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1.
Int J Cancer ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712628

RESUMO

The relationship between Helicobacter pylori (H. pylori) infection and upper gastrointestinal (UGI) cancers is complex. This multicenter, population-based cohort study conducted in seven areas in China aimed to assess the correlation between current H. pylori infection and the severity of UGI lesions, as well as its association with the risk of gastric cancer (GC) and esophageal cancer (EC). From 2015 to 2017, 27,085 participants (aged 40-69) completed a standardized questionnaire, and underwent a 13C-urea breath test. Then a subset underwent UGI endoscopy to assess the UGI lesion detection rates. All individuals were followed up until December 2021 to calculate the hazard ratios (HRs) for UGI cancers. H. pylori infection prevalence was 45.9%, and among endoscopy participants, 22.2% had gastric lesions, 19.2% had esophageal lesions. Higher detection rates of gastric lesions were noted in the H. pylori-positive population across all lesion severity levels. Over a median follow-up of 6.3 years, 104 EC and 179 GC cases were observed, including 103 non-cardia gastric cancer (NCGC) cases and 76 cardia gastric cancer (CGC) cases. H. pylori-infected individuals exhibited a 1.78-fold increased risk of GC (HR 1.78, 95% confidence interval [CI] 1.32-2.40) but no significant increase in EC risk (HR 1.07, 95% CI 0.73-1.57). Notably, there was a higher risk for both NCGC and CGC in H. pylori-infected individuals. This population-based cohort study provides valuable evidence supporting the association between current H. pylori infection and the risk of both NCGC and CGC. These findings contribute to the empirical basis for risk stratification and recommendations for UGI cancer screening.

2.
Signal Transduct Target Ther ; 9(1): 131, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740785

RESUMO

Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants. Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in the N-terminal domain (NTD) of the S protein, which interferes with the RBD in the neighboring S protein. The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex. Furthermore, a nano-IgM construct (MN235), engineered by fusing N235 with the human IgM Fc region, displays prevention via inducing S1 shedding and cross-linking virus particles. Compared to N235, MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro. The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo, suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Epitopos , Imunoglobulina M , SARS-CoV-2 , Anticorpos de Domínio Único , Glicoproteína da Espícula de Coronavírus , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/química , Humanos , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/genética , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/farmacologia , Epitopos/imunologia , Epitopos/genética , Epitopos/química , Animais , COVID-19/imunologia , COVID-19/virologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/química , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/genética , Imunoglobulina M/imunologia , Imunoglobulina M/genética , Camundongos , Domínios Proteicos , Microscopia Crioeletrônica
3.
Angew Chem Int Ed Engl ; : e202405444, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637320

RESUMO

Unlocking the full potential of mRNA immunotherapy necessitates targeted delivery to specific cell subsets in the spleen. Four-component lipid nanoparticles (LNPs) utilized in numerous clinical trials are primarily limited in hepatocyte and muscular targeting, highlighting the imperative demand for targeted and simplified non-liver mRNA delivery systems. Herein, we report the rational design of one-component ionizable cationic lipids to selectively deliver mRNA to the spleen and T cells with high efficacy. Unlike the tertiary amine-based ionizable lipids involved in LNPs, the proposed cationic lipids rich in secondary amines can efficiently deliver mRNA both in vitro and in vivo as the standalone carriers. Furthermore, these vectors facilitate efficacious mRNA delivery to the T cell subsets following intravenous administration, demonstrating substantial potential for advancing immunotherapy applications. This straightforward strategy extends the utility of lipid family for extrahepatic mRNA delivery, offering new insights into vector development beyond LNPs to further the field of precise mRNA therapy.

4.
Food Chem X ; 22: 101333, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38595756

RESUMO

This study explored the feasibility of partially substituting NaCl with MgCl2 in preparing gel products from goose meat. Furthermore, the effects of synergistic interaction between different pH levels and NaCl concentrations on the structure and characteristics of the gels were explored by analyzing their secondary structure, microstructure, and water-distribution properties. The results showed that NaCl could be partially substituted by MgCl2, with the optimal preparation conditions: NaCl (0.83 mol/L), pH (7.3), MgCl2 (0.04 mol/L), heating temperature (79 °C), heating time (20 min), and solid-liquid ratio (1:3). Furthermore, the pH had a more significant impact on the gels' structure and characteristics than did NaCl concentration. Thus, our optimized method can reduce the usage of NaCl in the gel products while at the same time improving the characteristics of gel products under low-NaCl conditions by lowering pH, laying a solid theoretical foundation for producing low-NaCl protein gel products from goose meat.

5.
Food Chem X ; 21: 101240, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38434690

RESUMO

Encapsulation technology has been extensively used to enhance the stability, specificity, and bioavailability of essential food ingredients. Additionally, it plays a vital role in improving product quality and reducing production costs. This study presents a comprehensive classification of encapsulation techniques based on the state of different cores (solid, liquid, and gaseous) and offers a detailed description and analysis of these encapsulation methods. Specifically, it introduces the diverse applications of encapsulation technology in food, encompassing areas such as antioxidant, protein activity, physical stability, controlled release, delivery, antibacterial, and probiotics. The potential impact of encapsulation technology is expected to make encapsulation technology a major process and research hotspot in the food industry. Future research directions include applications of encapsulation for enzymes, microencapsulation of biosensors, and novel technologies such as self-assembly. This study provides a valuable theoretical reference for the in-depth research and wide application of encapsulation technology in the food industry.

6.
ACS Omega ; 9(7): 8229-8238, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38405502

RESUMO

The utilization of interfacial polymerization in the preparation of microcapsules with a slow-controlled release has been shown to effectively improve pesticide efficacy and reduce environmental pollution. In this study, polyurea microcapsules loaded with lambda-cyhalothrin were prepared by an interfacial polymerization method using modified isocyanate (MDI) as the wall material and GT-34 as the initiator. The microcapsules were fully characterized by optical microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, etc., and release behaviors were investigated. The results indicated that the microcapsules had a smooth surface and uniform distribution, the average particle size of the microcapsules was 1.97 µm, and the encapsulation efficiency of lambda-cyhalothrin microcapsules could reach 91.48%. Compared with other commercial formulations, the microcapsules exhibited an excellent sustained release property (>7 days) in a 50% acetonitrile aqueous solution (v/v). Subsequently, in vitro release studies showed that the lambda-cyhalothrin microcapsules could consistently control the release of the core materials at different pH, temperature, and MDI addition amount conditions. The release of lambda-cyhalothrin microcapsules was in accordance with the first-order model release, which was mainly by the Fickian diffusion mechanism. Furthermore, the biological activity on Myzus persicae showed that the microcapsules' persistence period was above 21 days, which was longer than that for the emulsifiable concentrate formulation.

7.
J Synchrotron Radiat ; 31(Pt 2): 260-267, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38252523

RESUMO

A method to optimize the thermal deformation of an indirectly cryo-cooled silicon crystal monochromator exposed to intense X-rays at a low-emittance diffraction-limited synchrotron radiation source is presented. The thermal-induced slope error of the monochromator crystal has been studied as a function of heat transfer efficiency, crystal temperature distribution and beam footprint size. A partial cooling method is proposed, which flattens the crystal surface profile within the beam footprint by modifying the cooling contact area to optimize the crystal peak temperature. The optimal temperature varies with different photon energies, which is investigated, and a proper cooling strategy is obtained to fulfil the thermal distortion requirements over the entire photon energy range. At an absorbed power up to 300 W with a maximum power density of 44.8 W mm-2 normal incidence beam from an in-vacuum undulator, the crystal thermal distortion does not exceed 0.3 µrad at 8.33 keV. This method will provide references for the monochromator design on diffraction-limited synchrotron radiation or free-electron laser light sources.

8.
Food Chem X ; 21: 101123, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38292675

RESUMO

The impact of exogenous limiting amino acids on protein gel formation was investigated to enhance the gelation properties of Landaise goose myofibrillar protein (MP). Amino acid composition and gel properties were analyzed, and homologous protein modeling and molecular docking techniques were used to simulate binding sites. Valine was identified as the first limiting amino acid. The addition of 0.075 % dl-valine proved optimal to enhance the gel strength (59.5 g) and water retention (76.76 %) of MP gels. Hydrophobic interactions and disulfide bonds were found to be the main forces maintaining conformational stability of the MP-dl-valine gels. The propyl group of dl-valine can form hydrophobic interactions with protein, contributing to stable complexes. DL valine could also strengthen chemical bonds and secondary structure, convert free water to immobile water, and improve the microstructure of the gel. Therefore, valine can be utilized as a nutritional and gel enhancer in Landaise goose meat products.

9.
Sci China Life Sci ; 67(1): 122-131, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37755589

RESUMO

China faces a disproportionate cancer burden to the population size and is undergoing a transition in the cancer spectrum. We extracted data in five aspects of cancer incidence, mortality, survival, staging distributions, and attribution to risk factors in China, the USA and worldwide from open-source databases. We conducted a comprehensive secondary analysis of cancer profiles in China in the above aspects, and compared cancer statistics between China and the USA. A total of 4,546,400 new cancer cases and 2,992,600 deaths occurred in China in 2020, accounting for 25.1% and 30.2% of global cases, respectively. Lifestyle-related cancers including lung cancer, colorectal cancer, and breast cancer showed an upward trend and have been the leading cancer types in China. 41.6% of new cancer cases and 49.3% of cancer deaths occurred in digestive-system cancers in China, and the cancers of esophagus, nasopharynx, liver, and stomach in China accounted for over 40% of global cases. Infection-related cancers showed the highest population-attributable fractions among Chinese adults, and most cancers could be attributed to behavioral and metabolic factors. The proportions of stage I for most cancer types were much higher in the USA than in China, except for esophageal cancer (78.2% vs. 41.1%). The 5-year relative survival rates in China have improved substantially during 2000-2014, whereas survival for most cancer types in the USA was significantly higher than in China, except for upper gastrointestinal cancers. Our findings suggest that although substantial progress has been made in cancer control, especially in digestive system cancers in China, there was still a considerable disparity in cancer burden between China and the USA. More robust policies on risk factors and standardized screening practices are urgently warranted to curb the cancer growth and improve the prognosis for cancer patients.


Assuntos
Neoplasias Esofágicas , Neoplasias Pulmonares , Neoplasias , Adulto , Humanos , Incidência , Neoplasias/diagnóstico , Neoplasias Esofágicas/epidemiologia , Fatores de Risco , China/epidemiologia
10.
Eur J Intern Med ; 120: 46-51, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37679281

RESUMO

BACKGROUND: Electrocardiogram (ECG) abnormalities indicating right ventricular strain have been reported to have prognostic value in severe cases of acute pulmonary embolism (PE). We aimed to analyze the prognostic significance of other quantitative ECG parameters in non-high-risk acute PE. METHODS: Consecutive patients with non-high-risk acute PE were prospectively enrolled. The following baseline ECG parameters were collected: rhythm, heart rate, QRS axis, right bundle branch block (RBBB) pattern, S1Q3T3 pattern, T-wave inversion, ST-segment elevation, Qr in lead V1, PR Interval, QRS complex duration, QT interval, P-wave amplitude and duration, R- and S-wave amplitudes. The primary endpoint was early discharge within three days. Associations between ECG parameters and early discharge were analyzed. RESULTS: Overall, 383 patients were enrolled (median age: 67 years, 57% female): 277 (72.3%) with low-risk and 106 (27.7%) with intermediate-risk. The two groups of patients differed in several ECG signs of right ventricular strain and many other quantitative parameters like R- and S-wave amplitudes. In the multivariate logistic regression analysis, the S-wave depth in lead V5 (S-V5) was the only independent prognostic factor for early discharge (odds ratio = 0.137, 95% confidence interval = 0.031-0.613, p = 0.009). The optimum cutoff value of S-V5 for predicting early discharge derived from the receiver operative characteristic curve was 0.15 mv (c-statistic = 0.66, p =0.003). CONCLUSIONS: Several ECG signs of right ventricular strain and many other quantitative parameters were associated with disease severity in non-high-risk acute PE. An S-V5 lesser than 0.15 mv was predictive for early discharge in these patients.


Assuntos
Eletrocardiografia , Embolia Pulmonar , Humanos , Feminino , Idoso , Masculino , Prognóstico , Arritmias Cardíacas , Doença Aguda , Embolia Pulmonar/complicações
11.
Sci China Life Sci ; 67(4): 711-719, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38155276

RESUMO

An increasing cancer incidence among adults younger than 50 years has been reported for several types of cancer in multiple countries. We aimed to report cancer profiles and trends among young adults in China. Data from the China Cancer Registry Annual Report were used to estimate incidence and mortality among young adults (ages 20-49 years) in China in 2017, and an age-period-cohort model was employed to estimate the average annual percent change (AAPC) in incidence and mortality from 2000 to 2017. All 25 cancer types were grouped into obesity- or overweight-associated cancers (12 cancer types) and additional cancers (13 cancer types). In 2017, there were 681,178 new cases and 214,591 cancer deaths among young adults in China. Among young adults, the most common cancers were thyroid, breast, cervical, liver, lung, and colorectal cancer, and the leading causes of cancer deaths were liver, lung, cervical, stomach, breast, and colorectal cancer. From 2000 to 2017, the cancer incidence increased for all cancers combined among young adults, with the highest AAPC (1.46%) for adults aged 20-24 years, while cancer mortality decreased, with the highest AAPC (-1.63%) for those aged 35-39 years. In conclusion, the cancer incidence in China has increased among young adults, while cancer mortality has decreased for nearly all ages. Cancer control measures, such as obesity control and appropriate screening, may contribute to reducing the increasing cancer burden among young adults.


Assuntos
Neoplasias Colorretais , Neoplasias , Humanos , Adulto Jovem , Neoplasias/prevenção & controle , Pesquisa , Sistema de Registros , Obesidade/complicações , Obesidade/epidemiologia , China/epidemiologia , Incidência
12.
Eur J Prev Cardiol ; 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966828

RESUMO

AIMS: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are reported to have cardiac benefits. The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. We aimed to investigate whether SGLT2 inhibitors can prevent AF occurrence in patients with cardiometabolic diseases. METHODS: We searched MEDLINE, EMBASE, and the Cochrane CENTRAL database up to July 1, 2023. Randomized, placebo-controlled trials of SGLT2 inhibitors in patients with diabetes, heart failure, chronic kidney diseases, or cardiometabolic risk factors were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated in the overall population and selected subgroups. RESULTS: Forty-six trials comprising 101 100 patients were included. Overall, no significant risk reduction of AF occurrence was observed with SGLT2 inhibitors, although there was a favorable trend (RR 0.90, 95% CI 0.80-1.01). In trials with follow-up durations of over one year, a similar result was achieved (RR 0.90, 95% CI 0.80-1.01). The results were consistent across different SGLT2 inhibitors, with RRs (95%CIs) of 0.82 (0.60-1.12) for canagliflozin, 0.87 (0.73-1.03) for dapagliflozin, 0.97 (0.78-1.22) for empagliflozin, 0.99 (0.66-1.50) for sotagliflozin, and 0.87 (0.58-1.29) for ertugliflozin. Analyses in different doses of SGLT2 inhibitors yielded similar results. The associations between SGLT2 inhibitors and AF occurrence were also absent in patients with diabetes, heart failure, and chronic kidney diseases. CONCLUSION: For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population.


The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population. Further research is warranted to investigate the potential benefit of SGLT2 inhibitors in AF.

13.
EBioMedicine ; 98: 104863, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37950995

RESUMO

BACKGROUND: Therapies are urgently required to ameliorate pathological cardiac hypertrophy and enhance cardiac function in heart failure. Our preliminary experiments have demonstrated that exogenous NADPH exhibits a positive inotropic effect on isolated heart. This study aims to investigate the positive inotropic effects of NADPH in pathological cardiac hypertrophy and heart failure, as well as the underlying mechanisms involved. METHODS: Endogenous plasma NADPH contents were determined in patients with chronic heart failure and control adults. The positive inotropic effects of NADPH were investigated in isolated toad heart or rat heart. The effects of NADPH were investigated in isoproterenol (ISO)-induced cardiac hypertrophy or transverse aortic constriction (TAC)-induced heart failure. The underlying mechanisms of NADPH were studied using SIRT3 knockout mice, echocardiography, Western blotting, transmission electron microscopy, and immunoprecipitation. FINDINGS: The endogenous NADPH content in the blood of patients and animals with pathological cardiac hypertrophy or heart failure was significantly reduced compared with age-sex matched control subjects. Exogenous NADPH showed positive inotropic effects on the isolated normal and failing hearts, while antagonism of ATP receptor partially abolished the positive inotropic effect of NADPH. Exogenous NADPH administration significantly reduced heart weight indices, and improved cardiac function in the mice with pathological cardiac hypertrophy or heart failure. NADPH increased SIRT3 expression and activity, deacetylated target proteins, improved mitochondrial function and facilitated ATP production in the hypertrophic myocardium. Importantly, inhibition of SIRT3 abolished the positive inotropic effect of NADPH, and the anti-heart failure effect of NADPH was significantly reduced in the SIRT3 Knockout mice. INTERPRETATION: Exogenous NADPH shows positive inotropic effect and improves energy metabolism via SIRT3 in pathological cardiac hypertrophy and heart failure. NADPH thus may be one of the potential candidates for the treatment of pathological cardiac hypertrophy or heart failure. FUNDING: This work was supported by grants from the National Natural Science Foundation of China (No. 81973315, 82173811, 81730092), Natural Science Foundation of Jiangsu Higher Education (20KJA310008), Jiangsu Key Laboratory of Neuropsychiatric Diseases (BM2013003) and the Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD).


Assuntos
Cardiomegalia , Cardiotônicos , Metabolismo Energético , Insuficiência Cardíaca , NADP , Sirtuína 3 , Adulto , Animais , Humanos , Camundongos , Ratos , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Camundongos Knockout , Miócitos Cardíacos/metabolismo , NADP/farmacologia , Sirtuína 3/genética , Sirtuína 3/metabolismo , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico
14.
Free Radic Biol Med ; 208: 748-758, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37774805

RESUMO

BACKGROUND: Fibroblast growth factor 21 (FGF21) regulates glycolipid metabolism and insulin homeostasis and acts as a cardioprotective factor by protecting against myocardial ischemia/reperfusion injury, hypertension, and vascular dysfunction. FGF21 has been reported to prevent Doxorubicin (Dox)-induced cardiotoxicity, and the related signaling pathway is worthy of further study. Connexin43 (Cx43) protein was reduced by Dox treatment, especially low phosphorylated form of Cx43. Thus the aim of study is to explore the protection effect of FGF21 on Dox induced cardiotoxicity by improving the expression of Cx43 and the involved signaling pathway. METHODS AND RESULTS: FGF21 inhibited apoptosis in Dox-treated mice and cardiomyocytes. FGF21 increased the levels of connexin43 phosphorylated at serine (S) 282 (p-Cx43 S282) and total Cx43 to inhibit Dox-induced apoptosis. By RNA sequencing, we found that deubiquitinase monocyte chemoattractant protein-induced protein 1 (MCPIP1) expression was increased by FGF21. We further found that FGF21 induced the phosphorylation of fibroblast growth factor receptor 1 (FGFR1), extracellular signal-regulated kinase 1 and 2 (Erk1/2), and Elk. Phosphorylated Elk translocated to the nucleus and increased the expression of MCPIP1. Then, MCPIP1 bound neural precursor cell expressed developmentally downregulated protein 4 (Nedd4), an E3 ubiquitination ligase, as shown by co-immunoprecipitation (Co-IP), and suppressed Cx43 ubiquitination and degradation, competitively inhibiting the binding of Cx43 with Nedd4. Thus Nedd4 could not bind and ubiquitinate Cx43, leading to the up-regulation of Cx43 and phosphorylation of Cx43 at S282. CONCLUSIONS: FGF21 inhibited the effects of Dox on cardiomyocytes by elevating the phosphorylation of Cx43 at S282 and total Cx43 expression. This study suggests a previously unknown mechanism for the FGF21-mediated enhancement of cardiomyocyte survival and provides an effective approach to protect against the adverse cardiac effects of Dox.


Assuntos
Cardiotoxicidade , Conexina 43 , Doxorrubicina , Fatores de Crescimento de Fibroblastos , Animais , Camundongos , Apoptose , Cardiotoxicidade/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Conexina 43/farmacologia , Doxorrubicina/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ubiquitinação , Fatores de Crescimento de Fibroblastos/metabolismo
15.
Medicine (Baltimore) ; 102(34): e34860, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37653838

RESUMO

The incidence and mortality of colon cancer are increasing, and effective biomarkers for its diagnosis are limited. 5-methylcytosine (5mC), a vital DNA methylation marker, plays important roles in gene expression, genomic imprinting, and transposon inhibition. This study aimed to identify the predictors of colon cancer prognosis and lay the foundation for research on therapeutic targets by detecting the levels of 5mC, 5-hydroxymethylcytosine (5hmC), 5-formyl cytosine (5fC), and 5-carboxylcytosine (5caC) in colon cancer and adjacent non-tumor tissues. A tissue microarray including 100 colon cancer tissue samples and 60 adjacent non-tumor tissue samples was used. The expression levels of 5mC and its ramifications were assessed by immunohistochemistry. According to the expression levels, patients were divided into moderately positive and strongly positive groups, and the correlation between clinicopathological characteristics and methylation marks was assessed using 2-sided chi-square tests. The prognostic values of 5mC, 5hmC, 5fC, and 5caC were tested using Kaplan-Meier analyses. Compared with adjacent non-tumor tissues, the overall levels of DNA methylation were lower in colon carcinoma lesions. However, the clinical parameters were not significantly associated with these methylation markers, except for 5hmC, which was associated with the age of cancer patients (P value = .043). Kaplan-Meier analysis disclosed that moderate positive group had a significantly shorter disease specific survival than strong positive group for patients with different levels of 5mC (65.2 vs 95.2 months, P = .014) and 5hmC (71.2 vs 97.5 months, P = .045). 5mC and its ramifications (5hmC, 5fC, and 5caC) can serve as biomarkers for colon cancer. 5mC and 5hmC are stable predictors and therapeutic targets in colon cancer. However, further understanding of its function will help to reveal the complex tumorigenic process and identify new therapeutic strategies.


Assuntos
5-Metilcitosina , Neoplasias do Colo , Humanos , Prognóstico , Metilação de DNA
16.
EClinicalMedicine ; 63: 102201, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37680952

RESUMO

Background: Endoscopy surveillance is recommended for mild-moderate dysplasia and negative endoscopy findings every 3 years and 5 years, respectively, but evidence is limited. This study aimed to assess long-term esophageal cancer (EC) incidence and mortality after a single endoscopy screening. Methods: We included individuals at high risk of EC aged 40-69 years who underwent endoscopy screening in 2007-2012 at six centres in rural China and had a baseline diagnosis of negative endoscopy findings, mild dysplasia, or moderate dysplasia. Participants were followed up for EC incidence and mortality. Cumulative incidence and mortality rates of EC were estimated by Kaplan-Meier analyses. Cox regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between baseline endoscopy diagnosis and the risk of EC incidence and mortality. EC incidence and mortality after a single endoscopy screening were compared with those of the population in rural China by the standardized incidence ratio (SIR) and standardized mortality ratio (SMR). Findings: A total of 42,827 participants (40,977 with negative endoscopy findings, 1562 with mild dysplasia, and 288 with moderate dysplasia) were included; 268 EC cases and 128 EC deaths were identified during a median follow-up of 10.62 years. The cumulative EC incidence at 10 years was 0.45% (0.38-0.52) in the group with negative endoscopy findings, 2.39% (1.62-3.16) in the mild dysplasia group, and 8.90% (5.57-12.24) in the moderate dysplasia group, and the cumulative EC mortality at 10 years was 0.23% (0.18-0.27), 0.96% (0.46-1.46), and 2.50% (0.67-4.33), respectively. Compared with individuals with negative endoscopy findings, the HRs for EC incidence and mortality in the mild dysplasia group were 3.52 (2.49-4.97) and 2.43 (1.41-4.19), and those in the moderate dysplasia group were 13.18 (8.78-19.76) and 6.46 (3.13-13.29), respectively. The SIR was 0.53 (0.40-0.70) for the group with negative endoscopy findings, 1.95 (1.69-2.24) for the mild dysplasia group, and 6.75 (6.25-7.28) for the moderate dysplasia group, with the SMRs of 0.43 (0.31-0.58), 1.07 (0.88-1.29) and 2.67 (2.36-3.01), respectively. Interpretation: Individuals with negative endoscopy findings after a single endoscopy screening had a lower EC risk than the general population for up to 10.62 years, while those with mild-moderate dysplasia had an elevated risk. Our results support endoscopy surveillance for mild-moderate dysplasia every 3 years and suggest extending the interval to 10 years after a negative endoscopy finding. Funding: National Key R&D Programme of China, Special Project of Beijing-Tianjin-Hebei Basic Research Cooperation, and Sanming Project of Medicine in Shenzhen.

17.
Int J Cancer ; 153(9): 1612-1622, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37548247

RESUMO

Cancer is a major contributor to global disease burden. Many countries experienced or are experiencing the transition that non-infection-related cancers replace infection-related cancers. We aimed to characterise burden changes for major types of cancers and identify global transition patterns. We focused on 10 most common cancers worldwide and extracted age-standardised incidence and mortality in 204 countries and territories from 1990 to 2019 through the Global Burden of Disease Study. Two-stage modelling design was used. First, we applied growth mixture models (GMMs) to identify distinct trajectories for incidence and mortality of each cancer type. Next, we performed latent class analysis to detect cancer transition patterns based on the categorisation results from GMMs. Kruskal-Wallis H tests were conducted to evaluate associations between transition patterns and socioeconomic indicators. Three distinct patterns were identified as unfavourable, intermediate and favourable stages. Trajectories of lung and breast cancers had the strongest association with transition patterns among men and women. The unfavourable stage was characterised by rapid increases in lung, breast and colorectal cancers alongside stable or decreasing burden of gastric, cervical, oesophageal and liver cancers. In contrast, the favourable stage exhibited rapid declines in most cancers. The unfavourable stage was associated with lower sociodemographic index, health expenditure, gross domestic product per capita and higher maternal mortality ratio (P < .001 for all associations). Our findings suggest that unfavourable, intermediate and favourable transition patterns exist. Countries and territories in the unfavourable stage tend to be socioeconomically disadvantaged, and tailored intervention strategies are needed in these resource-limited settings.


Assuntos
Neoplasias da Mama , Masculino , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Carga Global da Doença , Fatores Socioeconômicos , Saúde Global
18.
Environ Sci Pollut Res Int ; 30(40): 93142-93154, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37501029

RESUMO

In China, a large amount of soil lack available silicon, which leads to a decrease in crop yield. Furthermore, the solid waste coal tailings contain abundant minerals that are rich in silicon, which have not been fully utilized. In this work, we used Bacillus mucilaginosus as the leaching agent to convert insoluble silicon in coal tailings into available silicon for crop. After single-factor experiments, the optimal leaching conditions with bacterial dosage, coal tailings weight, initial pH, leaching temperature, and shaking speed were obtained. Kinetic analysis showed that the controlling process of the leaching was a chemical reaction. The leaching process was characterized by X-ray diffraction (XRD), scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS), Fourier transform infrared spectrometer (FT-IR), and high-performance liquid chromatography (HPLC). The results showed that bioleaching is a feasible and efficient method to extract silicon from coal tailings, with a maximum leaching amount of 260 mg L-1 after 16 days, which occupied 93% of the total effective silicon. In conclusion, this work demonstrates that bioleaching technology can effectively solve the problem of the environmental utilization of coal tailings by converting them into a soil improver that can provide beneficial nutrients for crop growth.


Assuntos
Carvão Mineral , Silício , Cinética , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Respir Med ; 217: 107369, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37494975

RESUMO

BACKGROUND: As an important place of material exchange, the homeostasis of the pulmonary circulation environment and function lays an essential foundation for the normal execution of various physiological functions of the body. Small metabolic molecules in the circulation can reflect the corresponding state of the pulmonary circulation. METHODS: We enrolled patients with Patent Foramen Ovale and obtained blood from the pulmonary arteries and veins through heart catheterization. UPLC-MS based untargeted metabolomics was used to compare the changes and metabolic differences of plasma between pulmonary vein and pulmonary artery. RESULTS: The plasma metabolomics revealed that pulmonary artery had a different metabolomic profile compared to venous. 1060 metabolites were identified, and 61 metabolites were differential metabolites. Purine, Amino acids, Nicotinamide, Tetradecanedioic acid and Bile acid were the most markedly. CONCLUSION: The differential metabolites are mostly related to immune inflammation and damage repaired. It is suggested that the pulmonary circulation is always in a steady state of injury and repair while pathological changes may be triggered when the homeostasis is broken. These changes play an important role in revealing the development process and etiology of lung homeostasis and related diseases. Relevant metabolites can be used as potential targets for further study of pulmonary circulation homeostasis.

20.
J Cardiol ; 82(6): 441-447, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37422074

RESUMO

OBJECTIVE: To detect the expression level of PIWI-interacting RNA in the serum of patients with acute myocardial infarction, and to explore the role of PIWI-interacting RNA in acute myocardial infarction. METHODS: RNA was extracted from the serum of acute myocardial infarction patients and healthy subjects, and high-throughput sequencing of PIWI-interacting RNAs was performed to screen differentially expressed PIWI-interacting RNAs. Quantitative polymerase chain reaction was used to detect the expression of four differentially expressed PIWI-interacting RNAs in 52 patients with acute myocardial infarction and 30 healthy people. Receiver operating characteristic (ROC) curve was further used to analyze the correlation between differentially expressed PIWI-interacting RNAs and the occurrence of acute myocardial infarction. Kyoto Encyclopedia of Genes and Genomes analysis was used to analyze the role of PIWI-interacting RNA in the occurrence of acute myocardial infarction. RESULTS: RNA sequencing and bioinformatics analysis revealed that most piRNAs were upregulated in AMI patients, with 195 upregulated and 13 downregulated. Among them, piR-hsa-9010, piR-hsa-28646, and piR-hsa-23619 were significantly up-regulated in the serum of patients with acute myocardial infarction, but their expression in the acute heart failure group and coronary heart disease group was not significantly different from that in the healthy group. ROC curve analysis showed that piR-hsa-9010, piR-hsa-28646, and piR-hsa-23619 had high diagnostic values in acute myocardial infarction. In vitro, there was no significant difference in the expression of piR-hsa-9010 among THP-1, HUVEC, and AC16, while the expression of piR-hsa-28646 and piR-hsa-23619 in HUVEC was significantly higher than that in THP-1 and AC16. Pathway analysis showed that piR-hsa-23619 was mainly involved in TNF signaling pathway, and piR-hsa-28646 was mainly involved in Wnt signaling pathway. CONCLUSION: piR-hsa-9010, piR-hsa-28646, and piR-hsa-23619 were significantly up-regulated in the serum of patients with acute myocardial infarction. It can be used as a new biomarker for the diagnosis of acute myocardial infarction, which may be a therapeutic target for acute myocardial infarction.


Assuntos
Infarto do Miocárdio , RNA de Interação com Piwi , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética
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