Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 451
Filtrar
1.
BMC Infect Dis ; 21(1): 1026, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592936

RESUMO

BACKGROUND: Cytomegalovirus (CMV) reactivation is associated with adverse prognoses of critically ill patients. However, the epidemiology and predictors of CMV reactivation in immunocompetent patients receiving mechanical ventilation (MV) are not clear. The aim of this study was to investigate the epidemiology and predictors of CMV reactivation in immunocompetent patients requiring MV. METHODS: A single-center, prospective observational study (conducted from June 30, 2017 to July 01, 2018) with a follow-up of 90 days (September 29, 2018) that included 71 CMV-seropositive immunocompetent patients with MV at a 37-bed university hospital general intensive care unit (ICU) in China. Routine detection of CMV DNAemia was performed once a week for 28 days (Days 1, 7, 14, 21, and 28). CMV serology, laboratory findings, and clinical data were obtained during hospitalization. RESULTS: Among 71 patients, 13 (18.3%) showed CMV reactivation within 28 days in the ICU. The median time to reactivation was 7 days. CMV reactivation was related to various factors, including body mass index (BMI), sepsis, N-terminal pro-b-type natriuretic peptide (NT-proBNP), blood urea nitrogen (BUN), and hemoglobin (Hb) levels (P < 0.05). In the multivariate regression model, BMI, Hb level, and sepsis were independently associated with CMV reactivation patients (P < 0.05). Moreover, the area under the receiver operating characteristic (AUROC) of BMI, Hb, and BMI combined with Hb was 0.69, 0.70, and 0.76, respectively. The duration of MV, hospitalization expense, length of ICU stay, and 90 day all-cause mortality rate in patients with CMV reactivation was significantly higher than in those without CMV reactivation (P < 0.05). CONCLUSIONS: Among immunocompetent patients with MV, the incidence of CMV reactivation was 18.3%. CMV reactivation was associated with several adverse prognoses. BMI, Hb, and sepsis were independent risk factors for CMV reactivation. BMI and Hb may predict CMV reactivation.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Estado Terminal , Infecções por Citomegalovirus/epidemiologia , Humanos , Respiração Artificial/efeitos adversos , Ativação Viral
2.
Hypertens Pregnancy ; : 1-10, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606403

RESUMO

PURPOSE: This study is aimed to elucidate the molecular mechanism of lncRNA SNHG7 on pre-eclampsia (PE). METHODS: The expression of SNHG7, miR-214-5p and TWIST1 in PE placental tissues was detected by qRT-PCR. The regulatory mechanism of SNHG7/miR-214-5p/TWIST1 axis on PE was determined using MTT, wound healing, transwell invasion, and western blot assays. RESULTS: In PE pregnancies, SNHG7 and TWIST1 were decreased, while miR-214-5p was increased.The elevated miR-214-5p and decreased TWIST1 partly eliminated the promoting effects of SNHG7 up-regulation on the viability and metastasis of JEG-3 cells. CONCLUSIONS: Up-regulated SNHG7 protects against PE through modulating the miR-214-5p/TWIST1 axi.

3.
Integr Med Res ; : 100778, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34608432

RESUMO

Background: The outbreak of Coronavirus disease 2019 (COVID-19) has caused more than 180 million infections and 3.9 million deaths. To date, emerging clinical evidence has shown the synergetic benefits of Chinese herbal injections in treating this contagious respiratory disease. This review aims to summarize and analyze the efficacy and safety of Chinese herbal injections in the therapy of COVID-19. Methods: The literature from 3 electronic databases, PubMed, CNKI, and Web of Science, were searched using the search terms "COVID-19", "SARS-CoV-2", "traditional Chinese medicine", "herb", "herbal", and "injection". Then the identified articles were comprehensively evaluated. Results: Limited data demonstrated that Chinese herbal injections could significantly improve the clinical outcomes of COVID-19 patients, especially in combination with conventional treatment strategies. The benefits of which were mainly associated with the relief of symptoms, prevention of secondary infection, regulation of inflammation and immune function. There was also evidence showing the inhibitory effects on SARS-CoV-2 replication in vitro. Nevertheless, available real-world data suggested the increased risk of adverse event. Furthermore, the defects of existing researches and the insights for discovering novel antiviral drugs were prospectively discussed. Conclusion: Evidence-based advances revealed that Chinese herbal injections such as XueBiJing injection and ShenMai injection, exerted potent effects against COVID-19. Further laboratory researches and clinical evaluation are needed to gather scientific evidence on the efficacy and safety.

4.
Adv Mater ; : e2103266, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34562030

RESUMO

Hydrogen peroxide (H2 O2 ) is an environment-friendly and efficient oxidant with a wide range of applications in different industries. Recently, the production of hydrogen peroxide through direct electrosynthesis has attracted widespread research attention, and has emerged as the most promising method to replace the traditional energy-intensive multi-step anthraquinone process. In ongoing efforts to achieve highly efficient large-scale electrosynthesis of H2 O2 , carbon-based materials have been developed as 2e- oxygen reduction reaction catalysts, with the benefits of low cost, abundant availability, and optimal performance. This review comprehensively introduces the strategies for optimizing carbon-based materials toward H2 O2 production, and the latest advances in carbon-based hybrid catalysts. The active sites of the carbon-based materials and the influence of coordination heteroatom doping on the selectivity of H2 O2 are extensively analyzed. In particular, the appropriate design of functional groups and understanding the effect of the electrolyte pH are expected to further improve the selective efficiency of producing H2 O2 via the oxygen reduction reaction. Methods for improving catalytic activity by interface engineering and reaction kinetics are summarized. Finally, the challenges carbon-based catalysts face before they can be employed for commercial-scale H2 O2 production are identified, and prospects for designing novel electrochemical reactors are proposed.

5.
Zhen Ci Yan Jiu ; 46(9): 751-6, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34558240

RESUMO

OBJECTIVE: To observe the effect of acupuncture on the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin (Endostatin, ES) mRNAs and proteins (angiogenesis related factors) in the ischemic penumbra region in rats with cerebral infarction (CI), so as to explore its underlying mechanisms in prolonging the time window of thrombolysis therapy for CI. METHODS: A total of 48 male SD rats were randomly divided into sham operation, model, medication (6 h thrombolysis) and acupuncture (Acupunct)+medication groups (n=12 in each group). The CI model was established using modified auto-thrombus method. Six hours after thrombolysis, recombinant human tissue plasminogen activator (rt-PA,10 mg/kg) was given to rats of the thrombolysis group through tail vein. Acupuncture was applied at "Shuigou"(CV26) and bilateral "Neiguan" (PC6) 2 h after successful modeling, and the needles were retained for 30 minutes. Cerebral blood flow (CBF) was monitored during modeling in each group, and the neurological deficit score (0-7 points) was given 2 h and 24 h after successful modeling according to Bederson's methods. The cerebral infarction volume was observed after triphenyltetrazole chloride (TTC) staining. The protein and mRNA expression levels of VEGF, bFGF and ES in the ischemic penumbra region of the right cerebral cortex were detected by Western blot and real-time PCR, separately. RESULTS: The neurological deficit score at both 2 h and 24 h after modeling, percentage of cerebral infarction volume, and the expression levels of VEGF, bFGF and ES proteins and mRNAs in the model group were significantly higher than those of the sham operation group (P<0.01, P < 0.05). Compared with the model group, the neurological deficit score 24 h (not at 2 h) after modeling and percentage of cerebral infarction volume, and the expression levels of ES protein and mRNA in the Acupunct+medication group (not in the medication group) were notably lower (P<0.05, P<0.01), while the expression levels of VEGF and bFGF proteins and mRNAs in the Acupunct +medication group (not in the medication group) were considerably higher (P<0.01, P<0.05). No significant differences were found between medication and model groups in the CI percentage, VEGF, bFGF and ES proteins and mRNAs (P>0.05). The therapeutic effect of Acupunct +medication group was significantly superior to that of medication in lowering neurological deficit score, percentage of CI volume and expression of ES protein and mRNA and in up-regulating the expression of VEGF and bFGF proteins and mRNAs (P<0.05, P<0.01). CONCLUSION: Acupuncture and timely intervention can prolong the time window of thrombolysis in CI rats, which may be related to its function in up-regulating the expression of VEGF and bFGF mRNAs and proteins and in down-regulating the expression of ES mRNA and protein in ischemic cerebral cortex.


Assuntos
Terapia por Acupuntura , Isquemia Encefálica , Animais , Isquemia Encefálica/genética , Isquemia Encefálica/terapia , Córtex Cerebral , Infarto Cerebral/genética , Infarto Cerebral/terapia , Masculino , Ratos , Ratos Sprague-Dawley , Terapia Trombolítica , Ativador de Plasminogênio Tecidual , Fator A de Crescimento do Endotélio Vascular/genética
7.
Trends Cell Biol ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34535364

RESUMO

Meal timing resets trillions of cellular circadian clocks in the body. Recent advances in multiomics demonstrate that clocks in peripheral tissues are differentially reset by feeding rhythm, and modulated by the central clock and the liver clock. This highlights the essential roles of tissue-specific regulation and intercellular signaling in clock synchronization.

8.
Clin Transl Med ; 11(9): e525, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34586737

RESUMO

N6 -methyladenosine (m6 A), the newest and most prevalent layer of internal epigenetic modification in eukaryotic mRNA, has been demonstrated to play a critical role in cancer biology. Increasing evidence has highlighted that the interaction between cancer stem cells (CSCs) and the tumor immune microenvironment (TIME) is the root cause of tumorigenesis, metastasis, therapy resistance, and recurrence. In recent studies, the m6 A modification has been tightly linked to this CSC-TIME interplay, participating in the regulation of CSCs and TIME remolding. Interestingly, the m6 A modification has also been identified as a novel decisive factor in the efficacy of immunotherapies-particularly anti-PD-1/PD-L1 monotherapies-by changing the plasticity of the TIME. Given the functional importance of the m6 A modification in the crosstalk between CSCs and the TIME, targeting m6 A regulators will open new avenues to overcome therapeutic resistance, especially for immune checkpoint-based immunotherapy. In the present review, we summarize the current landscape of m6 A modifications in CSCs and the TIME, and also prospect the underling role of m6 A modifications at the crossroads of CSCs and the TIME for the first time. Additionally, to provide the possibility of modulating m6 A modifications as an emerging therapeutic strategy, we also explore the burgeoning inhibitors and technologies targeting m6 A regulators. Lastly, considering recent advances in m6 A-seq technologies and cancer drug development, we propose the future directions of m6 A modification in clinical applications, which may not only help to improve individualized monitoring and therapy but also provide enhanced and durable responses in patients with insensitive tumors.

9.
Front Cell Infect Microbiol ; 11: 707107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532300

RESUMO

Endoplasmic reticulum (ER) stress-induced autophagy is closely associated with viral infection and propagation. However, the intrinsic link between ER stress, autophagy, and viral replication during foot-and-mouth disease virus (FMDV) infection is not fully elucidated. Our previous studies demonstrated that FMDV infection activated the ER stress-associated UPR of the PERK-eIF2a and ATF6 signaling pathway, whereas the IRE1a signaling was suppressed. We found that the activated-ATF6 pathway participated in FMDV-induced autophagy and FMDV replication, while the IRE1α pathway only affected FMDV replication. Further studies indicated that Sec62 was greatly reduced in the later stages of FMDV infection and blocked the activation of the autophagy-related IRE1α-JNK pathway. Moreover, it was also found that Sec62 promoted IRE1a phosphorylation and negatively regulated FMDV proliferation. Importantly, Sec62 may interact with LC3 to regulate ER stress and autophagy balance and eventually contribute to FMDV clearance via fusing with lysosomes. Altogether, these results suggest that Sec62 is a critical molecule in maintaining and recovering ER homeostasis by activating the IRE1α-JNK pathway and delivering autophagosome into the lysosome, thus providing new insights on FMDV-host interactions and novel antiviral therapies.


Assuntos
Vírus da Febre Aftosa , Animais , Autofagia , Estresse do Retículo Endoplasmático , Endorribonucleases , Proteínas Serina-Treonina Quinases , Replicação Viral
10.
Dalton Trans ; 50(40): 14325-14331, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34558579

RESUMO

Expanding the family of lanthanide terpyridine coordination polymers has yielded eighteen new complexes with two different phases, Ln(TPC)2(HCOO)(H2O) (Ln-1) and Ln(TPC)(HCOO)2 (Ln-2) (Ln = Sm-Lu, except Tm). Both structures are composed of lanthanide cations interconnected by 2,2':6',2''-terpyridine-4'-carboxylate ligands to yield one-dimensional chain topologies. However, the incorporation of an additional crystallographically unique decorative TPC ligand into Ln-1 gives rises to a distinct phase. The encapsulation of both metal- and ligand-based phosphors within single coordination polymers leads to dual-emission of the afforded materials. Furthermore, judicious lanthanide doping in heterometallic Ln-1 and Ln-2 allows for fine-tuning the photoluminescent colours over a wide range of gamut. Such a combination showcases the capability to fine-tune the emission colours from deep green, to red, and to blue. In addition, direct white-light emission upon UV excitation can be achieved in the SmxGd1-x-1 system.

11.
Atherosclerosis ; 333: 39-47, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34425526

RESUMO

BACKGROUND AND AIMS: Vascular smooth muscle cells (VSMCs) play a critical role in atherosclerosis. The family with sequence similarity 172, member A (FAM172A) is a novel protein and its role in atherosclerosis has not been explored so far. Therefore, our aim is to investigate whether FAM172A affects atheroprogression through VSMCs and its possible mechanism. METHODS: Fam172a-/- mice were generated using CRISPR/Cas9 technology. Fam172a-/- and Apoe-/- double knockout (Fam172a-/-/Apoe-/-) mice and their littermates (Fam172a+/+/Apoe-/-) were fed with a Western diet for 18 weeks to induce advanced atherosclerotic lesions. The role and mechanism of Fam172a in phenotypic switching, proliferation and migration of VSMCs were investigated through in vivo and in vitro experiments. RESULTS: Compared with Fam172a+/+/Apoe-/- mice, Fam172a-/-/Apoe-/- mice showed increased atherosclerotic lesion size and plaque instability such as increased necrotic core area and decreased fiber deposition. Additionally, knockout of Fam172a promoted expression of CD68 and KLF4 and decreased expression of α-SMA and SM22α in atherosclerotic lesions. Furthermore, overexpression of Fam172a promoted Movas cells proliferation and migration, increased expression of α-SMA and SM22α and decreased expression of KLF4. Meanwhile, knockdown of Fam172a in Movas cells and deletion of Fam172a in VSMCs from Fam172a-/-/Apoe-/- mice showed opposite phenotypes. Similar phenotypes were also observed in human aortic smooth muscle cells. CONCLUSIONS: Our results provide the first direct evidence that Fam172a has a protective role in advanced atherosclerosis by increasing atherosclerotic plaque stability and inhibiting transition of VSMCs from contractile to synthetic phenotype, which may be through KLF4-dependent pathway.

12.
Hum Mol Genet ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34368847

RESUMO

Genotype imputation is widely used in genetic studies to boost the power of GWAS, to combine multiple studies for meta-analysis and to perform fine mapping. With advances of imputation tools and large reference panels, genotype imputation has become mature and accurate. However, the uncertain nature of imputed genotypes can cause bias in the downstream analysis. Many studies have compared the performance of popular imputation approaches, but few investigated bias characteristics of downstream association analyses. Herein, we showed that the imputation accuracy is diminished if the real genotypes contain minor alleles. Although these genotypes are less common, which is particularly true for loci with low minor allele frequency, a large discordance between imputed and observed genotypes significantly inflated the association results, especially in data with a large portion of uncertain SNPs. The significant discordance of p-values happened as the p-value approached 0 or the imputation quality was poor. Although elimination of poorly imputed SNPs can remove false positive (FP) SNPs, it sacrificed, sometimes, more than 80% true positive (TP) SNPs. For top ranked SNPs, removing variants with moderate imputation quality cannot reduce the proportion of FP SNPs, and increasing sample size in reference panels did not greatly benefit the results as well. Additionally, samples with a balanced ratio between cases and controls can dramatically improve the number of TP SNPs observed in the imputation based GWAS. These results raise concerns about results from analysis of association studies when rare variants are studied, particularly when case-control studies are unbalanced.

14.
Diabetes Metab J ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34372627

RESUMO

Background: The association of serum retinol-binding protein (RBP) levels with nonalcoholic fatty liver disease (NAFLD) remains controversial. Furthermore, few studies have investigated their relationship in type 2 diabetes mellitus (T2DM) patients. Therefore, the aim of the present study was to explore the association between serum RBP levels and NAFLD in Chinese inpatients with T2DM. Methods: This cross-sectional, real-world study included 2,263 Chinese T2DM inpatients. NAFLD was diagnosed by abdominal ultrasonography. The subjects were divided into four groups based on RBP quartiles, and clinical characteristics were compared among the four groups. The associations of both RBP levels and quartiles with the presence of NAFLD were also analyzed. Results: After adjustment for sex, age, and diabetes duration, there was a significant increase in the prevalence of NAFLD from the lowest to the highest RBP quartiles (30.4%, 40.0%, 42.4%, and 44.7% for the first, second, third, and fourth quartiles, respectively, P<0.001 for trend). Fully adjusted multiple logistic regression analysis revealed that both increased RBP levels (odds ratio, 1.155; 95% confidence interval, 1.012 to 1.318; P=0.033) and quartiles (P=0.014 for trend) were independently associated with the presence of NAFLD in T2DM patients. Conclusion: Increased serum RBP levels were independently associated with the presence of NAFLD in Chinese T2DM inpatients. Serum RBP levels may be used as one of the indicators to assess the risk of NAFLD in T2DM patients.

15.
Org Lett ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34378938

RESUMO

A convenient catalytic protocol for efficiently constructing indoline-fused tetrahydroisoquinolines based on CuCoFe layered double hydroxide (LDH) has been described. Preliminary mechanistic studies show that indoline-fused tetrahydroisoquinolines are produced via domino coupling/cyclization reactions between tetrahydroisoquinolines and active methylene compounds, including malononitrile, malonates, and analogues. CuCoFe-LDH can accelerate the Csp3-Csp3 and Csp3-Csp2 formation reactions in a single step. The research thus presents a unique opportunity to develop a synthetic methodology for N-containing polycyclic compounds.

16.
J Cell Mol Med ; 25(18): 8920-8928, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34382339

RESUMO

Hypoxia as a crucial pathogenesis factor usually results in huge harmful effects on cardiac injury and dysfunction. Our previous study has uncovered the global transcriptome and translatome profiles of cardiomyocytes in vitro and in vivo to response to hypoxia by RNA sequencing and ribosome profiling sequencing. We observe a series of differential expressed genes between transcription and translation, which may be attributed to the hypoxia-specific binding affinity of nuclear cap-binding subunit 3 (NCBP3) at 5' untranslation region of target genes. Although we observe that NCBP3 can facilitate translational process in myocardium under hypoxia stress, the underlying molecular mechanism of NCBP3 for gene translation modulation remains unclear. In this study, we performed NCBP3 immunoprecipitation for mass spectrum and found that METTL3 and eIF4A2 particularly interacted with NCBP3 in hypoxic rat H9C2 cardiomyocytes. Furthermore, we observed that METTL3-mediated N6-methyladenosine (m6A) methylation was elevated in hypoxia, but compromised by NCBP3 or METTL3 knockdown. Finally, we also demonstrated that NCBP3/METTL3/eIF4A2 regulatory axis plays a specific role in cardiomyocytes undergoing hypoxic stress. Taken together, we unmasked NCBP3, a novel hypoxia-specific response protein functions as a scaffold to coordinate METTL3 and eIF4A2 for enhancing gene translation by m6A RNA methylation in cardiomyocytes upon hypoxic stress.

17.
Leuk Res ; 111: 106688, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34450501

RESUMO

BACKGROUND: Interstitial pneumonitis (IP), a fatal complication of DLBCL treatment, can bring great challenges to clinicians. We retrospectively investigated clinical characteristics and risk factors of previous IP patients, and analyzed their survival data. METHODS: 556 DLBCL patients receiving CHOP-like regimens were enrolled between 2013 and 2018 in Sichuan Cancer Hospital. FINDINGS: The IP incidences were 4.9 % (27/556), 1.1 % (2/186), 5.2 % (10/191) and 8.4 % (15/179) in CHOP, R-CHOP and R-CDOP groups respectively (P = 0.005). When IP was diagnosed, monocyte and IL-6 were significantly higher while CD4 and CD4/CD8 significantly lower compared to baseline. 81.5 % (22/27) of IP patients were pathogen-negative with good response to glucocorticoid monotherapy. Only one patient died while the others recovered from IP and subsequently underwent previous chemotherapy. 19.2 % (5/26) of IP patients experienced IP recurrence, likely due to the reason of lower initial dose or faster withdrawal speed of glucocorticoid. Multivariate analysis identified male, in addition to G-CSF, rituximab and pegylated liposomal doxorubicin as risk factors. The 3-year PFS and OS were 74.1 % and 46.9 % respectively for patients with IP. INTERPRETATION: We suggest that IL-6, monocyte and CD4 should be monitored closely, especially in R-CHOP/R-CDOP group. Sufficient initial dose and slow decrease of glucocorticoid based on radiographic remissions were critical strategies to reduce IP recurrence. We speculate that drug-induced immune imbalance could be trigger of developing IP, causing a lower intensity cytokine storm, resulting in a potential immunotherapy. This complication might bring benefit in patients' survival through a mechanism similar to PD-1.

18.
Chem Biol Interact ; 347: 109605, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34333021

RESUMO

Cell injury is a necessary and critical event during CaOx kidney stone formation. Sirt1 exerts a number of pleiotropic effects, protecting against renal cell injury. This study aims to explore the relationship between Sirt1 and CaOx kidney stone formation and the underlying mechanism. Sirt1 expression in renal tissues or HK-2 cells was detected by Western blot, immunohistochemistry and immunofluorescence. Apoptosis in renal tissues was examined by TUNEL staining. Renal pathological changes and the crystals deposition were detected by hematoxylin-eosin and Von Kossa staining. Crystal-cell adhesion and cell injury in HK-2 cells were assessed by atomic absorption spectrometry and flow cytometry, respectively. Sirt1 expression in nephrolithiasis patients was downregulated and the level of apoptosis was increased. Further study found that Sirt1 expression was decreased in both in vivo and in vitro models. Interestingly, the levels of cell injury were elevated in vivo and in vitro models. Suppressing Sirt1 expression promoted COM-induced crystal-cell adhesion and exacerbated cell injury. In contrast, increasing the expression of Sirt1 by lentivirus transfection in vitro and resveratrol administration in vivo, alleviated crystal deposition and cell damage. Our findings suggest that Sirt1 could inhibit kidney stone formation, at least in part, through attenuating CaOx -induced cell injury.


Assuntos
Oxalato de Cálcio/efeitos adversos , Cálculos Renais/metabolismo , Sirtuína 1/metabolismo , Idoso , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Oxalato de Cálcio/química , Oxalato de Cálcio/farmacologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Linhagem Celular , Cristalização , Feminino , Inativação Gênica , Glioxilatos , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Cálculos Renais/induzido quimicamente , Cálculos Renais/tratamento farmacológico , Cálculos Renais/patologia , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Necrose/induzido quimicamente , Necrose/metabolismo , Resveratrol/uso terapêutico , Sirtuína 1/genética
19.
J Mech Behav Biomed Mater ; 123: 104759, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34365100

RESUMO

Magnesium (Mg)-based composites, as biomaterials, have attracted widespread attention due to their adjustable mechanical properties like elastic modulus, ductility, ultimate tensile strength, and corrosion resistance. In this study, hydroxyapatite (HA) reinforced ZK61 Mg-matrix composites were prepared by powder metallurgy and hot extrusion methods. The influence of the content of HA (10 wt%, 20 wt%, and 30 wt%) on the microstructure, density, mechanical properties, corrosion property and biocompatibility were investigated. The results showed that the density and yield strength of the composites match those of natural bone. Moreover, the composite with 10 % HA (ZK61-10HA) exhibited the best corrosion resistance, as determined by the electrochemical measurement and immersion test in simulated body fluid (SBF) at 37 °C. In addition, the ZK61-10HA composite significantly enhanced the cell viability (≥78 %) compared with ZK61 alloy in vitro testing. It is demonstrated that the mechanical properties, corrosion resistance and biocompatibility of Mg alloy can be effectively controlled by adjusting the content of HA, which suggested that the ZK61-HA composites were promising candidates for degradable implant materials.


Assuntos
Durapatita , Magnésio , Ligas , Materiais Biocompatíveis/farmacologia , Corrosão , Teste de Materiais
20.
Eur J Cancer ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34462189

RESUMO

BACKGROUND: GLS-010 (zimberelimab) is a novel, fully human, anti-programmed death-1 monoclonal antibody that shows promising efficacy and safety in advanced solid tumors. This trial aimed to evaluate the efficacy and safety of GLS-010 (zimberelimab) in Chinese patients with relapsed or refractory classical Hodgkin lymphoma (r/r-cHL). METHODS: This phase II, single-arm, open-label, multicenter clinical trial was conducted at 24 centers in China and enrolled patients with r/r-cHL after two or more lines of therapy. The patients were administered intravenous GLS-010 (zimberelimab) (240 mg, once every 2 weeks) until progression, death, unacceptable toxicity, or consent withdrawal. The primary end-point was the objective response rate assessed by an independent radiology review committee (IRC). This study was registered (NCT03655483). RESULTS: Eighty-five patients were enrolled between August 2018 and August 2019. The median follow-up was 15.8 months. Seventy-seven patients (90.6%; 95% confidence interval [CI] 82.3-95.9) had an IRC-assessed objective response. The complete response rate was 32.9% (n = 28). The 12-month progression-free survival and overall survival rates were 78% (95% CI 67.5-85.6) and 99% (95% CI 91.9-99.8), respectively. Treatment-related adverse events (TRAEs) were observed in 92.9% of participants. Grade III or IV TRAEs occurred in 24 (28.2%) of the 85 participants. The most common grade III or IV TRAEs were abnormal hepatic function (5.9%), hyperuricemia (4.7%), decreased neutrophil count (3.5%), and increased weight (3.5%). Only one grade V AE, gastrointestinal infection, occurred. CONCLUSIONS: GLS-010 (zimberelimab) appears to be effective and safe for the treatment of Chinese patients with r/r-cHL. Long-term follow-up is required to confirm these clinical benefits.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...