Soil and Mineral Nutrients in Plant Health: A Prospective Study of Iron and Phosphorus in the Growth and Development of Plants.

Plants being sessile are exposed to different environmental challenges and consequent stresses associated with them. With the prerequisite of minerals for growth and development, they coordinate their mobilization from the soil through their roots. Phosphorus (P) and iron (Fe) are macro- and micronutrient; P serves as an important component of biological macromolecules, besides driving major cellular processes, including photosynthesis and respiration, and Fe performs the function as a cofactor for enzymes of vital metabolic pathways. These minerals help in maintaining plant vigor via alterations in the pH, nutrient content, release of exudates at the root surface, changing dynamics of root microbial population, and modulation of the activity of redox enzymes. Despite this, their low solubility and relative immobilization in soil make them inaccessible for utilization by plants. Moreover, plants have evolved distinct mechanisms to cope with these stresses and coregulate the levels of minerals (Fe, P, etc.) toward the maintenance of homeostasis. The present study aims at examining the uptake mechanisms of Fe and P, and their translocation, storage, and role in executing different cellular processes in plants. It also summarizes the toxicological aspects of these minerals in terms of their effects on germination, nutrient uptake, plant-water relationship, and overall yield. Considered as an important and indispensable component of sustainable agriculture, a separate section covers the current knowledge on the cross-talk between Fe and P and integrates complete and balanced information of their effect on plant hormone levels.

Study of Amiloride Binding to Human Serum Albumin: Insights from Thermodynamic, Spectroscopic, and Molecular Docking Investigations.

This study was undertaken to investigate the interaction between the sodium channel blocker amiloride (AML) and human serum albumin (HSA). A combination of multi-spectroscopic techniques and computational methods were employed to identify the AML binding site on HSA and the forces responsible for the formation of the HSA-AML complex. Our findings revealed that AML specifically binds to Sudlow's site II, located in subdomain IIIA of HSA, and that the complex formed is stabilized using van der Waals hydrogen-bonding and hydrophobic interactions. FRET analysis showed that the distance between AML and Trp214 was optimal for efficient quenching. UV-Vis spectroscopy and circular dichroism indicated minor changes in the structure of HSA after AML binding, and molecular dynamics simulations (MDS) conducted over 100 ns provided additional evidence of stable HSA-AML-complex formation. This study enhances understanding of the interaction between AML and HSA and the mechanism responsible.

CRISPR/Cas: An intriguing genomic editing tool with prospects in treating neurodegenerative diseases.

The CRISPR/Cas genome editing tool has led to a revolution in biological research. Its ability to target multiple genomic loci simultaneously allows its application in gene function and genomic manipulation studies. Its involvement in the sequence specific gene editing in different backgrounds has changed the scenario of treating genetic diseases. By unravelling the mysteries behind complex neuronal circuits, it not only paved way in understanding the pathogenesis of the disease but helped in the development of large animal models of different neuronal diseases; thereby opened the gateways of successfully treating different neuronal diseases. This review explored the possibility of using of CRISPR/Cas in engineering DNA at the embryonic stage, as well as during the functioning of different cell types in the brain, to delineate implications related to the use of this super-specialized genome editing tool to overcome various neurodegenerative diseases that arise as a result of genetic mutations.

Screening of natural compounds for identification of novel inhibitors against ß-lactamase CTX-M-152 reported among Kluyvera georgiana isolates: An in vitro and in silico study.

Multidrug resistance due to the expression of extended spectrum ß-lactamases (ESBLs) by bacterial pathogens is an alarming health concern with huge socio-economic burden. Here, 102 bacterial isolates from Wastewater treatment plants (WTPs) were screened for resistance to different antibiotics. Kirby-Bauer method and phenotypic disc confirmatory test confirmed the prevalence of 20 ESBLs. Polymerase chain reaction-based detection confirmed 11 blaCTX-M positive bacterial isolates. Genotyping of bacterial isolates by 16S rRNA gene sequencing showed the dissemination of blaCTX-M in Escherichia fergusonii, Escherichia coli, Shigella sp., Kluyvera georgiana and Enterobacter sp. Amongst Kluyvera georgiana isolates, two were harboring blaCTX-M-152. The 3D model of CTX-M-152 protein was generated using SwissProt and characterized by Ramachandran plot and SAVES. A library of natural compounds was screened to identify novel CTX-M-152 inhibitor(s). High-throughput virtual screening (HTVS), standard precision (SP) and extra precision (XP) docking led to the identification of five natural compounds (Naringin dihydrochalcone, Salvianolic acid B, Inositol, Guanosine and Ellagic acid) capable of binding to active site of CTX-M-152. Futher, characterization by MM-GBSA (Molecular Mechanism General Born Surface Area), and ADMET (Adsorption, Distribution, Metabolism, Excretion and Toxicity) showed that Ellagic acid was the most potent inhibitor of CTX-M-152. Molecular dynamics simulation also confirmed that Ellagic acid form a stable complex with CTX-M-152. The ability of Ellagic acid to inhibit growth of bacteria harboring CTX-M-152 was confirmed by MIC (Minimum Inhibitory Concentration; broth dilution method) and Zone of Inhibition (ZOI) studies with respect to Cefotaxime. The identification of a novel inhibitor of CTX-M-152 from a natural source holds promise for employment in the control of bacterial infections.

Mechanistic insights of CRISPR/Cas-mediated genome editing towards enhancing abiotic stress tolerance in plants.

Abiotic stresses such as temperature (high/low), drought, salinity, and others make the environment hostile to plants. Abiotic stressors adversely affect plant growth and development; and thereby makes a direct impact on overall plant productivity. Plants confront stress by developing an internal defense system orchestrated by compatible solutes, reactive oxygen species scavengers and phytohormones. However, routine exposure to unpredictable environmental stressors makes it essential to equip plants with a system that contributes to sustainable agricultural productivity, besides imparting multi-stress tolerance. The sustainable approach against abiotic stress is accomplished through breeding of tolerant cultivars. Though eco-friendly, tedious screening and crossing protocol limits its usage to overcome stress and in attaining the goal of global food security. Advancement on the technological front has enabled adoption of genomic engineering approaches to perform site-specific modification in the plant genome for improving adaptability, increasing the yield and in attributing resilience against different stressors. Of the different genome editing approaches, CRISPR/Cas has revolutionized biological research with wider applicability to crop plants. CRISPR/Cas emerged as a versatile tool in editing genomes for desired traits in highly accurate and precise manner. The present study summarizes advancement of the CRISPR/Cas genome editing tool in its adoption to manipulate plant genomes for novel traits towards developing high-yielding and climate-resilient crop varieties.

Adipogenic function of mouse tetranectin and identification of its functional domain.

Tetranectin (TN), a plasminogen (Plg) binding protein, enhances the Plg activator (PA)-catalyzed activation of Plg to plasmin (Pln). Previously, TN was identified as an adipogenic serum protein, which promotes adipocyte differentiation. In the present study, we investigated the adipogenic function of mouse TN using recombinant proteins (rmTNs) in full-length and domain-truncated forms. Adipocyte differentiation in TN-depleted-FBS-media was significantly enhanced by rmTNs supplementation. The adipogenic effect of rmTNs was found to be dependent on the presence of a Plg binding domain, indicating the domain is essential for the adipogenic function of mTN. In addition, these results suggested the involvement of Plg activation, however Plg, PA and Pln appeared to have no direct effect on adipocyte differentiation. This study demonstrates the adipogenic function of mTN, which is dependent on the Plg binding domain as its functional domain.

Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and In Silico Approaches.

Cyclobenzaprine hydrochloride (CBH) is a well-known muscle relaxant that is widely used to relieve muscle spasms and other pain associated with acute musculoskeletal conditions. In this study, we elucidated the binding characteristics of this muscle relaxant to human serum albumin (HSA). From a pharmaceutical and biochemical viewpoint, insight into the structure, functions, dynamics, and features of HSA-CBH complex holds great importance. The binding of CBH with this major circulatory transport protein was studied using a combination of biophysical approaches such as UV-VIS absorption, fluorescence quenching, and circular dichroism (CD) spectroscopy. Various in silico techniques, molecular docking and molecular dynamics, were also used to gain deeper insight into the binding. A reduction in the fluorescence intensities of HSA-CBH complex with a constant increase in temperature, revealed the static mode of protein fluorescence quenching upon CBH addition, which confirmed the formation of the HSA-CBH ground state complex. The alteration in the UV-VIS and far-UV CD spectrum indicated changes in both secondary and tertiary structures of HSA upon binding of CBH, further proving CBH binding to HSA. The analysis of thermodynamic parameters ∆H° and ∆S° showed that binding of CBH to HSA was dominated by intermolecular hydrophobic forces. The results of the molecular docking and molecular dynamics simulation studies also confirmed the stability of the complex and supported the experimental results.

Insight of the Interaction between 2,4-thiazolidinedione and Human Serum Albumin: A Spectroscopic, Thermodynamic and Molecular Docking Study.

Thiazolidinedione derivatives (TZDs) have attracted attention because of their pharmacological effects. For example, certain TZDs have been reported to ameliorate type II diabetes by binding and activating PPARs (peroxisome proliferator-activated receptors). Nonetheless, no information is available on the interaction between the heterocyclic 2, 4-thiazolidinedione (2,4-TZD) moiety and serum albumin, which could affect the pharmacokinetics and pharmacodynamics of TZDs. In this study, we investigated the binding of 2,4-TZD to human serum albumin (HSA). Intrinsic fluorescence spectroscopy revealed a 1:1 binding stoichiometry between 2,4-TZD and HSA with a binding constant (Kb) of 1.69 ± 0.15 × 103 M-1 at 298 K. Isothermal titration calorimetry studies showed that 2,4-TZD/HSA binding was an exothermic and spontaneous reaction. Molecular docking analysis revealed that 2,4-TZD binds to HSA subdomain IB and that the complex formed is stabilized by van der Waal's interactions and hydrogen bonds. Molecular dynamics simulation confirmed the stability of the HSA-TZD complex. Further, circular dichroism and 3D fluorescence studies showed that the global conformation of HSA was slightly altered by 2,4-TZD binding, enhancing its stability. The results obtained herein further help in understanding the pharmacokinetic properties of thiazolidinedione.

The onus of cannabinoids in interrupting the molecular odyssey of breast cancer: A critical perspective on UPRER and beyond.

Cannabinoids, commonly used for medicinal and recreational purposes, consist of various complex hydrophobic molecules obtained from Cannabis sativa L. Acting as an inhibitory molecule; they have been investigated for their antineoplastic effect in various breast tumor models. Lately, it was found that cannabinoid treatment not only stimulates autophagy-mediated apoptotic death of tumor cells through unfolded protein response (UPRER) activated downstream effectors, but also imposes cell cycle arrest. The exploitation of UPRER tumors as such is believed to be a major molecular event and is therefore employed in understanding the development and progression of breast tumor. Simultaneously, the data on clinical trials following administration of cannabinoid is currently being explored to find its role not only in palliation but also in the treatment of breast cancer. The present study summarizes new achievements in understanding the extent of therapeutic progress and highlights recent developments in cannabinoid biology towards achieving a better cure of breast cancer through the exploitation of different cannabinoids.

Towards understanding cellular structure biology: In-cell NMR.

To watch biological macromolecules perform their functions inside the living cells is the dream of any biologists. In-cell nuclear magnetic resonance is a branch of biomolecular NMR spectroscopy that can be used to observe the structures, interactions and dynamics of these molecules in the living cells at atomic level. In principle, in-cell NMR can be applied to different cellular systems to achieve biologically relevant structural and functional information. In this review, we summarize the existing approaches in this field and discuss its applications in protein interactions, folding, stability and post-translational modifications. We hope this review will emphasize the effectiveness of in-cell NMR for studies of intricate biological processes and for structural analysis in cellular environments.

Implications of molecular diversity of chitin and its derivatives.

Chitin is a long unbranched polysaccharide, made up of ß-1,4-linked N-acetylglucosamine which forms crystalline fiber-like structure. It is present in the fungal cell walls, insect and crustacean cuticles, nematode eggshells, and protozoa cyst. We provide a critical appraisal on the chemical modifications of chitin and its derivatives in the context of their improved efficacy in medical applications without any side effect. Recent advancement in nanobiotechnology has helped to synthesize several chitin derivatives having significant biological applications. Here, we discuss the molecular diversity of chitin and its applications in enzyme immobilization, wound healing, packaging material, controlled drug release, biomedical imaging, gene therapy, agriculture, biosensor, and cosmetics. Also, we highlighted chitin and its derivatives as an antioxidant, antimicrobial agent, anticoagulant material, food additive, and hypocholesterolemic agent. We envisage that chitin and chitosan-based nanomaterials with their potential applications would augment nanobiotechnology and biomedical industries.

Tetrameric assembly of hGBP1 is crucial for both stimulated GMP formation and antiviral activity.

Interferon-γ inducible human guanylate binding protein-1 (hGBP1) shows a unique characteristic that hydrolyses GTP to a mixture of GDP and GMP through successive cleavages, with GMP being the major product. Like other large GTPases, hGBP1 undergoes oligomerization upon substrate hydrolysis, which is essential for the stimulation of activity. It also exhibits antiviral activity against many viruses including hepatitis C. However, which oligomeric form is responsible for the stimulated activity leading to enhanced GMP formation and its influence on antiviral activity, are not properly understood. Using mutant and truncated proteins, our data indicate that transition-state-induced tetramerization is associated with higher rate of GMP formation. This is supported by chimaeras that are defective in both tetramerization and enhanced GMP formation. Unlike wild-type protein, chimaeras did not show allosteric interactions, indicating that tetramerization and enhanced GMP formation are allosterically coupled. Hence, we propose that after the cleavage of the first phosphoanhydride bond GDP·Pi-bound protein dimers transiently associate to form a tetramer that acts as an allosteric switch for higher rate of GMP formation. Biochemical and biophysical studies reveal that sequential conformational changes and interdomain communications regulate tetramer formation via dimer. Our studies also show that overexpression of the mutants, defective in tetramer formation in Rep2a cells do not inhibit proliferation of hepatitis C virus, indicating critical role of a tetramer in the antiviral activity. Thus, the present study not only highlights the importance of hGBP1 tetramer in stimulated GMP formation, but also demonstrates its role in the antiviral activity against hepatitis C virus.

Protein aggregation, misfolding and consequential human neurodegenerative diseases.

Proteins are major components of the biological functions in a cell. Biology demands that a protein must fold into its stable three-dimensional structure to become functional. In an unfavorable cellular environment, protein may get misfolded resulting in its aggregation. These conformational disorders are directly related to the tissue damage resulting in cellular dysfunction giving rise to different diseases. This way, several neurodegenerative diseases such as Alzheimer, Parkinson Huntington diseases and amyotrophic lateral sclerosis are caused. Misfolding of the protein is prevented by innate molecular chaperones of different classes. It is envisaged that work on this line is likely to translate the knowledge into the development of possible strategies for early diagnosis and efficient management of such related human diseases. The present review deals with the human neurodegenerative diseases caused due to the protein misfolding highlighting pathomechanisms and therapeutic intervention.

Testing the dependence of stabilizing effect of osmolytes on the fractional increase in the accessible surface area on thermal and chemical denaturations of proteins.

Here we have generated two different denatured states using heat- and guanidinium chloride (GdmCl)-induced denaturations of three disulfide bond free proteins (barstar, cytochrome-c and myoglobin). We have observed that these two denatured states of barstar and myoglobin are structurally and energetically different, for, heat-induced denatured state contains many un-melted residual structure that has a significant amount of secondary and tertiary interactions. We show that structural properties of the denatured state determine the magnitude of the protein stabilization in terms of Gibbs free energy change (ΔGD°) induced by an osmolyte, i.e., the greater the exposed surface area, the greater is the stabilization. Furthermore, we predicted the m-values (ability of osmolyte to fold or unfold proteins) using Tanford's transfer-free energy model for the transfer of proteins to osmolyte solutions. We observed that, for each protein, m-value is comparable with our experimental data in cases of TMAO (trimethylamine-N-oxide) and sarcosine. However, a significant discrepancy between predicted and experimental m-values were observed in the case of glycine-betaine.

Folding and stability studies on C-PE and its natural N-terminal truncant.

The conformational and functional state of biliproteins can be determined by optical properties of the covalently linked chromophores. α-Subunit of most of the phycoerythrin contains 164 residues. Recently determined crystal structure of the naturally truncated form of α-subunit of cyanobacterial phycoerythrin (Tr-αC-PE) lacks 31 N-terminal residues present in its full length form (FL-αC-PE). This provides an opportunity to investigate the structure-function relationship between these two natural forms. We measured guanidinium chloride (GdmCl)-induced denaturation curves of FL-αC-PE and Tr-αC-PE proteins, followed by observing changes in absorbance at 565nm, fluorescence at 350 and 573nm, and circular dichroism at 222nm. The denaturation curve of each protein was analyzed for ΔGD(∘), the value of Gibbs free energy change on denaturation (ΔGD) in the absence of GdmCl. The main conclusions of the this study are: (i) GdmCl-induced denaturation (native state↔denatured state) of FL-αC-PE and Tr-αC-PE is reversible and follows a two-state mechanism, (ii) FL-αC-PE is 1.4kcalmol(-1) more stable than Tr-αC-PE, (iii) truncation of 31-residue long fragment that contains two α-helices, does not alter the 3-D structure of the remaining protein polypeptide chain, protein-chromophore interaction, and (iv) amino acid sequence of Tr-αC-PE determines the functional structure of the phycoerythrin.

Insight into the function of tetranectin in human diseases: A review and prospects for tetranectin-targeted disease treatment.

Tetranectin (TN), a serum protein, is closely associated with different types of cancers. TN binds plasminogen and promotes the proteolytic activation of plasminogen into plasmin, which suggests that TN is involved in remodeling the extracellular matrix and cancer tissues during cancer development. TN is also associated with other diseases, such as developmental disorders, cardiovascular diseases, neurological diseases, inflammation, and diabetes. Although the functional mechanism of TN in diseases is not fully elucidated, TN binds different proteins, such as structural protein, a growth factor, and a transcription regulator. Moreover, TN changes and regulates protein functions, indicating that TN-binding proteins mediate the association between TN and diseases. This review summarizes the current knowledge of TN-associated diseases and TN functions with TN-binding proteins in different diseases. In addition, potential TN-targeted disease treatment by inhibiting the interaction between TN and its binding proteins is discussed.

Unleashed Treasures of Solanaceae: Mechanistic Insights into Phytochemicals with Therapeutic Potential for Combatting Human Diseases.

Plants that possess a diverse range of bioactive compounds are essential for maintaining human health and survival. The diversity of bioactive compounds with distinct therapeutic potential contributes to their role in health systems, in addition to their function as a source of nutrients. Studies on the genetic makeup and composition of bioactive compounds have revealed them to be rich in steroidal alkaloids, saponins, terpenes, flavonoids, and phenolics. The Solanaceae family, having a rich abundance of bioactive compounds with varying degrees of pharmacological activities, holds significant promise in the management of different diseases. Investigation into Solanum species has revealed them to exhibit a wide range of pharmacological properties, including antioxidant, hepatoprotective, cardioprotective, nephroprotective, anti-inflammatory, and anti-ulcerogenic effects. Phytochemical analysis of isolated compounds such as diosgenin, solamargine, solanine, apigenin, and lupeol has shown them to be cytotoxic in different cancer cell lines, including liver cancer (HepG2, Hep3B, SMMC-772), lung cancer (A549, H441, H520), human breast cancer (HBL-100), and prostate cancer (PC3). Since analysis of their phytochemical constituents has shown them to have a notable effect on several signaling pathways, a great deal of attention has been paid to identifying the biological targets and cellular mechanisms involved therein. Considering the promising aspects of bioactive constituents of different Solanum members, the main emphasis was on finding and reporting notable cultivars, their phytochemical contents, and their pharmacological properties. This review offers mechanistic insights into the bioactive ingredients intended to treat different ailments with the least harmful effects for potential applications in the advancement of medical research.

Elaeagnus umbellata: A miraculous shrub with potent health-promoting benefits from Northwest Himalaya.

Medicinal plants encompassing a series of bioactive compounds have gained significant importance for use in the treatment of different diseases. Of them, Elaeagnus umbellata Thunb. (Deciduous shrub found in dappled shade, and sunny hedge) exhibits high medicinal value, with a widespread distribution across the Pir Panjal region of the Himalayas. Fruits serve as an excellent source of vitamins, minerals, and other essential compounds that exhibits hypolipidemic, hepatoprotective, and nephroprotective effects. The phytochemical fingerprint of berries revealed them to have a high content of polyphenols (with major proportion of anthocyanins), followed by monoterpenes and vitamin C. Extract of fruits help in regulating the digestion and absorption of glucose and reduces inflammation and oxidative stress. The phytosterols upholding anticoagulant activity serve the purpose of causing decrease in angina and the blood cholesterol levels. Phytochemicals such as eugenol, palmitic acid, and methyl palmitate exhibit potent antibacterial activity against broad range of disease-causing agents. Additionally, a high percentage of essential oils attribute it with the property of being effective against heart ailments. The present study highlights the importance of E. umbellata in traditional medicinal practices, and summarizes the knowledge of its bioactive constituents and a snapshot vision of remarkable biological activities like antimicrobial, antidiabetic, antioxidant, etc towards understanding its role in the development of efficient drug regimens for use in the treatment of different diseases. It also underlines the need to explore the plant on nutritional aspects to strengthen the existing knowledge pertaining to health promoting potential of E. umbellata.

Plant Growth Promoting Rhizobacteria in Plant Health: A Perspective Study of the Underground Interaction.

Plants are affected by various environmental stresses such as high or low temperatures, drought, and high salt levels, which can disrupt their normal cellular functioning and impact their growth and productivity. These stressors offer a major constraint to the morphological, physiological, and biochemical parameters; thereby attributing serious complications in the growth of crops such as rice, wheat, and corn. Considering the strategic and intricate association of soil microbiota, known as plant growth-promoting rhizobacteria (PGPR), with the plant roots, PGPR helps plants to adapt and survive under changing environmental conditions and become more resilient to stress. They aid in nutrient acquisition and regulation of water content in the soil and also play a role in regulating osmotic balance and ion homeostasis. Boosting key physiological processes, they contribute significantly to the alleviation of stress and promoting the growth and development of plants. This review examines the use of PGPR in increasing plant tolerance to different stresses, focusing on their impact on water uptake, nutrient acquisition, ion homeostasis, and osmotic balance, as well as their effects on crop yield and food security.

Tetranectin targeting by epigallocatechin gallate suppresses colon cancer cell proliferation.

Tetranectin is a serum protein that binds to plasminogen and enhances its proteolytic activation, which underlies the involvement of tetranectin in the development of several carcinomas including colon cancer. In the present study, structure-based in silico screening of natural products showed that epigallocatechin gallate with anticancer effects binds to tetranectin. Binding to epigallocatechin gallate to tetranectin was confirmed by intrinsic fluorescence quenching assays and isothermal titration calorimetry. Furthermore, epigallocatechin gallate efficiently inhibited the activity of tetranectin to enhance the activation of plasminogen. We also found that tetranectin enhanced the proliferation of CT-26 colon cancer cells. Epigallocatechin gallate showed its cytotoxic effect on CT-26 cells due to its binding to tetranectin and the consequent suppression of the cell proliferation. These results demonstrate that the anticancer effect of epigallocatechin gallate is mediated, at least in part, by inhibiting tetranectin as a binding target.