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Chemotherapy-induced cognitive impairment (CICI) is a neurotoxic side effect of chemotherapy that has yet to have an effective treatment. Using cisplatin, a platinum-based chemotherapy together with excitatory cortical neurons derived from human induced pluripotent cells (iPSCs) to model of CICI, our recent study demonstrated that dysregulation of brain NAD +metabolism contributes to cisplatin-induced impairments in neurogenesis and cognitive function, which was prevented by administration of the NAD +precursor, nicotinamide mononucleotide (NMN). However, it remains unclear how cisplatin causes neurogenic dysfunction and the mechanism by which NMN prevents cisplatin-induced cognitive impairment. Given that mitochondrial dysfunction is thought to play a prominent role in age-related neurodegenerative disease and chemotherapy-induced neurotoxicity, we sought to explore if NMN prevents chemotherapy-related neurotoxicity by attenuating cisplatin-induced mitochondrial damage. We demonstrate that cisplatin induces neuronal DNA damage, increases generation of mitochondrial reactive oxygen species (ROS) and decreases ATP production, all of which are indicative of oxidative DNA damage and mitochondrial functional defects. Ultrastructural analysis revealed that cisplatin caused loss of cristae membrane integrity and matrix swelling in human cortical neurons. Notably, pretreatment with NMN prevents cisplatin-induced defects in mitochondria of human cortical neurons. Our results suggest that increased mitochondrial oxidative stress and functional defects play key roles in cisplatin-induced neurotoxicity. Thus, NMN may be an effective therapeutic strategy to prevent cisplatin-induced deleterious effects on mitochondria, making this organelle a key factor in amelioration of cisplatin-induced cognitive impairments.

Supplemental Digital Content is Available in the Text.A quasi-randomized controlled trial comparing home-based cardiac rehabilitation with usual care was undertaken with patients following coronary artery bypass graft surgery in Bangladesh, a lower- to middle-income country. The trial found cardiac rehabilitation was feasible and provided similar patient benefits to trials of cardiac rehabilitation based in high-income countries.

Two new sesquiterpenes, 4-methoxycarbonyl-7-(1-methylethyl)-6-oxo-3,3a,7,8,8a-pentahydroazulene-1-carboxylic acid (viscoazusone) and 1,4-dimethoxy-carbonyl-7-(1-methylethyl)-6-oxo-3,3a,7,8,8a-pentahydroazulene (viscoazulone), were isolated from the whole plant of Polygonum viscosum . The structures of these compounds were determined by spectroscopic means.

The effective use of local growth factors and cytokines may replace the lengthy staged surgical delay process. We tested the efficacy of basic fibroblast growth factor bFGF coadministered with sucralfate sucrose octasulfate on the rat dorsal flap model. A total of 76 male Wistar rats were used in this experiment. Four groups of the animals were divided. Group 1 n5 was the vehicle control saline soaked, group 2 n5 was sucrose octasulfate soaked 100 gml, 1 ml, group 3 n5 was bFGF soaked 1 gml, 1 ml, and group 4 n5 was both bFGF and sucrose octasulfate soaked. All agents were soaked equally in Gelfoam. The flap survival measured by the quantitative computerassisted morphologic analysis was significantly improved by day 5 postoperatively in the combined administration group compared with the vehicle control 81 and 53 percent, respectively p< 0.05. In lead oxidegelatin microangiography, there was enhanced pedicle vessel formation observed as well as the extended vessel sprouting up to very close to the distal end in combined group on day 5. The endogenous bFGF mRNA expressions shown by reverse transcriptasepolymerase chain reaction were detected in all four groups. The angiogenesis indicated by smooth muscle actin immunopositivity was significantly more enhanced in the combined group than the vehicle control 37.3 and 19.4, respectively p< 0.01. In the combined group, there was stronger immunopositivity for bFGF in epidermis and hair follicles observed, and more notably bFGFimmunopositive dermal fibroblasts were evident.

The chloroform extract of the culture filtrate of a Streptomyces sp. yielded a new antibacterial substance, the structure of which was elucidated as dehydroaltenusinic acid {1} by extensive analyses of its spectral data as well as by comparison with those of related compounds, dehydroaltenusin {2} and altenusin {3}. Compound 1 was found to exhibit significant inhibitory activity against a number of both Gram-positive and Gram-negative bacteria.

Platelet aggregation and plasma serotonin were studied during ischemia-reperfusion of the small intestine in dogs. Blood was withdrawn from the superior mesenteric vein before and 1 h after ischemia, then 5, 30 and 60 min after reperfusion. Dipyridamole (5 mg/kg body weight) and coenzyme Q10 (CoQ10; 10mg/kg body weight) were administered intravenously 5 min before reperfusion, following 1 h ischemia, in order to investigate their effects on platelet function and free serotonin. Ischemia-reperfusion resulted in an increased local free serotonin concentration together with an enhanced platelet response to ADP, collagen and arachidonic acid. Administration of dipyridamole and CoQ10 prior to reperfusion prevented, at least in part, augmented platelet activation and serotonin release. It appeared that dipyridamole was more potent than CoQ10. Our results may indicate a possible protective effect of dipyridamole on enhanced platelet activation during ischemia-reperfusion in dogs.

For bone defect reconstruction, locally administered cytokine plasmid was examined. Leukemia inhibitory factor LIF can bind to the osteoblast cell surface and induce bone formation both in vitro and in vivo. The authors investigated the local mouse LIF complementary deoxyribonucleic acid cDNA plasmid in the pcDNA 3 expression vector, which is promoted by cytomegalovirus and is stabilized by bovine growth hormone polyadenylation, with a gelatin sponge carrier. A total of 150 male wistar rats were used. They were divided into three groups. Group 1 N 30 was treated with the gelatin carrier of the pcDNA 3 vector, group 2 N 90 was treated with three different doses of LIF cDNA 0.1, 1, and 10g in the pcDNA 3vector plasmid along with the gelatin carrier, and group 3 N 30 was treated with recombinant human bone morphogenetic protein 2. Ten animals in each group were euthanized at 1, 3, and 5 weeks postoperatively. Animals treated with LIF cDNA showed significantly enhanced bone mineral density p< 0.05, as confirmed by dualenergy Xray absorptiometry DEXA, in 3 weeks compared with the control vehicle. By 3 weeks, the number of fibroblastlike cells and collagen fibers decreased, whereas the osteoblastlike cells increased inversely, as revealed during histological examination. LIF messenger ribonucleic acid demonstrated by in situ hybridization was observed most markedly in osteocytes of the LIF cDNAtreated group. Also, LIF peptide was detected in the same cell type by immunohistochemistry. Locally administered LIF cDNA plasmid in a gelatin carrier can increase bone density significantly, with subsequent bone formation, probably via osteocyte activation.