IgG antibodies mediated gold nanoparticles conjugated to methotrexate as targeted chemotherapy for lung cancer.

Vincamine, a natural chemical, was used as a reducing agent in the synthesis of IgG antibodies mediated biogenic gold nanoparticles (IgGAuNPs). Eventually, the synthesised IgGAuNPs were bioconjugated with the chemotherapeutic drug methotrexate (MTX-IgGAuNPs). The IgG isotype can target cancer cells through polymorphic Fc gamma receptors (FcγRs) and have therapeutic effects. They can restrict cell division by inhibiting different intracellular signal transduction pathways and activating NK cells and macrophages through antibody-dependent cellular cytotoxicity and macrophage-mediated antibody-dependent phagocytosis, respectively. Further, IgGAuNPs and MTX-IgGAuNPs were characterised by physical techniques. Moreover, 3D conformational changes in the structure of IgG were analysed by fluorescence spectroscopy during and after the synthesis of IgGAuNPs. Furthermore, the IgGAuNPs and MTX-IgGAuNPs were effective against lung cancer (A549 cells), while they were found to be non-toxic against normal cells (NRK cells). The effectiveness of IgGAuNPs and MTX-IgGAuNPs was examined by MTT cytotoxicity assay, DCFDA method for the production of ROS, and release of Cyt-c from the mitochondria for caspase-3-mediated apoptosis. Moreover, the confirmation of internalisation of particles into the nucleus was examined under the DAPI assay, and it was found that particles caused nuclear fragmentation, which was also an indication of apoptosis.

Differential gene expression analysis of RAGE-S100A6 complex for target selection and the design of novel inhibitors for anticancer drug discovery.

Receptor for advanced glycation end products (RAGE), a member of the immunoglobulin family, interactions with its ligands trigger downstream signaling and induce an inflammatory response linked to diabetes, inflammation, carcinogenesis, cardiovascular disease, and a variety of other human disorders. The interaction of RAGE and S100A6 has been associated with a variety of malignancies. For the control of RAGE-related illnesses, there is a great demand for more specialized drug options. To identify the most effective target for combating human malignancies associated with RAGE-S100A6 complex, we conducted single and differential gene expression analyses of S100A6 and RAGE, comparing normal and malignant tissues. Further, a structure-based virtual screening was conducted using the ZINC15 database. The chosen compounds were then subjected to a molecular docking investigation on the RAGE active site region, recognized by the various cancer-related RAGE ligands. An optimized RAGE structure was screened against a library of drug-like molecules. The screening results suggested that three promising compounds were presented as the top acceptable drug-like molecules with a high binding affinity at the RAGE V-domain catalytic region. We depicted that these compounds may be potential RAGE inhibitors and could be used to produce a successful medication against human cancer and other RAGE-related diseases based on their various assorted parameters, binding energy, hydrogen bonding, ADMET characteristics, etc. MD simulation on a time scale of 50 ns was used to test the stability of the RAGE-inhibitor complexes. Therefore, targeting RAGE and its ligands using these drug-like molecules may be an effective therapeutic approach.

Starch-Assisted Synthesis of Bi2S3 Nanoparticles for Enhanced Dielectric and Antibacterial Applications.

Starch [(C6H10O5) n ]-stabilized bismuth sulfide (Bi2S3) nanoparticles (NPs) were synthesized in a single-pot reaction using bismuth nitrate pentahydrate (Bi(NO3)3·5H2O) and sodium sulfide (Na2S) as precursors. Bi2S3 NPs were stable over time and a wide band gap of 2.86 eV was observed. The capping of starch on the Bi2S3 NPs prevents them from agglomeration and provides regular uniform shapes. The synthesized Bi2S3 NPs were quasispherical, and the measured average particle size was ∼11 nm. The NPs are crystalline with an orthorhombic structure as determined by powder X-ray diffraction and transmission electron microscopy. The existence and interaction of starch on the NP's surface were analyzed using circular dichroism. Impedance spectroscopy was used to measure the electronic behavior of Bi2S3 NPs at various temperatures and frequencies. The dielectric measurements on the NPs show high dielectric polarizations. Furthermore, it was observed that the synthesized Bi2S3 NPs inhibited bacterial strains (Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) and demonstrated substantial antibacterial activity.

Neodymium Selenide Nanoparticles: Greener Synthesis and Structural Characterization.

This investigation presents the greener biomimetic fabrication of neodymium selenide nanoparticles (Nd2Se3 NPs) deploying nitrate-dependent reductase as a reducing (or redox) agent, extracted from the fungus, Fusarium oxysporum. The Nd2Se3 NPs, with an average size of 18 ± 1 nm, were fabricated with the assistance of a synthetic peptide comprising an amino acid sequence (Glu-Cys)n-Gly, which functioned as a capping molecule. Further, the NPs were characterized using multiple techniques such as UV-Vis spectroscopy, fluorescence, dynamic light scattering (DLS), and XRD. The hydrodynamic radii of biogenic polydispersed Nd2Se3 NPs were found to be 57 nm with PDI value of 0.440 under DLS. The as-made Nd2Se3NPs were water-dispersible owing to the existence of hydrophilic moieties (-NH2, -COOH, -OH) in the capping peptide. Additionally, these functionalities render the emulsion highly stable (zeta potential -9.47 mV) with no visible sign of agglomeration which bodes well for their excellent future prospects in labeling and bioimaging endeavors.

Targeted non AR mediated smart delivery of abiraterone to the prostate cancer.

Prostate cancer is the second-deadliest tumor in men all over the world. Different types of drugs with various delivery systems and pathways were developed, but no one showed prominent results against cancer. Meanwhile, nanoparticles have shown good results against cancer. Therefore, in the given study, citrate mediated synthesized gold nanoparticles (CtGNPs) with immobilized survivin antibodies (SvGNPs) were bioconjugated to the substantially potent drug abiraterone (AbSvGNPs) to develop as a combinatorial therapeutic against prostate cancer. The AbSvGNPs are made up of CtGNPs, survivin antibodies, and abiraterone. The selected drug abiraterone (Abira) possesses exceptionally good activity against prostate cancer, but cancer cells develop resistance against this drug and it also poses several severe side effects. Meanwhile, survivin antibodies were used to deliver AbSvGNPs specifically into cancer cells by considering survivin, an anti-apoptotic overexpressed protein in cancer cells, as a marker. The survivin antibodies have also been used to inhibit cancer cells as an immunotherapeutic agent. Similarly, CtGNPs were discovered to inhibit cancer cell proliferation via several transduction pathways. The given bioconjugated nanoparticles (AbSvGNPs) were found to be substantially effective against prostate cancer with an IC50 of 11.8 and 7.3 µM against DU145 and PC-3 cells, respectively. However, it was found safe against NRK and showed less than 25% cytotoxicity up to 20µM concentration. The as-synthesized nanoparticles CtGNPs, SvGNPs, and AbSvGNPs were characterized by several physical techniques to confirm their synthesis, whereas the immobilization of survivin antibodies and bioconjugation of Abira was confirmed by UV-visible spectroscopy, DLS, TEM, FTIR, and zeta-potential. The anticancer potential of AbSvGNPs was determined by MTT, DAPI, ROS, MITO, TUNEL ASSAY, and caspase-3 activity against DU145 and PC3 cells.

Novel Bioengineered Antibacterial and Anticancer ZnO Nanoparticles.

Transition metal oxide NPs have delivered wide applications in various fields. Therefore, in this study, a novel fungus, Alternaria sp. (NCBI Accession No: MT982648) was isolated and characterized from the vicinity of medicinal plants. Eventually, in this method extracted proteins from isolated fungus were utilized to synthesize highly biocompatible zinc nanoparticles (ZnO NPs). The various physical techniques including UV-visible spectroscopy, TEM, HR-TEM, XRD, DLS, zeta potential, and FTIR were used to characterize particles. The UV-visible absorption (λMax) and binding energy for the as-synthesized particles were found to be 329 nm and 3.91 eV, respectively. Further, the polydispersed particles were revealed to have regular crystallinity with hexagonal wurtzite phase of ZnO with the spacing of ~2.46 Å under XRD and HR-TEM. The average size of a particle under TEM was found to be ~18 nm. The evaluation of various surface functional groups of particles was done by FTIR. The average hydrodynamic diameter of particles was found to be ~57 d. nm with 0.44 particle distribution index whereas the nanoemulsion stability was explained by Zeta potential (-9.47 mV). These particles were found to exhibit potential antibacterial and anticancer activities. They were found to be bactericidal against S. abony (MIC 5.73 µg/mL); B. pumilis (MIC 6.64 µg/mL); K. pneumonia (MIC 14.4 µg/mL); E. coli (MIC 8.7 µg/mL); B. subtilis (MIC 5.63 µg/mL) and S. aureus (MIC 12.04 µg/mL). Further, they are also found to be concentration-dependent anticancer and inhibited the growth of A549 cells (IC50-65.3 µg/mL) whereas they were found to demonstrate no any cytotoxicity against NRK normal kidney cell line. The internalization of particles into the nucleus (i.e., nuclear fragmentation and DNA damage) was confirmed by DAPI staining. The intracellular particles were found to generate excessive ROS. Further, the anticancer potential was also estimated by noticing a hike in oxidative stress parameters, cell viability, cell morphology, and change in mitochondrial membrane potential. We effectively synthesized potentially potent antibacterial and anticancer novel bioengineered ZnO NPs.

Effect of inflammation on bones in diabetic patients with periodontitis via RANKL/OPG system-A review.

Purpose: Diabetes mellitus and periodontitis are inflammatory diseases, the severity of inflammation results in the progression and persistence of both the disorders and affects bones. Diabetic complications aggravate in diabetic subjects having periodontitis; similarly, diabetic patients are more prone to developing gingivitis and periodontitis. Periodontal and diabetic inflammation disturbs bone homeostasis, which possibly involves both innate and adaptive immune responses. The pathogenic processes that link the two diseases are the focus of much research and it is likely that upregulated inflammation arising from each condition adversely affects the other. RANKL/OPG pathway plays a prominent role in periodontal and diabetic inflammation and bone resorption. Method: This review article summarises the literature on the link between inflammatory cytokines and the prevalence of disturbed bone homeostasis in diabetic patients with periodontitis. An extensive search was done in PubMed, Scopus, Medline and Google Scholar databases between April 2003 and May 2021. Result: A total of 27 articles, including pilot studies, case-control studies, cross-sectional studies, cohort studies, randomized control trials, longitudinal studies, descriptive studies and experimental studies, were included in our literature review. Conclusion: Since RANKL/OPG are cytokines and have immune responses, regulating these cytokines expression will help control diabetes, periodontitis and bone homeostasis. The growing evidence of bone loss and increased fracture risk in diabetic patients with periodontitis makes it imperative that health professionals carry out planned treatment focusing on monitoring oral health in diabetic patients; bone markers should also be evaluated in patients with chronic periodontitis with an impaired glycemic state.

RAGE Inhibitors for Targeted Therapy of Cancer: A Comprehensive Review.

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin family that is overexpressed in several cancers. RAGE is highly expressed in the lung, and its expression increases proportionally at the site of inflammation. This receptor can bind a variety of ligands, including advanced glycation end products, high mobility group box 1, S100 proteins, adhesion molecules, complement components, advanced lipoxidation end products, lipopolysaccharides, and other molecules that mediate cellular responses related to acute and chronic inflammation. RAGE serves as an important node for the initiation and stimulation of cell stress and growth signaling mechanisms that promote carcinogenesis, tumor propagation, and metastatic potential. In this review, we discuss different aspects of RAGE and its prominent ligands implicated in cancer pathogenesis and describe current findings that provide insights into the significant role played by RAGE in cancer. Cancer development can be hindered by inhibiting the interaction of RAGE with its ligands, and this could provide an effective strategy for cancer treatment.

Potentially Bioactive Fungus Mediated Silver Nanoparticles.

Fungal metabolites, proteins, and enzymes have been rich sources of therapeutics so far. Therefore, in this study, the hypha extract of a newly identified noble fungus (Alternaria sp. with NCBI Accession number: MT982648) was used to synthesize silver nanoparticles (F-AgNPs) to utilize against bacteria, fungi, and lung cancer. F-AgNPs were characterized by using physical techniques, including UV-visible spectroscopy, zeta potential, DLS, XRD, TEM, and HR-TEM. The particles were found to be polydispersed and quasi-spherical in shape under TEM. They had an average size of ~15 nm. The well dispersed particles were found to have consistent crystallinity with cubic phase geometry under XRD and HR-TEM. The presence of different functional groups on the surfaces of biosynthesized F-AgNPs was confirmed by FTIR. The particle distribution index was found to be 0.447 with a hydrodynamic diameter of ~47 d.nm, and the high value of zeta potential (-20.3 mV) revealed the stability of the nanoemulsion. These particles were found to be active against Staphylococcus aureus (multidrug resistance-MDR), Klebsiella pneumonia, Salmonella abony, and Escherichia coli (MDR) with MIC50 10.3, 12.5, 22.69, and 16.25 µg/mL, respectively. Particles also showed inhibition against fungal strains, including A. flavus, A. niger, T. viridens, and F. oxysporium. Their inhibition of biofilm formation by the same panel of bacteria was also found to be very promising and ranged from 16.66 to 64.81%. F-AgNPs also showed anticancer potential (IC50-21.6 µg/mL) with respect to methotrexate (IC50-17.7 µg/mL) against lung cancer cell line A549, and they did not result in any significant inhibition of the normal cell line BEAS-2. The particles were found to alter the mitochondrial membrane potential, thereby disturbing ATP synthesis and leading to high ROS formation, which are responsible for cell membrane damage and release of LDH, intracellular proteins, lipids, and DNA. A high level of ROS also elicits pro-inflammatory signaling cascades that lead to programmed cell death by either apoptosis or necrosis.

Gold Nanoparticle-Bioconjugated Aminoguanidine Inhibits Glycation Reaction: An In Vivo Study in a Diabetic Animal Model.

Proteins undergo glycation resulting in the generation of advanced glycation end products (AGEs) that play a central role in the onset and advancement of diabetes-associated secondary complications. Aminoguanidine (AG) acts as an antiglycating agent by inhibiting AGE generation by blocking reactive carbonyl species (RCS) like, methylglyoxal (MGO). Previous studies on antiglycating behavior of AG gave promising results in the treatment of diabetes-associated microvascular complications, but it was discontinued as it was found to be toxic at high concentrations (>10 mmol/L). The current article aims at glycation inhibition by conjugating gold nanoparticles (Gnp) with less concentration of AG (0.5-1.0 mmol/L). The HPLC results showed that AG-Gnp fairly hampers the formation of glycation adducts. Moreover, the in vivo studies revealed AG-Gnp mediated inhibition in the production of total-AGEs and -N ε -(carboxymethyl)lysine (CML) in the diabetic rat model. This inhibition was found to be directly correlated with the antioxidant parameters, blood glucose, insulin, and glycosylated hemoglobin levels. Furthermore, the histopathology of AG-Gnp-treated rats showed good recovery in the damaged pancreatic tissue as compared to diabetic rats. We propose that this approach might increase the efficacy of AG at relatively low concentrations to avoid toxicity and might facilitate to overcome the hazardous actions of antiglycating drugs.

Solanum xanthocarpum fruit extract promotes chondrocyte proliferation in vitro and protects cartilage damage in collagenase induced osteoarthritic rats (article reference number: JEP 114028).

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA), a degenerative joint disease, is characterized by cartilage erosion and matrix degradation. Solanum xanthocarpum Schrad. & Wendl. fruits (SXF) and leaves have long been used as folk remedy in the treatment of pain in rheumatism. AIM OF THE STUDY: This study was aimed to investigate the phytochemical components and protective benefits of SXF on in vitro chondrocytes proliferation, and in vivo suppression of collagenase-induced OA. MATERIALS AND METHODS: Phytochemical components in ethanolic SXF extract were evaluated using gas chromatography-mass spectrometry (GC-MS). Effect of SXF on in vitro cell proliferation of primary chondrocytes was determined by cell proliferation assay and cell cycle analysis by flow cytometry. OA was induced in the right knees of rats through intra-articular injection of collagenase type-II. To evaluate in vivo preventive function of SXF, body weight, blood ALP, histopathological changes in the knee joint, proteoglycan, and collagen content were determined. The mRNA expression of COL-2, MMP-3 and COX-2 genes through qRT-PCR was studied. Antioxidant activities, total phenolics and flavonoid contents of SXF were also examined. RESULTS: GC-MS analysis revealed that SXF constitutes 28 phytochemicals including flavonoids (3-methoxy apigenin, quercetin, luteolin), tannin (quinic acid), terpenes (oleanolic acid, lupeol, psi.psi carotene), phytosterols (campesterol, stigmasterol, ß-sitosterol), and ascorbic acid. In vitro studies demonstrated that SXF enhanced the cell proliferation in a dose-dependent manner and has no cytotoxic effect on primary chondrocytes. In vivo study suggests that SXF protects the cartilage destruction induced by collagenase. The histological study revealed that SXF restored the synthesis of collagen and proteoglycan, vital factors for cartilage restoration, and reduced the arthritic score. An up-regulation in COL-2 expression and suppression of MMP-3 and COX-2 were detected by qRT-PCR analysis. Thus, in vivo study suggests the protective effects of SXF on cartilage destruction induced by collagenase. CONCLUSIONS: Our results imply that SXF benefits and ameliorates OA by enhancing the chondrocytes proliferation and preventing the articular cartilage damage through the restoration of their structural molecules, arthritic score reduction, suppression of MMP-3 and COX-2 expression level and up regulation of COL-2 genes expression. These results suggest that SXF could be a promising alternative treatment candidate for osteoarthritis.

Vincamine, a safe natural alkaloid, represents a novel anticancer agent.

Vincamine, a well-known plant alkaloid, has been used as a dietary supplement and as a peripheral vasodilator to combat aging in humans. In this study, for the very first time, we demonstrated that vincamine can function as an anticancer agent in a human alveolar basal epithelial cell line A549 (IC50 = 309.7 µM). The anticancer potential of vincamine in A549 cells was assessed by molecular assays to determine cell viability, generation of intracellular ROS, nuclear condensation, caspase-3 activity and inhibition, and change in mitochondrial membrane potential (ΔΨm). In silico studies predicted that the anti-proliferative potential of vincamine is enhanced by its interaction with the apoptotic protein caspase-3, and that this interaction is driven by two hydrogen bonds and has a high free energy of binding (-5.64 kcal/mol) with an estimated association constant (Ka) of 73.67 µM. We found that vincamine stimulated caspase-3-dependent apoptosis and lowered mitochondrial membrane potential, which ultimately led to cytochrome C release. Vincamine was also found to quench hydroxyl free radicals and deplete iron ions in cancer cells. As a dietary supplement, vincamine is almost non-toxic in BEAS-2B and 3T3-L1 cells. Therefore, we propose that vincamine represents a safe anticancer agent in lung cancer cells. Its role in other cancers has yet to be explored.

Silk Cocoon-Derived Protein Bioinspired Gold Nanoparticles as a Formidable Anticancer Agent.

We synthesized bioinspired sericin encapsulated gold nanoparticles (SGNPs) using HAuCl4 as the starting material in a bottom-up approach. Further, two-dimensional (2D) and three-dimensional (3D) conformational changes (folding and unfolding) in sericin were studied using circular dichroism (CD) and fluorescence spectroscopy, respectively, during and after the synthesis of particles. Finally, the synthesized SGNPs were characterized using several physical techniques to ensure their correct synthesis and study the size, stability, and charge over the surface of particles. At the beginning of the reaction, when gold was in the ionic form (Au+³), sericin exhibited maximum electrostatic interaction and underwent unfolding. Au+³ reduced to Au during the reaction, and sericin regained its 3D confirmation due to a decrease in its native electrostatic interactions. However, CD revealed the same patterns of unfolding and folding; a decrease in α helix and an increase inß3 pleated sheets were noticed. Although the 3D structure of sericin was restored after the synthesis of SGNPs, it was substantially altered. In addition, certain changes in the 2D structure were observed; however, these did not alter the activity of sericin. Furthermore, Fourier-transform infrared spectroscopy (FTIR) confirmed these findings. The SGNPs were found to be effective against lung cancer (A549 cells), with an IC50 of 145.49 ßM, without exerting any toxic effects on normal cells (NRK cells). The effectiveness of SGNPs was examined by MTT cytotoxicity and nuclear fragmentation assays. Furthermore, we assessed their ability to produce excessive ROS and release Cyt-c from the mitochondria for caspase-3-mediated apoptosis.

Biostimulation of Rhodovulum sp., for enhanced degradation of di-n-butyl phthalate under optimum conditions.

Di-butyl phthalate (DBP) is an extensively applied synthetic plasticizer, toxic organic compound with elevated concentrations in aquatic and terrestrial ecosystem that cause serious risk to the human health. A marine bacterium Rhodovulum sp. DBP07 isolated from sea water with proficient of efficiently degrading DBP. The maximum DBP degradation (70.2%) and the cell growth (1.3 OD600nm) were observed at 600 mg/L. The DBP degradation characteristics of the isolate Rhodovulum sp. DBP07 with diverse preliminary concentrations of DBP was found to be 200 ˃ 400 ˃ 600 ˂ 800 ˂ 1000 mg/L DBP. Glucose was identified as most favorable nutrient factor for the enhanced growth and showed 79.8 and 77.4% of degradation rate at 5.0 and 2.0 g/L respectively. The influence of the carbon sources on DBP degradation was found to be Glucose ˃ fructose ˃ sucrose ˃ maltose ˃ lactose ˃ citric acid ˃ starch. Box-Behnken (BBD) statistical optimization results showed enhanced DBP biodegradation rate (91.1%) at pH 7.0, 3% of NaCl concentration with 3 days of incubation. Two intermediate compounds were observed in the retention times of 10.8 and 12.2 which are identified as diethyl phthalate (DEP) and mono-nbutyl phthalate (MBP) using Gas chromatography mass spectroscopy (GC-MS). Furthermore, the phthalate (pht) gene expression pattern under DBP stress was analyzed using RT-qPCR and the maximum fold change (5.7 fold) was observed at 3 day of incubation. Overall, the observed results indicate the possibility of utilizing Rhodovulum sp. for remediation of DBP contaminated environment.

Antiosteoarthritic effect of Punica granatum L. peel extract on collagenase induced osteoarthritis rat by modulation of COL-2, MMP-3, and COX-2 expression.

Osteoarthritis (OA) is a chronic degenerative and musculoskeletal disorder. The toxicity associated with nonsteroidal antiinflammatory drugs (NSAIDs) limits its use in the management of OA. To ameliorate these toxicities, natural antioxidants can be used as substitutes for the management of OA. Therefore, this study is aimed to investigate the prophylactic mechanisms of Punica granatum L. peel (PGP) in collagenase-induced OA rat compared with indomethacin. OA was induced in female Sprague Dawley rats by intraarticular injection of collagenase type-II and treated with PGP (250 and 500 mg/kg body wt) and a positive control (PC) indomethacin (3 mg/kg body wt). The results demonstrated that PGP reduced the collagenase induced OA as compared with indomethacin treated group through reducing blood ALP (P < .001) and significantly (P < .001) inhibited cartilage erosion as indicated in histological slides with retention of collagen and proteoglycan content. Quantitative real-time PCR analysis revealed the considerable (P < .05) upregulation in the expression of COL-2 gene and downregulation of MMP-3 and COX-2 genes in the PGP treated group. The high phenolic content (633 ± 1.16 mg/GAE) and flavonoid content (420.3 ± 2.14 mg/RE) contribute to the strong antioxidant activity with IC50 value (320 ± 2.2 µg/mL) of DPPH free radical scavenging activity. These results need further validation in clinical studies and thus, PGP could be developed as a preventive drug treatment for OA.

Sericin-functionalized GNPs potentiate the synergistic effect of levofloxacin and balofloxacin against MDR bacteria.

A gradual expansion in resistant bacterial strains against commercially available antibacterial agents is the serious concern of the given research. It poses critical problem for public health. Thus, the demand for new antimicrobial agents has increased the interest in newer technologies and innovative approaches are required to advance the diagnosis and elimination of causative organisms. In this study, the potential role of technologies based on gold nanoparticles (GNPs) has been evaluated. GNPs were synthesized by using a cysteine protease, sericin whose reducing properties were exploited to bioengineer NPs (SrGNPs) where sericin with the help of thiol groups encapsulated over the surface of GNPs. Further, SrGNPs were bioconjugated with levofloxacin (Levo) and balofloxacin (Balo) to increase the efficacy of these drugs. Here, the antibacterial action of SrGNPs and their bioconjugated counterparts comprising Levo (Levo-SrGNPs), Balo (Balo-SrGNPs), and Levo/Balo (Levo-Balo-SrGNPs) were examined against normal and multi-drug resistant (MDR) strains of E. coli and S. aureus. The minimum inhibitory concentration (MIC) of these bioconjugates against said bacteria were found less than their pure counterparts. Further, the synergistic role of SrGNPs in combination with Levo and Balo was also explained using Chou-Talalay (C-T) method. The synthesis and bioconjugation of SrGNPs were confirmed by UV-visible spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and zeta-potential.

Protein aggregation as a consequence of non-enzymatic glycation: Therapeutic intervention using aspartic acid and arginine.

Non-enzymatic glycation tempted AGEs of proteins are currently at the heart of a number of pathological conditions. Production of chemically stable AGEs can permanently alter the protein structure and function, concomitantly leading to dilapidated situations. Keeping in perspective, present study aims to report the glycation induced structural and functional modification of a cystatin type isolated from rai mustard seeds, using RSC-glucose and RSC-ribose as model system. Among the sugars studied, ribose was found to be most potent glycating agent as evident from different biophysical assays. During the course of incubation, RSC was observed to pass through a series of structural intermediates as revealed by circular dichroism, altered intrinsic fluorescence and high ANS binding. RSC incubation with ribose post day 36 revealed the possible buildup of ß structures as observed in CD spectral analysis, hinting towards the generation of aggregated structures in RSC. High thioflavin T fluorescence and increased Congo red absorbance together with enhanced turbidity of the modified form confirmed the aggregation of RSC. The study further revealed anti-glycation and anti-aggregation potential of amino acids; aspartic acid and arginine as they prevented and/or slowed down the process of AGEs and ß structure buildup in a concentration dependent manner with arginine proving to be the most effective one.

Incidence and antimicrobial profile of extended-spectrum ß-lactamase producing gram-negative bacterial isolates: An in-vitro and statistical analysis.

OBJECTIVES: There is an extensive incidence of extended-spectrum beta-lactamases (ESBLs), principally in the hospital environment across the world. The present study was designed to discover the frequency of ESBL-production among the clinical isolates of Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. The study also focused on determining their liability to the selected antimicrobials. METHODS: Two hundred ten (210) clinical specimens were tested for the occurrence of ESBL using the double-disc synergy test. The molecular, physicochemical, absorption, distribution, metabolism, excretion, and toxicity were checked through an online server. RESULTS: Among the screened clinical isolates, E. coli (n=44), K. pneumonia (n=34) and P. aeruginosa (n=14) were ESBL markers. The ESBL producing isolates exhibited co-resistance to diverse categories of antibiotics. It was observed that all the ESBL-producing isolates were sensitive towards imipenem and faropenem with minimal proportion of resistance. CONCLUSION: The imipenem and faropenem can be recommended as the drugs of selection due to a lesser amount of resistance as compared to other antibiotics in this study.

Tumor-targeted Drug Delivery by Nanocomposites.

BACKGROUND: Tumor-targeted delivery by nanoparticles is a great achievement towards the use of highly effective drug at very low doses. The conventional development of tumor-targeted delivery by nanoparticles is based on enhanced permeability and retention (EPR) effect and endocytosis based on receptor-mediated are very demanding due to the biological and natural complications of tumors as well as the restrictions on the design of the accurate nanoparticle delivery systems. METHODS: Different tumor environment stimuli are responsible for triggered multistage drug delivery systems (MSDDS) for tumor therapy and imaging. Physicochemical properties, such as size, hydrophobicity and potential transform by MSDDS because of the physiological blood circulation different, intracellular tumor environment. This system accomplishes tumor penetration, cellular uptake improved, discharge of drugs on accurate time, and endosomal discharge. RESULTS: Maximum drug delivery by MSDDS mechanism to target therapeutic cells and also tumor tissues and sub cellular organism. Poorly soluble compounds and bioavailability issues have been faced by pharmaceutical industries, which are resolved by nanoparticle formulation. CONCLUSION: In our review, we illustrate different types of triggered moods and stimuli of the tumor environment, which help in smart multistage drug delivery systems by nanoparticles, basically a multi-stimuli sensitive delivery system, and elaborate their function, effects, and diagnosis.

2'-Deoxyribose Mediated Glycation Leads to Alterations in BSA Structure Via Generation of Carbonyl Species.

The non-enzymatic glycosylation is a very common phenomenon in the physiological conditions which is mediated by distinct chemical entities containing reactive carbonyl species (RCS) and participates in the modification of various macromolecules particularly proteins. To date, various carbonyl species, i.e., glucose, fructose, D-ribose and methylglyoxal have been used frequently to assess the in-vitro non-enzymatic glycosylation. Similarly, 2'-Deoxyribose is one of the most abundant reducing sugar of the living organisms which forms the part of deoxyribonucleic acid and may react with proteins leading to the production of glycation intermediates, advanced glycation end products (AGEs) and highly reactive RCS. Thymidine phosphorylase derived degradation of thymidine contributes to the formation of 2'-Deoxyribose, therefore, acting as a major source of cellular 2'- Deoxyribose. Since albumin is a major serum protein which plays various roles including binding and transporting endogenous and exogenous ligands, it is more prone to be modified through different physiological modifiers; therefore, it may serve as a model protein for in-vitro experiments to study the effect of 2'Deoxyribose mediated modifications in the protein. In this study, Bovine Serum Albumin (BSA) was glycated with 50 and 100 mM 2'-Deoxyribose followed by examining secondary and tertiary structural modifications in BSA as compared to its native (unmodified) form by using various physicochemical techniques. We evident a significant modification in 2'-Deoxyribose-glycated BSA which was confirmed through increased hyperchromicity, keto amine moieties, carbonyl and hydroxymethylfurfural content, fluorescent AGEs, altered secondary structure conformers (α helix and ß sheets), band shift in the amide-I region and diminished free lysine and free arginine content. These modifications were reported to be higher in 100 mM 2'-Deoxyribose-glycated BSA than 50 mM 2'- Deoxyribose-glycated BSA. Our findings also demonstrated that the rate of glycation is positively affected by the increased concentration of 2'-Deoxyribose. The results of the performed study can be implied to uncover the phenomenon of serum protein damage caused by 2'-Deoxyribose leading towards diabetic complications and the number of AGE-related diseases.