The Antioxidant and anti-inflammatory Activity of Selenium and Lecithin Combination Against ethanol-induced Gastric Ulcer in mice via Modulating IGF-1/PTEN/Akt/FoxO3a Signaling.

Gastric ulcers are one of the most prevalent gastrointestinal disorders. The current study investigated the antioxidant and anti-inflammatory effects of selenium (Se) and lecithin (Lec) alone and in combination against ethanol-induced gastric ulcers in mice, and their ability to modulate insulin-like growth factor-1 (IGF-1)/ Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/ Protein kinase B (Akt)/ Forkhead box O3a (FoxO3a) signaling. The mice were divided into normal, ethanol, Se + ethanol, Lec + ethanol, Se + Lec + ethanol, and omeprazole + ethanol groups. Treatment with the selected doses was continued for 14 days before a single dose of absolute ethanol (5 ml/kg body weight) was administered to induce gastric ulcers in mice. The results showed that pretreatment with Se and Lec combination effectively decreased both the macro- and microscopic gastric lesions and increased the protection index compared to the ethanol group. Remarkably, the Se and Lec combination decreased the levels of reactive oxygen species, malondialdehyde, and cytochrome c and increased glutathione, glutathione peroxidase, and thioredoxin reductase activities in gastric tissues. The Se and Lec combination increased prostaglandin E2 and interleukin-10 levels but decreased tumor necrosis factor-α, interleukin-6 and interleukin-1ß levels compared to either treatment alone. Interestingly, this combination decreased the expression of IGF-1, p-Akt, and FoxO3a proteins and increased PTEN expression in gastric tissues. The gastric tissues examination by hematoxylin and eosin staining confirmed these results. Therefore, the Se and Lec combination showed superior protective effects against ethanol-induced gastric ulcers in mice, compared to either treatment alone, through antioxidant, and anti-inflammatory activities, in addition to modulating IGF-1/PTEN/Akt/FoxO3a pathway signaling.

Therapeutic effect of bromelain and papain on intestinal injury induced by indomethacin in male rats.

Objectives: Inflammatory bowel diseases (IBDs) are a multiple inflammatory status in small intestines and colon. Bromelain and Papain were cysteine proteases enzymes extracted from pineapple and papaya, and possess antioxidant and anti-inflammatory characteristics. Therefore, this comparative work aimed to examine the anti-inflammatory and antioxidant effect of bromelain and papain in intestinal inflammation of rats and to evaluate the most potent effect of both types of enzymes. Methods: Forty rats were used in this study (8 rats/group), G1: control group, G2: (Indo group) intestinal inflammation was induced by two doses of Indomethacin (7.5 mg/kg body weight) apart 24 h. G3: (Indomethacin + Bromelain) intestinal inflamed rats treated by oral dose of bromelain (1000 mg/kg/day). G4: (Indomethacin + Papain) intestinal inflamed rats treated by oral dose of papain (800 mg/kg/day). G5: (Indomethacin + Sulfasalazine) intestinal inflamed rats treated by oral dose of sulfasalazine (500 mg/kg/day). Oxidative stress and inflammatory markers were measured along with histological assessment. Results: Indomethacin-induced intestinal inflammation (in both Jejunum and Ileum) characterized by increased oxidative stress biomarkers: Xanthine oxidase, Catalase, Glutathione reductase, and Protein carbonyl and Inflammatory biomarkers: Tumor necrosis factor-α, Interleukin-10, Monocyte chemoattractant protein-1, Nuclear factor-kappa ß, C-reactive protein, and Prostaglandin E2, as compared to control rats. On the other hand, administering either bromelain or Papain would effectively decrease symptoms of intestinal inflammation and modulate biomarkers of oxidative stress and pro-inflammatory cytokines. Conclusion: Comparing results revealed that bromelain showed the most potent protective effect and possesses an apparent role in protection against the development of intestinal inflammation.

Edaravone alleviates methotrexate-induced testicular injury in rats: Implications on inflammation, steroidogenesis, and Akt/p53 signaling.

Edaravone (ED) is a neuroprotective drug with beneficial effects against several disorders due to its prominent antioxidant activity. However, its effect against methotrexate (MTX)-induced testicular damage was not previously investigated. Therefore, we aimed to investigate the ability of ED to prevent the oxidative stress, inflammation, and apoptosis induced by MTX on the rat testis and to examine whether ED administration modulated the Akt/p53 signaling and steroidogenesis process. Rats were allocated into; Normal, ED (20 mg/kg, PO, for 10 days), MTX (20 mg/kg, i.p., on the 5th day), and ED + MTX groups. The results showed that MTX group exhibited higher serum activities of ALT, AST, ALP, and LDH in addition to histopathological alterations in the rat testis, compared to normal group. Furthermore, MTX induced down-regulation of the steroidogenic genes; StAR, CYP11a1, and HSD17B3 and reduced FSH, LH, and testosterone levels. The MTX group also showed higher levels of MDA, NO, MPO, NF-kB, TNF-α, IL-6, IL-1ß, Bax, and caspase 3, as well as, lower levels of GSH, GPx, SOD, IL-10, Bcl2 compared to normal rats, p < 0.05. In addition, MTX treatment resulted in increased p53 expression and decreased p-Akt expression. Remarkably, ED administration significantly prevented all the biochemical, genetic, and histological damage induced by MTX. Hence, ED treatment protected the rat testis from apoptosis, oxidative stress, inflammation, and impaired steroidogenesis induced by MTX. This novel protective effect was mediated by decreasing p53 while increasing p-Akt protein expression.

Upregulation of miR-33 and miR-155 by gum acacia mitigates hyperlipidaemia and inflammation but not weight increase induced by Western diet ingestion in mice.

OBJECTIVE: This study, for the first time, investigates the effect of gum acacia (GA) on the expression of miR-33 and miR-155 and its association with the obesity and inflammation induced by Western diet (WD) consumption in mice. METHODS: Animals were divided into: normal diet (ND) group, WD group, GA group and GA + WD group. RESULTS: The WD group exhibited higher total body, liver, visceral fat weights, blood total cholesterol, triglycerides and glucose levels compared to ND group. The liver tissues showed severe inflammation and degeneration with higher hepatic TNF-α level. Interestingly, GA + WD group showed a decrease in the biochemical parameters and hepatic TNF-α level but had no effect on the weight increase. It also showed a significant upregulation of miR-33 and miR-155 compared to WD group. CONCLUSIONS: GA mitigated the hyperlipidaemia and inflammation but not weight increase induced by WD ingestion via upregulation of miR-33 and miR-155 while reducing TNF-α level.

Thymol protects against bleomycin-induced pulmonary fibrosis via abrogation of oxidative stress, inflammation, and modulation of miR-29a/TGF-ß and PI3K/Akt signaling in mice.

Idiopathic pulmonary fibrosis is a terminal lung ailment that shares several pathological and genetic mechanisms with severe COVID-19. Thymol (THY) is a dietary compound found in thyme species that showed therapeutic effects against various diseases. However, the effect of THY against bleomycin (BLM)-induced lung fibrosis was not previously investigated. The current study investigated the ability of THY to modulate oxidative stress, inflammation, miR-29a/TGF-ß expression, and PI3K/phospho-Akt signaling in lung fibrosis. Mice were divided into Normal, THY (100 mg/kg, p.o.), BLM (15 mg/kg, i.p.), BLM + THY (50 mg/kg, p.o.), and BLM + THY (100 mg/kg, p.o.) groups and treated for four weeks. The obtained results showed that BLM + THY (50 mg/kg) and BLM + THY (100 mg/kg) reduced fibrotic markers; α-SMA and fibronectin, inflammatory mediators; TNF-α, IL-1ß, IL-6, and NF-kB and oxidative stress biomarkers; MDA, GSH, and SOD, relative to BLM group. Lung histopathological examination by H&E and Masson's trichrome stains confirmed the obtained results. Remarkably, expression levels of TGF-ß, PI3K, and phospho-Akt were decreased while miR-29a expression was elevated. In conclusion, THY effectively prevented BLM-induced pulmonary fibrosis by exerting significant anti-oxidant and anti-inflammatory effects. Our novel findings that THY upregulated lung miR-29a expression while decreased TGF-ß and PI3K/Akt signaling are worthy of further investigation as a possible molecular mechanism for THY's anti-fibrotic actions.

Protective Effect of Portulaca oleracea Extract Against Lipopolysaccharide-Induced Neuroinflammation, Memory Decline, and Oxidative Stress in Mice: Potential Role of miR-146a and miR-let 7.

Neuroinflammation is an adaptive immune response to the central nervous system (CNS) injury induced by infection or toxins. MicroRNAs (miRs) showed critical roles in neuroinflammation as either proinflammatory or anti-inflammatory molecules. Interestingly, Portulaca oleracea (purslane) is an edible plant capable of ameliorating several diseases, including headache, burns, and diabetes; however, its effect on the neuroinflammation-associated miRs was not previously investigated. This study aimed to investigate the effect of aqueous purslane extract on the neuroinflammation induced by lipopolysaccharide (LPS) in mice and to identify its effect on animal cognition, oxidative stress, and expressions of miR-146a and miR-let 7. Adult mice were divided into the following groups: Normal group, LPS group, and Purslane+LPS group. Novel target recognition test, brain histopathology, and measurement of oxidative stress and inflammatory markers were performed. The results showed that LPS group exhibited significant decline in the cognitive memory, brain histopathological injury and a decrease in the number of intact neurons compared to the normal group. Furthermore, the LPS group showed a significant increase in malondialdehyde concentration, whereas superoxide dismutase and catalase activities were decreased. The LPS group also showed an increase in the inflammatory markers tumor necrosis factor-α and nuclear factor kappa B and downregulation of miR-146a and miR-let 7 expressions in the brain cells compared to the normal group, P value <.05. Interestingly, all these changes were reversed by administration of the aqueous purslane extract. In conclusion, the aqueous purslane extract protected from LPS-induced neuroinflammation and memory decline in mice through antioxidant and anti-inflammatory effect where upregulation of miR-146a and miR-1et 7 expressions was involved.

Evaluation of the hepatoprotective effect of curcumin-loaded solid lipid nanoparticles against paracetamol overdose toxicity: Role of inducible nitric oxide synthase.

Curcumin (Cur) is a natural compound that exhibited therapeutic effects against various liver injuries however Cur showed poor water solubility and bioavailability. This study aimed to design Cur-loaded solid lipid nanoparticles (SLNs) and to evaluate the hepatoprotective and antioxidant effects in a model of acute hepatotoxicity induced by paracetamol (PCM) overdose compared to the raw Cur and N-acetylcysteine (NAC). SLNs were prepared by emulsion/solvent evaporation method and 32 factorial design was employed. Wistar rats were divided into Control, PCM, PCM + NAC, PCM + raw Cur, and PCM + Cur-SLNs groups and treated orally for 14 days before receiving a single PCM dose. The Cur-loaded SLNs showed high entrapment efficiency % ranging between 69.1 and 92.1%, particle size (PS) between 217 and 506 nm, and zeta potential values between -17.9 and -25.5 mV. The in vivo results revealed that the PCM group exhibited deterioration of liver functions, pathological lesions on the liver tissues, severe oxidative stress, and increases in both the serum and hepatic iNOS levels. Remarkably, the PCM + Cur-SLNs group showed significantly better liver functions and tissue integrity compared to the PCM group. Furthermore, higher reduced glutathione and catalase but lower malondialdehyde and iNOS levels were observed. In conclusion, Cur-loaded SLNs effectively prevented the liver damage induced by PCM overdose through alleviating the oxidative stress and inhibiting the serum and hepatic iNOS expression in an effect comparable to NAC and better than raw Cur.

SARS-CoV-2 PCR positivity rate and seroprevalence of related antibodies among a sample of patients in Cairo: Pre-wave 2 results of a screening program in a university hospital.

BACKGROUND: Research has revealed that asymptomatic and pre-symptomatic infections are important contributors to the transmission of SARS-CoV-2 in populations. In Egypt, the true prevalence of infections is veiled due to the low number of screening tests. The aim of this study was to determine the SARS-CoV-2 PCR positivity rate as well the seroprevalence of the SARS-CoV-2 antibodies before the ultimate development of a second wave of the epidemic in Cairo, Egypt. METHODS: Our study was carried out between May 5 and the end of October 2020. It included all patients requiring admission to Ain Shams University hospitals. An interview questionnaire was used to collect demographic and clinical data. Laboratory tests for all participants included RT-PCR and total antibody assay for SARS-CoV-2. RESULTS: A total of 4,313 subjects were enrolled in our study, with females representing 56% of the sample. Adults and middle-aged individuals represented around 60% of the study sample. The positivity rate of SARS-CoV-2 PCR was 3.84% (95% CI 3.29-4.48), and the SARS-CoV-2 antibody seroprevalence was 29.82% (95% CI: 28.16-31.51). Males showed a higher risk for getting the COVID-19 infection, while middle-age group had significantly higher antibody seroprevalence rates. CONCLUSION: SARS-CoV-2 infection imposes a high burden on the community as detected by high seroprevalence rates.

Betaine downregulates microRNA 34a expression via a p53-dependent manner in cisplatin-induced nephrotoxicity in rats.

Cisplatin-induced nephrotoxicity limits its wide application as a chemotherapeutic drug. Betaine is a natural trimethylglycine compound involved in several biological reactions. In this study, the protective effect of betaine against cisplatin-induced nephrotoxicity through modulating the expression of microRNA 34a (miRNA 34a), p53, apoptosis, and inflammation was investigated. Adult Wistar rats were divided into normal group (received vehicle); betaine group (received 250 mg betaine/kg BW/day via oral gavage from Day 1 to Day 25); cisplatin group (received a single intraperitoneal dose of cisplatin at 5 mg/kg BW on Day 21) and betaine + cisplatin group (received the same doses of betaine and cisplatin). The results demonstrated that the cisplatin group exhibited severe kidney tissue damage and an increase in blood creatinine and urea levels. Furthermore, the cisplatin group showed a significant upregulation of miRNA 34a and higher levels of phospho-p53, caspase 3, cytochrome c, NFk B, and IL-1ß compared to the normal group. Remarkably, the betaine + cisplatin group showed significantly decreased blood creatinine and urea concentrations, decreased levels of miRNA 34a, phospho-p53, caspase 3, cytochrome c, NFk B, and IL-1ß as well as improved kidney tissue integrity compared to the cisplatin group. In conclusion, cisplatin-induced nephrotoxicity in rats was associated with upregulation of miRNA 34a expression, apoptosis, and inflammation in p53-dependent manner. These effects were reversed by betaine administration that ultimately improved the kidney function and tissue integrity.

Perceived efficacy of existing waterpipe tobacco warning labels versus novel enhanced generic and waterpipe-specific sets.

INTRODUCTION: Since 2008, Egypt has four existing generic bi-annually rotating warning labels (WLs) on 50% of the waterpipe tobacco packs (WTPs). The Ministry of Health Tobacco Control Unit proposed increasing WL size to 80%, removing colours and flavour imagery from WTPs, and plain packaging to help curb the rising epidemic of waterpipe tobacco smoking. Therefore, we measured the perceived efficacy of existing against novel enhanced (generic and waterpipe-specific) WTP WLs and the associated factors among Egyptian waterpipe smokers and nonsmokers. METHODS: A purposive quota sample of 2014 adults was surveyed in two rounds using face interviews. At each round, participants were randomly shown one of four existing WLs, then one of four novel WLs. Participants rated the perceived efficacy of existing and novel WLs regarding the salience, depth of processing, affective reactions, credibility, relevance, perceived harm and perceived behavioural control. Data were analysed using Generalized Estimating Equations. RESULTS: Participants rated novel WTP WLs with higher mean perceived efficacy scores than existing WLs for all measures, although both sets collectively scored modestly (59.7; 95% CI: 58.9-60.5 vs 53.0; 95% CI: 52.1-54.0, respectively; p<0.001). Relative to the existing WTP WLs, novel WLs were particularly able to induce higher salience, affective reactions, and depth of processing. Relative to the generic novel WTP WLs, waterpipe-specific WLs induced higher relevance, perceived harm, and affective reactions. Nonsmokers scored higher than waterpipe tobacco smokers, specifically for perceived behavioral control (65.0±32.5 vs 43.6±19.8, respectively; p<0.001). WTP WLs featuring proximal risks, such as dental effects (ß = 9.70; 95% CI: 7.00-12.40), fetal harm (ß = 9.42; 95% CI: 6.75-12.10), or toxic contents (ß = 9.14; 95% CI: 6.58-11.70) were strongly associated with participants' perceived efficacy scores. Among other independent factors, rural residence (ß = 24.09; 95% CI: 22.21-25.97), being a nonsmoker (ß = 10.51; 95% CI: 8.92-12.10), survey round 2 (ß = 6.96, 95% CI: 5.73-8.19), the novel WTP WL set (ß = 6.68; 95% CI: 6.19-7.17), and having higher education (ß = 6.31; 95% CI: 4.34-8.27) were highly associated with participants' perceived efficacy scores. CONCLUSIONS: Waterpipe-specific WLs on plain WTPs that feature proximal risks and address different population subgroups need to be developed in conjunction with awareness raising campaigns on WTS harms to reinforce the credibility of WTP WLs. Our findings suggest the proposed WTP WL enhancements by the Tobacco Control Unit may support a more effective WTP labelling policy within a comprehensive waterpipe-specific tobacco control framework.

Comparative study between bowel ultrasound and magnetic resonance enterography among Egyptian inflammatory bowel disease patients.

BACKGROUND: Bowel ultrasound and magnetic resonance enterography (MRE) are decisive medical imaging modalities for diagnosing and locating bowel lesions with its extramural extent and complications. They assess the degree of activity, help clinicians to identify patients in need of surgery, and can be used for patient follow-up. AIM: To compare the role of MRE and bowel ultrasound in diagnosis and follow-up of inflammatory bowel disease (IBD) patients in Egypt. METHODS: The study was conducted on 40 patients with IBD. All patients were subjected to clinical assessment, laboratory investigations, bowel ultrasound, MRE, and colonoscopy up to the terminal ileum with biopsies for histopathological examination. RESULTS: This study was conducted on 14 patients (35%) with ulcerative colitis and 26 patients (65%) with Crohn's disease; 34 (85%) of these patients had active disease. Bowel ultrasound detected different bowel lesions with the following accuracies: ileum (85%), large bowel (70%), fistula (95%), stricture and proximal dilatation (95%) and abscesses (100%). Also, it showed that statistically significance of bowel ultrasound in differentiation between remission and activity of IBD in comparison to MRE and colonoscopy. CONCLUSION: In comparison to MRE, bowel ultrasound is a useful, non-invasive, and feasible bedside imaging tool for the detection of inflammation, detection of complications, and follow-up of IBD patients when performed by the attending physician.

A novel chemoprotective effect of tiopronin against diethylnitrosamine-induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK-P53 signalling cascade.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Oxidative stress contributes significantly to HCC pathogenesis. In this study, we investigated the possible chemoprotective effect of the thiol group-containing compound, tiopronin, against HCC induced chemically by diethylnitrosamine (DENA) in rats. In addition, we elucidated the possible underlying molecular mechanism. Adult male Wistar rats were divided into: Control group, DENA-treated group and tiopronin + DENA-treated group. Liver function tests (ALT, AST, ALP, albumin, total and direct bilirubin) as well as alpha fetoprotein (AFP) concentration were measured in the sera of samples. Oxidative stress biomarkers such as malondialdehyde, nitric oxide, catalase and glutathione peroxidase were measured in the liver tissue homogenates. Determination of the phosphorylated apoptosis signal-regulating kinase 1 (phospho-ASK1), phospho-P38 and phospho-P53 proteins by western blotting, caspase 3 by immunofluorescence in addition to histopathological examination of the liver tissues were performed. Our results showed that tiopronin prevented the DENA-induced elevation of the liver function enzymes and AFP. It also preserved the activities of antioxidant enzymes as well as providing protection from the appearance of HCC histopathological features. Interestingly, tiopronin significantly decreased the expression level of phospho-ASK1, phospho-P38 and phospho-P53, caspase 3 in the liver tissues. These novel findings suggested that tiopronin is an antioxidant drug with a chemoprotective effect against DENA-induced HCC through maintaining the normal activity of ASK1/ P38 MAPK/ P53 signalling pathway.

Detecting liver fibrosis using a machine learning-based approach to the quantification of the heart-induced deformation in tagged MR images.

Liver disease causes millions of deaths per year worldwide, and approximately half of these cases are due to cirrhosis, which is an advanced stage of liver fibrosis that can be accompanied by liver failure and portal hypertension. Early detection of liver fibrosis helps in improving its treatment and prevents its progression to cirrhosis. In this work, we present a novel noninvasive method to detect liver fibrosis from tagged MRI images using a machine learning-based approach. Specifically, coronal and sagittal tagged MRI imaging are analyzed separately to capture cardiac-induced deformation of the liver. The liver is manually delineated and a novel image feature, namely, the histogram of the peak strain (HPS) value, is computed from the segmented liver region and is used to classify the liver as being either normal or fibrotic. Classification is achieved using a support vector machine algorithm. The in vivo study included 15 healthy volunteers (10 males; age range 30-45 years) and 22 patients (15 males; age range 25-50 years) with liver fibrosis verified and graded by transient elastography, and 10 patients only had a liver biopsy and were diagnosed with a score of F3-F4. The proposed method demonstrates the usefulness and efficiency of extracting the HPS features from the sagittal slices for patients with moderate fibrosis. Cross-validation of the method showed an accuracy of 83.7% (specificity = 86.6%, sensitivity = 81.8%).

Gene Expression of the Circulating Long Noncoding RNA H19 and HOTAIR in Egyptian Colorectal Cancer Patients.

Background: HOX transcript antisense RNA (HOTAIR) and H19 are two long noncoding RNAs that play vital functions in the development of colorectal cancer (CRC). Subjects and Methods: The expression level of HOTAIR and H19 in the sera samples of Egyptian CRC patients along with normal controls was evaluated by quantitative real-time PCR. The possible correlations with the biochemical and clinicopathological characteristics were determined. Results: The expression of HOTAIR and H19 showed 7.55- and 11.38-fold increased levels, respectively, in CRC patients compared to the controls (p < 0.001). Furthermore, HOTAIR expression in CRC patients with regional lymph node metastasis was significantly higher when compared with CRC patients without regional lymph node metastasis (p = 0.034). HOTAIR and H19 expression showed no significant correlation with tumor site or carcinoembryonic antigen concentration. The sensitivity and specificity of HOTAIR and H19 in the detection of CRC cases were calculated as 92.9% and 100%, respectively. Conclusion: HOTAIR and H19 expression levels are upregulated in Egyptian CRC patients, and therefore can be considered noninvasive diagnostic biomarkers with high sensitivity and specificity.

Substitution at Phenyl Rings of Chalcone and Schiff Base Moieties Accounts for their Antiproliferative Activity.

BACKGROUND: In a continuous combat against cancer, which is one of the leading causes of mortality now, chalcone and Schiff bases moieties have been incorporated and their antiproliferative activities and associated mechanisms against liver (HepG2) and breast (MCF-7) cell lines in addition to normal fibroblasts (WI-38) have been examined. METHODS: Derivatives 4 and 5 of Schiff bases only and chalcone derivatives of Schiff bases 1 and 2 were devoid of any antiproliferative activity. All three compounds (3, 6, and 7) with significant antiproliferative activity were selective and caused no growth inhibition in normal fibroblasts. Derivative 3 was a chalcone only with IC50 of ~20 µM and has a very interesting signature where it enhanced apoptosis in HepG2 by stimulating the expression of downstream execution caspase 3 without affecting neither p53 nor initiator caspase 9. In spite of the structural similarity between compounds 6 and 7, compound 6 discerned itself with a unique IC50 of ~ 10 µM. RESULTS: The antiproliferative activity of derivative 6 could be attributed to its unique capability of formation of free radicals such as phenoxide radicals which arrested the cell cycle through enhancing the expression of p53 and induced apoptosis by induction of both caspases 9 and 3. It was the only investigated derivative that inhibited the tyrosine kinase activity by 89%. CONCLUSIONS: The antiproliferative activity of the compounds under investigation considerably depended on the nature of the substituent at position 4 in phenyl rings of both chalcone and Schiff base fragments. Derivative 6 with electron withdrawing chlorine substitution on the phenyl ring of Schiff base fragment and an electron donating methoxy group on the phenyl ring of chalcone fragment was the most active member.

Involvement of PI3K/Akt pathway in the protective effect of hesperidin against a chemically induced liver cancer in rats.

Hesperidin is a flavanone glycoside that is found in the Citrus species and showed antioxidant, hepatoprotective as well as anticancer activity. This study investigated the effect of hesperidin on the PI3K/Akt pathway as a possible mechanism for its protective effect against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC). Adult Wistar rats were divided into Control group (received drug vehicle); DEN group (received 100 mg/L of DEN solution for 8 weeks), and hesperidin + DEN group (received 200 mg/kg body weight of hesperidin/day orally for 16 weeks + DEN solution as DEN group). Our findings showed that the administration of hesperidin significantly decreased the elevation in liver function enzymes, serum AFP level, and oxidative stress markers. Moreover, hesperidin administration suppressed DEN-induced upregulation of PI3K, Akt, CDK-2 protein expression, and preserved the integrity of the liver tissues from HCC formation. In conclusion, the hepatoprotective activity of hesperidin is mediated via its antioxidation and downregulation of the PI3K/Akt pathway.

Synthesis and Reactivity of 6,8-Dibromo-2-ethyl-4H-benzo[d][1,3]oxazin-4-one Towards Nucleophiles and Electrophiles and Their Anticancer Activity.

BACKGROUND: The genetic heterogeneity of tumor cells and the development of therapy-resistant cancer cells in addition to the high cost necessitate the continuous development of novel targeted therapies. METHODS: In this regard, 14 novel benzoxazinone derivatives were synthesized and examined for anticancer activity against two human epithelial cancer cell lines; breast MCF-7 and liver HepG2 cells. 6,8-Dibromo-2- ethyl-4H-benzo[d][1,3]oxazin-4-one was subjected to react with nitrogen nucleophiles to afford quinazolinone derivatives and other related moieties (3-12). Benzoxazinone 2 responds to attack with oxygen nucleophile such as ethanol to give ethyl benzoate derivative 13. The reaction of benzoxazinone 2 with carbon electrophile such as benzaldehyde derivatives afforded benzoxazinone derivatives 14a and 14b.The structure of the prepared compounds was confirmed with spectroscopic tools including IR, 1H-NMR, and 13C-NMR. RESULTS: Derivatives 3, 9, 12, 13, and 14b exhibited high antiproliferative activity and were selective against cancer cells showing no toxicity in normal fibroblasts. Derivative 3 with NH-CO group in quinazolinone ring was effective only against breast cells, while derivative 12 with NH-CO group in imidazole moiety was only effective against liver cells probably through arresting cell cycle and enabling repair mechanisms. The other derivatives (9, 13, and 14b) had broader antiproliferative activity against both cell lines. These derivatives enhance the expression of the p53 and caspases 9 and 3 to varying degrees in both cell lines. Derivative 14b caused the highest induction in the investigated genes and was the only derivative to inhibit the EGFR activity. CONCLUSIONS: The unique features about derivative 14b could be attributed to its high lipophilicity, high carbon content, or its extended conjugation through planar aromatic system. More investigations are required to identify the lead compound(s) in animal models.

MRI assessment of hepatocellular carcinoma after locoregional therapy.

Liver cirrhosis and hepatocellular carcinoma (HCC) constitute one of the major causes of morbidity, mortality, and high health care costs worldwide. Multiple treatment options are available for HCC depending on the clinical status of the patient, size and location of the tumor, and available techniques and expertise. Locoregional treatment options are multiple. The most challenging part is how to assess the treatment response by different imaging modalities, but our scope will be assessing the response to locoregional therapy for HCC by MRI. This will be addressed by conventional MR methods using LI-RADS v2018 and by functional MR using diffusion-weighted imaging, perfusion, and highlighting the value of the novel intravoxel incoherent motion (IVIM).

Modulation of JNK-1/ ß-catenin signaling by Lactobacillus casei, inulin and their combination in 1,2-dimethylhydrazine-induced colon cancer in mice.

Colon cancer is a complex disease that involves numerous genetic alterations that change the normal colonic mucosa into invasive adenocarcinoma. In the current study, the protective effects of inulin (prebiotic), Lactobacillus casei (L. casei, probiotic) and their combination (synbiotic) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male Swiss mice were evaluated. Animals were divided into: Control group, DMH-treated group, DMH plus inulin, DMH plus L. casei and DMH plus inulin plus L. casei-treated groups. Fecal microbiome analysis, biochemical measurements, histopathological examination of the colon tissues, immunostaining and Western blotting analysis of ß-catenin, GSK3ß and JNK-1 were performed. The prebiotic-, probiotic- and synbiotic-treated groups showed decreased levels of carcinoembryonic antigen and a lower number of aberrant crypt foci compared to the DMH-treated group with the synbiotic group exhibiting a superior effect. Furthermore, all treatments showed a body weight-reducing effect. Administration of inulin, L. casei or their combination increased the expression level of phospho-JNK-1 while they decreased the expression level of ß-catenin and phospho-GSK3ß. Remarkably, L. casei treatment resulted in enrichment of certain beneficial bacterial genera i.e. Akkermansia and Turicibacter. Therefore, administration of L. casei and inulin as a synbiotic combination protects against colon cancer in mice.