Aim: The present work describes the development of poly(lactic co-glycolic acid) (PLGA) nanoparticles (NPs) of rutin (RT) for the treatment of hepatocellular carcinoma in rats. Materials & methods: RT-loaded PLGA NPs (RT-PLGA-NPs) were prepared by double emulsion evaporation method. Further these are optimized by Box–Behnken design. PLGA NPs were evaluated for size, polydispersity index, drug-loading capacity, entrapment, gastric stability, in vitro drug release, in vivo preclinical studies and biochemical studies. Results: Preclinical evaluation of RT-PLGA-NPs for anticancer activity through oral route exhibited significant improvement in hepatic, hematologic and renal biochemical parameters. Highly superior activity was observed in regulating oxidative stress and inflammatory markers, antioxidant enzymes, cytokines and inflammatory mediators and their role on plasma membrane ATPases responsible for destruction in liver tissues. Conclusion: Histopathological evaluation indicated reduced incidence of hepa...

Dacarbazine (DZ) is poorly soluble in water with the short half-life in blood circulation, low rate of response with the toxic effect which ultimately limits its utilization of the treatment of skin cancer. In view of this background current study was designed for development of dacarbazine laden nanoparticle (DZNP) and dacarbazine laden nanocream (DZNC) topical delivery system for the treatment of melanoma. Firstly DZNP was prepared. By using DZNP its cream formulation prepared for topic drug delivery for melanoma. Dacarbazine nanoparticle and its cream were evaluated for morphology, drug load capacity, efficiency of nanoencapsulation and size of particle and zeta potential, Transmission Electron Microscopy (TEM), determination of pH, spreadability and viscosity, in vitro drug release capacity and its cytotoxic potential. The particle size of DZNP and DZNC was 16.3 ± 8.1 nm and 16.9 ± 7.8 nm respectively. pH value and spreadability of nanoparticle cream were found to be 6.7 ± 0.14 g cm/sec and 55.23 ± 3.13 g cm/sec respectively. Nanoencapsulation efficiency and Drug loading capacity were 67.4 ± 3.5% and 6.73 mg/10 mg respectively. IC50 of dacarbazine nanoparticle was 0.19 mg/ml while it was 0.63 mg/ml for nanoparticle cream. It can be concluded that DZNP and its cream can be effectively used as a topical formulation for the treatment of melanoma.

Objective: Alzheimer's disease (AD) is a devastating neurodegenerative disorder, characterized by the extracellular accumulations of amyloid beta (Aβ) as senile plaques and intracellular aggregations of tau in the form of neurofibrillary tangles (NFTs) in specific brain regions. In this review, we focus on the interaction of Aβ and tau with cytosolic proteins and several cell organelles as well as associated neurotoxicity in AD. Summary: Misfolded proteins present in cells accompanied by correctly folded, intermediately folded, as well as unfolded species. Misfolded proteins can be degraded or refolded properly with the aid of chaperone proteins, which are playing a pivotal role in protein folding, trafficking as well as intermediate stabilization in healthy cells. The continuous aggregation of misfolded proteins in the absence of their proper clearance could result in amyloid disease including AD. The neuropathological changes of AD brain include the atypical cellular accumulation of misfolded proteins as well as the loss of neurons and synapses in the cerebral cortex and certain subcortical regions. The mechanism of neurodegeneration in AD that leads to severe neuronal cell death and memory dysfunctions is not completely understood until now. Conclusion: Examining the impact, as well as the consequences of protein misfolding, could help to uncover the molecular etiologies behind the complicated AD pathogenesis.

Nuclear Factor-κappa B (NF-κB) is a family of critical transcription factors of the inflammatory pathway and plays an imperative role in the progression of various cancers such as breast, lung, liver, pancreatic, prostate and multiple types of lymphoma. NF- κB develops an inherent relationship between inflammation and cancer. It is a crucial factor that controls the ability of malignant and pre-neoplastic cells to prevent programmed cell death-based tumor-surveillance channels. Due to its high significance in the onset and progression of various cancers, it has become an excellent target for cancer therapy. The emerging targeted therapies provide a lot of hope, whereby a single protein or generally the target enzyme is completely blocked. Several natural compounds have shown anticancer and anti-inflammatory activities by inhibiting the NF-κB pathway in various cancer types. About 750 natural and synthetic inhibitors of the NF-κB have been reported. These inhibitors include microbial and viral proteins, small RNA/DNA, antioxidants, small molecules, peptides, and engineered constitutively active polypeptides, all of which may inhibit canonical and alternative NF-κB pathways. Thus, blocking or targeting the NF-κB-signaling pathways using natural and synthetic compounds could be a potential mechanism to cure the NF-κB induced tumors.

Several proteolytic systems including ubiquitin (Ub)-proteasome system (UPS), chaperonemediated autophagy (CMA), and macroautophagy are used by the mammalian cells to remove misfolded proteins (MPs). UPS mediates degradation of most of the MPs, where Ub-conjugated substrates are deubiquitinated, unfolded, and passed through the proteasome’s narrow chamber, and eventually break into smaller peptides. It has been observed that the substrates that show a specific degradation signal, the KFERQ sequence motif, can be delivered to and go through CMA-mediated degradation in lysosomes. Macroautophagy can help in the degradation of substrates that are prone to aggregation and resistant to both the CMA and UPS. In the aforesaid case, cargoes are separated into autophagosomes before lysosomal hydrolase-mediated degradation. Even though the majority of the aggregated and MPs in the human proteome can be removed via cellular protein quality control (PQC), some mutant and native proteins tend to aggregate into β-sheet-rich oligomers that exhibit resistance to all identified proteolytic processes and can, therefore, grow into extracellular plaques or inclusion bodies. Indeed, the buildup of protease-resistant aggregated and MPs is a usual process underlying various protein misfolding disorders, including neurodegenerative diseases (NDs) for example Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and prion diseases. In this article, we have focused on the contribution of PQC in the degradation of pathogenic proteins in NDs.