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1.
Materials (Basel) ; 17(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38591547

RESUMO

Electrochemical machining (ECM) has become more prevalent in titanium alloy processing. However, the presence of the passivation layer on the titanium alloys significantly impacts the performance of ECM. In an attempt to overcome the passivation effects, a high-temperature electrolyte or the addition of halogen ions to the electrolyte has been used. Still, it often results in compromised machining accuracy and surface roughness. This study applied laser and shaped tube electrolytic machining (Laser-STEM) for titanium alloy drilling, where the laser was guided to the machining zone via total internal reflection. The performance of Laser-STEM using different types of electrolytes was compared. Further, the effects of laser power and pulse voltage on the machining side gap, material removal rate (MRR), and surface roughness were experimentally studied while drilling small holes in titanium alloy. The results indicated that the use of passivating electrolytes improved the machining precision, while the MRR decreased with an increase in laser power during Laser-STEM. The MRR showed an increase while using aggressive electrolytes; however, at the same time, the machining precision deteriorated with the increase in laser power. Particularly, the maximum feeding rate of 6.0 mm/min for the tool electrode was achieved using NaCl solution as the electrolyte during Laser-STEM, marking a 100% increase compared to the rate without the use of a laser. Moreover, the model and equivalent circuits were also established to illustrate the material removal mechanisms of Laser-STEM in different electrolytes. Lastly, the processing of deep small holes with a diameter of 1.5 mm, a depth of 38 mm, and a surface roughness of Ra 2 µm was achieved via Laser-STEM without the presence of a recast layer and heat-affected zones. In addition, the cross-inner flow channels in the titanium alloys were effectively processed.

2.
Drug Resist Updat ; 74: 101085, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636338

RESUMO

Enhanced DNA repair is an important mechanism of inherent and acquired resistance to DNA targeted therapies, including poly ADP ribose polymerase (PARP) inhibition. Spleen associated tyrosine kinase (Syk) is a non-receptor tyrosine kinase acknowledged for its regulatory roles in immune cell function, cell adhesion, and vascular development. This study presents evidence indicating that Syk expression in high-grade serous ovarian cancer and triple-negative breast cancers promotes DNA double-strand break resection, homologous recombination (HR), and subsequent therapeutic resistance. Our investigations reveal that Syk is activated by ATM following DNA damage and is recruited to DNA double-strand breaks by NBS1. Once localized to the break site, Syk phosphorylates CtIP, a pivotal mediator of resection and HR, at Thr-847 to promote repair activity, particularly in Syk-expressing cancer cells. Inhibition of Syk or its genetic deletion impedes CtIP Thr-847 phosphorylation and overcomes the resistant phenotype. Collectively, our findings suggest a model wherein Syk fosters therapeutic resistance by promoting DNA resection and HR through a hitherto uncharacterized ATM-Syk-CtIP pathway. Moreover, Syk emerges as a promising tumor-specific target to sensitize Syk-expressing tumors to PARP inhibitors, radiation and other DNA-targeted therapies.

3.
Front Neurosci ; 18: 1287809, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38516311

RESUMO

Background and aim: Laryngopharyngeal reflux disease (LPRD) is primarily characterized by discomfort in the pharynx and has limited treatment options. This research aimed to assess the efficacy of transcutaneous auricular vagus nerve stimulation (tVNS) in patients with LPRD and delve into the potential underlying mechanisms. Methods: A total of 44 participants, diagnosed with LPRD were divided into two groups randomly. Twice-daily stimulation was delivered for 2 weeks for patients in experimental group, with stimulation ranging from 1.0 mA to 1.5 mA (n = 22), while the control group underwent sham tVNS (n = 22) with the same stimulation parameters and different anatomical location. The severity of symptoms and levels of anxiety and depression were monitored using questionnaires. High-resolution esophageal manometry data were collected, and the patients' autonomic function was assessed through heart rate variability analysis. Results: There was a positive correlation between reflux symptom index (RSI) scores and low frequency/high frequency (LF/HF) ratio (r = 0.619; p < 0.001), Hamilton anxiety scale (HAMA) scores (r = 0.623; p < 0.001), and Hamilton depression scale (HAMD) scores (r = 0.593; p < 0.001). Compared to the pre-tVNS phase, RSI (p < 0.001), HAMA (p < 0.001), and HAMD (p < 0.001) scores were significantly reduced after 2 weeks of treatment. Additionally, the resting pressure of the upper esophageal sphincter (UESP; p < 0.05) and lower esophageal sphincter (LESP; p < 0.05) showed significant enhancement. Notably, tVNS led to an increase in root mean square of successive differences (RMSSD; p < 0.05) and high frequency (HF; p < 0.05) within heart rate variability compared to the pre-treatment baseline. Compared to the control group, RSI (p < 0.001), HAMA (p < 0.001), and HAMD (p < 0.001) scores in tVNS group were significantly lower at the end of treatment. Similarly, the resting pressure of UESP (p < 0.05) and LESP (p < 0.05) in tVNS group were significantly higher than that of control group. Notably, RMSSD (p < 0.05) and HF (p < 0.05) in tVNS group were significantly higher than that of control group. Conclusion: This study demonstrated that tVNS as a therapeutic approach is effective in alleviating LPRD symptoms. Furthermore, it suggests that improvements in esophageal motility could be associated with vagus nerve-dependent mechanisms.

4.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 42(1): 46-55, 2024 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38475950

RESUMO

OBJECTIVES: This study aimed to explore the effect of pituitary tumor-transforming gene 1 (PTT-G1) on the invasion and proliferation of oral squamous cell carcinoma (OSCC) cell lines under the action of miR-362-3p. METHODS: The bioinformatics online database was used to query the expression of PTTG1 in head and neck squamous cell carcinoma (HNSCC). The expression of PTTG1 in the Cal-27, HN-30, and HOK cell lines was detected by Western blot. A wound-healing assay was used to determine the effect of PTTG1 on the migration ability of the OSCC cells. The Transwell assay was used to examine the changes in cell-invasion ability. 5-ethynyl-2'-deoxyuridine (EdU) cell-proliferation assay was used to detect changes in cell-proliferation ability. Bioinformatics approach predicted the upstream miRNA of PTTG1. The targeting relationship between miR-362-3p and PTTG1 was examined by the dual luciferase assay, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of miRNA in OSCC tissues. RESULTS: The ENCORI database showed that PTTG1 expression was up-regulated in OSCC tissues. Western blot confirmed that PTTG1 expression was up-regulated in Cal-27 and HN-30 cells than HOK cells. PTTG1 knockout can inhibit the migration, invasion, and proliferation of Cal-27 and HN-30 cells (P<0.05). Bioinformatics prediction websites predicted that the upstream miRNA of PTTG1 was miR-362-3p, and PTTG1 can bind to miR-362-3p. Results of qRT-PCR showed that miR-362-3p expression was downregulated in OSCC tissues compared with normal tissue (P<0.05). Transwell and EdU experiments confirmed that miR-362-3p knockdown can promote the invasion and proliferation of Cal-27 and HN-30 after PTTG1 knockdown. CONCLUSIONS: miR-362-3p can inhibit the invasion and proliferation of Cal-27 and HN-30 cells by targeting PTTG1.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Neoplasias Hipofisárias , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Neoplasias Hipofisárias/genética , Invasividade Neoplásica/genética , Movimento Celular/genética , MicroRNAs/genética , Proliferação de Células , Oncogenes , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
5.
J Cancer Res Clin Oncol ; 150(2): 69, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38305920

RESUMO

BACKGROUND: CCL11, a chemokine known for recruiting immune cells to the tumor microenvironment (TME), has an unclear role in the context of its expression, patient prognosis, and the presence of tumor-infiltrating immune cells (TILs) in breast cancer. METHODS: The expression of CCL11 in invasive breast cancer (BRCA) was analyzed using TCGA database. Survival curve and Cox regression analysis determined the potential of CCL11 as an independent prognostic indicator. GSEA performed functional analysis on genes related to CCL11. CIBERSORT algorithm quantified the infiltration level of immune cells with varying CCL11 expression. Lastly, the correlation between CCL11 expression and anticancer drug sensitivity was examined. Immunohistochemistry (IHC) and qRT-PCR confirmed CCL11 expression in clinical tissue samples. The anti-tumor efficacy of CCL11 was investigated using CCK-8, plate formation, transwell assay, and Western blot. RESULTS: CCL11 expression was elevated in BRCA tumor tissues compared to adjacent normal tissues. Recurrence-free survival (RFS) was longer in patients with high expression of CCL11. Enrichment and co-expression analyses revealed CCL11's association with numerous immune-related signaling pathways and genes. Validation studies confirmed high CCL11 expression in breast cancer tissues. In vitro experiments substantiated CCL11's anticancer effects in BRCA. CONCLUSION: CCL11 expression correlates with immune cell infiltration in breast cancer, indicating its potential as a prognostic biomarker for BRCA.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Algoritmos , Western Blotting , Microambiente Tumoral , Prognóstico , Quimiocina CCL11
6.
J Cancer Res Clin Oncol ; 150(2): 91, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347320

RESUMO

OBJECTIVES: To develop a model that can assist in the diagnosis and prediction of prognosis for head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Data from TCGA and GEO databases were used to generate normalized gene expression data. Consensus Cluster Plus was used for cluster analysis and the relationship between angiogenesis-associated gene (AAG) expression patterns, clinical characteristics and survival was examined. Support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) analyzes and multiple logistic regression analyzes were performed to determine the diagnostic model, and a prognostic nomogram was constructed using univariate and multivariate Cox regression analyses. ESTIMATE, XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, CIBERSORT algorithms were used to assess the immune microenvironment of HNSCC patients. In addition, gene set enrichment analysis, treatment sensitivity analysis, and AAGs mutation studies were performed. Finally, we also performed immunohistochemistry (IHC) staining in the tissue samples. RESULTS: We classified HNSCC patients into subtypes based on differences in AAG expression from TCGA and GEO databases. There are differences in clinical features, TME, and immune-related gene expression between two subgroups. We constructed a HNSCC diagnostic model based on nine AAGs, which has good sensitivity and specificity. After further screening, we constructed a prognostic risk signature for HNSCC based on six AAGs. The constructed risk score had a good independent prognostic significance, and it was further constructed into a prognostic nomogram together with age and stage. Different prognostic risk groups have differences in immune microenvironment, drug sensitivity, gene enrichment and gene mutation. CONCLUSION: We have constructed a diagnostic and prognostic model for HNSCC based on AAG, which has good performance. The constructed prognostic risk score is closely related to tumor immune microenvironment and immunotherapy response.


Assuntos
60489 , Benzoquinonas , Neoplasias de Cabeça e Pescoço , Lactamas Macrocíclicas , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Prognóstico , Imunoterapia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Microambiente Tumoral/genética
7.
Biochem Genet ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38261157

RESUMO

Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer and its incidence is rising globally. The molecular mechanisms of PTC progression remain unclear, hindering the development of effective treatments. This study focuses on hsa_circ_0008016 (circFGFR1), a circular RNA significantly up-regulated in PTC cells. Silencing circFGFR1 inhibited PTC cell proliferation and increased cell apoptosis, suggesting its role in PTC progression. The RNA-binding protein FUS was identified as a promoter of circFGFR1 formation. While circFGFR1 does not influence FGFR1 mRNA translation, it inhibits ubiquitination and degradation of FGFR1 protein, prolonging its half-life. CircFGFR1 also interacts with protein CBL, inhibiting CBL-mediated ubiquitination of FGFR1 proteins. Rescue assays confirmed circFGFR1 promotes PTC cell growth through mediating FGFR1. This study highlights the potential of circFGFR1 as a therapeutic target, offering insights into PTC's molecular mechanisms, and paving the way for novel treatment strategies.

8.
Mitochondrial DNA B Resour ; 9(1): 128-132, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38259357

RESUMO

The mitogenome of Bauhinia variegate was assembled and characterized in this study. The mitogenome size was 437,271 bp, and its GC content was 45.5%. 36 protein-coding genes, 17 tRNAs and 3 rRNAs were annotated in the mitogenome. A total of 12 MTPTs, ranging from 71 bp to 3562 bp, were identified in the mitogenome and covered 1.46% (6373 bp) of the mitogenome. Phylogenetic analysis of 15 species of Leguminosae based on 23 core protein-coding genes showed that B. variegata was sister to Tylosema esculentum, another member from the subfamily Cercidoideae. The mitogenome of B. variegata provides a valuable genetic resource for further phylogenetic studies of this family.

9.
J Gen Intern Med ; 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228988

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has led to an increase in alcohol-related liver disease (ALD). The aim of this study was to evaluate the magnitude of ALD hospitalization surge during the pandemic in the USA. MAIN MEASURES: A retrospective trend analysis of adult hospitalizations for ALD at acute care hospitals across the USA in 2016-2020 was conducted. Hospitalizations were identified using the International Classification of Diseases 10 codes for ALD and non-alcoholic-related liver disease. Outcomes measured included the predicted monthly volume of hospitalizations for ALD and inpatient mortality rates. KEY RESULTS: During the 2020 pandemic, monthly ALD hospitalizations reached 10,247 representing a 20.7% increase compared to pre-pandemic monthly average of 8490. Additional 4163 ALD hospitalizations occurred during the pandemic, in addition to a pre-pandemic uptrend. The peak of excess ALD hospitalizations was from May to October (monthly excess of 1138) decreasing to monthly excess of 280 in November and December. The excess increase in ALD hospitalizations was primarily observed in young adults, totaling 5256 cases affecting both male (2101 excess cases) and females (2041 excess cases). The age-standardized monthly mortality rate during the pandemic was notably higher than expected at 0.9% (95% CI 0.4 to 1.4%). CONCLUSIONS: The COVID-19 pandemic led to a significant increase in ALD hospitalizations, above and beyond the pre-existing upward trend, which tapered towards the end of 2020, suggesting a possible decline in the pandemic's impact. The excess increase in ALD hospitalizations was observed primarily in young adults and affected both males and females. These findings highlight the need for further attention to the long-term consequences of the pandemic.

10.
Biomacromolecules ; 24(12): 5989-5997, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-37962286

RESUMO

Myocardial infarction (MI) has been a serious threat to the health of modern people for a long time. The introduction of tissue engineering (TE) therapy into the treatment of MI is one of the most promising therapeutic schedules. Considering the intrinsic electrophysiological activity of cardiac tissue, we utilized 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)-oxidized cellulose nanofibrils (TOCNs) with excellent biocompatibility as the substrate, and sulfonated carbon nanotubes (SCNTs) with remarkable conductivity and water dispersibility as the electrically active material, to prepare TOCN-SCNT composite hydrogels. By adjusting the content of SCNTs from 0 to 5 wt %, TOCN-SCNT hydrogels exhibited conductivity ranging from 5.2 × 10-6 to 6.2 × 10-2 S cm-1. Just with 1 wt % incorporation of SCNTs, the hydrogel played a role in promoting the adhesive growth and proliferation of cells. The hydrogel expressed higher Connexin 43 (Cx-43) and cardiac troponin-T proteins compared with controls, demonstrating great potential in constructing a myocardial TE scaffold.


Assuntos
Celulose Oxidada , Nanotubos de Carbono , Humanos , Engenharia Tecidual , Nanotubos de Carbono/química , Hidrogéis/química , Tecidos Suporte/química , Celulose Oxidada/química
11.
Eur J Med Res ; 28(1): 405, 2023 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-37803421

RESUMO

Increased lymphangiogenesis and lymph node (LN) metastasis are thought to be important steps in cancer metastasis, and are associated with patient's poor prognosis. There is increasing evidence that the lymphatic system may play a crucial role in regulating tumor immune response and limiting tumor metastasis, since tumor lymphangiogenesis is more prominent in tumor metastasis and diffusion. Lymphangiogenesis takes place in embryonic development, wound healing, and a variety of pathological conditions, including tumors. Tumor cells and tumor microenvironment cells generate growth factors (such as lymphangiogenesis factor VEGF-C/D), which can promote lymphangiogenesis, thereby inducing the metastasis and diffusion of tumor cells. Nevertheless, the current research on lymphangiogenesis in gastric cancer is relatively scattered and lacks a comprehensive understanding. Therefore, in this review, we aim to provide a detailed perspective on molecules and signal transduction pathways that regulate gastric cancer lymphogenesis, which may provide new insights for the diagnosis and treatment of cancer.


Assuntos
Linfangiogênese , Neoplasias Gástricas , Humanos , Linfangiogênese/fisiologia , Neoplasias Gástricas/metabolismo , Metástase Linfática , Transdução de Sinais , Microambiente Tumoral
13.
J Evid Based Med ; 16(3): 332-341, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37735811

RESUMO

BACKGROUND: Participation in colonoscopies is an essential aspect of endoscopic training. The purpose of this study was to explore the impact of fellow/trainee participation on colonoscopy outcomes. METHODS: This meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO). From database inception to July 2022, studies investigating fellow involvement and colonoscopy outcomes were searched across Cochrane library, PubMed, and other databases. The random-effects model was applied to generate more conservative estimates. Sensitive analysis was conducted to explore whether the result would depend on a particular study. Egger's test and Begg's test were used to estimate the potential for publication bias. RESULTS: Seventeen studies including 30,062 participants were included. We found that fellow/trainee involvement enhanced the overall rates of adenoma detection and polyp detection (OR = 1.26, 95% CI = 1.14-1.40, p < 0.001; OR = 1.29, 95% CI = 1.02-1.63, p = 0.020, respectively). The mean number of adenoma/polyps per colonoscopy was also higher with fellow/trainee participation (MD = 0.12, 95% CI = 0.08-0.17, p < 0.001; MD = 0.15, 95% CI = 0.02-0.28, p = 0.020, respectively). CONCLUSION: In addition to its educational purpose, fellow or trainee involvement is associated with beneficial effects on colonoscopy outcomes.


Assuntos
Adenoma , Colonoscopia , Humanos , Animais , Ratos , Revisões Sistemáticas como Assunto , Colonoscopia/educação , Colonoscopia/métodos , Adenoma/diagnóstico , Hospitais de Ensino
14.
Sci Rep ; 13(1): 15519, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37726292

RESUMO

Calcific uremic arteriolopathy (CUA) is a severely morbid disease, affecting mostly dialyzed end-stage renal disease (ESRD) patients, associated with calcium deposits in the skin. Calcifications have been identified in ESRD patients without CUA, indicating that their presence is not specific to the disease. The objective of this retrospective multicenter study was to compare elastic fiber structure and skin calcifications in ESRD patients with CUA to those without CUA using innovative structural techniques. Fourteen ESRD patients with CUA were compared to 12 ESRD patients without CUA. Analyses of elastic fiber structure and skin calcifications using multiphoton microscopy followed by machine-learning analysis and field-emission scanning electron microscopy coupled with energy dispersive X-ray were performed. Elastic fibers specifically appeared fragmented in CUA. Quantitative analyses of multiphoton images showed that they were significantly straighter in ESRD patients with CUA than without CUA. Interstitial and vascular calcifications were observed in both groups of ESRD patients, but vascular calcifications specifically appeared massive and circumferential in CUA. Unlike interstitial calcifications, massive circumferential vascular calcifications and elastic fibers straightening appeared specific to CUA. The origins of such specific elastic fiber's alteration are still to be explored and may involve relationships with ischemic vascular or inflammatory processes.


Assuntos
Calciofilaxia , Falência Renal Crônica , Calcificação Vascular , Humanos , Tecido Elástico , Falência Renal Crônica/complicações , Margens de Excisão , Microscopia Eletrônica de Varredura
15.
Eur J Clin Pharmacol ; 79(11): 1475-1503, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37648741

RESUMO

PURPOSE: Aspirin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between aspirin use and the risk of occurrence of prostate cancer (PCa). The purpose of this study was to assess the effect of aspirin on clinical outcomes in patients with PCa in a meta-analysis and to explore the possible dose-response relationship. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of aspirin on the risk of PCa. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The across studies results show that aspirin use associated with lower incidence of PCa (RR: 0.96, 95% CI: 0.95-0.98), and reduced mortality (RR: 0.88, 95% CI: 0.82-0.95). The results of the subgroup analysis indicated that both cohort and population studies in the Americas showed a reduction in PCa incidence and mortality with aspirin use. A linear correlation was observed between dosage/duration of aspirin use and its protective effect. Additionally, post-diagnosis aspirin use was associated with decreased risk of PCa mortality. CONCLUSIONS: This meta-analysis revealed an independent correlation between the use of aspirin and reductions in both the incidence and mortality rates of PCa. However, randomized controlled trials did not find any association between aspirin use and PCa. Furthermore, the impact of aspirin on PCa occurrence was found to be dependent on both dosage and duration.


Assuntos
Aspirina , Neoplasias da Próstata , Masculino , Humanos , Aspirina/uso terapêutico , Incidência , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/induzido quimicamente , Risco
16.
Environ Sci Pollut Res Int ; 30(45): 100233-100247, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37612551

RESUMO

The results of environmental epidemiological studies regarding the relationship between human exposure to nickel and the risk of diabetes remain controversial. Therefore, we performed a meta-analysis to investigate the relationship between nickel exposure and diabetes. PubMed, Web of Science, and Embase electronic databases were thoroughly searched from their inception to May 2023 to obtain relevant studies. The random-effects model was employed to determine pooled odds ratios (ORs) and 95% confidence intervals (CIs). Stratified and sensitivity analyses were also performed. Cochran Q test and I2 statistic were employed to assess heterogeneity between studies. Begg's and Egger's tests were employed to evaluate publication bias. The indicated studies were evaluated using the ROBINS-E risk of bias tool. The dose-response relationship between nickel in urine and diabetes risk was estimated by restricted cubic spline. A total of 12 studies with 30,018 participants were included in this study. In this meta-analysis, comparing the highest vs. lowest levels of nickel exposure, the pooled ORs for diabetes were 1.42 (95% confidence interval 1.14-1.78) for urine and 1.03 (0.57-1.86) for blood, respectively. A linear relationship between urinary nickel and diabetes risk was discovered in the dose-response analysis (P nonlinearity = 0.6198). Each 1 µg/L increase of urinary nickel, the risk of diabetes increased by 7% (OR = 1.07, 95% CI 1.04-1.10). The risk of diabetes was positively correlated with urine nickel exposure, whereas the risk was not significantly correlated with blood nickel. In the future, more high-quality prospective studies are needed to validate this conclusion.


Assuntos
Líquidos Corporais , Diabetes Mellitus , Humanos , Níquel , Diabetes Mellitus/epidemiologia , Estudos Prospectivos , Razão de Chances
17.
J Gastroenterol Hepatol ; 38(11): 1971-1979, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37581244

RESUMO

BACKGROUND AND AIM: We aim to systematically investigate gastrointestinal (GI) hospitalizations in the United States during the early phase of the COVID-19 pandemic on a national level and the consequence that may inform practice and policies. METHODS: A retrospective cross-sectional analysis of adult hospitalizations with GI-related diagnoses or procedures in the United States in 2020 was used, with hospitalizations from 2016 to 2019 used for contextual information. RESULTS: Hospitalizations with principal and secondary GI diagnoses decreased by 13.3% and 8.2% from 2019 to 2020, respectively. Most GI diagnoses decreased in 2020, with a few exceptions including alcoholic liver disease (increased by 7.8% as a principal diagnosis) and acute liver failure (increased by 11.6% as a secondary diagnosis). The mortality rate of hospitalizations with GI disease increased in 2020 compared with 2019 (for principal diagnosis: adjusted odds ratio 1.08, 95% confidence interval 1.03-1.13, P = 0.001; for secondary diagnosis: adjusted odds ratio 1.10, 95% confidence interval 1.07-1.13, P < 0.001). Most GI procedures decreased except for a notable 8.3% increase in gastrostomy. The per-GI-hospitalization rate of procedures increased for hospitalizations with a principal GI diagnosis (56.4% vs 55.6%, P = 0.003) or unchanged for hospitalizations with secondary GI diagnoses (18.3% vs 18.2%, P = 0.512). CONCLUSION: The COVID-19 pandemic resulted in a decrease in the volume of GI hospitalizations and procedures in 2020, but there was an increase in the mortality rate and some specific diagnoses including alcoholic liver disease and acute liver failure. These findings will likely enlighten future research and healthcare resource allocation for GI diseases.


Assuntos
COVID-19 , Gastroenteropatias , Hepatopatias Alcoólicas , Falência Hepática Aguda , Adulto , Humanos , Estados Unidos/epidemiologia , Estudos Retrospectivos , Pacientes Internados , Estudos Transversais , Pandemias , COVID-19/epidemiologia , Hospitalização , Gastroenteropatias/epidemiologia , Gastroenteropatias/terapia
20.
PeerJ ; 11: e15703, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483962

RESUMO

Background: Phosphatidylinositol binding clathrin assembly protein interacting mitotic regulator (PIMREG) expression is upregulated in a variety of cancers. However, its potential role in breast cancer (BC) remains uncertain. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to gather relevant information. The expression of PIMREG and its clinical implication in BC were assessed by using Wilcoxon rank-sum test. The prognostic value of PIMREG in BC was evaluated through the Cox regression model and nomogram, and visualized by Kaplan-Meier survival curves. Genes/proteins that interact with PIMREG in BC were also identified through GeneMANIA and MaxLink. Gene set enrichment analysis (GSEA) was then performed. The correlations of the immune cell infiltration and immune checkpoints with the expression of PIMREG in BC were explored via TIMER, TISIDB, and GEPIA. Potential drugs that interact with PIMREG in BC were explored via Q-omic. The siRNA transfection, CCK-8, and transwell migration assay were conducted to explore the function of PIMREG in cell proliferation and migration. Results: PIMREG expression was significantly higher in infiltrating ductal carcinoma, estrogen receptor negative BC, and progestin receptor negative BC. High expression of PIMREG was associated with poor overall survival, disease-specific survival, and progression-free interval. A nomogram based on PIMREG was developed with a satisfactory prognostic value. PIMREG also had a high diagnostic ability, with an area under the curve of 0.940. Its correlations with several immunomodulators were also observed. Immune checkpoint CTLA-4 was significantly positively associated with PIMREG. HDAC2 was found as a potentially critical link between PIMREG and BRCA1/2. In addition, PIMREG knockdown could inhibit cell proliferation and migration in BC. Conclusions: The high expression of PIMREG is associated with poor prognosis and immune checkpoints in BC. HDAC2 may be a critical link between PIMREG and BRCA1/2, potentially a therapeutic target.


Assuntos
Neoplasias da Mama , Biologia Computacional , Peptídeos e Proteínas de Sinalização Intracelular , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Prognóstico , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Regulação para Cima , Transdução de Sinais , Técnicas de Silenciamento de Genes , Reprodutibilidade dos Testes
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