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1.
Int J Pharm ; 611: 121297, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34822966

RESUMO

Atherosclerosis (AS), with its intricate pathogenesis, is primarily responsible for the development and progression of cardiovascular diseases. Although drug development has made some achievements in AS therapy, limited targeting ability and rapid blood clearance remain great challenges for achieving superior clinical outcomes. Herein, ginsenoside (Re)- and catalase (CAT)-coloaded porous poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were prepared and then surface modified with U937 cell membranes (UCMs) to yield a dual targeted model and multimechanism treatment biomimetic nanosystem (Cat/Re@PLGA@UCM). The nanoparticles consisted of a core-shell spherical morphology with a favorable size of 112.7 ± 0.4 nm. Furthermore, UCM assisted the nanosystem in escaping macrophage phagocytosis and targeting atherosclerotic plaques. Meanwhile, loading with catalase might not only exhibit favorable antioxidant effects but also enable H2O2-responsive drug release ability. The Cat/Re@PLGA@UCM NPs also exhibited outstanding ROS scavenging properties, downregulating ICAM-1, TNF-α and IL-1ß, while preventing angiogenesis to attenuate the progression of AS. Moreover, the nanodrugs displayed 2.7-fold greater efficiency in reducing the atherosclerotic area in ApoE-/- mouse models compared to free Re. Our nanoformulation also displayed excellent biosafety in response to long-term administration. Overall, our study demonstrated the superiority of UCM-coated stimuli-responsive nanodrugs for effective and safe AS therapy.

2.
Colloids Surf B Biointerfaces ; 209(Pt 2): 112177, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34749194

RESUMO

Rapamycin (RAPA) functions as effectively clinical immunosuppressive agent, its significant tumor growth suppression effect via various pathways in diverse cancers, especially combined with photothermal therapy, is gaining a burgeoning attention. However, its critical defects, low solubility and poor stability, have severely hampered its further application. Herein, RAPA, indocyanine green (ICG) and epigallocatechin gallate (EGCG) serving as chemotherapeutic drug, photosensitizer and biomimetic coatings, respectively, were co-assembled into carrier-free, high biocompatible ICG-RAPA-EGCG nanoparticles (IRE NPs) for synergistic cancer therapy. Particularly, the bioinspired EGCG coatings not only improved the stability of IRE NPs under physiological conditions to avert NPs disassembly and drug release, but also maintained the photostability of ICG to achieve excellent photothermal response. The results indicated that the as-prepared IRE NPs displayed good monodispersity and enhanced stability at various stored media after introducing of EGCG. Compared with monotherapy of RAPA or ICG, IRE NPs showed higher dose-dependent toxicity in MCF-7 cells, HepG2 cells and HeLa cells, especially plus near-infrared laser irradiation. Furthermore, IRE NPs exhibited quicker uptake in cells, higher accumulation in tumor region (even in 48 h) than free ICG and effectively inhibited tumor growth without side effect in H22 tumor-bearing mice. Collectively, the carrier-free IRE NPs provided a simply alternative approach to fabricate RAPA/photosensitizer co-loaded nanoparticles for combinatorial tumor therapy.

3.
JPGN Rep ; 2(2)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34723254

RESUMO

Objectives: The relationship between vitamin D deficiency (VDD) and pediatric nonalcoholic fatty liver disease (NAFLD) remains uncertain due to conflicting results and few studies with histologic endpoints. We therefore used multiple imaging and histologic NAFLD endpoints to more comprehensively assess the association between VDD and NAFLD in a large pediatric population. Methods: Data were obtained from an ongoing pediatric NAFLD study in Bronx, NY. Briefly, overweight and obese children aged 2-18 years with alanine aminotransferase (ALT) levels ≥ 35 U/L were serially enrolled. Liver biopsy was obtained in accordance with clinical guidelines. All participants had liver imaging, namely, controlled attenuation parameter (CAP; Echosens, France) to assess steatosis and, to assess fibrosis, vibration controlled transient elastography (VCTE; FibroScan™, Echosens, France) and acoustic radiation force impulse (ARFI; Philips, Netherlands) imaging. Levels of 25-hydroxyvitamin D were measured serologically. Results: N=276 (88%) of 315 participants had 25-OH vitamin D results, of whom 241 (87%) were Hispanic, 199 (72%) were male, and 92 (33%) underwent liver biopsy. VDD was univariately associated with high waist circumference (p=0.004), high-density lipoprotein level (p=0.01), season (p=0.009), and CAP score (p=0.01). In multivariate analysis, only waist circumference (p=0.0002) and biopsy inflammation grade (p=0.03) were associated with VDD, though the latter had not approximated statistical significance in univariate analysis (p=0.56). There was no association between VDD and hepatic steatosis, ballooning, NAFLD Activity Score, ARFI or VCTE elasticity scores. Conclusions: VDD was not associated with NAFLD defined by imaging and histologic endpoints, except for a possible relation with histologic inflammation grade.

4.
Enzyme Microb Technol ; 151: 109916, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34649687

RESUMO

Alginate oligosaccharides are enzymolysis products of alginate with versatile bioactivities and their industrial preparation was limited by the insufficient activity and unsatisfying thermostability of alginate lyases. The structure-function information about PL18 alginate lyases was seldom reported since which few positive mutants of PL18 alginate lyases were generated. In present study, a mutant of PL18 alginate lyase E226K was expressed intracellularly and taken as parent for further modification. Site I211 at the lid loop 1 and sites E276, Y292 and R294 at the predicted entrance were chosen as engineering targets based on the E226K-PM4 binding mode in prereaction-state MD simulation and 29 mutants were constructed, from those, the variant E226K/I211T/R294V was screened out as the best mutant (showing 4.78-fold increased catalytic efficiency and the half-time t1/245℃ increased up to 557 min from 89 min). MD simulations indicated that the affinity of E226K/I211T/R294V towards alginate was improved due to the optimized energy distribution of active center, more flexible loops around catalytic cleft and larger substrate entrance. The more efficient proton transmitting endowed E226K/I211T/R294V higher activity and the more complicated intraprotein interactions together with stronger backbone rigidity were responsible for the improved thermostability of E226K/I211T/R294V than E226K. The success in this study enriches the structure-function information of PL18 alginate lyases and provides hints for their further design.


Assuntos
Alginatos , Polissacarídeo-Liases , Catálise , Oligossacarídeos , Polissacarídeo-Liases/genética , Polissacarídeo-Liases/metabolismo , Especificidade por Substrato
5.
BMC Cardiovasc Disord ; 21(1): 473, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598676

RESUMO

BACKGROUND: Trimetazidine (TMZ) pretreatment protects cardiomyocytes during cardiac surgery. TMZ may protect elderly patients with ischaemic heart disease (IHD) undergoing non-cardiac surgery. METHODS: This was a randomized, double-blind, placebo-controlled trial (registration #ChiCTR1900025018) of patients with IHD scheduled to undergo non-cardiac surgery at Shenzhen People's Hospital (Shenzhen, Guangdong Province, China) between June 2014 and September 2015, randomized to 60 mg TMZ or placebo 12 h before surgery. The primary endpoint was the occurrence of in-hospital cardiovascular events. The secondary endpoints were myocardial ischaemia on five-lead electrocardiogram (cECG), cardiac troponin I (cTnI) elevation, cardiac death, acute coronary events, heart failure, and arrhythmia requiring treatments. RESULTS: Compared with the placebo group, the TMZ group showed a lower occurrence of in-hospital cardiovascular events (primary endpoint, 20.0% vs. 37.5%, P = 0.02), myocardial ischaemia (15.0% vs. 32.5%, P < 0.01), cTnI elevation (2.5% vs. 10%, P < 0.01), acute coronary events (10.0% vs. 20.0%, P < 0.05), heart failure (0% vs. 2.5%, P < 0.05), and arrhythmia requiring treatment (17.5% vs. 35.0%, P < 0.05). There was no acute myocardial infarction during the 30-day postoperative period. CONCLUSIONS: In elderly patients with IHD undergoing non-cardiac surgery, TMZ pretreatment was associated with myocardial protective effects. Trial registration The trial was prospectively registered at http://www.chictr.org.cn/showproj.aspx?proj=41909 with registration number [ChiCTR1900025018] (7/8/2019).

6.
ACS Appl Mater Interfaces ; 13(41): 49482-49489, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34636536

RESUMO

Although organic artificial enzymes have been reported as biomimetic oxidation catalysts and are widely used for colorimetric biosensors, developing organic artificial enzymes with high enzymatic activity is still a challenge. Two-dimensional (2D) covalent organic frameworks (COFs) have shown superior potential in biocatalysts because of their periodic π-π arrays, tunable pore size and structure, large surface area, and thermal stability. The interconnection of electron acceptor and donor building blocks in the 2D conjugated COF skeleton can lead to narrower band gaps and efficient charge separation and transportation and thus is helpful to improve catalytic activity. Herein, a donor-acceptor 2D COF was synthesized using tetrakis(4-aminophenyl)pyrene (Py) as an electron donor and thieno[3,2-b]thiophene-2,5-dicarbaldehyde (TT) as an electron acceptor. Under visible light irradiation, the donor-acceptor 2D COF exhibited superior enzymatic catalytic activity, which could catalyze the oxidation of chromogenic substrates such as 3,3',5,5'-tetramethylbenzidine (TMB) by the formation of superoxide radicals and holes. Based on the above property, the photoactivated donor-acceptor 2D COF with enzyme-like catalytic properties was designed as a robust colorimetric probe for cheap, highly sensitive, and rapid colorimetric detection of glutathione (GSH); the corresponding linear range of GSH was 0.4-60 µM, and the limit of detection was 0.225 µM. This study not only presents the construction of COF-based light-activated nanozymes for environmentally friendly colorimetric detection of GSH but also provides a smart strategy for improving nanozyme activity.

7.
Int J Clin Pract ; : e14907, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551174

RESUMO

OBJECTIVE: The association between computed tomography (CT) and clinical severity of COVID-19 has been demonstrated. However, there are few studies on CT and laboratory indicators in patients in COVID-19. Our aim was to explore the correlation between chest CT images and laboratory indicators of patients with COVID-19 pneumonia. METHODS: This was a retrospective study of patients with COVID-19 diagnosed and treated at the Affiliated Hospital of Putian University from 24 January 2020 to 6 March 2020. The correlation test between first chest CT score and blood cell analysis, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), blood biochemistry and T lymphocyte subsets (T-Ls) was investigated. RESULTS: Among the 56 patients, there were 36 (64.3%) males and 20 (35.7%) females. The mean age of the patients was 46.54 ± 15.82 (range, 15-86) years. The CT score in the moderate group was higher than in the mild group (5.06 ± 0.77 vs 1.87 ± 0.88, P < .05), and higher in the severe group than in the moderate and mild groups (10.71 ± 4.21, P < .05). In addition, the ESR was significantly higher in the severe group than mild group (32.00 (26.04, 58.24) vs 11.00 (7.84, 24.70) mm/h, P < .05). The CD3, CD4, CD8 and CD4/CD8 cells were not different (all P > .05). The CT scores of all patients correlated positively with CRP, LDH and ESR (all P < .01). CONCLUSION: The chest CT characteristics of patients with COVID-19 correlated positively with CRP, ESR and LDH, which may use one of the indicators for the assessment of disease severity.

8.
Front Oncol ; 11: 704842, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395277

RESUMO

Purpose: To compare survival in different strategies, preoperative systemic treatment versus upfront surgery, in HER2-positive early breast cancer patients in the real world. Methods: According to the actual upfront treatment, eligible patients from 2012 to 2015 were classified as preoperative systemic treatment or upfront surgery group prospectively. The primary endpoint is disease-free survival; the second endpoint is overall survival. All the outcomes were examined in the propensity score matching model and inverse probability of treatment weighting model. Results: Included in the analysis were 1,067 patients (215 in the preoperative systemic treatment group, 852 in the upfront surgery group). In the propensity score matching model (matching at 1:1 ratio), the disease-free survival of the preoperative systemic treatment group was significantly higher than that of the upfront surgery group (hazard ratio, 0.572, 95%CI, 0.371-0.881, P, 0.012). In the inverse probability of treatment weighting model, there was no significant difference in disease-free survival between the two groups (hazard ratio, 0.946, 95%CI, 0.763-1.172, P, 0.609). For overall survival, there was no significant difference between the two groups. Conclusion: The HER2-positive patients who accepted preoperative systemic treatment had better disease-free survival than those who underwent upfront surgery by real-world statistic methods. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04249440.

9.
Med Sci Monit ; 27: e929835, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34417434

RESUMO

BACKGROUND Volatile anesthesia possesses cardioprotective properties, and it is widely used in patients undergoing coronary artery bypass surgery, but no randomized controlled trials (RCTs) are available on the use of sevoflurane-remifentanil versus propofol-remifentanil anesthesia for patients with coronary artery disease (CAD) during noncardiac surgery. This study was designed to compare the 2 different types of general anesthesia in patients with CAD undergoing noncardiac surgery at a single center. MATERIAL AND METHODS Patients with CAD undergoing noncardiac surgery were enrolled in an RCT conducted between March 2016 and December 2017. The participants were randomized to receive either sevoflurane-remifentanil or propofol-remifentanil anesthesia. The primary endpoint was occurrence of in-hospital cardiovascular events. The secondary endpoints included delirium, postoperative nausea and vomiting (PONV), Intensive Care Unit (ICU) length of stay (LOS), in-hospital morbidity and mortality, and hospital LOS. RESULTS A total of 164 participants completed the study (sevoflurane: 81; propofol: 83). The occurrence of in-hospital cardiovascular events did not differ between the 2 groups (42.6% vs 39.4%, P=0.86). The occurrence of delirium did not differ between the 2 groups after the operation. PONV had a higher frequency after sevoflurane anesthesia at 48 h compared with propofol. In-hospital morbidity and mortality, ICU LOS, and hospital LOS were similar between the 2 groups (all P>0.05). At 30 days after surgery, no between-group differences in cardiac morbidity and mortality were observed. CONCLUSIONS In this study, anesthesia using sevoflurane-remifentanil did not provide additional postoperative cardioprotection in comparison with propofol-remifentanil in patients with CAD undergoing noncardiac surgery.

10.
Colloids Surf B Biointerfaces ; 207: 112014, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34391166

RESUMO

Combined chemo-photothermal therapy of gold nanorods (GNRs) for cancer treatment shows better therapeutic efficiency than mono-chemotherapy, which has gained worldwide interests of scientists and clinician in both laboratory and clinic application. However, high cytotoxicity, declined delivery efficiency, and unsatisfactory therapy effect of the GNRs are still challenging in anti-cancer treatment. Herein, a series of pH-sensitively zwitterionic polypeptide conjugated GNRs were synthesized via a gold-thiol interaction for combination of chemo-photothermal therapy in cervical cancer treatment. The acid-labile hydrazone bond was utilized to incorporate the doxorubicin (DOX) for pH-sensitive drug release under tumoral environment. The as prepared GNRs conjugates demonstrated pH-triggered surface charge conversion from negative to positive when transporting from blood circulation to tumor extracellular environment, which can facilitate the cellular uptake via electrostatic interaction. After cellular internalization, the drug release was promoted by cleavage of the hydrazone in GNRs conjugates under cancer intracellular acid environment. As the effective near-infrared (NIR) photothermal materials, the as prepared GNRs conjugates can absorb NIR photo energy and convert it into heat under irradiation, which can efficiently kill the tumor cells. In cell assay, the GNRs conjugates displayed excellent biocompatibility against normal cell, enhanced cancer cell uptake, and remarkable cancer cell killing effects. In HeLa tumor-bearing mice, the GNRs conjugates demonstrated enhanced tumor inhibition efficacy by combination of chemo-photothermal therapy.


Assuntos
Nanotubos , Neoplasias do Colo do Útero , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Feminino , Ouro , Humanos , Camundongos , Peptídeos , Fototerapia , Terapia Fototérmica , Neoplasias do Colo do Útero/terapia
11.
Zhongguo Zhong Yao Za Zhi ; 46(11): 2634-2638, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296558

RESUMO

In the context of the new era, paying attention to maternal and child health and advocating prenatal and postnatal care can effectively improve the quality of the birth population. Traditional Chinese medicine has a long history of prenatal and postnatal healthcare with rich content, which is the theoretical basis of modern related services. With the social development and the improvement of people's awareness of prenatal and postnatal healthcare, people have gradually shifted the focus of prenatal and postnatal healthcare to the peri-pregnancy stage at present, namely that couples of childbearing age are guided to prepare for pregnancy under the premise of solving their basic diseases. Infertility is a common and refractory disease for women of childbearing age. Ovulation disorder is one of its common pathological mechanisms. Traditional Chinese medicine believes that kidney deficiency is the main cause and pa-thogenesis of anovulation infertility and blood stasis is an important factor throughout the disease course. In clinical practice, therapies for invigorating kidney and activating blood are safe and reliable to treat anovulatory infertility mainly by adjusting the hypothalamus-pituitary-ovarian axis, improving ovarian function, uterine environment and gamete quality and increasing endometrial volume. Under the guidance of the thought of prenatal and postnatal healthcare, the authors tried to explore the effect of therapies for kidney-tonifying and blood-activating in the treatment of anovulatory infertility in eugenics, with the purpose of providing ideas and basis for subsequent relevant clinical studies and contributing to prenatal and postnatal healthcare services.


Assuntos
Anovulação , Infertilidade Feminina , Criança , Eugenia (Ciência) , Feminino , Humanos , Infertilidade Feminina/tratamento farmacológico , Rim , Medicina Tradicional Chinesa , Ovulação , Gravidez
12.
Zhongguo Zhong Yao Za Zhi ; 46(11): 2650-2659, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296561

RESUMO

This study used network pharmacology and molecular docking to study the mechanism of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS). The active ingredients and potential drug targets of Bushen Cu-luan Decoction were obtained by searching the Traditional Chinese Medicine System Pharmacology(TCMSP) database, and the targets of PCOS by searching GeneCards. After the drug targets and disease targets were corrected by Uniprot, the intersection genes were obtained. STRING database and Cytoscape 3.7.2 were used for protein-protein interaction(PPI) analysis of the intersection genes. The ClueGO plug-in of Cytoscape 3.7.2 was employed to perform gene ontology(GO) enrichment and KEGG pathway enrichment for the intersection genes. Finally, molecular docking of the key active ingredients with the targets of Bushen Culuan Formula was performed using AutoDockVina and MGLtools. A total of 136 active ingredients and 314 drug targets of the decoction were obtained from TCMSP, and 136 disease targets from GeneCards. Finally, 49 drug-disease intersection genes were obtained. GO enrichment found that the genes were mainly involved in the regulation of muscle cell apoptosis, positive regulation of small molecule metabolism, core promoter binding, RNA polymerase Ⅱ regulation of pri-miRNA transcription, negative regulation of transmembrane transport and other biological functions. The enriched KEGG pathways mainly included MAPK, PI3 K-Akt, p53, and HIF-1 signaling pathways. The results of molecular docking showed that quercetin and PTGS2 can bind stably and interact through amino acid residues THR206, TRP387, ASN382, etc. This study preliminarily reveals the multi-component, multi-target, and multi-pathway mechanism of Bushen Culuan Formula in the treatment of PCOS-related infertility, which provides a basis for further research.


Assuntos
Medicamentos de Ervas Chinesas , Síndrome do Ovário Policístico , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Ontologia Genética , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/genética , Transdução de Sinais
13.
J Chromatogr A ; 1651: 462329, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34157477

RESUMO

Efficiently tunable capture of the glycosylated/phosphorylated proteins is critical to meet the need of in-depth glycoproteome and phosphoproteome studies. Reported here is a new bifunctional polymer monolithic column by introducing benzeneboronic acid and phosphonic acid onto monolithic column (denoted as poly (EDMA-co-VPBA-co-VPA) monolith) for tunable and specific enrichment of glycoproteins and phosphoproteins via switching different mobile phases. Based on boronate affinity and immobilized metal affinity, the as-prepared poly (EDMA-co-VPBA-co-VPA) monolith exhibited superior performance in selective separation of small molecules and biomacromolecules containing cis-diol/phosphate groups or not. And the frontal chromatography analysis showed that the binding capacity of the poly (EDMA-co-VPBA-co-VPA) monolith towards horseradish peroxidase (HRP, glycoprotein) or ß-casein (phosphoprotein) is four-fold higher than that of bovine serum albumin (BSA, non-glycosylated/phosphorylated protein). Furthermore, combined with mass spectrometry identification, the successful application in specific enrichment of glycopeptides/phosphopeptides from tryptic digests of HRP/ß-casein and direct capture of low abundant endogenous phosphopeptides from human serum proved great practicability in complex samples. This study provides a novel insight for fabricating the monolithic columns with multifunctionalization to facilitate further post-translational modification (PTM)-proteomics development.


Assuntos
Análise Química do Sangue/instrumentação , Cromatografia/instrumentação , Glicoproteínas/isolamento & purificação , Fosfoproteínas/isolamento & purificação , Polímeros/química , Ácidos Borônicos/química , Caseínas/metabolismo , Glicopeptídeos/isolamento & purificação , Peroxidase do Rábano Silvestre/metabolismo , Humanos , Fosfopeptídeos/química , Ácidos Fosforosos/química , Soroalbumina Bovina/isolamento & purificação
15.
Int J Pharm ; 605: 120784, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34111544

RESUMO

Diabetes is a metabolic disease caused by insufficient insulin secretion, action or resistance, in which insulin plays an irreplaceable role in the its treatment. However, traditional administration of insulin requires continuous subcutaneous injections, which is accompanied by inevitable pain, local tissue necrosis and hypoglycemia. Herein, a green and safe nanoformulation with unique permeability composed of insulin and ginsenosides is developed for transdermal delivery to reduce above-mentioned side effects. The ginsenosides are self-assembled to form shells to protect insulin from hydrolysis and improve the stability of nanoparticles. The nanoparticles can temporarily permeate into cells in 5 min and promptly excrete from the cell for deeper penetration. The insulin permeation is related to the disorder of stratum corneum lipids caused by ginsenosides. The skin acting as drug depot mantains the nanoparticles released continuously, therefore the body keeps euglycemic for 48 h. Encouraged by its long-lasting and effective transdermal therapy, ginsenosides-based nano-system is expected to deliver other less permeable drugs like proteins and peptides and benefit those who are with chronic diseases that need long-term medication.


Assuntos
Ginsenosídeos , Nanopartículas , Administração Cutânea , Sistemas de Liberação de Medicamentos , Insulina , Permeabilidade , Pele
16.
Infect Dis Poverty ; 10(1): 58, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33947468

RESUMO

BACKGROUND: Shanghai had a local outbreak of COVID-19 from January 21 to 24. Timely and precise strategies were taken to prevent further spread of the disease. We discussed and shared the experience of COVID-19 containment in Shanghai. PROCESS: The first two patients worked at two hospitals but no staff from the two hospitals were infected. The suspected case and his two close contacts were confirmed to be infected within 12 h. The testing rate of individuals was low. The scope of screening was minimized to two related districts and the close contact tracing was completed within 12 h, which were precise and cost-effective. CONCLUSIONS: Active monitoring, precise epidemiological investigation and timely nucleic acid testing help discover new cases, minimize the scope of screening, and interrupt the transmission.


Assuntos
COVID-19/epidemiologia , COVID-19/transmissão , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/prevenção & controle , China/epidemiologia , Busca de Comunicante , Complicações do Diabetes , Surtos de Doenças , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Quarentena/normas
17.
Front Pharmacol ; 12: 681424, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054555

RESUMO

Diabetic nephropathy the main reason for end stage renal disease is a common microvascular complication in patients with type 1 and type 2 diabetes. The interleukin-6 (IL-6), acting as a pleiotropic cytokine, play key roles in main autoimmune disorders. The recombinant anti-IL-6R fusion proteins (VHH-0031) constructed and obtained in our lab is a dual target-directed single domain-based fusion protein against the interleukin-6 receptor. This study aims to explore the renoprotective effect of VHH-0031 in diabetic nephropathy. VHH-0031 treatment alleviated renal inflammation, morphologic injury and renal insufficiency in both Goto-Kakizaki rats and STZ-induced Sprague Dawley rats. These renoprotective effects of VHH-0031 are associated with alleviating inflammation and suppression of the JAK2/STAT3 signaling pathway. The mesangial cells treated with VHH-0031 exhibited anti-proliferation, anti-inflammation and inactivation of JAK2/STAT3 pathway under high glucose condition. In conclusion, this study demonstrates that VHH-0031 exhibited a potent protective effect in kidney of diabetic rats and its mechanism may be concerned with the inhibition of the IL-6R/JAK2/STAT3 pathway of glomerular mesangial cells.

18.
Immunol Lett ; 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34033850

RESUMO

Invasion and metastasis of breast cancer cells is an important cause of death in breast cancer patients. In the tumor microenvironment, M2 polarization of macrophages can promote the invasion and metastasis of tumor cells. OVOL2 is an evolutionarily conserved transcription regulator, but its effect in macrophages has not been described previously. The aim of this study was to investigate the effects of OVOL2 on macrophage polarity and the role of these effects in the tumor metastasis. We found that overexpression of OVOL2 in macrophages significantly inhibited M2 polarization and thus inhibits breast cancer metastasis. We propose a novel mechanism in which OVOL2 inhibits M2 polarization of macrophages and thus reduces their ability to induce invasion and metastasis of breast cancer. By shedding new light on the regulation of metastasis in cancers, our study provides a new strategy for the targeted therapy of cancer.

19.
Chemistry ; 27(37): 9654-9660, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-33843095

RESUMO

l-Threonine aldolase from Actinocorallia herbida (AhLTA) is an ideal catalyst for producing l-threo-4-methylsulfonylphenylserine [(2S,3R)-1 b], a key chiral precursor for florfenicol and thiamphenicol. The moderate Cß stereoselectivity is the main obstacle to the industrial application of AhLTA. To address this issue, a combinatorial active-site saturation test (CAST) together with sequence conservatism analysis was applied to engineer the AhLTA toward improved Cß stereoselectivity. The optical mutant Y314R could asymmetrically synthesize l-threo-4-methylsulfonylphenylserine with 81 % diastereomeric excess (de), which is 23 % higher than wild-type AhLTA. Molecular dynamic (MD) simulations revealed that the mechanism for the improvement in Cß stereoselectivity of Y314R is due to the acylamino group of residues Arg314 controlling the orientation of substrate 4-methylsulfonyl benzaldehyde (1 a) in the active pocket by directed interaction with the methylsulfonyl group; this leads to asymmetric synthesis of l-threo-4-methylsulfonylphenylserine. The success in this study demonstrates that direct control of substrates in an active pocket is an attract strategy to address the Cß stereoselectivity problem of LTA and contribute to the industrial application of LTA.


Assuntos
Glicina Hidroximetiltransferase , Actinobacteria , Catálise , Domínio Catalítico , Glicina Hidroximetiltransferase/metabolismo , Especificidade por Substrato
20.
Lung ; 199(3): 299-305, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33876295

RESUMO

PURPOSE: To assess the risk factors, incidence and significance of pneumothorax in patients undergoing CT-guided lung biopsy. METHODS: Patients who underwent a CT-guided lung biopsy between August 10, 2010 and September 19, 2016 were retrospectively identified. Imaging was assessed for immediate and delayed pneumothorax. Records were reviewed for presence of risk factors and the frequency of complications requiring chest tube placement. 604 patients were identified. Patients who underwent chest wall biopsy (39) or had incomplete data (9) were excluded. RESULTS: Of 556 patients (average age 66 years, 50.2% women) 26.3% (146/556) had an immediate pneumothorax and 2.7% (15/556) required chest tube placement. 297/410 patients without pneumothorax had a delayed chest X-ray. Pneumothorax developed in 1% (3/297); one patient required chest tube placement. Pneumothorax risk was associated with smaller lesion sizes (OR 0.998; 95% CI (0.997, 0.999); [p = 0.002]) and longer intrapulmonary needle traversal (OR 1.055; 95% CI (1.033, 1.077); [p < 0.001]). Previous ipsilateral lung surgery (OR 0.12; 95% CI (0.031, 0.468); [p = 0.002]) and longer needle traversal through subcutaneous tissue (OR 0.976; 95% CI (0.96, 0.992); [p = 0.0034]) were protective of pneumothorax. History of lung cancer, biopsy technique, and smoking history were not significantly associated with pneumothorax risk. CONCLUSION: Delayed pneumothorax after CT-guided lung biopsy is rare, developing in 1% of our cohort. Pneumothorax is associated with smaller lesion size and longer intrapulmonary needle traversal. Previous ipsilateral lung surgery and longer needle traversal through subcutaneous tissues are protective of pneumothorax. Stratifying patients based on pneumothorax risk may safely obviate standard post-biopsy delayed chest radiographs.

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