Organoids as ex vivo culture system to investigate infection-host interaction in gastric pre-carcinogenesis.

Advancements in stem cell research have enabled the establishment of three-dimensional (3D) primary cell cultures, known as organoids. These culture systems follow the organization of an in vivo organ, as they enclose the different epithelial cell lines of which it is normally composed. Generation of these 3D cultures has bridged the gap between in vitro models, made up by two-dimensional (2D) cancer cell lines cultures, and in vivo animal models, that have major differences with human diseases. Organoids are increasingly used as a model to study colonization of gastric mucosa by infectious agents and to better understand host-microbe interactions and the molecular events that lead to infection, pathogen-epithelial cells interactions and mechanisms of gastric mucosal injury. In this review we will focus on the role of organoids as a tool to investigate molecular interactions of Helicobacter (H.) pylori and Epstein Barr Virus (EBV) and gastric mucosa and how these infections, that affect ≈ 45% of the world population, might progress to gastric cancer, a highly prevalent cancer and the third leading cause of cancer death.

Antinociceptive Investigations of Niranthin in Complete Freund’s Adjuvant-induced Chronic Pain in Mice

The main objectives of the present work are to determine the clinical effect of niranthin on visceral or somatic inflammatory pain. The study was performed to determine the effects of niranthin on visceral or somatic inflammatory hypersensitivity of adult Swiss albino mice by using complete Freund’s adjuvant (CFA) induced pain model. The effect of CFA injection was determined after 24 hours of injection by using an aesthesiometer such as Von Frey filaments to evaluate tactile acetone-evoked cooling and thermal sensitivity. We used a digital Plethysmometer to measure paw edema. Single dose of niranthin intraperitoneal injection (5 & 10 mg/kg) was injected into mice having CFA-induced mechanical hypersensitivity and after 30 minutes of administration, reduced mechanical hypersensitivity was observed. In addition, niranthin also reduced acetone-evoked hypersensitivity within 4 hours. Compared to DMSO, niranthin was most highly active to reduce CFA-induced paw edema. To reduce mechanical hypersensitivity, multiple doses of niranthin (bis in die (b.i.d.)) from 1st - 5th day and b.i.d. day 9th and 10th) were given and remarkable results were observed such as did not cause tolerance in multiple dosing and significantly reduced in CFA induced hypersensitivity. This work reported niranthin having antinociceptive activity and indicated that niranthin is conventionally active in the management of persistent pain.

Neuroinflammation and Behavioral Deficit in Rotenone-Induced Neurotoxicity in Rats and the Possible Effects of Butanolic Extract of Centaurea Africana

Background: Many studies have used rotenone (ROT) to create an experimental animal model of Parkinson's disease (PD) because of its ability to induce similar behavioral and motor deficits. PD is the most common age-related motoric neurodegenerative disorder. Neuroinflammation and apoptosis play an important role in the pathogenesis of this disease. Objective: This study investigated the effect of butanolic (n-BuOH) extract of Centaurea africana (200 mg/kg, 16 days) on a ROT-induced neurotoxicity model in male Wistar albino rats. Methods: Estimation of Tumor Necrosis Factor (TNF-α) and Nitric Oxide (NO) levels along with the myeloperoxidase (MPO) activity in brains was carried out in order to evaluate neuro-inflammation. Oxidative stress, Caspase 3 activity (apoptosis), and behavioral alterations were also evaluated. Results: In behavior assessment, using Ludolph Movement Analysis Scale, all ROT treated animals showed a decreased locomotor activity. The mitochondrial dysfunction induced by ROT was expressed by a decreased activity of complex I of the mitochondrial respiratory chain and increased lipid peroxidation and caspase 3. Co-treatment with the n-BuOH extract significantly restored the activity of complex I (65.41%) compared to treatment with ROT alone. The n-BuOH extract also reduced the neuroinflammation in rat brains by reducing MPO activity (75.12%), NO levels (77.43%), and TNF-α (71.48%) compared to the group treated with ROT. Conclusion: The obtained results indicated that C. africana n-BuOH extract exhibited a protective effect in rats.

The evaluation of safety property and apoptotic efficacy of α-L-Guluronic Acid (G2013), as a novel NSAID, under in vitro examination on L929 and hepatocellular carcinoma cell lines

Background: Many investigations have expanded this concept that liver chronic inflammation has an essential role in persistent cell damages along with altering the liver microenvironment leading to fibrosis, cirrhosis, and finally, hepatocellular carcinoma (HCC). To reduce inflammation and relieve symptoms, non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used; however, their long-term usage can lead to severe adverse events on vital organs like the liver. Interestingly, the α-L-Guluronic Acid (G2013), as a novel NSAID with immunomodulatory properties, has shown the inhibitory effects on inflammation and metastasis in experimental models. Objective: This study was conducted to determine the effects of G2013 on cytotoxicity and induction of apoptosis, as a new therapeutic target for cancer therapy, in the HepG2 cell line and the mouse fibroblast cell line L929, as a control. Methods: MTT assay and flow cytometry method were carried out using the different concentrations of G2013 (5, 15, 25, 50, 100, 200 and 400 μg/ml) in 3 distinct incubation times. Results: Our data showed that treatment of HepG2 cells with high concentration (400µg/mL) of G2013 could effectively cause a decrease in cell viability, so that they were statistically different after 72 hours compared to other concentrations (5 to 200 μg/ml) (P<0.05 and P<0.01, respectively). Moreover, the proportion of apoptosis of HepG2 cells at the dose of 200µg/mL considerably increased, suggesting that the induction of apoptosis by G2013 in HepG2 cells is dose- and time-dependent, which could promote its anticancer properties. Conclusion: The present study revealed that G2013 could induce apoptosis in the liver cancer model. Therefore, based on these findings, G2013 might be considered as a therapeutic option in cancer therapy.

Quality of Life of Healthcare Workers Suffering from Occupational Contact Dermatitis

Background: Healthcare workers are at a high risk of developing Occupational Dermatitis (OD). Affected workers often experience severe impairment of their Quality of Life (QoL). This study aimed to assess the skin-related QoL of healthcare workers with OD and to explore its related factors. Methods: A cross-sectional and exhaustive study was conducted among healthcare personnel of four public hospitals in the central region of Tunisia. All the cases of OD declared were included. Skin-related QoL was assessed using the validated Tunisian version of the “Dermatology Life Quality Index” (DLQI). Some related patents were discussed. Results: A total of 37 cases of OD were collected with an annual incidence of 4.2 cases per 10000 workers. The population was predominantly female (73%) and mean aged 44.7±9.4 years. Nurses were the most represented occupational category (38%). Allergic contact dermatitis was the most frequent diagnosis (96%). Use of gloves was the most frequently reported occupational hazard (86%). The most frequently affected sites were hands (97%). The median score of DLQI was five. Multivariate analysis showed an association between the impairment of skin-related QoL and female gender (p = 0.04; OR = 19.3,84), exposure to disinfecting chemicals in the workplace (p = 0.01; OR = 17,306) and the absence of occupational reclassification (p = 0.01; OR = 21,567). Conclusion: About one third of the population had an impaired quality of life. The score impairment was significantly related to female gender, exposure to disinfecting chemicals and the absence of occupational reclassification.