Mangiferin (mango) attenuates AOM-induced colorectal cancer in rat's colon by augmentation of apoptotic proteins and antioxidant mechanisms.

Mangiferin (MF) is a natural C-glucosylxantone compound that has many substantial curative potentials against numerous illnesses including cancers. The present study's goal is to appraise the chemo preventive possessions of MF on azoxymethane (AOM)-mediated colonic aberrant crypt foci (ACF) in rats. Rats clustered into 5 groups, negative control (A), inoculated subcutaneously with normal saline twice and nourished on 0.5% CMC; groups B-E injected twice with 15 mg/kg azoxymethane followed by ingestion of 0.5% CMC (B, cancer control); intraperitoneal inoculation of 35 mg/kg 5-fluorouracil (C, reference rats) or nourished on 30 mg/kg (D) and 60 mg/kg (E) of MF. Results of gross morphology of colorectal specimens showed significantly lower total colonic ACF incidence in MF-treated rats than that of cancer controls. The colon tissue examination of cancer control rats showed increased ACF availability with bizarrely elongated nuclei, stratified cells, and higher depletion of the submucosal glands compared to MF-treated rats. Mangiferin treatment caused increased regulation of pro-apoptotic (increased Bax) proteins and reduced the ß-catenin) proteins expression. Moreover, rats fed on MF had significantly higher glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lower malondialdehyde (MDA) concentrations in their colonic tissue homogenates. Mangiferin supplementation significantly down-shifted pro-inflammatory cytokines (transforming growth factor-α and interleukine-6) and up-shifted anti-inflammatory cytokines (interleukine-10) based on serum analysis. The chemo-protective mechanistic of MF against AOM-induced ACF, shown by lower ACF values and colon tissue penetration, could be correlated with its positive modulation of apoptotic cascade, antioxidant enzymes, and inflammatory cytokines originating from AOM oxidative stress insults.

Pinostrobin attenuates azoxymethane-induced colorectal cytotoxicity in rats through augmentation of apoptotic Bax/Bcl-2 proteins and antioxidants.

Objectives: Pinostrobin (5-hydroxy-7-methoxyflavanone; PN) is a natural active ingredient with numerous biological activities extensively utilized in tumour chemotherapy. The present study investigates the chemo-preventive potentials of PN on azoxymethane-mediated colonic aberrant crypt foci in rats. Methods: Sprague Dawley rats clustered into five groups, normal control (A) and cancer controls were subcutaneously injected with normal saline and 15 mg/kg azoxymethane, respectively, and nourished on 10% tween 20 and fed on 10% tween 20; reference control (C), injected with 15 mg/kg azoxymethane and injected (intraperitoneal) with 35 mg/kg 5-fluorouracil (5-FU); D and E rat groups received a subcutaneous injection of 15 mg/kg azoxymethane and nourished on 30 and 60 mg/kg of PN, respectively. Results: The acute toxicity trial showed a lack of any abnormal signs or mortality in rats ingested with 250 and 500 mg/kg of PN. The gross morphology of colon tissues revealed significantly lower total colonic aberrant crypt foci incidence in PN-treated rats than that of cancer controls. Histological examination of colon tissues showed increased aberrant crypt foci availability with bizarrely elongated nuclei, stratified cells and higher depletion of the submucosal glands in cancer controls. PN treatment caused positive modulation of apoptotic (Bax and Bcl-2) proteins and inflammatory cytokines (TNF-α, IL-6 and IL-10). Moreover, rats fed on PN had significantly higher antioxidants (superoxide dismutase) and lower malondialdehyde concentrations in their colon tissue homogenates. Conclusion: The chemoprotective efficiency of PN against azoxymethane-induced aberrant crypt foci is shown by lower aberrant crypt foci values and higher aberrant crypt foci inhibition percentage, possibly through augmentation of genes responsible for apoptotic cascade and inflammations originating from azoxymethane oxidative stress insults.

Solanum Procumbens-Derived Zinc Oxide Nanoparticles Suppress Lung Cancer In Vitro through Elevation of ROS.

Lung cancer is one of the cancers with high mortality rate. The current therapeutic regimens have only limited success rate. The current work highlights the potential of Solanum procumbens-derived zinc oxide nanoparticle (SP-ZnONP)-induced apoptosis in A549 lung cancer cells. Synthesized nanoparticles were confirmed by UV-Vis spectrophotometry, X-ray diffraction (XRD), dynamic light scattering analysis (DLS), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), and photoluminescence analysis. Lactate dehydrogenase (LDH), cytotoxicity, and cell viability assays revealed that the SP-ZnONP caused the cell death and the inhibition concentration (IC50) was calculated to be 61.28 µg/mL. Treatment with SP-ZnONPs caused morphological alterations in cells, such as rounding, which may have been caused by the substance's impact on integrins. Acridine orange/ethidium bromide dual staining revealed that the cells undergo apoptosis in a dose-dependent manner, which indicates the cell death. Furthermore, reactive oxygen species (ROS) were examined and it was shown that the nanoparticles elevated ROS levels, which led to lipid peroxidation. In short, the SP-ZnONPs increase the level of ROS, which in turn causes lipid peroxidation results in apoptosis. On the other hand, the SP-ZnONPs decrease nitric oxide level in A549 cells in a dose-dependent manner, which also supports the apoptosis. In conclusion, SP-ZnONPs would become a promising treatment option for lung cancer.

A ß-Sitosterol Encapsulated Biocompatible Alginate/Chitosan Polymer Nanocomposite for the Treatment of Breast Cancer.

ß−sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of ß−sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing ß−sitosterol encapsulated Alginate/Chitosan nanoparticles (ß−sito−Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of ß−sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of ß−sito−Alg/Ch/NPs was also studied. The pharmacokinetic parameters including Cmax, Tmax, half-life (t1/2), and bioavailability were measured for ß−sito−Alg/Ch/NPs as compared to ß−sito−suspension. The ß−sito−Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from ß−sito−Alg/Ch/NPs and ß−sito−suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from ß−sito−Alg/Ch/NPs and ß−sito−suspension. When compared to the ß−sito−suspension, the ß−sito−Alg/Ch/NPs demonstrated greater cytotoxicity (p < 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that ß−sito−Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the ß−sito−suspension.

Hepatoprotective effects of methanolic extract of green tea against Thioacetamide-Induced liver injury in Sprague Dawley rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Since ancient times, herbal medicines have been applied in the treatment of cancer. Tea, derivative from the dried leaves of Camellia sinensis (L.) Kuntze plant is the most popular beverage globally after water and is available in various forms. Green tea has been expansively investigated for its beneficial properties of cancer prevention and therapy. The goal of the research: The current study was conducted to evaluate the hepaprotective character of methanolic green tea extract and its mechanism of action contrary to thioacetamide (TAA)-produced liver fibrosis of Sprague Dawley rats. MATERIALS AND METHODS: Thirty rodents were equally placed in 5 clusters including normal control, TAA group as a positive control, silymarin as standard drug control, and treatment groups consisting of high dose and a low dose Camellia sinensis. Rats in experimental clusters by mouth fed with C. sinensis at 250 mg/kg or 500 mg/kg daily for 2 months. After 60 days, all rats were sacrificed. Blood specimens were gathered for liver biochemical examination. Livers of all groups were dissected out and subjected to histopathological examination through the Hematoxylin and Eosin stain, Masson trichrome, and immunohistochemistry stains (PCNA). Liver tissue homogenate was also analyzed for antioxidant activity parameters. RESULTS: Gross morphological examination showed a regular liver architecture in C. sinensis fed collections compared to the TAA sets. Histology of rat's liver fed with C. sinensis showed an important decrease in the liver index with hepatic cells propagation, mild cellular injury, and immunostaining showed significant down-expression of proliferating cell nuclear antigen (PCNA). TAA produced liver fibrosis through a significant increase in serum alanine transferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin. Total protein and albumin also decreased in the TAA group. Moreover, the reduction of antioxidant enzyme activity including superoxide dismutase and catalase as well as the increase in malondialdehyde was detected in the TAA control group. Meanwhile, an abnormal level of liver biochemical parameters was restored closer to the normal levels in serum of the C. sinensis-fed clusters. In addition, C. sinensis fed assemblies showed elevated antioxidative enzymes activity with a reduction in malondialdehyde level comparable to the levels in silymarin-treated rats. CONCLUSIONS: Green tea potentially inhibited the progression of liver cirrhosis, down -regulation of PCNA proliferation, prevented oxidation of hepatocytes, recovered SOD and CAT enzymes, condensed MDA and reduced cellular inflammation.

Piper sarmentosum Roxb. methanolic extract prevents stress-induced gastric ulcer by modulating oxidative stress and inflammation.

This study investigated the gastroprotective effect of Piper sarmentosum (PS) on stress-induced gastric ulcers in rats by measuring its effect on oxidative stress, gastric mucosal nitric oxide (NO), and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly divided into four groups; two control groups (non-stress and stress) and two treated groups supplemented with either methanolic PS extract (500 mg/kg body weight) or omeprazole (OMZ; 20 mg/kg) orally. After 28 days of treatment, the stress control, PS, and OMZ groups were subjected to water-immersion restrain stress (WIRS) for 3.5 h. Gastric tissue malondialdehyde (MDA), NO, superoxide dismutase (SOD), inducible NO synthase (iNOS), SOD mRNA, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels were measured. WIRS significantly increased gastric MDA, NO, and pro-inflammatory cytokine levels compared to the non-stressed control group. PS and omeprazole supplementation significantly reduced WIRS-exposure-induced gastric ulcers and MDA, iNOS, and IL-1ß levels. However, only PS reduced NO, TNF-α, and IL-6 levels, which were upregulated in this ulcer model. In conclusion, the gastroprotection afforded by PS is possibly mediated by gastric mucosal NO normalization through reduced iNOS expression and attenuation of inflammatory cytokines. PS showed a greater protective effect than omeprazole in reducing gastric lesions and NO, TNF-α, and IL-6 levels, and iNOS expression.

Intralesional pentoxifylline injection in localized alopecia areata.

BACKGROUND: Alopecia areata (AA) is a common non-scarring autoimmune disease that affects hair-bearing areas. A variety of therapeutic options has been used for treating this disease such as corticosteroids, minoxidil, methotrexate, cyclosporine, and azathioprine. Intralesional triamcinolone acetonide (TRA) injection is considered the first-line treatment in localized alopecia areata involving <50% of the scalp; however, intralesional steroid injections are associated with a variety of side effects. OBJECTIVE: The aim of this study was to evaluate the efficacy of pentoxifylline (PTX) vs triamcinolone acetonide intralesional in localized AA. PATIENTS AND METHODS: The sample included 75 patients (47 males and 28 females) aged 18-55 years, diagnosed as localized alopecia areata. The patients were treated by intralesional injection every three weeks up to five sessions. The patients were classified into three groups according to the used therapeutic modality. Group A: 25 patients treated by intralesional injection of TRA. Group B: 25 patients treated by combined intralesional injection of TRA and PTX injection. Group C: 25 patients treated by intralesional PTX injection. RESULTS: Both PTX and TRA intralesional injections were effective in the treatment of AA, but there was a statistically significant difference regarding the response to treatment between the three study groups (P value = 0.01). The highest response was reported in combined drug usage (TRA & PTX) followed by PTX alone and then TRA alone (72.0%, 60.0%, and 32.0%, respectively). CONCLUSION: Pentoxifylline intralesional injection is effective, easy to perform with little side effects for the treatment of localized alopecia areata.

Prevalence And Associated Factors Of Muscoskeletal Disorders Among Arabic Calligraphers Living In Saudi Arabia: A Cross-Sectional Study

@#Musculoskeletal disorders (MSDs) represent a significant occupational problem. Only limited research is available about the impact of MSD on the active Calligraphers. Uncertainty remains about MSD prevalence and associated factors among Arabic calligraphers in Saudi Arabia. A cross-sectional study was conducted among 124 Arabic calligraphers in Saudi Arabia. Data were collected by telephonic interviews using a structured questionnaire that consisted of the validated Standardized Nordic Questionnaire, socio-demographics and working characteristics. A total of 124 completed questionnaires were analyzed. The majority were men (96.8 %), worked for less than 10 hours/week (63.7%). The majority had musculoskeletal pain (59.7%) and about half of them worked for less than 15 years. The most commonly reported MSD was back pain (26.6%) followed by neck pain (21.0%) and shoulder pain (12.1%). In multiple logistic regression the significant predictors in the model were: not exercising (OR=7.1, 95% CI 2.6-19.2), age ≤40 (OR=2.8, 95% CI 1.1- 7.3), worked for ≤20 years (OR=3.4, 95% CI 1.3 -9.1) and being a professional calligrapher (OR=2.3, 95% CI 1.1 – 6.2). The total model is significant (p<0.001) and the adjusted r square= 0.37.MSDs among Arabic calligraphers in Saudi Arabia is relatively high; further clinical assessment is needed. We recommend that health authority in Saudi Arabia should increase the awareness among calligraphers about MSDs and its prevention.

Antidiabetic and antioxidant activity of ethyl acetate extract fraction of Moringa oleifera leaves in streptozotocin-induced diabetes rats via inhibition of inflammatory mediators

Objective: To evaluate the antioxidant and antidiabetic mechanism(s) of ethyl acetate extract fraction of Moringa oleifera (M. oleifera) leaves on streptozotocin-induced diabetes in male Sprague-Dawley rats. Methods: A total of 24 adult male rats were segregated randomly into four groups (6 rats each group). Streptozotocin-induced diabetes rats were given (oral gavage) ethyl acetate extract fraction of M. oleifera (200 mg/kg b.w.) for 30 d. The rats of control and experimental groups were sacrificed after 24 hours of final dose of treatment, to extract blood and pancreatic tissue for biochemical and histopathological analysis. Results: The ethyl acetate extract fraction of M. oleifera significantly reversed (P<0.05) the manifestation of streptozotocin on the levels of serum glucose & insulin, lipid profile, hepatic damage markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase), malondialdehyde formation, antioxidants (glutathione, Vitamin C & Vitamin E), antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) and pro-inflammatory cytokines (IL-1 β , TNF- α & IL-6). Histopathological analysis of pancreatic tissues was in concurrence with the biochemical results. Conclusions: These findings support that M. oleifera leaves have potent therapeutic effect on diabetes mellitus via increasing antioxidant levels and inhibition of pro-inflammatory mediators.

Antidiabetic and antioxidant activity of ethyl acetate extract fraction of Moringa oleifera leaves in streptozotocin-induced diabetes rats via inhibition of inflammatory mediators

Objective: To evaluate the antioxidant and antidiabetic mechanism(s) of ethyl acetate extract fraction of Moringa oleifera (M. oleifera) leaves on streptozotocin-induced diabetes in male Sprague-Dawley rats. Methods: A total of 24 adult male rats were segregated randomly into four groups (6 rats each group). Streptozotocin-induced diabetes rats were given (oral gavage) ethyl acetate extract fraction of M. oleifera (200 mg/kg b.w.) for 30 d. The rats of control and experimental groups were sacrificed after 24 hours of final dose of treatment, to extract blood and pancreatic tissue for biochemical and histopathological analysis. Results: The ethyl acetate extract fraction of M. oleifera significantly reversed (P<0.05) the manifestation of streptozotocin on the levels of serum glucose & insulin, lipid profile, hepatic damage markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase),malondialdehyde formation, antioxidants (glutathione, Vitamin C & Vitamin E), antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) and pro-inflammatory cytokines (IL-1β, TNF-α& IL-6). Histopathological analysis of pancreatic tissues was in concurrence with the biochemical results. Conclusions: These findings support that M. oleifera leaves have potent therapeutic effect on diabetes mellitus via increasing antioxidant levels and inhibition of pro-inflammatory mediators.

New insights on non-B non-C hepatocellular carcinoma in mid Delta Region, Egypt.

PURPOSE: The rate of hepatocellular carcinoma (HCC) is increasing worldwide, including in Egypt. Hepatitis B (HBV) and C (HCV) viruses are major risks. Non-B non-C HCC was reported in some countries. We investigated non-B non-C HCC-independent risk factors and associated profiles in viral hepatitis endemic region. METHODS: In a consecutive series, 281 patients were diagnosed with HCC and received for management, at Tanta University Hospitals, within the past 3 years. Demographic variables and environmental exposures were recorded by direct application of a modified questionnaire. Sera were tested for HCV (antibodies by ELISA and RNA by RT-PCR) and HBV (HBs Ag by ELISA and HBV DNA). Antinuclear antibody, serum copper, and iron were assessed in non-viral HCC. Liver biopsy was performed for HCC diagnosis and grading and liver tissue in all patients by histopathological and immunohistochemical methods to assess HBV and/or HCV etiology. RESULTS: Non-B non-C HCC patients were 13.87% of the total and were associated with multiple risks, predominantly pesticides (100%, p < 0.001) and super phosphate and ammonium sulfate fertilizers (94.87%, p < 0.001) with significant exposure in industry, farming, and residence. Their tumors were mainly solitary, smaller sizes, and of lower alpha-fetoprotein titers. The study showed insignificant increase in prevalence of non-B non-C HCC and had special characters. Multivariate analysis showed significance of pesticides and smoking as independent risks for non-B non-C HCC. CONCLUSIONS: Pesticides and smoking heavy exposure can be considered as primary risks for non-B non-C HCC. Phosphate and ammonium sulfate fertilizers were associations. The study will increase awareness for better prevention and management.

Frequencies of glutathione s-transferase (GSTM1, GSTM3 AND GSTT1) polymorphisms in a Malaysian population.

INTRODUCTION: Glutathione S-transferase (GST) is a xenobiotic metabolising enzyme (XME), which may modify susceptibility in certain ethnic groups, showing ethnic dependent polymorphism. The aim of this study was to determine GSTM1, GSTM3 and GSTT1 gene polymorphisms in a Malaysian population in Kuala Lumpur. MATERIAL AND METHODS: Blood or buccal swab samples were collected from 137 Form II students from three schools in Wilayah Persekutuan Kuala Lumpur. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Glutathione-S-transferase GSTM3 gene frequencies were 89% for AA, 10% for AB and 1% for BB. The gene frequencies for deleted GSTM1 and GSTT1 were 66% and 18% respectively. CONCLUSIONS: This study suggested that the Malay population is at risk for environmental diseases and provides the basis for gene-environment association studies to be carried out.