Antibiotic resistance in common pathogens, viz., Escherichia coli and Pseudomonas aeruginosa, poses a significant global health challenge in the management of hospital-acquired infections. Rapid detection of antibiotic resistance and pathogen identification, using techniques such as the gold nanoprobe-based hybridization assay, could aid the implementation of appropriate infection control strategies. The present work reports an assay for visual detection of antibiotic resistance associated with single-nucleotide mutations and pathogen identification. Specific single-stranded DNA probes targeting antibiotic resistance-associated single-nucleotide mutations [viz., cyaA (fosfomycin resistance), dacB (ceftazidime resistance), and species-specific genes (uidA and toxA) in E. coli and P. aeruginosa, respectively], were designed, synthesized, and conjugated with gold nanoparticles. The gold-nanoprobe hybridization assay was optimized using synthetic targets and subsequently evaluated using clinical isolates [E. coli (n = 25) and P. aeruginosa (n = 26)]. The limit-of-detection (LOD) was determined using genomic DNA and PCR amplicons. For the antibiotic resistance assay, the LOD for E. coli was 105 and 103 CFU/mL, whereas for P. aeruginosa, it was 104 and 102 CFU/mL, respectively. The results were compared using broth microdilution (gold-standard method) and Sanger sequencing. The assay results were consistent with DNA sequencing, confirming the presence of single-nucleotide mutations that confer antibiotic resistance. The LOD of bacterial identification assay was 104 CFU/mL using genomic DNA and 103 CFU/mL using PCR amplicons. The identification assay showed complete agreement with the MALDI-TOF, achieving 100% specificity. The visualization of results makes the assay suitable for identifying antibiotic-resistant strains in hospital environments, especially in resource-limited settings.
The review provides an in-depth analysis of various factors that affect the long-term success of implants and scrutinizes all available techniques for dental implant modifications, along with their advantages and limitations. Along with established and proposed strategies, newer trends such as responsive coatings, ‘omics’ and AI-based possibilities for translating research into clinical settings are discussed. The available scientific literature on dental implants, causes for their failures, and possible surface modification techniques was collected and analyzed. Strategies to prevent implant failures are presented as a comprehensive, structured review. A literature review of scientific research papers published over the last decade clearly indicates that surface modification of dental implants is critical for ensuring long-term success. Strategies aimed at surface changes consider the intrinsic antibacterial activity, surface texture, and geometry of the implant material. In both healthy and compromised patients, bio-functionalized surfaces can improve osseointegration and reduce peri-implantitis, boosting the success of dental implants. Dental implants, while promising, face hurdles that hinder their long-term success. Modifying implants through physical, chemical, or mechanical methods could potentially address these challenges. These techniques would require clinical validation before being fully integrated into clinical practice. Moreover, crucial factors such as immune response and in vivo testing are often overlooked.
Bacterial Cellulose (BC), a natural Carbon Nanomaterial (NCNM) is an extracellular polysaccharide produced fermentatively by specific bacterial genera. In static conditions, BC is produced at the air-liquid interface, as an easily visible moist hydrogel pellicle in a chemically 'pure' form. The pellicle contains individual fibers similar to 70 nm in width, forming bundles similar to 130 nm in thickness, which are crystalline in nature. Thus, the carbohydrate polymer (containing only C, H, and O as its constituents) per se qualifies as a 'natural' nanomaterial obtained by fermentation of agro wastes, which serve as carbon sources. The peculiar physicochemical and mechanical properties of bacterial cellulose, such as its purity, water-holding capacity, high tensile strength, flexibility, mouldability, sterilizable nature, high Young's modulus, and biological properties such as non-immunogenic and nontoxic nature, biocompatibility make it an appropriate material for biomedical and non-biomedical applications. Bacterial cellulose is easily convertible into carbon nanotubes and aerogels, which can have several applications such as biosensing, manufacture of reinforced materials, materials with thermal resistance characteristics, etc. The chapter overviews bacterial cellulose production using agro wastes and its applications.
Two-dimensional (2D) materials have attracted the attention of researchers all over the world since the discovery of graphene in 2004. Several routes of synthesis for graphene, transition metal dichalcogenides (TMDs), hexagonal boron nitride (hBN), black phosphorus (BP), metal oxides, MXenes, silicene, and other 2D materials were optimized. Due to their peculiar layered nature, 2D materials offer immense potential as sensors. Extremely high surface area to volume ratio, tunable band gap, the possibility of doping, and possibilities for surface modifications with specific biomolecules for bio-recognition are properties that allow the development of sensors. The mechanical properties and flexible nature of 2D materials have led to the inclusion of these in wearable electronics for biomonitoring. With the advancements in communication systems such sensors are set to revolutionize biomedicine. However, careful assessment of toxicity, biocompatibility, and design and implementation of strategies for safe disposal is required. Scalable production methods, material characterization protocols, and the establishment of uniform regulations and risk assessment guidelines would help the commercialization of 2D materials as sensor platforms.
Background: Zinc deficiency is strongly correlated with prolonged diabetes mellitus and diabetic nephropathy (DN). Previously, glucose-lowering, insulinomimetic, and beta -cell proliferative activities of zinc oxide nanoparticles (ZON) have been reported. Considering these pleiotropic effects, we hypothesized that ZON modulates multiple cellular pathways associated with necroptosis, inflammation, and renal fibrosis, which are involved in progressive loss of renal function. Aim: This study evaluated the effect of ZON on renal function, leading to the alleviation of DN in streptozotocin (STZ)-induced type 1 diabetic Wistar rats and proposed a probable mechanism for its activity. Methods: Wistar rats ( n = 6/group) were used as healthy controls, diabetic controls, diabetic rats treated with ZON (1, 3, and 10 mg/kg), and insulin controls. Urine and serum biochemical parameters, glomerular filtration rate (GFR), and renal histology were also evaluated. Cultured E11 podocytes were evaluated in vitro for markers of oxidative stress, proteins associated with the loss of renal function, and genes associated with renal damage. Key findings: STZ-treated rats receiving oral doses of ZON showed enhanced renal function, with no histological alterations in the kidney tissue. ZON inhibited the TGF- beta /Samd3 pathway in renal fibrosis; blocked Ripk1/ Ripk3/Mlkl mediated necroptosis and protected against hyperglycemia-induced pyroptosis. In E11 podocytes, ZON reduced oxidative stress under high glucose conditions and retained podocyte-specific proteins. Significance: A probable mechanism by which ZON prevents DN has been proposed, suggesting its use as a complementary therapeutic agent for the treatment of diabetic complications. To the best of our knowledge, this is the first study to demonstrate the in vitro effects of ZON in cultured podocytes.
Chronic wounds, particularly those infected with multidrug-resistant (MDR) pathogens, present significant challenges for effective healing. Silver nanoparticles (CAAgNPs) were synthsized using aqueous rhizome extract of Curcuma aromatica (CA), known for its wound-healing properties. CAAgNPs were incorporated in a chitosan (CS) dressing (CAAgNPs/CS) and tested for their wound healing potential, expecting synergistic action of AgNPs and phytochemicals capped on it. The porous nature of the CAAgNPs was confirmed using Field emission scanning electron microscopy. Fourier-transform infrared spectroscopy demonstrated a shift in peak intensity from 1589.06 to 1575.54 cm-1 for CAAgNPs/CS dressing confirming crosslinking with glutaraldehyde. Antibacterial activity of the dressings was cofirmed against isolates of Pseudomonas aeruginosa and Staphylococcus aureus. Wound healing studies were carried out using Wistar rats (six groups)- wound control, CS, CAAgNPs256/ CS, CAAgNPs512/CS, CAAgNPs1024/CS, and commercial dressings. Histological examination and direct red-80 staining demonstrated maximum epithelization and collagen deposition (58.02%) within CAAgNPs1024/CS groups on day 10. Increased hydroxyproline levels (76.51 mu g/mL) on day 7 for CAAgNPs1024/CS indicated maximum collagen formation. Reduced levels of inflammatory cytokines IL-6 (17.38 pg/mL) and TNF-alpha (80.38 pg/mL) on day 10 indicated quick wound healing without scar formation and damaging effects. The present study highlights the antibacterial and anti-inflammatory properties of CAAgNPs1024/CS dressings with a potential for wound healing applications.
The clinical success of implants depends on rapid osseointegration, and new materials are being developed considering the increasing demand. Considering cobalt (Co) antibacterial characteristics, we developed Co -deposited titanium (Ti) using direct current (DC) sputtering and investigated it as a new material for implant dentistry. The material was characterized using atomic absorption spectroscopy, scanning electron microscopy -energy dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. The material's surface topography, roughness, surface wettability, and hardness were also analyzed. The Co thin film (Ti-Co15) showed excellent antibacterial effects against microbes implicated in peri-implantitis. Furthermore, Ti-Co15 was compatible and favored the attachment and spreading of MG -63 cells. The alkaline phosphatase and calcium mineralization activities of MG -63 cells cultured on Ti-Co15 remained unaltered compared to Ti. These data correlated well with the time -dependent expression of ALP, RUNX-2, and BMP-2 genes involved in osteogenesis. The results demonstrate that Co -deposited Ti could be a promising material in implant dentistry.
Bone health is crucial at all stages of life. Several medical conditions and changes in lifestyle affect the growth, structure, and functions of bones. This may lead to the development of bone degenerative disorders, such as osteoporosis, osteoarthritis, rheumatoid arthritis, etc., which are major public health concerns worldwide. Accurate and reliable measurement and monitoring of bone health are important aspects for early diagnosis and interventions to prevent such disorders. Significant progress has recently been made in developing new sensing technologies that offer non-invasive, low-cost, and accurate measurements of bone health. In this review, we have described bone remodeling processes and common bone disorders. We have also compiled information on the bone turnover markers for their use as biomarkers in biosensing devices to monitor bone health. Second, this review details biosensing technology for bone health assessment, including the latest developments in various non-invasive techniques, including dual-energy X-ray absorptiometry, magnetic resonance imaging, computed tomography, and biosensors. Further, we have also discussed the potential of emerging technologies, such as biosensors based on nano- and micro-electromechanical systems and application of artificial intelligence in non-invasive techniques for improving bone health assessment. Finally, we have summarized the advantages and limitations of each technology and described clinical applications for detecting bone disorders and monitoring treatment outcomes. Overall, this review highlights the potential of emerging technologies for improving bone health assessment with the potential to revolutionize clinical practice and improve patient outcomes. The review highlights key challenges and future directions for biosensor research that pave the way for continued innovations to improve diagnosis, monitoring, and treatment of bone-related diseases.
Adipocyte is a predominant component of the omental adipose tissue that influences the tumor microenvironment and increases the risk of endometrial cancer progression (EC), however, little is known about the underlying mechanism. In this study, using a co-culture model, we found that the adipocyte-EC cell interaction promoted SIRT1 signaling in vitro and in vivo xenograft mice models. Furthermore, immunostaining of SIRT1 protein showed significantly higher expression of SIRT1 in endometrial cancer patients than in normal endometria. RNA sequencing analysis revealed HMMR (hyaluronan-mediated motility receptor), an oncogene, as a downstream effector of SIRT1 in adipocyte-associated EC. Transient knockdown and chromatin immunoprecipitation assays showed that SIRT1 inhibition impedes transcription of the HMMR gene via FOXM1, and reduced expression of HMMR in co-cultured EC cells blocks AURKA activation via TPX2, leading to cell cycle arrest. This is the first study to report the positive correlation between SIRT1 and HMMR in EC patient tumors and might be used as a potential biomarker in EC. Notably, SIRT1 regulates HMMR expression in a FOXM1-dependent manner, and interfering with SIRT1 may provide a promising strategy for the management of endometrial cancer.
Bacterial infections are a common cause of sepsis, often leading to high patient mortality. Such infections are challenging to treat due to bacterial resistance to many existing drugs. Erythromycin (Ery) is a macrolide antibiotic used against bacterial infections with reported resistance. Recently, synthetic poly-lactide co-glycolic acid (PLGA) polymer nanoparticles (NPs) have displayed improved drug delivery characteristics and biocompatibility. In this study, PLGA-Ery NPs were synthesized by the o/w emulsion diffusion method, having a particle size of 159 ± 23 nm and displayed 71.89 % of encapsulation efficiency. The PLGA-Ery NPs showed 1.5, 2.1 and 1.5-fold improved MIC and antibacterial efficacy against E. coli, S. aureus, and P. aeruginosa, respectively than the pure drug. As illustrated by scanning electron microscopy, PLGA-Ery NPs caused damage to the bacterial cell walls. Furthermore, a surface coating with PLGA-Ery NPs on a glass surface showed efficient inhibition (>90 %) of the biofilm formation by P. aeruginosa, as determined by fluorescence microscopy and MTT assay. This study demonstrates that PLGA-Ery NPs can increase the efficiency of erythromycin and can suppress the growth and biofilm formation of P. aeruginosa. Such polymeric nanoparticles drug nanoformulations have potential as an antimicrobial and as a surface coating for medical devices.
Dental implant failures caused by bacterial infections are a significant concern for dental implantologists. We modified the titanium surface by depositing silver (Ti-Ag) using direct current (DC) sputtering and confirmed the formation of a ‘nano coat’ by X-ray photoelectron spectroscopy (XPS), surface profilometry and energy dispersive spectroscopy (EDS). Scanning electron microscopy (SEM) and atomic force microscopy (AFM) revealed the deposition of a uniform nano Ag thin film. A gradual increase in thickness was observed, and the film thickness (530 nm) at 5 min deposition time (Ti-Ag5) resulted in a reduction of the water contact angle (WCA, 15%) and an increase in surface energy (SFE, 22%) in comparison to the uncoated Ti surface. Using inductively coupled plasma-atomic emission spectroscopy (ICP-AES), the slow, steady release of Ag from the coating was observed over 21 days. The Ti-Ag5 surface exhibited excellent antibacterial activity against Streptococcus oralis, Streptococcus sanguinis, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis, which belonged to the yellow, purple, and red complexes, representing specific periodontal pathogens. Furthermore, we observed excellent cytocompatibility of Ag-deposited Ti towards MG-63 osteoblasts with no inhibitory effect on their proliferative potential. Quantitation of alkaline phosphatase (ALP) activity, mineralization efficiency, and osteogenesis-related gene expression of MG-63 cells over 21 days was suggestive of rapid osseointegration. Overall, the ‘nano coat’ of Ag on Ti is indeed a prophylactic against peri-implantitis, ensuring increased implant success.
Global health and ecosystem concerns over mercury pollution require stringent monitoring. Herein, we showcase a novel approach for detecting trace Hg2+ ions in water using cyclic voltammetry (CV). Our approach involves modifying glassy carbon electrode (GCE) and screen printed electrode (SPE) surfaces with a nanocomposite of ascorbic acid-capped silver nanoparticles (AsAgNPs) embedded in nanocrystalline bacterial cellulose (AsAgNP-NBC). Analytical techniques confirmed the nanocomposite's stability and morphological characteristics, exhibiting high accuracy within a linear range of 10 nM to 1 mu M Hg2+ and a low limit of detection (LOD) of 3.531 nM. Additionally, on irradiation with 455 nm light source, AsAgNP-NBC modified SPE displayed a remarkable 9.6 times enhanced photocurrent, achieving an LOD of 3.95 pM, and enhanced photoresponsivity of 55.2 mA W-1, showcasing its potential for ultra-trace level detection. This cost-effective and biocompatible nanocomposite presents a promising alternative to conventional analytical methods for selective detection of trace Hg2+ ions in environmental samples.
Copper and other copper-containing compounds can be produced as nanoparticles by "green nanotechnologies." The most striking features of nanoparticles, such as their facile synthesis, easy synthesis process scalability, and abundance of raw materials (including precursors), have prompted their exploration in various agricultural applications. Particularly, preliminary data on their use as fungicidal agents and plant growth-promoting agents are now available. With these developments, it is expected that copper-based nanofungicides will emerge as "next-generation agrochemicals." A minimal impact on the environment during the production of nanomaterials will ensure their sustainable applications in the agricultural sector. Copper nanofungicidal formulations have many advantages. Besides providing the necessary antifungal activity, the nanofungicides, with their inherently low concentrations of copper, can benefit plant growth, resulting in increased yields. Furthermore, the associated ecotoxicological risks of nanofungicides are negligible. With the new advances, better and "smarter" nanoformulations tailored to release the active ingredient on demand can be made. These advanced nanofungicidal materials can go a long way towards preventing ecotoxicity in the environment and making agriculture much safer, which is very important.
Skin wounds are categorized as 'acute' or 'chronic' based on the healing process. Wound care is of utmost importance as the break in the skin barrier exposes the internal milieu to various commensal and pathogenic microbes. The usage of nanomaterials is a recent approach to facilitate wound healing by processes that operate singly or in tandem. Metal based nanomaterials show antibacterial, antifungal, and anti-inflammatory activities; and organic-inorganic, organic-organic nanocomposites as 'smart', 'advanced' materials would play a crucial role in wound care. Use of nanomaterials in wound care would revolutionarize treatment, thus lowering the economic burden.
The present study aimed to assess the efficacy of photofunctionalization on commercially available dental implant surfaces in a high-glucose environment. Discs of three commercially available implant surfaces were selected with various nano- and microstructural alterations (Group 1—laser-etched implant surface, Group 2—titanium–zirconium alloy surface, Group 3—air-abraded, large grit, acid-etched surface). They were subjected to photo-functionalization through UV irradiation for 60 and 90 min. X-ray photoelectron spectroscopy (XPS) was used to analyze the implant surface chemical composition before and after photo-functionalization. The growth and bioactivity of MG63 osteoblasts in the presence of photofunctionalized discs was assessed in cell culture medium containing elevated glucose concentration. The normal osteoblast morphology and spreading behavior were assessed under fluorescence and phase-contrast microscope. MTT (3-(4,5 Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and alizarin red assay were performed to assess the osteoblastic cell viability and mineralization efficiency. Following photofunctionalization, all three implant groups exhibited a reduced carbon content, conversion of Ti4+ to Ti3+, increased osteoblastic adhesion, viability, and increased mineralization. The best osteoblastic adhesion in the medium with increased glucose was seen in Group 3. Photofunctionalization altered the implant surface chemistry by reducing the surface carbon content, probably rendering the surfaces more hydrophilic and conducive for osteoblastic adherence and subsequent mineralization in high-glucose environment.
Alzheimer ' s disease (AD) is a progressive neurodegenerative disease characterized by ss-amyloid peptide (A ss(1-42)) deposits, with no definitive therapies. Recently, cyclic peptides have been considered potential therapeutics because of proteolytic stability and tight and precise binding to A ss(1-42). We modified the classic cyclic peptide viz., PPLeu, via a directed approach to arrive at a new ss-hairpin cyclic peptide BSBP8 (Mw 1450 Da), a potent anti-amyloidogenic agent. BSBP8 also disassembled pre-formed A ss(1- 42) fibrils and rescued neuronal cells from A ss(1- 42) induced cytotoxicity. In the Thioflavin T assay, BSBP8 showed similar to 82 % aggregation reduction when coincubated with A ss(1-42). Biophysical techniques, viz. Circular Dichroism, Fourier Transform Infrared Spectroscopy, and Atomic Force Microscopy substantiated these results. To achieve permeation of BSBP8 across the blood-brain barrier, the peptide was loaded onto poly D,L-lactide-co-glycolide nanoparticles (PLGA NPs). Compared to BSBP8 alone, the negatively charged ( 8.96 +/- 1.22 mV) spherical particles with a mean diameter of 223.2 +/- 3.52 nm, loaded with BSBP8 (2.86 % w/w) permeated across the BBB formed by the Madin-Darby canine kidney cells. In vivo biodistribution profile indicated similar to 9 %, 52 % and 20 % particle accumulation in the brain, liver, and kidney. Tissue retention of BSBP8-PLGA NPs was observed for at least seven days. It can be anticipated that this study will significantly promote the development of therapeutics for AD.
Extensive research has been conducted during 20th century to discover renewable natural polymers that are sustainable. Cellulose represents one such biomaterial which is abundant, renewable, and biodegradable. Both plant and microbial biomass can be processed to make cellulose. Bacterial cellulose (BC) is a prospective natural polymer produced by certain bacteria during their growth phase. BC is hydrophilic biopolymer, fibrous (20–100 nm diameter), and biocompatible. In contrast to plant cellulose, BC has the benefit of being in form, which is both, highly crystalline and extremely pure. This review provides a crisp summary of the synthesis and functionalization of BC, and its applications in the fields of biomedicine and the environment.
Biosynthesis of nanoparticles is compliant with principles of "green chemistry" and is considered an alternative to physical and chemical methods. When fungi and/or their metabolites are involved in the synthesis of nanoparticles, the particles synthesized are referred to as "myconanoparticles." Mostly the synthesis of metals (silver, gold, and copper), metal oxide, and rarely, bimetallic nanoparticles using fungi is reported. Applications of these myconanoparticles are realized in the health, agriculture, and environmental sectors. Particularly in agriculture, control of phytopathogens has been the focus. However, the veterinary sector is important because animal-derived foods make a substantial contribution to food security. In the last decade the possible applications of nanotechnology in the veterinary sector were proposed. However, the use of "mycosynthesized nanoparticles" in this field is still in its infancy. Thorough experimentation in veterinary animals and detailed studies on the impact of myconanoparticles on veterinary animals, humans, and the environment will ensure public acceptance of myconanotechnology in veterinary practice.
The pathological hallmark of many amyloid diseases is the aggregation and deposition of soluble proteins into toxic insoluble fibrils in various tissues. Without any definite cure for these proteinopathies, researchers have explored small molecules, antibodies, peptides, nanomaterials etc., as potential agents interacting with different conformational species of amyloid-forming proteins. Mainly, amyloid fibrillation inhibitors in the form of cyclic peptides (CPs) (based on amyloid and non-amyloid-forming protein sequences) show remarkable anti-amyloidogenic activity as well as chemical, thermal, and proteolytic stability over their linear counterparts. Furthermore, some 'add-on' attributes include ease of synthesis, amenability for chemical modification, precise and tight binding (high specificity) to target peptides, and biocompatibility. This article highlights the design, synthesis, bioactivity, and mechanistic evaluation of rationally designed CPs inhibitors against amyloid systems. This review also discusses the dual role of nanoparticles as inhibitors of amyloid fibrillation and as carriers for the delivery of therapeutic molecules across the blood–brain barrier. Thus, combining CPs and nanoparticles could represent ‘next-generation therapeutics’ for amyloid diseases.
Shrimp farming is an important socioeconomic activity worldwide. Infectious myonecrosis virus (IMNV) is an important shrimp virus responsible for significant mortality (up to 70