Association of lipid profile and obesity in patients with polycystic ovary syndrome.

Objective. Abnormal lipid profile and obesity increase the risk of polycystic ovary syndrome (PCOS). PCOS patients may have a greater risk of infertility, metabolic syndrome (MetS) and cardiovascular disease (CVD) due to abnormal lipid profile and obesity. The aim of the study was to find the association between abnormal lipid profile and obesity in patients with PCOS. Methods. In this case-control study, a total of 102 female subjects (51 diagnosed PCOS and 51 age-matched healthy controls) were enrolled, aged between 20-40 years. Biochemical parameters such as total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), very low-density lipoprotein-cholesterol (VLDL-C), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were estimated. Anthropometric parameters such as body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were recorded. A p<0.05 was considered statistically significant. Results. Mean of BMI, WC, WHR, LH, FSH, TC, TG, LDL-C, and VLDL-C was found significantly elevated in patients with PCOS as compared to controls (p<0.01). However, the mean of HDL-C was found significantly reduced in patients with PCOS as compared to controls (p<0.01). BMI has shown a significant positive correlation with WC (r=0.562, p<0.01) and WHR (r=0.580, p<0.01) among PCOS patients. LH has shown a significant positive correlation with FSH (r=0.572, p<0.01) among PCOS patients. TC has shown a significant positive correlation with TG (r=0.687, p<0.01), LDL-C (r=0.917, p<0.01), and VLDL-C (r=0.726, p<0.01) among PCOS patients. Conclusion. The results showed that abnormal lipid profile and obesity have a significant association with PCOS patients. Regular monitoring and treatment of PCOS patients are required to reduce the risk of infertility, MetS, and CVD.

Curcumin, its derivatives, and their nanoformulations: Revolutionizing cancer treatment.

Curcumin is a natural compound derived from turmeric and can target malignant tumor molecules involved in cancer propagation. It has potent antioxidant activity, but its effectiveness is limited due to poor absorption and rapid elimination from the body. Various curcumin derivatives have also shown anticancer potential in in-vitro and in-vivo models. Curcumin can target multiple signaling pathways involved in cancer development/progression or induce cancer cell death through apoptosis. In addition, curcumin and its derivatives could also enhance the effectiveness of conventional chemotherapy, radiation therapy and reduce their associated side effects. Lately, nanoparticle-based delivery systems are being developed/explored to overcome the challenges associated with curcumin's delivery, increasing its overall efficacy. The use of an imaging system to track these formulations could also give beneficial information about the bioavailability and distribution of the nano-curcumin complex. In conclusion, curcumin holds significant promise in the fight against cancer, especially in its nanoform, and could provide precise delivery to cancer cells without affecting normal healthy cells.

Differential expression of cancer stem cell markers and pro-inflammatory cytokine IL-1ß in the oral squamous cell carcinoma and oral submucosal fibrosis.

Objectives: The poor prognosis of oral squamous cell carcinoma (OSCC) is vastly due to late diagnosis. The oral submucosal fibrosis (OSMF) is often unnoticed pathology linked with high risk of malignancy. Recently, we demonstrated that the clinicopathological alterations in OSMF and OSCC patients were correlated with cancer stem cell (CSCs) markers (CD133 and CD44). However, the parallel alterations of interleukin-1 beta (IL-1ß) with CSCs expression are largely unexplored. Thus, we aimed to investigate the relationship between IL-1ß alterations and CSC marker expression in both OSMF and OSCC situations. Materials and Methods: A total of 135 people have signed up for the study. There were sixty each in OSMF and OSCC groups, as well as 15 healthy controls. Levels of serum IL-1ß were examined by ELISA. Immunohistochemistry (IHC) was used to examine the expression of CD133 and CD44. For evaluating differential CSCs expression, IHC scoring (0-4) was utilized. Results: The IHC results showed maximum subjects in the OSMF and OSCC displaying CD44 and CD133 positivity, although the extent of expression in terms of IHC scoring found variable. CD133 and CD44-positive subjects showed increased levels of IL-1ß in the OSMF and OSCC group. Nevertheless, the enhancement of IL-1ß is more pronounced in the OSCC cases. Further, we observed a direct link of IL-1ß levels with IHC scoring. Multivariate regression analysis demonstrated a significant role for CD44 and CD133 positivity in the increase of IL-1ß levels. Conclusion: We concluded that concurrent simultaneous changes in CSC biomarkers and IL-1ß may help with early detection of OSMF and OSCC conditions.

Interlinking of diabetes mellitus and cancer: An overview.

Cancer and diabetes mellitus (DM) are among the leading causes of mortality and morbidity in the global arena. Lately, several studies demonstrated that DM could promote cancer. However, the exact mechanism(s) highlighting this association are largely untouched and require comprehensive detailing. In the present review, we aimed to explore and decipher the possible mechanism of DM an cancer association. Hyperglycemia could be a subordinate plausible explanation of carcinogenesis in the diabatic patient. It is well known that high glucose levels may help in cancer proliferation. In addition, chronic inflammation, the other well-known factor of diabetes, could also play a role in carcinogenesis. Moreover, the numerous medicines to treat diabetes either increase or reduce cancer risk. Insulin is one of the potent growth factors that promotes cell propagation and induces cancer directly or via insulin like growth factor-1. On the other hand, hyperinsulinemia leads to an increased activity of growth factor-1 by inhibiting growth factor binding protein-1. To improve cancer prognosis, individuals with diabetes should be screened to discover cancer at an early stage and treated appropriately.

Awareness of COPD and Its Risk Factors Among the Adult Population of the Aseer Region, Saudi Arabia.

Introduction: Epidemiological studies are urgently needed to assess the prevalence of COPD in the region to determine the baseline, against which the future trends in the risk factor levels can be assessed and preventive strategies be planned to promote health among the population. Therefore, this study was undertaken to assess the awareness of COPD and its risk factors in Saudi Arabia. Materials and Methods: The cross-sectional study was conducted among the general adult population aged 18 years and above living in the Aseer region. A minimum sample of 385 was targeted, using the Raosoft sample size calculator. An online questionnaire was prepared in both English and Arabic language using Google forms and distributed among participants through social media. Results: It was observed that less than one-third (116, 30.12%) of the study population had ever heard about COPD. Nearly one-third spent time with smokers. Among all, 223 (57.3%) respondents had never heard and 46 (11.9%) respondents did not know anything about COPD. The majority correctly knew that the lungs are the primary organ affected by COPD (92, 79.3%). Age, sex, marital status, income, and occupation showed a significant association with COPD awareness. Nearly 41.4% knew that COPD progresses exclusively with age, COPD is more expensive for society than lung cancer (49.0%), cigarette smoking affects COPD (34.5%), COPD is fully recoverable with short-term antibiotics (35.0%), COPD lasts more than 18 months (48.1%), COPD can worsen with smoke exposure (37.4%), lead to disability (46.7%) and quitting smoking has an important role in preventing COPD (34.0%). Conclusion: The awareness regarding the disease was low among the respondents. Only one-third correctly knew that quitting smoking has an important role in preventing COPD. This study projects an urgent need of improving awareness of COPD and its risk factors in the general population.

Development and Evaluation of a TaqMan Real-Time PCR Assay for the Rapid Detection of Cross-Contamination of RD (Human) and L20B (Mouse) Cell Lines Used in Poliovirus Surveillance.

BACKGROUND: The cross-contamination of cell lines in culture is a persistent problem. Genetically modified L20B (Mouse) and RD (Human Rhabdomyosarcoma) cell lines are commonly used in poliovirus research, surveillance, and diagnostics. Cross-contamination between these cell lines leads to unreproducible results and unreliable surveillance data, negatively affecting public health. The gold standard method for cell authentication is Short Tandem Repeats analysis, which is time-consuming and expensive. The disadvantage of STR is limited detection of interspecies contamination. METHODS: This assay targets the mitochondrial cytochrome c oxidase subunit I (MTCO1) gene, a highly conserved and emergent DNA barcode region for detection of cross-contamination in RD and L20B cell lines. The MagNA Pure Compact instrument and ABI 7500 Fast Dx Real-time PCR systems were used for DNA extraction and to perform real-time PCR respectively. RESULTS: The newly developed assay is very sensitive with a limit of detection of 100 RD cells/1 million L20B/mL. The amplification efficiency and R2-value were 102.26% and 0.9969 respectively. We evaluated specificity of the assay with five human and four mouse cell lines, as well as monkey and rat cell lines. The assay showed no cross-reactivity with genomic DNA from human, mouse, rat, or monkey cell lines. The analytical sensitivity was also evaluated by spiking varying amounts of RD cells (0.001% - 10%) into L20B cells. There was no difference in CT values when running single-plex or duplex PCR reactions with similar experimental conditions. CONCLUSIONS: We have developed and validated a TaqMan real-time PCR assay, a sensitive method for the detection of cross-contamination of RD and L20B cell lines.

Isolated renal hydatid disease: laparoscopic approach to an uncommon entity (case report).

Hydatidosis is a parasitic disease, endemic in various parts of the World. It frequently involves liver and lungs and, rarely, other organs as well. Isolated renal hydatidosis is a rare entity that accounts for less than 3% of all hydatid cases. Surgery remains the mainstay of treatment. We hereby report a case of isolated renal hydatid cyst involving left kidney that was managed by laparoscopic approach.

Anti-Neuroinflammatory Potential of Polyphenols by Inhibiting NF-κB to Halt Alzheimer's Disease.

Alzheimer's disease (AD) is an irrevocable chronic brain disorder featured by neuronal loss, microglial accumulation, and progressive cognitive impairment. The proper pathophysiology of this life-threatening disorder is not completely understood and no exact remedies have been found yet. Over the last few decades, research on AD has mainly highlighted pathomechanisms linked to a couple of the major pathological hallmarks, including extracellular senile plaques made of amyloid-ß (Aß) peptides, and intracellular neurofibrillary tangles (NFTs) made of tau proteins. Aß can induce apoptosis, trigger an inflammatory response, and inhibit the synaptic plasticity of the hippocampus, which ultimately contributes to reducing cognitive functions and memory impairment. Recently, a third disease hallmark, the neuroinflammatory reaction that is mediated by cerebral innate immune cells, has become a spotlight in the current research area, assured by pre-clinical, clinical, and genetic investigations. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a cytokine producer, is significantly associated with physiological inflammatory proceedings and thus shows a promising candidate for inflammation- based AD therapy. Recent data reveal that phytochemicals, mainly polyphenol compounds, exhibit potential neuroprotective functions and these may be considered as a vital resource for discovering several drug candidates against AD. Interestingly, phytochemicals can easily interfere with the signaling pathway of NF-κB. This review represents the anti-neuroinflammatory potential of polyphenols as inhibitors of NF-κB to combat AD pathogenesis.

Solvent based optimization for extraction and stability of thymoquinone from Nigella sativa Linn. and its quantification using RP-HPLC.

The Nigella sativa pharmacological properties are mainly ascribed to its volatile oil, of which thymoquinone is an important bioactive component. Surprisingly, till date, no standard formulation or thymoquinone rich N. sativa extract is under clinical use probably due to its poor extraction and lesser stability in the already used solvents. In the present investigation solubility, extraction, percent composition and total antioxidant activity from the seeds of N. sativa was explored using five solvents. An HPLC method was standardized in an isocratic system (C-18 column, flow rate of 1.0 ml/min, mobile phase-water:methanol: 30:70, detection wavelength-254 nm, retention time-8.77 min) for quantification of thymoquinone. To further confirm the presence of thymoquinone in the respective extracts absorbance spectra analysis has been carried out and compared with pure thymoquinone. Additionally total antioxidant activity of Nigella sativa extracts has been evaluated using ascorbic acid as standard. Our results showed maximum percentage yield in aqueous extract while methanol having the least yield and the ethanol, benzene and hexane extracts exhibited moderate yields. A linear standard calibration curve of thymoquinone showed R2 as 0.999 and % RSD as 7.166. The HPLC analysis revealed maximum percentage composition of thymoquinone in the benzene extract, whereas in the hexane and methanol extracts the content was less. Aqueous and ethanol extracts displayed insignificant thymoquinone content. Absorbance spectra analysis confirms the presence of thymoquinone peak in the benzene, hexane and methanol extracts while aqueous and ethanol extracts showed minimal absorbance. Maximum total antioxidant activity was observed in the aqueous extract while minimum was observed in the methanolic extract. Weak positive (+ 0.3676) correlation was established between percent composition of thymoquinone and antioxidant activity among different extracts indicating that thymoquinone may not be the only factor for antioxidant activity, but other phytochemicals might also contribute. However, we for the first time demonstrated that the benzene extract of N. sativa has better solubility and percent composition of thymoquinone as compared to other solvents. It can be concluded that the solubility, differential composition of bioactive components among these extracts may have diverse effects on the total antiradical activity. Thus, our study provides insights on optimization and standardization of bioactive rich formulation of N. sativa.

MicroRNA expression profiling defines the impact of electronic cigarettes on human airway epithelial cells.

While all forms of tobacco exposure have negative health effects, the significance of exposure to electronic cigarettes (eCig) is not fully understood. Here, we studied the global effects of eCig on the micro RNA (miRNA) transcriptome in human lung epithelial cells. Primary human bronchial epithelial (NHBE) cells differentiated at air-liquid interface were exposed to eCig liquid. Exposure of NHBE to any eCig liquid resulted in the induction of oxidative stress-response genes including GCLM, GCLC, GPX2, NQO1 and HO-1. Vaporization of, and/or the presence of nicotine in, eCig liquid was associated with a greater response. We identified 578 miRNAs dysregulated by eCig exposure in NHBE, and 125 miRNA affected by vaporization of eCig liquid. Nicotine containing eCig vapor displayed the most profound effects upon miRNA expression. We selected 8 miRNAs (29A, 140, 126, 374A, 26A-2, 147B, 941 and 589) for further study. We validated increased expression of multiple miRNAs, including miR126, following eCig exposure. We also found significant reduction in the expression of two miR126 target genes, MYC and MRGPRX3, following exposure. These data demonstrated that eCig exposure has profound effects upon gene expression in human lung epithelial cells, some of which are epigenetically programmed at the level of miRNA regulation.

Galectins-A Potential Target for Cardiovascular Therapy.

Cells constantly adapt to external humoral cues like cytokines and hormones, but practically most cellular behavior is under locally guided control via cell-cell interactions. Galectins (Gals) are one of the most prominent members of the group of molecules involved in this intercellular signaling. They are the family of ß-galactoside specific lectins and consist of 15 different types, each with a specific function. They play crucial role in the immune system, inflammation, wound healing and carcinogenesis. In recent times, the role of Gals in the development of cardiovascular disease (CVD) has gained attention. Gals have been reported to act ambiguously by both relieving ischemia and accelerating atherosclerosis. Atherosclerosis can ultimately lead to myocardial infarction or ischemic stroke, which are both associated with Gals. There is also a role for Gals in the development of myocarditis by their influence on inflammatory processes. Moreover, Gal acts as a biomarker for the severity of myocardial ischemia and heart failure (HF). This review summarizes the association between Gals and the development and pathogenesis of CVD like atherosclerosis, stroke, myocardial infarction, and HF. A comprehensive outline of the association between Gals and more general mechanisms such as angiogenesis, arteriogenesis and atherosclerosis has also been provided. Modulation of Gal signaling holds great promise for the treatment of CVD as evident from preclinical studies.

Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.

The diagnosis of myelodysplastic syndrome (MDS) can be challenging, and may be facilitated by correlation with cytogenetic testing. Microarray analysis using comparative genomic hybridization and/or single-nucleotide polymorphism array can detect chromosomal abnormalities not seen by standard metaphase cytogenetics. We examined the ability of combined comparative genomic hybridization and single-nucleotide polymorphism analysis (hereafter referred to as 'combined array') to detect changes among 83 patients with unexplained cytopenias undergoing pathologic evaluation for MDS and compared results with 18 normal bone marrow controls. Thirty-seven patients (45%) were diagnosed with MDS, 12 patients (14%) were demonstrated to have 'indeterminate dyspoiesis' (insufficient for classification of MDS), 27 (33%) were essentially normal, and 7 patients (8%) had alternative pathologic diagnoses. Twenty-one MDS patients (57% of diagnoses) had effectively normal metaphase cytogenetics, but combined array showed that 5 of these (13% of MDS patients) harbored major cryptic chromosomal aberrations. Furthermore, nearly half of patients with 'indeterminate dyspoiesis' and 1 with normal morphology had clonal cytopenia(s) of undetermined significance by combined array analysis. Cryptic array findings among MDS patients and those with clonal cytopenias(s) included large-scale copy-neutral loss of heterozygosity (up to 118 Mb) and genomic deletion of loci implicated in MDS pathogenesis (eg, TET2 (4q22) and NUP98 (11p15)). By comparison, in MDS patients with abnormal metaphase cytogenetics, microarray mostly recapitulated findings seen by routine karyotype. Combined array analysis has considerable diagnostic yield in detecting cryptic chromosomal aberrations in MDS and in demonstrating aberrant clonal hematopoiesis in cytopenic patients with indeterminate morphologic dysplasia.

Recurrent copy number variants associated with bronchopulmonary dysplasia.

BACKGROUND: Variability in the incidence and severity of bronchopulmonary dysplasia (BPD) among premature infants suggests that genetic susceptibility plays a role in pathogenesis. An assessment of copy number variants (CNV) in BPD subjects may help to identify loci that harbor genetic susceptibility factors. METHODS: We conducted a retrospective analysis of clinical DNA microarray data from our institution. We identified 19 BPD subjects, and 2 controls groups (full-term and preterm) with no lung-related disease. We reanalyzed raw data from each of these subjects to identify recurrent CNV loci in BPD subjects. RESULTS: We identified three loci (at 11q13.2, 16p13.3, and 22q11.23-q12.1) with recurrent CNV in BPD subjects. The frequency of these CNV was significantly higher in BPD subjects when compared with at least one control group. We interrogated 21 genes residing within the recurrent CNV regions for development-associated changes in expression. Fifteen genes demonstrated significant changes in expression between the pseudoglandular and canalicular stage in human lungs, a time commensurate with birth at highest risk for BPD. We also identified pathways represented by the genes present within the recurrent loci. CONCLUSION: These data identify novel loci that may harbor genes contributing to the genetic susceptibility of BPD.

Integrating Qualitative and Quantitative Tools for the Detection and Identification of Lectins in Major Human Diseases.

Lectins are the (glyco)proteins that recognize and bind to specific sugar moieties without altering their structure. Galectins are mammalian lectins characterized by the presence of conserved 134 amino acids carbohydrate recognition domain and specificity for ß-galactosides. The involvement of lectins in diverse biological spectrum, especially some deadly human diseases like cancer, neurological disorders and cardiovascular disorders has proclaimed them as one of the important components of glycobiology, thereby seeking the methods of their detection and identification heavily desirable. In the present manuscript, we have provided a comprehensive outline of various methods of detection and identification of lectins employed till date, with their needs and usage varying according to the level of infrastructure of laboratories and around the world. In addition, a vision for some quick, highly sensitive and advanced methods for lectin detection and identification for diagnostic and therapeutic of various diseases is also provided.

Chronic unpredictable stress (CUS) enhances the carcinogenic potential of 7,12-dimethylbenz(a)anthracene (DMBA) and accelerates the onset of tumor development in Swiss albino mice.

Social stressors evolving from individual and population interactions produce stress reactions in many organisms (including humans), influencing homeostasis, altering the activity of the immunological system, and thus leading to various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) in cancer promotion and to assess oxidative stress outcomes in terms of various in vivo biochemical parameters, oxidative stress markers, DNA damage, and the development of skin tumors in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12-dimethylbenz(a)anthracene (DMBA) alone (topical), and DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical) and exposure to CUS prior to DMBA or DMBA-TPA treatments and sacrificed after 16 weeks of treatment. Prior exposure to CUS significantly increased the pro-oxidant effect of carcinogen, depicted by compromised levels of antioxidants in the circulation and skin, accompanied by enhanced lipid peroxidation, plasma corticosterone, and marker enzymes as compared to DMBA-alone or DMBA-TPA treatments. DNA damage results corroborated the above biochemical outcomes. Also, the development of skin tumors (in terms of their incidence, tumor yield, and tumor burden) in mice in the presence and absence of stress further strongly supported our above biochemical measurements. CUS may work as a promoter of carcinogenesis by enhancing the pro-oxidant potential of carcinogens. Further studies may be aimed at the development of interventions for disease prevention by identifying the relations between psychological factors and DNA damage.

Alterations in gene expression and DNA methylation during murine and human lung alveolar septation.

DNA methylation, a major epigenetic mechanism, may regulate coordinated expression of multiple genes at specific time points during alveolar septation in lung development. The objective of this study was to identify genes regulated by methylation during normal septation in mice and during disordered septation in bronchopulmonary dysplasia. In mice, newborn lungs (preseptation) and adult lungs (postseptation) were evaluated by microarray analysis of gene expression and immunoprecipitation of methylated DNA followed by sequencing (MeDIP-Seq). In humans, microarray gene expression data were integrated with genome-wide DNA methylation data from bronchopulmonary dysplasia versus preterm and term lung. Genes with reciprocal changes in expression and methylation, suggesting regulation by DNA methylation, were identified. In mice, 95 genes with inverse correlation between expression and methylation during normal septation were identified. In addition to genes known to be important in lung development (Wnt signaling, Angpt2, Sox9, etc.) and its extracellular matrix (Tnc, Eln, etc.), genes involved with immune and antioxidant defense (Stat4, Sod3, Prdx6, etc.) were also observed. In humans, 23 genes were differentially methylated with reciprocal changes in expression in bronchopulmonary dysplasia compared with preterm or term lung. Genes of interest included those involved with detoxifying enzymes (Gstm3) and transforming growth factor-ß signaling (bone morphogenetic protein 7 [Bmp7]). In terms of overlap, 20 genes and three pathways methylated during mouse lung development also demonstrated changes in methylation between preterm and term human lung. Changes in methylation correspond to altered expression of a number of genes associated with lung development, suggesting that DNA methylation of these genes may regulate normal and abnormal alveolar septation.

Current challenges to overcome in the management of type 2 diabetes mellitus and associated neurological disorders.

The increasing worldwide prevalence of type 2 diabetes mellitus (T2DM) and associated neurological disorders (NDs), such as Alzheimer disease and Parkinson's disease, have raised concerns about increasing health care and financial burden. Due to the overwhelming growth rate of T2DM and its strong association with NDs, there is an ever-growing and an urgent need to improve the diagnosis and management of the disease. Major hurdles in the management of T2DM comprise of striving for glycemic targets, polypharmacy, patient adherence and clinical inertia. The challenges occurring in the treatment of T2DM are mainly attributed to the complex heterogeneous nature of the disease and its close association with a wide variety of neurological, metabolic and cardiovascular disorders. To overcome these challenges, authors propose to focus on the treatment strategies that employ shared pathogenesis and common molecular denominators involved in the aetiology of T2DM and associated NDs. Impaired insulin signalling (as a result of perturbed redox status), insulin resistance and mitochondrial dysfunction are key molecular events that may lead to the pathogenesis of T2DM and associated NDs. However, effective management of these therapeutic strategies requires holistic experimental evidence from animal as well as clinical human studies. Therefore, a shift in the treatment paradigm from single point glycemic control to shared pathogenesis control would be an ideal approach to combat the alarming progression of diabetes and associated NDs. Therapeutic interventions focused on shared molecular pathogenesis, along with effective glycemic control, may provide protection from associated NDs.

Leukemia specific loss of heterozygosity of MHC in a CLL patient: disease state impacts timing of confirmatory typing.

A 63 year old white male with refractory B-CLL presented for allogeneic HSCT evaluation; HLA typing was performed on PBL at time of WBC = 53K, ALC = 47K and revealed homozygosity at Class I locus and heterozygosity at Class II locus. Two siblings were full mismatches with the recipient and an unrelated search initiated. The patient was treated with Fludaribine and Rituxan complicated by aplastic anemia and bacteremia. Prior to transplant, confirmatory typing performed on PB revealed two full haplotypes at Class I and II. Sample identification error and the presence of third party lymphocyte engraftment as a result of prior red cell or granulocyte transfusion(s) were ruled out by STR analysis of 8 loci of all samples, T and B cells from cryopreserved PB at blast crisis were HLA typed independently. T cell typing yielded both complete haplotypes (genotype verified by offspring HLA typing); B cells typed for homozygous haplotype indicating loss of heterozygosity of MHC locus. Microarray based comparative genomic hybridization of tumor cells confirmed LOH at 6p.

Significance of genome-wide analysis of copy number alterations and UPD in myelodysplastic syndromes using combined CGH - SNP arrays.

Genetic information is an extremely valuable data source in characterizing the personal nature of cancer. Chromosome instability is a hallmark of most cancer cells. Chromosomal abnormalities are correlated with poor prognosis, disease classification, risk stratification, and treatment selection. Copy number alterations (CNAs) are an important molecular signature in cancer initiation, development, and progression. Recent application of whole-genome tools to characterize normal and cancer genomes provides the powerful molecular cytogenetic means to enumerate the multiple somatic, genetic and epigenetic alterations that occur in cancer. Combined array comparative genomic hybridization (aCGH) with single nucleotide polymorphism (SNP) array is a useful technique allowing detection of CNAs and loss of heterozygosity (LOH) or uni-parental disomy (UPD) together in a single experiment. It also provides allelic information on deletions, duplications, and amplifications. UPD can result in an abnormal phenotype when the chromosomes involved are imprinted. Myelodysplastic syndromes (MDS) are the most common clonal stem cell hematologic malignancy characterized by ineffective hematopoiesis, which leads to rapid progression into acute myeloid leukemia. UPD that occurs without concurrent changes in the gene copy number is a common chromosomal defect in hematologic malignancies, especially in MDS. Approximately 40-50% of MDS patients do not have karyotypic abnormalities that are detectable using classical metaphase cytogenetic techniques (MC) because of inherent limitations of MC, low resolution and the requirement of having dividing cells. In this review, we highlight advances in the clinical application of microarray technology in MDS and discuss the clinical potential of microarray.

Brain region specific monoamine and oxidative changes during restraint stress.

BACKGROUND AND PURPOSE: Stress-induced central effects are regulated by brain neurotransmitters, glucocorticoids and oxidative processes. Therefore, we aimed to evaluate the simultaneous alterations in the monoamine and antioxidant systems in selected brain regions (frontal cortex, striatum and hippocampus) at 1 hour (h) and 24h following the exposure of restraint stress (RS), to understand their initial response and possible crosstalk. METHODS AND RESULTS: RS (150 min immobilization) significantly increased the dopamine levels in the frontal cortex and decreased them in the striatum and hippocampus, with selective increase of dopamine metabolites both in the 1h and 24h RS groups compared to control values. The serotonin and its metabolite levels were significantly increased in both time intervals, while noradrenaline levels were decreased in the frontal cortex and striatum only. The activities of superoxide dismutase, glutathione peroxidase and the levels of lipid peroxidation were significantly increased with significant decrease of glutathione levels in the frontal cortex and striatum both in the 1h and 24h RS groups. There was no significant change in the catalase activity in any group. In the hippocampus, the glutathione levels were significantly decreased only in the 1h RS group. CONCLUSIONS: Our study implies that the frontal cortex and striatum are more sensitive to oxidative burden which could be related to the parallel monoamine perturbations. This provides a rational look into the simultaneous compensatory central mechanisms operating during acute stress responses which are particular to precise brain regions and may have long lasting effects on various neuropathological alterations.