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EDITORIAL
Current Status of Cancer Burden: Global and Indian Scenario
Dhananjaya Saranath, Aparna Khanna
April 2014, 1(1):1-5
DOI:10.4103/2349-3666.240996  
Full text not available  [PDF] [CITATIONS]
  44 0 0
REVIEW ARTICLES
Physiology of embryo-endometrial cross talk
Deepak N Modi, Pradeep Bhartiya
April 2015, 2(1):83-104
DOI:10.4103/2349-3666.240622  
Implantation of the blastocyst stage embryo into the maternal endometrium is a critical determinant and a rate-limiting process for successful pregnancy. Embryo implantation requires synchronized changes in the endometrium before and after arrival of blastocyst into the uterine cavity. Extensive cross talks occur between the fetal and maternal compartments around the time of implantation which are reflected by morphologic, biochemical and molecular changes in the endometrial cells and the differentiating trophoblast cells. The embryo induced morphologic changes include occurrence of epithelial plaque reaction, stromal compaction and decidualization. Embryonic signals also alter the expression of a large number of transcription factors, growth factors and their receptors and integrins. Thus the embryo superimposes a unique signature on the receptive endometrium for successful implantation. Functionally, the embryo-endometrial cross talk is essential for endowing a “selector activity” to the receptive endometrium to ensure implantation of only a developmentally competent embryo. On selection, the decidua creates a conducive microenvironment for trophoblast invasion leading to placentation. Clinical evidences suggest that along with receptivity, a defective “selector” activity of the receptive uterus may be a cause of infertility and recurrent miscarriages. Defects in trophoblast invasion are associated with pregnancy complications like preeclampsia and intra-uterine growth retardation. It is envisaged that understanding of the embryo-endometrial dialogue leading to the “selector” activity, aids in development of appropriate therapeutic modalities for infertility related disorders and miscarriages. Conversely, it might also benefit the development of anti-implantation drugs for contraception.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  15 2,643 383
ORIGINAL ARTICLES
Nitrate stress-induced bioactive sulfated polysaccharides from Chlamydomonas reinhardtii
Jyoti Vishwakarma, Vaishnavi Parmar, Sirisha L Vavilala
January 2019, 6(1):7-16
DOI:10.4103/BMRJ.BMRJ_8_19  
Sulfated polysaccharides (SPs) are anionic carbohydrate polymers synthesized as extracellular or cell wall components by most of the algae and have potent bioactive properties. In the current study, Chlamydomonas reinhardtii (Cr) cells were attributed to sodium nitrate stress in concentrations such as 5 mM, 10 mM, 20 mM, 30 mM, and a control to determine the productivity and bioactivity of SPs. SPs are extracted by hot water method using 80% ethanol. The percentage yield of SPs increased with an increase in concentration of sodium nitrate as compared to control. Biochemical analysis of the extract showed an increase in carbohydrate content (22%–95%), uronic acid content (23%–60%), and sulfate content from control to 30 mM NaNO3-treated extracts. The amount of reducing and nonreducing sugars was found to be 6.16% and 89.06%, respectively, while the protein content is ~16%. The antioxidant potential of SPs showed increased antioxidant activity with an increase in concentration of NaNO3 stress. The analysis resulted in maximum chelating activity of 83.73% assayed in concentration range of 1–8 μg/ml, total antioxidant activity of 70.36% in concentration 0.05–2μg/ml, and hydroxyl radical scavenging activity of 79.52% in concentration 250–1000 μg/ml; reducing potential was observed with the highest absorbance of 0.87; the 2,2-diphenyl-1-picrylhydrazyl scavenging activity showed the highest activity of 63.61%, while the superoxide scavenging activity was 92% at 0.1–1 μg/ml. Furthermore, Cr-SPs inhibited the growth of Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacterial growth as indicated by clear zones that increased in size with an increasing concentration of NaNO3. These results provide opportunities to develop Cr-SPs as natural antioxidant and antibacterial agents.
  12 7,985 574
REVIEW ARTICLES
Areca nut use and cancer in India
Prakash C Gupta, Cecily S Ray
October 2015, 2(2):140-165
DOI:10.4103/2349-3666.240652  
Areca nut is widely used in India and the consumption has increased over the past two decades, with availability in new dry packaged forms (pan masala, gutka, mawa). Recent reports of increasing mouth cancer incidence have suggested an association with areca nut consumption. Here we have reviewed the evidence for carcinogenicity of areca nut, including epidemiological studies, several animal studies and mechanistic evidence. Studies primarily from India, providing odds ratios (ORs) or relative risks for precancers or cancer with use of areca nut without inclusion of tobacco is the focus of the review. Six case-control studies on oral submucous fibrosis (OSF) had significantly elevated ORs for use of areca nut in various forms. Six case-control studies on head and neck cancers, primarily oral cancer reported elevated ORs for chewing of betel quid without tobacco. Eight case control studies on oral cancer have reported elevated and significant ORs for betel quid with tobacco. A significant risk in oral cancer was noted in gutka users. Animal studies confirmed correlation between development of precancers or cancers and exposure to areca nut or pan masala without tobacco. Mechanistic evidence shows a role for areca nut alkaloids, polyphenols and copper in promoting carcinogenesis. Our review emphasizes control policies on areca nut products and appropriate mass communication programs for awareness of hazards of areca nut with emphasis on areca nut per se.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  6 2,478 353
Dendrimers based electrochemical biosensors
Saumya Nigam, Sudeshna Chandra, Dhirendra Bahadur
April 2015, 2(1):21-36
DOI:10.4103/2349-3666.240618  
Electrochemical biosensors are portable devices that permit rapid detection and monitoring of biological, chemical and toxic substances. In the electrochemical biosensors, the bioreceptor is incorporated into the transducer surface; and when in contact with the analyte, generates measurable signals proportional to the analyte concentration. Materials with high surface area, high reactivity, and easy dispersability, are most suited for use in biosensors. Dendrimers are nanomaterial gaining importance for fabrication of electrochemical biosensors. These are synthetic macromolecules with regularly branched tree-like and globular structure. The potential applications of dendrimers as biosensors are explored due to their geometric symmetrical structure, chemical stability, controlled shape and size, and varied surface functionalities, with adequate functional groups for chemical fixation. The current review provides multi-faceted use of dendrimers for developing effective, rapid, and versatile electrochemical sensors for biomolecules. The redox centers in the dendrimers play an important role in the electron transfer process during immobilization of biomolecules on the electrodes. This has led to an intensive use of dendrimer based materials for fabrication of electrochemical sensors with improved analytical parameters. The review emphasizes development of new methods and applications of electrochemical biosensors based on novel nanomaterials.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  6 2,103 283
ORIGINAL ARTICLES
Effect of contact load upon attrition-corrosion wear behavior of bio-composite materials: In vitro off-axis sliding contact-chewing simulation
Efe Cetin Yilmaz
January 2020, 7(1):17-22
DOI:10.4103/BMRJ.BMRJ_2_20  
Background: In recent years, the use of composite materials as biomaterials has been increasing in dentistry. It is important to perform in vitro experiments of biomaterials before living tissue. Aim: The purpose of this work was to examine the effect of contact load upon attrition-corrosion wear behavior of bio-composite materials: in vitro off-axis sliding contact chewing simulation. Material and Method: In this study, 2 mm × 12 mm (weight × diameter) cylindrical test specimens were prepared from Filtek Supreme and Clearfil AP-X bio-composite materials with different filler structure. The surface roughness and Vicker's Hardness values of the bio-composites were measured before the wear test procedures. Then, the test specimens were subjected to off-sliding abrasion test procedures under different mechanical loads in artificial saliva and citric acid medium. Wear volume loss of bio-composite materials was determined after wear test procedures using the three-dimensional noncontact profilometer. Results: As the mechanical loading increased, the loss of wear volume in both composite materials increased irrespective of test medium. However, this increase in wear volume loss in test specimens was more pronounced in the citric acid environment. Conclusion: As a result of, the organic matrix structure (such as Ba glass particle) of the composite material contributes to more volume loss in corrosive environment.
  5 6,040 406
RESEARCH ARTICLE
Cultivation and cryopreservation of cord tissue MSCs with Cord Blood AB Plasma
Manasi Taiwadekarr, Darshana Kadekar, Sonal Rangole, Nikhat Firdaus Khan, Vaijayanti Kale, Lalita Limaye
October 2014, 1(2):126-136
DOI:10.4103/2349-3666.240999  
Neonatal tissues, cord and placenta, are explored as alternate sources of mesenchymal stem cells (MSCs) for their therapeutic applications. Conventionally, MSCs isolated from cord tissues are maintained and propagated in FBS containing medium for promotion of growth and survival of cells. However, for therapeutic use, FBS use is not encouraged as it is of animal origin. Thus, there is a need for replacement of FBS by equally potent and clinically acceptable cost effective sources. The current study is designed to compare the effect of cord blood plasma (CBP) with MSC qualified FBS (M FBS) during culture and cryopreservation of MSCs. MSCs were isolated from cord and placenta and propagated in either M FBS or CBP. The efficiency of the cultures was analyzed by growth curve, morphology, phenotype and functionality. The cryo-protective role of the CBP was evaluated by using it in freezing medium of MSCs. Our data showed that CBP is equivalent to M FBS for culturing placental MSCs with respect to the phenotype, proliferation rate and differentiation to various lineages. However, cord MSCs displayed slow growth rate and reduction in surface expression of CD105 marker in CBP, whereas, the other parameters were comparable. Freezing of MSCs with CBP resulted in reduction of the late apoptotic and necrotic population. Thus, CBP imparts superior protection against cryogenic insults, and appears to be a valuable substitute to M FBS for cultivation and freezing of MSCs.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  5 2,142 277
REVIEW ARTICLE
Klotho: An emerging factor in neurodegenerative diseases
Gauri V Pathare, Kavita K Shalia
January 2019, 6(1):1-6
DOI:10.4103/BMRJ.BMRJ_3_19  
Soluble Klotho protein is present in blood, urine, and cerebrospinal fluid and works as a humoral factor exerting different biological effects. Several animal studies have demonstrated the association of age-related neurodegeneration with Klotho deficiency. Lower Klotho levels have been reported in patients suffering from cognitive impairment, dementia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and other neurodegenerative diseases. Due to its antiaging properties, Klotho is the obvious choice to be studied as a protective/therapeutic agent in neurobiology. In this review, we have attempted to shed light on the different neurodegenerative diseases affected by deficiency of Klotho and its neuroprotective role against pathogenicity of the disease.
  5 7,509 667
REVIEW ARTICLES
Mathematical modeling of viral epidemics: A review
Pratip Shil
October 2016, 3(2):195-215
DOI:10.4103/2349-3666.240612  
Mathematical models to describe transmission and propagation of diseases have gained momentum over the last hundred years. Formulated mathematical models are currently applied to understandthe epidemiology of various diseases including viral diseases viz Influenza, SARS, measles, etc. With the emergence of advanced computing tools, designing mathematical models and generating simulations (numerical solutions) have become feasible. There is an enormous scope for using mathematical models in studying epidemiology of viral diseases through transmission dynamics of outbreaks and in evaluating or predicting the effects of interventions and vaccinations. The influenza pandemic of 2009 and the recent Ebola epidemics of 2014-15 have generated renewed interest in mathematical modelling of epidemics. Here we present a review of the various mathematical models and their applications in the study of virus driven epidemics.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  5 2,745 398
ORIGINAL ARTICLES
Rainfall and dengue occurrences in India during 2010–2016
Pratip Shil
July-December 2019, 6(2):56-61
DOI:10.4103/BMRJ.BMRJ_15_19  
Background: A changing climate scenario coincided with the emergence and re-emergence of vectorborne diseases such as dengue, chikungunya, and Zika. The worldwide resurgence of dengue since 2005 has affected millions and generated huge disease burden, especially in the tropical developing countries including India. While India has a huge burden of dengue with all four serotypes causing outbreaks in different parts of the country, reports on climate and environmental effects on dengue are sparse. Aims and Objectives: To understand the influence of rainfall on dengue occurrences across India between 2010 and 2016, with emphasis on the most affected states. Methods: Dengue occurrence data was obtained by data mining from the NVBDCP and IDSP websites. Area-weighted-rainfall (ARF) were computed from the division-wise data. Statistical analyses performed to analyze the association between annual ARF and dengue occurrences. Spatio-temporal analyses of dengue outbreaks was conducted. Results: Spatio-temporal analyses revealed that high rainfall was positively associated with the number of cases in the northern states (Indo-gangetic Plains) whereas, the reverse was true for the southern (peninsular) states. The number of rural outbreaks of dengue had also been modulated by annual rainfall. Conclusion: Our study revealed the effect of rainfall on dengue in India. We conclude that rainfall influence the dengue occurrences differently in the northern and the southern states of India.
  4 8,279 724
REVIEW ARTICLES
Oral feeding with Arachidonic Acid (AA) and Docosahexanoic Acid (DHA) help in better recovery of haematopoiesis in sub-lethally irradiated mice
Kedar Limbkar, Vaijayanti Kale, Lalita Limaye
October 2016, 3(2):182-194
DOI:10.4103/2349-3666.240611  
Haematopoiesis is severely hampered after exposure to ionizing radiations. Role of polyunsaturated fatty acids (PUFAs) during embryonic development as well as during various physiological processes is well established. However, few studies on their effect on haematopoiesis are reported. Hence, we studied the effect of oral administration of PUFAs-AA/DHA on haematopoiesis of sub-lethally irradiated mice. To determine the optimal dose for haematopoiesis, non-irradiated healthy mice were orally fed with different doses of AA/DHA daily for ten days. Additionally, mice were sub lethally irradiated and kept for ten days on normal diet. Further, sub-lethally irradiated mice were orally fed with optimal dose of AA/DHA for ten days. Mice from the experiments were sacrificed after ten days and their bone marrow cells were harvested and analyzed for their total nucleated cell (TNC) count, side population (SP) and lin-Sca-1+c-kit+(LSK) phenotype. Peripheral blood collected from this set of mice was subjected to hemogram analysis. Daily dose of 8 mg AA/DHA for ten days was assessed as optimal for enhancing BM-MNCs and primitive HSCs in non-irradiated mice. Significant depletion in BM-MNCs, SP and LSK cells was observed in sub lethally irradiated mice compared to un-irradiated control mice. Feeding with DHA or AA in sub lethally irradiated mice showed significantly higher number of BM-MNCs and increased percentage of SP and LSK cells, suggesting that DHA and AA resulted in better recovery of hematopoietically compromised mice. The data indicated that DHA or AA may serve as useful dietary supplements in patients exposed to irradiation.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  4 2,244 283
CASE REPORT
A case of COVID-19 triggered Rhino-Orbital Pulmonary Mucormycosis in Central India
Chandra Pratap Singh Rathore, Shirin Ansari, Trupti Bajpai
January-June 2021, 8(1):25-28
DOI:10.4103/bmrj.bmrj_8_21  
Mucormycosis is a rare but fatal, invasive opportunistic fungal infection generally described among immunocompromised individuals. The ongoing pandemic coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 has severely compromised the immune system of patients thereby making them vulnerable to mucormycosis, especially when they are lined up with associated comorbidities. Here, we present a case of one such 64-year-old male patient being on corticosteroids and a case of long-standing diabetes mellitus and chronic kidney disease. COVID-19 triggered the mucormycosis in this patient thereby leading to a condition we have described as rhino-orbital pulmonary mucormycosis.
  3 3,521 427
ORIGINAL ARTICLES
Therapeutic benefit of resveratrol in 5-fluorouracil-induced nephrotoxicity in rats
Elias Adikwu, Innocent Biradee, Temitope Omolade Ogungbaike
July-December 2019, 6(2):72-77
DOI:10.4103/BMRJ.BMRJ_19_19  
Background: The prevention of nephrotoxicity caused by 5-fluorouracil (5-FU) can improve patients' adherence to treatment.Aim and Objective: This study assessed the ability of resveratrol (RES) to prevent 5-FU-induced nephrotoxicity in rats. Materials and Methods: Forty adult male albino rats randomized into eight groups of n = 5 were used. Group A (control) was administered with 0.2 mL of normal saline intraperitoneally (i.p.), whereas Groups B-D were administered with 10, 20, and 40 mg/kg of RES daily for 5 days respectively. Group E was administered with 20 mg/kg of 5-FU ip daily for 5 days. Groups F-H were administered with 10 mg/kg of RES + 20 mg/kg of 5-FU, 20 mg/kg of RES + 20 mg/kg of 5-FU, and 40 mg/kg of RES + 20 mg/kg of 5-FU ip daily for 5 days, respectively. Blood samples were collected after rats were sacrificed and evaluated for serum renal function biomarkers. Kidneys were evaluated for oxidative stress markers and histology. Results: Serum creatinine, urea, and uric acid levels were significantly (P < 0.001) increased, whereas total protein, albumin, potassium, sodium, chloride, and bicarbonate levels were significantly (P < 0.001) decreased in 5-FU-treated rats when compared to control. Kidney superoxide dismutase, glutathione, glutathione peroxidase, and catalase levels were significantly (P < 0.001) decreased, whereas malondialdehyde levels were significantly increased in 5-FU-treated rats when compared to control. Furthermore, the kidneys of 5-FU-treated rats showed tubular necroses and atrophic glomeruli. The aforementioned nephrotoxic changes were significantly abrogated in rats supplemented with 10 mg/kg (P < 0.05), 20 mg/kg (P < 0.01), and 40 mg/kg (P < 0.001) of RES when compared to 5-FU. Conclusion: RES may have therapeutic benefit in nephrotoxicity caused by 5-FU.
  3 6,866 565
Molecular docking study for evaluation of neuroprotective potential of sericin against cerebral stroke and exploring its biomaterial properties
Khushboo Maurya, Anand Kumar Pandey
January 2019, 6(1):17-24
DOI:10.4103/BMRJ.BMRJ_5_19  
Background: Cerebral stroke, the third leading cause of death worldwide results from the improper blood supply to the brain due to occlusions in the brain arteries. This leads to production of free radicals contributed by cyclo-oxygenases (COX), acid sensing ion channels (ASIC) and matrix metalloproteinases (MMPs) causing adverse conditions of inflammation, oxidative stress, and acidosis leading to neuronal death thereby proving these enzymes as potent targets. Sericin, a 38 amino acid long protein found in silk fiber is known for its anti-inflammatory and anti-oxidant property. Aim and Objectives: Inhibition of the above-mentioned targets by silk protein sericin to reduce the pathological features by structural interactions as well as reducing inflammation and oxidative stress due to the natural properties of compound. Methodology: In the present study we studied structural inhibition of effective targets by sericin through molecular docking analysis. Also, the semi crystalline nature of sericin was deduced through in silico XRD spectral analysis. Result: Structural inhibition through molecular docking analysis proved highly efficient inhibition. Also, the in silico XRD spectral analysis proved sericin to be a potential biomaterial for scaffold development. Conclusion: Sericin can not only act as an effective drug against cerebral ischemia but can also be used to develop scaffold to repair damaged brain.
  3 7,984 697
RESEARCH ARTICLE
Investigation of action potential propagation in a syncytium
Shailesh Appukuttan, Keith Brain, Rohit Manchanda
April 2017, 4(1):102-115
DOI:10.4103/2349-3666.240589  
Certain excitable cells, such as those in cardiac and smooth muscle, are known to form electrical syncytia. Cells within a syncytium are coupled to adjacent cells by means of structures known as gap junctions, which provide electrical continuity between cells. This results in the spread and propagation of electrical activity, such as action potentials (APs), from the originating cell to other cells in its syncytium. We propose that this ability of APs to propagate through an electrical syncytium depends on various syncytial features, and also the AP profile. The current study attempts to investigate these various factors using a computational approach. Simulations were conducted on a model of a three-dimensional syncytium using the NEURON simulation platform. The results confirm that the capacity of action potentials to propagate in a syncytium is influenced by the features of the action potential, and also the arrangement of cells within the syncytium. The excitability of biophysically identical cells was found to differ based on the size of the syncytium, their location within it, and the extent of gap junctional coupling between neighboring cells. Only a window of gap junctional coupling levels allowed both the initiation and propagation of action potentials. The results clearly exhibit the role of AP diversity and syncytial features in determining the spread of action potentials. This has significant implications for understanding the functioning of syncytial tissues, such as the detrusor smooth muscle, both in physiology and in disease.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  3 2,192 286
Human EGFR-2, EGFR and HDAC triple-inhibitor CUDC-101 enhances radiosensitivity of GBM cells
Cody D Schlaff, W Tristram Arscott, Ira Gordon, Kevin A Camphausen, Anita Tandle
April 2015, 2(1):105-119
DOI:10.4103/2349-3666.240616  
Radiotherapy remains the standard treatment for glioblastoma multiforme (GBM) following surgical resection. Given the aberrant expression of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) which may play a role in therapeutic resistance to receptor tyrosine kinase inhibitors, and the emerging use of histone deacetylase (HDAC) inhibitors as radiosensitizers, we defined the effects of CUDC-101, a triple inhibitor of HER2, EGFR and HDAC on the radiosensitivity of GBM cells. Clonogenic survival was used to determine the in vitro radiosensitizing potential of CUDC-101 on GBM, breast cancer, and normal fibroblast cell lines. Inhibitory activity was defined using immunoblots and DNA double strand breaks were evaluated using yH2AX foci. Effects of CUDC-101 on cell cycle and radiation-induced cell kill were determined using flow cytometry and fluorescent microscopy. CUDC-101 inhibited HER2, EGFR and HDAC and enhanced in vitro radiosensitivity of both GBM and breast cancer cell lines, with no effect on normal fibroblasts. Retention of yH2AX foci was increased by CUDC-101 alone and in combination with irradiation for 24 h. Treatment with CUDC-101 increased the number of cells in G2 and M phase, with only increase in M phase statistically significant. An increase in mitotic catastrophe was seen in a time-dependent fashion with combination treatment. The results indicate the tumor specific CUDC-101 enhanced radiosensitization in GBM, and suggest that the effect involves inhibition of DNA repair.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  3 2,364 330
Ovarian cancer: An ever challenging malady
Smrita Chaudhury, Amita Maheshwari, Pritha Ray
April 2014, 1(1):34-55
DOI:10.4103/2349-3666.240659  
Ovarian cancer is the fifth leading cause of cancer related deaths in women with a five year survival rate of only 30–40%. Amongst the three broad subgroups of ovarian cancer, epithelial ovarian cancer is the most common and is divided in mainly five subtypes based histology and clinical behaviour. In patients when the disease is still confined to ovaries, surgery alone is curative for more than 90% patients. Unfortunately, most women are diagnosed with advanced stage disease and recurs in majority despite of debulking surgery and initial response to chemotherapy. Thus ovarian cancer is still a challenge to clinicians which gets more complicated due to asymptomatic nature of the early stage disease and frequent development of resistance to standard therapies. Therefore, researchers worldwide are engaged in identifying markers for early detection of ovarian cancer, investigating molecular mechanisms of chemoresistance, improving detection methods and developing novel therapeutic measures. In this review, we attempt to discuss the contemporary research and challenges associated with epithelial ovarian cancer along with the future improvements in various areas such as early detection of ovarian cancer through Multiplex-Methylation specific PCR (MSP) assay and Serial Analysis of Gene expression (SAGE) assay and identifying new biomarkers, facilitating personalised chemotherapy regime by various chemo-response assays, novel drugs and targeted therapies which will aid in enhancing the overall survival rate in future and overcome this deadly gynaecologic disease.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  3 2,236 283
REVIEW ARTICLES
Clusterin in cancer: Dual role as a tumor suppressor gene and an oncogene
Rajashree Kadam, Tanuja Teni
October 2016, 3(2):130-156
DOI:10.4103/2349-3666.240609  
Clusterin (CLU), a heterodimeric and sulfated glycoprotein has been associated with various physiological functions. This molecular chaperone protein is ubiquitously expressed in diverse tissues and conserved across species. Differences in subcellular localization and possible existence of different CLU isoforms may contribute to its functional diversity. Increased or decreased expression of CLU has been observed in several cancers versus normal tissues and hence its role in tumorigenesis is controversial. Evidences from several studies imply that CLU may have a dual role as a tumor suppressor gene or an oncogene depending on the signal and cellular context. CLU possibly exerts its oncogenic role by inhibiting apoptosis, activating autophagy and modulating several signaling pathways like IGF-1/IGFR, EGFR, NF-kB, PI3K/AKT, TGFp and select miRNAs. CLU may exert its tumor suppressive effects by regulating cell cycle and inducing apoptosis. In cancer, loss of heterozygosity (LOH), copy number loss at CLU locus, epigenetic modifications and expression of select miRNAs may lead to the downregulation of CLU. Custirsen (OGX-011), a second generation antisense oligonucleotide that inhibits CLU expression and increases sensitivity of cancer cells to chemotherapeutic drugs, is currently in phase III clinical trials. CLU is an attractive target in several cancers, however for effective targeting, it is essential to know whether it acts as an oncogene or a tumor suppressor gene in a specific tissue/cellular context. The current review attempts to discuss the two contrasting roles of CLU in cancer and associated regulatory mechanisms. This review also sheds light on the complex CLU splice variants, the varied functional attributes supporting the dual roles in cancer and limitations of the CLU research that warrant attention.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  3 2,501 421
16S ribosomal RNA gene-based metagenomics: A review
Asmita Kamble, Shriya Sawant, Harinder Singh
January 2020, 7(1):5-11
DOI:10.4103/BMRJ.BMRJ_4_20  
With the advent of contemporary molecular tools, the conventional microbiological isolation, enrichment techniques, and approaches have changed considerably. Molecular techniques such as polymerase chain reaction, cloning, and sequencing have shown that the major percentage of microbial diversity in an ecosystem remain “unculturable” or “as yet uncultivable” due to the lack of information on their biology, limited selection media, and culture conditions that could support their growth. Identifying and knowing more about them have become an important objective in the microbiological research. The ecological, environmental, and functional implications of a microbial ecosystem can be deciphered by knowing its microbial composition and interactions. The areas of whole-cell and targeted gene metagenomics are playing a key role in accomplishing this objective. The present review discusses the 16S ribosomal RNA (16S rRNA) gene metagenomics approach, which has found major applications in identifying the composition of a given microbial ecosystem. Different systems, processes, and analysis tools are available to perform 16S rRNA metagenomics; however, there are few concerns that require more investigation to gain the maximum benefit of these techniques.
  3 11,375 970
RESEARCH ARTICLE
Determination of hyperglycaemia-induced epc dysfunction using a panel of cellular assays: Validation of experimental murine and human model systems
Kadambari Dixit, Meghana Kanitkar, Sheetal Kadam, Rucha Deshpande, Vaijayanti Kale
April 2017, 4(1):82-101
DOI:10.4103/2349-3666.240594  
Although human and murine Endothelial Progenitor Cells (EPCs) are routinely used for research, the results can only be imperfectly analyzed due to our limited understanding of source-specific differential responses to stress. Although the routinely used cellular and functional assays are effective for detection of EPC dysfunction (EPD) in single source test systems, there is lack of a universal detection system capable of detecting high glucose (HG) and/or Diabetes mellitus (DM)-induced EPD irrespective of source or site. To remedy this lacuna we compared the test systems from both cell sources. Comparison of sensitivity of various cellular assays revealed that of all the assays performed, only colony formation assays (CFU) showed comparable responses to diabetes/high glucose in both test systems, while cell adhesion assay (CAA), proliferation potential and viability differed in their responses to HG. On the other hand, the functional assays i.e. tubule formation, chemotactic migration assay and CXCR4 and VEGFR2 mRNA expression were uniformly affected by HG in vitro and DM in vivo. Interestingly, other parameters studied i.e. nitric oxide, reactive oxygen species (ROS) and manganese superoxide dismutase (MnSOD) showed dissimilar responses to HG and DM exposure. On this basis, we propose a panel of assays comprising CFU, tubule formation, chemotactic-migration and CXCR4 and VEGFR2 mRNA expression that can accurately detect HG-/DM-induced EPD irrespective of various systemic factors. These assays will also enhance uniformity across data sets and increase accuracy of EPD detection in human and murine systems.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  2 2,155 381
Phenotypic and functional characterization of a marrow-derived stromal cell line, M210B4 and its comparison with primary marrow stromal cells
Shweta Singh, Suprita Ghode, Moirangthem Ranjita Devi, Lalita Limaye, Vaijayanti Kale
April 2015, 2(1):120-133
DOI:10.4103/2349-3666.240617  
In vitro co-culture system consisting of bone marrow stromal cells (BMSCs) or mesenchymal stromal cell lines of marrow origin has provided important clues about the regulation of hematopoietic stem cells (HSCs) by their microenvironment or niche. In the current studies, we have compared phenotypic and functional characters of a marrow-derived mesenchymal stem cell line, M210B4, with BMSCs. We demonstrate that M210B4 resembles BMSCs in terms of phenotypic characters. Unlike the BMSCs, M210B4 differentiated only towards adipogenic lineage, and was refractory towards osteogenic differentiation. However, M210B4 cells exhibited a higher HSC-supportive ability as assessed by flow cytometry analyses of the output cells from co-cultures. We observed that M210B4 cells show a constitutively higher activation of p44/42 and p38 MAPK pathways compared to BMSCs, contributing to their higher HSC-support in vitro. Overall, the results show that M210B4 forms a suitable in vitro system to study HSC regulation in vitro.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  2 2,427 309
REVIEW ARTICLE
Size, site, and signaling: Three attributes of estrogen receptors
Junita Desouza, Sushama Gadkar, Dhanashree Jagtap, Geetanjali Sachdeva
July-December 2019, 6(2):37-48
DOI:10.4103/BMRJ.BMRJ_24_19  
Estrogens are implicated in a diverse range of functions varying from reproduction, circulation, skeletal health to neuroprotection. Estrogens are also being increasingly recognized for their pathological contribution to cancers of various organs. This has spurred several investigations on estrogen-initiated signaling mechanisms in various cell types in physiological and pathological conditions. Estrogens exert their biological actions through a class of conventional nuclear receptors known as estrogen receptors (ERs), majorly of two subtypes – ERα and ERβ, both encoded by different genes, and each has multiple isoforms. It is reported that different ER subtypes and their specific isoforms have overlapping and nonoverlapping functions. Moreover, ER functions are highly cell-context specific. Thus, it is difficult to propose a unified scheme for estrogen signaling. Another layer of complexity is added by diverse subcellular localization, i.e., nucleus, plasma membrane, and cytosol, of ERs in estrogen-responsive tissues. Size as well as site dictates the sequence of cellular events triggered by estrogen signaling. This review compiles the existing information on different subtypes, different isoforms, and different sites of subcellular localization of ERs.
  2 10,796 849
REVIEW ARTICLES
Cancer gene therapy: Prospects of using human sodium iodide symporter gene in non-thyroidal cancer
Shruti Dutta, Abhijit De
October 2015, 2(2):198-219
DOI:10.4103/2349-3666.240655  
Gene therapy is one of the promising therapeutic strategies evolved rapidly in the frontier of translational biology in cancer. To overcome the off target effect of conventional cancer therapies it is the most flourishing approach in present epoch. Various researches in this context are ongoing to eradicate devastating cancer cells with minimal or no side effects. Of the various gene therapy protocols developed, a set of genes called suicide genes, are being actively pursued as potential strategy. Briefly, this strategy involves tumor targeted delivery of a therapy/reporter gene to convert a systematically administered pro-drug into a cytotoxic drug which in turn induces tumor cell death. Additionally, advancement in small animal imaging modalities facilitates real-time monitoring of the delivered transgene by using appropriate imaging probe developed against the transgene. Non-invasive monitoring helps to realize precise transgene delivery and also aid to understand therapy response. In this background, we have reviewed potential suicide genes frequently explored for cancer treatment, which supports both diagnostic and therapeutic applications with special emphasis on sodium iodide symporter (NIS). Apart from its natural expression in thyroid, NIS protein expression has raised the possibility of using radioiodide therapy and diagnosis in few non-thyroidal cancers as well. In this review, we also covered various challenges to get NIS gene therapeutics from bench to bedside in various non-thyroidal cancers.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
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Selenium: Chemical biology, toxicology and radioprotection
Kavirayani Indira Priyadarsini, Beena Govind Singh, Amit Kunwar
April 2016, 3(1):52-72
DOI:10.4103/2349-3666.240605  
Selenium, a micronutrient and an active constituent of important redox enzymes like glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), has been investigated extensively by researchers all over the world for the last four to five decades. Both inorganic and organic selenium compounds are being evaluated as probable drugs or adjuvants for many viral infections and chronic diseases like cancer. Several clinical trials in cancer patients have confirmed that selenium supplementation helps in recovering from cancer therapy associated side effects and selenium itself does not interfere in cancer therapy. Efforts are on to develop new selenium compounds with anti-cancer properties. These aspects will be discussed in this article.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
  2 2,192 272
Chemoprotectants in cancer chemotherapy: An update
Abhishek Basu, Arin Bhattacharjee, Sudin Bhattacharya
October 2016, 3(2):157-181
DOI:10.4103/2349-3666.240610  
Cancer chemotherapeutic agents play an integral part in the management of patients with malignancy. However, chemotherapy is associated with significant toxicity with an adverse impact on the health of the patients. As a result the therapeutic outcome is influenced due to the inability to deliver sufficient dose-intensive therapy leading to treatment delays or cessation. Chemoprotectants have been developed in order to mitigate the toxicity associated with chemotherapeutic agents by providing organ-specific protection to normal tissues, without compromising the antitumor efficacy. The current review highlights chemoprotectants in the management of chemotherapeutics-associated toxicity, such as: amifostine, aprepitant, dexrazoxane, filgrastim, sargramostim, mesna, oprelvekin, palifermin, recombinant human erythropoietin etc. Additionally, the present status on the concurrent use of chemoprotectants in combination with chemotherapeutic agents, with focus on their safety is included. The advantageous role of these cytoprotective agents combined with chemotherapy remains controversial in clinical studies due to moderate protective efficacy for normal tissues and organs, risk of concomitant tumor protection and adverse reactions. Besides, the number of successful agents is rather small. Therefore, identification of novel approaches and chemoprotectants holds potential for better management of cancer with chemotherapy.
[ABSTRACT]   Full text not available  [PDF] [CITATIONS]
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