Comparative Proteomics of Inner Membrane Fraction from Carbapenem-Resistant Acinetobacter baumannii with a Reference Strain

Acinetobacter baumannii has been identified by the Infectious Diseases Society of America as one of the six pathogens that cause majority of hospital infections. Increased resistance of A. baumannii even to the latest generation of β-lactams like carbapenem is an immediate threat to mankind. As inner-membrane fraction plays a significant role in survival of A. baumannii, we investigated the inner-membrane fraction proteome of carbapenem-resistant strain of A. baumannii using Differential In-Gel Electrophoresis (DIGE) followed by DeCyder, Progenesis and LC-MS/MS analysis. We identified 19 over-expressed and 4 down-regulated proteins (fold change>2, p<0.05) in resistant strain as compared to reference strain. Some of the upregulated proteins in resistant strain and their association with carbapenem resistance in A. baumannii are: i) β-lactamases, AmpC and OXA-51: cleave and inactivate carbapenem ii) metabolic enzymes, ATP synthase, malate dehydrogenase and 2-oxoglutarate dehydrogenase: help in increased energy production for the survival and iii) elongation factor Tu and ribosomal proteins: help in the overall protein production. Further, entry of carbapenem perhaps is limited by controlled production of OmpW and low levels of surface antigen help to evade host defence mechanism in developing resistance in A. baumannii. Present results support a model for the importance of proteins of inner-membrane fraction and their synergistic effect in the mediation of resistance of A. baumannii to carbapenem

Emerging trends in point-of-care biosensing strategies for molecular architectures and antibodies of SARS-CoV-2

COVID-19, a highly contagious viral infection caused by the occurrence of severe acute respiratory syndrome coronavirus (SARS-CoV-2), has turned out to be a viral pandemic then ravaged many countries worldwide. In the recent years, point-of-care (POC) biosensors combined with state-of-the-art bioreceptors, and transducing systems enabled the development of novel diagnostic tools for rapid and reliable detection of biomarkers associated with SARS-CoV-2. The present review thoroughly summarises and discusses various biosensing strategies developed for probing SARS-CoV-2 molecular architectures (viral genome, S Protein, M protein, E protein, N protein and non-structural proteins) and antibodies as a potential diagnostic tool for COVID-19. This review discusses the various structural components of SARS-CoV-2, their binding regions and the bioreceptors used for recognizing the structural components. The various types of clinical specimens investigated for rapid and POC detection of SARS-CoV-2 is also highlighted. The importance of nanotechnology and artificial intelligence (AI) approaches in improving the biosensor performance for real-time and reagent-free monitoring the biomarkers of SARS-CoV-2 is also summarized. This review also encompasses existing practical challenges and prospects for developing new POC biosensors for clinical monitoring of COVID-19

Na-Montmorillonite-Dispersed Sustainable Polymer Nanocomposite Hydrogel Films for Anticancer Drug Delivery

Nanocomposite hydrogels have found a wide scope in regenerative medicine, tissue engineering, and smart drug delivery applications. The present study reports the formulations of biocompatible nanocomposite hydrogel films using carboxymethyl cellulose-hydroxyethyl cellulose-acrylonitrile-linseed oil polyol (CHAP) plain hydrogel and Na-montmorillonite (NaMMT) dispersed CHAP nanocomposite hydrogel films (NaCHAP) using solution blending technique. The structural, morphological, and mechanical properties of resultant nanocomposite hydrogel films were further investigated to analyze the effects of polyol and NaMMT on the characteristic properties. The synergistic effect of polyol and nanofillers on the mechanical strength and sustained drug-release behavior of the resultant hydrogel films was studied, which revealed that the increased cross-link density of hydrogels enhanced the elastic modulus (up to 99%) and improved the drug retention time (up to 72 h at both pHs 7.4 and 4.0). The release rate of cisplatin in nanocomposite hydrogel films was found to be higher in CHAP-1 (83 and 69%) and CHAP-3 (79 and 64%) than NaCHAP-3 (77 and 57%) and NaCHAP-4 (73 and 54%) at both pHs 4.0 and 7.4, respectively. These data confirmed that the release rate of cisplatin in nanocomposite hydrogel films was pH-responsive and increased with decrease of pH. All nanocomposite hydrogel films have exhibited excellent pH sensitivity under buffer solution of various pHs (1.0, 4.0, 7.4, and 9.0). The in vitro biocompatibility and cytotoxicity tests of these films were also conducted using 3-(4,5-dimethylthiazole-2-yl-2,5-diphenyl tetrazolium bromide) assay of human embryonic kidney (HEK-293) and human breast cancer (MCF-7) cell lines up to 48 h, which shows their biocompatible nature. However, cisplatin-loaded nanocomposite hydrogel films effectively inhibited the growth of human breast MCF-7 cancer cells. These studies suggested that the proposed nanocomposite hydrogel films have shown promising application in therapeutics, especially for anticancer-targeted drug delivery

Anti-inflammatory effects of CBD in human microglial cell line infected with HIV-1

Abstract Human immunodeficiency virus (HIV) infection is associated with a chronic inflammatory stage and continuous activation of inflammasome pathway. We studied the anti-inflammatory effects of the compound cannabidiol (CBD) in comparison with Δ (9)-tetrahydrocannabinol [Δ(9)-THC] in human microglial cells (HC69.5) infected with HIV. Our results showed that CBD reduced the production of various inflammatory cytokines and chemokines such as MIF, SERPIN E1, IL-6, IL-8, GM-CSF, MCP-1, CXCL1, CXCL10, and IL-1 β compared to Δ(9)-THC treatment. In addition, CBD led to the deactivation of caspase 1, reduced NLRP3 gene expression which play a crucial role in the inflammasome cascade. Furthermore, CBD significantly reduced the expression of HIV. Our study demonstrated that CBD has anti-inflammatory properties and exhibits significant therapeutic potential against HIV-1 infections and neuroinflammation

Interaction of nalidixic acid and ciprofloxacin with wild type and mutated quinolone-resistance-determining region of DNA gyrase A

147-153The quinolones exert their anti-bacterial activity by binding to DNA gyrase A (GyrA), an essential enzyme in maintenance of DNA topology within bacterial cell. The mutations conferring resistance to quinolones arise within the quinolone-resistance-determining region (QRDR) of GyrA. Therefore, quinolones interaction with wild and mutated GyrA can provide the molecular explanation for resistance. Resistant strains of Salmonella enterica of our hospital have shown mutations in the QRDR of GyrA of serine 83 (to phenylalanine or tyrosine) or aspartic acid 87 (to glycine or tyrosine). In order to understand the association between observed resistance and structural alterations of GyrA with respect to quinolone binding, we have studied the interaction of mutated QRDR of GyrA with nalidixic acid and ciprofloxacin by molecular modeling using GLIDE v4. Analysis of interaction parameters like G-score has revealed reduced interaction between nalidixic acid/ciprofloxacin with QRDR of GyrA in all four mutated cases of resistant strains. The mutation of Ser83 to Phe or Tyr shows least binding for nalidixic acid, while Asp87 to Gly or Tyr exhibits minimal binding for ciprofloxacin. The study also highlights the important role of arginines at 21, 91 and His at 45, which form strong hydrogen bonds (at almonella appears to be due to the decreased selectivity and affinity of nalidixic acid/ciprofloxacin to QRDR of GyrA

Recent advances, status, and opportunities of magneto-electric nanocarriers for biomedical applications

Magneto-electric (ME) materials with core-shell architecture where the core is made of magnetic materials have emerged as an attractive nanomaterial due to the coupling of magnetic and electric properties in the same material and the fact that both fields can be controlled which allows an on-demand, transport and release of loaded cargo. Over the last decade, biomedical engineers and researchers from various interdisciplinary fields have successfully demonstrated promising properties ranging from therapeutic delivery to sensing, and neuromodulation using ME materials. In this review, we systematically summarize developments in various biomedical fields using the nanoforms of these materials. Herein, we also highlight various promising biomedical applications where the ME nanocarriers are encapsulated in other materials such as gels and liposomes and their potential for promising therapeutics and diagnostic applications

Diagnostic potential of exosomal extracellular vesicles in oncology

Abstract Liquid biopsy can detect circulating cancer cells or tumor cell-derived DNA at various stages of cancer. The fluid from these biopsies contains extracellular vesicles (EVs), such as apoptotic bodies, microvesicles, exomeres, and exosomes. Exosomes contain proteins and nucleic acids (DNA/RNA) that can modify the microenvironment and promote cancer progression, playing significant roles in cancer pathology. Clinically, the proteins and nucleic acids within the exosomes from liquid biopsies can be biomarkers for the detection and prognosis of cancer. We review EVs protein and miRNA biomarkers identified for select cancers, specifically melanoma, glioma, breast, pancreatic, hepatic, cervical, prostate colon, and some hematological malignancies. Overall, this review demonstrates that EV biomolecules have great potential to expand the diagnostic and prognostic biomarkers used in Oncology; ultimately, EVs could lead to earlier detection and novel therapeutic targets. Clinical implications EVs represent a new paradigm in cancer diagnostics and therapeutics. The potential use of exosomal contents as biomarkers for diagnostic and prognostic indicators may facilitate cancer management. Non-invasive liquid biopsy is helpful, especially when the tumor is difficult to reach, such as in pancreatic adenocarcinoma. Moreover, another advantage of using minimally invasive liquid biopsy is that monitoring becomes more manageable. Identifying tumor-derived exosomal proteins and microRNAs would allow a more personalized approach to detecting cancer and improving treatment

Nanocomposite Hydrogels: Advances in Nanofillers Used for Nanomedicine

The ongoing progress in the development of hydrogel technology has led to the emergence of materials with unique features and applications in medicine. The innovations behind the invention of nanocomposite hydrogels include new approaches towards synthesizing and modifying the hydrogels using diverse nanofillers synergistically with conventional polymeric hydrogel matrices. The present review focuses on the unique features of various important nanofillers used to develop nanocomposite hydrogels and the ongoing development of newly hydrogel systems designed using these nanofillers. This article gives an insight in the advancement of nanocomposite hydrogels for nanomedicine