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1.
J Transl Med ; 19(1): 280, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193174

RESUMO

BACKGROUND: Colorectal cancer is the third most common diagnosis. Oxaliplatin is used as first-line treatment of colon cancer. However, oxaliplatin resistance greatly reduces its therapeutic effect. SRPK1 involves in pre-mRNA splicing and tumorigenesis. How SRPK1 mediates drug resistance in colon cancer is unknown. METHODS: The expression of SRPK1 was analyzed in the TCGA and the CPTAC pan-cancer samples and detected in colon cancer cell lines and tissues by IHC and western blot. The MTT and TUNEL assay were used to verify the anti-apoptosis ability of colon cancer cell. The activation of NF-κB was determined by luciferase assay and qRT-PCR. AKT, IKK, IκB and their phosphorylation level were verified by western blot. RESULTS: We found that SRPK1 expression was the second highest in TCGA and the CPTAC pan-cancer samples. The mRNA and protein levels of SRPK1 were increased in tissues from patients with colon cancer. SRPK1 was associated with clinical stage and TNM classifications in 148 cases of colon cancer patients. High SRPK1 levels correlated with poor prognosis (p < 0.001). SRPK1 overexpression enhanced the anti-apoptosis ability of colon cancer cells, whereas SRPK1 silencing had the opposite effect under oxaliplatin treatment. Mechanistically, SRPK1 enhances IKK kinase and IκB phosphorylation to promote NF-κB nuclear translocation to confer oxaliplatin resistance. CONCLUSIONS: Our findings suggest that SRPK1 participates in colon cancer progression and enhances the anti-apoptosis capacity to induce drug resistance in colon cancer cells via NF-κB pathway activation, and thus might be a potential pharmaceutically target for colon cancer treatment.

2.
Drug Dev Res ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34212407

RESUMO

Acute pancreatitis (AP) is an inflammatory gastrointestinal disorder affecting the pancreas. Previous study reported that tetraspanin 1 (TSPAN1) expression was significantly upregulated in the pancreas of AP patients. However, the underlying molecular mechanism of TSPAN1 in the pathogenesis of AP remains unclear. Thus, the aim of the present study was to investigate the potential role of TSPAN1 in development of AP. RT-qPCR was carried out to quantify the relative mRNA levels of TSPAN1 and anterior gradient-2 (AGR2). The CCK-8 assay was used to detect the cell viability. The TUNEL assay was performed to visualize the apoptotic cells. Western blot was performed to determine the expressions of proteins related to endoplasmic reticulum (ER) stress and apoptosis. ELISA kits were adopted to detect the concentration of inflammatory cytokines including TNF-α and IL-6. Finally, immunoprecipitation (IP) was used to verify the interaction between TSPAN1 and AGR2. TSPAN1 was upregulated in serum of AP patients and AP cell models. TSPAN1 silencing promoted the cell proliferation and inhibited inflammatory response in cerulein-induced AR42J cells. Moreover, TSPAN1 induced endoplasmic reticulum stress by binding AGR2. Interestingly, the overexpression of AGR2 abolished the effects of TSPAN1 silencing on cell proliferation and inflammatory response in cerulein-induced AR42J cells. In summary, TSPAN1 silencing protects against cerulein-induced pancreatic acinar cell injury through inhibiting ER stress-mediated by AGR2. Hence, TSPAN1 may serve as a promising therapeutic target for AP treatment.

3.
J Mol Cell Biol ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289037

RESUMO

The prevailing coronavirus disease (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has presented some neurological manifestations including hyposmia, hypogeusia, headache, stroke, encephalitis, Guillain‒Barre syndrome, and some neuropsychiatric disorders. Although several cell types in the brain express angiotensin converting enzyme-2 (ACE2), the main SARS-CoV-2 receptor, and other related proteins, it remains unclear whether the observed neurological manifestations are attributed to virus invasion into the brain or just comorbidities caused by dysregulation of systemic factors. Here, we briefly review the neurological manifestations of SARS-CoV-2, summarize recent evidence for the potential neurotropism of SARS-CoV-2, and discuss the potential mechanisms of COVID-19-associated neurological diseases.

4.
Org Lett ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289688

RESUMO

Anionic Diels-Alder chemistry of electron-deficient cross-conjugated vinylogous alkenones, providing highly stable sodium dienolate ion pairs as electron-rich dienes in the presence of a weak sodium base in THF, has been newly developed, leading to a single Diels-Alder adduct, in racemic form, in moderate to high yields (up to 97%, 37 examples).

5.
Colloids Surf B Biointerfaces ; 206: 111951, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34243032

RESUMO

Giant lipid vesicles (GLVs) are usually adopted as models of cell membranes and electroformation is the most commonly used method for GLV formation. However, GLV electroformation are known to be suppressed by the presence of salt and the mechanism is not clear so far. In this paper, the lipid hydration and GLV electroformation were investigated as a function of the concentration of sodium chloride by depositing the lipids on the bottom substrates and top substrates. In addition, the electrohydrodynamic force generated by the electroosmotic flow (EOF) on the lipid phase was calculated with COMSOL Multiphysics. It was found that the mechanisms for the failure of GLV electroformation in salt solutions are: 1) the presence of sodium chloride decreases the membrane permeability to aqueous solution by accelerating the formation of well-packed membranes, suppressing the swelling and detachment of the lipid membranes; 2) the presence of sodium chloride decreased the electrohydrodynamic force by increasing the medium conductivity.

6.
Lupus ; : 9612033211031009, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259057

RESUMO

BACKGROUND: SLE, which is common in women, is commonly treated with HCQ, an anti-inflammation medication. Reproductive-age women with SLE are prone to be impacted by endometriosis. This study analyzes the relationship between HCQ and endometriosis patients with SLE in order to determine whether HCQ is effective for treating the latter. METHODS: This population-based, retrospective cohort study analyzed the SLE risk in a cohort of newly diagnosed SLE patients with endometriosis during 2000 through 2013. Controls were selected at a 1:2 ratio through age-matching using the greedy algorithm. The Cox proportional hazard model was used to analyze the association between HCQ use and endometriosis incidence. Four different Cox regression models were used. Lastly, sensitivity analysis with PSOW and IPW was implemented to evaluate the hazard ratio (HR) of endometriosis after exposure with HCQ. RESULTS: In the cohort where age and sex matched high and low HCQ dosage, the average follow-up time was about 1 year. The cohort's overall incidence rates of endometriosis were 44.54 and 90.03 per 100000 person-month for high and low dosage respectively. The high dose group's conditional hazard ratio (aHR) for incidental endometriosis was 0.482 (CI = 0.191 to 1.213). The incidence rate and Kaplan-Meir curves of endometriosis were consistent with the results for the cohort. CONCLUSION: This study demonstrated that SLE patients continuously treated with HCQ have a lower risk of developing endometriosis. Clinically, HCQ can be beneficial for endometriosis patients with SLE.

7.
Genet Test Mol Biomarkers ; 25(7): 496-503, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34280010

RESUMO

Numerous studies investigating an association between the matrix metalloproteinase-1 (MMP-1) gene rs1799750 polymorphism and breast cancer (BC) risk have reported inconsistent results. Therefore, this meta-analysis was undertaken to obtain a more precise estimate of the possible association between this genetic locus and BC susceptibility. Methods: Eight eligible studies involving 3439 cases and 3517 controls were identified by searching the PubMed, Google, CNKI, and EMBASE databases systematically through October 1, 2020. Results: The MMP-1 rs1799750 polymorphism was associated with a reduced BC risk in the overall study population under the heterozygous model. Stratification analyses indicated that this association is strong in Asians. Conclusion: There is evidence of an association between the MMP-1 rs1799750 polymorphism and BC susceptibility, viewed as a decreased risk factor for BC. More extensive studies with more diverse ethnic populations are necessary to confirm these findings.

8.
Environ Int ; 156: 106761, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34284317

RESUMO

BACKGROUND: Phthalic acid esters (PAEs) are widely used as plasticizers in industrial process and consumer products. Nowadays, PAEs are ubiquitous in the environment and are reported to be associated with cardiorespiratory diseases. However, studies about the association between indoor airborne PAEs exposure and cardiorespiratory health were limited, and the potential biological mechanism remains under-recognized. METHODS: A randomized crossover trial was conducted on 57 healthy young adults in Beijing. Repeated health measurements were performed under real and sham indoor air purification with a washout interval of at least 2 weeks. The concentration of indoor airborne PAEs were determined by gas chromatography-orbit ion trap mass spectrometry. Health indicators including blood pressure, lung function, airway inflammation, and circulating biomarkers reflecting blood coagulation and systematic oxidative stress were measured. Linear mixed-effect model was used to examine the between-treatment differences in health indicators, and three models including single-constituent, constituent-fine particulate matter (PM2.5) joint, and single-constituent residual model were used to estimate the association between indoor airborne PAEs and health indicators. RESULTS: The indoor airborne PAEs were reduced effectively under real air purification. The total indoor airborne di-2-ethylhexyl phthalate (DEHP), bis (4-Methyl-2-pentyl) phthalate (DMPP), diphenyl phthalate (DPP), and diethyl phthalate (DEP) were identified to be most significantly associated with the increase of blood pressure and airway inflammation, and decrease of lung function. A doubling increase in DEHP, DMPP, DPP, DEP was associated with the increase of 17.2% (95% CI: 3.9%, 32.2%), 11.7% (95% CI: 3.5%, 20.6%), 7.0% (95% CI: 2.4%, 11.8%), 6.0% (95% CI: 1.8%, 10.4%) in FeNO, respectively, in single-constituent residual model. Significant associations between specific total indoor airborne PAEs and increased levels of health biomarkers including oxidized low-density lipoprotein (ox-LDL), 8-isoprostane (8-isoPGF2α), and soluble P-selectin (sP-selectin) were observed. CONCLUSION: Indoor airborne PAEs may cause adverse cardiorespiratory health effects in young healthy adults, and indoor air purification could ameliorate the adverse cardiorespiratory effects.

9.
Environ Health Prev Med ; 26(1): 74, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34273955

RESUMO

BACKGROUND: Ambient fine particle (PM2.5) pollution is an important public health problem in China. Short-term ambient PM2.5 exposure is associated with increased mortality of respiratory diseases. However, few evidence was available on the effect of exposure to ambient PM2.5 on the years of life lost (YLL) from respiratory diseases in the elderly. Furthermore, birth season which is frequently applied as a proxy for environmental exposure in early life may influence the health outcome in the later life. Nevertheless, the modification effect of birth season on the relationship of PM2.5 exposure and respiratory health need to be explored. METHODS: A time-stratified case-crossover design was used to analyze YLL from respiratory diseases in the elderly related to ambient PM2.5 exposure between 2013 and 2016 in Ningbo, China. The modification effect of birth season was explored by subgroup comparisons between different birth seasons. RESULTS: Each 10 µg/m3 increase in daily ambient PM2.5 was associated with an increment of 1.61 (95% CI 0.12, 3.10) years in YLL from respiratory diseases in the elderly population. Individuals who were born in winter had significantly higher YLL from respiratory diseases associated with ambient PM2.5 exposure than those who were born in other seasons. CONCLUSIONS: Birth season which reflects the early-life PM2.5 exposure level that may influence the lung development has a potential effect on the disease burden of respiratory diseases related to ambient PM2.5 exposure in later life. The results would provide theoretical basis to protect vulnerable population defined by birth season when exploring the adverse effects of ambient PM2.5 in the respiratory health.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição Ambiental/efeitos adversos , Expectativa de Vida , Material Particulado/efeitos adversos , Transtornos Respiratórios/etiologia , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos/análise , Causas de Morte , China/epidemiologia , Estudos Cross-Over , Exposição Ambiental/análise , Humanos , Material Particulado/análise , Transtornos Respiratórios/mortalidade , Estações do Ano
10.
Front Cell Infect Microbiol ; 11: 691757, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277472

RESUMO

Schistosoma japonicum (S. japonicum) infection can induce serious organ damage and cause schistosomiasis japonica which is mainly prevalent in Asia and currently one of the most seriously neglected tropical diseases. Treatment of schistosomiasis largely depends on the drug praziquantel (PZQ). However, PZQ exhibits low killing efficacy on juvenile worms and the potential emergence of its drug resistance is a continual concern. Protein kinases (PKs) are enzymes that catalyze the phosphorylation of proteins and can participate in many signaling pathways in vivo. Recent studies confirmed the essential roles of PKs in the growth and development of S. japonicum, as well as in schistosome-host interactions, and researches have screened drug targets about PKs from S. japonicum (SjPKs), which provide new opportunities of developing new treatments on schistosomiasis. The aim of this review is to present the current progress on SjPKs from classification, different functions and their potential to become drug targets compared with other schistosomes. The efficiency of related protein kinase inhibitors on schistosomes is highlighted. Finally, the current challenges and problems in the study of SjPKs are proposed, which can provide future guidance for developing anti-schistosomiasis drugs and vaccines.


Assuntos
Preparações Farmacêuticas , Schistosoma japonicum , Esquistossomose , Animais , Ásia , Proteínas Quinases
11.
J Phys Chem A ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251201

RESUMO

A full-dimensional global potential energy surface (PES) for the KRb + KRb → K2Rb2* → K2 + Rb2 reaction is reported based on high-level ab initio calculations. The short-range part of the PES is fit with the permutationally invariant polynomial-neural network method, while the long-range parts of the PES in both the reactant and product asymptotes are represented by an asymptotically correct form. The long- and short-range parts are connected with intermediate-range parts to make them smooth. Within a statistical quantum model, this PES reproduces both the measured loss rates of ultracold KRb molecules and the K2 and Rb2 product state distributions, underscoring the important role of tunneling in ultracold chemistry. The PES also correctly predicts the lifetime of the K2Rb2* intermediate complex within the Rice-Ramsperger-Kassel-Marcus limit. It thus provides a reliable platform for future dynamical studies of the prototypical reaction.

12.
Pest Manag Sci ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34223694

RESUMO

BACKGROUND: The striped rice stem borer, Chilo suppressalis (Lepidoptera: Pyraidae), is one of the most serious rice pests in China. Chlorantraniliprole was used extensively for C. suppressalis control over the past ten years, and some field populations have developed high resistance. In this study, we report the chlorantraniliprole resistance status of C. suppressalis in China and the resistance mechanism. RESULTS: Significant geographical variations of chlorantraniliprole susceptibility were observed among 28 C. suppressalis field populations in 2019-2020. The LC50 values varied from 2907.874 mg L-1 (XS19) to 1.524 mg L-1 (QW19). Most tested field populations collected from Zhejiang, Jiangxi, Hunan and Anhui provinces in 2020 showed a high level of resistance to chlorantraniliprole (RR = 311.9-2060.1), whereas Jiangsu and Sichuan province populations remained susceptible. Analysis of RyR mutations showed that mutations of I4758M, Y4667D, Y4667C and Y4891F were present in resistant populations of C. suppressalis with different levels of chlorantraniliprole resistance. The frequency of the Y4667C mutation was correlated with chlorantraniliprole resistance in YY19 (RR = 702.6) and YY20 (RR = 1426.8) populations, with the homozygous mutation frequencies of 15.6% and 29.4%, respectively. High contributions of the I4758M and Y4667C double mutation to diamide resistance was demonstrated with CRISPR/Cas9-modified D. melanogaster. Flies bearing the Y4667C mutation (I4758M and Y4667C double mutation in C. suppressalis) exhibited high resistance to chlorantraniliprole (RR = 172.1), and moderate resistance to cyantraniliprole (RR = 79.2) and tetra chlorantraniliprole (RR = 43.6), which were higher than that of single mutations. CONCLUSIONS: Chlorantraniliprole resistance in C. suppressalis is intensifying in China. RyR double mutations (i.e. I4758M and Y4667C) confer higher diamide resistance than single mutations.

13.
Public Health ; 196: 165-171, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34229128

RESUMO

OBJECTIVE: The objective of this study was to review evidence on the effectiveness of vaccination in the prevention of human papilloma virus (HPV) infection at the cervix, anal, and oral. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The key search limitations are as follows: "Human Papilloma Virus", "Papilloma Virus, Human" "Human Papillomavirus Virus", "HPV" and "oral", "anus", "anal", "penis", "cervical," and "vaccine". Randomized controlled studies were searched and analyzed the risk ratio by Review Manager 5.3; funnel plot was adopted for publication bias analysis. RESULTS: Five randomized controlled studies enrolling 13,686 participants were retrieved, analyzed, and showed that HPV vaccination can effectively block HPV infection at cervical, anal, and oral. Subgroup analysis, moreover, proved that HPV 16/18 is more effective than HPV 6/11/16/18 in preventing anal and oral infections. CONCLUSION: HPV vaccine is efficacious in preventing HPV infection not only at cervical but also at anal and oral, as evidence supported by relevant studies.

14.
J Mol Neurosci ; 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34218423

RESUMO

Progressive myoclonic epilepsy is a group of neurodegenerative diseases with complex clinical and genetic heterogeneity, which is associated with spontaneous or action-induced myoclonus and progressive neurodegeneration. Since 2020, 4 families with progressive myoclonic epilepsy-11 [OMIM#618876] have been reported with a very limited spectrum of SEMA6B pathogenic variants. In our study, whole-exome sequencing was used in a proband from a nonconsanguineous Chinese family presenting with growth retardation and recurrent atonic seizures. A deletion mutation (c.1960_1978del, p.Leu654Argfs*25) in the last exon of SEMA6B was detected, which is a de novo variant and pathogenic. The new genetic evidence we reported here strengthened the gene-disease relationship, and the gene curation level between SEMA6B and progressive myoclonic epilepsy-11 became "strong" following the ClinGen SOP. Therefore, the results of this study broaden the mutation spectrum of SEMA6B in different ethnic groups and strengthen the gene-disease relationship between SEMA6B and progressive myoclonic epilepsy-11.

15.
Pak J Pharm Sci ; 34(1(Special)): 423-428, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34275789

RESUMO

To investigate the effects of dexmedetomidine combined with citrate sufentanil on the prognosis of patients with severe pneumonia and respiratory failure requiring mechanical ventilation. 70 patients with severe pneumonia complicated with respiratory failure who were treated with mechanical ventilation were selected and divided into the combined group and the control group. The control group underwent mechanical ventilation treatment and used dexmedetomidine for sedation and analgesia, while the combined group had sufentanil analgesia in addition to the treatment of the control group. Ramsay sedation score, visual analogue scale (VAS) and pulmonary function indicators were compared between the two groups before treatment, 24h after treatment, and after extubation. After 24h treatment and extubation, the blood oxygen saturation (SpO2), oxygenation index (OI) and arterial oxygen partial pressure (PaO2) in the combined group were higher than those in the control group; at the same time, the serum interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and malondialdehyde (MDA) levels were lower (P<0.05). Mortality during hospitalization of the combined group was lower than the control group (P<0.05). Dexmedetomidine combined with sufentanil citrate can effectively improve sedative and analgesic effects, stress response, pulmonary function and prognosis in patients with severe respiratory failure requiring mechanical ventilation.

16.
Epileptic Disord ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34279234

RESUMO

OBJECTIVE: We aimed to identify new candidate pathogenic genes for atypical Rolandic epilepsy. METHODS: We retrospectively evaluated the data from 24 Chinese patients with atypical Rolandic epilepsy who underwent whole-exome sequencing. Data were analysed regarding the frequency of affected genes, previously reported disease-related genes, and evaluation based on Kyoto Encyclopaedia of Genes and Genomes (KEGG). RESULTS: We identified a frameshift mutation in the reported gene PRRT2, which is classified as pathogenic according to American College of Medical Genetics and Genomics guidelines (ACMG). We also identified a novel missense mutation in the PRRT2 gene in a family with three affected patients. Several other candidate genes were found in at least two patients, some of which were associated with other epilepsies (ADGRV1, CACNA1A, CHD2, CLCN2, HECW2, KIF1A, NPRL3, RELN and TSC2), while others were mainly associated with neuropsychiatric disease (SHANK3 and AUTS2). The KEGG analysis of 81 candidate genes associated with atypical Rolandic epilepsy identified a significant association with the GABAergic synapse. Candidate genes involved in the GABAergic synapse pathway included NSF, CACNA1A, as well as others. SIGNIFICANCE: Our study indicates that PRRT2 mutations may be associated with atypical Rolandic epilepsy. Moreover, we identified a number of unreported candidate genes, including ADGRV1, CHD2, CACNA1A, NSF, NPRL3, KIF1A, GJB2 and HECW2, also associated with atypical Rolandic epilepsy.

17.
Neural Plast ; 2021: 5560453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194487

RESUMO

Objectives: Previous researches have demonstrated that abnormal functional connectivity (FC) is associated with the pathophysiology of bipolar disorder (BD). However, inconsistent results were obtained due to different selections of regions of interest in previous researches. This study is aimed at examining voxel-wise brain-wide functional connectivity (FC) alterations in the first-episode, drug-naive patient with BD in an unbiased way. Methods: A total of 35 patients with BD and 37 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). Global-brain FC (GFC) was applied to analyze the image data. Support vector machine (SVM) was adopted to probe whether GFC abnormalities could be used to identify the patients from the controls. Results: Patients with BD exhibited increased GFC in the left inferior frontal gyrus (LIFG), pars triangularis and left precuneus (PCu)/superior occipital gyrus (SOG). The left PCu belongs to the default mode network (DMN). Furthermore, increased GFC in the LIFG, pars triangularis was positively correlated with the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with the scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) coding test and Stroop color. Increased GFC values in the left PCu/SOG can be applied to discriminate patients from controls with preferable sensitivity (80.00%), specificity (75.68%), and accuracy (77.78%). Conclusions: This study found increased GFC in the brain regions of DMN; LIFG, pars triangularis; and LSOG, which was associated with dyslipidemia and cognitive impairment in patients with BD. Moreover, increased GFC values in the left PCu/SOG may be utilized as a potential biomarker to differentiate patients with BD from controls.

18.
Ecotoxicol Environ Saf ; 222: 112484, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34237641

RESUMO

Exposure to particulate matter (PM) has been associated with DNA damage, but the relationships between PM, telomere length and cellular senescence remain unclear. This study aimed to investigate the effects and potential mechanisms of PM on telomere length and cellular senescence in human lung epithelial cells. Human lung epithelial A549 cells were exposed to PM for 24 h. Cell viability and cytotoxicity were measured by the WST-1 assay and the lactate dehydrogenase release, respectively. Cellular uptake of PM was observed using transmission electron microscopy. Telomere length was measured using qPCR and expressed as T/S ratio. Cell cycle progression was analyzed by flow cytometry. Expression of human telomerase reverse transcriptase (hTERT) and cell cycle regulators was measured using mRNA by qPCR and protein levels by Western blot. Cellular senescence was determined by the expression of senescence-associated ß-galactosidase (SA-ß-Gal) with fluorescent microscopy and flow cytometry. Exposed to PM at the concentration of 200 µg/ml decreased cell viability and increased LDH levels in culture medium. Remarkably increased uptake of PM, shortening of telomere length, induction of G0/G1 phase arrest, and increased expression of senescence hallmarks were observed after exposure to PM in A549 cells. PM exposure induced upregulation of p21 and downregulation of proliferating cell nuclear antigen (PCNA) and hTERT expression, but no significant change in p53 expression, in A549 cells. Overall, exposure to PM may downregulate hTERT and PCNA through p53-independent induction of p21 expression, leading to telomere shortening, G0/G1 arrest and the onset of cellular senescence in human lung epithelial cells.

19.
Comput Biol Med ; 135: 104622, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34242868

RESUMO

Nonalcoholic fatty liver disease (NAFLD), a leading cause of chronic hepatic disease, can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, it is extremely important to explore early diagnosis and screening methods. In this study, we developed models based on computer tongue image analysis technology to observe the tongue characteristics of 1778 participants (831 cases of NAFLD and 947 cases of non-NAFLD). Combining quantitative tongue image features, basic information, and serological indexes, including the hepatic steatosis index (HSI) and fatty liver index (FLI), we utilized machine learning methods, including Logistic Regression, Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), Adaptive Boosting Algorithm (AdaBoost), Naïve Bayes, and Neural Network for NAFLD diagnosis. The best fusion model for diagnosing NAFLD by Logistic Regression, which contained the tongue image parameters, waist circumference, BMI, GGT, TG, and ALT/AST, achieved an AUC of 0.897 (95% CI, 0.882-0.911), an accuracy of 81.70% with a sensitivity of 77.62% and a specificity of 85.22%; in addition, the positive likelihood ratio and negative likelihood ratio were 5.25 and 0.26, respectively. The application of computer intelligent tongue diagnosis technology can improve the accuracy of NAFLD diagnosis and may provide a convenient technical reference for the establishment of early screening methods for NAFLD, which is worth further research and verification.

20.
Comput Methods Programs Biomed ; 208: 106257, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34245951

RESUMO

OBJECTIVE: To evaluate the quantitative changes of respiratory functions for critically ill COVID-19 patients with mechanical ventilation, computational fluid dynamics (CFD) analysis was performed based on patient-specific three-dimensional airway geometry. METHODS: 37 cases of critically ill patients with COVID-19 admitted to the ICU of Huangshi Traditional Chinese Medicine Hospital from February 1st to March 20th, 2020 were retrospectively analyzed. 5 patients whose clinical data met the specific criteria were finally cataloged into death group (2 patients) and survival group (3 patients). The patient-specific three-dimensional airways were reconstructed from the central airways down to the 4th-5th bifurcation of the tracheobronchial tree. The volume changes of bronchi were calculated during the disease progression according to the comparison of two CT scans. Additionally, the changes of air flow resistance were analyzed using numerical simulation of CFD. RESULTS: Pearson correlation analysis demonstrated that there was negative correlation between the change of volume (ΔV) and the change of resistance (ΔR) for all COVID-19 patients (r=-0.7025). For total airway volume, an average decrease of -11.41±15.71% was observed in death group compared to an average increase of 1.86±10.80% in survival group (p=0.0232). For air flow through airways in lower lobe, the resistance increases for death group by 10.97±77.66% and decreases for survival group by -45.49±42.04% (p=0.0246). CONCLUSION: The variation of flow resistance in the airway could be used as a non-invasive functional evaluation for the prognosis and outcome of critically ill patients with COVID-19. The 'virtual' pulmonary function test by integrating follow-up CT scans with patient-derived CFD analysis could be a potentially powerful way in improving the efficiency of treatment for critically ill patients with COVID-19.

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