The Impact of Orthodontic Adhesive Containing Resveratrol, Silver, and Zinc Oxide Nanoparticles on Shear Bond Strength: An In Vitro Study.

Introduction The goal of orthodontic treatment is to provide patients with esthetic smiles and functional occlusion. Despite best efforts and continuous evolution of materials, white spot lesions present a persistent hindrance to the desired treatment outcome. Nanoparticles have shown efficacy in reducing microbial activity; however, currently, there is a need for natural anti-cariogenic compounds with minimal side effects. Resveratrol is a natural compound belonging to the polyphenol group and has shown promising anti-microbial efficacy. This study aimed to evaluate the influence of dentin bonding agents incorporated with the following three different nanoparticles on shear bond strength: silver nanoparticles (Ag-Np), zinc oxide nanoparticles (ZnO-Np), and resveratrol nanoparticles (RSV-Np). Materials and methods A total of 40 premolar teeth therapeutically extracted were assigned to four equal groups of n=10 each. Groups 1, 2, and 3 used experimental adhesives doped with silver, zinc oxide, and resveratrol nanoparticles, respectively. Group 4 was bonded using unmodified adhesive. The bonded teeth were then subjected to shear bond strength (SBS) testing which was measured using a Universal Testing Machine (model no. UNITEST-10; Pune, India: ACME Engineers). Statistical analyses were performed using SPSS version 21 (Armonk, NY: IBM Corp.), employing one-way ANOVA and Tukey's post-hoc test for pairwise comparisons. Results Shear bond strength testing revealed that the control group with unmodified adhesive (8.6 MPa) had the highest SBS, followed by RSV-Np (7.6 MPa), Ag-Np (6.3 MPa), and ZnO-Np (5.65 MPa). Although the experimental groups demonstrated decreased SBS compared to the control, the values for Ag-Np and RSV-Np fell within the acceptable range. Conclusion Resveratrol nanoparticles had the least impact on shear bond strength among the experimental groups. These findings suggest that the incorporation of resveratrol nanoparticles in dentin bonding agents can provide anti-cariogenic effect without significantly impacting the adhesive's mechanical properties thereby providing a new and promising alternative to synthetic nanoparticles. Further studies are recommended to optimize the balance between anti-microbial efficacy and bond strength in clinical applications.

Competence Regulation in Streptococcus pneumoniae and the Competence-targeted Anti-pneumococcal Strategies.

Natural transformation refers to the process in which bacteria acquire new traits by uptaking naked DNA from the environment and integrating it into their genome through homologous recombination when they are in the specialized physiological state of competence. The natural transformation was first described in Streptococcus pneumoniae. Since Frederick Griffith first described natural transformations in S. pneumoniae in 1928, this phenomenon has been studied extensively. Induction of competence before natural transformation has been reported to involve about 10% of the pneumococcal genome. In addition to natural transformation, multiple physiological processes are involved, including biofilm formation, bacteriocin production, and fratricide. In this review, we summarized current knowledge about natural transformation in S. pneumoniae and described its competence regulation mechanism. This review also introduces the development of novel drugs and vaccines against S. pneumoniae infection by utilizing the existing knowledge of competence and natural transformation.

Disruption of salt bridge interactions in the inter-domain cleft of the tubulin-like protein FtsZ of Escherichia coli makes cells sensitive to the cell division inhibitor PC190723.

FtsZ forms a ring-like assembly at the site of division in bacteria. It is the first protein involved in the formation of the divisome complex to split the cell into two halves, indicating its importance in bacterial cell division. FtsZ is an attractive target for developing new anti-microbial drugs to overcome the challenges of antibiotic resistance. The most potent inhibitor against FtsZ is PC190723, which is effective against all strains and species of Staphylococcus, including the methicillin- and multi-drug-resistant Staphylococcus aureus and strains of Bacillus. However, FtsZs from bacteria such as E. coli, Streptococcus, and Enterococcus were shown to be resistant to this inhibitor. In this study, we provide further evidence that the three pairwise bridging interactions, between residues S227 and G191, R307 and E198 and D299 and R202, between S7, S9, S10 ß-strands and the H7 helix occlude the inhibitor from binding to E. coli FtsZ. We generated single, double and triple mutations to disrupt those bridges and tested the effectiveness of PC190723 directly on Z-ring assembly in vivo. Our results show that the disruption of S227-G191 and R307-E198 bridges render EcFtsZ highly sensitive to PC190723 for Z-ring assembly. Ectopic expression of the double mutants, FtsZ S227I R307V results in hypersensitivity of the susceptible E. coli imp4213 strain to PC190723. Our studies could further predict the effectiveness of PC190723 or its derivatives towards FtsZs of other bacterial genera.

Prevalence and anti-microbial resistance of Staphylococcus spp. isolated from the environment and veterinary personnel in a Spanish veterinary teaching hospital.

Methicillin-resistant Staphylococcus (MRS) bacteria, including methicillin-resistant S. aureus and methicillin-resistant S. pseudintermedius (MRSP), pose a significant threat in veterinary medicine, given their potential for zoonotic transmission and their implications for companion animals and humans' health. This study aimed to assess the prevalence of MRS and anti-microbial resistance patterns at a university clinical hospital in Madrid, Spain. Samples were collected from both the environment and hospital staff at Veterinary Clinical Hospital of Alfonso X el Sabio University. Anti-microbial susceptibility assays, molecular detection of mecA gene and genetic relationships among the identified bacterial strains were performed. The study revealed an MRS prevalence of 1.50% in environmental samples, with MRSP accounting for 0.75% of the cases. Genetically related MRSP strains were found in different hospital areas. Among hospital staff, there was a MRS prevalence of 14.03%, including S. pseudintermedius and S. epidermidis strains. Antibiogram tests revealed multi-drug resistance among MRSP strains. Additionally, methicillin-resistant coagulase-negative staphylococci were isolated, suggesting potential cross-species transmission. This study underscores the presence of MRS in a veterinary clinical hospital, highlighting the significance of infection control through the implementation of protective measures, stringent hygiene practices among personnel and in the environment and responsible use of antibiotics. Further research is necessary to assess MRS incidence in animal patients and explore geographical variations, enhancing our understanding of MRS in veterinary medicine and addressing its challenges.

Evaluation of the Phytochemical Screening of Methanolic Seed Extracts of Tribulus terrestris: An In Vitro Application of Anti-cancer, Anti-oxidant, and Anti-microbial Activities.

BACKGROUND: Tribulus terrestris, a plant known for its pharmacological properties, was investigated in this study for its potential anticancer effects against oral cancer cells. The study aimed to explore the phytochemical composition of T. terrestris seed extract and evaluate its cytotoxic, pro-apoptotic, antioxidant, anti-inflammatory, and antimicrobial activities. MATERIALS AND METHODS: Methanolic seed extracts of T. terrestris were obtained and subjected to phytochemical analysis to identify bioactive compounds. The cytotoxic effect of the extract on oral cancer cells was evaluated using the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay, while pro-apoptotic effects were assessed through dual fluorescent staining. Antioxidant activity was measured using hydrogen peroxide and erythrocyte aggregation assays, while anti-inflammatory activity was evaluated through inhibition of albumin denaturation. RESULTS: Phytochemical analysis revealed the presence of alkaloids, tannins, saponins, flavonoids, and phenols in T. terrestris seed extract. The extract demonstrated concentration-dependent cytotoxicity against oral cancer cells, with 100 µg/mL showing significant growth inhibition. Pro-apoptotic effects were observed, with characteristic morphological changes in cancer cells treated with the extract. Antioxidant activity was demonstrated by the extract, with methanol fraction of a flower (MFF) exhibiting the highest capacity, followed by total trichome fraction (TTF), and a positive correlation between phenolic content and free radical scavenging effectiveness was noted. Antimicrobial activity against various pathogens, including bacteria and fungi, was also observed, with higher concentrations showing increased efficacy. CONCLUSION: The study concludes that methanolic extracts of T. terrestris possess significant anticancer, antioxidant, anti-inflammatory, and antimicrobial activities. These findings highlight the potential of T. terrestris as a candidate for further research and clinical applications, either alone or in combination with other agents, for the treatment of oral cancer and associated conditions.

Advancements in Green Nanoparticle Technology: Focusing on the Treatment of Clinical Phytopathogens.

Opportunistic pathogenic microbial infections pose a significant danger to human health, which forces people to use riskier, more expensive, and less effective drugs compared to traditional treatments. These may be attributed to several factors, such as overusing antibiotics in medicine and lack of sanitization in hospital settings. In this context, researchers are looking for new options to combat this worrying condition and find a solution. Nanoparticles are currently being utilized in the pharmaceutical sector; however, there is a persistent worry regarding their potential danger to human health due to the usage of toxic chemicals, which makes the utilization of nanoparticles highly hazardous to eukaryotic cells. Multiple nanoparticle-based techniques are now being developed, offering essential understanding regarding the synthesis of components that play a crucial role in producing anti-microbial nanotherapeutic pharmaceuticals. In this regard, green nanoparticles are considered less hazardous than other forms, providing potential options for avoiding the extensive harm to the human microbiome that is prevalent with existing procedures. This review article aims to comprehensively assess the current state of knowledge on green nanoparticles related to antibiotic activity as well as their potential to assist antibiotics in treating opportunistic clinical phytopathogenic illnesses.

Deciphering the Potentials of Cardamom in Cancer Prevention and Therapy: From Kitchen to Clinic.

Cardamom (cardamum) is a spice produced from the seeds of several Elettaria and Amomum plants of the Zingiberaceae family. Cardamom has been demonstrated to offer numerous benefits, including its antioxidant, antimicrobial, anti-inflammatory, and other metabolic (anti-diabetic) properties, and its potential to reduce cancer risk. Recently, researchers have extracted and tested multiple phytochemicals from cardamom to assess their potential effectiveness against various types of human malignancy. These studies have indicated that cardamom can help overcome drug resistance to standard chemotherapy and protect against chemotherapy-induced toxicity due to its scavenging properties. Furthermore, chemical compounds in cardamom, including limonene, cymene, pinene, linalool, borneol, cardamonin, indole-3-carbinol, and diindolylmethane, primarily target the programmed cell death lignin-1 gene, which is more prevalent in cancer cells than in healthy cells. This review provides the medicinal properties and pharmacological uses of cardamom, its cellular effects, and potential therapeutic uses in cancer prevention and treatment, as well as its use in reducing drug resistance and improving the overall health of cancer patients. Based on previous preclinical studies, cardamom shows significant potential as an anti-cancer agent, but further exploration for clinical use is warranted due to its diverse mechanisms of action.

Antimicrobial potential of Streptomyces sp. NP73 isolated from the forest soil of Northeast India against multi-drug resistant Escherichia coli.

This study reports the isolation and characterization of a Streptomyces sp. from soil, capable of producing bioactive secondary metabolites active against a variety of bacterial human pathogens. We targeted the antimicrobial activity against Escherichia coli ATCC-BAA 2469, a clinically relevant strain of bacteria harbouring resistance genes for carbapenems, extended spectrum beta-lactams, tetracyclines, fluoroquinones, etc. Preliminary screening using the spot inoculation technique identified Streptomyces sp. NP73 as the potent strain among the 74 isolated Actinomycetia strain. 16S rRNA gene and whole genome sequencing (WGS) confirmed its taxonomical identity and helped in the construction of the phylogenetic tree. WGS revealed the predicted pathways and biosynthetic gene clusters responsible for producing various types of antibiotics including the isolated compound. Bioactivity guided fractionation and chemical characterization of the active fraction, carried out using liquid chromatography, gas chromatography-mass spectrometry, infra-red spectroscopy, and nuclear magnetic resonance spectroscopy, led to the tentative identification of the active compound as Pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro-, a diketopiperazine molecule. This compound exhibited excellent antimicrobial and anti-biofilm properties against E. coli ATCC-BAA 2469 with an MIC value of 15.64 µg ml-1, and the low cytotoxicity of the compound identified in this study provides hope for future drug development.

Reduction of biofilm and pathogenic microorganisms using curcumin-mediated photodynamic inactivation to prolong food shelf-life.

Pathogenic microbial contamination (bacteria and fungi) in food products during production poses a significant global health risk, leading to food waste, greenhouse gas emissions, and aesthetic and financial losses. Bacteria and fungi, by forming solid biofilms, enhance their resistance to antimicrobial agents, thereby increasing the potential for cross-contamination of food products. Curcumin molecule-mediated photodynamic inactivation (Cur-m-PDI) technology has shown promising results in sterilizing microbial contaminants and their biofilms, significantly contributing to food preservation without compromising quality. Photosensitizers (curcumin) absorb light, leading to a chemical reaction with oxygen and producing reactive oxygen species (ROS) that effectively reduce bacteria, fungi, and biofilms. The mechanism of microorganism inhibition is caused by exposure to ROS generated via the type 1 pathway involving electron transfer (such as O2•-, H2O2, -OH•, and other radicals), the type 2 pathway involving energy transfer (such as 1O2), secondary ROS, and weakening of antioxidant enzymes. The effectiveness of the inactivation of microorganisms is influenced by the concentration of curcumin, light (source type and energy density), oxygen availability, and duration of exposure. This article reviews the mechanism of reducing microbial food contamination and inhibiting their biofilms through Cur-m-PDI. It also highlights future directions, challenges, and considerations related to the effects of ROS in oxidizing food, the toxicity of PDI to living cells and tissues, conditions/types of food products, and the stability and degradation of curcumin.

Investigation of bioactive phytochemical compounds of the Ethiopian medicinal plant using GC-MS and FTIR.

Medicinal plants Highly aromatic crude materials are utilized for treating warts as an alternative medicine to surgical treatment because they can be permanently removed from the body. Thus, this investigation aimed to extract plant material from Calotropis procera leaves, describe the phytochemical screening, analyze anti-microbial activities, determine the functional groups in FTIR, and identify the chemical compounds in GC-MS. The PH, specific gravity, and viscosity of the crude extracts of Calotropis procera were determined at 4.5, 0.79, and 0.49, respectively. Analyze the solubility of crude extracts; ethanol can dissolve while water does not. Flavonoids, alkaloids, phenols, tannins, and saponins were also present in the phytochemical screening tests of the Calotropis procera extracts, triterpenoids, terpenoids, and steroids were not present in the crude extract. Flavonoids, alkaloids, phenols, tannins, and saponins are the primary phytochemical components found in therapeutic plant material. The Calotropis procera crude extracts analyzed for functional groups by FT-IR contained a hydroxyl group, alkane, carbonyl, aldehyde, ketone, phenols, ester, alcohol, and methylene. The chemical compounds analyzed by GC-MS of Calotropis procera crude material were found to have 22 main compounds. Of 22 compounds, 5 compounds are active ingredients for the applications of medical purposes. The bioactive compounds found in the Calotropis procera plant extract are neophytadiene, hexahydrofarnesyl, lanosterol, 2,4-dimethylbenzo [H]quinolone, and squalene. Those bioactive compounds have anti-bacterial, analgesic, antipyretic, anti-inflammatory, antimicrobial, antioxidant, antiviral, and anti-cancer properties. In an in vitro antimicrobial activity test, the crude extract effectively inhibited more gram-positive bacteria than gram-negative bacteria. This collective reason is why the traditional therapist uses this Calotropis procera plant for the treatment of warts.

Synthesis of Graphene@C3N4-Cu Beads Nanocomposites and their Antimicrobial Efficacy Against Drug-Resistant Bacteria and Fungi.

BACKGROUND: Increased intake of drugs worldwide and the subsequent advent of resistance to existing antibiotics have globally threatened health organizations. To combat the problem of these drug-resistant infections, as an alternative approach, graphene (GN)-related nanomaterials have attracted significant interest because of their effective anti-microbial potential. The present study shows the synthesis and characterization of nanocomposite of GN with carbon nitride viz. g- C3N4, g-C3N4-Cu, and GN@g-C3N4-Cu. Further, we investigated the anti-microbial potential of these nanocomposites against strains of Gram-negative and Gram-positive bacteria, viz., a multidrug- resistant strain of Pseudomonas aeruginosa (MDRPA), a methicillin-resistant strain of Staphylococcus aureus ATCC33593 (MRSA), and an azole-sensitive fungal strain (Candida albicans ATCC14053). METHODS: The morphological characterization of GN@g-C3N4-Cu nanocomposite was executed by scanning electron microscopy, whereas the elemental analysis and their distribution were studied by energy-dispersive X-ray spectroscopy and elemental mapping methods. Furthermore, the anti-microbial and antibiofilm efficacies of g-C3N4, g-C3N4-Cu, and GN@g-C3N4-Cu nanocomposites were evaluated by disc diffusion, two-fold serial micro broth dilution, and 96 well microtiter plate methods. RESULTS: The ternary g-C3N4-Cu@GN, apart from the structures of g-C3N4-Cu, showed big sheets of GN. The observance of C, N, O, and Cu in the elemental analysis, as well as their uniform distribution in the mapping, indicated the successful fabrication of g-C3N4-Cu@GN. GN@g-C3N4-Cu followed by g-C3N4-Cu and (g-C3N4) exhibited significantly higher antimicrobial activity (zone of inhibition from 14.33 to 49.33 mm) against both the drug-resistant bacterial strains and azole-sensitive C. albicans. MICs of nanocomposites ranged from 32 -256 µg/ml against the tested strains. Whereas all three nanocomposites at sub-MICs (0.25 A- and 0.5 A- MICs) showed concentration- dependent inhibition of biofilm formation in MDRPA, MRSA, and C. albicans by allowing 11.35% to 32.59% biofilm formation. CONCLUSION: Our study highlights the enhanced efficiency of GN@g-C3N4-Cu nanocomposites as potential anti-microbial and antibiofilm agents to overcome the challenges of multi-drug-resistant bacteria and azole-sensitive fungi. Such kind of nanocomposites could be used to prevent nosocomial infections if coated on medical devices and food manufacturing instruments.

Exploring quinoxaline derivatives: An overview of a new approach to combat antimicrobial resistance.

Antimicrobial resistance (AMR) has emerged as a long-standing global issue ever since the introduction of penicillin, the first antibiotic. Scientists are constantly working to develop innovative antibiotics that are more effective and superior. Unfortunately, the misuse of antibiotics has resulted in their declining effectiveness over the years. By 2050, it is projected that approximately 10 million lives could be lost annually due to antibiotic resistance. Gaining insight into the mechanisms behind the development and transmission of AMR in well-known bacteria including Escherichia coli, Bacillus pumilus, Enterobacter aerogenes, Salmonella typhimurium, and the gut microbiota is crucial for researchers. Environmental contamination in third world and developing countries also plays a significant role in the increase of AMR. Despite the availability of numerous recognized antibiotics to combat bacterial infections, their effectiveness is diminishing due to the growing problem of AMR. The overuse of antibiotics has led to an increase in resistance rates and negative impacts on global health. This highlights the importance of implementing strong antimicrobial stewardship and improving global monitoring, as emphasized by the World Health Organization (WHO) and other organizations. In the face of these obstacles, quinoxaline derivatives have emerged as promising candidates. They are characterized by their remarkable efficacy against a broad spectrum of harmful bacteria, including strains that are resistant to multiple drugs. These compounds are known for their strong structural stability and adaptability, making them a promising and creative solution to the AMR crisis. This review aims to assess the effectiveness of quinoxaline derivatives in treating drug-resistant infections, with the goal of making a meaningful contribution to the global fight against AMR.

Bioactivity of synthetic peptides from Ecuadorian frog skin secretions against Leishmania mexicana, Plasmodium falciparum, and Trypanosoma cruzi.

Chagas disease, leishmaniasis, and malaria are major parasitic diseases disproportionately affecting the underprivileged population in developing nations. Finding new, alternative anti-parasitic compounds to treat these diseases is crucial because of the limited number of options currently available, the side effects they cause, the need for long treatment courses, and the emergence of drug-resistant parasites. Anti-microbial peptides (AMPs) derived from amphibian skin secretions are small bioactive molecules capable of lysing the cell membrane of pathogens while having low toxicity against human cells. Here, we report the anti-parasitic activity of five AMPs derived from skin secretions of three Ecuadorian frogs: cruzioseptin-1, cruzioseptin-4 (CZS-4), and cruzioseptin-16 from Cruziohyla calcarifer; dermaseptin-SP2 from Agalychnis spurrelli; and pictuseptin-1 from Boana picturata. These five AMPs were chemically synthesized. Initially, the hemolytic activity of CZS-4 and its minimal inhibitory concentration against Escherichia coli, Staphylococcus aureus, and Candida albicans were determined. Subsequently, the cytotoxicity of the synthetic AMPs against mammalian cells and their anti-parasitic activity against Leishmania mexicana promastigotes, erythrocytic stages of Plasmodium falciparum and mammalian stages of Trypanosoma cruzi were evaluated in vitro. The five AMPs displayed activity against the pathogens studied, with different levels of cytotoxicity against mammalian cells. In silico molecular docking analysis suggests this bioactivity may occur via pore formation in the plasma membrane, resulting in microbial lysis. CZS-4 displayed anti-bacterial, anti-fungal, and anti-parasitic activities with low cytotoxicity against mammalian cells. Further studies about this promising AMP are required to gain a better understanding of its activity.IMPORTANCEChagas disease, malaria, and leishmaniasis are major tropical diseases that cause extensive morbidity and mortality, for which available treatment options are unsatisfactory because of limited efficacy and side effects. Frog skin secretions contain molecules with anti-microbial properties known as anti-microbial peptides. We synthesized five peptides derived from the skin secretions of different species of tropical frogs and tested them against cultures of the causative agents of these three diseases, parasites known as Trypanosoma cruzi, Plasmodium falciparum, and Leishmania mexicana. All the different synthetic peptides studied showed activity against one of more of the parasites. Peptide cruzioseptin-4 is of special interest since it displayed intense activity against parasites while being innocuous against cultured mammalian cells, which indicates it does not simply hold general toxic properties; rather, its activity is specific against the parasites.

Recurrent Fungemia Due to Candida auris.

We present a case of recurrent multidrug-resistant Candida auris (C. auris) in a patient who required multiple hospitalizations. The patient's case was complicated by interval admissions to the intensive care unit for septic and hypovolemic shock for 12 months to manage C. auris fungemia. Despite adequate isolation precautions and appropriate antifungal treatment, this case demonstrates the profound implications of this emerging pathogen, specifically regarding invasive infections. Moreover, C. auris is rapidly becoming known as a multidrug-resistant organism, which limits treatment options and thus contributes to high mortality.

Antimicrobial Potential of Pomegranate and Lemon Extracts Alone or in Combination with Antibiotics against Pathogens.

Amidst the growing concern of antimicrobial resistance as a significant health challenge, research has emerged, focusing on elucidating the antimicrobial potential of polyphenol-rich extracts to reduce reliance on antibiotics. Previous studies explored the antifungal effects of extracts as potential alternatives to conventional therapeutic strategies. We aimed to assess the antibacterial and antifungal effects of standardised pomegranate extract (PE) and lemon extract (LE) using a range of Gram-negative and Gram-positive bacteria and two yeast species. Additionally, we assessed the antimicrobial activities of common antibiotics (Ciprofloxacin, Imipenem, Gentamicin, and Ceftazidime), either alone or in combination with extracts, against Staphylococcus aureus and Escherichia coli. PE displayed substantial antibacterial (primarily bactericidal) and antifungal effects against most pathogens, while LE exhibited antibacterial (mostly bacteriostatic) and antifungal properties to a lesser extent. When compared with antibiotics, PE showed a greater zone of inhibition (ZOI) than Ciprofloxacin and Ceftazidime (p < 0.01) and comparable ZOI to Gentamicin (p = 0.4) against Staphylococcus aureus. However, combinations of either PE or LE with antibiotics exhibited either neutral or antagonistic effects on antibiotic activity against Staphylococcus aureus and Escherichia coli. These findings contribute to the existing evidence regarding the antimicrobial effects of PE and LE. They add to the body of research suggesting that polyphenols exert both antagonistic and synergistic effects in antimicrobial activity. This highlights the importance of identifying optimal polyphenol concentrations that can enhance antibiotic activity and reduce antibiotic resistance. Further in vivo studies, starting with animal trials and progressing to human trials, may potentially lead to recommendation of these extracts for therapeutic use.

Anti-Microbial Drug Metronidazole Promotes Fracture Healing: Enhancement in the Bone Regenerative Efficacy of the Drug by a Biodegradable Sustained-Release In Situ Gel Formulation.

Nitroimidazoles comprise a class of broad-spectrum anti-microbial drugs with efficacy against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. Among these drugs, metronidazole (MTZ) is commonly used with other antibiotics to prevent infection in open fractures. However, the effect of MTZ on bone remains understudied. In this paper, we evaluated six nitroimidazole drugs for their impact on osteoblast differentiation and identified MTZ as having the highest osteogenic effect. MTZ enhanced bone regeneration at the femur osteotomy site in osteopenic ovariectomized (OVX) rats at the human equivalent dose. Moreover, in OVX rats, MTZ significantly improved bone mass and strength and improved microarchitecture compared to the vehicle-treated rats, which was likely achieved by an osteogenic mechanism attributed to the stimulation of the Wnt pathway in osteoblasts. To mitigate the reported neurological and genotoxic effects of MTZ, we designed an injectable sustained-release in situ gel formulation of the drug that improved fracture healing efficacy by 3.5-fold compared to oral administration. This enhanced potency was achieved through a significant increase in the circulating half-life and bioavailability of MTZ. We conclude that MTZ exhibits osteogenic effects, further accentuated by our sustained-release delivery system, which holds promise for enhancing bone regeneration in open fractures.

Engineering Whole-Cell Biosensors for Enhanced Detection of Environmental Antibiotics Using a Synthetic Biology Approach.

Bacterial Two component systems have evolved with many intricate sensory apparatuses for external stimuli like light, temperature, oxygen, pH and chemical compounds. Recent studies have shown the potential of two-component regulatory systems (TCSs) of bacteria in creating synthetic regulatory circuits for several applications. Antimicrobial resistance is increasing globally in both developing and developed countries and it is one of the foremost global threats to public health. The resistance level to a broad spectrum of antibiotics is rising every year by 5-10%. In this context, TCSs controlling microbial physiology at the transcriptional level could be an appropriate candidate for monitoring the antibiotics present in the environment. This review provided a wide opportunity to gain knowledge about the TCSs available in diverse species to sense the antibiotics. Further, this review explored the EMeRALD (Engineered Modularized Receptors Activated via Ligand-induced Dimerization) based biosensors to repurpose the sensing modules from the microbial TCSs using the synthetic biology approach.

Synthesis, Characterization, DNA Binding, Biological Significance, and Molecular Docking Approaches of a Palladium(II) Complex with Ciprofloxacin for More Efficient Therapy.

To evaluate the biotransformation and the mechanism of binding as well as the biological impact of metal-based- drugs involving Pd(II), known to have high potency and low toxicity for use as anticancer therapeutics, in the present study, a newly synthesized palladium (II) complex, [Pd(CPF)(OH2)2]2+ (where CPF is ciprofloxacin), has been synthesized and characterized and thoroughly evaluated for its antimicrobial properties. The interaction of the diaqua complex with CT-DNA and BSA was studied through various techniques, including UV-vis spectroscopy, thermal denaturation, viscometry, gel electrophoresis, ethanol precipitation, and molecular docking studies. The results indicate that the complex exhibits a robust binding interaction with CT-DNA, possibly via minor groove binding and (or) electrostatic interactions. Furthermore, the complex displays good binding affinity towards BSA, indicating its potential as a target for DNA and BSA in biological media. The invitro cytotoxicity assay reveals that this complex can be classified as a promising cell growth inhibitor against MCF-7, HT-29, and A549. Thus, this newly synthesized palladium (II) complex is a promising candidate for further exploration as a potential anticancer therapeutic.

Anti-Microbial, Thermal, Mechanical, and Gas Barrier Properties of Linear Low-Density Polyethylene Extrusion Blow-Molded Bottles.

Microbial contamination can occur on the surfaces of blow-molded bottles, necessitating the development and application of effective anti-microbial treatments to mitigate the hazards associated with microbial growth. In this study, new methods of incorporating anti-microbial particles into linear low-density polyethylene (LLDPE) extrusion blow-molded bottles were developed. The anti-microbial particles were thermally embossed on the external surface of the bottle through two particle deposition approaches (spray and powder) over the mold cavity. The produced bottles were studied for their thermal, mechanical, gas barrier, and anti-microbial properties. Both deposition approaches indicated a significant enhancement in anti-microbial activity, as well as barrier properties, while maintaining thermal and mechanical performance. Considering both the effect of anti-microbial agents and variations in tensile bar weight and thickness, the statistical analysis of the mechanical properties showed that applying the anti-microbial agents had no significant influence on the tensile properties of the blow-molded bottles. The external fixation of the particles over the surface of the bottles would result in optimum anti-microbial activity, making it a cost-effective solution compared to conventional compounding processing.

Comparative Evaluation of Anti-microbial Activity of Herbal, Homeopathic, and Conventional Dentifrices Against Oral Microflora Using the Disc Diffusion Method: An In Vitro Study.

Aim To assess the antimicrobial activity of herbal, homeopathic, and conventional dentifrices against oral microorganisms. Methodology Mueller Hilton agar was used to cultivate distinct strains of Streptococcus mutans and Enterococcus faecalis, whereas Candida albicans was cultured on a potato dextrose agar medium. Diffusion ratios of 1:5, 1:10, and 1:15 were obtained by diluting 1 gram of each dentifrice (KP Namboodiri, Homeodent, and Colgate Strong Teeth) in 4 ml, 9 ml, and 14 ml of distilled water, respectively. The culture medium was filled with sterile discs. Twenty µl of each dilution of prepared dentifrice formulations were incorporated using a micropipette. The agar plates were incubated for 24 hours at 37ºC. Result The findings indicate that there was a higher zone of inhibition against Streptococcus mutans with herbal dentifrice at 10 mm, 8 mm, and 6.5 mm, followed by conventional dentifrice at 10 mm, 7.5 mm, and 7 mm, and the lowest with homeopathic dentifrice at 8 mm, 7 mm, and 7 mm at 1:5, 1:10 and 1:15 dilutions, respectively. Conventional dentifrice was found to inhibit Enterococcus faecalis at 9 mm, 8 mm, and 7 mm with 1:5, 1:10, and 1:15 dilutions followed by herbal dentifrice at 9 mm, 7 mm with 1:5, 1:10 dilutions, and no inhibition at 1:15 dilution. In contrast, homeopathic dentifrice displayed no inhibition at 1:5, 1:10, and 1:15 dilutions. Neither homeopathic nor conventional dentifrices inhibited Candida albicans, but herbal dentifrices showed a 10 mm zone of inhibition at 1:10 dilution. Conclusion Conventional and herbal dentifrices were found to be more effective against Streptococcus mutans than the homeopathic dentifrice used in the study, whereas herbal dentifrice was more effective against Candida albicans when compared to conventional and homeopathic dentifrices.