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1.
J Mater Chem B ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35022632

RESUMO

Despite significant achievement in chemotherapy, the off-target actions and low pharmaceutical selectivity of the therapeutic agents still limit their clinical efficacy. Herein, a multifunctional nanoplatform which integrates chemotherapy, chemodynamic therapy (CDT) and photoactivation of TRPV1 channels has been successfully established for specific cancer therapy. Polydopamine (PDA) coated hollow prussian blue nanocages (hPBNCs) are used as the photothermal switches and drug carriers for loading chemotherapeutic drug, doxorubicin (Dox). Conjugating with the TRPV1 antibodies enables the nanoplatform to bind specifically to TRPV1 channels on the plasma membrane of the TRPV1-positive cancer cells and then activate them by local heating upon NIR irradiation, leading to the over-influx of Ca2+. Critically, the laser irradiation can be carefully controlled to not only open the TRPV1 channels but also avoid burning of tumors by hyperthermia. Moreover, the exposed hPBNCs in the acidic tumor cells can decompose endogenous H2O2 into ˙OH by Fenton reaction to realize CDT, which further aggravates cancer cell apoptosis. Together with the chemotherapy caused by Dox, our nanoplatform displays an enhanced anticancer effect both in vitro and in vivo. Our work provides a powerful means for site-specific cancer synergetic therapy with high spatial and temporal resolution.

2.
J Oncol ; 2021: 4758364, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899907

RESUMO

As one of the most serious complications of radiotherapy, osteoradionecrosis (ORN) seriously affects the quality of life of patients and even leads to death. Vascular injury and immune disorders are the main causes of bone lesions. The traditional conservative treatment of ORN has a low cure rate and high recurrent. Exosomes are a type of extracellular bilayer lipid vesicles secreted by almost all cell types. It contains cytokines, proteins, mRNA, miRNA, and other bioactive cargos, which contribute to several distinct processes. The favorable biological functions of mesenchymal stem cells-derived exosomes (MSC exosomes) include angiogenesis, immunomodulation, bone regeneration, and ferroptosis regulation. Exploring the characteristic of ORN and MSC exosomes can promote bone regeneration therapies. In this review, we summarized the current knowledge of ORN and MSC exosomes and highlighted the potential application of MSC exosomes in ORN treatment.

3.
Sci Rep ; 11(1): 24188, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34921217

RESUMO

Echinicola, carotenoid-pigmented bacteria, are isolated from various hypersaline environments. Carotenoid accumulation in response to salt stress can stabilize the cell membrane in order to survive. A pink-colored strain SCS 3-6 was isolated from the deep-sea sediment of the South China Sea. Growth was found to occur at 10-45 °C. The strain could tolerate 10% (w/v) NaCl concentration and grow at pH 5-9. The complete genome of SCS 3-6 comprises 5053 putative genes with a total 5,693,670 bp and an average G + C content of 40.11 mol%. The 16S rRNA gene sequence analysis indicated that strain SCS 3-6 was affiliated with the genus Echinicola, with the closely strains were Echinicola arenosa CAU 1574T (98.29%)and Echinicola shivajiensis AK12T (97.98%). For Echinicola species with available genome sequences, pairwise comparisons for average nucleotide identity (ANI) and in silico DNA-DNA hybridization (DDH) revealed ANIb values from 70.77 to 74.71%, ANIm values from 82.72 to 88.88%, and DDH values from 18.00 to 23.40%. To identify their genomic features, we compared their genomes with those of other Echinicola species. Phylogenetic analysis showed that strain SCS 3-6 formed a monophyletic clade. Genomic analysis revealed that strain SCS 3-6 possessed a complete synthetic pathway of carotenoid and speculated that the production was astaxanthin. Based on phenotypic and genotypic analyses in this study, strain SCS 3-6 is considered to represent a novel species of the genus Echinicola for which the name Echinicola marina sp. nov. is proposed. The type strain is SCS 3-6T (= GDMCC 1.2220T = JCM 34403T).

4.
Front Microbiol ; 12: 754352, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956119

RESUMO

Background: Tuberculosis recurrence is still a major problem for the control of tuberculosis, and the cause of the recurrence is still unclear. Methods: We retrospectively recruited 68 pairs of samples of Mycobacterium tuberculosis (MTB) from recurrent TB cases in Beijing Chest Hospital between January 2008 and December 2019. The whole-genome sequencing was conducted to analyze single-nucleotide polymorphism (SNP) and to identify whether recurrent disease was due to relapse or reinfection. The BACTEC MGIT was performed to compare differences in drug susceptibility profiles between two episodes. Results: 62 (91.2%) out of 68 confirmed recurrence were due to relapse, whereas the remaining six (8.8%) were due to reinfection. And there was a strong association between earlier relapse and underlying chronic diseases. In addition, the MTB isolates from non-diabetic patients had a higher mutation rate than those from diabetic patients. A community transmission was also identified in our cohort. Levofloxacin resistance was the most frequently observed drug resistance for 12.9% relapse cases. Conclusion: The relapse of a previous episode in Beijing. The underlying chronic diseases are associated with an earlier TB relapse. MTB isolates were more prone to develop levofloxacin resistance than moxifloxacin resistance after FQ exposure. The patients at high-risk for relapses deserve more careful investigation.

5.
J Healthc Eng ; 2021: 9938874, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956584

RESUMO

This study aimed to explore the influence of hesperidin on the polarization of microglia to clarify the key mechanism of regulating the polarization of M2 microglia. C57BL/6 mice were randomly divided into middle cerebral artery occlusion model group (MCAO group), MCAO + hesperidin treatment group (MCAO + hesperidin group), and sham group (sham operation group). The mice were assessed with neurological scores for their functional status. 2,3,5-Triphenyltetrazole chloride (TTC) was used to determine the volume of cerebral infarction. Hematoxylin and eosin (H&E) staining was performed to detect brain loss. The system with 1% O2, 5% CO2, and 92% N2 was applied to establish BV2 in vitro model induced by MCAO. TNF-α, IL-1ß, TGF-ß, and IL-10 levels of cytokines in the supernatant were detected by ELISA. RT-qPCR was used to detect mRNA levels of M1 iNOS, CD11b, CD32, and CD86, and mRNA levels of M2 CD206, Arg-1, and TGF-ß. The Iba-1, iNOS, and Arg-1 of microglia and protein levels of TLR4 and p-NF-κB related to the pathway were detected by Western blot. After treatment with hesperidin, BV2 cells induced by MCAO in vitro can reduce the proinflammatory cytokines of TNF-α and IL-1ß significantly, further upregulating anti-inflammatory cytokines of TGF-ß, IL-10 while inhibiting TLR4 and p-NF-κB expression. The MCAO-induced BV2 cells treated by TLR-4 inhibitor TAK-242 and NF-κB inhibitor BAY 11-7082 had similar polarization effects to those treated with hesperidin. This study found that hesperetin gavage treatment can improve the neurological deficit and regulate the polarization of microglia in MCAO mice. In vitro experiments further verified that hesperidin plays a neuroprotective role by inhibiting the TLR4-NF-κB pathway, thus providing new targets and strategies for neuroprotection and nerve repair after ischemic stroke.

6.
Chin J Integr Med ; 2021 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-34897593

RESUMO

OBJECTIVE: To explore the efficacy and safety of Zhuang medicine medicated thread moxibustion (ZMTM) on psoriasis vulgaris. METHODS: A multicenter, randomized, parallel controlled clinical trial was designed. A total of 241 outpatients with psoriasis vulgaris were randomly divided into a control group (120 cases) and a treatment group (121 cases) using a central block randomization from June 2015 to May 2018. The control group was treated with Western medicines alone including pidotimod dispersible tablets, vitamin B compound tablets, and compound cod liver oil-zinc oxide ointment. The treatment group was treated with ZMTM every 2 days combined with Western medicines. The two groups received continuous intervention for 30 days. The primary outcome was Psoriasis Area and Severity Index (PASI), and the secondary outcomes included Itch Rating Scale, Dermatology Quality of Life Index (DLQI), Hamilton Anxiety Rating Scale (HAMA), as well as PASI response rate. Meanwhile, adverse events were evaluated during the whole clinical trial. Follow-up was carried out 30 days after treatment. RESULTS: There were 5 cases of shedding in this trial. In intention-to-treat analysis, 236 cases were included and each group contained 118 cases. On the 30th and 60th days, PASI scores of patients in each group were significantly lower than that at baseline (P<0.01) and the PASI score reduction of the treatment group was greater than that of the control group (P<0.01). Itch Rating Scale, DLQI, and HAMA scale were decreased in both groups after treatment, and the treatment group showed a better therapeutic effect (P<0.01). The response rates of PASI 50 and 75 were significantly higher than those in the control group [81.4% (96/118), 43.2% (51/118) vs. 41.5% (49/118), 11.0% (13/118), respectively, P<0.05]. During follow-up, the improvements in scores of PASI, Itch Rating Scale, DLQI, and HAMA of the treatment group were significantly greater than those of the control group (P<0.01). The response rates of PASI 50 and 75 in the treatment group were significantly higher than those in the control group, respectively (both P<0.05). No obvious adverse reaction was found in either group. CONCLUSION: ZMTM combined with Western medicines showed a better therapeutic effect in the treatment of psoriasis vulgaris without obvious adverse reaction. (Trial Registration No. ChiCTR-IOR-16008159).

7.
Biosensors (Basel) ; 11(11)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34821654

RESUMO

The color palette of genetically encoded fluorescent protein indicators (GEFPIs) has expanded rapidly in recent years. GEFPIs with excitation and emission within the "optical window" above 600 nm are expected to be superior in many aspects, such as enhanced tissue penetration, reduced autofluorescence and scattering, and lower phototoxicity. Circular permutation of fluorescent proteins (FPs) is often the first step in the process of developing single-FP-based GEFPIs. This study explored the tolerance of two far-red FPs, mMaroon1 and mCarmine, towards circular permutation. Several initial constructs were built according to previously reported circularly permuted topologies for other FP analogs. Mutagenesis was then performed on these constructs and screened for fluorescent variants. As a result, five circularly permuted far-red FPs (cpFrFPs) with excitation and emission maxima longer than 600 nm were identified. Some displayed appreciable brightness and efficient chromophore maturation. These cpFrFPs variants could be intriguing starting points to further engineer far-red GEFPIs for in vivo tissue imaging.

8.
Front Pharmacol ; 12: 778613, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776988

RESUMO

Multi-target intervention and synergistic treatment are critical for the drug development of Alzheimer's disease (AD) due to its complex and multifactional nature. Oxidative stress and amyloid ß peptides (Aß) accumulation have been recognized as therapeutic targets for AD. Herein, with ability to inhibit Aß aggregation and the broad-spectrum antioxidant properties, the large amino acid mimicking selenium-doped carbon quantum dots (SeCQDs) are presented as novel nanoagents for multi-target therapy of AD. Compared with the precursor, selenocystine, SeCQDs which maintain the intrinsic properties of both selenium and carbon quantum dots (CQDs) possess good biocompatibility and a remarkable ROS-scavenging activity. Moreover, the functionalized α-carboxyl and amino groups on edge of SeCQDs can trigger multivalent interactions with Aß, leading to the ability of SeCQDs to inhibit Aß aggregation. In vivo study demonstrated that SeCQDs can significantly ameliorate the Aß induced memory deficits, reduce Aß accumulation and inhibit neuron degeneration in AD model rats. The versatility of functionalization and potential ability to cross the blood-brain barrier (BBB) make SeCQDs as prospective nanodrugs for treating AD.

9.
Open Life Sci ; 16(1): 1219-1224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805530

RESUMO

Rare small cell neuroendocrine carcinoma (SCNEC) cases showed alpha fetoprotein (AFP) expression in the endometrium. In this study, we reported a case of uterine SCNEC expressing AFP. In addition, a literature review was performed to investigate the potential mechanism and the clinicopathological features of SCNEC to provide clinical guidance. A 65-year-old female was referred to our hospital due to vaginal bleeding for 1 month in November 2020. The clinical features were summarized. After total hysterectomy and removal of bilateral appendages, the histological examination and immunohistochemistry examination were performed. Histological findings showed that the cancer cells were arranged in a nest-like pattern distributed in a lamellar manner. The smooth muscles of the uterus were invaded by cancer cells. Cancer cells were relatively consistent in size. Small glandular duct-like and rosettes-like structures were distinguished, together with necrotic tissues. The deep staining showed that the amount of cytoplasm was lower in the nucleus. Partial cancer cells had small nucleolus with an irregular profile. There were some mitotic figures. Immunohistochemistry examination indicated that there was a diffuse expression of CK, Syn, CgA, CD56, CK8/18, P16, AFP, HepPar-1, Glypican-3, and Ki67 (90%). In this case, we reported a SCNEC patient expressing AFP, Glypican-3, and HepPar-1.

10.
Emerg Microbes Infect ; 10(1): 2291-2299, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34779708

RESUMO

The emergence of drug-resistant tuberculosis (TB) constitutes a major challenge to TB control programmes. There is an urgent need to develop effective anti-TB drugs with novel mechanisms of action. Aspartate-semialdehyde dehydrogenase (ASADH) is the second enzyme in the aspartate metabolic pathway. The absence of the pathway in humans and the absolute requirement of aspartate in bacteria make ASADH a highly attractive drug target. In this study, we used ASADH coupled with Escherichia coli type III aspartate kinase (LysC) to establish a high-throughput screening method to find new anti-TB inhibitors. IMB-XMA0038 was identified as an inhibitor of MtASADH with an IC50 value of 0.59 µg/mL through screening. The interaction between IMB-XMA0038 and MtASADH was confirmed by surface plasmon resonance (SPR) assay and molecular docking analysis. Furthermore, IMB-XMA0038 was found to inhibit various drug-resistant MTB strains potently with minimal inhibitory concentrations (MICs) of 0.25-0.5 µg/mL. The conditional mutant strain MTB::asadh cultured with different concentrations of inducer (10-5 or 10-1 µg/mL pristinamycin) resulted in a maximal 16 times difference in MICs. At the same time, IMB-XMA0038 showed low cytotoxicity in vitro and vivo. In mouse model, it encouragingly declined the MTB colony forming units (CFU) in lung by 1.67 log10 dosed at 25 mg/kg for 15 days. In conclusion, our data demonstrate that IMB-XMA0038 is a promising lead compound against drug-resistant tuberculosis.

11.
World J Microbiol Biotechnol ; 37(12): 212, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738191

RESUMO

A promising bacterial strain for biodegrading dibutyl phthalate (DBP) was successfully isolated from activated sludge and characterized as a potential novel Microbacterium sp. USTB-Y based on 16S rRNA sequence analysis and whole genome average nucleotide identity (ANI). Initial DBP of 50 mg/L could be completely biodegraded by USTB-Y both in mineral salt medium and in DBP artificially contaminated soil within 12 h at the optimal culture conditions of pH 7.5 and 30 â„ƒ, which indicates that USTB-Y has a strong ability in DBP biodegradation. Phthalic acid (PA) was identified as the end-product of DBP biodegraded by USTB-Y using GC/MS. The draft genome of USTB-Y was sequenced by Illumina NovaSeq and 29 and 188 genes encoding for putative esterase/carboxylesterase and hydrolase/alpha/beta hydrolase were annotated based on NR (non redundant protein sequence database) analysis, respectively. Gene3781 and gene3780 from strain USTB-Y showed 100% identity with dpeH and mpeH from Microbacterium sp. PAE-1. But no phthalate catabolic gene (pht) cluster was found in the genome of strain USTB-Y. The results in the present study are valuable for obtaining a more holistic understanding on diverse genetic mechanisms of PAEs biodegrading Microbacterium sp. strains.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34619053

RESUMO

Background: To date, the clinical management of advanced hepatocellular carcinoma (HCC) patients remains tough and the mechanisms of E2F transcription factor 1 (E2F1) underlying HCC are obscure. Materials and Methods: Our study integrated datasets mined from several public databases to comprehensively understand the deregulated expression status of E2F1. Tissue microarrays and immunohistochemistry staining was used to validate E2F1 expression level. The prognostic value of E2F1 was assessed. In-depth subgroup analyses were implemented to compare the differentially expressed levels of E2F1 in HCC patients with various tumor stages. Functional enrichments were used to address the predominant targets of E2F1 and shedding light on their potential roles in HCC. Results: We confirmed the elevated expression of E2F1 in HCC. Subgroup analyses indicated that elevated E2F1 level was independent of various stages in HCC. E2F1 possessed moderate discriminatory capability in differentiating HCC patients from non-HCC controls. Elevated E2F1 correlated with Asian race, tumor classification, neoplasm histologic grade, eastern cancer oncology group, and plasma AFP levels. Furthermore, high E2F1 correlated with poor survival condition and pooled HR signified E2F1 as a risk factor for HCC. Enrichment analysis of differentially expressed genes, coexpressed genes, and putative targets of E2F1 emphasized the importance of cell cycle pathway, where CCNE1 and CCNA2 served as hub genes. Conclusions: We confirmed the upregulation of E2F1 and explored the prognostic value of E2F1 in HCC patients. Two putative targeted genes (CCNE1 and CCNA2) of E2F1 were identified for their potential roles in regulating cell cycle and promote antiapoptotic activity in HCC patients.

13.
Infect Drug Resist ; 14: 3979-3989, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34611415

RESUMO

Background: Multidrug-resistant tuberculosis (MDR-TB) isolates collected from Fujian province, China were assessed for molecular epidemiological characteristics. Analysis of isolate genotype profiles revealed that the Beijing genotype was associated with especially high drug resistance and community transmission rates. Methods: A total of 119 MDR-TB isolates obtained from TB patients in Fujian province were typed using 24-locus mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing and spoligotyping. Drug susceptibility testing of all isolates was conducted using the L-J proportion method, with pyrazinamide (PZA) susceptibility testing conducted using the Mycobacterium Growth Indicator Tube System 960 (MGIT 960). Results: We obtained 26 spoligotypes for the 119 isolates examined in this work. Spoligotyping results revealed that 80 (67.2%) isolates possessed the Beijing family genotypic profiles. Patients aged 25-44 years and ≥45 years were most likely to be infected by non-Beijing genotypes. The percentage of clustered cases with both PZA and ofloxacin (OFLX) resistance was significantly greater than the corresponding percentage for non-clustered cases. Of 44 PZA-resistant isolates, 28 isolates (63.6%) harbored pncA mutations, while pncA mutations were only detected in 7 (9.3%) PZA-susceptible isolates. Conclusion: Our data demonstrate that the Beijing genotype is the dominant lineage among MDR-TB strains circulating in Fujian. Thus, MDR-TB infections occurring within this province are not likely associated with recent transmission events. PZA and fluoroquinolone resistance profiles were found to be associated with clustered isolates. Mutation of pncA is the main driver of MDR-TB PZA resistance and is associated with mutation sites scattered throughout the entire pncA protein-coding region.

14.
Biomed Res Int ; 2021: 5565549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34664026

RESUMO

Objectives: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus causing substantial morbidity and mortality worldwide. We performed a cross-sectional investigation of SARS-CoV-2 clusters in Suzhou to determine the transmissibility of the virus among close contacts and to assess the demographic and clinical characteristics between index and secondary cases. Methods: We review the clustered patients with SARS-CoV-2 infections in Suzhou between 22 January and 29 February 2020. The demographic and clinical characteristics were compared between index and secondary cases. We calculated the basic reproduction number (R 0) among close contacts with SLI model. Results: By 22 February, 87 patients with SARS-CoV-2 infection were reported, including 50 sporadic and 37 clustered cases, who were generated from 13 clusters. On admission, 5 (20.8%) out of 24 secondary cases were asymptomatic. The male ratio of index cases was significantly higher than that of secondary cases. Additionally, the index cases were more likely to have fever and increased CRP levels than the secondary cases. The R 0 values of clusters displayed a significantly declining trend over time for all clusters. The relative risk of infection in blood-related contacts of cases versus unrelated contacts was 1.60 for SARS-CoV-2 (95% CI: 0.42-2.95). Conclusions: In conclusion, SARS-CoV-2 has great person-to-person transmission capability among close contacts. The secondary cases are more prone to have mild symptoms than index cases. There is no increased RR of secondary infection in blood relatives versus unrelated contacts. The high rate of asymptomatic SARS-CoV-2 infections highlights the urgent need to enhance active case finding strategy for early detection of infectious patients.


Assuntos
COVID-19/epidemiologia , Busca de Comunicante , Características da Família , SARS-CoV-2 , Adulto , COVID-19/transmissão , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
15.
J Immunol Res ; 2021: 7925903, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646890

RESUMO

Cavitation is a major pathological feature of pulmonary tuberculosis (TB). The study is aimed at investigating the mechanism of natural killer (NK) cells participating the cavity formation during Mycobacterium tuberculosis (MTB) infection. Human peripheral blood samples were donated by pulmonary TB patients with cavity or not. Real-time quantitative PCR and enzyme-linked immunosorbent assay were performed to analyze the expression of cytokines secreted by NK cells. And the cytotoxicity of NK cells was compared between two groups. Our data showed that NK cells were more abundant in cohorts of cavity. Increased abundance of granzyme A and granzyme B was observed in culture supernatants of NK cells isolated from cavitary TB patients, which also resulted in a higher level of nonviable MTB-infected monocytes. Our data firstly demonstrates that NK cells participate in cavity formation in pulmonary TB patients. The elevated level and increased cytotoxicity of NK cells accelerate the cavitary formulation.

16.
FASEB J ; 35(11): e22009, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34694026

RESUMO

Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains a major cause of morbidity and mortality worldwide. Increasing lines of evidence indicate that certain individuals, which are termed resisters, are naturally resistant to TB infection. The resister phenotype has been linked to host efficient innate immune responses, but the underlying mechanisms and the key immune factors remain unclear. Here, we find that upon Mtb infection, monocyte-derived macrophages (MDMs) from TB resisters exhibited distinctly higher production of TNF-α, IL-1ß and IL-6, higher ratio of bacteria in acidic vacuoles, and lower intracellular bacterial loads, as compared to that from the healthy controls, individuals with latent TB infection, and TB patients. Such enhanced anti-Mtb immune capacity of macrophages from resisters largely depends on histone deacetylase 6 (HDAC6), whose expression is specifically maintained in MDMs from TB resisters during Mtb infection. Furthermore, we demonstrate that HDAC6 is required for acidification of Mtb-containing phagosomes in macrophages, thus controlling the intracellular survival of Mtb. Taken together, these findings unravel an indispensable role of HDAC6 in human innate resistance against Mtb infection, suggesting that HDAC6 may serve as a marker for individual TB risk as well as a novel host-directed anti-TB therapeutic target.


Assuntos
Resistência à Doença , Desacetilase 6 de Histona/imunologia , Imunidade Inata , Macrófagos/imunologia , Tuberculose/imunologia , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Macrófagos/citologia , Masculino , Pessoa de Meia-Idade
17.
Artigo em Inglês | MEDLINE | ID: mdl-34502008

RESUMO

Previous COVID-19 tourism research has not considered the positive impact of a low-risk perception and a perception of the benefits of regional travel on taking alternative tourism. This study attempts to fill the research gap and examine the positive effect of these perceptions on tourists' attitudes to regional travel and intentions to undertake regional travel during the COVID-19 pandemic. A survey of 278 respondents confirmed that the perceived benefit positively influences tourists' attitudes and travel intentions, but that a low-risk perception only positively affects their attitudes. This study contributes to tourism risk management research by introducing the concept of a low-risk perception as a positive factor. For tourism recovery, it finds that relaxation, value, and convenience are benefits to drive people to travel.


Assuntos
COVID-19 , Pandemias , Humanos , Percepção , SARS-CoV-2 , Turismo , Viagem
18.
Antonie Van Leeuwenhoek ; 114(11): 1791-1804, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34392431

RESUMO

A bacterial lipase producing bacterium, designated SCS 2-3, was isolated from deep-sea sediment of the South China Sea. Phylogenetic analysis based on the 16S rRNA sequence revealed that strain SCS2-3 belonged to the genus Pseudomonas and had 98.56% similarity to P. xinjiangensis NRRL B-51270T as the closest relative strain. MLSA using four protein-coding genes (dnaK, gyrA, recA, and rpoB) showed strain SCS 2-3 to form a separate branch. ANI and in silico DDH values between strain SCS 2-3 and related type strains of Pseudomonas were less than 81.51% and 23.80%, respectively. Genome comparison showed that strain SCS 2-3 shared 1875 core gene families with other eight closely related type strains in Pseudomonas, and the number of strain-unique genes was 263. Through gene annotations, genes related to lipase were found in the genome. Furthermore, a combination of phenotypic, chemotaxonomic, phylogenetic and genotypic data clearly indicated that strain SCS 2-3 represents a novel species of the genus Pseudomonas, for which the name Pseudomonas nanhaiensis sp. nov. is proposed. The type strain is SCS 2-3T (= GDMCC 1.2219T = JCM 34440T).


Assuntos
Lipase , Pseudomonas , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/análise , Humanos , Lipase/genética , Hibridização de Ácido Nucleico , Filogenia , Pseudomonas/genética , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
19.
Chin Med J (Engl) ; 134(17): 2091-2101, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34334630

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs (miRs) to play cancer-promoting roles in cancer stem cells. However, the regulatory mechanism of AFAP1-AS1 in cervical cancer (CC) stem cells is unknown. The present study aimed to provide a new therapeutic target for the clinical treatment of CC. METHODS: Hyaluronic acid receptor cluster of differentiation 44 variant exon 6 (CD44v6)(+) CC cells were isolated by flow cytometry (FCM). Small interfering RNAs of AFAP1-AS1 (siAFAP1-AS1) were transfected into the (CD44v6)(+) cells. The levels of AFAP1-AS1 were measured by quantitative real-time PCR (qRT-PCR). Sphere formation assay, cell cycle analysis, and Western blotting were used to detect the effect of siAFAP1-AS1. RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor (VEGF)-C. RESULTS: CD44v6(+) CC cells had remarkable stemness and a high level of AFAP1-AS1. However, AFAP1-AS1 knockdown with siAFAP1-AS1 suppressed the cell cycle transition of G(1)/S phase and inhibited self-renewal of CD44v6(+) CC cells, the levels of the stemness markers octamer-binding transcription factor 4 (OCT4), osteopontin (OPN), and cluster of differentiation 133 (CD133), and the epithelial-mesenchymal transition (EMT)-related proteins Twist1, matrix metalloprotease (MMP)-9, and VEGF-C. In the mechanism study, miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+) CC cells. CONCLUSIONS: LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.


Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias do Colo do Útero , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular
20.
Infect Drug Resist ; 14: 3135-3143, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413657

RESUMO

Introduction: Interferon-γ release assays (IGRAs) can have high false-negative rates for active tuberculosis (TB) cases. Here we investigated factors, including potential anti-inflammatory mechanisms, that contributed to false-negative IGRA results. Methods: We established two cohorts. In the first cohort, we reviewed IGRA results for confirmed TB cases diagnosed in our hospital in 2018. Cases with false-negative IGRA results were analysed to identify factors contributing to false-negative results. In the second cohort, we prospectively studied IL-10 expression levels in peripheral blood mononuclear cells (PBMCs) of IGRAs-positive and IGRAs-negative TB cases after antigenic stimulation to correlate IL-10 expression with IGRAs results. Results: Of 1232 culture-confirmed TB cases, 1124 produced true-positive IGRA results and 108 had false-negative IGRA results. Multivariate logistic regression analysis identified glucocorticoid use and extrapulmonary TB as independent risk factors for false-negative IGRA results. Notably, IL-10 expression of the IGRA-negative group was significantly up-regulated as compared to that of the IGRA-positive group. The average cell supernatant IL-10 concentration of the IGRA-negative group was 4.77 pg/mL, a value that was statistically greater than the IGRA-positive group concentration (1.47 pg/mL, P = 0.007). After PBMCs pretreatment with BRD6989 (to enhance IL-10 secretion), average IFN-γ concentrations in cell supernatants from the IGRA-positive group significantly decreased from 59.73 pg/mL to 33.79 pg/mL (P = 0.011). By contrast, addition of AS101 (to inhibit IL-10 secretion) to false-negative group PBMCs led to an increase of average IFN-γ concentration in cell supernatants from 19.01 pg/mL to 45.10 pg/mL (P = 0.030), a result that was inversely correlated with IL-10 concentration. Conclusion: Our data demonstrate that increased IL-10 secretion by PBMCs is inversely correlated with IGRA assay results in culture-confirmed TB patients. Glucocorticoids use and extrapulmonary TB are significantly associated with false-negative IGRA results. Combination testing to measure IL-10 secretion and IFN-γ release is recommended to improve IGRAs specificity.

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