βhCG mediates immune suppression through upregulation of CD11b Gr1 myeloid derived suppressor cells, CD206 M2 macrophages, and CD4 FOXP3 regulatory T-cells in BRCA1 deficient breast cancers.

BRCA1 mutation is reported in about 70% of all triple negative breast cancers (TNBC), while BRCA1 defect due to promoter hypermethylation is seen in about 30%-60% of sporadic breast cancers. Although PARP inhibitors and platinum-based chemotherapy are used to treat these cancers, more efficient therapeutic approaches are required to overcome the resistance to treatment. Our previous findings have reported elevated βhCG expression but not αhCG in BRCA1 deficient breast cancers.

The effect of metallic dental restorations and implants in causing patient discomfort and artefacts during magnetic resonance imaging of the head and neck.

Context: Patients with metallic dental objects in their oral cavity are often associated with discomfort or artefacts during magnetic resonance imaging (MRI) of the head and neck.

Aim: This study was conducted to evaluate the effects of metallic dental objects in causing patient discomfort and artefacts during MRI of the head and neck region.

Design: This is an observational study including 538 participants from various specialized MRI centres in Kozhikode.

Retention Strength of Zirconia Crowns Cemented onto PEEK Abutments Using Two Different Types of Resin Cement With or Without Primer Application-An In Vitro Study.

Purpose: To evaluate the retention of zirconia crowns on polyetheretherketone (PEEK) abutments using different luting agents, with and without PEEK primer.

Materials And Methods: A total of 100 PEEK abutment replicas were fabricated, airborne particle-abraded with aluminum oxide, and divided into four groups (n = 25). A total of 100 zirconia crowns were fabricated and cemented using either adhesive resin cement or self-adhesive resin cement with and without PEEK primer; thus, the groups were: group AA-P (adhesive cement with primer); group AA-N (adhesive cement without primer); group SA-P (self-adhesive cement with primer); and group SA-N (self-adhesive cement without primer).

Modulation of BRCA1 mediated DNA damage repair by deregulated ER-α signaling in breast cancers.

BRCA1 mutation carriers have a greater risk of developing cancers in hormone-responsive tissues like breasts and ovaries. However, this tissue-specific incidence of BRCA1 related cancers remains elusive. The majority of the BRCA1 mutated breast cancers exhibit typical histopathological features of high-grade tumors, with basal epithelial phenotype, classified as triple-negative molecular subtype and have a higher percentage of DNA damage and chromosomal abnormality.

Exploration of novel TOSMIC tethered imidazo[1,2-a]pyridine compounds for the development of potential antifungal drug candidate.

New candidates of imidazo[1,2-a]pyridine were designed by combining 2-amino pyridine, TOSMIC and various assorted aldehydes to explore their antioxidant and antifungal potential. The design of these derivatives was based on utilizing the antifungal potential of azoles and TOSMIC moiety. These derivatives were synthesized by adopting multi-component reaction methodology, as it serves as a rapid and efficient tool to target structurally diverse heterocyclic compounds in quantitative yield.

Randomized clinical trial of zirconia and polyetheretherketone implant abutments for single-tooth implant restorations: A 5-year evaluation.

Statement Of Problem: Titanium-supported polyetheretherketone (PEEK) abutments provide an economic alternative to zirconia abutments in esthetically important areas. Research comparing the performance regarding esthetics, longevity, and biologic parameters of PEEK abutments is lacking.

Purpose: The purpose of this clinical study was to determine whether PEEK implant abutments provide similar esthetic and biologic parameters and survival rates as zirconia implant abutments.

Calcium alginate nanoparticle crosslinked phosphorylated polyallylamine to the controlled release of clindamycin for osteomyelitis treatment.

Osteomyelitis is one of the infections of the bone, and the treatment needs to the infection problems. Here, a local therapeutic approach for efficient drug delivery systems was designed to enhance the antibiotic drug's therapeutic activity. Calcium-Alginate nanoparticle (Ca-Alg) crosslinked phosphorylated polyallylamine (PPAA) was prepared through the salting-out technique, and it achieved 82.

Deregulated estrogen receptor signaling and DNA damage response in breast tumorigenesis.

Carriers of BRCA1 mutations have a higher chance of developing cancers in hormone-responsive tissues like the breast, ovary and prostate, compared to other tissues. These tumors generally exhibit basal-like characters and do not express estrogen receptor (ER) or progesterone receptor (PR). Intriguingly, BRCA1 mutated breast cancers have a less favorable clinical outcome, as they will not respond to hormone therapy.

Gene expression signatures: A tool for analysis of breast cancer prognosis and therapy.

Breast Cancer is the most predominant female cancer in developed as well as developing countries. The treatment strategies of breast cancers depends on an array of factors like age at diagnosis, menstrual status, dietary pattern, immunological response, genetic variations of the cancer cells etc. Recent technological advancements in cancer diagnosis lead to the emergence of gene expression pattern for better understanding of the tumor behavior.

BRCA1 promoter hypermethylation in human placenta: a hidden link with β-hCG expression.

Gestational trophoblastic diseases (GTD) are group of pregnancy-related tumors characterized by abnormal levels of 'β-hCG' with higher incidence in South-East Asia, especially India. Our laboratory has reported that wild-type BRCA1 transcriptionally regulates β-hCG in triple negative breast cancers (TNBCs). These factors culminated into analysis of BRCA1 status in GTD, which would emanate into elucidation of BRCA1- β-hCG relationship and unraveling etio-pathology of GTD.

Brcal Defective Breast Cancer Cells Induce in vitro Transformation of Cancer Associated Fibroblasts (CAFs) to Metastasis Associated Fibroblasts (MAF).

It is known that Cancer Associated Fibroblast (CAFs) from the primary tumor site can accompany cancer cells to a secondary site during the process of metastasis. We hypothesize that these CAFs could be transformed to an altered cell type, which can be called as Metastasis Associated Fibroblasts (MAF) in turn can support, and convoy cancer cells for metastasis. There are no published reports that have characterized and distinguished CAFs from MAF.

Stimulus-responsive zinc oxide-functionalized macromolecular humic acid nanocarrier for enhancement of antibacterial activity of ciprofloxacin hydrochloride.

Macromolecular of naturally occurring humic acid (HA) have garnered interest in the chemical, biological and medicine industry owing to their unique behavior, i.e., strong adsorptive and non-toxic nature.

BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer.

Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer.

Data on overlapping brain disorders and emerging drug targets in human Dopamine Receptors Interaction Network.

Intercommunication of Dopamine Receptors (DRs) with their associate protein partners is crucial to maintain regular brain function in human. Majority of the brain disorders arise due to malfunctioning of such communication process. Hence, contributions of genetic factors, as well as phenotypic indications for various neurological and psychiatric disorders are often attributed as sharing in nature.

CD4-gp120 interaction interface - a gateway for HIV-1 infection in human: molecular network, modeling and docking studies.

The major causative agent for Acquired Immune Deficiency Syndrome (AIDS) is Human Immunodeficiency Virus-1 (HIV-1). HIV-1 is a predominant subtype of HIV which counts on human cellular mechanism virtually in every aspect of its life cycle. Binding of viral envelope glycoprotein-gp120 with human cell surface CD4 receptor triggers the early infection stage of HIV-1.

Investigating the structural impact of S311C mutation in DRD2 receptor by molecular dynamics & docking studies.

Dopamine receptors (DR) are neuronal cell surface proteins that mediate the action of neurotransmitter dopamine in brain. Dopamine receptor D2 (DRD2) that belongs to G-protein coupled receptors (GPCR) family is a major therapeutic target for of various neurological and psychiatric disorders in human. The third inter cellular loop (ICL3) in DRD2 is essential for coupling G proteins and several signaling scaffold proteins.

Structural signatures of DRD4 mutants revealed using molecular dynamics simulations: Implications for drug targeting.

Human Dopamine Receptor D4 (DRD4) orchestrates several neurological functions and represents a target for many psychological disorders. Here, we examined two rare variants in DRD4; V194G and R237L, which elicit functional alterations leading to disruption of ligand binding and G protein coupling, respectively. Using atomistic molecular dynamics (MD) simulations, we provide in-depth analysis to reveal structural signatures of wild and mutant complexes with their bound agonist and antagonist ligands.

Hydroxyethylamine Based Phthalimides as New Class of Plasmepsin Hits: Design, Synthesis and Antimalarial Evaluation.

A novel class of phthalimides functionalized with privileged scaffolds was designed, synthesized and evaluated as potential inhibitors of plasmepsin 2 (Ki: 0.99 ± 0.1 μM for 6u) and plasmepsin 4 (Ki: 3.

Decentralization and decision space in the health sector: a case study from Karnataka, India.

Various attempts have been made in India with respect to decentralization, most significantly the 73rd Amendment to the Constitution of India (1993) which provided the necessary legal framework for decentralization to take place. However, the outcome has been mixed: an evaluation of the impact of decentralization in the health sector found virtually no change in health system performance and access to health services in terms of availability of health personnel or improvement in various health indicators, such as Infant Mortality Rates or Maternal Mortality Ratio. Subsequently, there has been a conscious effort under the National Rural Health Mission (NRHM)-launched in 2005-to promote decentralization of funds, functions and functionaries to lower levels of government; and Karnataka had a head-start since devolution of all 29 functions prescribed by the 73rd Amendment had already taken place in the state by the late 1990s.

Design, synthesis and biological evaluation of functionalized phthalimides: a new class of antimalarials and inhibitors of falcipain-2, a major hemoglobinase of malaria parasite.

Phthalimides functionalized with cyclic amines were synthesized, characterized and screened for their in vitro antimalarial efficacy against Plasmodium falciparum (Pf3D7). Of all the listed phthalimides evaluated, 14 and 24 were identified as potent antimalarial agents as advocated by assessment of their ability to inhibit [(3)H] hypoxanthine incorporation in the nucleic acid of parasites. In addition, phthalimides 14 and 24 were incubated for 60 and 90h and an enhanced antimalarial effect was noticed with increase in time to great extent.

New insights into schizophrenia disease genes interactome in the human brain: emerging targets and therapeutic implications in the postgenomics era.

Schizophrenia, a complex neurological disorder, is comprised of interactions between multiple genetic and environmental factors wherein each of the factors individually exhibits a small effect. In this regard a network-based strategy is best suited to capture the combined effect of multiple genes with their definite pattern of interactions. Given that schizophrenia affects multiple regions of the brain, we postulated that instead of any single specific tissue, a mutual set of interactions occurs between different regions of brain in a well-defined pattern responsible for the disease phenotype.

Structure and dynamics of DRD4 bound to an agonist and an antagonist using in silico approaches.

Human dopamine receptor D4 (DRD4), a member of G-protein coupled receptor (GPCR) family, plays a central role in cell signaling and trafficking. Dysfunctional activity of DRD4 can lead to several psychiatric conditions and, therefore, represents target for many neurological disorders. However, lack of atomic structure impairs our understanding of the mechanism regulating its activity.

Human Dopamine Receptors Interaction Network (DRIN): a systems biology perspective on topology, stability and functionality of the network.

Dopamine receptors (DR) are one of the major neurotransmitter receptors present in human brain. Malfunctioning of these receptors is well established to trigger many neurological and psychiatric disorders. Taking into consideration that proteins function collectively in a network for most of the biological processes, the present study is aimed to depict the interactions between all dopamine receptors following a systems biology approach.

(4'-Acet-yloxy-1,3,1'-trioxo-1,3,4,4a,4b,5,6,7,9,9a-deca-hydro-spiro-[indene-2,9'-pyrano[4,3-a]pyrrolizin]-3'-yl)methyl acetate.

In the title compound, C23H23NO8, the dihedral angle between the five- and six-membered rings of the indene-dione moiety is 3.09 (13)°. The mean plane of the five-membered ring (which has a flat envelope conformation with the spiro C atom as the flap) is inclined to the mean plane of the central five-membered ring of the pyrrolizine unit by 76.