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.

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.

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.

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.

Do all roads lead to the Rome? The glycation perspective!

Oxidative, carbonyl, and glycative stress have gained substantial attention recently for their alleged influence on cancer progression. Oxidative stress can trigger variable transcription factors, such as nuclear factor erythroid-2-related factor (Nrf2), nuclear factor kappa B (NF-κB), protein-53 (p-53), activating protein-1 (AP-1), hypoxia-inducible factor-1α (HIF-1α), ß-catenin/Wnt and peroxisome proliferator-activated receptor-γ (PPAR-γ). Activated transcription factors can lead to approximately 500 different alterations in gene expression, and can alter expression patterns of inflammatory cytokines, growth factors, regulatory cell cycle molecules, and anti-inflammatory molecules. These alterations of gene expression can induce a normal cell to become a tumor cell. Glycative stress resulting from advanced glycation end products (AGEs) and reactive dicarbonyls can significantly affect cancer progression. AGEs are fashioned from the multifaceted chemical reaction of reducing sugars with a compound containing an amino group. AGEs bind to and trigger the receptor for AGEs (RAGE) through AGE-RAGE interaction, which is a major modulator of inflammation allied tumors. Dicarbonyls like, GO (glyoxal), MG (methylglyoxal) and 3-DG (3-deoxyglucosone) fashioned throughout lipid peroxidation, glycolysis, and protein degradation are viewed as key precursors of AGEs. These dicarbonyls lead to the carbonyl stress in living organisms, possibly resulting in carbonyl impairment of proteins, carbohydrates, DNA, and lipoproteins. The damage caused by carbonyls results in numerous lesions, some of which are involved in cancer pathogenesis. In this review, the effects of oxidative, carbonyl and glycative stress on cancer initiation and progression are thoroughly discussed, including probable signaling pathways and the effects on tumorigenesis.

Oxidation, glycation and glycoxidation-The vicious cycle and lung cancer.

The combine effect of oxidative and glycative stress predisposed to glycoxidation, and their outcomes that play critical role in lung cancer have been examined in different ways. The therapeutic approaches for lung cancer are still unsatisfactory. We observe some unclear and decisive pathways which might play an important role in targeting lung cancer. The roadmap of signaling pathway includes p38 MAPK, NF-ƙB, TNF-α and AGE-RAGE binding affinity play role in the cell growth, proliferation, apoptosis inhibition and metastasis. The goal of this review is to achieve a new signaling map inside the lung cancer which is mediated by glycoxidative products mainly reactive dicarbonyls and advanced glycation end products (AGEs). Additionally, AGE-RAGE binding critically regulates the suppression and promotion of lung cancer via inhibition and activation of different signaling pathways. Hence, this review suggests the role of oxidation, glycation, and glycoxidation in lung cancer.

The in vivo and in vitro approaches for establishing a link between advanced glycation end products and lung cancer.

Advanced glycation end products (AGEs) are directly related to third aging-associated diseases, such as cardiovascular diseases, arteriosclerosis, and neurodegeneration. Likewise, these irreversible and nonenzymatic products have been reported to be involved in the progression of malignant cancers. In general, aging-associated diseases and the initiation of cancer have been subjects of interest for several years. Few studies on the role of AGEs in cancer have been performed on cell lines. Moreover, past investigations in the field of glycation biology still lack the knowledge of in vivo and in vitro approaches for cancer cells. Accordingly, we aimed to focus on and establish a link between cancer and glycation with respect to all the possible AGEs. In our study, the levels of carboxymethyllysine (CML) increased by 50.94% in an animal model of glycation, whereas in an animal model of cancer, the contents of CML increased by 45.94% compared with their negative controls. Similarly, fluorescent AGEs were also examined and were found to be increased by 65.3% and 58.63% in the animal models of glycation and cancer, respectively, compared with the control subjects. The protein carbonyl contents were also found to be enhanced in the animal models of glycation and cancer. In our study, the levels of reactive oxygen species were also found to be significantly increased in the in vitro model of cancer cells as compared with the controls. Such an initial breakthrough indicated that AGEs were present in the serum of the animal models of cancer and glycation.

Enhancing using glucose encapsulation, the efficacy of CdO NPs against multi-drug resistant Escherichia coli.

In this study, monodispersed, highly biocompatible and substantially stable glucose encapsulated CdO nanoparticles (G-CdO NPs) of uniform sizes were synthesized using a sol-gel route. In addition, naked CdO (n-CdO) NPs without any capping or surface functionalization were synthesized using the same method. These NPs were uniformly dispersed in an aqueous solution. The synthesis of G-CdO and n-CdO NP was confirmed by UV-Vis spectroscopy, transmission electron microscopy (TEM), zeta potential, and dynamic light scattering analyses. The average size of G-CdO and n-CdO NP was found to be 17±1and 27 ±â€¯1 nm, under TEM, respectively. X-ray diffraction analysis of G-CdO and n-CdO NPs confirmed their sizes to be 18.83 and 28.41 nm, respectively, and revealed their cubic crystal structures with no impurity. The surface functionalization of G-CdO NPs with glucose was confirmed by Nuclear Magnetic Resonance and Fourier-transform infrared spectroscopy analyses. As per our knowledge, this is the first report to investigate the potencies of G-CdO and n-CdO NPs against gram-negative and gram-positive multi-drug resistant (MDR) bacteria. The minimum inhibitory concentrations of G-CdO and n-CdO NPs were6.42 and 16.29 µg/ml, respectively, against Escherichia coli (NCIM 2571-MDR), whereas 7.5 µg/ml & 11.6 µg/ml, respectively against S. aureus (NCIM- 2079) as determined by the double dilution method. The minimum bactericidal concentration was determined at the concentration for which no growth was observed. TEM analysis of E. coli cells treated with G-CdO NPs revealed cell shrinkage and degraded cell membranes, while the cell surfaces of untreated viable cells were smooth.

Bioactivity guided fractionation and hypolipidemic property of a novel HMG-CoA reductase inhibitor from Ficus virens Ait.

BACKGROUND: The current perspective for the search of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor has been shifted towards a natural agent also having antioxidant property. Thus, this study was intended to isolate and identify the bioactive compounds from methanolic extract of Ficus virens bark (FVBM) and to evaluate their antioxidant, HMG-CoA reductase inhibitory and hypolipidemic activity. METHODS: Bioactivity guided fractionation and isolation of bioactive compound from FVBM extract has been done to isolate and characterize the potent HMG-CoA reductase (HMGR) inhibitor with antioxidant activity by using repeated extensive column chromatography followed by spectroscopic methods, including Infrared (IR), 1H & 13C nuclear magnetic resonance (NMR) and Mass spectrum analysis. The in vitro HMGR inhibition and enzyme kinetic assay was determined using HMG-CoA as substrate. In addition, antioxidant activity of the new isolated compound, was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and FRAP value. In-silico molecular informatics of HMGR enzyme type inhibition and pharmacokinetics data of the new compound was further evaluated through molecular docking and ADME-T studies. Further, in-vivo hypolipidemic property of FVBM extract and newly isolated compound was also analyzed in triton-WR 1339 induced rats. RESULTS: Thereby, we report the discovery of n-Octadecanyl-O-α-D-glucopyranosyl(6'→1″)-O-α-D-glucopyranoside (F18) as a novel HMG-CoA reductase inhibitor with strong antioxidant property. This inhibitor exhibited not only higher free radical scavenging activity but also marked HMG-CoA reductase inhibitory activity with an IC50 value of 84±2.8 ng/ml. This inhibitory activity concurred with kinetic study that showed inhibition constant (K i) of 84 ng/ml via an uncompetitive mode of inhibition. The inhibition was also corroborated by molecular docking analysis and in silico pharmacokinetics data. The in vivo study revealed that administration of FVBM extract (at higher dose, 100 mg/rat) and the inhibitor (1 mg/rat) to Triton WR-1339-induced hyperlipidemic rats significantly ameliorated the altered levels of plasma lipids and lipoproteins including hepatic HMG-CoA reductase activity; this effect was comparable to the effect of standard drug atorvastatin. CONCLUSIONS: The in vitro, in silico and in vivo results clearly demonstrated the antioxidant potential and therapeutic efficacy of the inhibitor as an alternate drug against hyperlipidemia.

Therapeutic intervention and molecular characterizations of bacteriocin producing Lysinibacillus sp., nov., isolated from food sample.

Many bacteriocins from Lactobacilli have been reported as immunostimulatory, preservatives, anticancerous and biocontroling. However, antimicrobial potential of Lysinibacillus is not much reported. In this study, an attempt was made to isolate and anticipate therapeutic potential of Lysinibacillus from spoiled food sample. We screened 125 Lactobacilli for their antagonistic nature against food borne and disease causing bacterial and fungal pathogens. Among them, one Bacillus was phenotypically, and 16S rRNA based, molecularly identified as Lysinibacillus species given with accession numbers JX416855 in NCBI. The type strain JX416855 has shown the 99% identity with the Lysinibacillus fusiformis, Lysinibacillus sphaericus and Lysinibacillus xylanilyticus. It was amylase, protease, gelatinase, nitrate reductase and urease negative and catalase positive. The growth conditions and bacteriocin activity were found optimum with MRS media at pH 7-10, Temp-35-40°C and salt tolerance at 1-3% which was optimized with MRS broth at pH 7.4, 37 °C, 1.5% NaCl for 48 h in shaking conditions @ 100 rpm. The isolate showed broad-spectrum antibacterial activity against gram positive (10-13 mm) and gram-negative (20mm) bacteria. It also strongly inhibited to fungus Aspergillus, Fusarium and Trichoderma. Bacteriocin from 60% ammonium sulphate fraction strongly inhibited to gram-negative R. planticola and Pseudomonas aeruginosa, which showed three protein bands of high molecular weight (nearly 40-70 kD) by SDS-PAGE analysis.

Glycoxidation of biological macromolecules: a critical approach to halt the menace of glycation.

Glycation is the result of covalent bonding of a free amino group of biological macromolecules with a reducing sugar, which results in the formation of a Schiff base that undergoes rearrangement, dehydration and cyclization to form a more stable Amadori product. The final products of nonenzymatic glycation of biomacromolecules like DNA, proteins and lipids are known as advanced glycation end products (AGEs). AGEs may be generated rapidly or over long times stimulated by distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. Both Schiff base and Amadori glycation products generate free radicals resulting in decline of antioxidant defense mechanisms and can damage cellular organelles and enzymes. This critical review primarily focuses on the mechanistic insight of glycation and the most probable route for the formation of glycation products and their therapeutic interventions. Furthermore, the prevention of glycation reaction using therapeutic drugs such as metformin, pyridoxamine and aminoguanidine (AG) are discussed with special emphasis on the novel concept of the bioconjugation of these drugs like, AG with gold nanoparticles (GNPs). At or above 10 mM concentration, AG is found to be toxic and therefore has serious health concerns, and the study warrants doing this novel bioconjugation of AG with GNPs. This approach might increase the efficacy of the AG at a reduced concentration with low or no toxicity. Using the concept of synthesis of GNPs with abovementioned drugs, it is assumed that toxicity of various drugs which are used at high doses can be minimized more effectively.

Antimicrobial potential of bacteriocin producing Lysinibacillus jx416856 against foodborne bacterial and fungal pathogens, isolated from fruits and vegetable waste.

In this study, antimicrobial potential, some probiotics properties and bacteriocin nature of Lysinibacillus, isolated from fruits and vegetable waste were evaluated. For this, 125 Lactobacillus isolates were tested against foodborne bacterial and fungal pathogens. Among these, an isolated Bacillus spp. showed significant aggregation-co-aggregation probiotics properties and potentially inhibits the foodborne gram positive microbial pathogens such as Staphylococcus aureus, (22 mm ZOI), Staphylococcus epedermidis and Bacillus cereus (18 mm). Phenotypically and molecularly it was identified as Lysinibacillus (NCBI accession no. JX416856) and it was found closest to Lysinibacillus fusiformis, Lysinibacillus sphaericus and Lysinibacillus xylanilyticus. Physico-biochemically, it was found to be negative for amylase, protease, gelatinase, nitrate reductase and urease while positive for catalase. The diagnostic fatty acid was 22;2 (3.51). The growth conditions and bacteriocin activity were found to be optimum with MRS media at pH 7-10, Temperature 35-40 °C and salt tolerance at 1-3%. Eventually its production was optimized with MRS broth at pH 7.6, 37 °C, for 36 h in shaking conditions at the rate of 100 rpm. Active bacteriocin was isolated at 60% ammonium sulfate precipitation. The molecular weight of given bacteriocin was found to be nearly 25-35 kDa by SDS-PAGE. Based on physico- biochemical properties, the isolated bacteriocin was to be categories in class II bacteriocin. The bacteriocin was found to be stable in the range of 4-80 °C temperature, 6-10 pH and even in the presence of surfactant (such as SDS and Tween 80). However, proteases like pepsin and trypsin were found to degrade the bacteriocin. Collectively, the broad spectrum inhibitory potential and physical stability offered the antimicrobial potential to Lysinibacillus, and its relevant bacteriocin might be used as an alternative food preservative or therapeutic agent to control spoilage of different food products.

Artificial intelligence derived categorizations significantly improve HOMA IR/ß indicators: Combating diabetes through cross-interacting drugs.

Improvements in the homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-ß) significantly reduce the risk of disabling diabetic pathies. Nanoparticle (AuNP-AgNP)-metformin are concentration dependent cross-interacting drugs as they may have a synergistic as well as antagonistic effect(s) on HOMA indicators when administered concurrently. We have employed a blend of machine learning: Artificial Neural Network (ANN), and evolutionary optimization: multiobjective Genetic Algorithms (GA) to discover the optimum regime of the nanoparticle-metformin combination. We demonstrated how to successfully employ a tested and validated ANN to classify the exposed drug regimen into categories of interest based on gradient information. This study also prescribed standard categories of interest for the exposure of multiple diabetic drug regimen. The application of categorization greatly reduces the time and effort involved in reaching the optimum combination of multiple drug regimen based on the category of interest. Exposure of optimum AuNP, AgNP and Metformin to Diabetic rats significantly improved HOMA ß functionality (∼63 %), Insulin resistance (HOMA IR) of Diabetic animals was also reduced significantly (∼54 %). The methods explained in the study are versatile and are not limited to only diabetic drugs.

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.

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.

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.

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.

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.

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.