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1.
Mol Ther Oncolytics ; 26: 304-313, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36090474

RESUMO

In this study, we investigate the synergistic effect of gemcitabine (Gem) and a novel DNA vaccine in the treatment of pancreatic cancer in mice and explore the anti-tumor mechanism of this combination therapy. Fibroblast activation protein α-expressing cancer-associated fibroblasts (FAPα+ CAFs), a dominant component of the tumor microenvironment (TME), have been shown to modulate the extracellular matrix (ECM) to promote the growth, invasion, and metastasis of pancreatic cancer (PC). Therefore, FAPα+ CAFs may be an ideal target for the treatment of PC. However, treatments that solely target FAPα+ CAFs do not directly affect tumor cells. We recently constructed a novel chimeric DNA vaccine (OsFS) against human FAPα and survivin, which simultaneously targets FAPα+ CAFs and tumor cells. In Panc02 tumor-bearing mice, OsFS vaccination not only reduced the proportion of immunosuppressive cells but also promoted the recruitment of tumor-infiltrating lymphocytes, which remodeled the TME to support anti-tumor immune responses. Furthermore, after depletion of regulatory T cells (Tregs) by metronomic low-dose Gem therapy, the anti-tumor effects of OsFS were enhanced. Taken together, our results indicate that the combination of the FAPα/survivin co-targeting DNA vaccine and low-dose Gem may be an effective therapy for PC.

2.
Public Health Nutr ; : 1-29, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098091

RESUMO

OBJECTIVE: To assess urban-rural disparities in the association between long-term exposure to high altitude and malnutrition among children under five years old. DESIGN: A three-stage, stratified, cluster sampling was used to randomly select eligible individuals from July to October 2020. The data of participants, including demographic characteristics, altitude of residence, and nutritional status, were collected via questionnaire and physical examination. SETTING: Tibet, China. PARTICIPANTS: Children under five years old in Tibet. RESULTS: 1,975 children under five years old were included in this study. We found that an additional 1,000 meters (m) increase in altitude was associated with decreased Z-scores of height for age (HFA) (ß=-0.23, 95%CI: -0.38 to -0.08), Z-scores of weight for age (WFA) (ß=-0.24, 95%CI: -0.39 to -0.10). The odds ratios (ORs) for stunting and underweight were 2.03 (95%CI: 1.51 to 2.73) and 2.04 (95%CI: 1.38 to 3.02) per 1000 m increase in altitude respectively; and ORs increased rapidly at an altitude above 3,500 m. The effects of long-term exposure to high altitudes on the prevalence of underweight in rural children were higher than that in urban children (P<0.05). CONCLUSIONS: High altitude exposure is tightly associated with malnutrition among children under five years old. Improving children's nutrition is urgently needed in areas above 3,500 m, especially in rural ones.

3.
Protein Pept Lett ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36098412

RESUMO

BACKGROUND: Accumulating evidence has demonstrated the immunomodulatory effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in rheumatoid arthritis and the tumor microenvironment, besides its known capacity of specifically inducing the apoptosis of cancer cells. Mice are common available animal models for studying the roles of TRAIL. However, mice express only a single TRAIL receptor (mTRAILR) with an intracellular death domain, in contrast to the two TRAIL receptors (TRAILR1 and TRAILR2) in humans. Moreover, human TRAIL binds weakly to mTRAILR, whereas mouse TRAIL has high affinity for the human TRAIL-Rs. Therefore, we considered that murine TRAIL would be more suitable than human TRAIL for exploring the immunoregulatory effect of TRAIL in immunocompetent mice or when using mouse cells as the target. To our knowledge, the detailed method for production of recombinant murine TRAIL has not been reported. OBJECTIVE: In this study, we aimed to design and express two soluble forms of murine TRAIL and verify the properties of the protein. METHODS: Recombinant murine TRAILs were expressed in Escherichia coli BL21 (DE3, and Ni-chelating affinity chromatography was used for protein purification. SDS-PAGE, GDS-PAGE and HPLC were applied to analyze the protein structure. The cytotoxicity of our purified murine TRAILs was evaluated in the TRAIL-sensitive human breast cancer ZR-75-30 cells and murine breast cancer 4T1 cells. Finally, validation of the tumor-killing ability of the murine protein in vivo. RESULTS: Two soluble forms of murine TRAILs (mT_N99 and mT_N188) were purified and demonstrated with high purity and trimeric structure. In addition, Zn2+ supplement was essential to produce soluble murine TRAILs in E.coli BL21 (DE3). The two purified soluble mTRAILs showed similar cytotoxicity to cancer cells, moreover, mT_N99 also showed a good anti-tumor effect in vivo and is more suitable for the treatment of murine tumor models. CONCLUSION: A production approach for recombinant murine TRAIL was determined, which covered the design of shortened forms, expression, purification and characterization.

4.
J Zhejiang Univ Sci B ; 23(9): 747-759, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111571

RESUMO

The mechanisms underlying pregnancy complications caused by advanced maternal age (AMA) remain unclear. We analyzed the cellular signature and transcriptomes of human placentas in AMA women to elucidate these mechanisms. Placental tissues from two AMA women and two controls were used for single-cell RNA-sequencing (scRNA-seq). Controls consisted of AMA women who did not experience any pregnancy complications and pregnant women below the age of 35 years without pregnancy complications. Trophoblast cells were obtained from the placentas of another six pregnant women (three AMA women and three controls), and in-vitro transwell assays were conducted to observe the cell invasion ability. Thirty additional samples (from 15 AMA women and 15 controls) were analyzed to verify the specific expression of serine protease inhibitor clade E member 1 (SERPINE1). Preliminary study of the role of SERPINE1 in cell invasion was carried out with HTR8-S/Vneo cells. High-quality transcriptomes of 27 |607 cells were detected. Three types of trophoblast cells were detected, which were further classified into eight subtypes according to differences in gene expression and Gene Ontology (GO) function. We identified 110 differentially expressed genes (DEGs) in trophoblast cells between the AMA and control groups, and the DEGs were enriched in multiple pathways related to cell invasion. In-vitro transwell assays suggested that the invading trophoblast cells in AMA women were reduced. SERPINE1 was specifically expressed in the trophoblast, and its expression was higher in AMA women (P<0.05). Transfection of human SERPINE1 (hSERPINE1) into HTR8-S/Vneo trophoblast cells showed fewer invading cells in the hSERPINE1 group. Impaired cell invasion may underlie the increased risk of adverse pregnancy outcomes in AMA women. Abnormal expression of SERPINE1 in extravillous trophoblast (EVT) cells appears to play an important role.


Assuntos
Placenta , Complicações na Gravidez , Adulto , Linhagem Celular , Movimento Celular , Feminino , Humanos , Idade Materna , Placenta/metabolismo , Gravidez , Gestantes , RNA/metabolismo , Inibidores de Serino Proteinase/metabolismo
5.
Front Neurosci ; 16: 946879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117612

RESUMO

Spinal cord injury (SCI) is a devastating condition with few treatment options. Metformin, a classical antidiabetic and antioxidant, has extended its application to experimental SCI treatment. Here, we performed a systematic review to evaluate the neurobiological roles of metformin for treating SCI in rats, and to assess the potential for clinical translation. PubMed, Embase, China National Knowledge Infrastructure, WanFang data, SinoMed, and Vip Journal Integration Platform databases were searched from their inception dates to October 2021. Two reviewers independently selected controlled studies evaluating the neurobiological roles of metformin in rats following SCI, extracted data, and assessed the quality of methodology and evidence. Pairwise meta-analyses, subgroup analyses and network analysis were performed to assess the roles of metformin in neurological function and tissue damage in SCI rats. Twelve articles were included in this systematic review. Most of them were of moderate-to-high methodological quality, while the quality of evidence from those studies was not high. Generally, Basso, Beattie, and Bresnahan scores were increased in rats treated with metformin compared with controls, and the weighted mean differences (WMDs) between metformin and control groups exhibited a gradual upward trend from the 3rd (nine studies, n = 164, WMD = 0.42, 95% CI = -0.01 to 0.85, P = 0.06) to the 28th day after treatment (nine studies, n = 136, WMD = 3.48, 95% CI = 2.04 to 4.92, P < 0.00001). Metformin intervention was associated with improved inclined plane scores, tissue preservation ratio and number of anterior horn motor neurons. Subgroup analyses indicated an association between neuroprotection and metformin dose. Network meta-analysis showed that 50 mg/kg metformin exhibited greater protection than 10 and 100 mg/kg metformin. The action mechanisms behind metformin were associated with activating adenosine monophosphate-activated protein kinase signaling, regulating mitochondrial function and relieving endoplasmic reticulum stress. Collectively, this review indicates that metformin has a protective effect on SCI with satisfactory safety and we demonstrate a rational mechanism of action; therefore, metformin is a promising candidate for future clinical trials. However, given the limitations of animal experimental methodological and evidence quality, the findings of this pre-clinical review should be interpreted with caution.

6.
J Med Chem ; 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36112701

RESUMO

Lysine-specific demethylase 5B (KDM5B) has been recognized as a potential drug target for cardiovascular diseases. In this work, we first found that the KDM5B level was increased in mouse hearts after transverse aortic constriction (TAC) and in Ang II-induced activated cardiac fibroblasts. Structure-based design and further optimizations led to the discovery of highly potent pyrazole-based KDM5B inhibitor TK-129 (IC50 = 0.044 µM). TK-129 reduced Ang II-induced activation of cardiac fibroblasts in vitro, exhibited good PK profile (F = 42.37%), and reduced isoprenaline-induced myocardial remodeling and fibrosis in vivo. Mechanistically, we found that KDM5B up-regulation in cardiac fibroblast activation was associated with the activation of Wnt-related pathway. The protective effects of TK-129 were associated with its KDM5B inhibition and blocking KDM5B-related Wnt pathway activation. Taken together, TK-129 may represent a novel KDM5-targeting lead compound for cardiac remodeling and fibrosis.

7.
Front Immunol ; 13: 966522, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091061

RESUMO

Prenatal stress can affect pregnant women in an epigenetic way during the critical period of conception of their offspring. The study aims to investigate the relationship between peritraumatic distress, prenatal perceived stress, depression, and glucocorticoid receptor (NR3C1) DNA methylation among pregnant women who experienced COVID-19 lockdown in China. Study data were collected from 30 pregnant women in Wuhan and Huanggang, China. The Peritraumatic Distress Inventory was used to measure peritraumatic distress, the Edinburgh Postnatal Depression Scale was used to measure depressive symptoms, and the Perceived Stress Scale was used to measure perceived stress. DNA methylation in the exon 1F promoter region of NR3C1 gene from the venous blood mononuclear cell genome was characterized by bisulfite sequencing. Correlation and linear regression were used for data analysis. The mean level of peritraumatic distress, perceived stress, and depression was 6.30 (SD = 5.09), 6.50 (SD = 5.41), and 6.60 (SD = 4.85), respectively, with 23.33% of pregnant women being depressed. The mean NR3C1 methylation was 0.65 (SD = 0.22). Prenatal depression was positively correlated with the degree of methylation in venous blood from the mother (r = 0.59, p = 0.001), and depression predicted methylation of NR3C1 gene at the CpG 8 site (ß = 0.05, p = 0.03). No association was found between peritraumatic distress as well as perceived stress and methylation of NR3C1. NR3C1 gene was susceptible to epigenetic modification of DNA methylation in the context of prenatal stress, and maternal depression was associated with increased NR3C1 methylation among women who experienced COVID-19 lockdown.


Assuntos
COVID-19 , Metilação de DNA , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Depressão/epidemiologia , Feminino , Humanos , Gravidez , Gestantes , Receptores de Glucocorticoides/genética , Estresse Psicológico
8.
Mol Ther ; 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104974

RESUMO

There has been no effective therapy for implant-associated Staphylococcus aureus (S. aureus) osteomyelitis, a devastating complication following orthopedic surgery. An immune-suppressive profile with up-regulated programmed cell death 1 / programmed death ligand 1 (PD-1/PD-L1) was identified based on our transcriptional data (GSE166522) from a mouse model of S. aureus osteomyelitis. PD-1/PD-L1 expression was up-regulated mainly in F4/80+ macrophages surrounding the abscess in S. aureus-infected bone. Mechanistically, PD-1/PD-L1 activated mitophagy to suppress production of mitochondrial ROS, thereby suppressing the bactericidal function of macrophages. Importantly, either anti-PD-1 or anti-PD-L1 or knock-out of PD-L1 adjuvant to gentamicin markedly reduced mitophagy in bone marrow F4/80+ cells, enhances bacterial clearance in bone tissue and implants, and reduced bone destruction in mice. Excitingly, PD-1/PD-L1 expression was also increased in the bone marrow from patients with S. aureus osteomyelitis. These findings uncovered a hitherto unknown function of PD-1/PD-L1-mediated mitophagy in suppressing bactericidal function of bone marrow macrophages.

9.
Innovation (Camb) ; : 100321, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36106026
10.
World J Clin Cases ; 10(20): 6999-7005, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-36051115

RESUMO

BACKGROUND: Neonatal hyperbilirubinemia is a common problem faced by pediatricians. The role of genetic factors in neonatal jaundice has been gradually recognized. This study aims to identify genetic variants that influence the bilirubin level in five patients using next-generation sequencing (NGS). CASE SUMMARY: Five neonates with severe hyperbilirubinemia were retrospectively studied. They exhibited bilirubin encephalopathy, hypothyroidism, ABO blood type incompatibility hemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency and premature birth, respectively. A customized 22-gene panel was designed, and NGS was carried out for these neonates. Eight variations (G6PD c.G1388A, HBA2 c.C369G, ABCC2 c.C3825G, UGT1A1 c.G211A, SPTB c.A1729G, EPB41 c.G520A, c.1213-4T>G and c.A1474G) were identified in these five neonates. Genetic mutations of these genes are associated with G6PD deficiency, thalassemia, Dubin-Johnson syndrome, Gilbert syndrome, hereditary spherocytosis, and hereditary elliptocytosis. One of the neonates was found to have compound variants of the EPB41 splice site c.1213-4T>G and c.G520A (p.E174K), but no elliptocyte was seen on his blood smear of 4 years old. CONCLUSION: Pathological factors of severe neonatal hyperbilirubinemia are complicated. Genetic variants may play an important role in an increased risk of neonatal hyperbilirubinemia, and severe jaundice in neonates may be related to a cumulative effect of genetic variants.

11.
Gut Liver ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36052612

RESUMO

Background/Aims: A full colonoscopy is currently required in children and adolescents with colorectal polyps, because of their potential of neoplastic transformation and complications such as intussusception. We aimed to analyze the associations of polyp characteristics in children and adolescents with colorectal polyps. Based on these findings, we also aimed to reevaluate the necessity of conducting a full colonoscopy. Methods: Pediatric patients <18 years of age who had undergone a colonoscopic polypectomy and those with <5 colorectal polyps were included in this multicenter, retrospective study. Baseline clinicodemographics, colonoscopic and histologic findings were investigated. Results: A total of 91 patients were included. Multivariate logistic regression analysis showed that polyp size was the only factor associated with the presence of any polyps located proximal to the splenic flexure (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.28 to 4.28; p=0.007). Furthermore, polyp location proximal to the splenic flexure and sessile morphology were associated with the presence of any adenomatous polyp (OR, 8.51; 95% CI, 1.43 to 68.65; p=0.023; OR, 18.41; 95% CI, 3.45 to 173.81; p=0.002, respectively). Conclusions: In children and adolescents presenting with <5 colorectal polyps, polyp size and the presence of any adenomatous polyp were positively associated with polyp location proximal to the splenic flexure. This finding supports the necessity of a full colonoscopic exam in pediatric patients with colorectal polyps for the detection of polyps before the occurrence of complications such as intussusception or neoplastic transformation.

12.
Arch Gerontol Geriatr ; 103: 104797, 2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36058044

RESUMO

Objective Most previous studies focusing on the association between depressive symptoms and lung function were conducted in patients with chronic lung diseases. This study aims to investigate the association of depressive symptoms with lung function among general Chinese middle-aged and older adults. Participants This study used data from the China Health and Retirement Longitudinal Study (CHARLS). Analyses were conducted with data from three waves (2011, 2013, and 2015) and restricted to those respondents aged 45 and older. Finally, 9487 individuals [mean age (SD) = 58.47 (9.19); female, 53.1%] were included in analysis. Methods Depressive symptoms were measured by the Chinese version of 10-item Center for Epidemiological Studies Depression Scale (CESD-10). Lung function was assessed by peak expiratory flow (PEF). Two-level linear mixed growth models were used to evaluate the longitudinal association between depressive symptoms and PEF. Results Depressive symptoms were significantly associated with PEF among general middle-aged and older adults (b = -1.85, p < 0.001) after adjusting for multiple confounding factors. A significant interaction between depressive symptoms and gender was found (b = 1.29, p < 0.001). The association between depressive symptoms and PEF was greater for men (b = -2.36, p < 0.001) than for women (b = -1.46, p < 0.001). Conclusions This longitudinal study found that increased depressive symptoms were associated with reduced PEF in middle-aged and older adults in China. Compared with women, men with a higher level of depressive symptoms experienced a greater decrement in PEF. Our findings suggest that it is possible to reduce the effects of PEF by improving psychological health among general middle-aged and older populations.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36078331

RESUMO

The evaluation of the livability of rural living spaces is an important aspect of rural sustainable development, which is related to the well-being of rural residents. This study proposes a new evaluation framework for assessing the livability pattern of rural living spaces from the major components of the daily activities of rural residents. It fully considers whether the living space within a certain geographical area can meet the needs of rural residents in terms of residence, employment, consumption, leisure, and other types of daily activities. This study also establishes a comprehensive index system that includes 36 indicators and develops a comprehensive assessment method for evaluating the livability pattern of rural living spaces. Moreover, this research conducts a case study on the spatial pattern of rural living spaces in China's Jianghan Plain in 2018. We determine that the livability of rural living spaces in Jianghan Plain exhibits an evident "grade difference" characteristic. The overall livability level is not high. Seven problem counties from three categories are delineated on the basis of the score status. The new framework and conclusions of this study are conducive to the future targeted construction of livable rural living spaces.


Assuntos
Atividades de Lazer , População Rural , China , Emprego , Humanos
14.
Medicine (Baltimore) ; 101(36): e30516, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086732

RESUMO

BACKGROUND: To assess the influence of marital status on the survival of patients with nasopharyngeal carcinoma (NPC), we used the Surveillance, Epidemiology, and End Results (SEER) database to analyze 5477 patients who were diagnosed with NPC from 2004 to 2016. METHODS: Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the influence of marital status on cause-specific survival (CSS) and overall survival (OS). Subgroup analyses was used to assess the influence of marital status on CSS based on different factors. RESULTS: For the 5477 patients, 61.5%, 22.4%, and 16.1% were married, single/unmarried, and separated/widowed/divorced, respectively. The separated/widowed/divorced group was more likely to be female (P < .001), had the highest proportion of elderly subjects (P < .001), were mostly Caucasian (P < .001), had pathological grade I/II (P < .001), were likely to undergo surgery (P = .032), and were registered in the northeast, north-central, and south (P < .001) regions. The 5-year CSS rates were 92.6%, 92.4%, and 85.1% in the married, single/unmarried, and separated/widowed/divorced groups, respectively (P < .001), and the 5-year OS rates were 60.7%, 54.6%, and 40.1%, respectively (P < .001). CONCLUSION: Marital status is an independent prognostic factor of NPC. Separated/widowed/divorced patients had a significantly increased risk of NPC-related death (hazard ratio [HR] = 2.180, 95% confidence interval [CI] 1.721-2.757, P < .001) compared to married patients. The single/unmarried (P = .355) group had a CSS similar to that of the unmarried group. Marital status is an independent prognostic factor of survival in NPC patients. Separated/widowed/divorced status increases the risk of NPC mortality.


Assuntos
Neoplasias Nasofaríngeas , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Estado Civil , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/epidemiologia , Programa de SEER
15.
Surg Infect (Larchmt) ; 23(7): 625-633, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36049075

RESUMO

Background: We performed a meta-analysis to confirm the efficacy of short-term compared with long-term administration of antimicrobial prophylaxis in gastric cancer surgery. Methods: Randomized controlled trials of the efficacy of short-term versus long-term administration of antimicrobial prophylaxis in gastric cancer surgery were searched using the MEDLINE, EMBASE, and the Cochrane Controlled Trials Register databases. The data were evaluated and statistically analyzed using RevMan version 5.3.0. Five studies including 2,053 participants who received short-term versus long-term administration of antimicrobial prophylaxis in gastric cancer surgery were considered. Results: There was no significant difference in the surgical site infection (SSI) rate between the short-term group and the long-term group (8.1% vs. 9.2%; odds ratio [OR], 0.87; 95% confidence interval [CI], 0.64-1.09; p = 0.39). Hierarchical analysis also showed no significant differences in incisional-site incisions, organ/space incisions, or leakage. Multivariable analysis showed no significant differences in gender, age (>65 years), body mass index (>25 kg/m2), D2, operation time (>3 hours), pathologic stage 3, blood loss, combined resection, diabetes mellitus, total gastrectomy, or blood transfusion between the two groups. Conclusions: Short-term administration of antimicrobial prophylaxis did not increase the incidence of SSIs after gastrectomy.


Assuntos
Anti-Infecciosos , Neoplasias Gástricas , Idoso , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Gastrectomia/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/cirurgia
16.
J Chromatogr A ; 1682: 463477, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36137342

RESUMO

Tea is a complex food matrix comprising of many structurally diverse compounds, of which catechins and their oxidised derivatives are of particular interest due to their nutritional functionality. However, these catechins and derivatives exist in various isomeric forms with few or no pure standards available, rendering their analysis challenging. A method combining multi-dimensional liquid chromatography (MDLC) and high-resolution mass spectrometry (HRMS) was developed for the characterisation of these compounds using Ceylon tea as a model. Based on a Plackett-Burman (PB) design, flow rate and initial methanol percentage were identified as the most significant factors (p < 0.05) affecting chromatogram coverage and resolution (Rs) for comprehensive two-dimensional LC (LCxLC) and heart-cutting two-dimensional LC (LC-LC) respectively. Central composite design (CCD) was then applied using these parameters for method optimisation and to identify second-order relationships between screened parameters. The optimised LCxLC (flow rate: 2.18 mL/min and initial methanol percentage: 28.0%) and LC-LC (flow rate: 0.86 mL/min and initial methanol percentage for different cuts: A- 10.0%; B- 15.8%; and C- 18.7%) methods were applied to the analysis of Ceylon tea samples from seven regions of Sri Lanka and demonstrated an improved separation of co-eluting isomeric compounds. Finally, with the mass spectral information from HRMS, a total of 31 compounds (eight monomers, 17 dimers, five trimers and one tetramer) were detected and putatively identified in Ceylon tea.

17.
Mol Psychiatry ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36131044

RESUMO

Although the link of white matter to pathophysiology of schizophrenia is documented, loss of myelin is not detected in patients at the early stages of the disease, suggesting that pathological evolution of schizophrenia may occur before significant myelin loss. Disrupted-in-schizophrenia-1 (DISC1) protein is highly expressed in oligodendrocyte precursor cells (OPCs) and regulates their maturation. Recently, DISC1-Δ3, a major DISC1 variant that lacks exon 3, has been identified in schizophrenia patients, although its pathological significance remains unknown. In this study, we detected in schizophrenia patients a previously unidentified pathological phenotype of OPCs exhibiting excessive branching. We replicated this phenotype by generating a mouse strain expressing DISC1-Δ3 gene in OPCs. We further demonstrated that pathological OPCs, rather than myelin defects, drive the onset of schizophrenic phenotype by hyperactivating OPCs' Wnt/ß-catenin pathway, which consequently upregulates Wnt Inhibitory Factor 1 (Wif1), leading to the aberrant synaptic formation and neuronal activity. Suppressing Wif1 in OPCs rescues synaptic loss and behavioral disorders in DISC1-Δ3 mice. Our findings reveal the pathogenetic role of OPC-specific DISC1-Δ3 variant in the onset of schizophrenia and highlight the therapeutic potential of Wif1 as an alternative target for the treatment of this disease.

18.
Pediatr Gastroenterol Hepatol Nutr ; 25(5): 432-440, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36148287

RESUMO

Purpose: Eating disorders often result in somatic complications, including cardiac abnormalities. Cardiac abnormalities may involve any part of the heart, including the cardiac conduction system, and can lead to sudden cardiac death. The current study aimed to evaluate the incidence of cardiac complications in pediatric patients with eating disorders and their associated factors. Methods: We retrospectively analyzed patients aged 10-18 years who were diagnosed with DSM-V (Diagnostic and Statistical Manual of Mental Disorder-V) eating disorders and underwent electrocardiography (ECG) and/or echocardiography between January 2015 and May 2020. Results: In total, 127 patients were included, of whom 113 (89.0%) were female. The median body mass index (BMI) was 15.05±3.69 kg/m2. Overall, 74 patients (58.3%) had ECG abnormalities, with sinus bradycardia being the most common abnormality (91.9%). Patients with ECG abnormalities had significantly lower BMI (14.35±2.78 kg/m2 vs. 16.06± 4.55 kg/m2, p<0.001) than patients without ECG abnormalities, as well as lower phosphorus and higher cholesterol levels. Among the 46 patients who underwent echocardiographic evaluation, 23 (50.0%) had echocardiographic abnormalities, with pericardial effusion being the most common (60.9%). The median left ventricular mass (LVM) and ejection fraction were 67.97±21.25 g and 66.91±28.76%, respectively. LVM and BMI showed a positive correlation (r=0.604, p<0.001). After weight gain, the amount of pericardial effusion was reduced in 3 patients, and 30 patients presented with normal ECG findings. Conclusion: Cardiac abnormalities are relatively frequent in patients with eating disorders. Physicians should focus on this somatic complication and careful monitoring is required.

19.
Front Immunol ; 13: 975363, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119092

RESUMO

Evaluation of the safety and immunogenicity of new vaccine platforms is needed to increase public acceptance of coronavirus disease 2019 (COVID-19) vaccines. Here, we evaluated the association between reactogenicity and immunogenicity in healthy adults following vaccination by analyzing blood samples before and after sequential two-dose vaccinations of BNT162b2 and ChAdOx1 nCoV-19. Outcomes included anti-S IgG antibody and neutralizing antibody responses, adverse events, and proinflammatory cytokine responses. A total of 59 and 57 participants vaccinated with BNT162b2 and ChAdOx1 nCoV-19, respectively, were enrolled. Systemic adverse events were more common after the first ChAdOx1 nCoV-19 dose than after the second. An opposite trend was observed in BNT162b2 recipients. Although the first ChAdOx1 nCoV-19 dose significantly elevated the median proinflammatory cytokine levels, the second dose did not, and neither did either dose of BNT162b2. Grades of systemic adverse events in ChAdOx1 nCoV-19 recipients were significantly associated with IL-6 and IL-1ß levels. Anti-S IgG and neutralizing antibody titers resulting from the second BNT162b2 dose were significantly associated with fever. In conclusion, systemic adverse events resulting from the first ChAdOx1 nCoV-19 dose may be associated with proinflammatory cytokine responses rather than humoral immune responses. Febrile reactions after second BNT162b2 dose were positively correlated with vaccine-induced immune responses rather than with inflammatory responses.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Anticorpos Neutralizantes , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Humanos , Imunoglobulina G , Interleucina-6
20.
Acta Orthop ; 93: 703-708, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069480

RESUMO

BACKGROUND AND PURPOSE: Identification of pathogens causing fracture-device-related infection (FDRI) is always a challenge as the positive rate of standard tissue sampling culture (TSC) remains unsatisfactory. This study evaluates the efficiency of implant surface culture (ISC) as an adjunct to standard TSC for identification of FDRI-associated microorganisms. PATIENTS AND METHODS: Between November 2020 and March 2022, patients diagnosed with FDRI defined by the International Fracture-Related Infection (FRI) Consensus Group, and indicated for implant removal, underwent both methods for bacteria detection. The test order of ISC and TSC was randomly selected for each patient included, as a within-person randomized design. For ISC, the recovered implants were gently covered with tryptic soy agar after rinsing with normal saline twice, and then incubated at 37℃ 5% CO2 for up to 14 days. For TSC, 5 specimens were sampled and sent to the Clinical Laboratory of Southern Medical University Nanfang Hospital, Guangzhou, for culture and identification. RESULTS: 42 consecutive patients were included, with a mean age of 46 years. The most frequent infection site and implant type were the tibia (21 cases) and plates with screws (30 cases), respectively. Altogether 21 patients were found with positive outcomes by both methods, and the identified pathogens were consistent. ISC found an additional 15 patients showing positive results, which were negative by TSC. Furthermore, the mean culture time of ISC was shorter than that of TSC (1.5 days vs. 3.2 days). INTERPRETATION: ISC may be a useful adjunct to TSC for detection of bacteria causing FDRI, with a relatively higher positive rate and a shorter culture time.


Assuntos
Infecções Bacterianas , Fraturas Ósseas , Remoção de Dispositivo , Fixação Interna de Fraturas , Fraturas Ósseas/cirurgia , Humanos , Pessoa de Meia-Idade , Próteses e Implantes
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