Surfactin-Conjugated Silver Nanoparticles as an Antibacterial and Antibiofilm Agent against Pseudomonas aeruginosa.

The emergence of antimicrobial resistance is an alarming global health concern and has stimulated the development of novel functional nanomaterials to combat multi-drug-resistant (MDR) bacteria. In this work, we demonstrate for the first time the synthesis and application of surfactin-coated silver nanoparticles as an efficient antibacterial and antibiofilm agent against the drug-resistant bacteria Pseudomonas aeruginosa for safe dermal applications. Our in vivo studies showed no significant superficial dermal irritation, edema, and erythema, while microscopic analysis revealed that surfactin-coated silver nanoparticles caused no pathological alterations at the applied concentrations. These results support the potential use of surfactin-coated silver nanoparticles against drug-resistant bacterial biofilm infections and in skin wound dressing applications.

Endophytic bacteria of Fagonia indica Burm. f revealed to harbour rich secondary antibacterial metabolites.

Endophytic bacteria are the source of novel bioactive compounds, used as therapeutic agent. Molecular docking is a computational technique use frequently, to find novel drugs targets and drugs-receptors interactions. The current study was designed to isolate and identify endophytic bacteria for the extraction of bioactive compounds. Further, to characterized extracts and to explore compounds interactions with bacterial cell wall and outer membrane synthesizing proteins. Endophytes were identified using 16s rRNA amplification technique. For bioactive compounds, solvent extraction method was followed and characterized further through GC-MS analysis. To find targets and drugs-receptors interactions, molecular docking studies and biological assays were performed. The isolated endophytes belong to five different genera namely Enterobacter, Bacillus, Erwinia, Stenotrophomonas and Pantoea. In case of antibacterial assay Stenotrophomonas maltophilia extract showed significant inhibitory zones (15.11±0.11mm and 11.3±0.16) against Staphylococcus caseolyticus and Acinetobacter baumanni, with MIC 33.3 and 50µg/mL respectively. Among the characterized fifty compounds, from endophytic bacteria "antibacterial compound" N-(5-benzyl-10b-hydroxy-2-methyl-3,6-dioxooctahydro-8H-oxazolo[3,2-α] pyrrolo[2,1c] pyrazin-2-yl)-7-methyl2,3,3a,3a1,6,6a,7,8,9,10,10a,10b-dodecahydro-1H-4λ2-indolo[4,3-fg]quinoline-9-carboxamide of bacteria Stenotrophomonas maltophilia were an excellent binder with MurF ligase active site, with binding energy of -10.2 kcal/mol. Extracts of endophytic bacteria composed of various pharmacologically active ingredients such as antibacterial compounds. Molecular docking studies provide important information regarding drug-receptor interaction, thus can be used in novel drug discovery.

Biofunctionalized Nano-antimicrobials - Progress, Prospects and Challenges.

The rapid emergence of multidrug-resistant bacterial strains highlights the need for the development of new antimicrobial compounds/materials to address associated healthcare challenges. Meanwhile, the adverse side effects of conventional antibiotics on human health urge the development of new natural product-based antimicrobials to minimize the side effects. In this respect, we concisely review the recent scientific contributions to develop natural product-based nano-antibiotics. The focus of the review is on the use of flavonoids, peptides, and cationic biopolymer functionalized metal/metal oxide nanoparticles as efficient tools to hit the MDR bacterial strains. It summarizes the most recent aspects of the functionalized nanoparticles against various pathogenic bacterial strains for their minimal inhibitory concentrations and mechanism of action at the cellular and molecular levels. In the end, the future perspectives to materialize the in vivo applications of nano-antimicrobials are suggested based on the available research.

Chemotherapeutic resistance of head and neck squamous cell carcinoma is mediated by EpCAM induction driven by IL-6/p62 associated Nrf2-antioxidant pathway activation.

Overexpression of epithelial cell adhesion molecule (EpCAM) has been associated with chemotherapeutic resistance, leads to aggressive tumor behavior, and results in an adverse clinical outcome. The molecular mechanism by which EpCAM enrichment is linked to therapeutic resistance via Nrf2, a key regulator of antioxidant genes is unknown. We have investigated the link between EpCAM and the Nrf2 pathway in light of therapeutic resistance using head and neck squamous cell carcinoma (HNSCC) patient tumor samples and cell lines. We report that EpCAM was highly expressed in Nrf2-positive and HPV-negative HNSCC cells. In addition, cisplatin-resistant tumor cells consisted of a higher proportion of EpCAMhigh cells compared to the cisplatin sensitive counterpart. EpCAMhigh populations exhibited resistance to cisplatin, a higher efficiency in colony formation, sphere growth and invasion capacity, and demonstrated reduced reactive oxygen species (ROS) activity. Furthermore, Nrf2 expression was significantly higher in EpCAMhigh populations. Mechanistically, expression of Nrf2 and its target genes were most prominently observed in EpCAMhigh populations. Silencing of EpCAM expression resulted in the attenuation of expressions of Nrf2 and SOD1 concomitant with a reduction of Sox2 expression. On the other hand, silencing of Nrf2 expression rendered EpCAMhigh populations sensitive to cisplatin treatment accompanied by the inhibition of colony formation, sphere formation, and invasion efficiency and increased ROS activity. The molecular mechanistic link between EpCAM expression and activation of Nrf2 was found to be a concerted interaction of interleukin-6 (IL-6) and p62. Silencing of p62 expression in EpCAMhigh populations resulted in the attenuation of Nrf2 pathway activation suggesting that Nrf2 pathway activation promoted resistance to cisplatin in EpCAMhigh populations. We propose that therapeutic targeting the Nrf2-EpCAM axis might be an excellent approach to modulate stress resistance and thereby survival of HNSCC patients enriched in EpCAMhigh populations.

Widespread expression of Sonic hedgehog (Shh) and Nrf2 in patients treated with cisplatin predicts outcome in resected tumors and are potential therapeutic targets for HPV-negative head and neck cancer.

BACKGROUND: Sonic hedgehog (Shh) and Nrf2 play a critical role in chemotherapeutic resistance. These two genes have been found to be dysregulated in head and neck squamous cell carcinomas (HNSCC). The purpose of this study was to analyze the expression, function and clinical prognostic relationship of Shh and Nrf2 in HNSCC in the context of therapeutic resistance and cancer stem cells (CSCs). METHODS: We analyzed a cohort of patients with HNSCC to identify potential therapeutic biomarkers correlating with overall survival (OS) as well as disease-free survival (DFS) from our own data and validated these results using The Cancer Genome Atlas dataset. Expression of Shh and Nrf2 was knocked down by siRNA and cell growth, sphere growth and chemotherapeutic resistance were evaluated. RESULTS: Widespread abundant expression of Shh and Nrf2 proteins were associated with shorter OS and DFS. The combination of Shh and Nrf2 expression levels was found to be a significant predictor of patient DFS. The tumor stromal index was correlated with Shh expression and inversely associated with shorter OS and DFS. Inhibition of Shh by siRNA or cyclopamine resulted in the attenuation of resistant CSC self-renewal, invasion, clonogenic growth and re-sensitization to the chemotherapeutic agents. Concomitant upregulation of Shh and Nrf2 proved to be an independent predictor of poor OS and DFS in patients with HNSCC. CONCLUSIONS: These findings suggest that Shh and Nrf2 could serve as therapeutic targets as well as promising dual prognostic therapeutic biomarkers for HNSCC.

Nanoparticles-assisted delivery of antiviral-siRNA as inhalable treatment for human respiratory viruses: A candidate approach against SARS-COV-2.

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has challenged healthcare structures across the globe. Although a few therapies are approved by FDA, the search for better treatment options is continuously on rise. Clinical management includes infection prevention and supportive care such as supplemental oxygen and mechanical ventilatory support. Given the urgent nature of the pandemic and the number of companies and researchers developing COVID-19 related therapies, FDA has created an emergency program to move potential treatments with already approved drugs to patients as quickly as possible in parallel to the development of new drugs that must first pass the clinical trials. In this manuscript, we have reviewed the available literature on the use of sequence-specific degradation of viral genome using short-interfering RNA (siRNA) suggesting it as a possible treatment against SARS-CoV-2. Delivery of siRNA can be promoted by the use of FDA approved lipids, polymers or lipid-polymer hybrids. These nanoparticulate systems can be engineered to exhibit increased targetability and formulated as inhalable aerosols.

Nano-biotechnology: a new approach to treat and prevent malaria.

Malaria, the exterminator of ~1.5 to 2.7 million human lives yearly, is a notorious disease known throughout the world. The eradication of this disease is difficult and a challenge to scientists. Vector elimination and effective chemotherapy for the patients are key tactics to be used in the fight against malaria. However, drug resistance and environmental and social concerns are the main hurdles in this fight against malaria. Overcoming these limitations is the major challenge for the 21st-century malarial researchers. Adapting the principles of nano-biotechnology to both vector control and patient therapy is the only solution to the problem. Several compounds such as lipids, proteins, nucleic acid and metallic nanoparticles (NPs) have been successfully used for the control of this lethal malaria disease. Other useful natural reagents such as microbes and their products, carbohydrates, vitamins, plant extracts and biodegradable polymers, are also used to control this disease. Among these particles, the plant-based particles such as leaf, root, stem, latex, and seed give the best antagonistic response against malaria. In the present review, we describe certain efforts related to the control, prevention and treatment of malaria. We hope that this review will open new doors for malarial research.

Eruca sativa seed oil: Characterization for potential beneficial Properties.

Eruca sativa (ES) seed oil is used in food preparation and as source of natural medication. Eruca sativa (ES) seed oil was analysed for phenolic composition using high performance liquid chromatography with diode array detection (HPLC-DAD), pigment contents, quality characteristics. The oil was fed to rabbits for two weeks. Serum biochemistry, haematological and liver histological parameters were studied. Results showed that quercetin, caffeic acid and chlorogenic acids were the major phenolic compounds. Lycopene and other pigments were present in considerable amounts. Animal studies showed that the body weight of rabbits decreases with the increase of ES oil. The level of serum glucose, total cholesterols, triglycerides and LDL-cholesterol decrease significantly, while an increase was observed in the HDL-cholesterol. The level of white blood cells including lymphocytes and mean corpuscular haemoglobin concentration increases, while a significant increase occurred in platelets count with the increase of ES seed oil dose. In the present study microscopic observations in control and the treated groups showed similar cytoarchitecture of the liver with no significant histological changes. It is concluded that Eruca sativa seed oil is a rich source of important phytochemicals with anti-obesity properties in selected animals.

An assessment on the role of endophytic microbes in the therapeutic potential of Fagonia indica.

BACKGROUND: Natural products of animals, plants and microbes are potential source of important chemical compounds, with diverse applications including therapeutics. Endophytic bacteria that are especially associated with medicinal plants presents a reservoir of therapeutic compounds. Fagonia indica has been recently investigated by numerous researchers because of its striking therapeutic potential especially in cancer. It is also reported that endophytes play a vital role in the biosynthesis of various metabolites; therefore we believe that endophytes associated with F. indica are of crucial importance in this regard. The present study aims successful isolation, molecular identification of endophytic bacteria and their screening for bioactive metabolites quantification and in vitro pharmacological activities. METHODS: 16S rRNA gene sequencing was used for the identification of isolated endophytic bacteria. Methanolic extracts were evaluated for total phenolic contents (TPC), total flavonoids contents (TFC), DPPH free radical scavenging activity, reducing power and total anti-oxidant assays were performed. And also screened for antibacterial and antifungal activities by disc diffusion method and their MIC were calculated by broth dilution method using microplate reader. Further, standard protocols were followed for antileishmanial activity and protein kinase inhibition. Analysis and statistics were performed using SPSS, Table curve and Origin 8.5 for graphs. RESULTS: Bacterial strains belonging to various genera (Bacillus, Enterobacter, Pantoea, Erwinia and Stenotrophomonas) were isolated and identified. Total phenolic contents and total flavonoids contents varies among all the bacterial extracts respectively in which Bacillus subtilis showed high phenolic contents 243 µg/mg of gallic acid equivalents (GAE) and Stenotrophomonas maltophilia showed high flavonoids contents 15.9 µg/mg quercitin equivalents (QA), total antioxidant capacity (TAC) 37.6 µg/mg of extract, reducing power (RP) 206 µg/mg of extract and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity with 98.7 µg/mL IC50 value. Although all the extracts tested were active to inhibit growth of selected pathogenic microbes (bacteria and fungi), but significant antibacterial activity was observed against Klebsiella pneumonia and B. subtilis. An Enterobacter cloaca was active against Leishmania tropica with IC50 value of 1.4 µg/mg extracts. B. subtilis and Bacillus tequilensis correspondingly exhibit significant protein kinase inhibition of 47 ± 0.72 and 42 ± 1.21 mm bald zones, indicating anti-infective and antitumor potential. CONCLUSIONS: Our findings revealed that crude extracts of selected endophytic bacteria from F. indica possess excellent biological activities indicating their potential as an important source of antibiotics (antifungal, antibacterial) compounds.

Arsenic-induced Histological Alterations in Various Organs of Mice.

Deposition of arsenic in mice through groundwater is well documented but little is known about the histological changes of organs by the metalloid. Present study was designed to evaluate arsenic-induced histological alterations in kidney, liver, thoracic artery and brain of mice which are not well documented yet. Swiss albino male mice were divided into 2 groups and treated as follows: Group 1: control, 2: arsenic (sodium arsenite at 10 mg/kg b.w. orally for 8 wks). Group 2 showed marked degenerative changes in kidney, liver, thoracic artery, and brain whereas Group 1 did not reveal any abnormalities on histopathology. We therefore concluded that arsenic induces histological alterations in the tested organs.