Flavone attenuates nicotine-induced lung injury in rats exposed to gamma radiation via modulating PI3K/Nrf2 and FoxO1/NLRP3 inflammasome.

Prolonged exposure to different occupational or environmental toxicants triggered oxidative stress and inflammatory reactions mediated lung damage. This study was designed to explore the influence and protective impact of flavone on lung injury in rats intoxicated with nicotine (NIC) and exposed to radiation (IR). Forty rats were divided into four groups; group I control, group II flavone; rats were administered with flavone (25 mg/kg/day), group III NIC + IR; rats were injected intraperitoneally with NIC (1 mg/kg/day) and exposed to γ-IR (3.5 Gy once/week for 2 weeks) while group IV NIC + IR + flavone; rats were injected with NIC, exposed to IR and administered with flavone. Redox status parameters and histopathological changes in lung tissue were evaluated. Nuclear factor-kappa B (NF-κB), forkhead box O-class1 (FoxO1) and nucleotide-binding domain- (NOD-) like receptor pyrin domain-containing-3 (NLRP3) gene expression were measured in lung tissues. Moreover, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and phosphatidylinositol three kinase (PI3K) were measured using ELISA kits. Our data demonstrates, for the first time, that flavone protects the lung from NIC/IR-associated cytotoxicity, by attenuating the disrupted redox status and aggravating the antioxidant defence mechanism via activation of the PI3K/Nrf2. Moreover, flavone alleviates pulmonary inflammation by inhibiting the inflammatory signaling pathway FOXO1/NF-κB/NLRP3- Inflammasome. Collectively, the obtained results exhibited a notable efficiency of flavone in alleviating lung injury induced by NIC and IR via modulating PI3K/Nrf2 and FoxO1/NLRP3 Inflammasome.

Melissa officinalis extract palliates redox imbalance and inflammation associated with hyperthyroidism-induced liver damage by regulating Nrf-2/ Keap-1 gene expression in γ-irradiated rats.

BACKGROUND: Melissa officinalis (MO) is a well-known medicinal plant species used in the treatment of several diseases; it is widely used as a vegetable, adding flavour to dishes. This study was designed to evaluate the therapeutic effect of MO Extract against hyperthyroidism induced by Eltroxin and γ-radiation. METHODS: Hyperthyroidism was induced by injecting rats with Eltroxin (100 µg/kg/ day) for 14 days and exposure to γ-radiation (IR) (5 Gy single dose). The hyperthyroid rats were orally treated with MO extract (75 mg/kg/day) at the beginning of the second week of the Eltroxin injection and continued for another week. The levels of thyroid hormones, liver enzymes and proteins besides the impaired hepatic redox status and antioxidant parameters were measured using commercial kits. The hepatic gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), Monocyte chemoattractant protein-1 (MCP-1) and fibrogenic markers such as transforming growth factor-beta1 (TGF-ß1) were determined. RESULTS: MO Extract reversed the effect of Eltroxin + IR on rats and attenuated the thyroid hormones. Moreover, it alleviated hyperthyroidism-induced hepatic damage by inhibiting the hepatic enzymes' activities as well as enhancing the production of proteins concomitant with improving cellular redox homeostasis by attenuating the deranged redox balance and modulating the Nrf2/Keap-1 pathway. Additionally, MO Extract alleviated the inflammatory response by suppressing the TNF- α and MCP-1 and prevented hepatic fibrosis via Nrf2-mediated inhibition of the TGF-ß1/Smad pathway. CONCLUSION: Accordingly, these results might strengthen the hepatoprotective effect of MO Extract in a rat model of hyperthyroidism by regulating the Nrf-2/ Keap-1 pathway.

The hepatotoxicity of γ-radiation synthesized 5-fluorouracil nanogel versus 5-fluorouracil in rats model.

INTRODUCTION: The clinical use of 5-fluorouracil (5-FU), a routinely used chemotherapy medication, has a deleterious impact on the liver. Therefore, it is necessary to find a less harmful alternative to minimize liver damage. This study was designed to see how 5-fluorouracil nanogel influenced 5-FU-induced liver damage in rats. METHODS: To induce liver damage, male albino rats were injected intraperitoneally with 5-FU (12.5 mg/kg) three doses/week for 1 month. The histopathological examination together with measuring the activities of serum alanine and aspartate aminotransferase enzymes (ALT and AST) were used to evaluate the severity of liver damage besides, hepatic oxidative stress and antioxidant markers were also measured. The hepatic gene expression of heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α) and interleukins (IL-1ß, IL-6) were detected. RESULTS: 5-Fu nanogel effectively attenuated 5-FU-induced liver injury by improving the hepatic structure and function (ALT and AST) besides the suppression of the hepatic inflammatory mediators (TNF- α, IL-1ß and IL-6). Additionally, 5-FU nanogel alleviated the impaired redox status and restored the antioxidant system via maintaining the cellular homeostasis Keap-1/Nrf2/HO-1 pathway. CONCLUSION: Consequently, 5-Fu nanogel exhibited lower liver toxicity compared to 5-FU, likely due to the alleviation of hepatic inflammation and the regulation of the cellular redox pathway.

Natural angiotensin converting enzyme inhibitors: A safeguard against hypertension, respiratory distress syndrome, and chronic kidney diseases.

Hypertension is a serious concern as it is one of the causes of kideny failure and pulmonary fibrosis. An important therapeutic strategy for treating chronic hypertension is to inhibit the angiotensin converting enzyme (ACE). ACE inhibition reduces kidney damage, pulmonary artery pressure, and high blood pressure. Due to their high efficacy and low risk of side effects, natural renin-angiotensin system inhibitors have drawn increasing attention over the past decades. Alkaloids, amino acids, anthocyanidins, flavonoids, glucosinolates, isoflavonoids, phenolic acids, polyphenolics, and triterpenoids are among the bioactive metabolites pocessing an impressive ACE inhibitory activity. Many herbs including Rosmarinus officinalis, Hibiscus sabdariffa, Curcuma longa, Rauwolfia serpentina, Emblica officinalis, Cynara scolymus, Punica granatum, Mucuna pruriens, Capsicum annuum, and Moringa olifera were found having ACE inhibitory activities comparable to captopril and enalpril. These enticing natural ACE inhibitors deserve to be a safeguard medicine against hypertension, respiratory distress syndrome, and chronic kidney diseases. More clinical trials are required before new natural compounds and herbs can be used to treat chronic hypertension and its ramifications, such as respiratory distress syndrome and kidney failure.

Antitumor activity of 5-fluorouracil polymeric nanogel synthesized by gamma radiation on a rat model of colon carcinoma: a proposed mechanism.

The use of 5-fluorouracil (5-FU) is associated with multifaceted challenges and poor pharmacokinetics. Accordingly, our study was designed to prepare 5-FU nanogel as a new form of the colon cancer chemotherapeutic drug 5-FU using polyacrylic acid and gelatin hybrid nanogel as efficient drug carriers. Alongside the in vivo chemotherapeutic evaluation, the anti-proliferative and anti-apoptotic efficacy were carried out for 5-FU nanogel against 1,2-dimethylhydrazine (DMH, 20 mg/kg) and γ-radiation (4 Gy)-prompted colon dysplasia in rats compared to 5-FU. The morphology and size of 5-FU nanogel were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) in addition to cytotoxicity assay. The expression of phosphoinositide-3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR); Toll-like receptor2 (TLR2)/nuclear factor kappa B), adenosine monophosphate (AMP)-activated protein kinase (AMPK) and its downstream autophagy-related genes in addition to apoptotic markers were measured in colon tissues. Results: 5-FU nanogel reduced the levels of the TLR2/ NF-κß as well as the expression of PI3K/AKT/mTOR. Moreover, it promoted autophagy through the activation of the AMPK and its downstream targets which consequently augmented the intrinsic and extrinsic apoptotic pathways. Conclusion: Collectively, these data might strengthen the therapeutic potential of 5-FU nanogel which can be used as an antitumor product for colon cancer.

Melissa officinalis extract suppresses endoplasmic reticulum stress-induced apoptosis in the brain of hypothyroidism-induced rats exposed to γ-radiation.

The purpose of this study was to demonstrate the neuroprotective effect of Melissa officinalis extract (MEE) against brain damage associated with hypothyroidism induced by propylthiouracil (PTU) and/or γ-radiation (IR) in rats. Hypothyroidism induction and/or exposure to IR resulted in a significant decrease in the serum levels of T3 and T4 associated with increased levels of lipid peroxidation end product, malondialdehyde (MDA), and nitrites (NO) in the brain tissue homogenate. Also, hypothyroidism and /or exposure to IR markedly enhance the endoplasmic reticulum stress by upregulating the gene expressions of the protein kinase RNA-like endoplasmic reticulum kinase (PERK), activated transcription factor 6 (ATF6), endoplasmic reticulum-associated degradation (ERAD), and CCAAT/enhancer-binding protein homologous protein (CHOP) in the brain tissue homogenate associated with a proapoptotic state which indicated by the overexpression of Bax, BCl2, and caspase-12 that culminates in brain damage. Meanwhile, the PTU and /or IR-exposed rats treated with MEE reduced oxidative stress and ERAD through ATF6. Also, the MEE treatment prevented the Bax and caspase-12 gene expression from increasing. This treatment in hypothyroid animals was associated with neuronal protection as indicated by the downregulation in the gene expressions of the microtubule-associated protein tau (MAPT) and amyloid precursor protein (APP) in the brain tissue. Furthermore, the administration of MEE ameliorates the histological structure of brain tissue. In conclusion, MEE might prevent hypothyroidism-induced brain damage associated with oxidative stress and endoplasmic reticulum stress.

ß-Sitosterol mitigates hepatocyte apoptosis by inhibiting endoplasmic reticulum stress in thioacetamide-induced hepatic injury in γ-irradiated rats.

The endoplasmic reticulum (ER) controls many biological functions besides maintaining the function of liver cells. Various studies reported the role of the ER stress and UPR signaling pathway in various liver diseases via triggering hepatocytes apoptosis. This study aims to investigate the suppressive effect of ß-sitosterol (ßS) on apoptosis associated with liver injury and ER stress. METHODS: Liver damage in rats was induced by TAA (150 mg/kg I.P twice a week/3 weeks) and γ-irradiation (single dose 3.5 Gy) and treated with ßS (20 mg/kg daily for 30 days). Serum aminotransferase activity, lipid profile and lipid metabolic factors were measured beside liver oxidative stress and inflammatory markers. Moreover, the hepatic expression of ER stress markers (inositol-requiring enzyme 1 alpha (IRE1α), X-box-binding protein 1 (XBP1) and CCAAT/enhancer binding protein homologous protein (CHOP) and apoptotic markers were detected together with histopathological examination. RESULTS: ßS diminished the aminotransferase activity, the oxidative stress markers as well as the inflammatory mediators. Furthermore, ßS lowered the circulating TG and TC and the hepatic lipotoxicity via the suppression of lipogenesis (Srebp-1c) and improved the ß-oxidation (Pparα and Cpt1a) together with the mitochondrial biogenesis (Pgc-1 α). Moreover, the upregulated levels of ER stress markers were reduced upon treatment with ßS, which consequently attenuated hepatic apoptosis. CONCLUSION: ßS relieves hepatic injury, ameliorates mitochondrial biogenesis, and reduces lipotoxicity and apoptosis via inhibition of CHOP and ER stress response.

Mesenchymal Stem Cells and Selenium Nanoparticles Synergize with Low Dose of Gamma Radiation to Suppress Mammary Gland Carcinogenesis via Regulation of Tumor Microenvironment.

Breast cancer is one of the most prevalent and deadliest cancers among women in the world because of its aggressive behavior and inadequate response to conventional therapies. Mesenchymal stem cells (MSCs) combined with green nanomaterials could be an efficient tool in cell cancer therapy. This study examined the curative effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) with selenium nanoparticles (SeNPs) coated with fermented soymilk and a low dose of gamma radiation (LDR) in DMBA-induced mammary gland carcinoma in female rats. DMBA-induced mammary gland carcinoma as marked by an elevation of mRNA level of cancer promoter genes (Serpin and MIF, LOX-1, and COL1A1) and serum level of VEGF, TNF-α, TGF-ß, CA15-3, and caspase-3 with the reduction in mRNA level of suppressor gene (FST and ADRP). These deleterious effects were hampered after treatment with BM-MSCs (1 × 106 cells/rat) once and daily administration of SeNPs (20 mg/kg body weight) and exposure once to (0.25 Gy) LDR. Finally, MSCs, SeNPs, and LDR notably modulated the expression of multiple tumor promoters and suppressor genes playing a role in breast cancer induction and suppression.

Luteolin loaded on zinc oxide nanoparticles ameliorates non-alcoholic fatty liver disease associated with insulin resistance in diabetic rats via regulation of PI3K/AKT/FoxO1 pathway.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem with high prevalence and morbidity associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. Nano-formulation of luteolin with Zn oxide in the form of Lut/ZnO NPs may improve the anti-diabetic property of each alone and ameliorate the insulin resistance thus management of NAFLD. This study aimed to measure the efficiency of Lut/ZnO NPs against insulin resistance coupled with NAFLD and T2DM. METHODS: A diabetic rat model with NAFLD was induced by a high-fat diet and streptozotocin (30 mg/kg I.P). Serum diabetogenic markers levels, lipid profile, and activity of liver enzymes were measured beside liver oxidative stress markers. Moreover, the hepatic expressions of PI3K/AKT/FoxO1/SERBP1c as well as heme oxygenase-1 were measured beside the histopathological examination. RESULTS: Lut/ZnO NPs treatment effectively reduced hyperglycemia, hyperinsulinemia, and ameliorated insulin resistance. Additionally, Lut/ZnO NPs improved the hepatic functions, the antioxidant system, and reduced the oxidative stress markers. Furthermore, the lipid load in the liver, as well as the circulating TG and TC, was minified via the suppression of lipogenesis and gluconeogenesis. Moreover, Lut/ZnO NPs activated the PI3K/AKT signaling pathway, hence inactivating FoxO1, therefore enhancing the hepatic cells' insulin sensitivity. CONCLUSION: Lut/ZnO NPs have a hepatoprotective effect and may relieve the progression of NAFLD by alleviating insulin resistance, ameliorating the antioxidant status, and regulating the insulin signal pathway.

Preparation of zinc oxide nanoparticles using laser-ablation technique: Retinal epithelial cell (ARPE-19) biocompatibility and antimicrobial activity when activated with femtosecond laser.

The unusual physical, chemical, and biological features of nanoparticles have sparked considerable attention in the ophthalmological applications. This study reports the synthesis and characterization of zinc oxide nanoparticles (ZnONPs) using laser-ablation at 100 mJ with different ablation times. The synthesized ZnONPs were spherical with an average size of 10.2 nm or 9.8 nm for laser ablation times of 20 and 30 min, respectively. The ZnONPs were screened for their antimicrobial activity against ophthalmological bacteria, methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa. The significant decrease in bacterial growth was observed after treatment with ZnONPs in combination with 400 nm femtosecond laser irradiation. ZnONPs were investigated for their antioxidant activity and biocompatibility towards retinal epithelial cells (ARPE-19). ZnONPs showed moderate antioxidant and free radical scavenging activity. ZnONPs prepared with an ablation time of 20 min were safer and more biocompatible than those prepared with an ablation time of 30 min, which were toxic to ARPE-19 cells with LC50 (11.3 µg/mL) and LC90 (18.3 µg/mL). In this study, laser ablation technique was used to create ZnONPs, and it was proposed that ZnONPs could have laser-activated antimicrobial activity for ophthalmological applications.

Development of functional glow-in-the-dark photoluminescence linen fabrics with ultraviolet sensing and shielding.

Linen fibres were coated with a glow-in-the-dark photoluminescence, flame-retarding, and hydrophobic smart nanocomposite using the pad-dry-curing process. Ecologically friendly ammonium polyphosphate and lanthanide-activated strontium aluminium oxide (LSAO) nanoparticles were immobilized into linen fabric using eco-friendly room-temperature-vulcanizing silicone rubber. Different analytical techniques were used to examine the morphological characteristics and elemental compositions of LSAO nanoparticles and treated linen textiles. The self-extinguishing properties of the treated linen textiles were tested for their fire resistance. After 24 washing cycles, the coated linen samples retained their flame-retarding properties. The treated linen's superhydrophobicity rose in direct proportion to the LSAO concentration. After being excited at 365 nm, the colourless luminescent film that was coated on linen surface gave out an emission wavelength of 519 nm. The photoluminescent linen was monitored to create a range of different colours, including off-white in daytime light and green under ultraviolet (UV) light radiation, according to the Commission Internationale de l'éclairage laboratory colorimetric coordinates and photoluminescence spectra. Emission, excitation, and lifetime spectral analysis of the treated linen revealed persistent phosphorescence. For mechanical and comfort evaluation, the coated linen textiles' bending length and air permeability were assessed. Good UV light shielding and enhanced antibacterial activity were detected in the treated linens.

Frequency and impact of DHODH, ABCG2 and CYP2C19 SNPs on the therapeutic efficacy, tolerability and toxicity of leflunomide.

Introduction: Leflunomide is one of the commonly used drugs in treatment of rheumatoid arthritis (RA), which on administration is converted into its active metabolite teriflunomide. Aim: Our aim is to evaluate the frequencies of dihydrooroate dehydrogenase (DHODH) (rs3213422), ABCG2 (rs2231142) and CYP2C19 (rs4244285) allele distribution among patients receiving leflunomide for RA and their possible impact on leflunomide performance in disease control. Patients & methods: Patients (>18 years) who fulfilled the 2010 ACR classification criteria for RA receiving leflunomide (20 mg/day) were included in the study. Disease activity score 28 was used to assess patients disease activity. Blood samples were collected for full blood count and blood chemistry. Genomic DNA was extracted from peripheral blood. The selection of SNPs was based on the criteria of minor allele frequency among Caucasians. Results: A significant association between the therapeutic outcome of leflunomide and DHODH genotyping was observed but not with CYP2C19 and ABCG2. Importantly, there is a significant association between DHODH (rs3213422) CC genotype and the number of patients with controlled disease. Conclusion: We strongly suggest that polymorphisms in the DHODH are the major factor affecting leflunomide pharmacogenetics and therapeutic efficacy.

The effect of femtosecond laser irradiation on the growth kinetics of Staphylococcus aureus: An in vitro study.

We investigated the effect of femtosecond laser irradiation on the growth kinetics of Staphylococcus aureus. In order to improve laser-based antimicrobial therapy and develop a clinically viable modality, various laser parameters such as laser light wavelength, laser power, exposure time, and energy density were studied. The INSPIRE HF100 laser system (Spectra Physics) provided the femtosecond laser light, which was pumped by a mode-locked femtosecond Ti: sapphire laser MAI TAI HP (Spectra Physics). The survival of the bacterial cells was monitored after irradiation by determination of growth rate using optical density, which is a rapid, simple, and reliable method. The growth rate of laser-exposed cultures was compared to control cultures. Fifteen minutes of exposure to femtosecond laser radiation with a wavelength of 390 nm and 400 nm at an average power of 50 mW was enough to significantly reduce bacterial viability, with a lag in the growth phase of 5 h longer than the control culture (P < 0.0001 by ANOVA and Tukey test).

Comparing the gender diversity and affiliation trends of the authors for two orthopaedics journals from the Arab world.

OBJECTIVES: Authorship trends, female authors' contributions, and the collaboration among institutions have been a concern in the medical field. This study primarily aims to report and compare the number of authors per article and the prevalence of female authors by comparing two orthopaedics journals from the Arab world. The secondary objective of this study is to evaluate the characteristics of the authors' affiliations and the pattern in institutions' collaborations and contributions to the published articles. METHODS: This cross-sectional study reviewed all articles (until July 2020) published in the Archives of the Egyptian Orthopaedic Journal (EOJ) (the official journal of the Egyptian Orthopaedic Association) and the Journal of Musculoskeletal Surgery and Research (JMSR) (the official journal of the Saudi Orthopaedic Association). RESULTS: We evaluated 383 and 122 articles from the EOJ and JMSR, respectively. The average number of authors per article was significantly higher for JMSR (4.3 ± 1.7) than EOJ (2.0 ± 1.0); p = 0.000. There was a significantly larger number of contributions by female authors in JMSR (75, 14.2%) than EOJ (2, 0.3%); p = 0.000. The average number of institutions per article was significantly larger for JMSR (2.1 ± 1.2) than EOJ (1.1 ± 0.3); p = 0.000. For the JMSR, the incidence of national institutions' cooperation (27.9%) and international institutions' contributions (53.3%) were significantly higher than their counterparts for the EOJ-6% and 4.7%, respectively; p = 0.000. CONCLUSION: The JMSR showed superiority regarding the number of authors per article and the prevalence of female authors. The incidence of national institutions' cooperation and international contributions were higher in the JMSR compared with the EOJ.

Cytotoxic Chemotherapy as an Alternative for Systemic Treatment of Advanced Hepatocellular Carcinoma in Developing Countries.

Systemic therapy options nowadays for advanced hepatocellular carcinoma (HCC) are either immunotherapy with immune checkpoint inhibitors or targeted therapy. As the incidence of liver cancer is much higher in developing countries, these new medications are not readily accessible for most of the patients. Cytotoxic chemotherapy agents are more available and affordable in developing countries. We are trying to explore the effectiveness of the newer cytotoxic agents in the systematic treatment for advanced HCC. This is a systematic review of all randomized controlled trials since 1997 that utilized systemic cytotoxic chemotherapy agents in the systemic treatment for advanced HCC using Scopus, PubMed, and Cochrane library up to February 2020. Six randomized trials were found. Different drugs and dosages were used, so it was statistically inappropriate to conduct a meta-analysis. No Phase III trial showed statistically significant overall survival (OS) benefit for cytotoxic chemotherapy, except subgroup analysis of Chinese patients in one study who had leucovorin, fluorouracil, and oxaliplatin (FOLFOX) regimen. There was no significant progression-free survival (PFS) or response rate in the Phase II trials. There are not enough data to infer the actual benefits of systemic cytotoxic chemotherapy in advanced HCC. However, oxaliplatin-based regimens may give feasible results. Health systems with limited access to targeted therapy and immunotherapy agents may use oxaliplatin-based regimens in clinical trials for advanced HCC. These results should be confirmed in multiple future randomized clinical trials.

Cinnamic acid nanoparticles modulate redox signal and inflammatory response in gamma irradiated rats suffering from acute pancreatitis.

Acute Pancreatitis (AP) is a multifactorial disease. It was characterized by severe inflammation and acinar cell destruction. Thus, the present study was initiated to evaluate the role the of Cinnamic acid nanoparticles (CA-NPs) as a modulator for the redox signaling pathway involved in the development of pancreatitis. AP in rats was induced by L-arginine and exposure to gamma radiation. The pancreatic injury was evaluated using biochemical and histological parameters. Upon the oral administration of CA-NPs, both the severity of acute pancreatitis and the serum levels of amylase and lipase were decreased. Furthermore, the malondialdehyde (MDA) levels of the pancreatic tissue were significantly reduced and the depletion of glutathione was considerably restored. The injury and apoptosis of pancreatic tissues were markedly improved by the reduction of the caspase-3 levels. Additionally, the alleviation of pancreatic oxidative damage by CA-NPs was accompanied by a down-regulation of the NLRP3, NF-κB, and ASK1/MAPK signaling pathways. Collectively, the current findings showed that CA-NPs could protect the pancreatic acinar cell from injury not only by its antioxidant, anti-inflammatory effect but also by modulation of the redox-sensitive signal transduction pathways contributed to acute pancreatitis severity. Accordingly, cinnamic acid nanoparticles have therapeutic potential for the management of acute pancreatitis.

Mesenchymal stem cells targeting PI3K/AKT pathway in leukemic model.

Mesenchymal stem cells have therapeutic properties that are related to their potentials for trans-differentiation, immunomodulation, anti-inflammatory, inhibitory effect on tumor proliferation, and induction of apoptosis. This study was performed to analyze the role of mesenchymal stem cells as an alternative for cellular signaling growth factors involved in the pathogenesis of leukemogenesis in rats. Treatment of rats with 7,12-dimethyl benz [a] anthracene induced leukemogenesis appeared as a significant decrease in hematological parameters with concomitant significant increase in bone marrow oxidative and inflammatory indices (transforming growth factor beta and interleukin-6) in comparison with normal groups. On the contrary, Western immunoblotting showed a significant increase in the signaling growth factors: PI3K, AKT, mTOR proteins and a significant decrease in PTEN in 7,12-dimethyl benz [a] anthracene-treated group. In addition, a significant increase in the transcript levels of B cell lymphoma-2 protein gene in the 7,12-dimethyl benz [a] anthracene group, while that of C-X-C motif chemokine receptor-4 and B cell lymphoma-2 protein associated x-protein were significantly downregulated compared to controls. Meanwhile, therapeutic mesenchymal stem cells treatment predict a significant improvement versus 7,12-dimethyl benz [a] anthracene group through the modulation of growth factors that confront bone marrow dysplasia. In the same direction treatment of 7,12-dimethyl benz [a] anthracene group with mesenchymal stem cells, it induced apoptosis and increased the homing efficacy to bone marrow. In conclusion, mesenchymal stem cells improve hematopoiesis and alleviate inflammation, and modulated PI3K/AKT signaling pathway contributed to experimental leukemogenesis.

Visfatin Serum Levels in Obese Type 2 Diabetic Patients: Relation to Proinflammatory Cytokines and Insulin Resistance.

Visfatin, an adipocytokine with insulin-mimetic activity, has been previously reported to associate with obesity. Herein, we aimed to investigate the serum level of visfatin and association with proinflammatory markers and insulin resistance in obese type 2 diabetic patients. A case control study was carried out among 80 diabetics and 40 non-diabetic healthy controls, after obtaining Anthropometric measurements and blood pressure. Serum level of visfatin and C-reactive protein (CRP) were measured by Enzyme Immunoassay. Interleukin 6 (IL6), tumor necrosis factor α (TNF-) were measured by ELISA and the homeostasis model assessment for insulin resistance was calculated as a marker of insulin resistance. Compared to healthy controls, diabetic patients showed a significant high serum levels of visfatin (40.33±9.98 vs 19.03±8.22), (P= 0.001), IL6 (12.06±2.69 vs 6.02±3.03), (P < 0.0001), TNF- (13.53±2.54 vs 8.70±3.40), P < 0.0001) and CRP (7.77±1.61 vs 6.01±1.99), (P=0.003). Also there was a strong positive correlation between serum level of visfatin, IL6, TNF- and CRP and some anthropometric characteristics including (WC,BMI and insulin resistance). Furthermore, among 80 diabetic patients, serum level of visfatin was positively correlated with IL6 (r=0.47, P < 0.0001), TNF- (r=0.62, P < 0.0001), CRP (r=0.4, P=0.002) respectively. In conclusion, there is a strong positive correlation between visfatin serum level and the inflammatory markers IL6, TNF- and CRP in type 2 diabetic patients. There is also a positive correlation with insulin resistance and BMI which indicates association of visfatin with obesity and type 2 diabetes mellitus.

Luteolin supplementation adjacent to aspirin treatment reduced dimethylhydrazine-induced experimental colon carcinogenesis in rats.

Previous studies have shown that aspirin is used in colon cancer treatment. However, long-term of Aspirin usage is limited to gastric and renal toxicity. Luteolin (LUT) has cancer prevention and anti-inflammatory effects. The present study was designed to investigate the effect of LUT supplementation and Aspirin treatment in dimethylhydrazine (DMH)-induced carcinogenesis in rats. DMH (20 mg/kg BW/week) treated rats received gavages with Aspirin (50 mg/kg BW/week) and LUT (0.2 mg/kg BW/day) for 15 weeks. DMH injections induce colon polyps and renal bleeding, significantly increasing carcinoembryonic antigen (CEA), cyclooxygenase-2 (COX-2), oxidative stress, and kidney function tests and reducing antioxidant markers. Either Aspirin or LUT gavages alone or combined produce a significant decrease in colon polyp number and size, significantly decreasing CEA, COX-2, and oxidative stress and increasing antioxidant markers. In conclusion, the supplementations of LUT adjacent to Aspirin in the treatment of DMH-induced carcinogenesis in rats reflect a better effect than the use of Aspirin alone.