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1.
PLoS One ; 19(10): e0311491, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39374217

RESUMO

BACKGROUND: Reducing exposure to risk factors and screening represent 2 major approaches to gastric cancer (GC) prevention, but public knowledge GC risk factors and screening behaviour remain unknown. We aimed to investigate public awareness of GC risk factors, adherence to screening, and barriers hindering screening practices in China. METHODS: This community-based household survey was conducted within Shijiazhuang, China, and 1490 residents were recruited through a multistage stratified cluster random sampling approach. A self-administered questionnaire was completed which consisted of three sections: demographics, awareness of GC risk factors, and personal screening behaviours. Factors associated with knowledge of risk factors and screening behaviours were evaluated using binary logistic regression analysis. RESULTS: The mean risk factor awareness score of 12 (7, 15) revealed insufficient knowledge in 51.1% of participants. Dietary lifestyle factors were better understood than physical activity and weight-related factors. Marital status (OR 1.967; 95% CI 1.415 to 2.734), higher income (OR 1.197; 95% CI 1.010 to 1.418), and a history of upper gastrointestinal problems (OR 0.048; 95% CI 1.002 to 1.311) were associated with higher awareness. Merely 21.5% underwent GC screening, with higher rates linked to older age (OR 1.642; 95% CI 1.418 to 1.902), higher education (OR 1.398; 95% CI 1.176 to 1.662), a history of upper gastrointestinal problems (OR 3.842; 95% CI 2.833 to 5.209), and moderate (OR 2.077; 95% CI 1.352 to 3.191) and high (OR 2.529; 95% CI 1.311 to 4.878) perceived GC risk. Notably, participants commonly refused gastroscopy due to the absence of symptoms or signs. CONCLUSIONS: In Shijiazhuang, more than half of participants demonstrated inadequate knowledge of GC risk factors, and screening participation rates were remarkably low. This emphasizes the need for targeted interventions to enhance GC awareness and significantly improve screening rates.


Assuntos
Detecção Precoce de Câncer , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Masculino , China/epidemiologia , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Idoso , Inquéritos e Questionários , Detecção Precoce de Câncer/estatística & dados numéricos , Detecção Precoce de Câncer/psicologia , Programas de Rastreamento , Adulto Jovem
2.
Parasit Vectors ; 17(1): 437, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39456030

RESUMO

BACKGROUND: Alveolar echinococcosis (AE), a fatal disease caused by Echinococcus multilocularis, often affects the liver, with tumor-like growth. However, the mechanism by which E. multilocularis evades host immune surveillance remains unclear. METHODS: We collected liver specimens from hepatic alveolar echinococcosis (HAE) patients and established a mouse model of E. multilocularis infection. Immunofluorescence staining and flow cytometry were performed to analyze programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) expression in human samples, while flow cytometry and quantitative real-time polymerase chain reaction (PCR) were performed for similar analyses in mouse samples. Cell proliferation and protoscolex (PSC) killing assays were designed to explore how E. multilocularis induces host immunosuppression. RESULTS: An inflammatory reaction band with high PD-1 and CTLA-4 expression was found in close liver tissue (CLT). The ratio of regulatory T cells (Tregs) was higher in CLT than in distant liver tissue (DLT), and Tregs in CLT tended to express higher levels of PD-1 and CTLA-4 than those in DLT from HAE patients. Echinococcus multilocularis-infected mice showed significantly elevated expression of PD-1 and CTLA-4 on splenocytes and peritoneal cells. PD-1/PD-L1 or CTLA-4 pathway blockade could relieve the immunosuppressive effects of Tregs from infected mice and enhance PSC killing by mouse splenocytes. CONCLUSIONS: E. multilocularis regulated the function of T cells via the PD-1/PD-L1- and CTLA-4-dependent pathways and subsequently evaded host immune attacks. These findings provide insights for investigating the pathogenic mechanism of AE.


Assuntos
Antígeno CTLA-4 , Modelos Animais de Doenças , Equinococose Hepática , Equinococose , Echinococcus multilocularis , Fígado , Receptor de Morte Celular Programada 1 , Linfócitos T Reguladores , Animais , Echinococcus multilocularis/imunologia , Antígeno CTLA-4/genética , Antígeno CTLA-4/metabolismo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Humanos , Camundongos , Equinococose/imunologia , Equinococose/parasitologia , Linfócitos T Reguladores/imunologia , Feminino , Fígado/parasitologia , Fígado/imunologia , Equinococose Hepática/imunologia , Equinococose Hepática/parasitologia , Masculino , Adulto , Pessoa de Meia-Idade , Tolerância Imunológica
3.
Front Oncol ; 14: 1472049, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39439952

RESUMO

Background: Asparaginase-associated pancreatitis (AAP) is a major challenge for continuing asparaginase therapy. We aimed to investigate the acute and long-term complications and survival rates related to first and second AAP episodes in Chinese children with haematological malignancies. Methods: We retrospectively analysed clinical data of children with pancreatitis who received asparaginase chemotherapy for acute lymphoblastic leukaemia (ALL), acute mixed cell leukaemia, and non-Hodgkin's lymphoma at Shanghai Children's Medical Center from November 2013 to November 2023. Results: Of the 76 children included in the study, 12 had local complications (15.79%), with no deaths recorded. Systemic complications manifested in 28 patients (36.84%), resulting in 3 deaths (3.95%). Four patients (5.26%) developed long-term complications (chronic pancreatitis or insulin-dependent diabetes mellitus). No significant differences in local or long-term complications were recorded between children in the asparaginase re-exposed (n=39) and non-re-exposed (n=45) groups. Among the re-exposed patients, eight (25.81%) experienced a second attack without fatalities or complications. Survival analysis of intermediate- to high-risk patients revealed a significantly higher event-free survival (EFS) rate for the re-exposed group than for the non-re-exposed group. The second AAP episode's occurrence and severity had no relation to the first AAP episode's severity, and the second AAP episode was significantly less severe than the first (p<0.001). Conclusions: The second AAP episode's occurrence is unrelated to the first AAP episode's severity, and the second AAP episode's severity is significantly lower than that of the first. Further, asparaginase therapy could improve EFS in children with intermediate and high-risk ALL.

4.
Org Lett ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291854

RESUMO

Herein, we reported a copper(0)-catalyzed reductive coupling of disulfurating reagents and (hetero)aryl/alkyl halides. Copper(0) can be directly inserted into tetrasulfide and then undergoes reductive coupling with (hetero)aryl Iodides to construct disulfide. The method features the unprecedented use of copper(0)-catalyzed disulfurating reagents (tetrasulfides) in cross-coupling chemistry and is convenient with broad substrate scopes, even applicable to different halogenated hydrocarbons. It is worth noting that the methodology is practical with the late-stage modification of bioactive scaffolds of pharmaceuticals. In the meantime, the synthesis of disulfides is successfully achieved on a gram scale, indicating the approach is highly valuable.

5.
Cancer Med ; 13(16): e70185, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39219190

RESUMO

BACKGROUND: Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV-related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)-negative HBV-related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. METHODS: This historical cohort study involved 1232 NA-treated HBeAg-negative patients who underwent curative hepatectomy for HBV-related HCC from 2014 to 2019. The recurrence-free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. RESULTS: Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348-3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537-4.942, p < 0.001 after PSM) in HBsAg-negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg-negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001). CONCLUSIONS: These findings demonstrate the potential for HBeAg-negative HBV-related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Antígenos E da Hepatite B , Vírus da Hepatite B , Neoplasias Hepáticas , Pontuação de Propensão , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Masculino , Feminino , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/etiologia , Pessoa de Meia-Idade , Antígenos E da Hepatite B/sangue , Prognóstico , Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Nucleosídeos/uso terapêutico , Estudos Retrospectivos , Adulto , Idoso , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia
6.
J Org Chem ; 89(18): 13386-13400, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39258469

RESUMO

A tandem cyclization reaction of enynones with tetrasulfides has been developed under manganese-promoted conditions, leading to the high-yield formation of various furanmethyl disulfides. This reaction is characterized by readily available starting materials, mild reaction conditions, and a broad substrate scope, making it attractive and practical. It provides a new strategy for the synthesis of disulfide-containing functionalized furans.

7.
PLoS Pathog ; 20(9): e1012550, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39321193

RESUMO

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), with a high mortality rate of up to 30%. The envelope glycoproteins of SFTSV, glycoprotein N (Gn) and glycoprotein C (Gc), facilitate the recognition of host receptors and the process of membrane fusion, allowing the virus to enter host cells. We previously reported a monoclonal antibody, mAb 40C10, capable of neutralizing different genotypes of SFTSV and SFTSV-related viruses. However, the specific neutralization mechanism is poorly understood. In this study, we elucidated the high-resolution structure of the SFTSV Gn head domain in complex with mAb 40C10, confirming that the binding epitope in the domain I region of SFTSV Gn, and it represented that a novel binding epitope of SFTSV Gn was identified. Through in-depth structural and sequence analyses, we found that the binding sites of mAb 40C10 are relatively conserved among different genotypes of SFTSV and SFTSV-related Heartland virus and Guertu virus, elucidating the molecular mechanism underlying the broad-spectrum neutralizing activity of mAb 40C10. Furthermore, we humanized of mAb 40C10, which is originally of murine origin, to reduce its immunogenicity. The resulting nine humanized antibodies maintained potent affinity and neutralizing activity. One of the humanized antibodies exhibited neutralizing activity at picomolar IC50 values and demonstrated effective therapeutic and protective effects in a mouse infection model. These findings provide a novel target for the future development of SFTSV vaccines or drugs and establish a foundation for the research and development of antibody therapeutics for clinical applications.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Phlebovirus , Humanos , Animais , Anticorpos Antivirais/imunologia , Phlebovirus/imunologia , Camundongos , Anticorpos Neutralizantes/imunologia , Febre Grave com Síndrome de Trombocitopenia/imunologia , Proteínas do Envelope Viral/imunologia , Anticorpos Monoclonais/imunologia , Epitopos/imunologia , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Amplamente Neutralizantes/imunologia
8.
Nurse Educ Today ; 143: 106382, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39236597

RESUMO

OBJECTIVES: The pressure of internal competition at the college level has increased in recent years in China with an impact on nursing students' learning and well-being. This study aimed to investigate the current situation and factors affecting professional identity, learner well-being and self-regulated learning of undergraduate nursing students in the Neijuan ecology of the "double tops" universities, and to explore the relationships between these three variables. METHODS: A cross-sectional design was adopted to conduct an online survey of 322 Chinese undergraduate nursing students from seven "double tops" universities. The survey included socio-demographics characteristics, students' professional identity, learner well-being, and self-regulated learning. RESULTS: Results of Pearson correlation analysis showed that professional identity was significantly and positively correlated with learner well-being (R = 0.795, p < 0.001); professional identity was significantly and positively correlated with self-regulated learning (R = 0.843, p < 0.001); and, self-regulated learning was significantly and positively correlated with learner well-being (R = 0.852, p < 0.001). After mediation effect testing, self-regulated learning had a mediating effect between professional identity and learner well-being (95 % CI 0.366-0.548, p < 0.001). Professional identity had a positive predictive effect on self-regulated learning (a = 0.570, p < 0.001), and self-regulated learning also had a positive predictive effect on learner well-being (b = 0.798, p < 0.001). The direct effect of professional identity on learner well-being (0.225) and its mediating effect (0.455) account for 33.1 % and 66.9 % of the total effect (0.680), respectively. CONCLUSIONS: The learner well-being of undergraduate Chinese nursing students is in the middle to upper range, and it is crucial to enhance professional identity and develop students' self-regulated learning to improve their learner well-being. This study provides empirical evidence to support the mediating effect of self-regulated learning on the relationship between professional identity and learner well-being among undergraduate nursing students in "double tops" universities. Universities are expected to strengthen career planning guidance and professional competence training for students as early as possible in order to develop quality nursing education programs that produce graduates who enter and remain in the workforce.


Assuntos
Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Estudantes de Enfermagem/estatística & dados numéricos , Estudos Transversais , Feminino , Masculino , Bacharelado em Enfermagem/métodos , China , Inquéritos e Questionários , Universidades/organização & administração , Identificação Social , Adulto Jovem , Aprendizagem , Adulto
9.
Infect Genet Evol ; 124: 105660, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39179014

RESUMO

Tick-borne encephalitis virus (TBEV) is a pathogen that causes febrile infectious diseases and neurological damage to humans. TBEVs are prevalent from Europe to Far Eastern Asia, including Northeastern China. The understanding of TBEV phylogeny in China has been limited owing to insufficient genomic data on Chinese TBEV strains. Here, six TBEV strains were isolated from ticks collected in Inner Mongolia. The transmission electron microscopy revealed spherical particles with an enveloped structure of 50-60 nm in diameter. Phylogenetic analysis showed that, two strains were classified as the Siberian subtype, while the remaining four were identified as the Far Eastern subtype. Migration analyses based on TBEV ORF and envelope (E) protein sequences revealed that Chinese TBEV strains were migrated from Russia and/or Kazakhstan into China. Hulun Buir and Mudanjiang, the northeastern region of China, are considered hotspots with multiple import and export routes of Chinese TBEV strains. These results promote the understanding of TBEV genetic variations and phylogeny in China and suggest the importance of improving investigation of TBEV prevalence, which would instrumental for vaccine design strategies and better preparation for controlling TBEV infection in humans.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos , Variação Genética , Filogenia , Animais , Humanos , China/epidemiologia , Vírus da Encefalite Transmitidos por Carrapatos/genética , Vírus da Encefalite Transmitidos por Carrapatos/classificação , Encefalite Transmitida por Carrapatos/virologia , Encefalite Transmitida por Carrapatos/epidemiologia , Genoma Viral , Proteínas do Envelope Viral/genética
10.
J Infect Dis ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996045

RESUMO

BACKGROUND: Thrombocytopenia is the major clinical feature associated with the severity of SFTS, but the mechanism by which it occurs remains unclear. METHODS: RNA transcriptome analyses were performed on platelets purified from SFTS patients and SFTSV-infected mice. The functions of differentially expressed genes (DEGs) in the platelets were characterized. ELISA, flow cytometry, and qRT-PCR were used to measure the levels of platelet activation, SFTSV infection in platelets, formation of neutrophil extracellular traps (NETs), transcription of DEGs and percent of platelets undergoing cell death. RESULTS: Enhanced neutrophil activation and interferon (IFN) signaling involved in the viral life cycle were common platelet responses in SFTS, which may consume increasing numbers of platelets. Other functional changes may be associated with different outcomes of SFTS. SFTSV infection led to platelet destruction by pyroptosis, apoptosis, necroptosis, and autophagy. In contrast to SFTS patients, platelets in SFTSV-infected mice mainly play a role in adaptive immunity, and platelet death was not as severe as in humans. CONCLUSIONS: The altered functions of platelets, such as mediating leukocyte activation and undergoing cell death, contribute to thrombocytopenia in SFTS patients. The different mechanisms of thrombocytopenia in mice, suggest that platelet functions should be considered in experimental animal models.

11.
J Med Internet Res ; 26: e53450, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39052335

RESUMO

BACKGROUND: Resilience is a protective factor in healthy aging, helping to maintain and recover physical and mental functions. The Resilience in Illness Model has proven effective in fostering resilience and well-being. Physical activity is crucial for older adults' independence and well-being, even as aging causes a progressive decline. Additionally, older adults face challenges such as spousal loss and physical disability, making preventive intervention strategies necessary. OBJECTIVE: This study aims to develop and evaluate a web-based program to enhance resilience, physical activity, and well-being among community-dwelling older adults. Additionally, we aim to gather feedback on the program's strengths and limitations. METHODS: A 4-week resilience-enhancing program was created, incorporating role-play and talk-in-interaction and focusing on 3 key skills: coping, control belief, and manageability. The program included scenarios such as becoming widowed and suffering a stroke, designed to engage older adults. A pilot test preceded the intervention. As a result of the COVID-19 pandemic, the program shifted from in-person to web-based sessions. A single-blind, parallel-group, randomized controlled trial was conducted. Participants aged over 65 years were recruited offline and randomly assigned to either an intervention or control group. A certified resilience practitioner delivered the program. Outcomes in resilience, physical activity, and well-being were self-assessed at baseline (T0), 4 weeks (T1), and 12 weeks (T2) after the program. A mixed methods approach was used to evaluate feedback. RESULTS: A web-based participatory program enhancing 3 skills-coping, control belief, and manageability for resilience-was well developed. Among 96 participants, 63 were randomized into the intervention group (n=31) and the control group (n=32). The mean age in the intervention group was 69.27 (SD 3.08) years and 74.84 (SD 6.23) years in the control group. Significant between-group differences at baseline were found in age (t45.6=-4.53, P<.001) and physical activity at baseline (t61=2.92, P=.005). No statistically significant between-group differences over time were observed in resilience (SE 7.49, 95% CI -10.74 to 18.61, P=.60), physical activity (SE 15.18, 95% CI -24.74 to 34.74, P=.74), and well-being (SE 3.74, 95% CI -2.68 to 11.98, P=.21) after controlling for baseline differences. The dropout rate was lower in the intervention group (2/31, 6%) compared with the control group (5/32, 16%). Moreover, 77% (24/31) of participants in the intervention group completed the entire program. Program feedback from the participants indicated high satisfaction with the web-based format and mentorship support. CONCLUSIONS: This study demonstrated that a web-based resilience-enhancing program is appropriate, acceptable, feasible, and engaging for community-dwelling older adults. The program garnered enthusiasm for its potential to optimize resilience, physical activity, and well-being, with mentorship playing a crucial role in its success. Future studies should aim to refine program content, engagement, and delivery methods to effectively promote healthy aging in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05808491; https://clinicaltrials.gov/ct2/show/NCT05808491.


Assuntos
Exercício Físico , Resiliência Psicológica , Humanos , Idoso , Feminino , Exercício Físico/psicologia , Masculino , COVID-19/prevenção & controle , COVID-19/psicologia , Intervenção Baseada em Internet , Adaptação Psicológica , Idoso de 80 Anos ou mais , Internet , Método Simples-Cego
13.
Artigo em Inglês | MEDLINE | ID: mdl-39083170

RESUMO

Women who undergo cesarean delivery have reported experiencing mood distress related to the surgery and postoperative pain. Heart rate variability biofeedback (HRVB) training is known to have positive effects on mental health, but its effects on women undergoing cesarean delivery have not yet been determined. This study evaluated the effects of an HRVB training intervention on stress, anxiety, and depression in women undergoing cesarean delivery. We hypothesized that 10 sessions of HRVB training could cumulatively improve emotion regulation in participants. This study was designed as a double-blinded randomized controlled trial involving a total of 86 enrolled women who were then divided into two groups: intervention and control. During their hospitalization, the intervention group underwent HRVB training daily, while both groups received standard perinatal care. Heart rate variability (HRV) was assessed using root mean square of successive differences (RMSSD), standard deviation of normal-to-normal intervals (SDNN), high-frequency power (HF) and low-frequency power (LF). HRV parameters, stress, anxiety, and depression were evaluated at baseline and on the fifth day after childbirth. Intention-to-treat (ITT) analyses examined change over time between groups. Although no significant effects were found for the RMSSD and HF, a significant increase was observed in SDNN (F = 13.43, p = < 0.001, ƞ2 = 0.14), and LF at post-assessment (F = 4.26, p = .04, ƞ2 = 0.05) compared to the control group. Except for the depression variable, stress (F = 6.11, p = .02, ƞ2 = 0.07) and anxiety (F = 8.78, p = .004, ƞ2 = 0.10) significantly decreased compared to the control group on the fifth postpartum day. Furthermore, post-hoc analysis showed that HRVB was more effective in decreasing mild to severe depressive symptoms (F = 7.60, p = .001, ƞ2 = 0.27). The intervention program successfully decreased self-perceived stress and anxiety in the postpartum period and relieved symptoms in more severely depressed participants. Our findings suggest that this program is suitable and beneficial for application in women during the early postpartum period following cesarean delivery.

14.
J Org Chem ; 89(12): 8804-8814, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38860924

RESUMO

1,4-/1,3-Regioselective bifunctionalization of 1,3-enynes with selenosulfonates in water under catalyst-free conditions for the construction of sulfonyl allene and 1,3-disulfonyl-conjugated dienes respectively have been developed. The reactions feature mild reaction conditions in aqueous solution and remarkable regioselectivity controlled by substrates.

15.
Am J Cancer Res ; 14(5): 2037-2054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859843

RESUMO

Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.

16.
PLoS Negl Trop Dis ; 18(6): e0012216, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38848311

RESUMO

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne viral pathogen that causes severe fever with thrombocytopenia syndrome (SFTS). The disease was initially reported in central and eastern China, then later in Japan and South Korea, with a mortality rate of 13-30%. Currently, no vaccines or effective therapeutics are available for SFTS treatment. In this study, three monoclonal antibodies (mAbs) targeting the SFTSV envelope glycoprotein Gn were obtained using the hybridoma technique. Two mAbs recognized linear epitopes and did not neutralize SFTSV, while the mAb 40C10 can effectively neutralized SFTSV of different genotypes and also the SFTSV-related Guertu virus (GTV) and Heartland virus (HRTV) by targeting a spatial epitope of Gn. Additionally, the mAb 40C10 showed therapeutic effect in mice infected with different genotypes of SFTSV strains against death by preventing the development of lesions and by promoting virus clearance in tissues. The therapeutic effect could still be observed in mice infected with SFTSV which were administered with mAb 40C10 after infection even up to 4 days. These findings enhance our understanding of SFTSV immunogenicity and provide valuable information for designing detection methods and strategies targeting SFTSV antigens. The neutralizing mAb 40C10 possesses the potential to be further developed as a therapeutic monoclonal antibody against SFTSV and SFTSV-related viruses.


Assuntos
Anticorpos Monoclonais , Anticorpos Antivirais , Camundongos Endogâmicos BALB C , Phlebovirus , Phlebovirus/imunologia , Phlebovirus/genética , Animais , Anticorpos Monoclonais/imunologia , Camundongos , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologia , Feminino , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/virologia , Epitopos/imunologia , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genética , Glicoproteínas/imunologia , Glicoproteínas/genética , Infecções por Bunyaviridae/imunologia , Infecções por Bunyaviridae/virologia , Infecções por Bunyaviridae/prevenção & controle , Humanos
17.
Crit Care Med ; 52(10): 1509-1519, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38940646

RESUMO

OBJECTIVES: The objective of this study was to investigate the dynamic profiles of myocardial injury biomarkers and their association with mortality in patients with severe fever with thrombocytopenia syndrome (SFTS). DESIGN: A retrospective cohort study. SETTINGS: Union Hospital in Wuhan, China. PATIENTS: A total of 580 patients with SFTS, observed between May 2014 and December 2021, were included in the final analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 580 patients with SFTS were enrolled in the study, comprised of 469 survivors and 111 nonsurvivors, with a 21-day fatality rate of 19.1%. The elevation of troponin I (TnI) was observed in 61.6% patients (357/580) with SFTS upon admission, and 68.4% patients (397/580) developed an abnormal TnI level during hospitalization. Multivariate logistic regression identified age, viral load, platelet count, creatinine level, and TnI level as potential risk factors for mortality in patients with SFTS. The results of restricted cubic splines revealed that when the TnI level (baseline TnI: 1.55 [lg (ng/L+1)], peak value: TnI 1.90 [lg (ng/L+1)]) exceeded a certain threshold, the predicted mortality of patients with SFTS increased alongside the rise in TnI levels. Mortality rate surpassed 40% among patients with SFTS with TnI greater than or equal to 10 times the upper limit of normal at admission (43.8%) or during hospitalization (41.7%). Older age, a history of cardiovascular disease, and higher d -dimer levels were potential risk factors for elevated TnI levels in patients with SFTS. CONCLUSIONS: Elevated TnI levels were prevalent among patients with SFTS and were strongly associated with an increased risk of mortality.


Assuntos
Biomarcadores , Febre Grave com Síndrome de Trombocitopenia , Troponina I , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos Retrospectivos , Troponina I/sangue , Idoso , Febre Grave com Síndrome de Trombocitopenia/sangue , Febre Grave com Síndrome de Trombocitopenia/mortalidade , China/epidemiologia , Fatores de Risco , Adulto
18.
Infect Dis (Lond) ; 56(9): 776-782, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38913503

RESUMO

BACKGROUND: Although the diverse communities of tick-borne viruses (TBVs) have recently been proposed, the threat of infection and exposure to TBVs among humans across Kenya has been poorly understood. OBJECTIVE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne viral agent associated with the epidemic of severe fever with thrombocytopenia syndrome (SFTS) disease in East Asian countries. This study investigated the seroprevalence of SFTSV among humans in Kenya. METHODS: Serum samples were collected from 459 healthy people in Kenya and tested for anti-SFTSV antibodies, which were further confirmed by immunofluorescence assays. Micro neutralization assays were performed to identify neutralising antibodies against SFTSV and SFTSV-related viruses. RESULTS: A high seroprevalence (162/459, 35.3%) of SFTSV was found in the samples from nine of the ten surveyed counties in Kenya, with higher rates in the eastern plateau forelands, semiarid and arid areas, and coastal areas than in the area aside Rift valley. The seropositive rate was slightly higher in women than in men and was significantly higher in the 55-64 age group. Neutralising activity against SFTSV was detected in four samples, resulting in a rate of 0.9%. No cross-neutralising activity against the SFTSV-related Guertu virus and Heartland virus was detected in the anti-SFTSV positive serum samples. CONCLUSION: The results provide serologic evidence of human exposure to SFTSV in Kenya and extend our understanding of SFTSV prevalence from Asia to Africa. The findings suggest an increasing threat of exposure to emerging TBVs and the need to investigate tick viromes in Kenya.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Humanos , Quênia/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Phlebovirus/imunologia , Estudos Soroepidemiológicos , Adulto , Anticorpos Antivirais/sangue , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Febre Grave com Síndrome de Trombocitopenia/virologia , Adolescente , Adulto Jovem , Idoso , Anticorpos Neutralizantes/sangue , Testes de Neutralização , Criança , Pré-Escolar , Idoso de 80 Anos ou mais
19.
Eur J Surg Oncol ; 50(7): 108396, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38754314

RESUMO

BACKGROUND: Optimal surgical recovery is critical to readiness to return to intended oncologic therapy (RIOT). The current study defined the value of patient-reported outcomes (PROs) in predicting the risk for delayed RIOT after oncologic hepatic resection. METHODS: In a prospective longitudinal study, perioperative symptoms were assessed using a valid PRO assessment tool, the MD Anderson Symptom Inventory module for hepatectomy perioperative care (MDASI-PeriOp-Hep), for 4 weeks after surgery. The timed up and go test (TUGT) was administered before surgery, by discharge day, and at the first postoperative follow-up visit. Multivariate logistic regression analysis assessed the predictive value of PROs for delayed RIOT. RESULTS: We enrolled 210 patients and analyzed 148 patients who received adjuvant chemotherapy and contributed more than 3 PRO assessments postoperatively. About 36 percent of the patients had delayed RIOT (>5 weeks, range 1-14 weeks). MDASI scores for drowsiness, fatigue, dry mouth, and interference with general activity, walking, and work on day 7 after discharge and MDASI scores for incisional tightness, fatigue, dry mouth, shortness of breath, and interference with work on day 14 after discharge were associated with delayed RIOT (all P < 0.05). Walking and general activity items on the MDASI-Interference subscale on day 7 after discharge were highly correlated with prolonged TUGT scores at discharge (P < 0.01). CONCLUSION: We defined clinically meaningful PROs on MDASI-PeriOp-Hep after hepatic resection that predicted increased risk of delayed RIOT. These findings highlight the importance PROs for monitoring symptoms and functioning 1-2 weeks after discharge to be implementing into perioperative care.


Assuntos
Hepatectomia , Neoplasias Hepáticas , Medidas de Resultados Relatados pelo Paciente , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Hepáticas/cirurgia , Estudos Prospectivos , Idoso , Estudos Longitudinais , Quimioterapia Adjuvante , Adulto , Fatores de Tempo , Fadiga/etiologia
20.
Sci Total Environ ; 932: 172829, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38692332

RESUMO

Permafrost serves as a natural cold reservoir for viral communities. However, little is known about the viromes in deep permafrost soil, as most studies of permafrost were restricted to shallow areas. Here, permafrost soil samples of up to 100 m in depth were collected from two sites in the Tuotuo River permafrost area on the Tibetan Plateau. We investigated the viral composition in these permafrost soil samples and analyzed the relationship of viral composition and diversity along with depths. Our study revealed that greater permafrost thickness corresponds to higher diversity within the viral community. Bacteriophages were found to be the dominant viral communities, with "kill the winner" dynamics observed within the Siphoviridae and Myoviridae. The abundance and diversity of viral communities may follow a potential pattern along soil layers and depths, influenced by pH, trace elements, and permafrost thickness. Notably, strong correlations were discovered between the content of inorganic elements, including B, Mg, Cr, Bi, Ti, Na, Ni, and Cu, and the viral composition. Moreover, we discovered highly conserved sequences of giant viruses at depth of 10, 20, and 50 m in permafrost, which play a crucial role in evolutionary processes. These findings provide valuable insights into the viral community patterns from shallow to 100-m-depth in high-elevation permafrost, offering crucial data support for the formulation of strategies for permafrost thaw caused by climate change and anthropogenic activities.


Assuntos
Pergelissolo , Tibet , Microbiologia do Solo , Viroma , Altitude , Monitoramento Ambiental , Solo/química , Vírus
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