Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 482
Filtrar
2.
BMC Nephrol ; 22(1): 172, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33971831

RESUMO

BACKGROUND: Patients with kidney disease may have concurrent hypertension and infection. Dihydropyridine calcium-channel blockers (CCB) are the most popular class of antihypertensive drugs used in clinical settings and can be metabolized by cytochrome P450 isoenzyme 3A4 (CYP3A4). Voriconazole is a commonly used antifungal treatment and a CYP3A4-inhibitor. Insufficient attention to drug interactions from the concomitant use of CCB and voriconazole may result in serious adverse reactions. CASE PRESENTATION: Here, we report a patient with acute kidney injury on stable anti-neutrophil cytoplasm antibody associated vasculitis who developed hyperkalemia resulting in sinus arrest with junctional escape rhythm attributed to drug interactions of CCB with voriconazole. This is a very rarely reported case and may be an under-recognized complication. After continuous renal replacement therapy and changing the anti-hypertensive drugs, symptoms, and laboratory abnormalities of the patient fully recovered. CONCLUSIONS: This case warns us of severe consequences of drug interactions. Co-prescription of CYP3A4-inhibitors with calcium-channel blockers increases the risk of hypotension and acute kidney injury, which may further induce hyperkalemia and arrhythmia.

3.
Cancers (Basel) ; 13(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803301

RESUMO

Hepatitis B virus (HBV) infection is a major etiological risk for the incidence of hepatocellular carcinoma (HCC), and HBV X protein (HBx) is essential for oncogenic transformation. It is not known that if HBx can sabotage the lysosomal system for transformation and tumorigenesis, or its mechanism if it does have an effect. Examining clinical data, we observed that the downregulation of lysosomal components and transcription factor EB (TFEB) was associated with a poor prognosis of HCC patients. In HCC cells, we found that expression of HBx suppressed TFEB, impaired biogenesis of autophagic-lysosome, and promoted cellular dissemination. HBx mediated downregulation of TFEB led to impairment of autophagic/lysosomal biogenesis and flux, and consequently, accumulation of integrin beta 1 (ITGB1) for motility of HCC cells. Conversely, TFEB, in a steady-state condition, through induction of lysosomal biogenesis restrained ITGB1 levels and limited mobility of HCC cells. Specifically, overexpression of TFEB upregulated and activated the cysteine proteases including cathepsin L (CTSL) to degrade ITGB1. Conversely, expression of cystatin A (CSTA) or cystatin B (CSTB), the cellular inhibitors of lysosomal cysteine proteinases, spared ITGB1 from degradation and promoted dissemination of HCC cells. Taken together, this study suggests a potential mechanism for HBV-mediated malignancy, showing that HBx mediated downregulation of TFEB leads to accumulation of ITGB1 for HCC cell migration.

4.
Front Immunol ; 12: 653989, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868295

RESUMO

Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase mediating trimethylation of H3K27, which represses gene expression and is critical to immune regulation. Inhibition of EZH2 is proved to have the potential of treating many diseases. However, whether inhibition of EZH2 affects type I interferon (IFN-I) signaling pathway, the abnormality of which is an important pathogenic mechanism for SLE, is still elusive. Here, we report, unexpectedly, a positive regulatory function of EZH2 in IFN-I signaling pathway, which contributes to the overactivation of IFN-I signaling pathway in SLE. We show that the expression of EZH2 was upregulated and positively correlated with the overexpression of interferon stimulated genes (ISGs) in both peripheral blood mononuclear cells and renal tissues of SLE patients. In vitro inhibition of EZH2 by either siRNAs or chemical inhibitors reduced the phosphorylation of STAT1 and the induction of ISGs stimulated by IFN-I. Additionally, inhibition of EZH2 interfered with the in vivo and ex vivo activation of IFN-I signaling pathway elicited by intravenous injection of adenovirus vector expressing mouse IFN-α5 and exogeneous stimulation with IFN-α, respectively. We evaluated the therapeutic effects of EZH2 inhibitor in NZB/NZW F1 mice which depend on IFN-I signaling pathway for the lupus-like disease development. Administration of EZH2 inhibitor prolonged the survival, reduced the levels of anti-dsDNA autoantibodies, and improved lupus nephritis of the mice. What's more, EZH2 inhibitor attenuated the expression of ISGs in the kidneys of these mice. In summary, we show that excessive EZH2 contributes to the overactivation of IFN-I signaling pathway in SLE. EZH2 inhibitor has the potential to inhibit IFN-I signaling pathway and alleviate lupus nephritis. Additionally, diverse disease driving pathways exist among systemic lupus erythematosus (SLE) patient, and even in the same patients. Common regulators of different pathogenic pathways can be multivalent therapeutic targets. Together with previous studies showing EZH2 is involved in T-cell and B-cell mediated immune responses, EZH2 could be a potent multivalent therapeutic target for SLE.

5.
Mol Med Rep ; 23(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33899119

RESUMO

Different degrees of myocardial ischemia­reperfusion injury during open­heart surgery are inevitable. Therapeutic hypothermia is an important technique for reducing ischemia­reperfusion injury; however, there are numerous potential adverse effects. Furthermore, the underlying molecular mechanisms of action of therapeutic hypothermia remain unclear. In the present study, rat hearts were perfused for 30 min and subjected to 30 min of regional ischemia, followed by 120 min of reperfusion. Animals received intraperitoneal injection of spectomycin B1 at 30 min prior to the start of surgery. Total myocardial area, infarct area, myocardial injury, and apoptosis were assessed. H9C2 cells were incubated for 24  h at 34˚C with 5% CO2 to simulate therapeutic hypothermic stress, and cell viability and mitochondrial injury were evaluated. The levels of protein SUMOylation, hypoxia­inducible factor (HIF)­1α and vascular endothelial growth factor (VEGF) were determined by western blot analysis. It was demonstrated that hypoxia significantly increased the overall modification by the small ubiquitin­related modifier protein (SUMO) of various proteins in cardiomyocytes, both in vitro and ex vivo. In turn, this increased the protein levels of HIF­1α, continuously stimulated downstream VEGF expression. Therapeutic hypothermia further increased protein SUMOylation, whereas inhibiting the SUMOylation pathway reduced the protective effect of therapeutic hypothermia on hypoxic cardiomyocytes. Overall, these data suggested that increasing SUMOylation of HIF­1α may be an important molecular mechanism underlying the protective effects of therapeutic hypothermia following hypoxia in myocardial cells. These findings may aid in the use of therapeutic hypothermia for treatment of myocardial ischemia­reperfusion and help avoid excessive side effects.


Assuntos
Hipotermia Induzida , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Sumoilação , Animais , Apoptose , Hipóxia Celular , Linhagem Celular , Células Cultivadas , Feminino , Traumatismo por Reperfusão Miocárdica/terapia , Ratos , Ratos Sprague-Dawley , Proteína SUMO-1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
mSphere ; 6(2)2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731468

RESUMO

Bacteria of different shapes have adopted distinct mechanisms to faithfully coordinate morphogenesis and segregate their chromosomes prior to cell division. Despite recent focuses and advances, the mechanism of cell division in ovococci remains largely unknown. Streptococcus suis, a major zoonotic pathogen that causes problems in human health and in the global swine industry, is an elongated and ellipsoid bacterium that undergoes successive parallel splitting perpendicular to its long axis. Studies on cell cycle processes in this bacterium are limited. Here, we report that MsmK (multiple sugar metabolism protein K), an ATPase that contributes to the transport of multiple carbohydrates, has a novel role as a cell division protein in S. suis MsmK can display ATPase and GTPase activities, interact with FtsZ via the N terminus of MsmK, and promote the bundling of FtsZ protofilaments in a GTP-dependent manner in vitro Deletion of the C-terminal region or the Walker A or B motif affects the affinity between MsmK and FtsZ and decreases the ability of MsmK to promote FtsZ protofilament bundling. MsmK can form a complex with FtsZ in vivo, and its absence is not lethal but results in long chains and short, occasionally anuclear daughter cells. Superresolution microscopy revealed that the lack of MsmK in cells leads to normal septal peptidoglycan walls in mother cells but disturbed cell elongation and peripheral peptidoglycan synthesis. In summary, MsmK is a novel cell division protein that maintains cell shape and is involved in the synthesis of the peripheral cell wall.IMPORTANCE Bacterial cell division is a highly ordered process regulated in time and space and is a potential target for the development of antimicrobial drugs. Bacteria of distinct shapes depend on different cell division mechanisms, but the mechanisms used by ovococci remain largely unknown. Here, we focused on the zoonotic pathogen Streptococcus suis and identified a novel cell division protein named MsmK, which acts as an ATPase of the ATP-binding cassette-type carbohydrate transport system. MsmK has GTPase and ATPase activities. In vitro protein assays showed that MsmK interacts with FtsZ and promotes FtsZ protofilament bundling that relies on GTP. Superresolution microscopy revealed that MsmK maintains cell shape and is involved in peripheral peptidoglycan synthesis. Knowledge of the multiple functions of MsmK may broaden our understanding of known cell division processes. Further studies in this area will elucidate how bacteria can faithfully and continually multiply in a constantly changing environment.

7.
Life Sci ; : 119365, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33741416

RESUMO

AIMS: Vascular smooth muscle cells (VSMCs) are involved in the pathogenesis of many human cardiovascular diseases. They modulate their phenotype from "contractile" to "synthetic" in response to changes in local environmental cues. How glutamine regulates the differentiation of VSMCs and the underlying mechanisms remain largely unknown. MAIN METHODS: Here, we explored the effects of various doses of glutamine (0 mM, 1 mM, 2 mM, and 4 mM) on the proliferation, migration, and phenotypic switch of human VSMCs in vitro. Glutamine dose-dependently enhanced VSMC proliferation, and markedly increased VSMC migration. KEY FINDINGS: Notably, glutamine promoted the phenotypic switch of VSMCs towards a synthetic phenotype, as evidenced by significantly decreased expression of contractile markers myosin heavy chain 11 (MYH11) and calponin while increased expression of synthetic markers collagen I and vimentin. Importantly, these changes upon glutamine treatments were attenuated after additional treatments with glutamine metabolism inhibitor BPTES. Additionally, glutamine downregulated miR-143 expression, and miR-143 inactivation alone resulted in enhanced proliferation, migration, and promoted the synthetic phenotype of VSMCs. Moreover, Thy-1 cell surface antigen (THY1) was validated as a downstream target of miR-143, and THY1 expression was upregulated by glutamine in VSMCs. Furthermore, either miR-143 overexpression or THY1 silencing abolished the effect of glutamine on proliferation, migration, and phenotypic switch of VSMCs, supporting a novel glutamine-miR-143-THY1 pathway in modulating VSMC functions. SIGNIFICANCE: This study demonstrated a novel mechanism of glutamine in modulation of VSMC phenotypic switch by targeting miR-143 and THY1, and provides significant insight on targeted therapy of patients with cardiovascular diseases.

8.
Biosci Biotechnol Biochem ; 85(4): 775-785, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33686395

RESUMO

This research aimed to evaluate the antihepatic fibrosis effect and explore the mechanism of Qiwei Qinggan Powder (QGS-7) in vivo and in vitro. Carbon tetrachloride (CCl4)-treated rats and hepatic stellate cells (HSCs) were used. QGS-7 treatment significantly improved the liver function of rats as indicated by decreased serum enzymatic activities of alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. Meanwhile, the hydroxyproline of liver was significantly decreased. Histopathological results indicated that QGS-7 alleviated liver damage and reduced the formation of fibrosis septa. Moreover, QGS-7 significantly attenuated expressions of Alpha smooth muscle actin, Collagen I, Janus kinase 2 (JAK2), phosphorylation-JAK2, signal transducer and activator of transcription 3 (STAT3), phosphorylation-STAT3 in the rat hepatic fibrosis model. QGS-7 inhibited HSC proliferation and promoted it apoptosis. QGS-7 may affect hepatic fibrosis through JAK2/STAT3 signaling pathway so as to play an antihepatic fibrosis role.

9.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33537820

RESUMO

Improving angiogenic capacity under hypoxic conditions is essential for improving the survival of skin grafts, as they often lack the necessary blood supply. The stable expression levels of hypoxia­inducible factor­1α (HIF­1α) in the nucleus directly affect the downstream vascular endothelial growth factor (VEGF) signaling pathway and regulate angiogenesis in a hypoxic environment. Astragaloside IV (AS­IV), an active component isolated from Astragalus membranaceus, has multiple biological effects including antioxidant and anti­diabetic effects, and the ability to provide protection from cardiovascular damage. However, the mechanisms underlying these effects have not previously been elucidated. The present study investigated whether AS­IV promotes angiogenesis via affecting the balance between ubiquitination and small ubiquitin­related modifier (SUMO) modification of HIF­1α. The results demonstrated that persistent hypoxia induces changes in expression levels of HIF­1α protein and significantly increases the proportion of dysplastic blood vessels. Further western blotting experiments showed that rapid attenuation and delayed compensation of SUMO1 activity is one of the reasons for the initial increase then decrease in HIF­1α levels. SUMO1 overexpression stabilized the presence of HIF­1α in the nucleus and decreased the extent of abnormal blood vessel morphology observed following hypoxia. AS­IV induces vascular endothelial cells to continuously produce SUMO1, stabilizes the HIF­1α/VEGF pathway and improves angiogenesis in hypoxic conditions. In summary, the present study confirmed that AS­IV stimulates vascular endothelial cells to continuously resupply SUMO1, stabilizes the presence of HIF­1α protein and improves angiogenesis in adverse hypoxic conditions, which may improve the success rate of flap graft surgery following trauma or burn.


Assuntos
Células Endoteliais da Veia Umbilical Humana/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Neovascularização Fisiológica/efeitos dos fármacos , Saponinas/farmacologia , Sumoilação/efeitos dos fármacos , Triterpenos/farmacologia , Hipóxia Celular/efeitos dos fármacos , Humanos
10.
Biol Chem ; 402(6): 717-727, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33580997

RESUMO

Long non-coding RNAs (lncRNAs) are involved in the occurrence and development of human cancers including lung adenocarcinoma (LUAD). SLC2A1-AS1 is a novel lncRNA that has been reported to be exceptionally expressed in several cancer types. However, the expression and role of SLC2A1-AS1 in cancer remains largely unclear. In this study, it was revealed that lncRNA SLC2A1-AS1 was notably over-expressed in LUAD and was closely correlated with patients' overall survival (OS). Knockdown of SLC2A1-AS1 could significantly restrain cell proliferation of LUAD in vitro, while over-expression of SLC2A1-AS1 had the accelerative effect. SLC2A1-AS1 enriched in the cytoplasm of LUAD cells could directly bind to miR-508-5p and negatively regulate its level. The inhibitory effect of miR-508-5p on LUAD cell proliferation was in part abrogated by SLC2A1-AS1 manipulation. Moreover, the transcription factor activating enhancer binding protein 2 α (TFAP2A) was highly expressed in LUAD and predicted worse patients' OS. TFAP2A could directly bind to the promoter region of SLC2A1-AS1 encoding gene and positively regulate the transcription of SLC2A1-AS1 in LUAD cells. Furthermore, TFAP2A-induced SLC2A1-AS1 promoted cell proliferation of lung squamous cell carcinoma (LUSC) and pancreatic adenocarcinoma (PAAD). Collectively, these findings suggest that TFAP2A-mediated lncRNA SLC2A1-AS1 works as an oncogene to drive cancer cell proliferation.

11.
Fish Shellfish Immunol ; 112: 46-55, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33609702

RESUMO

The present study aims to investigate the effects of dietary synbiotics supplementation methods on growth, feed utilization, hepatopancreas and intestinal histology, non-specific immunity and microbiota community of Pacific white shrimp (Litopenaeus vannamei). A control diet was designed to contain 18% fish meal (CON), and then 3 g kg-1 synbiotics (Bioture, consisting of Bacillus subtilis, Saccharomyces cerevisiae, ß-glucan and mannan oligosaccharide, etc) was supplemented to the control diet with three methods, directly adding in diets for pelleting (DAP), spraying diets after pelleting at once (SDA), spraying diets before feeding every day (SDE). Shrimp with initial body weight of 1.5 ± 0.12 g were fed one of the four diets for 56 days. The results showed that dietary synbiotics significantly increased the weight gain (WG), apparent digestibility coefficient (ADC) of crude protein (CP) and dry matter (DM), hepatopancreatic protease activity and decreased feed conversion ratio (FCR) (P < 0.05). Among the three synbiotics-added diets, SDE group showed the best growth with significantly higher WG than DAP group (P < 0.05). Serum activities of total superoxide dismutase, catalase, acid phosphatase, lysozyme and alkaline phosphatase of synbiotics-added groups were significantly higher, and serum malondialdehyde level was significantly lower than those of the control (P < 0.05). The intestinal villus width and villus number were also increased by the supplementation of synbiotics. The cumulative mortality was reduced in the three synbiotics-added groups after challenging with Vibrio parahaemolyticus (P < 0.05), and SDE group showed a significantly lower mortality than the control and DAP groups (P < 0.05). In intestinal microbiota composition, the abundance of Lactococcus tended to increase and Vibro tended to decreased in SDA and SDE groups. In conclusion, dietary synbiotics improved the growth, feed utilization, intestine health and non-specific immunity of Pacific white shrimp, and spraying synbiotics on diet presented better performance than adding synbiotics in diet for pelleting.

12.
Int Microbiol ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608776

RESUMO

Enterovirus A71 (EV-A71) is an important pathogen of severe hand, foot, and mouth disease (HFMD) in young children. This study aimed to retrospectively analyze the molecular epidemiology and recombination of EV-A71 in mainland China during 1987-2017. Phylogenetic tree showed that besides the previously reported subgenotypes A, B5, C0, C2, C3, and C4, a new subgenotype C6 emerged in mainland China. Recombination analysis indicated that C4 EV-A71 was derived from a common ancestor as a "double-recombinant" virus by intertypic recombination between C EV-A71 and CVA4, CVA5, CVA14, and CVA16 strains in P3 region and intratypic recombination between C and B EV-A71 strains in P2 region. The B5 EV-A71 shared high similarity with C EV-A71 in P1 region while it contained an unidentified sequence in P2 and P3 regions with two possible recombination patterns: one occurred between C4 EV-A71 and CVA3, CVA5, CVA6, CVA10, and CVA12 stains with one breakpoint in 3C, and the other occurred between C1, C2, C3, and C5 EV-A71 and CVA4, CVA5, CVA14, and CVA16 strains with two breakpoints in the 2A/2B junction and 3C. The C2 EV-A71 was probably a recombinant virus between C4 EV-A71 and CVA8 strains with two breakpoints located in the 5'UTR and 2A/2B junction. Moreover, an incredible recombination of C6 EV-A71 occurred between C4 and C2 EV-A71 with multiple breakpoints. Thus, continuous studies on EV-A71 genome characteristics are still useful and essential for monitoring emergence of new viruses and preventing HFMD outbreaks.

13.
Cell Biol Int ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33559901

RESUMO

Kidney renal clear cell carcinoma (KIRC) is a common malignant tumor in human genitourinary system. Previous studies have shown that the homeobox-D (HOXD) cluster genes, which belong to the homeobox (HOX) family, are involved in the progression of multiple types of cancer. However, the expression profile and prognostic values of the HOXD genes in KIRC remain largely unknown. Herein, we comprehensively analyzed the transcriptional levels and prognosis of HOXD genes in KIRC using four online The Cancer Genome Atlas analysis databases (GEPIA, UALCAN, starBase v3.0, and LinkedOmics). We found that several members of the HOXD gene family were abnormally expressed in KIRC and correlated with patient prognosis. The messenger RNA levels of HOXD1, HOXD8, and HOXD10 were significantly downregulated in KIRC tissues as compared with the normal tissues. Low expression of HOXD1 or HOXD8 predicted poor overall survival (OS) of KIRC patients, and downregulated HOXD1, HOXD3, or HOXD4 indicated unfavorable patient disease-free survival (DFS) in KIRC. Through integrated analysis, we found that HOXD1 was lowly expressed in KIRC and correlated with patient OS, DFS and advanced tumor stages. Moreover, gene set enrichment analysis showed that HOXD1 may be mainly implicated in cell cycle regulation, tumor growth factor-ß (TGF-ß) and Wnt signaling pathways in KIRC. Furthermore, both loss-of-function and gain-of-function experiments demonstrated that HOXD1 inhibited cell proliferation, cell cycle and the TGF-ß signaling in KIRC. Taken together, our findings suggest that HOXD1 is a novel potential tumor suppressor in KIRC.

14.
Sci Total Environ ; 772: 145023, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33581544

RESUMO

The individual impacts of elevated CO2 and heavy metals on soil nitrification have been widely reported. However, studies on the combined effects of elevated CO2 and heavy metals on soil nitrification are still limited. Here, a 135-day growth chamber experiment was conducted to investigate the impacts of elevated CO2 and cadmium (Cd) levels on soil nitrification in the rhizosphere of Robinia pseudoacacia L. seedlings. Elevated CO2 combined with Cd pollution generally stimulated ammonia monooxygenase (AMO), hydroxylamine oxidase (HAO), and nitrite oxidoreductase (NXR) activities. Compared to the control, the abundance of ammonia-oxidizing bacteria (AOB) at day 135 and ammonia-oxidizing archaea (AOA) increased significantly (p < 0.05) and the abundance of AOB at days 45 and 90 and that of the nitrite-oxidizing bacteria (NOB) decreased under elevated CO2 + Cd. Elevated CO2 mostly led to a significant (p < 0.05) decrease in soil nitrification intensity in the rhizosphere of R. pseudoacacia exposed to Cd. The effects of Cd, CO2, and their interaction on HAO and NXR activities were significant (p < 0.01). Soil pH, the C/N ratio, water-soluble organic carbon, water-soluble organic nitrogen (WSON), and total carbon were the dominant factors (p < 0.05) affecting nitrifying enzyme activities and nitrification intensity in rhizosphere soils. Elevated CO2 clearly affected AOA, AOB, and NOB community structures and dominant genera by shaping C/N ratio, pH, and Cd and WSON contents in rhizosphere soils under Cd exposure. Overall, the responses of pH, C/N ratio, WSON, and Cd to elevated CO2 led to changes in rhizosphere soil nitrification under the combination of elevated CO2 and Cd pollution.


Assuntos
Robinia , Poluentes do Solo , Amônia , Archaea , Cádmio/análise , Dióxido de Carbono/análise , Nitrificação , Oxirredução , Rizosfera , Plântula/química , Solo , Microbiologia do Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
15.
J Med Internet Res ; 23(3): e26482, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33617460

RESUMO

BACKGROUND: Since the beginning of the COVID-19 pandemic in late 2019, its far-reaching impacts have been witnessed globally across all aspects of human life, such as health, economy, politics, and education. Such widely penetrating impacts cast significant and profound burdens on all population groups, incurring varied concerns and sentiments among them. OBJECTIVE: This study aims to identify the concerns, sentiments, and disparities of various population groups during the COVID-19 pandemic through a cross-sectional study conducted via large-scale Twitter data mining infoveillance. METHODS: This study consisted of three steps: first, tweets posted during the pandemic were collected and preprocessed on a large scale; second, the key population attributes, concerns, sentiments, and emotions were extracted via a collection of natural language processing procedures; third, multiple analyses were conducted to reveal concerns, sentiments, and disparities among population groups during the pandemic. Overall, this study implemented a quick, effective, and economical approach for analyzing population-level disparities during a public health event. The source code developed in this study was released for free public use at GitHub. RESULTS: A total of 1,015,655 original English tweets posted from August 7 to 12, 2020, were acquired and analyzed to obtain the following results. Organizations were significantly more concerned about COVID-19 (odds ratio [OR] 3.48, 95% CI 3.39-3.58) and expressed more fear and depression emotions than individuals. Females were less concerned about COVID-19 (OR 0.73, 95% CI 0.71-0.75) and expressed less fear and depression emotions than males. Among all age groups (ie, ≤18, 19-29, 30-39, and ≥40 years of age), the attention ORs of COVID-19 fear and depression increased significantly with age. It is worth noting that not all females paid less attention to COVID-19 than males. In the age group of 40 years or older, females were more concerned than males, especially regarding the economic and education topics. In addition, males 40 years or older and 18 years or younger were the least positive. Lastly, in all sentiment analyses, the sentiment polarities regarding political topics were always the lowest among the five topics of concern across all population groups. CONCLUSIONS: Through large-scale Twitter data mining, this study revealed that meaningful differences regarding concerns and sentiments about COVID-19-related topics existed among population groups during the study period. Therefore, specialized and varied attention and support are needed for different population groups. In addition, the efficient analysis method implemented by our publicly released code can be utilized to dynamically track the evolution of each population group during the pandemic or any other major event for better informed public health research and interventions.


Assuntos
/epidemiologia , Mineração de Dados/métodos , Mídias Sociais/provisão & distribução , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , Grupos Populacionais , Fatores Sexuais , Adulto Jovem
16.
PLoS Pathog ; 17(2): e1009295, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33635920

RESUMO

To date, no reports have linked the multifunctional protein, staphylococcal nuclease domain-containing protein 1 (SND1), to host defense against intracellular infections. In this study, we investigated the role and mechanisms of SND1, by using SND1 knockout (SND1-/-) mice, in host defense against the lung infection of Chlamydia muridarum, an obligate intracellular bacterium. Our data showed that SND1-/- mice exhibited significantly greater body weight loss, higher organism growth, and more severe pathological changes compared with wild-type mice following the infection. Further analysis showed significantly reduced Chlamydia-specific Th1/17 immune responses in SND1-/- mice after infection. Interestingly, the dendritic cells (DCs) isolated from SND1-/- mice showed lower costimulatory molecules expression and IL-12 production, but higher IL-10 production compared with those from wild-type control mice. In the DC-T cell co-culture system, DCs isolated from SND1-/- infected mice showed significantly reduced ability to promote Chlamydia-specific IFN-γ producing Th1 cells but enhanced capacity to induce CD4+T cells into Foxp3+ Treg cells. Adoptive transfer of DCs isolated from SND1-/- mice, unlike those from wild-type control mice, failed to protect the recipients against challenge infection. These findings provide in vivo evidence that SND1 plays an important role in host defense against intracellular bacterial infection, and suggest that SND1 can promote Th1/17 immunity and inhibit the expansion of Treg cells through modulation of the function of DCs.

17.
Sensors (Basel) ; 21(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466482

RESUMO

The Loess Plateau, covering approximately 640,000 km2, has experienced the most severe soil erosion in the world. A greening tendency has been noticed since implementing the Grain to Green Program (GTGP), which may prevent further soil erosion. Therefore, understanding the underpinning basis of greening stability and persistence is important for sustainable improvement. Global Inventory Modeling and Mapping Studies (GIMMS) normalized difference vegetation index (NDVI) datasets for 1982-2013 were used to investigate the temporal stability and persistent time (PT) of vegetation over the Loess Plateau, utilizing the coefficient of variation (CV) and the estimation of tendencies of vegetation greening starting from the selected reference conditions. Two periods from 1982 to 1999 (as the reference period) and 2000 to 2013 were selected by considering the GTGP since 1999. The results indicate that: (1) A significant increase in vegetation cover occurred in the low NDVI area (NDVI < 0.3), with a high fluctuation from 2000 to 2013 compared with the reference period. Moreover, the fluctuation in vegetation is more related to precipitation variation since 1999. (2) Most areas recovered in the greening trend of the first period starting in 2009, occurring in 28.7% (2628 of 9148) of the total area. (3) The revegetated areas have a low PT and a high CVvi, that is, the revegetated areas need a long time to recover from disturbances. Therefore, we identify the sensitive areas with PT = 4; further management needs to be implemented for sustainable development in these areas. These results provide a method to quantify the stability and persistence of the complex interactions between vegetation greenness and environmental changes, particularly in fragile areas.


Assuntos
Mudança Climática , Ecossistema , Monitoramento Ambiental , China , Florestas , Humanos , Plantas , Estações do Ano , Análise Espaço-Temporal
18.
Ecotoxicol Environ Saf ; 210: 111878, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33418159

RESUMO

Flavonoids participate in several plant processes such as growth and physiological protection in adverse environments. In this study, we investigated the combined effects of eCO2 and cadmium (Cd)-contaminated soils on the total flavonoid and monomer contents in the leaves of Robinia pseudoacacia L. seedlings. Elevated CO2, Cd, and eCO2+ Cd increased the total flavonoids in the leaves relative to the control, and eCO2 mostly increased (p < 0.05) the total flavonoid content under Cd exposure. Elevated CO2 increased (p < 0.05) robinin, rutin, and acacetin contents in the leaves of 45-day seedlings and decreased (p < 0.05) the content of robinin and acacetin at 90 and 135 d under Cd exposure except for robinin at day 45 under Cd1 and acacetin on day 135 under Cd1. Quercetin content decreased (p < 0.05) under the combined conditions relative to Cd alone. Kaempferol in the leaves was only detected under eCO2 on day 135. The responses of total chlorophyll, total soluble sugars, starch, C, N, S, and the C/N ratio in the leaves to eCO2 significantly affected the synthesis of total flavonoids and monomers under Cd exposure. Overall, rutin was more sensitive to eCO2+ Cd than the other flavonoids. Cadmium, CO2, and time had significant interactive effects on the synthesis of flavonoids in the leaves of R. pseudoacacia L. seedlings. Elevated CO2 may improve the protection and defense system of seedlings grown in Cd-contaminated soils by promoting the synthesis of total flavonoids, although robinin, rutin, quercetin, and acacetin yields may reduce with time. Additionally, increased Cd in the leaves suggested that eCO2 could improve the phytoremediation of Cd-contaminated soils.


Assuntos
Cádmio/toxicidade , Dióxido de Carbono , Flavonoides/metabolismo , Folhas de Planta/efeitos dos fármacos , Robinia/efeitos dos fármacos , Poluentes do Solo/toxicidade , Biodegradação Ambiental , Clorofila/metabolismo , Folhas de Planta/metabolismo , Robinia/metabolismo , Plântula/efeitos dos fármacos , Plântula/metabolismo
19.
BMC Cancer ; 21(1): 33, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413231

RESUMO

BACKGROUND: Anterior gradient-2 (AGR2) is a proto-oncogene involved in tumorigenesis and cancer progression. AGR2, predominantly localized in the endoplasmic reticulum (ER), is also a secreted protein detected in the extracellular compartment in multiple cancers. However, the biological functions of intracellular and extracellular AGR2 remain to be elucidated. METHODS: Based on the biochemical structure of AGR2 protein, PANC-1 pancreatic cancer cells stably expressing ER-resident or secreted AGR2 were generated by a lentivirus-mediated stable overexpression system. The capacities of cell proliferation, migration, invasion and survival were assessed in PANC-1 stable cells. Moreover, EGFR expression and activation were determined to explore the possible mechanism of AGR2 roles in pancreatic cancer tumorigenesis. RESULTS: It was discovered that secreted AGR2, but not ER-resident AGR2, promotes cell proliferation, migration and invasion of PANC-1 cells. Moreover, the data indicated that both the ER-resident and the secreted AGR2 enhance the survival capacity of PANC-1 cells after tunicamycin-induced ER stress and gemcitabine treatment. However, EGFR expression and activation were not found to be involved in AGR2-dependent oncogenic phenotypes in PANC-1 cells. CONCLUSIONS: Secreted AGR2 is predominantly involved in cell proliferation, migration and invasion in PANC-1 pancreatic cancer cells. Both secreted and ER-resident AGR2 contribute to the survival of PANC-1 cells under the challenging conditions. These findings provide insight into how different localizations of AGR2 have contributed to pancreatic cancer growth, metastasis, and drug sensitivity.


Assuntos
Movimento Celular , Proliferação de Células , Desoxicitidina/análogos & derivados , Retículo Endoplasmático/patologia , Regulação Neoplásica da Expressão Gênica , Mucoproteínas/metabolismo , Proteínas Oncogênicas/metabolismo , Neoplasias Pancreáticas/patologia , Antimetabólitos Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Humanos , Mucoproteínas/genética , Invasividade Neoplásica , Proteínas Oncogênicas/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Células Tumorais Cultivadas
20.
JCI Insight ; 6(2)2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33491667

RESUMO

To date, there are no inhibitors that directly and specifically target activated STAT3 and c-Myc in the clinic. Although peptide-based inhibitors can selectively block activated targets, their clinical usage is limited because of low cell penetration and/or serum stability. Here, we generated cell-penetrating acetylated (acet.) STAT3, c-Myc, and Gp130 targeting peptides by attaching phosphorothioated (PS) polymer backbone to peptides. The cell-penetrating peptides efficiently penetrated cells and inhibited activation of the intended targets and their downstream genes. Locally or systemically treating tumor-bearing mice with PS-acet.-STAT3 peptide at low concentrations effectively blocked STAT3 in vivo, resulting in significant antitumor effects in 2 human xenograft models. Moreover, PS-acet.-STAT3 peptide penetrated and activated splenic CD8+ T cells in vitro. Treating immune-competent mice bearing mouse melanoma with PS-acet.-STAT3 peptide inhibited STAT3 in tumor-infiltrating T cells, downregulating tumor-infiltrating CD4+ T regulatory cells while activating CD8+ T effector cells. Similarly, systemic injections of the cell-penetrating c-Myc and Gp130 peptides prevented pancreatic tumor growth and induced antitumor immune responses. Taken together, we have developed therapeutic peptides that effectively and specifically block challenging cancer targets, resulting in antitumor effects through both direct tumor cell killing and indirectly through antitumor immune responses.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...