A review on interplay between small RNAs and oxidative stress in cancer progression.

Oxidative stress has been known to be the underlying cause in many instances of cancer development. The new aspect of cancer genesis that has caught the attention of many researchers worldwide is its connection to non-coding RNAs (ncRNAs). ncRNAs may not be protein coding, but in light of the more recent discovery of their wide range of functions, the term 'dark matter of the genome' has been rendered inapplicable. There is an extensive mention of colon cancer as an example, where some of these ncRNAs and their manipulations have seen significant progress. As of now, the focus is on discovering a non-invasive, cost-effective method for diagnosis that is easier to monitor and can be conducted before visible symptoms indicate cancer in a patient, by which time it may already be too late. The concept of liquid biopsies has revolutionized recent diagnostic measures. It has been possible to detect circulating parts of the cancer genome or other biomarkers in the patients' bodily fluids, resulting in the effective management of the disease. This has led these ncRNAs to be considered effective therapeutic targets and extrinsic modifications in several tumor types, proven to be effective as therapy. However, there is a vast scope for further understanding and pertinent application of our acquired knowledge and expanding it in enhancing the utilization of ncRNAs for a better prognosis, quicker diagnosis, and improved management of cancer. This review explores the prognosis of cancer and related mutations by scrutinizing small ncRNAs in the disease.

Role of Tumor Specific niche in Colon Cancer Progression and Emerging Therapies by Targeting Tumor Microenvironment.

Colorectal cancer is the third most common form of cancer worldwide leading to escalating mortality rates and mainly includes hereditary, sporadic and colitis-associated cancer development. The escalated mortality rates is due to the limited treatment options as this form of cancer is usually not easy to diagnose in its early stages and are highly invasive leading to rapid metastasis of the malignant cells to the neighbouring tissue. In order to combat this limitation several chemotherapeutic regimens are now being combined with targeted therapies after the knowledge acquired on the inevitable effects of the tumor microenvironment on the colon cancer growth and progress. The colon tumor niche mainly consists of a large mass of tumor cells along with various immune cells, inflammatory cells, tumor macrophages and fibroblasts that infiltrate the tumor as it is a site of predominant inflammation. Among cells of the microenvironment, mesenchymal stem cells (MSCs) exhibiting ability to evolve into cancer associated fibroblasts (CAFs) have recently generated a major interest in the field. The physiological state of the tumor microenvironment is closely connected to discrete steps of tumorigenesis. The colon cancer cells elicit various factors with their direct interaction with MSCs or via paracrine fashion, which modulate these cells to promote cancer instead of performing their innate function of abating cancer progression. This review intends to highlight the necessity to exploit the cellular landscape of tumor microenvironment of colon cancer and a detailed understanding of the interactions between tumor epithelial cells and their stromal/inflammatory elements will aid in future perspectives for designing therapeutic regimens targeting tumor microenvironment to improve the clinical outcome of colon cancer.

A Study of Correlation between Apolipoprotein B and Dyslipidemia in Type 2 Diabetes Patients and its Relation with Proteinuria- A Tertiary Care Hospital Based Study.

OBJECTIVES: Individual with diabetes may have several from of Dyslipidemia. Dyslipidemia has been considered to be factor that plays a risk in progression of micro vascular disease, especially in diabetes.1 The present study is intended to Study of correlation between Apolipoprotein B and Dyslipidemia in type 2 diabetes patients and prevalence of dyslipidemia in type 2 diabetic patients. MATERIAL AND METHODS: Prospective cross- sectional study conducted on 100 cases of type 2 diabetes mellitus. Groups are divided according to A/C ratio and association of dyslipidemia was seen. Serum Apolipoprotein B was measured using immunoturbidimetric method. RESULTS: Pearson's correlation analysis of Apo B with lipid parameters in diabetic patients showed that, LDL, TC and Tg were positively correlated with Apo- B. There was a positive and linear correlation between LDL and Tg. Apo- B was negatively correlated with HDL-C. CONCLUSION: The majority of patients studied had low HDL-C, elevated non HDL- C, elevated total cholesterol, elevated triglycerides, elevated LDL -C and elevated apo B. Apolipoprotein B had a positive linear correlation with total cholesterol, triglycerides, LDL-C, non-HDL-C. The strongest positive correlation was with nonHDL-C. Patients with low HDL-C had high apo B levels.

Hybrid RGSA and Support Vector Machine Framework for Three-Dimensional Magnetic Resonance Brain Tumor Classification.

A novel hybrid approach for the identification of brain regions using magnetic resonance images accountable for brain tumor is presented in this paper. Classification of medical images is substantial in both clinical and research areas. Magnetic resonance imaging (MRI) modality outperforms towards diagnosing brain abnormalities like brain tumor, multiple sclerosis, hemorrhage, and many more. The primary objective of this work is to propose a three-dimensional (3D) novel brain tumor classification model using MRI images with both micro- and macroscale textures designed to differentiate the MRI of brain under two classes of lesion, benign and malignant. The design approach was initially preprocessed using 3D Gaussian filter. Based on VOI (volume of interest) of the image, features were extracted using 3D volumetric Square Centroid Lines Gray Level Distribution Method (SCLGM) along with 3D run length and cooccurrence matrix. The optimal features are selected using the proposed refined gravitational search algorithm (RGSA). Support vector machines, over backpropagation network, and k-nearest neighbor are used to evaluate the goodness of classifier approach. The preliminary evaluation of the system is performed using 320 real-time brain MRI images. The system is trained and tested by using a leave-one-case-out method. The performance of the classifier is tested using the receiver operating characteristic curve of 0.986 (±002). The experimental results demonstrate the systematic and efficient feature extraction and feature selection algorithm to the performance of state-of-the-art feature classification methods.

An Unusual Presentation of Cobblestone Esophagus From Bisphosphonate Use.

Cobblestone esophagus is a rare finding that has been previously described in cases of eosinophilic esophagitis (EoE), candidiasis, Barrett's esophagus, or severe reflux esophagitis from distal gastrointestinal obstruction. We describe a case of asymptomatic cobblestone esophagus secondary to bisphosphonate use.  A 67-year-old female was seen in the clinic for evaluation of microcytic anemia that was incidentally picked up on routine chronic disease follow-up. She had no gastrointestinal symptoms. She has been taking oral alendronate 70mg once a week for osteoporosis since a year ago. Barium meal was performed as the patient initially opted for non-invasive testing, which incidentally showed a diffuse "cobblestone" appearance. Subsequent oesophago-gastro-duodenoscopy (OGD) showed diffuse white nodular lesions along the esophagus with a cobblestone appearance but no ulcer or mass. Segmental esophageal biopsies were negative for fungal stain and did not show any pathology. In the absence of infection, eosinophilic esophagitis, and dysplasia, her "cobblestone" esophagus was attributed to bisphosphonate use by diagnosis of exclusion. Alendronate acid was held off, and serial barium meals over the next year showed significant interval improvement.  Bisphosphonates, such as alendronate acid, are commonly associated with drug-induced esophagitis. With the cessation of the offending medication, there was indeed a significant improvement in our patient's serial barium meal. It is important to review the medication list when encountering patients who present with cobblestone esophagus, as some of these patients with drug-induced esophagitis may be asymptomatic clinically.

Approach to Abnormal Liver Biochemistries in the Primary Care Setting.

Liver biochemistries are commonly ordered in the primary care setting, and they may return abnormal even in an asymptomatic patient. Primary care physicians need to have a systematic way of interpreting any derangement in these tests so that further investigations, referrals, and management can be arranged appropriately. This review dwells into patterns of liver biochemistry derangement, common aetiologies to consider, history and examinations that are required, initial investigations to order, and when to refer urgently to the emergency department.

Vacancy-Engineered Nickel Ferrite Forming-Free Low-Voltage Resistive Switches for Neuromorphic Circuits.

Innovations in resistive switching devices constitute a core objective for the development of ultralow-power computing devices. Forming-free resistive switching is a type of resistive switching that eliminates the need for an initial high voltage for the formation of conductive filaments and offers promising opportunities to overcome the limitations of traditional resistive switching devices. Here, we demonstrate mixed charge state oxygen vacancy-engineered electroforming-free resistive switching in NiFe2O4 (NFO) thin films, fabricated as asymmetric Ti/NFO/Pt heterostructures, for the first time. Using pulsed laser deposition in a controlled oxygen atmosphere, we tune the oxygen vacancies together with the cationic valence state in the nickel ferrite phase, with the latter directly affecting the charge state of the oxygen vacancies. The structural integrity and chemical composition of the films are confirmed by X-ray diffraction and hard X-ray photoelectron spectroscopy, respectively. Electrical transport studies reveal that resistive switching characteristics in the films can be significantly altered by tuning the amount and charge state of the oxygen vacancy concentration during the deposition of the films. The resistive switching mechanism is seen to depend upon the migration of both singly and doubly charged oxygen vacancies formed as a result of changes in the nickel valence state and the consequent formation/rupture of conducting filaments in the switching layer. This is supported by the existence of an optimum oxygen vacancy concentration for efficient low-voltage resistive switching, below or above which the switching process is inhibited. Along with the filamentary switching mechanism, the Ti top electrode also enhances the resistive switching performance due to interfacial effects. Time-resolved measurements on the devices display both long- and short-term potentiation in the optimized vacancy-engineered NFO resistive switches, ideal for solid-state synapses achieved in a single system. Our work on correlated oxide forming-free resistive switches holds significant potential for CMOS-compatible low-power, nonvolatile resistive memory and neuromorphic circuits.

Estimation of Time Since Death From Potassium Levels in Vitreous Humor in Cases of Unnatural Death: A Facility-Based Cross-Sectional Study.

Background Estimation of time since death/postmortem interval (PMI) forms a crucial component for all autopsy surgeons. With the subjectivity that is prevalent with conventional morphological and physical signs of death, newer-age modalities such as chemical analysis provide better precision. The easy accessibility and the resistance to putrefaction make vitreous humor the best choice for such chemical analysis. Thus, the present study's aim is to estimate the time since death in cases of unnatural death by investigating the potassium level changes in the vitreous humor. Methodology This is a facility-based cross-sectional study conducted in the mortuary under the Department of Forensic Medicine in a public tertiary healthcare teaching hospital in South India between August and September 2022. Deceased individuals fulfilling the inclusion and exclusion criteria were recruited in the study. Vitreous samples were collected from a single eye and analyzed using an autoanalyzer for potassium values. After due derivations, postmortem intervals were calculated from potassium values, then they were compared with the PMIs estimated using physical signs and those determined using official police records. Data were entered using MS Excel 20 (Microsoft Corporation, Redmond, Washington) and analyzed using the Statistical Package for the Social Sciences (SPSS) software, version 20 (IBM Corp., Armonk, NY). Results Of the 100 deceased individuals included in the study, 68% were men, and the majority (24%) belonged to the age group of 53-62 years. A linear relationship is said to exist between vitreous potassium concentration and postmortem interval. No correlation was seen between the ambient temperature and the potassium levels of the vitreous humor. PMI confirmed by the potassium levels seconded the PMI given by the police records and physical signs (Rigor mortis) (Spearman's rho was statistically significant at the two-tailed level or at the 0.01 level with a kappa value of 0.88). Conclusion Potassium measurements in the vitreous humor to estimate the PMI are associated with improved accuracy and precision in determining the time since death. They are not affected by external factors, making them a reliable marker for the same.

Antioxidant and Antithrombotic Activities of Kenaf Seed (Hibiscus cannabinus) Coat Ethanol Extract in Sprague Dawley Rats.

Oxidative stress has been implicated in deadly lifestyle diseases, and antioxidants from plant sources are the primary option in the treatment regime. Kenaf seeds are the storehouse of potential natural antioxidant phytoconstituents. Perhaps, none of the studies documented the phytoconstituents and their antioxidant potential from Kenaf seed coat so far. Thus, the current study focuses on exploring the protective effect of Kenaf Seed Coat Ethanol Extract (KSCEE) against sodium nitrite and diclofenac-induced oxidative stress in vitro (red blood cell and platelets model) and in vivo (female Sprague Dawely rat's model) along with the antithrombotic activity. The infrared spectrophotometry data showed the heterogeneous functional groups (CH, OH, C = C, C = C-C) and aromatic rings. Reverse phase high-performance liquid chromatography and gas chromatography-mass spectrometry chromatogram of KSCEE also evidenced the presence of several phytochemicals. KSCEE displayed about 76% of DPPH scavenging activity with an IC50 value of 34.94 µg/ml. KSCEE significantly (***p < 0.001) normalized the stress markers such as lipid peroxidation, protein carbonyl content, superoxide dismutase, and catalase in sodium nitrite and diclofenac-induced oxidative stress in RBC, platelets, liver, kidney, and small intestine, respectively. Furthermore, KSCEE was found to protect the diclofenac-induced tissue destruction of the liver, kidney, and small intestine obtained from seven groups of female Sprague Dawely rats. KSCEE delayed the clotting time of platelet-rich plasma and platelet-poor plasma and activated partial thromboplastin time, suggesting its anticoagulant property. In addition, KSCEE also exhibited antiplatelet activity by inhibiting both adenosine diphosphate and epinephrine-induced platelet aggregation. In conclusion, KSCEE ameliorates the sodium nitrite and diclofenac-induced oxidative stress in red blood cells, platelets, and experimental animals along with antithrombotic properties.

Pennisetum glaucum Protein Extract Protects RBC, Liver, Kidney, Small Intestine from Oxidative Damage and Exhibits Anticoagulant, Antiplatelet Activity.

High level of exogenous ROS in the circulation affects RBC membrane integrity which facilitates the generation of endogenous RBC ROS, implicated in series of physiological changes primarily associated with thrombosis and vital tissue damage. Although, Pennisetum glaucum (pearl millet) stores abundance of proteins, their therapeutic potential is least explored. Thus, the purpose of this study is to examine the role of Pennisetum Glaucum Protein Extract (PGE) on oxidative stress induced cell/tissue damage and thrombosis.In this investigation, protein characterization was done by using SDS-PAGE, Native-PAGE, PAS-staining and HPLC. In-vitro oxidative stress was induced in RBC using sodium nitrite. While, in-vivo oxidative stress was induced in experimental rats using diclofenac. Stress markers and biochemical parameters were evaluated. Role of PGE on thrombosis was assessed by using, in-vitro plasma recalcification time, activated partial thromboplastin time, prothrombin time, mouse tail bleeding time (In-vivo) and platelet aggregation.PGE revealed varied range of molecular weight proteins on SDS-PAGE. PGE normalized the sodium nitrite induced oxidative damage of RBC and diclofenac induced oxidative damage in liver, kidney and small intestine. PGE exhibited anticoagulant effect by increasing the coagulation time of both PRP and PPP and mouse tail bleeding time. Furthermore, PGE prolonged the clotting time of only APTT but did not affect PT. PGE inhibited agonists ADP and epinephrine induced platelet aggregation.Our findings suggest, PGE could be a better contender in the management of oxidative stress and its associated diseases. ABBREVIATIONS: PGEPennisetum Glaucum protein ExtractAPPTActivated Partial Thromboplastin TimePTProthrombin TimeROSReactive Oxygen SpeciesPRPPlatelet Rich PlasmaPPPPlatelet Poor PlasmaSDS-PAGESodium Dodecyl Sulfate-Polyacrylamide Gel ElectrophoresisPASPeriodic Acid-schiff StainingODOptical DensityINRInternational Normalized RatioPBSPhosphate Buffered SalineSODSuperoxide DismutaseTCATrichloro Acetatic AcidDTNBDi-Thio-bis-NitroBenzoic acidSGOTSerum Glutamate Oxaloacetate TransaminaseSGPTSerum Glutamate Pyruvate TransaminaseALPAlkaline PhosphataseDFCDiclofenacSylSilymarinMEDMinimum Edema DoseMHDMinimum Hemorrhagic Dose.

Artabotrys odoratissimus Bark Extract Restores Ethanol Induced Redox Imbalance and Toxicity in Hepatocytes and In Vivo Model.

Alcohol-induced oxidative stress is a key player in the development of liver diseases, and herbal alternatives are important means of ameliorating the hepatotoxic effects. The study aimed to evaluate the hepatoprotective potentiality of Artabotrys odoratissimus, an important medicinal shrub from the family Annonaceae. The phenolic compounds from bark ethanol extract (BEE) were detected using RP-HPLC. The in vitro hepatoprotective activity against ethanol-induced damage was studied in HepG2 cells with cell viability assays, mitochondrial membrane potential (MMP) assay, reactive oxygen species (ROS) assay, double staining assay and western blotting. The in vivo mice model was used to evaluate the alcohol-induced stress with liver function enzymes, lipid profile and histopathology. All the thirteen phenolic compounds detected with HPLC were docked onto protein targets such as aspartate amino transferase (AST), alkaline phosphatase (ALP) and inducible nitric oxide synthase (NO). The RP-HPLC detected the presence of various phenolics including rutin, chlorogenic acid and catechin, amongst others. Co-administration of BEE with ethanol alleviated cell death, ROS and MMP in HepG2 cells compared to the negative control. The extract also modulated the MAP kinase/caspase-3 pathway, thereby showing protective effects in HepG2 cells. Also, pre-treatment for 14 days with the extract in the mice model before a single toxic dose (5 g/kg body weight) reduced the liver injury by bringing the levels of liver function enzymes, lipid profile and bilirubin to near normal. In silico analysis revealed that rutin showed the best binding affinity with all the target proteins in the study. These results provide evidence that BEE possesses significant hepatoprotective effects against ethanol-induced oxidative stress in hepatic cells and in vivo models, which is further validated with in silico analysis.

A novel family of small molecule HIF-1 alpha stabilizers for the treatment of diabetic wounds; an integrated in silico, in vitro, and in vivo strategy.

Hypoxia-inducible factor-1 alpha (HIF-1α) is a crucial regulator of wound healing, which includes epithelialization, angiogenesis, granulation, tissue development, and wound contraction. Even though diabetic wounds are hypoxic, HIF-1α levels are decreased during healing. Diabetic wound healing necessitates the modulation of hypoxia-induced responses by VHL-HIF-1α protein-protein inhibition. Our proposed hypothesis is to increase HIF-1α levels by inhibiting VHL and HIF-1α interactions by novel small bioactive molecules, accelerating diabetic wound healing. A three features (two aromatic rings and one hydrogen bond acceptor) pharmacophore hypothesis was generated from the existing HIF-1α modulators. Virtual screening was done based on the generated pharmacophore, and a library consisting of the top 20 out of 3728 compounds was selected using ZINCPharmer. Of the top 20 molecules, the pyrazole moiety was identified as the top "HIT". Five analogues of pyrazole were designed, and Scifinder ascertained the novelty. The designed compounds were synthesized and characterized by IR, Mass, and NMR. Preliminarily, we have carried out a scratch wound assay using 3T3L1 cell lines. All the synthesized compounds showed significant wound healing activity. Further, to validate the in vitro assay, the compound CI, which showed effective in vitro results was used for in vivo study. Using the diabetes mouse model, comprising streptozotocin-induced (STZ) diabetic mice and scratch wound assay, we demonstrated that inhibiting the VHL and HIF-1α connection is a promising strategy for treating diabetic ulcers. Molecules CI and CP were found to have substantial in silico, in vitro, and in vivo outcomes.

Clinical trial: seven-day vonoprazan- versus 14-day proton pump inhibitor-based triple therapy for first-line Helicobacter pylori eradication.

BACKGROUND: One-week triple therapy with vonoprazan is endorsed by Japanese guidelines as an alternative to proton pump inhibitor (PPI)-based triple therapy for first-line Helicobacter pylori eradication. This contrasts with Western guidelines recommending 2-week PPI-based triple therapy. AIM: To verify the non-inferiority of 1-week vonoprazan-based triple therapy versus 2-week PPI-based triple therapy as first-line H. pylori eradication in a multiracial Asian cohort. METHODS: Randomised controlled trial of treatment-naïve patients with H. pylori infection assigned 1:1 to either 7 days amoxicillin 1 g + clarithromycin 500 mg + vonoprazan 20 mg twice per day or 14 days amoxicillin 1 g + clarithromycin 500 mg + omeprazole OR esomeprazole OR rabeprazole 20 mg twice/day. Subjects were randomly assigned to each PPI 1:1:1 Demographics, H. pylori resistance, CYP 2C19 genotype, eradication success and safety profiles were compared between groups. RESULTS: Between June 2019 and June 2021, 252 of 1097 subjects screened were randomised. 244 (age [SD] 51.7 [14.6]) received vonoprazan- (n = 119) or PPI-based (n = 125) triple therapy. Eradication rates by intention-to-treat analysis were 87.4% (vonoprazan-based triple therapy) versus 88.0% (PPI-based triple therapy. By per protocol analysis: 96.3% (vonoprazan-based triple therapy) versus 94.0% (PPI-based triple therapy). Clarithromycin resistance predicted treatment failure on multivariate analysis: RR 11.4; 95% CI [1.4-96.3], p = 0.025. No significant differences in CYP 2C19 genotypes or adverse events occurred between groups. CONCLUSION: One-week vonoprazan-based triple therapy achieved comparable efficacy to 2-week PPI-based triple therapy and was well tolerated.

Scalp EEG recordings of pediatric epilepsy patients: A dataset for automatic detection of interictal epileptiform discharges from routine EEG.

Interictal Epileptiform Discharges (IEDs) in routine EEG is crucial evidence of epilepsy in one patient. Though some studies have reported on automated detection of IEDs, the availability of open benchmark datasets for evaluating these methods is limited. This article presents a scalp EEG dataset of pediatric epilepsy patients. The dataset contains 19 channel EEG recordings of 21 subjects who are advised to undergo routine EEG tests to diagnose epilepsy. Among these 21 subjects, IEDs are found in EEG recordings of 11 subjects as confirmed by neurologists. The routine EEG recordings of the remaining 10 subjects are free from IEDs. A 32 channel EEG machine is used to record the routine EEG, and an international 10-20 electrode placement system is used to place the electrodes on the subject's scalp. A longitudinal bipolar montage channel configuration is used to collect the signals. IEDs present in routine EEG of epileptic patients are annotated by a neuro-technician and are provided with the dataset. The raw EEG data is further segmented into 10 s epochs based on the annotations for easy analysis and validation in automated IED detection systems. These 10 s epochs are also included in the dataset. The dataset is very useful for modeling novel automated IED detection systems that reduce the burdens of neurologists or neurophysiologists. In addition, the usability of the proposed dataset has also been experimented on a model based on exponential energy and support vector machine. The classification performance of the model indicates that the proposed dataset can be used as a benchmark dataset for automated IED detection.

Study on acquisition of bacterial antibiotic resistance determinants in poultry litter.

Antibiotic resistance and the mode of transmission were investigated in bacteria isolated from poultry litter. Total aerobic heterotrophic bacteria were screened and identified for their resistance to different antibiotics such as ampicillin, streptomycin, erythromycin, tetracycline, chloramphenicol, kanamycin, tobramycin, and rifampicin. The distribution of bacteria found in the litter was Staphylococcus (29.1%), which was the predominant group, followed by Streptococcus (25%), Micrococcus (20.8%), Escherichia coli (12.5%), Salmonella (8.3%), and Aeromonas (4.1%). Fifty percent of these isolates were susceptible to ampicillin, 57% to erythromycin, 25% to tetracycline, 4% to chloramphenicol, 40% to kanamycin, 75% to streptomycin, 54% to tobramycin, and 4% to rifampicin. Three randomly selected isolates representing Staphylococcus, Streptococcus, and Micrococcus were examined for plasmids, and plasmid-curing and plasmid-induced transformation studies were conducted. Streptococcus and Micrococcus harbored a plasmid of 4.2 and 5.1 kb, respectively, whereas Staphylococcus did not harbor any plasmids. Plasmids were cured in Streptococcus and Micrococcus at a concentration of 75 and 100 microg/ mL of acridine orange, respectively, and transformation of 4.2- and 5.1-kb plasmids isolated from the Streptococcus and Micrococcus to plasmid-free E. coli DH5alpha strain was possible. In conjugation experiments, the antibiotic resistance profiles of transconjugant cells were found to be the same as the donors with the exception of Staphylococcus. The results of this study suggest that transformation and conjugation could be an important mechanism for horizontal gene transfer between bacteria in poultry litter. An understanding of the mechanism and magnitude of resistance gene transfer may provide a strategy to reduce the potential for dissemination of these genes.

Time-domain exponential energy for epileptic EEG signal classification.

Automatic classification and prediction of epileptic electroencephalogram (EEG) signal are of great concern to the research community due to its non-stationary and non-linear properties. Features with minimal computation cost are highly needed for the rapid real-time precise diagnosis and implementation in the EEG scanning devices. Even though energy is a well-known feature for the analysis of signals, it is very rarely used in EEG analysis. An exponential energy feature in the time domain is proposed in this study. The proposed exponential energy feature provides a classification accuracy of 89% in the Bern-Barcelona EEG dataset and 99.5% in the Ralph Andrzejak EEG dataset. The promising results open a wide applicability of exponential energy in biomedical signal analysis.

Spatial variation of trace element concentration and contamination assessment in the coral reef sediments of Lakshadweep Archipelago, Indian Ocean.

Surface sediments were collected from the shore and lagoons of Kavaratti, Kadmat and Agatti islands of Lakshadweep Archipelago and analysed for trace element concentration. The sediment contamination was assessed on the basis of geochemical, biological hazard and ecological risk indices. Except Cd and Pb, all the other trace elements selected for the study were below the contamination level. Compared to Kadmat, Kavaratti and Agatti were more polluted and the pollution was pronounced in lagoons than shore. Population pressure, untreated sewage, diesel based power generation, shipping and tourism activities contribute to sediment contamination. Statistical analysis revealed the association of trace elements with sedimentary characteristics due to anthropogenic sources.

Capillary Hemangioma: A Concurrent Presentation in Ovary and Fallopian Tube.

Hemangioma of the female genital tract is very uncommon. Histologically, these are predominantly cavernous type, with few capillary and mixed type reported in the literature. Hence, we report a case of concurrent occurrence of capillary hemangioma of the ovary and fallopian tube, an incidental finding.

A biphasic effect of TNF-α in regulation of the Keap1/Nrf2 pathway in cardiomyocytes.

Antagonizing TNF-α signaling attenuates chronic inflammatory disease, but is associated with adverse effects on the cardiovascular system. Therefore the impact of TNF-α on basal control of redox signaling events needs to be understand in more depth. This is particularly important for the Keap1/Nrf2 pathway in the heart and in the present study we hypothesized that inhibition of a low level of TNF-α signaling attenuates the TNF-α dependent activation of this cytoprotective pathway. HL-1 cardiomyocytes and TNF receptor1/2 (TNFR1/2) double knockout mice (DKO) were used as experimental models. TNF-α (2-5ng/ml, for 2h) evoked significant nuclear translocation of Nrf2 with increased DNA/promoter binding and transactivation of Nrf2 targets. Additionally, this was associated with a 1.5 fold increase in intracellular glutathione (GSH). Higher concentrations of TNF-α (>10-50ng/ml) were markedly suppressive of the Keap1/Nrf2 response and associated with cardiomyocyte death marked by an increase in cleavage of caspase-3 and PARP. In vivo experiments with TNFR1/2-DKO demonstrates that the expression of Nrf2-regulated proteins (NQO1, HO-1, G6PD) were significantly downregulated in hearts of the DKO when compared to WT mice indicating a weakened antioxidant system under basal conditions. Overall, these results indicate that TNF-α exposure has a bimodal effect on the Keap1/Nrf2 system and while an intense inflammatory activation suppresses expression of antioxidant proteins a low level appears to be protective.

Reductive unfolding and oxidative refolding of a Bowman-Birk inhibitor from horsegram seeds (Dolichos biflorus): evidence for "hyperreactive" disulfide bonds and rate-limiting nature of disulfide isomerization in folding.

Horsegram protease inhibitor belongs to the Bowman-Birk class (BBIs) of low molecular weight (8-10 kDa), disulfide-rich, "dual" inhibitors, which can bind and inhibit trypsin and chymotrypsin either independently or simultaneously. They have seven conserved disulfide bonds. Horsegram BBI exhibits remarkable stability against denaturants like urea, guanidine hydrochloride (GdmCl) and heat, which can be attributed to these conserved disulfide bonds. On reductive denaturation, horsegram BBI follows the "two-state" mode of unfolding where all the disulfide bonds are reduced simultaneously resulting in the fully reduced protein without any accumulation of partially reduced intermediates. Reduction with dithiothreitol (DTT) followed apparent first-order kinetics and the rate constants (k(r)) indicated that the disulfide bonds were "hyperreactive" in nature. Oxidative refolding of the fully reduced and denatured inhibitor was possible at very low protein concentration in the presence of "redox" combination of reduced and oxidized glutathiones. Simultaneous recovery of trypsin and chymotryptic inhibitory activities indicated the concomitant folding of both the inhibitory subdomains. Folding efficiency decreased in the absence of the glutathiones and in the presence of denaturants (6 M urea and 4 M GdmCl), indicating the importance of disulfide shuffling and the formation of noncovalent interactions and secondary structural elements, respectively, for folding efficiency. Folding rate was significantly improved in the presence of protein disulfide isomerase (PDI). A 3-fold enhancement of rate was observed in the presence of PDI at molar ratio of 1:20 (PDI/inhibitor), indicating that disulfide bond formation and isomerization to be rate limiting in folding. Peptide prolyl cis-trans isomerase (PPI) did not affect rate at low concentrations, but at molar ratios of 1:1.5 (PPI/inhibitor), there was 1.4-fold enhancement of the folding rate, indicating that the prolyl imidic bond isomerizations may be slowing down the folding reaction but were not rate limiting.