Physiology international最新文献

The classical myeloproliferative neoplasms are divided into chronic myeloid leukemia, and the Philadelphia negative polycythemia vera, essential thrombocythemia and primary myelofibrosis. These are heterogenous diseases, originating from the clonal proliferation of myeloid stem cells, resulting in increased mature cell numbers in one or more myeloid lineages. The most commonly seen mutations in the Philadelphia negative myeloproliferative neoplasms include those in Janus kinase, myeloproliferative leukemia protein and the calreticulin genes. Philadelphia negative myeloproliferative neoplasms occur infrequently, with a combined annual incidence of 2.58 per 100,000. There are many overlapping symptoms of Philadelphia negative MPNs, such as fatigue, night sweats, hepatosplenomegaly and circulatory symptoms due to increased cell numbers. Total Symptom Score of the MPN Symptom Assessment Form is used to assess symptom burden on patients. The most worrisome complications are thrombo-hemorrhagic events, and risk stratification is especially important as treatment of disease is based on their category. Phlebotomy and aspirin are the mainstay of treatment in low-risk polycythemia vera and essential thrombocythemia patients, whereas high-risk disease calls for additional cytoreduction, usually with hydroxyurea.

Background and aims: ADAMTS-4 is a protease enzyme involved in vascular remodeling and atherosclerosis. It was found to be upregulated in macrophages seen in atherosclerotic lesions. This study aimed to investigate the expression and regulation of ADAMTS-4 in oxidized LDL-induced human monocytes/macrophages system.

Methods: Peripheral blood mononuclear cells (PBMCs) isolated from human blood, and treated with oxidized LDL (50 μg mL-1) were used as the model system for the study. mRNA and protein expressions were studied by PCR, ELISA, and western blot analysis. ROS production and cell viability were determined by DCFDA staining and MTT assay, respectively.

Results: In the presence of oxidized LDL, monocytes get differentiated into macrophages, which were confirmed by the increased expression of macrophage differentiation markers and pro-inflammatory cytokine TNF-α. Oxidized LDL increased the mRNA and protein expression of ADAMTS-4 in monocytes/macrophages. N- Acetyl cysteine, ROS scavenger, downregulate the protein expression of ADAMTS-4. The expression of ADAMTS-4 was decreased significantly in the presence of NF-κB inhibitors. SIRT-1 activity was significantly downregulated in the macrophages and was reversed in the presence of the SIRT-1 agonist, resveratrol. Acetylation of NF-κB and hence the expression of ADAMTS-4 were significantly downregulated in the presence of SIRT-1 activator, resveratrol.

Conclusions: Our study suggests that oxidized LDL significantly upregulated the expression of ADAMTS-4 in the monocytes/macrophages through ROS- NF-κB- SIRT-1 pathway.

Functional conditions like lung function and exercise capacity are important limiting factors of chest surgery in lung cancer with co-morbidities (chronic obstructive pulmonary disease (COPD) and other chronic respiratory diseases). Pulmonary rehabilitation has a favourable effect on the cardiovascular system, metabolism, respiratory and peripheral muscles and lung mechanics. Our aim was to assess the role of pre-, post- and peri-operative pulmonary rehabilitation in lung cancer in this review. We sought to size up the importance of pulmonary rehabilitation in patients undergoing surgery with or without (neo)adjuvant treatment, radiotherapy, chemotherapy, chemoradiotherapy, major physiological impairments and complications. Searches were performed in PubMed and ClinicalTrials.gov databases using the terms "exercise", "rehabilitation", "small cell lung cancer", "non-small cell lung cancer", "exercise capacity", "chest surgery" and "quality of life" from inception to February 7th, 2022. Pulmonary rehabilitation has been recognized as an effective intervention to reduce lung cancer related symptoms and improve the pulmonary function, lung mechanics, chest kinematics, respiratory- and peripheral muscle function, physical activity and quality of life (QoL) of the patients. In conclusion, this review shows positive, highly encouraging and effective results of pulmonary rehabilitation in terms of the patients' lung function, functional mobility and quality of life. The tools for complex pulmonary rehabilitation have evolved considerably over the past two decades, thus this research has been conducted on a variety of studies about this subject and serves as a synthesis of the systematic and meta-analytic reviews.

Purpose: The frailty concept has become a fundamental part of daily clinical practice. In this study our purpose was to create a risk estimation method with a comprehensive aspect of patients' preoperative frailty.

Patients and methods: In our prospective, observational study, patients were enrolled between September 2014 and August 2017 in the Department of Cardiac Surgery and Department of Vascular Surgery at Semmelweis University, Budapest, Hungary. A comprehensive frailty score was built from four main domains: biological, functional-nutritional, cognitive-psychological and sociological. Each domain contained numerous indicators. In addition, the EUROSCORE for cardiac patients and the Vascular POSSUM for vascular patients were calculated and adjusted for mortality.

Results: Data from 228 participants were included for statistical analysis. A total of 161 patients underwent vascular surgery, and 67 underwent cardiac surgery. The preoperatively estimated mortality was not significantly different (median: 2.700, IQR (interquartile range): 2.000-4.900 vs. 3.000, IQR: 1.140-6.000, P = 0.266). The comprehensive frailty index was significantly different (0.400 (0.358-0.467) vs. 0.348 (0.303-0.460), P = 0.001). In deceased patients had elevated comprehensive frailty index (0.371 (0.316-0.445) vs. 0.423 (0.365-0.500), P < 0.001). In the multivariate Cox model an increased risk for mortality in quartiles 2, 3 and 4 compared with quartile 1 as a reference was found (AHR (95% CI): 1.974 (0.982-3.969), 2.306 (1.155-4.603), and 3.058 (1.556-6.010), respectively).

Conclusion: The comprehensive frailty index developed in this study could be an important predictor of long-term mortality after vascular or cardiac surgery. Accurate frailty estimation could make the traditional risk scoring systems more accurate and reliable.

Background: Basal cell carcinoma (BCC) is a prevalent cutaneous cancer with an increasing incidence. Nucleolar and spindle associated protein 1 (NUSAP1) is a cell proliferation-related protein that participates in the development of various cancers. However, its role and mechanism in BCC remain elusive.

Methods: The expression of NUSAP1 was detected by western blot. Gain- and loss-of-function assays were performed through the transfection of overexpression plasmid of NUSAP1 and si NUSAP1 into TE354.T cells. The role and mechanism of action of NUSAP1 in BCC were explored by cell counting kit-8 (CCK-8), colony formation, transwell, flow cytometry and western blot assays.

Results: NUSAP1 was highly expressed in TE354.T cells. Overexpression of NUSAP1 enhanced cell viability, colony forming numbers, numbers of migrated and invasive cells and the relative protein expression of RAD51, but reduced the apoptosis rate and the relative protein expression of γH2AX in TE354.T cells. Inverse results were obtained in these indicators after TE354.T cells were downregulated with NUSAP1. Moreover, the relative expression of proteins involved in the Hedgehog signaling pathway was increased by transfection of the overexpression plasmid of NUSAP1 into TE354.T cells, but decreased by the transfection of si NUSAP1 into TE354.T cells.

Conclusion: Both gain- and loss-of-function results revealed that NUSAP1 promoted proliferation, migration and invasion but attenuated apoptosis and DNA damage in BCC, which was involved in the activation of the Hedgehog signaling pathway.

Physical exercise represents one of the most effective approaches to anti-aging. The goal of this study was to verify the effects of different modes and intensities of exercise on longevity proteins in the skeletal muscle in midlife. Middle-aged mice were trained in aerobic or resistance exercise for 8 weeks, and the changes in sirtuin 1 (SIRT1), adenosine monophosphate-activated kinase (AMPK), and mammalian target of rapamycin (mTOR) pathways in the skeletal muscle were evaluated by western blotting. Long-term exercise had no effects on skeletal muscle SIRT1 abundance, whereas high-intensity aerobic exercise increased AMPK phosphorylation and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Low-intensity resistance exercise facilitated Akt/mTOR/p70 ribosomal protein kinase S6 (p70S6K) signaling but did not induce muscle hypertrophy. Conversely, high-intensity resistance exercise stimulated muscle hypertrophy without phosphorylation of mTOR signaling-related proteins. These results suggest the importance of setting exercise modes and intensities for anti-aging in midlife.

Electrical muscle stimulation (EMS) is a widely used method in sports and rehabilitation therapies to simulate physical exercise. EMS treatment via skeletal muscle activity improves the cardiovascular functions and the overall physical condition of the patients. However, the cardioprotective effect of EMS has not been proven so far, therefore, the aim of this study was to investigate the potential cardiac conditioning effect of EMS in an animal model. Low-frequency 35-min EMS was applied to the gastrocnemius muscle of male Wistar rats for three consecutive days. Their isolated hearts were then subjected to 30 min global ischemia and 120 min reperfusion. At the end of reperfusion cardiac specific creatine kinase (CK-MB) and lactate dehydrogenase (LDH) enzyme release and myocardial infarct size were determined. Additionally, skeletal muscle-driven myokine expression and release were also assessed. Phosphorylation of cardioprotective signaling pathway members AKT, ERK1/2, and STAT3 proteins were also measured. EMS significantly attenuated cardiac LDH and CK-MB enzyme activities in the coronary effluents at the end of the ex vivo reperfusion. EMS treatment considerably altered the myokine content of the stimulated gastrocnemius muscle without altering circulating myokine levels in the serum. Additionally, phosphorylation of cardiac AKT, ERK1/2, and STAT3 was not significantly different in the two groups. Despite the lack of significant infarct size reduction, the EMS treatment seems to influence the course of cellular damage due to ischemia/reperfusion and favorably modifies skeletal muscle myokine expressions. Our results suggest that EMS may have a protective effect on the myocardium, however, further optimization is required.

Background: The liver and kidney are organs affected by chemotherapy drugs such as cyclophosphamide (CP). This study examined the protective effects of treatment with saponin (SP) against CP-induced nephrotoxicity and hepatotoxicity.

Methods: 24 adult male mice were divided into four groups (N = 6): Control group, CP (15 mg kg-1), SP (2.5 mg kg-1) and CP + SP. After treatment, blood samples were collected for the determination of biochemical parameters. Liver and kidney samples were taken for histological analysis and assessment of oxidative stress and inflammatory markers.

Results: Cyclophosphamide decreased renal and liver functions and antioxidant enzymes, which significantly increased blood urea nitrogen and creatinine (BUN, Cr), liver enzyme levels, malondialdehyde, nuclear factor kappa β (NF-kB) and Interleukin 1 beta (IL-1B) concentrations. Moreover, histopathological findings of the CP group showed that there were acute tubular necrosis and glomerular atrophy in the renal tissues and lymphocyte infiltration in the liver samples. Treatment with saponin improved hepatic and renal functions, pathological changes and antioxidant capacity, and also decreased lipid peroxidation and inflammation.

Conclusion: It seems that saponin could exert a hepato-nephroprotective effect against cyclophosphamide toxicity.

Cellular senescence is a defense mechanism to arrest proliferation of damaged cells. The number of senescent cells increases with age in different tissues and contributes to the development of age-related diseases. Old mice treated with senolytics drugs, dasatinib and quercetin (D+Q), have reduced senescent cells burden. The aim of this study was to evaluate the effects of D+Q on testicular function and fertility of male mice. Mice (n = 9/group) received D (5 mg kg-1) and Q (50 mg kg-1) via gavage every moth for three consecutive days from 3 to 8 months of age. At 8 months mice were breed with young non-treated females and euthanized. The treatment of male mice with D+Q increased serum testosterone levels and sperm concentration and decreased abnormal sperm morphology. Sperm motility, seminiferous tubule morphometry, testicular gene expression and fertility were not affected by treatment. There was no effect of D+Q treatment in β-galactosidase activity and in lipofuscin staining in testes. D+Q treatment also did not affect body mass gain and testes mass. In conclusion, D+Q treatment increased serum testosterone levels and sperm concentration and decreased abnormal sperm morphology, however did not affect fertility. Further studies with older mice and different senolytics are necessary to elucidate the effects in the decline of sperm output (quality and quantity) associated with aging.

Purpose: According to current protocol, the separation of pancreatic head and body is performed at the level of superior mesenteric vein (SMV). Previous data indicate that the resection plane should be modified in portal annular pancreas. We presumed that the optimal line of pancreatic resections could also be different in other cases. Our aim is to simulate pancreatic resections in different planes and find the optimal resection line with the minimum number of cut vessels.

Main methods: 25 abdominal vascular corrosion casts were prepared, the aorta and the portal vein were cannulated. CT scans were taken on the casts, and specific planes were reconstructed simulating different resection lines. The total amount of cross sections of vessels were calculated in the different planes.

Results: In our series, the optimal plane is the SMV in 11/25, 2 cm left in 10/25, 1 cm left in 4/25, 1 cm right in 1/25 and 2 cm right in none of our cases. The group of left sided extension contain more than half of the cases. With left sided resections, the cut surface of the vessels may be lowered to even 29% compared to the SMV plane.

Conclusion: Our study revealed that pancreatic resections should be extended to the left side of the SMV in more than half of our cases. Therefore, the resection plane should be determined by preoperative imaging methods. Using DICOM viewer with multiplanar reconstruction, the resection planes can be simulated in clinical practice, which would reduce the risk of postoperative bleeding.