Molecular Modeling, Interacting Residues and other Structural Analyses for Human SOCS3, Gp130 and JAK Proteins: A Detailed Computational Approach for Proteins Involved in Feedback Inhibition

Background: When STAT3 is activated only by the IL6 family of proteins, then gp130 (having a phosphopeptide motif) interacts with human SOCS3 which further binds to JAK and inhibits its protein kinase activity. Interaction of gp130 with SOCS3 targets only the IL-6 signaling cascade. The interaction occurs when SOCS3 binds to a particular motif on gp130 (centered upon pTyr759) after its phosphorylation. Previously, wet laboratory studies were done but computational exploration for the participating residues remained unexplored. Methodology: The 3D structure of human SOCS3 protein was modeled and its stereo-chemical parameters were satisfied. Crystallographic structures of gp130-phosphopeptide and JAK were studied. After protein docking, the complex underwent minimization and molecular dynamics simulation. Different stability parameters and binding patterns with residues were evaluated Results, Discussion and Conclusion: The best modeled structure of SOCS3 protein was selected and found that it had three helices and seven sheets interspersed with coils. Arg133, Tyr137 and Tyr98 from SOCS3 formed manifold binding patterns with gp130 (mainly with pTyr759 and Glu758). Lys62, Lys63 and Arg65 from SOCS3 were also found to interact with Val762 of gp130. Interactions with JAK were also studied. Residue 53, 62-65, 98, 133, 136 and 137 formed the predominant binding pockets in SOCS3. They can serve as important target sites as well. Altogether, it created elctrostatically charged pockets to accommodate the partner proteins for each other. Gp130 phosphopeptide was observed to be tightly accommodated in the electrostatically positive zones on SOCS3 surface. Net area for solvent accessibility was also found to get drastically reduced implying high participation of residues. Earlier studies documented that the interaction of these three proteins occurs with affinity and have satisfactory association with each other. Here in this study, free energy of binding for the triple protein interaction through the ΔG values helped to infer that SOCS3 interacted spontaneously (in thermodynamic sense). Many helical conformations formed coiled-coils providing high flexibility to interact spontaneously. Most of the interactions were through the responsible SH2 domain (46-127 residue length) of SOCS3. Residues 53, 62-64 and 98 formed coils while the residue number 137adopted sheet conformation from coils. Future Scope: This study shall instigate to block the gp130-binding sites of SOCS3 through targeting of drugs, thereby preventing SOCS3-gp130 interaction. This would allow JAK-STAT signaling cascade which is paramount for several biological functions

The Impact of Microplastic on Human Health

Background: Microplastics are considered an emerging contaminant due to their wide distribution and production in the environment, representing constant exposure to humans. However, little is known about the effects it can trigger in the body. Objective: To establish a concrete relationship between microplastics and the human body, their means of production, exposure, systemic responses, and diseases caused by their presence Methods: In this context, a review article of foreign and national literature was developed, through the PubMed and Scielo Indexers, where studies were found that address the production of plastic, the paths that lead to the production of microplastics and the exposure and damage that it represents to human health, being possible to exclude the literary sums with a publication date before 2017 Results: hey showed that translocation of the residues occurs to the circulatory and lymphatic system via the respiratory and gastrointestinal tracts. Once in the body, microplastic can stimulate a chronic inflammatory response that functions as a precursor to neoplasia and fibrosis, or carry toxic compounds such as heavy metals, endogenous disruptors, biofilms, and persistent organic pollutants. In addition, lung biopsies have shown plastic fibers in patients with respiratory diseases, highlighting a potentially dangerous accumulation. Conclusion: The present moment demonstrates that experimental research to prove the effect of microplastics is extremely necessary, since the controversy among authors and the repetition of information already described affirm that the research done so far is not sufficient.

Oral Toxicity Studies, Histopathology and Anti-Diabetic activity of Polyherbal Extract in STZ induced diabetes in Rats

Background: Diabetes mellitus is a disease and endocrine disorder and it's a growing health problem in various countries. The prevalence of diabetes rises worldwide including South Africa 5.4% in 2025 increases as expected. The World Health Organization (WHO) estimated the diabetes mellitus problem in adults 173 million in developing counties. In this research observation of glucose levels indicated the diabetic state in Wistar rats by resulting from Streptozotocin administration and using a Metformin as a standard dose. This study demonstrated the acute oral toxicity and subacute oral toxicity of ethanolic extract of Saraca asoca leaves and Asparagus racemosus roots and showed the antidiabetic activity. Objective: To perform acute toxicity studies and sub-acute toxicity of the polyherbal ethanolic extract on the vital organ and isolated organ and record and noticed the visible changes on organs of each group of Wistar rats. Explore the hypoglycaemic action of the polyherbal extract of Saraca asoca and Asparagus racemosus. Methods: Wistar rats were divided into required groups for toxicity study first is acute oral toxicity 5,50, 300,2000 mg/kg body weight. Subacute oral toxicity studies were performed by administering a 250, 500, 1000mg/kg body weight. For demonstrating the antidiabetic activity the animals divided into 5 groups 1 normal control given saline group 2 standard dose Metformin compulsory dose groups 3 Streptozotocin-Induced diabetic 150mg/kg body weight body weight, groups 4 ethanolic extracts at a 100mg/kg groups 5 ethanolic extract 200mg/kg. On the last day of all the dosing period examined the Blood glucose levels and body weights of rat and histopathology studied were done by animal sacrifice and cut organs such as tissue pancreas, spleen, heart, lungs, liver, and kidney, placed on the slide and done a microscopic examination. Data selection has been complete by research papers from many databases such as NCBI, Web of science and Science direct and PubMed from year 1989 to 2020 by utilize research. skeywords such as “Antidiabetic”, “Saraca indica”, “Asparagus racemosus”, “ethanolic polyherbal extract”, “oral toxicity study”, “histopathology”, “Streptozotocin. Results : The polyherbal ethanolic extract of Saraca asoca and Asparagus racemosus at a dose of 100mg/kg and 200mg/kg was showed better effects against Streptozotocin-Induced diabetic 150mg/kg body weight body weight. All the extracts showed significantly (P <0.05) and it is safe and non-toxic nature by performed a toxicity study acute and subacute oral toxicity and the bodyweight are also improved, no inflammation and erosion are seen on any organs of Wistar rat by demonstrated a histopathology analysis. Conclusions: The polyherbal ethanolic extract of Saraca asoca and Asparagus racemosus showed hypoglycaemic activity against STZ-induced diabetes in experimental Wistar rats in Wistar rats. The results are shown beneficial effects of these ethanolic extract it helps in improving the changes in lipid metabolism, and protect the organs of Wistar rat liver, kidney, spleen, pancreas, lungs, heart against due to impairment of blood glucose and also in body weight. All organs were weighted and cut the tissue of organs and stained from eosin dye and changes observed by microscopy photos. no signs of inflammation and erosion.

The journey of Deinococcus radiodurans; a perspective

: Deinococcus radiodurans has been recognized for its robustness and recorded in the Guinness Book of World Records as the world's toughest known bacterium. In essence, the title comes from its ability to survive extreme conditions such as severe drought (desiccation) and radiation tolerance up to 15000 Gy, which is more than 250 times of E. coli and about 3000 times of humans. Due to its high tolerance to all kinds of genotoxic stress, such as desiccation, UV, X-rays, and oxidants, D. radiodurans is a well-suited model organism for microbial radiation resistance studies. The DNA damage-responsive gene expression is an important component of post-stress recovery where the cell shows a great multiplicity of genomes leading to the highly proficient recombinational DNA repair. This article pitches light on the unique properties of D. radiodurans, unfolding its journey so far as well as important molecular discoveries, prospects, and biotechnological applications.

The use of plant fibers for oligosaccharide production with libraries constructed by combinatorial enzyme technology

: Combinatorial chemistry involves the chemical or biological synthesis of libraries of the diverse structural population of a template molecule and the screening for the variants expressing desirable target properties. The approach has been a focus of research activity in modern drug discovery and biotechnology for accelerating the discovery and development of novel therapeutic and bioactive compounds. This review describes the application of combinatorial chemistry in enzyme technology as a novel technique and invention developed in our laboratory to construct oligosaccharide libraries in the conversion of plant fibers. The theory, mechanism, development, and application of this combinatorial enzyme approach are presented for the first time. The potential food and non-food uses of oligosaccharides are described. Citrus pectin and wheat insoluble fiber have been used as substrates for combinatorial enzyme reactions. Generation of libraries of structural variants of pectic oligosaccharides (oligoGalA) and feruloyl oligosaccharides (FOS) demonstrates the feasibility and usefulness of the technique in the transformation of plant biomass to value-added products.

Modelling cell growth and polyhydroxyalkanoate (PHA) polymer synthesis by Pseudomonas putida LS46 under oxygen-limiting conditions

Background: Polyhydroxyalkanoates (PHAs) are biodegradable, biocompatible, and non-toxic polymers synthesized by bacteria that may be used to displace some petroleum-based plastic materials. One of the major barriers to the commercialization of PHA biosynthesis is the high cost of production. Objective: Oxygen-limitation is known to greatly influence bacterial cell growth and PHA production. In this study, the growth and synthesis of medium chain length PHAs (mcl-PHAs) by Pseudomonas putida LS46, cultured in batch-mode with octanoic acid, under oxygen-limited conditions, was modeled. Methods: Four models, including the Monod model, incorporated Leudeking–Piret (MLP), the Moser model incorporated Leudeking–Piret (Moser-LP), the Logistic model incorporated Leudeking–Piret (LLP), and the Modified Logistic model incorporated Leudeking–Piret (MLLP) were investigated. Kinetic parameters of each model were calibrated by using the multi-objective optimization algorithm, Pareto Archived Dynamically Dimensioned Search (PA-DDS), by minimizing the sum of absolute error (SAE) for PHA production and growth simultaneously. Results and Conclusions: Among the four models, MLP and Moser-LP models adequately represented the experimental data for oxygen-limited conditions. However, the MLP and Moser-LP models could not adequately simulate PHA production under oxygen-excess conditions. Modeling cell growth and PHA will assist in the development of a strategy for industrial-scale production.

Dual synthesis of Silver and Iron oxide nanoparticles from edible greens Amaranthus Viridis and their in vitro antioxidant activity and antimicrobial studies

Background: There is an increasing commercial demand for nanoparticles due to their wide applicability in various areas such as chemistry, catalysis, energy and medicine. Metallic nanoparticles are traditionally synthesized by wet chemical techniques where the chemicals used are quite often toxic and flammable. Objective: In the present study, we described a simple, cost effective and environmentally-friendly technique for green synthesis of silver and iron nanoparticles by using the aqueous extract of leafy vegetable Amaranthus viridis as a reducing agent. Methods: The silver and Iron nanoparticles (Av-AgNPs, Av-IONPs) were characterized by different spectral methods. The surface Plasmon resonance spectrums of Av-AgNPs, Av-IONPs were recorded at 422nm and 261nm. The Scanning electron microscopy (SEM) analysis reveals that the Av-AgNPs, Av-IONPs are roughly spherical in shape. Energy dispersive absorption spectroscopy (EDAX) of biosynthesized Av-AgNPs, Av-IONPs indicates the reduction of silver ions to elemental silver and iron ions to elemental iron. Results: The particle size analysis of Av-AgNPs and Av-IONPs was carried out by Dynamic light scattering (DLS) method the results reveal that both Av-AgNPs and Av-IONPs were polydispered in nature. The average particle size of Av-AgNPs is 55.8 nm with a polydispered index (PI) of 0.297, similarly the average particle size of Av-IONPs is 80.6 nm with an polydispered index (PI) of 0.469. Zeta-potential of Av-AgNPs was detected at -24.6 mV and Av-IONPs were detected at 28.8 mV, the result reveals that they high stability due their high negative charge and positive charge respectively. The dual synthesized Av-AgNPs, Av-IONPs exhibits excellent antioxidant activity by DPPH, H2O2 and NO methods. DPPH was proven to be the best when compared with the other two methods. The biosynthesized Av-AgNPs, Av-IONPs proved to have very good antimicrobial activity against gram +ve and gram –ve bacteria. Conclusion: when compared with standard antibiotic. There were several reports on green synthesis of metal nanoparticles using various plant parts, but here edible leafy vegetable Amaranthus viridis was used for biosynthesis of both Av-AgNPs and Av-IONPs.

Molecular Study of Immune Evasion Cluster Genes in Clinical Isolates of Staphylococcus aureus

Aims: The aim of the present research was to highlight the prevalence of immune evasion cluster genes (IEC) sak, chp, scn, sea, sep among Staphylococcus aureus (S. aureus) clinical isolates. Background: The present study was a cross-sectional retrospective study, included one hundred isolates of S. aureus that were isolated from patients with nosocomial infections. S. aureus isolates were subjected to full microbiological identification and antibiotics sensitivity testing by the disc diffusion method. The presence of IEC genes scn, sea, sak, sep, chp was determined by polymerase chain reaction (PCR). Methods: The current study included 100 S. aureus isolates; 40% were classified as methicillin resistant. The isolates exhibited marked resistance to beta lactams antibiotics, the lowest resistance was to erythromycin, ciprofloxacin and vancomycin. The presence of one or more IEC was determined in 89 isolates. The prevalence of chp, sak, sea, sep and scn was 54%, 53%, 8%, 7% and 30%, respectively. Results: S. aureus isolates with IEC genes had increased resistance rates to the studied antibiotics; however, this increase was statistically insignificant either to beta-lactam antibiotics, such as amoxacillin/clavulinic acid (P=0.794), ampicillin (P=0.561), cefotaxim (P=0.271), ceftazidime (P=0.145), imipenem (P=0.589) or non beta-lactam antibiotics, such as amikacin (P=0.955) and trimethoprim/sulfamethoxazale (P=0.974). From 40 methicillin resistant Staphylococcus aureus (MRSA) strains, 37 isolates harbor one or more immune evasion cluster genes. Conclusion: The high prevalence of these genes among MRSA may explain its pathogenesis. There is a need for studies with a high number of isolates to verify the present findings.

General Aspects of Biodegradable Biopolymers and the Polyhydroxyalkanoates’ Family

Background: Plastic polymers are ubiquitous and life without them is practically impossible. Despite the advantages provided by the material, conventional plastics are also harmful to the environment and human health. Therefore, the search for alternatives, such as polyhydroxyalkanoates (PHAs), a family of biodegradable thermoplastic polyesters naturally produced by PHA-accumulating bacteria, such as Pseudomonas spp. and Ralstonia eutropha, through fermentative processes, is of paramount importance. Objectives: In the present work, the objective of the researchers was to develop a revisional study regarding biodegradable biopolymers and the PHAs’ importance and benefits for society and the environment. Methods: In this review, articles published since the year 2000, related to the different aspects of biodegradable plastics and PHAs, were accurately analyzed and reviewed. The subjects covered ranged from conventional plastics and the problems related to their large-scale production and the importance of biodegradable plastics, as well as PHAs, their positive aspects, and the feasibility of their use as an alternative to replace conventional plastics. Those subjects were extensively reviewed and concisely discussed. Results and Conclusions: The present study demonstrated the importance of biodegradable plastics and the PHAs’ family, its different application possibilities, and its viability as an alternative to replace conventional plastics, since it can mimic their characteristics efficiently, with the advantage of being biodegradable and produced from renewable sources.

Pseudomonas sp. a Dominant Population of Bacteria in the Cold Water of Mount Sabalan Crater ‎Lake

Background: Sabalan (Savalan) Lake is a stable crater lake locating at the summit of Sabalan, an inactive stratovolcano and the third highest mountain of Iran. Because of cold weather conditions, the lake is frozen in most months of the year. The biodiversity of microbial flora in this area needs to be explored to find its similarity with the arctic regions’ biodiversity. Objective: The psychrophilic bacterial population of Sabalan (Savalan) Crater Lake was identified. The current research is the first report of aquatic bacterial strains isolation and characterization from Sabalan Lake. Methods: Water sample collections were cultured on four different media, then colonies were isolated by the plating method. The phylogenetic features of the isolates were scrutinized and finally, the phenotypic characteristics were investigated using specific culture methods. Results: The results of morphological tests indicated that most isolates were Gram-negative and rod shape, which were able to grow between ˗4 and +37 ºC.‎ According to the phylogenetic analysis the isolated strains belong to Pseudomonas, Yersinia, Kocuria, and Micrococcus genera and about 60% of the isolates belong to the various species of Pseudomonas as a ‎dominant genus with abounded frequency. ‎In addition, several isolates showed 99% similarity with bacteria, which were previously isolated from Antarctic regions such as Pseudomonas antarctica and Micrococcus antarctica. Conclusion: It can be concluded that the microbial populations of cold areas is the same across the geographical distances. In addition, these bacterial strains could be a primitive source of new enzymes for technological applications such as biosurfactant production.