Publications by authors named "Yan Yang"

2,640 Publications

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Clinical practice guidelines for the treatment of allergic rhinitis in children with traditional Chinese medicine.

Anat Rec (Hoboken) 2021 Jul 29. Epub 2021 Jul 29.

Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Allergic rhinitis (AR) is one of the most common allergic diseases in children and it can lead to physical and mental health problems. Traditional Chinese medicine (TCM) plays an important role in understanding the phenotypes and treatment of AR. However, there are currently no normative clinical practice guidelines (CPGs) for the treatment of AR in children. The study aimed to develop an evidence-based CPG for the treatment of AR in children with TCM. Systematic literature research, expert questionnaire, and clinical evaluation after three rounds of surveys were adopted to form recommendations for treating children with AR using the Delphi method. Depending on the clinical manifestations, we finally recommended two decoctions with two Chinese patent medicines for an acute attack of AR and two decoctions for a chronic period of AR. For the acute attack of AR in children, Xinyi Qingfei decoction, Wenfei Zhiliu decoction, Xinqin granules, and Xinyi Biyan pills were suggested, whereas for the chronic period of AR, Buzhong Yiqi and Jingui Shenqi decoctions were recommended. The four external treatment methods suggested for the prevention and care of AR were body acupuncture, moxibustion, auricular point pressing, and acupoint application. The recommended levels of the suggested TCM strategies ranged from Grade B to D, indicating the weakness of the recommendations. TCM has the potential to offer new insights into phenotypes and the management of AR worldwide; however, more high-quality clinical studies are needed to improve the quality of evidence.
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http://dx.doi.org/10.1002/ar.24718DOI Listing
July 2021

Recent Advances in Stimulus-Responsive Nanocarriers for Gene Therapy.

Adv Sci (Weinh) 2021 07 16;8(14):2100540. Epub 2021 May 16.

Department of Stomatology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei Province 430030 China.

Gene therapy provides a promising strategy for curing monogenetic disorders and complex diseases. However, there are challenges associated with the use of viral delivery vectors. The advent of nanomedicine represents a quantum leap in the application of gene therapy. Recent advances in stimulus-responsive nonviral nanocarriers indicate that they are efficient delivery systems for loading and unloading of therapeutic nucleic acids. Some nanocarriers are responsive to cues derived from the internal environment, such as changes in pH, redox potential, enzyme activity, reactive oxygen species, adenosine triphosphate, and hypoxia. Others are responsive to external stimulations, including temperature gradients, light irradiation, ultrasonic energy, and magnetic field. Multiple stimuli-responsive strategies have also been investigated recently for experimental gene therapy.
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http://dx.doi.org/10.1002/advs.202100540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292848PMC
July 2021

Potential Role of CD47-Directed Bispecific Antibodies in Cancer Immunotherapy.

Front Immunol 2021 8;12:686031. Epub 2021 Jul 8.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.

The prosperity of immunological therapy for cancer has aroused enormous passion for exploiting the novel targets of cancer immunotherapy. After the approval of blinatumomab, a bispecific antibody (bsAb) targeting on CD19 for acute lymphoblastic leukemia, a few of CD47-targeted bsAbs for cancer immunotherapy, are currently in clinical research. In our review of CD47-targeted bsAbs, we described the fundamental of bsAbs. Then, we summarized the information of four undergoing phase I researches, reviewed the main toxicities relevant to CD47-targeted bsAb immunological therapy of on-target cytotoxicity to healthy cells and a remarkable antigen-sink. Finally, we described possible mechanisms of resistance to CD47-targeted bsAb therapy. More clinical researches are supposed to adequately confirm its security and efficacy in clinical practice.
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http://dx.doi.org/10.3389/fimmu.2021.686031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297387PMC
July 2021

Surface-confined guanidinium ionic liquid as a new type of stationary phase for hydrophilic interaction liquid chromatography.

J Sep Sci 2021 Jul 16. Epub 2021 Jul 16.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116023, China.

Guanidinium-based ionic liquids possess lower toxicity and greater designability than commonly used species and have presented good performances in liquid-phase extraction and stationary phase for capillary GC. In the present work, a novel type of surface-confined guanidinium ionic liquid stationary phase was developed by bonding a hexaalkylguanidinium ionic liquid N,N,N',N'-tetramethyl-N",N"-diallylguanidinium bromide onto the surface of 3-mercaptopropyl modified silica. The obtained surface-confined guanidinium ionic liquid silica materials were characterized by elemental analysis, infrared spectrum, and thermogravimetric analysis, and then packed as a HPLC column for the evaluation of chromatographic retention behavior. Typical polar compounds were used to evaluate the separation performances, and the changes of retention with water content in mobile phase further suggested the hydrophilic interaction liquid chromatography retention mechanism. Moreover, the effect of different chromatographic factors (salt concentration, mobile phase pH and column temperature) on retention was investigated with a series of compounds as test solutes to gain insights into the retention mechanism. The results indicated that the surface-confined guanidinium ionic liquid stationary phase exhibited a hydrophilic interaction liquid chromatography/anion-exchange mixed-mode retention behavior and possessed promising potential in separating a wide range of compounds as an alternative stationary phase for HPLC. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jssc.202100385DOI Listing
July 2021

Intratumor Heterogeneity of MIF Expression Correlates With Extramedullary Involvement of Multiple Myeloma.

Front Oncol 2021 29;11:694331. Epub 2021 Jun 29.

Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, China.

Macrophage migration inhibitory factor (MIF) has been shown to promote disease progression in many malignancies, including multiple myeloma (MM). We previously reported that MIF regulates MM bone marrow homing and knockdown of MIF favors the extramedullary myeloma formation in mice. Here, based on MIF immunostaining of myeloma cells in paired intramedullary and extramedullary biopsies from 17 patients, we found lower MIF intensity in extramedullary MM (EMM) versus intramedullary MM (IMM). Flow cytometry and histology analysis in xenograft models showed a portion of inoculated human MM cells lost their MIF expression (MIF) . Of note, IMM had dominantly MIF cells, while EMM showed a significantly increased ratio of MIF cells. Furthermore, we harvested the extramedullary human MM cells from a mouse and generated single-cell transcriptomic data. The developmental trajectories of MM cells from the MIF to MIF state were indicated. The MIF cells featured higher proliferation. The MIF ones were more quiescent and harbored abundant ribosomal protein genes. Our findings identified differential regulation of MIF expression in MM and suggested a potential pathogenic role of MIF in the extramedullary spread of disease.
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http://dx.doi.org/10.3389/fonc.2021.694331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276700PMC
June 2021

BMP-9 downregulates StAR expression and progesterone production by activating both SMAD1/5/8 and SMAD2/3 signaling pathways in human granulosa-lutein cells obtained from gonadotropins induced ovarian cycles.

Cell Signal 2021 Jul 13;86:110089. Epub 2021 Jul 13.

Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 40, Daxue Road, Zhengzhou, Henan 450052, China. Electronic address:

Bone morphogenetic proteins (BMPs) are expressed in different cell types of the human ovarian follicle and play important roles in the regulation of ovarian function. BMP-9, also known as growth differentiation factor-2 (GDF-2), belongs to the transforming growth factor-beta (TGF-β) superfamily. BMP-9 is mainly synthesized in the liver and secreted into the blood which allows it to regulate various physiological and pathological functions. To date, the expression of BMP-9 in the human ovary and its function in human granulosa cells remains unknown. In the present study, we detect the protein expression of BMP-9 in the human follicular fluid. Using the primary culture of human granulosa-lutein (hGL) cells obtained from patients undergoing in vitro fertilization as a cell model, we show that treatment with BMP-9 downregulates steroidogenic acute regulatory protein (StAR) expression and suppresses progesterone (P4) production. The expression levels of the P450 side-chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase (3β-HSD) are not affected by BMP-9 treatment. Mechanistically, treatment of hGL cells with BMP-9 activates both SMAD1/5/8 and SMAD2/3 signaling pathways. Blocking the activations of SMAD1/5/8 and SMAD2/3 by pharmacological inhibitors or knockdown of SMAD4 attenuates the inhibitory effects of BMP-9 on StAR expression and P4 production. This study reveals a novel function of BMP-9 in the regulation of ovarian steroidogenesis.
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http://dx.doi.org/10.1016/j.cellsig.2021.110089DOI Listing
July 2021

A review on two-dimensional materials for chemiresistive- and FET-type gas sensors.

Phys Chem Chem Phys 2021 Jul;23(29):15420-15439

State Key Laboratory of Materials Processing and Die Mould Technology, Huazhong University of Science and Technology (HUST), No. 1037, Luoyu Road, Wuhan 430074, China.

Two-dimensional (2D) materials have shown great potential for gas sensing applications due to their large specific surface areas and strong surface activities. In addition to the commonly reported chemiresistive-type gas sensors, field-effect transistor (FET)-type gas sensors have attracted increased attention due to their miniaturized size, low power consumption, and good compatibility with CMOS technology. In this review, we aim to discuss the recent developments in chemiresistive- and FET-type gas sensors based on 2D materials, including graphene, transition metal dichalcogenides, MXenes, black phosphorene, and other layered materials. Firstly, the device structure and the corresponding fabrication process of the two types of sensors are given, and then the advantages and disadvantages are also discussed. Secondly, the effects of intrinsic and extrinsic factors on the sensing performance of 2D material-based chemiresistive and FET-type gas sensors are also detailed. Subsequently, the current gas-sensing applications of 2D material-based chemiresistive- and FET-type gas sensors are systematically presented. Finally, the future prospects of 2D materials in chemiresistive- and FET-type gas sensing applications as well as the current existing problems are pointed out, which could be helpful for the development of 2D material-based gas sensors with better sensing performance to meet the requirements for practical application.
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http://dx.doi.org/10.1039/d1cp01890fDOI Listing
July 2021

Trimetazidine ameliorates hindlimb ischaemic damage in type 2 diabetic mice.

Ann Med 2021 12;53(1):1099-1107

Division of Endocrinology, Tongji Hospital, Huazhong University of Science & Technology, Wuhan, PR China.

Background: Ischaemia caused by lower extremity artery stenosis is the main cause of peripheral artery disease (PAD) in patients with diabetes. Trimetazidine (TMZ) has traditionally been used as an anti-ischaemic drug for coronary artery disease. The effect of TMZ on PAD in a diabetic animal model and the underlying molecular mechanisms remain unclear.

Methods: The db/db mice were challenged with femoral artery ligation (FAL), followed by TMZ treatment for 2 weeks. Scores on hindlimb ischaemia and function were evaluated. Histological and capillary density analyses of gastrocnemius were performed. The expression of vascular endothelial growth factor (VEGF) and myogenic regulators was also confirmed by Western blotting. We also detected serum intercellular adhesion molecule 1 (ICAM-1) level through ELISA.

Results: Diabetic mice exhibited limb ulceration and motor dysfunction after FAL while TMZ-treated db/db mice exhibited milder ischaemic impairment. Furthermore, decreased capillary density in the gastrocnemius muscles of ischaemic hindlimb and reduced expressions of VEGF, myogenic markers, and serum ICAM-1 could be partially reversed by TMZ treatment.

Conclusion: TMZ may alleviate hindlimb ischaemic damage in db/db mice, at least partly, through enhancing angiogenesis and promoting myogenesis in ischaemia region.Key messagesTMZ intervention could alleviate hindlimb ischaemic damage in db/db mice.TMZ intervention could enhance angiogenesis and stimulate myogenesis in ischaemia region.
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http://dx.doi.org/10.1080/07853890.2021.1925147DOI Listing
December 2021

FoxO4 negatively modulates USP10 transcription to aggravate the apoptosis and oxidative stress of hypoxia/reoxygenation-induced cardiomyocytes by regulating the Hippo/YAP pathway.

J Bioenerg Biomembr 2021 Jul 12. Epub 2021 Jul 12.

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei Province, China.

Acute myocardial infarction (AMI) is the main cause of death in the whole world. This study aimed to investigate whether forkhead box O4 (FoxO4) could negatively modulate ubiquitin specific peptidase 10 (USP10) transcription to aggravate the apoptosis and oxidative stress of hypoxia/reoxygenation (H/R)-induced cardiomyocytes through Hippo/YAP pathway. mRNA expression as well as protein expressions of USP10 and FoxO4 in H9C2 cells after H/R induction or transfection were respectively detected by Reverse transcription-quantitative (RT-q) PCR analysis and Western blot. The viability and apoptosis of H9C2 cells after H/R induction or transfection were respectively detected by CCK-8 and TUNEL assays. The expressions of lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in H9C2 cells after H/R induction or transfection were analyzed using appropriate kits and intracellular reactive oxygen species (ROS) levels were detected using a ROS Assay Kit. Dual luciferase reporter assay and Chromatin Immunoprecipitation (ChIP) have adopted to confirm the combination of USP10 and FoxO4. Western blot was also used to analyze the expression of apoptosis-related proteins and Hippo/YAP pathway-related proteins. As a result, USP10 expression was decreased in H/R-induced H9C2 cells in a time-dependent manner. USP10 overexpression increased the viability and suppressed the apoptosis and oxidative stress of H/R-induced H9C2 cells. In addition, FoxO4 modulated USP10 transcription. FoxO4 expression was increased in H9C2 cells induced by H/R. FoxO4 overexpression could reverse the protective effects of USP10 overexpression on H/R-induced H9C2 cells by regulating the Hippo/YAP signaling pathway. In conclusion, FoxO4 negatively modulated USP10 transcription to aggravate the apoptosis and oxidative stress of H/R-induced H9C2 cells via blocking Hippo/YAP pathway.
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http://dx.doi.org/10.1007/s10863-021-09910-7DOI Listing
July 2021

Glycolysis-Related Gene Expression Profiling Screen for Prognostic Risk Signature of Pancreatic Ductal Adenocarcinoma.

Front Genet 2021 23;12:639246. Epub 2021 Jun 23.

Department of Breast and Thyroid Surgery, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University, Wuhan, China.

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal. Although progress has been made in the treatment of PDAC, its prognosis remains unsatisfactory. This study aimed to develop novel prognostic genes related to glycolysis in PDAC and to apply these genes to new risk stratification. In this study, based on the Cancer Genome Atlas (TCGA) PAAD cohort, the expression level of glycolysis-related gene at mRNA level in PAAD and its relationship with prognosis were analyzed. Non-negative matrix decomposition (NMF) clustering was used to cluster PDAC patients according to glycolytic genes. Prognostic glycolytic genes, screened by univariate Cox analysis and LASSO regression analysis were established to calculate risk scores. The differentially expressed genes (DEGs) in the high-risk group and the low-risk group were analyzed, and the signal pathway was further enriched to analyze the correlation between glycolysis genes. In addition, based on RNA-seq data, CIBERSORT was used to evaluate the infiltration degree of immune cells in PDAC samples, and ESTIMATE was used to calculate the immune score of the samples. A total of 319 glycolysis-related genes were retrieved, and all PDAC samples were divided into two clusters by NMF cluster analysis. Survival analysis showed that PDAC patients in cluster 1 had shorter survival time and worse prognosis compared with cluster 2 samples ( < 0.001). A risk prediction model based on 11 glycolysis genes was constructed, according to which patients were divided into two groups, with significantly poorer prognosis in high-risk group than in low-risk group ( < 0.001). Both internal validation and external dataset validation demonstrate good predictive ability of the model (AUC = 0.805, < 0.001; AUC = 0.763, < 0.001). Gene aggregation analysis showed that DEGs highly expressed in high-risk group were mainly concentrated in the glycolysis level, immune status, and tumor cell proliferation, etc. In addition, the samples in high-risk group showed immunosuppressed status and infiltrated by relatively more macrophages and less CD8+T cell. These findings suggested that the gene signature based on glycolysis-related genes had potential diagnostic, therapeutic, and prognostic value for PDAC.
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http://dx.doi.org/10.3389/fgene.2021.639246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261051PMC
June 2021

Three-dimensional magnetic stannic disulfide composites for the solid-phase extraction of sulfonamide antibiotics.

J Chromatogr A 2021 Jun 29;1652:462372. Epub 2021 Jun 29.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116023, China; School of Chemical Engineering, Dalian University of Technology, Panjin 124221, China. Electronic address:

In the present work, three-dimensional (3D) and flower-like SnS materials were coated on the surface of [email protected] through an in-situ growth method. The 3D architecture could avoid the accumulation and reaggregation with better stability and was beneficial for the exposure of more active sites. The prepared magnetic SnS composites were used for the enrichment of sulfonamide antibiotics (SAs), and various experimental parameters affecting the extraction efficiency were investigated. The results showed the equilibrium of extraction and desorption towards target SAs could be reached within 3 min by using the [email protected] composites. Under optimized conditions, the proposed approach possessed good linearity in the range of 0.1-200 ng·mL with correlation coefficients r above 0.9964 and low limits of detection (LODs) from 0.025 to 0.250 ng·mL for the five target SAs. Moreover, good repeatability was obtained with the intra-day and inter-day precision in terms of relative standard deviations (RSDs) within 1.1%-10.8% and 7.4%-13.1%, and the recoveries under three spiked concentrations were between 81.8% and 119.7% with adequate accuracy. Different samples including tap water, milk and honey were collected for magnetic solid-phase extraction and determination of target SAs by using the obtained [email protected] composites to demonstrate the utility. All the results indicated that the proposed method had great potential for effective preconcentration and determination of SAs in complex samples.
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http://dx.doi.org/10.1016/j.chroma.2021.462372DOI Listing
June 2021

High ovarian GDF-8 levels contribute to elevated estradiol production in ovarian hyperstimulation syndrome by stimulating aromatase expression.

Int J Biol Sci 2021 11;17(9):2338-2347. Epub 2021 Jun 11.

Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Growth differentiation factor-8 (GDF-8), also known as myostatin, belongs to the transforming growth factor-beta (TGF-β) superfamily. GDF-8 is expressed in the ovary and regulates various ovarian functions. Ovarian hyperstimulation syndrome (OHSS) is one of the most serious disorders during fertilization treatment. Aromatase, encoded by the gene, is the enzyme that catalyzes the final step in estradiol (E2) biosynthesis. It has been demonstrated that high serum E2 levels are associated with the development of OHSS. However, the effects of GDF-8 on aromatase expression and its roles in the pathogenesis of OHSS remain unclear. The effect of GDF-8 on aromatase expression and the underlying mechanisms were explored by a series of experiments in primary human granulosa-lutein (hGL) and KGN cells. Rat OHSS model and human follicular fluid samples were used to examine the roles of the GDF-8 system in the pathogenesis of OHSS. We demonstrate that GDF-8 stimulates aromatase expression and E2 production in hGL and KGN cells. In addition, TGF-β type I receptor ALK5-mediated SMAD2/3 signaling is required for GDF-8-induced aromatase expression and E2 production. Using a rat OHSS model, we show that the aromatase and GDF-8 levels are upregulated in the ovaries of OHSS rats. Blocking the function of ALK5 by the administration of its inhibitor, SB431542, alleviates OHSS symptoms and the upregulation of aromatase. Clinical results reveal that the protein levels of GDF-8 are upregulated in the follicular fluid of OHSS patients. Moreover, the expression of GDF-8 is increased in hGL cells of OHSS patients. This study helps to elucidate the mechanisms mediating the expression of aromatase in human granulosa cells, which may lead to the development of alternative therapeutic approaches for OHSS.
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http://dx.doi.org/10.7150/ijbs.60332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241723PMC
June 2021

A systematic review and meta-analysis on the efficacy of statins in the treatment of atherosclerosis.

Ann Palliat Med 2021 Jun;10(6):6793-6803

Department of Cardiovascular Medicine, Heilongjiang Provincial Hospital, Harbin, China.

Background: It was a meta-analysis on the efficacy of statins in the treatment of atherosclerosis.

Methods: The PubMed, Medline, Embase, Web of Sciences, and other Chinese and English databases were used to retrieve literature on randomized controlled trials (RCTs) of statins in the treatment of atherosclerosis, published from January 2000 to January 2021. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was used to conduct bias risk assessment, and Review Manager 5.3 software (RevMan) was used for meta-analysis.

Results: A total of 12 articles with 1,180 participants were included in the meta-analysis. In the observation group, the plaque area [mean difference (MD) =-1.21; 95% confidence interval (CI): -2.03 to -0.38; Z =2.87; P=0.004], total cholesterol (TC) level (MD =-0.72; 95% CI: -1.01 to -0.43; Z =4.83; P<0.00001), triglyceride (TG) level (MD =-0.43; 95% CI: -0.76 to -0.09; Z =2.51; P=0.01), and the low-density lipoprotein (LDL-C) level (MD =-0.79; 95% CI: -1.41 to -0.18; Z =2.54; P=0.01) were lower, while the clinical effective rate (MD =3.64; 95% CI: 1.39 to 9.53; Z =2.64; P=0.008) was higher, and the difference was notable. No notable difference was noted in intra-media thickness (IMT) (MD =-0.41; 95% CI: -0.88 to -0.06; Z =1.7; P=0.09), hypersensitive C-reactive protein (hs-CRP) level (MD =-1.61; 95% CI: -3.59 to 0.37; Z =1.7; P=0.09), and high-density lipoprotein (HDL-C) level (MD =0.14; 95% CI: -0.02 to 0.30; Z =2.54; P=0.09) between the 2 groups.

Discussion: The use of statins in the treatment of atherosclerosis can reduce the levels of TC, TG, and LDL-C, mitigate clinical symptoms, and reduce blood lipids with good efficacy.
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http://dx.doi.org/10.21037/apm-21-1243DOI Listing
June 2021

Systematic review and meta-analysis of the efficacy of N-acetylcysteine in the treatment of acute exacerbation of chronic obstructive pulmonary disease.

Ann Palliat Med 2021 Jun;10(6):6564-6576

Department of Respiratory and Critical Care Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.

Background: Whether N-acetylcysteine (NAC) therapy can promote the improvement of clinical symptoms and lung function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has not been verified by large-scale randomized controlled trials, only a few small sample studies.

Methods: English databases were searched using a combination of the following terms: "chronic obstructive pulmonary disease", "acute exacerbation of chronic obstructive pulmonary disease", and "N-acetylcysteine". Studies examining NAC in the treatment of AECOPD were screened, so as to be a reference for the experimental group. Meta-analysis was performed using RevMan 5.3 software (Cochrane, Northern Europe), with a total of 15 included literatures.

Results: The heterogeneity test of improvement rate showed Chi2=1.89, df=7, I2=0% <50%, and P=0.97 (>0.01); the risk rate was 1.09, the 95% confidence interval (CI) was (1.04-1.14), Z=3.93, and P<0.0001. The heterogeneity test of forced expiratory volume in the first second (FEV1) showed that Tau2=63.39, Chi2=118.66, df=9, I2=92% >50%, and P=0.88 (<0.0001); the mean difference was 30.63 (95% CI: 25.48-35.78), Z=11.65, and P<0.0001. The results of the heterogeneity test of forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) showed that Tau2=60.03, Chi2=74.09, df=5, I2=93% >50%, and P<0.0001; the mean difference was 30.42 (95% CI: 24.00-36.85), Z=9.28, and P<0.0001. The heterogeneity test for glutathione sulfur transferase (GSH-ST) activity showed that Tau2=4.12, Chi2=58.12, df=5, I2=91% >50%, and P<0.0001; the mean difference was 3.10 (95% CI: 1.38-4.82), Z=3.63, and P=0.0004.

Conclusions: Our meta-analysis confirmed that NAC could promote the symptom improvement rate of patients with AECOPD, improve lung function in FEV1 and FEV1/FVC, and enhance the body's antioxidant capacity.
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http://dx.doi.org/10.21037/apm-21-1138DOI Listing
June 2021

Treating carbon-limited wastewater by DWTR and woodchip augmented floating constructed wetlands.

Chemosphere 2021 Jun 26;285:131331. Epub 2021 Jun 26.

Dooge Centre for Water Resources Research, School of Civil Engineering, University College Dublin, Belfield, Dublin 4, Ireland.

Floating constructed wetlands (FCWs) have attained tremendous popularity for water purification purposes. However, FCW functions establishment in nutrients removal from carbon-limited wastewater, especially in cold weather, is still a challenge. Here, two drinking water treatment residual (DWTR) based biocarriers (B-I: DWTR cakes, B-II: DWTR cakes combined with woodchips) have been augmented into FCW to enhance the nutrients (N and P) removal performance. Compared to the traditional FCW, the intensified FCWs simultaneously achieved higher N and P removal efficiencies, with average pollutants removal of 52.16 ± 11.51% for TN and 92.72 ± 1.61% for TP in FCW-I and 57.65 ± 9.43% for TN and 92.17 ± 2.55% for TP in FCW-II, respectively, while their removal in FCW-III of 27.74 ± 7.11% for TN and 17.91 ± 9.27% for TP. B-II performed best in overcoming the negative influence of low temperature in nutrients removal. Mass balance budget indicated that most P was enriched in DWTR based biocarriers. Thus it is feasible to recycle and recover P from the surface water. Furthermore, P in the sediment can be changed from active P to stable P, mitigating the internal P release risk. This study can help to expand the understanding of the intensified FCWs and promote the practical application of FCWs.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131331DOI Listing
June 2021

CIRP Secretion during Cardiopulmonary Bypass Is Associated with Increased Risk of Postoperative Acute Kidney Injury.

Thorac Cardiovasc Surg 2021 Jul 7. Epub 2021 Jul 7.

Department of Cardiovascular Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Background:  Systemic inflammation contributes to cardiac surgery-associated acute kidney injury (AKI). Cardiomyocytes and other organs experience hypothermia and hypoxia during cardiopulmonary bypass (CPB), which induces the secretion of cold-inducible RNA-binding protein (CIRP). Extracellular CIRP may induce a proinflammatory response.

Materials And Methods:  The serum CIRP levels in 76 patients before and after cardiac surgery were determined to analyze the correlation between CIRP levels and CPB time. The risk factors for AKI after cardiac surgery and the in-hospital outcomes were also analyzed.

Results:  The difference in the levels of CIRP (ΔCIRP) after and before surgery in patients who experienced cardioplegic arrest (CA) was 26-fold higher than those who did not, and 2.7-fold of those who experienced CPB without CA. The ΔCIRP levels were positively correlated with CPB time ( = 0.574,  < 0.001) and cross-clamp time ( = 0.54,  < 0.001). Multivariable analysis indicated that ΔCIRP (odds ratio: 1.003; 95% confidence interval: 1.000-1.006;  = 0.027) was an independent risk factor for postoperative AKI. Patients who underwent aortic dissection surgery had higher levels of CIRP and higher incidence of AKI than other patients. The incidence of AKI and duration of mechanical ventilation in patients whose serum CIRP levels more than 405 pg/mL were significantly higher than those less than 405 pg/mL (65.8 vs. 42.1%,  = 0.038; 23.1 ± 18.2 vs. 13.8 ± 9.2 hours,  = 0.007).

Conclusion:  A large amount of CIRP was released during cardiac surgery. The secreted CIRP was associated with the increased risk of AKI after cardiac surgery.
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http://dx.doi.org/10.1055/s-0041-1730450DOI Listing
July 2021

Combination of mesenchymal stem cells and FK506 prolongs heart allograft survival by inhibiting TBK1/IRF3-regulated-IFN-γ production.

Immunol Lett 2021 Jul 4;238:21-28. Epub 2021 Jul 4.

Organ Transplantation institute, School of Medicine, Xiamen University, Xiamen, Fujian, China; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, China; Medical College, Guangxi University, Nanning, Guangxi, China. Electronic address:

Lifelong immunosuppression use presents many serious side effects to transplant recipients. Previous studies have shown that mesenchymal stem cells (MSC) regulate the progress of inflammation and protect allograft function. However, the benefits of MSC combined with low-dose tacrolimus (FK506) has not been investigated in heart transplant recipients, and its mechanism deserves further investigation. SD Rat bone marrow-derived MSC were infused into recipient mouse (C57BL/6, B6) through the tail vein, followed by a BALB/c donor cervical ectopic heart transplantation on the next day of infusion. T-lymphocyte subsets and their functions were determined using flow cytometry, ELISA, and qPCR. Thereafter, in vitro and in vivo experiments were conducted to identify the mechanisms regarding MSC and FK506 combination (MF group) use in regulating IFN-γ signaling. MF group in the allogeneic heart transplantation mouse model inhibited acute rejection and prolonged mean survival time (MST) of grafts from 7 days (d) to 22d. Pathological examination of heart grafts suggested that inflammatory cell infiltration decreased, and tissue damage was significantly reduced in the MF group. IFN-γ mRNA expression levels in the grafts and recipients decreased, while IL-4 and TGF-β mRNA expression increased in the MF group. Phosphorylation of TBK1/IRF3 in recipient immune cells decreased under donor antigen stimulation. Combination use of MSC and FK506 can prolong graft survival, possibly by down-regulating TBK1/IRF3 phosphorylation, thus reducing IFN-γ production to prevent infiltration of inflammatory cells in the graft and extend graft survival. The findings provide a potential new approach to immunosuppression selection.
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http://dx.doi.org/10.1016/j.imlet.2021.06.007DOI Listing
July 2021

[Structure, function and application of serine carboxypeptidase-like acyltransferases from plants].

Sheng Wu Gong Cheng Xue Bao 2021 Jun;37(6):1887-1899

State Key Laboratory of Bioactive and Function of Natural Medicines & Key Laboratory of Biosynthesis of Natural Products of National Health Commission of the People's Republic of China, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.

Plant serine carboxypeptidase-like acyltransferases (SCPL-AT) have similar structural characteristics and high homology compared to the serine carboxypeptidase. They can transfer the acyl from acyl glucose esters to many natural products, participate in the acylation modification of plant secondary metabolites, enrich the structural diversity of natural products, and improve the physicochemical properties such as water solubility and stability of compounds. This review summarizes the structural characteristics, catalytic mechanism, functional characterization, and biocatalytic applications of SCPL-AT from plants. This will help to promote the functional characterization of these acyltransferase genes and the biosynthesis of useful plant secondary metabolites by synthetic biotechnology.
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http://dx.doi.org/10.13345/j.cjb.210179DOI Listing
June 2021

Protective effect of rhaponticin on ovariectomy-induced osteoporosis in rats.

J Biochem Mol Toxicol 2021 Jul 5:e22837. Epub 2021 Jul 5.

Department of Rehabilitation Medicine, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, China.

Rhaponticin is a constituent isolated from numerous medicinal herbs. It has been reported earlier that rhaponticin possesses numerous biological effects like antiallergic, antidiabetic, hepatoprotective, and antithrombosis. The goal of this exploration was to scrutinize the therapeutic potential of rhaponticin on ovariectomy (OVX)-triggered osteoporosis in rats. Female Sprague Dawley rats were arbitrarily allocated to a sham-operated control group I, group II, which underwent OVX, and groups III and IV that underwent OVX were administered with rhaponticin (10 and 20 mg/kg). Rhaponticin was supplemented orally after 4 weeks of OVX and continued for about 16 weeks. Our findings exhibit that rhaponticin prevented the BMD diminution of femurs, induced by OVX, and protected the worsening of trabecular microarchitecture that are assisted through a noteworthy decline in skeletal remodeling as noticed through the diminished status of bone markers in a dose-dependent manner (10 and 20 mg/kg). OVX rats treated with rhaponticin efficiently enhanced body weight, lipid profiles, uterine index, bone turnover markers, inflammatory markers, and augmented the incidence of calcium in the OVX rats. Rhaponticin was established to restrain the functions of acid phosphatase, estradiol, and bone gla protein in OVX rats. Also, rhaponticin displayed some beneficial effects on histomorphometric and histopathological examination. It was observed that tabular area and thickness were reinstated in sham control and rhaponticin-treated OVX rats. We recognized that rhaponticin did not induce a damaging outcome on the skeletal organization of OVX rats. Moreover, we denote that rhaponticin can be an exceptional agent for the treatment and deal with associated bone diseases.
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http://dx.doi.org/10.1002/jbt.22837DOI Listing
July 2021

Meta-analysis of high power short duration in atrial fibrillation ablation - a superior efficient ablation strategy.

Acta Cardiol 2021 Jul 5:1-19. Epub 2021 Jul 5.

Department of Cardiology, Shanghai Chest Hospital, Shanghai, China.

Background: The high power short duration (HPSD) approach was hoped to further improve the efficacy and safety in radiofrequency ablation of atrial fibrillation (AF), compared with Low power long duration (LPLD). However, the conclusion was controversial based on the previous limited data. The aim of this meta-analysis was to evaluate whether the clinical benefits of HPSD are superior to that of LPLD.

Methods: The PubMed, OVID, the Cochrane Library, and Elsevier's ScienceDirect databases were searched for clinical studies to compare HPSD and LPLD approach by simple search strings benefiting to a wider screened scope.

Results: Fifteen trials with 3255 patients were included in this analysis. Pooled analyses suggested that HPSD was associated with a lower recurrence of atrial tachyarrhythmias (ATAs) at 1-year follow-up (OR: 0.49; 95% CI: 0.35 to 0.67,  < .0001), benefitted from AF recurrence reduced (OR: 0.46; 95% CI: 0.31 to 0.67,  < .0001), rather than atrial tachycardia/atrial flutter (AT/AFL), but similar at 6 months follow-up, with a decreased oesophageal thermal injury (ETI) (OR: 0.48; 95% CI: 0.30 to 0.77,  = .002). Meanwhile, the HPSD approach benefitted to increase first-pass pulmonary vein isolation (FPI) (OR: 0.47; 95% CI: 0.34 to 0.64,  < .00001) and decrease acute pulmonary vein re-isolation (PVR) (OR: 0.45; 95% CI: 0.35 to 0.58,  < .00001), both mainly embodied in left pulmonary veins (PVs). HPSD showed a decreased procedural time (SMD: -0.95; 95% CI: -1.06 to -0.85,  < .00001), ablation number for pulmonary vein isolation (PVI) (SMD: -0.41; 95% CI: -0.58 to -0.24,  < .00001) and fluoroscopy time (SMD: -0.22; 95% CI: -0.32 to -0.12,  < .0001), which benefits from PVI + additional ablation strategy (SMD: -0.33; 95% CI: -0.46 to -0.21,  < .0001).

Conclusions: The HPSD approach was associated with decreasing post-ablation AF recurrence in the 1-year follow-up, ETI, acute PVR (increasing FPI correspondingly), procedural time, ablation number for PVI and fluoroscopy time, benefitted to improve clinical outcomes and procedural process with improved safety.
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http://dx.doi.org/10.1080/00015385.2021.1939512DOI Listing
July 2021

Changes in global terrestrial live biomass over the 21st century.

Sci Adv 2021 Jul 2;7(27). Epub 2021 Jul 2.

Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, USA.

Live woody vegetation is the largest reservoir of biomass carbon, with its restoration considered one of the most effective natural climate solutions. However, terrestrial carbon fluxes remain the largest uncertainty in the global carbon cycle. Here, we develop spatially explicit estimates of carbon stock changes of live woody biomass from 2000 to 2019 using measurements from ground, air, and space. We show that live biomass has removed 4.9 to 5.5 PgC year from the atmosphere, offsetting 4.6 ± 0.1 PgC year of gross emissions from disturbances and adding substantially (0.23 to 0.88 PgC year) to the global carbon stocks. Gross emissions and removals in the tropics were four times larger than temperate and boreal ecosystems combined. Although live biomass is responsible for more than 80% of gross terrestrial fluxes, soil, dead organic matter, and lateral transport may play important roles in terrestrial carbon sink.
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http://dx.doi.org/10.1126/sciadv.abe9829DOI Listing
July 2021

Decoupling mechanism of Acid Orange 7 decolorization and sulfate reduction by a Caldanaerobacter dominated extreme-thermophilic consortium.

J Hazard Mater 2021 Jun 25;419:126498. Epub 2021 Jun 25.

Center of Wastewater Resource Recovery, College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China. Electronic address:

The biological treatment of textile wastewater discharged from the dye baths and rinsing processes are challenged by both high temperatures of 50-80 °C and sulfate reduction. At present, most studies report azo dyes can be removed under mesophilic conditions, but the sulfate reduction is inevitable, consuming extra electron donors and producing undesirable sulfide. In this work, a Caldanaerobacter (> 97%) dominated extreme-thermophilic consortium (EX-AO7) was enriched using xylose as the substrate. The typical sulfate-reducing enzymes such as sulfite oxidase and sulfite reductase were not identified in enriched EX-AO7 by the metagenomic analysis. Then, the decolorization and sulfate reduction were expectedly decoupled by enriched EX-AO7 in extreme-thermophilic conditions, in which no sulfide was detected during the AO7 decolorization process. AO7 of 100 and 200 mg/L could be totally decolorized by EX-AO7. However, when 400 mg/L AO7 was added, the residual AO7 concentration was 22 ± 19 mg/L after 24 h, which was mainly due to the toxicity of AO7. Dosing zero-valent iron (ZVI) could also promote AO7 decolorization by 1.7 times since the addition of ZVI could provide a proliferative environment for EX-AO7 growth. Thereby, our work provides a new paradigm to promote the AZO dyes decolorization and minimize sulfate reduction.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126498DOI Listing
June 2021

CD38 Multi-Functionality in Oral Squamous Cell Carcinoma: Prognostic Implications, Immune Balance, and Immune Checkpoint.

Front Oncol 2021 15;11:687430. Epub 2021 Jun 15.

Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.

Background: CD38 belongs to the ribosyl cyclase family and is expressed on various hematological cells and involved in immunosuppression and tumor promotion. Although targeting CD38 antibodies has been approved for treatment of multiple myeloma, the function of CD38 in solid tumor, oral squamous cell carcinoma (OSCC) , has not been investigated.

Methods: This retrospective study included 92 OSCC samples and analyzed the spatial distribution of CD38 by immunohistochemistry (IHC). The values of diagnosis and prognosis of CD38 were evaluated. Additionally, 53 OSCC preoperative peripheral blood samples were used to be analyzed by flow cytometry. Tumor Immune Estimation Resource (TIMER) and cBioPortal databases were used to study CD38 level in various tumors and its correlation with tumor immune microenvironment in head and neck squamous cell carcinoma (HNSCC).

Results: CD38 ubiquitously presented in tumor cells (TCs), fibroblast-like cells (FLCs), and tumor-infiltrating lymphocytes (TILs). Patients with highly expressed CD38 in TCs (CD38) had higher TNM stage and risk of lymph node metastasis. Upregulation of CD38 in FLCs (CD38) was significantly associated with poor WPOI. Escalated CD38 in TILs (CD38) led to higher Ki-67 level of tumor cells. Moreover, patients with enhanced CD38 were susceptible to postoperative metastasis occurrence, and those with highly expressed CD38 independently predicted shorter overall and disease-free survival. Strikingly, patients with highly expressed CD38, but not CD38 and CD38, had significantly lower CD3CD4 T cells and higher ratio of CD3CD16CD56NK cells. The imbalance of immune system is attributed to dysregulated immune checkpoint molecules (VISTA, PD-1, LAG-3, CTLA-4, TIGIT, GITR) as well as particular immune cell subsets, which were positively correlated with CD38 expression in HNSCC.

Conclusion: CD38 is a poor prognostic biomarker for OSCC patients and plays a vital role in governing immune microenvironment and circulating lymphocyte homeostasis. Co-expression between CD38 and immune checkpoint molecules provides new insight into immune checkpoint therapy.
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http://dx.doi.org/10.3389/fonc.2021.687430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239289PMC
June 2021

Associations between Adherence to Four A Priori Dietary Indexes and Cardiometabolic Risk Factors among Hyperlipidemic Patients.

Nutrients 2021 Jun 24;13(7). Epub 2021 Jun 24.

School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518106, China.

Little is known about which currently available a priori dietary indexes provide best guidance for reducing cardiometabolic risk factors (CMRF) among hyperlipidemic patients. This study was designed to compare the associations between four a priori dietary indexes, including Diet Balance Index (DBI-16), Chinese Healthy Eating Index (CHEI), Mediterranean Diet Score (MDS) and Dietary Approaches to Stop Hypertension (DASH) and CMRF among hyperlipidemic patients. A total of 269 participants were enrolled into the cross-sectional study. DBI-16, CHEI, MDS, and DASH scores were calculated using established methods. CMRF was measured using standard methods. DBI-total scores (DBI-TS) were inversely associated with triglyceride concentrations and TC:HDL-C ratio, and positively associated with HDL-C and ApoA1 concentrations (all < 0.05), while the results for DBI-low bound scores (DBI-LBS) were opposite. DBI-high bound scores (DBI-HBS) and DASH scores were positively and inversely associated with glucose concentrations, respectively (both < 0.05). Higher diet quality distance (DQD) was positively associated with higher TC, LDL-C and ApoB concentrations, and TC:HDL-C and LDL-C:HDL-C ratios, and lower HDL-C and ApoA1 concentrations and ApoA1:ApoB ratio (all < 0.05). CHEI scores were inversely associated with triglyceride concentrations ( = 0.036). None of the dietary indexes was associated with blood pressures. DBI-16 provided most comprehensive evaluations of the overall diet quality and balance for optimizing cardiometabolic health among hyperlipidemic individuals.
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http://dx.doi.org/10.3390/nu13072179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308401PMC
June 2021

Proteomics Investigation of the Time Course Responses of RAW264.7 Macrophages to Infections With the Wild-Type and Twin-Arginine Translocation Mutant Strains of .

Front Cell Infect Microbiol 2021 14;11:679571. Epub 2021 Jun 14.

Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.

, a notorious intracellular pathogen, causes chronic infections in many mammals, including humans. The twin-arginine translocation (Tat) pathway transports folded proteins across the cytoplasmic membrane; protein substrates translocated by include ABC transporters, oxidoreductases, and cell envelope biosynthesis proteins. Previously, we showed that a Tat mutant of M28 exhibits reduced survival within murine macrophages. In this study, we compared the host responses elicited by wild-type M28 and its Tat-mutant strains ex vivo. We utilized label-free quantitative proteomics to assess proteomic changes in RAW264.7 macrophages after infection with M28 and its Tat mutants. A total of 6085 macrophage proteins were identified with high confidence, and 79, 50, and 99 proteins were differentially produced upon infection with the Tat mutant at 4, 24, and 48 hpi, respectively, relative to the wild-type infection. Gene ontology and KEGG enrichment analysis indicated that immune response-related proteins were enriched among the upregulated proteins. Compared to the wild-type M28 infection, the most upregulated proteins upon Tat-mutant infection included the cytosolic nucleic acid signaling pathway-related proteins IFIH1, DHX58, IFI202, IFI204, and ISG15 and the NF-B signaling pathway-related proteins PTGS2, CD40, and TRAF1, suggesting that the host increases the production of these proteins in response to Tat mutant infection. Upregulation of some proteins was further verified by a parallel reaction monitoring (PRM) assay. ELISA and qRT-PCR assays indicated that Tat mutant infection significantly induced proinflammatory cytokine (TNF-α and IL-6) and nitric oxide (NO) production. Finally, we showed that the Tat mutant displays higher sensitivity to nitrosative stress than the wild type and that treatment with the NO synthase inhibitor L-NMMA significantly increases the intracellular survival of the Tat mutant, indicating that NO production contributes to restricting Tat mutant survival within macrophages. Collectively, this work improves our understanding of host immune responses to Tat mutants and provides insights into the mechanisms underlying the attenuated virulence of Tat mutants.
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http://dx.doi.org/10.3389/fcimb.2021.679571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238042PMC
July 2021

Exploring the Key Genes and Identification of Potential Diagnosis Biomarkers in Alzheimer's Disease Using Bioinformatics Analysis.

Front Aging Neurosci 2021 14;13:602781. Epub 2021 Jun 14.

Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Alzheimer's disease (AD) is one of the major threats of the twenty-first century and lacks available therapy. Identification of novel molecular markers for diagnosis and treatment of AD is urgently demanded, and genetic biomarkers show potential prospects.

Method: We identify and intersected differentially expressed genes (DEGs) from five microarray datasets to detect consensus DEGs. Based on these DEGs, we conducted Gene Ontology (GO), performed the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, constructed a protein-protein interaction (PPI) network, and utilized Cytoscape to identify hub genes. The least absolute shrinkage and selection operator (LASSO) logistic regression was applied to identify potential diagnostic biomarkers. Gene set enrichment analysis (GSEA) was performed to investigate the biological functions of the key genes.

Result: We identified 608 consensus DEGs, several dysregulated pathways, and 18 hub genes. Sixteen hub genes dysregulated as AD progressed. The diagnostic model of 35 genes was constructed, which has a high area under the curve (AUC) value in both the validation dataset and combined dataset (AUC = 0.992 and AUC = 0.985, respectively). The model can also differentiate mild cognitive impairment and AD patients from controls in two blood datasets. Brain-derived neurotrophic factor (BDNF) and WW domain-containing transcription regulator protein 1 (WWTR1), which are associated with the Braak stage, Aβ 42 levels, and β-secretase activity, were identified as critical genes of AD.

Conclusion: Our study identified 16 hub genes correlated to the neuropathological stage and 35 potential biomarkers for the diagnosis of AD. WWTR1 were identified as candidate genes for future studies. This study deepens our understanding of the transcriptomic and functional features and provides new potential diagnostic biomarkers and therapeutic targets for AD.
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http://dx.doi.org/10.3389/fnagi.2021.602781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236887PMC
June 2021

Eosinophilic interstitial nephritis and cardiac insufficiency in Kimura's disease: a case report.

BMC Nephrol 2021 Jun 30;22(1):241. Epub 2021 Jun 30.

Department of Nephrology, The Third Affiliated Hospital of Soochow University, No. 185, Juqian Road, Changzhou, 213003, Jiangsu Province, China.

Background: Kimura's disease (KD) is a rare chronic inflammatory disease and the etiology remains uncharacterized. The typical manifestations are painless lymph node or subcutaneous masses. There is currently no report of prominent renal interstitial injury and cardiac insufficiency in KD.

Case Presentation: A 45-year-old man was referred to our hospital with dark urine, subcutaneous masses in forehead and right retroauricular, multiple lymphadenopathy and unexplained cardiac insufficiency. Renal biopsy demonstrated eosinophilic interstitial nephritis. Laboratory tests revealed eosinophilia and a high level of serum IgE. A biopsy of cervical lymph node was performed and KD was diagnosed. Treatment with oral prednisone resulted in a decrease of eosinophil, serum IgE, improvement of cardiac function, and regression of the subcutaneous mass.

Conclusions: We describe an extremely rare KD case presenting with eosinophilic interstitial nephritis, cardiac insufficiency and significant response to prednisone. The clinicians should improve the disease awareness and find optimal treatment.
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http://dx.doi.org/10.1186/s12882-021-02454-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243299PMC
June 2021

Smad3 gene C-terminal phosphorylation site mutation exacerbates CCl-induced hepatic fibrogenesis by promoting pSmad2L/C-mediated signaling transduction.

Naunyn Schmiedebergs Arch Pharmacol 2021 Aug 30;394(8):1779-1786. Epub 2021 Jun 30.

Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.

Current researches have confirmed that Smads, mediators of TGF-β signaling, are strictly controlled by domain-specific site phosphorylation in the process of hepatic disease. Usually, Smad3 phospho-isoform pSmad3L and pSmad3C are reversible and antagonistic; pSmad2L/C could act together with pSmad3L by stimulating PAI-1 expression and ECM synthesis to transmit fibrogenic signals. Our recent study found that pSmad3C mutation is supposed to perform a vigorous role on the early phase of liver injury and abates salvianolic acid B's anti-hepatic fibrotic-carcinogenesis. However, whether pSmad3C mutation expedites pSmad2L/C-mediated signaling transduction during hepatic fibrogenesis remains vague. Presently, Smad3 gene C-terminal phosphorylation site mutation heterozygote (pSmad3C) mice were constructed to probe if and how pSmad3C retards CCl-induced hepatic fibrogenesis by inhibiting pSmad2L/C-mediated signaling transduction. Twelve 6-week-old pSmad3C C57BL/6J mice were intraperitoneally injection with CCl for 6 weeks to induce liver fibrogenesis. Results showed that pSmad3C mutation aggravates the relative liver weight, biochemical parameters, collagenous fibers and fibrotic septa formation, contributes to fibrogenesis in HT-CCl mice. Furthermore, fibrotic-related proteins TGF-β, pSmad2C, pSmad2L, and PAI-1 were also increased in CCl-induced pSmad3C mice. These results suggest that pSmad3C mutation exacerbates hepatic fibrogenesis which relates to intensifying pSmad2L/C-mediated signaling transduction.
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http://dx.doi.org/10.1007/s00210-021-02114-1DOI Listing
August 2021

Asiaticoside-laden silk nanofiber hydrogels to regulate inflammation and angiogenesis for scarless skin regeneration.

Biomater Sci 2021 Jul;9(15):5227-5236

Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, USA.

Scarless skin regeneration remains a challenge due to the complicated microenvironment involved in wound healing. Here, the hydrophobic drug, asiaticoside (AC), was loaded inside silk nanofiber hydrogels to achieve bioactive and injectable matrices for skin regeneration. AC was dispersed in aqueous silk nanofiber hydrogels with retention of biological functions that regulated inflammatory reactions and vascularization in vitro. After implantation in full-thickness wound defects, these AC-laden hydrogel matrices achieved scarless wound repair. Inflammatory reactions and angiogenesis were regulated during inflammation and remodeling, which was responsible for wound regeneration similar to normal skin. Both in vitro and in vivo studies demonstrated promising applications of these AC-laden silk hydrogels towards scarless tissue regeneration.
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http://dx.doi.org/10.1039/d1bm00904dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319114PMC
July 2021

Reply.

J Hypertens 2021 Aug;39(8):1728-1729

Department of Endocrinology, Tongi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.

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http://dx.doi.org/10.1097/HJH.0000000000002883DOI Listing
August 2021
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