Glaucoma is the ultimate commonly acquired optic neuropathy. It signifies a public health challenge since it causes an irreversible blindness. The single known treatment of the disease is decreasing of intraocular pressure (IOP), which has been revealed to lessen glaucoma progress in a diversity of large proportions of clinical trials. Herein in this literature, we briefly define the optical Renin Angiotensin system (RAS) signaling pathway and define the most essential components, physiological actions of major angiotensin peptides, and the Renin Angiotensin system blockers. And discuss the potential implications of their modulators as a new therapeutic target in glaucoma. The literature has shown that the individual RAS modulators including, Angiotensin converting enzymes 1(ACE1) inhibitors, Angiotensin converting enzymes 2 (ACE2) Activators, Angiotensin receptor-1 (AT-1) blocker, and renin inhibitors have a potentials role in modulation of aqueous humour homodynamic, by neuroprotection of the retinal ganglion cells (RGC) and acceleration of the aqueous humour outflow. In conclusion, RAS modulators have an imperious role in lowering IOP, these compounds will pave the approach for prospect innovation, improvement, and publicizing of novel drugs to treat glaucoma and therefore, aid save vision for millions of people suffering with this slow progressive optic neuropathy.

Objectives: We examined the relations between blood cadmium and lead exposure and hearing impairments in the Iraqi people. Methods:We analyzed data from 51 individual 13-75 ages who had been randomly dispensed to the audiometry examination center at Al-Hilla Teaching Hospital (Babel) for each Iraqi civilian who said, "I suffering from the hearing problem." Pure-tone average (PTA) of auditory thresholds at frequencies of 0.5, 1, 2, and 4 kHz was calculated, and hearing impairment was described as a PTA >25 dB in either ear. Results:All patients who suffer from hearing impairment have serum lead level (23.14±1.76 µg/dL), which is a significantly elevated in comparison to control group (21.20±2.08 µg/dL). In addition to lead, the blood level of cadmium in people with hearing impairment was showed a significant elevation (0.28±0.05 µg/dL) in comparison to normal people (0.22±0.03 µg/dL). In general, this elevation remains within normal reference for the blood level of cadmium (0.5 µg/dL). Conclusions:The present study revealed that the environmental and occupational cadmium and lead coexposures lead to a significant elevation in the blood level of these metals and could have an essential part in the progression of hearing loss.

The systemic and resistant nature of the androgen-independent stage of prostate cancers makes it largely incurable even after intensive multimodal therapy. Apoptosis and epithelial-mesenchymal transition (EMT) are two fundamental events that are deeply linked to carcinogenesis. Hence, it is necessary to find a new combination of several therapies targeting apoptosis and EMT without causing side effects. Several recent studies have indicated that the Farnesoid X receptor is extensively associated with human tumorigenesis. The FXR agonist obeticholic acid (INT 747) has preliminarily exhibited a tumor suppressor potential. In this present study, we assess the potential synergism of FXR activation under nutrient deprivation in prostate cancer cell lines to investigate whether FXR activation enhances starvation-induced apoptosis in PC3 cells. In this study, PC-3 treatment with INT 747 significantly repressed cell proliferation and clonogenic potential. In addition, it significantly induced apoptosis of PC-3 cells and decreased their cancerogenic potential, as evaluated by annexin v apoptosis and transwell migration assay, respectively. The decreased expression of pro-caspase 3 by western blot analysis further confirmed INT 747-induced apoptosis. Furthermore, the fasting-mimicking diet (FMD) potentiated the antiproliferative, pro-apoptotic, and antimetastatic effects of INT 747. Mechanistically, these effects were mediated through the downregulation of cyclin D1 and upregulation of PTEN. In conclusion, INT 747 alone markedly decreases, and when combined with FMD abrogates the growth and migration of PC-3 cells.

Introduction. Chemotherapy with Cabazitaxel (CBZ) is a typical first-line treatment option for naïive castration-resistant prostate cancer resistant to docetaxel. On the other hand, Cabazitaxel's therapeutic success is constrained by chemoresistance and side effects.Aim. To assess whether 6 alpha-ethylchenodeoxycholic acid (6-ECDCA), a selective agonist for bile acid receptors will enhance the efficacy of CBZ in androgen-independent prostate cancer cells.Materials and methods. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay was used to assess the cytotoxicity of 6-ECDCA and CBZ medicines or their combinations against the human prostate cancer cell line (PC-3). The combination outcome suggested by Chou TC et al. was then evaluated using the combination index (CI) to find out the nature of synergism, antagonism, and additive effect of the drug’s combination. Furthermore, the Dose-Reduction Index (DRI) was determined to measure how many times the dose could be reduced for each drug in a synergistic combination.Results and discussion. Analysis of the dose-effect curve showed that the treatment of PC-3 cells with CBZ alone or combined with 6-ECDCA for 48 h led to 50 % cytotoxicity of 20.5 nM and 4.7 nM, respectively. 6-ECDCA at 1.77 µM had an additive effect based on the CI value, which was 1.02, while at 21.02 µM, the CI was 0.54 which designates a strong synergistic effect. The combination of CBZ and 6-ECDCA at a submaximal lower dose by 6-folds of each one produced a 95 % cell death than treatment with either agent alone.Conclusion. The Combination index plot showed CI ≤ l for all combinations used in this study, which indicates additive and synergistic interactions between CBZ and 6-ECDCA. The significant impact of 6-ECDCA in combination with CBZ for treating androgen-independent prostate cancer cells was confirmed by this study to be preferred to the treatment with a single drug.