Recent advances in anti-infective drug discovery最新文献

Background: Streptococcus mutans (S. mutans) is recognized as the primary oral pathogen responsible for dental caries. The formation of biofilms on tooth surfaces is a crucial virulence factor for S. mutans. This study aimed to investigate the antimicrobial and anti-biofilm effects of silicon dioxide nanoparticles (SiO2 NPs) and zinc oxide/zeolite nanocomposites (ZnO/Zeolite NCs) on S. mutans gene expression and biofilm formation.

Methods: Minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), sub-MIC, safranin staining, growth curve analysis, and MTT assays were performed to evaluate the anti-biofilm properties of the nanoparticles. The expression levels of the ftf, gtfB, vicR, and gbpB genes were evaluated by real-time PCR. Cytotoxic effects of the nanoparticles were measured by the MTT assay with human gingival fibroblast (HGF2PI2) cells.

Results: Both SiO2 NPs and ZnO/Zeolite NCs effectively inhibited S. mutans biofilm formation, with MTT assay results showing a 79% inhibition by SiO2 NPs and 95% by ZnO/Zeolite NCs. Additionally, both nanoparticles reduced the transcription levels of the ftf, gtfB, vicR, and gbpB genes, with no toxic effects observed on HGF2PI2 cells at a concentration of 32 mg/ml.

Discussion: These findings suggest that SiO2 NPs and ZnO/Zeolite NCs are promising agents against S. mutans biofilms, with potential applications in oral care products.

Conclusion: SiO2 NPs and ZnO/Zeolite NCs show significant potential for preventing biofilm formation by S. mutans, representing effective and cost-efficient antibacterial options for oral health.

Thymosins are a group of immunomodulatory peptides secreted by the thymus. They play an important role in immune function by inducing T-cell expression and inhibiting viral replication. In light of the COVID-19 pandemic caused by coronavirus, there has been renewed interest in their activity, resulting in a revival of patents claiming the use of thymosin to combat coronavirus. This article reviews patents on the therapeutic application of thymosin peptides against viruses. Conventionally, thymosin is administered via injection or infusion; however, recent research has explored alternative routes, including oral formulations. Thymosin administration is used to complement antiviral drug treatments. Similarly, recent antiviral regimens against SARS-CoV-2 may be supplemented with thymosin based on its proven immunopotentiating activity.

Introduction: Adolescents living with HIV 9 (ALHIV), particularly those with perinatal HIV, face unique challenges in achieving viral suppression, which is crucial for reducing morbidity, mortality, and HIV transmission. Despite global efforts to meet the UNAIDS 95-95-95 targets, viral suppression rates among ALHIV remain suboptimal. This study aimed to identify factors associated with viral suppression among adolescents aged 11-17 years with perinatal HIV in Indonesia.

Methods: This retrospective study was conducted in a hospital in Indonesia among 11-17- year-olds living with HIV. Hospital medical records from 2019 to 2022 were used to assess the participants' adherence and viral load suppression. We employed descriptive statistics, including frequencies, proportions, and regression analysis, to determine the relationship between demographic and clinical factors, adherence, and viral load suppression.

Result: The study achieved viral suppression in 69.4% of the participants. Multivariate analysis revealed that good adherence to ART (≥95%) was significantly associated with higher odds of viral suppression (AOR: 4.19, p < 0.01). A baseline CD4 count greater than 200 cells/μL (AOR: 3.20, p = 0.03) and the absence of a history of tuberculosis (AOR: 1.56, p = 0.04) significantly predicted viral suppression. Additionally, researchers observed a positive correlation between the duration of antiretroviral therapy (ART) and the viral suppression rate.

Discussion: The results of this study show that longer antiretroviral therapy (ART) duration increases the likelihood of achieving viral suppression. The results of this study are consistent with those of previous research, showing that adolescents who had been on ART for 6 to 12 months were more likely than those on treatment for a more extended period to experience viral non-suppression (viral load > 400 RNA copies/mL).

Conclusion: Viral suppression among ALHIV in Indonesia is influenced by adherence to ART, baseline immune status, and history of TB. Addressing barriers to adherence and integrating TB-HIV care are essential strategies to improve outcomes for this vulnerable population.

Introduction: The global rise in antimicrobial resistance highlights the urgent need for new therapeutic agents. This study investigates chalcone-based derivatives of gallic acid as potential antimicrobial compounds.

Method: Chalcone derivatives (2a-4c) were synthesized via methylation, Grignard reaction, Claisen-Schmidt condensation, and cyclization. Structural confirmation was achieved using FTIR, NMR, and mass spectrometry. The Docking studies were performed against HSP90α (PDB ID: 1UY6), and ADME properties were predicted using QikProp. Antimicrobial activity was assessed using microbroth dilution and agar well diffusion methods against S. aureus, E. coli, K. pneumoniae, A. baumannii, and C. albicans.

Results: Compounds 2d and 3c showed the strongest docking interactions with HSP90α, outperforming ciprofloxacin. MIC results indicated that 2d was most effective, with values as low as 0.39 μg/ml for E. coli and C. albicans. Other compounds, such as 3c and 4c, also showed significant activity (MIC 0.78-6.25 μg/ml). ADME profiling predicted high oral absorption and favorable drug-like properties for the most active compounds.

Discussion: Electron-withdrawing groups enhanced antimicrobial activity and binding affinity. Docking data supported the in vitro results, revealing key interactions within the HSP90α active site.

Conclusion: Chalcone derivatives, particularly 2d, show promise as broad-spectrum antimicrobial agents. Their structural and pharmacokinetic profiles support further development for therapeutic use.

Background: Infectious diseases caused by resistant microbes and oncological ailments pose a serious threat to human health. However, an effective and safe drug against them has not yet been found. Therefore, pyrimidine derivatives may be of interest as dual-acting drugs due to their potent antimicrobial and cytotoxic properties. The relevance of our research is confirmed by several recent patents dedicated to the antimicrobial and anticancer activity of pyrimidine-based molecules.

Objective: The purpose of this study was to evaluate the antimicrobial and cytotoxic activity of some 6-methyluracil derivatives of an amphiphilic nature in vitro.

Methods: Antimicrobial activity was studied by serial dilution. Cytotoxicity was tested using the MTT test. The mechanisms of antimicrobial and cytotoxic activity were analyzed using the methods of colorimetry, flow cytometry, and enzyme-linked immunosorbent assay.

Results: The tested compounds have high antibacterial activity against resistant strains of Staphylococcus aureus and some bacteria from the group of ESKAPE pathogens. Outstanding results were obtained for the lead compounds in the human duodenal adenocarcinoma cell line (HuTu-80), for which cytotoxicity was shown at the level of 5-fluorouracil with a high selectivity index (SI = 8.0-10.0). The mechanism of antibacterial action is associated with the permeabilization of the bacterial membrane. The cytotoxic effect is due to the arrest of the cell cycle in the G1 phase and the induction of mitochondrial apoptosis. The introduction of the hexynyl group into the C5 position of the pyrimidine ring leads to increased antibacterial and cytotoxic activity.

Conclusion: The conducted studies allow us to consider the tested compounds as a promising basis for the creation of new effective antibacterial and сytotoxic agents.

Panax ginseng has long been revered in traditional medicine for its various health benefits, pharmacological activities, and therapeutic potential. Panax ginseng is rich in bioactive compounds, primarily ginsenosides, as well as diverse metabolites, including flavonoids, terpenes, saponins, amino acids, and polysaccharides, which contribute to its therapeutic properties. Ginsenosides are categorized into dammarane and oleanane groups, with at least 289 ginsenosides identified across different Panax species. Moreover, the extraction method and solvent used significantly influence the composition and bioactivity of ginseng extracts, with ethanol and water extracts showing promising antioxidant and immunostimulatory effects. Clinical and preclinical studies have demonstrated Panax ginseng's efficacy in enhancing mental functioning and immune response, while also showing promise in protection from liver damage, osteoporosis, and hyperlipidemia. Additionally, Panax ginseng exhibits antimicrobial and antiviral activities, making it a valuable natural resource in combating infectious diseases. Ginsenosides exhibit anti-inflammatory properties by inhibiting NF-κB activation and proinflammatory cytokine production, while also enhancing the function of immune cells. Furthermore, ginsenosides regulate lipid metabolism, promote glucose uptake, and modulate insulin sensitivity, contributing to their anti-diabetic properties. Additionally, Panax ginseng demonstrates anti-oncogenic activity by inducing programmed cell death, inhibiting angiogenesis, and suppressing tumor growth in various cancer types. Panax ginseng exhibits neuroprotective effects across various neurological disorders, including Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple sclerosis, and major depressive disorder. Its mechanisms of action involve mitigating cell death, reducing oxidative stress, inhibiting apoptosis, modulating neurotransmitter levels, and regulating inflammatory responses. Importantly, Panax ginseng has low acute and subacute oral toxicity, further supporting its safety profile for human consumption. In conclusion, Panax ginseng emerges as a versatile herbal remedy with significant therapeutic implications across a wide range of health conditions.

Bacterial conjunctivitis is a common eye infection caused by bacteria, posing significant treatment challenges due to rising antibiotic resistance and the limitations of traditional therapies. Standard treatments, including topical antibiotics, often suffer from issues such as poor bioavailability, limited effectiveness, and patient adherence. Nanotechnology offers an innovative approach, providing potential solutions for more effective drug delivery, diagnostics, and therapeutic interventions. The objective of this study is to explore the role of nanotechnology in improving the management of bacterial conjunctivitis. Specifically, it examines how nanostructured drug carriers, such as nanoparticles, nanogels, and liposomes, can enhance ocular drug delivery and therapeutic outcomes. A key focus is on the influence of the hydrodynamic radius (Rh) in optimizing stability, solubility, and bioavailability. Nanotechnology has shown promise in improving the delivery of drugs for bacterial conjunctivitis by enhancing ocular penetration and prolonging the release of active agents. The hydrodynamic radius (Rh) of nanoparticles plays a critical role in stabilizing the colloidal structure of the formulation, preventing aggregation and sedimentation. Furthermore, optimizing Rh can increase the surface area-to-volume ratio, which is beneficial for improving the solubility of poorly soluble drugs, thereby enhancing their bioavailability. Nanotechnology- based systems can also enable the development of diagnostic tools, such as nanosensors, capable of quickly and accurately detecting bacterial pathogens, facilitating timely, targeted treatments and reducing unnecessary use of broad-spectrum antibiotics. The precise control of nanoparticle Rh enhances drug stability, bioavailability, and sustained release, ultimately improving patient compliance and therapeutic efficacy. The future of bacterial conjunctivitis treatment is promising, with further research focused on optimizing nanoparticle characteristics such as size, surface modification, and targeted drug delivery. However, challenges remain, particularly concerning the safety of nanoparticles, including potential risks to ocular tissues and long-term effects. Continued research, including in vitro and in vivo studies as well as clinical trials, is essential to establish the safety and clinical viability of these nanotechnology-based systems. With further advancements, nanotechnology could revolutionize treatment strategies for bacterial conjunctivitis, offering more targeted, patient-centered, and effective solutions for managing ocular infections and combating antibiotic resistance.

Introduction: Nanoparticles obtained through green synthesis playremarkable roles in biomedical applications. Urinary tract infections (UTIs) are a nightmare for the mass population, especially for women, and quinolone-resistant UTI bacteria worsen the situation. Our current investigation aimed to control quinolone-resistant pathogenic UTI bacteria with green-synthesized silver nanoparticles (AgNPs).

Methods: Visual observation of color change, UV-Vis spectroscopic analysis, FTIR (Fourier Transform Infrared Spectroscopy), DLS (Dynamic Light Scattering), XRD (X-ray Diffraction), and TEM (Transmission Electron Microscopy) techniques were used to effectively characterize the biosynthesized AgNPs. Klebsiella variicola, Pseudomonas sp., and Staphylococcus epidermidis bacteria were isolated and identified using biochemical and molecular identification techniques from urine samples of hospitalized patients with UTI. These bacteria showed quinolone resistance to up to fourth-generation antibiotics.

Results: The results elucidated the synthesis of spherical-shaped nano-silvers coated with Punica granatum polyphenols. These biosynthesized AgNPs showed moderate polydispersity and narrow distribution. The antibacterial efficiency of the AgNPs was determined against isolated bacterial strains. Klebsiella variicola and Staphylococcus epidermidis exhibited the highest sensitivity to the nanoparticles. Nanoparticles at a concentration of 128 μg/ml inhibited bacterial growth to a great extent and gave a maximum inhibition zone of 14.67 ± 0.577 mm in diameter for both bacterial strains. In addition, toxicity analysis of synthesized nanoparticles via brine shrimp lethality assay (BSLA) showed a very low cytotoxicity level (2398.83 μg/ml), depicting safety for human use.

Conclusion: We can conclude that Punica granatum leaf-synthesized AgNPs could possess significant biomedical applications as potential antibacterial agents due to their bactericidal activity and low cytotoxicity.

Rheumatoid arthritis is a chronic autoimmune disease with joint destruction and chronic inflammation symptoms. Conventional therapy focuses on the prevention of the progression of the disease and management of symptoms, rather than curing the disease. Emerging therapies have been developed to cure the disease, which combines conventional therapies with a novel drug delivery system. Novel therapies have better bioavailability, which is marked by reduced adverse reactions. In the following article, some of the emerging therapies focused on the notable advancement in the procurement of the RA include microRNA alteration, helper T-cell inhibition, drug repurposing, targeting sites for interleukins, and blocking of signaling pathways. Beyond pharmacological intervention, emerging therapies explore the modulation of the microbiome, epigenetic regulation, and the manipulation of immune tolerance mechanisms. These therapies offer hope for better disease control and potential advantages for future betterment.