Publications by authors named "Xu Huang"

392 Publications

Co-composting materials can further affect the attenuation of antibiotic resistome in soil application.

Waste Manag 2021 Sep 28;135:329-337. Epub 2021 Sep 28.

Key Lab of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China. Electronic address:

This study investigated the effects of representative co-substrate (corncob particles) and additive (brick granules) alone on antibiotic resistome of swine manure during composting and subsequent compost application. For relative abundances, four antibiotic resistance gene (ARG) types encoding resistance to aminoglycoside, multidrug, florfenicol-chloramphenicol-amphenicol-fluoroquinolone-quinolone, and sulfonamide increased remarkably during composting, whereas all the ARG types decreased after compost application. Interestingly, much more ARG subtypes (50.1% in total) were reduced in corncob addition treatment. Meanwhile, the addition of corncob particles lowered the relative abundance and diversity of ARGs more significantly. Microbial community exhibited conspicuous changes across the manure, compost, and soil samples where the dominant genera were completely different. Procrustes test proved the co-occurrence and driving effect of microbial community on resistome variation, especially in corncob addition treatment during composting. Network analysis demonstrated that the dissipation of the dominant genera such as Ruminofilibacter, Luteimonas, and Pseudidiomarina in the composts after application contributed greatly to the reduction in ARG relative abundance. Besides, the low abundance of mobile genetic elements (MGEs) in soil also accounted for the attenuation of ARGs to some extent. Our findings clearly proved that co-composting materials can further affect the attenuation of antibiotic resistome in soil application, which can help in understanding the spread and control of ARGs during agricultural process.
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http://dx.doi.org/10.1016/j.wasman.2021.09.016DOI Listing
September 2021

Combination Treatment with the Vimentin-Targeting Antibody hzVSF and Tenofovir Suppresses Woodchuck Hepatitis Virus Infection in Woodchucks.

Cells 2021 Sep 5;10(9). Epub 2021 Sep 5.

Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC 20057, USA.

Current treatment options for patients infected with hepatitis B virus (HBV) are suboptimal, because the approved drugs rarely induce cure due to the persistence of the viral DNA genome in the nucleus of infected hepatocytes, and are associated with either severe side effects (pegylated interferon-alpha) or require life-long administration (nucleos(t)ide analogs). We report here the evaluation of the safety and therapeutic efficacy of a novel, humanized antibody (hzVSF) in the woodchuck model of HBV infection. hzVSF has been shown to act as a viral entry inhibitor, most likely by suppressing vimentin-mediated endocytosis of virions. Targeting the increased vimentin expression on liver cells by hzVSF after infection with HBV or woodchuck hepatitis virus (WHV) was demonstrated initially. Thereafter, hzVSF safety was assessed in eight woodchucks naïve for WHV infection. Antiviral efficacy of hzVSF was evaluated subsequently in 24 chronic WHV carrier woodchucks by monotreatment with three ascending doses and in combination with tenofovir alafenamide fumarate (TAF). Consistent with the proposed blocking of WHV reinfection, intravenous hzVSF administration for 12 weeks resulted in a modest but transient reduction of viral replication and associated liver inflammation. In combination with oral TAF dosing, the antiviral effect of hzVSF was enhanced and sustained in half of the woodchucks with an antibody response to viral proteins. Thus, hzVSF safely but modestly alters chronic WHV infection in woodchucks; however, as a combination partner to TAF, its antiviral efficacy is markedly increased. The results of this preclinical study support future evaluation of this novel anti-HBV drug in patients.
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http://dx.doi.org/10.3390/cells10092321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466705PMC
September 2021

Synergistic cytotoxicity of dual PI3K/mTOR and FLT3 inhibition in FLT3-ITD AML cells.

Adv Biol Regul 2021 Sep 17;82:100830. Epub 2021 Sep 17.

Cellular Signaling Unit, Section of Human Morphology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, 41125, Italy. Electronic address:

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy, characterized by a heterogeneous genetic landscape and complex clonal evolution, with poor outcomes. Mutation at the internal tandem duplication of FLT3 (FLT3-ITD) is one of the most common somatic alterations in AML, associated with high relapse rates and poor survival due to the constitutive activation of the FLT3 receptor tyrosine kinase and its downstream effectors, such as PI3K signaling. Thus, aberrantly activated FLT3-kinase is regarded as an attractive target for therapy for this AML subtype, and a number of small molecule inhibitors of this kinase have been identified, some of which are approved for clinical practice. Nevertheless, acquired resistance to these molecules is often observed, leading to severe clinical outcomes. Therapeutic strategies to tackle resistance include combining FLT3 inhibitors with other antileukemic agents. Here, we report on the preclinical activity of the combination of the FLT3 inhibitor quizartinib with the dual PI3K/mTOR inhibitor PF-04691502 in FLT3-ITD cells. Briefly, we show that the association of these two molecules displays synergistic cytotoxicity in vitro in FLT3-ITD AML cells, triggering 90% cell death at nanomolar concentrations after 48 h.
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http://dx.doi.org/10.1016/j.jbior.2021.100830DOI Listing
September 2021

Cypermethrin triggers YY1-mediated testosterone biosynthesis suppression.

Ecotoxicol Environ Saf 2021 Dec 17;225:112792. Epub 2021 Sep 17.

NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute, 420 Baohuan Road, Chongqing 400020, China.

Cypermethrin (CYP), an extensively-used broad-spectrum pyrethroid pesticide, is regarded as a potential environmental endocrine disruptor with the anti-androgenic characteristic. To explore underlying roles of non-coding RNAs and the Jak/Stat pathway in CYP-mediated testosterone biosynthesis suppression, SD rats and Leydig cells were employed in this work. Results displayed that β-CYP decreased plasma testosterone levels and led to abnormal alterations of testicular histomorphology and ultrastructures. LncRNA XIST and miR-142-5p were co-localized in the cytoplasm of Leydig cells, but the expression of XIST was inhibited by β-CYP while that of miR-142-5p was induced. Then overexpressed miR-142-5p dampened the Jak1/Stat1 pathway by directly targeting Jak1. Transcription factors NFκB and YY1 impeded by β-CYP were positively regulated by the Jak1/Stat1 pathway. Bidirectional Co-IP and ChIP assays demonstrated that NFκB interacted with and modulated YY1 by directly binding to the promoter region of YY1. ChIP, qPCR, and YY1 knockdown/overexpression assays indicated that YY1 acted as a transcriptional activator to directly modulate steroidogenic StAR and 3β-HSD in Leydig cells. Taken together, miR-142-5p sponged by lncRNA XIST directly targets the Jak1/Stat1 pathway, which regulates steroidogenic StAR and 3β-HSD via NFκB and YY1, and ultimately dampens testosterone production in Leydig cells.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112792DOI Listing
December 2021

Screening and heterologous expression of flavone synthase and flavonol synthase to catalyze hesperetin to diosmetin.

Biotechnol Lett 2021 Nov 12;43(11):2161-2183. Epub 2021 Sep 12.

Longping Branch Graduate School of Hunan University, Changsha, 410125, People's Republic of China.

Objectives: In this study, 44 flavone synthases (FNS) and flavonol synthases (FLS) from different origins were collected. The instability index and conserved domain of the enzymes were analyzed through bioinformatics analysis, the results of which allowed us to screen suitable enzymes for constructing recombinant Escherichia coli. Defective enzymes were selected as controls.

Results: Native- and sodium dodecyl sulfate-polyacrylamide gel electrophoresis were conducted to isolate the heterologously expressed proteins. Liquid chromatography-mass spectrometry, H nuclear magnetic resonance, and ultra-performance liquid chromatography were performed to qualitatively and quantitatively analyze the products. The cellular transformation results showed that recombinant E. coli catalyzed the synthesis of diosmetin from hesperetin, and in vitro catalysis showed that heterologously expressed FNS/FLS played a catalytic role in this reaction. AnFNS (from Angelica archangelica) showed the highest substrate conversion (38.80% for cellular transformation, 12.93% for in vitro catalysis).

Conclusions: The catalytic capacity of FNS/FLS from different origins exhibited the expected results, indicating that bioinformatics analysis is useful for screening enzymes. In addition, the catalytic properties of AnFNS and CaFLS (from Camellia sinensis) differed significantly, although these enzymes are structurally similar. Based on this difference, C-2 was predicted as the key site for FNS/FLS catalytic synthesis of diosmetin rather than C-3.
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http://dx.doi.org/10.1007/s10529-021-03184-0DOI Listing
November 2021

Chronic Exposure to Alcohol Inhibits New Myelin Generation in Adult Mouse Brain.

Front Cell Neurosci 2021 27;15:732602. Epub 2021 Aug 27.

Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology, Third Military Medical University (Army Medical University), Chongqing, China.

Chronic alcohol consumption causes cognitive impairments accompanying with white matter atrophy. Recent evidence has shown that myelin dynamics remain active and are important for brain functions in adulthood. For example, new myelin generation is required for learning and memory functions. However, it remains undetermined whether alcohol exposure can alter myelin dynamics in adulthood. In this study, we examine the effect of chronic alcohol exposure on myelin dynamics by using genetic approaches to label newly generated myelin (NG2-CreERt; mT/mG). Our results indicated that alcohol exposure (either 5% or 10% in drinking water) for 3 weeks remarkably reduced mGFP + /NG2- new myelin and mGFP + /CC1 + new oligodendrocytes in the prefrontal cortex and corpus callosum of 6-month-old NG2-CreERt; mT/mG mice as compared to controls without changing the mGFP + /NG2 + oligodendrocyte precursor cells (OPCs) density, suggesting that alcohol exposure may inhibit oligodendrocyte differentiation. In support with these findings, the alcohol exposure did not significantly alter apoptotic cell number or overall MBP expression in the brains. Further, the alcohol exposure decreased the histone deacetylase1 (HDAC1) expression in mGFP + /NG2 + OPCs, implying epigenetic mechanisms were involved in the arrested OPC differentiation. Together, our results indicate that chronic exposure to alcohol can inhibit myelinogenesis in the adult mouse brain and that may contribute to alcohol-related cognitive impairments.
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http://dx.doi.org/10.3389/fncel.2021.732602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429601PMC
August 2021

Impact of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Inflammatory Response and Viral Clearance in COVID-19 Patients.

Front Cardiovasc Med 2021 19;8:710946. Epub 2021 Aug 19.

Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.

To evaluate the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) on the inflammatory response and viral clearance in coronavirus disease 2019 (COVID-19) patients. We included 229 patients with confirmed COVID-19 in a multicenter, retrospective cohort study. Propensity score matching at a ratio of 1:3 was introduced to eliminate potential confounders. Patients were assigned to the ACEI/ARB group ( = 38) or control group ( = 114) according to whether they were current users of medication. Compared to the control group, patients in the ACEI/ARB group had lower levels of plasma IL-1β [(6.20 ± 0.38) vs. (9.30 ± 0.31) pg/ml, = 0.020], IL-6 [(31.86 ± 4.07) vs. (48.47 ± 3.11) pg/ml, = 0.041], IL-8 [(34.66 ± 1.90) vs. (47.93 ± 1.21) pg/ml, = 0.027], and TNF-α [(6.11 ± 0.88) vs. (12.73 ± 0.26) pg/ml, < 0.01]. Current users of ACEIs/ARBs seemed to have a higher rate of vasoconstrictive agents (20 vs. 6%, < 0.01) than the control group. Decreased lymphocyte counts [(0.76 ± 0.31) vs. (1.01 ± 0.45)10/L, = 0.027] and elevated plasma levels of IL-10 [(9.91 ± 0.42) vs. (5.26 ± 0.21) pg/ml, = 0.012] were also important discoveries in the ACEI/ARB group. Patients in the ACEI/ARB group had a prolonged duration of viral shedding [(24 ± 5) vs. (18 ± 5) days, = 0.034] and increased length of hospitalization [(24 ± 11) vs. (15 ± 7) days, < 0.01]. These trends were similar in patients with hypertension. Our findings did not provide evidence for a significant association between ACEI/ARB treatment and COVID-19 mortality. ACEIs/ARBs might decrease proinflammatory cytokines, but antiviral treatment should be enforced, and hemodynamics should be monitored closely. Since the limited influence on the ACEI/ARB treatment, they should not be withdrawn if there was no formal contraindication.
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http://dx.doi.org/10.3389/fcvm.2021.710946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416906PMC
August 2021

Editorial: Special Issue on Innovative Multi-Disciplinary Approaches for Precision Studies in Leukemia.

Front Oncol 2021 17;11:744009. Epub 2021 Aug 17.

Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.

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http://dx.doi.org/10.3389/fonc.2021.744009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416083PMC
August 2021

Determination of the Median Effective Dose of Dexmedetomidine for the Prevention of Emergence Agitation in Geriatric Patients Undergoing Major Open Surgery With General Anesthesia: A Prospective, Double-Blinded, Dose-Response Trial.

Dose Response 2021 Jul-Sep;19(3):15593258211037153. Epub 2021 Aug 27.

Department of Anesthesiology, The Affiliated AnQing Municipal Hospitals of Anhui Medical University, AnQing, China.

Dexmedetomidine can effectively decrease the incidences of emergence agitation (EA) in adult patients, but there are major side effects related to increased dose of dexmedetomidine. The purpose of this study was to determine the median effective dose of dexmedetomidine in the prevention of EA among geriatric patients undergoing major open surgery with general anesthesia. A total of 50 geriatric patients were enrolled in this study. Dexmedetomidine 0.5 μg·kg·h continuous intravenous infusion was administered to the first patient. The next dose was increased or decreased by .05 depending on the response of the previous patient, according to the Dixon up-and-down method. An "effective" or "ineffective" response was determined based on the Riker sedation-agitation score (RSAS), we defined "effective" as RSAS<5, and "ineffective" as RSAS≥5. The ED50 of dexmedetomidine in prevention of EA was .30 μg·kg·h (95% CI, .27-.33) and the predicted ED95 was .42 μg·kg·h (95% CI, .38-.51). The incidence of bradycardia was significantly increased in the group without EA compared to the group with EA (57.1% vs 13.6%, P = .002). The ED50 of dexmedetomidine in prevention of EA was .30 μg·kg·h (95% CI, .27-.33) and the predicted ED95 was .42 μg·kg·h (95% CI, .38-.51). Bradycardia was the main complication.
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http://dx.doi.org/10.1177/15593258211037153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404654PMC
August 2021

Abnormal amyloid beta metabolism in systemic abnormalities and Alzheimer's pathology: Insights and therapeutic approaches from periphery.

Ageing Res Rev 2021 11 25;71:101451. Epub 2021 Aug 25.

Division of Life Sciences and Applied Life Science (BK 21plus), College of Natural Science, Gyeongsang National University, Jinju, 52828, Republic of Korea. Electronic address:

Alzheimer's disease (AD) is an age-associated, multifactorial neurodegenerative disorder that is incurable. Despite recent success in treatments that partially improve symptomatic relief, they have failed in most clinical trials. Re-holding AD for accurate diagnosis and treatment is widely known as a challenging task. Lack of knowledge of basic molecular pathogenesis might be a possible reason for ineffective AD treatment. Historically, a majority of therapy-based studies have investigated the role of amyloid-β (Aβ peptide) in the central nervous system (CNS), whereas less is known about Aβ peptide in the periphery in AD. In this review, we provide a comprehensive summary of the current understanding of Aβ peptide metabolism (anabolism and catabolism) in the brain and periphery. We show that the abnormal metabolism of Aβ peptide is significantly linked with central-brain and peripheral abnormalities; the interaction between peripheral Aβ peptide metabolism and peripheral abnormalities affects central-brain Aβ peptide metabolism, suggesting the existence of significant communication between these two pathways of Aβ peptide metabolism. This close interaction between the central brain and periphery in abnormal Aβ peptide metabolism plays a key role in the development and progression of AD. In conclusion, we need to obtain a full understanding of the dynamic roles of Aβ peptide at the molecular level in both the brain and periphery in relation to the pathology of AD. This will not only provide new information regarding the complex disease pathology, but also offer potential new clues to improve therapeutic strategies and diagnostic biomarkers for the successful treatment of AD.
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http://dx.doi.org/10.1016/j.arr.2021.101451DOI Listing
November 2021

Long non-coding RNA LINC00630 facilitates hepatocellular carcinoma progression through recruiting transcription factor E2F1 to up-regulate cyclin-dependent kinase 2 expression.

Hum Exp Toxicol 2021 Aug 21:9603271211038744. Epub 2021 Aug 21.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.

This study is aimed to investigate the role of long non-coding RNA 630 (LINC00630) in hepatocellular carcinoma (HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine LINC00630 expression in HCC cell lines and tissues. After LINC00630 was overexpressed or depleted in HCC cell lines, cell counting kit-8 (CCK-8) assay, BrdU assay, and flow cytometry were conducted for detecting HCC cell multiplication, apoptosis, and cell cycle progression. The catRAPID database was adopted to predict the binding relationship between LINC00630 and E2F transcription factor 1 (E2F1), and RNA pull-down and RNA immunoprecipitation (RIP) assays were carried out to verify this binding relationship. The binding of E2F1 to the cyclin-dependent kinase 2 (CDK2) promoter region was verified by dual-luciferase reporter gene assay and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assay. Western blotting was conducted to detect the protein expression of E2F1 and CDK2 in HCC cells. We report that LINC00630 expression was up-regulated in HCC and was significantly correlated with TNM stage and lymph node metastasis. LINC00630 overexpression facilitated HCC cell proliferation and cell cycle progression and inhibited the cell apoptosis, while LINC00630 knockdown had the opposite effects. LINC00630 directly bounds with E2F1. LINC00630 overexpression enhanced the binding of E2F1 to the CDK2 promoter region, thereby promoting CDK2 transcription, whereas knocking down LINC00630 inhibited CDK2 transcription. Collectively, LINC00630 promoted CDK2 transcription by recruiting E2F1 to the promoter region of CDK2, thereby promoting the malignant progression of HCC. Our data suggest that LINC00630 is a promising molecular target for HCC.
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http://dx.doi.org/10.1177/09603271211038744DOI Listing
August 2021

Two New Types of Homodiploid Fish and Polyploid Hybrids Derived from the Distant Hybridization of Female Koi Carp and Male Bighead Carp.

Mar Biotechnol (NY) 2021 Aug 16;23(4):628-640. Epub 2021 Aug 16.

State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.

Bighead carps  (Hypophthalmichthys nobilis) and silver carps (Hypophthalmichthys molitrix) represent an important component of freshwater ichthiofauna in its native range, though they might become mass propagation in other systems (North America) and the reason of concern for fisheries management. Therefore, understanding their reproductive traits and particularly in the context of hybridization with other cyprinids was of value to explain their rapid propagation as well as potential benefits for aquaculture due to their unique diet, behavior, growth potential, and tolerance to deteriorating environmental conditions in freshwater ecosystems. Distant hybridization is an effective tool to create different ploidy offspring with changed phenotypes and genotypes. In this study, we reported distant hybridization of female koi carp (Cyprinus carpio haematopterus, KOC, 2n = 100) × male bighead carp (Hypophthalmichthys nobilis, BIC, 2n = 48) and the spontaneous occurrence of two new "crucian" carp-like homodiploid fish (2nGCC-L; 2nCCC-L; 2n = 100), a new type of triploid hybrid (3nKB, 3n = 124), and a new type of tetraploid hybrid (4nKB, 4n = 148). The body color of 2nGCC-L and 2nCCC-L were gray and multicolor, respectively. Both phenotypes were similar to the crucian carp (Carassius auratus). The difference was that their heads were rounder than those of the crucian carp and they had higher backs. Compared with the KOC with two pairs of barbels and BIC without barbel, 2nGCC-L, 2nCCC-L, and 4nKB had no barbel, but 3nKB had one pair of barbels. Microsatellite patterns and 5S rDNA sequences confirmed that 2nGCC-L, 2nCCC-L, and 3nKB were of hybrid origin. In regard to feeding, KOC was omnivorous and BIC was a typical filter-feeder. However, the 2nGCC-L, 2nCCC-L, and 3nKB were omnivorous. The formation of four kinds of new offspring is a groundbreaking finding in fish genetic breeding and evolutionary biology.
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http://dx.doi.org/10.1007/s10126-021-10050-7DOI Listing
August 2021

Prediction of Healing Performance of Autogenous Healing Concrete Using Machine Learning.

Materials (Basel) 2021 Jul 21;14(15). Epub 2021 Jul 21.

Laboratory for Track Engineering and Operations for Future Uncertainties (TOFU Lab), School of Engineering, University of Birmingham, Birmingham B152TT, UK.

Cracks typically develop in concrete due to shrinkage, loading actions, and weather conditions; and may occur anytime in its life span. Autogenous healing concrete is a type of self-healing concrete that can automatically heal cracks based on physical or chemical reactions in concrete matrix. It is imperative to investigate the healing performance that autogenous healing concrete possesses, to assess the extent of the cracking and to predict the extent of healing. In the research of self-healing concrete, testing the healing performance of concrete in a laboratory is costly, and a mass of instances may be needed to explore reliable concrete design. This study is thus the world's first to establish six types of machine learning algorithms, which are capable of predicting the healing performance (HP) of self-healing concrete. These algorithms involve an artificial neural network (ANN), a k-nearest neighbours (kNN), a gradient boosting regression (GBR), a decision tree regression (DTR), a support vector regression (SVR) and a random forest (RF). Parameters of these algorithms are tuned utilising grid search algorithm (GSA) and genetic algorithm (GA). The prediction performance indicated by coefficient of determination (R) and root mean square error (RMSE) measures of these algorithms are evaluated on the basis of 1417 data sets from the open literature. The results show that GSA-GBR performs higher prediction performance (R = 0.958) and stronger robustness (RMSE = 0.202) than the other five types of algorithms employed to predict the healing performance of autogenous healing concrete. Therefore, reliable prediction accuracy of the healing performance and efficient assistance on the design of autogenous healing concrete can be achieved.
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http://dx.doi.org/10.3390/ma14154068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348520PMC
July 2021

Clinical factors associated with composition of lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired pneumonia.

Front Med 2021 Jul 24. Epub 2021 Jul 24.

China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, 100029, China.

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R = 0.033; P = 0.018), followed by acute kidney injury (AKI; R = 0.032; P = 0.011) and plasma MIP-1β level (R = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
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http://dx.doi.org/10.1007/s11684-021-0856-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302972PMC
July 2021

A Review of Conductive Carbon Materials for 3D Printing: Materials, Technologies, Properties, and Applications.

Materials (Basel) 2021 Jul 13;14(14). Epub 2021 Jul 13.

Innovation Center for Textile Science and Technology, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.

Carbon material is widely used and has good electrical and thermal conductivity. It is often used as a filler to endow insulating polymer with electrical and thermal conductivity. Three-dimensional printing technology is an advance in modeling and manufacturing technology. From the forming principle, it offers a new production principle of layered manufacturing and layer by layer stacking formation, which fundamentally simplifies the production process and makes large-scale personalized production possible. Conductive carbon materials combined with 3D printing technology have a variety of potential applications, such as multi-shape sensors, wearable devices, supercapacitors, and so on. In this review, carbon black, carbon nanotubes, carbon fiber, graphene, and other common conductive carbon materials are briefly introduced. The working principle, advantages and disadvantages of common 3D printing technology are reviewed. The research situation of 3D printable conductive carbon materials in recent years is further summarized, and the performance characteristics and application prospects of these conductive carbon materials are also discussed. Finally, the potential applications of 3D printable conductive carbon materials are concluded, and the future development direction of 3D printable conductive carbon materials has also been prospected.
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http://dx.doi.org/10.3390/ma14143911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307564PMC
July 2021

Morphological and hemodynamic analysis of the patient-specific renal cell carcinoma models.

J Biomech 2021 Sep 15;126:110636. Epub 2021 Jul 15.

Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing 100871, China.

Although the morbidity of renal cell carcinoma (RCC) has been increasing as the seventh most common tumours, to our knowledge, there is few studies foucsing on the hemodynamics of the renal artery (RA) with RCC. The objective of this study is to perform morphological and hemodynamic analysis of the RA and abdominal aorta artery (AAA) in the control healthy and RCC patient groups. Three-dimensional (3D) geometries are reconstructed from 18 control healthy subjects and 15 RCC patients based on Computed Tomography Angiography (CTA) images. There is higer in the lumen diameter of the RA (6.21 ± 0.89 mm) and curvature of the RA (1.2 ± 0.07) in the RCC patient group compared with the control healthy group (4.29 ± 1.08 mm, 1.1 ± 0.1), respectively. In the hemodynamic analysis, the surface area ratio (%) of low time-averaged wall shear stress (SAR-TAWSS) at the RA (10.65 ± 11.65) and AAA (48.49 ± 12.79) in the RCC patient group is significantly higher than that in the control healthy group (0.23 ± 0.22, 21.57 ± 20.5), respectively. It is found that RCC altered the morphology of the RA in the RCC patient group, which could deteriorate the hemodynamic environment of the RA and AAA. The finding in this study could enhance us to understand the progression of vascular disease caused by RCC.
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http://dx.doi.org/10.1016/j.jbiomech.2021.110636DOI Listing
September 2021

Risk Factors of Mortality From Pneumonia in Non-HIV Patients: A Meta-Analysis.

Front Public Health 2021 16;9:680108. Epub 2021 Jun 16.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.

We performed a meta-analysis to systematically review the risk factors of mortality from non-HIV-related pneumonia (PcP) and provide the theoretical basis for managing non-HIV-related PcP. PubMed, Embase, Web of Science, the Cochrane Library and CNKI databases were searched. A meta-analysis of the risk factors of mortality from non-HIV-related PcP was conducted. A total of 19 studies and 1,310 subjects were retrieved and included in the meta-analysis, including 485 and 825 patients in the non-survivor and survivor groups, respectively. In the primary analysis, age, concomitant with other pulmonary diseases at diagnosis of PcP, solid tumors, cytomegalovirus(CMV) co-infection, lactate dehydrogenase (LDH), lymphocyte count, invasive ventilation during hospitalization, and pneumothorax were associated with mortality from non-HIV-related PcP, whereas sex, albumin, PcP prophylaxis, use of corticosteroids after admission, and time from onset of symptoms to treatment were not associated with mortality from non-HIV-related PcP. The mortality rate of non-HIV-infected patients with PcP was still high. Age, concomitant with other pulmonary diseases at diagnosis of PcP, solid tumors, CMV co-infection, LDH, lymphocyte count, invasive ventilation during hospitalization, and pneumothorax were risk factors of mortality from non-HIV-related PcP. Improved knowledge of prognostic factors is crucial to guide early treatment.
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http://dx.doi.org/10.3389/fpubh.2021.680108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244732PMC
August 2021

Chidamide and Radiotherapy Synergistically Induce Cell Apoptosis and Suppress Tumor Growth and Cancer Stemness by Regulating the MiR-375-EIF4G3 Axis in Lung Squamous Cell Carcinomas.

J Oncol 2021 11;2021:4936207. Epub 2021 Jun 11.

Department of Radiation Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

As a selective histone deacetylase (HDAC) inhibitor developed in China, chidamide has been applied for the treatment of refractory peripheral T-cell lymphoma (PTCL) and multiple solid tumors, including lung cancer. However, the underlying mechanisms are not well elucidated. In our present study, we found that chidamide and radiation acted synergistically to suppress cell and xenograft growth of lung squamous cell carcinoma cells by inducing cell apoptosis. Moreover, chidamide alone or a combination of chidamide and radiation treatment inhibited cancer cell stemness. miRNA microarray analysis demonstrated that miR-375 was the highest upregulated microRNA (miRNA) in NCI-2170 and NCI-H226 cells treated with chidamide alone or treated with chidamide plus radiation, compared with normal control. Inhibition of miR-375 attenuated the promoting effect of chidamide alone and chidamide plus radiation-induced NCI-2170 and NCI-H226 cell apoptosis and reverted the suppression of cancer stemness caused by chidamide alone or chidamide plus radiation treatment. Moreover, EIF4G3, a scaffold protein in the translation initiation complex, was found to be a direct target of miR-375 based on the luciferase reporter assay and western blot analysis. Interestingly, both chidamide alone and chidamide plus radiation treatments suppressed the mRNA and protein expression of EIF4G3. Silence of EIF4G3 also induced cell apoptosis and suppressed tumor growth in NCI-2170 and NCI-H226 cells. These data suggest that chidamide shows a synergistic effect with radiation therapy on lung squamous cell carcinomas by modulating the miR-375-EIF4G3 axis, which may afford an effective strategy to overcome the drug resistance of chidamide in clinical cancer therapy.
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http://dx.doi.org/10.1155/2021/4936207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214506PMC
June 2021

Formation of autotriploid Carassius auratus and its fertility-related genes analysis.

BMC Genomics 2021 Jun 10;22(1):435. Epub 2021 Jun 10.

State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploid Fish Reproduction and Breeding of the State Education Ministry, College of Life Sciences, Hunan Normal University, Hunan, 410081, Changsha, People's Republic of China.

Background: Formation of triploid organism is useful in genetics and breeding. In this study, autotriploid Carassius auratus (3nRR, 3n = 150) was generated from Carassius auratus red var. (RCC, 2n = 100) (♀) and autotetraploid Carassius auratus (4nRR, 4n = 200) (♂). The female 3nRR produced haploid, diploid and triploid eggs, whereas the male 3nRR was infertile. The aim of the present study was to explore fertility of potential candidate genes of 3nRR.

Results: Gonadal transcriptome profiling of four groups (3 females RCC (FRCC), 3 males 4nRR (M4nRR), 3 males 3nRR (M3nRR) and 3 females 3nRR (F3nRR)) was performed using RNA-SEq. A total of 78.90 Gb of clean short reads and 24,262 differentially expressed transcripts (DETs), including 20,155 in F3nRR vs. FRCC and 4,107 in M3nRR vs. M4nRR were identified. A total of 106 enriched pathways were identified through KEGG enrichment analysis. Out of the enriched pathways, 44 and 62 signalling pathways were identified in F3nRR vs. FRCC and M3nRR vs. M4nRR, respectively. A total of 80 and 25 potential candidate genes for fertility-related in F3nRR and M3nRR were identified, respectively, through GO, KEGG analyses and the published literature. Moreover, protein-protein interaction (PPI) network construction of these fertility-associated genes were performed. Analysis of the PPI networks showed that 6 hub genes (MYC, SOX2, BMP4, GATA4, PTEN and BMP2) were involved in female fertility of F3nRR, and 2 hub genes (TP53 and FGF2) were involved in male sterility of M3nRR.

Conclusions: Establishment of autotriploid fish offers an ideal model to study reproductive traits of triploid fish. RNA-Seq data revealed 6 genes, namely, MYC, SOX2, BMP4, GATA4, PTEN and BMP2, involved in the female fertility of the F3nRR. Moreover, 2 genes, namely, TP53 and FGF2, were related to the male sterility of the M3nRR. These findings provide information on reproduction and breeding in triploid fish.
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http://dx.doi.org/10.1186/s12864-021-07753-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191051PMC
June 2021

Association between genetic variants in and inflammatory bowel disease risk in Caucasians: a meta-analysis and trial sequential analysis.

Expert Rev Clin Immunol 2021 Aug 14;17(8):915-921. Epub 2021 Jun 14.

Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan Hubei Province, China.

Objective: The published studies regarding the relationships between zinc finger 365 (ZNF365) polymorphisms and inflammatory bowel disease (IBD) risk in Caucasians have yielded conflicting results. Therefore, we performed a meta-analysis to clarify this issue.

Methods: The Electronic databases of PubMed, Web of Science, Wiley Online Library, and EMBASE were searched for eligible studies up to 31 November 2020. The quality of eligible studies was evaluated using the Newcastle-Ottawa Scale. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) under different genetic models were calculated to assess the strength of associations.

Results: A total of 22 relevant case-control studies with 9542 ulcerative colitis (UC) patients and 13,886 controls, as well as 13,651 Crohn's disease (CD) patients and 15,256 controls, were involved in our meta-analysis. rs10761659 polymorphism significantly decreased CD and UC risk (except for the heterozygous model and the dominant model in UC), and rs10995271 polymorphism was significantly associated with UC (except for the heterozygous model and dominant model) rather than CD.

Conclusions: The meta-analysis demonstrated that the rs10761659 polymorphism might be a protective factor for both UC and CD in Caucasians, while the rs10995271 polymorphism might be a risk factor for UC rather than CD in Caucasians.
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http://dx.doi.org/10.1080/1744666X.2021.1939012DOI Listing
August 2021

A KDM4A-PAF1-mediated epigenomic network is essential for acute myeloid leukemia cell self-renewal and survival.

Cell Death Dis 2021 06 3;12(6):573. Epub 2021 Jun 3.

Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.

Epigenomic dysregulation is a common pathological feature in human hematological malignancies. H3K9me3 emerges as an important epigenomic marker in acute myeloid leukemia (AML). Its associated methyltransferases, such as SETDB1, suppress AML leukemogenesis, whilst H3K9me3 demethylases KDM4C is required for mixed-lineage leukemia rearranged AML. However, the specific role and molecular mechanism of action of another member of the KDM4 family, KDM4A has not previously been clearly defined. In this study, we delineated and functionally validated the epigenomic network regulated by KDM4A. We show that selective loss of KDM4A is sufficient to induce apoptosis in a broad spectrum of human AML cells. This detrimental phenotype results from a global accumulation of H3K9me3 and H3K27me3 at KDM4A targeted genomic loci thereby causing downregulation of a KDM4A-PAF1 controlled transcriptional program essential for leukemogenesis, distinct from that of KDM4C. From this regulatory network, we further extracted a KDM4A-9 gene signature enriched with leukemia stem cell activity; the KDM4A-9 score alone or in combination with the known LSC17 score, effectively stratifies high-risk AML patients. Together, these results establish the essential and unique role of KDM4A for AML self-renewal and survival, supporting further investigation of KDM4A and its targets as a potential therapeutic vulnerability in AML.
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http://dx.doi.org/10.1038/s41419-021-03738-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175737PMC
June 2021

[Risk factors and diagnostic methods of intensive care unit-acquired weakness].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Apr;33(4):460-465

Respiratory Center, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, World Health Organization Collaborating Center for Tobacco Cessation and Respiratory Diseases Prevention, Beijing 100029, China. Corresponding author: Huang Linna, Email:

Objective: To explore the risk factors of intensive care unit-acquired weakness (ICU-AW) and the characteristics of Medical Research Council (MRC) score and electromyogram.

Methods: A case control study was conducted. Patients with mechanical ventilation ≥ 7 days and MRC score admitted to department of respiratory and critical care medicine of China-Japan Friendship Hospital from September 2018 to January 2020 were enrolled, and they were divided into ICU-AW group (MRC score < 48) and non-ICU-AW group (MRC score ≥ 48) according to MRC score. The general situation, past medical history, related risk factors, MRC score, respiratory support mode, laboratory examination results, electromyogram examination results, ICU-AW related treatment, outcome and length of ICU stay were collected, and the differences between the two groups were compared. The risk factors of ICU-AW were analyzed by binary multivariate Logistic regression, and the characteristics of MRC score and electromyogram were analyzed.

Results: A total of 60 patients were enrolled in the analysis, including 17 patients in ICU-AW group and 43 patients in non-ICU-AW group. Univariate analysis showed that there were significant differences in acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, brain natriuretic peptide (BNP), blood urea nitrogen (BUN) on the first day of ICU admission and the ratio of invasive mechanical ventilation between ICU-AW group and non-ICU-AW group [APACHE II score: 21 (18, 25) vs. 18 (15, 22), SOFA score: 7 (5, 12) vs. 5 (3, 8), BNP (ng/L): 364.3 (210.1, 551.2) vs. 160.1 (66.8, 357.8), BUN (mmol/L): 9.9 (6.2, 17.0) vs. 6.0 (4.8, 9.8), invasive mechanical ventilation ratio: 88.2% vs. 46.5%, all P < 0.05]. Binary multivariate Logistic regression analysis showed no independent risk factor for ICU-AW. The average MRC score of 17 ICU-AW patients was 33±11. The limb weakness was symmetrical, and the proximal limb weakness was the main manifestation. Electromyography examination showed that the results of nerve conduction examination in ICU-AW patients mainly revealed that the amplitude of compound muscle action potential (CMAP) and sensory nerve action potentials (SNAP) were decreased, and the conduction velocity was slowed down; needle electromyography showed increased area of motor unit potential (MUP), prolonged time limit and a large number of spontaneous potentials. Prognosis evaluation showed that compared with non-ICU-AW group, patients in ICU-AW group underwent more tracheotomy (70.6% vs. 11.6%), longer length of ICU stay (days: 57±52 vs. 16±8), and more rehabilitation treatment (58.8% vs. 14.0%), and the differences were statistically significant (all P < 0.01).

Conclusions: The occurrence of ICU-AW may be related to high APACHE II score and SOFA score, high levels of BNP and BUN on the first day of ICU admission and the proportion of invasive mechanical ventilation, but the above factors are not independent risk factors for ICU-AW. The MRC score of ICU-AW patients was characterized by symmetrical limb weakness, mainly proximal limb weakness; in electromyography examination, the nerve conduction examination results mainly showed that CMAP and SNAP amplitude were decreased, and conduction velocity was slowed down; needle electromyography examination showed increased MUP area, prolonged duration and a large number of spontaneous potentials.
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http://dx.doi.org/10.3760/cma.j.cn121430-20201117-00716DOI Listing
April 2021

CTU findings of duplex kidney in kidney: A rare duplicated renal malformation.

Open Med (Wars) 2021 19;16(1):651-654. Epub 2021 Apr 19.

Department of Radiology, Longgang District People's Hospital of Shenzhen & The Third Affiliated Hospital (Provisional) of The Chinese University of Hong Kong, Shenzhen, Guangdong Province, 518172, China.

Duplex kidney is a common congenital malformation appeared as duplication of pelvis and ureter. However, renal duplication within sinus renalis is an extremely rare variation of the renal collecting system. In this study, we report a case of an asymptomatic kidney disease in a 33-year-old man, who demonstrates abnormal echo of renal sinus anomaly discovered incidentally in ultrasound examination. Computed tomography urography (CTU) exhibited the other small duplex kidney located in renal sinus. In the excretory phase images, the contrast medium within its small renal pelvis could be seen to flow into the right major renal calices. This case exhibited a very rare anatomical variation of duplicated renal malformation.
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http://dx.doi.org/10.1515/med-2021-0271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060981PMC
April 2021

Niche separation and weak interactions in the high tidal zone of saltmarsh-mangrove mixing communities.

Ecol Evol 2021 May 25;11(9):3871-3883. Epub 2021 Mar 25.

Key Laboratory of Urban Pollutant Conversion Institute of Urban Environment Chinese Academy of Sciences Xiamen China.

Saltmarsh-mangrove ecotones occur at the boundary of the natural geographic distribution of mangroves and salt marshes. Climate warming and species invasion can also drive the formation of saltmarsh-mangrove mixing communities. How these coastal species live together in a "new" mixed community is important in predicting the dynamic of saltmarsh-mangrove ecosystems as affected by ongoing climate change or human activities. To date, the understanding of species interactions has been rare on adult species in these ecotones.Two typical coastal wetlands were selected as cases to understand how mangrove and saltmarsh species living together in the ecotones. The leaves of seven species were sampled from these coastal wetlands based on their distribution patterns (living alone or coexisting) in the high tidal zone, and seven commonly used functional traits of these species were analyzed.We found niche separation between saltmarsh and mangrove species, which is probably due to the different adaptive strategies they adopted to deal with intertidal environments.Weak interactions between coexisting species were dominated in the high tidal zone of the two saltmarsh-mangrove communities, which could be driven by both niche differentiation and neutral theory.Synthesis. Our field study implies a potential opportunity to establish a multispecies community in the high tidal zone of saltmarsh-mangrove ecotones, where the sediment was characterized by low salinity and high nitrogen.
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http://dx.doi.org/10.1002/ece3.7263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093676PMC
May 2021

Identification and characterization of B220/B220 subpopulations in murine Gr1CD11b cells during tumorigenesis.

Oncoimmunology 2021 04 14;10(1):1912472. Epub 2021 Apr 14.

State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.

Although all murine MDSCs are defined as Gr1CD11b, their true immunophenotype remains elusive. In this study, we found murine Gr1CD11b cells can be divided into two subsets: Gr1CD11bB220 and Gr1CD11bB220, especially in the spleen tissues. Unlike the dominant B220 subset, the B220 subpopulation was not induced by tumor . Moreover, Gr1CD11bB220 cells from tumor-bearing mice spleens were unable to induce arginase 1 and inducible nitric oxide synthase expression, inhibit T cell proliferation, or promote tumor growth in primary tumor site. Nevertheless, these cells suppressed tumor metastasis and reduced cancer cell motility , while Gr1CD11bB220 cells from tumor-bearing mice spleens promoted tumor metastasis and enhanced cancer cell motility. Furthermore, both the polymorphonuclear (PMN-MDSCs) and monocytic MDSCs (Mo-MDSCs) could be further divided into B220 and B220 subsets; interestingly, tumor only induced the expansion of B220 PMN-MDSCs and B220 Mo-MDSCs, but not the B220 counterparts. Compared with B220 PMN-MDSCs and B220 Mo-MDSCs, the Ly6GLy6CCD11bB220 and Ly6GLy6CCD11bB220 cells from tumor-bearing mice spleens exhibited a more mature phenotype without immunosuppressive activity. Additionally, IL-6 deficiency attenuated the tumor-induced accumulation of MDSCs, B220 MDSCs and B220 PMN-MDSCs but increased the percentages of Gr1CD11bB220, Ly6GLy6CCD11bB220, and Ly6GLy6CCD11bB220 cells, indicating the opposing roles of the IL-6 signaling pathway in the expansion of B220 MDSCs and their B220 counterparts. Taken together, our findings indicate that the B220 subset is a distinct subset of Gr1CD11b cells functionally different from the B220 subpopulation during tumorigenesis and induction of MDSCs to B220 cells may be helpful for cancer therapy.
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http://dx.doi.org/10.1080/2162402X.2021.1912472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057082PMC
April 2021

Alendronate-functionalized hypoxia-responsive polymeric micelles for targeted therapy of bone metastatic prostate cancer.

J Control Release 2021 06 29;334:303-317. Epub 2021 Apr 29.

Institute of Special Environmental Medicine, Nantong University, Nantong, People's Republic of China. Electronic address:

Bone metastasis is one of the leading causes of cancer-related death and remains incurable in spite of great efforts. Bone-targeted nanoparticle-based drug carriers can overcome the difficulties in delivering therapeutic agents to metastatic bone and endowing them with a stimuli-responsive feature for controllable drug release can further maximize their therapeutic outcome. In light of hypoxic microenvironment of bone metastasis, we herein reported a bone-targeted and hypoxia-responsive polymeric micelle system for effective treatment of bone metastatic prostate cancer. The micelles were self-assembled from a polyethylene glycol and poly-l-lysine based copolymer using alendronate as a bone-targeted moiety and azobenzene as a hypoxia-responsive linker, showing a high affinity to metastatic bone and a high sensitivity in responding to hypoxia in vitro. In vivo studies further showed that after a selective accumulation in metastatic bone, the micelles could respond to hypoxic bone metastasis for rapid drug release to an effective therapeutic dosage. As a result, the micelles could suppress tumor growth in bone and inhibit bone destruction by inhibiting osteoclast activity and promoting osteoblast activity, achieving an enhanced therapeutic outcome with relieved bone pain and prolonged survival time. Bone-targeted and hypoxia-responsive nanocarriers therefore represent a promising advancement for treating bone metastasis. To our best knowledge, it might be the first example of the application of hypoxia-responsive nanocarriers in treating bone metastasis.
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http://dx.doi.org/10.1016/j.jconrel.2021.04.035DOI Listing
June 2021

Treatment with the Immunomodulator AIC649 in Combination with Entecavir Produces Antiviral Efficacy in the Woodchuck Model of Chronic Hepatitis B.

Viruses 2021 04 9;13(4). Epub 2021 Apr 9.

Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC 20057, USA.

As current interventions for chronic hepatitis B (CHB) rarely induce cure, more effective drugs are needed. Short-term treatment of woodchucks with the novel immunomodulator AIC649, a parapoxvirus-based stimulator of toll-like receptor 9 dependent and independent pathways, has been shown to reduce viral DNA and surface antigen via a unique, biphasic response pattern. The present study evaluated long-term AIC649 treatment in combination with Entecavir for potency and safety in woodchucks. AIC649 monotreatment induced modest reductions in serum viral DNA and surface and e antigens that were associated with the same biphasic response pattern previously observed. Entecavir monotreatment reduced transiently viremia but not antigenemia, while AIC649/Entecavir combination treatment mediated superior viral control. Undetectability of viral antigens and elicitation of antibodies in AIC649/Entecavir-treated woodchucks correlated with the expression of interferons and suppression of viral replication in liver. Combination treatment was well tolerated, and liver enzyme elevations were minor and transient. It was concluded that the AIC649-mediated effects were most likely based on an improvement and/or reconstitution of antiviral immune responses that are typically deficient in CHB. As a combination partner to Entecavir, the antiviral efficacy of AIC649 was markedly enhanced. This preclinical study supports future evaluation of AIC649 for treatment of human CHB.
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http://dx.doi.org/10.3390/v13040648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069054PMC
April 2021

MicroRNA-1269b inhibits gastric cancer development through regulating methyltransferase-like 3 (METTL3).

Bioengineered 2021 12;12(1):1150-1160

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan Hubei Province, China.

The dysregulation of microRNAs (miRNAs) expression is relevant to the progression of many tumors. As reported, the abnormal expression of miR-1269b is pivotal in certain cancers' progression. This work was designed to study the role and hidden mechanism of miR-1269b in gastric cancer (GC) progression. In this work, we proved that miR-1269b was lowly expressed in GC tissues and cell lines, which was associated with larger tumor size and lymph node metastasis. MiR-1269b overexpression repressed the multiplication, migration and invasion of GC cells while miR-1269b inhibition had the opposite effects. Methyltransferase-like 3 (METTL3) was identified as the direct target of miR-1269b in GC cells, and its overexpression reversed the inhibitory effect of transfection of miR-1269b mimics on GC cell viability, migration and invasion. On all accounts, these data indicated that miR-1269b inhibits GC progression via targeting METTL3.
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http://dx.doi.org/10.1080/21655979.2021.1909951DOI Listing
December 2021

Harpagide exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress via SERCA following oxygen-glucose deprivation/reoxygenation injury.

Neurosci Lett 2021 05 1;753:135874. Epub 2021 Apr 1.

College of Pharmacy, Zhe Jiang Chinese Medical University, Hangzhou, 310053, China. Electronic address:

Cerebrovascular diseases endanger human health, and the physiological and pathological processes of cerebral ischemia/reperfusion injury (CIRI) are critical for the occurrence of these diseases and as targets for their treatment. Here, we evaluated the effects of harpagide-mediated pharmacological and genetic inhibition of sarco-endoplasmic reticulum Ca-ATPase (SERCA) in vitro in PC12 cells. The molecular mechanism by which harpagide protects PC12 cells against oxygen-glucose deprivation/reoxygenation (OGD/R) injury was investigated by evaluating the cell survival rate with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, assessing apoptosis by flow cytometry, determining the intracellular Ca concentration ([Ca]) by laser scanning confocal microscopy (LSCM), and measuring the expression of proteins related to SERCA and endoplasmic reticulum stress (ERS) by Western blotting. The results revealed that harpagide significantly decreased thapsigargin (TG)-induced apoptosis of PC12 cells, downregulated the expression of ERS-related markers, considerably improved the TG-induced expression of SERCA-related proteins and reduced the [Ca], suggesting that harpagide effectively inhibited ERS directly. Moreover, harpagide did not significantly reduce OGD/R-induced apoptosis but increased the expression of ERS markers in PC12/SERCA cells, indicating that harpagide targets SERCA to protect against CIRI by suppressing ERS-mediated apoptosis.
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http://dx.doi.org/10.1016/j.neulet.2021.135874DOI Listing
May 2021

Risk factors for cerebral infarction in Takayasu arteritis: a single-centre case-controlled study.

Rheumatology (Oxford) 2021 Mar 27. Epub 2021 Mar 27.

Department of Rheumatology and Allergy, Xuanwu Hospital, Capital Medical University, Xicheng District, Beijing, China.

Objectives: We aimed to investigate the clinical features of Takayasu arteritis (TA) with cerebral infarction (CI) and the risk factors for CI.

Methods: The study analysed 122 consecutive patients with TA retrospectively. The clinical characteristics of TA patients with and without CI were compared. Binary logistic regression analysis was performed to determine risk factors for CI in TA patients.

Results: CI was present in 42 (34.4%) of 122 patients with TA. There were 33 patients with ischemic stroke and 11 with asymptomatic lacunar infarction, including two patients with both types of infarction. The CI group had a significantly higher proportion of males, higher prevalence of blurred vision, and higher Indian Takayasu Clinical Activity Score (ITAS) 2010 than the non-CI group. Binary logistic regression analysis indicated that hyperlipidaemia (OR 5.549, p = 0.021), ITAS 2010 (OR 1.123, p = 0.023), number of involved arteries (OR 1.307, p = 0.018), and middle cerebral artery (MCA) involvement (OR 4.013, p = 0.029) were significantly associated with CI in patients with TA. Receiver operating characteristic curves indicated fair performance of the ITAS 2010 (> 6) and number of involved arteries (> 7) for distinguishing TA patients at risk of CI from those without such risk.

Conclusion: Hyperlipidaemia, higher ITAS 2010, larger number of involved arteries, and MCA involvement are independent risk factors for CI in TA patients.
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http://dx.doi.org/10.1093/rheumatology/keab308DOI Listing
March 2021
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