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Byline: Vishal. Tandon, B. Kapoor, G. Bano, S. Gupta, Z. Gillani, S. Gupta, D. Kour P-glycoprotein (P-gp) is a 170 kDa membrane-bound protein, an energy-dependent efflux transporter driven by ATP [...]

In the past few decades, the pressure of higher food production to satisfy the demand of ever rising population has inevitably increased the use synthetic agrochemicals which have deterioration effects. Biostimulants containing beneficial microbes (single inoculants and microbial consortium) were found as an ideal substitute of synthetic chemical fertilizers. In recent years, microbial consortium is known as a better bioinoculant in comparison to single inoculant bioformulation because of multifarious plant growth-promoting advantages. Looking at the advantageous effect of consortium, in present investigation, different bacteria were isolated from rhizospheric soil and plant samples collected from the Himalayan mountains on the green slopes of the Shivaliks, Himachal Pradesh. The isolated bacteria were screened for nitrogen (N) fixation, phosphorus (P) solubilization and potassium (K) solubilization plant growth promoting attributes, and efficient strains were identified through 16S rRNA gene sequencing and BLASTn analysis. The bacteria showing a positive effect in NPK uptake were developed as bacterial consortium for the growth promotion of eggplant crop. A total of 188 rhizospheric and endophytic bacteria were sorted out, among which 13 were exhibiting nitrogenase activity, whereas 43 and 31 were exhibiting P and K solubilization traits, respectively. The selected three efficient and potential bacterial strains were identified using 16S rRNA gene sequencing as Enterobacter ludwigii EU-BEN-22 (N-fixer; 35.68 ± 00.9 nmol C 2 H 4 per mg protein per h), Micrococcus indicus EU-BRP-6 (P-solubilizer; 201 ± 0.004 mg/L), and Pseudomonas gessardii EU-BRK-55 (K-solubilizer; 51.3 ± 1.7 mg/mL), and they were used to develop a bacterial consortium. The bacterial consortium evaluation on eggplant resulted in the improvement of growth (root/shoot length and biomass) and physiological parameters (chlorophyll, carotenoids, total soluble sugar, and phenolic content) of the plants with respect to single culture inoculation, chemical fertilizer, and untreated control. A bacterial consortium having potential to promote plant growth could be used as bioinoculant for horticulture crops growing in hilly regions., (© 2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Over recent years, the scientific community has acknowledged the crucial role of certain microbial strains inhabiting the intestinal ecosystem in promoting human health, and participating in various beneficial functions for the host. These microorganisms are now referred to as next-generation probiotics and are currently considered as biotherapeutic products and food or nutraceutical supplements. However, the majority of next-generation probiotic candidates pose nutritional demands and exhibit high sensitivity towards aerobic conditions, leading to numerous technological hurdles in large-scale production. This underscores the need for the development of suitable delivery systems capable of enhancing the viability and functionality of these probiotic strains. Currently, potential candidates for next generation probiotics (NGP) are being sought among gut bacteria linked to health, which include strains from the genera Bacteroids, Faecalibacterium , Akkermansia and Clostridium . In contrast to Lactobacillus spp. and Bifidobacterium spp., NGP, particularly Bacteroids spp. and Clostridium spp., appear to exhibit greater ambiguity regarding their potential to induce infectious diseases. The present review provides a comprehensive overview of NGPs in terms of their health beneficial effects, regulation framework and risk assessment targeting relevant criteria for commercialization in food and pharmaceutical markets., Competing Interests: The authors declare that they have no known competing financialinterestsor personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

A new area of biotechnology is nanotechnology. Nanotechnology is an emerging field that aims to develope various substances with nano-dimensions that have utilization in the various sectors of pharmaceuticals, bio prospecting, human activities and biomedical applications. An essential stage in the development of nanotechnology is the creation of nanoparticles. To increase their biological uses, eco-friendly material synthesis processes are becoming increasingly important. Recent years have shown a lot of interest in nanostructured materials due to their beneficial and unique characteristics compared to their polycrystalline counterparts. The fascinating performance of nanomaterials in electronics, optics, and photonics has generated a lot of interest. An eco-friendly approach of creating nanoparticles has emerged in order to get around the drawbacks of conventional techniques. Today, a wide range of nanoparticles have been created by employing various microbes, and their potential in numerous cutting-edge technological fields have been investigated. These particles have well-defined chemical compositions, sizes, and morphologies. The green production of nanoparticles mostly uses plants and microbes. Hence, the use of microbial nanotechnology in agriculture and plant science is the main emphasis of this review. The present review highlights the methods of biological synthesis of nanoparticles available with a major focus on microbially synthesized nanoparticles, parameters and biochemistry involved. Further, it takes into account the genetic engineering and synthetic biology involved in microbial nanobiosynthesis to the construction of microbial nanofactories., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Microbes are a worthwhile organism of the earth that could be formulated as consortium which can be utilized as biofertilizers. Consortium-based bioinoculants or biofertilizers are superior to single strain-based inoculants for sustainable agricultural productivity and increased micronutrient content in yield. The aim of present study was to evaluate the effect of different combinations of beneficial bacteria that are more effective than single-based bioinoculants. The current work focuses on the isolation of rhizospheric microorganisms from various cereals and pseudocereal crops and the development of a single inoculum as well as a bacterial consortium which were evaluated on wheat crop. A total 214 rhizospheric bacteria were sorted out and, screened for mineral solubilizing attributes i.e., phosphorus, potassium, zinc and selenium solubilization. Among all the bacterial isolates, four potential strains exhibiting P, K, Zn and Se-solubilizing attributes were identified with the help of 16S rRNA gene sequencing as Rahnella aquatilis EU-A3Rb1, Erwinia aphidicola EU-A2RNL1, Brevibacillus brevis EU-C3SK2, and Bacillus mycoides EU-WRSe4, respectively. The identified strains formulated as a consortium which were found to improve the plant growth and physiological parameters in comparison to single culture inoculants and control. To the best of our knowledge, the present investigation is the first report that has developed the consortium from bacterial strains Rahnella aquatilis EU-A3Rb1, Erwinia aphidicola EU-A2RNL1, Brevibacillus brevis EU-C3SK2, and Bacillus mycoides EU-WRSe4. A combination of bacterial strains could be used as liquid inoculants for cereal crops growing in mountainous regions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

In the present scenario, growing population demands more food, resulting in the need for sustainable agriculture. Numerous approaches are explored in response to dangers and obstacles to sustainable agriculture. A viable approach is to be exploiting microbial consortium, which generate diverse biostimulants with growth-promoting characteristics for plants. These bioinoculants play an indispensable role in optimizing nutrient uptake efficiency mitigating environmental stress. Plant productivity is mostly determined by the microbial associations that exist at the rhizospheric region of plants. The engineered consortium with multifunctional attributes can be effectively employed to improve crop growth efficacy. A number of approaches have been employed to identify the efficient consortia for plant growth and enhanced crop productivity. Various plant growth-promoting (PGP) microbes with host growth-supporting characteristics were investigated to see if they might work cohesively and provide a cumulative effect for improved growth and crop yield. The effective microbial consortia should be assessed using compatibility tests, pot experimentation techniques, generation time, a novel and quick plant bioassay, and sensitivity to external stimuli (temperature, pH). The mixture of two or more microbial strains found in the root microbiome stimulates plant growth and development. The present review deals with mechanism, formulation, inoculation process, commercialization, and applications of microbial consortia as plant bioinoculants for agricultural sustainability., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The field of nanotechnology has the mysterious capacity to reform every subject it touches. Nanotechnology advancements have already altered a variety of scientific and industrial fields. Nanoparticles (NPs) with sizes ranging from 1 to 100 nm (nm) are of great scientific and commercial interest. Their functions and characteristics differ significantly from those of bulk metal. Commercial quantities of NPs are synthesized using chemical or physical methods. The use of the physical and chemical approaches remained popular for many years; however, the recognition of their hazardous effects on human well-being and conditions influenced serious world perspectives for the researchers. There is a growing need in this field for simple, non-toxic, clean, and environmentally safe nanoparticle production methods to reduce environmental impact and waste and increase energy productivity. Microbial nanotechnology is relatively a new field. Using various microorganisms, a wide range of nanoparticles with well-defined chemical composition, morphology, and size have been synthesized, and their applications in a wide range of cutting-edge technological areas have been investigated. Green synthesis of the nanoparticles is cost-efficient and requires low maintenance. The present review highlights the synthesis of the nanoparticles by different microbes, their characterization, and their biotechnological potential. It further deals with the applications in biomedical, food, and textile industries as well as its role in biosensing, waste recycling, and biofuel production., (© 2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Crocetin is a promising phyto-based molecule to treat Alzheimer's disease (AD). The chemical structure of crocetin is incongruent with various standard structural features of CNS drugs. As poor pharmacokinetic behavior is the major hurdle for any candidate to become a drug, we elucidated its druggable characteristics by implementing in silico, in vitro, and in vivo approaches, as limited ADME/PK information is available. Results demonstrate several attributes of crocetin based on rules of drug-likeness, lipophilicity, p K a , P-gp inhibitory activity, plasma stability, RBC partitioning, metabolic stability, CYP inhibitory action, blood-brain barrier (BBB) permeability, oral bioavailability, and pharmacokinetic interaction with marketed anti-Alzheimer's drugs (memantine, donepezil, galantamine, and rivastigmine). However, aqueous solubility, chemical stability, plasma protein binding, and P-gp induction are some concerns associated with this molecule that should be taken into consideration during its further development. Overall results indicate favorable ADME/PK behavior and potential druggable candidature of crocetin., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

EIDD-1931 is the active form of molnupiravir, an orally effective drug approved by the United States Food and Drug Administration (USFDA) against COVID-19. Pharmacokinetic alteration can cause untoward drug interaction (drug-drug/disease-drug), but hardly any information is known about this recently approved drug. Therefore, we first investigated the impact of the arthritis state on the oral pharmacokinetics of EIDD-1931 using a widely accepted complete Freund's adjuvant (CFA)-induced rat model of rheumatoid arthritis (RA) after ascertaining the disease occurrence by paw swelling measurement and X-ray examination. Comparative oral pharmacokinetic assessment of EIDD-1931 (normal state vs arthritis state) showed that overall plasma exposure was augmented (1.7-fold) with reduced clearance (0.54-fold), suggesting its likelihood of dose adjustment in arthritis conditions. In order to elucidate the effect of EIDD-1931 treatment at a therapeutic regime (normal state vs arthritis state) on USFDA-recommended panel of cytochrome P450 (CYP) enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) for drug interaction using the same disease model, we monitored protein and mRNA expressions (rat homologs) in liver tissue by western blotting (WB) and real time-polymerase chain reaction (RT-PCR), respectively. Results reveal that EIDD-1931 treatment could strongly influence CYP3A4 and CYP2C8 among experimental proteins/mRNAs. Although CYP2C8 regulation upon EIDD-1931 treatment resembles similar behavior under the arthritis state, results dictate a potentially reverse phenomenon for CYP3A4. Moreover, the lack of any CYP inhibitory effect by EIDD-1931 in human/rat liver microsomes (HLM/RLM) helps to ascertain EIDD-1931 treatment-mediated disease-drug interaction and the possibility of drug-drug interaction with disease-modifying antirheumatic drugs (DMARDs) upon coadministration. As elevated proinflammatory cytokine levels are prevalent in RA and nuclear factor-kappa B (NF-kB) and nuclear receptors control CYP expressions, further studies should focus on understanding the regulation of affected CYPs to subside unexpected drug interaction., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Endophytic microbes are plant-associated microorganisms that reside in the interior tissue of plants without causing damage to the host plant. Endophytic microbes can boost the availability of nutrient for plant by using a variety of mechanisms such as fixing nitrogen, solubilizing phosphorus, potassium, and zinc, and producing siderophores, ammonia, hydrogen cyanide, and phytohormones that help plant for growth and protection against various abiotic and biotic stresses. The microbial endophytes have attained the mechanism of producing various hydrolytic enzymes such as cellulase, pectinase, xylanase, amylase, gelatinase, and bioactive compounds for plant growth promotion and protection. The efficient plant growth promoting endophytic microbes could be used as an alternative of chemical fertilizers for agro-environmental sustainability. Endophytic microbes belong to different phyla including Euryarchaeota, Ascomycota, Basidiomycota, Mucoromycota, Firmicutes, Proteobacteria, and Actinobacteria. The most pre-dominant group of bacteria belongs to Proteobacteria including α-, β-, γ-, and δ-Proteobacteria. The least diversity of the endophytic microbes have been revealed from Bacteroidetes, Deinococcus-Thermus, and Acidobacteria. Among reported genera, Achromobacter, Burkholderia, Bacillus, Enterobacter, Herbaspirillum, Pseudomonas, Pantoea, Rhizobium, and Streptomyces were dominant in most host plants. The present review deals with plant endophytic diversity, mechanisms of plant growth promotion, protection, and their role for agro-environmental sustainability. In the future, application of endophytic microbes have potential role in enhancement of crop productivity and maintaining the soil health in sustainable manner., (© 2023. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Koenimbine (1), a carbazole alkaloid isolated from Murraya koenigii, belongs to the Rutaceae family. Various pharmacological effects such as anti-diabetic, melanogenesis inhibition, anti-diarrheal, anti-cancer, and anti-inflammatory properties of koenimbine have already been reported. In the current study, we investigated the anti-inflammatory role of koenimbine (1) and its novel semi-synthetic derivative 8-methoxy-3,3,5-trimethylpyrano[3,2-a] carbazole-11(3H)-yl) (3-(trifluoromethyl) phenyl) methanone (1G) in both in vitro and in vivo biological systems. Our results demonstrated that the anti-inflammatory activity of 1G significantly lowered the production of NO, pro-inflammatory cytokines (IL-6, TNF-α & IL-1β), LTB4 following LPS stimulation in RAW 264.7 macrophages. Furthermore, 1G significantly attenuated the expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose dependent manner and also decreased the production of reactive oxygen species (ROS) in LPS-activated RAW 264.7 cells. In addition, the oral administration of 1G reduced the inflammatory response in carrageenan-induced paw edema in BALB/C mice. Moreover, it effectively reduced NO, IL-6, IL-1β & TNF-α levels, liver markers (AST, ALT), and kidney markers (BUN, CRE, and Urea). Also, 1G reverted the infiltration of inflammatory cells and tissue damage in lungs, liver and kidney enhanced the survival rate in LPS-challenged mice. 1G blocks NF-κB p65 from translocating into the nucleus and activating inflammatory gene transcription. These results illustrated that 1G suppresses the inflammatory effects both in-vitro and in-vivo studies via downregulating the nuclear factor kappa-B (NF-κB) signaling pathway. In conclusion, our results demonstrate that semi-synthetic derivative 1G can effectively attenuate the inflammatory response via NF-κB and MAPK signaling pathways; suggesting 1G is a potential novel anti-inflammatory drug candidate in treating inflammatory disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Sickle cell disease (SCD) is a rare inherited disorder in which red blood cells (RBCs) under oxidative stress have altered sickle shape resulting in clinical complications. In this study, a library of pure natural products were screened to see their effectiveness in preventing sickling induced in blood samples of SCA patients , ex-vivo . The results indicated that baicalin ( 1 ) and naringenin ( 2 ), reduced sickling by 46.03 and 37.48 percent, respectively, compared to positive control, 4-hydroxybenzoic acid (4-HBA), which inhibited RBC sickling by 56.87 percent. As a result of this screening, two compounds, baicalin ( 1 ) and naringenin ( 2 ), have been identified as potent sickling inhibitors. Study has clearly shown promising role of flavonoids for the management of SCD crisis for that not effective therapy is available. These phytochemicals or plant extracts can be explored further as an alternative anti-sickling remedy, owing to their high efficacy in the management of SCD crisis.

Acute respiratory distress syndrome (ARDS) is a critical form of acute lung injury (ALI). Here, we investigated the effect of a defined combination of ten pure phytochemicals in equal proportions of weight (NPM) from plants, recommended by Ayurveda for any protective action against lipopolysaccharide (LPS)-induced ALI. Results indicate that NPM markedly improved protein and neutrophil contents, myeloperoxidase and hydroxyproline levels, oxidative stress markers (glutathione and malonaldehyde), inflammatory cytokines, and genes (IL-6, TNF-α, TGF-β, and NF-κB/IκBα) in BALF/lung tissue. The histopathological examination of the lung revealed the shielding effect of NPM against ALI. NPM exhibited a protective effect on the lung by reducing oxidative stress and inhibiting inflammation. A substantial drop in favipiravir's oral exposure was observed in ALI-state compared to normal-state, but oral exposure upon NPM treatment in ALI-state followed similar behaviour of favipiravir alike normal-state without NPM treatment. Overall, results offer potential insight into Ayurvedic recommendations for immunity boosting during ALI situations.

Cold stress leads to the disruption of the cellular homeostasis in plants and generation of reactive oxygen species (ROS) and productivity losses. In the present study, 94 psychrotrophic phosphorus-solubilizing bacteria with multiple plant growth-promoting (PGP) capabilities were isolated from rhizosphere of wheat. The most efficient strain EU-KL94 showing highest amount of solubilized phosphorus and maximum number of PGP attributes was identified using 16S rRNA sequencing as Ochrobactrum thiophenivorans. Ochrobactrum thiophenivorans EU-KL94 along with recommended doses of the chemical fertilizers as controls were used for alleviation of cold stress in oats. The strain improved the root and shoot length, dry and fresh weight, proline, glycine betaine, chlorophyll content as well as the superoxide dismutase (SOD) and glutathione reductase (GR) activities of oats under cold stress conditions. Ochrobactrum thiophenivorans with all promising plant growth activities under cold stress could be used as an environmental friendly strategy for mitigation of low temperature stress. To the best of our knowledge, Ochrobactrum thiophenivorans has been reported for the first time as P-solubilizer and as bioinoculants in oats for cold stress mitigation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The use of adjuvant therapy is an attractive approach to manage sickle cell disease (SCD) symptomatically. The present study aimed to investigate the potential of ellagic acid as an adjuvant therapy with hydroxyurea (HU), a key drug for SCD with myelosuppressive toxic effects. A panel of experiments was performed using SCD patient's blood (ex vivo) and transgenic mice model of SCD (in vivo). Ellagic acid exhibited the following beneficial pharmacological actions: (a) potent anti-sickling, polymerization inhibitory, and inherent non-hemolytic activity; (b) pronounced action to abrogate HU-induced neutropenia and to improve key hematological parameters during SCD (RBC, Hb, platelet levels); (c) considerable action to foster vascular tone (L-proline); (d) marked attenuating effect against oxidative stress (nitrotyrosine, hypoxanthine, MDA, GSH); (e) substantial inhibitory role against inflammation (analgesic activity and regulation of hemin, TNF-α, IL-1β, NF-κB/IκBα); (f) remarkable outcome of declining vaso-occlusive crisis (P-selectin, ERK1/2); (g) notable shielding deed against elevated biochemical marker for organ toxicity (creatinine); (h) noticeably prevented histopathological alterations of the spleen. Additionally, the pharmacokinetic study results of HU in the presence and absence of ellagic acid using a mouse model demonstrate that ellagic acid could be safely co-administered with HU. Overall findings suggest that ellagic acid is a promising candidate for adjuvant therapy in SCD based on its own significant ability against SCD and potentiating capability of HU action via targeting improvement at the various stages of pathophysiological complications during SCD and minimizing HU-induced toxicological manifestations., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Diclofenac is a widely prescribed anti-inflammatory drug having cardiovascular complications as one of the main liabilities that restrict its therapeutic use. We aimed to investigate for any role of rutin against diclofenac-induced cardiac injury with underlying mechanisms as there is no such precedent to date. The effect of rutin (10 and 20 mg/kg) was evaluated upon concomitant oral administration for fifteen days with diclofenac (10 mg/kg). Rutin significantly attenuated diclofenac-induced alterations in the serum cardiac markers (LDH, CK-MB, and SGOT), serum cytokine levels (TNF-α and IL-6), and oxidative stress markers (MDA and GSH) in the cardiac tissue. Histopathological examination and Scanning Electron Microscopy (SEM) findings displayed a marked effect of rutin to prevent diclofenac-mediated cardiac injury. Altered protein expression of myocardial injury markers (cTnT, FABP3, and ANP) and apoptotic markers (Bcl-2 and Caspase-3) in the cardiac tissue upon diclofenac treatment was considerably shielded by rutin treatment. MYL3 was unaffected due to diclofenac or rutin treatment. Rutin also significantly improved diclofenac-induced gastrointestinal and hepatic alterations based on the observed ameliorative effects in key mediators, oxidative stress markers, histopathology examination, and SEM findings. Overall results suggest that rutin can protect the diclofenac-induced cardiac injury by lowering oxidative stress, inhibiting inflammation, and reducing apoptosis. Further research work directs toward the development of phytotherapeutics for cardioprotection.

Sickle cell disease (SCD) is accompanied by several complications, which emanate from the sickling of erythrocytes due to a point mutation in the β -globin chain of hemoglobin. Sickled erythrocytes are unable to move smoothly through small blood capillaries and therefore, cause vaso occlusion and severe pain. Apart from pain, continuous lysis of fragile sickled erythrocytes leads to the release of heme, which is a strong activator of the NLRP3 inflammasome, thus producing chronic inflammation in sickle cell disease. In this study, we identified flurbiprofen among other COX-2 inhibitors to be a potent inhibitor of heme-induced NLRP3 inflammasome. We found that apart from being a nociceptive agent, flurbiprofen exerts a strong anti-inflammatory effect by suppressing NF-κB signaling, which was evidenced by reduced levels of TNF- α and IL-6 in wild-type and sickle cell disease Berkeley mice models. Our data further demonstrated the protective effect of flurbiprofen on liver, lungs, and spleen in Berkeley mice. The current sickle cell disease pain management regime relies mainly on opiate drugs, which is accompanied by several side effects without modifying the sickle cell disease-related pathology. Considering the potent role of flurbiprofen in inhibiting NLRP3 inflammasome and other inflammatory cytokines in sickle cell disease, our data suggests that it can be explored further for better sickle cell disease pain management along with the possibility of disease modification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kour, Ali, Khajuria, Sharma, Ghosh, Kaur, Mahajan, Ramajayan, Bharate, Bhardwaj, Sawant, Reddy and Kumar.)

The quest for increasing agricultural yield due to increasing population pressure and demands for healthy food has inevitably led to the indiscriminate use of chemical fertilizers. On the contrary, the exposure of the crops to abiotic stress and biotic stress interferes with crop growth further hindering the productivity. Sustainable agricultural practices are of major importance to enhance production and feed the rising population. The use of plant growth promoting (PGP) rhizospheric microbes is emerging as an efficient approach to ameliorate global dependence on chemicals, improve stress tolerance of plants, boost up growth and ensure food security. Rhizosphere associated microbiomes promote the growth by enhancing the uptake of the nutrients, producing plant growth regulators, iron chelating complexes, shaping the root system under stress conditions and decreasing the levels of inhibitory ethylene concentrations and protecting plants from oxidative stress. Plant growth-promoting rhizospheric microbes belong to diverse range of genera including Acinetobacter, Achromobacter, Aspergillus, Bacillus, Burkholderia, Flavobacterium, Klebsiella, Micrococcus, Penicillium, Pseudomonas, Serratia and Trichoderma. Plant growth promoting microbes are an interesting aspect of research for scientific community and a number of formulations of beneficial microbes are also commercially available. Thus, recent progress in our understanding on rhizospheric microbiomes along with their major roles and mechanisms of action under natural and stressful conditions should facilitate their application as a reliable component in the management of sustainable agricultural system. This review highlights the diversity of plant growth promoting rhizospheric microbes, their mechanisms of plant growth promotion, their role under biotic and abiotic stress and status of biofertilizers. The article further focuses on the role of omics approaches in plant growth promoting rhizospheric microbes and draft genome of PGP microbes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Globally, man-made agrochemicals plays crucial role in plant growth promotion and boost crop yield. The agrochemicals overuse leaves the detrimental damage on the environment and humans. Biostimulants developed from single or multiple microbes (archaea, bacteria, and fungi) could be the appropriate alternative of agrochemical which sustains the agriculture as well as environment. In the present investigation, 93 beneficial bacteria associated with rhizospheric and endophytic region were isolated using diverse growth media. The isolated bacteria were screened for macronutrients availing traits including dinitrogen fixation, phosphorus and potassium solubilization. The bacterial consortium was developed using selected bacteria with multifunctional attributes and evaluated for the growth promotion of finger millet crop. Three potent NPK strains were identified as Erwinia rhapontici EU-FMEN-9 (N-fixer), Paenibacillus tylopili EU-FMRP-14 (P-solubilizer) and Serratia marcescens EU-FMRK-41 (K-solubilizer) using 16S rRNA gene sequencing and BLAST analysis. The developed bacterial consortium inoculation on finger millet resulted in the improvement of growth and physiological parameters with respect to chemical fertilizer and control. The compatible mixture of bacteria was found to have more ability to increase the growth of finger millet and it might be utilized as biostimulants for nutri-cereal crops growing in hilly regions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Low-temperature stress can seriously impair plant physiology. Chilling injury leads to a complex array of cellular dysfunctions, and symptoms include chlorosis, sterility, loss of vigor, wilting, and even death of the plants. Furthermore, phosphorus limitations additionally halt the growth of plants. Low-temperature adaptive plant growth-promoting microbes through various direct and indirect mechanisms help in the survival of plants under stress conditions. The present investigation deals with isolation of P-solubilizing psychrotrophic bacteria from diverse cultivars of wheat grown in the Keylong region of Himachal Pradesh. A total of 33 P-solubilizing bacterial isolates were obtained. P-solubilizers were screened for different plant growth-promoting (PGP) attributes of K and Zn solubilization, production of IAA, siderophores, and different hydrolytic enzymes. Among 33 P-solubilizers, 8 efficient strains exhibiting multiple PGP attributes were used as bioinoculants for wheat under low-temperature stress in different in vitro and in vivo experiments. The psychrotrophic bacterial isolates positively influenced the growth and physiological parameters as well as nutrient uptake and yield of wheat and efficiently alleviated low-temperature stress. The potential of low-temperature stress adaptive and PGP microbes can be utilized in agricultural sector for amelioration of low-temperature stress and plant growth promotion. The present study deals with the isolation of psychrotrophic P-solubilizers with multiple PGP attributes and their role in alleviation of cold stress in wheat., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Bedaquiline (BDQ) is a new class of anti-tubercular (anti-TB) drugs and is currently reserved for multiple drug resistance (MDR-TB). However, after receiving fast-track approval, its clinical studies demonstrate that its treatment is associated with hepatotoxicity and labeled as 'boxed warning' by the USFDA. No data is available on BDQ to understand the mechanism for drug-induced liver injury (DILI), a severe concern for therapeutic failure/unbearable tolerated toxicities leading to drug resistance. Therefore, we performed mechanistic studies to decipher the potential of BDQ at three dose levels (80 to 320 mg/kg) upon the repeated dose administration orally using a widely used mice model for TB. Results of BDQ treatment at the highest dose level showed that substantial increase of hepatic marker enzymes (SGPT and SGOT) in serum, oxidative stress marker levels (MDA and GSH) in hepatic tissue, and pro-inflammatory cytokine levels (TNF-α, IL-6, and IL-1β) in serum compared to control animals. Induction of liver injury situation was further evaluated by Western blotting for various protein expressions linked to oxidative stress (SOD, Nrf2, and Keap1), inflammation (NF-ĸB and IKKβ), apoptosis (BAX, Bcl-2, and Caspase-3) and drug metabolism enzymes (CYP3A4 and CYP2E1). The elevated plasma level of BDQ and its metabolite (N-desmethyl BDQ) were observed, corresponding to BDQ doses. Histopathological examination and SEM analysis of the liver tissue corroborate the above-mentioned findings. Overall results suggest that BDQ treatment-associated generation of its cytotoxic metabolite could act on CYP2E1/NF-kB pathway to aggravate the condition of oxidative stress, inflammation, and apoptosis in the liver and precipitating hepatotoxicity., Competing Interests: Declaration of competing interest The authors have no potential conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Microbes play crucial functions in maintaining the health and growth of the plants directly or indirectly by supplying nutrients. These microbes could be used as biofertilizers for the enhancement of soil health and growth of crops. In preset investigation, potential microbes from endophytic and rhizospheric region of Aegilops kotschyi growing in green slopes of Shivaliks, Himachal Pradesh were sorted out and screened for plant growth promoting attributes including phosphorus and potassium solubilization. The potential bacterial strains were identified through 16S rRNA gene sequencing and developed as microbial consortium for the plant growth of wheat and wild wheat relative Aegilops kotschyi . A total 125 isolates of bacteria were sorted out and among them 36 were found as P-solubilizers and 19 showed K-solubilization attribute and two highly potential bacterial strain were identified as Bacillus tropicus EU-ARP-44 (P-solubilizer; 270.5 ± 0.00 mg L -1 ) and B. megaterium EU-ARK-23 (K-Solubilizer; 51.3 ± 1.7 mg mL -1 ). The microbial consortium of Rahnella sp. strain EU-A3SNfb (N-fixer; MN294545), B. tropicus EU-ARP-44 (P-solubilizer) and B. megaterium EU-ARK-23 (K-solubilizer) evaluation in Aegilops kotschyi and wheat crop resulted in the enhancement of growth as well as physiological parameter including shoot/root length, fresh/dry weight and chlorophyll, carotenoid, total soluble sugar content, phenolic and flavonoid content as compared to un-inoculated control. Microbial consortium consisting of potential plant growth promoting (PGP) bacterial strains could be used as biofertilizer and bioinoculants in cereals crop growing in hilly region., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

The Himalayas are one of the most mystical, yet least studied terrains of the world. One of Earth's greatest multifaceted and diverse montane ecosystems is also one of the thirty-four global biodiversity hotspots of the world. These are supposed to have been uplifted about 60-70 million years ago and support, distinct environments, physiography, a variety of orogeny, and great biological diversity (plants, animals, and microbes). Microbes are the pioneer colonizer of the Himalayas that are involved in various bio-geological cycles and play various significant roles. The applications of Himalayan microbiomes inhabiting in lesser to greater Himalayas have been recognized. The researchers explored the applications of indigenous microbiomes in both agricultural and environmental sectors. In agriculture, microbiomes from Himalayan regions have been suggested as better biofertilizers and biopesticides for the crops growing at low temperature and mountainous areas as they help in the alleviation of cold stress and other biotic stresses. Along with alleviation of low temperature, Himalayan microbes also have the capability to enhance plant growth by availing the soluble form of nutrients like nitrogen, phosphorus, potassium, zinc, and iron. These microbes have been recognized for producing plant growth regulators (abscisic acid, auxin, cytokinin, ethylene, and gibberellins). These microbes have been reported for bioremediating the diverse pollutants (pesticides, heavy metals, and xenobiotics) for environmental sustainability. In the current perspectives, present review provides a detailed discussion on the ecology, biodiversity, and adaptive features of the native Himalayan microbiomes in view to achieve agro-environmental sustainability., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Glabridin is chemically an isoflavane class of natural phenols and is found mainly in the roots of Glycyrrhiza glabra . It has several beneficial pharmacological actions for the management of inflammatory disorders as well as can counteract drug-induced toxic effects. On the other hand, methotrexate (MTX) is the first-line disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis. However, its treatment is associated with major side effects like hepatotoxicity. In the quest to explore a suitable combination therapy that can improve the efficacy and reduce the hepatotoxicity of MTX, we hypothesized that glabridin might serve the purpose for which there is no literature precedent to date. We explored the antiarthritic efficacy of MTX in the presence or the absence of glabridin using Mycobacterium-induced arthritic model in rats. The results of reduction in paw swelling, inhibition of serum cytokines (TNF-α, IL-6, and IL-1β), and improvement in the bone joints from radiological and histopathological findings suggest that glabridin can substantially augment the antiarthritic efficacy of MTX. Further, results of concomitant glabridin treatment with MTX in the experimental time frame demonstrate that glabridin could considerably prevent the MTX-induced hepatic alteration in serum biochemical markers (SGPT and SGOT) and oxidative stress markers (malondialdehyde (MDA) and glutathione reduced (GSH)). Moreover, glabridin showed a marked effect in impeding the regulation of NF-κB/IκBα and Nrf2/Keap1 pathways in the hepatic tissues. The results of simultaneous administration of glabridin with MTX in the rat model indicate that glabridin had no pronounced effect of causing severe alteration in the pharmacokinetic behavior of MTX. In summary, glabridin can significantly potentiate the antiarthritic efficacy of MTX and can also minimize its hepatotoxicity via the inhibition of inflammation and oxidative stress. Further research should be performed to develop glabridin as a phytotherapeutics for the improved efficacy and better tolerability of MTX at the reduced dose level of MTX., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Agriculture faces challenges to fulfil the rising food demand due to shortage of arable land and various environmental stressors. Traditional farming technologies help in fulfilling food demand but they are harmful to humans and environmental sustainability. The food production along with agro-environmental sustainability could be achieved by encouraging farmers to use agro-environmental sustainable products such as biofertilizers and biopesticides consisting of live microbes or plant extract instead of chemical-based inputs. The eco-friendly formulations play a significant role in plant growth promotion, crop yield and repairing degraded soil texture and fertility sustainably. Mineral solubilizing microbes that provide vital nutrients like phosphorus, potassium, zinc and selenium are essential for plant growth and development and could be developed as biofertilizers. These microbes could be plant associated (rhizospheric, endophytic and phyllospheric) or inhabit the bulk soil and diverse extreme habitats. Mineral solubilizing microbes from soil, extreme environments, surface and internal parts of the plant belong to diverse phyla such as Ascomycota, Actinobacteria, Basidiomycota, Bacteroidetes, Chlorobi, Cyanobacteria, Chlorophyta, Euryarchaeota, Firmicutes, Gemmatimonadetes, Mucoromycota, Proteobacteria and Tenericutes. Mineral solubilizing microbes (MSMs) directly or indirectly stimulate plant growth and development either by releasing plant growth regulators; solubilizing phosphorus, potassium, zinc, selenium and silicon; biological nitrogen fixation and production of siderophores, ammonia, hydrogen cyanide, hydrolytic enzymes and bioactive compound/secondary metabolites. Biofertilizer developed using mineral solubilizing microbes is an eco-friendly solution to the sustainable food production system in many countries worldwide. The present review deals with the biodiversity of mineral solubilizing microbes, and potential roles in crop improvement and soil well-being for agricultural sustainability., (© 2022 Society for Applied Microbiology.)

Hydroxyurea (HU) is the key drug to treat Sickle cell anemia (SCA). However, its treatment is associated with the liability of myelosuppression. The present study aimed to investigate the potential of epicatechin as a supplementation therapy for the symptomatic management of SCA under HU therapy. A panel of experiments were performed at first to observe epicatechin's effect on sickling and hemolytic behaviour using SCA patient's blood (ex vivo). Thereafter, the effect of HU in the presence or absence of epicatechin was investigated on cytokine inhibition in rat splenocytes (ex vivo) as well as alterations in hematological parameters and kidney function tests in rats (in vivo). Then, any effect of epicatechin on pharmacokinetic modulation of HU in rats was elucidated along with the underlying mechanism using a battery of in vitro and in vivo models. Epicatechin exhibited potent action on anti-sickling, polymerization inhibition, and erythrocyte membrane stability. It did not show any inherent hemolytic activity and reduced TNF-α level during concomitant administration with HU. Based on hematological changes in rats, epicatechin treatment aided to the beneficial effect of HU and prevented the treatment-linked disadvantageous effects of HU like neutropenia. The plasma exposure of HU was significantly augmented in rats upon simultaneous oral administration of epicatechin with HU. Down-regulation of Oatp1b2 and catalase possibly contributed to the pharmacokinetic interaction of HU. Epicatechin is found to be a promising candidate and should be explored at a reduced dose level of HU towards offsetting the dose-dependent myelosuppressive effect of HU under the frame of supplementation therapy in SCA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Climate change is emerging as a crucial issue with global attention and leading to abiotic stress conditions. There are different abiotic stress which affects the crop production among which drought is known to be most destructive stress affecting crop productivity and world's food security. Different approaches are under consideration to increase adaptability of the plants under drought stress with plant-microbe interactions being a greater area of focus. Stress-adaptive microbes either from the rhizosphere, internal tissue, or aerial parts of plants have been reported which through different mechanisms help the plants to cope up with drought and also promote their growth. These mechanisms include the accumulation of osmolytes, decrease in the inhibitory levels of ethylene by aminocyclopropane-1-carboxylate (ACC) deaminase enzyme, and furnishing the unavailable nutrients to plants. Microbial genera including Azotobacter, Bacillus, Ochrobactrum, Pseudomonas, and Serratia are known to be self-adaptive and growth promoters under drought stressed conditions. Stress-adaptive plant growth promoting (PGP) microbes thus are excellent candidates for stress alleviation in drought environment to provide maximum benefits to the plants. The present review deals with the effect of the drought stress on plants, biodiversity of the drought-adaptive microbes, mechanisms of the drought stress alleviation through enhancement of stress alleviators, reduction of the stress aggravators, and modification of the molecular pathways as well as the multiple PGP attributes of the drought-adaptive microbes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Drought stress is among the most destructive stresses for agricultural productivity. It interferes with normal metabolic activities of the plants resulting, a negative impact on physiology and morphology of the plants. The management of drought stress requires various adaptive and alleviation strategies in which stress adaptive microbiomes are exquisite bioresources for plant growth and alleviation of drought stress. Diverse drought adaptive microbes belonging to genera Achromobacter, Arthrobacter, Aspergillus, Bacillus, Pseudomonas, Penicillium and Streptomyces have been reported worldwide. These bioresources exhibit a wide range of mechanisms such as helping plant in nutrient acquisition, producing growth regulators, lowering the levels of stress ethylene, increasing the concentration of osmolytes, and preventing oxidative damage under water deficit environmental conditions. Horticulture is one of the potential agricultural sectors to speed up the economy, poverty and generation of employment for livelihood. The applications of drought adaptive plant growth promoting (PGP) microbes as biofertilizers and biopesticides for horticulture is a potential strategy to improve the productivity and protection of horticultural crops from abiotic and biotic stresses for agricultural sustainability., Competing Interests: The authors declare no conflict of interest., (© 2022 Published by Elsevier Ltd.)

Bioinoculants provide better opportunity for ecological farming practices to improve the plant growth and enhanced crop productivity. Different types of bioinoculants containing single microbial culture and multiple microbial strains in single formulation could be used for agricultural sustainability. The different efficient microbial strain in single formulation as a consortium is an emerging trend in the present era. The present study deals with the isolation of nitrogen fixing, phosphorus and potassium solubilizing microbes from rhizospheric soil and root's internal tissues of different cereal/pseudocereal crops and their application as a microbial consortium for the growth of cereal crops. A total of 152 rhizospheric and endophytic bacteria were isolated and screened for the plant growth promoting (PGP) traits of nitrogen fixation, solubilization of phosphorus, and potassium. Among all the isolates, nine were found to fix nitrogen, fifteen and eleven exhibited phosphorus and potassium solubilization activity, respectively. Three selected efficient bacterial strains were identified using 16S rRNA gene sequencing as Erwinia sp. EU-B2SNL1 (N-fixer), Chryseobacterium arthrosphaerae EU-LWNA-37 (P-solubilizer), and Pseudomonas gessardii EU-MRK-19 (K-solubilizer). The inoculation of these three bacterial strains on barley crop as single inoculum and as microbial consortium enhanced the growth and physiological parameters including root/shoot length and biomass, chlorophyll, carotenoids, phenolics, flavonoids and soluble sugar content in comparison with untreated control. The microbial consortium was found to be more effective as compared to single inoculum. The microbial consortium of nitrogen fixing and mineral solubilizing microbes could be used as biofertilizer for plant growth and soil health., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Published by Elsevier Ltd.)

Andrographolide is one of the main active principles of Andrographolide paniculata and has been extensively explored for its therapeutic use. Current studies focus on phytotherapeutics-based adjuvant therapy to symptomatically treat sickle cell anemia (SCA) as there is no specific drug/gene therapy available to date. The present study aimed to explore the potential of andrographolide as an adjuvant therapy for SCA in the presence or absence of hydroxyurea (HU), a key drug for SCA treatment. A panel of ex vivo and in vivo experimentations was performed to explore the antisickling activity of andrographolide, followed by evaluating pharmacokinetic and pharmacodynamic (PK/PD) activities in the presence of HU. Andrographolide showed significant antisickling activity using blood from SCA patients (ex vivo) and did not show any deleterious effect to cause hemolysis using rat blood (ex vivo). It displayed a substantial decrease in HU-induced decline in splenic lymphocyte proliferation and cytokine level (TNF-α and IFN-γ) using rat splenocytes (ex vivo). Concomitant oral administration of andrographolide with HU in rats for 15 days exhibited a noticeable improvement in the RBC count and hemoglobin levels comparable to the efficacy of l-glutamine (in vivo). Simultaneous administration of andrographolide with HU caused no marked effect on any pharmacokinetic parameters of HU except the highest plasma concentration of HU and its corresponding time point, which significantly dropped and delayed, respectively (in vivo). No considerable effect of andrographolide was observed on urease and horseradish peroxidase activity (in vitro). Overall, results suggest that andrographolide has several beneficial actions to be an adjuvant therapy to symptomatically manage SCA, but it should be avoided during the prescribed therapy of HU., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Endophytic fungal communities have attracted a great attention to chemists, ecologists, and microbiologists as a treasure trove of biological resource. Endophytic fungi play incredible roles in the ecosystem including abiotic and biotic stress tolerance, eco-adaptation, enhancing growth and development, and maintaining the health of their host. In recent times, endophytic fungi have drawn a special focus owing to their indispensable diversity, unique distribution, and unparalleled metabolic pathways. The endophytic fungal communities belong to three phyla, namely Mucoromycota, Basidiomycota, and Ascomycota with seven predominant classes Agaricomycetes, Dothideomycetes, Eurotiomycetes, Mortierellomycotina, Mucoromycotina, Saccharomycetes, and Sordariomycetes. In a review of a huge number of research finding, it was found that endophytic fungal communities of genera Aspergillus, Chaetomium, Fusarium, Gaeumannomyces, Metarhizium, Microsphaeropsis, Paecilomyces, Penicillium, Piriformospora, Talaromyces, Trichoderma, Verticillium, and Xylaria have been sorted out and well characterized for diverse biotechnological applications for future development. Furthermore, these communities are remarkable source of novel bioactive compounds with amazing biological activity for use in agriculture, food, and pharmaceutical industry. Endophytes are endowed with a broad range of structurally unique bioactive natural products, including alkaloids, benzopyranones, chinones, flavonoids, phenolic acids, and quinines. Subsequently, there is still an excellent opportunity to explore novel compounds from endophytic fungi among numerous plants inhabiting different niches. Furthermore, high-throughput sequencing could be a tool to study interaction between plants and endophytic fungi which may provide further opportunities to reveal unknown functions of endophytic fungal communities. The present review deals with the biodiversity of endophytic fungal communities and their biotechnological implications for agro-environmental sustainability., (© 2022. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Industrialization and modernization of agricultural systems contaminated lithosphere, hydrosphere, and biosphere of the Earth. Sustainable remediation of contamination is essential for environmental sustainability. Myco-remediation is proposed to be a green, economical, and efficient technology over conventional remediation technologies to combat escalating pollution problems at a global scale. Fungi can perform remediation of pollutants through several mechanisms like biosorption, precipitation, biotransformation, and sequestration. Myco-remediation significantly removes or degrades metal metals, persistent organic pollutants, and other emerging pollutants. The current review highlights the species-specific remediation potential, influencing factors, genetic and molecular control mechanism, applicability merits to enhance the bioremediation efficiency. Structure and composition of fungal cell wall is crucial for immobilization of toxic pollutants and a subtle change on fungal cell wall structure may significantly affect the immobilization efficiency. The utilization protocol and applicability of enzyme engineering and myco-nanotechnology to enhance the bioremediation efficiency of any potential fungus was proposed. It is advocated that the association of hyper-accumulator plants with plant growth-promoting fungi could help in an effective cleanup strategy for the alleviation of persistent soil pollutants. The functions, activity, and regulation of fungal enzymes in myco-remediation practices required further research to enhance the myco-remediation potential. Study of the biotransformation mechanisms and risk assessment of the products formed are required to minimize environmental pollution. Recent advancements in molecular "Omic techniques"and biotechnological tools can further upgrade myco-remediation efficiency in polluted soils and water., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aberrant activation of NLRP3 inflammasome has been implicated in several inflammatory diseases. Autophagy is one of the primary mechanisms that regulate NLRP3 inflammasome activity. In this study, we attempted to target NLRP3 inflammasome activity by a synthetic compound IIIM-941. We found that IIIM-941 inhibits ATP induced NLRP3 inflammasome by induction of autophagy through AMPK pathway in bone marrow derived macrophages (BMDMs) and J774A.1 cells. It was interesting to observe that IIIM-941 did not show any inhibitory activity against LPS induced pro-inflammatory cytokines TNF-α and IL-6. The anti-NLRP3 activity of IIIM-941 was significantly reversed when we attempted to block autophagy by using either pharmacological inhibitor bafilomycin A1or by using siRNA against AMPK. Further, we found that IIIM-941 downregulated the expression of NLRP3 and prevented the oligomerization of ASC to exert its anti-NLRP3 inflammasome effect in J774A.1 cells. We validated inhibitory activity of IIIM-941 against NLRP3 in three different mice models. The anti-inflammatory effect of IIIM-941 was highly significant in ATP induced peritoneal inflammation model. IIIM-941 was similarly effective in suppressing MSU induced IL-1β in the air pouch model of inflammation without affecting the levels of TNF-α and IL-6. Finally, oral efficacy of IIIM-941 was also proved in MSU indued foot paw edema model of inflammation in mice at 10 and 20 mg/kg (b.w.). The compounds like IIIM-941 can be explored further for the development of therapies against diseases such as Alzheimer's disease and Parkinson's disease, where hampered autophagy and NLRP3 activation play a crucial role in the pathological development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ali, Gupta, Wani, Sharma, Abdullaha, Kour, Choudhary, Bharate, Singh and Kumar.)

Nucleotide-binding domain leucine-rich repeat family pyrin domain containing 3 (NLRP3) inflammasome complex regulates the caspase-1 activity and subsequent processing of interleukin-1β (IL-1β). Various inflammatory diseases involve the activation of inflammasome complexes; thus, the intervention in complex formation via small molecules offers a new therapeutic opportunity. The structure-guided design and synthesis of a series of methoxystilbenes and methoxy-2-phenylnaphthalenes identified new inhibitors of NLRP3 inflammasome complex. The tetramethoxystilbene 4o and trimethoxy 2-phenylnaphthalene 1t inhibit the release of a mature form of IL-1β in J774A.1 cells with IC 50 values of 1.39 and 2.07 μM, respectively. Mechanistic investigation revealed that tetramethoxystilbene 4o blocks the oligomerization of apoptosis-associated speck-like protein (ASC), which is the vital step in the formation of NLRP3 inflammasome assembly, thus preventing the activation of caspase-1 and the IL-1β release. Treatment of LPS+ATP challenged mice with 20 mg/kg of 4o significantly suppressed the levels of IL-1β. The data presented herein warrant further investigation of methoxystilbenes in disease-specific models of inflammatory diseases., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Hydroxyurea (HU) is the first-ever approved drug by USFDA for sickle cell anemia (SCA). However, its treatment is associated with severe side effects like myelosuppression. Current studies are focused on the supplementation therapy for symptomatic management of SCA. In the present study, we aimed to explore rutin's and gallic acid's potential individually, for concomitant therapy with HU using pharmacokinetic and pharmacodynamic approaches since there is no such precedent till date. In vivo pharmacokinetic studies of HU in rats showed that rutin could be safely co-administered with HU, while gallic acid significantly raised the plasma concentration of HU. Both the phytochemicals did not have any marked inhibitory effect on urease but have considerable effects on horseradish peroxidase enzyme. The experimental phytoconstituents displayed a very low propensity to cause in vitro hemolysis. Gallic acid markedly enhanced the HU-induced decrease in lymphocyte proliferation. A substantial improvement by rutin or gallic acid was observed in HU-induced reduction of the main hematological parameters in rats. Combined treatment of HU with rutin and gallic acid reduced serum levels of both IL-6 and IL-17A. Overall, both rutin and gallic acid are found to have promising phytotherapy potential with HU. Further exploration needs to be done on both candidates for use as phytotherapeutics for SCA., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Over the past few decades, the rapid development of agriculture and industries has resulted in contamination of the environment by diverse pollutants, including heavy metals, polychlorinated biphenyls, plastics, and various agrochemicals. Their presence in the environment is of great concern due to their toxicity and non-biodegradable nature. Their interaction with each other and coexistence in the environment greatly influence and threaten the ecological environment and human health. Furthermore, the presence of these pollutants affects the soil quality and fertility. Physicochemical techniques are used to remediate such environments, but they are less effective and demand high costs of operation. Bioremediation is an efficient, widespread, cost-effective, and eco-friendly cleanup tool. The use of microorganisms has received significant attention as an efficient biotechnological strategy to decontaminate the environment. Bioremediation through microorganisms appears to be an economically viable and efficient approach because it poses the lowest risk to the environment. This technique utilizes the metabolic potential of microorganisms to clean up contaminated environments. Many microbial genera have been known to be involved in bioremediation, including Alcaligenes, Arthrobacter, Aspergillus, Bacillus, Burkholderia, Mucor, Penicillium, Pseudomonas, Stenotrophomonas, Talaromyces, and Trichoderma. Archaea, including Natrialba and Haloferax, from extreme environments have also been reported as potent bioresources for biological remediation. Thus, utilizing microbes for managing environmental pollution is promising technology, and, in fact, the microbes provide a useful podium that can be used for an enhanced bioremediation model of diverse environmental pollutants.

Endophytic microbes are known to live asymptomatically inside their host throughout different stages of their life cycle and play crucial roles in the growth, development, fitness, and diversification of plants. The plant-endophyte association ranges from mutualism to pathogenicity. These microbes help the host to combat a diverse array of biotic and abiotic stressful conditions. Endophytic microbes play a major role in the growth promotion of their host by solubilizing of macronutrients such as phosphorous, potassium, and zinc; fixing of atmospheric nitrogen, synthesizing of phytohormones, siderophores, hydrogen cyanide, ammonia, and act as a biocontrol agent against wide array of phytopathogens. Endophytic microbes are beneficial to plants by directly promoting their growth or indirectly by inhibiting the growth of phytopathogens. Over a long period of co-evolution, endophytic microbes have attained the mechanism of synthesis of various hydrolytic enzymes such as pectinase, xylanases, cellulase, and proteinase which help in the penetration of endophytic microbes into tissues of plants. The effective usage of endophytic microbes in the form of bioinoculants reduce the usage of chemical fertilizers. Endophytic microbes belong to different phyla such as Actinobacteria, Acidobacteria, Bacteroidetes, Deinococcus-thermus, Firmicutes, Proteobacteria, and Verrucomicrobia. The most predominant and studied endophytic bacteria belonged to Proteobacteria followed by Firmicutes and then by Actinobacteria. The most dominant among reported genera in most of the leguminous and non-leguminous plants are Bacillus, Pseudomonas, Fusarium, Burkholderia, Rhizobium, and Klebsiella. In future, endophytic microbes have a wide range of potential for maintaining health of plant as well as environmental conditions for agricultural sustainability. The present review is focused on endophytic microbes, their diversity in leguminous as well as non-leguminous crops, biotechnological applications, and ability to promote the growth of plant for agro-environmental sustainability.

The structure-guided virtual screening (VS) has proved to be successful strategy in identification of new scaffolds for biological targets. The overactivity of NLRP3 inflammasome has been implicated in variety of inflammatory diseases including Alzheimer's disease. The up-regulation of estrogen-receptor β (ER-β) activity has been directly linked with inhibition of NLRP3 inflammasome activity. In the present study, we report discovery of new NLRP3 inflammasome inhibitors via ER-β crystal structure (PDB: 5TOA) guided virtual screening of 20,000 compound library. For experimental validation, top 10 ligands were selected based on structure novelty, docking score, prime MMGB/SA binding affinity and interaction pattern analysis. Amongst the tested compounds, three thiazolidin-4-ones IIIM-1268, IIIM-1269 and IIIM-1270 and benzo[cd]indol-2-one IIIM-1266 have shown 73, 69, 75 and 77% suppression of IL-1β release in mouse macrophages (J774A.1 cells) at 10 µM. Benzylidene-thiazolidine-2,4-diones IIIM-1268 and IIIM-1270 inhibited IL-1β release with IC 50 of 2.3 and 3.5 µM and also significantly decreased the protein expression level of mature form of IL-1β in western-blot analysis. IIIM-1266 and IIIM-1270 displayed bidentate H-bonding with Arg 346 and Glu 305 residues in the active site of ER-β; and they also strongly occupied the ADP-binding site of NLRP3 protein. The results presented herein, indicate that ER-β guided VS can be successfully used to identify new NLRP3 inflammasome inhibitors, which may have potential in the development of novel anti-Alzheimer agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The present protocol describes an efficient, metal-free regioselective synthesis of 2-aroyl-3-arylimidazo[1,2-a]pyridines from 1,3-diaryl-prop-2-en-1-ones and 2-aminopyridine. The iodine-NH 4 OAc promoted reaction offers a novel route in the synthesis of 2-aroyl-3-arylimidazo[1,2-a]pyridines. This protocol offers significant flexibility in accessing medicinally important 2-aroyl-3-arylimidazo[1,2-a]pyridines with various substitution patterns.

In the title mol-ecule, C15H11Cl2NOS, the dihedral angle between the phenyl and benzene rings is 72.24 (1)°. In the crystal, pairs of N-H⋯S hydrogen bonds form dimers with twofold rotational symmetry. The dimers are connected by weak C-H⋯O hydrogen bonds, forming a two-dimensional network parallel to (001). An intra-molecular O-H⋯S hydrogen bond is also observed.

In the title mol-ecule, C11H12N4S2, the dihedral angle between the triazole and benzene rings is 21.31 (5)°. A weak intra-molecular C-H⋯S hydrogen bond generates an S(6) ring motif. In the crystal, pairs of N-H⋯S hydrogen bonds form inversion dimers. In addition, π-π inter-actions are observed between the benzene rings, with a centroid-centroid separation of 3.7599 (11) Å.

In the title mol-ecule, C10H12N4SO, the triazole ring forms a dihedral angle of 73.0 (5)° with the benzene ring. The meth-oxy group is approximtely coplanar with the benzene ring with a C C-O-Cmeth-yl torsion angle of 4.7 (3)°. In the crystal, N-H⋯S hydrogen bonds connect pairs of inversion-related mol-ecules, which are in turn connected by N-H⋯N hydrogen bonds into chains of rings along [010]. Weak C-H⋯O hydrogen bonds connect these chains into a two-dimensional network parallel to (-102).

The "Malaria Evolution in South Asia" (MESA) program project is an International Center of Excellence for Malaria Research (ICEMR) sponsored by the US National Institutes of Health. This US-India collaborative program will study the origin of genetic diversity of malaria parasites and their selection on the Indian subcontinent. This knowledge should contribute to a better understanding of unexpected disease outbreaks and unpredictable disease presentations from Plasmodium falciparum and Plasmodium vivax infections. In this first of two reviews, we highlight malaria prevalence in India. In particular, we draw attention to variations in distribution of different human-parasites and different vectors, variation in drug resistance traits, and multiple forms of clinical presentations. Uneven malaria severity in India is often attributed to large discrepancies in health care accessibility as well as human migrations within the country and across neighboring borders. Poor access to health care goes hand in hand with poor reporting from some of the same areas, combining to possibly distort disease prevalence and death from malaria in some parts of India. Corrections are underway in the form of increased resources for disease control, greater engagement of village-level health workers for early diagnosis and treatment, and possibly new public-private partnerships activities accompanying traditional national malaria control programs in the most severely affected areas. A second accompanying review raises the possibility that, beyond uneven health care, evolutionary pressures may alter malaria parasites in ways that contribute to severe disease in India, particularly in the NE corridor of India bordering Myanmar Narayanasamy et al., 2012., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In the title compound, C(16)H(16)ClNO(2)S(2), the piperidine ring is in a chair conformation. In the coumarin ring system, the dihedral angle between the benzene and pyran rings is 3.5 (1)°. In the crystal, a weak C-H⋯O hydrogen bond links mol-ecules into chains along [001]. In addition, π-π stacking inter-actions are present involving the benzene and pyran rings, with a centroid-to-centroid distance of 3.712 (2) Å. The crystal studied is a nonmerohedral twin with refined components 0.221 (1) and 0.779 (1).