Insight in Quinazoline-based HDAC Inhibitors as Anti-cancer Agents.

Cancer remains a primary cause of death globally, and effective treatments are still limited. While chemotherapy has notably enhanced survival rates, it brings about numerous side effects. Consequently, the ongoing challenge persists in developing potent anti-cancer agents with minimal toxicity. The versatile nature of the quinazoline moiety has positioned it as a pivotal component in the development of various antitumor agents, showcasing its promising role in innovative cancer therapeutics. This concise review aims to reveal the potential of quinazolines in creating anticancer medications that target histone deacetylases (HDACs).

Unravelling co-catalyst integration methods in Ti-based metal-organic gels for photocatalytic H2 production.

The synthesis, characterization and photocatalytic hydrogen evolution reaction (HER) performance of a series of metal-organic gels (MOGs) constructed from titanium(IV)-oxo clusters and dicarboxylato linkers (benzene-1,4-dicarboxylato and 2-aminobenzene-1,4-dicarboxylato) are described. All the MOGs exhibit a microstructure comprised of metal-organic nanoparticles intertwined into a highly meso-/macroporous structure, as demonstrated by cryogenic transmission electron microscopy and gas adsorption isotherms. Comprehensive chemical characterization enabled the estimation of the complex formula for these defective materials, which exhibit low crystallinity and linker vacancies. To gain deeper insights into the local structure, X-ray absorption fine structure (XAFS) spectroscopy experiments were performed and compared to that of the analogous crystalline metal-organic framework. Additionally, the ultraviolet-visible absorption properties and optical band gaps were determined from diffuse reflectance spectroscopy data. The MOGs were studied as light absorbers for the sacrificial photocatalytic HER under simulated solar light irradiation using a platinum co-catalyst by either (1) in situ photodeposition or (2) ex situ doping process, through a post-synthetic metalation of the MOG structure. The chemical analysis of the metalation, along with high-angle annular dark-field scanning transmission electron microscopy, revealed that although the in situ addition of the co-catalyst led to greater HER rates (227 vs. 110 µmolH2 gMOG-1 h-1 for in situ and ex situ, respectively), the ex situ modification provided a finer distribution of platinum nanoparticles along the porous microstructure and, as a result, it led to a more efficient utilization of the co-catalyst (45 vs. 110 mmolH2 gPt-1 h-1).

Estimation of dietary intake of sodium, potassium, phosphorus and protein in healthy Indian population and patients with chronic kidney disease.

Introduction: Poor nutritious diet is a major risk element for non-communicable diseases (NCD), which are of considerable public health concern. Given the diverse dietary patterns in India, precise determination of nutrient consumption is crucial for disease management. The present study assessed the dietary intake of sodium, potassium, protein, and phosphorus among North Indians. Methods: This cross-sectional study included healthy adults and adults with stage 2 to 4 chronic kidney disease (CKD). We analysed sodium, protein, potassium and phosphorus intakes using one-time 24-h urinary excretion. Dietary intake was also analysed in subgroups based on sex, body mass index, blood pressure and abdominal obesity. We evaluated the performance of various equations available to estimate sodium intake using a spot urine sample with respect to the sodium excretion measured in a 24-h urine sample. Descriptive statistics was used along with t-test for statistical significance. Results: A total of 404 subjects (182 adult healthy subjects and 222 adults with CKD) with a mean age of 47.01 ± 11.46 years were studied. Mean dietary intakes of sodium, salt, potassium, protein and phosphorus were 2.94 ± 1.68 g/day, 7.42 ± 4.24 g/day, 1.43 ± 0.59 g/day, 47.67 ± 14.73 g/day and 0.86 ± 0.39 g/day, respectively. There were no differences in nutrient consumption between adults who were healthy and those with CKD. Consumption of sodium, salt, protein, potassium, and phosphorus among healthy population vs. those with CKD were 2.81 ± 1.60 vs. 3.05 ± 1.73 g/day (p = 0.152), 7.08 ± 4.04 vs. 7.70 ± 4.37 g/day (p = 0.143), 47.16 ± 14.59 vs. 48.08 ± 14.86 g/day (p = 0.532), 1.38 ± 0.59 vs. 1.48 ± 0.58 g/day (p = 0.087) and 0.86 ± 0.41 vs. 0.87 ± 0.37 g/day (p = 0.738), respectively. Men had higher consumption of these nutrients than women. Compared to non-hypertensives, hypertensive subjects had higher consumption of salt (8.23 ± 4.89 vs. 6.84 ± 3.59 g/day, p = 0.002) and potassium (1.51 ± 0.63 vs. 1.38 ± 0.55 g/day, p = 0.024), however, no difference were found in protein and phosphorus intakes. In terms of performance of equations used to estimate 24-h sodium intake from spot urinary sodium concentration against the measured 24-h urinary sodium excretion, INTERSALT 2 equation exhibited the least bias [1.08 (95% CI, -5.50 to 7.66)]. Conclusion: The study shows higher-than-recommended salt and lower-than-recommended potassium intake in the north Indian population compared to those recommended by guidelines. The dietary protein intake is below the recommended dietary allowance. These findings help the development of targeted policies for dietary modification to reduce the risk of the development and progression of CKD.

In-silico identification and exploration of small molecule coumarin-1,2,3-triazole hybrids as potential EGFR inhibitors for targeting lung cancer.

Globally, lung cancer is a significant public health concern due to its role as the leading cause of cancer-related mortalities. The promising target of EGFR for lung cancer treatment has been identified, providing a potential avenue for more effective therapies. The purpose of the study was to design a library of 1843 coumarin-1,2,3-triazole hybrids and screen them based on a designed pharmacophore to identify potential inhibitors targeting EGFR in lung cancer with minimum or no side effects. Pharmacophore-based screening was carried out and 60 hits were obtained. To gain a better understanding of the binding interactions between the compounds and the targeted receptor, molecular docking was conducted on the 60 screened compounds. In-silico ADME and toxicity studies were also conducted to assess the drug-likeness and safety of the identified compounds. The results indicated that coumarin-1,2,3-triazole hybrids COUM-0849, COUM-0935, COUM-0414, COUM-1335, COUM-0276, and COUM-0484 exhibit dock score of - 10.2, - 10.2, - 10.1, - 10.1, - 10, - 10 while reference molecule - 7.9 kcal/mol for EGFR (PDB ID: 4HJO) respectively. The molecular docking and molecular dynamics simulations revealed that the identified compounds formed stable interactions with the active site of EGFR, indicating their potential as inhibitors. The in-silico ADME and toxicity studies showed that the compounds had favorable drug-likeness properties and low toxicity, further supporting their potential as therapeutic agents. Finally, we performed DFT studies on the best-selected ligands to gain further insights into their electronic properties. The findings of this study provide important insights into the potential of coumarin-1,2,3-triazole hybrids as promising EGFR inhibitors for the management of lung cancer.

Rheumatoid arthritis synovial fluid shows enrichment of T-cells producing GMCSF which are polyfunctional for TNFα and IFNγ.

OBJECTIVES: GMCSF+T-cells may be involved in pathogenesis of rheumatoid arthritis (RA), and polyfunctionality may be a marker of pathogenicity. Although, higher frequencies of CD4+GMCSF+ T-cells have been reported, there are no data on CD8+GMCSF+ T-cells or polyfunctionality.Our objective was to enumerate frequencies of CD8+GMCSF+ T cells in RA blood and synovial fluid (SF), and assess their polyfunctionality, memory phenotype and cytotoxic ability. METHODS: This study included RA patients (blood samples,in some with paired synovial fluid (SF)), healthy controls (HC) (blood) and SpA patients (SF). In some RA patients' blood was sampled twice, before and 16-24 weeks after methotrexate (MTX) treatment. After mononuclear cell isolation from blood and SF, ex-vivo stimulation using PMA/Ionomycin was done, and cells were stained (surface and intracellular after permeabilisation/fixation). Subsequently, frequencies of GMCSF+CD8+ and CD4+ T-cells, polyfunctionality (TNFα, IFNγ, IL-17), phenotype (memory) and perforin/granzyme expression were assessed by flowcytometry. RESULTS: There was no significant difference in frequencies of GMCSF+CD8+ (3.7, 4.1%, p=0.540) or GMCSF+CD4+ T-cells (4.5, 5.2%, p=0.450) inblood of RA and HC. However, there was significant enrichment of both CD8+GMCSF+ (5.8, 3.9%, p=0.0045) and CD4+GMCSF+ (8.5, 4.5%, p=0.0008) T-cells inSF compared to blood in RA patients. Polyfunctional triple cytokine positive TNFα+IFNγ+GMCSF+CD8+T-cells (81, 36%, p=0.049) and CD4+T-cells (48, 32%, p=0.010) was also higher in SF compared to blood in RA. CD8+ T cells showed higher frequency of effector-memory phenotype and granzyme-B expression in RA-SF. On longitudinal follow-up, blood CD4+GMCSF+ T-cells significantly declined (4.6, 2.9%, p=0.0014) post-MTX. CONCLUSIONS: We report a novel finding of enrichment of CD8+GMCSF+ in addition to CD4+GMCSF+ T-cells in RA-SF. These cells showed higher polyfunctionality for TNFα and IFNγ, and effector memory phenotype suggesting their involvement in RA pathogenesis.

Growth performance, meat quality and hematological parameters of broiler chickens fed safflower seed.

The aim of the current study was to determine the effects of dietary supplementation of safflower seed (SS) on the growth performance and hematological parameters of broiler birds along with the physicochemical, textural and sensory attributes of chicken meat. A total of 200 male chickens (7-days-old) were distributed into 5 groups (40 chickens in each) with 5 replicates of 8 chicks in a 42-day experiment. Each group was allocated to one of 5 dietary treatments, i.e., 0, 2.5, 5, 7.5, and 10% SS. The experimental diets were formulated for starter (7 to 21 days) and finisher (22 to 42 days) phases. Inclusion of SS in the diet improved growth performances in treatment groups between 7 and 42 days. The highest and lowest body weights were observed at the 5% SS and 0% SS levels, respectively. The physicochemical attributes of breast and thigh meat were found (P > 0.05) except for crude fat. The crude fat was significantly (P < 0.05) increased with increasing levels of SS in the diet. The inclusion of SS in the diet did not negatively impact the textural properties, i.e., hardness, cohesiveness, springiness, gumminess, chewiness, and shear force of breast and thigh meat. There was no significant difference in the sensory parameters of cooked chicken meat with increasing levels of SS in the diet. The results demonstrated a significant (P < 0.01) improvement in hematological parameters in the blood samples of broiler chickens fed diet supplemented with various levels of SS for five weeks. These findings suggest that, SS may be used as an oil seed for broiler chicken feed.

Quantitative in situ synchrotron X-ray analysis of the ALD/MLD growth of transition metal dichalcogenide TiS2 ultrathin films.

We present the results of a full quantitative analysis of X-ray absorption spectroscopy (XAS) performed in situ during the growth of ultrathin titanium disulfide (TiS2) films via an innovative two-step process, i.e. atomic layer deposition/molecular layer deposition (ALD/MLD) followed by annealing. This growth strategy aims at separating the growth process from the crystallization process by first creating an amorphous Ti-thiolate that is converted later to crystalline TiS2via thermal annealing. The simultaneous analysis of Ti and S K-edge XAS spectra, exploiting the insights from density functional theory calculations, allows us to shed light on the chemical and structural mechanisms underlying the main steps of growth. The nature of the bonding at the base of the interface creation with the SiO2 substrate is disclosed in this study. Evidence of a progressive incorporation of S in the amorphous Ti-thiolate is given. Finally, it is shown that the annealing step plays a critical role since the transformation of the Ti-thiolate into nanocrystalline TiS2 and the loss of S are simultaneously induced, validating the two-step synthesis approach, which entails distinct growth and crystallization steps. These observations contribute to a deeper understanding of the bonding mechanism at the interface and provide insights for future research in this field and the generation of ultra-thin layered materials.

Design, synthesis, biological evaluations and in silico studies of N-substituted 2,4-thiazolidinedione derivatives as potential a-glucosidase inhibitors.

Diabetes mellitus is considered as one of the principal global health urgencies of the twenty first century. In the present investigation, novel N-substituted 2,4-thiazolidinedione derivatives were designed, synthesized, and characterized by spectral techniques. All the newly synthesized N-substituted 2,4-thiazolidinedione derivatives were tested for in vitro α-glucosidase inhibitory activities and compounds A-12 and A-14 were found to be the most potent which were further subjected to in-vivo disaccharide loading test. The most potent compound was also found to be non-toxic in cytotoxicity studies. Further, docking studies were carried out to investigate the binding mode and key interactions with amino acid residues of α-glucosidase. Molecular dynamic simulations studies for the compounds acarbose, A2, A12, and A14 were done with α-glucosidase protein. Further, ΔG was calculated for acarbose, A2, A12, and A14. In silico studies and absorption, distribution, metabolism, excretion (ADME) prediction studies were also executed to establish the 'druggable' pharmacokinetic profiles. Here, we have developed novel N-substituted TZD analogues with different alkyl groups as α-glucosidase inhibitors.Communicated by Ramaswamy H. Sarma.

Assessment of Probiotic and Antioxidant Potential of Indigenous Lactobacillus Strains Isolated from Human Faecal Samples.

This study aimed to isolate and characterize probiotic Lactobacilli from human faecal samples of Jammu region of India and evaluation of their antioxidative properties. A total of 29 Lactobacillus strains were isolated and tested for their ability to withstand different pH levels, high concentrations of bile salt and lysozyme along with their adhesion ability to different hydrocarbons and auto-aggregation. Selected probiotic Lactobacillus isolates were further examined for their antioxidant potential using ABTS, DPPH methods, and the ability to scavenge superoxide and hydroxyl radicals. The results showed that Lactobacillus LpJ1 (7.93 ± 0.23) and LpJ5 (7.93 ± 0.59) had the highest cell viability at a pH of 2.5, while Lactobacillus LpJ16 (7.91 ± 0.48) had the highest resistance to bile salts. Many of the isolates also demonstrated good tolerance to lysozyme. The adhesion abilities of these isolates were characterized by cell surface hydrophobicity and auto aggregation which ranged between 50.32% to 77.8% and 51.02% to 78.95% respectively. In addition, Lactobacillus LpJ5 and LpJ8 showed excellent antioxidant activity. Based on these findings, the selected probiotic strains could be potential candidates for use in functional food to reduce oxidative stress.

Synthesis of Metallo-Chromone Porphyrin Nano-Starch Sensitizers as Photodynamic Therapeutics for the Eradication of Enterococci Dental Pathogens.

Photodynamic therapy (PDT), as an advanced, alternative, and promising treatment, can inhibit dental pathogens. PDT employs the activation of photosensitizers via the light of a particular wavelength and molecular oxygen to inhibit dental pathogens. Herein, we present a comprehensive study on the synthesis and characterization of three chromone-porphyrins [Zn(II)-5-[4-chromone]-15-(4-phenyl)porphyrin (ZnCP), 5-[4-chromone]-15-(4-12 phenyl)porphyrin (DMCP), and Pd(II)-5-[4-chromone]-15-(4-phenyl)porphyrin (PdCP)]. Next, the computational study was also performed to establish the correlation between photophysical properties and theoretical calculations for those chromone-porphyrins using density functional theory and time-dependent density functional theory. Furthermore, chromone-porphyrins were encapsulated in starch nanoparticles to develop soluble nano-starch sensitizers (ZnCP-SNPs, DMCP-SNPs, and PdCP-SNPs) via the nanoprecipitation technique. Upon green light exposure, these nano-starch sensitizers exhibited excellent singlet oxygen generation ability. Moreover, final nanoformulations have been explored for pH responsiveness. Based on our intriguing findings, the chromone-porphyrin-loaded nano-starch sensitizers displayed great potential as prospective PDT to treat enterococci dental pathogens.

Modelling of compression ignition engine by soft computing techniques (ANFIS-NSGA-II and RSM) to enhance the performance characteristics for leachate blends with nano-additives.

Integrating nanoparticles in waste oil-derived biodiesel can revolutionize its performance in internal combustion engines, making it a promising fuel for the future. Nanoparticles act as combustion catalysts, enhancing combustion efficiency, reducing emissions, and improving fuel economy. This study employed a comprehensive approach, incorporating both quantitative and qualitative analyses, to investigate the influence of selected input parameters on the performance and exhaust characteristics of biodiesel engines. The focus of this study is on the potential of using oils extracted from food waste that ended up in landfills. The study's results are analysed and compared with models created using intelligent hybrid prediction approaches including adaptive neuro-fuzzy inference system, Response surface methodology-Genetic algorithm, and Non sorting genetic algorithm. The analysis takes into account engine load, blend percentage, nano-additive concentration, and injection pressure, and the desired responses are the thermal efficiency and specific energy consumption of the brakes, as well as the concentrations of carbon monoxide, unburned hydrocarbon, and oxides of nitrogen. Root-mean-square error and the coefficient of determination were used to assess the predictive power of the model. Comparatively to Artificial Intelligence and the Response Surface Methodology-Genetic Algorithm model, the results provided by NSGA-II are superior. This is because it achieved a pareto optimum front of 24.45 kW, 2.76, 159.54 ppm, 4.68 ppm, and 0.020243% for Brake Thermal Efficiency, Brake Specific Energy Consumption, Oxides of nitrogen, Unburnt Hydro Carbon, and Carbon monoxide. Combining the precision of ANFIS's prediction with the efficiency of NSGA-optimization II's gives a reliable and thorough evaluation of the engine's settings. The qualitative assessment considered practical aspects and engineering constraints, ensuring the feasibility of applying the parameters in real-world engine applications.

From Theory to Practice: A Sustainable Solution to Water Scarcity by Using a Hybrid Solar Distiller with a Heat Exchanger and Aluminum Oxide Nanoparticles.

The study presently conducted focused on analyzing a solar-powered desalination setup that had a double slope. It can recycle blackish water into drinking water with solar energy. Not only does this result in a significant decrease in carbon emissions but it also represents an environmentally beneficial alternative that is particularly suited for arid locations that are lacking of electrical infrastructure. This system was equipped with a PVT system which makes the system self-sustainable and a CPC collector and implemented the use of aluminum oxide (Al2O3) nanoparticles to enhance its energy efficiency. Energy matrices, economic analysis, and life cycle conversion efficiency were evaluated. The study was conducted annually in New Delhi, with input data provided by IMD in Pune, India. MATLAB was used for the analytical calculations. Energy and exergy were utilized to determine the average annual energy output, which was found to be 8.5%. Additionally, the average energy payback time was calculated to be 16.16%, the average energy payback factor was 13.91%, and the average life cycle cost conversion efficiency was 7.15% higher. The proposed system demonstrated superior performance compared to the previous system in terms of annual yield, energy payback time (EPBT), efficiency of life cycle cost (LCCE), and factor of energy payback (EPBF). The hybrid system has the potential to meet the future demand for potable water and become self-sustainable.

Combined Effect of Operating Parameters and Nanoparticles on the Performance of a Diesel Engine: Response Surface Methodology-Coupled Genetic Algorithm Approach.

This paper's goal is to ascertain the optimum input parameters and nanoparticle concentrations for least emission and better performance by utilizing the genetic algorithm (GA) and response surface methodology (RSM) in a single-cylinder diesel engine running with 20% blend of biodiesel derived from Manilkara zapota seeds. Experiments to be conducted on the engine were designed with a central composite design (CCD) with input parameters of loads (20-100%), nanoparticle concentrations (NPCs, 0-80 ppm), compression ratios (CRs, 16.5-18.1), injection pressures (IPs, 190-230 bar), and injection timings [ITs, 17-29° bTDC (before top dead center)], and the engine response was recorded. The comparative analysis of optimization tools RSM and GA was employed for finding the ideal setting of engine input parameters and nanoparticle concentrations based on the maximization of performance [brake thermal efficiency (BTE) and brake-specific fuel consumption (BSFC)] and minimization of emissions [(hydrocarbon (HC), carbon monoxide (CO), and nitrogen oxides (NOx)]. The best result was obtained by the RSM method. The optimized input parameters were recorded at a load of 59.36%, an NPC of 80 ppm, a CR of 18.1, an IP of 192.02 bar, and an IT of 18.62° bTDC. At these optimized settings, the performance and emissions were 32.4767% BTE, 0.1905 kg/kW h BSFC, 26.8436 ppm HC, 0.0272% CO, and 83.854 ppm NOx emissions from the engine. The developed model was validated through a confirmatory experiment, and the prediction error was within 8%. Thus, the applied model is appropriate for improving the engine's emission and performance attributes.

Quorum sensing inhibitors as Therapeutics: Bacterial biofilm inhibition.

The overuse and inappropriate use of antibiotics to treat bacterial infections has led to the development of multiple drug resistant strains. Biofilm is a complex microorganism aggregation defined by the presence of a dynamic, sticky, and protective extracellular matrix made of polysaccharides, proteins, and nucleic acids. The infectious diseases are caused by bacteria that flourish within quorum sensing (QS) mediated biofilms. Efforts to disrupt biofilms have enabled the identification of bioactive molecules produced by prokaryotes and eukaryotes. The QS system is quenched predominantly by these molecules. The phenomenon is also termed as quorum sensing (QS). Both synthetic and natural substances have been discovered to be useful in QS. This review describes natural and synthetic quorum sensing inhibitors (QSIs) with the potential to treat bacterial infections. It includes the discussion on quorum sensing, mechanism of quorum sensing, effect of substituents on the activity. These discoveries could result in effective therapies using far lower dosages of medications, particularly antibiotics, are currently needed.

Immune Control of Avian Influenza Virus Infection and Its Vaccine Development.

The avian influenza A virus (AIV) is naturally prevalent in aquatic birds, infecting different avian species and transmitting from birds to humans. Both AIVs, the H5N1 and H7N9 viruses, have the potential to infect humans, causing an acute influenza disease syndrome in humans, and are a possible pandemic threat. AIV H5N1 is highly pathogenic, whereas AIV H7N9 has comparatively low pathogenicity. A clear insight into the disease pathogenesis is significant to understand the host's immunological response, which in turn facilitates the design of the control and prevention strategies. In this review, we aim to provide comprehensive details on the pathogenesis and clinical features of the disease. Moreover, the innate and adaptive immunological responses to AIV and the recent studies conducted on the CD8+ T cell immunity against AIVs are detailed upon. Further, the current status and advancement in the development of AIV vaccines, along with the challenges, are also discussed. The information provided will be helpful in combating the transmission of AIV from birds to humans and, thus, preventing severe outbreaks leading to pandemics worldwide.

A randomized trial of once daily versus twice daily dosing of oral iron in CKD.

We investigated the effect of two dosing regimens of oral iron on iron status and hematological parameters in patients with CKD. In this single center, open label, randomized, active controlled clinical trial, stable adult patients with CKD stage G3-4 with percentage transferrin saturation (%TSAT) ≤ 30% and serum ferritin ≤ 500 ng/ml were eligible. Participants were randomized to receive either 100 mg of ferrous ascorbate once daily (OD group) or 100 mg of ferrous ascorbate twice daily (BD group, total daily dose 200 mg). The primary outcome was change in %TSAT between groups over 12 weeks. The secondary outcomes were changes in other iron status and hematological parameters, serum interleukin-6 (IL-6) and hepcidin. 80 participants were enrolled out of which 76 completed the study. Change in %TSAT was not significantly different between groups (ß = - 1.43, 95% CI - 3.99 to 1.12, BD group as reference). The rise in serum ferritin was less in the OD group as compared to BD group (ß = - 0.36, 95% CI - 0.61 to - 0.10) whereas MCHC increased in the OD group as compared to decrease in the BD group (ß = 0.37, 95% CI 0.067-0.67). These observations need exploration to ascertain the impact of different oral iron dosing strategies in CKD.

Green synthesis of lignin-based nanoparticles as a bio-carrier for targeted delivery in cancer therapy.

Polymeric magnetic nanoparticles have shown higher efficacy in cancer diagnosis and treatment than conventional chemotherapies. Lignin is an abundantly available natural polymer that can be selectively modified using a rapidly expanding toolkit of biocatalytic and chemical reactions to yield 'intelligent' theranostic-nanoprobes. We aim to valorize lignin to develop a natural polymeric-magnetic-nano-system for the targeted delivery of methotrexate. In the current study, we synthesized nanoparticles of lignin and iron oxide with methotrexate using a new approach of anti-solvent precipitation with ultrasonication. The ensuing nanoparticles are magnetic, smooth, polyhedral with characteristic dimension of 110-130 nm. The drug loading and encapsulation efficiencies were calculated to be 66.06 % and 64.88 %, respectively. The nanoparticles exhibit a concentration-dependent release of methotrexate for the initial 24 h, followed by sustained release. Moreover, formulation is non-hemolytic and scavenges radicals owing to the antioxidant property of lignin. Additionally, methotrexate delivered using the nanoparticles exhibited higher cytotoxicity in cellular-viability assays employing breast cancer and macrophage cell lines compared to the pure form of the drug. Synergistic action of lignin, iron oxide, and methotrexate contribute to enhanced caspase-3 activity and reduced glutathione levels in the breast cancer cells, as well as elevated internalization of the drug on account of increased receptor-mediated endocytosis.

Synthesis, biological evaluation and in silico studies of 2-aminoquinolines and 1-aminoisoquinolines as antimicrobial agents.

The current study reports synthesis of 2-aminoquinolines and 1-aminoisoquinolines derivatives and their characterization. Further, in vitro studies were conducted to determine antimicrobial activities. Compound 3 h showed maximum activity against B. subtilis (IC50: 0.10±0.02 µM) and E. coli (IC50: 0.13±0.01 µM) whereas compound 3i showed higher antimicrobial activity against E. coli (IC50: 0.11±0.01) and C. viswanathii (IC50: 0.10±0.05 µM). Safety profiles of the most potent derivatives were evaluated utilizing cell viability assay using RAW 264.7 and HeLa cell lines and in vitro hemolytic assay was carried out freshly isolated RBC from healthy rat. Furthermore, in silico studies, like molecular docking, binding free energy calculations and ADME predictions were done to get the best lead candidates. Additionally, molecular dynamic simulation for 100 ns was performed to know stability of protein and ligand complex. The active compounds were found to be non-toxic and non-hemolytic and hold great promise to become newer antimicrobial agents.

Expression of heterologous heparan sulphate binding protein of Helicobacter pylori on the surface of Lactobacillus rhamnosus GG.

Helicobacter pylori (H. pylori) is one of most commonly found pathogen in the stomach. In spite of emergence of different treatment strategies, H. pylori infection remains difficult to treat. The bioengineered probiotic lactobacilli that could displace H. pylori and simultaneously present immunogenic peptides such as heparan sulphate binding protein (Hsbp) to elicit immune response could emerge as a potential therapeutic agent. The aim of this study was to discover the anti-H. pylori activities and faster exclusion of H. pylori from host cells by the recombinant strain of Lactobacillus expressing the immunogenic Hsbp protein. The results were promising and showed a 65% reduction in H. pylori adhesion after two hours of pre-incubation with recombinant-LGG and HeLa S3 cells, followed by the adhesion of H. pylori pathogen (P < 0.002). Additionally, 36% and 39% reduction were examined in co-incubation and post-incubation with recombinant-LGG, respectively. When challenged with H. pylori, the proinflammatory cytokine expression was also down regulated in recombinant-LGG treated HeLa S3 cells. This promising result provides a new insight of bioengineered probiotic lactobacilli which could displace H. pylori and simultaneously has immunogenic properties thereby may be useful to prevent H. pylori infection. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03428-4.

Levofloxacin loaded clove oil nanoscale emulgel promotes wound healing in Pseudomonas aeruginosa biofilm infected burn wound in mice.

Owing to their tolerance to antibiotics, bacterial biofilms continue to pose a threat to mankind and are leading cause for non-healing of burn wounds. Within the biofilm matrix, antibiotics become functionally inactive due to restricted penetration and enzymatic degradation leading to rise of antimicrobial resistance. The objective of present investigation was to develop and characterize levofloxacin (LFX) loaded clove oil nanoscale emulgel (LFX-NE gel) and evaluate its in vivo therapeutic efficacy in Pseudomonas aeruginosa biofilm infected burn wound in mice. The optimized emulgel was found to possess good texture profile and showed shear thinning behavior. In vitro release study demonstrated complete drug release in 8 h and emulgel was found to be stable for 3 months at 25 °C and 40 °C. In vivo study revealed biofilm dispersal, complete wound closure, re-epithelialization and collagen deposition by LFX-NE gel in comparison to various control groups. LFX-NE gel was able to clear the infection within 7 days of treatment and promote wound healing as well. Therefore, administration of LFX-incorporated NE gel could be a beneficial treatment strategy for P. aeruginosa biofilm-infected burn wounds.