Novel enhancement of interfacial interaction and properties in biodegradable polymer composites using green chemically treated spent coffee ground microfiller.

This study investigates the potential of utilizing green chemically treated spent coffee grounds (SCGs) as micro biofiller reinforcement in Poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) biopolymer composites. The aim is to assess the impact of varying SCG concentrations (1 %, 3 %, 5 %, and 7 %) on the functional, thermal, mechanical properties and biodegradability of the resulting composites with a PHBV matrix. The samples were produced through melt compounding using a twin-screw extruder and compression molding. The findings indicate successful dispersion and distribution of SCGs microfiller into PHBV. Chemical treatment of SCG microfiller enhanced the interfacial bonding between the SCG and PHBV, evidenced by higher water contact angles of the biopolymer composites. Field Emission Scanning Electron Microscopy (FE-SEM) confirmed the successful interaction of treated SCG microfiller, contributing to enhanced mechanical characteristics. A two-way ANOVA was conducted for statistical analysis. Mass losses observed after burying the materials in natural soil indicated that the composites degraded faster than the pure PHBV polymer suggesting that both composites are biodegradable, particularly at high levels of spent coffee grounds (SCG). Despite the possibility of agglomeration at higher concentrations, SCG incorporation resulted in improved functional properties, positioning the green biopolymer composite as a promising material for sustainable packaging and diverse applications.

Isolation and biochemical characterization of novel acid phosphatase and zinc-dependent acid phosphatase from the chicken's brain.

The AcPase exhibits a specific activity of 31.32 U/mg of protein with a 728-fold purification, and the yield of the enzyme is raised to 3.15 %. The Zn2+-dependent AcPase showed a purification factor of 1.34 specific activity of 14 U/mg of proteins and a total recovery of 5.14. The SDS-PAGE showed a single band corresponding to a molecular weight of 18 kDa of AcPase and 29 kDa of Zn2+-dependent AcPase. The AcPase enzyme has shown a wide range of substrate specificity for p-NPP, phenyl phosphate and FMN, while in the case of ZnAcPase α and ß-Naphthyl phosphate and p-NPP were proved to be superior substrates. The divalent metal ions like Mg2+, Mn2+, and Ca2+ increased the activity, while other substrates decreased the enzyme activity. The Km (0.14 mM) and Vmax (21 µmol/min/mg) values of AcPase were higher than those of Zn2+-AcPase (Km = 0.5 mM; Vmax = 9.7 µmol/min/mg). The Zn2+ ions activate the Zn2+-AcPase while Fe3+, Al3+, Pb2+, and Hg2+ showed inhibition on enzyme activity. Molybdate, vanadate and phosphate were found to be competitive inhibitors of AcPase with Ki values 316 µM, 185 µM, and 1.6 mM, while in Zn2+-AcPase tartrate and phosphate also showed competitive inhibition with Ki values 3 mM and 0.5 mM respectively.

Repositioning of anti-infective compounds against monkeypox virus core cysteine proteinase: a molecular dynamics study.

Monkeypox virus (MPXV) core cysteine proteinase (CCP) is one of the major drug targets used to examine the inhibitory action of chemical moieties. In this study, an in silico technique was applied to screen 1395 anti-infective compounds to find out the potential molecules against the MPXV-CCP. The top five hits were selected after screening and processed for exhaustive docking based on the docked score of ≤ -9.5 kcal/mol. Later, the top three hits based on the exhaustive-docking score and interaction profile were selected to perform MD simulations. The overall RMSD suggested that two compounds, SC75741 and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23 nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔGTOTAL from -21.59 to -15 kcal/mol. This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate.

Status of vancomycin-resistant Enterococcus in species of wild birds: A systematic review and meta-analysis.

Wild birds could be a reservoir of medically relevant microorganisms, particularly multidrug-resistant Enterococcus spp. Resistant bacteria's epidemiology and transmission between animals and humans has grown, and their zoonotic potential cannot be ignored. This is the first study to evaluate the status of vancomycin resistant enterococci (VRE) in various wild bird species using meta-analysis and a systematic review. In this study, the pooled prevalence was obtained by analyzing data from published articles on the occurrence of VRE in wild bird species. It's unclear how the antibiotic resistance gene transfer cycle affects wild birds. Google Scholar and PubMed were used to conduct the research. The data and study methodology was assessed and extracted by two reviewers independently, with a third reviewing the results. Heterogeneity between study and publication bias were analyzed using the random effect model. Thirty-eight studies were included in the meta-analysis. 382 out of the 4144 isolates tested, were VRE. The pooled prevalence of VRE among wild birds was estimated at 11.0% (95% CI; 6.9 -17.2%; I2 = 93.204%; P < 0.001). There was high variability between study (t2 = 2.156; heterogeneity I2 = 93.204% with chi-square (Q) = 544.413, degrees of freedom (df) = 37, and P < 0.001). Egger's test verified the funnel plot's bias, while result from the leave-one-out forest plot had no effect on the pooled prevalence.

Antifungal drug discovery for targeting Candida albicans morphogenesis through structural dynamics study.

In response to the escalating threat of drug-resistant fungi to human health, there is an urgent need for innovative strategies. Our focus is on addressing this challenge by exploring a previously untapped target, yeast casein kinase (Yck2), as a potential space for antifungal development. To identify promising antifungal candidates, we conducted a thorough screening of the diverse-lib drug-like molecule library, comprising 99,288 molecules. Five notable drug-like compounds with diverse-lib IDs 24334243, 24342416, 17516746, 17407455, and 24360740 were selected based on their binding energy scores surpassing 11 Kcal/mol. Our investigation delved into the interaction studies and dynamic stability of these compounds. Remarkably, all selected molecules demonstrated acceptable RMSD values during the 200 ns simulation, indicating their stable nature. Further analysis through Principal Component Analysis (PCA)-based Free Energy Landscape (FEL) revealed minimal energy transitions for most compounds, signifying dynamic stability. Notably, the two compounds exhibited slightly different behaviour in terms of energy transitions. These findings mark a significant breakthrough in the realm of antifungal drugs against C. albicans by targeting the Yck2 protein. However, it is crucial to note that additional experimental validation is imperative to assess the efficacy of these molecules as potential antifungal candidates. This study serves as a promising starting point for further exploration and development in the quest for effective antifungal solutions.Communicated by Ramaswamy H. Sarma.

Antiviral actions of natural compounds against dengue virus RNA dependent RNA polymerase: insights from molecular dynamics and Gibbs free energy landscape.

Dengue fever, a major global health challenge, affects nearly half the world's population and lacks effective treatments or vaccines. Addressing this, our study focused on natural compounds that potentially inhibit the dengue virus's RNA-dependent RNA polymerase (RdRp), a crucial target in the viral replication cycle. Utilizing the MTiOpenScreen webserver, we screened 1226 natural compounds from the NP-lib database. This screening identified four promising compounds ZINC000059779788, ZINC0000044404209, ZINC0000253504517 and ZINC0000253499146), each demonstrating high negative binding energies between -10.4 and -9.9 kcal/mol, indicative of strong potential as RdRp inhibitors. These compounds underwent rigorous validation through re-docking and a detailed 100 ns molecular dynamics (MD) simulation. This analysis affirmed the dynamic stability of the protein-ligand complexes, a critical factor in the effectiveness of potential drug candidates. Additionally, we conducted essential dynamics and free energy landscape calculations to understand the structural transitions in the RdRp protein upon ligand binding, providing valuable insights into the mechanism of inhibition. Our findings present these natural molecules as promising therapeutic agents against the dengue virus. By targeting the allosteric site of RdRp, these compounds offer a novel approach to hinder the viral replication process. This research significantly contributes to the search for effective anti-dengue treatments, positioning natural compounds as potential key players in dengue virus control strategies.Communicated by Ramaswamy H. Sarma.

Nano guardians of the heart: A comprehensive investigation into the impact of silver nanoparticles on cardiovascular physiology.

Globally, cardiovascular diseases (CVDs) constitute the leading cause of death at the moment. More effective treatments to combat CVDs are urgently required. Recent advances in nanotechnology have opened the door to new avenues for cardiovascular health treatment. Silver nanotechnology's inherent therapeutic powers and wide-ranging applications have made it the center of focus in recent years. This review aims to analyze the chemical, physical, and biological processes ofproducing AgNPs and determine their potential utility as theranostics. Despite significant advances, the precise mechanism by which AgNPs function in numerous biological systems remains a mystery. We hope that at the end of this review, you will better understand how AgNPs affect the cardiovascular system from the research done thus far. This endeavor thoroughly investigates the possible toxicological effects and risks associated with exposure to AgNPs. The findings shed light on novel applications of these versatile nanomaterials and point the way toward future research directions. Due to a shortage of relevant research, we will limit our attention to AgNPs as they pertain to CVDs. Future research can use this opportunity to investigate the many medical uses of AgNPs. Given their global prevalence, we fully endorse academics' efforts to prioritize nanotechnological techniques in pursuing risk factor targeting for cardiovascular diseases. The critical need for innovative solutions to this widespread health problem is underscored by the fact that this technique may help with the early diagnosis and treatment of CVDs.

Alkaline protease functionalized hydrothermal synthesis of novel gold nanoparticles (ALPs-AuNPs): A new entry in photocatalytic and biological applications.

Researchers are consistently investigating novel and distinctive methods and materials that are compatible for human life and environmental conditions This study aimed to synthesize gold nanoparticles (ALPs-AuNPs) using for the first time an alkaline protease (ALPs) derived from Phalaris minor seed extract. A series of physicochemical techniques were used to inquire the formation, size, shape and crystalline nature of ALPs-AuNPs. The nanoparticles' ability to degrade methylene blue (MB) through photocatalysis under visible light irradiation was assessed. The findings demonstrated that ALPs-AuNPs exhibited remarkable efficacy by destroying 100 % of MB within a mere 30-minute irradiation period. In addition, the ALPs-AuNPs demonstrated remarkable effectiveness in inhibiting the growth of gram-positive (S. aureus) and gram-negative (E. coli) bacteria. The inhibition zones examined against the two bacterial strains were 23(±0.3) mm and 19(±0.4); 13(±0.3) mm and 11(±0.5) mm under light and dark conditions respectively. The ALPs-AuNPs exhibited significant antioxidant activity by effectively scavenging 88 % of stable and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. As a result, the findings demonstrated that the environmentally friendly ALPs-AuNPs showed a strong potential for MB degradation and bacterial pathogen treatment.

Utilization of nanotechnology and experimental design in the development and optimization of a posaconazole‒calendula oil nanoemulgel for the treatment of mouth disorders.

Introduction: Essential oil‒based nanoemulsions (NEs) are the subjects of extensive investigation due to their potential to address a variety of oral health issues. NEs are delivery systems that improve lipid medicine solubility and distribution to intended sites. The goal of the current study was to create and enhance a self-nanoemulsifying drug delivery paradigm based on calendula oil (CO) and decorated with chitosan (CS) that could deliver posaconazole (PSZ) for the treatment of gingivitis. Method: Employing a response-surface Box‒Behnken design, PSZ-CO-CS NEs were created with varying amounts of PSZ (10, 15, and 20 mg), percentages of CO (6%, 12%, and 18%), and percentages of CS (0.5%, 1.5%, and 2.5%). Results and conclusion: The optimized formulation resulted in a 22-mm bacterial growth suppression zone, 25-mm fungal growth inhibition zone, droplet sizes of 110 nm, and a viscosity of 750 centipoise (cP). Using the appropriate design, the ideal formulation was produced; it contained 20 mg of PSZ, 18% of CO, and 1.35% of CS. Furthermore, the optimal formulation had a more controlled drug release, larger inhibition zones of bacterial and fungal growth, and desirable rheologic properties. Additionally, the optimized formulation substantially lowered the ulcer index in rats when tested against other formulations. Thus, this investigation showed that PSZ-CO-CS NEs could provide efficient protection against microbially induced gingivitis.

Overview of reemerging mpox infection with a focus on neurological manifestations.

Mpox, a reemerging zoonotic disease caused by the mpox virus, has garnered increasing attention due to its potential for severe clinical manifestations. While the cutaneous and systemic presentations of mpox have been well-documented, its neurological complications have recently emerged as an area of concern. This review provides a brief overview of the neurological aspects of mpox infection, highlighting the key findings and challenges in understanding and managing these complications. Neurological manifestations in mpox patients range from mild symptoms such as headaches and dizziness to more severe conditions, including encephalitis and seizures. The pathogenesis of neurological involvement is not yet fully elucidated but is thought to involve viral dissemination to the central nervous system. This dissemination may occur through haematogenous or neuronal routes, contributing to the diverse clinical spectrum observed. Early recognition and diagnosis of neurological complications in mpox are crucial for implementing appropriate therapeutic interventions and improving patient outcomes.

Journey into tomorrow: cardiovascular wellbeing transformed by nano-scale innovations.

Worldwide, cardiovascular diseases (CVDs) account for the vast majority of deaths and place enormous financial strains on healthcare systems. Gold nanoparticles, quantum dots, polymeric nanoparticles, carbon nanotubes, and lipids are innovative nanomaterials promising in tackling CVDs. In the setting of CVDs, these nanomaterials actively impact cellular responses due to their distinctive properties, including surface energy and topographies. Opportunities to more precisely target CVDs have arisen due to recent developments in nanomaterial science, which have introduced fresh approaches. An in-depth familiarity with the illness and its targeted mechanisms is necessary to use nanomaterials in CVDs effectively. We support the academic community's efforts to prioritize Nano-technological techniques in addressing risk factors linked with cardiovascular diseases, acknowledging the far-reaching effects of these conditions. The significant impact of nanotechnology on the early detection and treatment of cardiovascular diseases highlights the critical need for novel approaches to this pressing health problem, which is affecting people worldwide.

Heartfelt living: Deciphering the link between lifestyle choices and cardiovascular vitality.

Cardiovascular diseases (CVDs) are still leading to a significant number of deaths worldwide despite the remarkable advancements in medical technology and pharmacology. Managing patients with established CVDs is a challenge for healthcare providers as it requires reducing the chances of recurring cardiovascular events. On the other hand, changing one's way of life can also significantly impact this area, reducing the likelihood of cardiovascular disease and death through their unique advantages. Consequently, it is advisable for healthcare providers to regularly advise their patients with coronary issues to participate in organized physical exercise and improve their overall physical activity. Additionally, patients should adhere to a diet that promotes heart health, cease smoking, avoid exposure to secondhand smoke, and address any psychosocial stressors that may heighten the risk of cardiovascular problems. These lifestyle therapies, whether used alongside drug therapy or on their own in patients who may have difficulty tolerating medications, face financial barriers, or experience ineffectiveness, can substantially reduce cardiovascular mortality and the likelihood of recurring cardiac events. Despite the considerable advancements in creating interventions, it is still necessary to determine the optimal intensity, duration, and delivery method for these interventions. Furthermore, it is crucial to carry out further investigations incorporating extended monitoring and assessment of clinical outcomes to get a more comprehensive comprehension of the efficacy of these therapies. Presenting the findings within the framework of "lifestyle medicine," this review seeks to offer a thorough synopsis of the most recent scientific investigations into the potential of behavioral modifications to lower cardiovascular disease risk.

Application of temperature-dependent and steered molecular dynamics simulation to screen anti-dengue compounds against Marburg virus.

Marburg virus infections are extremely fatal with a fatality range of 23% to 90%, therefore there is an urgent requirement to design and develop efficient therapeutic molecules. Here, a comprehensive temperature-dependent molecular dynamics (MD) simulation method was implemented to identify the potential molecule from the anti-dengue compound library that can inhibit the function of the VP24 protein of Marburg. Virtual high throughput screening identified five effective binders of VP24 after screening 484 anti-dengue compounds. These compounds were treated in MD simulation at four different temperatures: 300, 340, 380, and 420 K. Higher temperatures showed dissociation of hit compounds from the protein. Further, triplicates of 100 ns MD simulation were conducted which showed that compounds ID = 118717693, and ID = 5361 showed strong stability with the protein molecule. These compounds were further validated using ΔG binding free energies and they showed: -30.38 kcal/mol, and -67.83 kcal/mol binding free energies, respectively. Later, these two compounds were used in steered MD simulation to detect its dissociation. Compound ID = 5361 showed the maximum pulling force of 199.02 kcal/mol/nm to dissociate the protein-ligand complex while ID = 118717693 had a pulling force of 101.11 kcal/mol/nm, respectively. This ligand highest number of hydrogen bonds with varying occupancies at 89.93%, 69.80%, 57.93%, 52.33%, and 50.63%. This study showed that ID = 5361 can bind with the VP24 strongly and has the potential to inhibit its function which can be validated in the in-vitro experiment.Communicated by Ramaswamy H. Sarma.

Bioprospecting of Meliaceae family phytomolecules for the treatment of monkeypox virus infection: a QSAR modeling and MD simulation approach.

Recent monkeypox virus (MPXV) infections show the risk of MPXV transmission that persists today and the significance of surveillance and quick response methods to stop the virus's spread. Currently, the monkeypox virus infection is not specifically treated. In this study, QSAR models were designed using known inhibitors of cysteine proteinase from the vaccinia virus, where the Random Forest model and Ridge model had showed the best correlation between predicted and observed EC50. These models were used to screen Maliaceae family phytochemicals against MPXV cysteine proteinase. The compound, IMPHY010637 was detected in top 5 from both the QSAR screening models and showed best docked score (-8.6 kcal/mol) and thus selected for further investigation. Further, the IMPHY010637 showed interaction with the catalytic residue His241 of the protein as reported in earlier studies. The ADMET analysis of the compound showed the acceptable drug-like properties of IMPHY010637. However, these properties could be improved after experimental validation of protein-ligand binding. Both docked complex and poses created in 100 ns MD simulation of the protein-ligand complex showed the presence of multiple hydrogen bonds. RMSD and conformation analysis showed stable binding of IMPHY010637 with the cysteine proteinase of MPXV at its active site. Compared to the known inhibitor, IMPHY010637 showed better binding with the protein as observed by the PCA and MM/GBSA analysis. This study concluded IMPHY010637 as a potential inhibitor for the cysteine proteinase of MPXV using computational methods that could be tested in in-vitro experiments.Communicated by Ramaswamy H. Sarma.

Utilising biosensor-based approaches for identifying neurotropic viruses.

Neurotropic viruses, with their ability to invade the central nervous system, present a significant public health challenge, causing a spectrum of neurological diseases. Clinical manifestations of neurotropic viral infections vary widely, from mild to life-threatening conditions, such as HSV-induced encephalitis or poliovirus-induced poliomyelitis. Traditional diagnostic methods, including polymerase chain reaction, serological assays, and imaging techniques, though valuable, have limitations. To address these challenges, biosensor-based methods have emerged as a promising approach. These methods offer advantages such as rapid results, high sensitivity, specificity, and potential for point-of-care applications. By targeting specific biomarkers or genetic material, biosensors utilise technologies like surface plasmon resonance and microarrays, providing a direct and efficient means of diagnosing neurotropic infections. This review explores the evolving landscape of biosensor-based methods, highlighting their potential to enhance the diagnostic toolkit for neurotropic viruses.

Investigation of Zika virus methyl transferase inhibitors using steered molecular dynamics.

Zika virus (ZIKV) spread is considered a major public health threat by the World Health Organization (WHO). There are no vaccines or drugs available to control the infection of the Zika virus, therefore a highly effective medicinal molecule is urgently required. In this study, a computationally intensive investigation was performed to identify a potent natural compound that could inhibit the ZIKV NS5 methyltransferase. This research approach is based on target-based drug identification principles where the native inhibitor SAH (S-adenosylhomocysteine) of ZIKV NS5 methyltransferase was selected as a reference. High-throughput virtual screening and tanimoto similarity coefficient were applied to the natural compound library for ranking the potential candidates. The top five compounds were selected for interaction analysis, MD simulation, total binding free energy through MM/GBSA, and steered MD simulation. Among these compounds, Adenosine 5'-monophosphate monohydrate, Tubercidin, and 5-Iodotubercidin showed stable binding to the protein compared to the native compound, SAH. These three compounds also showed less fluctuations in RMSF in contrast to native compound. Additionally, the same interacting residues observed in SAH also made strong interactions with these three compounds. Adenosine 5'-monophosphate monohydrate and 5-Iodotubercidin had greater total binding free energies than the reference ligand. Moreover, the dissociation resistance of all three compounds was equivalent to that of the reference ligand. This study suggested binding properties of three-hit compounds that could be used to develop drugs against Zika virus infections.Communicated by Ramaswamy H. Sarma.

Immunoinformatics-Driven Strategies for Advancing Epitope-Based Vaccine Design for West Nile Virus.

The West Nile virus (WNV) is the causative agent of West Nile disease (WND), which poses a potential risk of meningitis or encephalitis. The aim of the study was to design an epitope-based vaccine for WNV by utilizing computational analyses. The epitope-based vaccine design process encompassed WNV sequence collection, phylogenetic tree construction, and sequence alignment. Computational models identified B-cell and T-cell epitopes, followed by immunological property analysis. Epitopes were then modeled and docked with B-cell receptors, MHC I, and MHC II. Molecular dynamics simulations further explored dynamic interactions between epitopes and receptors. The findings indicated that the B-cell epitope QINHHWHKSGSSIG, along with three T-cell epitopes (FLVHREWFM for MHC I, NPFVSVATANAKVLI for MHC II, and NAYYVMTVGTKTFLV for MHC II), successfully passed the immunological evaluations. These four epitopes were further subjected to docking and molecular dynamics simulation studies. Although each demonstrated favorable affinities with their respective receptors, only NAYYVMTVGTKTFLV displayed a stable interaction with MHC II during MDS analysis, hence emerging as a potential candidate for a WNV epitope-based vaccine. This study demonstrates a comprehensive approach to epitope vaccine design, combining computational analyses, molecular modeling, and simulation techniques to identify potential vaccine candidates for WNV.

Enhancement of antifungal activity and transdermal delivery of 5-flucytosine via tailored spanlastic nanovesicles: statistical optimization, in-vitro characterization, and in-vivo biodistribution study.

Aim and background: This current study aimed to load 5-flucytosine (5-FCY) into spanlastic nanovesicles (SPLNs) to make the drug more efficient as an antifungal and also to load the 5-FCY into a hydrogel that would allow for enhanced transdermal permeation and improved patient compliance. Methods: The preparation of 5-FCY-SPLNs was optimized by using a central composite design that considered Span 60 (X1) and the edge activator Tween 80 (X2) as process variables in achieving the desired particle size and entrapment efficiency. A formulation containing 295.79 mg of Span 60 and 120.00 mg of Tween 80 was found to meet the prerequisites of the desirability method. The optimized 5-FCY-SPLN formulation was further formulated into a spanlastics gel (SPG) so that the 5-FCY-SPLNs could be delivered topically and characterized in terms of various parameters. Results: As required, the SPG had the desired elasticity, which can be credited to the physical characteristics of SPLNs. An ex-vivo permeation study showed that the greatest amount of 5-FCY penetrated per unit area (Q) (mg/cm2) over time and the average flux (J) (mg/cm2/h) was at the end of 24 h. Drug release studies showed that the drug continued to be released until the end of 24 h and that the pattern was correlated with an ex-vivo permeation and distribution study. The biodistribution study showed that the 99mTc-labeled SFG that permeated the skin had a steadier release pattern, a longer duration of circulation with pulsatile behavior in the blood, and higher levels in the bloodstream than the oral 99mTc-SPNLs. Therefore, a 5-FCY transdermal hydrogel could possibly be a long-acting formula for maintenance treatment that could be given in smaller doses and less often than the oral formula.

Fabrication and optimization of phospholipids-based phase separation in-situ gel loaded with BMP-2 nanosized emulsion for bone defect.

Introduction: The health, development, and/or survival of a newborn can be impacted by congenital abnormalities such as cleft lip (CLP) and palate, one of alveolar bone defects that emerge thru pregnancy. Therefore, the primary purpose of this study is to use phospholipids-based phase separation in-situ gel (PPSG) in combination with bone morphogenetic protein-2 nanoemulsion (BMP-2-NE) to aid repairing alveolar bone defects. Methods: To investigate how formulation parameters, such as the concentrations of BMP-2 aqueous solution, LauroglycolTM FCC, and Labrafac PG oil, affect NE qualities including droplet size and stability index, an l-optimal co-ordinate exchange statistical design was opted. Injectable PPSG with the best NE formulation was tested for viscosity characteristics, gel strength, water absorption, and in-vitro BMP-2 release. In rabbits, the percentage of BMP-2 that was still in the maxilla after 14 days was assessed. Results: Collected results revealed that the droplet size and stability index of optimal NE were discovered to be 68 2.0 nm and 96 1.3%, respectively. When mixed with water, optimal BMP-2 NE loaded PPSG became viscous and reached a gel strength of 41 s, which is adequate for injectable in-situ gels. In comparison to BMP-2 solution loaded in-situ gel, the in-vivo studies indicated that the newly created BMP-2 NE loaded PPSG produced a sustained and controlled release of BMP-2 that continued for 336 h (14 days). Further, 8% of the BMP-2 was still entrapped and not completely dissolved after 14 days, thus, created formulation allowed a higher percentage of BMP-2 to remain in rabbits' maxilla for longer time. Conclusion: PPSG that has been loaded with BMP-2 NE may therefore be a promising, fruitful, and less painful paradigm for the noninvasive therapy of CLP with significant effect and extended release.

A Review of the Resistance Mechanisms for ß-Lactams, Macrolides and Fluoroquinolones among Streptococcus pneumoniae.

Streptococcus pneumoniae (S. pneumoniae) is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of S. pneumoniae as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like ß-lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of S. pneumoniae infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in S. pneumoniae against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes ß-lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of S. pneumoniae may aid researchers in developing a more efficacious antibiotic in future endeavors.