Integration of maternal genome into the neonate genome through breast milk mRNA transcripts and reverse transcriptase

Human milk samples contain microvesicles similar to the retroviruses. These microvesicles contain mRNA transcripts and possess reverse transcriptase activity. They contain about 14,000 transcripts representing the milk transcriptome. Microvesicles are also enriched with proteins related to “caveolar-mediated endocytosis signaling” pathway. It has recently been reported that microvesicles could be transferred to other cells by endocytosis and their RNA content can be translated and be functional in their new location. A significant percentage of the mammalian genome appears to be the product of reverse transcription, containing sequences whose characteristics point to RNA as a template precursor. These are mobile elements that move by way of transposition and are called retrotransposons. We thought that retrotransposons may stem from about 14,000 transcriptome of breast milk microvesicles, and reviewed the literature. The enhanced acceptance of maternal allografts in children who were breast-fed and tolerance to the maternal MHC antigens after breastfeeding may stem from RNAs of the breast milk microvesicles that can be taken up by the breastfed infant and receiving maternal genomic information. We conclude that milk microvesicles may transfer genetic signals from mother to neonate during breastfeeding. Moreover, transfer of wild type RNA from a healthy wet-nurse to the suckling neonate through the milk microvesicles and its subsequent reverse transcription and integration into the neonate genome could result in permanent correction of the clinical manifestations in genetic diseases

Ozone Therapy and Hyperbaric Oxygen Treatment in Lung Injury in Septic Rats

Various therapeutic protocols were used for the management of sepsis including hyperbaric oxygen (HBO) therapy. It has been shown that ozone therapy (OT) reduced inflammation in several entities and exhibits some similarity with HBO in regard to mechanisms of action. We designed a study to evaluate the efficacy of OT in an experimental rat model of sepsis to compare with HBO. Male Wistar rats were divided into sham, sepsis+cefepime, sepsis+cefepime+HBO, and sepsis+cefepime+OT groups. Sepsis was induced by an intraperitoneal injection of Escherichia coli; HBO was administered twice daily; OT was set as intraperitoneal injections once a day. The treatments were continued for 5 days after the induction of sepsis. At the end of experiment, the lung tissues and blood samples were harvested for biochemical and histological analysis. Myeloperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, IL-1β and TNF-α, were found to be ameliorated by the adjuvant use of HBO and OT in the lung tissue when compared with the antibiotherapy only group. Histologic evaluation of the lung tissue samples confirmed the biochemical outcome. Our data presented that both HBO and OT reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for OT. The current study demonstrated that the administration of OT as well as HBO as adjuvant therapy may support antibiotherapy in protecting the lung against septic injury. HBO and OT reduced tissue oxidative stress, regulated the systemic inflammatory response, and abated cellular infiltration to the lung demonstrated by findings of MPO activity and histopathologic examination. These findings indicated that OT tended to be more effective than HBO, in particular regarding serum IL-1β, lung GSH-Px and histologic outcome

Altered HDL particle in sickle cell disease

Background Hypocholesterolemia is the most frequently encountered lipid abnormality in sickle cell disease (SCD). We enrolled pediatric patients to determine the relationships between lipid profile and parameters of hemolysis, oxidative stress and chronic inflammation in SCD. Methods The study involved 35 pediatric SCD patients and 19 healthy controls. Patients were crisis-free and had not received transfusions for the last 3 months. Total cholesterol, triglyceride, HDL-C, LDL-C, VLDL-C, apolipoprotein A1, apolipoprotein B, LCAT, LDH, bilirubin, haptoglobin, iron, ferritin, hemin, serum amyloid A (SAA), myeloperoxidase (MPO), uric acid, ALT and GGT levels were evaluated in patients’ blood. Results Patients had hypocholesterolemia depicted by lower levels of total cholesterol, HDL-C, LDL-C, as well as Apolipoprotein A1 and Apolipoprotein B compared to controls. The chronic hemolysis of SCD was evident in patients by higher LDH and bilirubin and almost undetectable haptoglobin levels. Hemin levels (as a measure of oxidized heme) were significantly increased in patients with SCD. Inflammation markers, SAA and MPO, were significantly increased in the patients as well. There were negative correlations between HDL-C and LDH, and Apo A1 and SAA. Hemin was positively correlated to MPO. Conclusion Hemolysis was associated with decreased HDL –C, and Inflammation was linked to decreased apolipoprotein A1 levels in our SCD patients. Therefore, we suggest that the HDL particle is altered during the course of the disease. The altered HDL in SCD may become dysfunctional and result with a slowing down of the reverse cholesterol transport.PubMedWoSScopu

Vitamin D Deficiency And Its Association With Inflammatory Markers, Lipid Profile And Regulatory T-Cells In Pediatric Sickle Cell Disease Patients

We investigated vitamin D deficiency in pediatric sickle cell disease patients and its association with selected bone, lipid and inflammatory parameters. The study included 64 patients (33 SS and 31 SB) and 21 carriers (AS). Blood was obtained to assess levels of vitamin D, WBC, CRP, Ca, P, ALP, PTH, triglyceride, total cholesterol, LDL, VLDL, HDL, IL-2, IL-12, TNF-alpha, IL-4, IL-6, IL-10 and regulatory T cells. The patients were grouped according to their genotype (SS, SB) and vitamin D status (low or normal). Carriers were also grouped as low or normal vitamin D. Laboratory findings were similar between low and normal Vit D groups in SS, SB and AS genotypes except a lower IL-12 in SB-low vitamin D compared SB-normal vitamin D group. Acute chest syndrome was more frequent in SS-low Vit D (63%) compared to SS-normal Vit D (25%), SB-low Vit D (21%) and SB-normal Vit D (33%) (P = 0.045). Both SS and SB with low vitamin D had higher VLDL (P = 0.006 and P = 0.022), TNF-alpha (P = 0.001) and regulatory T cells (P = 0.000) compared to AS-low vitamin D. Both SS and SB with normal vitamin D had higher levels of regulatory T cells (P = 0.000) compared to AS-normal vitamin D. Vit D was not a modifier of selected inflammation, bone and lipid parameters in sickle cell disease. Acute chest syndrome was comparably more frequent in SS-low vitamin D. Increase of regulatory T cells in the patients was a result of chronic inflammation in sickle cell disease.Wo

Parp Inhibition Prevents Acetaminophen-Induced Liver Injury and Increases Survival Rate in Rats

Background/aim: Acetaminophen (APAP) overdose results in severe liver damage that may develop into acute liver failure. Recent studies have demonstrated that inhibition of poly(ADP-ribose) polymerase (PARP) decreases tissue necrosis and inflammation. We evaluated the efficacy of 3-aminobenzamide (3-AB), a PARP inhibitor, in a rodent model of APAP-induced hepatotoxicity. Materials and methods: Twenty-four Sprague-Dawley rats were divided equally into 3 experimental groups: sham group, APAP group, and APAP + 3-AB group. In the experimental treatment groups APAP was administered orally at 1 g/kg and, in the APAP + 3-AB group, 3-AB was administered intraperitoneally at a dose of 20 mg/kg exactly 1 h after APAP treatment. Surviving animals were euthanized 48 h after initial APAP administration. Blood samples and liver tissues were collected for histopathological and biochemical analysis. Results: A panel of oxidative stress parameters, as well as serum aspartate aminotransferase, alanine aminotransferase, neopterin, and nitrite/nitrate and histological injury scores, were significantly reduced among the APAP + 3-AB treatment group relative to the group treated with APAP alone (P < 0.05, APAP vs. APAP + 3-AB). Conclusion: The present study demonstrates that 3-AB inhibited APAP-induced hepatic injury and reduced neopterin levels. Results of the present study indicate that PARP inhibitors may be an effective adjuvant therapy resulting in improved outcomes in APAP-induced hepatotoxicity.WoSScopu

Comparison Of The Effects Of Dexmedetomidine Vs. Ketamine In Cardiac Ischemia/Reperfusion Injury In Rats - Preliminary Study

Objectives. Following ischemia/reperfusion injury, antioxidant defense mechanisms may remain insufficient depending on the duration of ischemia which is caused by any reason (MI, after percutaneous coronary intervention, during cardiac surgery). After that, free oxygen radicals increasing within the cell cause structural deterioration. Cytokines which activate a series of reactions that cause tissue damage and inflammatory response are released during reperfusion of ischemic tissues. In this study, we aimed to compare the effects of dexmedetomidine and ketamine in cardiac ischemia/reperfusion injury. Material and Methods. The study included 18 rats randomly divided into three groups. Group I/R (n = 6): control, Group I/R-K (n = 6): ketamine, and Group I/R-D (n = 6): dexmedetomidine. Before the 10 min surgery, after the 20 min ischemia and 20 min reperfusion period, hemodynamic parameters were compared among the three groups. After the 45 min ischemia and 120 min reperfusion period, tissue samples were obtained from the rat hearts, and MDA, SOD, GSH-Px, IL-1 beta and TNF-alpha levels were compared. Results. MDA and GSH-Px levels were significantly higher in the control group compared to the ketamine and dexmedetomidine groups. However, both levels were similar in the ketamine and dexmedetomidine groups. SOD levels were significantly lower in the ketamine and dexmedetomidine groups compared to the control group, but they were similar in the ketamine and dexmedetomidine groups. IL-1 beta levels were similar in all groups. TNF-alpha levels were significantly lower in the ketamine and dexmedetomidine groups compared to the control group. They were similar in the ketamine and dexmedetomidine groups. Conclusions. According to our study, it can be concluded that dexmedetomidine and ketamine have similar effects on reducing myocardial ischemia reperfusion injury. Dexmedetomidine provides better heart rate control but causes hypotension, so, because of cardiac depression, we think that its clinical use may necessitate further investigationWoSScopu