Identification of neo-andrographolide compound targeting NS1 Lys14: an important residue in NS1 activity driving dengue pathogenesis.

Dengue virus is part of the flaviviruses that spread through the Aedes mosquito species and causes vascular leakage and multiple organ failure. The non-structural protein 1 (NS1) is involved in the replication of Dengue virus. The glycosylated dimeric and hexameric form of NS1 is the biologically active form. Therefore, in this study, the NS1 protein was modeled in dimeric form which is predominantly present inside the host cell. The dimeric model was validated and it was glycosylated at ASN130 and ASN207 with oligomannose. This model was simulated for 100 ns to retrieve the global minima structure. The andrographolide and its four derivatives were docked non-specifically against the dimeric glycosylated NS1 protein. The neo-andrographolide compound showed strong interactions with favorable binding energy of -8.2 kcal/mol and electrostatic binding affinity of -8.9 kcal/mol. All docked ligand-protein complexes were simulated for 100 ns. The molecular dynamics simulation analysis comprising of root mean square deviation and fluctuation, the radius of gyration, hydrogen bonding, potential energy, principal component analysis, SASA, DSSP, Free energy Landscape, MM-PBSA and Electrostatic binding affinity revealed about the stability of complex systems. These andrographolide and its derivatives was found to be interacting with Lys14 and this residue was reported as one of the important residues in NS1 activity. Among all compounds, the neo-andrographolide compound has the promising potential to inhibit the activity of the NS1 which is necessary for the Dengue virus replication.Communicated by Ramaswamy H. Sarma.

The dimeric NS1 protein structure was modeled and glycosylated at ASN130 and ASN 207 with Oligo-mannose.The minimized structure was used for molecular docking studies with andrographolide and its derivatives.The Lys14 residue is well interfered by all compounds but based on molecular dynamics and binding affinity studies, neo-andrographolide compound has the promising potential to inhibit the activity of the NS1.

AI Based Diagnosis of Pneumonia.

Pneumonia is a lung infection caused by bacteria, viruses and fungi. In this infection, the air sac (alveoli) of the lungs gets inflamed and breathing becomes difficult which causes mild to severe illness among people. They are diagnosed by performing chest X-ray, blood test, pulse oximetry. Pneumonia can also be identified using lung sounds that are recorded in the digital stethoscope. In this proposed work, a software is developed to diagnose pneumonia from the lung sound using gradient boosting algorithm. Lung sounds give enough symptoms for pneumonia identification. Lung sounds are recorded by doctors using Electronic Stethoscope. The recorded lung sounds are processed using audacity software. This software separates the required sound from unwanted noises. The healthy individual's audio files are labelled as 0 and the pneumonia patient's audio files are labelled as 1 for training the algorithm. During diagnosis study and the performance evaluation with various machine learning algorithms like support vector machine and k-nearest neighbours (KNN) algorithms, it was observed that the gradient boosting algorithm exhibits good identification property with 97 percent accuracy. This proposed method also reveals excellent diagnoses of pneumonia over other artificial intelligence and deep learning techniques. This method can also be used to predict Covid affected lungs sounds.

Treatment of dairy industry wastewater by combined aerated electrocoagulation and phytoremediation process.

As dairy industries has been emerged as one of the most rapidly developing industry in both small as well as large scale, the volume of effluent generated is also very high. In the present study, aerated electrocoagulation combined with phytoremediation treatment was conducted in dairy industry wastewater. Electrocoagulation was performed with aluminium and iron electrodes and effect of various operating parameters such as electrode combination, pH, and voltage were tested. Electrocoagulation was found effective at neutral pH and its efficiency increased with increase in applied voltage. The maximum COD removal efficiency of 86.4% was obtained in case of Al-Fe electrode combination with aeration at 120 min reaction time, initial pH 7, voltage 5 V. Significant growth of Canna indica was observed in electrocoagulation treated wastewater compared to raw dairy wastewater. COD removal of 97% was achieved when combined electrocoagulation and phytoremediation process was used. Thus, it proves to be a proficient method for the treatment of dairy industry wastewater. In addition to the above, bacterial toxicity tests were performed to investigate the toxic nature of wastewater and the results showed that both treated and untreated wastewater favoured bacterial growth.

Treatment of mixed industrial wastewater by electrocoagulation and indirect electrochemical oxidation.

Treatment of mixed industrial wastewater is a challenging task due to its high complexity. This work scrutinizes the electrochemical treatment of mixed industrial wastewater, specifically electrocoagulation and indirect electrochemical oxidation processes through COD and color removal studies. Both processes are found to be more efficient at the wastewater pH. Monopolar connection was found more effective than bipolar connection for the removal of COD and color from wastewater. The monopolar connection removed COD up to 55% and color 56% whereas bipolar connection leads to the removal of 43% and 48% respectively at wastewater pH with an applied voltage 1.5 V in the course of 1 h of electrolysis. In the case of indirect electrochemical oxidation process using graphite electrodes, the COD and color abatement efficiencies of the indirect electrochemical oxidation process were found as 55% and 99.8%, respectively within 1 h of electrolysis conducted at pH 7.7, applied voltage 4 V, and NaCl concentration 1 g L-1. This work also highlights the importance of the presence of electrolytes in the indirect electrochemical oxidation process as the external addition of sodium chloride significantly enhanced both COD and color elimination efficiency.

Mixed industrial wastewater treatment by combined electrochemical advanced oxidation and biological processes.

Nowadays, because the quality and quantity of mixed industrial wastewater keep fluctuating in recent times, the treatment of mixed industrial wastewater has gained more attention. The main target of this study is to degrade the wastewater through a combination of electrochemical advanced oxidation processes (EAOPs) and biological treatment. To enhance the biodegradability of the wastewater, Electro-Fenton process, along with external persulphate addition, was applied before the biological treatment. The effect of voltage, catalyst concentration and persulphate dosage was studied. The optimized conditions selected for the experiments were pH-3, effective area-25 cm2, electrode spacing-1 cm while voltage-10 V, persulphate dosage-200 mg L-1, and catalyst dosage-10 mg L-1 were optimized during the experiments leading towards 60% of COD removal efficiency in course of 1 h of electrolysis. Addition of tert-butyl alcohol and ethanol revealed the existence of sulphate and hydroxyl radicals as the major oxidants that help in pollutant degradation by combining EAOPs and biological treatment. Overall 94% COD removal efficiency was achieved. Therefore, for the organic pollutant degradation, combined process serves to be an efficient and effective treatment option.

Use of water quality index and multivariate statistical techniques for the assessment of spatial variations in water quality of a small river.

Rapid urban development has led to a critical negative impact on water bodies flowing in and around urban areas. In the present study, 25 physiochemical and biological parameters have been studied on water samples collected from the entire section of a small river originating and ending within an urban area. This study envisaged to assess the water quality status of river body and explore probable sources of pollution in the river. Weighted arithmetic water quality index (WQI) was employed to evaluate the water quality status of the river. Multivariate statistical techniques namely cluster analysis (CA) and principal component analysis (PCA) were applied to differentiate the sources of variation in water quality and to determine the cause of pollution in the river. WQI values indicated high pollution levels in the studied water body, rendering it unsuitable for any practical purpose. Cluster analysis results showed that the river samples can be divided into four groups. Use of PCA identified four important factors describing the types of pollution in the river, namely (1) mineral and nutrient pollution, (2) heavy metal pollution, (3) organic pollution, and (4) fecal contamination. The deteriorating water quality of the river was demonstrated to originate from wide sources of anthropogenic activities, especially municipal sewage discharge from unplanned housing areas, wastewater discharge from small industrial units, livestock activities, and indiscriminate dumping of solid wastes in the river. Thus, the present study effectively demonstrates the use of WQI and multivariate statistical techniques for gaining simpler and meaningful information about the water quality of a lotic water body as well as to identify of the pollution sources.

Gene Expression in Parp1 Deficient Mice Exposed to a Median Lethal Dose of Gamma Rays.

There is a current interest in the development of biodosimetric methods for rapidly assessing radiation exposure in the wake of a large-scale radiological event. This work was initially focused on determining the exposure dose to an individual using biological indicators. Gene expression signatures show promise for biodosimetric application, but little is known about how these signatures might translate for the assessment of radiological injury in radiosensitive individuals, who comprise a significant proportion of the general population, and who would likely require treatment after exposure to lower doses. Using Parp1-/- mice as a model radiation-sensitive genotype, we have investigated the effect of this DNA repair deficiency on the gene expression response to radiation. Although Parp1 is known to play general roles in regulating transcription, the pattern of gene expression changes observed in Parp1-/- mice 24 h postirradiation to a LD50/30 was remarkably similar to that in wild-type mice after exposure to LD50/30. Similar levels of activation of both the p53 and NFκB radiation response pathways were indicated in both strains. In contrast, exposure of wild-type mice to a sublethal dose that was equal to the Parp1-/- LD50/30 resulted in a lower magnitude gene expression response. Thus, Parp1-/- mice displayed a heightened gene expression response to radiation, which was more similar to the wild-type response to an equitoxic dose than to an equal absorbed dose. Gene expression classifiers trained on the wild-type data correctly identified all wild-type samples as unexposed, exposed to a sublethal dose or exposed to an LD50/30. All unexposed samples from Parp1-/- mice were also correctly classified with the same gene set, and 80% of irradiated Parp1-/- samples were identified as exposed to an LD50/30. The results of this study suggest that, at least for some pathways that may influence radiosensitivity in humans, specific gene expression signatures have the potential to accurately detect the extent of radiological injury, rather than serving only as a surrogate of physical radiation dose.

Composite wastewater treatment by aerated electrocoagulation and modified peroxi-coagulation processes.

Treatment of composite wastewater generating from the industrial estates is a great challenge. The present study examines the applicability of aerated electrocoagulation and modified peroxi-coagulation processes for removing color and COD from composite wastewater. Iron plates were used as anodes and cathodes in both electrochemical processes and experiments were carried out in a working volume of 2 L. Aeration enhanced the efficiency of electrocoagulation process significantly. More than 50% of COD and 60% of color were removed after 1 h of electrocoagulation process operated at pH 3 and applied voltage of 1 V. Efficiency of the modified peroxi-coagulation process was significantly higher than that of aerated electrocoagulation. COD and color removal efficiencies of the modified peroxi-coagulation process were found as 77.7% and 97%, respectively after 1 h of electrolysis operated at 1 V, solution pH 3 and 50 mM hydrogen peroxide addition. This improved efficiency of modified peroxi-coagulation compared to aerated electrocoagulation is mainly due to the attack of in-situ generated hydroxyl radicals.

Probing the interaction of troxerutin with transfer RNA by spectroscopic and molecular modeling.

The studies on the interaction between tRNA (transfer RNA) and small molecules are an area of remarkable recent attention. For this notion a fundamental knowledge of the molecular features involving the interaction of small molecules with tRNA is crucial. Hence, in the present study we have investigated the interaction of TXER (troxerutin), natural bioflavonoid rutin derivative with yeast tRNA by using various spectroscopic techniques and molecular docking studies. The UV absorption and fluorescence emission studies demonstrated external binding of TXER on tRNA with low binding constant values as compared to strong binders. Circular dichroism (CD) spectroscopy study revealed that TXER did not show any significant modification on native conformation of tRNA. Furthermore in electrochemical study, the complex of TXER-tRNA did not expose any noticeable positive potential peak shift which indicated an interaction of TXER with tRNA by electrostatic or external binding mode. The docking study showed that the hydrogen and hydrophobic interactions were involved in binding of TXER-tRNA with docking score -7.0 kcal/mol. These findings led us to confirm the interaction of TXER on tRNA through external binding with low binding affinity, indicating its potential bioapplication in the future.

Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1.

Ionizing radiation causes degeneration of myelin, the insulating sheaths of neuronal axons, leading to neurological impairment. As radiation research on the central nervous system has predominantly focused on neurons, with few studies addressing the role of glial cells, we have focused our present research on identifying the latent effects of single/ fractionated -low dose of low/ high energy radiation on the role of base excision repair protein Apurinic Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells' differentiation. Apurinic endonuclease-1 is predominantly upregulated in response to oxidative stress by low- energy radiation, and previous studies show significant induction of Apurinic Endonuclease-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of protons cause latent damage to spinal cord architecture while fractionation of HZE (28Si) induce increase in APE1 with single dose, which then decreased with fractionation. The oligodendrocyte progenitor cells differentiation was skewed with increase in immature oligodendrocytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects.

Spectroscopic and molecular docking studies on the interaction of troxerutin with DNA.

Troxerutin (TXER) is a derivative of naturally occurring bioflavonoid rutin. It possesses different biological activities in rising clinical world. The biological activity possessed by most of the drugs mainly targets on macromolecules. Hence, in the current study we have examined the interaction mechanism of TXER with calf thymus DNA (CT-DNA) by using various spectroscopic methods, isothermal titration calorimetry (ITC) and molecular docking studies. Further, DNA cleavage study was carried out to find the DNA protection activity of TXER. UV-absorption and emission spectroscopy showed low binding constant values via groove binding. Circular dichroism study indicates that TXER does not modify native B-form of DNA, and it retains the native B-conformation. Furthermore, no effective positive potential peak shift was observed in TXER-DNA complex during electrochemical analysis by which it represents an interaction of TXER with DNA through groove binding. Molecular docking study showed thymine guanine based interaction with docking score -7.09 kcal/mol. This result was compared to experimental ITC value. The DNA cleavage study illustrates that TXER does not cause any DNA damage as well as TXER showed DNA protection against hydroxyl radical induced DNA damage. From this study, we conclude that TXER interacts with DNA by fashion of groove binding.

Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme.

We report use of PEG-DSPE coated oxidized graphene nanoribbons (O-GNR-PEG-DSPE) as agent for delivery of anti-tumor drug Lucanthone (Luc) into Glioblastoma Multiformae (GBM) cells targeting base excision repair enzyme APE-1 (Apurinic endonuclease-1). Lucanthone, an endonuclease inhibitor of APE-1, was loaded onto O-GNR-PEG-DSPEs using a simple non-covalent method. We found its uptake by GBM cell line U251 exceeding 67% and 60% in APE-1-overexpressing U251, post 24h. However, their uptake was ~38% and 29% by MCF-7 and rat glial progenitor cells (CG-4), respectively. TEM analysis of U251 showed large aggregates of O-GNR-PEG-DSPE in vesicles. Luc-O-GNR-PEG-DSPE was significantly toxic to U251 but showed little/no toxicity when exposed to MCF-7/CG-4 cells. This differential uptake effect can be exploited to use O-GNR-PEG-DSPEs as a vehicle for Luc delivery to GBM, while reducing nonspecific cytotoxicity to the surrounding healthy tissue. Cell death in U251 was necrotic, probably due to oxidative degradation of APE-1.

Identification, quantification of bioactive constituents, evaluation of antioxidant and in vivo acute toxicity property from the methanol extract of Vernonia cinerea leaf extract.

CONTEXT: Vernonia cinerea (L.) Less [Compositae (Asteraceae)] is used traditionally for several medical purposes such as inflammation, pain, fever, and cancer. OBJECTIVES: The present study identified the bioactive constituents in the methanol extract of Vernonia cinerea leaf and evaluated its antioxidant activity and acute toxicity. METHODS: The identification of phytochemicals was accomplished by GC-MS and the major antioxidant phenolic compounds in the extract were quantified by HPTLC analysis. To quantify the essential elements, atomic absorption spectrophotometeric analysis was carried out. Total phenol and flavonoid content was measured by Folin-Ciocalteau reagent and 2% aluminium chloride, respectively. RESULTS: GC-MS analysis identified the presence of 27 phytoconstituents. The predominant phenolic compound in the extract as quantified by HPTLC was gallic acid (1.92 mg/g) followed by rutin (0.705 mg/g), quercetin (0.173 mg/g), caffeic acid (0.082 mg/g) and ferulic acid (0.033 mg/g). The following elements were quantified: Fe (0.050 ppm), Mn (0.022 ppm), Co (0.0180 ppm), Pb (0.029 ppm), Hg (3.885 ppm) and Se (4.5240 ppm). The antioxidant activity of the extract increased with increasing concentration and the correlation (r²) for all in vitro assays were satisfactory. CONCLUSIONS: V. cinerea extract has significant (p < 0.05) antiradical activity. Hence, V. cinerea may have potential medicinal value and can be used in the formulation of pharmacological products for degenerative diseases.

Comorbidities among HIV-infected injection drug users in Chennai, India.

BACKGROUND & OBJECTIVE: HIV-infected injection drugs users (IDUs) are known to have high rates of co-infections. A few reports exist on comorbidities among HIV-infected IDUs in India. We carried out a retrospective study to analyse data on comorbidities in India and treatment challenges faced when treating HIV-infected IDUs in India. METHODS: A retrospective chart review of 118 HIV-infected IDUs who accessed care at the YRG Centre for Substance Abuse-Related Research, Chennai, between August 2005 and February 2006 was done. Demographic, laboratory and clinical information was extracted from medical records. Descriptive demographic and clinical characteristics and distributions of comorbidities across CD4 cell count strata were analysed. RESULTS: All IDUs were male with a median age of 35.5 yr. The majority were married with average monthly income less than INR 3000 per month. The prevalence of hepatitis B and C infections were 11.9 and 94.1 per cent, respectively. Other common co-morbidities included oral candidiasis (43.2%), tuberculosis (33.9%), anaemia (22.9%), lower respiratory tract infections (16.1%), cellulitis (6.8%), herpes zoster (9.3%) and herpes simplex (9.3%). Among participants with CD4+ < 200 cells/microl, the prevalence of TB was 60 per cent. INTERPRETATION & CONCLUSION: IDUs in Chennai were commonly co-infected with HBV, HCV and tuberculosis, complicating use of antiretroviral and anti-tuberculous therapy. The current regimens available for the management of HIV and TB in India may need to be re-assessed for IDUs given the potential for increased rates of hepatotoxicity.

Biotechnological conversion of agro-industrial wastewaters into biodegradable plastic, poly beta-hydroxybutyrate.

Waste activated sludge generated from a combined dairy and food processing industry wastewater treatment plant was evaluated for its potential to produce biodegradable plastic, poly beta-hydroxybutyric acid (PHB). Deproteinized jowar grain-based distillery spentwash yielded 42.3% PHB production (w/w), followed by filtered rice grain-based distillery spentwash (40% PHB) when used as substrates. Addition of di-ammonium hydrogen phosphate (DAHP) resulted in an increase in PHB production to 67% when raw rice grain-based spentwash was used. Same wastewater, after removal of suspended solids by filtration and with DAHP supplementation resulted in lower PHB production (57.9%). However, supplementing other wastes with DAHP led to a substantial decrease in PHB content in comparison to what was observed in the absence of DAHP.

Production and recovery process of polyhydroxybutyrate (PHB) from waste activated sludge.

Polyhydroxybutyrate (PHB) is bacterial storage polyester, currently receiving much attention because of its biodegradable potential. Production of microbial polymers is expensive due to supplementary carbon source and downstream processing cost. The present study aimed at reducing the fermentation carbon source cost by using waste activated sludge and wastewater, and evaluating the use of proper solvent for the recovery of PHB from activated sludge to minimize the downstream cost. To improve the recovery process efficiency, different strategies for the extraction and recovery of the polymer from the waste activated sludge were applied. The maximum solubility of PHB (80%) was observed in chloroform, and precipitation with methanol (95%) was observed. Impurities interference in the PHB recovery process was also studied. By using these optimized recovery processes with optimized C:N ratio 10, the maximum product recovery was observed to be 62.3% (w/w). The results are presented and discussed in this paper.

Production of biodegradable plastics from activated sludge generated from a food processing industrial wastewater treatment plant.

Most of the excess sludge from a wastewater treatment plant (60%) is disposed by landfill. As a resource utilization of excess sludge, the production of biodegradable plastics using the sludge has been proposed. Storage polymers in bacterial cells can be extracted and used as biodegradable plastics. However, widespread applications have been limited by high production cost. In the present study, activated sludge bacteria in a conventional wastewater treatment system were induced, by controlling the carbon: nitrogen ratio to accumulate storage polymers. Polymer yield increased to a maximum 33% of biomass (w/w) when the C/N ratio was increased from 24 to 144, where as specific growth yield decreased with increasing C/N ratio. The conditions which are required for the maximum polymer accumulation were optimized and are discussed.

A study to assess depression, its correlates and suicidal behaviour in epilepsy.

Fifty subjects with seizure disorder were compared with thirty subjects with bronchial asthma and assessed for depression and suicidal behaviour. 34% of the epilepsy group had a diagnosis of major depressive episode compared to 13.3% of Bronchial Asthma group, which demonstrated a significant difference. Complex partial seizures and use of phenobarbitone had significant association with depression. 16% of the epilepsy group had a history of atleast one suicidal attempt in the previous year with 88% using anticonvulsants. 20% of the group also expressed current suicidal ideation, which correlated with Hamilton Depression Rating Scale total scores.