The Bacterial Quorum-Sensing Signal 2-Aminoacetophenone Rewires Immune Cell Bioenergetics through the PGC-1α/ERRα Axis to Mediate Tolerance to Infection.

How bacterial pathogens exploit host metabolism to promote immune tolerance and persist in infected hosts remains elusive. To achieve this, we show that Pseudomonas aeruginosa (PA), a recalcitrant pathogen, utilizes the quorum sensing (QS) signal 2-aminoacetophenone (2-AA). Here, we unveil how 2-AA-driven immune tolerization causes distinct metabolic perturbations in macrophages mitochondrial respiration and bioenergetics. We present evidence indicating that these effects stem from decreased pyruvate transport into mitochondria. This reduction is attributed to decreased expression of the mitochondrial pyruvate carrier (MPC1), which is mediated by diminished expression and nuclear presence of its transcriptional regulator, estrogen-related nuclear receptor alpha (ERRα). Consequently, ERRα exhibits weakened binding to the MPC1 promoter. This outcome arises from the impaired interaction between ERRα and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Ultimately, this cascade results in diminished pyruvate influx into mitochondria and, consequently reduced ATP production in tolerized macrophages. Exogenously added ATP in infected macrophages restores the transcript levels of MPC1 and ERRα and enhances cytokine production and intracellular bacterial clearance. Consistent with the in vitro findings, murine infection studies corroborate the 2-AA-mediated long-lasting decrease in ATP and acetyl-CoA and its association with PA persistence, further supporting this QS signaling molecule as the culprit of the host bioenergetic alterations and PA persistence. These findings unveil 2-AA as a modulator of cellular immunometabolism and reveal an unprecedented mechanism of host tolerance to infection involving the PGC-1α/ERRα axis in its influence on MPC1/OXPHOS-dependent energy production and PA clearance. These paradigmatic findings pave the way for developing treatments to bolster host resilience to pathogen-induced damage. Given that QS is a common characteristic of prokaryotes, it is likely that 2-AA-like molecules with similar functions may be present in other pathogens.

Cytokinin and indole-3-acetic acid crosstalk is indispensable for silicon mediated chromium stress tolerance in roots of wheat seedlings.

The rising heavy metal contamination of soils imposes toxic impacts on plants as well as other life forms. One such highly toxic and carcinogenic heavy metal is hexavalent chromium [Cr(VI)] that has been reported to prominently retard the plant growth. The present study investigated the potential of silicon (Si, 10 µM) to alleviate the toxicity of Cr(VI) (25 µM) on roots of wheat (Triticum aestivum L.) seedlings. Application of Si to Cr(VI)-stressed wheat seedlings improved their overall growth parameters. This study also reveals the involvement of two phytohormones, namely auxin and cytokinin and their crosstalk in Si-mediated mitigation of the toxic impacts of Cr(VI) in wheat seedlings. The application of cytokinin alone to wheat seedlings under Cr(VI) stress reduced the intensity of toxic effects of Cr(VI). In combination with Si, cytokinin application to Cr(VI)-stressed wheat seedlings significantly minimized the decrease induced by Cr(VI) in different parameters such as root-shoot length (10.8% and 13%, respectively), root-shoot fresh mass (11.3% and 10.1%, respectively), and total chlorophyll and carotenoids content (13.4% and 6.8%, respectively) with respect to the control. This treatment also maintained the regulation of proline metabolism (proline content, and P5CS and PDH activities), ascorbate-glutathione (AsA-GSH) cycle and nutrient homeostasis. The protective effect of Si and cytokinin against Cr(VI) stress was minimized upon supplementation of an inhibitor of polar auxin transport- 2,3,5-triiodobenzoic acid (TIBA) which suggested a potential involvement of auxin in Si and cytokinin-mediated mitigation of Cr(VI) toxicity. The exogenous addition of a natural auxin - indole-3-acetic acid (IAA) confirmed auxin is an active member of a signaling cascade along with cytokinin that aids in Si-mediated Cr(VI) toxicity alleviation as IAA application reversed the negative impacts of TIBA on wheat roots treated with Cr(VI), cytokinin and Si. The results of this research are also confirmed by the gene expression analysis conducted for nutrient transporters (Lsi1, CCaMK, MHX, SULT1 and ZIP1) and enzymes involved in the AsA-GSH cycle (APX, GR, DHAR and MDHAR). The overall results of this research indicate towards possible induction of a crosstalk between cytokinin and IAA upon Si supplementation which in turn stimulates physiological, biochemical and molecular changes to exhibit protective effects against Cr(VI) stress. Further, the information obtained suggests probable employment of Si, cytokinin and IAA alone or combined in agriculture to maintain plant productivity under Cr(VI) stress and data regarding expression of key genes can be used to develop new crop varieties with enhanced resistance against Cr(VI) stress together with its reduced load in seedlings.

Unlocking a 'lock-key' mechanism governing pollen-pistil interactions.

Pollen-pistil interactions ensure genetic diversity and shape the reproductive success of plants. Lan et al. recently revealed that the interaction among various receptor-like kinases, cell-wall proteins, and stigmatic RALF peptides (sRALFs) or pollen RALF peptides (pRALFs) on the stigma surface govern the penetration of pollen tubes in members of the Brassicaceae.

Understanding Knowledge and Attitude of Farmers towards Antibiotic Use and Antimicrobial Resistance in Jhunjhunu District, Rajasthan India.

The misuse of antibiotics in veterinary practices by farmers is harming livestock production and food safety and leading to the rise of antibiotic resistance (AMR). This can also transfer resistant bacteria from animals to humans, posing a serious public health threat. However, we have not paid enough attention to understanding how farmers behave in this regard. Our study aims to explore farmers' behaviors and identify the factors that influence their choices. To conduct this study, we used a questionnaire with 40 questions and surveyed 208 farmers in Jhunjhunu district, Rajasthan. We analyzed the data using SPSS. Here are the key findings: About 58.3% of the farmers have some awareness of antibiotics, and 49.5% are aware of antimicrobial resistance (AMR). Notably, as the level of education increases, so does awareness of antibiotics. Unfortunately, 63.9% of the farmers are not aware of the withdrawal time, and 64% have no idea about the presence of antibiotic residues during this period. Around 75% of farmers vaccinate their animals, but approximately 56.9% of individuals have never undergone an antibiotic sensitivity test (ABST) for milk. Around 48.6% of farmers are unaware of government testing centers. Several factors hinder farmers from implementing proper animal management practices, such as the high fees of veterinarians. When their animals become sick, their first choice is home remedies, followed by using old prescriptions. Additionally, 63.9% stop treatment once the animal looks better. A significant portion (83.8%) of farmers rely on local pharmacists for medicine. It has been determined that there is no significant correlation between education, experience, age, and the level of awareness concerning withdrawal periods, the existence of government antibiotic sensitivity test (ABST) centers, and entities responsible for sending samples for ABST. In our qualitative analysis, focus groups identified significant barriers to following best farm practices and spreading awareness about AMR. These findings suggest that addressing AMR in livestock requires a comprehensive approach. This should include targeted education and awareness programs for farmers, as well as improved access to veterinary services.

Integrated Agricultural Practices and Engineering Technologies Enhance Synergies of Food-Energy-Water Systems in Corn Belt Watersheds.

Interconnected food, energy, water systems (FEWS) require systems level understanding to design efficient and effective management strategies and policies that address potentially competing challenges of production and environmental quality. Adoption of agricultural best management practices (BMPs) can reduce nonpoint source phosphorus (P) loads, but there are also opportunities to recover P from point sources, which could also reduce demand for mineral P fertilizer derived from declining geologic reserves. Here, we apply the Integrated Technology-Environment-Economics Model to investigate the consequences of watershed-scale portfolios of agricultural BMPs and environmental and biological technologies (EBTs) for co-benefits of FEWS in Corn Belt watersheds. Via a pilot study with a representative agro-industrial watershed with high P and nitrogen discharge, we show achieving the nutrient reduction goals in the watershed; BMP-only portfolios require extensive and costly land-use change (19% of agricultural land) to perennial energy grasses, while portfolios combining BMPs and EBTs can improve water quality while recovering P from corn biorefineries and wastewater streams with only 4% agricultural land-use change. The potential amount of P recovered from EBTs is estimated as 2 times as much as the agronomic P requirement in the watershed, showing the promise of the P circular economy. These findings inform solution development based on the combination of agricultural BMPs and EBTs for the cobenefits of FEWS in Corn Belt watersheds.

Epigallocatechin Gallate (EGCG), an Active Phenolic Compound of Green Tea, Inhibits Tumor Growth of Head and Neck Cancer Cells by Targeting DNA Hypermethylation.

Head and neck cancers are among the deadliest cancers, ranked sixth globally in rates of high mortality and poor patient prognoses. The prevalence of head and neck squamous cell carcinoma (HNSCC) is associated with smoking and excessive alcohol consumption. Despite several advances in diagnostic and interventional methods, the morbidity of subjects with HNSCC has remained unchanged over the last 30 years. Epigenetic alterations, such as DNA hypermethylation, are commonly associated with several cancers, including HNSCC. Thus, epigenetic changes are considered promising therapeutic targets for chemoprevention. Here, we investigated the effect of EGCG on DNA hypermethylation and the growth of HNSCC. First, we assessed the expression levels of global DNA methylation in HNSCC cells (FaDu and SCC-1) and observed enhanced methylation levels compared with normal human bronchial epithelial cells (NHBE). Treatment of EGCG to HNSCC cells significantly inhibited global DNA hypermethylation by up to 70-80% after 6 days. Inhibition of DNA hypermethylation in HNSCC cells was confirmed by the conversion of 5-methylcytosine (5-mc) into 5-hydroxy methylcytosine (5hmC). DNA methyltransferases regulate DNA methylation. Next, we checked the effect of EGCG on the expression levels of DNA methyltransferases (DNMTs) and DNMT activity. Treatment of EGCG to HNSCC cells significantly reduced DNMT activity to 60% in SCC-1 and 80% in FaDu cells. The protein levels of DNMT3a and DNMT3b were downregulated in both cell lines after EGCG treatment. EGCG treatment to HNSCC cells reactivated tumor suppressors and caused decreased cell proliferation. Our in vivo study demonstrated that administration of EGCG (0.5%, w/w) as a supplement within an AIN76A diet resulted in inhibition of tumor growth in FaDu xenografts in nude mice (80%; p < 0.01) compared with non-EGCG-treated controls. The growth inhibitory effect of dietary EGCG on the HNSCC xenograft tumors was associated with the inhibition of DNMTs and reactivation of silenced tumor suppressors. Together, our study provides evidence that EGCG acts as a DNA demethylating agent and can reactivate epigenetically silenced tumor suppressors to inhibit the growth of HNSCC cells.

Development of gamma-tocotrienol as a radiation medical countermeasure for the acute radiation syndrome: current status and future perspectives.

INTRODUCTION: The possibility of exposure to high doses of total- or partial-body ionizing radiation at a high dose rate due to radiological/nuclear accidents or terrorist attacks is increasing. Despite research and development during the last six decades, there is a shortage of nontoxic, safe, and effective radiation medical countermeasures (MCMs) for radiological and nuclear emergencies. To date, the US Food and Drug Administration (US FDA) has approved only four agents for the mitigation of hematopoietic acute radiation syndrome (H-ARS). AREA COVERED: We present the current status of a promising radiation countermeasure, gamma-tocotrienol (GT3; a component of vitamin E) as a radiation MCM that has been investigated in murine and nonhuman primate models of H-ARS. There is significant work with this agent using various omic platforms during the last few years to identify its efficacy biomarkers. EXPERT OPINION: GT3 is a newer type of radioprotector having significant injury-countering potential and is currently under advanced development for H-ARS. As a pre-exposure drug, it requires only single doses, lacks significant toxicity, and has minimal, ambient temperature storage requirements; thus, GT3 appears to be an ideal MCM for military and first responders as well as for storage in the Strategic National Stockpile.

A Review of Radiation-Induced Alterations of Multi-Omic Profiles, Radiation Injury Biomarkers, and Countermeasures.

Increasing utilization of nuclear power enhances the risks associated with industrial accidents, occupational hazards, and the threat of nuclear terrorism. Exposure to ionizing radiation interferes with genomic stability and gene expression resulting in the disruption of normal metabolic processes in cells and organs by inducing complex biological responses. Exposure to high-dose radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, cerebrovascular, and many other organ-specific injuries. Altered genomic variations, gene expression, metabolite concentrations, and microbiota profiles in blood plasma or tissue samples reflect the whole-body radiation injuries. Hence, multi-omic profiles obtained from high-resolution omics platforms offer a holistic approach for identifying reliable biomarkers to predict the radiation injury of organs and tissues resulting from radiation exposures. In this review, we performed a literature search to systematically catalog the radiation-induced alterations from multi-omic studies and radiation countermeasures. We covered radiation-induced changes in the genomic, transcriptomic, proteomic, metabolomic, lipidomic, and microbiome profiles. Furthermore, we have covered promising multi-omic biomarkers, FDA-approved countermeasure drugs, and other radiation countermeasures that include radioprotectors and radiomitigators. This review presents an overview of radiation-induced alterations of multi-omics profiles and biomarkers, and associated radiation countermeasures.

Model for Evaluating Antimicrobial Therapy To Prevent Life-Threatening Bacterial Infections following Exposure to a Medically Significant Radiation Dose.

More evidence is needed to support recommendations for medical management of acute radiation syndrome (ARS) and associated infections resulting from a radiological/nuclear event. While current guidelines recommend the administration of antibiotics to chemotherapy patients with febrile neutropenia, the clinical benefit is unclear for acute radiation injury patients. A well-characterized nonhuman primate (NHP) model of hematopoietic ARS was developed that incorporates supportive care postirradiation. This model evaluated the efficacy of myeloid growth factors within 24 to 48 h after total body irradiation (TBI). However, in this model, NHPs continued to develop life-threatening bacterial infections, even when granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor was administered in combination with antibiotic monotherapy. In this study, we evaluated the efficacy of combination antibiotic therapies administered to NHPs following 7.4-Gy TBI to understand the occurrence of bacterial infection in NHPs with hematopoietic ARS. We compared enrofloxacin-linezolid, enrofloxacin-cefepime, and enrofloxacin-ertapenem to enrofloxacin monotherapy. The primary endpoint was 60-day postirradiation mortality, with secondary endpoints of overall survival time, incidence of bacterial infection, and bacteriologic culture with antimicrobial susceptibility testing. We observed that enrofloxacin-ertapenem significantly increased survival compared to enrofloxacin monotherapy. Bacteria isolated from nonsurviving macaques with systemic bacterial infections exhibited uniform resistance to enrofloxacin and variable resistance to beta-lactam antibiotics, linezolid, gentamicin, and azithromycin. Multidrug antibiotic resistance was observed in Enterococcus spp. and Escherichia coli. We conclude that antibiotic combination therapies appear to be more effective than monotherapy alone but acknowledge that more work is needed to identify an optimal antimicrobial therapy.

Silicon nanoforms in crop improvement and stress management.

Although, silicon - the second most abundant element in the earth crust could not supersede carbon (C) in the competition of being the building block of life during evolution, yet its presence has been reported in some life forms. In case of the plants, silicon has been reported widely to promote the plant growth under normal as well as stressful situations. Nanoform of silicon is now being explored for its potential to improve plant productivity and its tolerance against various stresses. Silicon nanoparticles (SiNPs) in the form of nanofertilizers, nanoherbicides, nanopesticides, nanosensors and targeted delivery systems, find great utilization in the field of agriculture. However, the mechanisms underlying their uptake by plants need to be deciphered in detail. Silicon nanoformss are reported to enhance plant growth, majorly by improving photosynthesis rate, elevating nutrient uptake and mitigating reactive oxygen species (ROS)-induced oxidative stress. Various studies have reported their ability to provide tolerance against a range of stresses by upregulating plant defense responses. Moreover, they are proclaimed not to have any detrimental impacts on environment yet. This review includes the up-to-date information in context of the eminent role of silicon nanoforms in crop improvement and stress management, supplemented with suggestions for future research in this field.

Mapping the National Phosphorus Recovery Potential from Centralized Wastewater and Corn Ethanol Infrastructure.

Anthropogenic discharge of excess phosphorus (P) to water bodies and increasingly stringent discharge limits have fostered interest in quantifying opportunities for P recovery and reuse. To date, geospatial estimates of P recovery potential in the United States (US) have used human and livestock population data, which do not capture the engineering constraints of P removal from centralized water resource recovery facilities (WRRFs) and corn ethanol biorefineries where P is concentrated in coproduct animal feeds. Here, renewable P (rP) estimates from plant-wide process models were used to create a geospatial inventory of recovery potential for centralized WRRFs and biorefineries, revealing that individual corn ethanol biorefineries can generate on average 3 orders of magnitude more rP than WRRFs per site, and all corn ethanol biorefineries can generate nearly double the total rP of WRRFs across the US. The Midwestern states that make up the Corn Belt have the largest potential for P recovery and reuse from both corn biorefineries and WRRFs with a high degree of co-location with agricultural P consumption, indicating the untapped potential for a circular P economy in this globally significant grain-producing region.

Phosphorus in soils and fluvial sediments from a Cerrado biome watershed under agricultural expansion.

Over the past decades, lands alongside Gurguéia River have witnessed rapid expansion of soybean agriculture which has increased soil degradation and affected nutrient concentration in sediment, especially phosphorus (P). The present study aimed to quantify the P concentration in soils under different land uses (i.e., croplands, grasslands, and cerrado) and fluvial sediments (suspended sediment, channel bank, and riverbed sediments), assessing pollution over the main watercourse in cerrado biome Gurguéia watershed, located in Piauí State, Brazil. In total, 136 composite soil samples at a depth of 0-5 cm, under different land uses, as well as 51 composite fluvial sediment samples were collected over the watershed. The land use change from native cerrado had resulted in an increase of total phosphorus (TP) whose concentration was higher in cropland areas, followed by suspended sediment, channel bank, and riverbed sediments. This high concentration in cropland areas resulted from phosphate fertilizer inputs. The transfer of phosphorus to water bodies was evidenced, since an increase of TP was observed in suspended sediment, channel bank and riverbed  sediments. Mineralogical signatures in sediments were identified by X-ray diffraction analysis which showed the occurrence of kaolinite, illite, smectite, iron oxides, and other minerals in lesser proportions. The presence of 1:1 minerals was higher in riverbed sediments and downstream sampling points, while 2:1 minerals were present in higher proportions in suspended sediment and channel bank sediment, as well as at the upstream and middle sampling points. This finding shows that land use change from cerrado to cropland due to soybean agriculture expansion might increase P discharges from terrestrial to aquatic environments, with sediments being the major carrier of this element.

Effect of Supplementation of Vitamin C and Thiamine on the Outcome in Sepsis: South East Asian Region.

INTRODUCTION: The global burden of sepsis is overwhelming and novel therapeutic agents is the need of the hour. The present study was designed to understand the role of Malondialdehyde as a marker of the oxidative stress in sepsis, as well as the effect of supplementation of Vitamin C and Thiamine in patients of sepsis. METHODS: 80 patients of sepsis were randomly divided into 4 groups of 20 each. Twenty age-sex matched healthy volunteers were chosen as controls. The first group received Vitamin C, the second group received Thiamine, the third group received both and the fourth group received neither. Vitamin C (2g 8 hourly) and Thiamine (200 mg 12 hourly) were given intravenously for five days. The outcome was recorded in terms of mortality in the various groups as well as by the improvement in SOFA scores (ΔSOFA). The serum levels of Vitamin C, Thiamine and Malondialdehyde were estimated. RESULTS: Among the 80 patients, 17 (21%) were in septic shock. The mortality rate was 10% overall, and 47% among patients of septic shock. No additional mortality benefit was observed in the groups supplemented with Vitamin C and Thiamine. However, the ΔSOFA score in patients who received both Vitamin C and Thiamine was significantly higher as compared to the other groups. The mean malondialdehyde level was higher in patients of sepsis (1.81±1.18 µmol/l) as compared with healthy controls (0.78 ± 0.36 µmol/l). The Vitamin C level and Thiamine level (estimated indirectly by TPP effect), at presentation were 5.14±4.19 ng/ml and 52.99±28.45 % in patients of sepsis, which was significantly lower than that in healthy controls, in whom the levels were 14.64±5.51 ng/ml and 27.55±13.67% respectively. CONCLUSION: Vitamin C and Thiamine supplementation is a cost-effective approach with a good safety profile. Additional studies including a larger population is required to study the mortality benefits and reaffirm our findings.

Application of zinc oxide nanoparticles as fertilizer boosts growth in rice plant and alleviates chromium stress by regulating genes involved in oxidative stress.

Chromium toxicity impairs the productivity of rice crops and raises a major concern worldwide and thus, it calls for unconventional and sustainable means of crop production. In this study, we identified the implication of zinc oxide nanoparticles (ZnO NPs) in promoting plant growth and ameliorating chromium-induced stress in seedlings of rice (Oryza sativa). This investigation demonstrates that the exogenous supplementation of ZnO NPs at 25 µM activates defense mechanisms conferring rice seedlings significant tolerance against stress imposed by the exposure of 100 µM Cr(VI). Further, supplementation of this nanofertilizer reversed the inhibitory effects of Cr(VI) on growth and photosynthetic efficiency. The growth promotion was primarily associated with the function of ZnO NPs in inducing activity of antioxidative enzymes i.e. APX, DHAR, MDHAR and GR belonging to the ascorbate-glutathione cycle in the Cr-exposed seedlings, exceeding the levels in control. The overexpression of these antioxidative genes correlated concomitantly with the decrease of oxidants including SOR and H2O2 and the increase in the levels of non-enzymatic antioxidants: AsA and GSH.

Synergistic action of silicon nanoparticles and indole acetic acid in alleviation of chromium (CrVI) toxicity in Oryza sativa seedlings.

The present study investigates ameliorative effect of silicon nanoparticles (SiNPs) and indole acetic acid (IAA) alone and in combination against hexavalent chromium (CrVI) toxicity in rice seedlings. The results of the study revealed protective effects of SiNPs and IAA against CrVI toxicity. The 100 µM of CrVI imposed toxic effects in rice seedlings at morphological, physiological and biochemical levels which coincided with increased level of intracellular CrVI and declined level of endogenous nitric oxide (NO). The CrVI enhanced levels of superoxide radicals (SOR) (59.51% and 50.1% in shoot and root, respectively) and H2O2 (19.5% and 23.69% in shoot and root, respectively). However, when SiNPs and IAA were applied to plants under CrVI stress, they enhanced tolerance and defence mechanisms as manifested in terms of increased biomass, endogenous NO, photosynthetic pigments, and antioxidants level. It was also noticed that CrVI arrested cell cycle at G2/M phase whereas growth was restored as compared to control when SiNPs and IAA were supplemented. Thus, the hypothesis that combined application of SiNPs and IAA will be effective in alleviating CrVI toxicity is validated from the results of this study. Moreover, in SiNPs and IAA-mediated mitigation of CrVI toxicity, endogenous NO has a positive role. The importance of the study will be that the combination of SiNPs and IAA can be utilized against heavy metal stress and even when supplied alone, they will enhance the crop productivity parameters with and without stress conditions.

Ethylene needs endogenous hydrogen sulfide for alleviating hexavalent chromium stress in Vigna mungo L. and Vigna radiata L.

Chromium toxicity to crops is a big scientific issue of the present time. Thus, continuous scientific attempts have been taken for reducing chromium toxicity in crop plants. In this study, we have tested potential of ethylene (ET) and hydrogen sulfide (H2S) in alleviating hexavalent chromium [(Cr(VI)] stress in two pulse crops i.e. black bean and mung bean. Cr(VI) declined growth (by 21 % and 27 % in black and mung bean, respectively) and also negatively affected photosynthesis in both pulse crops due to accumulation of Cr(VI) and cell death in roots. Under similar conditions, levels of reactive oxygen species (ROS) were enhanced but antioxidant defense system showed differential responses. The addition of AVG (an inhibitor of ethylene biosynthesis) and PAG (an inhibitor of H2S biosynthesis) with Cr(VI) further increased toxicity of Cr(VI) suggesting that endogenous H2S and ET are important for tolerating Cr(VI) toxicity. But supplementation of either ET or H2S alleviated Cr(VI) toxicity. Interestingly, ET did not rescue negative effects of PAG under Cr(VI) stress but NaHS rescued negative effect of AVG. Overall, results indicate that though both ET and H2S are able in alleviating Cr(VI) stress but endogenous H2S is crucial in ET-mediated mitigation of Cr(VI) stress. Furthermore, H2S appears to be a downstream signal of ET in alleviating Cr(VI) stress in two pulse crops.

Effect of Yoga on Blood Pressure in Prehypertension: A Systematic Review and Meta-Analysis.

INTRODUCTION: Prehypertension is a precursor for developing hypertension and is a risk factor for cardiovascular diseases. Yoga therapy may have a role in lowering the blood pressures in prehypertension and hypertension. This systematic review aims to synthesize the available literature for the same. Methodology. Databases such as PubMed, Embase, Scopus, and Web of Science were searched for randomised control trials only in the time duration of 2010-2021. The main outcome of interest was systolic and diastolic blood pressures. Articles were screened based on the inclusion criteria, and 8 articles were recruited for the review. Meta-analysis was done for suitable articles. RevMan 5.4 by Cochrane was used for meta-analysis and forest plot construction. Risk of bias was determined using the Downs and Black checklist by three independent authors. RESULTS: The meta-analysis of the articles favoured yoga intervention over the control intervention. Yoga therapy had significantly reduced the systolic pressure (-0.62 standard mean difference, at IV fixed 95% CI: -0.83, -0.41) and diastolic pressure (-0.81 standard mean difference, at IV random 95% CI: -1.39, -0.22). Secondary outcome measures studied were heart rate, weight, BMI, waist circumference, and lipid profile. The main protocol of yoga therapy included postures, breathing exercises, and different meditation techniques. A significant reduction in secondary outcomes was observed, except for HDL values in lipid profile which showed a gradual increase in yoga group in comparison with alternative therapy. CONCLUSION: Yoga therapy has shown to be significant in the reduction of systolic and diastolic pressure in prehypertensive population. Supporting evidence lacks in providing a proper structured dosage of yoga asanas and breathing techniques. Considering the existing literature and evidence, Yoga therapy can be used and recommended in prehypertensive population and can be beneficial in reducing the chances of developing hypertension or cardiovascular diseases.

Endogenous indole-3-acetic acid and nitric oxide are required for calcium-mediated alleviation of copper oxide nanoparticles toxicity in wheat seedlings.

The action of nanoparticles is increasingly being studied in recent years to minimize their toxic impacts. Besides this, efforts are also being made to minimize their toxicity in crop plants by using various chemicals, i.e. nutrients, donors of signaling molecules, plant hormones, and so on. However, associated alleviatory mechanisms are still not well known. Therefore, in the present study, we have investigated the toxicity of CuONPs and its mitigation by exogenously applied calcium (Ca). The focus was on whether indole-3-acetic acid (IAA) or endogenous nitric oxide (NO) has any role in accomplishing this task. CuONPs declined wheat growth due to increased accumulation of Cu and oxidative stress markers such as superoxide radicals, hydrogen peroxide, and lipid peroxidation (malondialdehyde) and it was also accompanied by a decline in endogenous NO. CuONPs also altered the redox status of ascorbate and glutathione by inhibiting the activity of their regenerating enzymes. This collectively leads to cell death in wheat seedlings. However, exogenous supplementation of Ca mitigated toxic effects of CuONPs by reducing the excess accumulation of Cu, which caused remarkable enhancement in growth, protein contents, photosynthetic pigments, and endogenous NO; altogether protecting wheat roots from cell death. Interestingly, addition of 2,3,5-triiodobenzoic acid (TIBA) further increased CuONPs toxicity even in the presence of Ca, but the addition of IAA rescued this effect of TIBA. These results clearly show that Ca mitigates CuONPs toxicity in wheat seedlings by involving IAA. Further, the results also showed that endogenous NO has a positive and indispensable role in Ca-mediated mitigation of CuONPs toxicity in wheat seedlings.

Histochemical Techniques in Plant Science: More Than Meets the Eye.

Histochemistry is an essential analytical tool interfacing extensively with plant science. The literature is indeed constellated with examples showing its use to decipher specific physiological and developmental processes, as well as to study plant cell structures. Plant cell structures are translucent unless they are stained. Histochemistry allows the identification and localization, at the cellular level, of biomolecules and organelles in different types of cells and tissues, based on the use of specific staining reactions and imaging. Histochemical techniques are also widely used for the in vivo localization of promoters in specific tissues, as well as to identify specific cell wall components such as lignin and polysaccharides. Histochemistry also enables the study of plant reactions to environmental constraints, e.g. the production of reactive oxygen species (ROS) can be traced by applying histochemical staining techniques. The possibility of detecting ROS and localizing them at the cellular level is vital in establishing the mechanisms involved in the sensitivity and tolerance to different stress conditions in plants. This review comprehensively highlights the additional value of histochemistry as a complementary technique to high-throughput approaches for the study of the plant response to environmental constraints. Moreover, here we have provided an extensive survey of the available plant histochemical staining methods used for the localization of metals, minerals, secondary metabolites, cell wall components, and the detection of ROS production in plant cells. The use of recent technological advances like CRISPR/Cas9-based genome-editing for histological application is also addressed. This review also surveys the available literature data on histochemical techniques used to study the response of plants to abiotic stresses and to identify the effects at the tissue and cell levels.

Adhatoda vasica rescues the hypoxia-dependent severe asthma symptoms and mitochondrial dysfunction.

Severe asthma is a chronic airway disease that exhibits poor response to conventional asthma therapies. Growing evidence suggests that elevated hypoxia increases the severity of asthmatic inflammation among patients and in model systems. In this study, we elucidate the therapeutic effects and mechanistic basis of Adhatoda vasica (AV) aqueous extract on mouse models of acute allergic as well as severe asthma subtypes at physiological, histopathological, and molecular levels. Oral administration of AV extract attenuates the increased airway resistance and inflammation in acute allergic asthmatic mice and alleviates the molecular signatures of steroid (dexamethasone) resistance like IL-17A, KC (murine IL-8 homologue), and HIF-1α (hypoxia-inducible factor-1α) in severe asthmatic mice. AV inhibits HIF-1α levels through restoration of expression of its negative regulator-PHD2 (prolyl hydroxylase domain-2). Alleviation of hypoxic response mediated by AV is further confirmed in the acute and severe asthma model. AV reverses cellular hypoxia-induced mitochondrial dysfunction in human bronchial epithelial cells-evident from bioenergetic profiles and morphological analysis of mitochondria. In silico docking of AV constituents reveal higher negative binding affinity for C and O-glycosides for HIF-1α, IL-6, Janus kinase 1/3, TNF-α, and TGF-ß-key players of hypoxia inflammation. This study for the first time provides a molecular basis of action and effect of AV whole extract that is widely used in Ayurveda practice for diverse respiratory ailments. Further, through its effect on hypoxia-induced mitochondrial dysfunction, the study highlights its potential to treat severe steroid-resistant asthma.