Synthesis and bioactivity of a novel surfactin-based lipopeptide for mRNA delivery.

The effective delivery of messenger ribonucleic acid (mRNA) to specific cell types and target tissues poses a significant challenge in nonviral therapeutic strategies. Lipid-based nanoparticles (LNPs) have emerged as a leading carrier system for delivering mRNA, particularly for infectious diseases, such as COVID-19. This study aimed to describe the synthesis of a novel lipopeptide based on surfactin, a naturally occurring surfactant. Additionally, a series of novel LNPs were rationally designed, based on the modified surfactin, OleSurf, and were formulated and optimized. The physicochemical properties, morphologies, and stabilities of the particles were evaluated. All formulations containing OleSurf produced particles with a diameter <80 nm and an encapsulation efficiency >95%. OleSurf LNPs demonstrated excellent transfection efficiency and luciferase expression with no cytotoxicity, compared to lipofectamine 2000, a known transfection reagent, and were comparable to the DLin-MC3-DMA lipid. OleSurf-based LNPs behaved as efficient mRNA carriers and showed enhanced mRNA-binding capabilities, associated with facilitated intracellular release, endosomal escape, and protection from endonuclease degradation. In addition, OleSurf-LNPs showed a higher mRNA delivery efficiency, a more advantageous biodistribution pattern, and an improved safety profile in vivo. Overall, the novel OleSurf LNPs presented an optimal delivery platform for mRNA therapeutics.

Nucleic acid binding affinity and antioxidant activity of N-m-Tolyl-4-Chlorophenoxyacetohydroxamicacid.

Hydroxamic acids represent a group of weak organic acids, both naturally occurring and synthetically derived, characterized by the general formula RC(= O)N(R'OH). In this study, we investigated the binding behavior of N-m-tolyl-4-chlorophenoxyaceto hydroxamic acid with calf thymus DNA (ct-DNA) and torula yeast RNA (t-RNA) through a combination of techniques including UV-visible spectroscopy, fluorescence emission analysis, viscometry, and computational simulations using AutoDock4 software. Our findings reveal that the mode of binding between the compound and the nucleic acids is consistent with intercalation. Competitive binding experiments demonstrated that the complex competes effectively with ethidium bromide (EB) for binding to ct-DNA/t-RNA, displacing EB from its binding sites. Additionally, the introduction of the compound into the DNA-EB system resulted in a quenching of fluorescence emission peaks. Analysis of absorption spectra indicated a red shift and hypochromic shift when the compound interacted with DNA, further supporting the intercalative binding mode. The calculated binding constant (Kb) value for the compound is 6.62 × 104 M-1 and 5.40 × 103 M-1 indicating a strong interaction with ct-DNA and t-RNA respectively. We determined the Stern-Volmer constants for ct-DNA and t-RNA as 9.96 × 104 M-1 and 8.13 × 105 M-1, respectively. The binding free energy values for ct-DNA/t-RNA were calculated to be - 3.741 × 107 and - 5.425 × 108 kcal/mol, respectively. Viscometric studies corroborated the UV results, showing a continuous increase in relative viscosity of ct-DNA/t-RNA solutions with the addition of the optimal hydroxamic acid concentration. Furthermore, we assessed the antioxidant activity of the compound using DPPH-radical scavenging and ß-carotene linoleic acid assays. Gel electrophoresis results demonstrated the compound's remarkable efficacy in preventing DNA damage. Collectively, all experimental evidence supports the conclusion that N-m-tolyl-4-chlorophenoxyaceto hydroxamic acid binds to ct-DNA/t-RNA through an intercalative mechanism, which is consistent with our molecular docking simulations.

In-vitro and in-silico analysis and antitumor studies of novel Cu(II) and V(V) complexes of N-p-Tolylbenzohydroxamic acid.

Copper(L2Cu) and vanadium(L2VOCl) complexes of N-p-tolylbenzohydroxamic acid (LH) ligand have been investigated for DNA binding efficacy by multiple analytical, spectral, and computational techniques. The results revealed that complexes as groove binders as evidenced by UV absorption. Fluorescence studies including displacement assay using classical intercalator ethidium bromide as fluorescent probe also confirmed as groove binders. The viscometric analysis too supports the inferences as strong groove binders for both the complexes. Molecular docking too exposed DNA as a target to the complexes which precisely binds L2Cu, in the minor groove region while L2VOCl in major groove region. Molecular dynamic simulation performed on L2Cu complex revealing the interaction of complex with DNA within 20 ns time. The complex stacked into the nitrogen bases of oligonucleotides and the bonding features were intrinsically preserved for longer simulation times. In-vitro cytotoxicity study was undertaken employing MTT assay against the breast cancer cell line (MCF-7). Potential cytotoxic activities were observed for L2Cu and L2VOCl complexes with IC50 values of showing 71 % and 74 % of inhibition respectively.

Blood-based microRNA profiling unveils complex molecular dynamics in breast cancer.

BACKGROUND: Breast cancer, a genetically intricate disease with diverse subtypes, exhibits heightened incidence globally. In this study, we aimed to investigate blood-based microRNAs (miRNAs) as potential biomarkers for breast cancer. The primary objectives were to explore the role of miRNAs in cancer-related processes, assess their differential expression between breast cancer patients and healthy individuals, and contribute to a deeper understanding of the molecular underpinnings of breast cancer. METHODS: MiRNA extraction was performed on 40 breast cancer patients and adjacent normal tissues using a commercial RNA isolation kit. Total RNA quantification and quality assessment were conducted with advanced technologies. MiRNA profiling involved reverse transcription, labeling, and hybridization on Agilent human miRNA arrays (V2). Bioinformatics analysis utilized the DIANA system for target gene prediction and the DIANA-mirPath tool for pathway enrichment analysis. Selected miRNAs underwent validation through quantitative real-time PCR. RESULTS: Principal component analysis revealed overlapping miRNA expression patterns in primary and malignant breast tumors, underscoring the genetic complexity involved. Statistical analysis identified 54 downregulated miRNAs in malignant tumors and 38 in primary tumors compared to controls. Bioinformatics analysis implicated several pathways, including Wnt, TGF-b, ErbB, and MAPK signaling. Validation through qRT-PCR confirmed altered expression of hsa-miR-130a, hsa-miR-21, hsa-miR-223, and hsa-let-7c key miRNAs, highlighting their significance in breast cancer. The results from microarray were further validated by qPCR and the expression of which are downregulated in breast cancer was detected. CONCLUSION: This study provides significant insights into distinct miRNA expression patterns in normal and malignant breast tissues. The overlapping miRNA profiles in primary and malignant tumors underscore the complexity of genetic regulation in breast cancer. The identification of deregulated miRNAs and affected pathways contributes to our understanding of breast cancer pathogenesis. The validated miRNAs hold potential as diagnostic and prognostic markers, offering avenues for further clinical exploration in breast cancer research.

Modulation of lncRNA NEAT1 overturns the macrophages based immune response in M. tuberculosis infected patients via miR-373 regulation.

There is a lack of studies which explore and clarify the interactions that occur between host macrophage and Mycobacterium tuberculosis with regard to microRNA such as LNCNEAT1 and miR-373. The current study determines the mechanisms involved in the control of M. tuberculosis infection by macrophage using LNCNEAT1 and miR-373. The researchers collected different samples from healthy individuals, pulmonary TB patients, and samples like hMDMs cells and H37Rv infected MTB to determine the concentrations of inflammatory factors. The impact of NEAT1 and miR-373 upon macrophages was analyzed in NEAT1-specific siRNA (si-NEAT1), NEAT1 over-expression vector (pcDNA3.1-NEAT1), miR-373 mimic, miR-373 inhibitor (anti-miR-373), and negative control, and macrophages infected with H37Ra. The results inferred that among pulmonary TB patients, NEAT1 got heavily expressed while the expression level of miR-373 was poor. The number of inflammatory factors with pulmonary TB was notably higher. This got further amplified in macrophages after being infected with H37Ra, while no such observations found for miR-373. During post-transfection, low concentration of inflammatory factors was observed while the cells in si-NEAT1 group got proliferated in low volume compared to both pcDNA3.1-NEAT1 group and NEAT1 negative control group. However, the capability of apoptosis was higher compared to the other two groups (p < 0.05). There was an increase observed in inflammatory factors as well as proliferation in anti-miR-373 group compared to miR-373 mimics and miR-373-negative control group while a significant decline was observed in apoptosis. LNCNEAT1 aggravated the number of inflammatory factors in macrophages that got infected with MTB while on the other end, it mitigated both phagocytosis as well as the cellular immunity of macrophages. In addition to this, it enhanced the proliferation of infected cells and inhibited apoptosis via targeted regulation of miR-373, thus resulting in the development of TB.

Genetic implications of PSMA expression variability in breast cancer subtypes with a focus on triple-negative breast cancer.

Prostate-specific membrane antigen (PSMA) is a protein frequently found to be overexpressed in various non-prostate cancer types. Our investigation, based on data from the TCGA databases, revealed a wide range of differential PSMA (encoded by FOLH1 gene) mRNA expressions across several cancer types, with notable findings in triple-negative breast carcinoma. This preclinical study delves into the molecular underpinnings of utilizing PSMA-targeting radiopharmaceuticals within specific breast cancer subtypes. We conducted a transcriptomic expression analysis of PSMA across different subtypes of breast cancer, focusing particularly on the triple-negative breast cancer (TNBC) subset. Our analysis encompassed 1100 patients from The Cancer Genome Atlas dataset. We observed a broad distribution of PSMA mRNA expressions across various subgroups within these cancer types. Notably, a subset of triple-negative breast cancer exhibited higher PSMA mRNA expression compared to non-triple-negative breast cancer. Intriguingly, we found that higher PSMA mRNA expression was associated with favorable outcomes in terms of distant metastasis-free and relapse-free survival in patients. Within a subset of TNBC patients, there is a prevalent overexpression of PSMA, which appears to be linked with improved relapse-free and distant metastasis-free survival. Our study succinctly highlights the significance of PSMA overexpression in TNBC and its potential impact on patient outcomes and provides a clear and concise overview of the study's contributions to breast cancer research.

Immune cell ratio and coagulation markers in assessing prognosis of asthma: a cross-sectional study from Saudi Arabia.

Asthma affects a significant number of individuals in Saudi Arabia, with increasing prevalence worldwide, leading to a considerable impact on their quality of life and frequent hospitalizations. In this study, we aimed to explore the relationship between the immune cell ratio and coagulation markers, specifically to identify the occurrence of coagulation abnormalities associated with asthma. To achieve this, we assessed asthma history and severity using a questionnaire while analyzing coagulation biomarkers through venous blood samples. The biomarkers examined included d-dimer, prothrombin time (PT), partial thromboplastin time (PTT), and the international normalized ratio (INR). In addition, we evaluated various hematological parameters such as blood cell counts and hemoglobin (HGB) levels. Our findings revealed compelling evidence, showing significantly elevated levels of d-dimer and the eosinophil-to-neutrophil (ENR) ratio in asthma cases compared to the controls. Moreover, we observed a positive correlation between d-dimer levels and the ENR, with each unit increase in d-dimer associated with a 0.0006 increase in the ENR among asthma cases. These results highlight the potential of assessing ENR and d-dimer levels as predictive indicators for disease prognosis and the development of coagulation abnormalities in individuals with asthma. By shedding light on the relationship between immune cell ratios and coagulation markers in the context of asthma, our study contributes to a better understanding of disease progression and the associated complications. These insights can potentially lead to improved management strategies and better outcomes for asthma patients.

Antimicrobial, anticancer, and biofilm inhibition studies of highly reduced graphene oxide (HRG): In vitro and in silico analysis.

Background: Bacterial infections and cancers may cause various acute or chronic diseases, which have become serious global health issues. This requires suitable alternatives involving novel and efficient materials to replace ineffective existing therapies. In this regard, graphene composites are being continuously explored for a variety of purposes, including biomedical applications, due to their remarkable properties. Methods: Herein, we explore, in-vitro, the different biological properties of highly reduced graphene oxide (HRG), including anti-cancer, anti-bacterial, and anti-biofilm properties. Furthermore, to analyze the interactions of graphene with proteins of microbes, in silico docking analysis was also carried out. To do this, HRG was prepared using graphene oxide as a precursor, which was further chemically reduced to obtain the final product. The as-prepared HRG was characterized using different types of microscopic and spectroscopic techniques. Results: The HRG revealed significant cytotoxic ability, using a dose-dependent anti-cell proliferation approach, which substantially killed human breast cancer cells (MCF-7) with IC50 of 29.51 ± 2.68 µg/mL. The HRG demonstrated efficient biological properties, i.e., even at low concentrations, HRG exhibited efficient anti-microbial properties against a variety of microorganisms. Among the different strains, Gram-positive bacteria, such as B. subtilis, MRSA, and S. aureus are more sensitive to HRG compared to Gram-negative bacteria. The bactericidal properties of HRG are almost similar to a commercially available effective antibiotic (ampicillin). To evaluate the efficacy of HRG against bacterial biofilms, Pseudomonas aeruginosa and MRSA were applied, and the results were compared with gentamycin and ampicillin, which are commonly applied standard antibiotics. Notably, HRG demonstrated high inhibition (94.23%) against P.aeruginosa, with lower MIC (50 µg/mL) and IC50 (26.53 µg/mL) values, whereas ampicillin and gentamicin showed similar inhibition (90.45% and 91.31% respectively) but much higher MIC and IC50 values. Conclusion: Therefore, these results reveal the excellent biopotential of HRG in different biomedical applications, including cancer therapy; antimicrobial activity, especially anti-biofilm activity; and other biomedicine-based therapies. Based on the molecular docking results of Binding energy, it is predicted that pelB protein and HRG would form the best stable docking complex, and high hydrogen and hydrophobic interactions between the pelB protein and HRG have been revealed. Therefore, we conclude that HRG could be used as an antibiofilm agent against P. aeruginosa infections.

Mechanistic behaviour of Chlorella vulgaris biofilm formation onto waste organic solid support used to treat palm kernel expeller in the recent Anthropocene.

The capacity to maximize the proliferation of microalgal cells by means of topologically textured organic solid surfaces under various pH gave rise to the fundamental biophysical analysis of cell-surface attachment in this study. The substrate used in analysis was palm kernel expeller (PKE) in which the microalgal cells had adhered onto its surface. The findings elucidated the relevance of surface properties in terms of surface wettability and surface energy in relation to the attached microalgal growth with pH as the limiting factor. The increase in hydrophobicity of PKE-microalgae attachment was able to facilitate the formation of biofilm better. The pH 5 and pH 11 were found to be the conditions with highest and lowest microalgal growths, respectively, which were in tandem with the highest contact angle value at pH 5 and conversely for pH 11. The work of attachment (Wcs) had supported the derived model with positive values being attained for all the pH conditions, corroborating the thermodynamic feasibility. Finally, this study had unveiled the mechanism of microalgal attachment onto the surface of PKE using the aid of extracellular polymeric surfaces (EPS) from microalgae. Also, the hydrophobic nature of PKE enabled excellent attachment alongside with nutrients for microalgae to grow and from layer-by-layer (LbL) assembly. This assembly was then isolated using organosolv method by means of biphasic solvents, namely, methanol and chloroform, to induce detachment.

Clinical Assessment of Cytokine Profiles and Haematological Parameters in Patients with Systemic Lupus Erythematosus: A Cross-Sectional Study from Saudi Arabia.

BACKGROUND: Systemic lupus erythematosus (SLE)-related hematological disorders have different pathogenic mechanisms involving immune dysregulation as well as microangiopathy. The current study aimed to assess the relationship between pro- and anti-inflammatory cytokines and SLE-related hematological abnormalities for Saudi Patients. METHODS: The current cross-sectional study including 140 participants was performed at the Prince Mohammad bin Abdulaziz Hospital (PMAH), Riyadh, Saudi Arabia. Two blood samples were collected from each of the study participants for evaluation of the haematological indices including complete blood count (CBC), erythrocyte sedimentation rate (ESR), and cytokine profile (i.e., tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)). Statistical analyses were performed using the Statistical Package of Social Sciences (SPSS) software, v25. RESULTS: Haematological abnormalities were documented in 63% of SLE patients, and anaemia was the highest at 52%. Haemoglobin levels were found to be significantly lower among SLE patients compared to the controls (p < 0.001). In the cytokine profiles, the levels of TNF-α (p < 0.001), IL-6 (p < 0.001), and IL-10 (p = 0.009) were significantly higher among SLE patients compared to the controls. A positive correlation was also identified between TNF-α, platelet count, red cell distribution width (RDW), and ESR. CONCLUSIONS: Haematological abnormalities were found to be the most common among SLE patients. Further, the correlation between cytokine profile and haematological indices indicates the influence of cytokines in the development of haematological abnormalities. Understanding hematological abnormalities and cytokines' role in the pathogenesis of these abnormalities may aid in the early diagnosis and development of more specific SLE disease therapies.

Effect of hematocrit, galactose and ascorbic acid on the blood glucose readings of three point-of-care glucometers.

Glucometers are commonly used in a variety of healthcare settings and use in critically ill patients should not be assumed without appropriate tool validation. The study objective was to evaluate the accuracy of three point-of-care glucometers (POCGs) to assess glucose concentration in human blood sample. The POCGs tested included three different instruments and utilized three factors (hematocrit [Hct], galactose and ascorbic acid) in glucose measurements to determine the glucometers' accuracy and compared to the reference laboratory biochemical analyzer (Cobs 8000, Roche, Basal, Switzerland). In this study, the Nova StatStrip glucometer showed no significant variation compared to the laboratory method at high glucose level with various Hct%. ACCU-Chek Inform II overestimated the glucose results at Hct 22% and underestimated at Hct 62%. The Freestyle glucometer showed lower glucose levels compared to the Cobas 8000 at Hct 62%. The ACCU-Check showed significant increase of blood glucose with low Hct% levels when compared to the laboratory method. The Freestyle showed a decreased level of glucose with high Hct 62% interference compared to the Cobas 8000. Galactose interference 100 and 200 mg/dL dramatically affected the accuracy of ACCU-Chek Inform II. Nevertheless, among all three POCGs in this study, the Nova StatStrip showed the most reliable and stable results for glucose level in the presence of interference. Especially, those in critical care units, whereas the Freestyle Precision Pro and ACCU-Chek Inform II were insufficiently accurate for critically ill patients.

Identification of Doxorubicin as Repurposing Inhibitory Drug for MERS-CoV PLpro.

Middle East respiratory syndrome coronavirus (MERS-CoV), belonging to the betacoronavirus genus can cause severe respiratory illnesses, accompanied by pneumonia, multiorgan failure, and ultimately death. CoVs have the ability to transgress species barriers and spread swiftly into new host species, with human-to-human transmission causing epidemic diseases. Despite the severe public health threat of MERS-CoV, there are currently no vaccines or drugs available for its treatment. MERS-CoV papain-like protease (PLpro) is a key enzyme that plays an important role in its replication. In the present study, we evaluated the inhibitory activities of doxorubicin (DOX) against the recombinant MERS-CoV PLpro by employing protease inhibition assays. Hydrolysis of fluorogenic peptide from the Z-RLRGG-AMC-peptide bond in the presence of DOX showed an IC50 value of 1.67 µM at 30 min. Subsequently, we confirmed the interaction between DOX and MERS-CoV PLpro by thermal shift assay (TSA), and DOX increased ΔTm by ~20 °C, clearly indicating a coherent interaction between the MERS-CoV PL protease and DOX. The binding site of DOX on MERS-CoV PLpro was assessed using docking techniques and molecular dynamic (MD) simulations. DOX bound to the thumb region of the catalytic domain of the MERS-CoV PLpro. MD simulation results showed flexible BL2 loops, as well as other potential residues, such as R231, R233, and G276 of MERS-CoV PLpro. Development of drug repurposing is a remarkable opportunity to quickly examine the efficacy of different aspects of treating various diseases. Protease inhibitors have been found to be effective against MERS-CoV to date, and numerous candidates are currently undergoing clinical trials to prove this. Our effort follows a in similar direction.

Nanostructured Antibiotics and Their Emerging Medicinal Applications: An Overview of Nanoantibiotics.

Bacterial strains resistant to antimicrobial treatments, such as antibiotics, have emerged as serious clinical problems, necessitating the development of novel bactericidal materials. Nanostructures with particle sizes ranging from 1 to 100 nanometers have appeared recently as novel antibacterial agents, which are also known as "nanoantibiotics". Nanomaterials have been shown to exert greater antibacterial effects on Gram-positive and Gram-negative bacteria across several studies. Antibacterial nanofilms for medical implants and restorative matters to prevent bacterial harm and antibacterial vaccinations to control bacterial infections are examples of nanoparticle applications in the biomedical sectors. The development of unique nanostructures, such as nanocrystals and nanostructured materials, is an exciting step in alternative efforts to manage microorganisms because these materials provide disrupted antibacterial effects, including better biocompatibility, as opposed to minor molecular antimicrobial systems, which have short-term functions and are poisonous. Although the mechanism of action of nanoparticles (NPs) is unknown, scientific suggestions include the oxidative-reductive phenomenon, reactive ionic metals, and reactive oxygen species (ROS). Many synchronized gene transformations in the same bacterial cell are essential for antibacterial resistance to emerge; thus, bacterial cells find it difficult to build resistance to nanoparticles. Therefore, nanomaterials are considered as advanced solution tools for the fields of medical science and allied health science. The current review emphasizes the importance of nanoparticles and various nanosized materials as antimicrobial agents based on their size, nature, etc.

Analysis of CCND1 protein and circulatory antioxidant enzyme activity association in oral squamous cell carcinoma.

Antioxidants are involved in the process of cellular damage prevention, which is considered as an avenue for cancer development. Free radicals are produced in the body upon exposure to stress, cigarette smoke, alcohol, toxins found in personal care products, pesticides in foods, radiation from the sun, viruses, germs or fungi etc. CCND1/CyclinD1 protein was found to be overexpressed in Oral squamous cell carcinoma. One hundred patients with oral squamous cell carcinoma were recruited along with hundred controls for this study from MNJ institute of Oncology with the approval of Ethics Committee, 5 ml blood samples were collected from each patient and centrifuged to collect serum for various assays. The antioxidant enzymes like catalase, SOD, GPX and GST were estimated using enzymatic assays. Results were expressed as unit of activity for mg of protein. Insilco analysis is performed using STRING v 11 Protein interaction tool. The patients with oral cancer had significantly reduced activities of SOD, GST and GPX (1.49 ± 0.49, 3.97 ± 0.86 and 10.7 ± 0.73 respectively) compared to healthy controls (4.37 ± 1.43, 6.10 ± 1.12 and 13.8 ± 1.25 respectively) (p < 0.005). However no significant difference was observed with regard to catalase activity (2.71 ± 6.51 and 4.03 ± 1.48) (p = 0.28). The proteins interaction PPI enrichment p-value was found to be 3.22e-10 predicted significantly more interactions. Our research findings shown that there was a decline in activity of superoxide dismutase, glutathione peroxidase and glutathione s transferase in addition, personal habits like smoking play a major role in the development and progression of oral carcinogenesis and based on Insilco analysis results CCND1/Cyclin D1 could be the potential therapeutic target in oral squamous cell carcinoma.

Preparation, characterization, and in vitro-in silico biological activities of Jatropha pelargoniifolia extract loaded chitosan nanoparticles.

Jatropha pelargoniifolia (JP) is a medicinal plant that is widely used in traditional medicine owing to its broad range of therapeutic activities. Despite its promising pharmacological activities, the use of plant extracts has several limitations which can be overcome using pharmaceutical nanotechnology. The aim of this study was to systematically investigate the effect of nanoencapsulation on the antimicrobial and anticancer activities of JP extract. JP-loaded chitosan nanoparticles (JP-CSNPs) were prepared using the ionic gelation method and characterized in terms of size, polydispersity index, zeta potential, encapsulation efficiency, and release profile. Transmission electron microscopy was used to observe the morphology of the nanoparticles. The mean particle size, zeta potential, and encapsulation efficiency of optimized JP-CSNPs were 185.5 nm, 44 mV, and 78.5%, respectively. The release profile of the JP-CSNPs was mainly dependent on the pH of the surrounding medium, and the JP extract was released in a controlled manner over time. The total phenolic and flavonoid contents in JP extract were 191.8 mg GAE/g extract and 51.4 mg of QE/g extract, respectively. The results of a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed that JP-CSNPs retained the antioxidant activity of unencapsulated JP extract. JP-CSNPs also exhibited higher antimicrobial activity against gram-positive bacteria than against gram-negative bacteria, and their minimum inhibitory concentration was 1.6-fold lower than that of blank nanoparticles, indicating the synergy between JP extract and nanoparticles. In vitro cytotoxicity studies using A549 human lung adenocarcinoma cells revealed that JP-CSNPs had a 2-fold lower half-maximal inhibitory concentration than free extract. Molecular docking analyses revealed that the active phytoconstituent of JP extract, linarin, binds strongly to the active sites of bacterial DNA gyrase B and human DNA topoisomerase IIα and thus, may inhibit their activities. Computational analysis results supported the in vitro finding that JP-CSNPs act as an anticancer and antimicrobial agent. Taken together, the results of this study highlighted the advantages of using CSNPs as a nanocarrier for herbal extracts, thus providing a potential strategy for improving plant-based therapeutics.

In vitro investigation of biophysical interactions between Ag(I) complexes of bis(methyl)(thia/selena)salen and ct-DNA via multi-spectroscopic, physicochemical and molecular docking methods along with cytotoxicity study.

Four silver(I) (Ag(I)) complexes: 1.PF6 , 2.PF6 , 1.ClO4 and 2.ClO4 of bis(methyl)thia salen (1) and bis (methyl)selena salen (2) with two different counter anions (PF6 - and ClO4 - ) have been investigated for DNA binding properties. In vitro interactional association between the Ag(I) complexes and ct-DNA has been examined by performing spectroscopic titrations on absorption spectrophotometer and fluorescence spectrophotometer. A competitive binding study has also been done using a fluorescence spectrophotometer with ethidium bromide as a classical intercalator. The spectroscopic methods revealed a major groove. Viscometry and agarose gel electrophoresis experiments have also been performed as physicochemical methods to confirm the binding of complex molecules with DNA. Molecular docking analysis has been executed to obtain the theoretical insight into the mode of binding. The docking study demonstrated the major groove binding of all four complexes to the DNA with electrostatic metal-phosphate interactions (between the metal and the backbone of DNA) and hydrophobic interactions. Cytotoxicity of the complexes has been studied on the Human Fibroblast foreskin (HFF) cell line. The cytotoxicity results showed positive gesture for moving ahead to the next level of screening; the values were above 10 µM which are appreciated for the normal cell lines.

SARS-CoV-2: Insight in genome structure, pathogenesis and viral receptor binding analysis - An updated review.

The novel coronavirus disease (COVID-19) a global pandemic outbreak is an emerging new virus accountable for respiratory illness caused by SARS-CoV-2, originated in Wuhan city, Hubei province China, urgently calls to adopt prevention and intervention strategies. Several viral epidemics such as severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003 and H1N1 influenza in 2009 were reported since last two decades. Moreover, the Saudi Arabia was the epicenter for Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The CoVs are large family with single-stranded RNA viruses (+ssRNA). Genome sequence of 2019-nCoV, shows relatively different homology from other coronavirus subtypes, categorized in betacoronavirus and possibly found from strain of bats. The COVID-19 composed of exposed densely glycosylated spike protein (S) determines virus binding and infiltrate into host cells as well as initiate protective host immune response. Recently published reviews on the emerging SARS-CoV-2 have mainly focused on its structure, development of the outbreak, relevant precautions and management trials. Currently, there is an urgency of pharmacological intervention to combat this deadly infectious disease. Elucidation of molecular mechanism of COVID-19 becomes necessary. Based on the current literature and understanding, the aim of this review is to provide current genome structure, etiology, clinical prognosis as well as to explore the viral receptor binding together functional insight of SARS-CoV-2 infection (COVID-19) with treatment and preventive measures.

Mn3O4 nanoparticles: Synthesis, characterization and their antimicrobial and anticancer activity against A549 and MCF-7 cell lines.

Due to their inexpensive and eco-friendly nature, and existence of manganese in various oxidation states and their natural abundance have attained significant attention for the formation of Mn3O4 nanoparticles (Mn3O4 NPs). Herein, we report the preparation of Mn3O4 nanoparticles using manganese nitrate as a precursor material by utilization of a precipitation technique. The as-prepared Mn3O4 nanoparticles (Mn3O4 NPs) were characterized by using X-ray powder diffraction (XRD), UV-Visible spectroscopy (UV-Vis), High-Resolution Transmission electron microscopy (HRTEM), Field emission scanning electron microscopy (FESEM), Thermal gravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FT-IR). The antimicrobial properties of the as-synthesized Mn3O4 nanoparticles were investigated against numerous bacterial and fungal strains including S. aureus, E. coli, B. subtilis, P. aeruginosa, A. flavus and C. albicans. The Mn3O4 NPs inhibited the growth of S. aureus with a minimum inhibitory concentration (MIC) of 40 µg/ml and C. albicans with a MIC of 15 µg/ml. Furthermore, the Mn3O4 NPs anti-cancer activity was examined using MTT essay against A549 lung and MCF-7 breast cancer cell lines. The Mn3O4 NPs revealed significant activity against the examined cancer cell lines A549 and MCF-7. The IC50 values of Mn3O4 NPs with A549 cell line was found at concentration of 98 µg/mL and MCF-7 cell line was found at concentration of 25 µg/mL.

Size-Dependent Phagocytic Uptake and Immunogenicity of Gliadin Nanoparticles.

The main objective of the present study was to investigate the hemo and immune compatibility of gliadin nanoparticles as a function of particle size. Gliadin nanoparticles of different size were prepared using a modified antisolvent nanoprecipitation method. The hemolytic potential of gliadin nanoparticles was evaluated using in vitro hemolysis assay. Phagocytic uptake of gliadin nanoparticles was studied using rat polymorphonuclear (PMN) leukocytes and murine alveolar peritoneal macrophage (J774) cells. In vivo immunogenicity of gliadin nanoparticles was studied following subcutaneous administration in mice. Gliadin nanoparticles were non-hemolytic irrespective of particle size and hence compatible with blood components. In comparison to positive control zymosan, gliadin nanoparticles with a size greater than 406 ± 11 nm showed higher phagocytic uptake in PMN cells, while the uptake was minimal with smaller nanoparticles (127 ± 8 nm). Similar uptake of gliadin nanoparticles was observed in murine alveolar peritoneal macrophages. Anti-gliadin IgG antibody titers subsequent to primary and secondary immunization of gliadin nanoparticles in mice were in the increasing order of 406 ± 11 nm < 848 ± 20 nm < coarse suspension). On the other hand, gliadin nanoparticles of 127 ± 8 nm in size did not elicit immunogenic response. Phagocytosis and immunogenicity of gliadin nanoparticles are strongly influenced by particle size. The results of this study can provide useful information for rational design of protein-based nanomaterials in drug delivery applications.