Animal and in vitro experiments
Abstract: Objective: To assess the expression of ARHGEF19 in human breast cancer, investigate its role in breast cancer, and clarify the mechanism. Methods: Bioinformatics analysis, immunoblot, quantitative PCR, and immunohistochemical (IHC) assays were performed to assess ARHGEF19 expression in breast cancer. CCK-8 and Edu assays were conducted to reveal its role in breast cancer cell proliferation. Flow cytometry (FCM) assays and immunoblot were performed to confirm its effects on breast cancer apoptosis. Immunoblot was also performed to clarify the mechanism. Finally, tumor growth assays were aimed to confirm the role of ARHGEF19 in mice. Results: We observed that ARHGEF19 was highly expressed in human breast cancer. ARHGEF19 promoted breast cancer cell growth in vitro, and suppressed apoptosis. In addition, we found that ARHGEF19 could activate the MAPK pathway in breast cancer cells. Our findings further confirmed that ARHGEF19 contributed to breast cancer growth in mice. Conclusion: We observed that ARHGEF19 promoted the growth of breast cancer in vitro and in vivo via MAPK pathway, and presume it could serve as a breast cancer therapeutic target.
Keywords: ARHGEF19, proliferation, apoptosis, MAPK pathway, therapeutic target
Abstract: Background and aims: The prevalence of non-alcoholic fatty liver disease has been alarmingly increased with no lines of effective treatment. Vanillic acid is a naturally occurring polyphenol with promising therapeutic effects. Exercise is well known to be an effective tool against obesity and its consequences. Thus, we aim to study the effect of vanillic acid alone and along with exercise on fatty liver induced by a high-fat diet in a rat model and to investigate possible novel mechanisms involved in their action. Methods: In this study, 40 male rats were divided equally into five groups: control (standard chow diet), HFD (high-fat diet), HFD+VA (HFD+ vanillic acid (50 mg/kg/day orally), HFD+EX (HFD+ swimming exercise 5 days/ week), HFD+VA+EX (HFD+ vanillic acid+ swimming exercise) for eight weeks. Results: Body mass, liver weight, liver enzymes, cholesterol, and triglycerides were significantly decreased in the combined VA+EX group, with marked improvement in hyperglycemia, hyperinsulinemia, and consequently HOMA-IR index compared to the HFD group. These improvements were also reflected in the pathological view. VA and swimming, either solely or in combination, markedly increased hepatic and circulating fibroblast growth factor 21. Additionally, VA and swimming increased the immunohistochemical expression of the autophagosomal marker LC3 and decreased the expression of P62, which is selectively degraded during autophagy. Conclusions: These results suggest the hepatoprotective effect of VA and swimming exercise against fatty liver and the involvement of FGF21 and autophagy in their effect.
Keywords: HFD, vanillic acid, swimming exercise, FGF21, autophagy
Abstract: Background: Near-infrared spectroscopy (NIRS) technology can evaluate muscle metabolism and oxygenation. NIRS-based oximeters can measure skeletal muscle oxygen delivery and utilization during static and dynamic work non-invasively. Our goal was to assess the value and usability of NIRS technology in chronic obstructive pulmonary disease (COPD) rehabilitation program. Methods: Forty patients with COPD participated in a 4-week inpatient rehabilitation program that included breathing exercises and personalized cycle/treadmill training adjusted to the functional capacity, physical activity and comorbidities of the patients. A NIRS muscle oxygen monitor was used to measure tissue oxygenation and hemoglobin levels. Total hemoglobin index, average muscle oxygenation, minimal and maximal muscle oxygenation were recorded before and after the rehabilitation program. Results: Rehabilitation resulted improvement in 6 min walking distance (6MWD:335.3 ± 110. vs. 398.3 ± 126.2 m; P < 0.01), maximal inspiratory pressure (MIP: 57.7 ± 22.7 vs. 63.6 ± 18.0 cmH2O; P < 0.01), chest wall expansion (CWE: 2.84 ± 1.26 vs, 4.00 ± 1.76 cm; P < 0.01), breath hold time (BHT: 25.8 ± 10.6 vs. 29.2 ± 11.6 s; P < 0.01) and grip strength (GS: 24.9 ± 11.9 vs. 27.0 ± 11.4 kg; P < 0.01). Quality of life improvement was monitored by COPD Assessment Test (CAT: 17.00 ± 8.49 vs. 11.89 ± 7.3, P < 0.05). Total hemoglobin index (tHb: 12.8 ± 1.3% vs. 12.8 ± 1.4), average muscle oxygenation (SmO2: 67.5 ± 14.4% vs. 65.2 ± 20.4%) showed a tendency for improvement. Maximal muscle oxygenation decreased (SmO2 max: 98.0 ± 20.5% vs. 90.1 ± 14.3%; P < 0.01). Minimal muscle oxygenation increased (SmO2 min: 42.6 ± 12.6% vs. 54.8 ± 14.3%; P < 0.01). Conclusions: NIRS results showed that muscle oxygenation and microcirculation can be described as a high-risk factor in COPD patients. The 4-week rehabilitation improves functional parameters, quality of life and tissue oxygenation levels in COPD patients.
Abstract: Purpose: The aim of the present cross-sectional study was to investigate the relationship between depression and intermittent claudication (IC), independently of traditional risk factors. Main methods: The sample consisted of 300 individuals (Mage 5 65.3 ± 8.7 years, 61.0% female) recruited from the offices of 33 general practitioners. Participants’ medical history and the presence of major cardiovascular risk factors were recorded. Participants completed the Edinburgh Claudication Questionnaire. The role of depression (assessed by a shortened version of the Beck Depression Inventory) in predicting IC was examined using a binary logistic regression analysis - controlled for sex, age, hypertonia, diabetes, smoking, hypercholesterinemia, hazardous drinking, and body mass index (BMI). Results: The descriptive data indicated that the prevalence of depression was 57.9% in the IC subgroup and 16.1% in those free of IC. The bivariate analyses indicated that hypercholesterinemia, smoking, hazardous drinking, BMI, and depression were significantly associated with IC. Male sex and age showed a trend toward being a significant correlate of IC. Results of the multivariate analyses indicated that depressive symptomatology was significant in predicting IC (OR: 1.08 (1.05-1.11)), even after controlling for lifestyle and traditional risk factors such as smoking, hazardous drinking, and BMI. Among traditional risk factors, smoking (OR: 2.44 (1.26-4.74)), hazardous drinking (OR: 1.19 (1.02-1.40)), and hypercholesterinemia (OR: 2.17 (1.26-3.75)) showed a significant, positive relationship with IC. Conclusions: These results underscore the importance of a multidisciplinary approach that focuses on supporting health-related behavioral changes and managing mental health symptoms when providing care for patients with IC.
Keywords: intermittent claudication, lower extremity arterial disease, peripheral arterial disease, depression, vascular disease