Development Of Resistance Research Articles

Lipopolysaccharide-induced alterations in the liver metabolome of St. Croix and Suffolk sheep

The development of resistance in parasites due to overuse of anthelmintics has resulted in a marked decrease in the efficacy of these drug classes. Recent research efforts have focused on exploring alternatives such as selection for parasite-resistant breeds with the implication that immunocompetence may align with parasite resistance. Two breeds that are often investigated are the St. Croix (STC), a resistant hair breed, and Suffolk (SUF), a susceptible wool breed sheep. The liver plays a vital role in metabolism in the body and metabolizes lipopolysaccharide (LPS), which triggers whole body response through the production of appropriate metabolites, cytokines and immune cells. The objective of this study was to investigate the breed differences in liver metabolome of sheep, with divergent resistance to parasites, in response to LPS. Both STC and SUF sheep (n = 9/breed) were challenged with LPS intravenously. Rectal temperatures and sheep grimace score (SGS) were recorded hourly, for each animal, and averaged across the study for both breeds. The average rectal temperature throughout the study was similar for STC and SUF sheep (40.4°C and 40.2°C respectively), but the pattern of response was different. STC had an average SGS of 0.8 while SUF had an average of 3.3. Liver biopsies were collected from 3 sheep that were not challenged with LPS (HR0; n = 3/breed), two hours post-challenge (HR2; n = 3/breed), and six hours post-challenge (HR6; n = 3/breed). Liver tissue samples were subjected to quantitative untargeted metabolome analysis using chemical isotope labeling/liquid chromatography-mass spectrometry. Pathway analysis of the HR0 metabolome data revealed that 8 pathways (and their associated metabolites) including beta-alanine metabolism, arginine and proline metabolism and glutathione metabolism were altered (false discovery rate-adjusted P-value (FDR) ≤ 0.05) between STC and SUF sheep. At HR2, 10 altered pathways such as folate biosynthesis, taurine and hypotaurine metabolism, and glutathione metabolism. At HR6, only 2 pathways (glycerophospholipid metabolism and purine metabolism) were altered (FDR ≤ 0.05) between STC and SUF sheep. Results highlight the differences in hepatic metabolome and physiological response to LPS challenge that exist between SUF and STC. These findings suggest breed-specific differences in metabolic response to immune challenge, potentially influencing the divergent resistance of the two breeds to parasitic infections.

Involvement of Janus kinase-dependent Bcl-xL overexpression in steroid resistance of group 2 innate lymphoid cells in asthma.

The mechanisms underlying the development of steroid resistance in asthma remain unclear. To establish whether as well as the mechanisms by which the activation of Janus kinases (JAKs) is involved in the development of steroid resistance in asthma, murine steroid-resistant models of the proliferation of group 2 innate lymphoid cells (ILC2s) in vitro and asthmatic airway inflammation in vivo were analysed. ILC2s in the lungs of BALB/c mice were sorted and then incubated with IL-33, thymic stromal lymphopoietin (TSLP), and/or IL-7 with or without dexamethasone (10 nM), the pan-JAK inhibitor, delgocitinib (1-10 000 nM), and/or the Bcl-xL inhibitor, navitoclax (1-100 nM), followed by the detection of viable and apoptotic cells. The anti-apoptotic factor, Bcl-xL was detected in ILC2s by flow cytometry. As a steroid-resistant asthma model, ovalbumin (OVA)-sensitized BALB/c mice were intratracheally challenged with OVA at a high dose of 500 μg four times. Dexamethasone (1 mg/kg, i.p.), delgocitinib (3-30 mg/kg, p.o.), or navitoclax (30 mg/kg, p.o.) was administered during the challenges. Cellular infiltration into the lungs was analysed by flow cytometry. Airway remodelling was histologically evaluated. The following results were obtained. (1) Cell proliferation concomitant with a decrease in apoptotic cells was induced when ILC2s were cultured with TSLP and/or IL-7, and was potently inhibited by dexamethasone. In contrast, when the culture with TSLP and IL-7 was performed in the presence of IL-33, the proliferative response exhibited steroid resistance. Steroid-resistant ILC2 proliferation was suppressed by delgocitinib in a concentration-dependent manner. (2) The culture with IL-33, TSLP, and IL-7 induced the overexpression of Bcl-xL, which was clearly inhibited by delgocitinib, but not by dexamethasone. When ILC2s were treated with navitoclax, insensitivity to dexamethasone was significantly cancelled. (3) The development of airway remodelling and the infiltration of ILC2s into the lungs in the asthma model were not suppressed by dexamethasone, but were dose-dependently inhibited by delgocitinib. Combination treatment with dexamethasone and either delgocitinib or navitoclax synergistically suppressed these responses. Therefore, JAKs appear to play significant roles in the induction of steroid resistance by up-regulating Bcl-xL in ILC2s. The inhibition of JAKs and Bcl-xL has potential as pharmacotherapy for steroid-resistant asthma, particularly that mediated by ILC2s.

Progress and application of lung-on-a-chip for lung cancer

Lung cancer is a malignant tumour with the highest incidence and mortality worldwide. Clinically effective therapy strategies are underutilized owing to the lack of efficient models for evaluating drug response. One of the main reasons for failure of anticancer drug therapy is development of drug resistance. Anticancer drugs face severe challenges such as poor biodistribution, restricted solubility, inadequate absorption, and drug accumulation. In recent years, “organ-on-a-chip” platforms, which can directly regulate the microenvironment of biomechanics, biochemistry and pathophysiology, have been developed rapidly and have shown great potential in clinical drug research. Lung-on-a-chip (LOC) is a new 3D model of bionic lungs with physiological functions created by micromachining technology on microfluidic chips. This approach may be able to partially replace animal and 2D cell culture models. To overcome drug resistance, LOC realizes personalized prediction of drug response by simulating the lung-related microenvironment in vitro, significantly enhancing therapeutic effectiveness, bioavailability, and pharmacokinetics while minimizing side effects. In this review, we present an overview of recent advances in the preparation of LOC and contrast it with earlier in vitro models. Finally, we describe recent advances in LOC. The combination of this technology with nanomedicine will provide an accurate and reliable treatment for preclinical evaluation.

The Role of αvβ3 Integrin in Cancer Therapy Resistance

A relevant challenge for the treatment of patients with neoplasia is the development of resistance to chemo-, immune-, and radiotherapies. Although the causes of therapy resistance are poorly understood, evidence suggests it relies on compensatory mechanisms that cells develop to replace specific intracellular signaling that should be inactive after pharmacological inhibition. One such mechanism involves integrins, membrane receptors that connect cells to the extracellular matrix and have a crucial role in cell migration. The blockage of one specific type of integrin is frequently compensated by the overexpression of another integrin dimer, generally supporting cell adhesion and migration. In particular, integrin αvβ3 is a key receptor involved in tumor resistance to treatments with tyrosine kinase inhibitors, immune checkpoint inhibitors, and radiotherapy; however, the specific inhibition of the αvβ3 integrin is not enough to avoid tumor relapse. Here, we review the role of integrin αvβ3 in tumor resistance to therapy and the mechanisms that have been proposed thus far. Despite our focus on the αvβ3 integrin, it is important to note that other integrins have also been implicated in drug resistance and that the collaborative action between these receptors should not be neglected.

NSAIDs for early management of acute respiratory infections.

To review the rationale for and the potential clinical benefits of an early approach to viral acute respiratory infections with NSAIDs to switch off the inflammatory cascade before the inflammatory process becomes complicated. It has been shown that in COVID-19 as in other viral respiratory infections proinflammatory cytokines are produced, which are responsible of respiratory and systemic symptoms. There have been concerns that NSAIDs could increase susceptibility to SARS-CoV-2 infection or aggravate COVID-19. However, recent articles reviewing experimental research, observational clinical studies, randomized clinical trials, and meta-analyses conclude that there is no basis to limit the use of NSAIDs, which may instead represent effective self-care measures to control symptoms. The inflammatory response plays a pivotal role in the early phase of acute respiratory tract infections (ARTIs); a correct diagnosis of the cause and a prompt therapeutic approach with NSAIDs may have the potential to control the pathophysiological mechanisms that can complicate the condition, while reducing symptoms to the benefit of the patient. A timely treatment with NSAIDs may limit the inappropriate use of other categories of drugs, such as antibiotics, which are useless when viral cause is confirmed and whose inappropriate use is responsible for the development of resistance.

Topical Toxicity and Repellency Profiles of 17 Essential Oil Components against Insecticide-Resistant and Susceptible Strains of Adult Musca domestica (Diptera: Muscidae)

The house fly is a significant pest in agriculture and human health that is increasingly difficult to manage due to multiple limitations including resistance development. To explore alternative pesticides, the topical toxicity and repellency profiles of 17 essential oil components (EOCs) were evaluated against a resistant and a susceptible strain of house fly, Musca domestica L., using topical application and Y-tube olfactometers, respectively. Six of the most toxic EOCs based on the LD50 were further investigated against a susceptible strain of house fly. Thymol, (+)-pulegone, eugenol, and carvacrol were always the top four most toxic chemicals tested against the resistant house fly strain. Little to no resistance was observed to the top six EOCs based on the comparison of the results between resistant and susceptible house fly strains. P-Cymene, citronellic acid, R-(+)-limonene, linalool, γ-terpinene, estragole, and eugenol were repellent to adult house flies at certain concentrations while (-)-carvone and thymol were attractive to adult house flies. This screening of a wide variety of individual EOCs provides a stronger foundation of information for further research. This should encourage further investigation into the topical toxicity and repellency in field studies, which will provide more insight into the performance of biopesticides for house fly management and potential commercialization.

#707 Effectiveness of a personalized approach to the treatment of patients with chronic coronary syndrome with type 2 diabetes and renal dysfunction

Abstract Background and Aims To evaluate the effectiveness of complex personalized treatment of patients with chronic coronary syndrome (CCS) with type 2 diabetes mellitus (T2DM). Method We observed patients with chronic stable angina pectoris III (FC) (Group I, 16) and CV IV FC (Group II, 18) with T2DM who underwent planned stenting of the coronary arteries (SCA). At baseline and after 3 and 6 months, we studied cholesterol, LDL cholesterol and HDL cholesterol, triglycerides (TG), ALT and AST, total bilirubin (TB), polymorphism of the CYP2C19 and 9p21 genes (rs 2383206 and rs 10757272), assessed myocardial viability (ECHOCG, MSCT), an ultrasound of the liver was performed. Against the background of basic therapy (antiplatelet agents, statins, beta blockers, ACE inhibitors), patients received a herbal hepatoprotector. Results Initial lipid parameters in patients with CCS and T2DM: cholesterol—6.9 mmol/l; LDL cholesterol –3.6; HDL cholesterol –1.1; TG –2.5 mmol/l. Parameters of global and regional systolic function were reduced. At the end of observation, lipid content: cholesterol—5.0; LDL cholesterol—2.3; HDL cholesterol –1.18; TG—1.61 mmol/l. Statins and antiplatelet agents were well tolerated, and there were no cases of withdrawal. Enzyme activity (ALT, AST), OB content were within normal values. The genetic studies carried out helped to select the most effective and safe doses of antiplatelet drugs and statins and significantly reduced the risk of complications and drug resistance. The hepatoprotector had a beneficial effect on the condition and function of the liver and improved the tolerability of medications. A personalized approach to the treatment of CCS was carried out taking into account the results of genetic testing with the selection of optimal doses of drugs. When the genotypes of CYP2C19*17 (rs 12248560) CC, ST and TT were distributed, the dose of antiplatelet agents was increased, and when the genotypes of the CYP2C19 gene (rs 4244285) GG, AG and AA were distributed, they were reduced. Assessment of myocardial viability, selection of doses of statins and antiplatelet agents according to individual characteristics, as well as a hepatoprotector increased the effectiveness and safety of treatment. SCA and basic treatment had an impact on the pathogenetic links of CCS, which is especially important in the treatment of patients with concomitant T2DM. Conclusion A personalized approach to the treatment of patients with CCS with T2DM who require SCA, taking into account the functional state and viability of the myocardium, the pharmacogenetic characteristics of the drugs, increases the effectiveness of revascularization, prevents the development of resistance, side effects and complications.

Veterinary Drug Residues in the Food Chain as an Emerging Public Health Threat: Sources, Analytical Methods, Health Impacts, and Preventive Measures

Veterinary medications are necessary for both contemporary animal husbandry and food production, but their residues can linger in foods obtained from animals and pose a dangerous human risk. In this review, we aim to highlight the sources, occurrence, human exposure pathways, and human health effects of drug residues in food-animal products. Following the usage of veterinary medications, pharmacologically active compounds known as drug residues can be found in food, the environment, or animals. They can cause major health concerns to people, including antibiotic resistance development, the development of cancer, teratogenic effects, hypersensitivity, and disruption of normal intestinal flora. Drug residues in animal products can originate from variety of sources, including water or food contamination, extra-label drug use, and ignoring drug withdrawal periods. This review also examines how humans can be exposed to drug residues through drinking water, food, air, and dust, and discusses various analytical techniques for identifying these residues in food. Furthermore, we suggest some potential solutions to prevent or reduce drug residues in animal products and human exposure pathways, such as implementing withdrawal periods, monitoring programs, education campaigns, and new technologies that are crucial for safeguarding public health. This review underscores the urgency of addressing veterinary drug residues as a significant and emerging public health threat, calling for collaborative efforts from researchers, policymakers, and industry stakeholders to develop sustainable solutions that ensure the safety of the global food supply chain.

Evolution of HBV antiviral resistance: A threat to current therapeutic strategies

Evolution of HBV antiviral resistance: A threat to current therapeutic strategies

Evolution of copper coupons resistance in Enterobacteriaceae strains isolated from high-contact surfaces in hospital

Evolution of copper coupons resistance in Enterobacteriaceae strains isolated from high-contact surfaces in hospital

Immune Regulation and Immune Therapy in Melanoma: Review with Emphasis on CD155 Signalling

Melanoma is commonly diagnosed in a younger population than most other solid malignancies and, in Australia and most of the world, is the leading cause of skin-cancer-related death. Melanoma is a cancer type with high immunogenicity; thus, immunotherapies are used as first-line treatment for advanced melanoma patients. Although immunotherapies are working well, not all the patients are benefitting from them. A lack of a comprehensive understanding of immune regulation in the melanoma tumour microenvironment is a major challenge of patient stratification. Overexpression of CD155 has been reported as a key factor in melanoma immune regulation for the development of therapy resistance. A more thorough understanding of the actions of current immunotherapy strategies, their effects on immune cell subsets, and the roles that CD155 plays are essential for a rational design of novel targets of anti-cancer immunotherapies. In this review, we comprehensively discuss current anti-melanoma immunotherapy strategies and the immune response contribution of different cell lineages, including tumour endothelial cells, myeloid-derived suppressor cells, cytotoxic T cells, cancer-associated fibroblast, and nature killer cells. Finally, we explore the impact of CD155 and its receptors DNAM-1, TIGIT, and CD96 on immune cells, especially in the context of the melanoma tumour microenvironment and anti-cancer immunotherapies.

Knowledge and perception of cereal farmers and extension agents on fungicide use in northern Ghana.

Agricultural pesticide use in sub-Saharan Africa has doubled over the past three decades, with a greater relative increase for fungicides. As pesticide inputs continue to rise, so does the potential for the development of resistance. Here, we report on a survey conducted to understand pesticide resistance awareness, pesticide-use knowledge and practices of growers and agricultural extension officers (AEOs) in the cereals growing-belt of northern Ghana, with emphasis on fungicides. The results may inform development of strategies for improving pesticide literacy including resistance awareness, extension services and crop protection outcomes. The survey revealed a low level of pesticide-use knowledge for AEOs and growers. This was more so for growers with low education, predominantly women. Education level (and indirectly gender) influenced perceived effectiveness of fungicides and levels of adoption of cultural and agrochemical best practices. Only 28% of growers and 11% of AEOs practiced crop and fungicide rotations, respectively. More than half (53%) of the respondents indicated that fungicides used in northern Ghana are not effective. Given the low level of pesticide literacy of AEOs and growers, training programs on best practice for the use of pesticides, with targeted initiatives for female growers, would improve crop protection outcomes and safety. The limited adoptions of crop rotation and repeated use of fungicides with the same active ingredients, along with >50% of respondents reporting 'fungicides not working' suggest the potential presence of fungicide resistance cases in growers' fields in the Northern region of Ghana. Further work is needed to determine the incidence of resistance in the region. It is recommended that a key policy priority should focus on understanding broader agrochemical-use practices, crop losses and household-level food security in the presence of resistance risks. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

A Mathematical Analysis of Competitive Dynamics and Aggressive Treatment in the Evolution of Drug Resistance in Malaria Parasites

Experimental evidence supports the counterintuitive notion that rapid eradication of pathogens within a host, infected with both drug-sensitive and -resistant malaria parasites, can actually accelerate the evolution of drug-resistant pathogens. This study aims to analyze the competitive dynamics between these two strains through a mathematical model and evaluate the impact of aggressive treatment on the spread of drug resistance. We conducted equilibrium, uncertainty, and sensitivity analyses to assess the model, identifying and measuring the influence of key factors on the outcome variable (the population of drug-resistant parasites). Both equilibrium and local sensitivity analyses concurred that the density of drug-resistant parasites is notably affected by genetic instability, the production rate of red blood cells, the number of merozoites, and competition factors. Conversely, there is a negative relationship between genetic instability and one of the competition coefficients. Global sensitivity analysis offers a comprehensive examination of the impact of each input parameter on the temporal propagation of drug resistance, effectively accounting for the interplay among parameters. Both local and global sensitivity analyses underscore the continuous impact of drug treatment on the progression of drug resistance over time. This paper anticipates exploring the underlying mechanisms of drug resistance and providing theoretical support for developing more effective drug treatment strategies.

La evolución prospectiva de las redes sociales desde la perspectiva de la neurofenomenología

The purpose of the present article is to identify neurophenomenological aspects that influence the future development of social networks and to develop a corresponding concept of regulatory policy. The following methods are used in the article: collection and analysis of information, modeling of a conditional social network, systematization and separation of neurophenomenological factors, determination of functional dependencies, development of analytical conclusions and proposals. It was established that instigators and a favorable environment of social networks form prerequisites for the spread of negative information campaigns (conditional attacks). At the same time, it is mathematically proven that with minimal development of resistance to information attacks among users of social media platforms, the potential for stabilizing the information environment of social networks and promoting sustainable advancement of natural society was determined. Based on the research results, it was determined that fostering critical thinking skills, maintaining information stability, and practicing sound personal digital hygiene among users are key factors in upholding the overall stability of social networks. Additionally, these practices promote sustainable development of a psychologically healthy community. Additional investigations are focused on elaborating the notion of regulatory policy to facilitate the prospective advancement of social networks.

Piceatannol: a renaissance in antibacterial innovation unveiling synergistic potency and virulence disruption against serious pathogens.

In the relentless battle against multi-drug resistant Gram-negative bacteria, piceatannol emerges as a beacon of hope, showcasing unparalleled antibacterial efficacy and a unique ability to disrupt virulence factors. Our study illuminates the multifaceted prowess of piceatannol against prominent pathogens-Proteus mirabilis, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Notably, piceatannol demonstrated a remarkable ability to inhibit biofilm formation, reduce bacterial mobility, and diminish extracellular enzyme synthesis.Mechanistic insights into piceatannol's activity unraveled its impact on membrane potential, proton motive force, and ATP production. Furthermore, our study delved into piceatannol's anti-quorum sensing (QS) activity, showcasing its potential to downregulate QS-encoding genes and affirming its affinity to critical QS receptors through molecular docking. Crucially, piceatannol exhibited a low propensity for resistance development, positioning it as a promising candidate for combating antibiotic-resistant strains. Its mild effect on red blood cells (RBCs) suggests safety even at higher concentrations, reinforcing its potential translational value. In an in vivo setting, piceatannol demonstrated protective capabilities, significantly reducing pathogenesis in mice infected with P. aeruginosa and P. mirabilis. This comprehensive analysis positions piceatannol as a renaissance in antibacterial innovation, offering a versatile and effective strategy to confront the evolving challenges posed by resilient Gram-negative pathogens.

Biocidal efficacy of olefinic N-alkylamides against Aedes aegypti and Culex quinquefasciatus larvae

Mosquito-borne diseases are a major public-health concern worldwide. The development of resistance in mosquitoes to the existing larvicides and the associated-risks necessitates the exploration of novel molecules to control vector-borne pathogens. This study demonstrates that N-alkylamides [2E,4E-N-isobutyl-undeca-2,4-diene-8,10-diynamide (1) and 2E,4E,8Z,10E-N-isobutyl-dodeca-2,4,8,10-tetraenamide (2)] of Acmella ciliata exhibit biocidal action against Aedes aegypti and Culex quinquefasciatus larvae. The LC50 for 1 and 2 were 44.19 and 18.28 ppm against Aedes larvae, and 30.89 and 11.75 ppm against Culex larvae, respectively. We further observed that the chain length, degree of unsaturation, and terminal methylation influence the larvicidal efficacy of N-alkylamides. HPLC-assisted quantification revealed that the content of both 1 (19.01 mg/g) and 2 (68.55 mg/g) was maximum in the flowers of A. ciliata. Thus, this study concludes that N-alkylamides are promising alternatives to control mosquito larvae and can be used as standard for quantitation in test samples.

Interfacial thermal resistance between mechanically exfoliated nm-thick MoS2 and silicon from −60 °C to 50 °C based on ns-ET Raman technique

In the miniaturization and integration development of micro-devices, the large thermal contact resistance significantly affects the overall performance of micro-devices, which is influenced by both interfacial contact condition and material properties. However, the temperature dependence of interfacial thermal resistance of realistic materials remains unclear. In this work, the interfacial thermal resistance between nm-thick MoS2 nanosheets and Si substrate is measured by using the ns energy transport state-resolved Raman (ns ET-Raman) technique. By comparing the experimental data with finite difference numerical simulation, the real value of the interfacial thermal resistance is determined. By changing the ambient temperature from -60 °C to 50 °C, the interfacial thermal resistance against temperature curve is obtained. As the environmental temperature deviates from room temperature, a large increasement of the interfacial thermal resistance can be observed. As temperature goes back to room temperature, the unreversible interfacial thermal resistance indicates that the large thermal expansion mismatch deteriorates the contact situation. In the last, the interfacial thermal resistance evolution under varying environmental temperatures from both experiments and modeling results in literatures are compared and discussed to illustrate the effect of different interface formation methods. For epitaxial and CVD grown materials, the interfacial thermal resistance generally reduces with raising ambient temperature. While for mechanically exfoliated samples, the effect of thermal expansion mismatch and the resulting gaps dominate the interfacial thermal resistance, which leads to non-monotonous temperature dependency with a valley located at room temperature.

De Novo Antimicrobial Peptide Design with Feedback Generative Adversarial Networks.

Antimicrobial peptides (AMPs) are promising candidates for new antibiotics due to their broad-spectrum activity against pathogens and reduced susceptibility to resistance development. Deep-learning techniques, such as deep generative models, offer a promising avenue to expedite the discovery and optimization of AMPs. A remarkable example is the Feedback Generative Adversarial Network (FBGAN), a deep generative model that incorporates a classifier during its training phase. Our study aims to explore the impact of enhanced classifiers on the generative capabilities of FBGAN. To this end, we introduce two alternative classifiers for the FBGAN framework, both surpassing the accuracy of the original classifier. The first classifier utilizes the k-mers technique, while the second applies transfer learning from the large protein language model Evolutionary Scale Modeling 2 (ESM2). Integrating these classifiers into FBGAN not only yields notable performance enhancements compared to the original FBGAN but also enables the proposed generative models to achieve comparable or even superior performance to established methods such as AMPGAN and HydrAMP. This achievement underscores the effectiveness of leveraging advanced classifiers within the FBGAN framework, enhancing its computational robustness for AMP de novo design and making it comparable to existing literature.

Preparation and Effects of Manganese Oxide Nanoparticles Against Quinolone-Resistant Bacteria Isolated from Hospital Wastewater

Background: The widespread administration of quinolones may have led to an increase in bacterial resistance development. Objective: To synthesize and characterize manganese oxide nanoparticles (MnO2NPs) and evaluate their effects on the viability and biofilm formation of quinolone-resistant gram-positive and negative pathogenic bacteria. Methods: We prepared MnO2NPs using the photo-irradiation method and recorded their characteristics using XRD, TEM, and SEM. Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa were collected from the wastewater of Baghdad hospitals during the period from July 3rd to July 14th, 2023. We used the VITEK2 system to confirm and identify all of the isolates. We conducted biofilm formation and antibiotic susceptibility tests using nalidixic acid, ciprofloxacin, norfloxacin, aztreonam, levofloxacin, and ofloxacin, and also detected the qnrA and qnrB genes. Finally, we evaluated the effects of the prepared nanoparticles on the viability and biofilm formation of bacterial isolates. Results: MnO2NPs characterizations showed a diffraction peak at 2θ values with 21 nm average sizes; qnrA and qnrB genes were found in three and four isolates, respectively; and significant effects of MnO2NPs against viability and biofilm formation were recorded. Conclusions: The synthesized nanoparticles have antibacterial and anti-biofilm activities against a variety of bacteria possessing qnr genes. Even multi-resistant bacterial isolates have the potential to be strong antimicrobial agents against these pathogens.

Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma

BackgroundDrug resistance poses a significant challenge in cancer treatment, particularly as a leading cause of therapy failure. Cisplatin, the primary drug for lung adenocarcinoma (LUAD) chemotherapy, shows effective treatment outcomes. However, the development of resistance against cisplatin is a major obstacle. Therefore, identifying genes resistant to cisplatin and adopting personalized treatment could significantly improve patient outcomes.MethodsBy examining transcriptome data of cisplatin-resistant LUAD cells from the GEO database, 181 genes associated with cisplatin resistance were identified. Using univariate regression analysis, random forest and multivariate regression analyses, two prognostic genes, E2F7 and FAM83A, were identified. This study developed a prognostic model utilizing E2F7 and FAM83A as key indicators. The Cell Counting Kit 8 assay, Transwell assay, and flow cytometry were used to detect the effects of E2F7 on the proliferation, migration, invasiveness and apoptosis of A549/PC9 cells. Western blotting was used to determine the effect of E2F7 on AKT/mTOR signaling pathway.ResultsThis study has pinpointed two crucial genes associated with cisplatin resistance, E2F7 and FAM83A, and developed a comprehensive model to assist in the diagnosis, prognosis, and evaluation of relapse risk in LUAD. Analysis revealed that patients at higher risk, according to these genetic markers, had elevated levels of immune checkpoints (PD-L1 and PD-L2). The prognostic and diagnosis values of E2F7 and FAM83A were further confirmed in clinical data. Furthermore, inhibiting E2F7 in lung cancer cells markedly reduced their proliferation, migration, invasion, and increased apoptosis. In vivo experiments corroborated these findings, showing reduced tumor growth and lung metastasis upon E2F7 suppression in lung cancer models.ConclusionOur study affirms the prognostic value of a model based on two DEGs, offering a reliable method for predicting the success of tumor immunotherapy in patients with LUAD. The diagnostic and predictive model based on these genes demonstrates excellent performance. In vitro, reducing E2F7 levels shows antitumor effects by blocking LUAD growth and progression. Further investigation into the molecular mechanisms has highlighted E2F7’s effect on the AKT/mTOR signaling pathway, underscoring its therapeutic potential. In the era of personalized medicine, this DEG-based model promises to guide clinical practice.