A novel micronutrients and methyl jasmonate cocktail of elicitors via seed priming improves drought tolerance by mitigating oxidative stress in rice (Oryza sativa L.).

Drought is a major limiting factor for rice (Oryza sativa L.) production globally, and a cost-effective seed priming technique using bio-elicitors has been found to have stress mitigating effects. Till date, mostly phytohormones have been preferred as bio-elicitors, but the present study is a novel attempt to demonstrate the favorable role of micronutrients-phytohormone cocktail, i.e., iron (Fe), zinc (Zn), and methyl jasmonate (MJ) via seed priming method in mitigating the deleterious impacts of drought stress through physio-biochemical and molecular manifestations. The effect of cocktail/priming was studied on the relative water content, chlorophyll a/b and carotenoid contents, proline content, abscisic acid (ABA) content, and on the activities of ascorbate peroxidase (APX), superoxide dismutase (SOD), NADPH oxidase (Nox), and catalase (CAT). The expressions of drought-responsive genes OsZn-SOD, OsFe-SOD, and Nox1 were found to be modulated under drought stress in contrasting rice genotypes -N-22 (Nagina-22, drought-tolerant) and PS-5 (Pusa Sugandh-5, drought-sensitive). A progressive rise in carotenoids (10-19%), ABA (18-50%), proline (60-80%), activities of SOD (27-62%), APX (46-61%), CAT (50-80%), Nox (16-30%), and upregulated (0.9-1.6-fold) expressions of OsZn-SOD, OsFe-SOD, and Nox1 genes were found in the primed plants under drought condition. This cocktail would serve as a potential supplement in modern agricultural practices utilizing seed priming technique to mitigate drought stress-induced oxidative burst in food crops.

Attenuated maladaptive emotion processing as a potential mediator of the relationship between dispositional mindfulness and mental health.

The emotion processing and regulation mechanisms by which dispositional (personality trait) mindfulness exerts its positive effects on mental health remain unclear. Here, we tested, using structural equation modeling, whether the relationship between higher dispositional mindfulness and better mental health is mediated by reduced maladaptive processing of emotional information (e.g., expressive suppression, impoverished emotional experiences, unprocessed emotions, avoidance, externalizing strategies) and associated lower negative affect, enhanced adaptive processing of emotional information (e.g., cognitive reappraisal) and associated higher positive affect, or a combination of these two emotion processing styles. Dispositional mindfulness, mental health, diverse emotional constructs with adaptive and maladaptive dimensions (including range and differentiation of emotional experiences, use of specific emotion regulation strategies, emotion processing deficits, negative affect repair strategies, negative mood regulation expectancies), and positive and negative affect were assessed using self-report measures in a non-clinical sample of 256 adults. The relationship between higher dispositional mindfulness and better mental health was found to be best explained by reduced maladaptive emotion processing styles and associated lower negative affect, rather than by enhanced adaptive emotion processing and higher positive affect. Further research should investigate whether the same mechanisms explain psychological benefits of cultivated mindfulness in people with low dispositional mindfulness and/or with mental health disorders following mindfulness skills training.

Towards the development of phytoextract based healthy ageing cognitive booster formulation, explored through Caenorhabditis elegans model.

The positive effect of herbal supplements on aging and age-related disorders has led to the evolution of natural curatives for remedial neurodegenerative diseases in humans. The advancement in aging is exceedingly linked to oxidative stress. Enhanced oxidative stress interrupts health of humans in various ways, necessitating to find stress alleviating herbal resources. Currently, minimal scientifically validated health and cognitive booster resources are available. Therefore, we explored the impact of plant extracts in different combinations on oxidative stress, life span and cognition using the multicellular transgenic humanized C. elegans, and further validated the same in Mus musculus, besides testing their safety and toxicity. In our investigations, the final product-the HACBF (healthy ageing cognitive booster formulation) thus developed was found to reduce major aging biomarkers like lipofuscin, protein carbonyl, lipid levels and enhanced activity of antioxidant enzymes. Further confirmation was done using transgenic worms and RT-PCR. The cognitive boosting activities analyzed in C. elegans and M. musculus model system were found to be at par with donepezil and L-dopa, the two drugs which are commonly used to treat Parkinson's and Alzheimer's diseases. In the transgenic C. elegans model system, the HACBF exhibited reduced aggregation of misfolded disease proteins α-synuclein and increased the health of nicotinic acetylcholine receptor, levels of Acetylcholine and Dopamine contents respectively, the major neurotransmitters responsible for memory, language, learning behavior and movement. Molecular studies clearly indicate that HACBF upregulated major genes responsible for healthy aging and cognitive booster activities in C. elegans and as well as in M. musculus. As such, the present herbal product thus developed may be quite useful for healthy aging and cognitive boosting activities, and more so during this covid-19 pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s13237-022-00407-1.

Metaheuristic algorithm integrated neural networks for well-test analyses of petroleum reservoirs.

In recent years, well-test research has witnessed several works to automate reservoir model identification and characterization using computer-assisted models. Since the reservoir model identification is a classification problem, while its characterization is a regression-based task, their simultaneous accomplishment is always challenging. This work combines genetic algorithm optimization and artificial neural networks to identify and characterize homogeneous reservoir systems from well-testing data automatically. A total of eight prediction models, including two classifiers and six regressors, have been trained. The simulated well-test pressure derivatives with varying noise percentages comprise the training samples. The feature selection and hyperparameter tuning have been performed carefully using the genetic algorithm to enhance the prediction accuracy. The models were validated using nine simulated and one real-field test case. The optimized classifier identifies all the reservoir models with a classification accuracy higher than 79%. In addition, the statistical analysis approves that the optimized regressors accurately perform the reservoir characterization with mean relative errors of lower than 4.5%. The minimized manual interference reduces human bias, and the models have significant noise tolerance for practical applications.

Sesquiterpenoids isolated from davana (Artemisia pallens Wall. ex DC) mitigates parkinsonism in Caenorhabditis elegans disease model.

Parkinson's disease (PD) is a multifactorial ailment that severely affects the viability of dopaminergic neurons leading to progressive loss of motor control. The current regimen for PD treatment includes synthetic drugs that lack efficacy and cause serious side effects. Consequently, recent drug development studies are focusing on alternative medicines from plant sources. Artemisia pallens Wall. ex DC, commonly known as davana, is an annual aromatic herb cultivated in southern India. Given the diverse traditional and scientifically documented therapeutic effects of A. pallens, the pharmacological potential of the isolates of the plant, namely bicyclogermacrene (D1), cis-davanone (D3), and cis-hydroxy davanone (D5), was tested for anti-Parkinson's activity in Caenorhabditis elegans model. The tested compounds alleviated α-synuclein (α-syn) aggregation and maximum decline was observed in 25 µM D1 supplemented worms. Additionally, D1 modulated dopamine regulated nonanol-1 repulsion and locomotory behaviour of C. elegans validating its future use as a dopamine-enhancing agent. The genetic regulation mediating the above effects validated through the qPCR study showed that D1 supplementation displayed its anti-Parkinson's effect through upregulation of the antioxidant defence system genes (superoxide dismutase (sod)-1, sod-2, and sod-4) and PD associated pdr-1 gene that maintains the mitochondrial proteostasis. The molecular docking studies of C. elegans PDR-1 with D1 further confirmed its contribution in D1 induced abridgment of Parkinson disease linked pathologies in C. elegans disease model. Hence, this article proposes D1 as an effective regimen for curtailing the Parkinson disease linked pathologies through mechanism of maintaining cellular redox state and proteostasis.

Deciphering the change in root system architectural traits under limiting and non-limiting phosphorus in Indian bread wheat germplasm.

The root system architectures (RSAs) largely decide the phosphorus use efficiency (PUE) of plants by influencing the phosphorus uptake. Very limited information is available on wheat's RSAs and their deciding factors affecting phosphorus uptake efficiency (PupE) due to difficulties in adopting scoring values used for evaluating root traits. Based on our earlier research experience on nitrogen uptake efficiency screening under, hydroponics and soil-filled pot conditions, a comprehensive study on 182 Indian bread wheat genotypes was carried out under hydroponics with limited P (LP) and non-limiting P (NLP) conditions. The findings revealed a significant genetic variation, root traits correlation, and moderate to high heritability for RSAs traits namely primary root length (PRL), total root length (TRL), total root surface area (TSA), root average diameter (RAD), total root volume (TRV), total root tips (TRT) and total root forks (TRF). In LP, the expressions of TRL, TRV, TSA, TRT and TRF were enhanced while PRL and RAD were diminished. An almost similar pattern of correlations among the RSAs was also observed in both conditions except for RAD. RAD exhibited significant negative correlations with PRL, TRL, TSA, TRT and TRF under LP (r = -0.45, r = -0.35, r = -0.16, r = -0.30, and r = -0.28 respectively). The subclass of TRL, TSA, TRV and TRT representing the 0-0.5 mm diameter had a higher root distribution percentage in LP than NLP. Comparatively wide range of H' value i.e. 0.43 to 0.97 in LP than NLP indicates that expression pattern of these traits are highly influenced by the level of P. In which, RAD (0.43) expression was reduced in LP, and expressions of TRF (0.91) and TSA (0.97) were significantly enhanced. The principal component analysis for grouping of traits and genotypes over LP and NLP revealed a high PC1 score indicating the presence of non-crossover interactions. Based on the comprehensive P response index value (CPRI value), the top five highly P efficient wheat genotypes namely BW 181, BW 103, BW 104, BW 143 and BW 66, were identified. Considering the future need for developing resource-efficient wheat varieties, these genotypes would serve as valuable genetic sources for improving P efficiency in wheat cultivars. This set of genotypes would also help in understanding the genetic architecture of a complex trait like P use efficiency.

Neuromodulatory potential of Asparagus racemosus and its bioactive molecule Shatavarin IV by enhancing synaptic acetylcholine level and nAChR activity.

Cholinergic dysfunction has been commonly known to be associated with plethora of neurodegenerative disorders and also serves as a biomarker. Recently, cholinergic system demonstrated that acetylcholine has major role in regulation of its function therefore the main therapeutic regimens towards disease management have been focused on increasing acetylcholine levels. The current study explores the potential of Asparagus racemosus extract (ARE) and its bioactive molecule Shatavarin IV (SIV) in improving cholinergic transmission via utilizing Caenorhabditis elegans considering as a model system. Observations and results obtained through this study have clearly showed significant modulation in cholinergic function by increasing acetylcholine (ACh) levels and the nicotinic acetylcholine receptors (nAChRs) activity. Further exploration on mechanistic facet pointed towards ARE and SIV modulatory potential through increased synaptic ACh level by blocking acetyl cholinesterase at enzyme level and by regulating increment in transcript level of cha-1, and cho-1 that are directly responsible for the synthesis of ACh. Further, the up-regulation of unc-38 and unc-50 transcripts could be the reason for enhanced nAChR activity and investigation on stress modulator activity showed excellent efficiency of ARE and SIV in diminishing ROS thereby lowering the oxidative damage.

Coping With COVID-19: Mindfulness-Based Approaches for Mitigating Mental Health Crisis.

The novel coronavirus disease COVID-19 that first emerged in Wuhan, China, in Nov-Dec 2019 has already impacted a significant proportion of the world population. Governments of many countries imposed quarantines and social distancing measures in 2020, many of which remain in place, to mitigate the spread of the SARS-Cov-2 virus causing the COVID-19 disease. The direct impact of COVID-19 on people infected with the virus, their families and the health care workers, as well as the impact of the mitigation measures such as quarantine, social distancing, and self-isolation on the rest of the population have contributed to a global mental health pandemic, including anxiety, depression, panic attacks, posttraumatic stress symptoms, psychosis, addiction, obsessive-compulsive disorder, and suicidality. These effects are present acutely (for example, due to fear of contamination or losing loved ones, effects of quarantine/isolation, withdrawal of community and social services, etc.) and may continue long after the pandemic is over (for example, due to bereavement, unemployment, financial losses, etc). The COVID-19 pandemic has triggered mental health problems in people without previous history of mental illness, as well as worsened the symptoms in those with pre-existing psychiatric diagnosis. Therefore, the global effort is called for to deal with this mental health pandemic secondary to COVID-19 itself to address the emergence of new as well as the exacerbation of the existing mental health issues. Conversely, this global context provides an extraordinary opportunity for studying individual differences in response to and resilience in the face of physical and psychological threat, challenge to "normal" way of life, and long-term uncertainty. In this viewpoint article we outline the particular suitability of mindfulness, its skills and mechanisms, as an approach to the prevention and management of mental health issues, as well as to the promotion of well-being and building the foundations of adaptability and flexibility in dealing with the long-term uncertainty and profound changes to the social, economic, and possibly political systems as this pandemic continues to unfold.

Swertiamarin from Enicostemma littorale, counteracts PD associated neurotoxicity via enhancement α-synuclein suppressive genes and SKN-1/NRF-2 activation through MAPK pathway.

The elusive targets and the multifactorial etiology of Parkinson's disease (PD) have hampered the discovery of a potent drug for PD. Furthermore, the presently available medications provide only symptomatic relief and have failed to mitigate the pathogenesis associated with PD. Therefore, the current study was aimed to evaluate the prospective of swertiamarin (SW), a secoiridoid glycoside isolated from a traditional medicinal plant, Enicostemma littorale Blume to ameliorate the characteristic features of PD in Caenorhabditis elegans. SW (25 µM) administration decreased the α-synuclein (α-syn) deposition, inhibited apoptosis and increased dopamine level mediated through upregulating the expression of genes linked to ceramide synthesis, mitochondrial morphology and function regulation, fatty acid desaturase genes along with stress responsive MAPK (mitogen-activated protein kinase) pathway genes. The neuroprotective effect of SW was evident from the robust reduction of 6-hydroxydopamine (6-OHDA) induced dopaminergic neurodegeneration independent of dopamine transporter (dat-1). SW mediated translational regulation of MAPK pathway genes was observed through increase expression of SKN-1 and GST-4. Further, in-silico molecular docking analysis of SW with C. elegans MEK-1 showed a promising binding affinity affirming the in-vivo results. Overall, these novel finding supports that SW is a possible lead for drug development against the multi- factorial PD pathologies.

Age-induced diminution of free radicals by Boeravinone B in Caenorhabditis elegans.

Oxidative damage is accrual of molecular deterioration from reactive oxygen species (ROS) while decrease in generation of ROS is related with free radical scavenging enzymes. Boerhaavia diffusa L. (Nyctaginaceae) derived novel molecule Boeravinone B (BOB) possesses a variety of pharmacological activities, yet their anti-aging potential has not been explored. The aim of the present study was to elucidate the mechanism of BOB mediated oxidative stress resistance and lifespan extension in Caenorhabditis elegans. The results showed that the BOB significantly extends the lifespan of C. elegans with its anti-oxidative potential via reducing accumulation of reactive oxygen species (ROS). BOB was found to recover the shortened lifespan of oxidative stress prone mutants mev-1 and gas-1 (14.75 and 16.11%, respectively). Additionally, this finding supported by the reduced ROS levels seen in BOB treated worms. Further, the effective concentration of BOB (25 µM) significantly enhanced the expressions of target genes such as superoxide dismutase (SOD-3), glutathione-S-transferase (GST-4) and heat shock protein (HSP-16.2) fused to green fluorescent protein (GFP), and it does so by modulating the stress-related signaling pathways (SEK-1) and transcription factors (SKN-1/Nrf and DAF-16/Foxo). Moreover, BOB exposure (25 µM) caused significant changes of age-dependent biomarkers such as pharyngeal pumping, body bend, locomotor activity and lipofuscin accumulation were also showed that BOB retards the aging. Overall, the findings highlight the antioxidant supplement triggering pharmaceutical potential of BOB which may serve as a new future perspective for healthy aging or delayed onset of oxidative related diseases.

Withanolide A extends the lifespan in human EGFR-driven cancerous Caenorhabditis elegans.

The conserved EGFR pathway is linked with multiple cancers in humans including breast, ovarian, and lung carcinoma. Withanolide A, one of the major withanolidal active compounds isolated from the Withania somnifera, extends lifespan and ameliorates stress resistance in wild-type C. elegans by targeting the Insulin/IGF-1 signaling pathway. Up-regulation of IGF1 can transactivate EGFR which inturn reduces longevity and promotes tumor development in an organism. We examined the effects of Withanolide A on the lifespan of a human EGFR-driven C. elegans transgenic model exhibiting the multivulva (Muv) phenotype. The results showed that WA extends the lifespan of both wild human EGFR-driven C. elegans model (human wild-type tyrosine kinase) as well as models bearing single (L858R), and double mutations (T790M-L858R). The lifespan extension observed in these transgenic strains was 20.35, 24.21 and 21.27%, respectively. Moreover, the reduced fat levels were noticed in both wild-type N2 worms and transgenic strains. These observations support the heathspan promoting effect of WA as lipid-rich diet has been reported to promote tumor development. In view of the fact that most of the well known FDA approved drugs such as gefitinib fail to inhibit the EGFR-associated cancers because of these mutations, the present findings show the potential of Withanolide A as a foreseen future nutraceutical to improve the average survival of cancer patients.

Anti-biofilm and anti-virulence potential of 3,7-dimethyloct-6-enal derived from Citrus hystrix against bacterial blight of rice caused by Xanthomonas oryzae pv. oryzae.

The present investigation for the first time explains the anti biofilm and anti virulence potential of Kaffir lime oil (KLO) and its major constituent, Citronellal (3,7-dimethyloct-6-enal) against Xanthomonas oryzae pv. oryzae, causal organism of bacterial blight disease of rice. KLO at 500 ppm showed potential activity against X. oryzae pv. oryzae. Among the major components identified, citronellal (CIT) at 75 µM concentration was found to significantly inhibit biofilm along with the swimming and swarming potential of X. oryzae pv. oryzae. In contrary, CIT did not affect the metabolic status and growth kinetics of the bacterial cells. Gene expression analysis showed down regulation in motA, cheD, cheY, flgF, gumC, xylanase, endogluconase, cellulose, cellobiosidase, virulence and rpfF transcript levels by citronellal treatment. However, an insignificant effect of 75 µM CIT treatment was observed on motB, flgE, pilA, estY, pglA, protease and lytic genes expression. Finally, the observations recorded were in confirmity with the virulence leaf clip test as lesion length was significantly decreased (39%) in CIT treatment as compared to the control leaves inoculated with only X. oryzae pv. oryzae. Overall, the findings obtained advocate the use of CIT for promising anti biofilm and anti virulence activity which in turn can be used for managing the blight disease in rice.

5-Desmethylnobiletin augments synaptic ACh levels and nicotinic ACh receptor activity: A potential candidate for alleviation of cholinergic dysfunction.

Cholinergic function is compromised in plethora of neurodegenerative disorders especially Alzheimer's disease. Increasing acetylcholine (ACh) levels has been the mainstay in majority of the therapeutic regimens, accepted for management of disease. The present study investigates the efficacy of 5-Desmethylnobiletin (DN), a polymethoxyflavone in augmenting cholinergic function using Caenorhabditis elegans as a model organism. The studies revealed significant elevation in cholinergic transmission mediated through increased levels of ACh and activity of nicotinic acetylcholine receptors (nAChR). Further investigation into the mechanistic aspects indicated that DN enhanced cholinergic function through down modulation of acetylcholinesterase activity at enzyme and transcript level along with upregulation of non alpha subunit, unc-29 which could be linked with enhanced nAChR activity as evident from levamisole assay. Additionally, studies on antioxidant properties, implicated significant potential of DN in curtailing ROS, both in vivo and in vitro. Our studies present DN as a phytomolecule with novel biological activities which could be exploited and researched upon for therapeutic avenues in terms of cholinergic function and antioxidant potential.

3ß-Hydroxy-urs-12-en-28-oic acid confers protection against ZnONPs induced adversity in Caenorhabditis elegans.

Despite their well reported potent risk towards human health and environment Zinc oxide nanoparticles (ZnONPs) find an extensive commercial usage due to their antimicrobial properties. Here, we evaluated the efficacy of a natural triterpene ursolic acid (3ß-hydroxy-urs-12-en-28-oic acid; UA) for overcoming the cytotoxic challenges of ZnONPs employing Ceanorhabditis elegans. The 24h LC50 of Zn-ONPs (<50nm TEM) was deduced as 4.75mgL-1. UA (25µM) was observed to defend against this toxicity by attenuating Reactive Oxygen Species (ROS) resulting into better survival at 2mgL-1 in a time dependent behavior. However, reproductive health remains compromised. Our study identifies UA as a natural inducer of metallothionein proteins along with antioxidant potential. We demonstrate that UA induces upregulation of predominantly antioxidant genes, including the superoxide dismutases (sod-1, sod-5 and sod-3), glutathione S-transferase 7 (gst-7), heat shock protein (hsp-16.2) along with the metal exposure responsive metallothionein (mtl-1 and mtl-2). Moreover, UA also restores elevated transcript levels of gst-4 during ZnONPs stress conditions to normal by directly scavenging ROS owing to its own antioxidant potential. Altogether, the toxic aspects of NPs that can be avoided compensated or postponed by supplementation of phytochemical(s) in biological system underscore their potential implications in near future.

Microbial interference mitigates Meloidogyne incognita mediated oxidative stress and augments bacoside content in Bacopa monnieri L.

Microbial interference plays an imperative role in plant development and response to various stresses. However, its involvement in mitigation of oxidative stress generated by plant parasitic nematode in plants remains elusive. In the present investigation, the efficacy of microbe's viz., Chitiniphilus sp. MTN22 and Streptomyces sp. MTN14 single and in combinations was examined to mitigate oxidative stress generated by M. incognita in medicinal plant, Bacopa monnieri. Microbial combination with and without pathogen also enhanced the growth parameters along with secondary metabolites (bacoside) of B. monnieri than the pathogen inoculated control. The study showed that initially the production of hydrogen peroxide (H2O2) was higher in dual microbes infected with pathogen which further declined over M. incognita inoculated control plants. Superoxide dismutase and free radical scavenging activity were also highest in the same treatment which was linearly related with least lipid peroxidation and root gall formation in B. monnieri under the biotic stress. Microscopic visualization of total reactive oxygen species (ROS), H2O2, superoxide radical and programmed cell death in host plant further extended our knowledge and corroborated well with the above findings. Furthermore, scanning electron microscopy confirmed good microbial colonization on the host root surface around nematode penetration sites in plants treated with dual microbes under pathogenic stress. The findings offer novel insight into the mechanism adopted by the synergistic microbial strains in mitigating oxidative stress and simultaneously stimulating bacoside production under pathogenic stress.

1-Methyl-4-propan-2-ylbenzene from Thymus vulgaris Attenuates Cholinergic Dysfunction.

Cholinergic dysfunction is manifested in a plethora of neurodegenerative and psychiatric disorders such as Alzheimer's, Parkinson's, and Huntington's diseases. The extent of cholinergic affliction is maximum in Alzheimer's disease which is a progressive neurodegenerative disorder involving death of cholinergic neurons. To this date, the therapeutic management of cholinergic dysfunction is limited to provide symptomatic relief through the use of acetylcholinesterase (Ache) inhibitors only. The present study elaborates the potential of thyme oil and its individual components in curtailing cholinergic deficits. We found that thyme oil augments neurotransmission by modulating synaptic acetylcholine (Ach) levels and nicotinic acetylcholine receptor activity, being orchestrated through upregulation of genes cho-1, unc-17 and unc-50. Studies on individual components revealed para-cymene (1-methyl-4-propan-2-ylbenzene) as the active component of thyme oil, contributing its effects through upregulation of cho-1, cha-1, unc-17 and unc-50, while downregulating ace-1 and ace-2. Interestingly, thymol and gamma-terpinene which although were devoid of any activity individually, exhibited significantly enhanced synaptic Ach levels and nicotinic acetylcholine receptor (nAchR) responsiveness, when administered in combination. Our findings advocate thyme oil and its constituents as potential candidates for amelioration of cholinergic dysfunction. The study is speculated to make a way for a new line of "phytomolecules-based drugs" from the diverse pool of natural compounds.

An antidiabetic polyherbal phytomedicine confers stress resistance and extends lifespan in Caenorhabditis elegans.

An Ayurvedic polyherbal extract (PHE) comprising six herbs viz. Berberis aristata, Cyperus rotundus, Cedrus deodara, Emblica officinalis, Terminalia chebula and Terminalia bellirica is mentioned as an effective anti-hyperglycemic agent in 'Charaka Samhita', the classical text of Ayurveda. Previously, antidiabetic drug metformin was found to elicit antiaging effects and PHE was also found to exhibit antidiabetic effects in humans. Therefore, we screened it for its in vivo antioxidant antiaging effect on stress and lifespan using human homologous Caenorhabditis elegans model system. The effect on aging is evaluated by studying effect of PHE on mean survival in worms. The stress modulatory potential was assessed by quantification of intracellular ROS level, autofluorescent age pigment lipofuscin, oxidative and thermal stress assays. Additionally, stress response was quantified using gene reporter assays. The 0.01 µg/ml dose of PHE was able to enhance mean lifespan by 16.09% (P < 0.0001) in C. elegans. Furthermore, PHE treated worms demonstrated oxidative stress resistance in both wild type and stress hypersensitive mev-1 mutant along with upregulation of stress response genes sod-3 and gst-4. The delayed aging under stress can be attributed to its direct reactive oxygen species-scavenging activity and regulation of some age associated genes like daf-2, daf-16, skn-1, sod-3 and gst-4 in wild-type worms. Additonally, PHE delayed age related paralysis phenotype in CL4176 transgenic worms. Altogether, our results suggest PHE significantly improves the oxidative stress and life span in C. elegans. Overall the present study suggests this polyherbal formulation might play important role in regultaing aging and related complications like diabetes.

Withanolide A offers neuroprotection, ameliorates stress resistance and prolongs the life expectancy of Caenorhabditis elegans.

Withanolide A (steroidal lactone) forms the major constituent of the most popular herbal drug in Ayurvedic medicine, Ashwagandha. It has been used since ancient times as an alternative medicine for the treatment of a variety of age related disorders. Here we provide multiple lines of evidence indicating that Withanolide A improves healthspan, delays age-associated physiological changes and also extends the lifespan of Caenorhabditis elegans. We also report several neuroprotective benefits of this natural product, including its anti-amyloidogenic effects, alleviation of α-synuclein aggregation and neuroprotection through modulation of neural mediators like acetylcholine. We observed that Withanolide A mediates lifespan extension and promotes stress resistance via insulin/insulin-like growth factor signaling pathway. Such findings could be helpful to develop a therapeutic medicine from this natural product for the prevention or reversal of age-related ailments and to improve the survival of patients suffering from Alzheimer's or Parkinson's disease.

Successful use of levosimendan as a primary inotrope in pediatric cardiac surgery: An observational study in 110 patients.

CONTEXT: Levosimendan is a new generation inotrope with calcium sensitizing properties and proven benefits in adults. AIMS: This study investigates the use of levosimendan as a first line inotrope in congenital heart surgery. SETTINGS AND DESIGN: Prospective, observational study in a tertiary care center. MATERIALS AND METHODS: One hundred and ten patients undergoing congenital cardiac surgery received levosimendan at a loading dose of 12 mcg/kg during rewarming on cardiopulmonary bypass followed by continuous infusion of 0.1 mcg/kg/min for 48 h. Hemodynamic parameters were recorded at the time of admission to Intensive Care Unit, and at 3 h, 6 h, 12 h, 24 h, and 48 h thereafter. STATISTICAL ANALYSIS: Categorical variables were compared using Chi-square test. Non-normally distributed quantitative variables were compared between groups using Kruskal-Wallis test. RESULTS: At discharge from operating room (OR), 36 (32.7%) patients required levosimendan alone to maintain optimum cardiac output, 59 (53.6%) patients required the addition of low-dose adrenaline (<0.1 mcg/kg/min) and 15 (13.6%) patients required either increment in adrenaline to high-dose (≥0.1 mcg/kg/min) or starting another inotrope/vasoactive agent. Overall, there were five mortalities. Hypotension leading to discontinuation of levosimendan was not found in any patient. Arrhythmias were observed in three patients. Fifty-four patients were extubated in the OR. CONCLUSIONS: Levosimendan-based inotropic regime offers optimized cardiac output with a well-controlled heart rate and a low incidence of arrhythmias in patients undergoing all categories of congenital heart surgeries.

Microbe-based technology ameliorates glandular trichomes, secondary metabolites and antioxidants in Pelargonium graveolens L'Hér.

BACKGROUND: Despite the vast exploration of microbes for plant health, there is a lack of knowledge about the synergistic effects of specific microorganisms in sustainable agriculture, especially in medicinal plants such as Pelargonium graveolens L'Hér. The aim of this study was to evaluate how synergistic microbes Trichoderma harzianum ThU, Glomus intraradices and Bacillus subtilis CIM affected crop productivity, secondary metabolites and glandular trichome number in P. graveolens. RESULTS: The results demonstrated a significant (P < 0.05) increase in plant growth, secondary metabolites, total chlorophyll, carotenoids, carbohydrates, total phenolics, total flavonoids, free radical-scavenging activity and total antioxidant capacity of P. graveolens treated with synergistic bioinoculants as compared with the control. Most interestingly, an increase in essential oil by 32% in the treatment with all three microbes was observed. Furthermore, the principal aroma compounds citronellol and geraniol also increased in the same treatment. A positive and direct correlation was observed between essential oil content and number of glandular trichomes in all treatments. CONCLUSION: The present study highlights an explicit amalgamation of prospective microbes showing potential for synergism that act as biostimulants in enhancing plant production and improving the antioxidant and aroma profile of P. graveolens. © 2016 Society of Chemical Industry.