readthrough agent. However, some reports suggest that ataluren is ineffective at suppressing PTCs. To further evaluate the effectiveness of ataluren as a readthrough agent, we examined its ability to suppress PTCs in a variety of previously untested models. Using NanoLuc readthrough reporters expressed in two different cell types, we found that ataluren stimulated a significant level of readthrough. We also explored the ability of ataluren to suppress a nonsense mutation associated with Mucopolysaccharidosis I-Hurler (MPS I-H), a genetic disease that is caused by a deficiency of α-L-iduronidase that leads to lysosomal accumulation of glycosaminoglycans (GAGs). Using mouse embryonic fibroblasts (MEFs) derived from Idua-W402X mice, we found that ataluren partially rescued α-L-iduronidase function and significantly reduced GAG accumulation relative to controls. Two-week oral administration of ataluren to Idua-W402X mice led to significant GAG reductions in most tissues compared to controls. Together, these data reveal important details concerning the efficiency of ataluren as a readthrough agent and the mechanisms that govern its ability to suppress PTCs.

Key Messages: Ataluren promotes readthrough of PTCs in a wide variety of contexts. Ataluren reduces glycosaminoglyan storage in MPS I-H cell and mouse models. Ataluren has a bell-shaped dose-response curve and a narrow effective range.
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http://dx.doi.org/10.1007/s00109-022-02232-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329424PMC
August 2022
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