Protein arginine methyltransferase 1, a major regulator of biological processes.

Protein arginine methyltransferase 1 (PRMT1) is a major type I arginine methyltransferase that catalyzes the formation of monomethyl and asymmetric dimethylarginine in protein substrates. It was first identified to asymmetrically methylate histone H4 at the third arginine residue forming the H4R3me2a active histone mark. However, several protein substrates are now identified as being methylated by PRMT1.

Directional preference for glioblastoma cancer cell membrane encapsulated nanoparticle population: A probabilistic approach for cancer therapeutics.

Background: Selective cancer cell recognition is the most challenging objective in the targeted delivery of anti-cancer agents. Extruded specific cancer cell membrane coated nanoparticles, exploiting the potential of homotypic binding along with certain protein-receptor interactions, have recently proven to be the method of choice for targeted delivery of anti-cancer drugs. Prediction of the selective targeting efficiency of the cancer cell membrane encapsulated nanoparticles (CCMEN) is the most critical aspect in selecting this strategy as a method of delivery.

Combinational therapeutics to combat cancer.

Mono-therapeutics is rarely effective as a treatment option, which limits the survival of patients in advanced grade aggressive cancers. Combinational therapeutics (multiple drugs for multiple targets) to combat cancer is gaining momentum in recent years. Hence, it is of interest to document known data for combinational therapeutics in cancer treatment.

Biologically Active α-Amino Amide Analogs and γδ T Cells-A Unique Anticancer Approach for Leukemia.

Advanced stage cancers are aggressive and difficult to treat with mono-therapeutics, substantially decreasing patient survival rates. Hence, there is an urgent need to develop unique therapeutic approaches to treat cancer with superior potency and efficacy. This study investigates a new approach to develop a potent combinational therapy to treat advanced stage leukemia.

Optimization of methods for peripheral blood mononuclear cells isolation and expansion of human gamma delta T cells.

Human Vg9/Vδ2 T cells (γδ T cells) are immune surveillance cells both in innate and adaptive immunity and are a possible target for anticancer therapies, which can induce immune responses in a variety of cancers. Small non-peptide antigens such as zoledronate can do activation and expansion of T cells in vitro. It is evident that for adoptive cancer therapies, large numbers of functional cells are needed into cancer patients.

Insights into Multifunctional Nanoparticle-Based Drug Delivery Systems for Glioblastoma Treatment.

Glioblastoma (GB) is an aggressive cancer with high microvascular proliferation, resulting in accelerated invasion and diffused infiltration into the surrounding brain tissues with very low survival rates. Treatment options are often multimodal, such as surgical resection with concurrent radiotherapy and chemotherapy. The development of resistance of tumor cells to radiation in the areas of hypoxia decreases the efficiency of such treatments.

New Framework for the Discovery of PRC2 Inhibitors: Epigenetic Drugs.

Over the past several years, remarkable progress towards the recognition of new therapeutic targets in tumor cells has led to the discovery and development of newer scaffolds of anti-tumor drugs. The exploration and exploitation of epigenetic regulation in tumor cells are of immense importance to both the pharmaceutical and academic biomedical literatures. Epigenetic mechanisms are indispensable for the normal development and maintenance of tissue-specific gene expression.

DNA methylation inhibition in myeloma: Experience from a phase 1b study of low-dose continuous azacitidine in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma.

The DNA methyltransferase inhibitor azacytidine (aza) may reactivate pathways associated with plasma cell differentiation, cell cycle control, apoptosis, and immune recognition and thereby restore sensitivity to lenalidomide (len) and dexamethasone (dex) in relapsed and/or refractory multiple myeloma (RRMM). We aimed to develop an aza regimen that reaches epigenetically active levels 8 times in 28 days with less bone marrow toxicity than the myeloid malignancy standard of 7 consecutive doses to enable safe combination with len. Aza was escalated from 30 mg/m once a week up to a predefined maximum of 50 mg/m twice a week in combination with GFR-adjusted len (≥ 60 mL/min: 25 mg, 3059 mL/min: 10 mg) day 1 to 21 every 28 days and dex 40 mg once a week followed by a limited expansion study to a total N of 23 at the highest tolerated dose.

Glycation and Oxidative Stress Increase Autoantibodies in the Elderly.

Aging causes gradual changes in free radicals, antioxidants, and immune-imbalance in the elderly. This study aims to understand links among aging, gluco-oxidative stress, and autoantibodies in asymptomatic individuals. In vitro glycation of human serum albumin (Gly-HSA) induces appreciable biochemical changes.

Synergistic fungicidal activity with low doses of eugenol and amphotericin B against Candida albicans.

Candida albicans frequently causes variety of superficial and invasive disseminated infections in HIV infected patients. Further, the emergence of non albicans species causing candidiasis predominantly in patients with advanced immune-suppression and drug resistance brings great apprehension. Hence, in this study we evaluate the capability of eugenol (EUG), a natural compound in combination with less toxic concentrations of amphotericin B (AmpB) for enhanced antifungal effects and reduced toxicity.

Polycomb repressive complex 2 inhibitors: emerging epigenetic modulators.

Polycomb repressive complex 2 (PRC2) plays a significant part in histone methylation - trimethylating K27 at H3, an epigenetic hallmark of gene silencing. Inhibition of PRC2 has been reported as a promising strategy for the treatment of various cancers. Significant efforts have been made toward the development of PRC2 inhibitors and some of them have progressed to clinical trials.

Understanding the mode of binding mechanism of doripenem to human serum albumin: Spectroscopic and molecular docking approaches.

The infections caused by multidrug resistant bacteria are widely treated with carabapenem antibiotics as a drug of choice, and human serum albumin (HSA) plays a vital role in binding with drugs and affecting its rate of delivery and efficacy. So, we have initiated this study to characterize the mechanism of doripenem binding and to locate its site of binding on HSA by using spectroscopic and docking approaches. The binding of doripenem leads to alteration of the environment surrounding Trp-214 residue of HSA as observed by UV spectroscopic study.

Sulfaguanidine cocrystals: Synthesis, structural characterization and their antibacterial and hemolytic analysis.

Sulfaguanidine (SG), belongs to the class of sulfonamide drug used as an effective antibiotic. In the present work, using crystal engineering approach two novel cocrystals of SG were synthesized (SG-TBA and SG-PT) with thiobarbutaric acid (TBA) and 1,10-phenanthroline (PT), characterized by solid state techniques viz., powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and the crystal structures were determined by single crystal X-ray diffraction studies.

Enhanced Killing and Antibiofilm Activity of Encapsulated Cinnamaldehyde against .

sp. impelled opportunistic infection in immune-compromised patients ensuing from asymptomatic colonization to pathogenic forms. Moreover, slow spread of species inducing refractory mucosal and invasive infections brings acute resistance to antifungal drugs.

Photoinactivation of multidrug resistant bacteria by monomeric methylene blue conjugated gold nanoparticles.

Multidrug resistant (MDR) bacterial infections have become a severe threat to the community health due to a progressive rise in antibiotic resistance. Nanoparticle-based photodynamic therapy (PDT) is increasingly been adopted as a potential antimicrobial option, yet the cytotoxicity associated with PDT is quite unspecific. Herein, we show Concanavalin-A (ConA) directed dextran capped gold nanoparticles (GNP-ConA) enhanced the efficacy and selectivity of methylene blue (MB) induced killing of multidrug resistant clinical isolates.

Anthelmintic Potential of Thymoquinone and Curcumin on Fasciola gigantica.

Fasciolosis an economically important global disease of ruminants in the temperate and tropical regions, caused by Fasciola hepatica and F. gigantica, respectively, also poses a potential zoonotic threat. In India alone it causes huge losses to stakeholders.

Breaking the Spell: Combating Multidrug Resistant 'Superbugs'.

Multidrug-resistant (MDR) bacteria have become a severe threat to community wellbeing. Conventional antibiotics are getting progressively more ineffective as a consequence of resistance, making it imperative to realize improved antimicrobial options. In this review we emphasized the microorganisms primarily reported of being resistance, referred as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacteriaceae) accentuating their capacity to "escape" from routine antimicrobial regimes.

Myeloma is characterized by stage-specific alterations in DNA methylation that occur early during myelomagenesis.

Epigenetic changes play important roles in carcinogenesis and influence initial steps in neoplastic transformation by altering genome stability and regulating gene expression. To characterize epigenomic changes during the transformation of normal plasma cells to myeloma, we modified the HpaII tiny fragment enrichment by ligation-mediated PCR assay to work with small numbers of purified primary marrow plasma cells. The nano-HpaII tiny fragment enrichment by ligation-mediated PCR assay was used to analyze the methylome of CD138(+) cells from 56 subjects representing premalignant (monoclonal gammopathy of uncertain significance), early, and advanced stages of myeloma, as well as healthy controls.

Inhibition of N-terminal lysines acetylation and transcription factor assembly by epirubicin induced deranged cell homeostasis.

Epirubicin (EPI), an anthracycline antitumour antibiotic, is a known intercalating and DNA damaging agent. Here, we study the molecular interaction of EPI with histones and other cellular targets. EPI binding with histone core protein was predicted with spectroscopic and computational techniques.

Direct chromatin PCR (DC-PCR): hypotonic conditions allow differentiation of chromatin states during thermal cycling.

Current methods to study chromatin configuration are not well suited for high throughput drug screening since they require large cell numbers and multiple experimental steps that include centrifugation for isolation of nuclei or DNA. Here we show that site specific chromatin analysis can be achieved in one step by simply performing direct chromatin PCR (DC-PCR) on cells. The basic underlying observation was that standard hypotonic PCR buffers prevent global cellular chromatin solubilization during thermal cycling while more loosely organized chromatin can be amplified.

A proteomic approach for exploring biofilm in Streptococcus mutans.

Biofilm formation by Streptococcus mutans is considered as its principal virulence factor, causing dental caries. Mutants of S. mutans defective in biofilm formation were generated and analyzed to study the collective role of proteins in its formation.

Mitoxantrone induced impediment of histone acetylation and structural flexibility of the protein.

Mitoxantrone (MTX), a choice of drug in cancer chemotherapeutic regime, is a potent and less toxic among anthracycline class of drugs. Here, we study the molecular interaction of MTX, with histone and its acetylation dynamics. Its binding with histone core protein was predicted with CD and UV-visible spectroscopic techniques.

Synthesis and spectroscopic studies on the Schiff base ligand derived from condensation of 2-furaldehyde and 3,3'-diaminobenzidene, L and its complexes with Co(II), Ni(II), Cu(II) and Zn(II): comparative DNA binding studies of L and its Cu(II) and Zn(II) complexes.

The Schiff base ligand, N,N'-bis-(2-furancarboxaldimine)-3,3'-diaminobenzidene (L) obtained by condensation of 2-furaldehyde and 3,3'-diaminobenzidene, was used to synthesize the mononuclear complexes of the type, [M(L)](NO3)2 [M=Co(II), Ni(II), Cu(II) and Zn(II)]. The newly synthesized ligand, (L) and its complexes have been characterized on the basis of the results of the elemental analysis, molar conductance, magnetic susceptibility measurements and spectroscopic studies viz, FT-IR, 1H and 13C NMR, mass, UV-vis and EPR. EPR, UV-vis and magnetic moment data revealed a square planar geometry for the complexes with distortion in Cu(II) complex and conductivity data show a 1:2 electrolytic nature of the complexes.

Role of histone acetylation in cell physiology and diseases: An update.

Although the role of histone acetylation in gene regulation has been the subject of many reviews, their impact on cell physiology and pathological states of proliferation, differentiation and genome stability in eukaryotic cells remain to be elucidated. Therefore, this review will discuss the molecular, physiological and biochemical aspects of histone acetylation and focus on the interplay of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in different disease states. Current treatment strategies are mostly limited to enzyme inhibitors, though potential lies in targeting other imperative chromatin remodeling factors involved in gene regulation.