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1.
JTO Clin Res Rep ; 5(6): 100678, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38846810

RESUMO

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.

2.
Cardiovasc Res ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900927

RESUMO

AIMS: MicroRNA-126 (miR-126), one of the most abundant microRNAs in platelets, is involved in the regulation of platelet activity and the circulating miR-126 is reduced during antiplatelet therapy. However, whether intraplatelet miR-126 plays a role in thrombosis and platelet inhibition remains unclear. METHODS AND RESULTS: Here, using tissue-specific knockout mice, we reported that the deficiency of miR-126 in platelets and vascular endothelial cells significantly prevented thrombosis and prolonged bleeding time. Using chimeric mice, we identified that the lack of intraplatelet miR-126 significantly prevented thrombosis. Ex vivo experiments further demonstrated that miR-126-deficient platelets displayed impaired platelet aggregation, spreading and secretory functions. Next, miR-126 was confirmed to target phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) in platelet, which encodes a negative regulator of the PI3 K/AKT pathway, enhancing platelet activation through activating the integrin αIIbß3-mediated outside-in signaling. After undergoing myocardial infarction (MI), chimeric mice lacking intraplatelet miR-126 displayed reduced microvascular obstruction and prevented MI expansion in vivo. In contrast, overexpression of miR-126 by the administration of miR-126 agonist (agomiR-126) in wild-type mice aggravated microvascular obstruction and promoted MI expansion, which can be almost abolished by aspirin administration. In patients with cardiovascular diseases, antiplatelet therapies, either aspirin alone or combined with clopidogrel, decreased the level of intraplatelet miR-126. The reduction of intraplatelet miR-126 level was associated with the decrease of platelet activity. CONCLUSIONS: Our murine and human data reveal that (i) intraplatelet miR-126 contributes to platelet activity and promotes thrombus formation, and (ii) the reduction of intraplatelet miR-126 contributes to platelet inhibition during antiplatelet therapy.

3.
BMC Med ; 22(1): 206, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769523

RESUMO

BACKGROUND: Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. METHODS: We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8-11), moderate (4-7), and low (0-3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). RESULTS: The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE. CONCLUSIONS: Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk.


Assuntos
Sistema ABO de Grupos Sanguíneos , Metanálise como Assunto , Estudos Observacionais como Assunto , Sistema do Grupo Sanguíneo Rh-Hr , Revisões Sistemáticas como Assunto , Humanos , Revisões Sistemáticas como Assunto/métodos , Estudos Observacionais como Assunto/métodos
4.
Chem Biodivers ; : e202400832, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712949

RESUMO

Two new cytochalasans, marcytoglobosins A (1) and B (2) were isolated from the marine sponge associated fungus Chaetomium globosum 162105, along with six known compounds (3-8). The complete structures of two new compounds were determined based on 1D/2D NMR and HR-MS spectroscopic analyses coupled with ECD calculations. All eight isolates were evaluated for their antibacterial activity. Among them, compounds 3-8 displayed antibacterial effects against Staphylococcus epidermidis, Bacillus thuringiensis, Pseudomonas syringae pv. Actinidiae, Vibrio alginolyticus, and Edwardsiella piscicida with minimum inhibitory concentration (MIC) values ranging from 10 to 25 µg/mL.

5.
Heliyon ; 10(8): e28817, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38699705

RESUMO

Background: Elderly patients undergoing surgery are prone to cognitive decline known as perioperative neurocognitive disorders (PND). Several studies have shown that the microglial activation and the decrease of short-chain fatty acids (SCFAs) in gut induced by surgery may be related to the pathogenesis of PND. The purpose of this study was to determine whether microglia and short-chain fatty acids were involved in cognitive dysfunction in aged rats. Methods: Male wild-type Wistar rats aged 11-12 months were randomly divided into control group (Ctrl: Veh group), propionic acid group (Ctrl: PA group), exploratory laparotomy group (LP: Veh group) and propionic acid + exploratory laparotomy group (LP: PA group) according to whether exploratory laparotomy (LP) or PA pretreatment for 21 days was performed. The motor ability of the rats was evaluated by open field test on postoperative day 3 (POD3), and then the cognitive function was evaluated by Y-maze test and fear conditioning test. The expression of IL-1ß, IL-6, RORγt and IL-17A mRNA in hippocampus was detected by RT-qPCR, the expression of IL-17A and IL-17RA in hippocampus was detected by Western blot, and the activation of microglia was detected by immunofluorescence. Results: The PND rat model was successfully established by laparotomy. Compared with Ctrl: Veh group, the body weight of LP: Veh group decreased, the percentage of spontaneous alternations in Y maze decreased (P < 0.001), and the percentage of freezing time in contextual fear test decreased (P < 0.001). Surgery triggers neuroinflammation, manifested as the elevated levels of the inflammatory cytokines IL-1ß (P < 0.001) and IL-6 (P < 0.001), the increased expression of the transcription factor RORγt (P = 0.0181, POD1; P = 0.0073, POD5)and major inflammatory cytokines IL-17A (P = 0.0215, POD1; P = 0.0071, POD5), and the increased average fluorescence intensity of Iba1 (P < 0.001, POD1; P < 0.001, POD5). After PA preconditioning, the recovery of rats in LP: PA group was faster than that in LP: Veh group as the body weight lost on POD1 (P = 0.0148) was close to the baseline level on POD5 (P = 0.1846), and they performed better in behavioral tests. The levels of IL-1ß (P < 0.001) and IL-6 (P = 0.0035) inflammatory factors in hippocampus decreased on POD1 and the average fluorescence intensity of Iba1 decreased (P = 0.0024, POD1; P < 0.001, POD5), representing the neuroinflammation was significantly improved. Besides, the levels of RORγt mRNA (P = 0.0231, POD1; P = 0.0251, POD5) and IL-17A mRNA (P = 0.0208, POD1; P = 0.0071, POD5) in hippocampus as well as the expression of IL-17A (P = 0.0057, POD1; P < 0.001, POD5) and IL-17RA (P = 0.0388) decreased. Conclusion: PA pretreatment results in reduced postoperative neuroinflammation and improved cognitive function, potentially attributed to the regulatory effects of PA on Th17-mediated immune responses.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 595-602, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660872

RESUMO

OBJECTIVE: To explore the stimulation conditions, optimal culture time and infection time of C57BL/6J mice CD3+ T cells in vitro, so as to improve the infection efficiency of CD19 chimeric antigen receptor T cells (mCD19 CAR-T). METHODS: Purified C57BL/6J mice CD3+ T cells were cultured in anti-CD3/CD28 coated, anti-CD3 coated+soluble anti-CD28 and anti-CD3 coated, respectively. The cells were stimulated in above three conditions for 12 h and 24 h, following with 24 h, 48 h and 72 h incubation and then the number of cell clones was recorded. C57BL/6J mice CD3+ T cells were stimulated for 12 h, 24 h, and 36 h under the above three conditions, then interleukin (IL)-2 (100 U/ml) was added. The number of cell clones was recorded under microscope at 24 h, 48 h, and 72 h of culture. After 24 h of stimulation, CD3+ T cells derived from C57BL/6J mice were infected with retrovirus for 48 h to establish mCD19 CAR-T cells, and the percentage of GFP+ CAR-T cells was detected by flow cytometry. RESULTS: The infection efficiency of mCD19 CAR-T cells derived from C57BL/6J mice was only 5.23% under the optimized conditions of mCD19 CAR-T cells derived from BALB/c mice. The number of clones of C57BL/6J mice CD3+ T cells was the highest in anti-CD3 coated+soluble anti-CD28 group after stimulated for 24 h and followed cultured for 48 h. After 24 hours of stimulation under the above conditions and 48 hours of culture with IL-2, the number of T cell proliferating clones in the anti-CD3 coated+soluble anti-CD28 group was significantly increased compared with the same group without IL-2, and the infection efficiency of CAR-T cells in this group reached 17.63%±4.17%. CONCLUSION: The optimal conditions for constructing CAR-T cells from C57BL/6J mice CD3+ T cells are different from those of BABL/c mice. T cells stimulated by anti-CD3 coated+soluble anti-CD28+IL-2 can obtain mCD19 CAR-T cells with the highest efficiency after retrovirus infection.


Assuntos
Antígenos CD19 , Camundongos Endogâmicos C57BL , Receptores de Antígenos Quiméricos , Linfócitos T , Animais , Camundongos , Linfócitos T/imunologia , Interleucina-2 , Complexo CD3 , Imunoterapia Adotiva/métodos , Receptores de Antígenos de Linfócitos T , Antígenos CD28 , Retroviridae
7.
Biomed Environ Sci ; 37(1): 71-84, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38326722

RESUMO

Objective: To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC). Methods: The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay. Results: The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells. Conclusion: Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.


Assuntos
Neoplasias Colorretais , Exossomos , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Exossomos/genética , Exossomos/metabolismo , Proliferação de Células/genética , Neoplasias Colorretais/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
8.
Sci Total Environ ; 912: 168722, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38008317

RESUMO

In this study, the relative bioavailability (RBA) of nitrated polycyclic aromatic hydrocarbons (NPAHs) in soil samples (n = 30) was assessed using an in vivo mouse model. Based on the correlation between the bioaccessibility data obtained from the Tenax improved traditional Fed ORganic Estimation human Simulation Test (FOREhST) in vitro method (TITF) and the bioavailability data obtained from in vivo experiments, the TITF method was further optimized and simplified by referring to the "Pharmacopoeia of the People's Republic of China: Volume IV, 2020" to adjust the formulation and parameters of the gastrointestinal fluid (GIF) in order to establish a simpler and lower cost in vitro method for the determination of the bioaccessibilities of NPAHs. The dose-accumulation relationship of the in vivo experiment showed that the linear dose-response was better in adipose tissue (R2 = 0.77-0.93), and the accumulation of NPAHs in adipose tissue was higher than that in kidney or liver tissue. Depending on the mouse adipose model, the NPAHs-RBA ranged from 1.88 % to 73.92 %, and a strongly significant negative relationship (R2 = 0.94, p < 0.05) was found between the NPAHs-RBA and Log Kow. The simplified experiment of the TITF showed that the composition of the GIF medium had a significant effect on the bioaccessibilities of NPAHs. The NPAH bioaccessibilities measured by the Tenax improved simplified FOREhST method (TISF) (9.0-36.5 %) were higher than that of the traditional FOREhST method (6.8-22.8 %) but significantly lower than that of the TITF method (16.8-55.2 %). With an increase in the bile concentration in the GIF (from 6 to 10 g/L), the bioaccessibilities of NPAHs increased from 9.0 to 36.5 % to 12.9-42.4 %. The accuracies of the four in vitro methods for predicting the bioavailabilities of NPAHs was in the following order: Tenax improved simplified FOREhST method with increased bile concentration (TITF-IB) (R2 = 0.54-0.87) ≈ TITF (R2 = 0.55-0.85) > TISF (R2 = 0.41-0.77) > FOREhST (R2 = 0.02-0.68). These results indicated that the simple in vitro method could also effectively predict the bioavailabilities of NPAHs.


Assuntos
Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Animais , Camundongos , Monitoramento Ambiental/métodos , Solo , Disponibilidade Biológica , Nitratos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise
9.
Food Chem ; 440: 138244, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38142554

RESUMO

Flusilazole is a triazole fungicide with residues that are potentially toxic to humans. It enters the human body mainly through food, although its bactericidal activity is substantial. In this study, an electrochemical sensor Fe/Fe2O3@C with a core-shell structure was constructed to efficiently detect flusilazole by annealing MIL-53(Fe) which was prepared by a simple solvothermal method. Transmission electron microscopy and scanning electron microscopy were used to characterize the apparent morphology of MIL-53(Fe) and Fe/Fe2O3@C, and their structures were further characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, powder X-ray diffraction, and the mapping of elements by energy dispersive spectroscopy. The electrochemical behavior of Fe/Fe2O3@C in the detection of flusilazole was evaluated by differential pulse voltammetry under optimal conditions. The results of the study indicate that the Fe/Fe2O3@C electrochemical sensor displayed excellent detection capabilities for flusilazole, where the sensor exhibited a wide detection range from 1.00 × 10-4 to 1.00 × 10-12 mol/L with an incredibly low LOD of 593 fM, making it highly sensitive to trace amounts of flusilazole. Moreover, Fe/Fe2O3@C demonstrated superior reproducibility, stability, and resistance to interference, highlighting its reliability in practical applications. The sensor was also successfully utilized to quantitatively detect flusilazole in various real samples, which suggests that Fe/Fe2O3@C has broad-spectrum environmental resistance and can effectively and rapidly detect flusilazole residues in different types of food items and environmental matrices. The study also delved into the mechanism of Fe/Fe2O3@C for the detection of flusilazole, providing a deeper understanding of the functionality of this sensor. Overall, these findings emphasize the practical significance of Fe/Fe2O3@C as an electrochemical sensor, showcasing its potential for real-world applications in food safety and environmental monitoring.


Assuntos
Inocuidade dos Alimentos , Silanos , Triazóis , Humanos , Reprodutibilidade dos Testes , Microscopia Eletrônica de Varredura , Técnicas Eletroquímicas/métodos
10.
JAMA Netw Open ; 6(11): e2343219, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37976067

RESUMO

Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied. Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI. Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023. Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI. Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively). Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.


Assuntos
Stents Farmacológicos , Intervenção Coronária Percutânea , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Inibidores da Agregação Plaquetária/efeitos adversos , Clopidogrel/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Úlcera/etiologia , Stents Farmacológicos/efeitos adversos , Aspirina/efeitos adversos , Hemorragia/induzido quimicamente
11.
Cell Death Dis ; 14(10): 700, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880221

RESUMO

We here tested the potential activity and the underlying mechanisms of neuroligin-3 (NLGN3) against ischemia-reperfusion-induced neuronal cell injury. In SH-SY5Y neuronal cells and primary murine cortical neurons, NLGN3 activated Akt-mTOR and Erk signalings, and inhibited oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced cytotoxicity. Akt activation was required for NLGN3-induced neuroprotection. Gαi1/3 mediated NLGN3-induced downstream signaling activation. NLGN3-induced Akt-S6K1 activation was largely inhibited by Gαi1/3 silencing or knockout. Significantly, NLGN3-induced neuroprotection against OGD/R was almost abolished by Gαi1/3 silencing or knockout. In vivo, the middle cerebral artery occlusion (MCAO) procedure induced NLGN3 cleavage and secretion, and increased its expression and Akt activation in mouse brain tissues. ADAM10 (A Disintegrin and Metalloproteinase 10) inhibition blocked MCAO-induced NLGN3 cleavage and secretion, exacerbating ischemic brain injury in mice. Neuronal silencing of NLGN3 or Gαi1/3 in mice also inhibited Akt activation and intensified MCAO-induced ischemic brain injury. Conversely, neuronal overexpression of NLGN3 increased Akt activation and alleviated MCAO-induced ischemic brain injury. Together, NLGN3 activates Gαi1/3-Akt signaling to protect neuronal cells from ischemia-reperfusion injury.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , Neuroblastoma , Traumatismo por Reperfusão , Animais , Humanos , Camundongos , Lesões Encefálicas/metabolismo , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Neuroblastoma/metabolismo , Neurônios/metabolismo , Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/metabolismo
12.
Front Public Health ; 11: 1252741, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37736088

RESUMO

Introduction: There is limited evidence regarding particulate matter (PM)'s short-term effects on pulmonary tuberculosis (PTB) hospital admission. Our study aimed to determine the short-term associations of the exposure to ambient PM with aerodynamic diameters <2.5 µm (PM2.5) and < 10 µm (PM10) with hospital admission for PTB in Hainan, a tropical province in China. Methods: We collected individual data on patients hospitalized with PTB, PM2.5, PM10, and meteorological data from 2016 to 2019 in Hainan Province, China. Conditional logistic regression models with a time-stratified case-crossover design were used to assess the short-term effects of PM2.5 and PM10 on hospital admission for PTB at a spatial resolution of 1 km × 1 km. Stratified analyses were performed according to age at admission, sex, marital status, administrative division, and season of admission. Results: Each interquartile range (IQR) increases in the concentrations of PM2.5 and PM10 were associated with 1.155 (95% confidence interval [CI]: 1.041-1.282) and 1.142 (95% CI: 1.033-1.263) hospital admission risks for PTB at lag 0-8 days, respectively. The stratified analyses showed that the effects of PM2.5 and PM10 were statistically significant for patients aged ≥65 years, males, married, and those residing in prefecture-level cities. Regarding seasonal differences, the associations between PM and hospital admission for PTB were statistically significant in the warm season but not in the cold season. The effect of PM2.5 was consistently stronger than that of PM10 in most subgroups. Conclusion: Short-term exposure to PM increases the risk of hospital admission for PTB. The potential impact of PM with smaller aerodynamic diameter is more detrimental. Our findings highlight the importance of reducing ambient PM level to alleviate the burden of PTB.


Assuntos
Material Particulado , Tuberculose Pulmonar , Masculino , Humanos , Material Particulado/efeitos adversos , Estudos Cross-Over , China/epidemiologia , Tuberculose Pulmonar/epidemiologia , Hospitais
13.
Front Neurosci ; 17: 1221512, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547144

RESUMO

Introduction: Efficiently recognizing emotions is a critical pursuit in brain-computer interface (BCI), as it has many applications for intelligent healthcare services. In this work, an innovative approach inspired by the genetic code in bioinformatics, which utilizes brain rhythm code features consisting of δ, θ, α, ß, or γ, is proposed for electroencephalography (EEG)-based emotion recognition. Methods: These features are first extracted from the sequencing technique. After evaluating them using four conventional machine learning classifiers, an optimal channel-specific feature that produces the highest accuracy in each emotional case is identified, so emotion recognition through minimal data is realized. By doing so, the complexity of emotion recognition can be significantly reduced, making it more achievable for practical hardware setups. Results: The best classification accuracies achieved for the DEAP and MAHNOB datasets range from 83-92%, and for the SEED dataset, it is 78%. The experimental results are impressive, considering the minimal data employed. Further investigation of the optimal features shows that their representative channels are primarily on the frontal region, and associated rhythmic characteristics are typical of multiple kinds. Additionally, individual differences are found, as the optimal feature varies with subjects. Discussion: Compared to previous studies, this work provides insights into designing portable devices, as only one electrode is appropriate to generate satisfactory performances. Consequently, it would advance the understanding of brain rhythms, which offers an innovative solution for classifying EEG signals in diverse BCI applications, including emotion recognition.

14.
Food Chem ; 428: 136802, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37421661

RESUMO

Diflubenzuron is widely used as a benzoylurea insecticide, and its impact on human health should not be underestimated. Therefore, the detection of its residues in food and the environment is crucial. In this paper, octahedral Cu-BTB was fabricated using a simple hydrothermal method. It served as a precursor for synthesizing Cu/Cu2O/CuO@C with a core-shell structure through annealing, creating an electrochemical sensor for the detection of diflubenzuron. The response of Cu/Cu2O/CuO@C/GCE, expressed as ΔI/I0 exhibited a linear correlation with the logarithm of the diflubenzuron concentration ranging from 1.0 × 10-4 to 1.0 × 10-12 mol·L-1. The limit of detection (LOD) was determined to be 130 fM using differential pulse voltammetry (DPV). The electrochemical sensor demonstrated excellent stability, reproducibility, and anti-interference properties. Moreover, Cu/Cu2O/CuO@C/GCE was successfully employed to quantitatively determine diflubenzuron in actual food samples (tomato and cucumber) and environmental samples (Songhua River water, tap water, and local soil) with good recoveries. Finally, the possible mechanism of Cu/Cu2O/CuO@C/GCE for monitoring diflubenzuron was thoroughly investigated.


Assuntos
Diflubenzuron , Humanos , Reprodutibilidade dos Testes , Cobre/química , Água , Técnicas Eletroquímicas/métodos , Eletrodos
15.
J Cosmet Dermatol ; 22(11): 3152-3158, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37231973

RESUMO

OBJECTIVE: This study aims to compare the plasma metabolic profiles of patients with herpes labialis with healthy controls and identify the biomarkers of herpes labialis. SUBJECTS AND METHODS: We collected 18 patients with herpes labialis and 20 healthy individuals. Plasma samples from both groups were analyzed using gas chromatography-mass spectrometry (GC-MS). RESULTS: According to the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), we found that metabolic profiles had changed in patients with herpes labialis compared to the controls. By further selecting the different metabolites according to the variable importance in the projection (VIP) and p valve of t-tests, we found that acetic acid, pyroglutamic acid, alanine, ethanedioic acid, cyclohexaneacetic acid, pyruvic acid, d-mannose, phosphoric acid, l-amphetamine, and citric acid were decreased in patients with herpes labialis, while sedoheptulose and ethylamine were increased. Pathway analysis showed that herpes labialis may affect the amino acid and energy metabolism. CONCLUSIONS: Our findings may contribute to elucidating the metabolic basis of herpes labialis and provide a new perspective for further research on the "Shang-Huo" state in traditional Chinese medicine (TCM).

16.
ACS Omega ; 8(19): 16612-16619, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37214714

RESUMO

The metallic elements in high-temperature coal tar pitch (HCTP) will affect the properties of carbon materials produced from the HCTP. The study on the metallic elements in HCTP is essential for the quality improvement of its derived carbon materials. In this paper, the content of 15 metallic elements in HCTP and its four group components, including n-heptane-soluble substance (HS), n-heptane-insoluble-toluene-soluble substance (HI-TS), toluene-insoluble-quinoline-soluble substance (TI-QS), and quinoline-insoluble substance (QI), was determined. The results show that the content of Na, Ca, Fe, Mg, Zn, K, Pb, and Al is more than 100 ppm and is much higher than that of other metallic elements. The content of Ni, V, Cr, Mo, Sb, Cu, and Mn ranges from 0 to 50 ppm. By mass calculation of the contents of four group components in HCTP, it can be concluded that Na and Fe are randomly distributed in the group components. Al, Zn, Pb, V, and Mn are mainly distributed in the inorganic form in the QI component. Ca, Mg, K, Ni, Cr, Mo, Sb, and Cu are mainly distributed in the small molecular group components such as HS and HI-TS.

17.
World J Pediatr ; 19(10): 961-971, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36877432

RESUMO

BACKGROUND: The intrauterine environment has a profound and long-lasting influence on the health of the offspring. However, its impact on the postnatal catch-up growth of twin children remains unclarified. Therefore, this study aimed to explore the maternal factors in pregnancy associated with twin offspring growth. METHODS: This study included 3142 live twin children born to 1571 mothers from the Beijing Birth Cohort Study conducted from 2016 to 2021 in Beijing, China. Original and corrected weight-for-age standard deviation scores of the twin offspring from birth to 36 months of age were calculated according to the World Health Organization Child Growth Standards. The corresponding weight trajectories were identified by the latent trajectory model. Maternal factors in pregnancy associated with the weight trajectories of the twin offspring were examined after adjustment for potential confounders. RESULTS: Five weight trajectories of the twin children were identified, with 4.9% (154/3142) exhibiting insufficient catch-up growth, 30.6% (961/3142), and 46.8% (1469/3142) showing adequate catch-up growth from different birth weights, and 15.0% (472/3142) and 2.7% (86/3142) showing various degrees of excessive catch-up growth. Maternal short stature [adjusted odds ratio (OR) = 0.691, 95% confidence interval (CI) = 0.563-0.848, P = 0.0004] and lower total gestational weight gain (GWG) (adjusted OR = 0.774, 95% CI = 0.616-0.972, P = 0.03) were associated with insufficient catch-up growth of the offspring. Maternal stature (adjusted OR = 1.331, 95% CI = 1.168-1.518, P < 0.001), higher pre-pregnancy body mass index (BMI) (adjusted OR = 1.230, 95% CI = 1.090-1.387, P < 0.001), total GWG (adjusted OR = 1.207, 95% CI = 1.068-1.364, P = 0.002), GWG rate (adjusted OR = 1.165, 95% CI = 1.027-1.321, P = 0.02), total cholesterol (TC) (adjusted OR = 1.150, 95% CI = 1.018-1.300, P = 0.03) and low-density lipoprotein-cholesterol (LDL-C) (adjusted OR = 1.177, 95% CI = 1.041-1.330) in early pregnancy were associated with excessive growth of the offspring. The pattern of weight trajectories was similar between monochorionic and dichorionic twins. Maternal height, pre-pregnancy BMI, GWG, TC and LDL-C in early pregnancy were positively associated with excess growth in dichorionic twins, yet a similar association was observed only between maternal height and postnatal growth in monochorionic twins. CONCLUSION: This study identified the effect of maternal stature, weight status, and blood lipid profiles during pregnancy on postnatal weight trajectories of the twin offspring, thereby providing a basis for twin pregnancy management to improve the long-term health of the offspring.


Assuntos
Trajetória do Peso do Corpo , Gravidez de Gêmeos , Pré-Escolar , Feminino , Humanos , Lactente , Gravidez , Peso ao Nascer , Índice de Massa Corporal , LDL-Colesterol , Estudos de Coortes , Aumento de Peso , Recém-Nascido
18.
Ecotoxicol Environ Saf ; 255: 114789, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36933484

RESUMO

Exposure of human to parabens (commonly used preservatives) is inevitable due to their extensively applied in numerous consumer products. Thus, a reliable noninvasive matrix reflecting long-term exposure to parabens is essential for human biomonitoring study. Human nails are potentially a valuable alternative for measuring intergrated exposure to parabens. In this work, we collected 100 paired nail and urine samples from university students in Nanjing, China, and measured simultaneously for six parent parabens and four metabolites. Methylparaben (MeP), ethylparaben (EtP), and propylparaben (PrP) were three predominant paraben analogue in both matrices, with the median concentrations being 12.9, 0.753, and 3.42 ng/mL in urine, and 1540, 154, and 961 ng/g in nail, respectively, while 4-hydroxybenzoic acid (4-HB) and 3,4-dihydroxybenzoic acid (3,4-DHB) were the most abundant metabolites (median values of 143 and 35.9 ng/mL, respectively) in urine. Gender-related analysis suggested that females exposed to more higher parabens than males. Significantly positive correlations were found between levels of MeP, PrP, EtP, and OH-MeP (r = 0.54-0.62, p < 0.01) in paired urine and nail samples. Our result here suggests that human nails, as an emerging biospecimen, are a potentially valuable biological matrix to evaluate human long-term exposure to parabens.


Assuntos
Unhas , Parabenos , Masculino , Feminino , Humanos , Parabenos/análise , Unhas/química , Exposição Ambiental/análise
19.
J Affect Disord ; 331: 121-129, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36948469

RESUMO

BACKGROUND: Existing research has suggested that depression results in disorders of glucose metabolism in the organism which causing insufficient energy supply. However, the overall changes in glucose metabolism that arise from depression have not been clarified. METHODS: In this study, the depression-like behavior in chronically unpredictable mild stressed rats was investigated, and the fate of glucose was tracked through isotope tracing and mass spectrometry, with a focus on metabolite changes in cecal contents. RESULTS: As indicated by the results, the isotopic results of cecal contents can indicate the metabolic end of the organism. Moreover, the TCA cycle activity was notably reduced, and the gluconeogenesis pathway was abnormally up-regulated in the CUMS-induced rats. The organism expedited other glucose metabolism pathways to make up for the insufficiency of energy. As a result, the activity of the inefficient glycolysis pathway was increased. LIMITATIONS: Existing research has only investigated the metabolism of 13C-glucose, and lipids and proteins have been rarely explored. CONCLUSIONS: The chronic unpredictable mild stress can inhibit the entry of pyruvate into mitochondria in SD rats, such that the activity of TCA is reduced, and insufficient energy supply is caused. The organism is capable of expediting other glucose metabolism rate pathways to make up for the insufficiency of energy, whereas it still cannot compensate for the loss of energy. As a result, CUMS-induced rats exhibited high-rate and low-efficiency glucose metabolism.


Assuntos
Depressão , Metabolômica , Ratos , Animais , Ratos Sprague-Dawley , Metabolômica/métodos , Glucose , Estresse Psicológico/metabolismo , Modelos Animais de Doenças
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 380-385, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-36949702

RESUMO

Objective: To explore the status quo and influencing factors of feeding behaviors of micronutrient powders (MNP), or yingyangbao in Pinyin, the Chinese Romanization system, of baby caregivers in remote rural areas of Sichuan Province. Methods: In 2019, caregivers of babies aged 6 to 24 months from 6 counties of Sichuan Province were selected as the respondents of the survey through a multistage cluster random sampling method. Data concerning the baby caregivers' attitude of behavior, subjective norms, behavioral intention, and feeding behaviors about MNP feeding were collected with a questionnaire through a structured interview. Based on the theory of reasoned action, a structural equation model was constructed to explore the influencing factors of feeding behaviors. Results: A total of 1002 valid samples were included in the study. The effective feeding rate of MNP among the baby caregivers was 55.49%. The results of model analysis suggested that attitude of behavior ( ß direct=0.212, 95% CI: 0.105-0.327), subjective norm ( ß direct=0.123, 95% CI: 0.016-0.228), and behavioral intention ( ß direct=0.162, 95% CI: 0.093-0.224) could have a significant direct impact on MNP feeding behaviors. Behavior attitude ( ß indirect=0.044, 95% CI: 0.023-0.073) and subjective norms ( ß indirect=0.018, 95% CI: 0.001-0.040) could have a significant indirect impact on MNP feeding behaviors through the intermediary of behavioral intention. Among the three theoretical elements, attitude of behavior had the largest total effect on the feeding behavior ( ß total=0.256, 95% CI: 0.148-0.366). Conclusion: The effective feeding rate of MNP among baby caregivers in remote rural areas of Sichuan Province is low. The attitude of behavior and subjective norms of caregivers may have a direct impact on their feeding behavior, and both attitude of behavior and subjective norms can have an indirect impact on the feeding behavior through the intermediary of behavioral intention. The influence of attitude of behavior attitude on feeding behavior is greater than that of subjective norms. Future intervention plans for promoting effective MNP feeding should incorporate health education for baby caregivers and their important social relations. Thus, baby caregivers' attitude and willingness for MNP feeding will be strengthened and the effective feeding rate of MNP will be improved accordingly.


Assuntos
Cuidadores , Micronutrientes , Lactente , Humanos , Pós , Teoria do Comportamento Planejado , Comportamento Alimentar , China
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