Explore the vast range of titles available.

Background: A disintegrin and metalloproteinases (ADAMs) have emerged as therapeutic targets in many cancers. ADAM10 was particularly studied in hepatocellular carcinoma (HCC) for its potential role in hepatocarcinogenesis and HCC progression. Objective: To investigate the immunohistochemical (IHC) expression of ADAM10 in HCCs and the adjacent noncancerous tissues from 70 HCC patients, attempting to elucidate any association between ADAM10 and HCC development and/or progression. Materials and Methods: IHC staining for anti-ADAM10 was performed using horseradish peroxidase technique. An extent and intensity-dependent scoring was applied dividing samples into high- and low-expression groups. HCCs were statistically compared in relation with gender, age, cirrhosis, hepatitis C virus (HCV) status, alpha-fetoprotein (AFP) serum level, tumor size, multiplicity, encapsulation/invasion, grade, histological pattern and variant, mitosis, necrosis, vascular emboli, portal thrombosis, stage, recurrence, and mortality. Kaplan-Meier's method was used to analyze disease-free and overall survival (DFS and OS). Results: ADAM10 was expressed in 77.1% of HCCs compared with 42.9% of noncancerous tissues. Differential expression showed significant statistical difference (P = 0.02), as 38.6% of HCCs showed high expression, whereas 92.8% of noncancerous samples showed low expression. No significant differences were observed when high- and low-ADAM10 expression HCCs were compared with respect to all tested prognostic parameters except the HCV status. Patients whose tumors showed high-ADAM10 expression had relatively longer DFS and OS times, but with insignificant log-rank differences. Conclusions: ADAM10 is frequently expressed in HCCs compared with noncancerous hepatic tissues suggesting its role in hepatocarcinogenesis, especially in association with HCV. It has no association with HCC progression or survival. Further studies should be sought to investigate its validity as a therapeutic target.

Toxoplasma gondii is a worldwide prevalent parasite. The infection has been linked to variable inflammatory effects including neuroinflammation. Biochanin A (BCA) is an isoflavone, known for its anti-inflammatory and anti-oxidative properties. In this study, we examined the effect of BCA on the brain and liver inflammatory lesions in a murine model with chronic toxoplasmosis. Mice were divided in to six groups: non-infected control, non-infected BCA-treated, and four infected groups with Toxoplasmagondii Me49-type II cystogenic strain: infected control, BCA (50 mg/kg/day)-treated, combined BCA/cotrimoxazole-treated and cotrimoxazole (370 mg/kg/day) alone-treated. Gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS) was evaluated by quantitative real-time PCR in the brain and liver tissues. In the infected control group, an upregulation of TNF-α and IL-1β mRNA expression levels was found. However, a downregulation of iNOS expression was detected in the brain of infected control mice. In both BCA- and combined-treated groups, the brain and liver tissues showed significantly reduced inflammatory lesions compared to the infected control mice with inhibited TNF-α and IL-1β mRNA levels. The iNOS expression levels in the brain tissues of BCA group were significantly higher than the levels of the infected control group. BCA alone or combined significantly reduced T. gondii cyst count in the brain tissues. In conclusion, the anti-inflammatory activity of BCA was demonstrated in the brain tissues of mice with chronic toxoplasmosis with decreased TNF-α and IL-1β expression levels and increased iNOS expression levels.

Purpose The autophagy process is critical for cell survival, homeostasis, and functions. Autophagy deregulation was linked to several liver diseases; however, little is known about autophagy status during schistosomiasis and praziquantel (PZQ) treatment. This study is exploring autophagy status during schistosomiasis and praziquantel treatment in the hepatocytes, macrophages, and hepatic stellate cells (HSCs) in mice, and linking the variations in these levels to the parasitic parameters. Methods CD-1 Swiss female albino mice were allocated into three groups: negative control, Schistosoma mansoni ( S. mansoni )-infected, and the third group was S. mansoni- infected and treated with PZQ. Liver sections were stained for autophagy markers (LC3 and P62) by immunohistochemistry. Results At 12 weeks post infection, P62 increased in S. mansoni -infected mice in hepatocytes, macrophages, and HSCs compared to negative controls ( P  = 0.038, P  < 0.001, P  = 0.004, respectively) and decreased in PZQ-treated group compared to S. mansoni -infected mice in hepatocytes and macrophages only ( P  < 0.001, P  = 0.004, respectively). LC3 displayed higher levels in S. mansoni- infected mice compared to negative controls in hepatocytes, macrophages, and HSCs ( P  = 0.01, P  < 0.001, P  < 0.001, respectively), while in PZQ-treated group, it decreased in macrophages and HSCs compared to S. mansoni -infected mice ( P  = 0.016, P  < 0.001, respectively). Correlations were found between the number of eggs and autophagy status, mostly in HSCs. Conclusion Schistosomiasis inhibits autophagy in hepatocytes, macrophages, and HSCs, while PZQ treatment reverses autophagy levels in hepatocytes and macrophages, but not in HSCs. More research is needed to understand the autophagy behavior in HSCs during different stages of schistosomiasis to promote development of autophagy-based anti-fibrotic drugs.

This experiment aimed to investigate the effect of dietary  Nigella sativa  on the cell-mediated immune response. Eighteen male Wistar rats were divided equally into a control group and treated groups that received black seeds at rates of 30 and 50 g/kg in the diet (Sa30 and Sa50 groups, respectively, for 30 days. The weight gain, feed intake, feed conversion ratio (FCR), and cell-mediated immune response were monitored after the injection of 0.1 mL of 10% phytohemagglutinin (PHA). The intumesce index, serum total antioxidant capacity (TAC), catalase (CAT), interleukin-12 (IL-12), gamma interferon (γ-IF) and tumor necrosis factor alpha (TNF-α) were determined. Histopathological examination and an immunohistochemistry analysis of splenic caspase-3 and CD8 were performed. Nigella sativa  significantly improved the weight gain and FCR. Intumesce index of Sa50 group was significantly increased. Nigella sativa significantly increased TAC, CAT, IL-12, γ-IF and TNF-α. A histological examination of PHA-stimulated foot pads showed increased leukocyte infiltration and edema in a dose-dependent pattern. Splenic caspase-3 and CD8 showed significant decreases and increases, respectively, in the Sa30 and Sa50 groups. The results indicate that Nigella sativa seeds exhibit immunostimulatory function through their antioxidant potential, induction of cytokine production, promotion of CD8 expression and reduction of splenic apoptosis.

Background Pyocyanin is a secondary metabolite secreted by P. aeruginosa . It is a redox-active blue/green phenazine pigment that has various beneficial applications. The present study aims at screening the production of pyocyanin among clinical and environmental P. aeruginosa isolates in Dakahlya governorate, Egypt. Thereafter, large-scale production, purification, structure elucidation, and assessment of the biological activity of the highest pyocyanin producers were targeted. Results Pyocyanin from the highest clinical (PsC05) and environmental (PsE02) producers were subjected to large-scale production, followed by purification using silica gel column. Pyocyanin was characterized using TLC, UV-Vis, 1  H NMR, and FTIR spectroscopy to confirm its structure and purity. Purified pyocyanin showed remarkable antimicrobial efficacy against all tested food-borne pathogens, MDR/XDR clinically isolated bacteria and C. albicans . Furthermore, it showed a substantial effect on biofilm inhibition and eradication of pre-formed biofilm against strong biofilm producing bacterial pathogens. However, it had limited antibiofilm activity against C. albicans . Pyocyanin from PsC05 had higher antioxidant and radicals scavenging activity than that from PsE02 as determined by FRAP, DPPH, and ABTS assays. Likewise, pyocyanin from PsC05 was more active against tested cancer cell lines, especially human Breast Cancer (MCF-7) and Colorectal Carcinoma (HCT-116), than that from PsE02. More importantly, it showed minimal cytotoxicity to normal cells. Conclusions P. aeruginosa clinical and environmental isolates produce pyocyanin pigment in varying amounts. Pyocyanin exhibits substantial anti-bacterial, and anti-fungal activity; thus, enhancing its medical applicability. It could be used to inhibit and/or eradicate biofilm from the surfaces of medical devices which is a chief source of nosocomial infections. Its antioxidant along with cytotoxic activity against cancer cell lines, make it a promising contender for use as a substitute for synthetic agents in cancer treatment.

Ceramic materials are increasingly used in micro-electro-mechanical systems (MEMS) as they offer many advantages such as high-temperature resistance, high wear resistance, low density, and favourable mechanical and chemical properties at elevated temperature. However, with the emerging of additive manufacturing, the use of ceramics for functional and structural MEMS raises new opportunities and challenges. This paper provides an extensive review of the manufacturing processes used for ceramic-based MEMS, including additive and conventional manufacturing technologies. The review covers the micro-fabrication techniques of ceramics with the focus on their operating principles, main features, and processed materials. Challenges that need to be addressed in applying additive technologies in MEMS include ceramic printing on wafers, post-processing at the micro-level, resolution, and quality control. The paper also sheds light on the new possibilities of ceramic additive micro-fabrication and their potential applications, which indicates a promising future.

This study investigated the ameliorative potential of methanolic date flesh extract (MDFE) against cisplatin-induced hepatic injury. Twenty male rats (weighing 180–200 g) were allocated into four groups: control; date flesh (DF) group (oral 600 mg/kg MDFE for 21 days); Cis group (7.5 mg/kg i.p. at day 16); and date flesh/cisplatin (DF/Cis) group (oral 600 mg/kg MDFE for 21 days and 7.5 mg/kg i.p. at day 16). Hepatic biochemical parameters in sera, and inflammatory and oxidant/antioxidant hepatic biomarkers were estimated. Hepatic histological changes and the immunohistochemistry of cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), and alpha smooth muscle actin (α-SMA) were assessed. Pretreatment with MDFE decreased Cis-triggered liver biochemical parameters, oxidative stress, inflammatory biomarkers, and histological damage. Moreover, MDFE treatment reduced Cis-induced hepatic NF-κB, COX-2, and α-SMA protein expression. MDFE exerted a hepatoprotective effect when used concomitantly with Cis. Its effect was mediated via its antioxidant and anti-inflammatory ingredients.

Background and Objectives: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world. Due to failure of the traditional drugs to produce a complete cure for AD, the search for new safe and effective lines of therapy has attracted the attention of ongoing research. Canagliflozin is an anti-diabetic agent with proven efficacy in the treatment of neurological disorders in which mitochondrial dysfunction, oxidative stress, apoptosis, and autophagy play a pathophysiological role. Elucidation of the potential effects of different doses of canagliflozin on AD induced by aluminium chloride in rats and exploration of the molecular mechanisms that may contribute to these effects were the primary objectives of the current study. Materials and Methods: In a rat model of AD, the effect of three different doses of canagliflozin on the behavioural, biochemical, and histopathological alterations induced by aluminium chloride was assessed. Results: Canagliflozin administered to aluminium chloride-treated animals induced dose-dependent normalisation in the behavioural tests, augmentation of the antioxidant defence mechanisms, inhibition of TXNIP/NLRP3 inflammasome signalling, modulation of the SIRT1/HMGB1 axis, interference with the pro-inflammatory and the pro-apoptotic mechanisms, and restoration of the mitochondrial functions and autophagy in the hippocampal tissues to approximately baseline values. In addition, canagliflozin exhibited an interesting dose-dependent ability to repress aluminium chloride-induced histopathological changes in the brain. Conclusions: The effects of canagliflozin on oxidative stress, mitochondrial functions, inflammatory pathways, and autophagy signals may open new gates towards the mitigation of the pathologic features of AD.

Trypanosomiasis is a protozoan disease transmitted via Trypanosoma brucei. This study aimed to examine the metabolic profile and anti-trypanosomal effect of methanol extract of Thunbergia grandifolia leaves. The liquid chromatography-high resolution electrospray ionisation mass spectrometry (LC-HRESIMS) revealed the identification of fifteen compounds of iridoid, flavonoid, lignan, phenolic acid, and alkaloid classes. The extract displayed a promising inhibitory activity against T. brucei TC 221 with MIC value of 1.90 μg/mL within 72 h. A subsequent in silico analysis of the dereplicated compounds (i.e. inverse docking, molecular dynamic simulation, and absolute binding free energy) suggested both rhodesain and farnesyl diphosphate synthase as probable targets for two compounds among those dereplicated ones in the plant extract (i.e. diphyllin and avacennone B). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling of diphyllin and avacennone were calculated accordingly, where both compounds showed acceptable drug-like properties. This study highlighted the antiparasitic potential of T. grandifolia leaves.

A series of 1H-benzo[f]chromene moieties (4a-z) were synthesised under Ultrasonic irradiation and confirmed with spectral analyses. Derivative 4i solely possessed an X-ray single crystal. The anti-proliferative efficacy of the desired molecules has been explored against three cancer cells: MCF-7, HCT-116, and HepG-2 with the cytotoxically active derivatives screened against MCF-7/ADR and normal cells HFL-1 and WI-38. Furthermore, compounds 4b-d, 4k, 4n, 4q, and 4w, which possessed good potency against MCF-7/ADR, were tested as permeability glycoprotein (P-glycoprotein [P-gp]) expression inhibitors. The attained data confirmed that 4b-d, 4q, and 4w exhibited strong expression inhibition against the P-gp alongside its cytotoxic effect on MCF-7/ADR. The western blot results and Rho123 accumulation assays showed that compounds 4b-d, 4q, and 4w effectively inhibited the P-gp expression and efflux function. Meanwhile, 4b-d, 4q, and 4w induced apoptosis and accumulation of the treated MCF-7/ADR cells in the G1 phase and 4k and 4n in the S phase of the cell cycle.