Impact of carbonic anhydrase 9 gene polymorphism on the progression of colorectal cancer.

Colorectal cancer (CRC) is a commonly occurring tumor type worldwide, and its development is governed by a connection between genetic variations and acquired factors. Carbonic anhydrase 9 (CA9) is a cell-surface pH modulator that has been demonstrated to contribute to key steps of cancer progression. Here, we attempted to interrogate the effect of CA9 gene polymorphisms on the development of CRC in 470 cases and 470 gender- and age-matched non-cancer controls. We found that none of three CA9 single-nucleotide polymorphisms (SNPs) tested, including rs2071676, rs3829078, and rs1048638, was significantly associated with the occurrence of CRC. Yet, while evaluating the clinicopathological variables, cases carrying at least one reference allele (G allele) of rs2071676 tended to develop poorly differentiated tumors less frequently than those who are homozygous for the alternative allele (A allele) of rs2071676 (GA+GG vs AA; OR, 0.483; 95% CI, 0.242-0.963; p=0.036). Further stratification revealed that as compared to homozygous carriers of the alternative allele (AA), cases of colon cancer bearing at least one reference allele of rs2071676 (GA+GG) less frequently developed poorly differentiated tumors (OR, 0.449; 95% CI, 0.221-0.911; p=0.024) and lymphovascular invasion (OR, 0.570; 95% CI, 0.361-0.900; p=0.015). Such genetic effect was exclusively observed in colon cancer but not in rectal cancer. Our results indicate an anatomical site-specific impact of CA9 gene polymorphisms on modulating the progression of colorectal malignancies.

Effect of tissue inhibitor of metalloproteinases-3 genetics polymorphism on clinicopathological characteristics of uterine cervical cancer patients in Taiwan.

Single nucleotide polymorphisms (SNPs) of tissue inhibitor of metalloproteinases-3 (TIMP-3) have been revealed to be related to various cancers. To date, no study explores the relationships between TIMP-3 polymorphisms and uterine cervical cancer. The purposes of this research were to investigate the associations among genetic variants of TIMP-3 and development and clinicopathological factors of uterine cervical cancer, and patient 5 years survival in Taiwanese women. The study included 123 patients with invasive cancer and 97 with precancerous lesions of uterine cervix, and 300 control women. TIMP-3 polymorphisms rs9619311, rs9862 and rs11547635 were checked and their genotypic distributions were determined by real-time polymerase chain reaction. It showed that women with genotypes CT/TT in rs9862 were found to display a higher risk of developing cervical cancer with moderate and poor cell differentiation. Moreover, it revealed that cervical cancer patients carrying genotypes CC in rs9619311 exhibited a poorer 5 years survival, as compared to those with TT/TC in Taiwanese women, using univariate analysis. In addition, pelvic lymph node metastasis was determined to independently predict 5 years survival in cervical cancer patients using multivariate analysis. Conclusively, TIMP-3 SNPs polymorphisms rs9619311 are related to cervical patient survival in Taiwanese women.

Association of dipeptidyl peptidase IV polymorphism with clinicopathological characters of oral cancer.

OBJECTIVE: To evaluate the associations between dipeptidyl peptidase IV (DPP4) single-nucleotide polymorphism (SNP) and clinicopathological characteristics of oral cancer. METHODS: Four loci of DPP4 SNPs (rs7608798 A/G, rs3788979 C/T, rs2268889 T/C, and rs6741949 G/C) were genotyped by using the TaqMan allelic discrimination in 1238 oral cancers patients and 1197 non-cancer individuals. RESULTS: The percentage of DPP4 SNP rs2268889 TC + CC was significantly higher in the oral cancer participants compared to the control group (odds ratio [OR]: 1.178, 95% confidence interval (CI): 1.004-1.382, p = 0.045). Among 1676 smokers, DPP4 polymorphisms carriers with betel quid chewing were found to have an 8.785- to 10.903-fold risk to have oral cancer compared to DPP4 wild-type carriers without betel quid chewing. Similar trend was found in individuals with alcohol consumption. Moreover, the oral cancer individuals without cigarette smoking history with at least one varied C allele of DPP4 rs2268889 had a significantly higher percentage of large tumor size with the wild-type TT homozygote (p = 0.011). CONCLUSIONS: The DPP4 SNP may correlate to the development of oral cancer in those with cigarette smoking and alcohol consumption. Besides, the DPP4 SNP rs2268889 could relate to worse clinical course of oral cancer in non-smokers.

Targeting of Mcl-1 Expression by MiRNA-3614-5p Promotes Cell Apoptosis of Human Prostate Cancer Cells.

MicroRNA (miRNA) acts as a critical regulator of growth in various human malignancies. However, the role of miRNA-3614 in the progression of human prostate cancer remains unknown. In this study, our results demonstrated that miRNA-3614-5p exerts a significant inhibitory effect on cell viability and colony formation and induces sub-G1 cell cycle arrest and apoptosis in human prostate cancer cells. Myeloid cell leukemia-1 (Mcl-1) acts as a master regulator of cell survival. Using the miRNA databases, miRNA-3614-5p was found to regulate Mcl-1 expression by targeting positions of the Mcl-1-3' UTR. The reduction of Mcl-1 expression by miRNA-3614-5p was further confirmed using an immunoblotting assay. Pro-apoptotic caspase-3 and poly (ADP-ribose) polymerase (PARP) were significantly activated by miRNA-3614-5p to generate cleaved caspase-3 (active caspase-3) and cleaved PARP (active PARP), accompanied by the inhibited Mcl-1 expression. These findings were the first to demonstrate the anti-growth effects of miRNA-3614-5p through downregulating Mcl-1 expression in human prostate cancer cells.

A pilot crossover trial assessing the exercise performance patients chronic obstructive pulmonary disease.

Noninvasive ventilation improves exercise performance in patients with chronic obstructive pulmonary disease (COPD). However, the effect of helmet ventilation (HV) on the short-term self-paced exercise performance of patients with COPD remains unclear. This study investigated the use of HV during a 6 min walk test (6MWT) and analyzed its short-term cardiopulmonary outcomes in patients with stable COPD. A single-site crossover trial was conducted in a pulmonary rehabilitation outpatient department. A total of 20 stable patients with COPD without disability were enrolled. The participants performed 6MWTs with and without HV on two consecutive days. The outcome measures were the distance walked in the 6MWT and the physiological and cardiopulmonary parameters. The mean difference in meters walked between the HV-aided and unaided walk tests was 15.4 ± 37.2 (95% confidence interval: - 2.03 to 32.8 m; p = .145). During the 6MWT, the peak heart rate was significantly higher when walking was aided by HV than when it was unaided (p < .001). The energy expenditure index, walking speed, oxygen saturation nadir, and hemodynamic parameters were comparable. Although carbon dioxide levels inside the helmet increased after the walk test, the participants' transcutaneous carbon dioxide measurements remained unchanged. HV did not improve the short-term self-paced exercise performance in patients with stable mild-to-moderate COPD. Further research should focus on noninvasive ventilation delivered via helmets in exercise training to determine the setting strategy, breathing circuit configuration, and effects of regular exercise.ClinicalTrial.gov: NCT04156724; IRB number: C108032.

Effects of high-flow nasal cannula with oxygen on self-paced exercise performance in COPD: A randomized cross-over trial.

INTRODUCTION: Studies have demonstrated that noninvasive ventilation improves exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). The role of heated humidified high-flow nasal cannula (HFNC) therapy in patients with COPD on self-paced exercise performance remains unclear. Therefore, the purpose of the present study was to determine whether HFNC-aided supplemental oxygen during a 6-minute walk test (6MWT) would change self-paced exercise performance and cardiopulmonary outcomes in patients with stable COPD. METHODS: A single-site, cross-over trial was conducted in a pulmonary rehabilitation outpatient department. This study enrolled 30 stable COPD patients without disability. The participants with and without HFNC performed 6MWTs on 2 consecutive days. Outcomes were the distance walked in the 6MWT, physiological, and cardiopulmonary parameters. RESULTS: Those performing HFNC-aided walking exhibited a longer walking distance than those performing unaided walking. The mean difference in meters walked between the HFNC-aided and unaided walking scenarios was 27.3 ±â€Š35.6 m (95% CI: 14.4-40.5 m). The energy expenditure index was significantly lower when walking was aided by HHHNFC rather than unaided (median: 1.21 beats/m walked vs median: 1.37 beats/m walked, P < .001). However, there were no differences in transcutaneous carbon dioxide tension between HHHNFC and non-HHHNFC patients. CONCLUSION: Walking distance and arterial oxygen saturation improved in stable COPD patients receiving HFNC with additional oxygen support. However, HFNC did not affect transcutaneous carbon dioxide tension and the self-reported dyspnea score during the walking test. The present study demonstrated the feasibility and safety of using HFNC in self-paced exercise. TRIAL REGISTRATION: NCT03863821.

A pilot study of short-term hemodynamic effects of negative pressure ventilation in chronic obstructive pulmonary disease assessed using electrical cardiometry.

BACKGROUND: Pulmonary rehabilitation combined with negative pressure ventilation (NPV) demonstrated benefits in patients with chronic obstructive pulmonary disease (COPD). The effect of NPV remains unknown. This study aims to clarify the short-term response of the hemodynamic outcome of NPV in patients with COPD undergoing pulmonary rehabilitation program by electrical cardiometry. METHODS: This is an observational retrospective study of COPD patients who had been treated in a pulmonary rehabilitation unit with NPV between January 2018 and December 2019 that were enrolled to analyze the hemodynamic outcomes. RESULTS: Thirty patients with COPD that were undergoing a pulmonary rehabilitation program and were regularly receiving NPV were enrolled. Cardiac output (p < .001) and heart rate (p < .001) showed a significant decrease after NPV. Stroke volume did not demonstrate significant change (p = .15). There was a significant decrease in thoracic fluid content (p = .016) and a significant increase in stroke volume variation (p = .038) systemic vascular resistance (p < .001) and left ventricular ejection time (p < .001). Other hemodynamic parameters were all comparable before and after NPV. CONCLUSIONS: Negative pressure ventilation demonstrated an impact on hemodynamics in patients with chronic obstructive pulmonary disease undergoing pulmonary rehabilitation. Electrical cardiometry is a feasible method of determining the hemodynamic effects of negative pressure ventilation. Thoracic fluid content significantly decreased immediately after the NPV.

Using LIBS as a diagnostic tool in pediatrics beta-thalassemia.

Beta-thalassemia major is a common inherited single-gene disorder. Thalassemic patients are at risk of changes in some important trace elements. To detect alteration of iron, copper, zinc, and calcium serum levels in beta-thalassemia major patients, laser-induced breakdown spectroscopy (LIBS) was used. This study was conducted on 40 beta-thalassemia major and 40 healthy young patients (age: 12-18 years old; male:female = 1:1). Venous blood samples were collected from both groups and analyzed for the serum levels of iron, calcium, zinc, and copper by exposing the samples to LIBS. The intensities of the tested elements were detected using the Kestrel Spec computer software and analyzed with an SPSS 25 program. Thalassemic patients had significantly higher serum iron (p = < 0.001) and copper (p = < 0.005) while they had significantly lower serum zinc (p = < 0.005) and calcium (p= > 0.005) when compared with control. Also, thalassemic patients had significantly lower body weight and height as they were less than the 3rd percentile by 82.5% and p < 0.001. LIBS is a safe and efficient tool to detect alteration of some serum trace elements in beta-thalassemia patients.

The Impact of Aerobic Exercise and Badminton on HDL Cholesterol Levels in Taiwanese Adults.

Elevated levels of high-density lipoprotein cholesterol (HDL-C) have been associated with a decreased risk of coronary heart disease (CHD). An active lifestyle is necessary to improve HDL-C, including (but not limited to) physical exercise. Research on the association between badminton, an intermittent exercise, and HDL-C is limited. We investigated the impact of aerobic exercise and badminton on HDL-C levels in Taiwanese adults. The sociodemographic data of 7543 participants, comprising 3472 men and 4071 women aged between 30 and 70 years, were retrieved from the Taiwan Biobank. The participants were grouped into three exercise categories-no exercise, aerobic exercise, and badminton exercise. The HDL-C levels were compared using an analysis of variance (ANOVA). Multivariate linear regression models were used to determine the associations between HDL and exercise. Comparing the other two groups to the no-exercise group, the individuals who were engaged in aerobic and badminton exercise were significantly associated with higher HDL-C levels (ß = 1.4077; p < 0.0001 and ß = 5.6052; p = 0.0079, respectively). Aerobic exercise and badminton were also associated with higher HDL-C levels among carriers of the lipoprotein lipase (LPL) rs328 genotypes. Aerobic exercise and regular badminton were associated with higher levels of HDL-C, with the badminton group being more significant.

Association between Aerobic Exercise and High-Density Lipoprotein Cholesterol Levels across Various Ranges of Body Mass Index and Waist-Hip Ratio and the Modulating Role of the Hepatic Lipase rs1800588 Variant.

Changes in concentrations of high-density lipoprotein cholesterol (HDL-C) are modified by several factors. We examined the relationship between aerobic exercise and HDL-C among different categories of body mass index (BMI) and waist-hip ratio (WHR) and the impact of rs1800588 variant in the hepatic lipase (LIPC) gene. We analyzed data from 6184 men and 8353 women aged 30-70 years. Participants were grouped into two WHR categories: Normal (0 < WHR < 0.9 for men and 0 < WHR < 0.8 for women) and abnormal (WHR ≥ 0.9 for men and WHR ≥ 0.8 for women). The BMI categories were: Underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24 kg/m2), overweight (24 ≤ BMI < 27 kg/m2), and obese (BMI ≥ 27 kg/m2). Multivariate linear regression models were used to investigate associations between HDL-C and exercise. Aerobic exercise was significantly associated with higher HDL-C (ß = 1.18325; p < 0.0001) when compared with no exercise. HDL-C was significantly lower in persons with abnormal compared to those with normal WHR (ß = -3.06689; p < 0.0001). Compared with normal weight, overweight and obese categories were associated with lower HDL-C, with ß values of -4.31095 and -6.44230, respectively (p < 0.0001). Unlike rs1800588 CT and TT genotypes, associations between aerobic exercise and HDL were not significant among CC carriers no matter their BMI or WHR.

The Impact of Aerobic Exercise and Badminton on HDL Cholesterol Levels in Adult Taiwanese.

Elevated levels of high-density lipoprotein cholesterol (HDL-C) have been associated with a decreased risk of coronary heart disease (CHD). An active lifestyle is necessary in order to improve lipid HDL-C, including (but not limited to) physical exercise. Research on the association between badminton, an intermittent exercise, and HDL-C is limited. We investigated the impact of aerobic exercise and badminton on HDL-C levels in Taiwanese adults. The sociodemographic data of 7797 participants comprising 3559 men and 4238 women aged between 30 to 70 years were retrieved from the Taiwan Biobank. The participants were grouped into three exercise categories-no exercise, aerobic exercise, and badminton exercise. The HDL-C levels were compared using an analysis of variance (ANOVA). The multivariate linear regression models were used to determine the associations between HDL and exercise. Comparing the other two groups to the no-exercise group, the individuals who were engaged in aerobic and badminton exercise were significantly associated with a higher HDL-C (ß =1.3154; p <0.0001 and ß = 6.5954; p = 0.0027, respectively). Aerobic exercise and badminton were also associated with higher HDL-C levels among carriers of the lipoprotein lipase (LPL) rs328 genotypes. Aerobic exercise and regular badminton were associated with higher levels of HDL-C, with the badminton group being more significant.

Metabolic Syndrome and Cardiovascular Risk Factors in Obese Adolescent.

BACKGROUND: Childhood and adolescent obesity is associated with insulin resistance, abnormal glucose metabolism, hypertension, dyslipidemia, inflammation, liver disease, and compromised vascular function. The purpose of this study was to determine the prevalence of cardiovascular risk factor abnormalities and metabolic syndrome in a sample of obese adolescent as prevalence data might be helpful in improving engagement with obesity treatment in future. The high blood lipid levels and obesity are the main risk factors for cardio vascular diseases. Atherosclerotic process begins in childhood. AIM: This study aimed to investigate the relationship between obesity in adolescent and their blood lipids levels and blood glucose level. METHODS: This study was conducted with 100 adolescents of both gender age 12-17 years and body mass index (BMI) greater than 95th percentiles and 100 normal adolescents as control group. The blood samples were collected from all adolescents after overnight fasting (10 hours) to analyze blood lipids (Total cholesterol, high density lipoprotein, low density lipoprotein) and hematological profile (Hemoglobin, platelets and red blood cell, C reactive protein and fasting blood glucose. RESULTS: There were statistical difference between the two groups for red blood cells (P<0.001), Hemoglobin (P < 0.001) and platelets (P = 0.002), CRP (P = 0.02). Positive correlation was found between the two groups as regards total cholesterol (P = 0.0001), P value was positive for HDL (P = 0.005 and Atherogenic index P value was positive (P = 0.002). Positive correlation was found between the two group as regards fasting blood glucose (P = 0.001). CONCLUSION: Saturated fat was associated with elevated lipid levels in obese children. These results reinforce the importance of healthy dietary habits since child-hood in order to reduce the risks of cardiovascular diseases in adulthood.

Inflammatory cytokines, apoptotic, tissue injury and remodeling biomarkers in children with congenital heart disease.

The present study aims to evaluate specific biomarkers involved in congenital heart disease (CHD), and whether there is a significant differences between the levels of these biomarkers in the cyanotic CHD (CCHD) and acyanotic CHD (ACHD). We prospectively measured tumor necrosis factor (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), vasoendothelial growth factor (VEGF), troponin T, creatin kinase MB (CKMB), and Caspase 3 levels in 120 consecutive children with CHD (60 cyanotic and 60 a cyanotic with age 1:4 years), and 30 healthy control children. Significant elevated levels of inflammatory markers; TNF-α, IL-6 and CRP was detected in CHD, with percentage increase in cyanotic than a cyanotic subjects as compared to the normal one. Apoptotic biomarker; caspase 3 showed also significant increases in CCHD than ACHD. In addition, tissue injury mechanisms included troponin T and CKMB, exhibited significant increase in cyanotic than a cyanotic CHD. The present results demonstrate also, significant enhancement in remodeling process (VEGF), in cyanotic than a cyanotic patients. Thus, it could be concluded that, the children with CCHD were shown to have elevated levels of inflammatory cytokines, caspase 3, troponin T, and CKMB as these biomarkers may implicated in cardiac functional status.

Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV) paediatric patients (8-14 years) were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-β1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), hyaluronic acid (HA), procollagen type III amino-terminal peptide (PIIINP) and osteopontin (OPN), were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05). The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.

Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children.

The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV) paediatric patients (8-14 years) were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-ß1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), hyaluronic acid (HA), procollagen type III amino-terminal peptide (PIIINP) and osteopontin (OPN), were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05). The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.