Physiology international最新文献

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.

Purpose: Chlorogenic acid (CA) is a polyphenolic compound, found in many herbs and foods including coffee, berries and potatoes. Anti-inflammatory, anti-oxidant, anti-cancer and anti-apoptotic effects of CA have been proven in many tissues. Testicular inflammation and apoptosis are essential factors in male infertility that could result from endoplasmic reticulum (ER) stress. ER stress leads to unfolding and misfolding of nascent proteins and thereby provokes cellular inflammatory and apoptotic pathways. This study was designed to assess the effects of CA on ER stress-induced testis inflammation and apoptosis.

Methods: To do this, male mice were divided into six groups. The control, vehicle and CA groups received saline, DMSO and 50 mg kg-1 CA. Tunicamycin (TM (was injected to induce ER stress (TM group). In the CA20-TM and CA50-TM groups, 20 mg kg-1 CA and 50 mg kg-1 CA were administered one hour before TM injection. After thirty hours, animals were sacrificed and testes were removed. Hematoxylin & eosin staining, ELISA assay and real-time PCR were performed.

Results: CA administration significantly downregulated gene expression of TNFα, IL6, P53, Bax/Bcl2 ratio and caspase3. It also reduced testis levels of ALP, NF-κB, TNFα and caspse3. Finally, CA relieved structural changes in seminiferous tubules.

Conclusions: This study demonstrated that the positive effects of CA on the attenuation of ER-stress induced inflammation and apoptosis might be due to the inhibition of NF-κB and thereby suppression of inflammatory and apoptotic pathways.

Background: Contrast enhanced ultrasound (CEUS) is increasingly used in the evaluation of renal lesions, however, its availability remains limited. Thus, sensitive noncontrast ultrasound evaluation of renal lesion vascularity is an unmet need.

Methods: In this single-center, retrospective study we assessed microvascular flow imaging (MV-flow) compared to CEUS in the evaluation of complex renal cysts and solid lesions. Out of 92 patients 28 were evaluated with both CEUS and MV-flow. Color Doppler, CEUS, and MV-flow was performed in 13 cases, whilst MV-flow, CEUS, and contrast-enhanced MV-flow (CE-MV-flow) was done in 16 cases. The CEUS diagnosis was considered gold standard.

Results: MV-flow showed a substantial agreement with the CEUS diagnosis (weighted Kappa = 0.806), excluding equivocal lesions (Bosniak 2F). MV-flow substantially outperformed color Doppler (weighted Kappa = 0.77 vs. 0.133). The agreement of CE-MV-flow and MV-flow was comparable (weighted Kappa = 0.79 vs. 0.69).

Conclusion: MV-flow significantly improves evaluation of renal lesion vascularity compared to conventional techniques. However, the sensitivity is limited for equivocal lesions (e.g. Bosniak 2F cysts). Thus, MV-flow should be used as an ancillary technique, not as a substitute to CEUS. Current MV-flow presets are ill-suited for postcontrast imaging, therefore specific presets optimized for this purpose are needed to establish its potential.

We aimed to examine the effects of brain ischemia-reperfusion (IR) especially on serum parameters or liver enzymes, free radicals, cytokines, oxidatively damaged DNA, spermidine/spermine N-1-acetyltransferase (SSAT). The effects of addition of putrescine on IR will be evaluated in terms of inflammation and oxidant-antioxidant balance in liver.The study was conducted on 46 male Albino Wistar rats weighing 200-250 g. The rats were grouped into: 1-Sham group (n = 6). 2-IR group (n = 8): The carotid arteries were ligated for 30-min and reperfusion was achieved for 30-min under general anesthesia. 3-Ischemia + putrescine + reperfusion group (IPR) (n = 8): Unlike the IR group, a single dose of 250 μmol kg-1 putrescine was given by gavage at the beginning of reperfusion. In putrescine treatment groups in addition to the procedures performed in the IR group a total of 4 doses of 250 μmol kg-1 putrescine were given at 12-h intervals, with the first dose immediately after 30-min reperfusion (4-IR+putrescine group (IR+P1) (n = 8)); 3 h after the 30-min reperfusion (5-IR+putrescine group (IR+P2) (n = 8)); 6 h after the 30-min reperfusion (6-IR+putrescine group (IR+P3) (n = 8)). ALT, AST, ATP, NO, SSAT, 8-OHdG levels were analyzed in the serum, and liver samples. NF-κB and IL-6 levels were analyzed in the liver samples.Brain IR causes inflammatory, oxidative and DNA damage in the liver, and putrescine supplementation through gavage reduces liver damage by showing anti-inflammatory and antioxidant effects.

Hypothermic conditions enhance the incidence of cardiovascular diseases due to increased blood pressure. Cold-induced adaptive thermogenesis increased mitochondrial biogenesis and function in skeletal muscles and adipocytes. Here, we studied the effect of intermittent cold exposure on the regulators of cardiac mitochondrial biogenesis, function, and its regulation by SIRT-3. Intermittent cold exposed mice hearts showed normal histopathology with increased mitochondrial antioxidant and metabolic function, as evidenced by an increase in the activity and expression of MnSOD and SDH. A substantial increase in mitochondrial DNA copy number and increase in the expression of PGC-1α and its downstream targets NRF-1 and Tfam indicated the possibility of enhanced cardiac mitochondrial biogenesis and function on intermittent cold exposure. Increased mitochondrial SIRT-3 level and decreased total protein lysine acetylation indicate increased sirtuin activity in cold exposed mice hearts. Ex vivo cold mimic using norepinephrine showed a significant increase in PGC-1α, NRF-1, and Tfam levels. AGK-7, a SIRT-3 inhibitor, reversed the norepinephrine-induced upregulation of PGC-1α and NRF-1, indicating the role of SIRT-3 on the production of PGC-1α and NRF-1. Inhibition of PKA with KT5720 in norepinephrine treated cardiac tissue slices indicates the role of PKA in regulating the production of PGC-1α and NRF-1. In conclusion, intermittent cold exposure upregulated the regulators of mitochondrial biogenesis and function through PKA and SIRT-3 mediated pathway. Our results emphasize the role of intermittent cold-induced adaptive thermogenesis in overcoming chronic cold-induced cardiac damage.