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1.
Environ Toxicol ; 37(1): 161-170, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34652879

RESUMO

Long non-coding RNA (lncRNA) LINC00514 is a cancer-related lncRNA that has been proven to be implicated in the progression of several cancers. However, the biological function of LINC00514 in cervical squamous cell carcinoma (CSCC) remains unclear. Thus, we aimed to identify the LINC00514 expression profile in CSCC and determine its exact mechanism. Our results showed that the expression of LINC00514 was up-regulated in human CSCC tissues and cell lines. Knockdown of LINC00514 significantly inhibited the proliferation and invasion of CSCC cells, as well as suppressed tumorigenesis of CSCC in vivo. In addition, LINC00514 was found to work as a miRNA sponge for miR-708-5p and suppressed the expression of miR-708-5p in CSCC cells. Homeobox B3 (HOXB3) was found to be a target gene of miR-708-5p. Rescue assays demonstrated that miR-708-5p inhibitor attenuated the effects of LINC00514 knockdown on cell proliferation and invasion in CSCC cells. In addition, overexpression of HOXB3 reversed the inhibitory effects of miR-708-5p mimics on cell proliferation and invasion. Taken together, our findings for the first time elucidated that lncRNA LINC00514 promotes the proliferation and invasion through the miR-708-5p/HOXB3 axis in CSCC. Thus, LINC00514/miR-708-5p/HOXB3 axis might be a promising therapeutic target for the treatment of CSCC.

2.
Front Public Health ; 9: 727234, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858921

RESUMO

Background: As more and more countries enter the low-transmission phase, maintaining prevention awareness among the population is critical to prevent a secondary outbreak. With large-scale interpersonal communication, whether Chinese residents can maintain a high awareness of prevention and control and adhere to the use of masks during the Chinese New Year of 2021 is worth studying. Methods: A cross-sectional survey was conducted in China from February 4 to 26, 2021. A convenient sampling strategy was adopted to recruit participators. Participants were asked to fill out the questions that assessed the questionnaire on face mask use. Descriptive statistics were used to assess the mask-wearing behaviors of the public. A binary logistic regression analysis was performed to identify the risk factors affecting mask-wearing behaviors. Results: A total of 2,361 residents filled out the questionnaire. In the mixed-effect logistic regression analysis, Chinese residents who were older (OR = 7.899, 95%CI = 4.183-14.916), employed (OR = 1.887, 95%CI = 1.373-2.594), had a chronic disease (OR = 1.777, 95%CI = 1.307-2.418), reused face masks (OR = 22.155, 95%CI = 15.331-32.016) and have read the face mask instructions (OR = 3.552, 95%CI = 1.989-6.341) were more likely to use face masks in interpersonal communication during the Spring Festival; while people who have breathing discomfort caused by face masks (OR = 0.556, 95%CI = 0.312-0.991) and considered that using masks repeatedly is wasteful (OR = 0.657, 95%CI = 0.482-0.895) were more unlikely to use face masks. Conclusions: Our results revealed that 83.86% of people wore face masks during the Chinese New Year; however, some aspects require further promotion. By investigating the use of masks by Chinese residents during the Spring Festival and its influencing factors, we can reflect the prevention awareness of the residents during the low transmission period of COVID-19, which can provide a reference for Chinese and global public health policymakers.

3.
Front Cell Dev Biol ; 9: 770899, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805177

RESUMO

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe side effect of long-term administration of bisphosphonates such as zoledronic acid (ZA), but its pathogenesis remains unclear. Impairment of the clearance of apoptotic cells (termed "efferocytosis") by ZA may be associated with the pathogenesis of BRONJ. The aim of this study was to investigate whether ZA might inhibit macrophage efferocytosis and promote osteocytic apoptosis, and the underlying mechanisms responsible for the disturbing balance between clean and generation of osteocytic apoptosis. We found that ZA significantly promoted the apoptosis of osteocyte and pre-osteoblast via BRONJ mouse models and in vitro MC3T3-E1 but also inhibited the efferocytosis of macrophage on apoptotic cells. Moreover, supplement with geranylgeraniol (GGOH), a substrate analog for geranylgeranylation of Rac1, could restore Rac1 homeostasis and rescue macrophage efferocytosis. GGOH partially inhibits MC3T3-E1 apoptosis induced by ZA via downregulation of Rac1/JNK pathway. We also examined the Rac1 distribution and activation conditions in bone marrow-derived macrophages (BMDMs) and MC3T3-E1 under ZA treatment, and we found that ZA impaired Rac1 migration to BMDM membrane, leading to round appearance with less pseudopodia and efferocytosis inhibition. Moreover, ZA simultaneously activated Rac1, causing overexpression of P-JNK and cleaved caspase 3 in MC3T3-E1. Finally, the systemic administration of GGOH decreased the osteocytic apoptosis and improved the bone healing of the extraction sockets in BRONJ mouse models. Taken together, our findings provided a new insight and experimental basis for the application of GGOH in the treatment of BRONJ.

4.
Brain Res Bull ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34808323

RESUMO

Folic acid (FA) supplementation in early pregnancy is recommended to protect against birth defects. But excess FA has exhibited neurodevelopmental toxicity. We previously reported that the mice treated with 2.5-fold the dietary requirement of FA one week before mating and throughout pregnancy and lactation displayed abnormal behaviors in the offspring. Here we found the levels of non-phosphorylated ß-catenin (active) were increased in the brains of weaning and adult FA-exposed offspring. Meanwhile, demethylation of protein phosphatase 2A catalytic subunit (PP2Ac), which suppresses its enzyme activity in regulatory subunit dependent manner, was significantly inhibited. Among the upstream regulators of ß-catenin, PI3K/Akt/GSK-3ß but not Wnt signaling was stimulated in FA-exposed brains only at weaning. In mouse neuroblastoma N2a cells, knockdown of PP2Ac or leucine carboxyl methyltransferase-1 (LCMT-1), or overexpression of PP2Ac methylation-deficient mutant decreased ß-catenin dephosphorylation. These results suggest that excess FA may activate ß-catenin via suppressing PP2Ac demethylation, providing a novel mechanism for the influence of FA on neurodevelopment.

5.
Circ Res ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34814703

RESUMO

Background: The sarcoplasmic reticulum (SR) Ca2+-ATPase 2 (SERCA2) mediates a2+-reuptake into SR and thereby promotes cardiomyocyte relaxation, whereas the ryanodine receptor (RYR) mediates a2+-release from SR and triggers contraction. a2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) regulates activities of SERCA2 through phosphorylation of phospholamban (PLN) and RYR through direct phosphorylation. However, the mechanisms for CaMKIIδ anchoring to SERCA2-PLN and RYR and its regulation by local a2+-signals remain elusive. The objective of this study was to investigate CaMKIIδ anchoring and regulation at SERCA2-PLN and RYR. Methods: A role for A-kinase anchoring protein 18δ (AKAP18δ) in CaMKIIδ anchoring and regulation was analyzed by bioinformatics, peptide arrays, cell-permeant peptide technology, immunoprecipitations, pull-downs, transfections, immunoblotting, proximity ligation, FRET-based CaMKII activity and ELISA-based assays, whole cell and SR-vesicle fluorescence imaging, high-resolution microscopy, adenovirus transduction, adeno-associated virus injection, structural modeling, surface plasmon resonance and alpha screen technology. Results: Our results show that AKAP18δ anchors and directly regulates CaMKIIδ activity at SERCA2-PLN and RYR, via two distinct AKAP18δ regions. An N-terminal region (AKAP18δ-N) inhibited CaMKIIδ through binding of a region homologous to natural CaMKII inhibitor peptide and Thr17-PLN region. AKAP18δ-N also bound CaM, introducing a second level of control. Conversely, AKAP18δ-C, which shares homology to neuronal CaMKIIα activator peptide (N2B-s), activated CaMKIIδ by lowering the apparent a2+-threshold for kinase activation and inducing CaM trapping. While AKAP18δ-C facilitated faster a2+-reuptake by SERCA2 and a2+-release through RYR, AKAP18δ-N had opposite effects. We propose a model where the two unique AKAP18δ regions fine-tune a2+-frequency-dependent activation of CaMKIIδ at SERCA2-PLN and RYR. Conclusions: AKAP18δ anchors and functionally regulates CaMKII activity at PLN-SERCA2 and RYR, indicating a crucial role of AKAP18δ in regulation of the heartbeat. To our knowledge this is the first protein shown to enhance CaMKII activity in heart and also the first AKAP reported to anchor a CaMKII isoform, defining AKAP18δ also as a CaM-KAP.

6.
Sheng Wu Gong Cheng Xue Bao ; 37(11): 3781-3788, 2021 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-34841783

RESUMO

Intestinal microbes have an adjuvant therapeutic effect on neurological disorders (such as Parkinson's, depression, and Alzheimer's disease). It affects brain function and host behavior through the neural pathways, the immune pathways and the microbial metabolites, the so-called gut-brain axis. This article summarizes the recent advances in the role of the microbe-gut-brain axis in neurological disorders, in order to provide new ideas for the treatment of neurodegenerative diseases.


Assuntos
Microbioma Gastrointestinal , Doenças Neurodegenerativas , Encéfalo , Meio Ambiente , Humanos
7.
BMC Gastroenterol ; 21(1): 444, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823485

RESUMO

BACKGROUND: Nowadays, liver transplantation has become a main therapy for end-stage liver disease. However, studies show that there are high mortality and severe complications after liver transplantation. Although gastrointestinal dysfunction is a common and major complication after liver transplantation, there was rarely relative research. This study aims to elucidate the factors about ileus after liver transplantation and patients' survival. METHODS: We collected and analyzed the data (n = 318, 2016-2019) from the First Affiliated Hospital of Xi'an Jiaotong University. After excluding cases, a total of 293 patients were included for this study. The subjects were divided into a non-ileus group and an ileus group. We reviewed 38 variables (including preoperative, operative and postoperative relative factors). Additionally, other complications after liver transplantation and survival data were compared between two groups. RESULTS: Of the 293 patients, 23.2% (n = 68) experienced postoperative ileus. Ileus patients were not different with non-ileus patients in preoperative, operative and postoperative factors. HBV-positive patients with ileus had a lower MELD score (P = 0.025), and lower postoperative total bilirubin was correlated with ileus (P = 0.049). Besides, Child-Pugh score of HCC patients with ileus was low (P = 0.029). The complications after liver transplantation were not different between two groups. Compared with the patients without ileus, the patients with ileus had a higher mortality rate. CONCLUSION: According to our research, ileus-patients had a lower 1-year survival rates. The preoperative MELD score and postoperative total bilirubin of HBV-positive patients with ileus were lower, and Child-Pugh score of HCC patients with ileus was also lower.


Assuntos
Carcinoma Hepatocelular , Doença Hepática Terminal , Íleus , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Íleus/etiologia , Transplante de Fígado/efeitos adversos , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
8.
Front Psychiatry ; 12: 766127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803773

RESUMO

Background: By investigating the incidence of post-traumatic stress disorder (PTSD) among residents during a period of low transmission, this study reflects the long-term impact of coronavirus disease 2019 (COVID-19) and identify which categories of residents are more likely to develop PTSD due to an acute infectious disease crisis, facilitating the development of targeted strategies to protect mental health after outbreaks of similar acute infectious diseases in the future. Methods: A cross-sectional survey was conducted in China from 4 to 26 February 2021. A convenience sampling strategy was adopted to recruit participants. Participants were asked to complete the PTSD Checklist for DSM-5 (PCL-5). A multivariable linear stepwise regression analysis model was used to identify which factors were associated with PTSD in residents of China. Results: A total of 2,361 Chinese residents completed the questionnaire. The mean PCL-5 score for the respondents was 13.65 (SD = 8.66), with 219 (9.28%) patients having probable PTSD symptoms. Respondents who were female (ß = 0.038), had a relative or friend who had contracted COVID-19 (ß = 0.041), and had poor health (ß = 0.184) had higher PCL-5 scores, while the population aged over 60 years (ß = -0.063), who agreed that COVID-19 information was released in a timely manner (ß = -0.347), who had experienced a relatively limited impact of COVID-19 on their life (ß = -0.069), and who agreed that the local prevention initiatives were sophisticated (ß = -0.165) had lower PTSD scores. Conclusions: Outbreaks of acute infectious diseases can have long-term psychological health effects in the general population. In addition, health policy makers need to be concerned about and implement measures to support the mental health of vulnerable groups.

9.
Int Urogynecol J ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34842940

RESUMO

INTRODUCTION AND HYPOTHESIS: This study was aimed at exploring the mediating role of the prolonged second stage of labor (PSSL) in the association between delivery mode and urinary incontinence (UI) among postpartum women in Shandong, China. METHODS: A cross-sectional study involving postnatal women from the Women's Pelvic Floor Functional Health Center in Shandong, China, was conducted. An electronic questionnaire was used to collect the data between June 2020 and February 2021. UI was assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). Logistic regression and multiple linear regression were employed to explore the association among delivery mode, PSSL, and UI, and the mediating role of PSSL. RESULTS: Among the total of 5,586 postpartum women included in this study, the prevalence of UI was 13.3%. Among the 742 patients with UI, the prevalence of stress urinary incontinence (78.3%) was greater than urge urinary incontinence (8.6%), mixed urinary incontinence (9.3%), and others (3.8%). After adjusting for controlling variables, delivery mode was found to be significantly associated with PSSL, whereby women with vaginal delivery were more likely to be in PSSL, and women with PSSL had a higher probability of suffering from UI. PSSL played a partial mediating effect in delivery mode and UI. CONCLUSIONS: This study provided evidence that the effect of delivery mode on UI was partially mediated by PSSL among postpartum women in Shandong, China. Strategies to prevent PSSL should be actively adopted to reduce the risk of UI in women.

10.
Mol Med ; 27(1): 149, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837956

RESUMO

BACKGROUND: Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited. METHODS: In this study, giemsa staining, phalloidin staining, immunofluorescence and flow cytometry were used to identify the effects of 3,3'-di-O-methylellagic acid 4'-glucoside (DMAG), a natural ellagic acid derived from Sanguisorba officinalis L. (SOL) on megakaryocyte differentiation in HEL cells. Then, thrombocytopenia mice model was constructed by X-ray irradiation to evaluate the therapeutic action of DMAG on thrombocytopenia. Furthermore, the effects of DMAG on platelet function were evaluated by tail bleeding time, platelet aggregation and platelet adhesion assays. Next, network pharmacology approaches were carried out to identify the targets of DMAG. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the underling mechanism of DMAG against thrombocytopenia. Finally, molecular docking simulation, molecular dynamics simulation and western blot analysis were used to explore the relationship between DAMG with its targets. RESULTS: DMAG significantly promoted megakaryocyte differentiation of HEL cells. DMAG administration accelerated platelet recovery and megakaryopoiesis, shortened tail bleeding time, strengthened platelet aggregation and adhesion in thrombocytopenia mice. Network pharmacology revealed that ITGA2B, ITGB3, VWF, PLEK, TLR2, BCL2, BCL2L1 and TNF were the core targets of DMAG. GO and KEGG pathway enrichment analyses suggested that the core targets of DMAG were enriched in PI3K-Akt signaling pathway, hematopoietic cell lineage, ECM-receptor interaction and platelet activation. Molecular docking simulation and molecular dynamics simulation further indicated that ITGA2B, ITGB3, PLEK and TLR2 displayed strong binding ability with DMAG. Finally, western blot analysis evidenced that DMAG up-regulated the expression of ITGA2B, ITGB3, VWF, p-Akt and PLEK. CONCLUSION: DMAG plays a critical role in promoting megakaryocytes differentiation and platelets production and might be a promising medicine for the treatment of thrombocytopenia.

11.
Drug Alcohol Depend ; 229(Pt B): 109134, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34847483

RESUMO

OBJECTIVE: This study aimed to investigate the association between alcohol consumption and the prevalence of stroke in Chinese adults aged 40 years and over. METHOD: We conducted a cross-sectional analysis among 113,573 Chinese adults aged ≥ 40 years in the China National Stroke Prevention Project (2014-2015) to examine correlations of alcohol consumption with the prevalence of stroke. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), controlling for various confounders, e.g., gender, age, smoking, physical activity and other health conditions. RESULTS: Within the study population, a total of 12,753 stroke survivors were identified. The prevalence of light to moderate and of heavy alcohol consumption was 10.1% and 5.7% respectively. The multivariate logistic regression results show that light to moderate alcohol consumption was associated with reduced risk of stroke of all types [0.91 (95%CI: 0.85-0.97)] and of ischemic stroke [0.90 (0.84-0.97)]. No association was found between alcohol consumption and hemorrhagic stroke. Compared with abstainers, the adjusted ORs of all stroke were 0.83 (0.75-0.92) for those who drank 11-20 years, and no association was found between 1 and 10 years or over 20 years of drinking and risk of stroke. CONCLUSIONS: These results indicate that light to moderate alcohol consumption may be protective against all and ischemic stroke, and heavy drinking was not significantly associated with risk of all stroke in China. No association between alcohol consumption and hemorrhagic stroke was found.

12.
Front Psychol ; 12: 679538, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594261

RESUMO

Background: Home quarantine is an important strategy to contain the mass spread of the coronavirus disease 2019 (COVID-19) pandemic. However, there are a dearth of studies on the prevalence and risk factors of home quarantine strategy implementation among residents. This study aims to assess the state of home quarantine strategy implementation among Chinese residents, which could provide a reference for quarantine policymakers around the world during the pandemic. Method: We conducted a cross-sectional survey of 3,398 residents in China by adopting a convenience sampling strategy. We measured the prevalence and risk factors of home quarantine strategy implementation with the Center for Epidemiological Studies-Depression Scale (CES-D), 10-item Connor-Davidson Resilience Scale (CD-RISC 10), and Perceived Social Support Scale (PSSS). A multivariable model was used to determine the factors associated with home quarantine strategy implementation. Results: A total of 2,936 (86.4%) respondents carried out home quarantine. There were some factors significantly associated with home quarantine strategy implementation among Chinese residents during the COVID-19 outbreak. Respondents who were male, lived in western and central China, were aware of the primary symptoms of COVID-19, were willing to accept recommendations on relevant protective measures, understood local quarantine measures, had better resilience, and had better social support were more likely to engage in home quarantine. Respondents who were married, were employed, were healthy, and had high depression scores were more likely to refuse to follow home quarantine guidance. Conclusions: Gender, region, marital status, employment status, health status, awareness of the primary symptoms of COVID-19, willingness to accept recommendations on relevant protective measures, understanding of local quarantine measures, depression, psychological resilience, and perceived social support were the main factors affecting the implementation of residents' home quarantine strategy. Health service policymakers should adopt relevant measures to improve the prevalence of home quarantine strategy implementation among residents during the pandemic.

13.
Phys Chem Chem Phys ; 23(34): 18712-18723, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34612409

RESUMO

A challenge in the application of two-dimensional (2D) SnS in gas-sensing field is that the SnS monolayer is highly sensitive to oxidizing gases, whereas it is naturally deactivated towards reducing gases. The non-sensitivity of SnS to reducing gases is a problem that needs to be solved urgently in an economic and effective manner. Hence, in this work, we propose a strategy of applying strain modulation on the SnS monolayer to optimize its sensitivity and selectivity for reducing gases fundamentally. Generally, the strain modulation applied on a semiconductor gives rise to a change in its band gap (BG). Based on the first-principles calculations, the strain on SnS was found to induce strong degeneracy and energy-level splitting. Unusually, the tensile strain (≥3%) applied could transform the SnS monolayer from indirect-gap semiconductors to direct-gap semiconductors, manifesting a promising optical application prospect but not appropriate for the gas-sensing filed. Comparatively, the compressive strain (≥3%) on SnS could generate new electronic states at the edge of the conduction band of the SnS monolayer, which increases the conductivity and the weak interaction. Thus, the adsorption of reducing gases on the SnS monolayer is enhanced from physisorption to chemisorption, resulting in a considerable increase in the sensitivity performance to the three reducing gas molecules (NH3, H2S, and CO). The induced symmetry breaking of the SnS monolayer under compressive strain leads to much higher surface activation towards reducing gases, which improves its adsorption capability and the ability of screening oxidizing gas molecules. The present work provides key information for novel designs of strain-sensitive dual-function sensors based on SnS.

14.
J Appl Microbiol ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706134

RESUMO

AIMS: COVID-19 pandemic caused by SARS-CoV-2 has become a public health crisis worldwide. In this study, we aimed at demonstrating the neutralizing potential of the IgY produced after immunizing chicken with a recombinant SARS-CoV-2 spike protein S1 subunit. METHODS AND RESULTS: E. coli BL21 carrying plasmid pET28a-S1 was induced with IPTG for the expression of SARS-CoV-2 S1 protein. The recombinant His-tagged S1 was purified and verified by SDS-PAGE, Western blot and biolayer interferometry (BLI) assay. Then S1 protein emulsified with Freund's adjuvant was used to immunize layer chickens. Specific IgY against S1 (S1-IgY) produced from egg yolks of these chickens exhibited a high titer (1:25,600) and a strong binding affinity to S1 (KD  = 318 nmol L-1 ). The neutralizing ability of S1-IgY was quantified by a SARS-CoV-2 pseudotyped virus-based neutralization assay with an IC50  value of 0.99 mg ml-1 . In addition, S1-IgY exhibited a strong ability in blocking the binding of SARS-CoV-2 S1 to hACE2, and it could partially compete with hACE2 for the binding sites on S1 by BLI assays. CONCLUSIONS: We demonstrated here that after immunization of chickens with our recombinant S1 protein, IgY neutralizing antibodies were generated against the SARS-CoV-2 spike protein S1 subunit; therefore, showing the potential use of IgY to block the entry of this virus. SIGNIFICANCE AND IMPACT OF THE STUDY: IgY targeting S1 subunit of SARS-CoV-2 could be a promising candidate for pre- and post-exposure prophylaxis or treatment of COVID-19. Administration of IgY-based oral preparation, oral or nasal spray may have profound implications for blocking SARS-CoV-2.

15.
Appl Microbiol Biotechnol ; 105(21-22): 8427-8440, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34625821

RESUMO

Aging is associated with gut microbiota alterations, characterized by changes in intestinal microbial diversity and composition. However, no study has yet focused on investigating age-related changes in the low-abundant but potentially beneficial subpopulations of gut lactic acid bacteria (LAB) and Bifidobacterium. Our study found that the subjects' age correlated negatively with the alpha diversity of the gut bifidobacterial microbiota, and such correlation was not observed in the gut LAB subpopulation. Principal coordinate analysis (PCoA) and analysis of distribution of operational taxonomic units (OTUs) revealed that the structure and composition of the gut bifidobacterial subpopulation of the longevous elderly group were rather different from that of the other three age groups. The same analyses were applied to identify age-dependent characteristics of the gut LAB subpopulation, and the results revealed that the gut LAB subpopulation of young adults was significantly different from that of all three elderly groups. Our study identified several potentially beneficial bacteria (e.g., Bifidobacterium breve and Bifidobacterium longum) that were enriched in the longevous elderly group (P < 0.05), and the relative abundance of Bifidobacterium adolescentis decreased significantly with the increase in age (P < 0.05). Although both bifidobacteria and LAB are generally considered as health-promoting taxa, their age-dependent distribution varied from each other, suggesting their different life stage changes and potentially different functional roles. This study provided novel species-level gut bifidobacterial and LAB microbiota profiles of a large cohort of subjects and identified several age-or longevity-associated features and biomarkers. KEY POINTS: • The alpha diversity of the gut bifidobacterial microbiota decreased with age, while LAB did not change. • The structure and composition of the gut bifidobacterial subpopulation of the longevous elderly group were rather different from that of the other three age groups. • Several potentially beneficial bacteria (e.g., Bifidobacterium breve and Bifidobacterium longum) that were enriched in the longevous elderly group.


Assuntos
Bifidobacterium longum , Microbioma Gastrointestinal , Lactobacillales , Idoso , Envelhecimento , Bifidobacterium , Fezes , Humanos
16.
Front Physiol ; 12: 724372, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690801

RESUMO

The disrupted organisation of the ryanodine receptors (RyR) and junctophilin (JPH) is thought to underpin the transverse tubule (t-tubule) remodelling in a failing heart. Here, we assessed the nanoscale organisation of these two key proteins in the failing human heart. Recently, an advanced feature of the t-tubule remodelling identified large flattened t-tubules called t-sheets, that were several microns wide. Previously, we reported that in the failing heart, the dilated t-tubules up to ~1 µm wide had increased collagen, and we hypothesised that the t-sheets would also be associated with collagen deposits. Direct stochastic optical reconstruction microscopy (dSTORM), confocal microscopy, and western blotting were used to evaluate the cellular distribution of excitation-contraction structures in the cardiac myocytes from patients with idiopathic dilated cardiomyopathy (IDCM) compared to myocytes from the non-failing (NF) human heart. The dSTORM imaging of RyR and JPH found no difference in the colocalisation between IDCM and NF myocytes, but there was a higher colocalisation at the t-tubule and sarcolemma compared to the corbular regions. Western blots revealed no change in the JPH expression but did identify a ~50% downregulation of RyR (p = 0.02). The dSTORM imaging revealed a trend for the smaller t-tubular RyR clusters (~24%) and reduced the t-tubular RyR cluster density (~35%) that resulted in a 50% reduction of t-tubular RyR tetramers in the IDCM myocytes (p < 0.01). Confocal microscopy identified the t-sheets in all the IDCM hearts examined and found that they are associated with the reticular collagen fibres within the lumen. However, the size and density of the RyR clusters were similar in the myocyte regions associated with t-sheets and t-tubules. T-tubule remodelling is associated with a reduced RyR expression that may contribute to the reduced excitation-contraction coupling in the failing human heart.

17.
Front Oncol ; 11: 722797, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660289

RESUMO

Periodontitis is closely related to oral cancer, but the molecular mechanism of periodontal pathogens involved in the occurrence and development of oral cancer is still inconclusive. Here, we demonstrate that, in vitro, the cell proliferation ability and S phase cells of the periodontitis group (colonized by Porphyromonas gingivalis and Fusobacterium nucleatum, P+) significantly increased, but the G1 cells were obviously reduced. The animal models with an in situ oral squamous cell carcinoma (OSCC) and periodontitis-associated bacteria treatment were constructed, and micro-CT showed that the alveolar bone resorption of mice in the P+ group (75.3 ± 4.0 µm) increased by about 53% compared with that in the control group (48.8 ± 1.3 µm). The tumor mass and tumor growth rate in the P+ group were all higher than those in the blank control group. Hematoxylin-eosin (H&E) staining of isolated tumor tissues showed that large-scale flaky necrosis was found in the tumor tissue of the P+ group, with lots of damaged vascular profile and cell debris. Immunohistochemistry (IHC) of isolated tumor tissues showed that the expression of Ki67 and the positive rate of cyclin D1 were significantly higher in tumor tissues of the P+ group. The qRT-PCR results of the expression of inflammatory cytokines in oral cancer showed that periodontitis-associated bacteria significantly upregulated interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-18, apoptosis-associated speck-like protein containing a CARD (ASC) (up to six times), and caspase-1 (up to four times), but it downregulated nuclear factor (NF)-κB, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), and IL-1ß (less than 0.5 times). In addition, the volume of spleen tissue and the number of CD4+ T cells, CD8+ T cells, and CD206+ macrophages in the P+ group increased significantly. IHC and Western blotting in tumor tissues showed that expression levels of γ-H2AX, p-ATR, RPA32, CHK1, and RAD51 were upregulated, and the phosphorylation level of CHK1 (p-chk1) was downregulated. Together, we identify that the periodontitis-related bacteria could promote tumor growth and proliferation, initiate the overexpressed NLRP3, and activate upstream signal molecules of ATR-CHK1. It is expected to develop a new molecular mechanism between periodontitis-related bacteria and OSCC.

18.
J Exp Clin Cancer Res ; 40(1): 340, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706747

RESUMO

BACKGROUND: The zinc transporters Zrt- and Irt-related protein (ZIP/SLC39) are overexpressed in human tumors and correlate with poor prognosis; however, their contributions to carcinogenesis and chemoresistance in osteosarcoma (OS) remain unclear. METHODS: We collected 64 OS patient tissues with (n = 12) or without (n = 52) chemotherapy. The expression levels of ZIP10 were measured by immunohistochemistry and applied to prognostic analysis. ZIP10 was knocked down or overexpressed in OS cell lines to explore its effect on proliferation and chemoresistance. RNA sequencing, quantitative real-time PCR, and western blotting analysis were performed to explore ZIP10-regulated downstream target genes. A xenograft mouse model was established to evaluate the mechanisms by which ZIP10 modulates chemoresistance in OS cells. RESULTS: The expression of ZIP10 was significantly induced by chemotherapy and highly associated with the clinical outcomes of OS. Knockdown of ZIP10 suppressed OS cell proliferation and chemoresistance. In addition, ZIP10 promoted Zn content-induced cAMP-response element binding protein (CREB) phosphorylation and activation, which are required for integrin α10 (ITGA10) transcription and ITGA10-mediated PI3K/AKT pathway activation. Importantly, ITGA10 stimulated PI3K/AKT signaling but not the classical FAK or SRC pathway. Moreover, overexpression of ZIP10 promoted ITGA10 expression and conferred chemoresistance. Treatment with the CREB inhibitor 666-15 or the PI3K/AKT inhibitor GSK690693 impaired tumor chemoresistance in ZIP10-overexpressing cells. Finally, a xenograft mouse model established by subcutaneous injection of 143B cells confirmed that ZIP10 mediates chemotherapy resistance in OS cells via the ZIP10-ITGA10-PI3K/AKT axis. CONCLUSIONS: We demonstrate that ZIP10 drives OS proliferation and chemoresistance through ITGA10-mediated activation of the PI3K/AKT pathway, which might serve as a target for OS treatment.

19.
Front Neurol ; 12: 694966, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712195

RESUMO

A 29-year-old female experienced chronic progressive peripheral neuropathy since childhood and was diagnosed with Charcot-Marie-Tooth disease (CMT) at age 15. She developed recurrent, fever-induced rhabdomyolysis (RM) at age 24. EMG studies showed decreased amplitude of compound muscle action potential, declined motor conductive velocity, and absence of sensor nerve action potential. Acylcarnitine analysis revealed elevated C16-OH, C18-OH, and C18:1-OH. Muscle biopsy showed scattered foci of necrotic myofibers invaded by macrophages, occasional regenerating fibers, and remarkable muscle fiber type grouping. Whole-exome sequencing identified two novel heterozygous mutations: c.490G>A (p.G164S) and c.686G>A (p.R229Q) in HADHB gene encoding the ß-subunit of mitochondrial trifunctional protein (MTP). Reduction of long-chain fatty acid via dietary restrictions alleviated symptoms effectively. Our study indicates that the defect of the MTP ß-subunit accounts for both CMT and RM in the same patient and expands the clinical spectrum of disorders caused by the HADHB mutations. Our systematic review of all MTPD patients with dietary treatment indicates that the effect of dietary treatment is related to the age of onset and the severity of symptoms.

20.
Front Psychol ; 12: 700376, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646194

RESUMO

Background: The outbreak of coronavirus disease 2019 (COVID-19) has contributed to depression and anxiety among the general population in China. The purpose of this study is to investigate the prevalence and associated factors of these psychological problems among Chinese adults during the period of low transmission, which could reflect the long-term depression and anxiety of the COVID-19 outbreak. Methods: A cross-sectional survey was conducted in China from 4 to 26 February 2021. Convenient sampling strategy was adopted to recruit participators. Participants were asked to filled out the questions that assessed questionnaire on the residents' depression and anxiety. Results: A total of 2,361 residents filled out the questionnaire. The mean age was 29.72 years (SD = 6.94) and majority of respondents were female (60.10%). Among the respondents, 421 (17.83%), 1470 (62.26%), and 470 (19.91%) were from eastern, central, and western China, respectively. 1704 (72.17%) consented COVID-19 information has been disclosed timely. 142 (6.01%) and 130 (5.51%) patients suffered from depression and anxiety symptoms. Furthermore, some influencing factors were found, including marital status, place of residence, employment status. Conclusion: This study revealed that anxiety and depression still are potential depression and anxiety for some residents, which suggested early recognition and initiation of interventions during the period of low transmission is still indispensable.

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