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1.
Front Immunol ; 15: 1424197, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983866

RESUMO

Background: Lung squamous cell carcinoma (LUSC) ranks among the carcinomas with the highest incidence and dismal survival rates, suffering from a lack of effective therapeutic strategies. Consequently, biomarkers facilitating early diagnosis of LUSC could significantly enhance patient survival. This study aims to identify novel biomarkers for LUSC. Methods: Utilizing the TCGA, GTEx, and CGGA databases, we focused on the gene encoding Family with Sequence Similarity 20, Member A (FAM20A) across various cancers. We then corroborated these bioinformatic predictions with clinical samples. A range of analytical tools, including Kaplan-Meier, MethSurv database, Wilcoxon rank-sum, Kruskal-Wallis tests, Gene Set Enrichment Analysis, and TIMER database, were employed to assess the diagnostic and prognostic value of FAM20A in LUSC. These tools also helped evaluate immune cell infiltration, immune checkpoint genes, DNA repair-related genes, DNA methylation, and tumor-related pathways. Results: FAM20A expression was found to be significantly reduced in LUSC, correlating with lower survival rates. It exhibited a negative correlation with key proteins in DNA repair signaling pathways, potentially contributing to LUSC's radiotherapy resistance. Additionally, FAM20A showed a positive correlation with immune checkpoints like CTLA-4, indicating potential heightened sensitivity to immunotherapies targeting these checkpoints. Conclusion: FAM20A emerges as a promising diagnostic and prognostic biomarker for LUSC, offering potential clinical applications.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/imunologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biologia Computacional/métodos , Bases de Dados Genéticas , Proteínas que Contêm Bromodomínio , Proteínas do Tecido Nervoso , Fatores de Transcrição , Antígenos Nucleares
2.
PLoS One ; 19(7): e0306518, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38980862

RESUMO

OBJECTIVE: To evaluate the effects of Tai Chi in the treatment of patients with chronic low back pain by Meta-analysis and to investigate its influencing factors. METHODS: The study searched eight databases (PubMed, Embase, The Cochrane Library, Web of Science, China Knowledge Network, Wanfang, VIP, and CBM) from inception to October 2023. Two investigators independently selected 10 eligible randomized controlled trials (RCT) against inclusion and exclusion criteria, followed by data extraction and study quality assessment by ROB 2. The outcomes of interest were pain intensity and disability. The studies were combined using meta-analysis when statistical pooling of data was possible. The quality of the evidence was assessed using the GRADE approach. RESULTS: 10 randomized controlled studies with a total sample of 886 cases were included, of which 4 (40%) were assessed as low risk of bias. The effect size of Tai Chi for chronic low back pain was [Weighted Mean Difference (WMD) with 95% Confidence Interval (CI) = -1.09 (-1.26, -0.92), p < 0.01], all achieving large effect sizes and statistically significant; the effect size for disability was [Standard Mean Difference (SMD) with 95% CI = -1.75 (-2.02, -1.48), p < 0.01], and the combined effect sizes of physical health and mental health for quality of life were [WMD (95% CI) = 4.18 (3.41, 4.95), p < 0.01; WMD (95% CI) = 3.23 (2.42, 4.04), p < 0.01] respectively. The incidence of adverse reactions was low. Meta regression and subgroup analysis showed that there was no significant effect on intervention measures (Tai Chi alone, Tai Chi as additional therapy, water Tai Chi), Tai Chi school (Chen and Yang) and the number of total intervention sessions (> 30 and ≤ 30). The evidence quality evaluation showed that the evidence of pain, physical health of quality of life and mental health score was medium quality, while the evidence of disability and adverse reactions was low quality. CONCLUSIONS: Tai Chi has an obvious effect of in relieving chronic low back pain. Tai Chi alone and Tai Chi as supplementary therapy have good effects. Tai Chi in water have not been verified. Chen style Tai Chi and Yang's Tai Chi, intervention more than 30 times or less than 30 times had no significant difference in the effect of intervention on CLBP.


Assuntos
Dor Crônica , Dor Lombar , Tai Chi Chuan , Dor Lombar/terapia , Humanos , Dor Crônica/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Qualidade de Vida
3.
Clin Pharmacol Ther ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38962850

RESUMO

Bispecific T-cell Engagers (TCEs) are promising anti-cancer treatments that bind to both the CD3 receptors on T cells and an antigen on the surface of tumor cells, creating an immune synapse, leading to killing of malignant tumor cells. These novel therapies have unique development challenges, with specific safety risks of cytokine release syndrome. These on-target adverse events fortunately can be mitigated and deconvoluted from efficacy via innovative dosing strategies, making clinical pharmacology key in the development of these therapies. This review assesses dose selection and the role of quantitative clinical pharmacology in the development of the first eight approved TCEs. Model informed drug development (MIDD) strategies can be used at every stage to guide TCE development. Mechanistic modeling approaches allow for (1) efficacious yet safe first-in-human dose selection as compared with in vitro minimum anticipated biological effect level (MABEL) approach; (2) rapid escalation and reducing number of patients with subtherapeutic doses through model-based adaptive design; (3) virtual testing of different step-up dosing regimens that may not be feasible to be evaluated in the clinic; and (4) selection and justification of the optimal clinical step-up and full treatment doses. As the knowledge base around TCEs continues to grow, the relevance and utilization of MIDD strategies for supporting the development and dose optimization of these molecules are expected to advance, optimizing the benefit-risk profile for cancer patients.

4.
Cell Commun Signal ; 22(1): 315, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849890

RESUMO

BACKGROUND: Aberrant inflammatory responses drive the initiation and progression of various diseases, and hyperactivation of NLRP3 inflammasome is a key pathogenetic mechanism. Pharmacological inhibitors of NLRP3 represent a potential therapy for treating these diseases but are not yet clinically available. The natural product butein has excellent anti-inflammatory activity, but its potential mechanisms remain to be investigated. In this study, we aimed to evaluate the ability of butein to block NLRP3 inflammasome activation and the ameliorative effects of butein on NLRP3-driven diseases. METHODS: Lipopolysaccharide (LPS)-primed bone-marrow-derived macrophages were pretreated with butein and various inflammasome stimuli. Intracellular potassium levels, ASC oligomerization and reactive oxygen species production were also detected to evaluate the regulatory mechanisms of butein. Moreover, mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis were used to test whether butein has protective effects on these NLRP3-driven diseases. RESULTS: Butein blocks NLRP3 inflammasome activation in mouse macrophages by inhibiting ASC oligomerization, suppressing reactive oxygen species production, and upregulating the expression of the antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2). Importantly, in vivo experiments demonstrated that butein administration has a significant protective effect on the mouse models of LPS-induced peritonitis, dextran sodium sulfate-induced colitis, and high-fat diet-induced non-alcoholic steatohepatitis. CONCLUSION: Our study illustrates the connotation of homotherapy for heteropathy, i.e., the application of butein to broaden therapeutic approaches and treat multiple inflammatory diseases driven by NLRP3.


Assuntos
Chalconas , Inflamassomos , Lipopolissacarídeos , Macrófagos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Espécies Reativas de Oxigênio , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Chalconas/farmacologia , Chalconas/uso terapêutico , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Inflamassomos/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Modelos Animais de Doenças , Colite/induzido quimicamente , Colite/patologia , Colite/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia
5.
Cells ; 13(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38920649

RESUMO

Mycobacterium tuberculosis causes 6.4 million cases of tuberculosis and claims 1.6 million lives annually. Mycobacterial adhesion, invasion of host cells, and subsequent intracellular survival are crucial for the infection and dissemination process, yet the cellular mechanisms underlying these phenomena remain poorly understood. This study created a Bacillus Calmette-Guérin (BCG) transposon library using a MycomarT7 phage carrying a Himar1 Mariner transposon to identify genes related to mycobacteria adhesion and invasion. Using adhesion and invasion model screening, we found that the mutant strain B2909 lacked adhesion and invasion abilities because of an inactive fadD18 gene, which encodes a fatty-acyl CoA ligase, although the specific function of this gene remains unclear. To investigate the role of FadD18, we constructed a complementary strain and observed that fadD18 expression enhanced the colony size and promoted the formation of a stronger cord-like structure; FadD18 expression also inhibited BCG growth and reduced BCG intracellular survival in macrophages. Furthermore, FadD18 expression elevated levels of the proinflammatory cytokines IL-6, IL-1ß, and TNF-α in infected macrophages by stimulating the NF-κB and MAPK signaling pathways. Overall, the FadD18 plays a key role in the adhesion and invasion abilities of mycobacteria while modulating the intracellular survival of BCG by influencing the production of proinflammatory cytokines.


Assuntos
Citocinas , Mycobacterium tuberculosis , Citocinas/metabolismo , Macrófagos/microbiologia , Macrófagos/metabolismo , Mycobacterium bovis , Camundongos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Animais , Humanos , NF-kappa B/metabolismo , Viabilidade Microbiana , Aderência Bacteriana
6.
Cureus ; 16(5): e60845, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38910777

RESUMO

OBJECTIVE: We explored the value of a standardized patient-based situational simulation teaching method in general surgery internships. METHODS: A prospective, single-blind, randomized controlled trial was conducted with clinical medicine undergraduates from the 2020 cohort of our university as subjects. These students were randomly divided into a traditional teaching (TT) group and a combined teaching (CT) group based on their internship schedules. The TT group followed the conventional teaching model, while the CT group engaged in the standardized patient-based situational simulation teaching method. The study compared differences in pre-internship theoretical scores, post-internship theoretical scores, medical record writing quality, and student satisfaction between the two groups. RESULTS: The CT group (n=108) significantly outperformed the TT group (n=104) in post-internship theoretical scores and medical record writing quality (all P<0.05) and showed marked improvement in stimulating students' interest in learning (P=0.015), enhancing clinical diagnostic and treatment abilities (P<0.001), improving doctor‒patient communication skills (P<0.001), strengthening medical mission sense (P<0.001), reinforcing physicians' sense of responsibility (P<0.001), and facilitating the application of learned knowledge (P<0.001). These differences were statistically significant. CONCLUSION: The standardized patient-based situational simulation teaching method (CT) in general surgery internships has been highly recognized by students and can enhance their clinical competency, offering considerable value for broader.

7.
Int J Biol Macromol ; : 133402, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925177

RESUMO

Cuticle proteins, in conjunction with chitin, compose the insect exoskeleton, and play a key role in the growth, development, and molting of insects. However, the specific functions of most cuticular protein genes in the growth, development, and reproductive processes of the pea aphid (Acyrthosiphon pisum) remain unclear. In this study, we have identified six cuticle protein genes in the pea aphid, namely ApCP7, ApCP10, ApCP19, ApCP19.8-like, ApCP35 and ApCP62. We found that the expression levels of six genes were highly expressed during the adult stage, and except for ApCP10, which is highly expressed in the pea aphid cuticle, other genes were highly expressed in the ovaries. Subsequently, we observed that the survival rate and fecundity of pea aphid were significantly lower than those of the control group after silencing ApCP7 and ApCP62 through RNA interference. Furthermore, when ApCP7 transcript levels were reduced, aphid encountered difficulties in molting, were smaller in body sizes, and exhibited a darker body color. These results indicate that ApCP7 and ApCP62 are involved in the development and reproduction of pea aphid, and could be used as RNAi targets for controlling pea aphid.

8.
Comb Chem High Throughput Screen ; 27(5): 786-796, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38773797

RESUMO

OBJECTIVE: Diabetic osteoporosis (DOP) belongs to the group of diabetes-induced secondary osteoporosis and is the main cause of bone fragility and fractures in many patients with diabetes. The aim of this study was to determine whether Ziyin Bushen Fang (ZYBSF) can improve DOP by inhibiting autophagy and oxidative stress. METHODS: Type 1 diabetes mellitus (T1DM) was induced in rats using a high-fat high-sugar diet combined with streptozotocin. Micro-CT scanning was used to quantitatively observe changes in the bone microstructure in each group. Changes in the serum metabolites of DOP rats were analyzed using UHPLC-QTOF-MS. The DOP mouse embryonic osteoblast precursor cell model (MC3T3-E1) was induced using high glucose levels. RESULTS: After ZYBSF treatment, bone microstructure significantly improved. The bone mineral density, trabecular number, and trabecular thickness in the ZYBSF-M and ZYBSF-H groups significantly increased. After ZYBSF treatment, the femur structure of the rats was relatively intact, collagen fibers were significantly increased, and osteoporosis was significantly improved. A total of 1239 metabolites were upregulated and 1527 were downregulated in the serum of T1DM and ZYBSF-treated rats. A total of 20 metabolic pathways were identified. In cellular experiments, ZYBSF reduced ROS levels and inhibited the protein expression of LC3II / I, Beclin-1, and p-ERK. CONCLUSION: ZYBSF may improve DOP by inhibiting the ROS/ERK-induced autophagy signaling pathway.


Assuntos
Autofagia , Medicamentos de Ervas Chinesas , Osteoporose , Estresse Oxidativo , Animais , Autofagia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Camundongos , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Ratos Sprague-Dawley , Estreptozocina , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Densidade Óssea/efeitos dos fármacos
9.
Cell Commun Signal ; 22(1): 293, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802896

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe and fatal disease. Although mesenchymal stem cell (MSC)-based therapy has shown remarkable efficacy in treating ARDS in animal experiments, clinical outcomes have been unsatisfactory, which may be attributed to the influence of the lung microenvironment during MSC administration. Extracellular vesicles (EVs) derived from endothelial cells (EC-EVs) are important components of the lung microenvironment and play a crucial role in ARDS. However, the effect of EC-EVs on MSC therapy is still unclear. In this study, we established lipopolysaccharide (LPS) - induced acute lung injury model to evaluate the impact of EC-EVs on the reparative effects of bone marrow-derived MSC (BM-MSC) transplantation on lung injury and to unravel the underlying mechanisms. METHODS: EVs were isolated from bronchoalveolar lavage fluid of mice with LPS - induced acute lung injury and patients with ARDS using ultracentrifugation. and the changes of EC-EVs were analysed using nanoflow cytometry analysis. In vitro assays were performed to establish the impact of EC-EVs on MSC functions, including cell viability and migration, while in vivo studies were performed to validate the therapeutic effect of EC-EVs on MSCs. RNA-Seq analysis, small interfering RNA (siRNA), and a recombinant lentivirus were used to investigate the underlying mechanisms. RESULTS: Compared with that in non-ARDS patients, the quantity of EC-EVs in the lung microenvironment was significantly greater in patients with ARDS. EVs derived from lipopolysaccharide-stimulated endothelial cells (LPS-EVs) significantly decreased the viability and migration of BM-MSCs. Furthermore, engrafting BM-MSCs pretreated with LPS-EVs promoted the release of inflammatory cytokines and increased pulmonary microvascular permeability, aggravating lung injury. Mechanistically, LPS-EVs reduced the expression level of isocitrate dehydrogenase 2 (IDH2), which catalyses the formation of α-ketoglutarate (α-KG), an intermediate product of the tricarboxylic acid (TCA) cycle, in BM-MSCs. α-KG is a cofactor for ten-eleven translocation (TET) enzymes, which catalyse DNA hydroxymethylation in BM-MSCs. CONCLUSIONS: This study revealed that EC-EVs in the lung microenvironment during ARDS can affect the therapeutic efficacy of BM-MSCs through the IDH2/TET pathway, providing potential strategies for improving the therapeutic efficacy of MSC-based therapy in the clinic.


Assuntos
Células Endoteliais , Vesículas Extracelulares , Isocitrato Desidrogenase , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Síndrome do Desconforto Respiratório , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/transplante , Animais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/metabolismo , Células Endoteliais/metabolismo , Humanos , Camundongos , Transplante de Células-Tronco Mesenquimais/métodos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Lipopolissacarídeos/farmacologia , Transdução de Sinais , Lesão Pulmonar Aguda/terapia , Lesão Pulmonar Aguda/metabolismo , Movimento Celular
10.
J Pediatr Gastroenterol Nutr ; 79(1): 42-47, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38747032

RESUMO

The gastrointestinal (GI) manifestations in children with hypermobile Ehlers-Danlos syndrome/joint hypermobility syndrome (hEDS/JHS) are not well described. We investigated the prevalence of GI disorders in children and young adults with hEDS/JHS through a single-center retrospective review. Demographic data, clinical history, symptoms, and diagnostic studies were reviewed. Of 435 patients with hEDS/JHS, 66% were females (age 5-28 years). We noted a high prevalence of constipation (61%), dysphagia (32%), dyspepsia and/or gastroparesis (25%), eosinophilic esophagitis (EoE) (21%), and celiac disease (4%) in our cohort. Upper endoscopy and gastric emptying scans had the highest yield to detect abnormalities. Motility studies were abnormal in 31% of the 80 patients who underwent them. Dysphagia symptoms are significantly associated with EoE. Thirty-three percent of dysphagia patients had EoE, versus 16% of non-dysphagia patients (p < 0.001). Screening hEDS/JHS patients for GI issues should be routine, with further investigations and referrals guided by identified symptoms.


Assuntos
Gastroenteropatias , Instabilidade Articular , Humanos , Feminino , Adolescente , Masculino , Criança , Prevalência , Estudos Retrospectivos , Adulto Jovem , Adulto , Pré-Escolar , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Instabilidade Articular/epidemiologia , Instabilidade Articular/complicações , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Síndrome de Ehlers-Danlos/complicações , Síndrome de Ehlers-Danlos/epidemiologia , Esofagite Eosinofílica/epidemiologia , Esofagite Eosinofílica/complicações , Constipação Intestinal/epidemiologia , Constipação Intestinal/etiologia , Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Dispepsia/epidemiologia , Dispepsia/etiologia
11.
Medicine (Baltimore) ; 103(19): e37981, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728508

RESUMO

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ±â€…1.08 vs 3.00 ±â€…1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ±â€…1.43 vs 1.69 ±â€…1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ±â€…1.13 vs 2.80 ±â€…0.99, P = .022), preference for warmth and pressure (1.44 ±â€…1.06 vs 1.36 ±â€…1.10, P = .041), and poor appetite and indigestion (0.78 ±â€…0.66 vs 1.32 ±â€…0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety.


Assuntos
Medicamentos de Ervas Chinesas , Gastrite Atrófica , Humanos , Gastrite Atrófica/tratamento farmacológico , Feminino , Masculino , Método Duplo-Cego , Pessoa de Meia-Idade , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Adulto , Resultado do Tratamento , Doença Crônica , Medicina Tradicional Chinesa/métodos , Idoso , Gastroscopia
12.
PLoS One ; 19(5): e0304098, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38809895

RESUMO

BACKGROUND: Obesity, characterized by excessive body fat accumulation, is associated with various chronic health conditions. Body fat plays a crucial role in health outcomes, and nutrient intake is a contributing factor. Menopause further influences body fat, but the precise relationships between nutrients and fat mass distribution in pre- and post-menopausal women are unclear. METHODS: Data from 4751 adult women aged ≥18 years old (3855 pre-menopausal, 896 post-menopausal) with completed information were obtained from the National Health and Examination Survey (NHANES) from 2011 to 2018. Multivariate linear regression models were used to examine the associations between protein, carbohydrate, fat intake and total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android to gynoid ratio (A/G), subcutaneous adipose tissue mass (SAT), visceral adipose tissue mass (VAT). Subgroup analyses, stratified by menopausal status, were also conducted. Additionally, we employed smoothing curve fitting techniques to investigate potential non-linear relationships between fat mass distribution and nutrient intake. RESULTS: Compared with pre-menopausal women, post-menopausal women had higher body fat, BMI, and metabolic indicators but lower nutrient intake (All p<0.05). In the overall analysis, we found significant correlations between nutrient intake and fat mass. Specifically, protein intake was negatively correlated with TPF (ß = -0.017, 95% CI: -0.030, -0.005), APF (ß = -0.028, 95% CI: -0.044, -0.012), GPF (ß = -0.019, 95% CI: -0.030, -0.008), while fat intake showed positive correlations with these measures (SAT: ß = 2.769, 95% CI: 0.860, 4.678). Carbohydrate intake exhibited mixed associations. Notably, body fat mass-nutrient intake correlations differed by menopausal status. Generally speaking, protein intake showed negative correlations with body fat distribution in pre-menopausal women but positive correlations in post-menopausal women. Carbohydrate intake revealed significant negative associations with abdominal and visceral fat in post-menopausal women, while fat intake was consistently positive across all fat distribution indices, especially impacting visceral fat in post-menopausal women. CONCLUSION: Dietary intake plays a crucial role in body fat distribution, with menopausal status significantly influencing the impact of nutrients on specific fat distribution metrics. The study emphasizes the need for dietary guidelines to consider the nutritional needs and health challenges unique to women at different life stages, particularly concerning menopausal status, to effectively manage obesity.


Assuntos
Pós-Menopausa , Pré-Menopausa , Humanos , Feminino , Pós-Menopausa/fisiologia , Pessoa de Meia-Idade , Adulto , Nutrientes , Distribuição da Gordura Corporal , Índice de Massa Corporal , Proteínas Alimentares/administração & dosagem , Inquéritos Nutricionais , Idoso , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Gorduras na Dieta/administração & dosagem
13.
J Inflamm Res ; 17: 3187-3200, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779429

RESUMO

Background: Natural killer (NK) cells are key regulators of immune defense in sepsis-induced acute respiratory distress syndrome (ARDS), yet the characteristics of NK cell clusters in ARDS remain poorly understood. Methods: A prospective and observational study enrolled septic patients with ARDS or not was conducted to determine the percentage of NK cells via flow cytometry. The transcriptomes of peripheral blood mononuclear cells (PBMCs) from healthy controls, patients with sepsis only, and patients with sepsis-induced ARDS were profiled. Vitro experiments were performed to confirm the mechanism mediating MX1+NK cell infiltration. Results: A total of 115 septic patients were analyzed, among whom 63 patients developed ARDS and 52 patients did not. Decreased NK percentages were found in sepsis with ARDS patients (%, 7.46±4.40 vs 11.65±6.88, P=0.0001) compared with sepsis-only patients. A lower percentage of NK cells showed a significant increase in 28-day mortality. Single-cell sequencing analysis revealed distinct characteristics of NK cells in sepsis-induced ARDS, notably the identification of a unique cluster defined as MX1+NK cells. Flow cytometry analysis showed an elevated percentage of MX1+NK cells specifically in individuals with sepsis-induced ARDS, compared with patients with sepsis only. Pseudo-time analysis showed that MX1+NK cells were characterized by upregulation of type I interferon-induced genes and other pro-inflammatory genes. MX1+NK cells can respond to type I interferons and secrete type I interferons themselves. Ligand-receptor interaction analysis also revealed extensive interaction between MX1+NK cells and T/B cells, leading to an uncontrolled inflammatory response in ARDS. Conclusion: MX1+NK cells can respond to type I interferons and secrete type I interferons themselves, promoting the development of sepsis-induced ARDS. Interfering with the infiltration of MX1+NK cells could be a therapeutic approach for this disease. Due to the limited sample size, a larger sample size was needed for further exploration.

14.
Front Immunol ; 15: 1383936, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638432

RESUMO

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of xenotransplantation research. It begins by examining the mechanisms through which xenotransplantation activates both the classical and alternative complement pathways. It then assesses the current landscape of xenotransplantation from donor pigs, with a particular emphasis on the innovative strides made in genetically engineering pigs to evade complement system activation. These modifications are critical in mitigating the discordance between pig endogenous retroviruses and human immune molecules. Additionally, the review discusses pharmacological interventions designed to support transplantation. By exploring the intricate relationship between the complement system and xenotransplantation, this retrospective analysis not only underscores the scientific and clinical importance of this field but also sheds light on the potential pathways to overcoming one of the major barriers to the success of xenografts. As such, the insights offered here hold significant promise for advancing xenotransplantation from a research concept to a viable clinical reality.


Assuntos
Ativação do Complemento , Rejeição de Enxerto , Animais , Humanos , Suínos , Transplante Heterólogo , Animais Geneticamente Modificados , Estudos Retrospectivos , Rejeição de Enxerto/prevenção & controle , Proteínas do Sistema Complemento
15.
Water Res ; 255: 121548, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38569357

RESUMO

Rhizoremediation of wetland plants is an environmentally friendly strategy for sediment phosphorous (P) removal, the basic underlying principle of which is the complex interactions between roots and microorganisms. This study investigated the immobilization and mobilization mechanisms of P in the rhizosphere of wetland plants using high-resolution spatial visualization techniques and metagenomic sequencing. Two-dimensional visualization of the spatial distribution of P, iron (Fe) and manganese (Mn) indicated that the sequestration of Fe-oxides rather than Mn-oxides caused the depletion of labile P, resulting in an increase in the Fe-adsorbed P fraction. Plants altered the rhizospheric environments and P-cycling microbial community to mobilize low-availability P from sediments. Mineral P solubilization and organic P mineralization were enhanced by local acidification and increased phosphatase activity, respectively. Microbial P mobilization also increased with increasing relative abundances of P solubilization and mineralization genes (gcd and phnW) and decreasing P transportation genes (ugpA, ugpB, and pit) genes in the rhizosphere. These processes led to the remobilization of 10.04 % of inorganic P, and 15.23 % of organic P, in the rhizosphere during the incubation period. However, the resupply of P via the above processes did not compensate for the depletion of rhizospheric P via root uptake and mineral sequestration. Our results provide novel insights into the mechanisms of rhizospheric P cycling, which will help to inform future phytoremediation strategies.

16.
Am J Chin Med ; 52(2): 315-354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38553799

RESUMO

Liver diseases and their related complications endanger the health of millions of people worldwide. The prevention and treatment of liver diseases are still serious challenges both in China and globally. With the improvement of living standards, the prevalence of metabolic liver diseases, including non-alcoholic fatty liver disease and alcoholic liver disease, has increased at an alarming rate, resulting in more cases of end-stage liver disease. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently needed. Glycyrrhizin (GL), a triterpene glycoside from the roots of licorice plants, possesses a wide range of pharmacological and biological activities. Currently, GL preparations (GLPs) have certain advantages in the treatment of liver diseases, with good clinical effects and fewer adverse reactions, and have shown broad application prospects through multitargeting therapeutic mechanisms, including antisteatotic, anti-oxidative stress, anti-inflammatory, immunoregulatory, antifibrotic, anticancer, and drug interaction activities. This review summarizes the currently known biological activities of GLPs and their medical applications in the treatment of liver diseases, and highlights the potential of these preparations as promising therapeutic options and their alluring prospects for the treatment of liver diseases.


Assuntos
Ácido Glicirrízico , Hepatopatias , Humanos , Ácido Glicirrízico/farmacologia , Ácido Glicirrízico/uso terapêutico , Hepatopatias/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Estresse Oxidativo
18.
BMC Surg ; 24(1): 82, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443901

RESUMO

BACKGROUND: From year to year, the proportion of people living with overweight and obesity in China rises, along with the prevalence of diseases linked to obesity. Although bariatric surgery is gaining popularity, there are still several issues with its promotion compared to Western nations. Since less developed places in China are more widespread due to disparities in the development of different regions, there has been little exploration of the factors that might be related to acceptance of bariatric surgery in these regions. METHODS: Patients who visited the Department of Gastrointestinal Surgery at the North Sichuan Medical College Affiliated Hospital from 2018 to 2022 and had obesity or other relevant metabolic problems were surveyed using a questionnaire. The relationship between demographic factors, socioeconomic status, and acceptance of bariatric surgery was analyzed. RESULTS: Of 334 patients, 171 had bariatric surgery. BMI, education level, marriage history, medical insurance, family support, and a history of type 2 diabetes were all linked to having bariatric surgery, according to a univariate analysis. In a multivariate analysis, BMI (P = 0.02), education (P = 0.02), family support (P<0.001), medical insurance coverage (P<0.001), and history of type 2 diabetes (P = 0.004) were all positively associated with a willingness to have bariatric surgery. Among 163 non-bariatric patients with obesity, 15.3% were not opposed to surgery but preferred trying medication first, 54.6% leaned towards medical therapy, and 30% were hesitant. Additionally, a majority of patients (48.55%) often lacked adequate knowledge about weight reduction therapy. Age, height, gender, smoking, drinking, family history of type 2 diabetes, education, and marital status did not significantly differ (P > 0.05). CONCLUSIONS: Many patients are concerned about the safety of surgical treatment and the possibility of regaining weight. Due to the relatively high cost of bariatric surgery, they tend to choose medical treatment. To enhance the acceptance of bariatric surgery in underdeveloped regions of China, it is crucial to focus on disseminating knowledge about bariatric surgery, offer pertinent health education to the community, and foster support from patients' families. The government should pay more attention to obesity and provide support in the form of medical insurance.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Humanos , Obesidade/complicações , Obesidade/cirurgia , Sobrepeso , China/epidemiologia
19.
J Perinatol ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431756

RESUMO

OBJECTIVE: To evaluate factors associated with borderline/clinical range Child Behavior Checklist (CBCL) scores in opioid-exposed children. STUDY DESIGN: Retrospective study of 94 children with prenatal opioid exposure evaluated with the CBCL at age 2 years. RESULTS: Twenty-eight children (30%) had borderline/clinical findings on the CBCL, with 27% scoring borderline/clinical for Externalizing Problems. In the multivariable model, lower Bayley-III motor scores and discharge home with mother with safety plan were associated with borderline/clinical Externalizing Problems. Medication treatment for neonatal opioid withdrawal syndrome (NOWS) was associated with normal Externalizing Problems scores. Treatment with clonidine or phenobarbital was associated with scores in the normal range in all broadband CBCL measures. CONCLUSION: Specific factors are associated with behavioral and emotional challenges measured by borderline/clinical CBCL scores among opioid-exposed children.

20.
Life Sci ; 341: 122471, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38301875

RESUMO

AIMS: Disruption of the insulin signaling pathway leads to insulin resistance (IR). IR is characterized by impaired glucose and lipid metabolism. Elevated levels of circulating glutamate are correlated with metabolic indicators and may potentially predict the onset of metabolic diseases. Glutamate receptor antagonists have significantly enhanced insulin sensitivity, and improved glucose and lipid metabolism. Exercise is a well-known strategy to combat IR. The aims of our narrative review are to summarize preclinical and clinical findings to show the correlations between circulating glutamate levels, IR and metabolic diseases, discuss the causal role of excessive glutamate in IR and metabolic disturbance, and present an overview of the exercise-induced alteration in circulating glutamate levels. MATERIALS AND METHODS: A literature search was conducted to identify studies on glutamate, insulin signaling, and exercise in the PubMed database. The search covered articles published from December 1955 to January 2024, using the search terms of "glutamate", "glutamic acid", "insulin signaling", "insulin resistance", "insulin sensitivity", "exercise", and "physical activity". KEY FINDINGS: Elevated levels of circulating glutamate are correlated with IR. Excessive glutamate can potentially hinder the insulin signaling pathway through various mechanisms, including the activation of ectopic lipid accumulation, inflammation, and endoplasmic reticulum stress. Glutamate can also modify mitochondrial function through Ca2+ and induce purine degradation mediated by AMP deaminase 2. Exercise has the potential to decrease circulating levels of glutamate, which can be attributed to accelerated glutamate catabolism and enhanced glutamate uptake. SIGNIFICANCE: Glutamate may act as a mediator in the exercise-induced improvement of insulin sensitivity.


Assuntos
Resistência à Insulina , Insulina , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Ácido Glutâmico , Transdução de Sinais , Glucose/metabolismo
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