Mechanism of Action of Bone Marrow Mesenchymal Stem Cell in Combination with miR-36b Therapy in Cellular Repair of Septic Lung Injury

Our study aims to assess the role of BMSCs (MSCs) transplantation in combination with miR-36b in the repair of septic lung injury. MSCs were cultured by the paste-wall method and characterized. MSCs combined with miR-36b medium were added to lung-injured cells for 14 days followed by analysis of cell viability by CCK-8 assay, GLUT3 expression and apoptosis by western blot. After 1 and 3 days of growth of MSCs progeny under electron microscopy, the MSCs showed long shuttle-shaped morphology. MSCs in combination with miR-36b resulted in enhanced proliferative capacity of lung-injured cells and enhanced protein expression of GLUT3. CCK-8 assay showed increased viability of lung-injured cells and elevated protein and mRNA expression of GLUT3. Meanwhile, the expression of apoptosis-related proteins was significantly down-regulated. In conclusion, MSCs in combination with miR-36b therapy may ameliorate lung injury by promoting lung cell proliferation through inhibition of apoptotic pathway.

Effects of 5′,8′-Cyclo-2′-Deoxypurines on the Base ExcisionRepair of Clustered DNA Lesions in Nuclear Extracts of the XPC Cell Line

Clustered DNA lesions (CDL) containing 5′,8-cyclo-2′-deoxypurines (cdPus) are an example of extensive abnormalities occurring in the DNA helix and may impede cellular repair processes. The changes in the efficiency of nuclear base excision repair (BER) were investigated using (a) two cell lines, one of the normal skin fibroblasts as a reference (BJ) and the second from Xeroderma pigmentosum patients’ skin (XPC), and (b) synthetic oligonucleotides with single- and double-stranded CDL (containing 5′,8-cyclo-2′-deoxyadenosine (cdA) and the abasic (AP) site at various distances between lesions). The nuclear BER has been observed and the effect of both cdA isomers (5′R and 5′S) presence in the DNA was tested. CdPus affected the repair of the second lesion within the CDL. The BER system more efficiently processed damage in the vicinity of the ScdA isomer and changes located in the 3′-end direction for dsCDL and in the 5′-end direction for ssCDL. The presented study is the very first investigation of the repair processes of the CDL containing cdPu considering cells derived from a Xeroderma pigmentosum patient.

Protective effect of resveratrol against hexavalent chromium-induced genotoxic damage in Hsd:ICR male mice

It is well-established that exposure to hexavalent chromium [Cr(VI)] induces genotoxic damage. The aim of this study was to examine the ability of resveratrol to counteract hexavalent chromium [Cr(VI)]-induced genetic damage, as well as possible pathways that may be associated with this protection. Hsd:ICR male mice were divided into groups of 5 each and treated as follows: a) control 1, distilled water; b) control 2, ethanol 30%; c) resveratrol, 50 mg/kg by gavage; d) CrO3, 20 mg/kg intraperitoneally; and e) resveratrol in addition to CrO3 (resveratrol+CrO3), with resveratrol administered 4 hr prior to CrO3. The frequency of micronuclei (MN) and cytotoxicity were measured in peripheral blood at 0, 24, 48 and 72 hr, while 8-hydroxydeoxyguanosine (8-OHdG, 7,8-dihydro-8-oxodeoxyguanosine) adduct repair levels, endogenous antioxidant system biomarkers and apoptosis at 48 hr after treatments. Resveratrol administration increased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). CrO3 treatment elevated GPx and CAT activities. Resveratrol reduced the frequency of Cr(VI)-induced rise in MN and without significant effect on levels of 8-OHdG adduct when administered alone, suggesting that this polyphenol-mediated cellular repair does not involve 8-OHdG adduct formation. Concomitant administration of resveratrol and Cr(VI)-resulted in return of activities of SOD, GPx and CAT to control levels accompanied by decreased glutathione levels suggesting that the endogenous antioxidant system might play an important role in resveratrol-mediated inhibition of Cr(VI)-induced oxidant toxicity. The increase in apoptotic cell number in resveratrol+CrO3 group as well as diminished necrosis further affirms that resveratrol effectively blocked the actions of Cr(VI).

Sedation-Led chEmotherapy Evades Pain (S.L.E.E.P.)

Chemotherapy and other invasive therapies are often limited by side effects, pain and negative experiences that can limit adherence to the therapy itself. Such negative components add to the patient's depressive state due to the disease. This research project proposes the use of deep sedation during chemotherapy sessions or other disabling therapies in the treatment of tumors or other severe diseases. The proposed protocol provides for an ad hoc hospitalization which could be during the night, during the day or limited to a few hours. Administration during sleep eliminates the memory and the negative impact the treatment has on the rest of the patient's daily life. This approach also agrees with the evidence of the circadian rhythm of cellular repair processes, which is greater at sunrise and sunset and linked to a good quantity and quality of sleep. In conclusion, this project aims to reduce the negative impact and increase the adherence to and efficacy of the therapy itself.

Engineered glycomaterial implants orchestrate large-scale functional repair of brain tissue chronically after severe traumatic brain injury

Severe traumatic brain injury (sTBI) survivors experience permanent functional disabilities due to significant volume loss and the brain’s poor capacity to regenerate. Chondroitin sulfate glycosaminoglycans (CS-GAGs) are key regulators of growth factor signaling and neural stem cell homeostasis in the brain. However, the efficacy of engineered CS (eCS) matrices in mediating structural and functional recovery chronically after sTBI has not been investigated. We report that neurotrophic factor functionalized acellular eCS matrices implanted into the rat M1 region acutely after sTBI significantly enhanced cellular repair and gross motor function recovery when compared to controls 20 weeks after sTBI. Animals subjected to M2 region injuries followed by eCS matrix implantations demonstrated the significant recovery of “reach-to-grasp” function. This was attributed to enhanced volumetric vascularization, activity-regulated cytoskeleton (Arc) protein expression, and perilesional sensorimotor connectivity. These findings indicate that eCS matrices implanted acutely after sTBI can support complex cellular, vascular, and neuronal circuit repair chronically after sTBI.

Cellular repair mechanisms triggered by exposure to silver nanoparticles and ionic silver in embryonic zebrafish cells

The dynamic interplay between toxicity pathways (oxidative stress, calcium disturbances, genetic damage) caused by nanoparticles and the repair mechanisms of inhibition of cell division and induction of cell death is explored in zebrafish embryo cells.