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1.
J Mech Behav Biomed Mater ; 124: 104807, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34492404

RESUMO

New fabrication methods and lubrication materials must be developed to improve the lubrication performance of artificial joints and increase the lubrication duration. Herein, a novel polyvinyl alcohol/polyethylene glycol/graphene oxide (PVA/PEG/GO) hydrogel was prepared by a physical cross-linking method, and then the hydrogel and its sustained-release solution were used as lubricant for friction evaluation. The results demonstrated that the slow-release gel solution has good lubrication performance, and coefficient of friction (COF) is only 0.04, which is much lower than the COF of distilled water (about 0.08) under the same conditions. The structure characterization results revealed that no new materials are formed in the gel. The results of thermogravimetric analyses and differential scanning calorimetry demonstrated that the addition of GO may improve the network crosslinking structure of the PVA/PEG hydrogel and improve its mechanical strength. In addition, PVA/PEG/GO hydrogel has superior self-healing function. The self-healing hydrogel did not break again after being pulled under 200 G of weights. The PVA/PEG/GO hydrogel with excellent slow-release lubricating performance and self-healing properties provides a novel candidate for design of long-term lubricating artificial joints, and is expected to promote the progress of artificial joint lubrication applications.

2.
Comput Intell Neurosci ; 2021: 9969322, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475950

RESUMO

To explore the influence of weather conditions on the choice of the intercity travel mode of travelers, four modes of traveler transportation were studied in Xi'an, China, in March 2019: airplane, high-speed rail, conventional train, and express bus. The individual characteristics of travelers and intercity travel activity data were obtained, and they were matched with the weather characteristics at the departure time of the travelers. The Bayesian multinomial logit regression was employed to explore the relationship between the travel mode choice and weather characteristics. The results showed that temperature, relative humidity, rainfall, wind, air quality index, and visibility had significant effects on the travel mode selection of travelers, and the addition of these variables could improve the model's predictive performance. The research results can provide a scientific decision basis for traveler flow transfer and the prediction of traffic modes choice due to the effects of climate change.


Assuntos
Poluição do Ar , Poluição do Ar/análise , Teorema de Bayes , Transportes , Viagem , Tempo (Meteorologia)
3.
J Med Chem ; 64(18): 13658-13675, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34432448

RESUMO

Enlightened by the available structural biology information, a novel series of dihydrothiopyrano[4,3-d]pyrimidine derivatives were rationally designed via scaffold hopping and molecular hybridization strategies. Notably, compound 20a yielded exceptionally potent antiviral activities (EC50 = 4.44-54.5 nM) against various HIV-1 strains and improved resistance profiles (RF = 0.5-5.6) compared to etravirine and rilpivirine. Meanwhile, 20a exhibited reduced cytotoxicity (CC50 = 284 µM) and higher SI values (SI = 5210-63992). Molecular dynamics simulations were performed to rationalize the distinct resistance profiles. Besides, 20a displayed better solubility (sol. = 12.8 µg/mL) and no significant inhibition of the main CYP enzymes. Furthermore, 20a was characterized for prominent metabolic stability and in vivo safety properties. Most importantly, the hERG inhibition profile of 20a (IC50 = 19.84 µM) was a remarkable improvement. Overall, 20a possesses huge potential to serve as a promising drug candidate due to its excellent potency, low toxicity, and favorable drug-like properties.

4.
Int J Biol Macromol ; 189: 668-677, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34453980

RESUMO

A general and effective strategy was developed for improving simultaneously the mechanical strength and antibacterial performance of biopolymer-based films. The well-dispersed zinc oxide (ZnO) nanoparticles were in-situ loaded on non-toxic natural palygorskite (PAL) nanorod to form an antibacterial PAL@ZnO composite nanorod, which can be embedded into chitosan/gelatin (CS/GL) film to produce the composite films with noticeably enhanced mechanical properties and antibacterial activity against S. aureus and E. coli bacteria (inhibition zones are 21.82 ± 0.95 mm and 16.36 ± 1.64 mm, respectively). The toughness of films enhances to 35.13 ± 0.95 MPa and the moisture uptake decreases to 23.74 ± 0.02% after embedding 3% and 9% of PAL@ZnO, respectively. In addition, incorporating PAL@ZnO nanorods also significantly enhanced the water resistance, and thermal stability of film. This work provides an alternative way for the development of antibacterial films with potential applications in many fields such as food packing.

5.
ACS Appl Mater Interfaces ; 13(33): 38979-38989, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433249

RESUMO

Chronic infections caused by Pseudomonas aeruginosa pose severe threats to human health. Traditional antibiotic therapy has lost its total supremacy in this battle. Here, nanoplatforms activated by the clinical microenvironment are developed to treat P. aeruginosa infection on the basis of dynamic borate ester bonds. In this design, the nanoplatforms expose targeted groups for bacterial capture after activation by an acidic infection microenvironment, resulting in directional transport delivery of the payload to bacteria. Subsequently, the production of hyperpyrexia and reactive oxygen species enhances antibacterial efficacy without systemic toxicity. Such a formulation with a diameter less than 200 nm can eliminate biofilm up to 75%, downregulate the level of cytokines, and finally promote lung repair. Collectively, the biomimetic design with phototherapy killing capability has the potential to be an alternative strategy against chronic infections caused by P. aeruginosa.


Assuntos
Antibacterianos/química , Verde de Indocianina/química , Nanocápsulas/química , Fármacos Fotossensibilizantes/química , Polímeros/química , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/radioterapia , Células A549 , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Composição de Medicamentos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Humanos , Verde de Indocianina/farmacologia , Raios Infravermelhos , Masculino , Metacrilatos/química , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Pseudomonas aeruginosa/efeitos dos fármacos
6.
J Mol Cell Biol ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34450627

RESUMO

Modern diets, which often feature high levels of fat and charcoal-grilled meat, contribute to the pathogenesis of obesity and nonalcoholic fatty liver disease (NAFLD), resulting in liver cancer progression. Benzo(a)pyrene (B[a]P) is a common environmental and foodborne pollutant found in smoke and fire-grilled foods, which can have an adverse effect on human health. Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer and the second leading cause of cancer-related deaths worldwide. The epidemiological studies suggest that both environmental risk factors and chronic liver injury including NAFL are important for HCC development, but the precise mechanisms linking eating habits to hepato-carcinogenesis remain unclear. In the present study, we demonstrated that various miRNAs in B[a]P-exposed tumor cells contribute to tumor metastasis, among which miR-650 could be the most potent inducer. Furthermore, we found that suppressor of cytokine signaling 3 (SOCS3) is directly regulated by miR-650 and its suppression regulates the activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) cascade. Our findings reveal a possible adverse outcome pathway of SOCS3/JAK/STAT3 regulation in B[a]P-induced HCC progress. These results provide a better understanding of the adverse effects of chronic exposure to B[a]P on human health.

7.
PLoS One ; 16(8): e0256352, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34403456

RESUMO

Rapid tests for SARS-COV-2 infection are important tools for pandemic control, but current rapid tests are based on proprietary designs and reagents. We report clinical validation results of an open-access lateral flow assay (OA-LFA) design using commercially available materials and reagents, along with RT-qPCR and commercially available comparators (BinaxNOW® and Sofia®). Adult patients with suspected COVID-19 based on clinical signs and symptoms, and with symptoms ≤7 days duration, underwent anterior nares (AN) sampling for the OA-LFA, Sofia®, BinaxNOW ™, and RT-qPCR, along with nasopharyngeal (NP) RT-qPCR. Results indicate a positive predictive agreement with NP sampling as 69% (60% -78%) OA-LFA, 74% (64% - 82%) Sofia®, and 82% (73% - 88%) BinaxNOW™. The implication for these results is that we provide an open-access LFA design that meets the minimum WHO target product profile for a rapid test, that virtually any diagnostic manufacturer could produce.


Assuntos
Antígenos Virais/análise , COVID-19/diagnóstico , Imunoensaio , SARS-CoV-2/metabolismo , Área Sob a Curva , COVID-19/virologia , Humanos , Nasofaringe/virologia , Sistemas Automatizados de Assistência Junto ao Leito , RNA Viral/análise , RNA Viral/metabolismo , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade
8.
Electrophoresis ; 42(19): 1900-1913, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34240427

RESUMO

Capillary electrophoresis sodium dodecyl sulfate (CE-SDS) is an analytical method to assess the purity of proteins, commonly applied to monoclonal antibodies (mAbs) in the biopharmaceutical industry. To address the need to standardize the CE-SDS method in the pharmaceutical industry and to enhance the confidence in method transfer between laboratories operating different commercial capillary electrophoresis (CE) instrument platforms, an interlaboratory CE-SDS method validation was organized involving 13 laboratories in 13 companies on four different types of commercial capillary electrophoresis instruments. In the validation, a commercial mAb therapeutic was used as the sample. The validation process followed the analytical guidelines set by the ICH guidelines (International Conference for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use). The method's precision, accuracy, linearity and range, and limit of quantitation (LOQ) were validated in the study. Variations of all the parameters validated in the study passed the pre-set criteria defined at the beginning of the study. The definition was based on previously published works and the intended application purpose of the CE-SDS method for mAbs. The study proved that the CE-SDS method fits its intended application purpose as a size impurity assay and size heterogeneity characterization assay for mAb therapeutic products. This study is the first time a CE-SDS method is validated by multiple laboratories using different commercial CE instrument platforms and on a commercial mAb therapeutic. Its results will enhance the confidence of the biopharmaceutical industry to develop CE-SDS methods and transfer CE-SDS methods between different laboratories.

9.
Biomed Pharmacother ; 139: 111711, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243617

RESUMO

Platelet Rich Plasma (PRP) can activate angiogenic and osteogenic pathways, making it a highly promising therapeutic agent for bone growth. Super active platelet lysate (sPL) is derived from platelet-rich plasma (PRP) through ultra-low temperature freeze-thawing. The aim of this study was to evaluate the potential therapeutic effect of sPL on glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). sPL increased the proliferation of GC-treated osteoblasts and endothelial cells, and inhibited apoptosis in vitro. Furthermore, sPL promoted healing of necrotic bone tissues in a rat ONFH model by restraining GC-induced apoptosis and increase autophagy of the osteoblasts. Overall, the results of this study provide a theoretical basis for the clinical application of sPL in ONFH.


Assuntos
Autofagia/efeitos dos fármacos , Plaquetas/metabolismo , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/prevenção & controle , Cabeça do Fêmur/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Plasma Rico em Plaquetas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
10.
Emerg Microbes Infect ; 10(1): 1519-1529, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34278967

RESUMO

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern. S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants. Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay. The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1. Lentil lectin also showed antiviral activity against SARS-CoV and MERS-CoV. We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection. Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity. Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment. This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.


Assuntos
Antivirais/farmacologia , Lens (Planta)/química , Extratos Vegetais/farmacologia , Lectinas de Plantas/farmacologia , SARS-CoV-2/efeitos dos fármacos , Animais , Antivirais/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Lectinas de Plantas/química , SARS-CoV-2/crescimento & desenvolvimento , Sementes/química
11.
Cell Cycle ; 20(15): 1487-1499, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34229586

RESUMO

Oxidative stress mediated apoptotic and pyroptotic cell death contributes to intervertebral disc (IVD) degeneration, and platelet-rich plasma (PRP) exerts protective effects to attenuate IVD degeneration. Hence, the present study aimed to validate this issue and uncover the potential underlying mechanisms. The mice and cellular models for IVD degeneration were established by using puncture method and H2O2 exposure, respectively, and we evidenced that NLRP3-mediated cell pyroptosis, apoptosis and inflammatory responses occurred during IVD degeneration progression in vitro and in vivo. Then, the PRP-derived exosomes (PRP-exo) were isolated and purified, and we noticed that both PRP-exo and ROS scavenger (NAC) reversed the detrimental effects of H2O2 treatment on the nucleus pulposus (NP) cells. Further results supported that PRP-exo exerted its protective effects on H2O2 treated NP cells by modulating the Keap1-Nrf2 pathway. Mechanistically, PRP-exo downregulated Keap1, resulting in the release of Nrf2 from the Keap1-Nrf2 complex, which further translocated from cytoplasm to nucleus to achieve its anti-oxidant biological functions, and H2O2 treated NP cells with Nrf2-deficiency did not respond to PRP-exo treatment. In addition, miR-141-3p was enriched in PRP-exo, and miR-141-3p targeted the 3' untranslated region (3'UTR) of Keap1 mRNA for its degradation, leading to Nrf2 translocation. Furthermore, overexpression of miR-141-3p ameliorated the cytotoxic effects of H2O2 on NP cells, which were abrogated by upregulating Keap1 and silencing Nrf2. Taken together, we concluded that PRP secreted exosomal miR-141-3p to activate the Keap1-Nrf2 pathway, which helped to slow down IVD degeneration.

12.
Front Endocrinol (Lausanne) ; 12: 646720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34322090

RESUMO

We have previously shown that biochanin A exhibits neuroprotective properties in the context of cerebral ischemia/reperfusion (I/R) injury. The mechanistic basis for such properties, however, remains poorly understood. This study was therefore designed to explore the manner whereby biochanin A controls endoplasmic reticulum (ER) stress, apoptosis, and inflammation within fetal rat primary cortical neurons in response to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, and in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R) injury. For the OGD/R in vitro model system, cells were evaluated after a 2 h OGD following a 24 h reoxygenation period, whereas in vivo neurological deficits were evaluated following 2 h of ischemia and 24 h of reperfusion. The expression of proteins associated with apoptosis, ER stress (ERS), and p38 MAPK phosphorylation was evaluated in these samples. Rats treated with biochanin A exhibited reduced neurological deficits relative to control rats following MCAO/R injury. Additionally, GRP78 and CHOP levels rose following I/R modeling both in vitro and in vivo, whereas biochanin A treatment was associated with reductions in CHOP levels but further increases in GRP78 levels. In addition, OGD/R or MCAO/R were associated with markedly enhanced p38 MAPK phosphorylation that was alleviated by biochanin A treatment. Similarly, OGD/R or MCAO/R injury resulted in increases in caspase-3, caspase-12, and Bax levels as well as decreases in Bcl-2 levels, whereas biochanin A treatment was sufficient to reverse these phenotypes. Together, these findings thus demonstrate that biochanin A can alleviate cerebral I/R-induced damage at least in part via suppressing apoptosis, ER stress, and p38 MAPK signaling, thereby serving as a potent neuroprotective agent.

13.
Oncol Rep ; 46(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34328197

RESUMO

A prevalent type of bone tumor, osteosarcoma (OS) is prone to pulmonary metastasis, which results in a high relapse risk and poor prognosis for patients. The progression of OS is significantly associated with the expression of long non­coding (lnc)RNA H19. To the best of our knowledge, however, the exact molecular mechanism of this lncRNA has not been fully investigated. The present study verified the effect of H19 on the proliferation and invasion of osteosarcoma cells via in vivo and in vitro experiments, including Cell Counting Kit­8, western blot, reverse transcription­quantitative PCR, wound healing and Transwell assays. H19 was found to be overexpressed in OS compared with corresponding normal adjacent tissue. In addition, H19 served as a competing endogenous ncRNA targeting microRNA­29a­3p and activating LIM and SH3 domain protein 1 and modulating the OS cell phenotype. The results of the present study may improve understanding of OS pathogenesis.

14.
Biomed Pharmacother ; 139: 111386, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243594

RESUMO

Renal interstitial fibrosis (RIF) is a common pathological response in a broad range of prevalent chronic kidney diseases and ultimately leads to renal failure and death. Although RIF causes a high morbi-mortality worldwide, effective therapeutic drugs are urgently needed. Myofibroblasts are identified as the main effector during the process of RIF. Multiple types of cells, including fibroblasts, epithelial cells, endothelial cells, macrophages and pericytes, contribute to renal myofibroblasts origin, and lots of mediators, including signaling pathways (Transforming growth factor-ß1, mammalian target of rapamycin and reactive oxygen species) and epigenetic modifications (Histone acetylation, microRNA and long non-coding RNA) are participated in renal myofibroblasts activation during renal fibrogenesis, suggesting that these mediators may be the promising targets for treating RIF. In addition, many small molecules show profound therapeutic effects on RIF by suppressing the origin and activation of renal myofibroblasts. Taken together, the review focuses on the mechanisms of the origin and activation of renal myofibroblasts in RIF and the small molecules against them improving RIF, which will provide a new insight for RIF therapy.


Assuntos
Fibrose/tratamento farmacológico , Rim/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Fibroblastos/efeitos dos fármacos , Humanos , Transdução de Sinais/efeitos dos fármacos
15.
J Orthop Surg Res ; 16(1): 451, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261504

RESUMO

INTRODUCTION: To compare the clinical outcomes and the radiographic features between tibial condylar valgus osteotomy (TCVO) and open wedge high tibial osteotomy (OWHTO). New insight into the indication criteria for TCVO was also clarified for achieving satisfactory results. MATERIALS AND METHODS: Sixty-three knees with medial-compartment osteoarthritis were retrospectively studied. Thirty-four knees with subluxated lateral joint and depression of the medial tibial plateau underwent TCVO and the rest underwent OWHTO. Among the 63 knees included, 27 knees with a pre-operative femorotibial angle (FTA) ≥ 185° were defined as severe varus (subgroup S, 15 in STCVO group and 12 in SHTO group). Lower limb alignment, intra-, and extra-articular congruency were evaluated according to the radiograph obtained before and 24 months after surgery. The visual analog scale (VAS) score and Hospital for Special Surgery (HSS) score were obtained to assess the clinical results. Opening angle and distance of the opening gap in each group were measured by intra-operative fluoroscopy. RESULTS: During the 2-year follow-up period, the mean HSS score increased from 70.3 to 81.4 in HTO group and 65.9 to 87.3 in TCVO group (p < 0.05). The mean VAS score decreased from 5.9 to 2.6 and 6.0 to 2.1, respectively (p < 0.01). Pre-operative FTA was restored to 172.9° in HTO group and 171.3° in TCVO group, and percentage of mechanical axis (%MA) was improved to 59.7% and 61.2%, respectively. Joint line convergence angle (JLCA) was slightly restored and medial tibial plateau depression (MTPD) was relatively the same before and after OWHTO, while these parameters improved greatly (from 6.4° to 1.2° and - 8.0° to 5.9°, p < 0.01) in TCVO group. More undercorrected knees were observed in SHTO group than STCVO group (58.3% and 13.3%, p < 0.05). Opening angle and distance of the opening gap were larger in TCVO group (19.1° and 14.0 mm) than those in OWHTO group (9.3° and 10.1 mm, p < 0.05). CONCLUSION: Compared to OWHTO, TCVO had priority in treating advanced knee OA with intra-articular deformity. However, TCVO had a limited capacity to correct the varus angle. Besides, TCVO might be suitable for medial-compartment OA with a pre-operative FTA ≥ 185°.

16.
Front Immunol ; 12: 623610, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093519

RESUMO

Severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) strongly hampered the broad clinical applicability of chimeric antigen receptor T cell (CAR-T) therapy. Vascular endothelial activation has been suggested to contribute to the development of CRS and ICANS after CAR-T therapy. However, therapeutic strategies targeting endothelial dysfunction during CAR-T therapy have not been well studied yet. Here, we found that tumor necrosis factor α (TNFα) produced by CAR-T cells upon tumor recognition and interleukin 1ß (IL1ß) secreted by activated myeloid cells were the main cytokines in inducing endothelial activation. Therefore, we investigated the potential effectiveness of TNFα and IL1ß signaling blockade on endothelial activation in CAR-T therapy. The blockade of TNFα and IL1ß with adalimumab and anti-IL1ß antibody respectively, as well as the application of focal adhesion kinase (FAK) inhibitor, effectively ameliorated endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Moreover, adalimumab and anti-IL1ß antibody exerted synergistic effect on the prevention of endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Our results indicate that TNFα and IL1ß blockade might have therapeutic potential for the treatment of CAR-T therapy-associated CRS and neurotoxicity.


Assuntos
Adalimumab/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Imunoterapia Adotiva , Interleucina-1beta/antagonistas & inibidores , Células Mieloides/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/efeitos dos fármacos , Inibidores do Fator de Necrose Tumoral/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Antígenos CD19/genética , Antígenos CD19/imunologia , Antígenos CD19/metabolismo , Linhagem Celular Tumoral , Técnicas de Cocultura , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/metabolismo , Síndrome da Liberação de Citocina/prevenção & controle , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/imunologia , Humanos , Imunoterapia Adotiva/efeitos adversos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Células Mieloides/imunologia , Células Mieloides/metabolismo , Síndromes Neurotóxicas/imunologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
17.
J Colloid Interface Sci ; 602: 504-512, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34144304

RESUMO

Developing effective and robust novel electrocatalysts for direct alcohol fuel cells has been gaining much attention. However, the widely used Pt catalyst suffers from limitations including the sluggish kinetics, severe CO poisoning, and catalyst lost caused by aggregation and Ostwald ripening during alcohol oxidation reaction. Herein, dendritic intermetallic PtSnBi nanoalloys were synthesized via a facile hydrothermal approach with high electrocatalytic performance and enhanced CO resistance for methanol oxidation reaction (MOR) and ethanol oxidation reaction (EOR) owing to the synergism of the chosen three elements and unique three-dimensional morphology. Specifically, the PtSnBi nanoalloys display 4.6 and 6.7 times higher of mass activity (7.02 A mg-1Pt) and specific activity (16.65 mA cm-2) toward MOR than those of commercial Pt/C, respectively. The mass activity of PtSnBi nanoalloys still retains 75.7% of the initial value after 800 cycles of stability test, superior to Pt/C (38.0%). The dual-functional effect of Sn, optimized electronic structure by the ligand effect, and unique atomic arrangement are responsible for the enhanced MOR activity and stability of PtSnBi nanoalloys. Furthermore, the PtSnBi nanoalloys with highlighted anti-CO poisoning capacity also improve the electrocatalytic performance toward EOR, indicating their great promise as broad energy electrocatalysts.

18.
Pediatr Neurosurg ; 56(5): 407-415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34175844

RESUMO

BACKGROUND: This study aimed to investigate the clinical outcome and related risk factors of fetal lateral ventriculomegaly (VM). METHODS: A retrospective analysis was performed on 255 cases diagnosed as fetal VM. Prenatal imaging examination was carried out. The pregnancy outcomes were investigated through follow-up. According to the prognosis of children, they were divided into case group and control group. Multivariate logistic regression was used to analyze the factors influencing the prognosis of hydrocephalus. RESULTS: After excluding the cases with either loss of follow-up or incomplete information, 102 cases were followed up. Twelve cases with poor prognosis were set as the case group. According to the maternal age, gestational age, gender of children, and follow-up time, 3 cases were selected from the other 90 cases for each child in the case group, respectively, and selected as the control group. Paired comparative analysis was performed on 48 cases. Using prognosis as a dependent variable, multivariate logistic regression analysis of the statistically significant factors indicated that the change speed of width ratio (CSWR) and maximum lateral ventricular width (MW) were associated with fetal prognosis. CONCLUSIONS: Our results suggested that CSWR and MW may have the value of predicting fetal prognosis.

19.
FASEB J ; 35(7): e21751, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34156114

RESUMO

Rat Thy-1 nephritis (Thy-1N) is an animal model of human mesangioproliferative glomerulonephritis (MsPGN), accompanied by glomerular mesangial cell (GMC) proliferation and extracellular matrix (ECM) deposition. Although sublytic C5b-9 formed on GMC membrane could induce cell proliferation, the mechanism is still unclear. In this study, we first demonstrated that the level of SRY related HMG-BOX gene 9 (SOX9), general control nonderepressible 5 (GCN5), fibroblast growth factor 1 (FGF1) and platelet-derived growth factor α (PDGFα) was all elevated both in the renal tissues of Thy-1N rats (in vivo) and in the GMCs (in vitro) with sublytic C5b-9 stimulation. Then, we not only discovered that sublytic C5b-9 caused GMC proliferation through increasing SOX9, GCN5, FGF1 and PDGFα expression, but also proved that SOX9 and GCN5 formed a complex and combined with FGF1 and PDGFα promoters, leading to FGF1 and PDGFα gene transcription. More importantly, GCN5 could mediate SOX9 acetylation at lysine 62 (K62) to enhance SOX9 binding to FGF1 or PDGFα promoter and promote FGF1 or PDGFα synthesis and GMC proliferation. Besides, the experiments in vivo also showed that FGF1 and PDGFα expression, GMC proliferation and urinary protein secretion in Thy-1N rats were greatly reduced by silencing renal SOX9, GCN5, FGF1 or PDGFα gene. Furthermore, the renal tissues of MsPGN patients also exhibited positive expression of these genes mentioned above. Collectively, our findings indicate that GCN5, SOX9 and FGF1/PDGFα can form an axis and play an essential role in sublytic C5b-9-triggered GMC proliferation, which might provide a novel insight into the pathogenesis of Thy-1N and MsPGN.


Assuntos
Proliferação de Células/genética , Proliferação de Células/fisiologia , Complexo de Ataque à Membrana do Sistema Complemento/genética , Rim/fisiologia , Células Mesangiais/fisiologia , Nefrite/genética , Transcrição Genética/genética , Acetilação , Animais , Linhagem Celular , Matriz Extracelular/genética , Fator 1 de Crescimento de Fibroblastos/genética , Humanos , Masculino , Fator de Crescimento Derivado de Plaquetas/genética , Regiões Promotoras Genéticas/genética , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição SOX9/genética , Antígenos Thy-1/genética , Fatores de Transcrição de p300-CBP/genética
20.
Biomacromolecules ; 22(7): 2834-2849, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34164980

RESUMO

Antibiotics are currently first-line therapy for bacterial infections. However, the curative effect of antibiotic remedies is limited due to increasingly prevalent bacterial resistance. The strategy to reverse intrinsic acquired drug resistance presents a promising option for reinvigorating antibiotic therapy. Here, we developed a ß-lactamase-inhibiting macromolecule composed of benzoxaborole and dextran for precise transport of ß-lactam antibiotics to strains overexpressing ß-lactamase. Benzoxaborole-derived nanotherapeutics enabled specific recognition and rapid internalization, and the nanotherapeutics with a high affinity toward bacteria distinctly inhibited the catalytic activity of bacterially secreted ß-lactamase by a reversible competitive mechanism. Thus, the system entrapping cefoxitin harbored a significantly enhanced ability to kill drug-resistant Escherichia coli compared to the ability of the drug by specifically overcoming the membrane barrier and acquired resistance mechanism of ß-lactamase overproduction. The reversible competitive nanotherapeutics exhibited a robust therapeutic efficacy in rat wounds infected with drug-resistant bacteria; the efficacy was due to efficient bacterial elimination and collateral benzoxaborole-dependent amelioration of the inflammatory response. The above results offered insights into the facile design of precise macromolecular adjuvants to exclusively reverse the acquired bacterial resistance mechanism and increase the utility of antibiotic therapies against antibiotic-resistant bacterial infections.


Assuntos
Antibacterianos , Bactérias Gram-Negativas , Animais , Antibacterianos/farmacologia , Escherichia coli , Testes de Sensibilidade Microbiana , Ratos , beta-Lactamases
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