Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.

Neutrophils are a component of the tumor microenvironment and have been predominantly associated with cancer progression. Using a genetic approach complemented by adoptive transfer, we found that neutrophils are essential for resistance against primary 3-methylcholantrene-induced carcinogenesis. Neutrophils were essential for the activation of an interferon-γ-dependent pathway of immune resistance, associated with polarization of a subset of CD4- CD8- unconventional αß T cells (UTCαß). Bulk and single-cell RNA sequencing (scRNA-seq) analyses unveiled the innate-like features and diversity of UTCαß associated with neutrophil-dependent anti-sarcoma immunity. In selected human tumors, including undifferentiated pleomorphic sarcoma, CSF3R expression, a neutrophil signature and neutrophil infiltration were associated with a type 1 immune response and better clinical outcome. Thus, neutrophils driving UTCαß polarization and type 1 immunity are essential for resistance against murine sarcomas and selected human tumors.

A Comparative Analysis on the Innate Immune Responses of Cirrhinus mrigala Challenged with Pseudomonas aeruginosa and Fusarium oxysporum.

Microbes are the most significant ubiquitous pathogens that cause serious infections in freshwater fish, leading to tremendous economic losses. The present study was designed to investigate the extent of changes in cytokine expression, hemato-biochemical parameters, and tissue histology of Cirrhinus mrigala (C. mrigala) challenged with Pseudomonas aeruginosa (P. aeruginosa) and Fusarium oxysporum (F. oxysporum). Fish were divided into three major groups: control, P. aeruginosa-challenged, and F. oxysporum-challenged. The infection in both challenge assays was allowed to progress until 7 days post infection. Upregulated expression of TNF-α and IL-1ß was found in blood, gills, livers, and kidneys of the challenged fish. Significant differences were noted in hematological parameters of challenged fish. Alanine aminotransferase, aspartate aminotransferase, and alkaline aminotransferase levels also showed significant differences in infected and control groups. An increase in serum albumin and globulin and a decrease in total protein were noted in infected groups as compared to the control group. Severe histological alterations were noted in gill, liver, and kidney tissues of the infected groups as compared to control. The order of histological alteration index for P. aeruginosa challenge was liver > kidney > gills, and for F. oxysporum challenge it was kidney > liver > gills. These changes in fish infected by P. aeruginosa and F. oxysporum can be used as an effective and subtle index to monitor the physiological and pathological conditions of fish.

Studying the Mechanism of Interaction of Doxofylline with Human Lysozyme: A Biophysical and In Silico Approach.

In this study, multiple spectroscopic and computational methods were utilized to investigate the binding mechanism of doxofylline with lysozyme. The in vitro methods were used to obtain the binding kinetics and thermodynamics. UV-vis spectroscopy indicated the formation of complex between doxofylline and lysozyme. The Gibb's free energy and binding constant from UV-vis data was obtained as -7.20 kcal M-1 and 1.929 × 105 M-1, respectively. Doxofylline successfully quenched the fluorescence of lysozyme, confirming the formation of complex. The kq and Ksv values for the quenching of lysozyme's fluorescence by doxofylline were 5.74 × 1011 M-1 s-1 and 3.32 × 103 M-1, respectively. These values signified a moderate binding affinity between doxofylline and lysozyme. In synchronous spectroscopy, red shifts were observed for indicating the changes in microenvironment of lysozyme following the binding of doxofylline. The secondary structural analysis was determined using circular dichroism (CD) which revealed an increase in % α-helical as a result of doxofylline interaction. The binding affinity and flexibility of lysozyme upon complexation have been revealed via molecular docking and molecular dynamic (MD) simulations, respectively. According to the many parameters of the MD simulation, the lysozyme-doxofylline complex was stable under physiological conditions. All during the simulation time, hydrogen bonds were continuously present. The MM-PBSA binding energy for lysozyme and doxofylline binding was found to be -30.55 kcal mol-1.

Tenofovir antiviral drug solubility enhancement with ß-cyclodextrin inclusion complex and in silico study of potential inhibitor against SARS-CoV-2 main protease (Mpro).

Tenofovir (TFR) is an antiviral drug commonly used to fight against viral diseases infection due to its good potency and high genetic barrier to drug resistance. In physiological conditions, TFR is less water soluble, more unstable, and less permeable, limiting its effective therapeutic applications. In addition to their use in treating the Coronavirus disease 2019 (COVID-19), cyclodextrins (CDs) are also being used as a molecule to develop therapies for other diseases due to its enhance solubility and stability. This study is designed to synthesize and characterization of ß-CD:TFR inclusion complex and its interaction against SARS-CoV-2 (MPro) protein (PDB ID;7cam). Several techniques were used to characterize the prepared ß-CD:TFR inclusion complex, including UV-Visible, FT-IR, XRD, SEM, TGA, and DSC, which provided appropriate evidence to confirm the formation. A 1:1 stoichiometry was determined for ß-CD:TFR inclusion complex in aqueous medium from UV-Visible absorption spectra by using the Benesi-Hildebrand method. Phase solubility studies proposed that ß-CD enhanced the excellent solubility of TFR and the stability constant was obtained at 863 ± 32 M-1. Moreover, the molecular docking confirmed the experimental results demonstrated the most desirable mode of TFR encapsulated into the ß-CD nanocavity via hydrophobic interactions and possible hydrogen bonds. Moreover, TFR was validated in the ß-CD:TFR inclusion complex as potential inhibitors against SARS-CoV-2 main protease (Mpro) receptors by using in silico methods. The enhanced solubility, stability, and antiviral activity against SARS-CoV-2 (MPro) suggest that ß-CD:TFR inclusion complexes can be further used as feasible water-insoluble antiviral drug carriers in viral disease infection.

In-Silico Analysis of Phytocompounds of Olea europaea as Potential Anti-Cancer Agents to Target PKM2 Protein.

Globally, cancer is the second leading cause of mortality and morbidity. The growth and development of cancer are extremely complex. It is caused by a variety of pathways and involves various types of enzymes. Pyruvate kinase M2 (PKM2) is an isoform of pyruvate kinase, that catalyses the last steps of glycolysis to produce energy. PKM2 is relatively more expressed in tumour cells where it tends to exist in a dimer form. Various medicinal plants are available that contain a variety of micronutrients to combat against different cancers. The phytocompounds of the olive tree (Olea europaea) leaves play an important role in inhibiting the proliferation of several cancers. In this study, the phytocompounds of olive leaf extract (OLE) were studied using various in silico tools, such as pkCSM software to predict ADMET properties and PASS Online software to predict anticancer activity. However, the molecular docking study provided the binding energies and inhibition constant and confirmed the interaction between PKM2 and the ligands. The dynamic behaviour, conformational changes, and stability between PKM2 and the top three hit compounds (Verbascoside (Ver), Rutin (Rut), and Luteolin_7_O_glucoside (Lut)) are studied by MD simulations.

Modulation of antioxidant defence system in response to berberine in Candida albicans.

Emergence of multidrug resistant species of Candida is evolving, which advocates an urgent need for the development of new therapeutic strategies and antifungal drugs. Activation of antioxidant defence system in Candida albicans is known as forefront mechanism to escape drug toxicity. This study evaluated the role of antioxidant defence genes in the susceptibility to fluconazole in C. albicans and also determined the effect of berberine on growth, antioxidant enzymes and the expression of their genes in C. albicans isolates. Expression of major antioxidant genes was significantly increased in fluconazole-resistant isolates in comparison with the susceptible group. Antifungal susceptibility against berberine showed MIC values ranging from 125 to 500 µg/ml. Berberine treatment caused upregulation of mRNA expression and enzymatic activities of the targeted major antioxidants. Interestingly, C. albicans exhibited efficient antioxidant response at lower concentrations but could not sufficiently alleviate berberine-induced oxidative stress occurring at concentrations greater than 250 µg/ml. Therefore, berberine could serve as a potent Reactive Oxygen Species (ROS)-inducing agent, disrupting the antioxidant system especially in fluconazole-resistant C. albicans to overcome antifungal drug resistance. TAKE AWAYS: Evaluated the role of antioxidant enzymes in FLC resistance in C. albicans Studied the effect of berberine on growth of different C. albicans isolates Investigated the modulation of antioxidant enzymes by berberine in C. albicans Studied the effect of berberine on antioxidant gene expression in C. albicans.

Scientifically Formulated Avocado Fruit Juice: Phytochemical Analysis, Assessment of Its Antioxidant Potential and Consumer Perception.

The study's purpose was to find and create a nourishing fruit juice made from avocado to suit nutritional and health demands. In this regard, the avocado juice was formulated using a statistical technique, and its biochemical and phytochemical characteristics were evaluated. Statistically formulated fruit juice was evaluated for its sensory characteristics, proximate composition, nutrients and vitamins, total phenols and flavonoids, and for its antioxidant ability, in addition to a shelf-life test. The optimal amount of all ingredients included in the mathematical model for the preparation of the juice was 150 g of Persea americana (Avocado) fruit pulp, 12.5 g of honey and 100 mL of water. In fact, the composition of avocado juice was found to have higher phenolic (910.36 ± 0.215 mg EAG g-1/mL) and flavonoid (56.32 ± 1.26 mg QE g-1/ mL) amounts. DPPH, ABTS and FRAP antioxidant assays tended to be high compared with a standard. The shelf-life analysis indicated that the processed avocado juice (V7) had a long shelf life. In view of all these merits, a statistically formulated recipe for avocado fruit juice was recommended for the formulation of the most preferred health drink.

Reusable Nano-Zirconia-Catalyzed Synthesis of Benzimidazoles and Their Antibacterial and Antifungal Activities.

In this article, a zirconia-based nano-catalyst (Nano-ZrO2), with intermolecular C-N bond formation for the synthesis of various benzimidazole-fused heterocycles in a concise method is reported. The robustness of this reaction is demonstrated by the synthesis of a series of benzimidazole drugs in a one-pot method. All synthesized materials were characterized using 1HNMR, 13CNMR, and LC-MS spectroscopy as well as microanalysis data. Furthermore, the synthesis of nano-ZrO2 was processed using a standard hydrothermal technique in pure form. The crystal structure of nano-ZrO2 and phase purity were studied, and the crystallite size was calculated from XRD analysis using the Debye-Scherrer equation. Furthermore, the antimicrobial activity of the synthesized benzimidazole drugs was evaluated in terms of Gram-positive, Gram-negative, and antifungal activity, and the results were satisfactory.

Synergistic antimicrobial activity of N-methyl substituted pyrrolidinium-based ionic liquids and melittin against Gram-positive and Gram-negative bacteria.

In pharmaceutical industry, the prodrug approaches and drug-drug conjugates are being now vastly used to optimize the efficacy of the drugs for multipurpose. The combination or conjugation of antimicrobials agents with natural antimicrobials may lead to better synergistic antimicrobial activity. Currently, many publications show the potential of ionic liquids (ILs) as novel antimicrobials and even as active pharmaceutical ingredients. The current study showed the synthesis of novel pyrrolidinium-based ILs (Cx, x = 4, 6, 8, 10, 12) and their antibacterial activity alone and in combination with antimicrobial peptide, melittin (MEL), against clinically relevant microorganism, E. coli and S. aureus. The cytotoxicity of synthesized ILs was administered on HEK 293 cell line using MTT assay. The obtained results showed the dependency of antibacterial activity of ILs on alkyl chain length (C4 < C6 < C8 < C10 < C12). The remarkable improvement in the antibacterial efficiency of MEL was seen with ILs; however, antibacterial effect is more pronounced with IL having large alkyl chain length (C8, C10, and C12) at their minimal concentration with MEL to disrupt the cell membrane. In addition, the binding study and haemocompatibility results showed favourable biocompatibility and stability which could potentially improve its utility for the biomedical field. KEY POINTS: • The combination of melittin and pyrrolidinium-based ILs showed improved antibacterial activity against E. coli and S. aureus which may be used for developing new antibacterial agents. • Moreover, the cytotoxicity and haemocompatibility results showed excellent biocompatibility of the combinations on human cell line and human serum albumin, respectively, which could potentially improve its utility for the biomedical field.

Isolation and in vitro assessment of chicken gut microbes for probiotic potential.

Poultry production occupies an important place in the economy of any country. High broiler production in recent years has badly affected its profitability due to bad feed quality, excessive use of chemotherapeutic agents, emergence of diverse pathogens, and the deficiencies in management practices during rearing cycle. Microbiological improvement of the meat quality using potential probiotics can be beneficial for broiler farming. Present study was initiated to isolate chicken gastrointestinal tract (GIT) bacteria with probiotic potential. To isolate probiotics from chicken gut, alimentary canal of chickens of known sizes and ages was suspended in ringers soln. Under shaking conditions for overnight followed by serial dilutions of ringers soln. Bacterial isolates were analyzed via growth curve analysis, biochemical testing using RapID™ NF Plus Panel kit, molecular characterization, antimicrobial activity assay, antibiotic sensitivity assay, GIT adherence assay, bile salt and gastric acid resistant assay, and cholesterol assimilation assay. Four bacteria isolated in present study were identified as Limosilactobacillus antri strain PUPro1, Lactobacillus delbrueckii strain PUPro2, Lacticaseibacillus casei strain PUPro3, and Ligilactobacillus salivarius strain PUPro4. L. delbrueckii strain PUPro2 grew extremely fast. All isolates exhibited exceptional resistance to increasing concentrations of NaCl and bile salts with value of p >0.5. L. delbrueckii strain PUPro2 adhered to chicken ileum epithelial cells and demonstrated the highest viable counts of 320 colony forming units (CFUs). Antagonistic action was found in all isolates against P. aeruginosa, B. subtilis, B. proteus, and S. aureus, with value of p >0.5. Antibiotic susceptibility testing showed sensitivity to all the antibiotics used. Cholesterol assimilation was detected in all bacteria, with values ranging from 216.12 to 192.2 mg/dL. All isolates exhibited γ-hemolysis. In future, these bacteria might be tested for their impact on broilers meat quality and growth and can be recommended for their use as supplements for broilers diet with positive impact on poultry production.

Niosomal Bupropion: Exploring Therapeutic Frontiers through Behavioral Profiling.

Bupropion (Bup) belongs to the norepinephrine-dopamine reuptake inhibitor (NDRI) class and it is the only FDA-approved drug of its class for the treatment of major depressive disorder (MDD), sold under the name of Wellbutrin. Although bupropion is effective in suppressing the symptoms, its regular use and overdose might lead to seizures and liver failure. Thus, we aimed to nanoformulate bupropion onto a niosomal vesicle to improve its efficacy and achieve the same therapeutic effect at lower scheduled doses. A thin film hydration method was adopted to synthesize and optimize Bup entrapped niosomes using three different surfactants of the sorbitan ester series (Span 20, 40, and 60) in combination with cholesterol. The optimization data determined that the niosome formulated with a cholesterol-to-surfactant ratio of 1:1.5 is the most stable system, with the Bup entrapped niosomes containing Span 20 (Bup@N20C) exhibiting minimal in vitro and in vivo toxicity, and demonstrating the sustained release of Bup in artificial cerebrospinal fluid (ACSF). The Bup@N20C formulation showed increased exploration activity and reduced irregular movements in reserpine-induced depression in the adult zebrafish model, suggesting the potential for mood improvement through the suppression of depression-like behavior which was established by statistical analysis and trajectory data. The Bup@N20C-treated group even surpasses the treatment effect of the positive control group and is comparable to the control group. Hence, it can be inferred that niosomal formulations of Bup represent a promising delivery system capable of achieving the brain delivery of the cargo by bypassing the blood-brain barrier facilitated by their small architectural structure.

In-Vivo Bactericidal Potential of Mangifera indica Mediated Silver Nanoparticles against Aeromonas hydrophila in Cirrhinus mrigala.

The present study reports the green synthesis of silver nanoparticles from leaves' extract of Mangifera indica (M. indica) and their antibacterial efficacy against Aeromonas hydrophila (A. hydrophila) in Cirrhinus mrigala (C. mrigala). The prepared M. indica mediated silver nanoparticles (Mi-AgNPs) were found to be polycrystalline in nature, spherical in shapes with average size of 62 ± 13 nm. C. mrigala (n = ±15/group) were divided into six groups i.e., G1: control, G2: A. hydrophila challenged, G3: A. hydrophila challenged + Mi-AgNPs (0.01 mg/L), G4: A. hydrophila challenged + Mi-AgNPs (0.05 mg/L), G5: A. hydrophila challenged + Mi-AgNPs (0.1 mg/L) and G6: A. hydrophila challenged + M. indica extract (0.1 mg/L). Serum biochemical, hematological, histological and oxidative biomarkers were evaluated after 15 days of treatment. The liver enzyme activities, serum proteins, hematological parameters and oxidative stress markers were found to be altered in the challenged fish but showed retrieval effects with Mi-AgNPs treatment. The histological analysis of liver, gills and kidney of the challenged fish also showed regaining effects following Mi-AgNPs treatment. A CFU assay from muscle tissue provided quantitative data that Mi-AgNPs can hinder the bacterial proliferation in challenged fish. The findings of this work suggest that M. indica based silver nanoparticles can be promising candidates for the control and treatment of microbial infections in aquaculture.

Deep reinforcement learning enables adaptive-image augmentation for automated optical inspection of plant rust.

This study proposes an adaptive image augmentation scheme using deep reinforcement learning (DRL) to improve the performance of a deep learning-based automated optical inspection system. The study addresses the challenge of inconsistency in the performance of single image augmentation methods. It introduces a DRL algorithm, DQN, to select the most suitable augmentation method for each image. The proposed approach extracts geometric and pixel indicators to form states, and uses DeepLab-v3+ model to verify the augmented images and generate rewards. Image augmentation methods are treated as actions, and the DQN algorithm selects the best methods based on the images and segmentation model. The study demonstrates that the proposed framework outperforms any single image augmentation method and achieves better segmentation performance than other semantic segmentation models. The framework has practical implications for developing more accurate and robust automated optical inspection systems, critical for ensuring product quality in various industries. Future research can explore the generalizability and scalability of the proposed framework to other domains and applications. The code for this application is uploaded at https://github.com/lynnkobe/Adaptive-Image-Augmentation.git.

Assessment of Dietary Supplementation of Lactobacillus rhamnosus Probiotic on Growth Performance and Disease Resistance in Oreochromis niloticus.

Probiotics play a significant role in aquaculture by improving the growth, health, and survival rate of fish against pathogenic organisms. In the present study, we have evaluated the effects of a Lactobacillus rhamnosus (L. rhamnosus) probiotic on growth performance and disease resistance in Oreochromis niloticus (O. niloticus) fingerlings. Four different concentrations of L. rhamnosus (T1: 0.5 × 1010, T2: 1 × 1010, T3: 1.5 × 1010, and T4: 2 × 1010 CFU/kg feed) were administered to fish over a period of three months. L. rhamnosus treated fish revealed a high growth increment as compared to the control, and the values of macromolecules (amino acids, fatty acids, and carbohydrates) varied significantly among the treated and control groups. Levels of thyroid hormones were noted to be high in the probiotic-treated groups. A challenge assay was performed with Aeromonas hydrophila (A. hydrophila). The optimum calculated concentration of probiotics from the growth assay (1.5 × 1010 CFU/kg feed) was used for the challenge assay. Fish were divided into four groups as follows: control (Con), probiotic-treated (PL), infected (I), and infected + probiotic-treated (I + PL) groups. Significant variations in hematological parameters were observed among control and treated groups. Histopathological changes were recorded in infected fish, while the infected + probiotic-treated group showed less deformations indicating the positive effect of the probiotic supplementation. The survival rate of fish was also better in the probiotic-treated group. Based on these findings, we conclude that probiotic supplementation enhances the growth and improves immunity of O. niloticus. Therefore, we propose that probiotics can be used as promising feed supplements for promoting fish production and disease resistance in aquaculture.

Application of BCXZM Composite for Arsenic Removal: EPS Production, Biotransformation and Immobilization of Bacillus XZM on Corn Cobs Biochar.

This study determined the effect of Bacillus XZM extracellular polymeric substances (EPS) production on the arsenic adsorption capacity of the Biochar-Bacillus XZM (BCXZM) composite. The Bacillus XZM was immobilized on corn cobs multifunction biochar to generate the BCXZM composite. The arsenic adsorption capacity of BCXZM composite was optimized at different pHs and As(V) concentrations using a central composite design (CCD)22 and maximum adsorption capacity (42.3 mg/g) was attained at pH 6.9 and 48.9 mg/L As(V) dose. The BCXZM composite showed a higher arsenic adsorption than biochar alone, which was further confirmed through scanning electron microscopy (SEM) micrographs, EXD graph and elemental overlay as well. The bacterial EPS production was sensitive to the pH, which caused a major shift in the -NH, -OH, -CH, -C=O, -C-N, -SH, -COO and aromatic/-NO2 peaks of FTIR spectra. Regarding the techno economic analysis, it was revealed that USD 6.24 are required to prepare the BCXZM composite to treat 1000 gallons of drinking water (with 50 µg/L of arsenic). Our findings provide insights (such as adsorbent dose, optimum operating temperature and reaction time, and pollution load) for the potential application of the BCXZM composite as bedding material in fixed-bed bioreactors for the bioremediation of arsenic-contaminated water in future.

Fabrication and Characterization of PVA-WPI Based Nanofiber Mats for Improved Viability of Lactobacillus rhamnosus GG.

In the current study, whey protein-based nanofibers were fabricated to encapsulate Lactobacillus rhamnosus. Purposely, different ratios of PVA (polyvinyl alcohol) and WPI (whey protein isolate) were blended to fabricate nanofibers. Nanofiber mats were characterized in terms of particle size, diameter, tensile strength, elongation at break, and loading efficiency. Morphological and molecular characterizations were carried out using scanning electron microscopy (SEM) and Fourier transform infrared (FTIR). Moreover, in vitro viability under simulated gastrointestinal (GI) conditions and thermal stability were also assessed. The results reveal that by increasing the PVA concentration, the conductivity increased while the viscosity decreased. SEM micrographs showed that probiotics were successfully loaded within the nanofiber. The FTIR spectra show strong bonding between the encapsulating materials with the addition of probiotics. In vitro and thermal analyses revealed that the survival of encapsulated probiotics significantly (p < 0.05) improved. In a nutshell, PVA-WPI composite nanofibers have promising potential when used to enhance the viability and stability of probiotics under adverse conditions.

Role of Citrullus colocynthis and Psidium guajava Mediated Green Synthesized Silver Nanoparticles in Disease Resistance against Aeromonas hydrophila Challenge in Labeo rohita.

Green synthesis of metallic nanoparticles is an auspicious method of preparing nanoparticles using plant extracts that have lesser toxicity to animal cells and the host. In the present work, we analyzed the antibacterial activity of Citrullus colocynthis and Psidium guajava-mediated silver nanoparticles (Cc-AgNPs and Pg-AgNPs, respectively) against Aeromonas hydrophila (A. hydrophila) in an in vivo assay employing Labeo rohita (L. rohita). L. rohita were divided into six groups for both Cc-AgNPs and Pg-AgNPs treatments separately: Control, A. hydrophila infected, A. hydrophila + Ampicillin, A. hydrophila + Cc/Pg-AgNPs (25 µg/L), A. hydrophila + Cc/Pg-AgNPs (50 µg/L), and A. hydrophila + Cc/Pg-AgNPs (75 µg/L). Changes in different bio-indicators such as hematological, histological, oxidative stress, and cytokine analysis were observed. Interestingly, the infected fish treated with both types of AgNPs (Cc-AgNPs and Pg-AgNPs) exhibited a higher survival rate than the untreated infected fish and demonstrated signs of recovery from the infection, providing a compelling indication of the positive impact of phytosynthesized AgNPs. Disruptions in hematological and histological parameters were found in the infected fish. Both Cc-AgNPs and Pg-AgNPs showed recovery on the hematological and histological parameters. Analysis of oxidative stress and cytokine markers also revealed provoking evidence of the positive impact of Cc-AgNPs and Pg-AgNPs treatment against disease progression in the infected fish. The major finding of the study was that the higher concentrations of the nanoparticles (50 µg/L in the case of Cc-AgNPs and 75 µg/L in the case of Pg-AgNPs) were more effective in fighting against disease. In conclusion, our work presents novel insights for the use of green-synthesized AgNPs as economic and innocuous antibacterial candidates in aquaculture.

Synthesis and Characterization of Sulfur Nanoparticles of Citrus limon Extract Embedded in Nanohydrogel Formulation: In Vitro and In Vivo Studies.

The study aimed to synthesize non-noxious, clean, reliable, and green sulfur nanoparticles (SNPs) from Citrus limon leaves. The synthesized SNPs were used to analyze particle size, zeta potential, UV-visible spectroscopy, SEM, and ATR-FTIR. The prepared SNPs exhibited a globule size of 55.32 ± 2.15 nm, PDI value of 0.365 ± 0.06, and zeta potential of -12.32 ± 0.23 mV. The presence of SNPs was confirmed by UV-visible spectroscopy in the range of 290 nm. The SEM image showed that the particles were spherical with a size of 40 nm. The ATR-FTIR study showed no interaction, and all the major peaks were preserved in the formulations. An antimicrobial and antifungal study of SNPs was carried out against Gram-positive bacteria (Staph. aureus, Bacillus), Gram-negative bacteria (E. coli and Bordetella), and fungal strains (Candida albicans). The study showed that Citrus limon extract SNPs exhibited better antimicrobial and antifungal activities against Staph. aureus, Bacillus, E. coli, Bordetella, and Candida albicans at a minimal inhibitory concentration of 50 µg/mL. Different antibiotics were used alone and in combination with SNPs of Citrus limon extract to evaluate their activity against various strains of bacteria and fungal strains. The study showed that using SNPs of Citrus limon extract with antibiotics has a synergistic effect against Staph.aureus, Bacillus, E. coli, Bordetella, and Candida albicans. SNPs were embedded in nanohydrogel formulations for in vivo (wound healing) studies. In preclinical studies, SNPs of Citrus limon extract embedded within a nanohydrogel formulation (NHGF4) have shown promising results. To be widely used in clinical settings, further studies are needed to evaluate their safety and efficacy in human volunteers.

Assessing Leaching of Potentially Hazardous Elements from Cookware during Cooking: A Serious Public Health Concern.

The intake of toxic metals from cooking utensils through food is of growing concern to the medical community. This intake poses serious risk to human health. In many developing countries, different types of contaminated metals scraps are used to make cooking utensils. The leaching of both nutritionally essential and toxic metals in significant quantities from cookware during the cooking process results in food contamination and poses a substantial health risk. In the present study, the leaching of some toxic and potentially toxic metals from cooking utensils into different solutions and food was investigated. A preliminary survey indicated that the majority of individuals tend to use aluminum cookware due to its affordability, overlooking the potential health risks associated with these inexpensive and lower-quality cooking utensils. XRF analysis revealed that aluminum, steel, and copper cookware had K, Ca, Pb, Cd, Ni, V, Sn Mo, Zn, Bi, and Tb as contaminants. In addition, aluminum (3.2 ± 0.25 to 4.64 ± 0.20 g/kg) and copper cookware (2.90 ± 0.12 g/kg) were highly contaminated with lead. The time and pH-dependent study revealed that leaching of metals (Al, Pb, Ni, Cr, Cd, Cu, and Fe, etc.) into food was predominantly from anodized and non-anodized aluminum cookware. More metal leaching was observed from new aluminum cookware compared to old. Acidic food was found to cause more metals to leach during cooking. Blood metal analysis of the local population revealed the presence of high concentrations of Al, Pb, Cd, and Ni. In conclusion, leaching of toxic or potentially toxic metals from cookware into food, especially from anodized and non-anodized aluminum cookware, poses a potential public health risk. Practical applications: Cooking utensils are routinely used for the preparation of food. However, the harmful impact posed by these essential items is largely unknown. The current research briefly explains the toxic metals leaching from cookware in a pH-dependent manner and leaves a message to the public, especially in developing countries like Pakistan, regarding the type of cookware suitable for cooking purposes.

Association of Inflammatory Cytokine Levels with Extra Glandular Manifestations, Fatigue, and Disease Activity in Primary Sjögren's Syndrome in Saudi Patients: A Cross-Sectional Study.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease that can cause fatigue and extraglandular manifestations (EGMs). pSS is associated with cytokine network dysregulation, which may be related to the immune-mediated destruction of exocrine glands. OBJECTIVE: We determined cytokine levels and their relationship to EGMs, the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI), and fatigue in Saudi patients with pSS. METHODS: This study was a cross-sectional, single-center study. We included forty-one patients and 71 controls. Serum samples were collected from random healthy people and pSS patients who were followed in the rheumatology and pulmonary clinics of King Saud University Medical City in Riyadh, Saudi Arabia. Levels of the frequently studied cytokines were measured using Luminex xMAP technology. Each ESSDAI score and EGM were recorded, and the Arabic version of the fatigue severity scale (FSS) was applied to assess fatigue. The main outcome measures were cytokine levels in pSS Saudi patients using/not using immune-suppressive medications (ISMs). RESULTS: Thirty-six (87.8%) patients had one or more EGMs, and the mean ESSDAI score was 9.95 ± 7.73. There was a significant decrease in TNFα and IL-21 levels in the pSS group compared to those in the control group (p = 0.034 and p < 0.001, respectively), whereas IL-12 levels were significantly elevated in the pSS group (p = 0.002). Cytokine levels in patients who used ISMs were the same as those in patients who did not use medications. Decreased IL-1ß (p = 0.014), IL-2 (p = 0.035), IL-6 (p = 0.014), and IL-35 (p = 0.010) levels were observed in patients who had EGMs. Patients who had low disease activity exhibited low IL-10 (p = 0.018) and high IFN-α (p = 0.049), IFN-ß (p = 0.049), IL-1ß (p = 0.006), and IL-35 (p = 0.032) levels compared to patients with high disease activity. A negative association between a positive fatigue score and IL-1ß (p = 0.010), IL-2 (p = 0.037), IFN-α (p = 0.025), TNFα (p = 0.030), IL-17 (p = 0.029), IL-12 (p = 0.046), and IL-21 (p = 0.005) levels was found. CONCLUSIONS: Cytokine profiles correlate with EGMs, ESSDAI, and fatigue. Patients with controlled disease activity have a normal cytokine profile that is similar to that of controls.