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1.
J Ethnopharmacol ; 334: 118523, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38969149

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: HLA-B*35:01 has been identified as a risk allele for Polygonum multiflorum Thunb.-induced liver injury (PMLI). However, the immune mechanism underlying HLA-B*35:01-mediated PMLI remains unknown. AIM OF THE STUDY: To characterize the immune mechanism of HLA-B*35:01-mediated PMLI. MATERIALS AND METHODS: Components of P. multiflorum (PM) bound to the HLA-B*35:01 molecule was screened by immunoaffinity chromatography. Both wild-type mice and HLA-B*35:01 transgenic (TG) mice were treated with emodin. The levels of transaminases, histological changes and T-cell response were assessed. Splenocytes from emodin-treated mice were isolated and cultured in vitro. Phenotypes and functions of T cells were characterized upon drug restimulation using flow cytometry or ELISA. Emodin-pulsed antigen-presenting cells (APCs) or glutaraldehyde-fixed APCs were co-cultured with splenocytes from emodin-treated transgenic mice to detect their effect on T-cell activation. RESULTS: Emodin, the main component of PM, could non-covalently bind to the HLA-B*35:01-peptide complexes. TG mice were more sensitive to emodin-induced immune hepatic injury, as manifested by elevated aminotransferase levels, infiltration of inflammatory cells, increased percentage of CD8+T cells and release of effector molecules in the liver. However, these effects were not observed in wild-type mice. An increase in percentage of T cells and the levels of interferon-γ, granzyme B, and perforin was detected in emodin-restimulated splenocytes from TG mice. Anti-HLA-I antibodies inhibited the secretion of these effector molecules induced by emodin. Mechanistically, emodin-pulsed APCs failed to stimulate T cells, while fixed APCs in the presence of emodin could elicit the secretion of T cell effector molecules. CONCLUSION: The HLA-B*35:01-mediated CD8+ T cell reaction to emodin through the P-I mechanism may contribute to P. multiflorum-induced liver injury.

2.
Anal Chem ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38975729

RESUMO

Plant samples with irregular morphology are challenging for longitudinal tissue sectioning. This has restricted the ability to gain insight into some plants using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Herein, we develop a novel technique termed electromagnetic field-assisted frozen tissue planarization (EMFAFTP). This technique involves using a pair of adjustable electromagnets on both sides of a plant tissue. Under an optimized electromagnetic field strength, nondestructive planarization and regularization of the frozen tissue is induced, allowing the longitudinal tissue sectioning that favors subsequent molecular profiling by MALDI-MSI. As a proof of concept, flowers, leaves and roots with irregular morphology from six plant species are chosen to evaluate the performance of EMFAFTP for MALDI-MSI of secondary metabolites, amino acids, lipids, and proteins among others in the plant samples. The significantly enhanced MALDI-MSI capabilities of these endogenous molecules demonstrate the robustness of EMFAFTP and suggest it has the potential to become a standard technique for advancing MALDI-MSI into a new era of plant spatial omics.

3.
Clin Transl Med ; 14(7): e1750, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38943041

RESUMO

BACKGROUND: Serotonin (5-hydroxytryptamine) is a multifunctional bioamine serving as a neurotransmitter, peripheral hormone and mitogen in the vertebrate system. It has pleiotropic activities in central nervous system and gastrointestinal function via an orchestrated action of serotonergic elements, particularly serotonin receptor-mediated signalling cascades. The mitogenic properties of serotonin have garnered recognition for years and have been exploited for repurposing serotonergic-targeted drugs in cancer therapy. However, emerging conflicting findings necessitate a more comprehensive elucidation of serotonin's role in cancer pathogenesis. MAIN BODY AND CONCLUSION: Here, we provide an overview of the biosynthesis, metabolism and action modes of serotonin. We summarise our current knowledge regarding the effects of the peripheral serotonergic system on tumourigenesis, with a specific emphasis on its immunomodulatory activities in human cancers. We also discuss the dual roles of serotonin in tumour pathogenesis and elucidate the potential of serotonergic drugs, some of which display favourable safety profiles and impressive efficacy in clinical trials, as a promising avenue in cancer treatment. KEY POINTS: Primary synthesis and metabolic routes of peripheral 5-hydroxytryptamine in the gastrointestinal tract. Advanced research has established a strong association between the serotonergic components and carcinogenic mechanisms. The interplay between serotonergic signalling and the immune system within the tumour microenvironment orchestrates antitumour immune responses. Serotonergic-targeted drugs offer valuable clinical options for cancer therapy.


Assuntos
Neoplasias , Serotonina , Transdução de Sinais , Humanos , Serotonina/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
4.
Nanoscale ; 16(26): 12534-12540, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38874930

RESUMO

The III-V nanowire (NW) structure is a good candidate for developing photodetectors. However, high-density surface states caused by the large surface-to-volume ratio severely limit their performance, which is difficult to solve in conventional ways. Here, a robust surface passivation method, using a thin layer of ZnO capping, is developed for promoting NW photodetector performance. 11 cycles of ZnO, grown on pure zinc blende high-quality GaAs NWs by atomic layer deposition, significantly alleviates the undesirable effect of the surface states, without noticeable degradation in NW morphology. An average 20-fold increase in micro-photoluminescence intensity is observed for passivated NWs, which leads to the development of detectors with high responsivity, specific detectivity, and optical gain of 9.46 × 105 A W-1, 3.93 × 1014 Jones, and 2.2 × 108 %, respectively, under low-intensity 532 nm illumination. Passivated NW detectors outperform their counterparts treated by conventional methods, so far as we know, which shows the potential and effectiveness of thin ZnO surface passivation on NW devices.

5.
JMIR Res Protoc ; 13: e56484, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885500

RESUMO

BACKGROUND: Vascular cognitive impairment (VCI) persistently impairs cognition and the ability to perform activities of daily living, seriously compromising patients' quality of life. Previous studies have reported that disorders of serum iron metabolism and iron deposition in the brain can lead to inflammation, abnormal protein aggregation and degeneration, and massive neuronal apoptosis in the central nervous system, which in turn leads to a progressive decline in cognitive processes. Our previous clinical studies have found acupuncture to be a safe and effective intervention for treating VCI, but the specific mechanisms require further exploration. OBJECTIVE: The objective of the trial is to evaluate the clinical efficacy of Tongdu Xingshen acupuncture and to investigate whether it can improve VCI by regulating brain iron deposition and body iron metabolism. METHODS: In total, 42 patients with VCI and 21 healthy individuals will participate in this clinical trial. The 42 patients with VCI will be randomized into acupuncture and control groups, while the 21 healthy individuals will be in the healthy control group. Both the control and acupuncture groups will receive conventional medical treatment and cognitive rehabilitation training. In addition, the acupuncture group will receive electroacupuncture treatment with Tongdu Xingshen for 30 minutes each time, 6 times a week for 4 weeks. Meanwhile, the healthy control group will not receive any intervention. All 3 groups will undergo baseline assessments of brain iron deposition, serum iron metabolism, and neuropsychological tests after enrollment. The acupuncture and control groups will be evaluated again at the end of 4 weeks of treatment, as described earlier. By comparing neuropsychological test scores between groups, we will examine the efficacy of Tongdu Xingshen acupuncture in treating VCI. Additionally, we will test the correlations between neuropsychological test scores, brain iron deposition, and body iron metabolism indexes to explore the possible mechanisms of Tongdu Xingshen acupuncture in treating VCI. RESULTS: Participants are currently being recruited. The first participant was enrolled in June 2023, which marked the official start of the experiment. As of the submission of the paper, there were 23 participants. The recruitment process is expected to continue until June 2025, at which point the processing and analysis of data will begin. As of May 15, 2024, up to 30 people have been enrolled in this clinical trial. CONCLUSIONS: This study will provide data on the effects of Tongdu Xingshen acupuncture on cerebral iron deposition as well as somatic iron metabolism in patients with VCI. These results will help to prove whether Tongdu Xingshen acupuncture can improve VCI by regulating brain iron deposition and body iron metabolism, which will provide the clinical and theoretical basis for the wide application of acupuncture therapy in VCI rehabilitation. TRIAL REGISTRATION: China Clinical Registration Agency ChiCTR2300072188; https://tinyurl.com/5fcydtkv. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/56484.


Assuntos
Terapia por Acupuntura , Encéfalo , Disfunção Cognitiva , Ferro , Humanos , Terapia por Acupuntura/métodos , Ferro/metabolismo , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto
6.
ACS Appl Mater Interfaces ; 16(23): 30147-30156, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38822780

RESUMO

The pretreatment of the Cu(In,Ga)Se2 (CIGS) absorption layer using an alkali element can effectively improve the photoelectric conversion efficiency (PCE) of CIGS solar cells. Here, we propose using NaF layer pretreatment below the CIGS absorption layer deposited by a three-stage process. Sodium ions in NaF can effectively suppress the diffusion of Ga elements and form a steep gradient backscatter layer on the back of the CIGS absorption layer, thereby passivating solar cell defects, inhibiting carrier recombination, promoting carrier transmission and collection, improving open circuit voltage (VOC), short circuit current (Jsc), and filling factor (FF), and further improving the PCE.

7.
BMC Infect Dis ; 24(1): 603, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898395

RESUMO

BACKGROUND: the mortality associated with severe malaria due to Plasmodiun falciparum remains high despite improvements in malaria management. Case prensentation: this case series aims to describe the efficacy and safety of the exchange transfusion combined with artesunate (ET-AS) regimen in severe P. falciparum malaria. Eight patients diagnosed with severe P. falciparum malaria were included. All patients underwent ET using the COBE Spectra system. The aimed for a post-exchange hematocrit of 30%. Half the estimated blood volume was removed and replaced using fresh frozen plasma. The regimen was well-tolerated without complications. The parasite clearance time ranged from 1 ~ 5 days. Five patients with cerebral malaria exhibited full improved consciousness within 3 days, while patient2 with hemolysis improved on day 2. Liver function improved within 1 ~ 6 days, and patient 1 and patient 6 showed improvements renal function on days 18 and 19, respectively. The length of intensive care unit stay range from 2 ~ 10 days, and all patients treated with ET-AS remained in the hospital for 3 ~ 19 days. CONCLUSIONS: these preliminary results suggest that ET-AS regimens are a safe and effective therapy for severe P. falciparum malaria and can benefit patients in clinical settings.


Assuntos
Antimaláricos , Artemisininas , Artesunato , Transfusão Total , Malária Falciparum , Humanos , Artesunato/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/terapia , Masculino , Adulto , Feminino , Antimaláricos/uso terapêutico , Antimaláricos/administração & dosagem , Pessoa de Meia-Idade , Artemisininas/uso terapêutico , Resultado do Tratamento , Adulto Jovem , Plasmodium falciparum/efeitos dos fármacos , Idoso , Terapia Combinada
8.
Front Endocrinol (Lausanne) ; 15: 1321622, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904041

RESUMO

Background: The triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women. Methods: This cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer. Results: Multivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19-2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13-17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09-1.68), 1.27 (1.05-1.54), 1.26 (1.05-1.52), and 1.32 (1.08-1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44-3.87). Conclusion: The TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.


Assuntos
Glicemia , Neoplasias da Mama , Triglicerídeos , Humanos , Feminino , Neoplasias da Mama/sangue , Neoplasias da Mama/epidemiologia , Pessoa de Meia-Idade , Triglicerídeos/sangue , Estudos Transversais , China/epidemiologia , Adulto , Glicemia/análise , Glicemia/metabolismo , Idoso , Fatores de Risco , Estudos Longitudinais , População do Leste Asiático
9.
Food Chem ; 456: 139883, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38870803

RESUMO

Wild soybean (Glycine soja) is known for its high flavonoid contents, yet the distribution of flavonoids in the seeds is not well understood. Herein, we utilized matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and metabolomics methods to systematically investigate flavonoid differences in the seed coats and embryos of G. soja and G. max. The results of flavonoid profiles and total flavonoid content analyses revealed that flavonoid diversity and abundance in G. soja seed coats were significantly higher than those in G. max whereas the levels were similar in embryos. Specifically, 23 unique flavonoids were identified in the seed coats of G. soja, including procyanidins, epicatechin derivatives, and isoflavones. Using MALDI-MSI, we further delineated the distribution of the important flavonoids in the cotyledons, hypocotyls, and radicles of the two species. These findings imply that G. soja holds considerable breeding potential to enhance the nutritional and stress resistance traits of G. max.

11.
Diabetes Obes Metab ; 26(7): 2956-2968, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38699782

RESUMO

AIM: To investigate the effects of adenosine kinase (ADK), a key enzyme in determining intracellular adenosine levels, on ß cells, and their underlying mechanism. METHODS: Genetic animal models and transgenic immortalized cells were applied to study the effect of ADK on islet beta-cell proliferation and function. The beta-cell mass and response to glucose were measured in vivo using mice with beta-cell-specific ADK overexpression, and in vitro using ADK-overexpressed immortalized beta-cell. RESULTS: The expression of ADK in human islets at high abundance, especially in ß cells, was decreased during the process of ß-cell proliferation. Additionally, a transgenic mouse model (ADKtg/tg /Mip-Cre) was generated wherein the mouse Insulin1 gene promoter specifically overexpressed ADK in pancreatic ß cells. The ADKtg/tg /Mip-Cre model exhibited impaired glucose tolerance, decreased fasting plasma insulin, loss of ß-cell mass, and inhibited ß-cell proliferation. Proteomic analysis revealed that ADK overexpression inhibited the expression of several proteins that promote cell proliferation and insulin secretion. Upregulating ADK in the ß-cell line inhibited the expression of ß-cell related regulatory molecules, including FoxO1, Appl1, Pxn, Pdx-1, Creb and Slc16a3. Subsequent in vitro experiments indicated that the inhibition of ß-cell proliferation and the decreased expression of Pdx-1, Creb and Slc16a3 were rescued by DNA methyltransferase 3A (DNMT3A) knockdown in ß cells. CONCLUSION: In this study, we found that the overexpression of ADK decreased the expression of several genes that regulate ß cells, resulting in the inhibition of ß-cell proliferation and dysfunction by upregulating the expression of DNMT3A.


Assuntos
Adenosina Quinase , Proliferação de Células , DNA (Citosina-5-)-Metiltransferases , DNA Metiltransferase 3A , Células Secretoras de Insulina , Camundongos Transgênicos , Regulação para Cima , Células Secretoras de Insulina/metabolismo , Animais , Camundongos , Humanos , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , Adenosina Quinase/genética , Adenosina Quinase/metabolismo , Masculino , Secreção de Insulina , Insulina/metabolismo
12.
Am J Clin Nutr ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729573

RESUMO

BACKGROUND: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVES: Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

13.
Sci Rep ; 14(1): 10187, 2024 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702381

RESUMO

Neurexins (Nrxns) are critical for synapse organization and their mutations have been documented in autism spectrum disorder, schizophrenia, and epilepsy. We recently reported that conditional deletion of Nrxn2, under the control of Emx1Cre promoter, predominately expressed in the neocortex and hippocampus (Emx1-Nrxn2 cKO mice) induced stereotyped patterns of behavior in mice, suggesting behavioral inflexibility. In this study, we investigated the effects of Nrxn2 deletion through two different conditional approaches targeting presynaptic cortical neurons projecting to dorsomedial striatum on the flexibility between goal-directed and habitual actions in response to devaluation of action-outcome (A-O) contingencies in an instrumental learning paradigm or upon reversal of A-O contingencies in a water T-maze paradigm. Nrxn2 deletion through both the conditional approaches induced an inability of mice to discriminate between goal-directed and habitual action strategies in their response to devaluation of A-O contingency. Emx1-Nrxn2 cKO mice exhibited reversal learning deficits, indicating their inability to adopt new action strategies. Overall, our studies showed that Nrxn2 deletion through two distinct conditional deletion approaches impaired flexibility in response to alterations in A-O contingencies. These investigations can lay the foundation for identification of novel genetic factors underlying behavioral inflexibility.


Assuntos
Comportamento Animal , Camundongos Knockout , Proteínas do Tecido Nervoso , Fatores de Transcrição , Animais , Camundongos , Proteínas do Tecido Nervoso/genética , Masculino , Moléculas de Adesão de Célula Nervosa/genética , Deleção de Genes , Aprendizagem em Labirinto/fisiologia , Reversão de Aprendizagem/fisiologia , Proteínas de Homeodomínio/genética , Hipocampo/metabolismo , Moléculas de Adesão Celular Neuronais/genética , Condicionamento Operante
14.
Front Bioeng Biotechnol ; 12: 1373419, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737538

RESUMO

Atopic dermatitis (AD) is a common inflammatory skin disease that significantly affects patients' quality of life. This study aimed to evaluate the therapeutic potential of cell-free fat extract (FE) in AD. In this study, the therapeutic effect of DNCB-induced AD mouse models was investigated. Dermatitis scores and transepidermal water loss (TEWL) were recorded to evaluate the severity of dermatitis. Histological analysis and cytokines measurement were conducted to assess the therapeutic effect. Additionally, the ability of FE to protect cells from ROS-induced damage and its ROS scavenging capacity both in vitro and in vivo were investigated. Furthermore, we performed Th1/2 cell differentiation with and without FE to elucidate the underlying therapeutic mechanism. FE reduced apoptosis and cell death of HaCat cells exposed to oxidative stress. Moreover, FE exhibited concentration-dependent antioxidant activity and scavenged ROS both in vitro and vivo. Treatment with FE alleviated AD symptoms in mice, as evidenced by improved TEWL, restored epidermis thickness, reduced mast cell infiltration, decreased DNA oxidative damage and lower inflammatory cytokines like IFN-γ, IL-4, and IL-13. FE also inhibited the differentiation of Th2 cells in vitro. Our findings indicate that FE regulates oxidative stress and mitigates Th2-mediated inflammation in atopic dermatitis by inhibiting Th2 cell differentiation, suggesting that FE has the potential as a future treatment option for AD.

15.
Front Endocrinol (Lausanne) ; 15: 1343255, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38681772

RESUMO

Stem cell-based therapies exhibit considerable promise in the treatment of diabetes and its complications. Extensive research has been dedicated to elucidate the characteristics and potential applications of adipose-derived stromal/stem cells (ASCs). Three-dimensional (3D) culture, characterized by rapid advancements, holds promise for efficacious treatment of diabetes and its complications. Notably, 3D cultured ASCs manifest enhanced cellular properties and functions compared to traditional monolayer-culture. In this review, the factors influencing the biological functions of ASCs during culture are summarized. Additionally, the effects of 3D cultured techniques on cellular properties compared to two-dimensional culture is described. Furthermore, the therapeutic potential of 3D cultured ASCs in diabetes and its complications are discussed to provide insights for future research.


Assuntos
Tecido Adiposo , Diabetes Mellitus , Humanos , Tecido Adiposo/citologia , Diabetes Mellitus/terapia , Animais , Técnicas de Cultura de Células/métodos , Células-Tronco Mesenquimais/citologia , Complicações do Diabetes/terapia , Diferenciação Celular , Técnicas de Cultura de Células em Três Dimensões/métodos
16.
Front Endocrinol (Lausanne) ; 15: 1333595, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567307

RESUMO

Introduction: Acetaldehyde dehydrogenase 2 (ALDH2) had reported as a prominent role in the development of cardiometabolic diseases among Asians. Our study aims to investigate the relationship between ALDH2 polymorphism and cardiometabolic risk factors in East Asian population. Method: We searched databases of PubMed, Web of Science, and Embase updated to Oct 30th, 2023. We extracted data of BMI, Hypertension, SBP, DBP, T2DM, FBG, PPG, HbA1c, TG, TC, LDL-C and HDL-C. Result: In total, 46 studies were finally included in our meta-analysis, containing, 54068 GG and, 36820 GA/AA participants. All outcomes related to blood pressure revealed significant results (hypertension OR=0.83 [0.80, 0.86]; SBP MD=-1.48 [-1.82, -1.14]; DBP MD=-1.09 [-1.58, -0.61]). FBG showed a significant difference (MD=-0.10 [-0.13, -0.07]), and the lipid resulted significantly in some outcomes (TG MD=-0.07 [-0.09, -0.04]; LDL-C MD=-0.04 [-0.05, -0.02]). As for subgroups analysis, we found that in populations without severe cardiac-cerebral vascular diseases (CCVDs), GG demonstrated a significantly higher incidence of T2DM (T2DM OR=0.88 [0.79, 0.97]), while the trend was totally opposite in population with severe CCVDs (T2DM OR=1.29 [1.00, 1.66]) with significant subgroup differences. Conclusion: Our updated meta-analysis demonstrated that ALDH2 rs671 GG populations had significantly higher levels of BMI, blood pressure, FBG, TG, LDL-C and higher risk of hypertension than GA/AA populations. Besides, to the best of our knowledge, we first report GG had a higher risk of T2DM in population without severe CCVDs, and GA/AA had a higher risk of T2DM in population with severe CCVDs.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023389242.


Assuntos
Aldeído-Desidrogenase Mitocondrial , Diabetes Mellitus Tipo 2 , Hipertensão , Humanos , Aldeído-Desidrogenase Mitocondrial/genética , Povo Asiático/genética , Fatores de Risco Cardiometabólico , LDL-Colesterol , População do Leste Asiático , Hipertensão/epidemiologia , Hipertensão/genética
17.
Toxicol Res (Camb) ; 13(2): tfae051, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38638451

RESUMO

Aim: To explore the differential genes in Parkinson's disease (PD) through a preliminary GEO database, and to investigate the possible mechanisms. Materials and Methods: The PD differentially expressed genes (DEGs) were analyzed by the microarray method. Then, these DEGs were applied to KEGG and GO analyses to predict the related signaling pathways and molecular functions. Comparison of GRAMD1C expression levels in the putamen of normal and Parkinson's patients by bioinformatic analysis. PC12 cells were cultured to construct a 6-hydroxydopamine (6-OHDA)-induced Parkinson's cell model. RT-qPCR was performed to detect the efficiency of GRAMD1C siRNA. MTT assay was conducted to examine the proliferation of cells. Then, the apoptosis of each group of cells was measured by flow cytometry. Western blot was carried out to determine the expression of apoptosis-related proteins. Results: Through bioinformatics, GRAMD1C was confirmed to be one of the most significantly upregulated genes in PD. Furthermore, GRAMD1C was notably enhanced in the PD patients and 6-OHDA-induced PC12 cells. Besides, 6-OHDA stimulation significantly reduced PC12 cell proliferation, and it reverted with the GRAMD1C siRNA. Moreover, the flow cytometry results showed that knockdown of GRAMD1C could effectively reduce the high apoptosis rate of PC12 cells induced by 6-OHDA treatment. Similarly, western blot results found that 6-OHDA stimulation markedly increased the expression levels of Bax and Caspase 3Caspase 3 and decreased the Bcl-2 expression in PC12 cells, and GRAMD1C knockdown reversed these changes. Conclusion: GRAMD1C is upregulated in PD, and may affect the PD process through the apoptotic pathway.

18.
Front Cell Infect Microbiol ; 14: 1351607, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562965

RESUMO

Objective: Thrombocytopenia is commonly associated with infectious diseases and serves as an indicator of disease severity. However, reports on its manifestation in conjunction with Klebsiella pneumoniae liver abscess (KPLA) are scarce. The present study sought to elucidate the correlation between thrombocytopenia and KPLA severity and delve into the etiological factors contributing to the incidence of thrombocytopenia. Materials and methods: A retrospective analysis of the clinical data from patients with KPLA admitted between June 2012 and June 2023 was performed. Baseline characteristics, biochemical assessments, therapeutic interventions, complications, and clinical outcomes were compared between patients with and without thrombocytopenia. To investigate the potential etiologies underlying thrombocytopenia, the association between platelet count reduction and thrombophlebitis was examined, with a particular focus on platelet consumption. Furthermore, bone marrow aspiration results were evaluated to assess platelet production anomalies. Results: A total of 361 KPLA patients were included in the study, among whom 60 (17%) had concurrent thrombocytopenia. Those in the thrombocytopenia group exhibited significantly higher rates of thrombophlebitis (p = 0.042), extrahepatic metastatic infection (p = 0.01), septic shock (p = 0.024), admissions to the intensive care unit (p = 0.002), and in-hospital mortality (p = 0.045). Multivariate analysis revealed that thrombocytopenia (odds ratio, 2.125; 95% confidence interval, 1.114-4.056; p = 0.022) was independently associated with thrombophlebitis. Among the thrombocytopenic patients, eight underwent bone marrow aspiration, and six (75%) had impaired medullar platelet production. After treatment, 88.6% of thrombocytopenic patients (n = 47) demonstrated recovery in their platelet counts with a median recovery time of five days (interquartile range, 3-6 days). Conclusions: Thrombocytopenia in patients with KPLA is indicative of increased disease severity. The underlying etiologies for thrombocytopenia may include impaired platelet production within the bone marrow and augmented peripheral platelet consumption as evidenced by the presence of thrombophlebitis.


Assuntos
Infecções por Klebsiella , Abscesso Hepático , Trombocitopenia , Tromboflebite , Humanos , Estudos Retrospectivos , Klebsiella pneumoniae , Infecções por Klebsiella/complicações , Infecções por Klebsiella/epidemiologia , Abscesso Hepático/epidemiologia , Trombocitopenia/complicações , Gravidade do Paciente , Tromboflebite/complicações
19.
Indian J Pediatr ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557821

RESUMO

OBJECTIVES: To construct a nomogram that predicts the risk of surgery in patients with necrotizing enterocolitis (NEC). METHODS: This retrospective cohort study recruited patients diagnosed with NEC at the Children's Hospital of Soochow University from 2013 to 2023. The neonates were divided into conservative and surgical-treatment groups. Univariate and multivariate logistic regressions were performed to identify factors influencing surgical risk, and a predictive model was constructed. RESULTS: This study comprised 154 cases of NEC, 103 cases (66.9%) in the conservative group and 51 cases (33.1%) in the surgical group. Multivariate logistic regression analysis revealed that increased bloody stools [odds ratio (OR) 5.066; 95% confidence interval (CI) 1.7396-14.7532; p = 0.0029), oxygen inhalation (OR 1.8278; 95% CI 1.2113-2.7581; p = 0.0041), use of vasoconstrictors (OR 4.4446; 95% CI 1.7157-11.5137; p = 0.0021), portal venous gas (OR 4.5569; 95% CI 1.6324-12.7209; p = 0.0038), and blood sodium (OR 0.8339; 95% CI 0.7477-0.9301; p = 0.0011) were independent factors of surgical risk. The area under the nomogram's receiver operating characteristic (ROC) curve was 0.886. Decision curve analysis (DCA) and calibration curves demonstrated good predictive performance for the nomogram. CONCLUSIONS: The nomogram effectively assessed the risk of surgical intervention in NEC patients, providing new insights and references for diagnosing and treating NEC.

20.
Environ Res ; 252(Pt 1): 118779, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38552825

RESUMO

Numerous application of pyrethroid insecticides has led to their accumulation in the environment, threatening ecological environment and human health. Its fate in the presence of iron-bearing minerals and natural organic matter under light irradiation is still unknown. We found that goethite (Gt) and humic acid (HA) could improve the photodegradation of bifenthrin (BF) in proper concentration under light irradiation. The interaction between Gt and HA may further enhance BF degradation. On one hand, the adsorption of HA on Gt may decrease the photocatalytic activity of HA through decreasing HA content in solution and sequestering the functional groups related with the production of reactive species. On the other hand, HA could improve the photocatalytic activity of Gt through extending light absorption, lowing of bandgap energy, hindering the recombination of photo-generated charges, and promoting the oxidation and reduction reaction on Gt surface. The increased oxygen vacancies on Gt surface along with the reduction of trivalent iron and the nucleophilic attack of hole to surface hydroxyl group contributed to the increasing photocatalytic activity of Gt. Electron paramagnetic resonance and quenching studies demonstrated that both oxidation species, such as hydroxyl radical (•OH) and singlet oxygen (1O2), and reducing species, such as hydrogen atoms (H•) and superoxide anion radical (O2•-), contributed to BF degradation in UV-Gt-HA system. Mass spectrometry, ion chromatography, and toxicity assessment indicated that less toxic C23H22ClF3O3 (OH-BF), C9H10ClF3O (TFP), C14H14O2 (OH-MBP), C14H12O2 (MBP acid), C14H12O3 (OH-MBP acid), and chloride ions were the main degradation products. The production of OH-BF, MPB, and TFP acid through oxidation and the production of MPB and TFP via reduction were the two primary pathways of BF degradation.


Assuntos
Substâncias Húmicas , Compostos de Ferro , Minerais , Oxirredução , Piretrinas , Substâncias Húmicas/análise , Minerais/química , Compostos de Ferro/química , Piretrinas/química , Fotólise , Inseticidas/química
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