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1.
Br J Nutr ; : 1-8, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38600624

RESUMO

Soft drink consumption has become a highly controversial public health issue. Given the pattern of consumption in China, sugar-sweetened beverage is the main type of soft drink consumed. Due to containing high levels of fructose, a soft drink may have a deleterious effect on handgrip strength (HGS) due to oxidative stress, inflammation and insulin resistance. However, few studies show an association between soft drink consumption and HGS in adults. We aimed to investigate the association between soft drink consumption and longitudinal changes in HGS among a Chinese adult population. A longitudinal population-based cohort study (5-year follow-up, median: 3·66 years) was conducted in Tianjin, China. A total of 11 125 participants (56·7 % men) were enrolled. HGS was measured using a handheld digital dynamometer. Soft drink consumption (mainly sugar-containing carbonated beverages) was measured at baseline using a validated FFQ. ANCOVA was used to evaluate the association between soft drink consumption and annual change in HGS or weight-adjusted HGS. After adjusting for multiple confounding factors, the least square means (95 % CI) of annual change in HGS across soft drink consumption frequencies were -0·70 (-2·49, 1·09) for rarely drinks, -0·82 (-2·62, 0·97) for < 1 cup/week and -0·86 (-2·66, 0·93) for ≥ 1 cup/week (Pfor trend < 0·05). Likewise, a similar association was observed between soft drink consumption and annual change in weight-adjusted HGS. The results indicate that higher soft drink consumption was associated with faster HGS decline in Chinese adults.

2.
Sci Rep ; 14(1): 8758, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627582

RESUMO

Multidimensional health function impairments are common in older patients with chronic kidney disease (CKD). The purpose of this study was to explore whether the risk or severity of geriatric syndrome increased with a decline in renal function. This survey was conducted for CKD patients aged ≥ 60 years and hospitalized at West China Hospital of Sichuan University (Center of Gerontology and Geriatrics, Nephrology, and Endocrinology) and Chengdu Kangfu Kidney Disease Hospital from September 01, 2013 to June 30, 2014. Patients underwent multidimensional individualized assessments by trained doctors. Logistic regression analysis found that the risk of assisted walking (P = 0.001) and urinary incontinence (P = 0.039) increased with a decline in renal function. Regression analysis revealed that the scores of activities of daily living (P = 0.024), nutritional status (P = 0.000), total social support (P = 0.014), and objective support (P = 0.000) decreased with a decline in renal function.


Assuntos
Geriatria , Insuficiência Renal Crônica , Idoso , Humanos , Estudos Transversais , Atividades Cotidianas , Avaliação Geriátrica/métodos , Insuficiência Renal Crônica/diagnóstico
3.
Heliyon ; 10(8): e29326, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38628712

RESUMO

Objectives: The impact of N7-methylguanosine (m7G) on tumor progression and the regulatory role of microRNAs (miRNAs) in immune function significantly influence breast cancer (BC) prognosis. Investigating the interplay between m7G modification and miRNAs provides novel insights for assessing prognostics and drug responses in BC. Materials and methods: RNA sequences (miRNA and mRNA profiles) and clinical data for BC were acquired from the Cancer Genome Atlas (TCGA) database. A miRNA signature associated with 15 m7G in this cohort was identified using Cox regression and LASSO. The risk score model was evaluated using Kaplan-Meier and time-dependent ROC analysis, categorizing patients into high-risk and low-risk groups. Functional enrichment analyses were conducted to explore potential pathways. The immune system, including scores, cell infiltration, function, and drug sensitivity, was examined and compared between high-risk and low-risk groups. A nomogram that combines risk scores and clinical factors was developed and validated. Single-sample gene set enrichment analysis (ssGSEA) was employed to explore m7G-related miRNA signatures and immune cell relationships in the tumor microenvironment. Additionally, drug susceptibility was compared between risk groups. Results: Fifteen m7G-related miRNAs were independently correlated with overall survival (OS) in BC patients. Time-dependent ROC analysis yielded area under the curve (AUC) values of 0.742, 0.726, and 0.712 for predicting 3-, 5-, and 10-year survival rates, respectively. The Kaplan-Meier analysis revealed a significant disparity in OS between the high-risk and low-risk groups (p = 1.3e-6). Multiple regression identified the risk score as a significant independent prognostic factor. An excellent calibration nomogram with a C-index of 0.785 (95 % CI: 0.728-0.843) was constructed. In immune analysis, low-risk patients exhibited heightened immune function and increased responsiveness to immunotherapy and chemotherapy compared to high-risk patients. Conclusion: This study systematically analyzed m7G-related miRNAs and revealed their regulatory mechanisms concerning the tumor microenvironment (TME), pathology, and the prognosis of BC patient. Based on these miRNAs, a prognostic model and nomogram were developed for BC patients, facilitating prognostic assessments. These findings can also assist in predicting treatment responses and guiding medication selection.

4.
Prev Med ; : 107971, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657685

RESUMO

OBJECTIVE: Various lifestyle factors including smoking, alcohol, physical activity, sedentary behavior, diet quality, sleep behavior, and overweight have been related to metabolic dysfunction-associated steatotic liver disease (MASLD); however, their joint impact on risk of MASLD is not well known. We prospectively investigated the association between a combination of lifestyle factors and risk of MASLD. METHODS: This prospective cohort study included 13,303 participants (mean age: 39.1 ±â€¯11.3 years, female: 60.1%) in China. A novel healthy lifestyle score was created combining seven healthy factors: not smoking, no alcohol intake, regular physical activity, short sedentary time, healthy diet, healthy sleep, and healthy weight. Incident MASLD cases were ascertained annually by liver ultrasound and cardiometabolic risk factors. Multivariable Cox proportional hazards regression models were used to estimate the association of healthy lifestyle score with risk of MASLD. RESULTS: Within 48,036 person-years of follow-up, 2823 participants developed MASLD. After adjusting for age, sex, education, occupation, household income, personal and family history of disease, and total energy intake, compared with participants with 0-2 healthy lifestyle factors, the multivariable hazard ratios (95% confidence interval) of MASLD were 0.81 (0.73, 0.89), 0.67 (0.61, 0.75), and 0.55 (0.49, 0.62) for healthy lifestyle score of 3, 4, and 5-7, respectively (P for trend <0.0001). Such associations were consistent across subgroup and sensitivity analyses. CONCLUSION: Our results indicate that a higher healthy lifestyle score is associated with a lower risk of MASLD.

5.
Food Funct ; 15(8): 4436-4445, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38563400

RESUMO

Background: Garlic has antioxidant, anti-inflammatory, cardiovascular improvement and other beneficial effects on human health. However, few studies have evaluated the association of garlic intake with the risk of depressive symptoms. The aim of this prospective cohort was to examine the association between the frequency of raw garlic consumption and depressive symptoms in the general adult population. Methods: A total of 7427 participants (mean ± standard deviation: 39.7 ± 10.5 years) without baseline depressive symptoms were included in the cohort study. Garlic consumption was assessed using a validated food frequency questionnaire, and depressive symptoms were assessed by a Chinese version of the Self-rating Depression Scale score (SDS score ≥ 45). Multivariable Cox proportional hazards models were used to determine the association between garlic consumption and the risk of depressive symptoms. Results: This study identified 1070 cases of depressive symptoms during a median follow-up of 2.0 years, with a depression prevalence of 73.4 cases per 1000 person-years. After multivariate adjustment, the hazard ratios (95% confidence intervals) for depressive symptoms in males were 1.00 (reference) for almost never, 1.05 (0.84, 1.32) for ≤1 time per week, 1.16 (0.90, 1.49) for 2-3 times per week, and 1.31 (0.97, 1.78) for ≥4 times per week, and in females, they were 1.00 (reference) for almost never, 0.85 (0.69, 1.06) for ≤1 time per week, 0.72 (0.54, 0.97) for 2-3 times per week, and 0.78 (0.53, 1.13) for ≥4 times per week. Conclusion: In a large general population, we demonstrate for the first time that moderate raw garlic consumption is associated with a reduced risk of depressive symptoms in females, but not in males. Additional prospective studies with long-term follow-up and randomized controlled trials are necessary to confirm the preliminary results of the current study.


Assuntos
Depressão , Alho , Humanos , Alho/química , Masculino , Feminino , Adulto , Depressão/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos de Coortes , Modelos de Riscos Proporcionais , Fatores de Risco , China/epidemiologia
6.
iScience ; 27(3): 109168, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38439965

RESUMO

Distant metastasis is the main cause of death in patients with colorectal cancer (CRC). A better understanding of the mechanisms of metastasis can greatly improve the outcome of patients with CRC. Accumulating evidence suggests that circRNA plays pivotal roles in cancer progression and metastasis, especially acting as a miRNA sponge to regulate the expression of the target gene. A public database bioinformatics analysis found that miR-1825 was highly expressed in CRC tissues. In this study, miR-1825 was highly expressed in CRC tissues, which was positively correlated with lymph node metastasis and distant metastasis. In vitro and in vivo experiments confirmed that miR-1825 was positively correlated with the proliferation and migration of CRC cells. This event can be inhibited by circTBC1D22A. CircTBC1D22A can directly interact with miR-1825 and subsequently act as a miRNA sponge to regulate the expression of the target gene ATG14, which collectively advances the autophagy-mediated progression and metastasis of CRC.

7.
World J Gastrointest Oncol ; 16(2): 475-492, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425404

RESUMO

BACKGROUND: B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear. AIM: To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC. METHODS: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells. RESULTS: In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells. CONCLUSION: B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.

8.
Front Microbiol ; 15: 1295822, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38328432

RESUMO

Background: Ulcerative colitis (UC) is a refractory disease worldwide. Liver injury can be found clinically with UC, and now, it is found that gut dysbiosis is an important mechanism in the pathogenesis of UC. Sargentodoxa cuneata has been used as a traditional Chinese medicine and is commonly used clinically for the treatment of UC. The main objective of this study was to investigate the intrinsic mechanisms of Sargentodoxa cuneata in the treatment of UC and its associated liver injuries from the perspective of intestinal flora and related metabolites. Methods: Ultra-performance liquid chromatography-mass spectrometry was used to identify the components in the aqueous extract of Sargentodoxa cuneata (AESc). Mice with UC induced by dextran sulfate sodium were used to study the effects of AESc on UC and its associated liver injuries. Furthermore, 16S rRNA gene sequencing and analysis were performed on intestinal contents, and correlation analysis of intestinal flora with short-chain fatty acids (SCFAs) and organic acids was performed. Results: A total of 114 compounds were identified in AESc. AESc improved disease activity index scores, liver index, and colon length in mice with UC and had a good protective effect on intestine and liver injuries. Moreover, the administration of AESc regulated gut microbiota dysbiosis and the levels of a few SCFAs and organic acids in mice with UC. In addition, the correlation analysis results showed that the Megamonas and Bifidobacterium were the key intestinal flora related to the levels of differential SCFAs and organic acids in mice with UC after AESc intervention. Conclusion: AESc has a good protective effect on UC and UC related liver injuries. Modulation of the intestinal flora and its metabolites (SCFAs and a few organic acids) is an important pathway for AESc in the treatment of UC and also provides a rationale for the clinical use of Sargentodoxa cuneata in the treatment of UC.

9.
iScience ; 27(3): 109243, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38420592

RESUMO

Accurate tumor diagnosis by pathologists relies on identifying specific morphological characteristics. However, summarizing these unique morphological features in tumor classifications can be challenging. Although deep learning models have been extensively studied for tumor classification, their indirect and subjective interpretation obstructs pathologists from comprehending the model and discerning the morphological features accountable for classifications. In this study, we introduce a new approach utilizing Style Generative Adversarial Networks, which enables a direct interpretation of deep learning models to detect significant morphological characteristics within datasets representing patients with deficient mismatch repair/microsatellite instability-high gastric cancer. Our approach effectively identifies distinct morphological features crucial for tumor classification, offering valuable insights for pathologists to enhance diagnostic accuracy and foster professional growth.

10.
Arch Microbiol ; 206(3): 109, 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38369664

RESUMO

A horizontal biotrickling filter (HBTF) was designed to understand the toluene removal process and microbial community structures. The start-up time of the HBTF, immobilized by the dominant fungi was only about 6 days and the toluene removal efficiency was found to be more than 95% when the inlet toluene concentration remained at around 1560.0 mg/m3. In the stable operation stage of the HBTF, based on not greatly reducing the removal efficiency, a simple and convenient periodic commutation was adopted to reduce the pressure drop (△P) and regulate the distribution of microorganisms in the packing area of the HBTF. The △P decreased from about 90 Pa to 10 Pa after the commutation, which indicated its feasibility. The performance of the HBTF was improved by changing the inlet direction of waste gas flow. When the inlet concentration of toluene was about 640 mg/m3, the removal efficiency was nearly 70.0% before commutation and it remained 95.0-98.0% after commutation. Microbial abundance and diversity analysis showed that the corresponding Shannon-Weiner index was 2.73 and 1.84, respectively. The front section of the HBTF, which was exposed to toluene earlier, consistently exhibited higher microbial diversity than that in the back section. Following commutation, microbial diversity decreased in both the front and back sections, with a maximum decline of around 50%. The main fungi treating toluene were Aplanochytrium, Boletellus, and Exophiala.


Assuntos
Microbiota , Tolueno , Biodegradação Ambiental , Filtração , Reatores Biológicos/microbiologia
11.
J Inflamm Res ; 17: 1095-1104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384373

RESUMO

Background: To explore the association between the number of missing teeth and the prevalence of hyperlipidemia in a Chinese adult population. Methods: 13,932 adults were investigated in the TCLSIH cohort study. The number of missing teeth was determined at baseline through a self-reported questionnaire, and then classified into three categories: 0, 1-2, and ≥3. We defined hyperlipidemia as total cholesterol (TC) ≥ 5.17 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L or low-density lipoprotein (LDL) cholesterol ≥ 3.37 mmol/L or a self-report of physician-diagnosed hyperlipidemia during follow-up visits. Cox proportional-hazards regression models were employed to assess the relationship between the number of missing teeth and incident hyperlipidemia. Results: A total of 6756 first-incident cases of hyperlipidemia occurred during 42,048 person-years of follow-up (median follow-up, 4.2 years). After adjusted confounders, multivariable HRs and 95% CI for incident of hyperlipidemia across the categories of missing teeth were as follows: in male participants, 1.00 (reference), 1.10 (0.98, 1.22), and 1.03 (0.91, 1.16) (P for trend = 0.30); in female participants, 1.00 (reference), 1.09 (0.99, 1.19), and 1.18 (1.04, 1.33) (P for trend < 0.01). Conclusion: The number of missing teeth is associated with an increased risk of hyperlipidemia in female participants but not in male participants. Systemic chronic inflammation may potentially mediate this association.

12.
Int J Biol Macromol ; 258(Pt 2): 129116, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171192

RESUMO

Vascular Plant One­zinc Finger (VOZ) transcription factor can respond to a variety of abiotic stresses, however its function in cotton and the molecular mechanisms of response to salt tolerance remained unclear. In this study, we found that GhVOZ1 is highly expressed in stamen and stem of cotton under normal conditions. The expression of GhVOZ1 increased significantly after 3 h of salt treatment in three-leaf staged upland cotton. Overexpressed transgenic lines of GhVOZ1 in Arabidopsis and upland cotton were treated with salt stress and we found that GhVOZ1 could respond positively to salt stress. GhVOZ1 can regulate Arabidopsis Vacuolar Proton Pump Pyrophosphatase (H+-PPase) gene (AVP1) expression through specific binding to GCGTCTAAAGTACGC site on GhAVP1 promoter, which was examined through Dual-luciferase assay and Electrophoretic mobility shift assay (EMSA). AVP1 expression was significantly increased in Arabidopsis with GhVOZ1 overexpression, while GhAVP1 expression was decreased in virus induced gene silenced (VIGS) cotton plants of GhVOZ1. Knockdown of GhAVP1 expression in cotton plants by VIGS showed decreased superoxide dismutase (SOD) and peroxidase (POD) activities, whereas an increased malondialdehyde (MDA) content and ultimately decreased salt tolerance. The GhVOZ1-AVP1 module could maintain sodium ion homeostasis through cell ion transport and positively regulate the salt tolerance in cotton, providing new ideas and insights for the study of salt tolerance.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Gossypium/genética , Tolerância ao Sal/genética , Arabidopsis/genética , Plantas Geneticamente Modificadas/genética , Proteínas de Arabidopsis/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Pirofosfatase Inorgânica/genética , Pirofosfatase Inorgânica/metabolismo
13.
Sci Rep ; 14(1): 625, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182871

RESUMO

Diabetic nephropathy (DN), a common microvascular complicating disease of diabetes. Lupenone, a pentacyclic triterpenoid, has anti-inflammatory effects and can prevent type 2 diabetes mellitus and treat renal damage, however, the effects and mechanisms of lupenone in DN remain unclear. Thereby,the MTT method was used to investigate the antiproliferative effect of lupenoneon the cell line rat glomerular mesangial cells (HBZY-1). Molecular docking was used to investigate the combination of lupenone and MCP-1, IL-1ß, TNF-α, IKKß, IκBα, and NF-κB p65 proteins. The expression of mRNA of the pro-inflammatory cytokines (MCP-1, IL-1ß and TNF-α) and the NF-κB signalling pathway in HBZY-1 cells were assessed by RT-PCR. The protein expressions of pro-inflammatory cytokines and NF-κB pathway were got by Western blot. Result showed that lupenone inhibited the proliferative activity of HBZY-1 cells at non-cytotoxic concentrations. Molecular docking results showed that lupenone combined well with the target proteins. Moreover, lupenone could significantly reduced the mRNA and protein expressions for pro-inflammatory cytokines and IKKß, p-p65 and p-IκBα. Lupenone may play an anti-inflammatory role in DN treatment by inhibiting the NF-κB signalling pathway. These results provided a new understanding of the pharmacological mechanisms of lupenone in treatment of DN.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Triterpenos , Animais , Ratos , NF-kappa B , Simulação de Acoplamento Molecular , Inibidor de NF-kappaB alfa , Quinase I-kappa B , Fator de Necrose Tumoral alfa , Triterpenos/farmacologia , Citocinas/genética , Interleucina-1beta , Anti-Inflamatórios/farmacologia , RNA Mensageiro
14.
Prev Med ; 179: 107844, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176446

RESUMO

OBJECTIVE: A variety of unhealthy sleep behaviors have been shown to be associated with an increased risk of urologic cancers. However, little is known about the association between the overall sleep patterns and urologic cancers. To prospectively investigate the associations between a healthy sleep pattern and the risks of urologic cancers, including bladder cancer (BCa) and renal cell carcinoma (RCC). METHODS: In this prospective cohort study, 377,144 participants free of cancer at baseline were recruited from the UK Biobank. Data on sleep behaviors were collected through questionnaires at recruitment. The incident urologic cancer cases were determined through linkage to national cancer and death registries. We established a healthy sleep score according to five sleep traits (sleep duration, chronotype, insomnia, snoring, and daytime sleepiness). Cox proportional hazard regression models were used to calculate the adjusted hazard ratios and 95% confidence intervals to assess the relationship between the healthy sleep score and the risk of urologic cancers. RESULTS: During a median of ≥9 years of follow-up, we identified 1986 incident urologic cancer cases, including 1272 BCa cases and 706 RCC cases. Compared with the participants with a poor sleep pattern (score of 0-2), the multivariable-adjusted hazard ratio and 95% confidence interval were 0.85 (0.75 to 0.96) for urologic cancers, 0.80 (0.68 to 0.93) for BCa, and 0.91 (0.74, 1.12) for RCC, respectively, for those with the healthier sleep pattern (score of 4-5). CONCLUSION: Our results indicate that a healthy sleep pattern is associated with lower risks of urologic cancers.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Estudos Prospectivos , Carcinoma de Células Renais/complicações , Sono , Ronco/complicações , Neoplasias Renais/epidemiologia , Neoplasias Renais/complicações , Fatores de Risco
15.
Psychol Health Med ; : 1-14, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053313

RESUMO

This study aimed to identify group variations in adolescent impulsivity and explore the connections between latent categories of impulsivity and psychological symptoms, social anxiety, and internet addiction. The research involved 2,378 participants from three middle schools in Guangdong Province, China. We assessed the impact of impulsivity levels (measured by BBIS) on depression (measured by KADS-11), anxiety (measured by SCARED), social anxiety (measured by SASC), and internet addiction (measured by YDQ). Latent profile analysis was employed to examine the diversity in adolescent impulsivity, establish latent classifications, and investigate the variances in psychological symptoms, social anxiety, and internet addiction. The middle school students were categorized into five latent groups based on their BBIS scores. Statistical analysis revealed five impulsivity categories, strongly linked to psychological symptoms and social anxiety but less strongly associated with internet addiction. The high impulsivity group (C5) exhibited higher scores in psychological symptoms and social anxiety compared to other groups, whereas the poor self-regulation group (C3) displayed greater psychological symptoms, social anxiety scores, and internet addiction than the impulsive behavior group (C4). Future investigations should investigate the underlying factors contributing to the observed differences among these groups.

16.
BMC Cancer ; 23(1): 1189, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049758

RESUMO

BACKGROUND: Estrogen receptor-positive and progesterone receptor-negative (ER + /PR-) breast cancer comprise a special type. More than 10% breast cancer patients belonged to ER + /PR-. METHODS: In order to better understand this patient population, we utilized a unique dataset from China, examining the clinicopathological features and genomic profiles of ER + /PR- breast cancers. Our study involved three cohorts: Cohort 1 included 2120 unselected ER-positive female patients with re-evaluated clinicopathological and survival data; Cohort 2 comprised 442 ER-positive females who underwent genetic testing; and Cohort 3 consisted of 77 ER-positive/HER2-negative females tested with MammaPrint and BluePrint. RESULTS: Patients were stratified into four categories based on the PR/ER ratio. Clinically, ER + /PR- tumors (PR/ER ratio = 0) showed the lowest proportion of T1 tumors (10.88%) and highest proportion of HER2-positive tumors (28.36%) than did other ER + /PR + tumors groups. The ER + /PR- group contained a higher number of underweight patients (20.20%). Independently of HER2 status, ER + /PR- patients demonstrated the poorest prognosis. Genomically, the most prevalent mutations were PIK3CA (50%) in ER + /PR + tumors and TP53 (65%) in ER + /PR- tumors. ER + /PR- tumors presented more frequent mutations in TP53, ERBB2, CDK12, SPEN, and NEB, with mutation rates of 65%, 42%, 27%, 13%, and 10%, respectively. Additionally, the Tumor Mutational Burden (TMB) was higher in the ER + /PR- group compared to the ER + /PR + group. The MammaPrint score for the ER + /PR-/HER2- group was significantly lower than that of other groups. In the BluePrint analysis, only four patients were classified as Basal-Type, all of whom were ER + /PR-/HER2-. CONCLUSIONS: In this study, we identified the clinical and genetic characteristics of ER + /PR- breast cancer patients in China. Distinct PR statuses indicated different biological processes of ER + breast cancer and survival outcomes. Future treatment strategies may need to be tailored for ER + /PR- patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Receptor ErbB-2/genética , Biomarcadores Tumorais , Receptores de Progesterona/genética , Mutação , Receptores de Estrogênio/genética
17.
J Med Chem ; 66(24): 16680-16693, 2023 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-38069814

RESUMO

Echinococcosis is a global public health issue that generally occurs in areas with developed animal husbandry. In search of safe and effective therapeutic agents against echinococcosis, we designed and synthesized new 1,3-substituted ß-carboline derivatives based on harmine. Among them, compounds 1a, 1c, and 1e displayed potent inhibitory activity against Echinococcus granulosus in vitro, significantly better than albendazole and harmine. The morphological detection revealed that 1a, 1c, and 1e significantly changed the ultrastructure of Echinococcus granulosus protoscolices (PSCs). Furthermore, pharmacokinetic studies suggested that 1a possessed a better metabolic property. Encouragingly, 1a exhibited a highest cyst inhibition rate as 76.8% in vivo and did not display neurotoxicity in mice. Further mechanistic research illustrated that 1a has the potential to induce autophagy in PSCs, which may be responsible for the therapeutic effect of the drugs. Together, 1a could be a promising therapeutic agent against echinococcosis, warranting further study.


Assuntos
Equinococose , Echinococcus granulosus , Camundongos , Animais , Harmina/farmacologia , Harmina/uso terapêutico , Equinococose/tratamento farmacológico , Echinococcus granulosus/ultraestrutura , Albendazol/farmacocinética , Albendazol/uso terapêutico
18.
Molecules ; 28(22)2023 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-38005385

RESUMO

Ulcerative colitis (UC) is an intractable disease prevalent worldwide. While ethyl acetate extract from decoction of Sargentodoxa cuneata (EAdSc) has potential anti-inflammatory activity, its effects on UC remain unknown. In this study, the constituent compounds discussed in the literature and identified by gas chromatography and mass spectrometry (GC-MS) were collected, and the blood-soluble components of EAdSc were identified by liquid chromatography-mass spectrometry. The network pharmacology analysis and molecular docking analysis were performed to explore the potential underlying mechanism and active ingredients of EAdSc against UC. Furthermore, mice with dextran sulfate sodium (DSS)-induced UC were used to study the therapeutic effects and validate the mechanism of EAdSc against UC. A total of 53 compounds from EAdSc were identified in the literature and by GC-MS, and 22 blood-soluble EAdSc components were recognized. Network pharmacology analysis revealed that multiple inflammatory signaling pathways are involved in EAdSc's anti-UC activity. Furthermore, molecular docking analysis showed that the eleutheroside A, liriodendrin, epicatechin, 2-methoxy-4-vinylphenol, catechin, androsin, coumaroyltyramine, and catechol may be active against UC through the TLR4/NF-κB/NLRP3 pathway. EAdSc reduced the disease activity, macroscopic colon damage, and histological damage indices, as well as inhibiting DSS-induced spleen enlargement and colon shortening. In addition, EAdSc decreased the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-17, as well as the expression of TLR4, NF-κB p65, NLRP3, and Caspase-1 mRNA in colon tissues. These results provide insights into the anti-UC effects and underlying mechanisms of EAdSc and help elucidate the active ingredients of EAdSc in the treatment of UC.


Assuntos
Catequina , Colite Ulcerativa , Colite , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , NF-kappa B/metabolismo , Simulação de Acoplamento Molecular , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like/metabolismo , Colo/metabolismo , Catequina/farmacologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Colite/metabolismo
19.
Food Funct ; 14(24): 10955-10963, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38010908

RESUMO

Background: Whole-grain contains a range of beneficial nutrients, which are thought to play a role in the prevention of chronic diseases. However, the association between whole-grain consumption and the risk of developing carotid atherosclerosis (CA) has not been sufficiently elucidated. We, therefore, conducted this study to investigate the relationship between whole-grain consumption and CA in the general adult population. Methods: This prospective cohort study included a total of 2166 participants (19.2-84.6 years, 55.0% men) without a history of cardiovascular disease, cancer, and CA at baseline. A validated food frequency questionnaire was used to assess whole-grain consumption. Measurements of CA include carotid intima-media thickness (IMT) and carotid plaque. IMT thickening is defined as: IMT ≥ 1.0 mm or a carotid bifurcation IMT ≥ 1.2 mm. Carotid plaque is defined as: distinct area protruding ≥1.5 mm into the vascular lumen of the carotid artery. Cox proportional hazards regression models were used to examine the association of whole-grain consumption with incident CA. Results: A total of 538 (341 men) first incident cases of CA occurred during 5585 person-years of follow-up (median follow-up: 4.2 years). After adjusting for demographic characteristics, lifestyle factors, dietary intake, individual and family history of disease, the multivariable HRs (95% CIs) for incident CA were 1.00 (reference) for <1 time per week, 1.10 (0.85, 1.43) for 1 time per week, 0.95 (0.75, 1.20) for 2-6 times per week, and 1.12 (0.80, 1.56) for ≥1 times per day, respectively (P for trend = 0.99). Similar results were observed in stratified analyses by the main covariates and sensitivity analyses. Conclusion: Our data indicate that whole-grain consumption had no significant association with the risk of CA in an adult Chinese population. In our study population, there is a low consumption of whole-grain, which may limit our ability to see an association. Further cohort studies or randomized controlled trials are needed to confirm our results.


Assuntos
Doenças das Artérias Carótidas , Placa Aterosclerótica , Masculino , Adulto , Humanos , Feminino , Estudos de Coortes , Espessura Intima-Media Carotídea , Estudos Prospectivos , Fatores de Risco , Doenças das Artérias Carótidas/epidemiologia , Inflamação/epidemiologia
20.
Int J Behav Nutr Phys Act ; 20(1): 130, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37924067

RESUMO

BACKGROUND: Several previous studies have shown that excessive screen time is associated with an increased prevalence of dementia, Parkinson's disease (PD), and depression. However, the results have been inconsistent. This study aimed to prospectively investigate the association between different types of screen time and brain structure, as well as the incidence of dementia, Parkinson's disease, depression, and their multimorbidity status. METHODS: We included 473,184 participants initially free of dementia, PD, and depression from UK Biobank, as well as 39,652 participants who had magnetic resonance imaging (MRI) data. Screen time exposure variables including TV viewing and computer using were self-reported by participants. Cox proportional hazards regression models were used to estimate the association between different types of screen time and the incidence of dementia, Parkinson's disease, depression, and their multimorbidity status. Multiple linear regression models were used to assess the linear relationship between different types of screen time and MRI biomarkers in a subgroup of participants. RESULTS: During the follow up, 6,096, 3,061, and 23,700 participants first incident cases of dementia, PD, and depression respectively. For moderate versus the lowest computer uses, the adjusted HRs (95% CIs) were 0.68 (0.64, 0.72) for dementia, 0.86 (0.79, 0.93) for PD, 0.85 (0.83, 0.88) for depression, 0.64 (0.55, 0.74) for dementia and depression multimorbidity, and 0.59 (0.47, 0.74) for PD and depression multimorbidity. The multivariable HRs (95% CIs) for the highest versus the lowest group of TV viewing time were 1.28 (1.17, 1.39) for dementia, 1.16 (1.03, 1.29) for PD, 1.35 (1.29, 1.40) for depression, 1.49 (1.21, 1.84) for dementia and depression multimorbidity, and 1.44 (1.05, 1.97) for PD and depression multimorbidity. Moderate computer using time was negatively associated with white matter hyperintensity volume (ß = -0.042; 95% CI -0.067, -0.017), and positively associated with hippocampal volume (ß = 0.059; 95% CI 0.034, 0.084). Participants with the highest TV viewing time were negatively associated with hippocampal volume (ß = -0.067; 95% CI -0.094, -0.041). In isotemporal substitution analyses, substitution of TV viewing or computer using by equal time of different types of PA was associated with a lower risk of all three diseases, with strenuous sports showing the strongest benefit. CONCLUSION: We found that moderate computer use was associated with a reduced risk of dementia, PD, depression and their multimorbidity status, while increased TV watching was associated with a higher risk of these disease. Notably, different screen time may affect the risk of developing diseases by influencing brain structures. Replacing different types of screen time with daily-life PA or structured exercise is associated with lower dementia, PD, and depression risk.


Assuntos
Demência , Doença de Parkinson , Humanos , Doença de Parkinson/epidemiologia , Doença de Parkinson/complicações , Multimorbidade , Depressão/epidemiologia , Tempo de Tela , Demência/epidemiologia , Demência/complicações , Exercício Físico
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