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Hepatitis E virus is a primary cause of acute hepatitis worldwide. The present study attempts to assess the genetic variability and evolutionary divergence among HEV genotypes. A vaccine promising capsid-protein coding ORF-2 gene sequences of HEV was evaluated using phylogenetics, model-based population genetic methods and principal component analysis. The analyses unveiled nine distinct clusters as subpopulations for six HEV genotypes. HEV-3 genotype samples stratified into four different subgroups, while HEV-4 stratified into three additional subclusters. Rabbit-infectious HEV-3ra samples constitute a distinct cluster. Pairwise analysis identified marked genetic distinction of HEV-4c and HEV-4i subgenotypes compared to other genotypes. Numerous admixed, inter and intragenotype recombinant strains were detected. The MEME method identified several ORF-2 codon sites under positive selection. Some selection signatures lead to amino acid substitutions within ORF-2, resulting in altered physicochemical features. Moreover, a pattern of host-specific adaptive signatures was identified among HEV genotypes. The analyses conclusively depict that recombination and episodic positive selection events have shaped the observed genetic diversity among different HEV genotypes. The significant genetic diversity and stratification of HEV-3 and HEV-4 genotypes into subgroups, as identified in the current study, are noteworthy and may have implications for the efficacy of anti-HEV vaccines.
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Proteínas do Capsídeo , Variação Genética , Genótipo , Vírus da Hepatite E , Filogenia , Seleção Genética , Vírus da Hepatite E/genética , Vírus da Hepatite E/imunologia , Vírus da Hepatite E/classificação , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Animais , Humanos , Vacinas contra Hepatite Viral/imunologia , Vacinas contra Hepatite Viral/genética , Evolução Molecular , Hepatite E/virologia , Coelhos , Análise por Conglomerados , Recombinação Genética , Proteínas ViraisRESUMO
The COVID-19 pandemic caused unprecedented damage to humanity, and while vaccines have been developed, they are not fully effective against the SARS-CoV-2 virus. Limited targeted drugs, such as Remdesivir and Paxlovid, are available against the virus. Hence, there is an urgent need to explore and develop new drugs to combat COVID-19. This study focuses on exploring microbial natural products from soil-isolated bacteria Streptomyces sp. strain 196 and RI.24 as a potential source of new targeted drugs against SARS-CoV-2. Molecular docking studies were performed on holoRdRp and nsp13, two key factors responsible for virus replication factor. Our in silico studies, K-252-C aglycone indolocarbazole alkaloid (K252C) and daunorubicin were found to have better binding affinities than the respective control drugs, with K252C exhibiting binding energy of - 9.1 kcal/mol with holoRdRp and - 9.2 kcal/mol with nsp13, and daunorubicin showing binding energy at - 8.1 kcal/mol with holoRdRp and - 9.3 kcal/mol with nsp13. ADMET analysis, MD simulation, and MM/GBSA studies indicated that K252C and daunorubicin have the potential to be developed as targeted drugs against SARS-CoV-2. The study concludes that K252C and daunorubicin are potential lead compounds that might suppress the inhibition of SARS-CoV-2 replication among the tested microbial compounds and could be developed as targeted drugs against COVID-19. In the future, further in vitro studies are required to validate these findings.
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Produtos Biológicos , COVID-19 , Humanos , SARS-CoV-2 , Produtos Biológicos/farmacologia , Simulação de Acoplamento Molecular , Pandemias , Daunorrubicina/farmacologia , Inibidores de ProteasesRESUMO
Thymidylate kinase (TMPK) of monkeypox virus (MPXV) has emerged as a promising target for potential therapeutics due to its significant role in pyrimidine metabolism. While smallpox drugs are advised for treating monkeypox, the European Medicine Agency has sanctioned Tecovirimat due to its potent nanomolar activity. Nonetheless, there is a need for monkeypox-specific therapeutic options. In this work, we employed docking-based virtual screening and molecular dynamics (MD) simulations to identify myxobacterial secondary metabolites as promising anti-viral natural compounds capable of inhibiting thymidylate kinase. The computational pharmacokinetics and manual curation of top-scoring compounds identified six lead compounds that were compared in terms of protein-ligand contacts and protein-essential dynamics. The study shows that among the six candidates, Aurachin A and the Soraphinol analogues such as Soraphinol A and Soraphinol C remain very stable compared to other compounds, enabling the active site integrity via a stable dynamics pattern. We also show that other compounds such as Phenoxan, Phenylnannolone C, and 8E-Aurafuron B remain unstable and have a negative impact on the active site integrity and may not be suitable binders for TMPK protein. Analyzing the Aurachin A and Soraphinol A binding, the established hydrogen bonds with Arg93 and the conserved hydrophobic interaction with Tyr101 are consistent with previous experimental interactions. Additionally, a deeper insight into the indole and the aromatic ring interaction through π-π stacking and π-cation interactions, as well as the background of Aurachin A and Soraphinol A as a bioactive compound, has significant implications not only for its potential as a promising drug but also for directing future drug discovery efforts targeting the TMPK protein.
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The current study aimed to evaluate the physicochemical properties of Fernandoa adenophylla. Powder studies were carried out to estimate the quantitative physicochemical characteristics of the crude drug, including moisture content, ash content, and extractive values. Using a Soxhlet apparatus and different analytical grade solvents, 3 sample extracts of a crude drug were made. To evaluate the potentially toxic nature, an acute oral toxicity study was performed as per OECD guideline no. 423. Sample extracts were tested and analyzed by ANOVA for pharmacological potential (analgesic, antipyretic, and antidiabetic) using Wister-Albino rats. Where physicochemical analysis indicated purity, quality, and presence of organic/inorganic materials in crude drug extracts, no sign of mortality was found up to 2000â mg/kg of body weight of Fernandoa adenophyllas extracts. Analgesic activity was observed in all sample extracts, whereas only chloroform and ethanolic extracts expressed antipyretic and antidiabetic potential. Ethanolic extract was found to be most potent in pharmacological potential as 200â mg/kg extract dose exhibited %age pain inhibition of 55.12 % and reduced body temperature from 39.78±0.03 °C to 37.22±0.02 °C in hyperthermic rats. A decrease in blood glucose levels up to 57.88 % was observed on the 21st day of the treatment with 500â mg/kg ethanolic extract.
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Analgésicos , Antipiréticos , Frutas , Hipoglicemiantes , Extratos Vegetais , Ratos Wistar , Animais , Ratos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Frutas/química , Antipiréticos/farmacologia , Antipiréticos/química , Antipiréticos/isolamento & purificação , Masculino , Glicemia/efeitos dos fármacos , Glicemia/análise , Dor/tratamento farmacológico , Dor/induzido quimicamente , FemininoRESUMO
The most common type of environmental contamination is petroleum hydrocarbons. Sustainable and environmentally friendly treatment strategies must be explored in light of the increasing challenges of toxic and critical wastewater contamination. This paper deals with the bacteria-producing biosurfactant and their employment in the bioremediation of hydrocarbon-containing waste through a microbial fuel cell (MFC) with Pseudomonas aeruginosa (exoelectrogen) as co-culture for simultaneous power generation. Staphylococcus aureus is isolated from hydrocarbon-contaminated soil and is effective in hydrocarbon degradation by utilizing hydrocarbon (engine oil) as the only carbon source. The biosurfactant was purified using silica-gel column chromatography and characterised through FTIR and GCMS, which showed its glycolipid nature. The isolated strains are later employed in the MFCs for the degradation of the hydrocarbon and power production simultaneously which has shown a power density of 6.4 W/m3 with a 93% engine oil degradation rate. A biogenic Fe2O3 nanoparticle (NP) was synthesized using Bambusa arundinacea shoot extract for anode modification. It increased the power output by 37% and gave the power density of 10.2 W/m3. Thus, simultaneous hydrocarbon bioremediation from oil-contamination and energy recovery can be achieved effectively in MFC with modified anode.
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Fontes de Energia Bioelétrica , Petróleo , Biodegradação Ambiental , Técnicas de Cocultura , Bactérias/metabolismo , Petróleo/análise , Hidrocarbonetos/química , EletrodosRESUMO
Objective: Evaluation of contemporary disinfection techniques, Moringa Oleifera (M.Oleifera), Phycocyanin activated by photodynamic therapy (PDT), and Chitosan, on S.mutans survival rate and bond integrity of composite to carious-affected dentin (CAD). Methods: The in vitro study was conducted at King Saud University and concluded within three months. Sixty mandibular teeth with cavities extending to the middle third of the dentin were sterilized. S.mutans was inoculated onto the CAD surface of twenty samples. The samples were randomly divided into four groups (n: 15) based on various disinfection regimes. Group-1 received 2% CHX, Group-2 Phycocyanin activated by photodynamic therapy (PDT), Group-3 Chitosan, and Group-4 M.oleifera. S.mutans survival rate was calculated. Ten CAD samples from each group were restored using composite. The bond integrity of samples was assessed using a Universal testing machine (UTM) and failure mode using a stereomicroscope. Analysis of variance (ANOVA) and Tukey's Post Hoc test were used to calculate statistical significance (p=0.05). Results: Group-2 samples subjected to Phycocyanin activated using PDT, displayed minimal survival rate (0.24 ± 0.05 CFU/ml) of S.mutans.Group-1 samples treated with CHX exhibited the highest count of S.mutans (0.69 ± 0.12 CFU/ml). The most robust bond was observed in Group-3 (Chitosan) samples (19.33 ± 0.47 MPa). In contrast, SBS values were lowest in Group-1 (CHX) treated study samples (13.17 ± 1.88 MPa). Conclusion: Chitosan, Phycocyanin activated by PDT, and Moringa Oleifera extract exhibit potential as viable substitutes for chlorhexidine (CHX) in clinical settings, presenting the possibility of better eradication of S.mutans and greater adhesive strength to CAD.
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Croton bonplandianus, a natural source traditionally used for treating various illnesses, including rheumatoid arthritis, was evaluated in this study. The effects of ethanolic extracts (CBEE) and aqueous fractions (CBAF) of C. bonplandianus leaves on arthritis-induced inflammation were studied using an albino rat model of inflammation induced by Freund's complete adjuvant. Eight test groups (n = 5 per group) and one vehicle control were used to evaluate the antiarthritic effects of different doses of CBEE and CBAF (125 mg.kg-1, 250 mg.kg-1, and 500 mg.kg-1) on days 5, 10, 15, and 20 compared to arthritic and vehicle controls. Arthritis severity was assessed using macroscopic arthritis grading, histological analysis, body weights, and paw thickness. CBEE and CBAF were found to reduce the prevalence of arthritis, increase body weight, and decrease paw inflammation compared to the vehicle control group by the 23rd day. In addition, they showed no effect on biochemical parameters, but a significant difference (p < 0.05) in hematological parameters compared to the arthritic control group. The study identified Hentriacontane compound as a potential contributor to the anti-inflammatory effect of C. bonplandianus, as it showed the lowest dock score for IL-1ß and IL-6. Palmitoylethanol amide was identified as a potential contributor to the anti-inflammatory effect of TNF-α. Gene expression of IL-6, IL-1ß, and TNF-α was down-regulated significantly (p < 0.05) in a dose-dependent manner in all treatment groups compared to the arthritic control group. In conclusion, this study validated the anti-arthritic and anti-inflammatory properties of CBEE and CBAF in a time and dose-dependent manner.
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KRASG12D are the most prevalent oncogenic mutations and a promising target for solid tumor therapies. However, its inhibition exhibits tremendous challenge due to the necessity of high binding affinity to obviate the need for covalent binders. Here we report the evidence of a novel class of Imidazo[1,2-a]pyridine derivative as potentially significant novel inhibitors of KRASG12D, discovered through extensive ligand-based screening against 2-[(2R)-piperidin-2-yl]-1H-indole, an important scaffold for KRASG12D inhibition via switch-I/II (S-I/II) pocket. The proposed compounds exhibited similar binding affinities and overlapped pose configurations to 2-[(2R)-piperidin-2-yl]-1H-indole, serving as a reliable starting point for drug discovery. Comparative free energy profiles demonstrated that C4 [2-methyl-3-((5-phenyl-1H-1,2,4-triazol-3-yl)methyl)imidazo[1,2-a]pyridine] effectively shifted the protein to a stable low-energy conformation via a prominent transition state. The conformational changes across the transition revealed the conformational shift of switch-I and II to a previously known off-like conformation of inactive KRASG12D with rmsd of 0.91 Å. These conformations were even more prominent than the privileged scaffold 2-[(2R)-piperidin-2-yl]-1H-indole. The representative structure overlay of C4 and another X-ray crystallography solved BI-2852 bound inactive KRASG12D revealed that Switch-I and II exhibited off-like conformations. The cumulative variance across the first eigenvalue that accounted for 57 % of the collective variance validated this on-to-off transition. In addition, the relative interaction of C4 binding showed consistent patterns with BI-2852. Taken together, our results support the inhibitory activity of [2-methyl-3-((5-phenyl-1H-1,2,4-triazol-3-yl)methyl)imidazo[1,2-a]pyridine] by shifting active KRASG12D to an inactive conformation.
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Proteínas Proto-Oncogênicas p21(ras) , Piridinas , Piridinas/química , Piridinas/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/química , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Humanos , Imidazóis/química , Imidazóis/farmacologia , Conformação Proteica , Simulação de Acoplamento Molecular , Ligação Proteica , MutaçãoRESUMO
Na-l-Thyroxine (Na-l-Thy) is a frequently prescribed synthetic hormone for hypothyroidism treatment. Despite its efficacy, its hydrophobic nature poses a challenge for achieving optimal bioavailability. To address this, researchers explored various delivery methods, including micro-formulations and nano-formulations, for precise and prolonged release of hydrophobic and hydrophilic drugs. In this study, we developed micro-formulations with cyclodextrin and chitosan. Docking studies identified γ-cyclodextrin as the preferred option for forming a stable complex with Na-l-Thyroxine compared to α, and ß-cyclodextrins. Two micro-formulations were prepared compared: Na-l-Thyroxine loaded on chitosan (CS + Na-l-Thy) and Na-l-Thyroxine and γ-cyclodextrin inclusion complex (IC) loaded on chitosan (CS + IC). CS + IC exhibited superior encapsulation efficiency (91.25 %) and loading capacity (18.62 %) compared to CS + Na-l-Thy (encapsulation efficiency: 70.24 %, loading capacity: 21.18 %). Characterization using FTIR, SEM, and TGA validated successful encapsulation of Na-l-Thy in spherical microparticles with high thermal stability. In-vitro release studies at pH 1.2 and 7.4 showed that the CS + IC microparticles displayed gradual, consistent drug release compared to CS + Na-l-Thy -Thy. Both formulations showed faster release at pH 1.2 than at pH 7.4. Reaction kinetics analysis of release studies of CS + Na-l-Thy and CS + IC were best described by Higuchi kinetic model and Korsemeyer-Peppas kinetic model respectively. This study suggests that the CS + IC microparticles are an effective and stable delivery system for sustained release of hydrophobic Na-l-Thy.
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Quitosana , Ciclodextrinas , Nanopartículas , gama-Ciclodextrinas , Quitosana/química , Tiroxina , Preparações Farmacêuticas , Portadores de Fármacos/química , Nanopartículas/químicaRESUMO
BACKGROUND: Herpes simplex virus type 1 (HSV-1) is associated with Alzheimer's disease, which goes into a cycle of latency and reactivation. The present study was envisaged to understand the reasons for latency and specific molecular patterns present in the HSV-1. OBJECTIVE: The objective is the molecular dissection of Herpes simplex virus type 1 to elucidate molecular mechanisms behind latency and compare its codon usage patterns with genes modulated during Alzheimer's disease as a part of host-pathogen interaction. METHODS: In the present study, we tried to investigate the potential reasons for the latency of HSV-1 virus bioinformatically by determining the CpG patterns. Also, we investigated the codon usage pattern, the presence of rare codons, codon context, and protein properties. RESULTS: The top 222 codon pairs graded based on their frequency in the HSV-1 genome revealed that with only one exception (CUG-UUU), all other codon pairs have codons ending with G/C. Considering it an extension of host-pathogen interaction, we compared HSV-1 codon usage with that of codon usage of genes modulated during Alzheimer's disease, and we found that CGT and TTT are only two codons that exhibited similar codon usage patterns and other codons showed statistically highly significant different codon preferences. Dinucleotide CpG tends to mutate to TpG, suggesting the presence of mutational forces and the imperative role of CpG methylation in HSV-1 latency. CONCLUSIONS: Upon comparison of codon usage between HSV-1 and Alzheimer's disease genes, no similarities in codon usage were found as a part of host-pathogen interaction. CpG methylation plays an imperative role in latency HSV-1.
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Doença de Alzheimer , Herpes Simples , Herpesvirus Humano 1 , Humanos , Herpesvirus Humano 1/genética , Uso do Códon , Doença de Alzheimer/genética , Interações Hospedeiro-Patógeno/genética , Herpes Simples/metabolismoRESUMO
Improved and contemporary agriculture relies heavily on pesticides, yet some can be quite persistent and have a stable chemical composition, posing a significant threat to the ecology. Removing harmful effects is upon their degradability. Biodegradation must be emphasized to lower pesticide degradation costs, especially in the soil. Here, a decision-making system was used to determine the best microbial strain for the biodegradation of the pyrethroid-contaminated soil. In this system, the criteria chosen as: pH (C1), Temp (C2), RPM (C3), Conc. (C4), Degradation (%) (C5) and Time required for degradation(hrs) (C6); and five alternatives were Bacillus (A1), Acinetobacter (A2), Escherichia (A3), Pseudomonas (A4), and Fusarium (A5). The best alternative was selected by applying the TOPSIS (technique for order performance by similarity to ideal solution) method, which evaluates based on their closeness to the ideal solution and how well they meet specific requirements. Among all the specified criteria, Acinetobacter (A2) was the best and optimal based on the relative closeness value (( R i ∗ ) = 0.740 (A2) > 0.544 (A5) > 0.480 (A1) > 0.403 (A4) > 0.296 (A3)). However, the ranking of the other alternatives is also obtained in the order Fusarium (A5), Bacillus (A1), Pseudomonas (A4), Escherichia (A3). Hence this study suggests Acinetobacter is the best microbial strain for biodegradation of pyrethroids; while least preference should be given to Escherichia. Acinetobacter, versatile metabolic nature with various xenobiotic compounds' degradation ability, is gram-negative, aerobic, coccobacilli, nonmotile, and nonspore forming bacteria. Due to less study about Acinetobacter it is not in that much frame as the other microorganisms. Hence, considering the Acinetobacter strain for the biodegradation study will give more optimal results than the other microbial strains. Novelty of this study, the TOPSIS method is applied first time in selecting the best microbial strain for the biodegradation of pyrethroid-contaminated soil, considering this selection process as multi-criteria decision-making (MCDM) problem.
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Biodegradação Ambiental , Piretrinas , Microbiologia do Solo , Poluentes do Solo , Piretrinas/metabolismo , Poluentes do Solo/metabolismo , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação , Bacillus/metabolismo , Bacillus/genética , Fusarium/metabolismo , Tomada de Decisões , Pseudomonas/metabolismo , Pseudomonas/genética , Acinetobacter/metabolismo , Acinetobacter/genéticaRESUMO
Inflammatory bowel disease (IBD) is an inflammatory disorder of the gastrointestinal tract. The present study attempted to understand the codon usage preferences in genes associated with IBD progression. Compositional analysis, codon usage bias (CUB), Relative synonymous codon usage (RSCU), RNA structure, and expression analysis were performed to obtain a comprehensive picture of codon usage in IBD genes. Compositional analysis of 62 IBD-associated genes revealed that G and T are the most and least abundant nucleotides, respectively. ApG, CpA, and TpG dinucleotides were overrepresented or randomly used, while ApC, CpG, GpT, and TpA dinucleotides were either underrepresented or randomly used in genes related to IBD. The codons influencing the codon usage the most in IBD genes were CGC and AGG. A comparison of codon usage between IBD, and pancreatitis (non-IBD inflammatory disease) indicated that only codon CTG codon usage was significantly different between IBD and pancreatitis. At the same time, there were codons ATA, ACA, CGT, CAA, GTA, CCT, ATT, GCT, CGG, TTG, and CAG for whom codon usage was significantly different for IBD and housekeeping gene sets. The results suggest similar codon usage in at least two inflammatory disorders, IBD and pancreatitis. The analysis helps understand the codon biology, factors affecting gene expression of IBD-associated genes, and the evolution of these genes. The study helps reveal the molecular patterns associated with IBD.
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Assessment of the antimicrobial, micro tensile bond strength (µTBS), and degree of conversion (DC) of fifth-generation adhesive modified using photoactivated 0.5% rose bengal (RB) and photoactivated RB-doped titanium dioxide nanoparticles (TiO2NPs) in different concentrations (2% and 5%) as compared with the unmodified adhesive bonded to the carious affected dentin (CAD). Forty mandibular molars with caries progression up to the middle third of the dentin, as per the International Caries Detection and Assessment System (ICDAS) score of 4 and 5 were included. Specimens were divided into four groups based on etch and rinse adhesive (ERA) modification group 1: unmodified ERA, group 2: photoactivated 0.5% RB photosensitizer (PS) modified ERA, group 3: photoactivated RB-doped 2 wt% TiO2NPs adhesive, group 4: photoactivated RB-doped 5 wt% TiO2NPs adhesive. Followed by adhesive and composite restoration on the CAD surface. All the specimens were thermocycled and an assessment of µTBS and failure pattern analysis was performed. The antibacterial potency of RB and RB-doped TiO2NPs (2% and 5%) followed by their activation using visible light against Streptococcus mutans (S.mutans) were tested. The survival rate of S.mutans was assessed using the Kruskal-Wallis test. The analysis of µTBS involved the use of ANOVA, followed by a post-hoc Tukey honestly significant difference (HSD) multiple comparisons test. Group 1 (Unmodified ERA) (0.52 ± 0.31 CFU/mL) treated samples unveiled the highest means of bacterial survival and lowest µTBS (11.32 ± 0.63 MPa). Nevertheless, group 4: photoactivated RB-doped 5 wt% TiO2NPs adhesive displayed the lowest outcomes of S.mutans survival (0.11 ± 0.02 CFU/mL) and highest bond strength (18.76 ± 1.45 MPa). The photoactivated RB-doped 2 wt% TiO2NPs in adhesive demonstrated promising enhancements in both µTBS and antibacterial efficacy against S.mutans. However, it is noteworthy that this modification led to a decrease in the DC of the adhesive. RESEARCH HIGHLIGHTS: Unmodified ERA-treated samples unveiled the highest bacterial survival and the lowest µTBS. Photoactivated RB-doped 5 wt% TiO2NPs adhesive displayed the lowest S.mutans survival rate and highest bond strength. DC decreased with an increase in concentration of TiO2.
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Recently, there has been significant interest in photocatalytic reactions involving graphitic carbon nitride (g-C3N4) due to its sp2-hybridized carbon and nitrogen content and it is an ideal candidate for blending with other materials to enhance performance. Here, we have synthesized and analyzed both doped and undoped g-C3N4 nanoparticles. Specifically, we co-doped sulfur (S) into g-C3N4, integrated it with ZnO particles, and investigated the photocatalytic potential of these nanocomposites to remove Safranin-O dye. The initial step involved the preparation of pure g-C3N4 through calcination of urea. Subsequently, S-g-C3N4 was synthesized by calcining a mixture of urea and thiourea with a 3 : 1 ratio. Finally, the ZnO-S-g-C3N4 composite was synthesized using the liquid exfoliation technique, with distilled water serving as the exfoliating solvent. These samples were characterized by advanced techniques, including UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), energy dispersive X-ray (EDX) and scanning electron microscopy (SEM), to assess their crystallinity, morphology, optical properties, and phase purity. Subsequently, these nanocomposites were employed in catalytic and photocatalytic processes to remove the Safranin-O dye (SO). The results highlighted the formation of Z-scheme junction responsible for ZnO-S-g-C3N4's significant performance improvement. The comparison of results demonstrated that S-g-C3N4 and ZnO-S-g-C3N4 composites revealed an effective removal of Safranin-O dye in the presence of UV-light as compared to pure g-C3N4, as it was attributed to the phenomenon of improved separation of photogenerated charge carriers as a result of heterojunction formation between S-g-C3N4 and ZnO interfaces. In addition to improving photocatalytic performance, this study presents a facile route for producing ZnO-S-g-C3N4 composite with superior adsorption capabilities and selectivity.
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5-Fluorouracil (5-FU) has been the primary drug used in chemotherapy for colorectal carcinoma, and localizing the drug would be effective in avoiding its side effects and improving therapeutic outcomes. One approach to achieve this is by encapsulating the drug in microbeads. Alginate microbeads, in particular, exhibit promising pH-sensitive properties, making them an attractive option for colon targeting. Thus, the main aim of this study is to formulate and characterize 5-FU-encapsulated alginate microbeads as a pH-sensitive drug delivery system for controlled release in the gastrointestinal tract. In this study, the alginate microbeads encapsulating 5-FU was manufactured using electrospray methods. This method offers the advantages of promoting the formulation of uniformly small-sized microbeads with improved performance in terms of swelling and diffusion rates. The size and shape of the 5-FU microbeads are 394.23 ± 3.077 µm and have a spherical factor of 0.026 ± 0.022, respectively, which are considered acceptable and indicative of a spherical shape. The microbeads' encapsulation efficiency was found to be 69.65 ± 0.18%, which is considered high in comparison to other literature. The attenuated total reflectance - Fourier transform infrared spectroscopy (ATR-FTIR) data confirmed the complexation of sodium alginate with calcium ions, along with the encapsulation of 5-FU in the microbeads matrix. The 5-FU microbeads displayed pH-dependent swelling, exhibiting less swelling in simulated gastric fluid (SGF) than in simulated intestinal fluid (SIF). Additionally, the release of 5-FU from the microbeads is pH-dependent, with the cumulative percentage drug release being higher in simulated intestinal fluid than in SGF. The data indicate that the 5-FU microbeads can be utilized for the delivery of 5-FU in colon-targeted therapy, potentially leading to improved tumor treatment.
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Aim: Hydrogen sulfide and nitricoxide possess cytoprotective activity and in vivo, they are generated from exogenous sodium hydrosulfide and L-arginine respectively. Cisplatin is a major chemotherapeutic agent used to treat cancer and has a high incidence of nephrotoxicity as a side effect. The study aim was to explore the effects of NaHS and L-arginine or their combination on cisplatin induced nephrotoxicity in rats. Methods: Wistar Kyoto rats were given a single intraperitoneal dose of cisplatin (5 mg/kg) followed either by NaHS (56 µmol/kg, i. p.), L-arginine (1.25 g/L in drinking water) or their combination daily for 28-days. Post-mortem plasma, urine and kidney samples were collected for biochemical assays and histopathological analysis. Results: Cisplatin decreased body weights and increased urinary output, while plasma creatinine and urea levels were elevated, but sodium and potassium concentrations were diminished. The renal function parameters, blood urea nitrogen and creatinine clearance, were raised and decreased respectively. Regarding markers of reactive oxygen species, plasma total superoxide dismutase was reduced, whereas malondiadehyde was augmented.Cisplatin also diminished plasma and urinary H2S as well as plasma NO, while NaHS and L-arginine counteracted this activity on both redox-active molecules. Cisplatin cotreatment with NaHS, and/or L-arginine exhibited a reversal of all other measured parameters. Conclusion: In current study, NaHS and L-arginine as monotherapy protected the rats from cisplatin-induced nephrotoxicity but the combination of both worked more effectively suggesting the augmented anti-inflammatory and antioxidative potential of test treatments when administered together.
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Polyelectrolyte complexes (PECs) formed by the interaction between oppositely charged polymers have emerged as promising carriers for accomplishing colon-specific release. In this study, we have explored the potential of polyelectrolyte complexes between a succinate derivative of Leucaena leucocephala galactomannan and cationic guar gum for colon delivery of synbiotic. The PECs were prepared using a polyelectrolyte complexation method and characterized. The PECs exhibited excellent stability, with high encapsulation efficiency for both probiotics (95.53 %) and prebiotics (83.33 %). In vitro studies demonstrated enhanced survivability and proliferation of the encapsulated probiotics in the presence of prebiotics (93.29 %). The SEM images revealed a smooth and firm structure with reduced number of pores when both prebiotic and probiotic were encapsulated together. The treatment with synbiotic PECs in acetic acid induced IBD rats significantly relieves colitis symptoms as was evident from colon/body ratio, DAI score and histopathology studies. An increase in the protein and reduced glutathione levels and reduction in superoxide dismutase activity was observed in colitic rats that received synbiotic treatment as compared to colitic rats. Overall, this study highlights the potential of Leucaena leucocephala succinate-cationic guar gum PECs as a promising system for colon-specific synbiotic delivery, with implications for improved gut health and the treatment of various gastrointestinal disorders.
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Mitochondrial dysfunction is the leading cause of neurodegenerative disorders like Alzheimer's disease and Parkinson's disease. Mitochondria is a highly dynamic organelle continuously undergoing the process of fission and fusion for even distribution of components and maintaining proper shape, number, and bioenergetic functionality. A set of genes governs the process of fission and fusion. OPA1, Mfn1, and Mfn2 govern fusion, while Drp1, Fis1, MIEF1, and MIEF2 genes control fission. Determination of specific molecular patterns of transcripts of these genes revealed the impact of compositional constraints on selecting optimal codons. AGA and CCA codons were over-represented, and CCC, GTC, TTC, GGG, ACG were under-represented in the fusion gene set. In contrast, CTG was over-represented, and GCG, CCG, and TCG were under-represented in the fission gene set. Hydropathicity analysis revealed non-polar protein products of both fission and fusion gene set transcripts. AGA codon repeats are an integral part of translational regulation machinery and present a distinct pattern of over-representation and under-representation in different transcripts within the gene sets, suggestive of selective translational force precisely controlling the occurrence of the codon. Out of six synonymous codons, five synonymous codons encoding for leucine were used differently in both gene sets. Hence, forces regulating the occurrence of AGA and five synonymous leucine-encoding codons suggest translational selection. A correlation of mutational bias with gene expression and codon bias and GRAVY and AROMA signifies the selection pressure in both gene sets, while the correlation of compositional bias with gene expression, codon bias, protein properties, and minimum free energy signifies the presence of compositional constraints. More than 25% of codons of both gene sets showed a significant difference in codon usage. The overall analysis shed light on molecular features of gene sets involved in fission and fusion.
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Haem oxygenase-1 (HO-1) is a ubiquitously expressed gene involved in cellular homoeostasis, and its imbalance in expression results in various disorders. To alleviate such disorders, HO-1 gene expression needs to be modulated. Codon usage bias results from evolutionary forces acting on any nucleotide sequence and determines the gene expression. Like codon usage bias, codon pair bias also exists, playing a role in gene expression. In the present study, HO-1 gene was recoded by manipulating codon and codon pair bias, and four such constructs were made through codon/codon pair deoptimization and codon/codon pair optimization to reduce and enhance the HO-1 gene expression. Codon usage analysis was done for these constructs for four tissues brain, heart, pancreas and liver. Based on codon usage in different tissues, gene expression of these tissues was determined in terms of the codon adaptation index. Based on the codon adaptation index, minimum free energy, and translation efficiency, constructs were evaluated for enhanced or decreased HO-1 expression. The analysis revealed that for enhancing gene expression, codon pair optimization, while for reducing gene expression, codon deoptimization is efficacious. The recoded constructs developed in the study could be used in gene therapy regimens to cure HO-1 over or underexpression-associated disorders.
RESUMO
The ongoing Russian-Ukrainian conflict has caused a significant displacement of individuals, with an estimated five million Ukrainians seeking temporary refuge in other countries. We conducted a survey among Ukrainians in various countries worldwide using a convenience sample and analyzed 144 responses. The participants were divided into two groups: group 1, consisting of 92 Ukrainian refugees who were forced to leave their country due to the conflict, and group 2, comprising 52 individuals who did not change their place of residence. Data were collected through a structured online questionnaire consisting of socio-demographic questions, Depression, Anxiety, and Stress Scale-21, Insomnia Severity Index, and Symptom Checklist-90 during May-November 2022. We found that there were statistically significantly higher levels of obsessive-compulsive symptoms, depression, hostility, and overall distress in group 1. Group 1 had a higher risk of depression, anxiety, and stress, but not insomnia. In our study, refugee status, dissatisfaction with the state of health, job loss, suffering due to hostilities, and the received support from volunteers, friends, or relatives were the most important factors for the mental disorders. A bi-directional relationship was discovered between anxiety and insomnia, with both symptoms being associated with COVID-19 and subsequent psychiatric disorders. This study highlights the mental health and sleep problems faced by Ukrainian refugees as a result of the conflict linked to numerous social factors. Ukrainian refugees need social support programs and special attention to their mental health to facilitate their post-migration adaptation and integration into the host society.