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1.
J Adv Res ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39243941

RESUMO

INTRODUCTION: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear. OBJECTIVES: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment. METHODS: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital. RESULTS: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects. CONCLUSIONS: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.

2.
Hematology ; 29(1): 2399430, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39248713

RESUMO

BACKGROUND: Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time. CONCLUSIONS: Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.


Assuntos
Anticorpos Monoclonais , Mieloma Múltiplo , Insuficiência Renal , Humanos , Anticorpos Monoclonais/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/etiologia , Insuficiência Renal/mortalidade , Resultado do Tratamento
3.
Theranostics ; 14(13): 5102-5122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267784

RESUMO

Rationale: Extrachromosomal circular DNA is a hallmark of cancer, but its role in shaping the genome heterogeneity of urothelial bladder carcinoma (UBC) remains poorly understood. Here, we comprehensively analyzed the features of extrachromosomal circular DNA in 80 UBC patients. Methods: We performed whole-genome/exome sequencing (WGS/WES), Circle-Seq, single-molecule real-time (SMRT) long-read sequencing of circular DNA, and RNA sequencing (RNA-Seq) on 80 pairs of tumor and AT samples. We used our newly developed circular DNA analysis software, Circle-Map++ to detect small extrachromosomal circular DNA from Circle-Seq data. Results: We observed a high load and significant heterogeneity of extrachromosomal circular DNAs in UBC, including numerous single-locus and complex chimeric circular DNAs originating from different chromosomes. This includes highly chimeric circular DNAs carrying seven oncogenes and circles from nine chromosomes. We also found that large tumor-specific extrachromosomal circular DNAs could influence genome-wide gene expression, and are detectable in time-matched urinary sediments. Additionally, we found that the extrachromosomal circular DNA correlates with hypermutation, copy number variation, oncogene amplification, and clinical outcome. Conclusions: Overall, our study provides a comprehensive extrachromosomal circular DNA map of UBC, along with valuable data resources and bioinformatics tools for future cancer and extrachromosomal circular DNA research.


Assuntos
Variações do Número de Cópias de DNA , DNA Circular , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/genética , Humanos , DNA Circular/genética , Variações do Número de Cópias de DNA/genética , Sequenciamento Completo do Genoma/métodos , Heterogeneidade Genética , Masculino , Feminino , Sequenciamento do Exoma/métodos , Idoso , Mutação/genética
4.
PLoS One ; 19(8): e0308537, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39186566

RESUMO

INTRODUCTION: Diabetic peripheral neuropathy (DPN), a widely prevalent complication in patients with type 2 diabetes, exerts a significant influence on patients' overall health and financial circumstances. Photobiomodulation therapy is one of the means of physical therapy for DPN. Although preliminary findings suggest the efficacy of photobiomodulation therapy in alleviating peripheral neuropathy, the existing literature lacks substantial evidence regarding its safety and effectiveness specifically in the context of diabetes-related peripheral neuropathy. Therefore, we plan to arrive at more distinct findings through systematic evaluation and meta-analysis. METHODS: We will conduct a comprehensive search for studies published from the beginning until October 1, 2023, using various databases including Web of Science, Embase, Cochrane Library, PubMed, AMED, Wanfang database, VIP database, China National Knowledge Infrastructure, and the Chinese Biomedical Literature database. Simultaneously, we will also search for the WHO International Clinical Trial Registration Platform, China Clinical Trial Registration Platform, and Clinical Trials.gov. Gray literature will be retrieved using Google Scholar and opengrey.edu. Only randomized controlled trials in Chinese and English were included, with no restrictions on publication status. The primary outcomes will include change of symptom scores, change of nerve conduction velocity. Additional outcomes will encompass quality of life, change in pain, blood glucose levels after fasting and 2 hours after eating, levels of glycosylated hemoglobin, and any adverse events associated with photobiomodulation therapy. Reman V.5.4 and R language will be used for the meta-analysis. Assessment of potential bias will be conducted through Cochrane risk of bias 2 tool (RoB 2.0) and Physiotherapy Evidence Database (PEDro) scale. Registration: PROSPERO (registration number: CRD42023466586). DISCUSSION: This meta-analysis aims to assess the efficacy and safety of photobiomodulation therapy as a potential treatment for diabetic peripheral neuropathy (DPN), and providing a straightforward and convenient therapeutic for patients. Additionally, it expands the range of treatment alternatives available to healthcare professionals managing DPN.


Assuntos
Neuropatias Diabéticas , Terapia com Luz de Baixa Intensidade , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/radioterapia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/radioterapia , Terapia com Luz de Baixa Intensidade/efeitos adversos , Terapia com Luz de Baixa Intensidade/métodos , Metanálise como Assunto , Qualidade de Vida , Revisões Sistemáticas como Assunto , Resultado do Tratamento
5.
Hum Vaccin Immunother ; 20(1): 2394255, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-39208849

RESUMO

In the post-COVID-19 pandemic era, influenza virus infections continuously lead to a global disease burden. Evaluating vaccine effectiveness against influenza infection is crucial to inform vaccine design and vaccination strategy. In this study, we recruited 1120 patients with influenza-like illness (ILI) who attended fever clinics of 4 sentinel hospitals in the Ili Kazakh Autonomous Prefecture, Xinjiang Uygur Autonomous Region, China, from January 1 to April 7, 2024. Using a test-negative design, we estimated influenza vaccine effectiveness (VE) of 54.7% (95% CrI: 23.7, 73.1) against medical-attended influenza infection, with 62.3% (95% CrI: 29.3, 79.8) against influenza A, and 51.2% (95% CrI: 28.7, 83.0) against influenza B. Despite the moderate VE estimated in this study, influenza vaccination remains the most important approach to prevent influenza at the community level.


Assuntos
Vacinas contra Influenza , Influenza Humana , Eficácia de Vacinas , Humanos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , China/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos de Casos e Controles , Adolescente , Idoso , Adulto Jovem , Criança , Vacinação/estatística & dados numéricos , Pré-Escolar , Estações do Ano , Vírus da Influenza B/imunologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/imunologia , Lactente , Vírus da Influenza A/imunologia
6.
FASEB J ; 38(17): e70019, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39215561

RESUMO

Non-proliferative diabetic retinopathy (NPDR) is the early stage of diabetic retinopathy (DR) and is a chronic oxidative stress-related ocular disease. Few treatments are approved for early DR. This study aimed to investigate the pathogenic mechanisms underlying the retinal micro-vasculopathy induced by diabetes and to explore an early potential for treating early DR in a mouse model. The mouse model of type 1 diabetes was established by intraperitoneal injection of streptozotocin (STZ, 180 mg/kg), which was used as the early DR model. The body weight and blood glucose mice were measured regularly; The retinal vascular leakage in the early DR mice was determined by whole-mount staining; Label-free quantitative proteomic analysis and bioinformatics were used to explore the target proteins and signaling pathways associated with the retinal tissues of early DR mice; To detect the effects of target protein on endothelial cell proliferation, migration, and tube formation, knockdown and overexpression of VEGF-B were performed in human retinal vascular endothelial cells (HRECs); Western blotting was used to detect the expression of target proteins in vitro and in vivo; Meanwhile, the therapeutic effect of VEGF-B on vascular leakage has also been evaluated in vitro and in vivo. The protein expressions of vascular endothelial growth factor (VEGF)-B and the Rho GTPases family member CDC42 were reduced in the retinal tissues of early DR. VEGF-B upregulated the expression of CDC42/ZO1/VE-cadherin and prevented hyperglycemia-induced vascular leakage in HRECs. Standard intravitreal VEGF-B injections improved the retinal vascular leakage and neurovascular response in early DR mice. Our findings demonstrated, for the first time, that in diabetes, the retinal vessels are damaged due to decreased VEGF-B expression through downregulation of CDC42/ZO1/VE-cadherin expression. Therefore, VEGF-B could be used as a novel therapy for early DR.


Assuntos
Antígenos CD , Caderinas , Diabetes Mellitus Experimental , Retinopatia Diabética , Hiperglicemia , Proteína cdc42 de Ligação ao GTP , Animais , Proteína cdc42 de Ligação ao GTP/metabolismo , Camundongos , Caderinas/metabolismo , Retinopatia Diabética/metabolismo , Retinopatia Diabética/prevenção & controle , Retinopatia Diabética/etiologia , Retinopatia Diabética/patologia , Hiperglicemia/metabolismo , Masculino , Antígenos CD/metabolismo , Antígenos CD/genética , Humanos , Diabetes Mellitus Experimental/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Proteína da Zônula de Oclusão-1/genética , Transdução de Sinais , Camundongos Endogâmicos C57BL , Vasos Retinianos/metabolismo , Vasos Retinianos/patologia , Células Endoteliais/metabolismo , Retina/metabolismo , Retina/patologia , Permeabilidade Capilar
7.
Exp Neurol ; 381: 114921, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39142369

RESUMO

The dysregulation of Angiotensin-converting enzyme 2 (ACE2) in central nervous system is believed associates with COVID-19 induced cognitive dysfunction. However, the detailed mechanism remains largely unknown. In this study, we performed a comprehensive system genetics analysis on hippocampal ACE2 based on BXD mice panel. Expression quantitative trait loci (eQTLs) mapping showed that Ace2 was strongly trans-regulated, and the elevation of Ace2 expression level was significantly correlated with impaired cognitive functions. Further Gene co-expression analysis showed that Ace2 may be correlated with the membrane proteins in Calcium signaling pathway. Further, qRT-PCR confirmed that SARS-CoV-2 spike S1 protein upregulated ACE2 expression together with eight membrane proteins in Calcium Signaling pathway. Moreover, such elevation can be attenuated by recombinant ACE2. Collectively, our findings revealed a potential mechanism of Ace2 in cognitive dysfunction, which could be beneficial for COVID-19-induced cognitive dysfunction prevention and potential treatment.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Disfunção Cognitiva , Locos de Características Quantitativas , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/complicações , COVID-19/psicologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/etiologia , Camundongos , SARS-CoV-2 , Hipocampo/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Masculino , Humanos , Biologia de Sistemas/métodos
8.
Int J Biol Macromol ; 278(Pt 1): 134613, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39127284

RESUMO

In the present study, the in vivo absorption and fecal excretion of a purified fraction of polysaccharides from the fruits of Lycium barbarum L. (LBPs-4) in rats were investigated by labelling LBPs-4 with fluorescein isothiocyanate (FITC). It was found that the fluorescent labeled LBPs-4 (LBPs-4-FITC) was not detected in the plasma within 24 h following the administration of a single dose of LBPs-4-FITC (100 mg/kg of body weight) to rats, indicating that LBPs-4 was hardly absorbed in its prototype form. Instead, a smaller fragment dissociated from LBPs-4-FITC was observed in feces and was accumulated in a time-dependent manner, suggesting that LBPs-4 was excreted into the feces with a form of degradation. Meanwhile, we observed that LBPs-4-FTIC could modulate the fecal bacterial community profile via increasing the relative abundances of Bacteroides ovatus and Alistipes and promote the production of acetic acid. Furthermore, the monoculture experiment confirmed that LBPs-4 could be metabolized into smaller fragment by B. ovatus, producing acetic acid. Collectively, our study provides information on the destiny of LBPs-4 after oral administration: non-absorbed but moved to the large intestine and catabolized by gut microbiota, especially B. ovatus.


Assuntos
Fezes , Frutas , Lycium , Polissacarídeos , Animais , Fezes/química , Lycium/química , Ratos , Frutas/química , Polissacarídeos/química , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Ratos Sprague-Dawley
9.
Food Funct ; 15(16): 8477-8487, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39054889

RESUMO

2-O-ß-D-Glucopyranosyl-L-ascorbic acid (AA-2ßG) from Lycium barbarum fruits has diverse bioactivities, yet its absorption and digestion are poorly understood. Therefore, the in vivo absorption of AA-2ßG in rats was investigated in the present study. After oral administration to SD rats, AA-2ßG was absorbed intact, reaching a peak plasma concentration of 472.32 ± 296.64 nM at 90 min, with fecal excretion peaking at 4-8 h and decreasing rapidly by 12-24 h, indicating a prolonged intestinal presence. Furthermore, the digestibility under simulated gastrointestinal conditions and the impact on the gut flora through in vitro fermentation of AA-2ßG were investigated. The results reveal that AA-2ßG resisted in in vitro simulated digestion, indicating potential interactions with the gut microbiota. The results of in vitro fermentation showed that AA-2ßG regulated the composition of the gut microbiota by promoting Oscillospiraceae, Faecalibacterium, Limosilactobacillus, and Fusicatenibacter, while inhibiting Enterococcus, Phocaeicola, Bacteroides, and Streptococcus. Furthermore, at the species level, AA-2ßG promoted the growth of Limosilactobacillus mucosae and Faecalibacterium prausnitzii, and inhibited the growth of Enterococcus. F. prausnitzii is a major producer of n-butyric acid, and the results of short-chain fatty acids also demonstrated a significant promotion of n-butyric acid. Therefore, the study on the absorption, excretion, and regulatory effects of AA-2ßG on the gut microbiota supported its potential development as a functional food additive to enhance intestinal health and prevent diseases.


Assuntos
Ácido Ascórbico , Digestão , Fermentação , Frutas , Microbioma Gastrointestinal , Lycium , Ratos Sprague-Dawley , Microbioma Gastrointestinal/efeitos dos fármacos , Lycium/química , Animais , Ratos , Frutas/química , Humanos , Ácido Ascórbico/farmacologia , Ácido Ascórbico/metabolismo , Ácido Ascórbico/análogos & derivados , Masculino , Bactérias/classificação , Bactérias/metabolismo , Fezes/microbiologia , Absorção Intestinal
10.
Huan Jing Ke Xue ; 45(7): 4052-4062, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022953

RESUMO

Microplastics are among the most difficult new pollutants to remove in wastewater treatment plants. In order to explore the occurrence form, size distribution, composition, removal efficiency, migration law, and fate behavior characteristics of microplastic particles in sewage plants, taking a sewage treatment plant in Hohhot as an example, a total of 17 sampling sites were set up. The LAS X software counted the shape, abundance, and size of microplastics and conducted a full-process analysis. The results showed that: fibrous microplastics had the highest abundance and widest distribution and were the main form of existence, accounting for 61.8% of the total abundance; the size of microplastics ranged mainly between 0 and 1.00 mm, and among the four sizes, the abundance of microplastics 0.25 to 0.50 mm in China was the highest, accounting for 32.9%. Among the eight types of plastic components detected, polyester substances (PET, PBT), cellulose, and polypropylene (PP) were the main components, accounting for 25%, 21%, and 17%, respectively. The influent abundance of the sewage plant was (73 ±5) n·L-1, the effluent abundance was (14 ±2) n·L-1, and the overall removal rate was (80.8 ±12.1)%. Among the three treatment stages of the sewage plant, only the primary treatment played a role in removal, and the abundance of microplastics surged in the secondary treatment. Different structures playing a major role in the removal of microplastics were fine grids (49.2 ±7.4)% and secondary sedimentation tanks (92.4 ±13.9)%. Microplastics mainly existed in the form of fibers, fragments, and films. The proportion of fibers was approximately 70%, and the size of fragments was mainly concentrated between 0.50 and 5.00 mm. Most fragments were in the range of 5.00 mm, accounting for 50%, making them the main form apart from fibrous. The film-like size was mostly concentrated in the range of less than 0.50 mm, accounting for more than 10%. Therefore, improving the removal of small-sized fibrous and film-like microplastics and large-sized fragmented microplastic particles can effectively reduce the pollution risk of microplastics in the environment caused by sewage plant drainage.


Assuntos
Cidades , Microplásticos , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água , Microplásticos/análise , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação , China , Esgotos/química , Plásticos , Tamanho da Partícula , Polipropilenos , Monitoramento Ambiental
11.
J Clin Endocrinol Metab ; 109(10): 2692-2707, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-38709677

RESUMO

CONTENT: The correlation between visceral obesity index (VAI) and diabetes and accuracy of early prediction of diabetes are still controversial. OBJECTIVE: This study aims to review the relationship between high level of VAI and diabetes and early predictive value of diabetes. DATA SOURCES: The databases of PubMed, Cochrane, Embase, and Web of Science were searched until October 17, 2023. STUDY SELECTION: After adjusting for confounding factors, the original study on the association between VAI and diabetes was analyzed. DATA EXTRACTION: We extracted odds ratio (OR) between VAI and diabetes management after controlling for mixed factors, and the sensitivity, specificity, and diagnostic 4-grid table for early prediction of diabetes. DATA SYNTHESIS: Fifty-three studies comprising 595 946 participants were included. The findings of the meta-analysis elucidated that in cohort studies, a high VAI significantly increased the risk of diabetes mellitus in males (OR = 2.83 [95% CI, 2.30-3.49]) and females (OR = 3.32 [95% CI, 2.48-4.45]). The receiver operating characteristic, sensitivity, and specificity of VAI for early prediction of diabetes in males were 0.64 (95% CI, .62-.66), 0.57 (95% CI, .53-.61), and 0.65 (95% CI, .61-.69), respectively, and 0.67 (95% CI, .65-.69), 0.66 (95% CI, .60-.71), and 0.61 (95% CI, .57-.66) in females, respectively. CONCLUSION: VAI is an independent predictor of the risk of diabetes, yet its predictive accuracy remains limited. In future studies, determine whether VAI can be used in conjunction with other related indicators to early predict the risk of diabetes, to enhance the accuracy of prediction of the risk of diabetes.


Assuntos
Obesidade Abdominal , Humanos , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Diabetes Mellitus/epidemiologia , Fatores de Risco , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino
12.
Biomed Pharmacother ; 176: 116807, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795644

RESUMO

Metabolic syndrome (MetS) is a widespread and multifactorial disorder, and the study of its pathogenesis and treatment remains challenging. Autophagy, an intracellular degradation system that maintains cellular renewal and homeostasis, is essential for maintaining antimicrobial defense, preserving epithelial barrier integrity, promoting mucosal immune response, maintaining intestinal homeostasis, and regulating gut microbiota and microbial metabolites. Dysfunctional autophagy is implicated in the pathological mechanisms of MetS, involving insulin resistance (IR), chronic inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, with IR being a predominant feature. The study of autophagy represents a valuable field of research with significant clinical implications for identifying autophagy-related signals, pathways, mechanisms, and treatment options for MetS. Given the multifactorial etiology and various potential risk factors, it is imperative to explore the interplay between autophagy and gut microbiota in MetS more thoroughly. This will facilitate the elucidation of new mechanisms underlying the crosstalk among autophagy, gut microbiota, and MetS, thereby providing new insights into the diagnosis and treatment of MetS.


Assuntos
Autofagia , Microbioma Gastrointestinal , Resistência à Insulina , Síndrome Metabólica , Autofagia/fisiologia , Microbioma Gastrointestinal/fisiologia , Síndrome Metabólica/microbiologia , Síndrome Metabólica/metabolismo , Humanos , Resistência à Insulina/fisiologia , Animais , Transdução de Sinais
13.
J Neurosci ; 44(26)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38777602

RESUMO

The striatum plays a central role in directing many complex behaviors ranging from motor control to action choice and reward learning. In our study, we used 55 male CFW mice with rapid decay linkage disequilibrium to systematically mine the striatum-related behavioral functional genes by analyzing their striatal transcriptomes and 79 measured behavioral phenotypic data. By constructing a gene coexpression network, we clustered the genes into 13 modules, with most of them being positively correlated with motor traits. Based on functional annotations as well as Fisher's exact and hypergeometric distribution tests, brown and magenta modules were identified as core modules. They were significantly enriched for striatal-related functional genes. Subsequent Mendelian randomization analysis verified the causal relationship between the core modules and dyskinesia. Through the intramodular gene connectivity analysis, Adcy5 and Kcnma1 were identified as brown and magenta module hub genes, respectively. Knock outs of both Adcy5 and Kcnma1 lead to motor dysfunction in mice, and KCNMA1 acts as a risk gene for schizophrenia and smoking addiction in humans. We also evaluated the cellular composition of each module and identified oligodendrocytes in the striatum to have a positive role in motor regulation.


Assuntos
Adenilil Ciclases , Corpo Estriado , Animais , Camundongos , Masculino , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Adenilil Ciclases/genética , Comportamento Animal/fisiologia , Redes Reguladoras de Genes/genética , Transcriptoma
14.
BMC Bioinformatics ; 25(1): 177, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704528

RESUMO

BACKGROUND: Hepatitis B virus (HBV) integrates into human chromosomes and can lead to genomic instability and hepatocarcinogenesis. Current tools for HBV integration site detection lack accuracy and stability. RESULTS: This study proposes a deep learning-based method, named ViroISDC, for detecting integration sites. ViroISDC generates corresponding grammar rules and encodes the characteristics of the language data to predict integration sites accurately. Compared with Lumpy, Pindel, Seeksv, and SurVirus, ViroISDC exhibits better overall performance and is less sensitive to sequencing depth and integration sequence length, displaying good reliability, stability, and generality. Further downstream analysis of integrated sites detected by ViroISDC reveals the integration patterns and features of HBV. It is observed that HBV integration exhibits specific chromosomal preferences and tends to integrate into cancerous tissue. Moreover, HBV integration frequency was higher in males than females, and high-frequency integration sites were more likely to be present on hepatocarcinogenesis- and anti-cancer-related genes, validating the reliability of the ViroISDC. CONCLUSIONS: ViroISDC pipeline exhibits superior precision, stability, and reliability across various datasets when compared to similar software. It is invaluable in exploring HBV infection in the human body, holding significant implications for the diagnosis, treatment, and prognosis assessment of HCC.


Assuntos
Vírus da Hepatite B , Integração Viral , Vírus da Hepatite B/genética , Humanos , Integração Viral/genética , Software , Aprendizado Profundo , Masculino , Feminino , Hepatite B/genética , Hepatite B/virologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Biologia Computacional/métodos
15.
Mol Phylogenet Evol ; 196: 108072, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38615706

RESUMO

While the diversity of species formation is broadly acknowledged, significant debate exists regarding the universal nature of hybrid species formation. Through an 18-year comprehensive study of all Populus species on the Qinghai-Tibet Plateau, 23 previously recorded species and 8 new species were identified. Based on morphological characteristics, these can be classified into three groups: species in section Leucoides, species with large leaves, and species with small leaves in section Tacamahaca. By conducting whole-genome re-sequencing of 150 genotypes from these 31 species, 2.28 million single nucleotide polymorphisms (SNPs) were identified. Phylogenetic analysis utilizing these SNPs not only revealed a highly intricate evolutionary network within the large-leaf species of section Tacamahaca but also confirmed that a new species, P. curviserrata, naturally hybridized with P. cathayana, P. szechuanica, and P. ciliata, resulting in 11 hybrid species. These findings indicate the widespread occurrence of hybrid species formation within this genus, with hybridization serving as a key evolutionary mechanism for Populus on the plateau. A novel hypothesis, "Hybrid Species Exterminating Their Ancestral Species (HSEAS)," is introduced to explain the mechanisms of hybrid species formation at three different scales: the entire plateau, the southeastern mountain region, and individual river valleys.


Assuntos
Especiação Genética , Hibridização Genética , Filogenia , Polimorfismo de Nucleotídeo Único , Populus , Populus/genética , Populus/classificação , Tibet
16.
Food Sci Nutr ; 12(4): 2379-2392, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628207

RESUMO

Previous findings showed that anthocyanins from Lycium ruthenicum Murray (ACN) reduced HFD-induced hypercholesterolemia by regulating gut microbiota, but the mechanism has not been fully understood. The objective of this research was to know whether the cholesterol-lowering impact of ACN in HFD-induced ApoE-/- mice is related to the gut microbiota-bile acid (BA) metabolism. Twenty-four male ApoE-/- mice were divided into three groups: the Control group, the HFD group, and the HFD + ACN group. Here, we showed that ACN intervention reduced HFD-induced body weight serum concentrations of TC and LDL-C and ameliorated lipid accumulation in the liver and adipose tissues. Besides, ACN altered gut microbiota composition in HFD-fed ApoE-/- mice. Moreover, UHPLC-MS/MS analysis revealed that ACN intervention significantly increased the ratio of conjugated to unconjugated BAs in feces induced by HFD, attributed to the increase in conjugated BAs and decrease in unconjugated BAs. Finally, the correlation analysis indicated that the above changes in fecal BA profile were linked with an increase in Bifidobacterium, Allobaculum and a decrease in Ileibacterium, Helicobacter, Rikenellaceae_RC9_gut_group, Blautia, Odoribacter, and Colidextribacter. In summary, ACN could alleviate HFD-induced hypercholesterolemia in ApoE-/- mice, which was associated with the improvement of gut microbiota and modulation of fecal BA profile.

17.
Sci Rep ; 14(1): 5581, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38448473

RESUMO

In order to study the evolutionary law of roof migration on Gob-Side Entry Retaining, this paper takes the gob-side entry retaining in the comprehensive mining face of the Ningtiaota coal mine as the engineering background, and analyzes the evolutionary law of the overlying rock layer on the roof at different locations during the roadway stay and the stress distribution around the roadway through numerical simulation software, which shows that there is a concentration of stress inside the Flexible formwork concrete wall, and therefore the maximum settlement of the roof on the side of Flexible formwork concrete wall is 35.35 mm, due to the existence of "arch-shaped" decompression area from the working face. Therefore, the maximum settlement of the roof slab on the side of flexible formwork concrete wall was 35.35 mm. Due to the existence of "arch-shaped" decompression area on the roof and floor of roadway, the settlement of the roof slab on both sides of the roadway gradually increased when it was from - 20 to 10 m away from the working face, and the central position had the following pattern of firstly decreasing and then gradually increasing, and then exceeding the top of the roadway. After decreasing and then gradually increasing, after 10 m ahead of the working face, the two sides of the roadway roof subsidence law and the central part of the roadway to maintain the same; the use of cutting the top of the flexible mold concrete wall support technology as a means of controlling the top of the roof along the empty roadway subsidence, the analysis shows that the roof after roof cutting of the amount of subsidence have been reduced, the maximum difference in the rate of change of the displacement is 0.011%, and the maximum difference in the amount of subsidence of 4.98 mm; through the field monitoring data analysis of the pressure of mining The peak value of the influence curve of the working face is located at 19 m of the working face, 9 m of the lagging working face and 19 m of the roadway outside the working face are less affected by the additional mining stress field, comparing the fracture brokenness of the roadway roof before and after the roof cutting, the fracture area in the uncut section is much larger than that in the section of the roof cutting.

18.
Sci Rep ; 14(1): 5708, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459118

RESUMO

In a coal mine in the northern region of Shaanxi Province, China, a facing-mining excavating roadway exists, which is intended to be retained for subsequent working face safety services. This paper investigates the deformation and damage characteristics of the surrounding rock in different stages using FLAC 3D numerical simulation, taking the facing-mining excavating roadway of this coal mine as the research context. At 20 m ahead of the working face, a discontinuous plastic zone appears in the surrounding rock of the roadway, a phenomenon attributed to the varying hardness of the lithologyand termed 'plastic zone jumping.' The numerical simulation results have been were verified using drill hole peeping. Real-time monitoring of the roadway's stability is conducted on-site, showing that the roadway is significantly affected by mining at the 50 m point ahead of the working face. Based on the numerical simulation and on-site monitoring results, the support strength was increased at 50 m from the working face along the roadway, and a new support scheme was adopted. In the lagging section of the roadway, where mining pressure is strongly evident, differentiated reinforcement using anchor rods, anchor ropes, and W steel belts has been employed, resulting in a satisfactory on-site effect.

20.
Diabetes Obes Metab ; 26(5): 1775-1788, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38385898

RESUMO

AIM: The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause non-alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidaemia, etc. We aimed to systematic investigate the key factors related to hepatic glucose metabolism, which may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus. MATERIALS AND METHODS: Oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes of BXD mice under chow and high-fat diet conditions were collected from GeneNetwork. QTL mapping was conducted to pinpoint genomic regions associated with glucose homeostasis. Candidate genes were further nominated using a multi-criteria approach and validated to confirm their functional relevance in vitro. RESULTS: Our results demonstrated that plasma glucose levels in OGTT were significantly affected by both diet and genetic background, with six genetic regulating loci were mapped on chromosomes 1, 4, and 7. Moreover, TEAD1, MYO7A and NDUFC2 were identified as the candidate genes. Functionally, siRNA-mediated TEAD1, MYO7A and NDUFC2 knockdown significantly decreased the glucose uptake and inhibited the transcription of genes related to insulin and glucose metabolism pathways. CONCLUSIONS: Our study contributes novel insights to the understanding of hepatic glucose metabolism, demonstrating the impact of TEAD1, MYO7A and NDUFC2 on mitochondrial function in the liver and their regulatory role in maintaining in glucose homeostasis.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Diabetes Mellitus Tipo 2/complicações , Dieta Hiperlipídica , Glucose/metabolismo , Resistência à Insulina/fisiologia , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo
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