A comparison increasing the photodegradation power of a Ag/g-C3N4 /CoNi-LDH nanocomposite: Photocatalytic activity toward water treatment.

For environmental applications, it is crucial to rationally design and synthesize photocatalysts with positive exciton splitting and interfacial charge transfer. Here, a novel Ag-bridged dual Z-scheme Ag/g-C3N4/CoNi-LDH plasmonic heterojunction was successfully synthesized using a simple method, with the goal of overcoming the common drawbacks of traditional photocatalysts such as weak photoresponsivity, rapid combination of photo-generated carriers, and unstable structure. These materials were characterized by XRD, FT-IR, SEM, TEM UV-Vis/DRS, and XPS to verify the structure and stability of the heterostructure. The pristine LDH, g-C3N4, and Ag/g-C3N4/CoNi-LDH composite were investigated as photocatalysts for water remediation, an environmentally motivated process. Specifically, the photocatalytic degradation of tetracycline was studied as a model reaction. The performance of the supports and composite catalyst were determined by evaluating both the degradation and adsorption phenomenon. The influence of several experimental parameters such as catalyst loading, pH, and tetracycline concentration were evaluated. The current study provides important data for water treatment and similar environmental protection applications.

Long-Term Exposure of Fresh and Aged Nano Zinc Oxide Promotes Hepatocellular Carcinoma Malignancy by Up-Regulating Claudin-2.

Background: Tumor development and progression is a long and complex process influenced by a combination of intrinsic (eg, gene mutation) and extrinsic (eg, environmental pollution) factors. As a detoxification organ, the liver plays an important role in human exposure and response to various environmental pollutants including nanomaterials (NMs). Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and remains a serious threat to human health. Whether NMs promote liver cancer progression remains elusive and assessing long-term exposure to subtoxic doses of nanoparticles (NPs) remains a challenge. In this study, we focused on the promotional effects of nano zinc oxide (nZnO) on the malignant progression of human HCC cells HepG2, especially aged nZnO that has undergone physicochemical transformation. Methods: In in vitro experiments, we performed colony forming efficiency, soft agar colony formation, and cell migration/invasion assays on HepG2 cells that had been exposed to a low dose of nZnO (1.5 µg/mL) for 3 or 4 months. In in vivo experiments, we subcutaneously inoculated HepG2 cells that had undergone long-term exposure to nZnO for 4 months into BALB/c athymic nude mice and observed tumor formation. ZnCl2 was administered to determine the role of zinc ions. Results: Chronic low-dose exposure to nZnO significantly intensified the malignant progression of HCC cells, whereas aged nZnO may exacerbate the severity of malignant progression. Furthermore, through transcriptome sequencing analysis and in vitro cellular rescue experiments, we demonstrated that the mechanism of nZnO-induced malignant progression of HCC could be linked to the activation of Claudin-2 (CLDN2), one of the components of cellular tight junctions, and the dysregulation of its downstream signaling pathways. Conclusion: Long-term exposure of fresh and aged nZnO promotes hepatocellular carcinoma malignancy by up-regulating CLDN2. The implications of this work can be profound for cancer patients, as the use of various nanoproducts and unintentional exposure to environmentally transformed NMs may unknowingly hasten the progression of their cancers.

Mannose targeting of poly(lactic-co-glycolic acid): a promising approach for improving sublingual allergen-specific immunotherapy.

OBJECTIVE: One of the most effective treatments for allergic respiratory diseases is allergen-specific sublingual immunotherapy (SLIT). While, mannose targeting has been applied in various immunostimulatory approaches, but it has not been investigated in sublingual allergen-specific immunosuppressive treatment. This study assesses mannose targeting for the ovalbumin (Ova) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles(NPs). METHODS: The emulsion-solvent evaporation method was employed for the synthesis of PLGA NPs containing Ova, and subsequently they attached to D-mannose. Ova-sensitized mice underwent treatment in different ways: subcutaneous administration of 10 µg Ova, sublingual administration of 5 and 10 µg Ova loaded in PLGA NPs, 5 and 10 µg Ova loaded in mannose-targeted PLGA NPs, 10 µg Ova, and 10 µg Ova loaded in dendritic cell-specific aptamer-attached PLGA NPs. Serum Ova-specific IgE and IgG2a levels, as well as IFN-γ, IL-4, IL-10, and IL-17a levels in the supernatant of Ova-stimulated splenocytes were measured. Splenocyte proliferation was assessed using an MTT assay, and also lung histological examinations, and nasal lavage fluid cell counting were performed. RESULTS: Ova-specific IgE, IL-4, IL-17a levels, eosinophil cell count, and splenocyte proliferation were remarkably reduced in the mice treated with mannose or aptamer targeted NPs compared to other groups. Also, IL-10 and IFN-γ levels were remarkably increased in the targeted NPs groups. CONCLUSION: Our findings indicated that mannose targeting of PLGA NPs could decrease allergen dose and improve immunomodulatory effects of SLIT. However, this approach suggests an effective formulation for SLIT in the mice model, further studies with common allergens are needed for application in humans.

Green Synthesis of New Derivatives of Iminothiazole Using Cefixime and Removing Organic Pollutants from Aqueous Environment by Employing Cu@KF/Clinoptilolite NPs.

AIMS AND OBJECTIVE: In this research, multicomponent reactions of cefixime, isothiocyanates, and alkyl bromides were carried out for the synthesis of new iminothiazole derivatives with high yields in water as the solvent at room temperature in the presence of catalytic amounts of Cu@KF/CP NPs as catalysts. Also, the ability of Cu@KF/Clinoptilolite nanoparticles (NPs) to adsorb and remove 4-NP and cefixime from water was investigated. The Cu@KF/Clinoptilolite nanoparticles were synthesized by employing a water extract of Petasites hybridus rhizomes. MATERIALS AND METHODS: For this experiment, all of the components obtained from Fluka and Merck were subjected to further purification. The antibiotic used in this investigation, cefixime, was obtained from a pharmaceutical facility situated in Sari, Mazandaran, Iran. The antibiotic factory is located in Sari City, Iran. All solutions were prepared using distilled water. The shape of Cu@KF/CP nanoparticles was analyzed using images obtained from a Holland Philips XL30 scanning electron microscope. An analysis was performed on the crystalline structure of Cu@KF/CP nanoparticles (NPs), and a room temperature X-ray diffraction (XRD) examination was carried out utilizing a Holland Philips Xpert X-ray powder diffractometer. The X-ray diffraction (XRD) examination was conducted using CuK radiation, which has a wavelength of 0.15406 nm. The analysis covered a 2ε angle range from 20 to 80°. The nanostructures that were produced were chemically analyzed using X-ray energy dispersive spectroscopy (EDS) with an S3700N equipment. The morphology and dimensions of Cu@KF/CP nanoparticles were characterized using a Philips EM208 transmission electron microscope operated at an acceleration voltage of 90 kV. RESULTS: The primary objective of this study was to develop a sustainable approach for producing new iminothiazole derivatives 4. This was achieved using a highly efficient three-component reaction combining cefixime 1, isothiocyanates 2, and alkyl bromides 3. The reaction was carried out in water at ambient temperature, using Cu@KF/CP NPs as a highly effective catalyst, leading to excellent yields. Moreover, the study findings showed that the synthesized compounds demonstrated a significant antioxidant activity compared to conventional antioxidants. The antibacterial efficacy of the synthesized compounds was evaluated against both Gram-positive and Gram-negative bacteria. Furthermore, Cu@KF/CP nanoparticles were utilized to adsorb CFX and 4-NP from water-based solutions. CONCLUSION: This study showcases the effective synthesis of innovative iminothiazole derivatives through the use of multicomponent reactions, involving the combination of cefixime, isothiocyanates, and alkyl bromides. The reactions were conducted in a water-based solvent. The reactions were carried out at room temperature, utilizing Cu@KF/CP NPs as catalysts. The Cu@KF/CP nanoparticles, a newly developed heterogeneous nanocatalyst, were synthesized and evaluated utilizing X-ray diffraction (XRD), fieldemission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) research techniques. Cu@KF/CP nanoparticles are utilized to adsorb CFX and 4-NP from water-based solutions. The objects were manufactured using a straightforward and uncomplicated approach. The BET surface area of Cu@KF/CP NPs was measured to be 201.8 m2/g. The experimental equilibrium data was evaluated by applying the isotherms of the Langmuir, Freundlich, Dubinin-Radushkevich, and Redlich-Peterson models. Additionally, we examined the catalytic efficiency of Cu@KF/CP nanoparticles (NPs) in reducing various colors in water.

Synergistic efficacy of ZnO quantum dots, Ag NPs, and nitazoxanide composite against multidrug-resistant human pathogens as new trend of revolutionizing antimicrobial treatment.

Antibiotic resistance is currently becoming a more serious threat to global health, especially in severe nosocomial infections treatment by multidrug-resistant bacteria. This research provides a new way of synergizing green-synthesis for zinc oxide quantum dots (ZnO-QDs with hexagonal crystals) that are 7 nm in diameter and zero-valent Ag cubic crystals that are 67 nm in size embedded with nitazoxanide substrate (NAZ). Instrumental characterization like SEM, TEM, EDAX, and FT-IR and comprehensive antimicrobial studies were conducted to study the incorporation behavior of composites based on Ag NPs/ZnO QDs/NAZ. This combination has not been hitherto addressed anywhere else in the published literature, as well as commercial viability. In this context, we have precisely tuned nanoparticle to nitazoxanide ratio for designing the formulation demonstrating potent activity against MDR infections. By employing nitazoxanide as a scaffold and careful decoration thereof antimicrobial potency has been unlocked overriding conventional therapies. In addition, Ag NPs/ZnO-QDs/nitazoxanide (G6) formula exhibited a therapeutic efficacy span of 96.15 ± 1.68% to 99.57 ± 0.20% against MDR human infections post 48 h incubation; a breakthrough in therapeutic efficacy levels has been achieved by our method. Accordingly, ZnO QDs/Ag NPs/NAZ composite offered potential multidrug resistant human pathogens as a new trend of revolutionizing antimicrobial treatment.

Mapping new psychoactive substances: Leveraging GIS technology for advanced global surveillance and policy support.

The escalating challenge of New Psychoactive Substances (NPS) necessitates enhanced global monitoring and analysis capabilities. This study introduces an advanced interactive visualization tool that employs Geographic Information System (GIS) technologies to improve the functionality of the UNODC's Early Warning Advisory. The tool enables dynamic observation and analysis of NPS's geographical and temporal distribution, thereby facilitating a comprehensive understanding of their public health impacts. By incorporating detailed choropleth maps and annual and cumulative bar charts, the tool allows policymakers and researchers to visually track and analyze trends in NPS usage and control efforts across different regions. The results demonstrate the tool's effectiveness in providing actionable insights, which support the strategic development of public health policies and interventions to curb the global rise in NPS usage. This initiative illustrates the essential role of digital tools in enhancing public health strategies and responses to emerging drug trends. This rising challenge underscores the urgent need for innovative solutions in monitoring drug trends, a theme explored in this paper. The web tool is available at https://nps-vis.cmdm.tw, and the code is available at https://github.com/CMDM-Lab/nps-vis.

Biogenic synthesis and characterization of antimicrobial, antioxidant, and antihemolytic zinc oxide nanoparticles from Desertifilum sp. TN-15 cell extract.

Cyanobacteria, being a prominent category of phototrophic organism, exhibit substantial potential as a valuable source of bioactive compounds and phytonutrients, including liposomes, amino derivatives, proteins, and carotenoids. In this investigation, a polyphasic approach was employed to isolate and characterize a newly discovered cyanobacterial strain from a rice field in the Garh Moor district of Jhang. Desertifilum sp. TN-15, a unique and less explored cyanobacterial strain, holds significant promise as a novel candidate for the synthesis of nanoparticles. This noticeable research gap underscores the novelty and untapped potential of Desertifilum sp. TN-15 in the field of nanomedicine. The characterization of the biogenically synthesized ZnO-NPs involved the application of diverse analytical techniques. Ultraviolet-visible spectroscopy revealed a surface plasmon resonance peak at 298 nm. Fourier transform infrared spectral analysis was utilized to confirm the involvement of biomolecules in the biogenic synthesis and stability. Scanning electron microscopy was employed to probe the surface morphology of the biogenic ZnO-NPs unveiling their size of 94.80 nm and star-shaped. Furthermore, X-ray diffraction analysis substantiated the crystalline nature of ZnO-NPs, with a crystalline size measuring 46 nm. To assess the physical stability of ZnO-NPs, zeta potential and dynamic light scattering measurements were conducted, yielding values of + 31.6 mV, and 94.80 nm, respectively, indicative of favorable stability. The antibacterial capabilities of Desertifilum sp. TN-15 are attributed to its abundance of bioactive components, including proteins, liposomes, amino derivatives, and carotenoids. Through the synthesis of zinc oxide nanoparticles (ZnO-NPs) with this strain, we have effectively used these chemicals to generate nanoparticles that exhibit noteworthy antibacterial activity against Staphylococcus aureus (MIC: 30.05 ± 0.003 µg/ml). Additionally, the ZnO-NPs displayed potent antifungal activity and antioxidant properties, as well as significant antihemolytic effects on red blood cells (IC50: 4.8 µg/ml). Cytotoxicity assessment using brine shrimps revealed an IC50 value of 3.1 µg/ml. The multifaceted actions of the biogenically synthesized ZnO-NPs underscore their potential applications in pharmacological and therapeutic fields. This study proposes a novel method for ZnO-NPs production utilizing the recently identified cyanobacterial strain Desertifilum sp. TN-15, highlighting the growing significance of biological systems in the environmentally friendly fabrication of metallic oxide nanomaterials.

State-of-the-art application of nanoparticles in radiotherapy: a platform for synergistic effects in cancer treatment.

Radiotherapy (RT) is a gold standard cancer treatment worldwide. However, RT has limitations and many side effects. Nanoparticles (NPs) have exclusive properties that allow them to be used in cancer therapy. Consequently, the combination of NP and RT opens up a new frontier in cancer treatment. Among NPs, gold nanoparticles (GNPs) are the most extensively studied and are considered ideal radiosensitizers for radiotherapy due to their unique physicochemical properties and high X­ray absorption. This review analyzes the various roles of NPs as radiosensitizers in radiotherapy of glioblastoma (GBS), prostate cancer, and breast cancer and summarizes recent advances. Furthermore, the underlying mechanisms of NP radiosensitization, including physical, chemical, and biological mechanisms, are discussed, which may provide new directions for next-generation GNP optimization and clinical transformation.

Biocompatibility, antimicrobial efficacy, and therapeutic potential of cobalt carbonate nanoparticles in wound healing, sex hormones, and metabolic regulation in diabetic albino mice.

Nanotechnology enables the manipulation of materials at the nanoscale, offering innovative solutions in various fields. Nanoparticles, with their small size and unique properties, have significant applications in the biomedical filed. The current study was designed to assess the biological applications of self-synthesized cobalt carbonate (CoCO3) nanoparticles. The crystalline structure and chemical composition of the CoCO3-NPs were confirmed by SEM, XRD, and FTIR techniques. We observed the 16.58 nm size of novelly synthesized CoCO3 NPS. The scanning electron microscope study confirmed a uniform cubic spinel structure. The biocompatibility and antimicrobial activity were checked in an invitro setup. We exposed albino mice to these synthesized NPs to study wound healing and metabolic effects. The results of biocompatibility analysis indicated hemolytic activity in a dose-dependent way, which showed no cytotoxic effect except at a higher concentration. Furthermore, the results showed enhanced wound healing processes in CoCO3-NP-treated albino mice as compared to the control group. CoCO3-NPs have considerable effect on the thyroid hormone and insulin levels in albino mice. The levels of T3, T4, and insulin were increased in a dose-dependent manner. Interactions between CoCO3-NPs and thyroxine and insulin were confirmed through molecular docking. We confirmed the antimicrobial efficiency of the nanoparticles using MIC values and zones of inhibition against Staphylococcus haemolyticus and Staphylococcus aureus. Despite their concentration-dependent biocompatibility concerns, the results are promising, as CoCO3-NPs hold potential for use in medical practice, particularly in advanced wound management and microbe inhibition.

Size-Dependent Elemental Composition in Individual Magnetite Nanoparticles Generated from Coal-Fired Power Plant Regulating Their Pulmonary Cytotoxicity.

High-resolution characterization of magnetite nanoparticles (MNPs) derived from coal combustion activities is crucial to better understand their health-related risks. In this study, size distribution and elemental composition of individual MNPs from various coal fly ashes (CFAs) collected from a representative coal-fired power plant were analyzed using a single-particle inductively coupled plasma time-of-flight mass spectrometry technique. Majority (61-80%) of MNPs were identified as multimetal (mm)-MNPs, while the contribution of single metal (sm)-MNPs to the total increased throughout all the CFAs, reaching the highest in fly ash escaped through the stack (EFA). Among Fe-rich MNPs, Fe-sole and Fe-Al matrices were predominant, and Fe-sole MNPs were identified as the important carrier for toxic metals, with the highest mass contributions of toxic metals therein. Toxic potency results showed that the oxidative stress induced by MNPs was 1.2-2.2 times greater than those of <1 µm fractions in CFAs, while the reduction in cell viability showed no significant difference, elucidating that these MNPs can induce more distinct oxidative stress compared to cell toxicity. Based on structural equation model, MNP size can both directly and indirectly regulate the toxic potency, and the indirect regulation is through a size-dependent elemental composition of MNPs, including toxic metals. sm-MNPs and Fe-rich MNPs with Fe-sole, Fe-Cr, and Fe-Zn matrices can regulate the oxidative stress, whereas Cr, Zn, and Pb associated with Fe-sole, Fe-Al, Si-Fe, and Al-Fe MNPs showed significant effects on cell viability.

Impeding microbial biofilm formation and Pseudomonas aeruginosa virulence genes using biologically synthesized silver Carthamus nanoparticles.

Long-term antibiotic treatment results in the increasing resistance of bacteria to antimicrobials drugs, so it is necessary to search for effective alternatives to prevent and treat pathogens that cause diseases. This study is aimed for biological synthesis of silver Carthamus nanoparticles (Ag-Carth-NPs) to combat microbial biofilm formation and Pseudomonas aeruginosa virulence genes. Ag-Carth-NPs are synthesized using Carthamus tenuis aqueous extract as environmentally friendly method has no harmful effect on environment. General factorial design is used to optimize Ag-Carth-NPs synthesis using three variables in three levels are Carthamus extract concentration, silver nitrate concentration and gamma radiation doses. Analysis of response data indicates gamma radiation has a significant effect on Ag-Carth-NPs production. Ag-Carth-NPs have sharp peak at λ max 425 nm, small and spherical particles with size 20.0 ± 1.22 nm, high stability up to 240 day with zeta potential around - 43 ± 0.12 mV, face centered cubic crystalline structure and FT-IR spectroscopy shows peak around 620 cm-1 that corresponding to AgNPs that stabilized by C. tenuis extract functional moiety. The antibacterial activity of Ag-Carth-NPs against pathogenic bacteria and fungi was determined using well diffusion method. The MIC values of Ag-Carth-NPs were (6.25, 6.25, 3.126, 25, 12.5, 12.5, 25 and 12.5 µg/ml), MBC values were (12.5, 12.5, 6.25, 50, 25, 25, 50 and 25 µg/ml) and biofilm inhibition% were (62.12, 68.25, 90.12, 69.51, 70.61, 71.12, 75.51 and 77.71%) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Candida tropicalis and Candida albicans respectively. Ag-Carth-NPs has bactericidal efficacy and significantly reduced the swarming, swimming motility, pyocyanin and protease production of P. aeruginosa. Furthermore, P. aeruginosa ToxA gene expression was significantly down regulated by 81.5%, while exoU reduced by 78.1%, where lasR gene expression reduction was 68%, while the reduction in exoU was 66% and 60.1% decrease in lasB gene expression after treatment with Ag-Carth-NPs. This activity is attributed to effect of Ag-Carth-NPs on cell membrane integrity, down regulation of virulence gene expression, and induction of general and oxidative stress in P. aeruginosa. Ag-Carth-NPs have no significant cytotoxic effects on normal human cell (Hfb4) but have IC50 at 5.6µg/mL against of HepG-2 cells. Limitations of the study include studies with low risks of silver nanoparticles for in vitro antimicrobial effects and its toxicity.

A novel injectable boron doped-mesoporous nano bioactive glass loaded-alginate composite hydrogel as a pulpotomy filling biomaterial for dentin regeneration.

BACKGROUND: Different materials have been used as wound dressings after vital pulp therapies. Some of them have limitations such as delayed setting, difficult administration, slight degree of cytotoxicity, crown discoloration and high cost. Therefore, to overcome these disadvantages, composite scaffolds have been used in regenerative dentistry. This study aims to construct and characterize the physicochemical behavior of a novel injectable alginate hydrogel loaded with different bioactive glass nanoparticles in various concentrations as a regenerative pulpotomy filling material. METHODS: Alginate hydrogels were prepared by dissolving alginate powder in alcoholic distilled water containing mesoporous bioactive glass nanoparticles (MBG NPs) or boron-doped MBG NPs (BMBG NPs) at 10 and 20 wt% concentrations. The mixture was stirred and incubated overnight in a water bath at 50 0 C to ensure complete solubility. A sterile dual-syringe system was used to mix the alginate solution with 20 wt% calcium chloride solution, forming the hydrogel upon extrusion. Then, constructed hydrogel specimens from all groups were characterized by FTIR, SEM, water uptake percentage (WA%), bioactivity and ion release, and cytotoxicity. Statistical analysis was done using One-Way ANOVA test for comparisons between groups, followed by multiple pairwise comparisons using Bonferroni adjusted significance level (p < 0.05). RESULTS: Alginate/BMBG loaded groups exhibited remarkable increase in porosity and pore size diameter [IIB1 (168), IIB2 (183) (µm)]. Similarly, WA% increased (~ 800%) which was statistically significant (p < 0.05). Alginate/BMBG loaded groups exhibited the strongest bioactive capability displaying prominent clusters of hydroxyapatite precipitates on hydrogel surfaces. Ca/P ratio of precipitates in IIA2 and IIB1 (1.6) were like Ca/P ratio for stoichiometric pure hydroxyapatite (1.67). MTT assay data revealed that the cell viability % of human gingival fibroblast cells have declined with increasing the concentration of both powders and hydrogel extracts in all groups after 24 and 48 h but still higher than the accepted cell viability % of (˃70%). CONCLUSIONS: The outstanding laboratory performance of the injectable alginate/BMBGNPs (20 wt%) composite hydrogel suggested it as promising candidate for pulpotomy filling material potentially enhancing dentin regeneration in clinical applications.

Long-term and multiscale assessment of methanogenesis enhancement mechanisms in magnetite nanoparticle-mediated anaerobic digestion reactor.

Magnetite nanoparticles (Fe3O4-NPs) have been demonstrated to be involved in direct interspecies electron transfer between syntrophic bacteria, yet a comprehensive assessment of the ability of Fe3O4-NPs to cope with process instability and volatile fatty acids (VFAs) accumulation in scaled-up anaerobic reactors is still lacking. Here, we investigated the start-up characteristics of an expanded granular sludge bed (EGSB) with Fe3O4-NPs as an adjuvant at high organic loading rate (OLR). The results showed that the methane production rate of R1 (with Fe3O4-NPs) was approximately 1.65 folds of R0 (control), and effluent COD removal efficiency was maintained at approximately 98.32% upon 20 kg COD/(m3·d) OLR. The components of volatile fatty acids are acetate and propionate, and the rapid scavenging of propionate accumulation was the difference between R1 and the control. The INT-ETS activity of R1 was consistently higher than that of R0 and R2, and the electron transfer efficiencies increased by 68.78% and 131.44%, respectively. Meanwhile, the CV curve analysis showed that the current of R1 was 40% higher than R3 (temporary addition of Fe3O4-NPs), indicating that multiple electron transfer modes might coexist. High-throughput analysis further revealed that it was difficult to reverse the progressive deterioration of system performance with increasing OLR by simply reconfiguring bacterial community structure and abundance, demonstrating that the Fe3O4-NPs-mediated DIET pathway is a prerequisite for establishing multiple electron transfer systems. This study provides a long-term and multi-scale assessment of the gaining effect of Fe3O4-NPs in anaerobic digestion scale-up devices, and provides technical support for their practical engineering applications.

Potential of ZnO nanoparticles for multi-drug resistant Escherichia coli having CRISPR-Cas from poultry market in Lahore.

BACKGROUND AND OBJECTIVES: Apart from known factors such as irrational use of antibiotics and horizontal gene transfer, it is now reported that clustered regularly interspaced short palindromic repeats (CRISPR) are also associated with increased antimicrobial resistance. Hence, it is critical to explore alternatives to antibiotics to control economic losses. Therefore, the present study aimed to determine not only the association of CRISPR-Cas system with antibiotic resistance but also the potential of Zinc Oxide nanoparticles (ZnO-NPs) for avian pathogenic Escherichia coli (APEC) isolated from poultry market Lahore. MATERIALS AND METHODS: Samples (n = 100) were collected from live bird markets of Lahore, and isolates were confirmed as Escherichia coli (E. coli) using the Remel One fast kit, and APEC was identified using PCR. The antibiotic resistance pattern in APEC was determined using the minimum inhibitory concentration (MIC), followed by genotypic confirmation of antibiotic-resistant genes using the PCR. The CRISPR-Cas system was also identified in multidrug-resistant (MDR) isolates, and its association with antibiotics was determined using qRT-PCR. The potential of ZnO-NPs was evaluated for multidrug-resistant (MDR) isolates by MIC. RESULTS: All isolates of APEC were resistant to nalidixic acid, whereas 95% were resistant to chloramphenicol and 89% were resistant to streptomycin. Nineteen MDR APEC were found in the present study and the CRISPR-Cas system was detected in all of these MDR isolates. In addition, an increased expression of CRISPR-related genes was observed in the standard strain and MDR isolates of APEC. ZnO-NPs inhibited the growth of resistant isolates. CONCLUSIONS: The findings showed the presence of the CRISPR-Cas system in MDR strains of APEC, along with the potential of ZnO-NPs for a possible solution to proceed. This highlights the importance of regulating antimicrobial resistance in poultry to reduce potential health consequences.

New psychoactive substances - 96 cases of deaths related to their use based on the material originating from forensic toxicological practice.

Among the emerging investigative fields, forensic medicine and toxicology lead to analyzing fatalities in medico-legal expert opinion formulating. While discussing the problem, the authors have selected 96 fatal cases from their expert practice including the period from 2010 to 2023, in which deaths were connected with taking new psychoactive substances (NPS's) belonging to various chemical categories, mainly synthetic cathinones (SC), synthetic cannabinoids (SCan) and non-medical synthetic opioids (NSO). In the investigated cases, toxicological analysis revealed 37 NPS's and their 9 metabolites. The cases involved the use of SC's (64 cases - 67 %), Scan's, including their metabolites (10 cases - 10 %) and NSO's, including their metabolites (6 cases - 6 %). The remaining cases involved the simultaneous use of NSO with SC and/or SCan, including their metabolites (8 cases - 8 %), or SC with SCan (5 cases - 5 %). In three cases (3 %), compounds belonging to other groups were taken. In twenty-five cases, more than one NPS was found. Moreover, in twenty-seven cases, ethyl alcohol was also detected at the concentration range of 0.6-3.6 ‰. The concentration of xenobiotics determined in blood represented extensive ranges of concentration. The victims were at the age of 16-58 years of life. The group included eleven women (11 %). Generally, the deaths related to NPS's were predominantly of an accidental character (81 %), while the manner of death in sixteen cases (17 %) was suicide, including hanging (5 cases), jumping from a great height (3 cases), self-injury and exsanguination (1 case), as well as acute drug intoxication (6 cases) and intoxication with central nervous system hypoxia after an hanging (1 case). Among the analyzed cases there were two victims of homicide (2 %), in one of which the perpetrator being under the influence of the mixture of the synthetic opioid U-47700 and synthetic cannabinoid AB-FUBINACA. In twenty-eight cases, medications used in psychiatry were found, which suggested that the victims were struggling with mental problems before death. As it was implied by the available information, more than 36 % of the victims had mental problems.

Antivirulence activities of Rutin-loaded chitosan nanoparticles against pathogenic Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is an infectious bacterium that is frequently found in healthcare settings and the community. This study aimed to prepare rutin-loaded chitosan nanoparticles (Rut-CS NPs) and assess their antibacterial activity against pathogenic strains of S. aureus. RESULTS: The synthesized Rut-CS NPs exhibited an amorphous morphology with a size ranging from 160 to 240 nm and a zeta potential of 37.3 mV. Rut-CS NPs demonstrated significant antibacterial activity against S. aureus strains. Following exposure to Rut-CS NPs, the production of staphyloxanthin pigment decreased by 43.31-89.63%, leading to increased susceptibility of S. aureus to hydrogen peroxide. Additionally, visual inspection of cell morphology indicated changes in membrane integrity and permeability upon Rut-CS NPs exposure, leading to a substantial increase (107.07-191.08%) in cytoplasmic DNA leakage in the strains. Furthermore, ½ MIC of Rut-CS NPs effectively inhibited the biofilm formation (22.5-37.5%) and hemolytic activity (69-82.59%) in the S. aureus strains. CONCLUSIONS: Our study showcases that Rut-CS NPs can serve as a novel treatment agent to combat S. aureus infections by altering cell morphology and inhibiting virulence factors of S. aureus.

Self-Assembly Hypoxic and ROS Dual Response Nano Prodrug as a New Therapeutic Approach for Glaucoma Treatments.

Glaucoma is an irreversible blinding eye disease characterized by retinal ganglion cell (RGC) death.Previous studies have demonstrated that protecting mitochondria and activating the CaMKII/CREB signaling pathway can effectively protect RGC and axon. However, currently treatments are often unsatisfactory, and the pathogenesis of glaucoma requires further elucidation. In this study, a ROS-responsive dual drug conjugate (OLN monomer) is first designed that simultaneously bonds nicotinamide and oleic acid. The conjugate self-assembled into nanoparticles (uhOLN-NPs) through the aggregation of multiple micelles and possesses ROS scavenging capability. Then, a polymer with a hypoxic response function is designed, which encapsulates uhOLN-NPs to form nanoparticles with hypoxic and ROS responses (HOLN-NPs). Under hypoxia in RGCs, the azo bond of HOLN-NPs breaks and releases uhOLN-NPs. Meanwhile, under high ROS conditions, the thioketone bond broke, leading to the dissociation of nano-prodrug. The released nicotinamide and oleic acid co-scavenge ROS and activate the CaMKII/CREB pathway, protecting mitochondria in RGCs. HOLN-NPs exhibit a significantly superior protective effect on R28 cells in glutamate models of glaucoma. The accumulation of HOLN-NPs in retinal RGCs lead to significant inhibition of RGC apoptosis and axonal damage in vivo. Notably, HOLN-NPs provide a new therapeutic approach for patients with neurodegenerative disease.

Facile synthesis of ZnO nanoparticles using Nigella Sativa extract and its role as catalyst in production of bio-oil and degradation of methylene blue dye.

Zinc Oxide (ZnO) nanoparticles (NPs) were synthesized using an environmentally benign biogenic approach employing an extract of kernels of Nigella Sativa (kalonji). The presence of primary and secondary metabolites in Nigella Sativa extract acted as the capping and reducing agent. The as-synthesized ZnO NPs were characterized using various advanced techniques i.e., UV, SEM, XRD, EDS, TGA, DSC, and FTIR spectra. UV characterization of ZnO NPs revealed a peak within the 350-400 cm-1 range, confirming their successful formation. XRD spectra revealed that the particles possess a nano-rods and platelets structure, with an average size of 65 nm. XRD analysis revealed that the particles possess a size of 65 nm with a nano-rods and platelets structure. FTIR spectra of the ZnO NPs exhibited a peak at a wavenumber range of 500-600 cm-1. The newly fabricated ZnO NPs were utilized in a pyrolysis reaction for the production of high-yield bio-oil, resulting in a maximum yield of 65.6 % at 350 °C. The spectra of the bio-oil display distinct peaks at 1340 cm-1, 2923.6 cm-1, and 1617 cm-1, which suggest the existence of phenolic and carbonyl chemicals. After incubating for 24 h under UV light, they also demonstrated significant catalytic degradation of methylene blue dye. The highest degradation was recorded to be an average of 71 % in 60 min of UV exposure. Taken together, ZnO NPs developed by eco-benign methods have the potential to be implemented as a novel catalytic system in the production of bio-oil as well as the remediation of dye-harboring industrial wastewater.

Targeting DNA damage repair mechanism by using RAD50-silencing siRNA nanoparticles to enhance radiotherapy in triple negative breast cancer.

Radiotherapy (RT) is one of major therapeutic modalities in combating breast cancer. In RT, ionizing radiation is employed to induce DNA double-strand breaks (DSBs) as a primary mechanism that causes cancer cell death. However, the induced DNA damage can also trigger the activation of DNA repair mechanisms, reducing the efficacy of RT treatment. Given the pivotal role of RAD50 protein in the radiation-responsive DNA repair pathways involving DSBs, we developed a novel polymer-lipid based nanoparticle formulation containing RAD50-silencing RNA (RAD50-siRNA-NPs) and evaluated its effect on the RAD50 downregulation as well as cellular and tumoral responses to ionizing radiation using human triple-negative breast cancer as a model. The RAD50-siRNA-NPs successfully preserved the activity of the siRNA, facilitated its internalization by cancer cells via endocytosis, and enabled its lysosomal escape. The nanoparticles significantly reduced RAD50 expression, whereas RT alone strongly increased RAD50 levels at 24 h. Pretreatment with RAD50-siRNA-NPs sensitized the cancer cells to RT with ∼2-fold higher level of initial DNA DSBs as determined by a γH2AX biomarker and a 2.5-fold lower radiation dose to achieve 50 % colony reduction. Intratumoral administration of RAD50-siRNA-NPs led to a remarkable 53 % knockdown in RAD50. The pretreatment with RAD50-siRNA-NPs followed by RT resulted in approximately a 2-fold increase in DNA DSBs, a 4.5-fold increase in cancer cell apoptosis, and 2.5-fold increase in tumor growth inhibition compared to RT alone. The results of this work demonstrate that RAD50 silencing by RAD50-siRNA-NPs can disrupt RT-induced DNA damage repair mechanisms, thereby significantly enhancing the radiation sensitivity of TNBC MDA-MB-231 cells in vitro and in orthotopic tumors as measured by colony forming and tumor regrowth assays, respectively.