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1.
Sci Total Environ ; 815: 152754, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34995588

RESUMO

Nanomaterials play a crucial role in various areas due to their extraordinary chemical and physical properties. Loading microscopic nanomaterials onto macrostructures is inevitable for their implementation from laboratory experiments to practical applications. Nevertheless, the geometries of conventional supporting structures are usually limited and nanomaterials are easy to be inhomogeneously distributed, aggregated, and lost. Therefore, controllably configuring nanomaterials into sophisticated three-dimensional macroscopic structures without sacrificing their inherent properties remains challenging. Here we utilize the advantages of 3D printing technology to realize this purpose. As a proof-of-concept, the application of 3D stereolithography printed macrostructures containing TiO2 nano particles (TiO2 NPs) for direct adsorption removal of As(III) in water was demonstrated. The morphology and distribution of TiO2 NPs mounted on printed macrostructures were initially characterized. Then batch adsorption experiments were conducted to investigate the effect of the 3D printing process, TiO2 NPs doped concentration and TiO2 NP size as well as adsorption kinetics and isotherms. We also demonstrated that 3D printed adsorption structures could be easily reused over 10 times and were effective for raw arsenic-polluted groundwater samples. Our findings show that 3D printing provides a promising route to design and fabricate customized macrostructures endowed with specific properties of nanomaterials.

2.
J Pharm Pharm Sci ; 25: 9-23, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34995471

RESUMO

OBJECTIVE: Previous studies on the efficacy and safety of genotype-guided antiplatelet therapy in patients with coronary artery disease (CAD) or undergoing percutaneous coronary intervention (PCI) have been inconclusive. AIM: We conducted a meta-analysis to evaluate if the genotype-guided antiplatelet strategy is superior to the standard therapy in patients with CAD or undergoing PCI. METHOD: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to October 1st, 2021. Studies reporting efficacy and safety outcomes in the genotype-guided treatment and standard treatment groups were included. The two groups were statistically compared. RESULT: Eleven randomized controlled trials (RCTs) involving 11740 patients were included in this meta-analysis. Compared with the standard treatment group, the genotype-guided group had significant lower risks of all efficacy outcomes, including major adverse cardiovascular events (MACEs) (RR 0.60, 95%, CI 0.44-0.82, P=0.001), all-cause death (RR 0.70, 95% CI 0.51-0.95, P=0.02), cardiovascular death (RR 0.71, 95% CI 0.53-0.95, P=0.02), myocardial infarction (RR 0.53, 95% CI 0.42-0.67, P<0.0001), stroke (RR 0.64, 95% CI 0.41-0.98, P=0.04), stent thrombosis (RR 0.63, 95% CI 0.43-0.91, P=0.01) and targeted vessel revascularization (RR 0.79, 95% CI 0.67-0.92, P=0.003). There was no significant difference in any bleeding events between the two groups. As a result of the subgroup analyses, the genotype-guided treatment was more likely to reduce the incidence of MACEs in the subgroup where the proportion of patients with ACS was ≥ 90%, and subgroup of the Chinese population. CONCLUSION: Genotype-guided antiplatelet treatment could reduce the risk of MACEs without increasing the risk of bleeding events as compared with the standard treatment in patients with CAD or those undergoing PCI. In addition, Genotype-guided antiplatelet treatment might benefit Chinese population or patients with ACS.

3.
Int J Hyperthermia ; 39(1): 8-14, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34936851

RESUMO

PURPOSE: To assess the absorption rate and factors related to the development of benign thyroid nodules (BTNs) following image-guided microwave ablation (MWA). MATERIALS AND METHODS: This retrospective study reviewed nodule efficacy in patients who underwent MWA of BTNs between January 2016 and January 2018. The endpoint was a third-year follow-up. Nodules were categorized into those showing complete absorption (volumes with less than 100% volume reduction ratio (VRR) and those showing partial absorption (100% VRR)). Univariable and multivariable regression analyses were carried out to identify variables that were associated with nodule absorption rates. RESULTS: A total of 173 BTNs (median volume= 4.23 ml; 25-75 percentiles= 2.27-9.00 ml) from 173 patients were evaluated. 49.7% (86/173) of patients had nodules that became completely absorbed. The mean VRRs of all BTNs were 18.0%, 78.7%, 89.0%, 94.5%, and 97.1% at the 1-, 6-,12-, 24- and 36- month follow-ups. At the 3-year follow-up time point, nodule characteristics related to nodule VRR included nodule volume (adjusted odds ratio [AOR], 1.1 [95% CI: 1.0, 1.2]; p = 0.03) and nodule margin (AOR, 5.3 [95% CI: 1.8, 16.0]; p < 0.01). Treatment-related characteristics included energy per ml in nodular volume (AOR, 1.0 [95% CI: 1.0, 1.0]; p < 0.01) and blockage of peripheral flow (AOR, 3.3 [95% CI: 1.3 8.3]; p = 0.01). CONCLUSIONS: US-guided image-guided MWA results in satisfactory long-term outcomes for the patients with BTNs. Factors related to nodule absorption rate were the volume and margin of the nodule, energy per ml in nodular volume and blockage of peripheral flow.

4.
Bioresour Technol ; 343: 125896, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34649059

RESUMO

This study for the first time bioreduced Te(IV) using elemental sulfur (S0) as electron donor, achieving 91.17%±0.8% conversion with reaction rate of 0.77 ± 0.01 mg/L/h in a 60-day cultivation. Characterization using X-ray photoelectron spectroscopy and X-ray power diffraction analyses confirmed that most removed Te(IV) was reduced to elemental Te(0) deposits, while ion chromatogram analysis showed that most S(0) was oxidized to sulfite and sulfate. High-throughput 16S rRNA gene sequencing indicated that the Te(IV) reduction coupled to S(0) oxidation was mediated synergistically by a microbial consortia with S(0)-oxidizing bacteria (Thiobacillus) to generate volatile fatty acids as metabolites and Te(IV)-reducing bacteria (Rhodobacter) to consume formed volatile fatty acids to yield Te(0). The synergy between these two strains presents a novel bioremediation consortium to efficiently treat Te(IV) wastewaters.


Assuntos
Elétrons , Enxofre , Oxirredução , RNA Ribossômico 16S/genética , Sulfatos
5.
Environ Sci Technol ; 56(1): 403-413, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34923819

RESUMO

The use of commercial products containing engineered nanomaterials in realistic scenarios may lead to the accumulation of exogenous particles in brain tissues. In this study, we simulated the use of silver (Ag) nasal spray in humans using Sprague-Dawley rats at 0.04 mg/kg/day. Silver-containing particles were explicitly identified in the rat brain after the administration of nasal sprays containing colloidal Ag or silver ions (Ag+) for 2 weeks using multiple methods. The accumulation of Ag-containing particles showed a delayed effect in different brain regions of the rats, with the mass concentration of particles increasing continuously for 1-2 weeks after the termination of administration. The size of the observed Ag-containing particles extracted from the brain tissues ranged from 18.3 to 120.4 nm. Further characterization by high-resolution transmission electron microscopy with energy-dispersive spectroscopy showed that the nanoparticles comprised both Ag and sulfur (S), with Ag/S atomic ratios of 1.1-7.1, suggesting that Ag-containing particles went through a series of transformations prior to or during their accumulation in the brain. Collectively, these findings provide evidence for the accumulation and transformation of Ag-containing particles in the rat brain, indicating a realistic risk to brain health resulting from the application of Ag-containing commercial products.

7.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-473620

RESUMO

The recently reported B.1.1.529 Omicron variant of SARS-CoV-2 includes 34 mutations in the spike protein relative to the Wuhan strain that initiated the COVID-19 pandemic, including 15 mutations in the receptor binding domain (RBD). Functional studies have shown omicron to substantially escape the activity of many SARS-CoV-2-neutralizing antibodies. Here we report a 3.1 [A] resolution cryo-electron microscopy (cryo-EM) structure of the Omicron spike protein ectodomain. The structure depicts a spike that is exclusively in the 1-RBD-up conformation with increased mobility and inter-protomer asymmetry. Many mutations cause steric clashes and/or altered interactions at antibody binding surfaces, whereas others mediate changes of the spike structure in local regions to interfere with antibody recognition. Overall, the structure of the omicron spike reveals how mutations alter its conformation and explains its extraordinary ability to evade neutralizing antibodies. HighlightsO_LISARS-CoV-2 omicron spike exclusively adopts 1-RBD-up conformation C_LIO_LIOmicron substitutions alter conformation and mobility of RBD C_LIO_LIA subset of omicron mutations change the local conformation of spike C_LIO_LIThe structure reveals the basis of antibody neutralization escape C_LI

8.
Acta Biomater ; 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34971787

RESUMO

Magnesium (Mg) and some of its alloys are considered promising biodegradable metallic biomaterials for bone implant applications. The osteogenesis effect of Mg alloys is widely reported; however, the underlying mechanisms are still not clear. In this study, pure Mg, Mg-3Zn, and Mg-2Zn-1Mn were prepared, and their degradation behavior, biocompatibility, and osteogenesis effect were systematically assessed both in vitro and in vivo. Primary rat bone marrow-derived mesenchymal stem cells (BMSCs) were used to evaluate the biocompatibility of the prepared Mg alloys, and a rat femur fracture model was used to assess the stimulating effect of these alloys on bone-tissue formation. Mg-2Zn-1Mn showed higher corrosion resistance and more stable degradation behavior than pure Mg and Mg-3Zn. Extracts of the three materials showed significant stimulating effects on osteogenic differentiation of BMSCs along with non-cytotoxicity. Implantation of Mg-2Zn-1Mn wires into the femur of rats demonstrated superior histocompatibility, stable degradation, and notable promotion of osteogenesis without systemic toxicity. Moreover, the results of both in vitro and in vivo assessments demonstrated that bone morphogenetic proteins and fibroblast growth factor receptors are involved in the stimulating effect of Mg alloys. STATEMENT OF SIGNIFICANCE: This work reports the degradation behavior, biocompatibility, and osteogenic effect of pure Mg and Mg-3Zn and Mg-2Zn-1Mn alloys in both in vitro and in vivo conditions. Mg-2Zn-1Mn showed higher corrosion resistance and more stable degradation behavior than pure Mg and Mg-3Zn. The extracts of the three materials showed a significant stimulating effect on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) along with non-cytotoxicity. Mg-2Zn-1Mn wires implanted into the femur of rats showed good histocompatibility, stable degradation, and notable promotion of osteogenesis without systemic toxicity. The results of the present study suggest that bone morphogenetic proteins (BMPs) and fibroblast growth factor receptors (FGFRs) are involved in the stimulating effect of Mg alloys on osteogenesis.

9.
Medicine (Baltimore) ; 100(52): e28458, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34967386

RESUMO

ABSTRACT: This study aimed to assess the impact of the pharmacist-led intervention on perioperative antibiotic prophylaxis by standardizing the cephalosporin intradermal skin test in the orthopedic department.A pre-and postintervention study was conducted among patients in the Orthopedics Department at the Beijing Chao-Yang Hospital in China. Use of intradermal skin test, perioperative antibacterial prophylaxis, and cost of care were compared between the preintervention population (admitted from 6/1/2018 to 8/31/2018) and postintervention population (admitted from 1/1/2019 to 3/31/2019). Logistic regression and generalized linear regression were used to assess the intervention impact.425 patients from the preintervention period and 448 patients from the postintervention period were included in the study. After the implementation of the pharmacist intervention program, there was a decrease in the utilization of intradermal skin tests, from 95.8% to 16.5% (P < .001). Patients were more likely to have cephalosporin as prophylactic antimicrobials (OR = 5.28, P < .001) after the implementation. The cost of antimicrobials was significantly reduced by $150.21 (P < .001) for each patient.Pharmacist-involved intervention can reduce the utilization of cephalosporins skin tests and decrease the prescription of unnecessary high-cost antimicrobials.

10.
Curr Drug Metab ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825867

RESUMO

OBJECTIVE: The aim of the study was to investigate a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of rivaroxaban and evaluate the correlation between plasma concentration and anti-Xa activity in patients using oral rivaroxaban. METHODS: In this study, the plasma concentration of rivaroxaban and anti-Xa factor activities was determined in 125 patients, and the relationship between the two variables was analysed by SPSS 21.0 software. RESULTS: The results showed that the plasma concentrations of oral rivaroxaban patients were significantly correlated with the activity of the anti-Xa factor (Spearman's r = 0.990, p < 0.05). CONCLUSION: The plasma concentrations of rivaroxaban are a potentially useful monitoring indicator to assess the patient's bleeding risk if testing for plasma anti-Xa activity is not available.

11.
Emerg Microbes Infect ; : 1-34, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34836485

RESUMO

The repeated emergence of highly pathogenic human coronaviruses as well as their evolving variants highlight the need to develop potent and broad-spectrum antiviral therapeutics and vaccines. By screening monoclonal antibodies (mAbs) isolated from COVID-19-convalescent patients, we found one mAb, 2-36, with cross-neutralizing activity against SARS-CoV. We solved the cryo-EM structure of 2-36 in complex with SARS-CoV-2 or SARS-CoV spike, revealing a highly conserved epitope in the receptor-binding domain (RBD). Antibody 2-36 neutralized not only all current circulating SARS-CoV-2 variants and SARS-COV, but also a panel of bat and pangolin sarbecoviruses that can use human angiotensin-converting enzyme 2 (ACE2) as a receptor. We selected 2-36-escape viruses in vitro and confirmed that K378 T in SARS-CoV-2 RBD led to viral resistance. Taken together, 2-36 represents a strategic reserve drug candidate for the prevention and treatment of possible diseases caused by pre-emergent SARS-related coronaviruses. Its epitope defines a promising target for the development of a pan-sarbecovirus vaccine.

12.
iScience ; 24(11): 103393, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34746689

RESUMO

We compared the functional properties of spike (S) glycoproteins from the original SARS-CoV-2 strain (D614) (Wuhan, China), the globally dominant D614G strain, and emerging geographic variants: B.1.1.7 (United Kingdom), B.1.351 (South Africa), P.1 (Brazil), and B.1.1.248 (Brazil/Japan). Compared with D614G, the emerging variants exhibited an increased affinity for the receptor, ACE2, and increased ability to infect cells with low ACE2 levels. All variants lost infectivity similarly at room temperature and 37°C; however, in the cold, B.1.1.7 was more stable, and P.1 and B.1.1.248 were less stable. Shedding of the S1 glycoprotein from the S contributed to virus inactivation in the cold. B.1.351, P.1, and B.1.1.248 were neutralized by convalescent and vaccinee sera less efficiently than the other variants. S glycoprotein properties such as requirements for ACE2 levels on the target cell, functional stability in the cold, and resistance to host neutralizing antibodies potentially contribute to the outgrowth of emerging SARS-CoV-2 variants.

13.
Front Oncol ; 11: 750323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804937

RESUMO

Chidamide has demonstrated significant clinical benefits for patients with relapsed/refractory (R/R) PTCL in previous studies. This multi-center observational study was aimed to evaluate the objective response rate (ORR), overall survival (OS), and safety of chidamide. From February 2015 to December 2017, 548 patients with R/R PTCL from 186 research centers in China were included in the study. Among the 261 patients treated with chidamide monotherapy, ORR was 58.6% and 55 patients (21.1%) achieved complete response (CR). Among the 287 patients receiving chidamide-containing combination therapies, ORR was 73.2% and 73 patients (25.4%) achieved CR. The median OS of all patients was 15.1 months. The median OS of patients receiving chidamide monotherapy and combination therapies was 433 and 463 days, respectively. These results demonstrate a significant survival advantage of chidamide treatments as compared with international historical records. Common adverse effects (AEs) were hematological toxicities. Most AEs in both monotherapy and combined treatments were grade 1-2. No unanticipated AEs occurred. In conclusion, chidamide-based therapy led to a favorable efficacy and survival benefit for R/R PTCL. Future studies should explore the potential advantage of chidamide treatment combined with chemotherapy.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34603473

RESUMO

Traditional Chinese drugs (TCDs) have been widely used in clinical practice in China and many other regions for thousands of years. Nowadays TCD's bioactive ingredients and mechanisms of action are being identified. However, the lack of standardized terminologies or ontologies for the description of TCDs has hindered the interoperability and deep analysis of TCD knowledge and data. By aligning with the Basic Formal Ontology (BFO), an ISO-approved top-level ontology, we constructed a community-driven TCD ontology (TCDO) with the aim of supporting standardized TCD representation and integrated analysis. TCDO provides logical and textual definitions of TCDs, TCD categories, and the properties of TCDs (i.e., nature, flavor, toxicity, and channel tropism). More than 400 popular TCD decoction pieces (TCD-DPs) and Chinese medicinal materials (CMMs) are systematically represented. The logical TCD representation in TCDO supports computer-assisted reasoning and queries using tools such as Description Logic (DL) and SPARQL queries. Our statistical analysis of the knowledge represented in TCDO revealed scientific insights about TCDs. A total of 36 TCDs with medium or high toxicity are most densely distributed, primarily in Aconitum genus, Lamiids clade, and Fabids clade. TCD toxicity is mostly associated with the hot nature and pungent or bitter flavors and has liver, kidney, and spleen channel tropism. The three pairs of TCD flavor-nature associations (i.e., bitter-cold, pungent-warm, and sweet-neutral) were identified. The significance of these findings is discussed. TCDO has also been used to support the development of a web-based traditional Chinese medicine semantic annotation system that provides comprehensive annotation for individual TCDs. As a novel formal TCD ontology, TCDO lays out a strong foundation for more advanced TCD studies in the future.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1540-1547, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627437

RESUMO

OBJECTIVE: To analyze the disease types, clinical manifestations, efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant myeloproliferative neoplasms (MPN), and provide a reference for the diagnosis, treatment and prognosis of MPN. METHODS: The clinical characteristics, diagnosis, therapeutic efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant MPN were analyzed comprehensitively by combining a clinical case diagnosed and treated in our hospital with literature cases from CNKI and PubMed databases. RESULTS: A total of 38 related literatures were retrieved from the two databases by searching "JAK2 V617F" and "BCR-ABL" as key words from 1990 to 2019, and 59 cases were involved. Among all the 60 cases, 41 were males (68.3%) with a median age of 61 (32-77) years old, while 19 were females (31.7%) with a median age of 58 (21-82) years old. The BCR-ABL fusion gene and JAK2 V617F mutation were found simultaneously in 21 cases (35%), 19 cases (31.7%) with JAK2 V617F mutation were found during the treatment of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Ph+CML was detectable in 20 cases (33.3%) during the treatment of JAK2 V617F mutation positive MPN. Polycythemia vera (PV) was the most common MPN coexisting with CML (30%), followed by essential thrombocythemia (ET) (26.7%) and primary myelofibrosis (PMF) (21.7%). In addition, there were 13 cases (21.7%) not classified in the literature. Among the 60 cases, 35 CML patients were clearly staged, including 31 in the chronic phase, 3 in the accelerated phase, and 1 in the blast crisis phase. As for the subtypes of BCR-ABL fusion gene, there were 30 cases with clear classification, including 28 cases of p210, 1 case of p190 and 1 case of p230. CONCLUSION: As cases of BCR-ABL and JAK2 V617F double-mutant MPN are reported, simultaneous detection of JAK2 V617F mutation and BCR-ABL fusion gene in MPN patients is necessary to avoid misdiagnosis and missed diagnosis.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Trombocitemia Essencial , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/genética , Adulto Jovem
17.
Emerg Infect Dis ; 28(1)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34647864

RESUMO

We report severe acute respiratory syndrome coronavirus 2 in semen by using quantitative reverse transcription PCR during the late convalescent phase. Virus was associated with adequate humoral and cell-mediated responses, suggesting possible seeding of the immune-privileged testes. We provide longitudinal semen quality data for 6 other men, including 3 who had oligozoospermia.

18.
bioRxiv ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34671769

RESUMO

The repeated emergence of highly pathogenic human coronaviruses as well as their evolving variants highlight the need to develop potent and broad-spectrum antiviral therapeutics and vaccines. By screening monoclonal antibodies (mAbs) isolated from COVID-19-convalescent patients, we found one mAb, 2-36, with cross-neutralizing activity against SARS-CoV. We solved the cryo-EM structure of 2-36 in complex with SARS-CoV-2 or SARS-CoV spike, revealing a highly conserved epitope in the receptor-binding domain (RBD). Antibody 2-36 neutralized not only all current circulating SARS-CoV-2 variants and SARS-COV, but also a panel of bat and pangolin sarbecoviruses that can use human angiotensin-converting enzyme 2 (ACE2) as a receptor. We selected 2-36-escape viruses in vitro and confirmed that K378T in SARS-CoV-2 RBD led to viral resistance. Taken together, 2-36 represents a strategic reserve drug candidate for the prevention and treatment of possible diseases caused by pre-emergent SARS-related coronaviruses. Its epitope defines a promising target for the development of a pan-sarbecovirus vaccine.

19.
Front Pharmacol ; 12: 747450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658883

RESUMO

Remdesivir, a nucleotide analog prodrug, has displayed pharmacological activity against SARS-CoV-2. Recently, eicosanoids are widely involved in regulating immunity and inflammation for COVID-19 patients. Rats were intravenously administered remdesivir at a dose of 5 mg/kg, and series of blood samples were collected before and after treatment. Targeted metabolomics regarding the eicosanoid profile were investigated and quantitated simultaneously using the previously reported reliable HPLC-MS/MS method. Additionally, interplay relationship between metabolomics and pharmacokinetic parameters was performed using the Pearson correlation analysis and PLS model. For the longitudinal metabolomics of remdesivir, metabolic profiles of the same rat were comparatively substantial at discrete sampling points. The metabolic fingerprints generated by individual discrepancy of rats were larger than metabolic disturbance caused by remdesivir. As for the transversal metabolomics, the prominent metabolic profile variation was observed between the baseline and treatment status. Except for TXB2, the inflammatory- and immunology-related eicosanoids of resolvin D2, 5-HEPE, 5-HETE, and DHA were significantly disturbed and reduced after single administration of remdesivir (p < 0.05, p < 0.001). Moreover, the metabolite of PGE2 correlated with GS-441524 (active metabolite of remdesivir) concentration and pharmacokinetic parameters of Cmax, AUC0-t, AUC0-infinity, and CL significantly. Eicosanoid metabolic profiles of remdesivir at both longitudinal and transversal levels were first revealed using the robust HPLC-MS/MS method. This initial observational eicosanoid metabolomics may lighten the therapy for fighting COVID-19 and further provide mechanistic insights of SARS-CoV-2 virus infection.

20.
Front Physiol ; 12: 709123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658906

RESUMO

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus, which is associated with fibrosis and microRNAs (miRs). This study estimated the mechanism of miR-195-5p in endothelial mesenchymal transition (EndMT) and myocardial fibrosis in DCM. After the establishment of DCM rat models, miR-195-5p was silenced by miR-195-5p antagomir. The cardiac function-related indexes diastolic left ventricular anterior wall (LVAW, d), systolic LVAW (d), diastolic left ventricular posterior wall (LVPW, d), systolic LVPW (d), left ventricular ejection fraction (LVEF), and fractional shortening (FS) were measured and miR-195-5p expression in myocardial tissue was detected. Myocardial fibrosis, collagen deposition, and levels of fibrosis markers were detected. Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (HG) and miR-195-5p was silenced. The levels of fibrosis proteins, endothelial markers, fibrosis markers, EndMT markers, and transforming growth factor beta 1 (TGF-ß1)/Smads pathway-related proteins were measured in HUVECs. The interaction between miR-195-5p and Smad7 was verified. In vivo, miR-195-5p was highly expressed in the myocardium of DCM rats. Diastolic and systolic LVAW, diastolic and systolic LVPW were increased and LVEF and FS were decreased. Inhibition of miR-195-5p reduced cardiac dysfunction, myocardial fibrosis, collagen deposition, and EndMT, promoted CD31 and VE-cadehrin expressions, and inhibited α-SMA and vimentin expressions. In vitro, HG-induced high expression of miR-195-5p and the expression changes of endothelial markers CD31, VE-cadehrin and fibrosis markers α-SMA and vimentin were consistent with those in vivo after silencing miR-195-5p. In mechanism, miR-195-5p downregulation blocked EndMT by inhibiting TGF-ß1-smads pathway. Smad7 was the direct target of miR-195-5p and silencing miR-195-5p inhibited EndMT by promoting Smad7 expression. Collectively, silencing miR-195-5p inhibits TGF-ß1-smads-snail pathway by targeting Smad7, thus inhibiting EndMT and alleviating myocardial fibrosis in DCM.

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