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1.
Med Gas Res ; 13(2): 72-77, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36204786

RESUMO

Diabetic peripheral neuropathy (DPN) is a complex disorder caused by long-standing diabetes. Oxidative stress was considered the critical creed in this DPN pathophysiology. Hydrogen has antioxidative effects on diabetes mellitus and related complications. However, there is still no concern on the beneficial effects of hydrogen in DPN. This paper aimed to evaluate the effects of exogenous hydrogen to reduce the severity of DPN in streptozotocin-induced diabetic rats. Compared with hydrogen-rich saline treatment, hydrogen inhalation significantly reduced blood glucose levels in diabetic rats in the 4th and 8th weeks. With regard to nerve function, hydrogen administration significantly attenuated the decrease in the velocity of motor nerve conduction in diabetic animals. In addition, hydrogen significantly attenuated oxidative stress by reducing the level of malondialdehyde, reactive oxygen species, and 8-hydroxy-2-deoxyguanosine and meaningfully enhanced the antioxidant capability by partially restoring the activities of superoxide dismutase. Further studies showed that hydrogen significantly upregulated the expression of nuclear factor erythroid-2-related factor 2 and downstream proteins such as catalase and hemeoxygenase-1 in the nerves of diabetic animals. Our paper showed that hydrogen exerts significant protective effects in DPN by downregulating oxidative stress via the pathway of nuclear factor erythroid-2-related factor 2, which suggests its potential value in clinical applications.


Assuntos
Diabetes Mellitus Experimental , Neuropatias Diabéticas , Fármacos Neuroprotetores , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Glicemia , Catalase/metabolismo , Catalase/farmacologia , Catalase/uso terapêutico , Desoxiguanosina/metabolismo , Desoxiguanosina/farmacologia , Desoxiguanosina/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/metabolismo , Hidrogênio , Malondialdeído , NAD/metabolismo , NAD/farmacologia , NAD/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Ratos , Espécies Reativas de Oxigênio , Estreptozocina , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Superóxido Dismutase/uso terapêutico
2.
Med Gas Res ; 13(1): 23-28, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35946219

RESUMO

Demyelination of the cerebral white matter is the most common pathological change after carbon monoxide (CO) poisoning. Notch signaling, the mechanism underlying the differentiation of astrocytes and oligodendrocytes, is critical to remyelination of the white matter after brain lesion. The purpose of this work was to determine the effects of hyperbaric oxygen (HBO) on Notch signaling pathway after CO poisoning for the explanation of the protective effects of HBO on CO-poisoning-related cerebral white matter demyelination. The male C57 BL/6 mice with severe CO poisoning were treated by HBO. And HBO therapy shortened the escape latency and improved the body mass after CO poisoning. HBO therapy also significantly suppressed protein and mRNA levels of Notch1 and Hes5 after CO poisoning. Our findings suggested that HBO could suppress the activation of Notch signaling pathway after CO poisoning, which is the mechanism underlying the neuroprotection of HBO on demyelination after severe CO poisoning.


Assuntos
Intoxicação por Monóxido de Carbono , Doenças Desmielinizantes , Oxigenoterapia Hiperbárica , Animais , Intoxicação por Monóxido de Carbono/terapia , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/terapia , Masculino , Camundongos , Oxigênio , Transdução de Sinais
3.
Transl Stroke Res ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36385451

RESUMO

M1 microglial activation is crucial for the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH), and there is growing evidence that glucose metabolism is frequently involved in microglial activation. However, the molecular mechanism of glycolysis and its role in M1 microglial activation in the context of EBI are not yet fully understood. In this study, firstly, the relationship between aerobic glycolysis and M1 microglial activation as well as SAH-induced EBI was researched in vivo. Then, intervention on mammalian target of rapamycin (mTOR) was performed to investigate the effects on glycolysis-dependent M1 microglial activation and EBI and its relationship with hypoxia-inducible factor-1α (HIF-1α) in vivo. Next, Hif-1α was inhibited to analyze its role in aerobic glycolysis, M1 microglial activation, and EBI in vivo. Lastly, both in vivo and in vitro, mTOR inhibition and Hif-1α enhancement were administered simultaneously, and the combined effects were further confirmed again. The results showed that aerobic glycolysis and M1 microglial polarization were increased after SAH, and glycolytic inhibition could attenuate M1 microglial activation and EBI. Inhibition of mTOR reduced glycolysis-dependent M1 microglial polarization and EBI severity by down-regulating HIF-1α expression, while enhancement had the opposite effects. Blockading HIF-1α had the similar effects as suppressing mTOR, while HIF-1α agonist worked against mTOR antagonist when administered simultaneously. In conclusion, the present study showed new evidence that aerobic glycolysis induced by mTOR/HIF-1α might promote EBI after SAH by activating M1 microglia. This finding provided new insights for the treatment of EBI.

4.
Front Pharmacol ; 13: 963614, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386155

RESUMO

High invasiveness is a biological and clinical characteristic of glioblastoma and predicts poor prognosis of patients. Quercetin, a natural flavonoid compound, exhibits anticancer activity. However, we have a limited understanding of the possible underlying mechanism of quercetin in glioblastoma. In this study, we investigated the anticancer effect of quercetin in human glioblastoma cells. Our results showed that quercetin markedly suppressed the viability of glioblastoma cells in vitro and in vivo, and significantly inhibited glioblastoma cell migration and invasion. Moreover, quercetin reversed EMT-like mesenchymal phenotype and reduced the expression levels of EMT-related markers. Furthermore, we found that quercetin suppressed GSK-3ß/ß-catenin/ZEB1 signaling in glioblastoma. Taken together, our results demonstrate that quercetin inhibited migration and invasion of human glioma cells by suppressing GSK3ß/ß-catenin/ZEB1 signaling. Our study provides evidence that quercetin is a promising therapeutic natural compound to treat glioblastoma.

5.
Front Psychol ; 13: 1000541, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389570

RESUMO

Since the COVID-19 pandemic, the tourism economy has been seriously affected. China has implemented a direct traveling management mechanism and recovered from the pandemic faster than the rest of the world. However, the COVID-19 situation is complicated and uncontrollable because of the available unclear information including difficult medical terminologies. This study attempts to find the determinants of the travel intention of China's tourists in the post-COVID-19 epidemic. Along with information overload and perception risk, an expanded research model of the Theory of Planned Behavior (TPB) was employed to propose the theoretical framework of this study. A survey was conducted among 518 tourists who spend their holiday in Hainan, which is a popular tourist destination in China. The empirical results show that information overload positively and significantly impacted perceived risk. Furthermore, perceived risk negatively affects the intention to travel. Perceived risk also negatively affected the attitude toward traveling. However, response self-efficacy did not have a significant effect on the intention to travel. Finally, based on the analysis results, this study proposes relevant research contributions and practical recommendations with management implications for the travel industries.

6.
Lipids Health Dis ; 21(1): 119, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376975

RESUMO

BACKGROUND AND AIMS: The role of serum lipoprotein(a) [Lp(a)] levels in atrial fibrillation (AF) is still uncertain, especially in the Chinese population. Here, we aimed to elucidate the potential relationship between Lp(a) quantiles and AF. METHODS: All data were collected through inpatients with electronic health records from the Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. The propensity score matching (PSM) method was used to match control and case groups. Interactions between AF, Lp(a) quantiles, and other clinical indices were analyzed by logistic regression and stratified analysis. Statistical analyses were performed with IBM SPSS statistical software and R software. RESULTS: From 2017 to 2021, 4,511 patients with AF and 9,022 patients without AF were 1:2 matched by the propensity score matching method. A total of 46.9% of the study group was women, and the baseline mean age was 65 years. The AF group exhibited lower median Lp(a) than the non-AF group (15.95 vs. 16.90 mg/dL; P < 0.001). Based on the Lp(a) quantiles, the study population was divided into four groups: Q1 (≤ 8.71 mg/dL), Q2 (8.71-16.54 mg/dL), Q3 (16.54-32.42 mg/dL) and Q4 (> 32.42 mg/dL). The AF prevalence of each group decreased from 34.2% (Q1) to 30.9% (Q4) (P < 0.001). Lp(a) quantiles 1-3 significantly increased AF to 1.162-fold (1.049-1.286), 1.198-fold (1.083-1.327), and 1.111-fold (1.003-1.231) in the unadjusted logistic regression model, respectively. In the adjusted model, Lp(a) < 32.42 mg/dL still showed a significant inverse association with AF. In the stratified analysis, Lp(a) levels in female patients exhibited a significant negative correlation with AF (OR of Q1: 1.394[1.194-1.626], P = 0.001). Age and hypertension did not affect the adverse correlation. CONCLUSION: Low circulating Lp(a) levels were associated with AF, especially in the female Han population, suggesting that Lp(a) may be useful for risk stratification of AF in female individuals.


Assuntos
Fibrilação Atrial , Hipertensão , Humanos , Feminino , Idoso , Lipoproteína(a) , Estudos Retrospectivos , Prevalência , Fatores de Risco
7.
J Adv Res ; 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36396045

RESUMO

INTRODUCTION: Acquired resistance to BRAF inhibitor vemurafenib is frequently observed in metastatic colorectal cancer (CRC), and it is a thorny issue that results in treatment failure. As adaptive responses for vemurafenib treatment, a series of cellular bypasses are response for the adaptive feedback reactivation of ERK signaling, which warrant further investigation. OBJECTIVES: We identified ARF1 (ADP-ribosylation factor 1) as a novel regulator of both vemurafenib resistance and cancer metastasis, its molecular mechanism and potential inhibitor were investigated in this study. METHODS: DIA-based quantitative proteomics and RNA-seq were performed to systematic analyze the profiling of vemurafenib-resistant RKO cells (RKO-VR) and highly invasive RKO cells (RKO-I8), respectively. Co­immunoprecipitation assay was performed to detect the interaction of ARF1 and IQGAP1 (IQ-domain GTPase activating protein 1). An ELISA-based drug screen system on FDA-approved drug library was established to screen the compounds against the interaction of ARF1-IQGAP1.The biological functions of ARF1 and LY2835219 were determined by transwell, western blotting, Annexin V-FITC/PI staining and in vivo experimental metastasis assays. RESULTS: We found that ARF1 strongly interacted with IQGAP1 to activate ERK signaling in VR and I8 CRC cells. Deletion of IQGAP1 or inactivation of ARF1 (ARF-T48S) restored the invasive ability induced by ARF1. As ARF1-IQGAP1 interaction is essential for ERK activation, we screened LY2835219 as novel inhibitor of ARF1-IQGAP1 interaction, which inactivated ERK signaling and suppressed CRC metastasis and vemurafenib-resistance in vitro and in vivo with no observed side effect. Furthermore, LY2835219 in combined treatment with vemurafenib exerted significantly inhibitory effect on ARF1-mediated cancer metastasis than used independently. CONCLUSION: This study uncovers that ARF1-IQGAP1 interaction-mediated ERK signaling reactivation is critical for vemurafenib resistance and cancer metastasis, and that LY2835219 is a promising therapeutic agent for CRC both as a single agent and in combination with vemurafenib.

8.
BMC Med Inform Decis Mak ; 22(1): 305, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36434650

RESUMO

PURPOSE: The association of patent foreman ovale (PFO) and cryptogenic stroke has been studied for years. Although device closure overall decreases the risk for recurrent stroke, treatment effects varied across different studies. In this study, we aimed to detect sub-clusters in post-closure PFO patients and identify potential predictors for adverse outcomes. METHODS: We analyzed patients with embolic stroke of undetermined sources and PFO from 7 centers in China. Machine learning and Cox regression analysis were used. RESULTS: Using unsupervised hierarchical clustering on principal components, two main clusters were identified and a total of 196 patients were included. The average age was 42.7 (12.37) years and 64.80% (127/196) were female. During a median follow-up of 739 days, 12 (6.9%) adverse events happened, including 6 (3.45%) recurrent stroke, 5 (2.87%) transient ischemic attack (TIA) and one death (0.6%). Compared to cluster 1 (n = 77, 39.20%), patients in cluster 2 (n = 119, 60.71%) were more likely to be male, had higher systolic and diastolic blood pressure, higher body mass index, lower high-density lipoprotein cholesterol and increased proportion of presence of atrial septal aneurysm. Using random forest survival (RFS) analysis, eight top ranking features were selected and used for prediction model construction. As a result, the RFS model outperformed the traditional Cox regression model (C-index: 0.87 vs. 0.54). CONCLUSIONS: There were 2 main clusters in post-closure PFO patients. Traditional cardiovascular profiles remain top ranking predictors for future recurrence of stroke or TIA. However, whether maximizing the management of these factors would provide extra benefits warrants further investigations.

9.
Nutrients ; 14(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36364726

RESUMO

Exclusive enteral nutrition (EEN) can induce remission in patients with pediatric Crohn's disease (CD). This study aims to depict EEN's modification of bile acid (BA) metabolism in pediatric CD and explores the effect of the EEN-enriched BA in inhibiting the inflammatory response. The twelve enrolled pediatric CD patients showed BA dysmetabolism, represented by decreased levels of fecal secondary and unconjugated BAs as determined by UPLC-TQMS, which were accompanied by gut microbiota dysbiosis and reduced BA-metabolizing bacteria including Eubacterium and Ruminococcus genera, assessed by shotgun metagenomic sequencing. EEN treatment induced remission in these patients at eight weeks, and nine patients remained in stable remission for longer than 48 weeks. EEN improved BA dysmetabolism, with some enriched BAs, including hyocholic acid (HCA), α-muricholic acid (αMCA), strongly associated with decreased severity of CD symptoms. These BAs were significantly correlated with the increased abundance of certain bacteria, including Clostridium innocuum and Hungatella hathewayi, which express 3ß-hydroxysteroid dehydrogenase and 5ß-reductase. HCA could suppress TNF-α production by CD4+ T cells in the peripheral blood mononuclear cells (PBMCs) of CD patients. Moreover, intraperitoneal injection of HCA could attenuate dextran sulfate sodium (DSS)-induced mouse colitis. Our data suggests that BA modification may contribute to the EEN-induced remission of pediatric CD.


Assuntos
Nutrição Enteral , Microbiota , Camundongos , Animais , Indução de Remissão , Leucócitos Mononucleares , Bactérias , Anti-Inflamatórios , Ácidos e Sais Biliares
10.
Front Surg ; 9: 1005898, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425892

RESUMO

Objective: To compare the return to work (RTW) time between single-port laparoscopic surgery (SPLS) and multiport laparoscopic surgery (MPLS) for benign ovarian tumors. Methods: A cross-sectional cohort study was conducted, which consisted of 335 women of reproductive age with benign ovarian tumors and who were keen on returning to work as early as possible. Surgical outcomes, postoperative pain score, postoperative satisfaction with the cosmesis score (CS), and the RTW time of the SPLS group were compared with those of the MPLS group. Besides, the RTW time and CS were calculated from the questionnaire survey by a single specialized gynecologist. Results: Women who met the inclusion criteria were included in the SPLS (n = 106) and MPLS groups (n = 229). The RTW time in the SPLS group (22.13 ± 27. 06 days) was significantly shorter than that in the MPLS group (46.08 ± 57.86 days) (P < 0.001). The multivariate Cox analysis results showed that age (HR = 0.984, 95% CI, 0.971-0.997, P = 0.020), SPLS (HR = 3.491, 95% CI, 2.422-5. 032, P < 0.001), and return to normal activity time (HR = 0.980, 95% CI, 0.961-0.998, P = 0.029) were independent factors of the RTW time. Conclusions: SPLS may be advantageous in terms of shortening the RTW time for women with benign ovarian tumors.

11.
Psych J ; 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36428096

RESUMO

Emotion processing and beliefs about pleasure can influence the development and severity of depressive symptoms. This cluster analysis study aimed to profile a large sample of college students using pleasure experience, emotion expression and regulation as well as beliefs about pleasure. We also aimed to validate the resultant clusters in terms of depressive symptoms. A set of checklists capturing beliefs about pleasure and the three facets of emotion processing was administered to 1028 college students. A two-stage cluster analysis was used to analyze the profile of these emotional aspects in these college students. Our results showed that a three-cluster solution best fit the data. Cluster 1 (n = 536) was characterized by moderate levels of beliefs about pleasure, pleasure experience, emotion expression, and regulation; Cluster 2 (n = 402) was characterized by generally high levels of beliefs about pleasure, pleasure experience, emotion expression, and regulation; Cluster 3 (n = 90) was characterized by relatively low levels of beliefs about pleasure, pleasure experience, emotion expression, and regulation. The three clusters differed significantly in the severity of depressive symptoms. Our findings suggest the existence of three emotional subtypes, which may be useful in early detection of youth at risk of developing depression.

12.
Vet Microbiol ; 275: 109593, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36323175

RESUMO

Porcine sapelovirus (PSV) is an important emerging swine pathogen that causes diarrhoea, respiratory distress, severe reproductive system and neurological disorders in pigs, posing huge threat to swine industry. However, there are no effective serological diagnostic products and the epitope characterization of PSV VP1 protein is still largely unknown. In current study, we successfully expressed recombinant His-VP1 protein by prokaryotic expression system and the recombinant VP1 protein had good immunogenicity. BALB/C mice were then selected and immunized with purified recombinant VP1 protein, and two monoclonal antibodies (Mabs) 9F10 and 15E4 against VP1 were successfully prepared by hybrioma technology. The isotype of these two Mabs were identified and showed that Mab 9F10 with the heavy chain subtype was IgG1 and the light chain subtype was kappa. Mab 15E4 was identified as IgG2 for the heavy chain subtype and Kappa for the light chain subtype. The antigen epitopes of prepared two VP1 Mabs were clearly identified. The minimal unit of B cell specific epitope recognized by Mab 15E4 was 203YDGDG207 and conserved in different strain genotypes of PSV, indicating this epitope may be a good target for serological detection of PSV. However, the epitope recognized by Mab 9F10 was 8QAIVNRT14 and varied greatly among different PSV strains. Structural modeling analysis showed that the identified two novel B cell epitopes were located on the surface of VP1. Our study provides useful tool for the establishment the serological detection methods of PSV and may support the study of VP1 protein function.

14.
Food Chem ; 405(Pt B): 134862, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36410219

RESUMO

A facile, efficient and reliable method was designed and established to analyze the plant growth regulators (PGRs) in citrus fruit, based on a simplified dispersive solid-phase extraction (d-SPE) using a shaped zirconium-based metal-organic framework (UiO-66-PDMS bead) as the sorbent. In this method, UiO-66-PDMS beads directly extracted the targets from the homogenized and could be easily separated with a tweezer. It avoided the centrifugation or filtration operation required in normal d-SPE, greatly simplifying the d-SPE process. Moreover, the matrix substances were efficiently removed by this d-SPE process. The method showed good linearities (R2 ≥ 0.9995) and limits of detection (0.09-0.17 ng/g). The recoveries were in the range of 80.7-97.5 %. The intra-day and inter-day precisions were 1.5-6.3 % and 4.6-11.7 %, respectively. Additionally, the adsorption interactions between UiO-66-PDMS bead and PGRs were studied by ATR-FTIR and UV-vis DRS. Furthermore, the method was employed to screen the PGRs in ten different citrus fruits.

15.
Heart Surg Forum ; 25(5): E698-E708, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36317904

RESUMO

OBJECTIVE: To evaluate whether M2 macrophage-derived exosomes protect against MI/R injury and reveal the protective mechanism of exosomes [Kourembanas 2015]. METHODS: I/R model injury was induced by temporary left anterior descending coronary artery occlusion in Sprague-Dawley (SD) rats, macrophages isolated from bone marrow-derived macrophages (BMDMs) were induced to M2 polarization, and H9C2 cells subjected to hypoxia/reperfusion (H/R) were used to establish an in vitro model. I/R-induced rats and H/R-induced H9C2 cells were treated with M2-exos in vivo and in vitro, respectively. Masson staining was performed to observe myocardial fibrosis in rats. Immunohistochemical (IHC) staining of myocardial tissues showed the expression of NLRP3 inflammasome activation and pyrolysis. Exosomes derived from IL-4-treated macrophages (M2-exos) were detected by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western bolt. Western bolt was performed to determine the protein level, including NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1ß, cleaved IL-1ß, gasdermin D (GSDMD), and N-terminus of gasdermin D (GSDMD-N). RESULTS: Activity of NLRP3 inflammasome and existence of pyroptosis in the rats subjected to MI/R were significantly higher than those in the control (P < 0.05). Moreover, we confirmed the accumulation of ROS during I/R injury in cardiomyocytes. M2-exos protected against I/R injury and reduced activity of NLRP3 inflammasome and existence of pyroptosis, accompanied with attenuating oxidative stress. In vitro studies showed similar effects, H9c2 cells co-cultured with M2-exos could attenuated H/R-induced cell injury, while M2-exos suppressed the expression of NLRP3 inflammasome and pyroptosis (P < 0.05).


Assuntos
Exossomos , Traumatismo por Reperfusão Miocárdica , Ratos , Animais , Piroptose , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Inflamassomos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Exossomos/metabolismo , Ratos Sprague-Dawley , Reperfusão , Macrófagos/metabolismo
16.
J Dig Dis ; 2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36208299

RESUMO

OBJECTIVE: To evaluate the efficacy of fecal microbiota transplantation (FMT) in functional gastrointestinal disorders (FGIDs) children with abdominal bloating and changes in the gut microbiome and metabolome. METHODS: Twelve pediatric FGID patients with predominant abdominal bloating who underwent FMT were enrolled in the study. The clinical responses were assessed at 8 weeks after FMT. Fecal bacterial composition was determined by 16S rRNA gene sequencing. The fecal metabolome was measured by targeted metabolomics analysis. RESULTS: The median age of the 12 children with FGID was 6 years, and 9 were boys. Abdominal bloating was relieved in all pediatric FGID patients by FMT at 8 weeks. Meanwhile, FMT significantly improved the symptoms of abdominal pain and diarrhea. The alpha diversity was significantly lower in the FGID children, and the fecal microbial community (beta diversity) was separate from that of healthy control (HC). The relative abundances of multiple bacterial genera were significantly changed in the feces of the pediatric FGID patients. The levels of several short-chain fatty acids (SCFAs) were lower, and lactic acid concentrations were higher in FGID patients than in HC. The altered bacterial composition was correlated with changes in the fecal metabolite profile and clinical symptoms in FGID patients. FMT modulated the fecal microbiome and metabolome in FGID children toward a healthy state. CONCLUSION: FMT relieves abdominal bloating and modulates the fecal microbiome and metabolome toward a healthy state in children with FGIDs. Our findings suggest that FMT may provide an alternative therapy for children with FGID and abdominal bloating. This article is protected by copyright. All rights reserved.

17.
Angew Chem Int Ed Engl ; : e202210338, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266741

RESUMO

The first copper-catalyzed regiodivergent cyanoboration of internal allenes with B2 pin2 (bis(pinacolato)diboron) and NCTS (N-cyano-N-phenyl-p-toluenesulfonamide) derivatives is reported. The ß,γ- and α,ß-cyanoborylated products were synthesized with high regio- and stereo-selectivity. Computational studies revealed that nucleophilic addition of allylcopper or related intermediates on cyanation reagent is the regio- and stereo-determining step, while transmetalation with B2 pin2 is the rate-determining step. The nucleophilic addition step proceeds via inner-sphere mechanism in the CuI /P(o-tol)3 and CuI /Xantphos (P(o-tol)3 =tris(o-methylphenyl)phosphine, Xantphos=4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) catalytic systems and via outer-sphere mechanism in the CuII /Xantphos catalytic system, respectively.

18.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(10): 1136-1142, 2022 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-36305115

RESUMO

OBJECTIVES: To investigate the risk factors for acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) in children. METHODS: A retrospective analysis was performed on the medical data of 111 children who underwent HSCT from January 2018 to January 2020. A multivariate logistic regression analysis was used to identify the risk factors for AKI. The Kaplan-Meier survival analysis was used to compare the prognosis in children with different grades of AKI. RESULTS: Graft-versus-host disease (grade Ⅱ-Ⅳ) (OR=4.406, 95%CI: 1.501-12.933, P=0.007), hepatic veno-occlusive disease (OR=4.190, 95%CI: 1.191-14.740, P=0.026), and thrombotic microangiopathy (OR=10.441, 95%CI: 1.148-94.995, P=0.037) were closely associated with the development of AKI after HSCT. The children with stage Ⅲ AKI had a lower 1-year survival rate than those without AKI or with stage Ⅰ AKI or stage Ⅱ AKI (28.6%±12.1% vs 82.8%±5.2%/81.7%±7.4%/68.8%±11.6%; P<0.05). CONCLUSIONS: Children with stage Ⅲ AKI after HSCT have a higher mortality rate. Graft-versus-host disease, hepatic veno-occlusive disease, and thrombotic microangiopathy are closely associated with the development of AKI after HSCT.


Assuntos
Injúria Renal Aguda , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Criança , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/complicações , Fatores de Risco , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Microangiopatias Trombóticas/complicações
19.
medRxiv ; 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36263067

RESUMO

Post-acute sequelae of SARS-CoV-2 infection (PASC) affects a wide range of organ systems among a large proportion of patients with SARS-CoV-2 infection. Although studies have identified a broad set of patient-level risk factors for PASC, little is known about the contextual and spatial risk factors for PASC. Using electronic health data of patients with COVID-19 from two large clinical research networks in New York City and Florida, we identified contextual and spatial risk factors from nearly 200 environmental characteristics for 23 PASC symptoms and conditions of eight organ systems. We conducted a two-phase environment-wide association study. In Phase 1, we ran a mixed effects logistic regression with 5-digit ZIP Code tabulation area (ZCTA5) random intercepts for each PASC outcome and each contextual and spatial factor, adjusting for a comprehensive set of patient-level confounders. In Phase 2, we ran a mixed effects logistic regression for each PASC outcome including all significant (false positive discovery adjusted p-value < 0.05) contextual and spatial characteristics identified from Phase I and adjusting for confounders. We identified air toxicants (e.g., methyl methacrylate), criteria air pollutants (e.g., sulfur dioxide), particulate matter (PM 2.5 ) compositions (e.g., ammonium), neighborhood deprivation, and built environment (e.g., food access) that were associated with increased risk of PASC conditions related to nervous, respiratory, blood, circulatory, endocrine, and other organ systems. Specific contextual and spatial risk factors for each PASC condition and symptom were different across New York City area and Florida. Future research is warranted to extend the analyses to other regions and examine more granular contextual and spatial characteristics to inform public health efforts to help patients recover from SARS-CoV-2 infection.

20.
Discov Med ; 34(172): 83-95, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36281029

RESUMO

Sepsis is a life-threatening organ dysfunction caused by the maladjustment of the body's response to infection. Abnormal immune response plays an important role in the progression of sepsis, and immunomodulatory therapy is a promising therapeutic strategy for sepsis. Great efforts have been made recently to elucidate the mechanism by which immune dysfunction contributes to sepsis, and identify potential biomarkers and targets for the diagnosis and therapy of sepsis induced by emerging pathogens, especially for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)that causes COVID-19. In this review, we summarize recent progress on the understanding of immune dysregulation involved in sepsis, and highlight potential biomarkers and targets to evaluate immune status of the patients with sepsis for individualized and precise immunotherapy.


Assuntos
COVID-19 , Sepse , Humanos , SARS-CoV-2 , COVID-19/terapia , Sepse/terapia , Sepse/diagnóstico , Fatores Imunológicos , Imunoterapia , Biomarcadores
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