Nano-formulations for Ophthalmic Treatments

Ocular disorders encompass a multitude of diseases that are unique in their cause, therapy and degree of severity. Due to distinctive morphology of the eye, efficient ocular drug delivery has proven to be a difficult task. Current treatments of ophthalmological diseases include the usage of both intrusive as well as nonintrusive methods such as injections, eye drops, ointments, gels etc. The current state of the art drug delivery methods are associated with low bioavailability and therefore nanotechnology based drug delivery approached are evolving as for improving the therapeutic index of currently used drugs against variety of ocular disorders. This review highlights the recent developments in nano-formulations for ophthalmic treatment and also offers discussions towards the future prospectus of nano-formulations in the mainstream of ophthalmic diseases

Evaluation of anti-inflammatory activity of selected medicinal plants used in Indian traditional medication system in vitro as well as in vivo

The present study was carried out to evaluate in vivo and in vitro anti-inflammatory potential of selected medicinal plants used in Indian traditional medication. The sequentially extracted plant samples as, Cissus quadrangularis, Plumbago zeylanica, Terminalia bellarica and Terminalia chebula in water, ethanol and hexane were evaluated in-vitro for COX-1 and 2 inhibitory and antioxidant activities. The in vivo anti-inflammatory activity of selected samples showing promising COX-2 inhibition was assessed using carrageenan and Phorbol Myristate Acetate (PMA) induced mice edema animal model. The results obtained reveals that most of the plants were found to inhibit COX-2 activity as compared to COX-1. It was observed that the extracts of T. bellarica (73.34 %) and T. chebula (74.81 %) showed significant COX-2 selective inhibition as compared to other samples. The ethanol extract of the selected plants demonstrated effective DPPH, OH and superoxide radical scavenging activity. In vivo anti-inflammatory study shows that, T. bellarica and T. chebulla had a significant impact on inhibition of edema formation. The cytotoxicity evaluation study of ethanolic fraction of selected medicinal plants indicates that the selected samples have no effect on cell viability. HPTLC fingerprint of flavonoids of the selected samples was also prepared as a measure of quality control. The results obtained may be useful in strengthening the standardization of the selected botanicals. Moreover the selected plants can be considered as a resource for searching novel anti-inflammatory agents possessing COX-2 inhibition

<span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Virtual screening and docking exploration on estrogen receptor: An <i>in silico</i> approach to decipher novel anticancer agents</span>

389-395Breast cancer is a prominent disorder that affects mostly mid aged women with a high intensity, upsetting every ninth women of ten. The available drugs and treatments fall back as they do not completely eradicate the cancerous cells from body. Hence, newer and more effective drugs and treatments against breast cancer are the need-of-hour. The increased level of estrogen within body increases the chance of breast cancer, whereas the regular concentration plays significant role in normal cell functioning. Melatonin is popularly used as an anti-estrogenic compound, whereas violacein an active secondary metabolite secreted by bacteria like ‘Chromobacterium violaceum’ has strong structural similarity with melatonin and, thus, possess latency of being tested for its anti-cancerous activity. In the current study, docking and virtual screening was utilized to prove the fact that violacein and similar compounds can bind more efficiently to estrogen receptor than that of melatonin and, hence, has potential to emerge as lead anti-estrogenic compound in treatment of breast cancer. </span

Long non-coding RNA and Evolving drug resistance in lung cancer

Non-small cell lung cancer (NSCLC) is one of the most devastating cancers with a high incidence and mortality rates of all cancers. Locally advanced or metastatic NSCLC patients can benefit from platinum-based chemotherapy and targeted therapy drugs. Nevertheless, primary or acquired drug resistance will result in ineffective treatment, leading to tumor progression. The detailed mechanism underlying drug resistance to NSCLC are complicated and result from various factor. Among them, long noncoding RNAs (lncRNAs) have been found to be critically involved in NSCLC development and play a vital role in mediating therapy resistance. In this review, we attempt to systematically summarize the mechanisms underlying the lncRNA-mediated resistance to chemotherapy agents and targeted therapy drugs against lung cancer

Repurposing of neprilysin inhibitor ‘sacubitrilat’ as an anti-cancer drug by modulating epigenetic and apoptotic regulators

Abstract Modifications in the epigenetic landscape have been considered a hallmark of cancer. Histone deacetylation is one of the crucial epigenetic modulations associated with the aggressive progression of various cancer subtypes. Herein, we have repurposed the neprilysin inhibitor sacubitrilat as a potent anticancer agent using in-silico protein–ligand interaction profiler (PLIP) analysis, molecular docking, and in vitro studies. The screening of PLIP profiles between vorinostat/panobinostat and HDACs/LTA4H followed by molecular docking resulted in five (Sacubitrilat, B65, BDS, BIR, and NPV) FDA-approved, experimental and investigational drugs. Sacubitrilat has demonstrated promising anticancer activity against colorectal cancer (SW-480) and triple-negative breast cancer (MDA-MB-231) cells, with IC50 values of 14.07 μg/mL and 23.02 μg/mL, respectively. FACS analysis revealed that sacubitrilat arrests the cell cycle at the G0/G1 phase and induces apoptotic-mediated cell death in SW-480 cells. In addition, sacubitrilat inhibited HDAC isoforms at the transcriptomic level by 0.7–0.9 fold and at the proteomic level by 0.5–0.6 fold as compared to the control. Sacubitrilat increased the protein expression of tumor-suppressor (p53) and pro-apoptotic makers (Bax and Bid) by 0.2–2.5 fold while decreasing the expression of anti-apoptotic Bcl2 and Nrf2 proteins by 0.2–0.5 fold with respect to control. The observed cleaved PARP product indicates that sacubitrilat induces apoptotic-mediated cell death. This study may pave the way to identify the anticancer potential of sacubitrilat and can be explored in human clinical trials

Therapeutic implications of cancer stem cells in prostate cancer

Prostate cancer, one of the most frequently occurring cancers in men, is a heterogeneous disease involving multiple cell types within tumors. This tumor heterogeneity at least partly results from genomic instability leading to sub-clonal cellular differentiation. The differentiated cell populations originate from a small subset of cells with tumor-initiating and stem-like properties. These cells, termed prostate cancer stem cells (PCSCs), play crucial roles in disease progression, drug resistance, and relapse. This review discusses the origin, hierarchy, and plasticity of PCSCs; methods for isolation and enrichment of PCSCs; and various cellular and metabolic signaling pathways involved in PCSC induction and maintenance, as well as therapeutic targeting