Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 316
Filtrar
1.
J Hazard Mater ; 439: 129634, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36104897

RESUMO

The effects of land use on pollutant loads in sediments have been well documented; however, its influence on spatial variations in sediment toxicity remains largely unknown. In the present study, the toxicological effects of 17 sediments collected from Guangzhou waterways were evaluated using two benthic invertebrates (Chironomus dilutus and Hyalella azteca), along with quantification of heavy metals and arsenic in the sediments. The impacts of land-use configuration on sediment toxicity and occurrence of heavy metals and arsenic were analyzed. The sediments presented moderate lethality (<40 %) in the two test species and significantly altered their enzymatic activity, including the activities of oxidative stress biomarkers and acetylcholine esterase. Metals (Ag, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) and arsenic were detected in all the sediments, with total concentrations ranging from 238 to 1019 mg/kg of dry weight. Both the toxicity and chemical results displayed spatially dependent patterns but were related to different land use types. Toxicity was most influenced by agricultural and aquacultural activities, while metal and arsenic pollution was most influenced by urban land areas. The present findings are expected to provide essential knowledge for developing strategies that reduce the chemical pollution and ecotoxicological risk in sediments.


Assuntos
Arsênio , Metais Pesados , Poluentes Químicos da Água , Arsênio/análise , Arsênio/toxicidade , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Metais Pesados/análise , Metais Pesados/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
2.
Artigo em Inglês | MEDLINE | ID: mdl-36101936

RESUMO

INTRODUCTION: The pivotal efficacy study assessed efficacy and safety of GSK's AS04-HPV-16/18 vaccine in Chinese women aged 18-25 years up to 6 years. The present extension study, performed 4 years later, offered AS04-HPV-16/18 vaccination to placebo recipients. Vaccine safety and its long-term protective effect were assessed at Year 10. METHODS: All 6051 women who received AS04-HPV-16/18 or the placebo during the initial study (NCT00779766) were invited to phase III/IV, open-label, partially controlled extension Year 10 study (NCT03629886). Placebo recipients were offered three-dose AS04-HPV-16/18 vaccination and followed up over 12 months to assess the safety. Cervical samples from all women were examined. Vaccine efficacy (VE) against incident infections and cytological lesions associated with HPV-16/18 and other oncogenic types was assessed as exploratory objective. RESULTS: Among 3537 women (out of 6051) enrolled in the extension study, 1791 women (mean age 32.7 years; standard deviation 1.8 years) received AS04-HPV-16/18 and reported no serious adverse events, potential immune-mediated diseases, or adverse pregnancy outcomes related to vaccination. Among 6051 women, VE against incident HPV-16, -18, and -16/18 infections up to Year 10 was 82.8% (95% confidence interval: 72.5-89.7), 79.8% (64.5-89.2), and 80.8% (72.4-87.0), respectively. VE against HPV-16/18 ASC-US+, CIN1+, and CIN2+ was 92.7% (82.2-97.7), 94.8% (67.4-99.9), and 90.5% (34.6-99.8), respectively. CONCLUSION: AS04-HPV-16/18 vaccine showed an acceptable safety profile in Chinese women vaccinated at age 26 years or above, and a long-term protection similar to other efficacy trials worldwide.

3.
Angew Chem Int Ed Engl ; : e202204576, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35979844

RESUMO

Aptamers face challenges for use outside the ideal conditions in which they are developed. These difficulties are most palpable in vivo due to nuclease activities, rapid clearance, and off-target binding. Herein, we demonstrate that a polyphosphodiester-backboned molecular brush can suppress enzymatic digestion, reduce non-specific cell uptake, enable long blood circulation, and rescue the bioactivity of a conjugated aptamer in vivo. The backbone along with the aptamer is assembled via solid-phase synthesis, followed by installation of poly(ethylene glycol) (PEG) side chains using a two-step process with near-quantitative efficiency. The synthesis allows for precise control over polymer size and architecture. Consisting entirely of building blocks that are generally recognized as safe for therapeutics, this novel molecular brush is expected to provide a highly translatable route for aptamer-based therapeutics.

4.
Nat Mach Intell ; 4(1): 73-83, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35991585

RESUMO

Time-lapse images of cells and tissues contain rich information of dynamic cell behaviors, which reflect the underlying processes of proliferation, differentiation and morphogenesis. However, we lack computational tools for effective inference. Here, we exploit Deep Reinforcement Learning (DRL) to infer cell-cell interactions and collective cell behaviors in tissue morphogenesis from 3D, time-lapse images. We used Hierarchical DRL (HDRL), known for multiscale learning and data efficiency, to examine cell migrations based on images with ubiquitous nuclear label and simple rules formulated from empirical statistics of the images. When applied to C. elegans embryogenesis, HDRL reveals a multi-phase, modular organization of cell movement. Imaging with additional cellular markers confirms the modular organization as a novel migration mechanism, which we term sequential rosettes. Furthermore, HDRL forms a transferable model that successfully differentiates sequential rosettes-based migration from others. Our study demonstrates a powerful approach to infer the underlying biology from time-lapse imaging without prior knowledge.

5.
Proc Natl Acad Sci U S A ; 119(29): e2113180119, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858356

RESUMO

The mutant form of the guanosine triphosphatase (GTPase) KRAS is a key driver in human tumors but remains a challenging therapeutic target, making KRASMUT cancers a highly unmet clinical need. Here, we report a class of bottlebrush polyethylene glycol (PEG)-conjugated antisense oligonucleotides (ASOs) for potent in vivo KRAS depletion. Owing to their highly branched architecture, these molecular nanoconstructs suppress nearly all side effects associated with DNA-protein interactions and substantially enhance the pharmacological properties of the ASO, such as plasma pharmacokinetics and tumor uptake. Systemic delivery to mice bearing human non-small-cell lung carcinoma xenografts results in a significant reduction in both KRAS levels and tumor growth, and the antitumor performance well exceeds that of current popular ASO paradigms, such as chemically modified oligonucleotides and PEGylation using linear or slightly branched PEG. Importantly, these conjugates relax the requirement on the ASO chemistry, allowing unmodified, natural phosphodiester ASOs to achieve efficacy comparable to that of chemically modified ones. Both the bottlebrush polymer and its ASO conjugates appear to be safe and well tolerated in mice. Together, these data indicate that the molecular brush-ASO conjugate is a promising therapeutic platform for the treatment of KRAS-driven human cancers and warrant further preclinical and clinical development.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia de Alvo Molecular , Oligonucleotídeos Antissenso , Proteínas Proto-Oncogênicas p21(ras) , Animais , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/terapia , Camundongos , Oligonucleotídeos Antissenso/química , Oligonucleotídeos Antissenso/uso terapêutico , Polietilenoglicóis , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Transl Lung Cancer Res ; 11(5): 735-743, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35693280

RESUMO

Background: Tracheal cancer is a rare malignancy of which previous reports are mostly case reports or small series. Herein, we sought to evaluate the clinical characteristics, surgical treatments, and prognosis of surgically treated primary tracheal cancer patients. Methods: Patients with primary tracheal cancer who had received surgery in our center between January 2000 and December 2020 were enrolled. Clinical and surgical features were collected by retrospective review of medical records and follow-up was done by telephone interview. The statistical tests were two-sided. Results: A total of 128 patients were included in the study, 49.2% of whom were male, and the average age was 49.4±13.6 years. The most common histological subtype was adenoid cystic carcinoma (ACC; 78/128, 60.9%) followed by squamous cell carcinoma (SCC; 24/128, 18.8%). The percentage of tumors located in the cervical trachea, thoracic trachea, and carina were 50%, 41.4%, and 8.6%, respectively. Among those analyzed, 32.0% of the primary tumors had invaded adjacent organs (E2 disease) and 7.8% of patients had lymph node involvement. Tracheal resection plus reconstruction (with or without thyroidectomy) was the predominant surgical procedure, followed by carinal resection with neocarina. Radical resection (R0) was performed on 61.7% of patients and 63 (49.2%) patients received adjuvant therapy. Compared to ACC, SCC patients had significantly higher risk of tumor of the carina, nodal metastasis, and complications. The 5-year overall survival (OS) for the entire cohort was 84.5% and factors associated with poor prognosis included carinal tumor [hazard ratio (HR) =10.206; P<0.001], E2 disease (HR =8.870; P=0.001), lymph node metastasis (HR =15.197; P<0.001), and postoperative complications (HR =12.497; P=0.001). Conclusions: The two major subtypes of tracheal cancer are ACC and SCC. Tumor location, extension, lymph node metastasis and complication are survival related factors for surgically treated patients.

7.
Environ Pollut ; 307: 119603, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35691443

RESUMO

Mutations are an important origin of antibiotic resistance in bacteria. While there is increasing evidence showing promoted resistance mutations by environmental stresses, no retrospective research has yet been conducted on this phenomenon and its mechanisms. Herein, we summarized the phenomena of stress-elevated resistance mutations in bacteria, generalized the regulatory mechanisms and discussed the environmental and human health implications. It is shown that both chemical pollutants, such as antibiotics and other pharmaceuticals, biocides, metals, nanoparticles and disinfection byproducts, and non-chemical stressors, such as ultraviolet radiation, electrical stimulation and starvation, are capable of elevating resistance mutations in bacteria. Notably, resistance mutations are more likely to occur under sublethal or subinhibitory levels of these stresses, suggesting a considerable environmental concern. Further, mechanisms for stress-induced mutations are summarized in several points, namely oxidative stress, SOS response, DNA replication and repair systems, RpoS regulon and biofilm formation, all of which are readily provoked by common environmental stresses. Given bacteria in the environment are confronted with a variety of unfavorable conditions, we propose that the stress-elevated resistance mutations are a universal phenomenon in the environment and represent a nonnegligible risk factor for ecosystems and human health. The present review identifies a need for taking into account the pollutants' ability to elevate resistance mutations when assessing their environmental and human health risks and highlights the necessity of including resistance mutations as a target to prevent antibiotic resistance evolution.


Assuntos
Poluentes Ambientais , Raios Ultravioleta , Antibacterianos/farmacologia , Bactérias/genética , Ecossistema , Poluentes Ambientais/toxicidade , Mutação
9.
Curr Zool ; 68(3): 265-273, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35592348

RESUMO

Sex-biased dispersal is common in group-living animals. Due to differences in local demographic and environmental factors, sex-biased dispersal presents many irregular patterns. In this study, a habituated, individually identified Yunnan snub-nosed monkey Rhinopithecus bieti group was observed over 9 years; 192 dispersal events, including 97 male dispersal events (25 natal dispersal and 72 secondary dispersal) and 95 female dispersal events (34 natal dispersal and 61 secondary dispersal) were observed. Males and females showed different dispersal paths, dispersal ages, and dispersal patterns. Females had 2 dispersal paths, whereas males had 4 paths. In terms of age of dispersal, the male age of natal dispersal was younger than for females. Males prefer single dispersal, whereas females prefer parallel dispersal. Our study indicates that the dispersal pattern of R. bieti should be classified as a bisexual dispersal pattern. The differences in dispersal path, average age at dispersal, and dispersal path pattern indicate that Yunnan snub-nosed monkeys may still retain a loose matrilineal social system.

10.
Nano Lett ; 22(10): 4058-4066, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35522597

RESUMO

Nucleic-acid-based immune adjuvants have been extensively investigated for the design of cancer vaccines. However, nucleic acids often require the assistance of a carrier system to improve cellular uptake. Yet, such systems are prone to carrier-associated adaptive immunity, leading to difficulties in a multidose treatment regimen. Here, we demonstrate that a spherical nucleic acid (SNA)-based self-adjuvanting system consisting of phosphodiester oligonucleotides and vitamin E can function as a potent anticancer vaccine without a carrier. The two functional modules work synergistically, serving as each other's delivery vector to enhance toll-like receptor 9 activation. The vaccine rapidly enters cells carrying OVA model antigens, which enables efficient activation of adaptive immunity in vitro and in vivo. In OVA-expressing tumor allograft models, both prophylactic and therapeutic vaccinations significantly retard tumor growth and prolong animal survival. Furthermore, the vaccinations were also able to reduce lung metastasis in a B16F10-OVA model.


Assuntos
Vacinas Anticâncer , Imunoterapia , Neoplasias , Ácidos Nucleicos , Receptor Toll-Like 9 , Adjuvantes Imunológicos/uso terapêutico , Animais , Imunoterapia/métodos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/tratamento farmacológico , Ácidos Nucleicos/uso terapêutico , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/uso terapêutico
12.
Front Surg ; 9: 807811, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392054

RESUMO

Background: Colorectal cancer is a common malignant tumor appearing in the gastrointestinal tract. Surgical resection is recognized as the best means to improve patient survival. However, it is controversial whether early oral feeding (EOF) after elective colorectal resection demonstrates safety and efficacy in concerned clinical outcomes. Methods: We searched PubMed, Embase, Cochrane Library, and CNKI from inception to September 2021. Two authors independently screened the retrieved records and extracted data. EOF was defined as feeding within 24 h after surgery, while traditional oral feeding (TOF) was defined as feeding that started after the gastrointestinal flatus or ileus was resolved. The primary outcome was nasogastric tube insertion, and the secondary outcomes were the length of hospital stay and total complications. Categorical data were combined using odds ratio (OR), and continuous data were combined using mean difference (MD). Results: We screened 10 studies from 34 records after full-text reading, with 1,199 patients included in the analysis. Nasogastric tube reinsertion (OR 1.69; 95% CI 1.08 to 2.64, p=0.02) was more frequent in the EOF group, and older ages (>60 years) were associated with higher risk of nasogastric tube reinsertion (OR 2.05; 95% CI 1.05 to 3.99, p = 0.04). Reduced length of hospital stay (MD -1.76; 95% CI -2.32 to -1.21; p < 0.01) and the rate of total complications (OR 0.49; 95% CI 0.37 to 0.65, p < 0.01) were observed in EOF compared with TOF. Conclusions: EOF was safe and effective for patients undergoing elective colorectal surgery, but the higher rate of nasogastric tube reinsertion compared with TOF should not be ignored.

14.
Front Immunol ; 13: 789274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300324

RESUMO

Wound healing is a dynamic and highly regulated process that can be separated into three overlapping and interdependent phases: inflammation, proliferation, and remodelling. This review focuses on the inflammation stage, as it is the key stage of wound healing and plays a vital role in the local immune response and determines the progression of wound healing. Inflammatory cells, the main effector cells of the inflammatory response, have been widely studied, but little attention has been paid to the immunomodulatory effects of wound healing in non-inflammatory cells and the extracellular matrix. In this review, we attempt to deepen our understanding of the wound-healing microenvironment in the inflammatory stage by focusing on the interactions between cells and the extracellular matrix, as well as their role in regulating the immune response during the inflammatory stage. We hope our findings will provide new ideas for promoting tissue regeneration through immune regulation.


Assuntos
Lesões dos Tecidos Moles , Cicatrização , Matriz Extracelular , Humanos , Imunomodulação , Inflamação , Cicatrização/fisiologia
15.
PLoS Comput Biol ; 18(3): e1009972, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35353812

RESUMO

One of the unique traits of membrane proteins is that a significant fraction of their hydrophobic amino acids is exposed to the hydrophobic core of lipid bilayers rather than being embedded in the protein interior, which is often not explicitly considered in the protein structure and function predictions. Here, we propose a characteristic and predictive quantity, the membrane contact probability (MCP), to describe the likelihood of the amino acids of a given sequence being in direct contact with the acyl chains of lipid molecules. We show that MCP is complementary to solvent accessibility in characterizing the outer surface of membrane proteins, and it can be predicted for any given sequence with a machine learning-based method by utilizing a training dataset extracted from MemProtMD, a database generated from molecular dynamics simulations for the membrane proteins with a known structure. As the first of many potential applications, we demonstrate that MCP can be used to systematically improve the prediction precision of the protein contact maps and structures.


Assuntos
Bicamadas Lipídicas , Proteínas de Membrana , Aminoácidos/química , Bicamadas Lipídicas/química , Proteínas de Membrana/metabolismo , Simulação de Dinâmica Molecular , Probabilidade
16.
Comput Struct Biotechnol J ; 20: 685-699, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35140888

RESUMO

The gut microbiomes of non-human primates have received a great deal of attention due to their close relationship to humans. In recent years, these studies have mainly focused on the gut microbiome of wild primates, which will be helpful to understanding the evolution of primates and their gut microbiomes (e.g., gut microbiome plasticity and diet flexibility). However, there is still a lack of basic information on the gut microbiomes from wild populations. Here, we investigated the gut microbial composition (16S rRNA gene) and function (metagenome and metagenome-assembled genomes (MAGs)) of Yunnan snub-nosed monkey populations in Weixi County, Yunnan Province, China, that had diets either completely based on wild-foraging or were regularly supplemented with human provisioned food. We found a significant difference in the gut microbiome between these two populations: the gut microbiome of the wild-foraging (no food provision) population was enriched genes involved in the detoxification of bamboo cyanide (high proportion of bamboo shoot intake) and chitin (from insect diet) digestion, while the gut microbiome of the food provisioned (e.g., fruits) wild populations were enriched genes involved in carbohydrate metabolism. Moreover, the gut microbiome of the wild-foraging population shared a putatively functional convergence with the gut microbiome of wild bamboo-eating pandas: such as microbes and genes involved in the cyanide detoxification. Therefore, the gut microbiome of the Yunnan snub-nosed monkey displayed the potential plasticity in response to diet flexibility. Long-term food-provisioning of the wild population has led to dramatic changes in gut microbial composition, function, and even antibiotic resistance. The antibiotic resistance profile for the wild Yunnan snub-nosed monkey population could be considered the baseline and an important piece of information for conservation.

17.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(2): 220-223, 2022 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-35172409

RESUMO

OBJECTIVE: To explore the effectiveness of thin free lateral femoral circumflex artery perforator flaps that dissected under the superficial fascia in repair of scar contracture deformity in hand and foot. METHODS: Between January 2017 and October 2020, 15 patients with scar contracture deformity in hand or foot were admitted. There were 9 males and 6 females; aged 6-42 years, with a median age of 23 years. Scar contracture lasted from 1 to 21 years, with a median of 13 years. There were 11 cases of scar contracture deformities in the hands and 4 cases in the feet, all of which showed different degrees of hand and foot joint dysfunction. After the scar contracture was released, the size of wounds ranged from 6 cm×4 cm to 9 cm×8 cm, including 12 cases with exposure of blood vessels, nerves, or tendons, and 4 cases with tendon defects. A thin free lateral circumflex femoral artery perforator flap that dissected under the superficial fascia was used to repair the wound. The size of flap ranged from 6.0 cm×5.0 cm to 10.0 cm×8.5 cm. Fascia strips were used to reconstruct tendons and the donor sites were sutured directly. RESULTS: The venous vascular crisis occurred in 1 flap, and the flap survived successfully after treatment. The rest flaps survived well, and the wounds healed by first intention. All incisions at donor sites healed by first intention. All patients were followed up 6-12 months after operation, with an average of 9 months. The flaps were in good shape and texture. The functions of the affected hand had been restored to a large extent. According to the upper limb function evaluation standard of the Society of Hand Surgery of the Chinese Medical Association, 7 cases were excellent and 4 cases were good. The deformity of the toe joint of the affected foot significantly improved. No muscular hernia, sensory numbness, or other complications occurred at the donor sites. CONCLUSION: The thin free lateral femoral circumflex artery perforator flap that dissected under the superficial fascia is an effective method to repair scar contracture deformity of hand and foot with well appearance, good function recovery, and less complication of the donor sites.


Assuntos
Contratura , Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos , Lesões dos Tecidos Moles , Adolescente , Adulto , Criança , Cicatriz/cirurgia , Contratura/etiologia , Contratura/cirurgia , Feminino , Artéria Femoral/cirurgia , Mãos/cirurgia , Humanos , Masculino , Retalho Perfurante/irrigação sanguínea , Procedimentos Cirúrgicos Reconstrutivos/métodos , Transplante de Pele , Lesões dos Tecidos Moles/complicações , Lesões dos Tecidos Moles/cirurgia , Resultado do Tratamento , Extremidade Superior/cirurgia , Adulto Jovem
18.
Integr Zool ; 17(1): 168-180, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34751507

RESUMO

Multilevel society is one of the most complex social systems in natural ecosystems and is a typical feature among some primates. Given the potential connection between social behavior and gut microbiome composition, the multilevel social system could affect the primate gut microbiome. Here, based on long-term observation (e.g. social unit dynamics, transfer, and behavior), we investigated this potential integrating 16S rRNA gene amplicon sequencing and behavior data in Yunnan snub-nosed monkeys (Rhinopithecus bieti), which possess a multilevel social group based on one male units (OMUs, each unit with several breeding females and their offspring) and all-male unit (AMU, several bachelor males residing together). We found that the mean unweighted Unifrac distance between adult males from different OMUs was significantly lower than that between adult females from different OMUs (paired Wilcoxon test, P = 0.007). There was no significant difference in the mean unweighted Unifrac distance between females within the same OMU or between females from different OMUs. These findings indicated the potential connection between the defense and invasion of social units and the gut microbiome community in wild Yunnan snub-nosed monkeys. We speculated that the resident males of OMUs displaying a significantly higher similarity in the gut microbial community than that of adult females in separate OMUs might be associated with the sexual differences in their interactions and from previously having cohabitated together in the AMU. Therefore, this study suggested that multilevel societies might have an effect on the gut microbial community in this wild nonhuman primate species.


Assuntos
Colobinae , Microbioma Gastrointestinal , Animais , China , Ecossistema , Feminino , Masculino , RNA Ribossômico 16S/genética , Comportamento Social
19.
Neurosci Res ; 177: 25-37, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34740726

RESUMO

Patients with TLE are prone to tolerance to antiepileptic drugs. Based on the perspective of molecular targets for drug resistance, it is necessary to explore effective drug resistant genes and signaling pathways for the treatment of TLE. We performed gene expression profiles in hippocampus of patients with drug-resistant TLE and identified ROCK2 as one of the 20 most significantly increased genes in hippocampus. In vitro and in vivo experiments were performed to identify the potential role of ROCK2 in epileptogenesis. In addition, the activity of Stat3 pathway was tested in rat hippocampal tissues and primary cultured astrocytes. The expression levels of ROCK2 in the hippocampus of TLE patients were significantly increased compared with the control group, which was due to the hypomethylation of ROCK2 promoter. Fasudil, a specific Rho-kinase inhibitor, alleviated epileptic seizures in the pilocarpine rat model of TLE. Furthermore, ROCK2 activated the Stat3 pathway in pilocarpine-treated epilepsy rats, and the spearman correlation method confirmed that ROCK2 is associated with Stat3 activation in TLE patients. In addition, ROCK2 was predominantly expressed in astrocytes during epileptogenesis, and induced epileptogenesis by activating astrocyte cell cycle progression via Stat3 pathway. The overexpressed ROCK2 plays an important role in the pathogenesis of drug-resistant epilepsy. ROCK2 accelerates astrocytes cell cycle progression via the activation of Stat3 pathway likely provides the key to explaining the process of epileptogenesis.


Assuntos
Epilepsia do Lobo Temporal , Pilocarpina , Animais , Astrócitos/metabolismo , Modelos Animais de Doenças , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Hipocampo/metabolismo , Humanos , Pilocarpina/farmacologia , Ratos , Fator de Transcrição STAT3/metabolismo , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/farmacologia
20.
J Hazard Mater ; 422: 126858, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34419845

RESUMO

Toxicological effects of nanoplastics have been demonstrated in a variety of organisms, yet their impacts on bacteria, especially on the antibiotic resistance evolution remain under explored. Herein, we report individual and combined effects of nano-polystyrene (nano-PS) and erythromycin (ERY) on growth and resistance mutations of Escherichia coli. The toxicity of nano-PS was dependent on size and functional modifications, with 30 nm and amino-modified PS (PS-NH2, 200 nm) showing the greatest toxicity. Adsorption of nano-PS onto bacterial surface and the subsequent increase of intracellular ROS or the probable mechanical damage were considered as the primary toxic mechanisms. Furthermore, nano-PS increased the bacterial resistance mutations, which was due to the oxidative damage to DNA and the SOS response. In addition, PS-NH2 presented synergistic effects with ERY while non-modified PS had no impact, although both of them showed adsorption capacity to ERY. This was likely because the positively charged PS-NH2 acted as a carrier of ERY and enhanced the interactions between ERY and the bacteria. Our findings raised the concerns about the risk of nanoplastics in accelerating the bacterial resistance evolution, and highlighted the necessity of including combined effects of nanoplastics and co-contaminants in risk assessment.


Assuntos
Nanopartículas , Poliestirenos , Adsorção , Eritromicina/farmacologia , Escherichia coli/genética , Mutação , Nanopartículas/toxicidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...