In Vivo and in Vitro activity of colistin-conjugated bimetallic silver-copper oxide nanoparticles against Pandrug-resistant Pseudomonas aeruginosa.

BACKGROUND: Addressing microbial resistance urgently calls for alternative treatment options. This study investigates the impact of a bimetallic formulation containing colistin, silver, and copper oxide on a pandrug-resistant, highly virulent Pseudomonas aeruginosa (P. aeruginosa) isolate from a cancer patient at the National Cancer Institute, Cairo University, Egypt. METHODS: Silver nanoparticles (Ag NPs), copper oxide nanoparticles (CuO NPs), and bimetallic silver-copper oxide nanoparticles (Ag-CuO NPs) were synthesized using gamma rays, combined with colistin (Col), and characterized by various analytical methods. The antimicrobial activity of Col-Ag NPs, Col-CuO NPs, and bimetallic Col-Ag-CuO NPs against P. aeruginosa was evaluated using the agar well diffusion method, and their minimum inhibitory concentration (MIC) was determined using broth microdilution. Virulence factors such as pyocyanin production, swarming motility, and biofilm formation were assessed before and after treatment with bimetallic Col-Ag-CuO NPs. The in vivo efficacy was evaluated using the Galleria mellonella model, and antibacterial mechanism were examined through membrane leakage assay. RESULTS: The optimal synthesis of Ag NPs occurred at a gamma ray dose of 15.0 kGy, with the highest optical density (OD) of 2.4 at 375 nm. Similarly, CuO NPs had an optimal dose of 15.0 kGy, with an OD of 1.5 at 330 nm. Bimetallic Ag-CuO NPs were most potent at 15.0 kGy, yielding an OD of 1.9 at 425 nm. The MIC of colistin was significantly reduced when combined with nanoparticles: 8 µg/mL for colistin alone, 0.046 µg/mL for Col-Ag NPs, and 0.0117 µg/mL for Col-Ag-CuO NPs. Bimetallic Col-Ag-CuO NPs reduced the MIC four-fold compared to Col-Ag NPs. Increasing the sub-inhibitory concentration of bimetallic nanoparticles from 0.29 × 10-2 to 0.58 × 10-2 µg/mL reduced P. aeruginosa swarming by 32-64% and twitching motility by 34-97%. At these concentrations, pyocyanin production decreased by 39-58%, and biofilm formation was inhibited by 33-48%. The nanoparticles were non-toxic to Galleria mellonella, showing 100% survival by day 3, similar to the saline-treated group. CONCLUSIONS: The synthesis of bimetallic Ag-CuO NPs conjugated with colistin presents a promising alternative treatment for combating the challenging P. aeruginosa pathogen in hospital settings. Further research is needed to explore and elucidate the mechanisms underlying the inhibitory effects of colistin-bimetallic Ag-CuO NPs on microbial persistence and dissemination.

Exploring the anti-protozoal mechanisms of Syzygium aromaticum phytochemicals targeting Cryptosporidium parvum lactate dehydrogenase through molecular dynamics simulations.

Cryptosporidium parvum (C. parvum), a protozoan parasite, is known to induce significant gastrointestinal disease in humans. Lactate dehydrogenase (LDH), a protein of C. parvum, has been identified as a potential therapeutic target for developing effective drugs against infection. This study utilized a computational drug discovery approach to identify potential drug molecules against the LDH protein of C. parvum. In the present investigation, we conducted a structure-based virtual screening of 55 phytochemicals from the Syzygium aromaticum (S. aromaticum). This process identified four phytochemicals, including Gallotannin 23, Eugeniin, Strictinin, and Ellagitannin, that demonstrated significant binding affinity and dynamic stability with LDH protein. Interestingly, these four compounds have been documented to possess antibacterial, antiviral, anti-inflammatory, and antioxidant properties. The docked complexes were simulated for 100 ns using Desmond to check the dynamic stability. Finally, the free binding energy was computed from the last 10ns MD trajectories. Gallotannin 23 and Ellagitannin exhibited considerable binding affinity and stability with the target protein among all four phytochemicals. These findings suggest that these predicted phytochemicals from S. aromaticum could be further explored as potential hit candidates for developing effective drugs against C. parvum infection. The in vitro and in vivo experimental validation is still required to confirm their efficacy and safety as LDH inhibitors.

Changing patterns of bacterial profile and antimicrobial resistance in high-risk patients during the COVID-19 pandemic at a tertiary oncology hospital.

The widespread evolution of phenotypic resistance in clinical isolates over the years, coupled with the COVID-19 pandemic onset, has exacerbated the global challenge of antimicrobial resistance. This study aimed to explore changes in bacterial infection patterns and antimicrobial resistance during the COVID-19 pandemic. This study involved the periods before and during COVID-19: the pre-pandemic and pandemic eras. The surveillance results of bacterial isolates causing infections in cancer patients at an Egyptian tertiary oncology hospital were retrieved. The Vitek®2 or Phoenix systems were utilized for species identification and susceptibility testing. Statistical analyses were performed comparing microbiological trends before and during the pandemic. Out of 2856 bacterial isolates, Gram-negative bacteria (GNB) predominated (69.7%), and Gram-positive bacteria (GPB) comprised 30.3% of isolates. No significant change was found in GNB prevalence during the pandemic (P = 0.159). Elevated rates of Klebsiella and Pseudomonas species were demonstrated during the pandemic, as was a decrease in E. coli and Acinetobacter species (P < 0.001, 0.018, < 0.001, and 0.046, respectively) in hematological patients. In surgical patients, Enterobacteriaceae significantly increased (P = 0.012), while non-fermenters significantly decreased (P = 0.007). GPB species from either hematological or surgical wards exhibited no notable changes during the pandemic. GNB resistance increased in hematological patients to carbapenems, amikacin, and tigecycline and decreased in surgical patients to amikacin and cefoxitin (P < 0.001, 0.010, < 0.001, < 0.001, and 0.016, respectively). The study highlights notable shifts in the microbial landscape during the COVID-19 pandemic, particularly in the prevalence and resistance patterns of GNB in hematological and surgical wards.

Biofilm-mediated infections by multidrug-resistant microbes: a comprehensive exploration and forward perspectives.

A biofilm is a collection of microorganisms organized in a matrix of extracellular polymeric material. Biofilms consist of microbial cells that attach to both surfaces and each other, whether they are living or non-living. These microbial biofilms can lead to hospital-acquired infections and are generally detrimental. They possess the ability to resist the human immune system and antibiotics. The National Institute of Health (NIH) states that biofilm formation is associated with 65% of all microbial illnesses and 80% of chronic illnesses. Additionally, non-device-related microbial biofilm infections include conditions like cystic fibrosis, otitis media, infective endocarditis, and chronic inflammatory disorders. This review aims to provide an overview of research on chronic infections caused by microbial biofilms, methods used for biofilm detection, recent approaches to combat biofilms, and future perspectives, including the development of innovative antimicrobial strategies such as antimicrobial peptides, bacteriophages, and agents that disrupt biofilms.

Association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Egyptian children and adolescents.

BACKGROUND: Given the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents. METHODS: This was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA. RESULTS: The ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46-3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49-2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6-9.7]; P < 0.001. CONCLUSIONS: The ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents. IMPACT: Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19. To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents. The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19. The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.

The synergistic effect of nanocurcumin and donepezil on Alzheimer's via PI3K/AKT/GSK-3ß pathway modulating.

Alzheimer's disease (AD) hallmarks include amyloid-ßeta (Aß) and tau proteins aggregates, neurite degeneration, microglial activation with cognitive impairment. Phosphatidylinositol-3-kinase/protein kinase B/Glycogen synthase kinase-3-beta (PI3K/AKT/GSK-3) pathway is essential for neuroprotection, cell survival and proliferation by blocking apoptosis. This study aimed to assess protective role of nanocurcumin (NCMN) as strong antioxidant and anti-inflammatory agent with elucidating its synergistic effects with Donepezil as acetylcholinesterase inhibitor on AD in rats via modulating PI3K/AKT/GSK-3ß pathway. The experiment was performed on 70 male Wistar albino rats divided into seven groups (control, NCMN, Donepezil, AD-model, Donepezil co-treatment, NCMN only co-treatment, and NCMN+Donepezil combined treatment). Behavioral and biochemical investigations as cholinesterase activity, oxidative stress (malondialdehyde, reduced glutathione, nitric oxide, superoxidedismutase, and catalase), tumor necrosis factor-alpha, Tau, ß-site amyloid precursor protein cleaving enzyme-1 (BACE-1), Phosphatase and tensin homolog (Pten), mitogen-activated protein kinase-1 (MAPK-1), Glycogen synthase kinase-3-beta (GSK-3ß) and toll-like receptor-4 were evaluated. Treatment with NCMN improved memory, locomotion, neuronal differentiation by activating PI3K/AKT/GSK-3ß pathway. These results were confirmed by histological studies in hippocampus.

Exploring the Significance of Microglial Phenotypes and Morphological Diversity in Neuroinflammation and Neurodegenerative Diseases: From Mechanisms to Potential Therapeutic Targets.

Studying various microglial phenotypes and their functions in neurodegenerative diseases is crucial due to the intricate nature of their phenomics and their vital immunological role. Microglia undergo substantial phenomic changes, encompassing morphological, transcriptional, and functional aspects, resulting in distinct cell types with diverse structures, functions, properties, and implications. The traditional classification of microglia as ramified, M1 (proinflammatory), or M2 (anti-inflammatory) phenotypes is overly simplistic, failing to capture the wide range of recently identified microglial phenotypes in various brain regions affected by neurodegenerative diseases. Altered and activated microglial phenotypes deviating from the typical ramified structure are significant features of many neurodegenerative conditions. Understanding the precise role of each microglial phenotype is intricate and sometimes contradictory. This review specifically focuses on elucidating recent modifications in microglial phenotypes within neurodegenerative diseases. Recognizing the heterogeneity of microglial phenotypes in diseased states can unveil novel therapeutic strategies for targeting microglia in neurodegenerative diseases. Moreover, the exploration of the use of healthy isolated microglia to mitigate disease progression has provided an innovative perspective. In conclusion, this review discusses the dynamic landscape of mysterious microglial phenotypes, emphasizing the need for a nuanced understanding to pave the way for innovative therapeutic strategies for neurodegenerative diseases.

Genetic Association of Interleukin 16 Gene Polymorphisms (rs11556218 & rs4778889) with Type 1 Diabetes in Egyptian Children: A Case-Control Study.

BACKGROUND: Type 1 diabetes (T1D) is a serious chronic autoimmune condition. Even though the underlying reason for the onset of T1D is unknown, due to their effector and regulatory roles in immune responses, cytokines are essential in developing autoimmune disorders. Interleukin (IL)16 is an immunomodulatory cytokine implicated in several inflammatory and autoimmune diseases. OBJECTIVE: This study was designed to examine the association of IL16 gene polymorphisms, rs11556218 T > G and rs4778889 T > C, with the risk of T1D in Egyptian children. METHODS: Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, we analyzed rs11556218 T > G and rs4778889 T > C polymorphisms of the IL16 gene in 100 T1D subjects and 93 controls. RESULTS: Rs11556218 T > G polymorphism of the IL16 gene was not associated with the risk of developing T1D. Analysis of IL16 gene rs4778889 T > C showed that the TT genotype had a considerably higher risk of T1D than the TC genotype [OR = 2.195 (1.205-3.999)]. In comparison to patients with the C allele [OR = 0.6914 (0.38-1.2569)], patients with the T allele [OR = 1.45 (0.7956-2.6296)] were notably more likely to have T1D. A significant decrease was found in the frequency of GT (OR = 0.43, p = .03) and TC (OR = 0.32, p = .011) haplotypes of IL16 gene rs11556218 T > G and rs4778889 T > C polymorphisms in T1D patients compared with controls. CONCLUSION: IL16 gene rs4778889 T > C polymorphism might be associated with susceptibility to T1D. Egyptians with TT genotypes are more likely to develop T1D. However, GT and TC haplotypes of IL16 gene rs11556218 T > G and rs4778889 T > C polymorphisms highlight their protective role againstT1D disease.

Association of MTR and MTRR polymorphisms with recurrent pregnancy loss: a case control study.

BACKGROUND: In light of several epidemiological studies, the etiology of recurrent pregnancy loss is complex. One of the most frequent causes of women experiencing inexplicable recurrent pregnancy loss is maternal thrombophilia. Hence, the association between genetic polymorphisms causing thrombophilia and recurrent pregnancy loss needs to be explored. AIM: Is to study the relation of polymorphisms affecting folate pathway mainly, 5-Methytetrahydrofolate-Homocysteine Methyltransferase (MTR A2756G) and 5-Methytetrahydrofolate-Homocysteine MethyltransferaseReductase (MTRR A66G) with recurrent pregnancy loss. METHODS: It is a case-control study. Four hundred participants were enrolled. Two hundred participants with unexplained recurrent pregnancy loss (case group) and two hundred healthy fertile participants (control group). All participants were screened for (MTR A2756G) and (MTRR A66G). DNA was extracted using salting out method followed by genotyping via Real-time PCR. RESULTS: Mutant homozygous genotype (GG) in MTRR A66G was statistically significantly among RPL group in comparison to controls. (GG vs. AA) had odds ratio and confidence interval of 1.22(1.12-2.23), P = 0.012. (GG) increased the liability 1.2 folds for recurrent pregnancy loss. Mutant homozygous genotype (GG) in MTR A2756G was not correlated with the risk of recurrent pregnancy loss. (GG vs.AA) = (1.13(0.56-2.29)), P = 0.7 CONCLUSION: MTRR A66G increases susceptibly for recurrent pregnancy loss among Egyptian women.

Effect of human umbilical cord blood-mesenchymal stem cells on cisplatin-induced nephrotoxicity in rats.

BACKGROUND: Cisplatin-containing regimen is an effective treatment for several malignancies. However, cisplatin is an important cause of nephrotoxicity. So, many trials were performed to transplant stem cells systemically or locally to control cisplatin-induced nephrotoxicity. Stem cell therapeutic effect may be dependent on the regulation of inflammation and oxidant stress. AIM: To investigate the effect of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) on the histological structure, the oxidant stress, and the inflammatory gene expression in an experimental model of cisplatin-induced nephrotoxicity in rats. METHOD: The rats were divided into 6 equal groups (each of 10 rats): Group I included normal rats that received no treatment. Group II included healthy rats that received IV hUCB-MSCs. Group III included untreated cisplatin-induced nephrotoxic rats. Group IV included cisplatin-induced nephrotoxic rats that received magnesium (Mg) injections after injury. Group V was injected with hUCB-MSCs after injury. Group VI received both Mg and hUCB-MSCs after injury. In tissue homogenates, reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) activities were measured. Quantitative real-time-polymerase chain reaction (qRT-PCR) was performed to assess iNOS, TLR4, and NF-kB gene expression. Hematoxylin and eosin (H&E) staining was performed to study the histological structure of the kidney. Immunohistochemical staining of iNOS and NF-κB was performed, as well. RESULTS: Disturbed kidney functions, oxidative status, and histological structure were seen in the rats that received cisplatin. Treated groups showed improvements in kidney functions, oxidative status, and histological structure, particularly in the combined treatment group. CONCLUSION: In the cisplatin-induced nephrotoxicity model, hUCB-MSCs could improve the functional and morphological kidney structure by modulation of oxidative and inflammatory status.

Cytotoxic and Apoptotic Effects of Green Synthesized Silver Nanoparticles via Reactive Oxygen Species-Mediated Mitochondrial Pathway in Human Breast Cancer Cells.

Due to their exceptional physicochemical features, green synthesized silver nanoparticles (AgNPs) have been of considerable interest in cancer treatment. In the present study, for the first time, we aimed to green synthesize AgNPs from Euphorbia retusa and explore their anticancer potential on human breast cancer (MCF-7) cells. First, the green synthesized AgNPs (EU-AgNPs) were well characterized by UV-visible spectroscopy, Fourier transmission infrared (FTIR) spectrum, XRD, scanning and transmission electron microscopy (SEM and TEM), and EDX techniques. The characterization data exhibited that EU-AgNPs were spherical in shape and crystalline in nature with an average size of 17.8 nm. FTIR results established the presence of active metabolites in EU-AgNPs. Second, the anticancer effect of EU-AgNPs was evaluated against MCF-7 cells by MTT and neutral red uptake (NRU) assays. Moreover, morphological changes, ROS production, MMP, and apoptotic marker genes were also studied upon exposure to cytotoxic doses of EU-AgNPs. Our results showed that EU-AgNPs induce cytotoxicity in a concentration-dependent manner, with an IC50 value of 40 µg/mL. Morphological changes in MCF-7 cells exposed to EU-AgNPs also confirm their cytotoxic effects. Increased ROS and decreased MMP levels revealed that EU-AgNPs induced oxidative stress and mitochondrial membrane dysfunction. Moreover, ROS-mediated apoptosis was confirmed by elevated levels of proapoptotic marker genes (p53, Bax, caspase-3, and caspase-9) and reduced levels of an antiapoptotic gene (Bcl-2). Altogether, these findings suggested that EU-AgNPs could induce potential anticancer effects through ROS-mediated apoptosis in MCF-7 cells.

Detection of Hepatitis E Virus (HEV) Among Ruminant Animals.

BACKGROUND: HEV is endemic in several Middle Eastern countries including Saudi Arabia, which hosts the annual pilgrimage for Muslims from around the world. One of the Hajj rituals is the sacrifice of animals, including camels, cows, goats, and sheep. HEV Zoonosis is established in swine and other suspected species, including deer, rabbits, dromedary, and Bactrian camels. HEV was identified in small, domesticized animals like goats, cows, sheep, and horses. We previously investigated HEV seroprevalence in Camels. This study aimed to evaluate HEV seroprevalence in other highly consumed ruminants in Saudi Arabia, namely cows, sheep, and goats. METHODS: Sera from cows (n = 47), goats (n = 56), and sheep (n = 67) were analyzed for the presence of HEV-IgG by using in-house developed ELISA assays. RESULTS: The highest seroprevalence was found in sheep (62.7%), followed by cows (38.3%), and then goats (14.3%), with a p-value of < 0.001. No other demographic characteristics of the animals were significantly correlated with the HEV seroprevalence. CONCLUSIONS: This study provides baseline data as the first study on the seroprevalence of HEV in ruminant animals in Saudi Arabia. The high seroprevalence found in sheep and cows must be further investigated for the potential zoonotic HEV transmission to humans. Further studies are needed to investigate the active viremia in these animal species through nucleic acid detection and sequencing to provide data on the circulating HEV genotypes among the targeted animal species. The detection of HEV in different animal products, such as milk, liver, and others, also remains an important study area to consider.

Hepatitis B and Hepatitis C Infections among Female Inmates in a Prison in Jeddah, Saudi Arabia.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major health concerns worldwide. Recent data indicate a decline in prevalence in the Saudi population; however, there are no data on the prevalence in prisoners. This study is the first to investigate the prevalence of viral hepatitis in female inmates in Jeddah, Saudi Arabia. This study aimed to explore the prevalence of HBV and HCV infections and to assess the knowledge and attitudes related to these infections among inmates. METHODS: Inmates were interviewed using a pre-designed questionnaire, and their blood samples were tested for HBV and HCV infections using serology, PCR, and phylogenetic analysis. RESULTS: The overall prevalence of HBV infection in the study population was 4.4%. The age group > 25 years was predominantly affected; 11.1% of the infected cases were Saudi nationals, and 88.9% were non-Saudis. The prevalence of HCV infection was 2.4%. Among the studied variables, age and previous employment were significantly associated with positive HBV PCR, while conviction, knowledge about protection from sexually transmitted infections (STIs), knowledge about condom use for protection against STIs, and condom use for protection against STIs were significantly associated with HCV infection. CONCLUSIONS: This study shows higher HBV and HCV prevalence in the female prisoners in Briman prison compared to the general population. Uneducated prisoners, over 25 years old, and convicted of prostitution are more associated with both HBV and HCV infection. Future preventive plans should include screening new prisoners with these risk factors for HBV and HCV at the time of entry.

Graphene nanosheet reinforcement of polyurethane nanocomposite for green and sustainable photoluminescence, superhydrophobic, and anticorrosive paint.

A simple and environmentally friendly method was developed for smart and efficient waterborne polyurethane (PUR) paint. Sugarcane bagasse was recycled into reduced graphene oxide nanosheets (rGONSs). Both lanthanide-doped aluminate nanoparticles (LAN; photoluminescent agent, 7-9 nm) and rGONSs (reinforcement agent) were integrated into a waterborne polyurethane to produce a novel photoluminescent, hydrophobic, and anticorrosive nanocomposite coating. Using ferrocene-based oxidation under masked circumstances, graphene oxide nanosheets were produced from sugarcane bagasse. The oxidized semicarbazide (SCB) nanostructures were integrated into polyurethane coatings as a drying, anticorrosion, and crosslinking agent. Polyurethane coatings with varying amounts of phosphor pigment were prepared and subsequently applied to mild steel. The produced paints (LAN/rGONSs@PUR) were tested for their hydrophobicity, hardness, and scratch resistance. Commission Internationale de l'éclairage (CIE) Laboratory parameters and photoluminescence analysis established the opacity and colourimetric properties of the nanocomposite coatings. When excited at 365 nm, the luminescent transparent paints emitted a strong greenish light at 517 nm. The anticorrosion characteristics of the coated steel were investigated. The phosphor-containing (11% w/w) polyurethane coatings displayed the most pronounced anticorrosion capability and long-persistent luminosity. The prepared waterborne polyurethane paints were very photostable and durable.

Preparation of thermochromic ink from anthocyanidin-encapsulated alginate nanoparticles for anticounterfeiting applications.

In order to make commercial products less vulnerable to counterfeiting, thermochromic inks have proven to be a viable authentication strategy. Herein, we developed a thermochromic ink for authentication by combining an anthocyanidin (ACYD) extract with alginate (ALG). To increase the anthocyanidin/alginate ink stability, a mordant (ferrous sulfate) was employed to tie up the anthocyanidin biomolecules with alginate. ACYD was extracted from red-cabbage and then immobilized into alginate to serve as an environmentally friendly spectroscopic probe. Thermochromic composite inks (ACYD@ALG) were made by adjusting the content of anthocyanidin. A homogenous blue film (608 nm) was printed on a paper surface and investigated by the CIE Lab coordinate system. The blue color transformed into reddish (477 nm) when heated from 35°C to 65°C. Nanoparticles (NPs) of anthocyanidin/mordant (ACYD/M) were examined for their size and morphology to indicate diameters of 80-90 nm, whereas the ACYD/M-encapsulated alginate nanoparticles showed diameters of 120-150 nm. Multiple analytical techniques were utilized to examine the printed papers. The mechanical and rheological performance of both stamped sheets and ink fluid were explored. The cytotoxicity and antimicrobial efficacy of ink (ACYD@ALG) were investigated.

Preparation, Characterization, In Vitro Biological Evaluation, DFT Calculations, and Molecular Docking Investigations of 1H-Imidazole-2-Carboxylic acid and Histidine-Based Mixed-Ligand Complexes.

Mixed-ligand complexes incorporating 1H-Imidazole-2-Carboxylic acid (IMCA) and Histidine (LHIS) show promise for biomedical and biotechnological applications. This study synthesizes and characterizes FeIMCALHIS, CoIMCALHIS, and NiIMCALHIS coordination compounds using metal chloride salts (FeCl3.6H2O, CoCl2.6H2O, NiCl2.6H2O) in ethanolic solutions. The complexes are characterized by spectroscopic methods (IR, UV-vis, and mass spectra), elemental analysis, conductivity, magnetic, and thermal analysis. Molar conductivity indicates their non-electrolytic nature. UV-vis spectra reveal absorption bands with pathochromic shifts, and electronic spectra show characteristic metal-ligand transitions, indicating their structural configuration and coordination geometry. 3D geometry optimization shows six-coordination around Fe(III) and Co(II) in FeIMCALHIS and CoIMCALHIS, and four-coordination around Ni(II) in NiIMCALHIS. Analysis of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) suggests decreased electron donation ability upon coordination. Electronic structure parameters (HOMO, LUMO, ionization potential, energy gap, electron affinity, chemical potentials, and electronegativity) provide further insights into stability and reactivity. The metal complexes exhibit enhanced antimicrobial, antioxidant, and anti-inflammatory activity compared to individual ligands, with FeIMCALHIS showing notable antimicrobial activity. Molecular docking analysis reveals strong binding interactions with target proteins, highlighting their potential therapeutic applications.

Design, Synthesis, and Molecular Docking of Novel Miscellaneous Chalcones as p38α Mitogen-Activated Protein Kinase Inhibitors.

New chalcones were synthesized and evaluated to serve as p38-α type of mitogen-activated protein kinase (MAPK) inhibitors. According to the National Cancer Institute, the findings indicated that at a 10 µM dosage, compounds 3a and 6 were the most active among all the compounds examined, with mean growth inhibition% of 94.83 and 58.49, respectively. In 5-dose testing, they showed anticancer activity in the micro-molar range with GI50 in the range of 1.41-46.1 and 2.07-31.3 µM, respectively. Besides, powerful activity, especially against the leukaemia cell lines and good selectivity to cancer cells compared to normal PCS-800-017 with a selectivity index=12.41 and 23.77, respectively. Compounds 3a and 6 inhibited p38α MAPK with IC50 values of 0.1462±0.0063 and 0.4356±0.0189 µM, correspondingly. 3a showed good inhibition for HL-60(TB) cells and induced cell cycle arrest in HL-60(TB) cells at the G2/M phase. Besides, it elevated the total apoptosis by 14.68-fold and increased the caspase-3 level by 3.52-fold compared with doxorubicin, which raised it by 4.30-fold, inducing apoptosis by acting as caspase-dependent inducers. These results suggest that 3a is a promising antiproliferative and p38α MAPK inhibitor, confirmed by molecular docking with high compatibility 3a with the p38α MAPK binding site.

Synthesis and Biological Evaluation of Benzamide Compounds as Insecticides Agents Against Spodoptera Frugiperda (Lepidoptera: Noctuidae).

Due to its severe damage, Spodoptera frugiperda is receiving attention as one of the biggest dangers to world food security. Although there are numerous insecticides that are widely and successfully used to control S. frugiperda, they do not have an immediate effect. In our work focusing for synthesized twelve novel benzamide derivatives and examined their insecticidal effectiveness against S. frugiperda larvae in their second & fourth larvae instars, with the aim of further improving the insecticidal activity based on combination principles. Several spectroscopic methods, including elemental analysis, NMR & infrared spectroscopy, were employed for confirming the structure of the newly designed products. It has been discovered that most compounds show good of promising efficacy. With an LC50 of 24.8 mg/L for larvae in the second instar & 56.2 mg/L for larvae in the fourth instar, compound 23 was the most active. Among all compounds 11, 22 and 20 exhibited excellent results. Furthermore, a number of biological and histopathological properties of the demonstration compounds of the produced goods under laboratory conditions were also examined. This work further demonstrates the anti-proliferation of S. frugiperda and offers fresh ideas for the manufacture of benzamide derivatives.

Metabolomic Profiling and DNA-Fingerprinting of Newly Recorded White-Flowered Populations of Salvia lanigera Poir. in Egypt.

Salvia lanigera Poir. is a small herbaceous perennial species with violet flowers that grows in low-altitude deserts, and sandy loam. During the collection of S. lanigera, unusual populations with white flowers were found. Therefore, the two populations (violet- and white-flowered) were subjected to comparative investigations, including DNA fingerprinting, chemical composition, and biological evaluation. The two populations showed DNA variations, with 6.66 % polymorphism in ISSR and 25 % in SCoT markers. GC/MS and UHPLC/HRMS of aqueous methanol extracts, led to the tentative identification of 43 and 50 compounds in both populations. In addition, the structures of nine compounds, including four first-time reported compounds in the species, were confirmed by NMR. Furthermore, the total extracts exhibited weak radical scavenging activity against DPPH and a lower inhibitory effect towards acetylcholinesterase. In conclusion, the obtained data suggested that the white-colored flower could be an additional important character record for the Egyptian S. lanigera.

New prospective insecticidal agents based on N-(arylcarbamothioyl)arylmide derivatives against Spodoptera frugiperda: Design, Synthesis, Toxicological, Biological, Biomedical Studies and Antibacterial Activity.

In this work, a novel series of N-(arylcarbamothioyl)arylmide) 2-11 were synthesized by treating One-Pot three-multicomponent of Aroyl chloride ammonium isothiocyanate and amine compounds under refluxing conditions. Using spectroscopic methods, the chemical structure of the novelty developed compounds were investigated. After five days, the proposed derivatives' insecticidal bioassay was assessed using the median lethal concentration (LC50) against the second & fourth larvae of Spodoptera frugiperda as toxicity agents. The findings showed that, to varying degrees, every tested substance exerted insecticidal effects on S. frugiperda larvae in both of their instars. Compound 9 was the most poisonous of them all, having an LC50 against larvae in their second and fourth instars of 60.45 and 123.21 mg/L, respectively. Additionally, a few biological and biochemical characteristics of the substances that were generated in a lab setting were also looked at. Furthermore, this work discusses how to discover novel compounds that may one day be employed as insecticidal agents. Finally, all the designed components were monitored for their antibacterial effectiveness toward both Gram-positive & Gram-negative bacteria.