Investigating the Anti-inflammatory Effect of Quinoline Derivative: N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine Hydrochloride Loaded Soluble Starch Nanoparticles Against Methotrexate-induced Inflammation in Experimental Model.

BACKGROUND: It is necessary to develop advanced therapies utilizing natural ingredients with anti-inflammatory qualities in order to lessen the negative effects of chemotherapeutics. RESULTS: The bioactive N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine hydrochloride (NIQBD) was synthesized. After that, soluble starch nanoparticles (StNPs) was used as a carrier for the synthesized NIQBD with different concentrations (50 mg, 100 mg, and 200 mg). The obtained StNPs loaded with different concentrations of NIQBD were coded as StNPs-1, StNPs-2, and StNPs-3. It was observed that, StNPs-1, StNPs-2, and StNPs-3 exhibited an average size of 246, 300, and 328 nm, respectively. Additionally, they also formed with homogeneity particles as depicted from polydispersity index values (PDI). The PDI values of StNPs-1, StNPs-2, and StNPs-3 are 0.298, 0.177, and 0.262, respectively. In vivo investigation of the potential properties of the different concentrations of StNPs loaded with NIQBD against MTX-induced inflammation in the lung and liver showed a statistically substantial increase in levels of reduced glutathione (GSH) accompanied by a significant decrease in levels of oxidants such as malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), matrix metalloproteinase 9/Gelatinase B (MMP-9), and levels of inflammatory mediators including interleukin 1-beta (IL-1ß), nuclear factor kappa-B (NF-κB) in both lung and liver tissues, and a significant decrease in levels of plasma homocysteine (Hcy) compared to the MTX-induced inflammation group. The highly significant results were obtained by treatment with a concentration of 200 mg/mL. Histopathological examination supported these results, where treatment showed minimal inflammatory infiltration and congestion in lung tissue, a mildly congested central vein, and mild activation of Kupffer cells in liver tissues. CONCLUSION: Combining the treatment of MTX with natural antioxidant supplements may help reducing the associated oxidation and inflammation.

Boosting Sinh Cosh Optimizer and arithmetic optimization algorithm for improved prediction of biological activities for indoloquinoline derivatives.

Quantitative Structure Activity Relation (QSAR) models are mathematical techniques used to link structural characteristics with biological activities, thus considered a useful tool in drug discovery, hazard evaluation, and identifying potentially lethal molecules. The QSAR regulations are determined by the Organization for Economic Cooperation and Development (OECD). QSAR models are helpful in discovering new drugs and chemicals to treat severe diseases. In order to improve the QSAR model's predictive power for biological activities of naturally occurring indoloquinoline derivatives against different cancer cell lines, a modified machine learning (ML) technique is presented in this paper. The Arithmetic Optimization Algorithm (AOA) operators are used in the suggested model to enhance the performance of the Sinh Cosh Optimizer (SCHO). Moreover, this improvement functions as a feature selection method that eliminates superfluous descriptors. An actual dataset gathered from previously published research is utilized to evaluate the performance of the suggested model. Moreover, a comparison is made between the outcomes of the suggested model and other established methodologies. In terms of pIC50 values for different indoloquinoline derivatives against human MV4-11 (leukemia), human HCT116 (colon cancer), and human A549 (lung cancer) cell lines, the suggested model achieves root mean square error (RMSE) of 0.6822, 0.6787, 0.4411, and 0.4477, respectively. The biological application of indoloquinoline derivatives as possible anticancer medicines is predicted with a high degree of accuracy by the suggested model, as evidenced by these findings.

Therapeutic Impact of Costus (Saussurea lappa) Against Ehrlich Solid Tumor-Induced Cardiac Toxicity and DNA Damage in Female Mice.

Breast cancer remains the most common cause of cancer deaths among women globally. Ehrlich solid tumor (EST) is a transplantable tumor model for simulating breast cancer. This study aims to describe the protective role of costus (Saussurea lappa) root against EST-induced cardiac toxicity. Forty female mice were randomly and equally divided into four groups (G1, control group; G2, costus group; G3, EST group; G4, EST + costus). The results showed that compared to the control, EST induced a significant increase in lactate dehydrogenase, creatine kinase, creatine kinase myoglobin, aspartate aminotransferase, and alkaline phosphatase activities; in potassium, chloride ion, cholesterol, triglyceride, and low density lipoprotein levels; in DNA damage and cardiac injury; and in p53 and vascular endothelial growth factor expression. Conversely, EST induced a significant decrease in sodium ion and high density lipoprotein levels and Ki67 expression compared to the control. Treatment of EST with costus improved cardiac toxicity, lipid profiles, electrolytes, and apoptosis, and protected against EST. This indicates the potential benefits of costus as an adjuvant in the prevention and treatment of cardiac toxicity.

A new route for manufacturing poly(aminophosphonic)-functionalized poly(glycidyl methacrylate)-magnetic nanocomposite - Application to uranium sorption from ore leachate.

A high-energy ball milling of magnetite nanoparticles with amino-phosphonic functionalized poly(glycidyl methacrylate) polymer is used for manufacturing a highly efficient magnetic sorbent for U(VI) sorption from aqueous solutions. The Uranyl ions were adsorbed through the binding with amine and phosphonic groups as confirmed by Fourier Transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses. The maximum sorption capacity (up to 270 mg U g-1) occurred at pH = 3-4; Langmuir isotherm well describes the sorption process. Small-size particles allow achieving fast uptake (within ≈90 min of contact); and the kinetic profiles are modeled by the pseudo-second order rate equation. Uranium is successfully desorbed from loaded sorbent using 0.25 M NaHCO3 solution: Sorbent can be recycled with minimal decrease in sorption and desorption efficiency for at least 6 cycles. The sorbent is efficiently used for U(VI) recovery from the acidic leachates of U-bearing ores (after precipitation pre-treatment). Sorption capacity approaches 190 mg U g-1 despite the presence of high concentrations of Fe and Si: the sorbent has a marked preference for U(VI) (confirmed by distribution ratios and selectivity coefficients).

A pilot study of Livin gene and Yes-associated protein 1 expression in hepatocellular carcinoma patients.

BACKGROUND: Livin gene and Yes-Associated Protein 1 (YAP1 (play a pivotal role in organ size control and tumorigenesis. AIM: In the present pilot study, we investigate the expression of Livin gene and YAP1 in hepatitis C virus (HCV) associated hepatocellular carcinoma (HCC) compared to other HCV patients and controls.Methods: the studied patients were divided into three groups 30 patients in each group in addition to 30 healthy subjects as a control group. Relative quantification of Livin gene and YAP-1 were assessed by quantitative Real Time RT-PCR (qPCR) in all studied patients and healthy controls. other laboratory investigations were done including complete blood count (CBC),international normalized ratio (INR) as well as liver function tests and tumor markers. RESULTS: Significant overexpression of Livin gene and YAP-1 was detected in HCC group followed by Hepatitis C Virus (HCV) untreated group then HCV treated group. The relative quantitation (RQ) of both genes showed positive correlation to the carcinoembryonic antigen (CEA) level and a significant relation was found between higher level of Livin and YAP1 genes and tumor size. The overall survival rate was low in those patients with high levels of Livin and YAP 1 genes so they were considered as indicators of a bad prognosis. CONCLUSION: There is overexpression of Livin gene and YAP1 in hepatocellular carcinoma patients. They can be used as indicators of bad prognosis of the disease pathway together with low survival rate.

Synthesis and in vitro antiproliferative activity of new 11-aminoalkylamino-substituted chromeno[2,3-b]indoles.

To search for new biological activities of the chromeno[2,3-b]indoles, the 5-oxa analog of the indolo[2,3-b]quinolines that are known to have a potent antitumor activity, a series of 11-amino derivatives with various substituents at the C-2 position were prepared. The synthesis of the chromeno[2,3-b]indole structure involves the cyclization of 2-phenoxy-3-indolecarboxylates 3, accessible from the indole-3-carboxylate 1 and phenols 2, producing the chromeno[2,3-b]indol-11(6H)-ones 4, which is followed by dehydroxychlorination with phosphorus oxychloride to afford the 11-chlorochromeno[2,3-b]indoles 5. The treatment of 5 with various amines produced the corresponding 11-aminated chromeno[2,3-b]indoles 6, while some of the 11-ω-aminoalkylamino derivatives 6 were transformed into the 11-ω-sulfonylaminoalkylamino derivatives 8. The antiproliferative activity of these 11-aminochromeno[2,3-b]indoles 6 and 8 in vitro were tested using MV4-11 (human leukemia), A549 (lung cancer), HCT116 (colon cancer), and the normal mice fibroblast (BALB/3T3) and their potencies were described.