Currently, the discovery of effective chemotherapeutic agents poses a major challenge to the field of cancer biology. The present study focuses on enhancing the therapeutic and anti cancer properties of atorvastatin calcium loaded BSA (ATV-BSA) nanoparticles in vitro.
BSA-ATV nanoparticles were prepared using desolvation technique. The process parameters were optimized based on the amount of desolvating agent, stabilization conditions as well as the concentration of the cross linker. The anti cancer properties of the protein coated ATV nanoparticles were tested on MiaPaCa-2 cell lines. In vitro release behavior of the drug from the carrier suggests that about 85% of the drug gets released after 72 hrs. Our studies show that ATV-BSA nanoparticles showed specific targeting and enhanced cytotoxicity to MiaPaCa-2 cells when compared to the bare ATV.
We hereby propose that the possible mechanism of cellular uptake of albumin bound ATV could be through caveolin mediated endocytosis. Hence our studies open up new facet for an existing cholesterol drug as a potent anti-cancer agent.
The efficient targeting and therapeutic efficacy of a combination of drugs (curcumin and 5-Fluorouracil [5FU]) and magnetic nanoparticles encapsulated poly(D,L-lactic-co-glycolic acid) nanoparticles, functionalized with two cancer-specific ligands are discussed in our work. This multifunctional, highly specific nanoconjugate resulted in the superior uptake of nanoparticles by cancer cells. Upon magnetic hyperthermia, we could harness the advantages of incorporating magnetic nanoparticles that synergistically acted with the drugs to destroy cancer cells within a very short period of time. The remarkable multimodal efficacy attained by this therapeutic nanoformulation offers the potential for targeting, imaging, and treatment of cancer within a short period of time (120 minutes) by initiating early and late apoptosis.
nanotechnology; curcumin; 5FU; folate; transferrin; PLGA nanoparticle; magnetic hyperthermia
Diabetes is the ninth leading cause of death in women globally. In South Asians mortality in women with diabetes stands second highest. There is a marked gender discrimination which is faced by women across South Asia esp in access to services and support for diabetes, resulting in high rates of morbidity and mortality in women with diabetes. The most important risk factor identified for the diabetes epidemic is obesity along with genetic susceptibility. Lack of health care, social and cultural disparity, discrimination at work, disparity in marriage, restricted medical facilities are prevalent. Diabetes and depression are common in women. Increasing age, low level of education, low socioeconomic conditions, difficulties posed in finding partners, frequent divorce and family history of psychiatric illness are significant risk factors for diabetes and depression. Such patients usually have poor metabolic control, higher complication rates, increased healthcare costs, lost productivity, lower quality of life as well as increased risk of death. Preconception counseling should be incorporated in the routine diabetes clinic visit for all women of childbearing potential. Women with diabetes should have information and access to contraception. Proper family planning counseling and psychological support can help stop practices such as female foeticide and multiple pregnancies. Psychological support to patients and their families are needed to break the barrier. There is emerging evidence that women with diabetes are more prone to untoward outcomes as compared to men. Central obesity, metabolic syndrome and the polycystic ovary syndrome show ethnic specific differences in South Asian women. Optimal sexuality is an integral part of holistic health. Shortage of trained female health care professionals, lack of privacy in over-crowded health care facilities, a social taboo attached to such matters, and lack of confidence in patients contribute to the neglect of sexual issues in women attending diabetes clinics across South Asia. Guidelines for counselling in female sexual dysfunction, written in culturally appropriate manner for South Asia, are needed. Diabetes affects women more severely because of their unique biological, cultural and socioeconomic circumstances. Women have limited access to health care facilities because of illiteracy, ignorance and negative social customs. Transcending the gender hierarchy and inequality is a formidable challenge. Sensitising men, empowering women on self care and providing peer support maybe the answer to this challenge. It is essential for health care providers to use appropriate coping mechanism such as building psychological contact with the patient, including family and friends as part of social support and empower patient with complete process of managing diabetes. Increasing awareness through the media, seminars, posters, group discussions and education, regular monitoring and consulting the doctor, support group for women and facilities for aerobic exercises are recommended. The health care systems should consider custom-designed prevention and control programs tailored for women based on local and regional attitudes on health care, cultural beliefs, and available social support systems. Policies that empower adolescent girls and young women to take control of their metabolic management must be encouraged. Provision of gender specific diabetes education with a holistic life-cycle approach is recommended.
South Asian region; Women with diabetes; gender disparity; health care access; social & cultural factors; Women empowerment
Though pericardial disease is common in patients with renal disease, purulent pericarditis is very rare. We report a fatal case of purulent pericarditis and sepsis due to methicillin-resistant Staphylococcus aureus in a 78-year-old male with systemic hypertension and renal disease along with the molecular characterization of its resistant mechanism.
Methicillin-resistant Staphylococcus aureus; multi-drug resistant; purulent pericarditis
In the face of chronic and emerging resistance of parasites to currently available drugs and constant need for new anti-malarials, natural plant products have been the bastion of anti-malarials for thousands of years. Moreover natural plant products and their derivatives have traditionally been a common source of drugs, and represent more than 30% of the current pharmaceutical market. The present study shows evaluation of anti-malarial effects of compound conessine isolated from plant Holarrhena antidysenterica frequently used against malaria in the Garhwal region of north-west Himalaya.
In vitro anti-plasmodial activity of compound was assessed using schizont maturation and parasite lactate dehydrogenase (pLDH) assay. Cytotoxic activities of the examined compound were determined on L-6 cells of rat skeletal muscle myoblast. The four-day test for anti-malarial activity against a chloroquine-sensitive Plasmodium berghei NK65 strain in BALB/c mice was used for monitoring in vivo activity of compound. In liver and kidney function test, the activity of alkaline phosphatase (ALP) was examined by p-NPP method, bilirubin by Jendrassik and Grof method. The urea percentage was determined by modified Berthelot method and creatinine by alkaline picrate method in serum of mice using ENZOPAK/CHEMPAK reagent kits.
Compound conessine showed in vitro anti-plasmodial activity with its IC50 value 1.9 μg/ml and 1.3 μg/ml using schizont maturation and pLDH assay respectively. The compound showed cytotoxity IC50= 14 μg/ml against L6 cells of rat skeletal muscle myoblast. The isolated compound from plant H. antidysenterica significantly reduced parasitaemia (at 10 mg/kg exhibited 88.95% parasite inhibition) in P. berghei-infected mice. Due to slightly toxic nature (cytotoxicity = 14), biochemical analysis (liver and kidney function test) of the serum from mice after administration of conessine were also observed.
The present investigation demonstrates that the compound conessine exhibited substantial anti-malarial property. The isolated compound could be chemically modified to obtain a more potent chemical entity with improved characteristics against malaria.
Endophytes, by residing within the specific chemical environment of host plants, form unique group of microorganisms. Microbially unexplored medicinal plants can have diverse and potential microbial association. The rhizome of ginger is very remarkable because of its metabolite richness, but the physiological processes in these tissues and the functional role of associated microorganisms remain totally unexplored. Through the current study, the presence of four different endophytic bacterial strains were identified from ginger rhizome. Among the various isolates, ZoB2 which is identified as Pseudomonas sp. was found to have the ability to produce IAA, ACC deaminase and siderophore. By considering these plant growth promoting properties, ZoB5 can expect to have considerable effect on the growth of ginger.
Endophytic bacteria; Indole 3 acetic acid; HPLC; Pseudomonas sp.; 16S rDNA sequencing
Comparison of the expression of 13 genes involved in arbuscular mycorrhizal (AM) symbiosis was performed in a wild type tomato (Solanum lycopersicum cv 76R) and its reduced mycorrhizal colonization mutant rmc in response to colonization with Glomus fasiculatum. Four defense-related genes were induced to a similar extent in the mutant and wild type AM colonized plants, indicating a systemic response to AM colonization. Genes related to nutrient exchange between the symbiont partners showed higher expression in the AM roots of wild type plants than the mutant plants, which correlated with their arbuscular frequency. A symbiosis receptor kinase that is involved in both nodulation and AM symbiosis was not expressed in the rmc mutant. The fact that some colonization was observed in rmc was suggestive of the existence of an alternate colonization signaling pathway for AM symbiosis in this mutant.
AM colonization; defense genes; nutrient exchange genes; reduced mycorrhizal colonization (rmc) tomato mutant; SYMRK
Although several evidence-based guidelines for managing diabetes are available, few, if any, focus on the psychosocial aspects of this challenging condition. It is increasingly evident that psychosocial treatment is integral to a holistic approach of managing diabetes; it forms the key to realizing appropriate biomedical outcomes. Dearth of attention is as much due to lack of awareness as due to lack of guidelines. This lacuna results in diversity among the standards of clinical practice, which, in India, is also due to the size and complexity of psychosocial care itself. This article aims to highlight evidence- and experience-based Indian guidelines for the psychosocial management of diabetes. A systemic literature was conducted for peer-reviewed studies and publications covering psychosocial aspects in diabetes. Recommendations are classified into three domains: General, psychological and social, and graded by the weight they should have in clinical practice and by the degree of support from the literature. Ninety-four recommendations of varying strength are made to help professionals identify the psychosocial interventions needed to support patients and their families and explore their role in devising support strategies. They also aid in developing core skills needed for effective diabetes management. These recommendations provide practical guidelines to fulfill unmet needs in diabetes management, and help achieve a qualitative improvement in the way physicians manage patients. The guidelines, while maintaining an India-specific character, have global relevance, which is bound to grow as the diabetes pandemic throws up new challenges.
Diabetes; India; management; psychosocial; recommendations
The prevalence of Diabetes is projected to increase to 80 million by 2030, placing an immense burden on the health care resources of our country. Thus, diabetes poses a challenge to health systems and the individual. Hence, it is necessary to look at adjuncts to effective management of Diabetes; adjuncts which are not resource intensive and are nearer to the community that people live in. Yoga holds promise as a therapeutic intervention and health promotion measure. This brief communication explores the studies done to date on the beneficial effects of Yoga on Diabetes.
Diabetes; adjuncts; Yoga
Segmental necrotizing granulomatous neuritis (SNGN) is a rare condition affecting the nerves of Hansen disease patients. This is usually seen as a complication in association with the skin lesions of Hansen disease. Though very rare, it can also be the first presenting symptom of pure neuritic leprosy. We hereby report 2 cases of SNGN—one case of pure neuritic leprosy with initial presentation as SNGN and another, a treated case of borderline tuberculoid leprosy which relapsed with skin lesions and associated SNGN in the peripheral nerve.
The spectrum of vascular lesions developing in breast or chest wall skin following lumpectomy or mastectomy and radiation is wide and ranges from atypical vascular lesions with a benign clinical behaviour to frankly malignant, angiosarcoma ranging histologically from well to poorly differentiated variety. Postmastectomy-postirradiation atypical vascular lesions (AVLs) are rare and develop in the skin adjacent to the mastectomy scar. About hundred cases have been reported in the literature so far. AVLs have also been reported in patients after breast conservation surgery within the breast parenchyma or in the skin around the scar. The incidence appears to be rising. The exact reason for this is not known. The newer modalities of radiation therapy may be contributory to the pathogenesis. More studies have to be done in this area to prove the causal relationship. We are reporting the cases of 2 patients with carcinoma of breast who developed postmastectomy-postirradiation atypical vascular lesions. The cases were received in our department within a 6-month period.
Background & objectives:
Cervical cancer has a major impact on woman's lives worldwide and one in every five women suffering from cervical cancer belongs to India. Hence the objectives of this study were to find the knowledge of women regarding cervical cancer, to determine screening practices and determinants, and to identify factors for non screening.
A cross-sectional study was conducted in Vypin Block of Ernakulam District, Kerala, India where four of the seven Panchayats were randomly chosen. Households were selected by systematic random sampling taking every second house in the tenth ward of the Panchayat till at least 200 women were interviewed. Thus, 809 women were interviewed from four Panchayats.
Mean age of the study population was 34.5 + 9.23 yr. Three fourths of the population (74.2%) knew that cervical cancer could be detected early by a screening test. Majority of respondents (89.2%) did not know any risk factor for cervical cancer. Of the 809 women studied, only 6.9 per cent had undergone screening. One third of the population were desirous of undergoing screening test but had not done it due to various factors. These factors related to knowledge (51.4%) such as no symptoms, not being aware of Pap test, not necessary, etc. This was followed by resource factors (15.1%) like no time, no money, etc. and psychosocial factors (10.2%) included lack of interest, fear of procedure, etc. Independent predictors for doing Pap test included age >35, having knowledge of screening for cervical cancer and Pap test (P<0.05).
Interpretation & conclusions:
Specific knowledge on cervical cancer screening is a critical element in determining whether a woman will undergo Pap test in addition to making cancer screening facilities available in the primary health centre.
Cervical cancer; knowledge; practice; screening
Coryneform bacteria belonging to the genus Brevibacterium have emerged as opportunistic pathogens. Of the nine known species of Brevibacterium isolated from human clinical samples, Brevibacterium casei is the most frequently reported species from clinical specimens. We report the first case of B. casei brain abscess in an immunocompetent patient successfully treated by surgery and antimicrobial therapy.
We report the first whole-genome sequences for five strains, two carried and three pathogenic, of the emerging pathogen Haemophilus haemolyticus. Preliminary analyses indicate that these genome sequences encode markers that distinguish H. haemolyticus from its closest Haemophilus relatives and provide clues to the identity of its virulence factors.
A lot of research has been directed on wellbeing and disability in many non-communicable disease conditions. In this context, health-related aspects of life and quality of life (QOL) are receiving a lot of focus. Many Quality of Health measures are available, of which World Health Organization Quality of Life (WHOQOL-BREF) is one of the most popular. Translating and adapting this tool is useful in view of research happening in a multicultural arena. Though translations into Hindi and other Indian languages including Tamil and Kannada have been done, a Malayalam version is not available. This paper discusses the steps adopted in this exercise and the challenges in translating WHOQOL-BREF to Malayalam from the original English version.
Malayalam; quality of life; World Health Organization Quality of Life BREF
The Polycomb group (PcG) protein, enhancer of zeste homologue 2 (EZH2), has an essential role in promoting histone H3 lysine 27 trimethylation (H3K27me3) and epigenetic gene silencing1–4. This function of EZH2 is important for cell proliferation and inhibition of cell differentiation, and is implicated in cancer progression5–10. Here, we demonstrate that under physiological conditions, cyclin-dependent kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2) phosphorylate EZH2 at Thr 350 in an evolutionarily conserved motif. Phosphorylation of Thr 350 is important for recruitment of EZH2 and maintenance of H3K27me3 levels at EZH2-target loci. Blockage of Thr 350 phosphorylation not only diminishes the global effect of EZH2 on gene silencing, it also mitigates EZH2-mediated cell proliferation and migration. These results demonstrate that CDK-mediated phosphorylation is a key mechanism governing EZH2 function and that there is a link between the cell-cycle machinery and epigenetic gene silencing.
Design of blood compatible surfaces is required to minimize platelet surface interactions and increase the thromboresistance of foreign surfaces when they are used as biomaterials especially for artificial blood prostheses. In this study, single wall carbon nanotubes (SWCNTs) and Zein fibrous nanocomposite scaffolds were fabricated by electrospinning and evaluated its antithrombogenicity and hydrophilicity. The uniform and highly smooth nanofibers of Zein composited with different SWCNTs content (ranging from 0.2 wt% to 1 wt%) were successfully prepared by electrospinning method without the occurrence of bead defects. The resulting fiber diameters were in the range of 100–300 nm without any beads. Composite nanofibers with and without SWCNT were characterized through a variety of methods including scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, and tensile mechanical testing. The water uptake and retention ability of composite scaffolds decreased whereas thermal stability increased with an addition of SWCNTs. Hemolytic property and platelet adhesion ability of the nanocomposite (Zein-SWCNTs) were explored. These observations suggest that the novel Zein-SWCNTs composite scaffolds may possibly hold great promises as useful antithrombotic material and promising biomaterials for tissue engineering application.
GLUT4 is a predominant insulin regulated glucose transporter expressed in major glucose disposal tissues such as adipocytes and muscles. Under the unstimulated state, GLUT4 resides within intracellular vesicles. Various stimuli such as insulin translocate this protein to the plasma membrane for glucose transport. In the absence of a crystal structure for GLUT4, very little is known about the mechanism of glucose transport by this protein. Earlier we proposed a homology model for GLUT4 and performed a conventional molecular dynamics study revealing the conformational rearrangements during glucose and ATP binding. However, this study could not explain the transport of glucose through the permeation tunnel.
To elucidate the molecular mechanism of glucose transport and its energetic, a steered molecular dynamics study (SMD) was used. Glucose was pulled from the extracellular end of GLUT4 to the cytoplasm along the pathway using constant velocity pulling method. We identified several key residues within the tunnel that interact directly with either the backbone ring or the hydroxyl groups of glucose. A rotation of glucose molecule was seen near the sugar binding site facilitating the sugar recognition process at the QLS binding site.
This study proposes a possible glucose transport pathway and aids the identification of several residues that make direct interactions with glucose during glucose transport. Mutational studies are required to further validate the observation made in this study.
Molecular chaperones are a class of proteins responsible for proper folding of a large number of polypeptides in both prokaryotic and eukaryotic cells. Newly synthesized polypeptides are prone to nonspecific interactions, and many of them make toxic aggregates in absence of chaperones. The eukaryotic chaperonin CCT is a large, multisubunit, cylindrical structure having two identical rings stacked back to back. Each ring is composed of eight different but similar subunits and each subunit has three distinct domains. CCT assists folding of actin, tubulin, and numerous other cellular proteins in an ATP-dependent manner. The catalytic cooperativity of ATP binding/hydrolysis in CCT occurs in a sequential manner different from concerted cooperativity as shown for GroEL. Unlike GroEL, CCT does not have GroES-like cofactor, rather it has a built-in lid structure responsible for closing the central cavity. The CCT complex recognizes its substrates through diverse mechanisms involving hydrophobic or electrostatic interactions. Upstream factors like Hsp70 and Hsp90 also work in a concerted manner to transfer the substrate to CCT. Moreover, prefoldin, phosducin-like proteins, and Bag3 protein interact with CCT and modulate its function for the fine-tuning of protein folding process. Any misregulation of protein folding process leads to the formation of misfolded proteins or toxic aggregates which are linked to multiple pathological disorders.
To analyze the haplotype of the Ezhava population of Kerala, south India, using 8 short tandem repeat (STR) loci on the Y chromosome and trace the paternal genetic lineage of the population.
Whole blood samples (n = 104) were collected from unrelated healthy men of the Ezhava population over a period of one year from October 2009. Genomic DNA was extracted by salting out method. All samples were genotyped for the 8 Y-STR loci by the AmpFiSTR Y-filer PCR Amplification Kit. The haplotype and allele frequencies were determined by direct counting and analyzed using Arlequin 3.1 software, and molecular variance was calculated with the Y-chromosome haplotype reference database online analysis tool, www.yhrd.org.
Among the 104 examined haplotypes, we found 98 unique ones. The average gene diversity was 0.669, with the highest diversity of 0.9462 observed for the biallelic Y-STR marker DYS 385. The allele frequency among DYS loci varied between 0.0096 and 0.75. Out of the 104 haplotypes, 10 were identical to the Jat Sikh population of Punjab, which is the greatest number among the Indian populations, and 4 to the Turkish population, which is the greatest number among the European populations. According to the allele frequency of Y-STR, the Ezhavas were genetically more similar to the Europeans (60%) than to the East Asians (40%).
The vast majority of haplotypes were observed only once, reflecting the enormous genetic heterogeneity of the Ezhavas. Based on the genotype, the Ezhavas showed more resemblance to Jat Sikh population of Punjab and the Turkish populations than to the East Asians, hence indicating a paternal lineage of European origin.
Recent phylogenetic analyses have identified Amborella trichopoda, an understory tree species endemic to the forests of New Caledonia, as sister to a clade including all other known flowering plant species. The Amborella genome is a unique reference for understanding the evolution of angiosperm genomes because it can serve as an outgroup to root comparative analyses. A physical map, BAC end sequences and sample shotgun sequences provide a first view of the 870 Mbp Amborella genome.
Analysis of Amborella BAC ends sequenced from each contig suggests that the density of long terminal repeat retrotransposons is negatively correlated with that of protein coding genes. Syntenic, presumably ancestral, gene blocks were identified in comparisons of the Amborella BAC contigs and the sequenced Arabidopsis thaliana, Populus trichocarpa, Vitis vinifera and Oryza sativa genomes. Parsimony mapping of the loss of synteny corroborates previous analyses suggesting that the rate of structural change has been more rapid on lineages leading to Arabidopsis and Oryza compared with lineages leading to Populus and Vitis. The gamma paleohexiploidy event identified in the Arabidopsis, Populus and Vitis genomes is shown to have occurred after the divergence of all other known angiosperms from the lineage leading to Amborella.
When placed in the context of a physical map, BAC end sequences representing just 5.4% of the Amborella genome have facilitated reconstruction of gene blocks that existed in the last common ancestor of all flowering plants. The Amborella genome is an invaluable reference for inferences concerning the ancestral angiosperm and subsequent genome evolution.
Glucose transporter 4 (GLUT4) is an insulin facilitated glucose transporter that plays an important role in maintaining blood glucose homeostasis. GLUT4 is sequestered into intracellular vesicles in unstimulated cells and translocated to the plasma membrane by various stimuli. Understanding the structural details of GLUT4 will provide insights into the mechanism of glucose transport and its regulation. To date, a crystal structure for GLUT4 is not available. However, earlier work from our laboratory proposed a well validated homology model for GLUT4 based on the experimental data available on GLUT1 and the crystal structure data obtained from the glycerol 3-phosphate transporter.
In the present study, the dynamic behavior of GLUT4 in a membrane environment was analyzed using three forms of GLUT4 (apo, substrate and ATP-substrate bound states). Apo form simulation analysis revealed an extracellular open conformation of GLUT4 in the membrane favoring easy exofacial binding of substrate. Simulation studies with the substrate bound form proposed a stable state of GLUT4 with glucose, which can be a substrate-occluded state of the transporter. Principal component analysis suggested a clockwise movement for the domains in the apo form, whereas ATP substrate-bound form induced an anti-clockwise rotation. Simulation studies suggested distinct conformational changes for the GLUT4 domains in the ATP substrate-bound form and favor a constricted behavior for the transport channel. Various inter-domain hydrogen bonds and switching of a salt-bridge network from E345-R350-E409 to E345-R169-E409 contributed to this ATP-mediated channel constriction favoring substrate occlusion and prevention of its release into cytoplasm. These data are consistent with the biochemical studies, suggesting an inhibitory role for ATP in GLUT-mediated glucose transport.
In the absence of a crystal structure for any glucose transporter, this study provides mechanistic details of the conformational changes in GLUT4 induced by substrate and its regulator.
Frontotemporal lobar degeneration (FTLD) is a highly heterogenous group of progressive neurodegenerative disorders characterized by atrophy of prefrontal and anterior temporal cortices. Recently, the research in the field of FTLD has gained increased attention due to the clinical, neuropathological, and genetic heterogeneity and has increased our understanding of the disease pathogenesis. FTLD is a genetically complex disorder. It has a strong genetic basis and 50% of patients show a positive family history for FTLD. Linkage studies have revealed seven chromosomal loci and a number of genes including MAPT, PGRN, VCP, and CHMB-2B are associated with the disease. Neuropathologically, FTLD is classified into tauopathies and ubiquitinopathies. The vast majority of FTLD cases are characterized by pathological accumulation of tau or TDP-43 positive inclusions, each as an outcome of mutations in MAPT or PGRN, respectively. Identification of novel proteins involved in the pathophysiology of the disease, such as progranulin and TDP-43, may prove to be excellent biomarkers of disease progression and thereby lead to the development of better therapeutic options through pharmacogenomics. However, much more dissections into the causative pathways are needed to get a full picture of the etiology. Over the past decade, advances in research on the genetics of FTLD have revealed many pathogenic mutations leading to different clinical manifestations of the disease. This review discusses the current concepts and recent advances in our understanding of the genetics of FTLD.
Frontotemporal lobar degeneration; genetic risk factors; microtubule-associated protein tau; mutations; progranulin; TDP-43
Microarrays are becoming a very popular tool for microbial detection and diagnostics. Although these diagnostic arrays are much simpler when compared to the traditional transcriptome arrays, due to the high throughput nature of the arrays, the data analysis requirements still form a bottle neck for the widespread use of these diagnostic arrays. Hence we developed a new online data sharing and analysis environment customised for diagnostic arrays.
Microbial Diagnostic Array Workstation (MDAW) is a database driven application designed in MS Access and front end designed in ASP.NET.
MDAW is a new resource that is customised for the data analysis requirements for microbial diagnostic arrays.