A novel vaccine construct against Zika virus fever: insights from epitope-based vaccine discovery through molecular modeling and immunoinformatics approaches.

The Zika virus (ZIKV) is an emerging virus associated with the Flaviviridae family that mainly causes infection in pregnant women and leads to several abnormalities during pregnancy. This virus has unique properties that may lead to pathological diseases. As the virus has the ability to evade immune response, a crucial effort is required to deal with ZIKV. Vaccines are a safe means to control different pathogenic infectious diseases. In the current research, a multi-epitope-based vaccination against ZIKV is being designed using in silico methods. For the epitope prediction and prioritization phase, ZIKV polyprotein (YP_002790881.1) and flavivirus polyprotein (>YP_009428568.1) were targeted. The predicted B-cell epitopes were used for MHC-I and MHC-II epitope prediction. Afterward, several immunoinformatics filters were applied and nine (REDLWCGSL, MQDLWLLRR, YKKSGITEV, TYTDRRWCF, RDAFPDSNS, KPSLGLINR, ELIGRARVS, AITQGKREE, and EARRSRRAV) epitopes were found to be probably antigenic in nature, non-allergenic, non-toxic, and water soluble without any toxins. Selected epitopes were joined using a particular GPGPG linker to create the base vaccination for epitopes, and an extra EAAAK linker was used to link the adjuvant. A total of 312 amino acids with a molecular weight (MW) of 31.62762 and an instability value of 34.06 were computed in the physicochemical characteristic analysis, indicating that the vaccine design is stable. The molecular docking analysis predicted a binding energy of -329.46 (kcal/mol) for TLR-3 and -358.54 (kcal/mol) for TLR-2. Moreover, the molecular dynamics simulation analysis predicted that the vaccine and receptor molecules have stable binding interactions in a dynamic environment. The C-immune simulation analysis predicted that the vaccine has the ability to generate both humoral and cellular immune responses. Based on the design, the vaccine construct has the best efficacy to evoke immune response in theory, but experimental analysis is required to validate the in silico base approach and ensure its safety.

Designing an mRNA Vaccine against P. jirovecii Involved in Fatal Pneumonia Infections via Comparative Proteomics and Reverse Vaccinology Approaches.

BACKGROUND: Pneumocystis jirovecii is the most emerging life-threating health problem that causes acute and fatal pneumonia infection. It is rare and more contagious for patients with leukemia and immune-deficiency disorders. Until now there is no treatment available for this infection therefore, it is needed to develop any treatment against this pathogen. METHODS: In this work, we used comparative proteomics, robust immune-informatics, and reverse vaccinology to create an mRNA vaccine against Pneumocystis jirovecii by targeting outer and transmembrane proteins. Using a comparative subtractive proteomic analysis of two Pneumocystis jirovecii proteomes, a distinct non-redundant Pneumocystis jirovecii (strain SE8) proteome was chosen. Seven Pneumocystis jirovecii transmembrane proteins were chosen from this proteome based on hydrophilicity, essentiality, virulence, antigenicity, pathway interaction, protein-protein network analysis, and allergenicity. OBJECTIVE: The reverse vaccinology approach was used to predict the immunogenic and antigenic epitopes of major histocompatibility complex (MHC) I, II and B-cells from the selected proteins on the basis of their antigenicity, toxicity and allergenicity. These immunogenic epitopes were linked together to construct the mRNA-based vaccine. To enhance the immunogenicity, suitable adjuvant, linkers (GPGPG, KK, and CYY), and PRDRE sequences were used. RESULTS: Through predictive modeling and confirmation via the Ramachandran plot, we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct's immunogenicity (GRAVY index: -0.271, instability index: 39.53, antigenicity: 1.0428). The physiochemical profiling of vaccine construct was predicted it an antigenic, efficient, and potential vaccine. Notably, strong interactions were observed between the vaccine construct and TLR-3/TLR-4 (-1301.7 kcal/mol-1 and -1374.7 kcal/mol-1). CONCLUSIONS: The results predicted that mRNA-based vaccines trigger a cellular and humoral immune response, making the vaccine potential candidate against Pneumocystis jirovecii and it is more suitable for in-vitro analysis and validation to prove its effectiveness.

Optimizing the resveratrol fragments for novel in silico hepatocellular carcinoma de novo drug design.

Hepatocellular carcinoma (HCC) incidence varies widely around the world and is impacted by factors such as the prevalence of chronic hepatitis B and C infections, alcohol intake, and access to healthcare. The proteins (BRAF_human, VGFR3_human, EGFR_human and UFO_human) play a vital role in hepatocellular carcinoma prognosis, which involves cell proliferation, cell growth, transmission of extracellular signals to the cell nucleus and consequently regulating many other cellular processes. Fostamatinib has been studied for its possible use in the treatment of hepatocellular cancer because it is a more convenient therapy choice for patients and has minor side effects on the human body. However, resveratrol phytochemical has been investigated for its potential use in the prevention and treatment of a wide range of disorders, including cancer, cardiovascular disease, diabetes, and neurological problems due to its frequently antioxidant, anti-inflammatory, and immune-modulating characteristics, which can aid in the prevention of chronic illnesses. This study developed de novo-based fragment-optimized resveratrol (FOR), enhancing therapeutic potential and lowering toxicity. The docking study was performed with four target proteins, and the findings reveal that the vascular endothelial growth factor receptor 3 protein possessed the highest binding energy values of -7.6 kcal/mol with FOR. Additionally, it completely fulfills the criteria of drug-likeliness rules. Thus, FOR proves to be an efficient drug candidate for future in-vivo studies against hepatocellular carcinoma.

Evaluating the MDCK cell permeability of greenly synthesize bimetallic Ag/Zn Nanoparticles using leaf extract of Vallaris solanacea as a potential antipesticide-resistant agent.

Bimetallic nanoparticles, particularly Ag/Zn bimetallic nanoparticles, have gained increasing attention due to their unique properties, making them suitable for a variety of applications such as catalysis, water treatment, and environmental remediation. This study aimed to elucidate the use of bimetallic nanoparticles of Ag/Zn as an alternative to resistant pesticides for pest control. Furthermore, this research demonstrates that BNPs can target specific pollutants and degrade them through various mechanisms. BNP docking with the Nilaparvata lugens cytochrome P450 (CYP6ER1) protein exhibited the lowest binding energy of -7.5 kcal/mol. The cell permeability analysis of BNP in plant cells reveals that the BNP has 0 % permeability towards any cell at -10 kcal/mol energy, which is the lowest free energy translocation pathway. The harmful leftover residues of the pesticides have a higher chance of degradability in case of interaction with BNP validated by chemical-chemical interaction analysis. Additionally, MDCK permeability coefficient of small molecules based on the regression model was calculated for BNP which authenticated the efficiency of BNP. Moreover, Swiss ADMET simulated absorption using a boiled egg model with no blood-brain barrier and gastrointestinal crossing for the expected BNP molecule has been observed. Significantly, the findings indicate that employing bimetallic nanoparticles like Ag/Zn is a crucial strategy for bioremediation because they proficiently decompose pesticides while posing no risk to humans. Our results will facilitate the design of novel BNPs materials for environmental remediation and pest control ensuring human health safety that are predicated on bimetallic nanoparticles.

Effects of novel beta-lactam, MC-100093, and ceftriaxone on astrocytic glutamate transporters and neuroinflammatory factors in nucleus accumbens of C57BL/6 mice exposed to escalated doses of morphine.

Chronic exposure to opioids can lead to downregulation of astrocytic glutamate transporter 1 (GLT-1), which regulates the majority of glutamate uptake. Studies from our lab revealed that beta-lactam antibiotic, ceftriaxone, attenuated hydrocodone-induced downregulation of GLT-1 as well as cystine/glutamate antiporter (xCT) expression in central reward brain regions. In this study, we investigated the effects of escalating doses of morphine and tested the efficacy of novel synthetic non-antibiotic drug, MC-100093, and ceftriaxone in attenuating the effects of morphine exposure in the expression of GLT-1, xCT, and neuroinflammatory factors (IL-6 and TGF-ß) in the nucleus accumbens (NAc). This study also investigated the effects of morphine and beta-lactams in locomotor activity, spontaneous alternation percentage (SAP) and number of entries in Y maze since opioids have effects in locomotor sensitization. Mice were exposed to moderate dose of morphine (20 mg/kg, i.p.) on days 1, 3, 5, 7, and a higher dose of morphine (150 mg/kg, i.p.) on day 9, and these mice were then behaviorally tested and euthanized on Day 10. Western blot analysis showed that exposure to morphine downregulated GLT-1 and xCT expression in the NAc, and both MC-100093 and ceftriaxone attenuated these effects. In addition, morphine exposure increased IL-6 mRNA and TGF-ß mRNA expression, and MC-100093 and ceftriaxone attenuated only the effect on IL-6 mRNA expression in the NAc. Furthermore, morphine exposure induced an increase in distance travelled, and MC-100093 and ceftriaxone attenuated this effect. In addition, morphine exposure decreased the SAP and increased the number of arm entries in Y maze, however, neither MC-100093 nor ceftriaxone showed any attenuating effect. Our findings demonstrated for the first time that MC-100093 and ceftriaxone attenuated morphine-induced downregulation of GLT-1 and xCT expression, and morphine-induced increase in neuroinflammatory factor, IL-6, as well as hyperactivity. These findings revealed the beneficial therapeutic effects of MC-100093 and ceftriaxone against the effects of exposure to escalated doses of morphine.

Role of diosmin in preventing doxorubicin-induced cardiac oxidative stress, inflammation, and hypertrophy: A mechanistic approach.

Chemotherapeutic drugs, such as doxorubicin (Dox), are commonly used to treat a variety of malignancies. However, Dox-induced cardiotoxicity limits the drug's clinical applications. Hence, this study intended to investigate whether diosmin could prevent or limit Dox-induced cardiotoxicity in an animal setting. Thirty-two rats were separated into four distinct groups of controls, those treated with Dox (20 mg/kg, intraperitoneal, i.p.), those treated with diosmin 100 mg plus Dox, and those treated with diosmin 200 mg plus Dox. At the end of the experiment, rats were anesthetized and sacrificed and their blood and hearts were collected. Cardiac toxicity markers were analyzed in the blood, and the heart tissue was analyzed by the biochemical assays MDA, GSH, and CAT, western blot analysis (NF-kB, IL-6, TLR-4, TNF-α, iNOS, and COX-2), and gene expression analysis (ß-MHC, BNP). Formalin-fixed tissue was used for histopathological studies. We demonstrated that a Dox insult resulted in increased oxidative stress, inflammation, and hypertrophy as shown by increased MDA levels and reduced GSH content and CAT activity. Furthermore, Dox treatment induced cardiac hypertrophy and damage, as evidenced by the biochemical analysis, ELISA, western blot analysis, and gene expression analysis. However, co-administration of diosmin at both doses, 100 mg and 200 mg, mitigated these alterations. Data derived from the current research revealed that the cardioprotective effect of diosmin was likely due to its ability to mitigate oxidative stress and inflammation. However, further study is required to investigate the protective effects of diosmin against Dox-induced cardiotoxicity.

Correction: Zaman et al. Synthesis and Evaluation of Thiol-Conjugated Poloxamer and Its Pharmaceutical Applications. Pharmaceutics 2021, 13, 693.

In the original publication, there was a mistake in one author name, Mohammed Alasmari should be Mohammed S [...].

Polysaccharide- and protein-based edible films combined with microwave technology for meat preservation.

To reduce food-borne bacterial infection caused by food spoilage, developing highly efficient food packing film is still an urgent need for food preservation. Herein, microwave-assisted antibacterial nanocomposite films CaO2@PVP/EA/CMC-Na (CP/EC) were synthesized using waste eggshell as precursor, egg albumen (EA) and sodium carboxymethylcellulose (CMCNa) as matrix by casting method. The size of CaO2@PVP (CP) nanoparticles with monodisperse spherical structures was 100-240 nm. When microwave and CP nanoparticles (0.05 mg/mL) were treated for 5 min, the mortality of E. coli and S. aureus could reach >97 %. Under microwave irradiation (6 min), the bactericidal rate of 2.5 % CP/EC film against E. coli and S. aureus reached 98.6 % and 97.2 %, respectively. After adding CP nanoparticles, the highest tensile strength (TS) and elongation at break (EB) of CP/EC film reached 19.59 MPa and 583.43 %, respectively. At 18 °C, the proliferation of bacterial colonies on meat can be significantly inhibited by 2.5 % CP/EC film. Detailed characterization showed that the excellent meat preservation activity was due to the synergistic effect of dynamic effect generated by ROS and thermal effect of microwave. This study provides a promising approach for the packaging application of polysaccharide- and protein-based biomass nanocomposite antibacterial edible films.

Statistical design and optimization of nano-transfersomes based chitosan gel for transdermal delivery of cefepime.

OBJECTIVES: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. METHODS: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. RESULTS: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. CONCLUSION: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.

Metabolomics analysis of potential functional metabolites in synbiotic ice cream made with probiotic Saccharomyces cerevisiae var. boulardii CNCM I-745 and prebiotic inulin.

Probiotic lactic acid bacteria have been widely studied, but much less was focused on probiotic yeasts in food systems. In this study, probiotic Saccharomyces cerevisiae var. boulardii CNCM I-745 was employed to prepare ice cream added with and without inulin (1%, w/v). Metabolomics analysis on the effect of inulin showed 84 and 147 differentially expressed metabolites identified in the ice cream samples from day 1 and day 30 of storage (-18 °C), respectively. Various potential functional metabolites were found, including citric acid, ornithine, D-glucuronic acid, sennoside A, stachyose, maltotetraose, maltopentaose, maltohexaose, maltoheptaose, cis-aconitic acid, gamma-aminobutyric acid, L-threonine, L-glutamic acid, tryptophan, benzoic acid, and trehalose. Higher expression of these metabolites suggested their possible roles through relevant metabolic pathways in improving survivability of the probiotic yeast and functionality of ice cream. This study provides further understanding on the metabolic characteristics of probiotic yeast that potentially affect the functionality of ice cream.

Effect of dual modifications with ultrasonication and succinylation on Cicer arietinum protein-iron complexes: Characterization, digestibility, in-vitro cellular mineral uptake and preparation of fortified smoothie.

The research aimed to evaluate the effect of ultrasonication and succinylation on the functional, iron binding, physiochemical, and cellular mineral uptake efficacy of chickpea protein concentrate. Succinylation resulted in significant improvements in the water-holding capacity (WHC) (25.47 %), oil-holding capacity (OHC) (31.38 %), and solubility (5.80 %) of the chickpea protein-iron complex. Mineral bioavailability significantly increased by 4.41 %, and there was a significant increase in cellular mineral uptake (64.64 %), retention (36.68 %), and transport (27.96 %). The ferritin content of the succinylated chickpea protein-iron complex showed a substantial increase of 66.31%. Furthermore, the dual modification approach combining ultrasonication and succinylation reduced the particle size of the protein-iron complex with a substantial reduction of 83.25 %. It also resulted in a significant enhancement of 51.5 % in the SH (sulfhydryl) content and 48.92 % in the surface hydrophobicity. Mineral bioavailability and cellular mineral uptake, retention, and transport were further enhanced through dual modification. In terms of application, the addition of single and dual-modified chickpea protein-iron complex to a fruit-based smoothie demonstrated positive acceptance in sensory attributes. Overall, the combined approach of succinylation and ultrasonication to the chickpea protein-iron complex shows a promising strategy for enhancing the physiochemical and techno-functional characteristics, cellular mineral uptake, and the development of vegan food products.

Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide-hydrazone derivatives of 3,4-dihydroxyphenylacetic acid.

A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by 1HNMR, 13CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC50 = 12.84 ± 0.52 µM), 4 (IC50 = 13.64 ± 0.58 µM), 12 (IC50 = 15.73 ± 0.71 µM), 13 (IC50 = 16.62 ± 0.47 µM), 15 (IC50 = 17.40 ± 0.74 µM), 3 (IC50 = 18.45 ± 1.21 µM), 7 (IC50 = 19.68 ± 0.82 µM), and 2 (IC50 = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC50 = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.

Molecular identification of Proteus mirabilis, Vibrio species leading to CRISPR-Cas9 modification of tcpA and UreC genes causing cholera and UTI.

Heavy metal accumulation increases rapidly in the environment due to anthropogenic activities and industrialization. The leather and surgical industry produces many contaminants containing heavy metals. Cadmium, a prominent contaminant, is linked to severe health risks, notably kidney and liver damage, especially among individuals exposed to contaminated wastewater. This study aims to leverage the natural cadmium resistance mechanisms in bacteria for bioaccumulation purposes. The industrial wastewater samples, characterized by an alarming cadmium concentration of 29.6 ppm, 52 ppm, and 76.4 ppm-far exceeding the recommended limit of 0.003 ppm-were subjected to screening for cadmium-resistant bacteria using cadmium-supplemented media with CdCl2. 16S rRNA characterization identified Vibrio cholerae and Proteus mirabilis as cadmium-resistant bacteria in the collected samples. Subsequently, the cadmium resistance-associated cadA gene was successfully amplified in Vibrio species and Proteus mirabilis, revealing a product size of 623 bp. Further analysis of the identified bacteria included the examination of virulent genes, specifically the tcpA gene (472 bp) associated with cholera and the UreC gene (317 bp) linked to urinary tract infections. To enhance the bioaccumulation of cadmium, the study proposes the potential suppression of virulent gene expression through in-silico gene-editing tools such as CRISPR-Cas9. A total of 27 gRNAs were generated for UreC, with five selected for expression. Similarly, 42 gRNA sequences were generated for tcpA, with eight chosen for expression analysis. The selected gRNAs were integrated into the lentiCRISPR v2 expression vector. This strategic approach aims to facilitate precise gene editing of disease-causing genes (tcpA and UreC) within the bacterial genome. In conclusion, this study underscores the potential utility of Vibrio species and Proteus mirabilis as effective candidates for the removal of cadmium from industrial wastewater, offering insights for future environmental remediation strategies.

Pharmacological evaluation and phytochemical profiling of butanol extract of L. edodes with in- silico virtual screening.

L. edodes (L. edodes) is the most consumed mushroom in the world and has been well known for its therapeutic potential as an edible and medicinal candidate, it contains dietary fibers, vitamins, proteins, minerals, and carbohydrates. In the current study butanolic extract of mushroom was used to form semisolid butanol extract. The current study aimed to explore biometabolites that might have biological activities in n-butanol extract of L. edodes using FT-IR and GC-MS and LC-MS. The synergistic properties of bioactive compounds were futher assessed by performing different biological assays such as antioxidant, anti-inflammatory and antidiabetic. FTIR spectra showed different functional groups including amide N-H group, Alkane (C-H stretching), and (C = C stretching) groups at different spectrum peaks in the range of 500 cm-1 to 5000 cm-1 respectively. GC-MS profiling of n-butanol extract depicted 34 potent biomolecules among those dimethyl; Morphine, 2TMS derivative; Benzoic acid, methyl ester 1-(2-methoxy-1-methylethoxy)-2-propanol were spotted at highest range. Results indicate that L. edodes n-butanol extract showed a maximum anti-inflammatory potential 91.4% at 300 mg/mL. Antioxidant activity was observed by measuring free radical scavenging activity which is 64.6% at optimized concentration along with good antidiabetic activity. In-silico study executed the biopotential of active ingredient morphine which proved the best docking score (- 7.0 kJ/mol) against aldose reductase. The in-silico drug design analysis was performed on biometabolites detected through GC-MS that might be a potential target for sulfatase-2 to treat ruminated arthritis. Morphine binds more strongly (- 7.9 kJ/mol) than other bioactive constituents indicated. QSAR and ADMET analysis shown that morphine is a good candidates against ruminated arthritis. The current study showed that L. edodes might be used as potent drug molecules to cure multiple ailments. As mushrooms have high bioactivity, they can be used against different diseases and to develop antibacterial drugs based on the current situation in the world in which drug resistance is going to increase due to misuse of antibiotics so new and noval biological active compounds are needed to overcome the situation.

Network-base approaches to identify therapeutic biomarkers in hepatocellular carcinoma and search for drug hunting utilizing molecular dynamics simulations.

The presence of conditions like Alpha-1 antitrypsin deficiency, hemochromatosis, non-alcoholic fatty liver diseases and metabolic syndrome can elevate the susceptibility to hepatic cellular carcinoma (HCC). Utilizing network-based gene expression profiling via network analyst tools, presents a novel approach for drug target discovery. The significance level (p-score) obtained through Cytoscape in the intended center gene survival assessment confirms the identification of all target center genes, which play a fundamental role in disease formation and progression in HCC. A total of 1064 deferential expression genes were found. These include MCM2 with the highest degree, followed by 4917 MCM6 and MCM4 with a 3944-degree score. We investigated the regulatory kinases involved in establishing the protein-protein interactions network using X2K web tool. The docking approach yields a favorable binding affinity of -8.7 kcal/mol against the target MCM2 using Auto-Dock Vina. Interestingly after simulating the complex system via AMBER16 package, results showed that the root mean square deviation values remained within 4.74 Å for a protein and remains stable throughout the time intervals. Additionally, the ligand's fit to the protein exhibited fluctuations at some intervals but remains stable. Finally, Gibbs free energy was found to be at its lowest at 1 kcal/mol which presents the real time interactive binding of the atomic residues among inhibitor and protein. The displacement of the ligand was measured showing stable movement and displacement along the active site. These findings increased our understanding for potential biomarkers in hepatocellular carcinoma and an experimental approach will further enhance our outcomes in future.Communicated by Ramaswamy H. Sarma.

Optimal Enzyme-Assisted Extraction of Phenolics from Leaves of Pongamia pinnata via Response Surface Methodology and Artificial Neural Networking.

This research work seeks to evaluate the impact of selected enzyme complexes on the optimised release of phenolics from leaves of Pongamia pinnata. After preliminary solvent extraction, the P. pinnata leaf extract was subjected to enzymatic treatment, using enzyme cocktails such as kemzyme dry-plus, natuzyme, and zympex-014. It was noticed that zympex-014 had a greater extract yield (28.0%) than kemzyme dry-plus (17.0%) and natuzyme (18.0%). Based on the better outcomes, zympex-014-based extract values were subsequently applied to several RSM parameters. The selected model is suggested to be significant by the F value (12.50) and R2 value (0.9669). The applicability of the ANN model was shown by how closely the projected values from the ANN were to the experimental values. In terms of total phenolic contents (18.61 mg GAE/g), total flavonoid contents (12.56 mg CE/g), and DPPH test (IC50) (6.5 g/mL), antioxidant activities also shown significant findings. SEM analysis also revealed that the cell walls were damaged during enzymatic hydrolysis, as opposed to non-hydrolysed material. Using GC-MS, five potent phenolic compounds were identified in P. pinnata extract. According to the findings of this study, the recovery of phenolic bioactives and subsequent increase in the antioxidant capacity of P. pinnata leaf extract were both positively impacted by the optimisation approaches suggested, including the use of zympex-014.

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment.

A library of novel bis-Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after structural confirmation by modern spectroscopic techniques. Among them, compound 8 (IC50 = 0.10 ± 0.05 µM), and 9 (IC50 = 0.13 ± 0.03 µM) exhibited promising inhibitory activity better than the standard drug acarbose (IC50 = 0.27 ± 0.04 µM). Similarly, derivatives (5, 6, 7, 10 and 4) showed significant to good inhibitory activity in the range of IC50 values from 0.32 ± 0.03 to 0.52 ± 0.02 µM. These derivatives were docked with the target protein to elucidate their binding affinities and key interactions, providing additional insights into their inhibitory mechanisms. The chemical nature of these compounds were reveal by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-311++G(d,p) basis set. The presence of intramolecular H-bonding was explored by DFT-d3 and reduced density gradient (RGD) analysis. Furthermore, various reactivity parameters were explored by performing TD-DFT at CAM-B3LYP/6-311++G(d,p) method.

Biodegradation of PVCs through in-vitro identification of Bacillus albus and computational pathway analysis of ABH enzyme.

Microplastics pose significant challenges to ecosystems and organisms. They can be ingested by marine and terrestrial species, leading to potential health risks and ecological disruptions. This study aims to address the urgent need for effective remediation strategies by focusing on the biodegradation of microplastics, specifically polyvinyl chloride (PVC) derivatives, using the bacterial strain Bacillus albus. The study provides a comprehensive background on the accumulation of noxious substances in the environment and the importance of harnessing biodegradation as an eco-friendly method for pollutant elimination. The specific objective is to investigate the enzymatic capabilities of Bacillus albus, particularly the alpha/beta hydrolases (ABH), in degrading microplastics. To achieve this, in-silico studies were conducted, including analysis of the ABH protein sequence and its interaction with potential inhibitors targeting PVC derivatives. Docking scores of - 7.2 kcal/mol were obtained to evaluate the efficacy of the interactions. The study demonstrates the promising bioremediation prospects of Bacillus albus for microplastics, highlighting its potential as a key player in addressing microplastic pollution. The findings underscore the urgent need for further experimental validation and practical implementation of Bacillus albus in environmental remediation strategies.

An Aedes-Anopheles Vaccine Candidate Supplemented with BCG Epitopes Against the Aedes and Anopheles Genera to Overcome Hypersensitivity to Mosquito Bites.

BACKGROUND: Skeeter syndrome is a severe local allergic response to mosquito bites that is accompanied by considerable inflammation and, in some cases, a systemic response like fever. People with the syndrome develop serious allergies, ranging from rashes to anaphylaxis or shock. The few available studies on mosquito venom immunotherapy have utilized whole-body preparations and small sample sizes. Still, owing to their little success, vaccination remains a promising alternative as well as a permanent solution for infections like Skeeter's. METHODS: This study, therefore, illustrated the construction of an epitope-based vaccine candidate against Skeeter Syndrome using established immunoinformatic techniques. We selected three species of mosquitoes, Anopheles melas, Anopheles funestus, and Aedes aegypti, to derive salivary antigens usually found in mosquito bites. Our construct was also supplemented with bacterial epitopes known to elicit a strong TH1 response and suppress TH2 stimulation that is predicted to reduce hypersensitivity against the bites. RESULTS: A quality factor of 98.9496, instability index of 38.55, aliphatic index of 79.42, solubility of 0.934747, and GRAVY score of -0.02 indicated the structural (tertiary and secondary) stability, thermostability, solubility, and hydrophilicity of the construct, respectively. The designed Aedes-Anopheles vaccine (AAV) candidate was predicted to be flexible and less prone to deformability with an eigenvalue of 1.5911e-9 and perfected the human immune response against Skeeter (hypersensitivity) and many mosquito-associated diseases as we noted the production of 30,000 Th1 cells per mm3 with little (insignificant production of Th2 cells. The designed vaccine also revealed stable interactions with the pattern recognition receptors of the host. The TLR2/vaccine complex interacted with a free energy of - 1069.2 kcal/mol with 26 interactions, whereas the NLRP3/vaccine complex interacted with a free energy of - 1081.2 kcal/mol with 16 molecular interactions. CONCLUSION: Although being a pure in-silico study, the in-depth analysis performed herein speaks volumes of the potency of the designed vaccine candidate predicting that the proposition can withstand rigorous in-vitro and in-vivo clinical trials and may proceed to become the first preventative immunotherapy against mosquito bite allergy.

Development and immunological evaluation of an mRNA-based vaccine targeting Naegleria fowleri for the treatment of primary amoebic meningoencephalitis.

More than 95% of patients fall victim to primary amoebic meningoencephalitis (PAM), a fatal disease attacking the central nervous system. Naegleria fowleri, a brain-eating microorganism, is PAM's most well-known pathogenic ameboflagellate. Despite the use of antibiotics, the fatality rate continues to rise as no clinical trials have been conducted against this disease. To address this, we mined the UniProt database for pathogenic proteins and selected assumed epitopes to create an mRNA-based vaccine. We identified thirty B-cell and T-cell epitopes for the vaccine candidate. These epitopes, secretion boosters, subcellular trafficking structures, and linkers were used to construct the vaccine candidate. Through predictive modeling and confirmation via the Ramachandran plot (with a quality factor of 92.22), we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct's immunogenicity (GRAVY index: 0.394, instability index: 38.99, antigenicity: 0.8). The theoretical model of immunological simulations indicated favorable responses from both innate and adaptive immune cells, with memory cells expected to remain active for up to 350 days post-vaccination, while the antigen was eliminated from the body within 24 h. Notably, strong interactions were observed between the vaccine construct and TLR-4 (- 11.9 kcal/mol) and TLR-3 (- 18.2 kcal/mol).