Meropenem loaded 4-arm-polyethylene-succinimidyl-carboxymethyl ester and hyaluronic acid based bacterial resistant hydrogel.

Developing an ideal vitreous substitute/implant is a current challenge. Moreover, implants (e.g., heart valves and vitreous substitutes), are associated with a high risk of bacterial infection when it comes in contact with cells at implant site. Due to infection, many implants fail, and the patient requires immediate surgery and suffers from post-operative problems. To overcome these problems in vitreous implants, we developed a bacterial resistant vitreous implant, where meropenem (Mer), an antibiotic, has been incorporated in a hydrogel prepared by crosslinking HA (deacetylated sodium hyaluronate) with 4-arm-polyethylene-succinimidyl-carboxymethyl-ester (PESCE). The HA-PESCE hydrogel may serve as a suitable artificial vitreous substitute (AVS). The pre-gel solutions of HA-PESCE without drug and with the drug are injectable through a 22 G needle, and the gel formation occurred in approx. 3 min: it indicates its suitability for in-situ gelation through vitrectomy surgery. The HA-PESCE hydrogel depicted desired biocompatibility, transparency (>90 %), water content (96 %) and sufficient viscoelasticity (G' >100 Pa) calculated after 1 month in-vitro, which are suitable for vitreous substitute. The HA-Mer-PESCE hydrogel showed improved biocompatibility, suitable transparency (>90 %), high water content (96 %), and suitable viscoelasticity (G' >100 Pa) calculated after 1 month in-vitro, which are suitable for vitreous substitute. Further, hydrogel strongly inhibits the growth of bacteria E.coli and S.aureus. The drug loaded hydrogel showed sustained in-vitro drug release by the Fickian diffusion-mediated process (by Korsmeyer-Peppas and Peppas Sahlin model). Thus, the developed hydrogel may be used as a potential bacterial resistant AVS.

Biosynthesis of folic acid appended PHBV modified copper oxide nanorods for pH sensitive drug release in targeted breast cancer therapy.

Multifunctional nanoplatforms as nanocarriers have attracted the interest of many scientists because they can achieve greater therapeutic effect in anticancer drug delivery to tumors with potential to improve cancer treatment, while currently available therapies are nonspecific and ineffectual. In present study, notable cancer therapeutic strategy which combines PEG functionalized poly (3-hydroxybutyric acid-co-hydroxyvaleric acid) (PHBV) nanospheres decorated with folic acid for delivery of paclitaxel (PTX) drug conjugated with copper oxide (CuO) nanoparticles (NPs) is proposed. Moreover, PTX loading with CuO NPs in PHBV nanosphere was done to increase its solubility and analyze its apoptotic effects in human breast cancer (MCF-7) cells. The pH-sensitive CuO-PTX@PHBV-PEG-FA nanosystem was successfully developed, as evidenced by number of characterizations. Resultant CuO-PTX@PHBV-PEG-FA NPs were 148.93 ± 10.5 nm in size, having 0.206 PDI, with -20.3 ± 0.6 mV zeta potential. MTT assay in MCF-7 cells was used to assess cell viability, while anticancer potential of CuO-PTX@PHBV-PEG-FA nanosystem was confirmed through different staining techniques. According to in vitro studies, FA-conjugated PHBV modified CuO-PTX targeted nanoparticles exhibited higher anticancer effect than free PTX probably due to binding interaction of folate receptor with cells that overexpress the target. This nanosystem has the potential to be a promising breast cancer treatment agent.

Involvement of Cdkal1 in the etiology of type 2 diabetes mellitus and microvascular diabetic complications: a review.

Diabetes Mellitus, being a polygenic disorder, have a set of risk genes involved in the onset of the insulin resistance, obesity and impaired insulin synthesis. Recent genome wide association studies (GWAS) shows the intimacy of CDK5 regulatory subunit Associated protein 1-Like 1 (Cdkal1) with the pathophysiology of the diabetes mellitus and its complications, although the exact molecular relation is still unknown. In this short review, we have summarized all the diverse biological roles of Cdkal1 in relation to the onset of diabetes mellitus. Variations in the Cdkal1 transcript are responsible for the accumulation of misfolded insulin and thus generating oxidative and ER stress in the pancreatic ß-cells, leading to their destruction. Recent studies have shown that Cdkal1 has an intrinsic thiomethyl transferase activity, which is essential for proper posttranslational processing of pre-proinsulin to produce mature insulin. Moreover, Cdkal1 has also been claimed as an endogenous inhibitor of cdk5, which prevents the cdk5-induced interruption in insulin synthesis through PDX1 translocation from nucleus to cytosol. Recent clinical studies have identified the risk single nucleotide polymorphisms (SNPs) of Cdkal1 as one of the root causes for the onset of diabetic complications. To the best of our knowledge, it is the first comprehensive review which elaborates most of the potential Cdkal1-dependent molecular mechanisms studied yet. In this review, we present a compiled and concise summary about all the diverse roles of Cdkal1 in the context of type 2 diabetes mellitus and its associated complications. This review will be helpful to target Cdkal1 as a potential option for the management of type 2 diabetes mellitus in future.

DNA binding, antitubercular, antibacterial and anticancer studies of newly designed piano-stool ruthenium(II) complexes.

The chemotherapeutic potential of ruthenium(II) complexes has recently attracted researchers' interest as antibacterial and anticancer agents. In this study, two novel half-sandwich imine-based Ru complexes ([Ru(p-cymene)Cl(L-1)][PF6] (Ru-1) and [Ru(p-cymene)Cl(L-2)][PF6] (Ru-2)) were reported for their deoxyribonucleic acid (DNA) binding and antitubercular, antibacterial, and anticancer activities. The molecular structure of Ru-2 was obtained by single-crystal X-ray crystallography. DNA interaction studies were conducted by UV-Vis absorbance and fluorescence spectral titration which gave rise to DNA binding constants (Kb) of 1.32 × 106 and 1.82 × 106 for Ru-1 and Ru-2, respectively and the Stern-Volmer binding constant (KSV) values for Ru-1 and Ru-2 were 1.7763 × 104 M-1 and 7.6 × 103 M-1, respectively. The in vitro antitubercular activity was evaluated against Mycobacterium tuberculosis H37Ra. The antibacterial potential of both the Ru-complexes was examined against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria. The half-maximal inhibitory concentration (IC50) values for the antitubercular activity of Ru-1 and Ru-2 were 4.87 ± 1.32 µM and 5.78 ± 0.54 µM, respectively. A cytotoxic study of these complexes was performed against the human breast cancer cell line (MCF-7) and the human embryonic kidney cell line (HEK293) (normal cells). The study revealed meaningful activity of the Ru-1 complex against (cancer) MCF-7 cells, while the viability of HEK293 (normal) cells in the presence of Ru-2 was higher as compared to a reference drug 5FU. We suggest that these kinds of Ru-complexes could have potential for application in metallopharmaceuticals.

Inhibitory effect of selected Indian honey on colon cancer cell growth by inducing apoptosis and targeting the ß-catenin/Wnt pathway.

Colon cancer is the most prevalent cause of death from cancer across the globe. Although chemotherapy drugs are predominantly used, their toxicity always remains a cause of concern. As an alternative to synthetic drugs, natural compounds or nutraceuticals are comparatively less toxic. Honey is widely used across different cultures as an alternative form of medicine. It represents a prominent source of plant-phenolic compounds and there is demonstrable evidence of its anti-oxidant and anti-microbial activities. The aim of the present work was to investigate the anti-proliferative effect of some Indian honeys and analyze their mechanism of action in colon cancer. In order to establish the composition-activity relationship, we evaluated the bioactive components present in selected honey samples by GC-MS and HPLC analysis. Indian honey samples showed a significant inhibitory impact on cell growth by restricting cell proliferation, causing apoptosis, and restricting the cell cycle in the G2/M phase specifically for colon cancer cells. The apoptotic activities, as imparted by the honey samples, were established by Annexin V/PI staining, real-time PCR, and immunoblot analyses. The treated cells showed increased expressions of p53 and caspases 3, 8, and 9, thus indicating the involvement of both extrinsic and intrinsic apoptotic pathways. The honey samples were also found to inhibit the ß-catenin/Wnt pathway. In the next phase of the study, the efficacy of these honey samples was evaluated in colon carcinoma induced SD-rats. Overall, these findings demonstrated that selected Indian honeys could be established as effective nutraceuticals for the prevention as well as cure of colon cancer.