Father’s obesity programs the adipose tissue in the offspring via the local renin–angiotensin system and MAPKs pathways,especially in adult male mice

Purpose

Studies demonstrated the influence of mother’s obesity on offspring. However, the father is also related to programming the future generation. The study aimed to evaluate the effects of father’s obesity upon white adipose tissue (WAT) remodeling, resulting in activation of signaling pathways and inflammation in male and female offspring.

Methods

Male C57BL/6 mice received control diet (lean father group; 17% energy from lipids) or high-fat diet (obese father group; 49% energy from lipids) for 8 weeks before mating. The mothers received control diet throughout the experiment. Mice were mated: lean mother and lean father, and lean mother and obese father. Offspring received control diet from weaning until 3 months of age when they were studied.

Results

In the offspring, father’s obesity led to decreased QUICKI with impairment of the insulin signaling pathway in both sexes. In line with these findings, in white adipose tissue, male offspring demonstrated hypertrophied adipocytes, enhanced proinflammatory cytokines, overactivation of components of the local renin–angiotensin system (RAS) and extracellular signal-regulated kinase 1/2 (ERK1/2), and inhibition of peroxisome proliferator-activated receptors (alpha and gamma).

Conclusions

We observed that father’s obesity influences the offspring in adult life, with an impairment in insulin homeostasis, adipocyte remodeling, and adipose tissue overexpression of IL-6 and TNF-alpha in male offspring. The activation of local RAS and ERK1/2, a concomitant PPAR diminishing, and impairment in phosphorylation of AKT and IRS-1 could explain at least in part the findings regardless of the increase in body mass in the offspring.

     

alpha- and epsilon-protein kinase C activity during smooth muscle cell apoptosis in response to gamma-radiation

The use of gamma-radiation in treatment of pelvic cancer is associated with injury of healthy surrounding tissues and disorders of intestinal motility; however, the cellular mechanisms involved are unclear. We tested the hypothesis that exposure of visceral smooth muscle cells (SMCs) to gamma-radiation induces apoptosis via activation of specific protein kinase C (PKC) isoforms. Cultured SMCs and slices from guinea pig ileum smooth muscle longitudinal layer (GPISMLL) were exposed to 10 to 50 Gy. Flow cytometry in gamma-radiated SMCs showed increased percentage of cells in the sub-G(0)/G(1) phase, a hallmark of apoptosis. gamma-Radiation-induced reduction in cell survival was partially but significantly alleviated with the PKC inhibitors. Sections of gamma-irradiated GPISMLL showed DNA fragmentation and apoptotic bodies analyzed by the terminal deoxynucleotidyl transferase dUTP nick-end labeling method, whereas the plasma and nuclear membranes were preserved. Confocal microscopy in gamma-radiated SMCs labeled with annexin V-fluorescein showed an increase in apoptotic cells and phosphatidylserine externalization. Contraction of GPISMLL strips in response to KCl and acetylcholine was reduced in tissues exposed to 30 and 50 Gy. gamma-Radiation of GPISMLL caused an increase in PKC activity in the particulate fraction, a decrease in the cytosolic fraction, and increased particulate/cytosolic PKC activity ratio. Western blot analysis revealed significant amounts of alpha- and epsilon-PKC in the cytosolic fraction of control GPISMLL. gamma-Radiation caused an increase in the amount of alpha- and epsilon-PKC in the particulate fraction and a decrease in the cytosolic fraction. Data suggest that gamma-radiation induces apoptosis, growth arrest, and contractile dysfunction in visceral SMCs of GPISMLL via activation and translocation of alpha- and epsilon-PKC isoforms.     

Genotoxicity of corrosion eluates obtained from endosseous implants

PURPOSE: Commercially pure titanium alloys are currently used as metallic biomaterials in implantology. Corrosion phenomena appear to play a decisive role in metallic implant long-term behavior. Thus, the goal of this study was to examine the genotoxic potential of corrosion eluates obtained from dental implants using Chinese ovary hamster cells in vitro by the single-cell gel (comet) assay. This technique detects deoxyribonucleic acid strand breaks in individual cells in alkaline conditions. MATERIALS AND METHODS: The materials tested included 3 dental implants commercially available. Each of the tested materials was corroded in a solution consisting of equal amounts of acetic acid and sodium chloride (0.1 M) for 1, 3, 7, 14, and 21 days. The Chinese ovary hamster cultures were then exposed to all corrosion eluates obtained from endosseous dental implants for 30 minutes at 37 degrees C. RESULTS: None of the eluates was found to exhibit genotoxicity, regardless of the type of dental implant used. CONCLUSION: The results suggest that all dental implants tested in this study did not induce deoxyribonucleic acid breakage as depicted by the single-cell gel (comet) assay.     

Effect of Morinda citrifolia fruit extract and its iridoid glycosides on blood fluidity

The aim of this study was to investigate the effect of Morinda citrifolia fruit on blood fluidity. M. citrifolia fruit extract (MCF-ext) was investigated for its influence on blood aggregation and fibrinolysis. MCF-ext inhibited polybrene-induced erythrocyte aggregation and thrombin activity. The fibrinolytic activity of MCF-ext, in the euglobulin lysis time test and fibrin plate assay, is reported here for the first time. One of the active compounds was an iridoid glycoside, asperulosidic acid. The results indicated that MCF-ext is a potentially useful health food which is capable of improving blood flow and preventing lifestyle-related diseases.     

St. Louis encephalitis virus: first isolation from a human in São Paulo State, Brazil

This paper reports the isolation of St. Louis encephalitis virus (SLEV) from a febrile human case suspected to be dengue, in S?o Pedro, S?o Paulo State. A MAC-ELISA done on the patient's acute and convalescent sera was inconclusive and hemagglutination inhibition test detected IgG antibody for flaviviruses. An indirect immunofluorescent assay done on the C6/36 cell culture inoculated with the acute serum was positive for flaviviruses but negative when tested with dengue monoclonal antibodies. RNA extracted from the infected cell culture supernatant was amplified by RT-PCR in the presence of NS5 universal flavivirus primers and directly sequenced. Results of BLAST search indicated that this sequence shares 93% nucleotide similarity with the sequence of SLEV (strain-MSI.7), confirmed by RT-PCR performed with SLEV specific primers. Since SLEV was identified as the cause of human disease, it is necessary to improve surveillance in order to achieve early detection of this agent in the state of S?o Paulo and in Brazil. This finding is also an alert to health professionals about the need for more complete clinical and epidemiological investigations of febrile illnesses as in the reported case. SLEV infections can be unrecognized or confused with other ones caused by an arbovirus, such as dengue.     

Are the Effects of High-Intensity Exercise Training Different in Patients with COPD Versus COPD+Asthma Overlap?

Purpose

This study aimed to investigate whether patients with chronic obstructive pulmonary disease (COPD) presenting asthma overlap (ACO) benefit similarly in comparison to patients with only COPD after a 12-week high-intensity exercise training (ET) program.

Methods

Subjects with a diagnosis of COPD alone or ACO were evaluated and compared before and after a high-intensity ET program composed of walking and cycling plus strengthening exercises of the upper and lower limbs (3 days/week, 3 months, 36 sessions). Assessments included spirometry, bioelectrical impedance, 6-min walk test (6MWT), London Chest Activity of Daily Living Scale (LCADL), Hospital anxiety and depression Scale, modified Medical Research Council Scale (mMRC), Saint George Respiratory Questionnaire (SGRQ), and respiratory and peripheral muscle strength [manovacuometry and 1-repetition maximum test (quadriceps femoris, biceps and triceps brachialis), respectively]. ACO was defined according to Sin et al. (Eur Respir J 48(3):664-673, 2016).

Results

The sample was composed of 74 subjects (57% male, age 67 ± 8 years, BMI 26 (21–32) kg/m², FEV₁ 47 ± 17%predicted), and 12 (16%) of them were classified as presenting ACO. Both groups improved pulmonary function, 6MWT, peripheral and inspiratory muscle strength, LCADL, and SGRQ after ET (p < 0.005 for all). There were no significant interactions between ACO and COPD on ET effects (p > 0.05 for all). Likewise, there was no difference in the proportion of patients achieving the minimum clinical important difference for 6MWT and mMRC.

Conclusion

High-intensity exercise training generates similar benefits in patients with COPD regardless of whether presenting asthma overlap or not.