Mitochondrial complex I subunit NDUFS8.2 modulates responses to stresses associated with reduced water availability.

Mitochondria are important sources of energy in plants and are implicated in coordination of a number of metabolic and physiological processes including stabilization of redox balance, synthesis and turnover of a number of metabolites, and control of programmed cell death. Mitochondrial electron transport chain (mETC) is the backbone of the energy producing process which can influence other processes as well. Accumulating evidence suggests that mETC can affect responses to environmental stimuli and modulate tolerance to extreme conditions such as drought or salinity. Screening for stress responses of 13 Arabidopsis mitochondria-related T-DNA insertion mutants, we identified ndufs8.2-1 which has an increased ability to withstand osmotic and oxidative stresses compared to wild type plants. Insertion in ndufs8.2-1 disrupted the gene that encodes the NADH dehydrogenase [ubiquinone] fragment S subunit 8 (NDUFS8) a component of Complex I of mETC. ndufs8.2-1 tolerated reduced water availability, retained photosynthetic activity and recovered from severe water stress with higher efficiency compared to wild type plants. Several mitochondrial functions were altered in the mutant including oxygen consumption, ROS production, ATP and ADP content as well as activities of genes encoding alternative oxidase 1A (AOX1A) and various alternative NAD(P)H dehydrogenases (ND). Our results suggest that in the absence of NDUFS8.2 stress-induced ROS generation is restrained leading to reduced oxidative damage and improved tolerance to water deficiency. mETC components can be implicated in redox and energy homeostasis and modulate responses to stresses associated with reduced water availability.

Mutation in Arabidopsis mitochondrial Pentatricopeptide repeat 40 gene affects tolerance to water deficit.

MAIN CONCLUSION: The Arabidopsis Pentatricopeptide repeat 40 (PPR40) insertion mutants have increased tolerance to water deficit compared to wild-type plants. Tolerance is likely the consequence of ABA hypersensitivity of the mutants. Plant growth and development depend on multiple environmental factors whose alterations can disrupt plant homeostasis and trigger complex molecular and physiological responses. Water deficit is one of the factors which can seriously restrict plant growth and viability. Mitochondria play an important role in cellular metabolism, energy production, and redox homeostasis. During drought and salinity stress, mitochondrial dysfunction can lead to ROS overproduction and oxidative stress, affecting plant growth and survival. Alternative oxidases (AOXs) and stabilization of mitochondrial electron transport chain help mitigate ROS damage. The mitochondrial Pentatricopeptide repeat 40 (PPR40) protein was implicated in stress regulation as ppr40 mutants were found to be hypersensitive to ABA and high salinity during germination. This study investigated the tolerance of the knockout ppr40-1 and knockdown ppr40-2 mutants to water deprivation. Our results show that these mutants display an enhanced tolerance to water deficit. The mutants had higher relative water content, reduced level of oxidative damage, and better photosynthetic parameters in water-limited conditions compared to wild-type plants. ppr40 mutants had considerable differences in metabolic profiles and expression of a number of stress-related genes, suggesting important metabolic reprogramming. Tolerance to water deficit was also manifested in higher survival rates and alleviated growth reduction when watering was suspended. Enhanced sensitivity to ABA and fast stomata closure was suggested to lead to improved capacity for water conservation in such environment. Overall, this study highlights the importance of mitochondrial functions and in particular PPR40 in plant responses to abiotic stress, particularly drought.

HeroMDAnalysis: an automagical tool for GROMACS-based molecular dynamics simulation analysis.

Background & objective: Molecular dynamics simulations (MDS) using GROMACS are among the commonly used computational experiments in the area of molecular biology and drug discovery. This article presents a project called HeroMDAnalysis, an automagical tool to analyze the GROMACS-based MDS trajectories and generate plots as high-quality images for various parameters. Materials & methods: The tool was built using bash shell programming, and graphical user interface was built using Zenity engine. Results & conclusion: This tool offers a simple, semiautomated, and relatively fast framework for what was previously a complex, manual, time-consuming and error-prone task, presenting a useful method for biochemists and synthetic chemists with no prior experience of the command line interface.

Computational identification of natural product leads that inhibit mast cell chymase: an exclusive plausible treatment for Japanese encephalitis.

A recent research has identified chymase, a mast cell-specific protease as an exclusive novel therapeutic target to prevent Japanese encephalitis virus (JEV) induced encephalitis. Interestingly, JEV activates mast cell specific chymase during its penetration through blood brain barrier (BBB) which eventually guide to viral encephalitis. Hence, in this study, natural chemical entities (NCE) from multiple databases (MPD3, TIPDB and MTDP) were virtually screened for their binding affinity as chymase inhibitors, a promising negotiator for prolong survival against JEV tempted encephalitis. Merged computational programs, Maestro software, QikProp, ProTox and Gromacs were applied to screen the NCEs against target receptor (PDB: 4KP0). Three hits (C00008437, C00014417 and 8141903) were identified after employing a series of sieves such as High Throughput Virtual Screening (HTVS), Standard precision (SP) and Xtra precision (XP) molecular docking simulations followed by desired pharmacokinetic-toxicity profile predictions and molecular dynamics (MD) examinations. Maestro simulations resulted in best three binding energy scores as -11.992 kcal/mol (first ranked; C00008437), -11.673 kcal/mol (second ranked; C00014417) and -11.456 kcal/mol (third ranked; 8141903), respectively. The top three hits revealed an ideal range of pharmacokinetic and toxicity descriptors values. In addition, MD simulations enabled us to confirm top hits higher selectivity toward chymase receptor. In conclusion, this might potentially represent remarkable novel classes with an effective chymase mediated treatment to combat JEV induced encephalitis, which need to justify with further detail studies.

Natural chemical entities from Arisaema genus might be a promising break-through against Japanese encephalitis virus infection: a molecular docking and dynamics approach.

Japanese encephalitis virus (JEV) infection affects millions of population worldwide whose incidence is increasing year by year and currently, no specific drugs are available for its treatment. However, vaccines are available for its prevention but not effective against all the clinical isolates. Thus, there is an urgent need for new chemical entities or exploration of existing molecules for its treatment. In the current study, we have undertaken virtual ligand screening (VLS) method to screen out selected phytoconstituents of Genus Arisaema against various targets (NS5, NS3 helicase, and NS2B-NS3 protease) of JEVs which exhibits vital role in replication, infection cycle and host interaction by using molecular docking followed by molecular dynamics (MD) simulations. Screened natural chemical entities displayed good binding affinity as well as optimum stability toward NS5 and NS3 helicase. Further, the drug likeliness evaluated by Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis was found to be in the acceptable range. In conclusion, these natural chemical entities could be considered as promising candidates for the development of anti-JEV drugs. However, further investigation is required to confirm their exact role in JEV infection through in vitro and in vivo experiments.Communicated by Ramaswamy H. Sarma.

Multifunctional modification of cotton using layer-by-layer finishing with chitosan, sodium lignin sulphonate and boric acid.

Functionally modified fabrics produced using sustainable techniques are in huge demand in today's world. In the present work, cotton fabric was modified using layer-by-layer two-stage finishing method using a solution of chitosan in citric acid (CS) and sodium lignin sulphonate (SLS) with boric acid (BA), thus granting several performance traits like wrinkle-free, antibacterial, flame retardant, UV protection and antioxidant properties. The finished fabric was evaluated for several textile properties like tensile strength, bending length, crease recovery, whiteness index and functional properties like antibacterial activity, UV protection, flame retardancy and antioxidant properties under standard conditions. The finished cotton showed an increase in CRA, antibacterial activity in the range 70-89%, UPF in the excellent range, much higher LOI values with a decrease in heat release and antioxidant activity of higher than 93%. The novel method of multifunctional finishing of cotton by layer-by-layer technique is explored.

Genus Arisaema: A Review of Traditional Importance, Chemistry and Biological Activities.

BACKGROUND: The Arisaema (Araceae) is a genus of approximately 180 perennial herbs widely distributed in the evergreen and deciduous forests. This genus (Arisaema) has been used as a medicinal agent since ancient times. Experimental investigations have shown a promising positive correlation with its folklore claim and this encourages us to report updated medicinal review (genus Arisaema) for future research. OBJECTIVE: This review aimed to summarize the ethnobotany, folklore uses, chemistry and biological activities. CONCLUSION: The comprehensive literature on genus Arisaema indicates the presence of terpenoids, flavonoids, and glycosphingolipids as the principal chemical constituents. Additionally, phytosterols, alkaloids, carboline derivatives and miscellaneous compounds were documented in plants of genus Arisaema. Biological investigations led to the credentials of antioxidant, anticancer, insecticidal, antimicrobial, anthelmintic and hepatoprotective activities. Following, several plant species are promising candidates for the treatment of cancer, parasitic diseases and microbial infection complications. Though, a lot of facets of this genus like phytoconstituents identification, mechanistic profile, adverse effects and clinical studies are still quite limited. Thus, this systematic review may act as a powerful tool in future studies for promoting health benefits against various health hazards.

Antiviral Activity of a Arisaema Tortuosum Leaf Extract and Some of its Constituents against Herpes Simplex Virus Type 2.

Infections caused by HSV-2 are a public health concern worldwide, and there is still a great demand for the discovery of novel anti-herpes virus agents effective against strains resistant to current antiviral agents. In this context, medicinal plants represent an alternative source of active compounds for developing efficient antiviral therapies. The aim of this study was to evaluate the antiviral activity of Arisaema tortuosum, a plant used in the traditional medicine of India. A chloroform soluble fraction of the leaves exhibited anti-HSV-2 activity with a selectivity index of 758. The extract was also active against acyclovir-resistant HSV-2 and HSV-1. The mechanism of action of the extract was investigated evidencing inhibition of both early and late events of the HSV-2 replicative cycle. A HPLC-PDA-MS/MS analysis showed the presence of flavonoids including apigenin and luteolin in the chloroform extract (CE). Apigenin and luteolin showed a high inhibitory activity with EC50 values of 0.05 and 0.41 µg/mL, respectively. Both compounds exhibited antiviral activity when added up to 6 h post infection and were able to reduce the viral progeny production. In addition, apigenin interfered with cell-to-cell virus spread.

Merged experimental guided computational strategy toward tuberculosis treatment mediated by alveolar macrophages mannose receptor.

Macrophage mannose receptor (MMR) is a C-type lectin that regulates the phagocytosis and phagocytosis-lysosome (P-L) fusion in tuberculosis. Mannose-capped lipoarabinomannan, a lipoglycan present at the surface of Mycobacterium tuberculosis, is an important factor in phagocyte attachment and internalization that is specific for MMR. Based on this idea, herein we have designed our experiment to understand the better site-specific delivery against tuberculosis. An experimental outcome was used as a basis to revisit the reverse experimental strategy for tuberculosis management. Stearic mannose was prepared from stearic acid incubation with the D-mannose. Interestingly, stearic mannose explained its internalization via stimulating actin-mediated phagocytic pathway of MMR experimentally. Following, an in silico strategy towards hypothetical designing of various mannose-stearyl conjugates (SBKK1-7) against tuberculosis, as binding promoter of MMR (PDB: 1EGI), was carried out using molecular docking and dynamics approaches. Overall, SPKK-5 viz. ortho stearic mannose showed a higher binding affinity with notable H-bonding and hydrophobic interactions. Pharmacokinetic and toxicity examinations illustrated an ideal range of descriptors values for apex screened compounds. Molecular dynamics simulations have confirmed its significant intactness with the MMR. Ultimately, the whole effort led to the identification of promising hit (SBKK-5), which positively correlates with the experimental work and furthermore need to explore its novel drug delivery systems with improved anti-tubercular therapy.Communicated by Ramaswamy H. Sarma.

A merged molecular docking, ADME-T and dynamics approaches towards the genus of Arisaema as herpes simplex virus type 1 and type 2 inhibitors.

An attempt toward screening of phytoconstituents (Arisaema genus) against herpes viruses (HSV-1 and HSV-2) was carried out using in silico approaches. Human HSV-1 and HSV-2 are accountable for cold sores genital herpes, respectively. Two drug targets, namely thymidine kinase (TK; PDB: 2ki5) serine protease (PDB: 1at3) were selected for HSV-1 and HSV-2. Initially, molecular docking tool was employed to screened apex hits phytoconstituents against herpes infections. ADME-T studies of top ranked were also further highlighted to achieve their effectiveness. Following, molecular dynamics studies were also examined to further optimize the stability of ligands. Glide scores and binding interactions of phytoconstituents were compared with Acyclovir, the main drug used in treatment of HSV, the screened top hits exhibited more glide scores and better binding for both HSV-1 and HSV-2 receptors. Additionally, ADME-T showed an ideal range for top hits while molecular dynamics results also illustrated stability of models. Ultimately, the whole efforts reveal to top three most promising hits for HSV-1 (39, 21, 19) and HSV-2 (20, 51, 19) receptors which can be explored further in wet lab experiments as promising agents against HSV infections.

Evaluation of In Silico Anti-parkinson Potential of ß-asarone.

INTRODUCTION: Parkinson's disease is affecting millions of people worldwide. The prevalence of Parkinson's disease is 0.3% globally, rising to 1% in more than 60 years of age and 4% in more than 80 years of age and the figures are thought to be doubled by 2030. Thus, there is a great need to identify novel therapeutic strategies or candidate drug molecule which can rescue neuronal degeneration. ß -asarone has the potential to act as a neuroprotective agent but regarding its role in Parkinson's disease, very few reports are available. Thus, this study was undertaken to unlock the potential of ß-asarone against Parkinson's disease. MATERIAL AND METHODS: The Absorption, Distribution, Metabolism, and Excretion (ADME) analysis has been done by using Swiss ADME Predictor. The interactions of ß-asarone with dopaminergic receptors were investigated by Glide Program 5.0. The crystal structures of dopamine receptors were retrieved from Research Collaboratory for Structural Bioinformatics- Protein Data Bank (RCSB-PDB). The structure of ß-asarone was drawn in Chem Draw Ultra 7.0.1. Finally, the toxicity of ß-asarone has been predicted by using online web-servers like Lazar and Protox. RESULTS AND DISCUSSION: The ADME data of current investigation has shown good oral bioavailability of ß-asarone. It also showed a good binding affinity towards dopaminergic receptors. Further, it was found to be interacting through hydrogen bond with different amino acid residues of D2 and D3 receptors. However, ß-asarone was predicted to be toxic in various species of rodents, as per the results of toxicity online web servers. CONCLUSION: Based on the current finding from ADME and docking studies, these preliminary results may act as effective precursor tool for the development of ß-asarone as a promising anti-Parkinson agent. However, furthermore experimental validation using in-vitro & in-vivo studies is needed to explore their therapeutic andtoxic effects.

Computational Breakthrough of Natural Lead Hits from the Genus of Arisaema against Human Respiratory Syncytial Virus.

BACKGROUND: To date, efforts for the prevention and treatment of human respiratory syncytial virus (RSV) infection have been still vain, and there is no safe and effective clinical accepted vaccine. Arisaema genus has claimed for various traditional bioactivities, but scientific assessments are quite limited. OBJECTIVE: This encouraged us to carry out our present study on around 60 phytoconstituents of different Arisaema species as a natural inhibitor against the human RSV. MATERIALS AND METHODS: Selected 60 phytochemical entities were evaluated on the docking behavior of human RSV receptor (PDB: 4UCC) using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA). Furthermore, kinetic properties and toxicity nature of top graded ligands were analyzed through QikProp and ProTox tools. RESULTS: Notably, rutin (glide score: -8.49), schaftoside (glide score: -8.18) and apigenin-6,8-di-C-ß-D-galactoside (glide score - 7.29) have resulted in hopeful natural lead hits with an ideal range of kinetic descriptors values. ProTox tool (oral rodent toxicity) has resulted in likely toxicity targets of apex-graded tested ligands. CONCLUSION: Finally, the whole efforts can be explored further as a model to confirm its anti-human RSV potential with wet laboratory experiments. SUMMARY: Rutin, schaftoside, and apigenin-6,8-di-C-ß-D-galactoside showed promising top hits docking profile against human respiratory syncytial virusMoreover, absorption, distribution, metabolism, excretion properties (QikProp) of top hits resulted within an ideal range of kinetic descriptorsProTox tool highlighted toxicity class ranges, LD50 values, and possible toxicity targets of apex-graded tested ligands. Abbreviations used: RSV: Respiratory syncytial virus, PRRSV: Porcine respiratory and reproductive syndrome virus, ADME-T: Absorption, distribution, metabolism, excretion, and toxicity.

In silico Prediction and Wet Lab Validation of Arisaema tortuosum (Wall.) Schott Extracts as Antioxidant and Anti-breast Cancer Source: A Comparative Study.

BACKGROUND: Globally, reactive oxygen species have served as an alarm predecessor toward pathogenesis of copious oxidative stress-related diseases. The researchers have turned their attention toward plant-derived herbal goods due to their promising therapeutic applications with minimal side effects. Arisaema tortuosum (Wall.) Schott (ATWS) is used in the traditional medicine since ancient years, but scientific assessments are relatively inadequate and need to be unlocked. OBJECTIVE: Our aim was designed to validate the ATWS tuber and leaf extracts as an inhibitor of oxidative stress using computational approach. MATERIALS AND METHODS: The reported chief chemical entities of ATWS were docked using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA) tool and further ATWS extracts (tubers and leaves) were validated with 2,2'-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), ferric-reducing ability of plasma (FRAP), and sulforhodamine B assays experimentally. RESULTS: In silico results showed notable binding affinity of ATWS phytoconstituents with the receptor (PDB: 3ERT). Experimentally, butanolic tuber fraction confirmed promising antioxidant potential (ABTS: IC50: 271.67 µg/ml; DPPH: IC50: 723.41 µg/ml) with a noteworthy amount of FRAP (195.96 µg/mg), total phenolic content (0.087 µg/mg), and total flavonoid content (7.5 µg/mg) while chloroform fraction (leaves) showed considerable reduction in the cell viability of MCF-7 cell line. CONCLUSION: The current findings may act as a precious tool to further unlock novel potential therapeutic agents against oxidative stress. SUMMARY: Quercetin showed top.ranked glide score with notable binding toward 3ERT receptorAmong extracts, butanolic tubers confirmed as promising antioxidant with remarkable amount of TPC and TFCIn addition, chloroform fraction (leaves) revealed considerable decline in the cell viability of MCF-7 cell line. Abbreviations used: ATWS: Arisaema tortuosum (Wall.) Schott, DPPH: 2,2'-diphenyl-1-picrylhydrazyl, ABTS: 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, FRAP: Ferric-reducing ability of plasma, TPC: Total phenolic content, TFC: Total flavonoid content, SRB: Sulforhodamine B.

Computational tool for immunotoxic assessment of pyrethroids toward adaptive immune cell receptors.

BACKGROUND: Pyrethroids have prominently known for their insecticidal actions worldwide, but recent reports as anticancer and antiviral applications gained a lot of interest to further understand their safety and immunotoxicity. OBJECTIVE: This encouraged us to carry out our present study to evaluate the interactions of pyrethroids toward adaptive immune cell receptors. MATERIALS AND METHODS: Type 1 and Type 2 pyrethroids were tested on T (CD4 and CD8) and B (CD28 and CD45) immune cell receptors using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA). In addition, top-ranked tested ligands were too explored for toxicity prediction in rodents using ProTOX tool. RESULTS: Pyrethroids (specifically type 2) such as fenvalerate (-5.534 kcal/mol: CD8), fluvalinate (-4.644 and - 4.431 kcal/mol: CD4 and CD45), and cypermethrin (-3.535 kcal/mol: CD28) have outcome in less energy or more affinity for B-cell and T-cell immune receptors which may later result in the immunosuppressive and hypersensitivity reactions. CONCLUSION: The current findings have uncovered that there is a further need to assess the Type 2 pyrethroids with wet laboratory experiments to understand the chemical nature of pyrethroid-induced immunotoxicity. SUMMARY: Fenvalerate showed apex glide score toward CD8 immune receptor, while fluvalinate confirmed top-ranked binding with CD4 and CD45 immune proteinsIn addition, cypermethrin outcame in top glide score against CD28 immune receptorTop dock hits (Type 2) pyrethroids have shown probable toxicity targets toward AOFA: Amine oxidase (flavin-containing) A and PGH1: Prostaglandin G/H synthase 1, respectively. Abbreviations used: PDB: Protein Data Bank; AOFA: Amine oxidase (flavin-containing) A; PGH 1: Prostaglandin G/H synthase 1.

"Jodhpur bezoar": giant polyurethane bezoar.

Acute upper gastrointestinal obstruction due to foreign body ingestion is rare (<6 % of all small intestinal obstruction). Bezoars tend to grow slowly and only thereafter cause obstruction, if any. Rapid formation of a bezoar within hours of ingestion of the offending substance is a unique entity. Here, we present a case of a 22-year-old Indian male who was brought in the emergency department with history of ingesting chemicals used for refrigerator insulation, with suicidal intent. Within hours, he was operated for suspected perforation. And on the operation table, we came across surprisingly a cast extending from the whole of the esophagus to as far as 2 ft of proximal jejunum! Probably the first of its kind ever known! And no breach in the gut could be found in spite of free gas under the dome of diaphragm, probably due to the chemicals sealing the rent as it solidified!

Adansonia digitata L. (baobab): A review of traditional information and taxonomic description

Adansonia digitata L. (Malvaceae) is commonly known as baobab tree native to Africa. Baobab is a multi-purpose tree which offers protection and provides food, clothing and medicine as well as raw material for many useful items. The fruit pulp, seeds, leaves, flowers, roots, and bark of baobab are edible and they have been studied by scientists for their useful properties. The fruit pulp have very high vitamin C, calcium, phosphorus, carbohydrates, fibers, potassium, proteins and lipids content, which can be used in seasoning as an appetizer and also make juices. Seeds contain appreciable quantities of phosphorus, magnesium, zinc, sodium, iron, manganese, whereas they have high levels of lysine, thiamine, calcium and iron. Baobab has numerous biological properties including antimicrobial, anti-malarial, diarrhoea, anaemia, asthma, antiviral, anti-oxidant and anti-inflammatory activities amongst others. Phytochemical investigation revealed the presence of flavonoids, phytosterols, amino acids, fatty acids, vitamins and minerals. The review summarizes the information on various aspects of traditional information, taxonomic description, medicinal properties and importantly nutritional value.