Increasing evidence shows the beneficial effects of fish oil on breast cancer growth and invasion in vitro and in animal models. Expression of CSF-1 (colony stimulating factor-1) by breast cancer cells acts as potent activator of malignancy and metastasis. In this report, we used two human breast cancer cell lines, MDA-MB-231 and MCF-7, to show that the bioactive fish oil component DHA (docosahexaenoic acid) inhibits expression of CSF-1 and its secretion from these cancer cells. We found that the tumor suppressor protein PTEN regulates CSF-1 expression through PI 3 kinase/Akt signaling via a transcriptional mechanism. The enhanced abundance of microRNA-21 (miR-21) in breast cancer cells contributes to the growth and metastasis. Interestingly, DHA significantly inhibited expression of miR-21. miR-21 Sponge, which derepresses the miR-21 targets, markedly decreased expression of CSF-1 and its secretion. Furthermore, miR-21-induced upregulation of CSF-1 mRNA and its transcription were prevented by expression of PTEN mRNA lacking 3′-untranslated region (UTR) and miR-21 recognition sequence. Strikingly, miR-21 reversed DHA-forced reduction of CSF-1 expression and secretion. Finally, we found that expression of miR-21 as well as CSF-1 was significantly attenuated in breast tumors of mice receiving a diet supplemented with fish oil. Our results reveal a novel mechanism for the therapeutic function of fish oil diet that blocks miR-21, thereby increasing PTEN levels to prevent expression of CSF-1 in breast cancer.
The data derived from epidemiological and animal models confirm a beneficial effect of fish oil (rich in ω-3 polyunsaturated fatty acids) in the amelioration of tumor growth and progression, including breast cancer. The breast cancer patients often develop bone metastasis evidenced by osteolytic lesions, leading to severe pain and bone fracture. Using a mouse model of MDA-MB-231 human breast cancer cell metastasis to bone, here we show that fish oil diet enriched in DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) prevents the formation of osteolytic lesions in bone, indicating suppression of cancer cell metastasis to bone. These results are supported by our data showing both DHA and EPA significantly attenuate the migration/invasion of MDA-MB-231 breast cancer cells in culture. The mechanism that limits breast cancer cells to selective metastasis to bone remains hitherto unexplored. Aberrant increased expression of CD44 is associated with generation of cancer stem cells, which contribute to metastasis of breast cancer cells. We demonstrate that DHA and EPA significantly inhibit the expression of CD44 protein and mRNA by a transcriptional mechanism. Furthermore, we show markedly reduced levels of CD44 mRNA and protein in the tumors of mice, which were fed fish oil diet than those in control diet. Our data provide the first evidence for a salutary effect of fish oil on breast cancer metastasis to bone. Our results identify a novel function of the fish oil active components, DHA and EPA, which target the cell-intrinsic pro-metastatic molecule CD44 to inhibit migration/invasion.
Sustained activation of Akt kinase acts as a focal regulator to increase cell growth and survival, which cause tumorigenesis including breast cancer. Statins, potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, display anticancer activity. The molecular mechanisms by which statins block cancer cell growth are poorly understood. We demonstrate that in the tumors derived from MDA-MB-231 human breast cancer cell xenografts, simvastatin significantly inhibited phosphorylation of Akt with concomitant attenuation of expression of the anti-apoptotic protein BclXL. In many cancer cells, BclXL is a target of NFκB. Simvastatin inhibited the DNA binding and transcriptional activities of NF κ B resulting in marked reduction in transcription of BclXL. Signals transmitted by anti-neoplastic mechanism implanted in the cancer cells serve to obstruct the initial outgrowth of tumors. One such mechanism represents the action of the tumor suppressor protein PTEN, which negatively regulates Akt kinase activity. We provide the first evidence for significantly increased levels of PTEN in the tumors of simvastatin-administered mice. Importantly, simvastatin markedly prevented binding of NFκB to the two canonical recognition elements, NFRE-1 and NFRE-2 present in the PTEN promoter. Contrary to the transcriptional suppression of BclXL, simvastatin significantly increased the transcription of PTEN. Furthermore, expression of NFκ B p65 subunit inhibited transcription of PTEN, resulting in reduced protein expression, which leads to enhanced phosphorylation of Akt. Taken together, our data present a novel bifaceted mechanism where simvastatin acts on a nodal transcription factor NFκ B, which attenuates the expression of anti-apoptotic BclXL and simultaneously derepresses the expression of anti-proliferative/proapoptotic tumor suppressor PTEN to prevent breast cancer cell growth.
Statin; Breast tumor; BclXL; Akt kinase
Up to 40% of acute ischaemic strokes in young adults are cryptogenic in nature, that is, no cause is determined. In more than half of these patients, patent foramen ovale (PFO) is seen along with an increased incidence of atrial septal aneurysm. The commonest method of investigation is echocardiography (preferably transoesophageal echocardiography). On the basis of available evidence, low risk patients are treated with antiplatelet agents and high risk patients with warfarin. There are inconclusive data on the efficacy of PFO closure to prevent stroke recurrence. However, if there is recurrent stroke or intolerance to medical therapy, percutaneous closure is carried out.
atrial septal defect; cryptogenic stroke; patent foramen ovale
Giardia lamblia is a microaerophilic human gastrointestinal parasite and considered as an early-diverged eukaryote. In vitro oxidative stress generation plays a significant role in cell cycle progression and cell death of this parasite. In the present study hydrogen peroxide, metronidazole, and a modified growth medium without cysteine and ascorbic acid have been chosen as oxidative stress-inducing agents. Cell cycle progression has been found to be regulated by different types of oxidative stresses. Apoptosis is not an established pathway in Giardia, which is devoid of ideal mitochondria, but in the present investigation, apoptosis-like programmed cell death has been found by the experiments like AnnexinV-FITC assay, DNA fragmentation pattern, etc. On the contrary, Caspase-9 assay, which confirms the caspase-mediated apoptotic pathway, has been found to be negative in all the stress conditions. Protease inhibitor assay confirmed that, even in absence of any proteases, programmed cell death does occur in this primitive eukaryote. All these results signify a novel pathway of programmed suicidal death in Giardia lamblia under oxidative stress. This is the first demonstration of protease-independent programmed cell death regulation in Giardia exclusive for its own specialties.
Giardia lamblia; oxidative stress; reactive oxygen species; programmed cell death; apoptosis; early branching eukaryotes
Using synthetic antisense RNA from the 5'-untranslated region of the beta-tubulin gene as probe in gel retardation assays, a heat stable RNA-binding factor was identified in promastigotes of the kinetoplastid protozoan Leishmania donovani. The same or similar factors interact with several small ribosomal RNA (srRNA) species and, more weakly, with tRNA, as shown by binding and competition experiments. Deletion analysis indicated involvement of repeated purine-rich motifs on the antisense RNA, in the reaction. Related, conserved motifs occur on at least two of the srRNAs. By a modified Western blot assay, the RNA-binding species was identified as a single, small polypeptide. The activity is apparently specific for the promastigote stage of the parasite, being undetectable in amastigotes. The properties of this RNA-binding factor suggest that it is a novel, previously uncharacterized protein.
To assess efficacy and safety of lornoxicam as analgesic after surgery on head and neck in comparison to tramadol. Forty five patients undergoing operations on head and neck were recruited and randomly assigned to two parallel groups—lornoxicam and tramadol, both given intramuscular on the first post-operative day followed by oral tablets for the consecutive 4 days. Treatment was given single blind. 10 cm visual analog scale (VAS) pain score and wound tenderness assessed by a 3-point ordinal scale were the primary efficacy parameters. Use of rescue medication and percentage of subjects having at least 50 % pain relief by 48 h were also compared as secondary parameters. The groups were comparable at baseline regarding age, sex and VAS score. There was steady decline in VAS pain score from baseline to study end in both the groups, indicating good analgesic efficacy with either drug. Between groups comparisons of VAS score showed no significant difference at any time point. Between groups comparisons of wound tenderness also showed no significant difference. Five patients on lornoxicam and one patient on tramadol experienced at least 50 % pain relief at 48 hours compared to baseline while five patients from the lornoxicam group and eight from the tramadol group required rescue medicine. The tolerability of lornoxicam appeared to be significantly superior to tramadol, with less number of patients experiencing adverse drug reactions. Lornoxicam is safe, effective and comparable to tramadol for relieving postoperative pain after operations on head and neck.
Lornoxicam; Tramadol; Post-operative pain; VAS score
Transforming growth factorβ (TGFβ)-induced canonical signal transduction is involved in glomerular mesangial cell hypertrophy; however, the role played by the noncanonical TGFβ signaling remains largely unexplored. TGFβ time-dependently stimulated eIF4E phosphorylation at Ser-209 concomitant with enhanced phosphorylation of Erk1/2 (extracellular signal regulated kinase1/2) and MEK (mitogen-activated and extracellular signal-regulated kinase kinase) in mesangial cells. Inhibition of Erk1/2 by MEK inhibitor or by expression of dominant negative Erk2 blocked eIF4E phosphorylation, resulting in attenuation of TGFβ-induced protein synthesis and mesangial cell hypertrophy. Expression of constitutively active (CA) MEK was sufficient to induce protein synthesis and hypertrophy similar to those induced by TGFβ. Pharmacological or dominant negative inhibition of phosphatidylinositol (PI) 3 kinase decreased MEK/Erk1/2 phosphorylation leading to suppression of eIF4E phosphorylation. Inducible phosphorylation of eIF4E at Ser-209 is mediated by Mnk-1 (mitogen-activated protein kinase signal-integrating kinase-1). Both PI 3 kinase and Erk1/2 promoted phosphorylation of Mnk-1 in response to TGFβ. Dominant negative Mnk-1 significantly inhibited TGFβ-stimulated protein synthesis and hypertrophy. Interestingly, inhibition of mTORC1 activity, which blocks dissociation of eIF4E-4EBP-1 complex, decreased TGFβ-stimulated phosphorylation of eIF4E without any effect on Mnk-1 phosphorylation. Furthermore, mutant eIF4E S209D, which mimics phosphorylated eIF4E, promoted protein synthesis and hypertrophy similar to TGFβ. These results were confirmed using phosphorylation deficient mutant of eIF4E. Together our results highlight a significant role of dissociation of 4EBP-1-eIF4E complex for Mnk-1-mediated phosphorylation of eIF4E. Moreover, we conclude that TGFβ-induced noncanonical signaling circuit involving PI 3 kinase-dependent Mnk-1-mediated phosphorylation of eIF4E at Ser-209 is required to facilitate mesangial cell hypertrophy.
Rheumatoid arthritis (RA) is an independent risk factor for adverse cardiovascular (CV) events that accounts for a significant proportion of mortality among these patients. Anti-CCP antibodies are associated with higher frequency of extra-articular manifestations and poorer outcomes in RA.
To determine the role of anti-cyclic citrullinated peptide (CCP) antibody as an independent risk factor for developing CV complications as documented by carotid intima medial thickness and abnormal echocardiography in established RA patients.
Materials and methods
Eighty patients of RA having disease duration of at least 3 years participated in this hospital-based, cross-sectional, and observational study. Forty patients were anti-CCP antibody positive. Patients of established RA having known CV risk factors, known heart disease, or family history of premature ischemic heart disease were excluded.
Anti-CCP positive group had early morning stiffness, tender and swollen joint count, and c-reactive protein (CRP) level significantly higher than those in anti-CCP negative group. Average intima-medial thicknesses of common carotid arteries were also significantly higher among anti-CCP positive group (P = 0.029) and were positively correlated with patients' age and disease duration. Lower left ventricular ejection fraction and left ventricular diastolic dysfunction were more commonly dispersed among the anti-CCP positive patients with P values of 0.01 and 0.034, respectively. Mild pericardial thickening was documented among 12.5% patients of anti-CCP positive group, while none of the anti-CCP negative patients had similar findings in echocardiography.
This study stressed on the important role of anti-CCP antibody in myocardial dysfunction due to inflammation in RA patients. Both atherosclerotic vascular involvement and cardiac abnormalities including pericardial, myocardial, and endocardial involvements were higher among anti-CCP positive RA patients. Hence, patients with high titer of anti-CCP antibody associated with prolonged disease duration and increased disease activity should be evaluated for CV morbidity more meticulously.
Anti-CCP antibody; Cardiovascular complications; Carotid intima-medial thickness; Rheumatoid arthritis
Cervical and endometrial carcinoma incidentally found in the surgical specimen with high risk pathological finding or with gross residual disease.
Material and Methods
Between 2004 and 2010, 320 cervical and endometrial cancer patients were treated with EBRT and brachytherapy after having undergone total/subtotal hysterectomy. Sixty patients were lost to follow-up.
Median follow-up was 21 months. Endometrial and cervical cancer with a high risk for local recurrence achieved CR 93.8 and 89 %, respectively. 56 % patients experienced CR with residual disease with cervical cancer. Median OS for endometrial and cervical cancer with residual disease was 8.5 and 24 months, respectively. Grade 3 adverse events were 5 and 3.5 % for rectum and bladder, respectively.
The incorporation of chemotherapy during pelvic radiotherapy followed by HDR interstitial brachytherapy for residual disease is inadequate and improves survival. We are still in learning phase of brachytherapy in post-operative gynaecological malignancy cases; expertise will be developed by practice.
Gynaecological malignancy; Hysterectomy; Brachytherapy; Survival
We conducted a survey to analyze the genetic epidemiology of trisomy 21 Down syndrome births in the Sundarban delta region of India. In this region, inhabitants are chiefly from marginalized poor tribal communities and have lived in extremely low socioeconomic condition for several generations. Microsatellite genotyping revealed an meiosis I/meiosis II ratio that is different from the previous reports on the Down syndrome populations from other parts of the world. Analyses of distribution of achiasmate nondisjunction at maternal meiosis I in interaction with different maternal age groups (young, middle, and old) revealed a very concordant pattern to that of urban and semi-urban Down syndrome cases previously studied by our group. However, the frequency of achiasmate meiosis is much lower, which suggests that extreme low socioeconomic exposure imparts risk of chromosomal nondisjunction even when the maternal chromosomes 21 engage in proper chiasma formation at prophase I of oogenesis.
Down syndrome; Maternal age; Nondisjunction; Socioeconomic exposure; Recombination; Sundarban population
The presence of brown adipose tissue (BAT) responsible for thermogenic energy dissipation has been revealed in adult humans and has high clinical importance. Due to limitations of current methods for BAT detection, analyzing the abundance and localization of BAT in the body has remained challenging. Here, we screen a combinatorial peptide library in mice and characterize a peptide (with the sequence CPATAERPC) that selectively binds to the vascular endothelium of BAT, but not of intraperitoneal white adipose tissue (WAT). We show that in addition to BAT, this peptide probe also recognizes the vasculature of BAT-like depots of subcutaneous WAT. Our results indicate that the CPATAERPC peptide localizes to BAT even in the absence of sympathetic nervous system stimulation. Finally, we demonstrate that this probe can be used to identify BAT depots in mice by whole body near-infrared (NIR) fluorescence imaging.
Hepatocellular carcinoma (HCC) is a multistep complex process, caused by many of genetic alteration. Insulin-like growth factors and their receptor have been widely implicated to HCC. Insulin-like growth factor-II (IGF-II) is a mitogenic polypeptide, found in various fetal and neonatal tissues of humans and rats and expresses in HCC. Here we investigated anticancer potential of phosphorothioate antisense oligonucleotides (ASOs) against three coding exons (exon-1/exon-2/exon-3) of IGF-II messenger ribonucleic acid in rat hepatocarcinogenesis model.
Materials and Methods:
During diethylnitrosamine and 2-acetylaminofluorene induced hepatocarcinogenesis, rats were treated with ASOs. Various biochemical and histological studies were conducted.
About 40% of carcinogen treated rats, which received two oligomers (against exon-1 or-3) did not show any hepatic lesion, hyperplastic nodule or tumor and remaining 60% of those rats showed lesion incidence and had about 59% and 55% reductions in the numbers of hepatic altered foci, respectively. Reductions in the total lesion-area when compared with carcinogen control rats were 64% and 53%, respectively for the animals treated with carcinogen and received the ASOs against exon-1/-3. Fluorescein isothiocyanate-labeled ASO reached in the hepatocytes in 2 h. No predominant IGF-II overexpression was observed in case of rats treated with the two ASOs. Treatment of the antisense IGF-II oligomers in carcinogen treated rats show better hepatocellular integrity along with several preneoplastic/neoplastic marker isoenzyme/enzyme modulations.
Two of the three antisense oligomer-types effectively controlled IGF-II overexpression, causing the delay of the development and/or progress of hepatic cancer in rats.
Antisense oligonucleotides; hepatic altered foci; hepatocellular carcinoma; hyperplastic nodules; insulin-like growth factor
Tuberculosis verrucosa cutis (TVC) is a common cutaneous form of paucibacillary tuberculosis in an individual with moderate to high degree of immunity to Mycobacterium tuberculosis infection. Clinical appearance of TVC is mostly very typical with well-defined warty plaques presenting mostly on hands, knees, ankle, and buttocks; however several atypical morphology of the lesions have also been described. We hereby report a case of TVC, masquerading as asymptomatic diffuse keratoderma of left foot for nine months, in an otherwise healthy individual, obstructing easy diagnosis of cutaneous tuberculosis. Diagnosis was confirmed by histopathology.
Diffuse keratoderma; tuberculosis verrucosa cutis; warty tuberculosis
Human papillomavirus (HPV) types 16/18 are reportedly most common in cervical cancer (CaCx) with geographical variation of genotypes. HPV16 predominates both in squamous cell carcinoma (SCC) and adenocarcinoma in India, contrary to reported global predominance of HPV18 in the latter. Our study was aimed to determine the occurrence of HPV16/18 among histopathological types of cervical intra-epithelial neoplasia (CIN) and invasive CaCx from North Bengal, India and to identify any major deviation from the known Indian scenario of distribution of HPV16/18 genotypes in cases of SCC and adenocarcinoma.
Materials and Methods:
This was a retrospective, cross-sectional, case-only type of study, in which 40 cases were histopathologically diagnosed as CIN/CaCx, on which polymerase chain reaction (PCR), deoxyribonucleic acid (DNA)-sequencing and bioinformatics by basic search local alignment tool were performed for HPV-genotyping.
The distribution of HPV genotypes among cases of SCC and adenocarcinoma was compared by Fisher's exact-test.
HPV was detected in 97.5% (39/40) cases. HPV16-infected cases (32/39; 82.05%) predominated over HPV18-infected ones (7/39; 17.95%). However, HPV18-only infection was significantly (P = 0.0045, one-sided Fisher's exact test) more among adenocarcinoma (3/4; 75%) than SCC (2/26; 7.69%) contrary to HPV16-only infection (SCC = 24/26, 92.31%; adenocarcinoma = 1/4; 25%) whereas both CIN3 cases were HPV16-positive.
Predominance of HPV18 over HPV16 in cases of adenocarcinoma in this region was contrasting to that of earlier Indian studies suggesting research on HPV18 related cervical carcinogenesis. PCR and DNA-sequencing could prove to be highly effective tools in HPV detection and genotyping. The study reported HPV16/18 infection in almost 98% of the cases, the knowledge about which might prove useful in future population based studies on HPV genotyping and designing of appropriate HPV-vaccines for this region.
Cervical cancer; histopathology; human papillomavirus 16/18; polymerase chain reaction; North Bengal
Carboplatin and paclitaxel as doublet are the standard therapeutic option for advanced stage ovarian carcinoma in the first line as well as relapse. Carboplatin with its better toxicity profile has replaced cisplatin as the first line drug. However, increase in incidence of carboplatin hypersensitivity is alarming. Severity of carboplatin hypersensitivity varies from a mild rash to life-threatening reactions. With an increase in the number of cycles the risk of hypersensitivity reactions increase, which jeopardizes the use of this highly effective drug in a significant proportion of patients. Prompt diagnosis and rapid therapeutic rescue are the key in severe life-threatening reactions. Managing patients with carboplatin hypersensitivity and planning subsequent therapy is thus a therapeutic challenge.
Carboplatin; desensitization; hypersensitivity
Psoralea corylifolia (Somraji) and Trigonella foenum-graecum L. (Methi), important medicinal plants widely used in India as folk medicine. Local people of West Bengal traditionally used the seeds of these plants to cure diabetes.
Present study was designed to investigate the antidiabetic efficacy of aqueous extract of seeds of these plants in separate or in composite manner in streptozotocin (STZ)-induced diabetic rat.
Materials and Methods:
Diabetes was induced by intramuscular injection of STZ at the dose of 40 mg/ml of citrate buffer/kg body weight. Fasting blood glucose (FBG), glyclated hemoglobin (HbA1C) and activities of hexokinase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase of liver in experimental animals were assessed. Hyperlipidemic state developed in the experimental diabetic rat was assessed by measuring the levels of total cholesterol, triglyceride, and lipoproteins in serum.
There was significant increased in the levels of FBG, HbA1C and lipid profiles along with diminution (P < 0.001) in the activities of hepatic hexokinase, glucose-6-phosphate dehydrogenase and elevation in glucose-6-phosphatase in diabetic control animals in respect to the untreated control. Significant recovery (P < 0.05) in the activities of above mentioned enzymes along with the correction in the levels of FBG, HbA1C and serum lipid profiles were noted towards the control level after the treatment of composite extract (i.e. 100 mg of Somraji: 100 mg of Methi, total 200 mg/kg body weight) than the individual extract (i.e. 200 mg of Somraji or 200 mg of Methi, per kg body weight) treatment.
Results suggest that composite extract of above plant parts has more potent antidiabetic efficacy than the individual extract.
Carbohydrate metabolic enzymes; glycogen; lipid profiles; streptozotocin
The U3-LTR region of leukemia viruses transactivates cancer-related signaling pathways through the production of a non-coding RNA transcript although the role of this transcript in virus infection remains unknown. In this study we demonstrate for the first time that an LTR-specific small non-coding RNA is produced from a FeLV-infected feline cell line. RNA cloning identified this as a 104 base transcript that originates from the U3-LTR region. We also demonstrate that in in vitro assays this LTR RNA transcript activates NFκB signaling. Taken together, our findings suggest a possible role for this LTR transcript in FeLV pathogenesis.
FeLV; LTR; non-coding RNA
Despite the devastating effect of suicide on numerous lives, there is still a lack of knowledge concerning its neurochemical aspects. There is increasing evidence that brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are involved in the pathophysiology and treatment of depression through binding and activating their cognate receptors TrkB and TrkA respectively. The present study was performed to examine whether the expression profiles of BDNF and/or TrkB as well as NGF and/or TrkA were altered in the hippocampus of postmortem brain of the participants, who had committed suicide and whether these alterations were associated with specific psychopathologic conditions. These studies were performed on the hippocampus of 21 suicide victims and 19 non-psychiatric control individuals. The protein and mRNA levels of BDNF, TrkB, NGF, and TrkA were determined by sandwich enzyme-linked immunosorbent assay, Western blot and reverse transcription-PCR. Given the importance of BDNF and NGF and their cognate receptors in mediating physiological functions, including cell survival and synaptic plasticity, our findings of reduced expression of BDNF, TrkB, NGF, and TrkA on both the protein and mRNA levels of postmortem brains of suicide victims suggest that these molecules may play an important role in the pathophysiological aspects of suicidal behavior.
brain-derived neurotrophic factor; nerve growth factor; suicide; postmortem brain; hippocampus; TrkB; TrkA; RT-PCR; ELISA
Keratoconus (KC; Mendelian Inheritance in Man (OMIM) 14830) is a bilateral, progressive corneal defect affecting all ethnic groups around the world. It is the leading cause of corneal transplantation. The age of onset is at puberty, and the disorder is progressive until the 3rd–4th decade of life when it usually arrests. It is one of the major ocular problems with significant social and economic impacts as the disease affects young generation. Although genetic and environmental factors are associated with KC, but the precise etiology is still elusive. Results from complex segregation analysis suggests that genetic abnormalities may play an essential role in the susceptibility to KC. Due to genetic heterogeneity, a recent study revealed 17 different genomic loci identified in KC families by linkage mapping in various populations. The focus of this review is to provide a concise update on the current knowledge of the genetic basis of KC and genomic approaches to understand the disease pathogenesis.
Disease pathogenesis; genetic heterogeneity; genetics and genomics; genome-wide association study; genomic loci; keratoconus; linkage mapping; molecular mechanisms; whole exome-genome sequencing
Keratoconus is a progressive corneal thinning disease associated with significant tissue remodeling activities and activation of a variety of signaling networks. However, it is not understood how differential gene and protein expression direct function in keratoconus corneas to drive the underlying pathology, ectasia. Research in the field has focused on discovering differentially expressed genes and proteins and quantifying their levels and activities in keratoconus patient samples. In this study, both microarray analysis of total ribonucleic acid (RNA) and whole proteome analyses are carried out using corneal epithelium and tears from keratoconus patients and compared to healthy controls. A number of structural proteins, signaling molecules, cytokines, proteases, and enzymes have been found to be deregulated in keratoconus corneas. Together, the data provide clues to the complex process of corneal degradation which suggest novel ways to clinically diagnose and manage the disease. This review will focus on discussing these recent advances in the knowledge of keratoconus biology from a gene expression and function point-of-view.
Deregulation; ectasia; gene expression; keratoconus; mass spectroscopy; proteomics; signaling pathways
Yellow mosaic disease, caused by a whitefly transmitted New World Begomovirus, named Corchorus golden mosaic virus (CoGMV), is emerging as a serious biotic constraint for jute fibre production in Asia. For rapid and sensitive diagnosis of the Begomovirus associated with this disease, a non-radiolabelled diagnostic probe, developed against the DNA A component of the east Indian isolate of CoGMV, detected the presence of the virus in infected plants and viruliferous whiteflies following Southern hybridization and nucleic acid spot hybridization tests. Presence of the virus was also confirmed when polymerase chain reaction amplification was performed using virus-specific primers on DNA templates isolated from infected plants and viruliferous whiteflies.
New world; Begomovirus; PCR; Probe; Hybridization
The aim of this study is to understand the mechanism of EGFR overexpression in head and neck squamous cell carcinoma (HNSCC). For this reason, expression/mutation of EGFR were analyzed in 30 dysplastic head and neck lesions and 148 HNSCC samples of Indian patients along with 3 HNSCC cell lines. In addition, deletion/methylation/mutation/expression of SH3GL2 (associated with EGFR degradation) and CDC25A (associated with dephosphorylation of EGFR) were analyzed in the same set of samples. Our study revealed high frequency of EGFR overexpression (66–84%), low frequency of gene amplification (10–32.5%) and absence of functional mutation in the dysplastic lesions and HNSCC samples. No correlation was found between protein overexpression and mRNA expression/gene amplification status of EGFR. On the other hand, frequent alterations (deletion/methylation) of SH3GL2 (63–77%) and CDC25A (37–64%) were seen in the dysplastic and HNSCC samples. Two novel single nucleotide polymorphism (SNPs) were found in the promoter region of SH3GL2. Reduced expression of these genes showed concordance with their alterations. Overexpression of EGFR and p-EGFR were significantly associated with reduced expression and alterations of SH3GL2 and CDC25A respectively. In-vitro demethylation experiment by 5-aza-2′-deoxycytidine (5-aza-dC) showed upregulation of SH3GL2 and CDC25A and downregulation of EGFR expression in Hep2 cell line. Poor patient outcome was predicted in the cases with alterations of SH3GL2 and CDC25A in presence of human papilloma virus (HPV) infection. Also, low SH3GL2 and high EGFR expression was a predictor of poor patient survival. Thus, our data suggests that overexpression of EGFR due to its reduced degradation and dephosphorylation is needed for development of HNSCC.
The International Consortium (FTDC) that revised the diagnostic criteria for behavioural variant frontotemporal dementia (bvFTD) did not have an Asian representation. Whether the revised criteria are equally useful in the early detection of Asian bvFTD patients therefore remains largely unexplored. Earlier studies have indicated differences in clinical manifestations in Indian and other Asian bvFTD patients when compared to western groups. There is an urgent need for clarification, given the projected exponential rise in dementia in these countries and the imminent clinical trials on bvFTD.
To assess how Indian bvFTD patients fulfil the FTDC criteria, hypothesizing that our patients might present differently early in the illness.
In a hospital-based retrospective observational study, we assessed 48 probable bvFTD patients, diagnosed according to the FTDC criteria, for the speed with which these criteria were fulfilled, the frequency of individual symptoms and their order of appearance during the illness.
Most of our patients presented with moderate to severe dementia, in spite of having relatively short onset to diagnosis times. Patients on average took 1.4 years from onset to meet the FTDC criteria, with 90% of them presenting with four or more symptoms at diagnosis. Disinhibition was the commonest symptom and the first symptom in most patients.
With most patients presenting with advanced and florid disease, the FTDC criteria have little additional impact in early identification of bvFTD in India. Modifying the criteria further could allow detection of Indian patients early enough for their inclusion in future clinical trials.
Obesity; Overweight; Children; Adolescent