A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT

Background. Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) 41 leading to increased fracture risk. Exercise-induced hormone 'irisin' in low dosage has been 42 shown to have a beneficial effect on bone metabolism by increasing osteoblast differentiation 43 and reducing osteoclast maturation, and inhibiting apoptosis and inflammation. We investigated 44 the role of irisin in treating diabetic osteopathy by observing its effect on trabecular bone. 45 Methods. DM1 was induced by intraperitoneal injection of streptozotocin 60 mg/kg body 46 weight. Irisin in low dosage (5 μg twice a week for 6 weeks I/P) was injected into half of the 47 control and 4-week diabetic male Wistar rats. Animals were sacrificed six months after induction 48 of diabetes. The trabecular bone in the femoral head and neck was analyzed using a micro-CT 49 technique. Bone turnover markers were measured using ELISA, Western blot, and RT-PCR 50 techniques. 51 Results. It was found that DM1 deteriorates the trabecular bone microstructure by increasing 52 trabecular separation (Tb-Sp) and decreasing trabecular thickness (Tb-Th), bone volume fraction 53 (BV/TV), and bone mineral density (BMD). Irisin treatment positively affects bone quality by 54 increasing trabecular number p < 0.05 and improves the BMD, Tb-Sp, and BV/TV by 21-28%. 55 The deterioration in bone microarchitecture is mainly attributed to decreased bone formation 56 observed as low osteocalcin and high sclerostin levels in diabetic bone samples p < 0.001. The 57 irisin treatment significantly suppressed the serum and bone sclerostin levels p < 0.001, 58 increased the serum CTX1 levels p < 0.05, and also showed non-significant improvement in 59 osteocalcin levels. 60 Conclusions. This is the first pilot study to our knowledge that shows that a low dose of irisin 61 marginally improves the trabecular bone in DM1 and is an effective peptide in reducing 62 sclerostin levels

A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT

Background: Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) leading to increased fracture risk. Exercise-induced hormone ‘irisin’ in low dosage has been shown to have a beneficial effect on bone metabolism by increasing osteoblast differentiation and reducing osteoclast maturation, and inhibiting apoptosis and inflammation. We investigated the role of irisin in treating diabetic osteopathy by observing its effect on trabecular bone.Methods: DM1 was induced by intraperitoneal injection of streptozotocin 60 mg/kg body weight. Irisin in low dosage (5 µg twice a week for 6 weeks I/P) was injected into half of the control and 4-week diabetic male Wistar rats. Animals were sacrificed six months after induction of diabetes. The trabecular bone in the femoral head and neck was analyzed using a micro-CT technique. Bone turnover markers were measured using ELISA, Western blot, and RT-PCR techniques. Results: It was found that DM1 deteriorates the trabecular bone microstructure by increasing trabecular separation (Tb-Sp) and decreasing trabecular thickness (Tb-Th), bone volume fraction (BV/TV), and bone mineral density (BMD). Irisin treatment positively affects bone quality by increasing trabecular number p &lt; 0.05 and improves the BMD, Tb-Sp, and BV/TV by 21–28%. The deterioration in bone microarchitecture is mainly attributed to decreased bone formation observed as low osteocalcin and high sclerostin levels in diabetic bone samples p &lt; 0.001. The irisin treatment significantly suppressed the serum and bone sclerostin levels p &lt; 0.001, increased the serum CTX1 levels p &lt; 0.05, and also showed non-significant improvement in osteocalcin levels. Conclusions: This is the first pilot study to our knowledge that shows that a low dose of irisin marginally improves the trabecular bone in DM1 and is an effective peptide in reducing sclerostin levels

Attenuated Bacteria as Immunotherapeutic Tools for Cancer Treatment

The use of attenuated bacteria as cancer therapeutic tools has garnered increasing scientific interest over the past 10 years. This is largely due to the development of bacterial strains that maintain good anti-tumor efficacy, but with reduced potential to cause toxicities to the host. Because of its ability to replicate in viable as well as necrotic tissue, cancer therapy using attenuated strains of facultative anaerobic bacteria, such as Salmonella, has several advantages over standard treatment modalities, including chemotherapy and radiotherapy. Despite some findings suggesting that it may operate through a direct cytotoxic effect against cancer cells, there is accumulating evidence demonstrating that bacterial therapy acts by modulating cells of the immune system to counter the growth of the tumor. Herein, we review the experimental evidence underlying the success of bacterial immunotherapy against cancer and highlight the cellular and molecular alterations in the peripheral immune system and within the tumor microenvironment that have been reported following different forms of bacterial therapy. Our improved understanding of these mechanisms should greatly aid in the translational application of bacterial therapy to cancer patients

Identification of early indicators of altered metabolism in normal development using a rodent model system

Although the existence of a close relationship between the early maternal developmental environment, fetal size at birth and the risk of developing disease in adulthood has been suggested, most studies, however, employed experimentally induced intrauterine growth restriction as a model to link this with later adult disease. Because embryonic size variation also occurs under normal growth and differentiation, elucidating the molecular mechanisms underlying these changes and their relevance to later adult disease risk becomes important. The birth weight of rat pups vary according to the uterine horn positions. Using birth weight as a marker, we compared two groups of rat pups – lower birth weight (LBW, 5th to 25th percentile) and average birth weight (ABW, 50th to 75th percentile) – using morphological, biochemical and molecular biology, and genetic techniques. Our results show that insulin metabolism, Pi3k/Akt and Pparγ signaling and the genes regulating growth and metabolism are significantly different in these groups. Methylation at the promoter of the InsII (Ins2) gene and DNA methyltransferase 1 in LBW pups are both increased. Additionally, the Dnmt1 repressor complex, which includes Hdac1, Rb (Rb1) and E2f1, was also upregulated in LBW pups. We conclude that the Dnmt1 repressor complex, which regulates the restriction point of the cell cycle, retards the rate at which cells traverse the G1 or G0 phase of the cell cycle in LBW pups, thereby slowing down growth. This regulatory mechanism mediated by Dnmt1 might contribute to the production of small-size pups and altered physiology and pathology in adult life