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1.
J Virol ; 98(5): e0159623, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38587378

RESUMO

Following acute herpes simplex virus type 2 (HSV-2) infection, the virus undergoes an asymptomatic latent infection of sensory neurons of dorsal root ganglia (DRG). Chemical and physical stress cause intermittent virus reactivation from latently infected DRG and recurrent virus shedding in the genital mucosal epithelium causing genital herpes in symptomatic patients. While T cells appear to play a role in controlling virus reactivation from DRG and reducing the severity of recurrent genital herpes, the mechanisms for recruiting these T cells into DRG and the vaginal mucosa (VM) remain to be fully elucidated. The present study investigates the effect of CXCL9, CXCL10, and CXCL11 T-cell-attracting chemokines on the frequency and function of DRG- and VM-resident CD4+ and CD8+ T cells and its effect on the frequency and severity of recurrent genital herpes in the recurrent herpes guinea pig model. HSV-2 latent-infected guinea pigs were immunized intramuscularly with the HSV-2 ribonucleotide reductase 2 (RR2) protein (Prime) and subsequently treated intravaginally with the neurotropic adeno-associated virus type 8 expressing CXCL9, CXCL10, or CXCL11 chemokines to recruit CD4+ and CD8+ T cells into the infected DRG and VM (Pull). Compared to the RR2 therapeutic vaccine alone, the RR2/CXCL11 prime/pull therapeutic vaccine significantly increased the frequencies of functional tissue-resident and effector memory CD4+ and CD8+ T cells in both DRG and VM tissues. This was associated with less virus in the healed genital mucosal epithelium and reduced frequency and severity of recurrent genital herpes. These findings confirm the role of local DRG- and VM-resident CD4+ and CD8+ T cells in reducing virus shedding at the vaginal site of infection and the severity of recurrent genital herpes and propose the novel prime-pull vaccine strategy to protect against recurrent genital herpes.IMPORTANCEThe present study investigates the novel prime/pull therapeutic vaccine strategy to protect against recurrent genital herpes using the latently infected guinea pig model. In this study, we used the strategy that involves immunization of herpes simplex virus type 2-infected guinea pigs using a recombinantly expressed herpes tegument protein-ribonucleotide reductase 2 (RR2; prime), followed by intravaginal treatment with the neurotropic adeno-associated virus type 8 expressing CXCL9, CXCL10, or CXCL11 T-cell-attracting chemokines to recruit T cells into the infected dorsal root ganglia (DRG) and vaginal mucosa (VM) (pull). We show that the RR2/CXCL11 prime-pull therapeutic vaccine strategy elicited a significant reduction in virus shedding in the vaginal mucosa and decreased the severity and frequency of recurrent genital herpes. This protection was associated with increased frequencies of functional tissue-resident (TRM cells) and effector (TEM cells) memory CD4+ and CD8+ T cells infiltrating latently infected DRG tissues and the healed regions of the vaginal mucosa. These findings shed light on the role of tissue-resident and effector memory CD4+ and CD8+ T cells in DRG tissues and the VM in protection against recurrent genital herpes and propose the prime-pull therapeutic vaccine strategy in combating genital herpes.


Assuntos
Quimiocina CXCL11 , Herpes Genital , Herpesvirus Humano 2 , Ribonucleotídeo Redutases , Animais , Feminino , Cobaias , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Quimiocina CXCL11/imunologia , Quimiocina CXCL11/metabolismo , Modelos Animais de Doenças , Gânglios Espinais/imunologia , Gânglios Espinais/virologia , Herpes Genital/imunologia , Herpes Genital/prevenção & controle , Herpesvirus Humano 2/imunologia , Células T de Memória/imunologia , Ribonucleotídeo Redutases/metabolismo , Vacinação , Vagina/virologia , Vagina/imunologia
2.
Nat Mater ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043929

RESUMO

Robotic tasks that require robust propulsion abilities such as jumping, ejecting or catapulting require power-amplification strategies where kinetic energy is generated from pre-stored energy. Here we report an engineered accumulated strain energy-fracture power-amplification method that is inspired by the pressurized fluidic squirting mechanism of Ecballium elaterium (squirting cucumber plants). We realize a light-driven hydrogel launcher that harnesses fast liquid vapourization triggered by the photothermal response of an embedded graphene suspension. This vapourization leads to appreciable elastic energy storage within the surrounding hydrogel network, followed by rapid elastic energy release within 0.3 ms. These soft hydrogel robots achieve controlled launching at high velocity with a predictable trajectory. The accumulated strain energy-fracture method was used to create an artificial squirting cucumber that disperses artificial seeds over metres, which can further achieve smart seeding through an integrated radio-frequency identification chip. This power-amplification strategy provides a basis for propulsive motion to advance the capabilities of miniaturized soft robotic systems.

3.
J Transl Med ; 22(1): 6, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167440

RESUMO

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.


Assuntos
Neoplasias da Mama , Animais , Camundongos , Humanos , Feminino , Neoplasias da Mama/patologia , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Ácidos Graxos , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo , PTEN Fosfo-Hidrolase/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica
4.
BMC Microbiol ; 24(1): 141, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38658829

RESUMO

BACKGROUND: Recent studies have more focused on gut microbial alteration in tuberculosis (TB) patients. However, no detailed study on gut fungi modification has been reported till now. So, current research explores the characteristics of gut microbiota (bacteria)- and mycobiota (fungi)-dysbiosis in TB patients and also assesses the correlation between the gut microbiome and serum cytokines. It may help to screen the potential diagnostic biomarker for TB. RESULTS: The results show that the alpha diversity of the gut microbiome (including bacteria and fungi) decreased and altered the gut microbiome composition of TB patients. The bacterial genera Bacteroides and Prevotella were significantly increased, and Blautia and Bifidobacterium decreased in the TB patients group. The fungi genus Saccharomyces was increased while decreased levels of Aspergillus in TB patients. It indicates that gut microbial equilibrium between bacteria and fungi has been altered in TB patients. The fungal-to-bacterial species ratio was significantly decreased, and the bacterial-fungal trans-kingdom interactions have been reduced in TB patients. A set model including Bacteroides, Blautia, Eubacterium_hallii_group, Apiotrichum, Penicillium, and Saccharomyces may provide a better TB diagnostics option than using single bacterial or fungi sets. Also, gut microbial dysbiosis has a strong correlation with the alteration of IL-17 and IFN-γ. CONCLUSIONS: Our results demonstrate that TB patients exhibit the gut bacterial and fungal dysbiosis. In the clinics, some gut microbes may be considered as potential biomarkers for auxiliary TB diagnosis.


Assuntos
Bactérias , Disbiose , Fungos , Microbioma Gastrointestinal , Humanos , Disbiose/microbiologia , Fungos/classificação , Fungos/isolamento & purificação , Fungos/genética , Masculino , Feminino , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Adulto , Pessoa de Meia-Idade , Tuberculose/microbiologia , Tuberculose/complicações , Fezes/microbiologia , Citocinas/sangue , Interleucina-17/sangue
5.
Invest New Drugs ; 42(3): 309-317, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38700579

RESUMO

BACKGROUND: Platinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present. AIM: This study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed. METHODS: This prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210 mg) over a period of 120 h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs). RESULTS: The mPFS was 6.5 months (95% confidence interval (CI): 3.8-9.1 m) while the mOS was 12.3 months (95% CI: 7.6-18.5 m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS. CONCLUSIONS: The incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients. CLINICALTRIALS: GOV: NCT05574998.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Endostatinas , Neoplasias Pulmonares , Paclitaxel , Pemetrexede , Proteínas Recombinantes , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Endostatinas/administração & dosagem , Endostatinas/efeitos adversos , Endostatinas/uso terapêutico , Feminino , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Infusões Intravenosas , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Estudos Prospectivos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Pemetrexede/administração & dosagem , Pemetrexede/efeitos adversos , Pemetrexede/uso terapêutico , Adulto , Intervalo Livre de Progressão
6.
J Exp Bot ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38706346

RESUMO

Rose black spot disease, caused by Marssonina rosae (syn. Diplocarpon rosae), is one of the most widespread diseases of field-grown roses worldwide. Pathogens have been found to interfere with or stimulate plant immune response through the secreted effectors. However, the molecular mechanism involved in inhibition of rose immune response by M. rosae effectors remains poorly understood. In this study, we identified the effector MrSEP43, which played a pivotal role in promoting the virulence of M. rosae and enhancing rose susceptibility by reducing callose deposition, H2O2 accumulation, and the expression of defense genes in jasmonic acid signaling pathway. Through Y2H, BiFC, and LUC assays, MrSEP43 was proved to interact with the rose orphan protein RcBROG. RcBROG, which was a positive regulator of defense against M. rosae, enhanced rose resistance by increasing callose deposition, H2O2 accumulation, and expression of RcERF1 in the ethylene signaling pathway. Overall, our findings suggested that the virulence effector MrSEP43 from M. rosae specifically targeted the orphan protein RcBROG to suppress rose immune response to M. rosae. These results provided new insight into how M. rosae manipulated and successfully colonized rose leaves, and were essential for preventing the breakdown of resistance to rose black spot disease.

7.
Microb Pathog ; 190: 106632, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537762

RESUMO

With the widespread introduction of the Hib conjugate vaccine, Nontypeable Haemophilus influenzae (NTHi) has emerged as the predominant strain globally. NTHi presents a significant challenge as a causative agent of chronic clinical infections due to its high rates of drug resistance and biofilm formation. While current research on NTHi biofilms in children has primarily focused on upper respiratory diseases, investigations into lower respiratory sources remain limited. In this study, we collected 54 clinical strains of lower respiratory tract origin from children. Molecular information and drug resistance features were obtained through whole gene sequencing and the disk diffusion method, respectively. Additionally, an in vitro biofilm model was established. All clinical strains were identified as NTHi and demonstrated the ability to form biofilms in vitro. Based on scanning electron microscopy and crystal violet staining, the strains were categorized into weak and strong biofilm-forming groups. We explored the correlation between biofilm formation ability and drug resistance patterns, as well as clinical characteristics. Stronger biofilm formation was associated with a longer cough duration and a higher proportion of abnormal lung imaging findings. Frequent intake of ß-lactam antibiotics might be associated with strong biofilm formation. While a complementary relationship between biofilm-forming capacity and drug resistance may exist, further comprehensive studies are warranted. This study confirms the in vitro biofilm formation of clinical NTHi strains and establishes correlations with clinical characteristics, offering valuable insights for combating NTHi infections.


Assuntos
Antibacterianos , Biofilmes , Infecções por Haemophilus , Haemophilus influenzae , Biofilmes/crescimento & desenvolvimento , Humanos , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/fisiologia , Haemophilus influenzae/isolamento & purificação , Haemophilus influenzae/genética , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/classificação , Antibacterianos/farmacologia , Pré-Escolar , Feminino , Masculino , Criança , Lactente , Testes de Sensibilidade Microbiana , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Microscopia Eletrônica de Varredura , Farmacorresistência Bacteriana , Sistema Respiratório/microbiologia , Sistema Respiratório/virologia
8.
Cancer Cell Int ; 24(1): 188, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811918

RESUMO

BACKGROUND: Breast cancer is a serious threat to women's health with high morbidity and mortality. The development of more effective therapies for the treatment of breast cancer is strongly warranted. Growing evidence suggests that targeting glucose metabolism may be a promising cancer treatment strategy. We previously identified a new glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor, DC-5163, which shows great potential in inhibiting tumor growth. Here, we evaluated the anticancer potential of DC-5163 in breast cancer cells. METHODS: The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model. RESULTS: DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor 18F-FDG and 18F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group. CONCLUSIONS: Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. 18F-FDG and 18F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163.

9.
Virol J ; 21(1): 74, 2024 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532424

RESUMO

BACKGROUND: To investigate the efficacy of different doses of corticosteroids in treating severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Between May 01, 2023, and June 20, 2023, 48 patients with severe COVID-19 pneumonia were treated at the Department of Respiratory and Critical Care Medicine of Jinan Fourth People's Hospital. The observation group (21 patients) received standard care and high-dose corticosteroids, (high-dose group). The control group (27 patients) received standard care and low-dose corticosteroids (low-dose group). We collected baseline data and recorded inflammatory marker levels after 3 days of treatment, body temperature recovery time, length of stay, and 28-day all-cause mortality. The results of outpatient follow-up were recorded after 1 month. RESULTS: There were no significant differences in 28-day mortality and length of stay. The number of days it took for body temperature to return to normal in the high-dose group was less than in the low-dose group. The high-dose group had significantly more reduced inflammatory factors (C-reactive protein (CRP), interleukin-6 (IL-6). A total of 20 discharged patients were given 8-16 mg of methylprednisolone, depending on chest computed tomography (CT) and clinical symptoms after 1 month; in all discharged patients using oral corticosteroids, CT features improved. CONCLUSION: High-dose corticosteroids had a significantly positive effect on the reduction of inflammatory factors and shortening body temperature recovery time. In the treatment of severe COVID-19 pneumonia, early administration of high-dose, short-course corticosteroids should be implemented.


Assuntos
COVID-19 , Pneumonia , Humanos , SARS-CoV-2 , Corticosteroides , Metilprednisolona
10.
Fish Shellfish Immunol ; 148: 109473, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38458502

RESUMO

Japanese flounder (Paralichthys olivaceus) is an economically crucial marine species, but diseases like hemorrhagic septicemia caused by Edwardsiella tarda have resulted in significant economic losses. E. tarda infects various hosts, and its pathogenicity in fish is not fully understood. Lipopolysaccharides (LPS) are components of the outer membrane of Gram-negative bacteria and are representative of typical PAMP molecules that cause activation of the immune system. The PoIEC cell line is a newly established intestinal epithelial cell line from P. olivaceus. In order to investigate whether it can be used as an in vitro model for studying the pathogenesis of E. tarda and LPS stimulation, we conducted RNA-seq experiments for the PoIECs model of E. tarda infection and LPS stimulation. In this study, transcriptome sequencing was carried out in the PoIEC cell line after treatment with LPS and E. tarda. A total of 62.52G of high-quality data from transcriptome sequencing results were obtained in nine libraries, of which an average of 87.96% data could be aligned to the P. olivaceus genome. Data analysis showed that 283 and 414 differentially expressed genes (DEGs) in the LPS versus Control (LPS-vs-Con) and E. tarda versus Control groups (Et-vs-Con), respectively, of which 60 DEGs were shared in two comparation groups. The GO terms were predominantly enriched in the extracellular space, inflammatory response, and cytokine activity in the LPS-vs-Con group, whereas GO terms were predominantly enriched in nucleus and positive regulation of transcription by RNA polymerase II in the Et-vs-Con group. KEGG analysis revealed that three immune-related pathways were co-enriched in both comparison groups, including the Toll-like receptor signaling pathway, C-type lectin receptor signaling pathway, and Cytokine-cytokine receptor interaction. Five genes were randomly screened to confirm the validity and accuracy of the transcriptome data. These results suggest that PoIEC cell line can be an ideal in vitro model for studies of marine fish gut immunity and pathogenesis of Edwardsiellosis.


Assuntos
Infecções por Enterobacteriaceae , Doenças dos Peixes , Linguado , Animais , Linguado/genética , Lipopolissacarídeos/farmacologia , Perfilação da Expressão Gênica/veterinária , Citocinas/genética , Edwardsiella tarda/fisiologia , Imunidade
11.
BMC Public Health ; 24(1): 1974, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044199

RESUMO

OBJECTIVE: Self-rated health (SRH) has been documented as an important predictor of quality of life among the elderly and its risk factors are vision-specific among elderly males. The aim of this study was to clarify vision-specific risk factors to SRH among elderly females without dementia in Chinese urban areas. METHODS: From March to November 2012, 2147 elderly women in Liaoning Province of China were selected using a stratified sampling method. After cognitive screening, 1956 participants without dementia were finally enrolled. A questionnaire including SRH, visual ability and factors including demographic characteristics, physical conditions, lifestyle factors, social psychological status and social activities were analyzed. Multivariate logistic regression was used to clarify the association of SRH with risk factors, while stepwise multivariate logistic regression was used to examine the vision-specific associations with SRH. RESULTS: The mean age was 73.6 ± 5.82 (mean ± SD). The percentages of good SRH in good and impaired visual ability groups were 36.2% and 24.4%, respectively. Most characteristics between elderly females with different visual abilities were significantly different. Visual ability had interactions with physical conditions, lifestyle factors and social activities to affect SRH. Among elderly females with good visual ability, depressive symptoms, rather than chronic disease had the strongest association with good SRH followed by marital status, regular diet, going out alone to distant places, taking a walk, smoking and alcohol consumption. In the impaired visual ability group, going out alone to distant places had the strongest association with good SRH followed by chronic disease, filial piety, taking a walk, participating in entertainment, ethnicity, quality of sleep, worrying about falling and alcohol consumption. CONCLUSIONS: Good SRH status was at a low level especially among elderly females with impaired visual ability and the risk factors differed between elderly females with different visual abilities. Social psychological status was crucial for SRH among elderly females with good visual ability whereas physical conditions were prominent for impaired visual ability group.


Assuntos
Nível de Saúde , População Urbana , Humanos , Feminino , Idoso , China/epidemiologia , Fatores de Risco , População Urbana/estatística & dados numéricos , Transtornos da Visão/epidemiologia , Transtornos da Visão/psicologia , Idoso de 80 Anos ou mais , Inquéritos e Questionários , População do Leste Asiático
12.
BMC Pediatr ; 24(1): 364, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802810

RESUMO

BACKGROUND: Randomized controlled trials (RCTs) are usually the basis of evidence-based medicine, but whether the results of RCTs can be correctly translated into clinical practice depends on the quality of the literature reported. In this study, we evaluated the general characteristics and quality of paediatric RCTs published in China to provide evidence for the reporting of paediatric RCTs and their application in clinical practice. METHODS: We conducted a cross-sectional observational study of paediatric RCTs published in paediatric journals in China between January 1, 1999, and December 30, 2022. All RCTs that included children (younger than 18 years old) were retrieved, and the general characteristics of the RCTs were extracted and analysed. The quality of the RCTs was assessed by the Cochrane quality assessment protocol. RESULTS: After screening 20 available paediatric journals, 3545 RCTs were included for analysis. The average annual growth rate of the number of published paediatric RCTs from 1999 to 2022 was 7.8% (P = 0.005, R2 = 0.311). Most of the studies were carried out in East China [1148 (32.4%]; the centres of the RCTs were mainly single-centre [3453 (97.4%], and the interventions were mainly medication [2442 (68.9%)]. Comparing RCTs published in 2017-2022 with RCTs published in 1999-2004, the quality of RCTs significantly improved in terms of random sequence generation, allocation concealment, blinding participants and personnel, incomplete outcome data and selective outcome reporting. RCTs published in multiple centres from the Chinese Science Citation Database were identified, and the approval of the ethics committee was of better quality for all the analysed risk of bias items. CONCLUSION: The number and quality of paediatric RCTs reported in China have improved in recent years, but the overall quality was relatively low. Special attention should be given to allocation concealment and blinding outcome assessment, and dropouts, adverse effects and sample size calculations should be reported. Promoting government policies, strengthening the standardization of journal publishing and advancing the registration of clinical trials are feasible measures.


Assuntos
Pediatria , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Transversais , China , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Humanos , Pediatria/normas , Criança , Publicações Periódicas como Assunto/normas
14.
J Med Internet Res ; 26: e46036, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713909

RESUMO

BACKGROUND: A plethora of weight management apps are available, but many individuals, especially those living with overweight and obesity, still struggle to achieve adequate weight loss. An emerging area in weight management is the support for one's self-regulation over momentary eating impulses. OBJECTIVE: This study aims to examine the feasibility and effectiveness of a novel artificial intelligence-assisted weight management app in improving eating behaviors in a Southeast Asian cohort. METHODS: A single-group pretest-posttest study was conducted. Participants completed the 1-week run-in period of a 12-week app-based weight management program called the Eating Trigger-Response Inhibition Program (eTRIP). This self-monitoring system was built upon 3 main components, namely, (1) chatbot-based check-ins on eating lapse triggers, (2) food-based computer vision image recognition (system built based on local food items), and (3) automated time-based nudges and meal stopwatch. At every mealtime, participants were prompted to take a picture of their food items, which were identified by a computer vision image recognition technology, thereby triggering a set of chatbot-initiated questions on eating triggers such as who the users were eating with. Paired 2-sided t tests were used to compare the differences in the psychobehavioral constructs before and after the 7-day program, including overeating habits, snacking habits, consideration of future consequences, self-regulation of eating behaviors, anxiety, depression, and physical activity. Qualitative feedback were analyzed by content analysis according to 4 steps, namely, decontextualization, recontextualization, categorization, and compilation. RESULTS: The mean age, self-reported BMI, and waist circumference of the participants were 31.25 (SD 9.98) years, 28.86 (SD 7.02) kg/m2, and 92.60 (SD 18.24) cm, respectively. There were significant improvements in all the 7 psychobehavioral constructs, except for anxiety. After adjusting for multiple comparisons, statistically significant improvements were found for overeating habits (mean -0.32, SD 1.16; P<.001), snacking habits (mean -0.22, SD 1.12; P<.002), self-regulation of eating behavior (mean 0.08, SD 0.49; P=.007), depression (mean -0.12, SD 0.74; P=.007), and physical activity (mean 1288.60, SD 3055.20 metabolic equivalent task-min/day; P<.001). Forty-one participants reported skipping at least 1 meal (ie, breakfast, lunch, or dinner), summing to 578 (67.1%) of the 862 meals skipped. Of the 230 participants, 80 (34.8%) provided textual feedback that indicated satisfactory user experience with eTRIP. Four themes emerged, namely, (1) becoming more mindful of self-monitoring, (2) personalized reminders with prompts and chatbot, (3) food logging with image recognition, and (4) engaging with a simple, easy, and appealing user interface. The attrition rate was 8.4% (21/251). CONCLUSIONS: eTRIP is a feasible and effective weight management program to be tested in a larger population for its effectiveness and sustainability as a personalized weight management program for people with overweight and obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT04833803; https://classic.clinicaltrials.gov/ct2/show/NCT04833803.


Assuntos
Inteligência Artificial , Comportamento Alimentar , Aplicativos Móveis , Humanos , Comportamento Alimentar/psicologia , Adulto , Feminino , Masculino , Obesidade/psicologia , Obesidade/terapia , Pessoa de Meia-Idade
15.
Eur Arch Otorhinolaryngol ; 281(8): 3959-3975, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38647686

RESUMO

PURPOSE: We performed this systematic review and meta-analysis to explore the impact of preoperative sarcopenia on postoperative complication risks after head and neck cancer (HNC) surgery. METHODS: We identified eligible studies by searching Ovid-MEDLINE, Ovid-Embase, EBM Reviews-Cochrane Central Register of Controlled Trials, Web of Science Core Collection, and Scopus. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. RESULTS: Twenty-one studies with a total of 3480 patients met our inclusion criteria. The presence of sarcopenia significantly increased the incidence of overall postoperative complications (OR = 1.72, 95% CI 1.23, 2.41; P = 0.002; I2 = 59%). Subgroup analyses showed a higher risk of postoperative complications in the populations in which sarcopenia was diagnosed with low L3-skeletal muscle index (L3-SMI) or low cross-sectional area of the rectus femoris, but not in the group that sarcopenia was diagnosed with low C3-SMI. Preoperative sarcopenia also substantially increased the risk of severe postoperative complications (OR = 2.26), pharyngocutaneous fistulas (OR = 2.15), free flap-related complications (OR = 1.63), and surgical site infections (OR = 1.84). We also found a tendency toward a higher incidence of wound complications and 30-day mortality in patients with sarcopenia. CONCLUSION: Preoperative sarcopenia is a negative prognostic indicator for postoperative complications in patients with HNC after surgery. To reduce the incidence of postoperative complications and improve poor prognosis, further attention needs to be paid to the evaluation and management of preoperative sarcopenia.


Assuntos
Neoplasias de Cabeça e Pescoço , Complicações Pós-Operatórias , Sarcopenia , Sarcopenia/complicações , Sarcopenia/epidemiologia , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias de Cabeça e Pescoço/cirurgia , Fatores de Risco
16.
J Environ Manage ; 351: 119864, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38109823

RESUMO

It is well accepted that tidal wetland vegetation performs a significant amount of water filtration for wetlands. However, there is currently little information on how various wetland plants remove nitrogen (N) and phosphorus (P) and how they differ in their denitrification processes. This study compared and investigated the denitrification and phosphorus removal effects of three typical wetland plants in the Yangtze River estuary wetland (Phragmites australis, Spartina alterniflora, and Scirpus mariqueter), as well as their relevant mechanisms, using an experimental laboratory-scale horizontal subsurface flow constructed wetland (CW). The results showed that all treatment groups with plants significantly reduced N pollutants as compared to the control group without plants. In comparison to S. mariqueter (77.2-83.2%), S. alterniflora and P. australis had a similar total nitrogen (TN)removal effectiveness of nearly 95%. With a removal effectiveness of over 99% for ammonium nitrogen (NH4+-N), P. australis outperformed S. alterniflora (95.6-96.8%) and S. mariqueter (94.6-96.5%). The removal of nitrite nitrogen (NO2--N)and nitrate nitrogen (NO3--N)from wastewater was significantly enhanced by S. alterniflora compared to the other treatment groups. Across all treatment groups, the removal rate of PO43--P was greater than 95%. P. australis and S. alterniflora considerably enriched more 15N than S. mariqueter, according to the results of the 15N isotope labeling experiment. While the rhizosphere and bulk sediments of S. alterniflora were enriched with more simultaneous desulfurization-denitrification bacterial genera (such as Paracoccus, Sulfurovum, and Sulfurimonas), which have denitrification functions, the rhizosphere and bulk sediments of P. australis were enriched with more ammonia-oxidizing archaea and ammonia-oxidizing bacteria. As a result, compared to the other plants, P. australis and S. alterniflora demonstrate substantially more significant ability to remove NH4+-N and NO2--N/NO3--N from simulated domestic wastewater.


Assuntos
Nitrogênio , Áreas Alagadas , Nitrogênio/análise , Fósforo/análise , Amônia , Dióxido de Nitrogênio , Águas Residuárias , Plantas , Poaceae , China
17.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2566-2574, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812157

RESUMO

This study aims to investigate the mitigating effect and mechanism of Cichorium glandulosum n-butanol extraction site(CGE) on the disease in carbon tetrachloride(CCl_4)-induced chronic liver injury model in rats. A chronic liver injury model was constructed by subcutaneous injection of CCl_4 olive oil solution, and after four weeks of CGE treatment, serum levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(AKP), hydroxyproline(HYP), interleukin-4(IL-4), interleukin-6(IL-6), malondialdehyde(MDA), superoxide dismutase(SOD), and tumor necrosis factor-α(TNF-α) were detected. Liver tissue was processed by hematoxylin-eosin(HE) staining and Masson staining to observe the structure of the rat liver. qPCR and Western blot were used to examine the expression of transforming growth factor-ß1(TGF-ß1)/small mothers against decapentaplegic(Smad), Toll-like receptor 4(TLR4), α-smooth muscle actin(α-SMA), and fibronectin(Fn) in rat liver tissue and hepatic stellate-T6(HSC-T6) and evaluate the inhibitory effect of CGE on HSC activation. The results showed that CGE could significantly reduce the serum levels of AST, ALT, AKP, HYP, and affect the levels of related inflammatory indexes including IL-4, IL-6, and TNF-α, and MDA in CCl_4-induced chronic liver injury in rats and had no effect on SOD activity, which could delay the process of liver injury, alleviate the hepatic collagen deposition and inflammatory infiltration, and had significant efficacy in mitigating chronic liver injury in rats. CGE could inhibit α-SMA and TLR4 protein expression in the liver tissue and reverse the increased TGF-ß1/Smad, Fn, and TLR4-related expression in HSC-T6 in vitro. The above results indicated that CGE exerted hepatoprotective effects in rats by inhibiting HSC activation and alleviated CCl_4-induced chronic liver injury in rats and could ameliorate inflammatory response and slight liver fibrosis in rat liver tissue. Its pharmacodynamic mechanism might be related to TGF-ß1/Smad and TLR4-related expression.


Assuntos
Tetracloreto de Carbono , Fígado , Ratos Sprague-Dawley , Animais , Ratos , Tetracloreto de Carbono/efeitos adversos , Masculino , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/lesões , 1-Butanol/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Malondialdeído/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Interleucina-4/genética , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/genética
18.
Meat Sci ; 213: 109470, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38479133

RESUMO

In this study, we examined the impact of adding Lactobacillus to the diet on fat distribution and meat quality of Sunit lambs. For 90 days, twenty-four lambs (19.31 ± 0.47 kg) were fed diets that contained 0 (NP), 6 (P1), 12 (P2), or 24 (P3) g of Lactobacillus casei/d. The results suggested that dietary supplementation with Lactobacillus decreased serum triglyceride in Sunit lambs (P < 0.001). The loin muscle area displayed notable increases in the P1 group (P < 0.05). Meanwhile, tail and visceral fat deposition of lambs were reduced when Lactobacillus was added to the diet (P < 0.05). Compared with the NP group, the values of shear force and cooking loss of in the P1 group exhibited a significant reduction, and intramuscular fat content increased significantly (P < 0.05). Additionally, the P1 group showed an increase in polyunsaturated fatty acids and a decrease in saturated fatty acids in the longissimus thoracis and biceps femoris muscles (P < 0.05). The P1 group showed downregulation of protein kinase AMP-activated catalytic subunit alpha 2 (AMPKα2) and carnitine palmitoyltransferase 1B expression in the longissimus thoracis muscle (P < 0.05). However, there was an upregulation of acetyl-CoA carboxylase (ACC), sterol regulatory element binding transcription factor 1 (SREBF1), and fatty acid synthase (FASN) expression (P < 0.05). In conclusion, feeding Sunit lambs 6 g/d of Lactobacillus as a dietary supplement may be a valuable way to improve fat distribution and meat quality. The AMPK/ACC and AMPK/SREBF1/FASN signaling pathways may be involved in this outcome.


Assuntos
Ração Animal , Dieta , Músculo Esquelético , Carne Vermelha , Carneiro Doméstico , Animais , Dieta/veterinária , Ração Animal/análise , Músculo Esquelético/química , Carne Vermelha/análise , Masculino , Suplementos Nutricionais , Tecido Adiposo , Lacticaseibacillus casei , Ácidos Graxos/análise , Triglicerídeos/sangue , Culinária
19.
Meat Sci ; 211: 109440, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38324956

RESUMO

This study aimed to investigate the effects of exercise on muscle fiber conversion, muscle development and meat quality in the biceps femoris (BF) muscle of Sunit sheep. Twelve Sunit sheep with similar body weight were divided into two groups: control group (C group) and exercise group (E group), E group lambs underwent 6 km of exercise training per day for 90 d. The findings revealed that compared with the C group, exercise training enhanced the expression of MyHC IIa mRNA, decreased the number ratio of type IIB muscle fibers and the expression of MyHC IIb mRNA (P < 0.05). Furthermore, the E group lamb displayed higher creatine kinase (CK) activity, and lactic acid levels (P < 0.05), while glycogen content and lactic dehydrogenase (LDH) activity showed opposite trends (P < 0.05). Exercise significantly up-regulated the mRNA expression of AMP-activated protein kinase α1 (AMPKα1), sirtuin1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), cytochrome c oxidase IV (COX IV), protein kinase B (Akt), mammalian target of rapamycin (mTOR) and p70 Ribosomal S6 Kinase 1 (p70s6k1) (P < 0.05), suggesting exercise promoted muscle fiber conversion by mediating AMPK/PGC-1α pathway, and improved skeletal muscle development via Akt/mTOR pathway. Besides, backfat thickness and pH45min value in the E group decreased significantly, while the pH24, a*, and shear force value increased significantly (P < 0.05). To conclude, this study suggested that exercise training can be used to alter muscle fiber characteristics and muscle development in lamb production.


Assuntos
Músculo Esquelético , Proteínas Proto-Oncogênicas c-akt , Animais , Ovinos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Serina-Treonina Quinases TOR/metabolismo , RNA Mensageiro/metabolismo , Carne , Desenvolvimento Muscular , Mamíferos/genética , Mamíferos/metabolismo
20.
Toxicol Res (Camb) ; 13(4): tfae102, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38993483

RESUMO

Background: Paclitaxel (PTX) is a commonly used as a chemotherapeutic drug for non-small cell lung cancer (NSCLC). Exploring the underlying mechanism of PTX resistance is of great significance for NSCLC treatment. Methods: The expression levels of RNA and protein were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The targeted relationship was confirmed by dual-luciferase reporter assay and RNA-pull down assay. The PTX resistance and cell proliferation were assessed by cell counting kit-8 (CCK-8) assay and 5-Ethynyl-2'-deoxyuridine (EDU) assay, respectively. Cell migration and invasion were analyzed by transwell assays. Cell apoptosis was analyzed by flow cytometry, and cell glycolysis was analyzed using the commercial kits. The role of circular RNA_0076305 (circ_0076305) in regulating the PTX sensitivity in vivo was explored in xenograft tumor model. Results: Circ_0076305 was up-regulated in PTX-resistant NSCLC tissues and cells. Mechanically, circ_0076305 bound to microRNA-936 (miR-936), and miR-936 targeted transmembrane serine protease 4 (TMPRSS4). Circ_0076305 could up-regulate TMPRSS4 expression by sponging miR-936 in NSCLC cells. miR-936 knockdown or TMPRSS4 overexpression reversed the anti-tumor effects of circ_0076305 knockdown in NSCLC cells with PTX treatment. Circ_0076305 silencing increased the PTX sensitivity of xenograft tumors in vivo. Conclusion: Circ_0076305 silencing promoted PTX sensitivity by targeting miR-936/TMPRSS4 axis in NSCLC cells.

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