Cutting Edge: Retinoic Acid Promotes Brain-homing of CD8+ T Cells during Congenital Cytomegalovirus Infection.

The most common congenital viral infection is CMV, which leads to numerous neurologic disabilities. Using a mouse model of congenital CMV, we previously determined that Ag-specific CD8+ T cells traffic to the brain in a CCR9-dependent manner. The mechanism by which these CD8+ T cells acquire a CCR9-dependent "brain-tropic" phenotype remains unclear.

The protective role of two oxindole derivatives is mediated by modulating NLRP3/caspase-1 and PI3K/AKT pathways in a preclinical animal model of hepatic ischemia reperfusion injury.

Unlabelled: Aim Hepatic ischemia reperfusion injury (HIRI) is a leading cause of mortality post liver transplantation, hypovolemic shock and trauma. In this study, we tested, on molecular bases, the possible protective role of two different derivatives of 2-oxindole in a preclinical model of HIRI in rats.

Main Methods: HIRI was operated in male Wistar albino rats and prophylactic treatment with oxindole-curcumin (Coxi) or oxindole-vanillin (Voxi) was carried out before the operation.

Design and synthesis of new dihydropyrimidine/sulphonamide hybrids as promising anti-inflammatory agents via dual mPGES-1/5-LOX inhibition.

A novel series of dihydropyrimidine/sulphonamide hybrids with anti-inflammatory properties have been developed and tested as dual mPGES-1/5-LOX inhibitors. assay, results showed that compounds , , , and were the most effective dual inhibitors of mPGES-1 and 5-LOX activities. Compound was the most potent dual inhibitor with IC values of 0.

Discovery and Anticancer Screening of Novel Oxindole-Based Derivative Bearing Pyridyl Group as Potent and Selective Dual FLT3/CDK2 Kinase Inhibitor.

Protein kinases regulate cellular activities and make up over 60% of oncoproteins and proto-oncoproteins. Among these kinases, FLT3 is a member of class III receptor tyrosine kinase family which is abundantly expressed in individuals with acute leukemia. Our previous oxindole-based hit has a particular affinity toward FLT3 (IC = 2.

Antibacterial and hemocompatibility potentials of nano-gold-cored alginate preparation against anaerobic bacteria from acne vulgaris.

Acne is a prevalent dermatological disease, with high global incidence, and is a health menace. The current study aimed to isolate and characterize the anaerobic bacteria responsible for the condition. Causes of a total of 70 acne-based bacterium isolates obtained from patients of mild, moderate, and severe acne, 24 were Clostridium innocuum, 21 were Lactobacillus plantarum, 13 were Anaerococcus prevotii, and 12 were Peptoniphilus asaccharolyticus.

New 2-oxoindole derivatives as multiple PDGFRα/ß and VEGFR-2 tyrosine kinase inhibitors.

Two new series of N-aryl acetamides 6a-o and benzyloxy benzylidenes 9a-p based 2-oxoindole derivatives were designed as potent antiproliferative multiple kinase inhibitors. The results of one-dose NCI antiproliferative screening for compounds 6a-o and 9a-p elucidated that the most promising antiproliferative scaffolds were 6f and 9f, which underwent five-dose testing. Notably, the amido congener 6f was the most potent derivative towards pancreatic ductal adenocarcinoma MDA-PATC53 and PL45 cell lines (IC = 1.

Enhanced Mucoadhesion of Thiolated β-Cyclodextrin by S-Protection with 2-Mercaptoethanesulfonic Acid.

This study aimed at designing an S-protected thiolated β-cyclodextrin (β-CD) exhibiting enhanced mucoadhesive properties. The native β-CD was thiolated with phosphorus pentasulfide resulting in a thiolated β-CD (β-CD-SH) and subsequently S-protected with 2-mercaptoethanesulfonate (MESNA) to form β-CD-SS-MESNA. The structure of the novel excipient was confirmed by H NMR and Fourier-transform infrared spectroscopy.

A density functional theory study on the potential application of Ni and Co doped ZnO nanosheets as a carrier for ciclopirox anticancer drug.

The Ni and Co doping effect on the ciclopirox (CPX) drug delivery performance of a ZnO ‎nanosheet (ZnO-NS) was investigated theoretically. Doping Ni and Co metals into the ZnO-NS ‎increased the adsorption energy of CPX from -7.9 to -27.

TD-DFT calculations, dipole moments, and solvatochromic properties of 2-aminochromone-3-carboxaldehyde and its hydrazone derivatives.

2-Aminochromone-3-carboxaldehyde (ACC) and its hydrazones (ACMHCA and ACMNPHTCA) with semicarbazide hydrochloride and -phenylthiosemicarbazide were synthesized and characterized by elemental analysis and spectral studies. The solvatochromic behavior of the title compounds in various solvents showed distinct bathochromic shifts on going from nonpolar to polar solvents, suggesting intramolecular-charge-transfer (ICT) solute-solvent interactions. The ground and excited state dipole moments of ACC, ACMHCA, and ACMNPHTCA were determined experimentally by the solvatochromic shift method using the Bilot-Kawski, Lippert-Mataga, Bakhshiev, Kawski-Chamma-Viallet functions, and a microscopic Reichardt's solvent polarity parameter ().

Combination of an Oxindole Derivative with (-)-β-Elemene Alters Cell Death Pathways in FLT3/ITD Acute Myeloid Leukemia Cells.

Acute myeloid leukemia (AML) is one of the cancers that grow most aggressively. The challenges in AML management are huge, despite many treatment options. Mutations in FLT3 tyrosine kinase receptors make the currently available therapies less responsive.

Indole-based FLT3 inhibitors and related scaffolds as potential therapeutic agents for acute myeloid leukemia.

Fms-like tyrosine kinase 3 (FLT3) mutation mechanisms are among the most common genetic abnormalities detected in about 30% of acute myeloid leukemia (AML) patients. These mutations are accompanied by poor clinical response, although all these progressions in identifying and interpreting biological AML bio-targets. Several small structured FLT3 inhibitors have been ameliorated to struggle against AML.

Biosynthesizing Extract-Mediated Silver Nanoparticles for MCF-7 Cell Lines Anti-Cancer Assay.

The unique consequence of green synthesis is that the mediator plant is able to release chemicals that are efficacious as reducing as well as stabilizing agents. In this work, the fruit pulp and leaf essences of have been used to manufacture silver nanoparticles through the green synthesis technique. The sculpturing of nanoparticles was accomplished by utilizing the reduction phenomenon that ensued due to the reaction between plant essences and the precursor solution.

Progress and prospects on vaccine development against monkeypox infection.

The monkeypox virus (MPOX) is an uncommon zoonotic illness brought on by an orthopoxvirus (OPXV). MPOX can occur with symptoms similar to smallpox. Since April 25, 2023, 110 nations have reported 87,113 confirmed cases and 111 fatalities.

Molecular modeling for sensing of cisplatin drug by graphdiyne: electronic study via DFT.

Context: By utilizing first-principles calculations, we studied the electronic properties of graphdiyne nanosheet (GDY) and its Si-doped counterpart, Si-GDY. Both GDY and Si-GDY sheet surfaces were examined for the drug cisplatin (CP) adsorption using adsorption energy, charge transfer, and changes in electrical conductivity as indicators. Pure GDY has little affinity for CP, according to this study.

Vanillin-Based Indolin-2-one Derivative Bearing a Pyridyl Moiety as a Promising Anti-Breast Cancer Agent via Anti-Estrogenic Activity.

The structure-based design introduced indoles as an essential motif in designing new selective estrogen receptor modulators employed for treating breast cancer. Therefore, here, a series of synthesized vanillin-substituted indolin-2-ones were screened against the NCI-60 cancer cell panel followed by in vivo, in vitro, and in silico studies. Physicochemical parameters were evaluated with HPLC and SwissADME tools.

New antiproliferative 3-substituted oxindoles inhibiting EGFR/VEGFR-2 and tubulin polymerization.

New 3-substituted oxindole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of compounds 6a-j was evaluated against 60 NCI cell lines. Among these tested compounds, compounds 6f and 6g showed remarkable antiproliferative activity, specifically against leukemia and breast cancer cell lines.

In silico drug discovery of SIRT2 inhibitors from natural source as anticancer agents.

Sirtuin 2 (SIRT2) is a member of the sirtuin protein family, which includes lysine deacylases that are NAD-dependent and organize several biological processes. Different forms of cancer have been associated with dysregulation of SIRT2 activity. Hence, identifying potent inhibitors for SIRT2 has piqued considerable attention in the drug discovery community.

NIR laser-conjugated glutathione-coated Mn-doped CuS nanoprisms as photothermal agent for cancer treatment.

The cancer treatment by laser-conjugated nanomaterial has become a new developing trend due of their unique physicochemical performance. The previous few studies reported the preparation of undoped CuS nanoprisms. The current research was concerned with the Mn doping effect on the CuS nanoprisms and its activity in tumor toxicity of M.

Discovery of oxindole-based FLT3 inhibitors as a promising therapeutic lead for acute myeloid leukemia carrying the oncogenic ITD mutation.

FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) patients. In the current study, the oxindole chemotype is employed as a structural motif for the design of new FLT3 inhibitors as potential hits for AML irradiation. Cell-based screening was performed with 18 oxindole derivatives and 5a-c inhibited 68%-73% and 83%-91% of internal tandem duplication (ITD)-mutated MV4-11 cell growth for 48- and 72-h treatments while only 0%-2% and 27%-39% in wild-type THP-1 cells.

Ni and Co binary and ternary complexes of 3-formylchromone: spectroscopic characterization, antimicrobial activities, docking and modeling studies.

Reactions of 3-formylchromone (L) with Ni(ii) and Co(ii) ions having different anions (acetate, perchlorate, nitrate, and chloride) yielded a series of binary and ternary octahedral complexes with the general formula [ML L' X (S) ]Z ·S, where M = Ni or Co, = 1-3, L' = auxiliary ligand = 8-hydroxyquinoline or 1,10-phenanthroline, = 1 or 2, X = acetate or chloride, = 0 or 2, S = HO or MeOH, = 0-2, Z = nitrate or perchlorate and = 0-1.5. Elemental and thermal analyses and infra-red, electronic, mass, magnetic susceptibility and molar conductivity measurements were successfully utilized to characterize the structures of the chromone complexes.

Patient Navigators for CKD and Kidney Failure: A Systematic Review.

Rationale & Objective: To what degree and how patient navigators improve clinical outcomes for patients with chronic kidney disease (CKD) and kidney failure is uncertain. We performed a systematic review to summarize patient navigator program design, evidence, and implementation in kidney disease.

Study Design: A search strategy was developed for randomized controlled trials and observational studies that evaluated the impact of navigators on outcomes in the setting of CKD and kidney failure.