Cisplatin, Cis-diamminedichloroplatinum (CDDP), is a platinum-based chemotherapy drug, and its chemotherapeutic use is restricted by nephrotoxicity. Inflammatory and apoptotic mechanisms play a central role in the pathogenesis of CDDP-induced acute kidney injury (AKI). The aim of this study was to compare the therapeutic potential of candesartan, angiotensin II receptor blocker, versus bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model of CDDP-induced nephrotoxicity. Adult male Wistar rats (n ¼ 40) were divided into four groups; Normal control: received saline injection, CDPP group: received CDDP injection (6 mg/kg single dose), Candesartan group: received candesartan (10 mg/kg/day) for 10 days þ CDDP at day 3, and Stem cells group: received CDDP þ BM-MSCs intravenously one day after CDDP injection. The rats were sacrificed seven days after CDDP injection. Significant elevation in serum creatinine and urea, renal levels of tumor necrosis factor (TNF)-a and monocyte chemoattractant protein (MCP)-1, renal expressions of nuclear factor kappa B (NF-kB), p38-mitogen-activated protein kinase (MAPK), caspase-3 and Bcl-2-associated x protein (Bax) were found in CDDP-injected rats when compared to normal rats. Both candesartan and BM-MSCs ameliorated renal function and reduced significantly the inflammatory markers (TNF-a , NF-jB, p38-MAPK and MCP-1) and apoptotic markers (caspase-3 and Bax) in renal tissue after CDDP injection. Candesartan as well as BM-MSCs have anti-inflammatory and anti-apoptotic actions and they can be used as nephroprotective agents against CDDP-induced nephrotoxicity. BM-MSCs is more effective than candesartan in amelioration of AKI induced by CDDP.
In this research work, nanofibrous hybrids are manufactured, characterized, and assessed as active antiviral and antibacterial membranes. In more detail, both polyvinyl alcohol (PVA) and thermoplastic polyurethane (TPU) nanofibrous (NF) membranes and their composites with embedded silver nanoparticles (Ag NPs) are manufactured by an electrospinning process. Their morphological structures have been investigated by a scanning electron microscope (SEM) which revealed a homogenous distribution and almost beads-free fibers in all manufactured samples. Characterization with spectroscopic tools has been performed and proved the successful manufacturing of Ag-incorporated PVA and TPU hybrid nanofibers. The crystalline phase of the nanofibers has been determined using an X-ray diffractometer (XRD) whose patterns showed their crystalline nature at an angle value (2θ) of less than 20°. Subsequent screening of both antiviral and antibacterial potential activities of developed nanohybrid membranes has been explored against different viruses, including SARS-Cov-2 and some bacterial strains. As a novel approach, the current work highlights potential effects of several polymeric hybrids on antiviral and antibacterial activities particularly against SARS-Cov-2. Moreover, two types of polymers have been tested and compared; PVA of excellent biodegradable and hydrophilic properties, and TPU of excellent mechanical, super elasticity, hydrophobicity, and durability properties. Such extreme polymers can serve a wide range of applications such as PPE, filtration, wound healing, etc. Consequently, assessment of their antiviral/antibacterial activities, as host matrices for Ag NPs, is needed for different medical applications. Our results showed that TPU-Ag was more effective than PVA-Ag as HIV-1 antiviral nanohybrid as well as in deactivating spike proteins of SARS-Cov-2. Both TPU-Ag and PVA-Ag nanofibrous membranes were found to have superior antimicrobial performance by increasing Ag concentration from 2 to 4 wt.%. Additionally, the developed membranes showed acceptable physical and mechanical properties along with both antiviral and antibacterial activities, which can enable them to be used as a promising functional layer in Personal Protective Equipment (PPE) such as (surgical gowns, gloves, overshoes, hair caps, etc.). Therefore, the developed functional membranes can support the decrease of both coronavirus spread and bacterial contamination, particularly among healthcare professionals within their workplace settings.
Homolog series based on three aromatic rings bearing terminal alkoxy chain of various lengths named 4-(4-(alkoxy)phenylimino)methyl)phenyl nicotinate (An) were synthesized. The alkoxy-chain length changed between 6, 8 and 16 carbons. Mesomorphic and optical properties were carried out via differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Elemental analyses, FT-IR and NMR spectroscopy were carried out to elucidate the molecular structures of the prepared derivatives. Mesomorphic results indicated that all the synthesized homologs (An) are monomorphic possessing the nematic (N) phase enantiotropically with wide thermal stability. Computational simulations were measured via density functional theory (DFT) theoretical calculation tool. The estimated thermal and geometrical parameters are in agreement with the experimental data. By discussing the estimated parameters, it was found that the molecular architecture, dipole moment and the polarizability of the investigated compounds are highly affected by the length of the attached terminal flexible chain and the location of the nitrogen atom in the other terminal aromatic ring. Binary phase diagrams of two corresponding homologs with different proportionating terminals were constructed, and their binary phase physical properties were discussed in terms of the temperature range and stability of the N phase.
Ginkgo biloba leaf extract (GIN) is a popular Chinese herbal medicine. It has a nephroprotective effect against the nephrotoxicity induced by the chemotherapeutic agent methotrexate (MTX). This work was designed to explore the testicular protective role of GIN on MTX-induced testicular injury in a rat model. The experimental protocol lasted for 10 days for the 4 studied groups. First group: received saline (normal control, NC group). The second group was administered GIN (100 mg/kg/day) orally for 10 days (GIN C). Third group: injected with MTX (20 mg/kg ip) only on the fifth day (MTX group). Fourth group: administered GIN for 10 days with MTX injection on the fifth day (GIN+MTX group). MTX induced testicular injury as evident by a marked rise in the malondialdehyde (MDA) content, interleukin-6 (IL-6) and IL-1β protein levels, nuclear factor kappa-B (NF-κB) protein expression, bcl-2 associated × protein (Bax) mRNA expression, p53 mRNA and protein expressions, and miRNA29-a expression along with a marked decline in the serum level of testosterone and superoxide dismutase (SOD) content in testicular tissue in relation to the NC group. Moreover, histopathological testicular damage with a notable decrease in the Johnsen score together with a significant elevation in the testicular injury score was observed in the MTX group in comparison to the NC group. The administration of GIN ameliorated the biochemical changes as well as the testicular histopathological findings and scores. GIN could protect against MTX-induced gonadotoxicity by its antioxidant, anti-inflammatory, antiapoptotic activities plus the regulation of the miRNA-29a testicular expression.
A new laterally fluorinated unsymmetric liquid crystalline homologous series, based on cinnamate linkage, named 2-fluoro-4-(4-(alkoxy)phenyl)diazenyl)phenyl cinnamate (In), was synthesized and evaluated via different experimental and computational tools. The series had different terminal alkoxy-chain lengths with a lateral F atom in the meta position with respect to the azo moiety. The experimental mesomorphic and optical investigations were carried out using differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Theoretical calculations and geometrical parameter predictions were conducted using the DFT program method at B3LYP/6-311G** level of theory. The results revealed that all the designed compounds exhibited the nematic (N) mesophase enantiotropically. The nematic stability and temperature range were impacted by the terminal alkoxy chain length. Compounds with the shortest chains (I6 and I8) showed a monotropic smectic A (SmA) phase, while the longest chain derivative, I16, possessed enantiotropic Sm A phase. Theoretical density functional theory (DFT) predictions were correlated with the practically observed data from the mesomorphic investigations. Data revealed that the terminal alkoxy and lateral F groups had an essential impact on the total energy of possible geometrical structures and their physical and thermal parameters.
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