Unraveling the signaling mechanism behind astrocytoma and possible therapeutics strategies: A comprehensive review.

BACKGROUND: A form of cancer called astrocytoma can develop in the brain or spinal cord and sometimes causes death. A detailed overview of the precise signaling cascade underlying astrocytoma formation has not yet been revealed, although various factors have been investigated. Therefore, our objective was to unravel and summarize our current understanding of molecular genetics and associated signaling pathways with some possible therapeutic strategies for astrocytoma. RECENT FINDINGS: In general, four different forms of astrocytoma have been identified in individuals, including circumscribed, diffuse, anaplastic, and multiforme glioblastoma, according to a recent literature review. All types of astrocytoma have a direct connection with some oncogenic signaling cascade. Common signaling is MAPK cascade, including Ras-Raf-ERK, up-regulated with activating EGFR/AKT/PTEN/mTOR and PDGFR. Recent breakthrough studies found that BRAF mutations, including KIAA1549: BRAF and BRAF V600E are responsible for astrocytoma progression. Additionally, cancer progression is influenced by mutations in some tumor suppressor genes, such as the Tp53/ATRX and MGMT mutant. As synthetic medications must cross the blood-brain barrier (BBB), modulating signal systems such as miRNA is the primary option for treating patients with astrocytoma. However, available surgery, radiation therapy, and experimental therapies such as adjuvant therapy, anti-angiogenic therapy, and EGFR-targeting antibody drug are the usual treatment for most types of astrocytoma. Similar to conventional anticancer medications, some phytochemicals slow tumor growth by simultaneously controlling several cellular proteins, including those involved in cell cycle regulation, apoptosis, metastatic spread, tyrosine kinase, growth factor receptor, and antioxidant-related proteins. CONCLUSION: In conclusion, cellular and molecular signaling is directly associated with the development of astrocytoma, and a combination of conventional and alternative therapies can improve the malignancy of cancer patients.

Boosting the Biocontrol Efficacy of Bacillus amyloliquefaciens DSBA-11 through Physical and Chemical Mutagens to Control Bacterial Wilt Disease of Tomato Caused by Ralstonia solanacearum.

Bacterial wilt disease of tomato (Solanum lycopersicum L.), incited by Ralstonia solanacearum (Smith), is a serious agricultural problem in India. In this investigation, chemical mutagenic agents (NTG and HNO2 treatment) and ultraviolet (UV) irradiation have been used to enhance the antagonistic property of Bacillus amyloliquefaciens DSBA-11 against R. solanacearum UTT-25 towards an effective management of tomato wilt disease. The investigation established the fact that maximum inhibition to R. solanacearum UTT-25 was exerted by the derivative strain MHNO2-20 treated with nitrous acid (HNO2) and then by the derivative strain MNTG-21 treated with NTG. The exertion was significantly higher than that of the parent B. amyloliquefaciens DSBA-11. These two potential derivatives viz. MNTG-21, MHNO2-20 along with MUV-19, and a wild derivative strain of B. amyloliquefaciens i.e.,DSBA-11 were selected for GC/MS analysis. Through this analysis 18 major compounds were detected. Among the compounds thus detected, the compound 3-isobutyl hexahydropyrrolo (1,2), pyrazine-1,4-dione (4.67%) was at maximum proportion in the variant MHNO2-20 at higher retention time (RT) of 43.19 s. Bio-efficacy assessment observed a record of minimum intensity (9.28%) in wilt disease and the highest bio-control (88.75%) in derivative strain MHNO2-20-treated plants after 30 days of inoculation. The derivative strain MHNO2-20, developed by treating B. amyloliquefaciens with nitrous acid (HNO2), was therefore found to have a higher bio-efficacy to control bacterial wilt disease of tomato under glasshouse conditions than a wild-type strain.

Application of soil amendments mitigates phytotoxic effects on Solanum melongena L. and Lycopersicon esculentum L. seedlings exposed to chlorpyrifos and dimethoate pesticides.

This field study was done to study the effects of pesticides chlorpyrifos and dimethoate singly and in combination with soil amendments like chemical fertilizer (CF), farmyard manure (FM), and 50% CF + 50% FM (CM) on various indices of growth, physio-biochemical parameters of brinjal, and their residual effect in tomato seedlings. As compared to the control, the decrease of 9.5 and 5.5%, 8.9 and 5.0% in fresh weight, dry weight respectively was recorded in the pesticide-only treatment in the brinjal crop. Pesticides when applied in combination with soil amendments depicted the highest growth of 105.4 and 118.2%, 104.1 and 115.1% in pesticides + CF treatment, 72.7 and 85.1%, 68.1 and 78.1% in pesticides + CM treatment, and 64.4 and 74.0%, 62.7 and 65.7% in pesticides + FM treatment compared to control. In tomato seedlings, the pesticides + CF treatment exhibited the lowest growth indices (25.5 and 31.9%, 26.4 and 28.8%) across the combined treatments while pesticide-only treatment depicted minimum growth compared to the control. In the case of photosynthesis rate and antioxidant activity, the combined treatments showed the trend as pesticides + CF > pesticides + CM > pesticides + FM in the brinjal crop; however, the trend became somewhat reversed in the tomato crop. The results indicated that soil-amended practices modulated pesticide-induced damage by upregulating photosynthetic performance, chlorophyll a fluorescence, and antioxidant balancing which might be associated with the mitigation of ROS-induced pesticide toxicity, and the effect was more pronounced with CM. Furthermore, our study was supported by non-metric-multidimensional scaling (NMDS)-constructed ordination plots by showing spatial patterns in different variables. The study might help in taking management decision to design mitigation actions for government and non-government agency at the farmers' level.

Current Scenario and Future Prospects of Endophytic Microbes: Promising Candidates for Abiotic and Biotic Stress Management for Agricultural and Environmental Sustainability.

Globally, substantial research into endophytic microbes is being conducted to increase agricultural and environmental sustainability. Endophytic microbes such as bacteria, actinomycetes, and fungi inhabit ubiquitously within the tissues of all plant species without causing any harm or disease. Endophytes form symbiotic relationships with diverse plant species and can regulate numerous host functions, including resistance to abiotic and biotic stresses, growth and development, and stimulating immune systems. Moreover, plant endophytes play a dominant role in nutrient cycling, biodegradation, and bioremediation, and are widely used in many industries. Endophytes have a stronger predisposition for enhancing mineral and metal solubility by cells through the secretion of organic acids with low molecular weight and metal-specific ligands (such as siderophores) that alter soil pH and boost binding activity. Finally, endophytes synthesize various bioactive compounds with high competence that are promising candidates for new drugs, antibiotics, and medicines. Bioprospecting of endophytic novel secondary metabolites has given momentum to sustainable agriculture for combating environmental stresses. Biotechnological interventions with the aid of endophytes played a pivotal role in crop improvement to mitigate biotic and abiotic stress conditions like drought, salinity, xenobiotic compounds, and heavy metals. Identification of putative genes from endophytes conferring resistance and tolerance to crop diseases, apart from those involved in the accumulation and degradation of contaminants, could open new avenues in agricultural research and development. Furthermore, a detailed molecular and biochemical understanding of endophyte entry and colonization strategy in the host would better help in manipulating crop productivity under changing climatic conditions. Therefore, the present review highlights current research trends based on the SCOPUS database, potential biotechnological interventions of endophytic microorganisms in combating environmental stresses influencing crop productivity, future opportunities of endophytes in improving plant stress tolerance, and their contribution to sustainable remediation of hazardous environmental contaminants.

Chick chorioallantoic membrane: a valuable 3D in vivo model for screening nanoformulations for tumor antiangiogenic therapeutics.

Drug discovery is an extensive process. From identifying lead compounds to approval for clinical application, it goes through a sequence of labor-intensive in vitro, in vivo preclinical screening and clinical trials. Among thousands of drugs screened only a few get approval for clinical trials. Furthermore, these approved drugs are often discontinued due to systemic toxicity and comorbidity at clinically administered dosages. To overcome these limitations, nanoformulations have emerged as the most sought-after strategy to safely and effectively deliver drugs within tumors at therapeutic concentrations. Most importantly, the employment of suitably variable preclinical models is considered highly critical for the therapeutic evaluation of candidate drugs or their formulations. A review of literature from the past 10 years on antiangiogenic nanoformulations shows the employment of limited types of preclinical models mainly the 2-dimensional (2D) monolayer cell culture and murine models as the mainstay for drug uptake, toxicity and efficiency studies. To top it all, murine models are highly expensive, time-consuming and require expertise in handling them. The current review highlights the utilization of the age-old chicken chorioallantoic membrane (CAM), a well-defined angiogenic model in the investigation of antiangiogenic compounds and nanoformulations in an economic framework. For practical applicability, we have evaluated the CAM model to demonstrate the screening of antiangiogenic compounds and that tumor cells can be implanted onto developing CAM for growing xenografts by recruiting host endothelial and other cellular components. In addition, the exploitation of CAM tumor xenograft models for the evaluation of nanoparticle distribution has also been reinforced by demonstrating that intravenously administered iron oxide nanoparticles (IONPs) passively accumulate and exhibit intracellular as well as extracellular compartment accumulation in highly vascular xenografts. Finally, the ethical considerations, benefits, and drawbacks, of using CAM as an experimental model for testing potential therapeutics are also highlighted.

Plant metabolite diosmin as the therapeutic agent in human diseases.

Plant-derived flavonoids have been the focus of research for many years mainly in the last decade owing to their therapeutic properties. So far, about 4000 flavonoids have been identified from plants and diosmin (a flavone glycoside) is one of them. Online databases, previous studies, and reviews have been used to gather information on anti-oxidant, immunomodulatory, anti-cancer, anti-parasitic, and anti-microbialproperties of diosmin. Effects of diosmin in combination with other flavonoids have been reviewed thoroughly and its administrative routes are also summarized. Additionally, we studied the effect of diosmin on critical protein networks. It exhibits therapeutic effects in diabetes and its associated complications such as neuropathy and dyslipidemia. Combination of diosmin with hesperidin is found to be very effective in the treatment of chronic venous insufficiency and haemorrhoids. Diosmin is an exquisite therapeutic agent alone as well as in combination with other flavonoids.

Colistin Resistance and Management of Drug Resistant Infections.

Colistin resistance is a globalized sensible issue because it has been considered a drug of the last-line resort to treat drug-resistant bacterial infections. The product of the mobilized colistin resistance (mcr) gene and its variants are the significant causes of colistin resistance, which is emerging due to the frequent colistin use in veterinary, and these genes circulate among the bacterial community. Apart from mcr genes, some other intrinsic genes and proteins are also involved in colistin resistance. Researchers focus on the most advanced genomics (whole genome sequencing), proteomics, and bioinformatics approaches to explore the question of colistin resistance. To combat colistin resistance, researchers developed various strategies such as the development of newer drugs, the repurposing of existing drugs, combinatorial treatment by colistin with other drugs, a nano-based approach, photodynamic therapy, a CRISPRi-based strategy, and a phage-based strategy. In this timeline review, we have discussed the development of colistin resistance and its management in developing countries.

Current advances and research prospects for agricultural and industrial uses of microbial strains available in world collections.

Microorganisms are an important component of the ecosystem and have an enormous impact on human lives. Moreover, microorganisms are considered to have desirable effects on other co-existing species in a variety of habitats, such as agriculture and industries. In this way, they also have enormous environmental applications. Hence, collections of microorganisms with specific traits are a crucial step in developing new technologies to harness the microbial potential. Microbial culture collections (MCCs) are a repository for the preservation of a large variety of microbial species distributed throughout the world. In this context, culture collections (CCs) and microbial biological resource centres (mBRCs) are vital for the safeguarding and circulation of biological resources, as well as for the progress of the life sciences. Ex situ conservation of microorganisms tagged with specific traits in the collections is the crucial step in developing new technologies to harness their potential. Type strains are mainly used in taxonomic study, whereas reference strains are used for agricultural, biotechnological, pharmaceutical research and commercial work. Despite the tremendous potential in microbiological research, little effort has been made in the true sense to harness the potential of conserved microorganisms. This review highlights (1) the importance of available global microbial collections for man and (2) the use of these resources in different research and applications in agriculture, biotechnology, and industry. In addition, an extensive literature survey was carried out on preserved microorganisms from different collection centres using the Web of Science (WoS) and SCOPUS. This review also emphasizes knowledge gaps and future perspectives. Finally, this study provides a critical analysis of the current and future roles of microorganisms available in culture collections for different sustainable agricultural and industrial applications. This work highlights target-specific potential microbial strains that have multiple important metabolic and genetic traits for future research and use.

Safer plant-based nanoparticles for combating antibiotic resistance in bacteria: A comprehensive review on its potential applications, recent advances, and future perspective.

BACKGROUND: Antibiotic resistance is one of the current threats to human health, forcing the use of drugs that are more noxious, costlier, and with low efficiency. There are several causes behind antibiotic resistance, including over-prescription of antibiotics in both humans and livestock. In this scenario, researchers are shifting to new alternatives to fight back this concerning situation. SCOPE AND APPROACH: Nanoparticles have emerged as new tools that can be used to combat deadly bacterial infections directly or indirectly to overcome antibiotic resistance. Although nanoparticles are being used in the pharmaceutical industry, there is a constant concern about their toxicity toward human health because of the involvement of well-known toxic chemicals (i.e., sodium/potassium borohydride) making their use very risky for eukaryotic cells. KEY FINDINGS AND CONCLUSIONS: Multiple nanoparticle-based approaches to counter bacterial infections, providing crucial insight into the design of elements that play critical roles in the creation of antimicrobial nanotherapeutic drugs, are currently underway. In this context, plant-based nanoparticles will be less toxic than many other forms, which constitute promising candidates to avoid widespread damage to the microbiome associated with current practices. This article aims to review the actual knowledge on plant-based nanoparticle products for antibiotic resistance and the possible replacement of antibiotics to treat multidrug-resistant bacterial infections.

Ethnodermatological use of medicinal plants in India: From ayurvedic formulations to clinical perspectives - A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional knowledge is a particular form of practice or skill set that was developed in ancient times and was sustained through generations via the passing of knowledge, essentially confined within a specific tribe, local people, or family lineages. Ethnodermatological use of medicinal plants in India is still a subject to conduct more studies to see if there is chemical, microbiological, and/or clinical evidence, from a scientific perspective, of their effectiveness for those skin disorders. Thus, this review can be the basis for further studies and may provide targets for drug development. AIM OF THE STUDY: We compile and emphasize the most important part of ethnodermatology, namely, traditional knowledge of medicinal plants and their applications for several skin diseases in India. We also include a brief review and explanation on dermatology in Ayurvedic and Unani medicine. We review the pharmacological activity of extracts derived from some of the most cited plants against problem skin diseases as well. MATERIALS AND METHODS: Different kinds of key phrases such as "Indian traditional ethnodermatology", "ethnodermatology", "ethnobotany", "skin diseases", "Ayurveda dermatology", "pharmacological activity" were searched in online search servers/databases such as Google Scholar (https://scholar.google.com/), ResearchGate (https://www.researchgate.net/), PubMed (https://pubmed.ncbi.nlm.nih.gov/), NISCAIR Online Periodicals Repository (NOPR) (http://nopr.niscair.res.in/). Based upon the analyses of data obtained from 178 articles, we formulated several important findings which are a summary shown in Tables. Tables. A total of 119 records of plants' uses have been found across India against 39 skin diseases. These are depicted with their localities of report, parts used, and preparation and administration methods against particular skin diseases. RESULTS: The knowledge and utilisation of herbal medicine in the Indian subcontinent has great potential to treat different kinds of human skin disorders. The administration of extracts from most of the plant species used is topical and few only are administrated orally. We also investigated the pharmacological activity of the extracts of the most cited plants against mice, bacterial and fungal pathogens, and human cells. CONCLUSIONS: Complementary therapy for dermatological problems and treatment remains the main option for millions of people in the Indian subcontinent. This review on the practices of ethnobotanical dermatology in India confirms the belief that their analysis will accelerate the discovery of new, effective therapeutic agents for skin diseases. However, more studies and clinical evidence are still required to determine if the identified species may contribute to skin condition treatment, particularly in atopic eczema. Today, ethnodermatology is a well-accepted international discipline and many new practices have been initiated in numerous countries. We hope this article will further accelerate the development of this area to identify a new generation of natural human skin treatments that will help meet the growing consumer demand for safe, sustainable, and natural treatments. In this context, research on plants utilised in ethnodermatology in India and elsewhere should be intensified.

SARS-CoV-2 and other pathogens in municipal wastewater, landfill leachate, and solid waste: A review about virus surveillance, infectivity, and inactivation.

This review discusses the techniques available for detecting and inactivating of pathogens in municipal wastewater, landfill leachate, and solid waste. In view of the current COVID-19 pandemic, SARS-CoV-2 is being given special attention, with a thorough examination of all possible transmission pathways linked to the selected waste matrices. Despite the lack of works focused on landfill leachate, a systematic review method, based on cluster analysis, allows to analyze the available papers devoted to sewage sludge and wastewater, allowing to focalize the work on technologies able to detect and treat pathogens. In this work, great attention is also devoted to infectivity and transmission mechanisms of SARS-CoV-2. Moreover, the literature analysis shows that sewage sludge and landfill leachate seem to have a remote chance to act as a virus transmission route (pollution-to-human transmission) due to improper collection and treatment of municipal wastewater and solid waste. However due to the incertitude about virus infectivity, these possibilities cannot be excluded and need further investigation. As a conclusion, this paper shows that additional research is required not only on the coronavirus-specific disinfection, but also the regular surveillance or monitoring of viral loads in sewage sludge, wastewater, and landfill leachate. The disinfection strategies need to be optimized in terms of dosage and potential adverse impacts like antimicrobial resistance, among many other factors. Finally, the presence of SARS-CoV-2 and other pathogenic microorganisms in sewage sludge, wastewater, and landfill leachate can hamper the possibility to ensure safe water and public health in economically marginalized countries and hinder the realization of the United Nations' sustainable development goals (SDGs).

Molecular phylogeny, structure modeling and in silico screening of putative inhibitors of aerolysin of Aeromonas hydrophila EUS112.

Aeromonas hydrophila, a Gram-negative bacterium, causes diseases in fish, resulting in excessive loss to the aquaculture industry. Aeromonas is a highly heterogeneous group of bacteria, and the heterogeneity of the genus is attributed to variation and diversity in the virulence factors and toxins among various Aeromonas strains. One of the major toxins aerolysin, secreted by the bacterium, causes hemorrhagic-septicemia and diarrhea and can serve as a drug target. Here, we describe characterization, molecular phylogeny, and homology modeling of the aerolysin of A. hydrophila strain EUS112 (AhEUS112) cloned in our lab. The encoded aerolysin is 485 amino acids long with an N-terminal signal sequence of 23 amino acids. Phylogenetic analysis of the aerolysin of AhEUS112 revealed that it belongs to a diverse group of toxins, showing maximum similarity with aerolysins of other Aeromonas strains followed by Vibrio toxin. The homology model of the mature aerolysin of AhEUS112 was generated using the crystal structure of a mutant aerolysin (PDB#3g4n) as the template, which showed that the encoded aerolysin exists as a channel protein. Validation of the generated model using bioinformatics tool confirmed it to be a good quality model that can be used for drug design. Molecular dock analysis revealed that drugs, aralia-saponin I, cyclamin, ardisiacrispin B, and aralia-saponin II bind to aerolysin with a higher affinity as compared to other drugs and at functionally important amino acids of aerolysin. Hence, these molecules can act as an effective therapeutics for inhibiting the aerolysin pore formation and curtail the severity of Aeromonas infection.Communicated by Ramaswamy H. Sarma.

FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients.

Background: FOXO3, a member of the FOX transcription factor family, is frequently described as being deregulated in cancer. Additionally, notable role of FOXO3 can be easily recognized in the process of ageing and survival. Even though various studies have been done to acknowledge the tumour-suppressive or oncogenic role of FOXO3 in cancer, still there exist a lack of understanding in terms of cancer prognosis and treatment. Therefore, to provide better insight, our study aims to evaluate the role and function of FOXO3 in breast cancer in Indian female patients. We examined the FOXO3 expression levels in breast cancer samples by analyzing mRNA and protein expression along with its clinicopathological parameters. Results: A total of 127 cases of breast cancer with equal normal cases (n=127) were assessed with methylation (MS-PCR), Immunohistochemistry (IHC), mRNA expression using Real-time PCR was analysed and 66.14% cases at mRNA level were found to be downregulated, while 81.10% of cases had little or very little protein expression. Our data state, the promoter hypermethylation of the FOXO3 gene and the downregulated protein expression are significantly correlated (p=0.0004). Additionally, we found a significant correlation between the level of FOXO3 mRNA with ER (p=0.04) and status of lymph node (p=0.01) along with this. Conclusion: Data suggests the prognostic significance and the tumour-suppressive role of FOXO3 in breast cancer cases studied in India. However, there is a need for the extended research targeting FOXO3 to measure its clinical potential and develop well-defined therapeutic strategies.

Buffalo Infection by Fasciola gigantica Transmitted by Radix acuminata in Uttar Pradesh, India: A Molecular Tool to Improve Snail Vector Epidemiology Assessments and Control Surveillance.

PURPOSE: Fascioliasis is caused by Fasciola species transmitted by freshwater Lymnaeidae snails and infecting herbivorous mammals and humans worldwide. In southern Asia, fascioliasis is a problem in livestock from the Near East to Bangladesh, where recent human infection reports are worrying. In this region, Fasciola gigantica is transmitted by species of the Radix auricularia superspecies group. In the densely populated northern Indian state of Uttar Pradesh, livestock appears infected throughout. The economic importance of buffaloes highlights the need to control their very high infection rates. METHODS: In the Gorakhpur area, a molecular method based on the two specific primer sets of genomic DNA was applied to fasciolids from buffaloes slaughtered in local abattoirs and cercariae from R. acuminata snails from freshwater collections. RESULTS: PCR products and sequences demonstrated that the cercariae belonged to F. gigantica and that R. acuminata acts as vector for its transmission to buffaloes. The 72.0% rate found in one transmission focus appears to be the highest worldwide record of fasciolid infection in a lymnaeid population. Lymnaeid prevalences and burdens found close to human communities indicate a very high infection risk. CONCLUSION: This method is simple, fast and cheap because there is no need for sequencing, it differentiates between fasciolid species and between fasciolids and other trematodes infecting R. acuminata, facilitates epidemiological surveys, and is useful for surveillance to evaluate the efficiency of control measures. Within climate change predictions, future increases of rain events and floods suggest the need for control and surveillance efforts in this endemic area.

Recombinant outer membrane protein OmpC induces protective immunity against Aeromonashydrophila infection in Labeorohita.

Aeromonashydrophila is an opportunistic pathogen that causes enormous loss to aquaculture industry. The outer membrane proteins of Aeromonas help in bacterium-host interaction, and are considered to be potential vaccine candidates. In the present study, we evaluated immunogenicity and protective efficacy of recombinant OmpC (rOmpC) of A. hydrophila in Indian major carp, Labeorohita. The rOmpC-vaccinated fish produced specific anti-rOmpC antibodies with a significant antibody titer, and the antisera could specifically detect the rOmpC in the cell lysates of Escherichia coli expressing rOmpC and cross-react with different Aeromonas lysates, indicating the suitability of the anti-rOmpC antisera to detect Aeromonas infection. A significant increase was noted in ceruloplasmin level, myeloperoxidase and anti-protease activities in transient and temporal manner the sera of the rOmpC-immunized fish as compared to PBS-control fish. Higher agglutination- and hemolytic activity titers in the anti-rOmpC antisera indicate stimulation of innate immunity. Expression of immune-related genes comprising various acute phase proteins, cytokines and inflammatory response molecules were modulated in the head kidney of rOmpC-immunized L. rohita. While IgM, IL1ß, and TLR-22 were significantly up-regulated at early time points (3 h-72 h), the others showed a transient augmentation at both early and later time points (SOD, lysozymes C and G, NKEF-B, C3, CXCa and TNF-α) in the rOmpC-immunized L. rohita in comparison to PBS-injected controls. These data suggest that the rOmpC-induced immune response is temporally regulated to confer immunity. In vivo challenge of the rOmpC-immunized fish with A. hydrophila showed significantly greater survival when compared to PBS-injected control fish. Thus, our results highlight the immunomodulatory role of rOmpC and demonstrate its protective efficacy in L. rohita, along with the use of anti-rOmpC antisera in detecting Aeromonas infections.

Secondary Metabolites From Halotolerant Plant Growth Promoting Rhizobacteria for Ameliorating Salinity Stress in Plants.

Soil salinization has emerged as one of the prime environmental constraints endangering soil quality and agricultural productivity. Anthropogenic activities coupled with rapid pace of climate change are the key drivers of soil salinity resulting in degradation of agricultural lands. Increasing levels of salt not only impair structure of soil and its microbial activity but also restrict plant growth by causing harmful imbalance and metabolic disorders. Potential of secondary metabolites synthesized by halotolerant plant growth promoting rhizobacteria (HT-PGPR) in the management of salinity stress in crops is gaining importance. A wide array of secondary metabolites such as osmoprotectants/compatible solutes, exopolysaccharides (EPS) and volatile organic compounds (VOCs) from HT-PGPR have been reported to play crucial roles in ameliorating salinity stress in plants and their symbiotic partners. In addition, HT-PGPR and their metabolites also help in prompt buffering of the salt stress and act as biological engineers enhancing the quality and productivity of saline soils. The review documents prominent secondary metabolites from HT-PGPR and their role in modulating responses of plants to salinity stress. The review also highlights the mechanisms involved in the production of secondary metabolites by HT-PGPR in saline conditions. Utilizing the HT-PGPR and their secondary metabolites for the development of novel bioinoculants for the management of saline agro-ecosystems can be an important strategy in the future.

Revisiting the plant growth-promoting rhizobacteria: lessons from the past and objectives for the future.

Plant beneficial rhizobacteria (PBR) is a group of naturally occurring rhizospheric microbes that enhance nutrient availability and induce biotic and abiotic stress tolerance through a wide array of mechanisms to enhance agricultural sustainability. Application of PBR has the potential to reduce worldwide requirement of agricultural chemicals and improve agro-ecological sustainability. The PBR exert their beneficial effects in three major ways; (1) fix atmospheric nitrogen and synthesize specific compounds to promote plant growth, (2) solubilize essential mineral nutrients in soils for plant uptake, and (3) produce antimicrobial substances and induce systemic resistance in host plants to protect them from biotic and abiotic stresses. Application of PBR as suitable inoculants appears to be a viable alternative technology to synthetic fertilizers and pesticides. Furthermore, PBR enhance nutrient and water use efficiency, influence dynamics of mineral recycling, and tolerance of plants to other environmental stresses by improving health of soils. This report provides comprehensive reviews and discusses beneficial effects of PBR on plant and soil health. Considering their multitude of functions to improve plant and soil health, we propose to call the plant growth-promoting bacteria (PGPR) as PBR.

Bulbine frutescens phytochemical inhibits notch signaling pathway and induces apoptosis in triple negative and luminal breast cancer cells.

Breast cancer (BCa) is the most commonly diagnosed lethal cancer in women worldwide. Notch signaling pathway is directly linked to BCa recurrence and aggressiveness. Natural remedies are becoming a prime choice to overcome against cancer due to lesser side effect and cost-effectiveness. Bulbine frutescens (Asphodelaceae), a traditional medicinal plant in South Africa possess bioactive flavonoids and terpenoids. Polar (methanol) and non-polar (hexane) B. frutescens plant extracts were prepared. GC-MS analysis revealed the differential presence of secondary metabolites in both methanolic and hexane extracts. We hereby first time evaluated the anticancer potential of B. frutescens methanolic and hexane extract in triple-negative and luminal BCa cells. B. frutescens extracts significantly decreased cell viability (IC50 4.8-28.4 µg/ml) and induced cell cycle arrest at G1 phase in MDA-MB-231 and T47D cells as confirmed by spectrophotometry and flow cytometry technique. RT-PCR analysis of cell cycle (cyclin D1, CDK4, and p21) and apoptosis modulating genes (caspase 3, Bcl2 and survivin) revealed upexpression of p21, and caspase 3, and down expression of cyclin D1, CDK4, Bcl2 and survivin genes in extract-treated BCa cells. Fluorescence spectrophotometry and confocal microscopy showed B. frutescens induced nuclear morphology and mitochondrial integrity disruption, and increased reactive oxygen species production in MDA-MB-231 and T47D cells. Flow cytometric apoptosis analysis of B. frutescens extracts treated MDA-MB-231 cells showed ≈13% increase in early apoptotic population in comparison to non-treated cells. Dual-Luciferase Reporter assay confirmed notch promoter inhibitory activity of B. frutescens extracts. Moreover, RTPCR analysis showed down regulation of notch responsive genes (Hes1 and Hey1) at transcription levels in extract-treated BCa cells. Western Blot analysis showed increased procaspase 3 protein expression in extract-treated BCa cells. In all the assays methanolic extract showed better anti-cancer properties. Literature-based identification of methanol soluble phytochemicals in B. frutescens and in silico docking study revealed Bulbineloneside D as a potent ϒ-secretase enzyme inhibitor. In comparison to standard notch inhibitor, lead phytochemical showed two additional hydrophobic interactions with Ala80 and Leu81 amino acids. In conclusion, B. frutescens phytochemicals have cell cycle arrest, ROS production, apoptosis induction, and mitochondria membrane potential disruption efficacy in breast cancer cells. B. frutescens phytochemicals have the ability to downregulate the notch signaling pathway in triple-negative and luminal breast cancer cells.