Bladder cancer is the 10th-most common cancer worldwide. The diagnosis and follow-up of patients require costly invasive methods and due to these expenses, bladder cancer continues to be one of the expensive malignancies. Early diagnosis is crucial in bladder cancer as it is in other cancers; therefore, non-invasive biomarkers for early diagnosis are very important. In this review, we aimed to focus on the most recent investigations on potential urinary micro RNA (miRNA) and protein biomarkers for bladder cancer diagnosis and their associated pathways. Studies performed by different groups were compiled and the biomarker properties of various proteins and miRNAs in the urine of bladder cancer patients were evaluated. Key studies were obtained by searching keywords “bladder cancer, urinary miRNA, urinary protein, urinary biomarker”. Targets and the pathways of the miRNAs and proteins were analyzed according to mirBase Catalogue and Panther Database. The major pathways that are targeted by aberrantly expressed miRNAs are Cholecystokinin receptor (CCKR), p53, Wnt signaling pathway, and feedback loops. We hereby conclude that urinary micro RNAs and proteins are promising candidates for bladder cancer diagnosis. It should be noted that urine collection, storage conditions, choice of fraction, and normalization strategies should be standardized.
The anti-catabolic bisphosphonate alendronate is considered as the first-line medical treatment in post-menopausal osteoporosis; but several side effects, including gastric mucosal injury, are associated with its use. The aim was to elucidate whether combined treatment with melatonin plus alendronate would be more advantageous in the maintenance of bone and the prevention of gastric side effects. Under anaesthesia, female Sprague-Dawley rats underwent bilateral ovariectomy (OVX), while control group had sham surgery. Four weeks after the surgery, OVX rats were treated with saline, melatonin (25 μg/mL/d), alendronate (70 μg/kg/wk), melatonin + alendronate, melatonin + melatonin receptor antagonist (luzindole, 10 μg/kg/d) or alendronate + melatonin + luzindole for 8 weeks. Rats were euthanized at the end of 12th week. Runx2 expression, apoptotic cells, and trabecular thickness were evaluated in tibiae, while gastric tissues were analysed for oxidative injury parameters. In all OVX groups, Runx2 expression was depressed. Saline-treated OVX group presented an extreme decrease in calcified area in opposition to melatonin-or alendronate-treated groups, while the bones in alendronate + melatonin-treated group were similar to those of the sham-operated group. Concomitant with the improvements examined histologically in bone tissues, quantitative TUNEL (+) cells were similarly lower in alendronate-or melatonin-treated groups. Oxidative gastric damage was increased in saline-or alendronate-treated groups, which were depressed in the presence of melatonin. Although melatonin and alendronate exerted similar supportive effects on the maintenance of bone mass, melatonin may have a more advantageous impact by protecting against OVX-induced gastric injury, which was aggravated by alendronate use.
Highlights:Our results demonstrate that alendronate and melatonin had similar supportive effects on the maintenance of bone mass, while melatonin prevented the gastric side effects of alendronate, making this combination an advisable therapeutic approach in the treatment of menopausal osteoporosis.
Skin and cartilage tissue specimens from 32 male and 13 female corpses aged between 17 and 50 years were collected within 24 h after the death. Each specimen was analyzed for the composition of dextro (D) and levo (L) forms of aspartate, glutamate, and alanine. Linear regression models were constructed using ln [(1 + D/L)/(1 - D/L] equation to define the relationship between the extent of racemization and the chronological age. Aspartate D/L rates from cartilage showed high correlation (r = 0.779, p < 0.001, n = 45). Aspartate D/L rates from skin showed very low correlation (r = 0.356, p < 0.002, n = 44). The multilinear regression model of both aspartate D/L rates of cartilage and skin tissues in 44 cases yielded a coefficient of r = 0.828 (p < 0.001). In conclusion, only racemization rate of Aspartate both in the skin and the cartilage tissues correlated with the chronological age. Our results may imply that the age can be estimated more precisely if two different tissue specimens are obtained from one corpse.
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