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Klotho: An emerging factor in neurodegenerative diseases
Gauri V Pathare, Kavita K Shalia
January 2019, 6(1):1-6
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.
  1,696 200 -
Size, site, and signaling: Three attributes of estrogen receptors
Junita Desouza, Sushama Gadkar, Dhanashree Jagtap, Geetanjali Sachdeva
July-December 2019, 6(2):37-48
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.
  1,702 126 -
Nitrate stress-induced bioactive sulfated polysaccharides from Chlamydomonas reinhardtii
Jyoti Vishwakarma, Vaishnavi Parmar, Sirisha L Vavilala
January 2019, 6(1):7-16
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.
  1,466 180 -
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
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.
  1,369 199 -
Transforming growth factor beta receptor 2 single-nucleotide polymorphism association with oral cancer and In silico identification of small drug-like molecules as inhibitors to transforming growth factor Beta-2 receptor
Shaleen Multani, Hetal Damani Shah, Dhananjaya Saranath
January 2019, 6(1):25-33
Objective: Oral cancer, in India, constitutes 26% of global oral cancer burden. The major risk factors include tobacco, areca nut, alcohol, and human papillomavirus 16/18; however, only 5%–10% of the high-risk individuals develop oral cancer, indicating the role of genomic variants in susceptibility to oral cancer. Conventional treatment options in oral cancer have resulted in relatively poor prognosis and an unmet need of treatment. In silico analysis, therefore, was performed to identify small drug-like molecules as potential inhibitors of transforming growth factor beta-2 receptor (TGFβRII). Materials and Methods: Seven single-nucleotide polymorphisms (SNPs) were analyzed in 500 histopathologically confirmed oral cancer samples and 500 long-term tobacco users (LTTUs) as controls using allelic discrimination real-time polymerase chain reaction or high-resolution melting analysis. The differential frequencies in oral cancer and LTTUs were calculated using SPSS software (version 19), and odds ratio (OR) to indicate risk to oral cancer using Hutchon.net. structure-based virtual screening of drug-like molecules was performed to identify lead inhibitor molecules to TGFβRII using Schrödinger Suite 2015-4. Results: Heterozygous GC genotype of TGFBR2 rs9843143 demonstrated increased risk ([P = 0.011; OR 1.61 [1.25–2.1]) while CC genotype showed decreased risk (P = 0.005; OR 0.61 [0.44–0.83]) to oral cancer. Increased/decreased risk to oral cancer was not observed for the other SNPs. In silico analysis identified six molecules as inhibitors of TGFβRII kinase domain from 17,723 conformers from Maybridge HitFinder library and 2685 conformers from MEGx AnalytiCon natural product library. Conclusion: SNP rs9843143 (TGFBR2) demonstrated a significant association (P < 0.05) with oral cancer and six potential inhibitors of TGFβRII kinase were identified using in silico analysis.
  1,349 152 1
Metastatic hepatocellular carcinoma manifesting as primary esophageal carcinoma: A rare case report
K Jayaprakash Shetty, HL Kishan Prasad, Shubha Bhat, Michelle Mathias, Vijith Shetty
January 2019, 6(1):34-36
Hepatocellular carcinoma (HCC) metastasizing to the esophagus and mimicking as a primary tumor of the esophagus is extremely rare, being present in <0.4% in some autopsy series. This report describes a case of 70-year-old male with metastatic HCC to esophagogastric junction causing diagnostic dilemma. An endoscopic examination revealed an ulcerative lesion in the lower end of the esophagus. The biopsy specimen obtained from a tumor revealed the pseudoglandular arrangement of tumor cells. Ultrasound abdomen showed liver nodule with biopsy confirming as HCC. Immunohistochemistry (IHC) of the esophageal mass showed positivity for Hep par 1, Glypican-3, Arginase, CA 19-9, CK 19, CDX2, pCEA, SATB2, and Ki-67 having 70% positivity confirming the HCC. Among these IHC panels, all are specific markers of HCC, but CDX2 and SATB2 were aberrantly expressed in our case. He was started on six cycles of chemotherapy (apristar 125 mg, epirubicin 40 mg, oxaliplatin 100 mg, and capecitabine 500 mg). After 8 months of follow-up, he was symptomatically improved. However, later, the patient was lost to follow-up. The accurate pretreatment staging and then providing stage-appropriate treatment is crucial in optimizing esophageal and hepatocellular cancer outcomes. Cases of premortem-diagnosed esophageal metastasis from HCC are extremely rare. Our case was ideal for IHC, which plays an important role in arriving at proper cases. Furthermore, it confirmed and highlighted the rare manifestations of hepatocellular carcinoma.
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Rainfall and dengue occurrences in India during 2010–2016
Pratip Shil
July-December 2019, 6(2):56-61
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.
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Surfactant Modified Graphene Oxide for the Detection of Dopamine
Diptesh Naik, Bhanudas Naik, Akshay Salkar, Vrushali S Joshi
October 2018, 5(2):64-73
A synthesis and characterization of a surfactant functionalize graphene oxide, and its potential applications for biosensor are presented. Graphene oxide was prepared using improved Hummer's method and modified with two different surfactants viz. cetyltrimethylammonium bromide (CTAB) and Sodium dodecyl sulfate (SDS) by chemical method. The formation of the product was confirmed by characterizing it with UV-Viz, IR spectroscopy and Scanning electron microscopy (SEM). Here, we report simple and low cost method to develop electrochemical dopamine sensor by drop-casting catalysts on graphite rod conducting phase. A developed sensor is used for the voltammetric detection of the micro - millimolar quantity of dopamine without any fouling of electrode surface. The kinetics of electron transfer in the dopamine oxidation reaction on the surface of a catalysts are investigated.
[ABSTRACT]   Full text not available  [PDF]  [Mobile Full text]  [EPub]
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Odontogenic Fibroma of Maxilla: A Rare Clinical Entity
Shashikant A Pol, Arjun Dass, Nitin Gupta
October 2018, 5(2):90-94
The odontogenic fibroma (OF) is a rare benign tumour of mesodermal origin characterized by varying amounts of inactive looking odontogenic epithelium embedded in a mature, fibrous stroma. The lesion appears frequently involving the anterior region, when fibroma occurs in the maxilla, whereas they tends to be located in the posterior area, involving the premolar and molar areas, when fibroma occurs in the mandible. We are presenting a case of 36 year old female patient who had cheek swelling and facial disfigurement for 1 year. Biopsy was suggestive of odontogenic tumor. Complete excision was done transorally with sublabial approach and was histopathologically called out as benign odontogenic tumour consistent with an Odontogenic Fibroma. Patient was asymptomatic till 6 months of followup. Desmoplastic fibroma and intra-osseous fibrogenic myxoma should be considered in the differential diagnosis. The tumour should be managed conservatively with enucleation and curettage.
[ABSTRACT]   Full text not available  [PDF]  [Mobile Full text]  [EPub]
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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
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.
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Ce 3+ Sensitized YPO 4 :Tb 3+ as Luminescent Probe for Selective Detection of Cu 2+ Ions
Naorem Shanta Singh, Ranjoy Wangkhem, Mehnaz Akhter Ahmed
October 2018, 5(2):74-89
Poly (acrylic acid) (PAA) modified water dispersible Ce 3+ (5 at.%) sensitized YPO 4 doped with Tb 3+ (5 at.%) nanocrystals were prepared by polyol method. Structural characterization was thoroughly studied with X-ray diffraction (XRD). Transmission electron microscopy (TEM) image indicate the rod shape morphology of the synthesized material. Fourier transform infrared (FTIR) spectroscopy confirms the surface functionalization of these nanorods. The sample shows the occurrence of strong energy transfer from Ce 3+ ions to Tb 3+ ions. The emission from Tb 3+ ions (green colour) could be selectively quenched with the addition of Cu 2+ ions upto ~89% compared to many of the heavy metal ions. It is established from the investigation the sensing is through dynamic quenching via resonance type energy transfer. The limit of detection calculated using Stern-Volmer relation is found to be 19 μM (~ 1 ppm). This nanophosphor could be a potential luminescent probe for Cu 2+ ions sensing.
[ABSTRACT]   Full text not available  [PDF]
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Protective effect of flavonoids from Foeniculum vulgare against ultraviolet-B-induced oxidative stress in human dermal fibroblasts
Juilee Patwardhan, Purvi Bhatt
July-December 2019, 6(2):62-71
Background: Traditionally, Foeniculum vulgare (fennel seeds) has been used for its antimicrobial, analgesic, antipyretic, antiflatulence, antispasmodic, and antiandrogenic activities. Materials and Methods: In the present study, the protective effect of flavonoids from fennel seeds was investigated against ultraviolet (UV)-B radiation-induced cell damage and oxidative stress in human dermal fibroblast (HDF) cells. Results: Flavonoid-enriched fraction (FEF) of fennel seeds showed high flavonoid content and antioxidant potential as well as the presence of a marker compound rutin. Pretreatment of HDF cells with the FEF (15–45 μg/ml) significantly protected against UV-B-induced cytotoxicity, endogenous enzymatic antioxidant depletion, oxidative DNA damage, intracellular reactive oxygen species generation, and apoptotic morphological changes. Conclusion: The current study proved for the first time that the FEF of fennel seeds reduced oxidative stress through the nuclear factor E2-related factor 2-antioxidant response elements pathway. Flavonoids from fennel seeds have a potential as UV-B protectants and can be explored against diseases, in which oxidative stress is closely implicated.
  734 69 -
Niosomes as Transdermal Drug Delivery System
Amruta Parmar, S Brijesh
October 2018, 5(2):54-63
Full text not available  [PDF]  [Mobile Full text]  [EPub]
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Sudeshna Chandra
October 2018, 5(2):52-53
Full text not available  [PDF]  [Mobile Full text]  [EPub]
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Analysis of spontaneous depolarization-linked hyperpolarizations in mouse detrusor smooth muscle cells
Mithun Padmakumar, Keith L Brain, Rohit Manchanda
July-December 2019, 6(2):49-55
Background: Urinary bladder detrusor smooth muscle cells exhibit spontaneous electrical activities comprising various signal types. Aims and Objectives: This article introduces and analyzes a rare category of signals observed in such activity, named spontaneous depolarization-linked hyperpolarization (sDLH). Materials and Methods: A mouse model was used in the study, where all the occurrences of sDLHs were pooled together from multiple intracellular recording sessions. Four features – (i) resting membrane potential (RMP) (R, in mV), (ii) depolarization amplitude (D, in mV), (iii) hyperpolarization amplitude (H, in mV), and (iv) time course of the hyperpolarization (T, in ms) – were evaluated from all sDLHs. Results: The analysis of results indicated that (a) the signals appear more frequently in cells with higher RMP, (b) the depolarization amplitudes seem to be distributed randomly and have no correlation with other features, (c) hyperpolarization amplitudes show two distinct clusters and exhibit strong correlation with the RMP, and (d) time course of hyperpolarization phase shows no distinct groups and is distributed in a window larger than that of any other signals seen in the intracellular recordings. With the help of the results obtained from the analysis, a hypothesis for the biophysical origin of these signals is proposed. Conclusions: This needs to be tested experimentally, and if proved right, would help extend the boundaries of our current understanding of the detrusor smooth muscle system.
  677 76 -
Evaluation of housekeeping genes for studies in breast cancer cell lines treated with progesterone
Aniket Parab, Jaykumar Kambli, Sujata Hake, Narendra Joshi
April 2018, 5(1):6-21
Real-time semi-quantitative PCR (qPCR) is extensively used to assess variations in gene expressions resulting from pathological conditions or biological responses. Normalization of qPCR data is required to control innate variations that occur during experimental procedures. Endogenous control genes (ECs), used for normalization of the data should be expressed constitutively and consistently across treatments groups. The aim of the present study was to identify the most suitable endogenous control genes for qPCR based analyses to study responses in breast cancer cell lines following exposure to Progesterone (P4). The expression and validity of five candidate ECs (PUM1, RPS13, RPL13A, TBCA and PSMB) were determined in three breast cancer cell lines following exposure to Progesterone. Gene expression data was analyzed using three methods, Normfinder, Bestkeeper, and Comparative delta Ct method. A significant difference in variance of expression levels of individual ECs under different growth conditions was observed. Expression of PUM1 and PSMB was minimally affected in breast cancer cell lines under the experimental conditions. Indeed, in the progesterone treated cells,PUM1 and PSMB were identified as the most stable EC genes by all three methods while TBCAand RPS13 were least stable. In breast cancer cell lines, our results highlight PSMB as another stably expressed endogenous control gene besides the previously identified PUM1. PSMB gene expression may thus provide an additional parameter for studies in breast cancers.
[ABSTRACT]   Full text not available  [PDF]
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Stability-indicating HPLC method for primaquine diphosphate: An application to niosomal formulation
Miloni Thakkar, S Brijesh
April 2018, 5(1):39-51
A novel, rapid, and precise stability-indicating gradient reverse-phase high performance liquid chromatographic method for the quantitative determination of primaquine diphosphate and its impurities was developed and validated. Efficient chromatographic separation was achieved on an Inertsil ODS-3V column (150 mm × 4.6 mm, 5.0 μm) with mobile phase containing phosphate buffer (0.05 M KH2PO4, pH 4.5) in gradient combination with acetonitrile at a flow rate of 1 mL/min and the analyte was monitored using a photo-diode array detector at a wavelength of 254 nm. The forced-degradation of primaquine diphosphate was carried out by exposing it to acidic, basic, neutral, thermal, photolytic, and oxidative stress conditions. The peaks of the degradation products obtained were well resolved from that of primaquine diphosphate, indicating that the method developed was specific and stability-indicating. Further, the method was validated according to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines, with respect to parameters such as specificity, precision, linearity, accuracy and robustness. The developed method could also be used for the quantification of primaquine diphosphate encapsulated in niosome formulation.
[ABSTRACT]   Full text not available  [PDF]
  442 125 -
Estimation of epidemiological parameters for historicalm ship outbreaks of influenza
Praveen Kumar, Anjali Kshirsagar, Pratip Shil
April 2018, 5(1):28-38
Periodic Influenza epidemics are a cause of concern world-wide due to heavy burden of disease consequently leading to economic distress mortality. In modern era, rapid international travel between populations makes the impact of air-borne diseases like Influenza more dramatic, as observed in the last pandemic due to Swine origin Influenza A/H1N1 2009. Though transmission of Influenza in humans has been studied in various settings, studies on ship outbreaks are sparse. The current research aims to analyze the historical Influenza outbreaks on sailing ships. Study revealed the pattern of transmission in isolated population and estimates the epidemiological parameters viz. basic reproduction number (R0), epidemic growth rate (r), transmission rate (β). High clustering lead to intense transmission with 0 high value of basic reproductive number, R0. Also, the study brought to light the limitations of analyzing 0 historical data.
[ABSTRACT]   Full text not available  [PDF]
  418 142 -
Telomere length maintenance mechanisms in cancer
Ekta Khattar
April 2018, 5(1):22-27
[ABSTRACT]   Full text not available  [PDF]
  364 159 -
Physiology of embryo-endometrial cross talk
Deepak N Modi, Pradeep Bhartiya
April 2015, 2(1):83-104
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]
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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
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]
  354 103 2
Clusterin in cancer: Dual role as a tumor suppressor gene and an oncogene
Rajashree Kadam, Tanuja Teni
October 2016, 3(2):130-156
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]
  352 96 -
Transplantation review: Liver, kidney, and pancreas transplantation
Rakesh Rai
July-December 2019, 6(2):78-81
  389 35 -
Visual inspection with acetic acid as a screening test for cervical cancer
Srabani Mittal, Jaydip Biswas, Partha Basu
April 2014, 1(1):23-33
Visual inspection with acetic acid (VIA) has been extensively investigated and accepted as potential alternative to cytology or Human Papilloma Virus (HPV) screening in limited resource settings. In developing countries, VIA may have several advantages over cytology or HPV screening. The consumables of the test are low-cost and readily available. VIA has potential of achieving large population coverage, as the test can be performed by a wide range of trained health care personnel and requires basic health infrastructure. It is a real-time test and offers logistic advantage of providing treatment for screen positive women during the same visit leading to high treatment coverage. The sensitivity and specificity estimates of VIA generally fall within the range of those reported for cytology and HPV testing. Randomized controlled trials evaluating test performance of VIA have demonstrated reduction in cervical cancer incidence and mortality in study population. The major limitation of VIA is that it is a subjective test and accuracy is dependent on the skill of trained providers. Low specificity and sub-optimal positive predictive value results in unnecessary referrals and/or treatment which can offset the perceived low cost of the test. VIA based screening programs are required to have clearly defined measurable indicators and a framework to identify the program strengths and weaknesses. Quality assurance of VIA is challenging specially because there is limited information on the test performance in multi-provider real programmatic setting. High quality training, periodic refresher courses, expertise of trained providers and close monitoring of performance indicators are required to ensure good quality VIA.
[ABSTRACT]   Full text not available  [PDF]
  338 86 -
Mathematical modeling of viral epidemics: A review
Pratip Shil
October 2016, 3(2):195-215
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]
  352 72 -