Amyloid-induced neurodegeneration: A comprehensive review through aggregomics perception of proteins in health and pathology.

Amyloidosis of protein caused by fibrillation and aggregation are some of the most exciting new edges not only in protein sciences but also in molecular medicines. The present review discusses recent advancements in the field of neurodegenerative diseases and therapeutic applications with ongoing clinical trials, featuring new areas of protein misfolding resulting in aggregation. The endogenous accretion of protein fibrils having fibrillar morphology symbolizes the beginning of neuro-disorders. Prognostic amyloidosis is prominent in numerous degenerative infections such as Alzheimer's and Parkinson's disease, Amyotrophic lateral sclerosis (ALS), etc. However, the molecular basis determining the intracellular or extracellular evidence of aggregates, playing a significant role as a causative factor in neurodegeneration is still unclear. Structural conversions and protein self-assembly resulting in the formation of amyloid oligomers and fibrils are important events in the pathophysiology of the disease. This comprehensive review sheds light on the evolving landscape of potential treatment modalities, highlighting the ongoing clinical trials and the potential socio-economic impact of novel therapeutic interventions in the realm of neurodegenerative diseases. Furthermore, many drugs are undergoing different levels of clinical trials that would certainly help in treating these disorders and will surely improve the socio-impact of human life.

Bacoside-A repressed the differentiation and lipid accumulation of 3T3-L1 preadipocytes by modulating the expression of adipogenic genes.

Obesity is one of the more complicated diseases, it can induce numerous life-threatening diseases mainly diabetes mellitus, cardiovascular disease, hypertension, and certain cancers. In this study, we assessed the efficacy of bacoside-A (a dammarane-type triterpenoid saponin derived from the plant Bacopa monniera Linn.) on the adipogenesis of 3T3-L1 preadipocytes. Results of this study illustrated that bacoside-A decreased the differentiation of 3T3-L1 cell, as evidenced by diminution of lipid droplets, which contains triglycerides and other lipids. During the differentiation process, transcription factors, which are mainly participating in adipogenesis such us CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPß, peroxisome proliferator-activated receptor-γ (PPARγ), and sterol regulatory element-binding protein-1c (SREBP-1c), expressions were significantly suppressed by bacoside-A. In addition, bacoside-A showed a potent reduction in genes precise to adipocytes such as lipoprotein lipase (LPL), fatty acid synthase (FAS), adipocyte fatty acid-binding protein (FABP4), and leptin expressions. Further, bacoside-A stimulated the phosphorylation of acetyl CoA carboxylase (ACC) and AMP-activated protein kinase (AMPK). These results demonstrated that bacoside-A has anti-adipogenic effects by regulating the transcription factors involved in adipocyte differentiation. Therefore, bacoside-A might be considered as a potent therapeutic agent for alleviating obesity and hyperlipidemia.

Characterization of physiochemical parameters & their effect on microbial content of smokeless tobacco products marketed in north India.

BACKGROUND OBJECTIVES: Smokeless tobacco (SLT) product consumption has profound public health implications for its users. The p H and moisture of SLTs determine the bioavailability of nicotine, the microbial structure dynamics and the amount of microbial conversion of tobacco alkaloids to carcinogenic tobacco-specific nitrosamines. This study aimed to characterize and compare the p H, moisture and alkaloid content of various SLT products. METHODS: Thirty-seven SLT samples including khaini , snus, moist snuff, gul , pan masala , zarda , Mainpuri kapoori and qiwam were collected from the retail market around the National Capital Region in north India and their p H, moisture, nicotine and alkaloid content were measured. The p H and total nicotine were used to calculate the amount of free nicotine, the readily absorbed form, for each product by applying the Henderson-Hasselbalch equation. RESULTS: The investigation showed that the SLTs varied drastically in their p H (5.36 to 10.27), moisture content (4.7 to 51.7%) and alkaloid content (0.82 to 35.87 mg/g). The p H and free nicotine levels of a product were found to be positively correlated, and the highest free nicotine content was reported in snus samples. Further, the moisture content was seen to impact the bacterial and fungal diversity in these samples. INTERPRETATION CONCLUSIONS: Studies to detect the presence of pathogenic microbiological genera as well as potentially toxic constituents are warranted. The use of SLTs as an alternative to cigarette smoking should be discouraged, and cessation programmes must call attention to their detrimental effects and emphasize on benefits of quitting SLT consumption.

In-silico and in-vitro functional validation of imidazole derivatives as potential sirtuin inhibitor.

Introduction: Epigenetic enzymes can interact with a wide range of genes that actively participate in the progression or repression of a diseased condition, as they are involved in maintaining cellular homeostasis. Sirtuins are a family of Class III epigenetic modifying enzymes that regulate cellular processes by removing acetyl groups from proteins. They rely on NAD+ as a coenzyme in contrast to classical histone deacetylases (HDACs) (Class I, II, and IV) that depend on Zn+ for their activation, linking their function to cellular energy levels. There are seven mammalian sirtuin isoforms (Sirt1-7), each located in different subcellular compartments. Sirtuins have emerged as a promising target, given that inhibitors of natural and synthetic sources are highly warranted. Imidazole derivatives are often investigated as sirtuin regulators due to their ability to interact with the binding site and modulate their activity. Imidazole bestows many possible substitutions on its ring and neighboring atoms to design and synthesize derivatives with specific target selectivity and improved pharmacokinetic properties, optimizing drug development. Materials and methods: Ligand preparation, protein preparation, molecular docking, molecular dynamics, density function theory (DFT) analysis, and absorption, distribution, metabolism, and excretion (ADME) analysis were performed to understand the interacting potential and effective stability of the ligand with the protein. RT-PCR and Western blot analyses were performed to understand the impact of ligands on the gene and protein expression of Class III HDAC enzymes. Results and discussion: We evaluated the sirtuin inhibition activity of our in-house compound comprised of imidazole derivatives by docking the molecules with the protein data bank. ADME properties of all the compounds used in the study were evaluated, and it was found that all fall within the favorable range of being a potential drug. The molecule with the highest docking score was analyzed using DFT, and the specific compound was used to treat the non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H460. The gene and protein expression data support the in-silico finding that the compound Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate has an inhibitory effect on nuclear sirtuins. In conclusion, targeting sirtuins is an emerging strategy to combat carcinogenesis. In this study, we establish that Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate possesses a strong inhibitory effect on nuclear sirtuins in NSCLC cell lines.

Silica sources for arsenic mitigation in rice: machine learning-based predictive modeling and risk assessment.

Arsenic (As) is a well-known human carcinogen, and the consumption of rice is the main pathway for the South Asian people. The study evaluated the impact of the amendments involving CaSiO3, SiO2 nanoparticles, silica solubilizing bacteria (SSB), and rice straw compost (RSC) on mitigation of As toxicity in rice. The translocation of As from soil to cooked rice was tracked, and the results showed that RSC and its combination with SSB were the most effective in reducing As loading in rice grain by 53.2%. To determine the risk of dietary exposure to As, the average daily intake (ADI), hazard quotient (HQ), and incremental lifetime cancer risk (ILCR) were computed. The study observed that the ADI was reduced to one-third (0.24 µg kg-1bw) under RSC+SSB treatments compared to the control. An effective prediction model was established using random forest model and described the accumulation of As by rice grains depend on bioavailable As, P, and Fe which explained 48.5, 5.07%, and 2.6% of the variation in the grain As, respectively. The model anticipates that to produce As benign rice grain, soil should have P and Fe concentration more than 30 mg kg-1 and 12 mg kg-1, respectively if soil As surpasses 2.5 mg kg-1.

Metabolomics-Based Mechanistic Insights into Revealing the Adverse Effects of Pesticides on Plants: An Interactive Review.

In plant biology, metabolomics is often used to quantitatively assess small molecules, metabolites, and their intermediates in plants. Metabolomics has frequently been applied to detect metabolic alterations in plants exposed to various biotic and abiotic stresses, including pesticides. The widespread use of pesticides and agrochemicals in intensive crop production systems is a serious threat to the functionality and sustainability of agroecosystems. Pesticide accumulation in soil may disrupt soil-plant relationships, thereby posing a pollution risk to agricultural output. Application of metabolomic techniques in the assessment of the biological consequences of pesticides at the molecular level has emerged as a crucial technique in exposome investigations. State-of-the-art metabolomic approaches such as GC-MS, LC-MS/MS UHPLC, UPLC-IMS-QToF, GC/EI/MS, MALDI-TOF MS, and 1H-HR-MAS NMR, etc., investigating the harmful effects of agricultural pesticides have been reviewed. This updated review seeks to outline the key uses of metabolomics related to the evaluation of the toxicological impacts of pesticides on agronomically important crops in exposome assays as well as bench-scale studies. Overall, this review describes the potential uses of metabolomics as a method for evaluating the safety of agricultural chemicals for regulatory applications. Additionally, the most recent developments in metabolomic tools applied to pesticide toxicology and also the difficulties in utilizing this approach are discussed.

Proximate Composition and Nutritional Values of Selected Wild Plants of the United Arab Emirates.

Wild plants supply food and shelter to several organisms; they also act as important sources of many nutrients and pharmaceutical agents for mankind. These plants are widely used in traditional medicinal systems and folk medicines. The present study analyzed the nutritional and proximate composition of various compounds in selected wild plants available in the UAE, viz., Chenopodium murale L., Dipterygium glaucum Decne., Heliotropium digynum Asch. ex C.Chr., Heliotropium kotschyi Gürke., Salsola imbricata Forssk., Tribulus pentandrus Forssk., Zygophyllum qatarense Hadidi. The predominant amino acids detected in the plants were glycine, threonine, histidine, cysteine, proline, serine, and tyrosine; the highest quantities were observed in H. digynum and T. pentandrus. The major fatty acids present were long-chain saturated fatty acids; however, lauric acid was only present in S. imbricata. The presence of essential fatty acids such as oleic acid, α-Linoleic acid, and linolenic acid was observed in H. digynum, S. imbricata, and H. kotschyi. These plants also exhibited higher content of nutrients such as carbohydrates, proteins, fats, ash, and fiber. The predominant vitamins in the plants were vitamin B complex and vitamin C. C. murale had higher vitamin A, whereas vitamin B complex was seen in T. pentandrus and D. glaucum. The phosphorus and zinc content were high in T. pentandrus; the nitrogen, calcium, and potassium contents were high in H. digynum, and D. glaucum. Overall, these plants, especially H. digynum and T. pentandrus contain high amounts of nutritionally active compounds and important antioxidants including trace elements and vitamins. The results from the experiment provide an understanding of the nutritional composition of these desert plant species and can be better utilized as important agents for pharmacological drug discovery, food, and sustainable livestock production in the desert ecosystem.

Osmolytes: Wonder molecules to combat protein misfolding against stress conditions.

The proper functioning of any protein depends on its three dimensional conformation which is achieved by the accurate folding mechanism. Keeping away from the exposed stress conditions leads to cooperative unfolding and sometimes partial folding, forming the structures like protofibrils, fibrils, aggregates, oligomers, etc. leading to several neurodegenerative diseases like Parkinson's disease, Alzheimer's, Cystic fibrosis, Huntington, Marfan syndrome, and also cancers in some cases, too. Hydration of proteins is necessary, which may be achieved by the presence of organic solutes called osmolytes within the cell. Osmolytes belong to different classes in different organisms and play their role by preferential exclusion of osmolytes and preferential hydration of water molecules and achieves the osmotic balance in the cell otherwise it may cause problems like cellular infection, cell shrinkage leading to apoptosis and cell swelling which is also the major injury to the cell. Osmolyte interacts with protein, nucleic acids, intrinsically disordered proteins by non-covalent forces. Stabilizing osmolytes increases the Gibbs free energy of the unfolded protein and decreases that of folded protein and vice versa with denaturants (urea and guanidinium hydrochloride). The efficacy of each osmolyte with the protein is determined by the calculation of m value which reflects its efficiency with protein. Hence osmolytes can be therapeutically considered and used in drugs.

A state-of-the-art review on cadmium uptake, toxicity, and tolerance in rice: From physiological response to remediation process.

Cadmium (Cd), a major contaminant of concern, has been extensively reviewed and debated for its anthropogenic global shifts. Cadmium levels in rice grains raise wide food safety concerns. The aim of this review is therefore to capture the dynamics of Cd in paddy soil, translocation pathways of Cd from soil to consumption rice, and assess its bio-accessibility in human consumption. In crop plants, Cd reduces absorption of nutrients and water, triggers oxidative stress, and inhibits plant metabolism. Understanding the mechanisms and behaviour of Cd in paddy soil and rice allows to explain, predict and intervene in Cd transferability from soil to grains and human exposure. Factors affecting Cd movement in soil, and further to rice grain, are elucidated. Recently, physiological and molecular understanding of Cd transport in rice plants have been advanced. Morphological-biochemical characteristics and Cd transporters of plants in such a movement were also highlighted. Ecologically viable remediation approaches, including low input cost agronomic methods, phytoremediation and microbial bioremediation methods, are emerging.

Ecotoxicological implications of residual pesticides to beneficial soil bacteria: A review.

Optimization of crop production in recent times has become essential to fulfil food demands of constantly increasing human populations worldwide. To address this formidable challenge, application of agro-chemicals including synthetic pesticides in intensive farm practices has increased alarmingly. The excessive and indiscriminate application of pesticides to foster food production however, leads to its exorbitant deposition in soils. After accumulation in soils beyond threshold limits, pesticides harmfully affect the abundance, diversity and composition and functions of rhizosphere microbiome. Also, the cost of pesticides and emergence of resistance among insect-pests against pesticides are other reasons that require attention. Due to this, loss in soil nutrient pool cause a substantive reduction in agricultural production which warrant the search for newer environmentally friendly technology for sustainable crop production. Rhizosphere microbes, in this context, play vital roles in detoxifying the polluted environment making soil amenable for cultivation through detoxification of pollutants, rhizoremediation, bioremediation, pesticide degradation, and stress alleviation, leading to yield optimization. The response of soil microorganisms to range of chemical pesticides is variable ranging from unfavourable to the death of beneficial microbes. At cellular and biochemical levels, pesticides destruct the morphology, ultrastructure, viability/cellular permeability, and many biochemical reactions including protein profiles of soil bacteria. Several classes of pesticides also disturb the molecular interaction between crops and their symbionts impeding the overall useful biological processes. The harmful impact of pesticides on soil microbes, however, is poorly researched. In this review, the recent findings related with potential effects of synthetic pesticides on a range of soil microbiota is highlighted. Emphasis is given to find and suggest strategies to minimize the chemical pesticides usage in the real field conditions to preserve the viability of soil beneficial bacteria and soil quality for safe and sustainable crop production even in pesticide contaminated soils.

Bacterial chitinases: genetics, engineering and applications.

Chitinases are a group of enzymes that catalyze chitin hydrolysis and are present in all domains of life. Chitinases belong to different glycosyl hydrolase families with great diversity in their sequences. Microorganisms such as bacteria and fungi produce chitinases for nutrition, and energy, and to parasitize the chitinous hosts. But chitinases from bacteria are of special interest due to their ubiquitous nature and ability to perform under extreme conditions. Chitinases produced by bacteria have been explored for their use in agriculture and industry. In agriculture, their main role is to control chitin-containing insect pests, fungal pathogens, and nematodes. In the seafood industry, they found their role in the management of processing wastes which are mainly chitinous substances. Chitinases are also used to synthesize low molecular weight chitooligomers which are proven bioactive compounds with activities such as anti-tumour, antimicrobial, and immunity modulation. Considering their importance in ecology and biotechnological applications, several bacterial chitinases have been studied in the last two decades. Despite their potential, bacterial chitinases have a few limitations such as low production and lack of secretion systems which make the wild-type enzymes unfit for their applications in industries and other allied sectors. This review is an attempt to collate significant works in bacterial chitinases and their application in various industries and the employment of various tools and techniques for improvement to meet industrial requirements.

A network-based pharmacological investigation to identify the mechanistic regulatory pathway of andrographolide against colorectal cancer.

Traditional cancer treatments have posed numerous obstacles, including toxicity, multiple drug resistance, and financial cost. On the contrary, bioactive phytochemicals used in complementary alternative medicine have recently increased attention due to their potential to modulate a wide range of molecular mechanisms with a less toxic effect. Therefore, we investigated the potential regulatory mechanisms of andrographolide to treat colorectal cancer (CRC) using a network pharmacology approach. Target genes of andrographolide were retrieved from public databases (PharmMapper, Swiss target prediction, Targetnet, STITCH, and SuperPred), while targets related to CRC were retrieved from disease databases (Genecards and DisGeNet) and expression datasets (GSE32323 and GSE8671) were retrieved from gene expression omnibus (GEO). Protein-protein interaction networks (PPI) were generated using STRING and Cytoscape, and hub genes were identified by topology analysis and MCODE. Annotation of target proteins was performed using Gene Ontology (GO) database DAVID and signaling pathway enrichment analysis using the Kyoto Encyclopedia and Genome Database (KEGG). Survival and molecular docking analysis for the hub genes revealed three genes (PDGFRA, PTGS2, and MMP9) were involved in the overall survival of CRC patients, and the top three genes with the lowest binding energy include PDGFRA, MET, and MAPK1. MET gene upregulation and PDGFRA and PTGS2 gene downregulation are associated with the survival of CRC patients, as revealed by box plots and correlation analysis. In conclusion, this study has provided the first scientific evidence to support the use of andrographolide to inhibit cellular proliferation, migration, and growth, and induce apoptosis by targeting the hub genes (PDGFRA, PTGS2, MMP9, MAPK1, and MET) involved in CRC migration and invasion.

Bacillus mojavensis, a Metal-Tolerant Plant Growth-Promoting Bacterium, Improves Growth, Photosynthetic Attributes, Gas Exchange Parameters, and Alkalo-Polyphenol Contents in Silver Nanoparticle (Ag-NP)-Treated Withania somnifera L. (Ashwagandha).

Discharge of nanoparticles (NPs) into aquatic and terrestrial ecosystems during manufacturing processes and from various commercial goods has become a significant ecotoxicological concern. After reaching soil systems, NPs cause deleterious effects on soil fertility, microbial activity, and crop productivity. Taking into consideration the medicinal importance of Withania somnifera (L.) (ashwagandha), the present study assessed the potential hazards of silver nanoparticles (Ag-NPs) and the toxicity amelioration by a metal-tolerant plant growth-promoting rhizobacterium (PGPR). Bacillus mojavensis BZ-13 (NCBI accession number MZ950923) recovered from metal-polluted rhizosphere soil, tolerated an exceptionally high level of Ag-NPs. The growth-regulating substances synthesized by B. mojavensis were increased with increasing concentrations (0-1000 µg mL-1) of Ag-NPs. Also, strain BZ-13 had the ability to form biofilm, produce alginate and exopolysaccharides (EPSs), as well maintain swimming and swarming motilities in the presence of Ag-NPs. Soil application of varying concentrations of Ag-NPs resulted in a dose-related reduction in growth and biochemical features of ashwagandha. In contrast, following soil inoculation, B. mojavensis relieved the Ag-NPs-induced phytotoxicity and improved plant productivity. Root, shoot length, dry biomass, and leaf area increased by 13, 17, 37, 25%, respectively, when B. mojavensis was applied with 25 mg/kg Ag-NPs when compared to noninoculated controls. Furthermore, the soil plant analysis development (SPAD) index, photosystem efficiency (Fv/Fm), PS II quantum yield (FPS II), photochemical quenching (qP), non-photochemical quenching (NpQ), and total chlorophyll and carotenoid content of BZ-13-inoculated plants in the presence of 25 mg Ag-NPs/kg increased by 33, 29, 41, 47, 35, 26, and 25%, respectively, when compared to noninoculated controls that were exposed to the same amounts of NPs. In addition, a significant (p ≤ 0.05) increase in 48, 18, 21, and 19% in withaferin-A (alkaloids), flavonoids, phenols, and tannin content, respectively, was recorded when plants were detached from bacterized and Ag-NP-treated plants. Leaf gas exchange parameters were also modulated in the case of inoculated plants. Furthermore, bacterial inoculation significantly decreased proline, lipid peroxidation, antioxidant enzymes, and Ag-NP's absorption and build-up in phyto-organs. In conclusion, soil inoculation with B. mojavensis may possibly be used as an alternative to protect W. somnifera plants in soil contaminated with nanoparticles. Therefore, phytohormone and other biomolecule-synthesizing and NP-tolerant PGPR strains like B. mojavensis might serve as an agronomically significant and cost-effective remediation agent for augmenting the yield and productivity of medicinally important plants like ashwagandha raised in soil contaminated with nanoparticles in general and Ag-NPs in particular.

EGFR-Based Targeted Therapy for Colorectal Cancer-Promises and Challenges.

Colorectal carcinoma (CRC) is the most lethal and common form of cancer in the world. It was responsible for almost 881,000 cancer deaths in 2018. Approximately 25% of cases are diagnosed at advanced stages with metastasis-this poses challenges for effective surgical control and future tumor-related mortality. There are numerous diagnostic methods that can be used to reduce the risk of colorectal carcinoma. Among these, targeted nanotherapy aims to eliminate the tumor and any metastasis. Active targeting can increase the effectiveness and quantity of drugs delivered to the target site. Antibodies that target overexpressed receptors on cell surfaces and indicators are coupled with drug-loaded carriers. The major target receptors of chemotherapeutic drugs delivery include VEGFR, EGFR, FGFR, HER2, and TGF. On account of its major and diverse roles in cancer, it is important to target EGFR in particular for better tumor selection, as EGFR is overexpressed in 25 to 82% of colorectal carcinoma cases. The EGFR monoclonal immunoglobulins cetuximab/panitumumab can thus be used to treat colorectal cancer. This review examines carriers that contain cetuximab-conjugated therapeutic drugs as well as their efficacy in anticancer activities.

Expression of DNA Mismatch Repair Proteins, PD1 and PDL1 in Barrett's Neoplasia.

BACKGROUND/AIM: Cancers with a microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) status respond to immune checkpoint inhibition (ICI). Regardless of the tumor type, MSI-H/dMMR status is a reliable biomarker for ICI responsiveness. This study aimed at determining the MSI-H status in precursor lesions to esophageal adenocarcinoma (EAC) such as Barrett's esophagus (BE) and BE with either low-grade dysplasia (LGD) or high-grade dysplasia (HGD). PATIENTS AND METHODS: We performed immunohistochemical staining (IHC) for PMS2, MSH6, PD1, and PD-L1. RESULTS: All cases of BE (50), LGD (48), and HGD (50) had intact PMS2 and MSH6 nuclear expression; were negative for PD1; and had a PD-L1 combined positive score (CPS) score <1. One EAC case (2%) was negative for PMS2 nuclear expression. One HGD case (2%) and two EAC cases (4%) were PD1 positive (CPS score <1 applied to PD1). One EAC case (2%) had a CPS score >1, and one EAC case (2%) was MSI-H. MSI-H tumors usually show PD-L1 expression, although the MSI-H EAC in this study had a PD-L1 CPS score of <1. CONCLUSION: Further studies investigating EAC and its precursor lesions for PD1, PD-L1, and dMMR status may be informative regarding the immunogenicity of the evolution of EAC.

Beijerinckia fluminensis BFC-33, a novel multi-stress-tolerant soil bacterium: Deciphering the stress amelioration, phytopathogenic inhibition and growth promotion in Triticum aestivum (L.).

Environmental challenges like drought, salinity, heavy metals and pesticides directly/indirectly influence the environment and decreased the agricultural output. During its long developmental stages, cereal crops including wheat is exposed to a variety of abiotic/biotic stressors. Certain beneficial soil bacteria that can ameliorate environmental stresses can be exploited as crop growth promoters/enhancers under adverse situations. In this study, Beijerinckia fluminensis BFC-33 (accession no. MT672580) isolated from potato rhizosphere tolerated variousabiotic (drought, salinity, temperature, heavy metals, and fungicides) stresses. Strain BFC-33 demonstrated multifarious plant-growth-promoting (PGP) characteristics, such as the production of indole-3-acetic acid, P-solubilization, ACC deaminase, ammonia, siderophore, HCN, EPS, and extracellular enzymes. The antagonistic potential of BFC-33 against major fungal pathogens was ranked: Alternaria alternata (79.2%)>Rhizoctonia solani (69%)>Fusarium oxysporum (23.5%)>Ustilaginoidea virens (17%). Furthermore, bacterization of wheat seeds witha multi-stress-tolerant strain revealed B. fluminensis as a plant growth enhancer and biocontrol agent. For instance, increase in root length (cm) in BFC-33 inoculated wheat exposed to abiotic and biotic stresses at the seedling stage was ranked: B. fluminensis (24.2)>B. fluminensis + 100µgTBZLmL-1 (21.3) = B. fluminensis + 2%PEG (21.3)>B. fluminensis + 100 mM NaCl (19.7)>B. fluminensis + 100µgPbmL-1 (19) = B. fluminensis 100µgMNZBmL-1 (19)>B. fluminensis + A. alternata (17.4)>B. fluminensis + 100µgCdmL-1 (17)>B. fluminensis + F. oxysporum (13.4). In addition, increase in carotenoid accumulation (mg g-1FW) in the foliage of BFC-33 inoculated wheat exposed to fungal infection was ranked: BFC-33 (3.88)>BFC-33+ A. alternata (3.0)>BFC-33+ R. solani (2.78)>BFC-33+ F. oxysporum (2.44). Moreover, BFC-33 inoculation significantly (p ≤ 0.05) reduced stress-induced stressor molecules (proline and TBARS) and electrolyte leakage. Furthermore, B. fluminensis BFC-33 potentially enhanced the defense responses in wheat seedlings by increasing phenylalanine ammonia lyase (PAL), ß-1,3 glucanase, and polyphenol oxidase (PPO), which play a significant role in protecting plants from phytopathogens. Even so, by successfully establishing a product with the requisite effects under field settings, selecting multi-stress-tolerant and antagonistic plant growth promoting rhizobacteria (PGPRs) would be helpful to end-users. Future use of native multi-stress-tolerant bacteria as biocontrol agents in conjunction with existing drought, salinity, heavy metal, and pesticide tolerance might contribute to global food security.

Tolerance of pesticides and antibiotics among beneficial soil microbes recovered from contaminated rhizosphere of edible crops.

A total of 45 beneficial soil bacterial isolates (15 each of Pseudomonas, Azotobacter and phosphate solubilizing bacteria: PSB) recovered from polluted rhizosphere soils were morphologically and biochemically characterized. Bacterial isolates produced indole-3-acetic acid (IAA), phenolate siderophores; SA (salicylic acid) and 2, 3-dihydroxy benzoic acid (2, 3-DHBA), 1-amino cyclopropane 1-carboxylate (ACC) deaminase, solubilised insoluble phosphate (Pi), secreted exopolysaccharides (EPS) and produced ammonia and cyanogenic compound (HCN). Isolates were tested for their tolerance ability against 12 different agrochemicals (chemical pesticides) and 14 antibiotics. Among Pseudomonas, isolate PS1 showed maximum (2183 µg mL-1) tolerance to all tested agrochemicals. Likewise, among all Azotobacter isolates (n = 15), AZ12 showed maximum (1766 µg mL-1) while AZ7 had lowest (950 µg mL-1) tolerance ability to all tested agrochemicals. Moreover, among phosphate solubilizing bacterial isolates, maximum (1970 µg mL-1) and minimum (1308 µg mL-1) tolerance to agrochemicals was represented by PSB8 and PSB13 isolates, respectively. The antibiotic sensitivity/resistance among isolates varied considerably. As an example, Pseudomonas spp. was susceptible to several antibiotics, and inhibition zone differed between 10 mm (polymyxin B) to 34 mm (nalidixic acid). Also, isolate PS2 showed resistance to erythromycin, ciprofloxacin, methicillin, novobiocin and penicillin. The resistance percentage to multiple antibiotics among Azotobacter isolates varied between 7 and 33%. Among PSB isolates, inhibition zone differed between 10 and 40 mm and maximum and minimum resistance percentage to multiple antibiotics was recorded as 47% and 20%, respectively. The persistence of pesticides in agricultural soil may contribute to an increase in multidrug resistance among soil microorganisms. In conclusion, plant growth promoting (PGP) substances releasing soil microorganisms comprising of inherent/intrinsic properties of pesticides tolerance and antibiotics resistance may provide an attractive, agronomically feasible, and long-term prospective alternative for the augmentation of edible crops. However, in future, more research is needed to uncover the molecular processes behind the development of pesticide tolerance and antibiotic resistance among soil microorganisms.

Clinically unsuspected primary hepatic mucosa-associated lymphoid tissue lymphoma collision with an intrahepatic cholangiocarcinoma: A case report and literature review.

A synchronous tumor represents two histologically distinct neoplasms occurring at the same anatomic site, each displaying a distinct tumorigenesis pathway; they can be primary, secondary, or a mixture. The occurrence of an adenocarcinoma and lymphoma has been reported in gastrointestinal and pulmonary sites; however, such a finding in hepatobiliary system remains elusive. Primary hepatic lymphoma is rare, while primary biliary mucosa-associated lymphoid tissue lymphoma is an even rarer event; hence, its collision with an intrahepatic cholangiocarcinoma could be entirely missed both in practice and in the literature. We herein reported a case of biliary mucosa-associated lymphoid tissue lymphoma occurring synchronously with an intrahepatic cholangiocarcinoma in a 78-year-old female following a biopsy-proven intrahepatic cholangiocarcinoma and hepatectomy. Microscopic examination identified atypical lymphoid population intermingled with this intrahepatic cholangiocarcinoma. An immunohistochemical panel uncovered an incidental mucosa-associated lymphoid tissue lymphoma occurring with this intrahepatic cholangiocarcinoma. This clinically missed entity led to comprehensive systemic investigation/staging, with subsequent detection of bone marrow involvement by stage IV lymphoma. This unique case highlights the importance of astute histomorphological evaluation and thorough ancillary studies in identifying a clinically unsuspected neoplasm in close contact with a known tumor.

Mesorhizobium ciceri as biological tool for improving physiological, biochemical and antioxidant state of Cicer aritienum (L.) under fungicide stress.

Fungicides among agrochemicals are consistently used in high throughput agricultural practices to protect plants from damaging impact of phytopathogens and hence to optimize crop production. However, the negative impact of fungicides on composition and functions of soil microbiota, plants and via food chain, on human health is a matter of grave concern. Considering such agrochemical threats, the present study was undertaken to know that how fungicide-tolerant symbiotic bacterium, Mesorhizobium ciceri affects the Cicer arietinum crop while growing in kitazin (KITZ) stressed soils under greenhouse conditions. Both in vitro and soil systems, KITZ imparted deleterious impacts on C. arietinum as a function of dose. The three-time more of normal rate of KITZ dose detrimentally but maximally reduced the germination efficiency, vigor index, dry matter production, symbiotic features, leaf pigments and seed attributes of C. arietinum. KITZ-induced morphological alterations in root tips, oxidative damage and cell death in root cells of C. arietinum were visible under scanning electron microscope (SEM). M. ciceri tolerated up to 2400 µg mL-1 of KITZ, synthesized considerable amounts of bioactive molecules including indole-3-acetic-acid (IAA), 1-aminocyclopropane 1-carboxylate (ACC) deaminase, siderophores, exopolysaccharides (EPS), hydrogen cyanide, ammonia, and solubilised inorganic phosphate even in fungicide-stressed media. Following application to soil, M. ciceri improved performance of C. arietinum and enhanced dry biomass production, yield, symbiosis and leaf pigments even in a fungicide-polluted environment. At 96 µg KITZ kg-1 soil, M. ciceri maximally and significantly (p ≤ 0.05) augmented the length of plants by 41%, total dry matter by 18%, carotenoid content by 9%, LHb content by 21%, root N by 9%, shoot P by 11% and pod yield by 15% over control plants. Additionally, the nodule bacterium M. ciceri efficiently colonized the plant rhizosphere/rhizoplane and considerably decreased the levels of stressor molecules (proline and malondialdehyde) and antioxidant defence enzymes viz. ascorbate peroxidise (APX), guaiacol peroxidise (GPX), catalase (CAT) and peroxidises (POD) of C. arietinum plants when inoculated in soil. The symbiotic strain effectively colonized the plant rhizosphere/rhizoplane. Conclusively, the ability to endure higher fungicide concentrations, capacity to secrete plant growth modulators even under fungicide pressure, and inherent features to lower the level of proline and plant defence enzymes makes this M. ciceri as a superb choice for augmenting the safe production of C. arietinum even under fungicide-contaminated soils.

Biological toxicity assessment of carbamate pesticides using bacterial and plant bioassays: An in-vitro approach.

In recent times, agricultural practices mainly rely on agrochemicals and pesticides to safe-guard edible crops against various pests and to ensure high yields. However, their indiscriminate use may cause severe environmental hazards that directly and negatively affect soil microorganisms and crop productivity. Considering these, present study was aimed to assess the toxicity of carbamate pesticides namely carbamoyl (CBL), methomyl (MML) and carbofuran (CBN) using bacterial and plant (Vigna mungo L.) bioassays. All pesticide doses (25-100 µg mL-1) showed negative effect on bacteria as well as plant. Growth, morphology, survival, cellular respiration and inner membrane permeability of Sinorhizobiumsaheli was hampered when exposed to pesticides. Pesticide induced morphological changes viz. aberrant margins; cellular cracking and distortion/damage in S. saheli were obvious under scanning electron microscope (SEM). The 100 µgCBNmL-1 had maximum inhibitory effect and it reduced survivability of S. saheli by 75%. In addition, biofilm formation ability of S. saheli was inhibited in a pesticides-dose dependent manner and it was statistically (p ≤ 0.05) significant. Pesticides indorsed significant changes in biomarker enzymatic assays and oxidative stress parameters towards S. saheli. Furthermore, at 100 µgCBNmL-1, germination efficiency, root, shoot length, plant survival and tolerance index of V. mungo were decrease by 50, 75, 65, 70 and 66%, respectively over control. Staining of pesticide treated roots with fluorescently labeled dyes propidium iodide (PI) and acridine orange (AO) showed increased oxidative stress, ROS generation and membrane permeability as revealed under confocal laser scanning microscope (CLSM). Furthermore, stressor metabolites and antioxidant enzymes in plant seedlings were progressively enhanced with increasing concentration of pesticides. Conclusively, present finding bestow an insights into a mechanistic approach of carbamate pesticide induced phyto, morpho and cellular toxic effects towards soil bacterium as well as plant with forthcoming implications for designing the pesticides to reduce their toxic/harmful effects.