Adsorption and bacterial performance of Nd2O3 modified Ag nanoparticles with enhanced degradation of methylene blue.

Our study focused on the optical behavior, methylene blue (MB) dye degradation potential, antibacterial performance, and silver and trioxide mineral interaction with different bacterial species. We found that the addition of silver nanoparticles (Ag NPs) to neodymium oxide (Nd2O3) resulted in a significant response, with an enlargement of the inhibition zone for bacterial species such as Staphylococcus aureus and Escherichia coli. Specifically, the inhibition zone for S. aureus increased from 9.3 ± 0.5 mm for pure Nd2O3 to 16.7 ± 0.4 mm for the Ag/Nd2O3 nano-composite, while for E. coli, it increased from 8.8 ± 0.4 mm for Nd2O3 to 15.9 ± 0.3 mm for Ag/Nd2O3. Furthermore, the optical behavior of the composites showed a clear band-gap narrowing with the addition of Ag NPs, resulting in enhanced electronic localization. The direct and indirect transitions reduced from 6.7 to 6.1 eV and from 5.2 to 2.9 eV, respectively. Overall, these results suggest that the Ag/Nd2O3 nano-composite has potential applications in sensor industries and water treatment, thanks to its enhanced optical behavior, antibacterial performance, and efficient MB degradation capabilities. In terms of MB degradation, the Ag/Nd2O3 mixed system exhibited more efficient degradation compared to pure Nd2O3. After 150 min, the MB concentration in the mixed system decreased to almost half of its starting point, while pure Nd2O3 only reached 33%.

Pregnenolone protects the liver against doxorubicin-induced cellular injury by anti-inflammatory, antioxidant, and antiapoptotic mechanisms: role of Keap1/Nrf2/HO-1 and P-glycoprotein.

OBJECTIVE: Doxorubicin (DOX) is a widely used cytotoxic anthracycline antibiotic characterized by increased adverse effects that limit its clinical usefulness. Pregnenolone is a pregnane X receptor (PXR) agonist that increases the expression of xenobiotic transporters with anti-inflammatory and antioxidant potential. Thus, we hypothesized that pregnenolone would protect against DOX-induced hepatotoxicity. MATERIALS AND METHODS: Male Wistar rats (180-200 g) were randomized into four groups (n = 7): Control, Control + Pregnenolone (35 mg/kg/day, orally), DOX (15 mg/kg, i.p.) single dose on day five, and Pregnenolone + DOX. All treatments continued for seven consecutive days. Twenty-four hours after the last treatment, serum and liver tissues were collected for biochemical and histopathological assessment. The possible interaction between pregnenolone and DOX on cell viability was tested in HepG2 cells in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: DOX treatment resulted in hepatic damage and fibrosis with increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver samples of the DOX-treated group showed increased oxidative stress [malondialdehyde (MDA) and total nitrite/nitrate and decreased reduced glutathione (GSH) and superoxide dismutase (SOD)], increased hepatic tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), transforming growth factor-beta1 (TGF-ß1), and mRNA of interleukin-1beta (IL-1ß) and interleukin-6 (IL-6). Pretreating the rats with pregnenolone antagonized these DOX-induced effects. Moreover, pregnenolone upregulated the hepatic expression of Nrf2, heme oxygenase-1 (HO-1), and P-glycoprotein and decreased Keap1, opposing the effects of DOX. Moreover, pregnenolone prevented the DOX-induced activation and nuclear translocation of NFκB and increased cleaved caspase-3. Pregnenolone potentiated DOX-mediated cytotoxicity in HepG2 cells. CONCLUSIONS: These results illustrate the protective effects of pregnenolone against DOX-induced hepatotoxicity without limiting its anticancer activity.

Venoms classification and therapeutic uses: a narrative review.

The mere glimpse of venomous animals has always terrified humans because of the devastating effects of their venoms. However, researchers across the globe have isolated therapeutically active ingredients from these venoms and continue to explore them for drug leads. These efforts lead to the discovery of therapeutic molecules that the US-FDA has approved to treat different diseases, such as hypertension (Captopril), chronic pain (Ziconotide), and diabetes (Exenatide). The main active constituents of most venoms are proteins and peptides, which gained more attention because of advancements in biotechnology and drug delivery. The utilization of newer screening approaches improved our understanding of the pharmacological complexity of venom constituents and facilitated the development of novel therapeutics. Currently, with many venom-derived peptides undergoing different phases of clinical trials, more are in pre-clinical drug development phases. This review highlights the various sources of venoms, their pharmacological actions, and the current developments in venom-based therapeutics.

The emerging role of lipid nanosystems and nanomicelles in liver diseases.

Nanoparticles (NPs) exhibit remarkable potential in the diagnosis and treatment of various liver ailments, including primary liver cancer or hepatocellular carcinoma (HCC), liver cirrhosis, viral hepatitis, and alcoholic and non-alcoholic liver diseases. High surface area-to-volume ratio with distinct physicochemical and bio-pharmaceutical properties have contributed numerous benefits to NPs, such as high intracellular uptake and efficient drug delivery capabilities stemming from their ability to encapsulate a diverse range of drugs. Lipid-based nanosystems have demonstrated significant potential as reliable and efficient transport vehicles for a variety of actives, including small interfering RNA, targeting the liver, owing to their excellent in vivo compatibility, biodegradable nature, and non-toxic properties. Multiple aspects of various lipid-based materials, lipid nanosystems like solid lipid NPs, nanovesicles such as nanoemulsions, liposomes, and nanomicelles for liver-specific active targeting have been comprehensively reviewed. Ongoing and completed clinical trials of lipid nanosystems developed for HCC, hepatic fibrosis, and hepatitis are tabulated. Types of receptors and ligands typically used for active liver targeting in HCC are extensively discussed. The US FDA's recent approval for the use of Onpattro (Patisiran) injection to treat polyneuropathy in adult patients is indicative of the rapid development of lipid nanosystems employed for hepatic targeting. Nanoemulsions loaded with diagnostic imaging agents for multi-modal liver imaging were briefly discussed. Emerging technologies are being developed to integrate desirable properties of nanoparticles (NPs), including high stability, efficient drug loading, opsonization avoidance, active liver targeting, and facilitation of endosomal escape. Clinical translations of many lipid NPs for drug and gene therapy applications targeting different liver diseases are expected in the near future.

Optical, Thermal, and Electrical Characterization of Polyvinyl Pyrrolidone/Carboxymethyl Cellulose Blend Scattered by Tungsten-Trioxide Nanoparticles.

The polymeric material polyvinyl pyrrolidine/carboxymethyl cellulose (PVP/CMC) was mixed with different quantities of tungsten-trioxide nanoparticles (WO3 NPs). The samples were created using the casting method and Pulsed Laser Ablation (PLA). The manufactured samples were analyzed by utilizing various methods. The halo peak of the PVP/CMC was located at 19.65°, confirming its semi-crystalline nature, as shown in the XRD analysis. FT-IR spectra of pure PVP/CMC composite and PVP/CMC composite incorporated with various contents of WO3 obtained a shift in band locations and change in intensity. Optical band gap was calculated via UV-Vis spectra, which decreased when increasing the laser-ablation time. Thermogravimetric analyses (TGA) curves showed that samples' thermal stability had improved. The frequency-dependent composite films were used to determine AC conductivity of the generated films. When increasing the content of tungsten-trioxide nanoparticles, both (ε') and (ε'') increased. The incorporation of tungsten trioxide enhanced the ionic conductivity of PVP/CMC/WO3 nano-composite to a maximum of 10-8 S/c. It is expected that these studies will have a significant impact on several utilizations, such as energy storage, polymer organic semiconductors, and polymer solar cells.

Physical and biological changes of copper oxide and hydroxyapatite filled in polycaprolactone scaffolds: Cellular growth behavior and antibacterial activity.

Burns have placed a devastating burden on public health because of leading to an increased risk of infection. Therefore, the development of an effective antibacterial dressing for wound healing is essential. The present work is mainly based on the fabrication of biodegradable polycaprolactone (PCL) films through a simple and cheap process of polymer casting using a novel combination of hydroxyapatite (HAP), cuprous oxide (Cu2O) NPs and graphene oxide (GO) nanosheets which have a great effect in preventing colonization and to modify the wound dreasing. The compositions played a key role in decreasing the contact angle of PCL from 47.02° to 11.53°. Further, the cell viability exhibited a viable cell ratio of 81.2% after 3 days of culturing. Moreover, the highest antibacterial activity was obtained from the film of Cu2O@PCl and showed high impact results in antibacterial behavior.

Fenofibrate ameliorates letrozole-induced polycystic ovary in rats via modulation of PPARα and TNFα/CD95 pathway.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a prevalent endocrine health problem during the childbearing period that seriously affects fertility in females. Fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, showed beneficial effects in models of endocrine disturbances. Thus, we evaluated the potential therapeutic effect of fenofibrate in experimental PCOS. MATERIALS AND METHODS: Rats received oral fenofibrate (300 mg/kg/day) for three weeks following a three-week PCOS induction regimen using oral letrozole (1 mg/kg/day). We determined the changes in body weight, levels of serum testosterone, insulin, anti-Müllerian hormone (AMH), ovarian malondialdehyde (MDA), superoxide dismutase (SOD), and tissue tumor necrosis factor-alpha (TNFα) and CD95 protein expressions. The tissue expression of interleukin-10 (IL10) and PPARα genes was determined. RESULTS: Letrozole-treated rats showed successful induction of PCOS, confirmed by histopathology and significantly increased body weight, testosterone, insulin, AMH, and MDA, and decreased SOD. Ovaries of untreated PCOS rats showed increased TNFα and CD95 and decreased PPARα and IL10 expression. Administration of fenofibrate ameliorated the letrozole-induced PCOS changes. CONCLUSIONS: Fenofibrate-mediated amelioration of PCOS in rats is attributed partly to its antioxidant, anti-inflammatory, and anti-apoptotic properties and activation of PPARα.

Subchronic administration of mitoxantrone and the influence of enzyme inhibitors on its induced cardiotoxicity in mice: role of NRF-2/CYP2E1.

OBJECTIVE: Mitoxantrone (MTX)- induced cardiotoxicity is a clinical concern that is limiting its use. The aim of this paper, therefore, was to investigate the subchronic administration of MTX plus nonspecific/specific inhibitors of CYP450/2E1, to assess the extent of oxidative-induced injury by measuring levels of oxidative cardiac and injury biomarkers in mice and to evaluate the effects of CYP2E1 on caspase 3 activity and nuclear factor erythroid 2-related factor-2 (NRF-2). MATERIALS AND METHODS: Mice (n = 32) were divided into four treatment groups of eight: control, MTX, MTX + 4-methlypyrazole (4MP) and MTX + disulfiram (Disf). After 6 weeks of treatments, blood and heart samples were collected. RESULTS: Liquid chromatography-mass spectrometry (LCMS) analysis of MTX-treated plasma samples revealed several metabolites with different retention times. Cardiac antioxidant enzymes and creatine kinase (CK) levels were not significantly different among the groups. However, cardiac troponin and caspase 3 activity were significantly raised, with increased CYP2E1 expressions and reduced NRF-2 expression. Tissue damage was observed in all the treatment groups, including MTX, leading to the conclusion that MTX-induced cardiotoxicity was mediated by CYP2E1 activity, which initiated caspase 3 production, and decreased NRF-2 expression. CONCLUSIONS: Therefore, agents that inhibit CPY2E1 expression might attenuate MTX-induced cardiotoxicity by increasing NRF-2 expression.

Protective mechanisms of piperine against acetaminophen-induced hepatotoxicity may be mediated through TGFBRAP1.

OBJECTIVE: To investigate the possible protective mechanisms of piperine against acetaminophen (APAP)-induced hepatotoxicity in mice. MATERIALS AND METHODS: Mice were given APAP (650 mg/kg i.p. once) with or without pretreatment with piperine (50 mg/kg/day orally for 3 days). RESULTS: APAP caused liver toxicity as indicated by increased serum alanine aminotransferase and liver microscopic pathology, decreased hepatic superoxide dismutase and glutathione reductase activities, without affecting nuclear factor erythroid 2-related factor 2 (Nrf2) expression. APAP administration induced inflammation and apoptosis manifested as increased NF-κB p65 and dysregulation of caspase 3/Bcl2 expression, respectively. In addition, APAP increased the expression of transforming growth factor-ß receptor-associated binding protein 1 (TGFBRAP1). On the other hand, pretreatment with piperine improved liver function and structure, reserved hepatic antioxidative defense, and attenuated inflammatory and apoptotic markers. Interestingly, piperine administration enhanced hepatic TGFBRAP1 expression compared to APAP alone. CONCLUSIONS: The hepatoprotective effects of piperine against APAP are mediated via its antioxidant, anti-inflammatory, and anti-apoptotic effects, in addition to regulation of TGFBRAP1.

Prevalence and types of genetic polymorphisms of CYP2C19 and their effects on platelet aggregation inhibition by clopidogrel.

OBJECTIVE: The current study was conducted to determine the distribution of genetic polymorphisms in CYP2C19 in Iraqi patients and their role in inter-individual variability of clopidogrel efficacy. PATIENTS AND METHODS: A prospective controlled study was done on 100 patients under high risk of cardiovascular diseases who started clopidogrel prophylactic therapy. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine the existence of the CYP2C19 gene mutation. Vasodilator-stimulated phosphoprotein (VASP) index baseline besides one-month post-therapy was analyzed by dual-color flow cytometry analysis. RESULTS: Eight gene mutations of CYP2C19 were found (*1/*1), (*1/*2), (*1/*3), (*1/*8), (*1/*17), (*2/*2), (*2/*4), and (*3/*3) with higher prevalent CYP2C19*1 gene. Homozygous CYP2C19*1 allele was shown to be the rapid metabolizer comparing to the heterozygous CYP2C19*1 allele, whereas, CYP2C19*2 and CYP2C19*3 were resistant alleles and were present in 28% of patients. The analysis of VASP phosphorylation produces accurate inter-individual response variability in platelets inhibition by antiplatelet drugs. CONCLUSIONS: In vitro gene analysis and VASP index improve the clinical outcome of a patient candidate to clopidogrel as prophylaxis in cardiovascular events.

A modified formula for accurate determination of three-dimensional birefringence of fiber using modified subfringe integration method.

The development of the use of interferometric techniques in the study of the optical properties of materials encouraged many researchers to work on the derivation and development of the theoretical considerations and the equations used in the calculations of those properties. The form of these equations depends on the technique used and the cross section of the sample, and also on the method of calculating the optical path difference of light across the sample studied. A modified formula to calculate the three-dimensional birefringence distribution of the fiber, without the need to determine the refractive indices of the fiber in the parallel and perpendicular directions, was presented. The phase distribution of the simulated and experiment interferograms was obtained using subfringe integration method. The results obtained from the new method were compared with the calculated results of a well-known method (Z method) and the figures presented showed that the results of the two methods were close to each other.

Mechanisms underlying gastroprotective effect of paeonol against indomethacin-induced ulcer in rats.

Paeonol, a natural phenolic compound, possesses diverse beneficial effects including antioxidant and anti-inflammatory effects. Gastric ulcer is still the most prevalent irritant illness among the gastrointestinal diseases. The present study explored the protective effect of paeonol at two dose levels in indomethacin (IND)-induced gastric ulcer in rats. Forty-eight male Wistar rats were arranged into six groups: control, paeonol-treated, IND-treated, IND/paeonol (low and high doses)-treated, and ranitidine-treated groups. The oxidative status was evaluated by determining malondialdehyde level, superoxide dismutase activity, reduced glutathione content as well as hemoxygenase-1 (HO-1) gene expressions, and the antioxidant protein; NAD(P)H quinone oxidoreductase 1 (NQO1) immunostaining. The pro-inflammatory genes nuclear factor κB (NF-κB) and interleukin 1ß (IL-1ß) were estimated together with the proapoptotic gene of caspase 3. IND caused multiple gastric ulcers with evident oxidative damage and elevated pro-inflammatory and proapoptotic markers. Paeonol protected significantly, in a dose-dependent manner, the gastric mucosa from ulcerative lesion of IND similar to the reference drug ranitidine. Paeonol pretreatment diminished gastric oxidative stress and restored the gastric antioxidant capacity by elevating gastric gene expression of HO-1 and protein expression of NQO1. Paeonol also reduced NF-κB, IL-1ß, and caspase 3 gene expressions. In conclusion, paeonol offered a gastroprotection dependent on its antioxidant, anti-inflammatory, and antiapoptotic effects.

Efficient adenoviral-mediated ornithine transcarbamylase expression in deficient mouse and human hepatocytes.

100% of primary human hepatocytes infected with an adenoviral vector carrying beta-galactosidase expressed the exogenous gene. Expression was also achieved in > 40% of adult mouse hepatocytes in vivo. Normal levels of activity were achieved in mouse ornithine transcarbamylase (OTC)-deficient primary hepatocytes using another adenoviral vector carrying human OTC cDNA. Study of OTC-deficient primary human hepatocytes from a single patient confirmed the utility of adenoviral delivery of OTC. We describe adenoviral-mediated exogenous gene expression in human and mouse hepatocytes in vitro and in mouse liver in vivo. Data suggest that adenoviral vectors may be useful for correcting OTC deficiency.

Patient selection may affect gene therapy success. Dominant negative effects observed for ornithine transcarbamylase in mouse and human hepatocytes.

We have achieved significant improvement of ornithine transcarbamylase deficiency (OTCD) in a mouse model through adenoviral-mediated gene transfer of the human ornithine transcarbamylase cDNA. Substantial reduction in orotic aciduria was observed within 24 h of treatment. Metabolic correction was later associated with phenotypic correction and moderate increase in enzymatic activity. In an effort to identify the level of gene expression required to achieve wild-type levels of enzyme activity we uncovered a dominant negative effect of the endogenous mutant protein on the activity of the delivered recombinant wild-type protein. This phenomenon is relevant to homomultimeric protein defects such as OTCD, represent a challenging category of disorders for gene therapy. Thus, although our findings indicate that adenoviral-mediated gene transfer may have potential as a short-term treatment for OTCD in humans and may be effective especially during catabolic crisis, the observations in this study suggest that careful patient selection based on mutation class may be essential for initial OTCD gene therapy trials, and perhaps, for other homomultimeric enzyme deficiencies being considered as gene therapy targets.

Ab initio and DFT studies of the molecular structures and vibrational spectra of succinonitrile.

The Molecular structure, conformational stability and vibrational frequencies of succinonitrile NCCH2CH2CN have been investigated with ab initio and density functional theory (DFT) methods implementing the standard 6-311++G* basis set. The potential energy surfaces (PES) have been explored at DFT-B3LYP, HF and MP2 levels of theory. In agreements with previous experimental results, the molecule was predicted to exist in equilibrium mixture of trans and gauche conforms with the trans form being slightly lower in energy. The vibrational frequencies and the corresponding vibrational assignments of succinonitrile in both C2h and C2 symmetry were examined theoretically and the calculated Infrared and Raman spectra of the molecule were plotted. Observed frequencies for normal modes were compared with those calculated from normal mode coordinate analysis carried out on the basis of ab initio and DFT force fields using the standard 6-311++G* basis set of the theoretical optimized geometry. Theoretical IR intensities and Raman activities are reported.

Using arteriovenous fistulae as a dual access for hemodialysis and total parenteral nutrition administration is feasible with a good outcome: a case series.

End stage renal failure patients requiring long term total parenteral nutrition (TPN) often have multiple central line placements due to line infection or occlusion. Sometimes this can cause central venous stenosis or even occlusion. We present three cases in this consecutive series, in which we have successfully used arteriovenous fistulae for both hemodialysis and long term TPN administration as an alternative route without any complications. We therefore think that native AVF and grafts can be used as dual access for hemodialysis and TPN administration provided careful case selection, counselling and follow-up.

Electron spin resonance spectral study of PVC and XLPE insulation materials and their life time analysis.

Electron spin resonance (ESR) study is carried out to characterize thermal endurance of insulating materials used in power cable industry. The presented work provides ESR investigation and evaluation of widely used cable insulation materials, namely polyvinyl chloride (PVC) and cross-linked polyethylene (XLPE). The results confirm the fact that PVC is rapidly degrades than XLPE. The study also indicates that colorants and cable's manufacturing processes enhance the thermal resistance of the PVC. It also verifies the powerfulness and the importance of the ESR-testing of insulation materials compared to other tests assumed by International Electrotechnical Commission (IEC) Standard 216-procedure, e.g. weight loss (WL), electric strength (ES) or tensile strength (TS). The estimated thermal endurance parameters by ESR-method show that the other standard methods overestimate these parameters and produce less accurate thermal life time curves of cable insulation materials.

Uncoupling protein-3: a muscle-specific gene upregulated by leptin in ob/ob mice.

We identified and partially characterized another member of the uncoupling protein termed UCP3. Human and mouse UCP3 protein sequences are 86% identical to each other, and 73% and 59% identical to UCP2 and UCP1, respectively. Expression of human UCP3 in yeast resulted in a drastic decrease of mitochondria membrane potential. Northern analysis showed that UCP3 was highly expressed in skeletal muscle in human, rat, and mouse. Mapping of UCP3 placed it to the same chromosomal region of UCP2 in both human and mouse, a region that is linked to obesity and hyperinsulinemia. Furthermore, adenovirus-mediated leptin expression in obese ob/ob mice led to increased expression of UCP3 in skeletal muscle. The data indicate that UCP3 encodes a muscle-specific uncoupling protein that may play an important role in the regulation of energy expenditure and development of obesity.

A rapid, quantitative functional assay for measuring leptin.

At present, leptin is quantitated using immuno-assays that measure leptin mass. Leptin biological activity is determined using protocols that measure feed consumption and weight reduction. These in vivo protocols are semi-quantitative and require large quantities of leptin. We describe a rapid, sensitive and quantitative in vitro assay for leptin using HEK-293 cells stably co-transfected with the leptin receptor Ob-Rb isoform and a STAT-inducible promoter regulating the firefly luciferase cDNA. The assay, performed in a 96-well format, has an EC50 of 150 pM and is linear from 3 to 700 pM of leptin. We demonstrate that the assay is capable of measuring leptin in plasma samples. We demonstrate that bacterially-expressed, recombinant leptin and in vivo expressed leptin are equipotent. Furthermore, we demonstrate that a leptin-derived peptide, leptin fragment 22-56, previously shown to be capable of reducing feed intake following ICV injection does not act directly through the leptin receptor.

Prostaglandin E(2) increases surfactant secretion via the EP(1) receptor in rat alveolar type II cells.

Prostaglandin E(2), the predominant cyclooxygenase metabolite of arachidonic acid in alveolar type II cells, can stimulate pulmonary surfactant secretion. The actions of prostaglandin E(2) are mediated by four prostaglandin E (EP) receptor subtypes designated EP(1), EP(2), EP(3) and EP(4). These subtypes couple to different signal transduction pathways. However, it is not clear which of these subtypes is expressed on type II cells and mediates surfactant secretion. We found that the four subtypes of EP receptors are expressed on the primary cultured alveolar type II cells from adult rats. We also concluded that EP(1) receptor appears to mediate prostaglandin E(2)-induced surfactant secretion through Ca(2+) mobilization.