Naturally occurring benzophenones and xanthones from Garcinia smeathmannii (Planch. & Triana) Oliv. displayed anti-inflammatory effects by modulating the activities of inflammatory mediators in LPS-stimulated RAW 264.7 macrophages.

Introduction: There is a growing interest in studying natural products for the identification of novel lead compounds for drug development for treating inflammatory diseases. Although some studies have focused anti-inflammatory activity of benzophenones and xanthones, exploring additional targets such as enzymes and cytokines, involved in their inflammatory response could provide more comprehensive understanding of the compounds' anti-inflammatory effects. In this study, four xanthones ananixanthone (1), smeathxanthone A (2), smeathxanthone B (3), and 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethyloct-2,6-dienyl) xanthone (4); and three benzophenones guttiferone O (5), guttiferone M (6), and aristophenone A (7) from Garcinia smeathmannii (Planch. & Triana) Oliv. were investigated for their effect on nitric oxide production, cyclooxygenase, lipoxygenase inhibition, and Th1/Th2 cytokines production in activated RAW 264.7 macrophages. Methods: The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and the 15-lipoxygenase activity respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit and measurement of Th1/Th2 cytokines was performed using a flow cytometer. Results: All the tested compounds exhibited a dose-dependent inhibition of NO production with varying degrees of inhibitory effects on 15-LOX activity. Compound (6), displays the best inhibitory effect on COX-1/COX-2 activity. A general trend of the tested compounds on cytokines profiles revealed that compound (5) showed a pronounced enhancement of anti-inflammatory cytokines (IL-4 and IL-10). Conclusion: This observation supports future exploration of ananixanthone (1), guttiferone O (5), and guttiferone (6) as potential candidates for the development of anti-inflammatory drugs.

The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis.

Background: Bronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma. Methods: This study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs. Results: The current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.

Linagliptin, a DPP-4 inhibitor, activates AMPK/FOXO3a and suppresses NFκB to mitigate the debilitating effects of diethylnitrosamine exposure in rat liver: Novel mechanistic insights.

Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies. Several potential molecular mechanisms have been proposed to explain these effects. However, the capacity of LNGTN to activate FOXO3a through AMPK activation has not been investigated. In our investigation, we examined the potential repurposing of LNGTN as a hepatoprotective agent against diethylnitrosamine (DENA) intoxication. Additionally, we assessed LNGTN's impact on apoptosis and autophagy. Following a 10-week administration of DENA, the liver underwent damage marked by inflammation and early neoplastic alterations. Our study presents the first experimental evidence demonstrating that LNGTN can reinstate the aberrantly regulated FOXO3a activity by elevating the nuclear fraction of FOXO3a in comparison to the cytosolic fraction, subsequent to AMPK activation. Moreover, noteworthy inactivation of NFκB induced by LNGTN was observed. These effects culminated in the initiation of apoptosis, the activation of autophagy, and the manifestation of anti-inflammatory, antiproliferative, and antiangiogenic outcomes. These effects were concomitant with improved liver function and microstructure. In conclusion, our findings open new avenues for the development of novel therapeutic strategies targeting the AMPK/FOXO3a signaling pathway in the management of chronic liver damage.

Exploring signaling pathway crosstalk in glioma by mapping miRNA and WNT pathways: A review.

Glioma is a significant healthcare burden; nevertheless, the particular genetic regulatory mechanism underpinning its onset and progression is still unknown. Recent research has focused in large part on trying to determine the underlying molecular pathways that contribute to the malignancy of this disease because of the difficulties in treating it. Many tumors have been linked to changes in the expression of microRNAs (miRNAs). miRNAs play a critical role in cancer development by controlling a wide variety of targets and signaling cascades. A rising body of evidence emphasizes WNT pathway dysregulation in glioma, despite the fact that it is dysregulated in many malignancies. Here, we give a detailed analysis of the roles played by miRNAs in the WNT pathway by glioma. We also demonstrate how the WNT pathway cooperates with miRNAs to control a variety of functions, including cell proliferation, invasion, migration, and epithelial-mesenchymal transition.

Impact of a longitudinal faculty development program on the quality of multiple-choice question item writing in medical education.

Background: Like many other academic programs, medical education is incomplete without a robust assessment plan. Objective: The study aimed to evaluate the impact of longitudinal faculty development program (FDP) on the examination item quality (EIQ) from a cohort of medical college faculty members. Methods: Item analysis (IA) of multiple-choice questions (MCQs) from a cohort of medical tutors over a 3-year period (2017 [S1], 2018 [S2], and 2019 [S3]) before and following once-per-week FDP was conducted. The questions were from three randomly selected courses: man and his environment (MEV) from phase 1, central nervous system (CNS) from phase 2, and internal medicine (MED) from phase 3. Data assessed were 480 MCQs from the final exams in the courses. The parameters considered in IA were the difficulty index, index of discrimination, nonfunctional distractors (NFDs), distractor efficiency for each question item, and Cronbach's alpha (CA) for the test as a whole. Comparison over the 3 years was made using Fisher's exact test and repeated-measures ANOVA with Bonferroni test as post hoc test. Results: Overall, out of 480 MCQs, 272 had no NFD (52 [19.52%], 104 [38.24%], and 116 [42.65%] in 2017, 2018, and 2019, respectively) with a significant difference between S3, S2, and S1 (P < 0.0001). The mean CA for the exams in S1, S2, and S3, respectively, were 0.51, 0.77, and 0.84, P < 0.0001. Conclusion: There was an improvement in EIQ following the implementation of longitudinal FDP. Thus, the need for active training and retraining of the faculty for a better EIQ cannot be overemphasized.

RésuméContexte: Comme beaucoup d'autres programmes universitaires, la formation médicale est incomplète sans un plan d'évaluation solide. Objectif: L'étude visait à évaluer l'impact du programme longitudinal de formation professorale (FDP) sur la qualité des éléments d'examen (EIQ) d'une cohorte de membres du corps professoral des facultés de médecine. Méthodes: Analyse des éléments (IA) des questions à choix multiples (QCM) d'une cohorte de tuteurs médicaux une période de trois ans (2017 [S1], 2018 [S2] et 2019 [S3]) avant et après le déroulement du FDP hebdomadaire a été effectuée. Les questions venaient de trois cours choisis au hasard: l'homme et son environnement (MEV) de la phase 1, le système nerveux central (SNC) de la phase 2 et interne médecine (MED) de la phase 3. Les données évaluées étaient 480 QCM des examens finaux des cours. Les paramètres considérés dans IA étaient l'indice de difficulté, l'indice de discrimination, les distracteurs non fonctionnels (NFD), l'efficacité du distracteur pour chaque question et le alpha (CA) pour le test dans son ensemble. La comparaison au cours des 3 années a été faite en utilisant le test exact de Fisher et l'ANOVA à mesures répétées avec Test de Bonferroni comme test post hoc. Résultats: Dans l'ensemble, sur 480 QCM, 272 n'avaient pas de NFD (52 [19,52%], 104 [38,24%] et 116 [42,65%] en 2017, 2018 et 2019, respectivement) avec une différence significative entre S3, S2 et S1 (P <0,0001). L'AC moyenne pour les examens en S1, S2 et S3, respectivement, était de 0,51, 0,77 et 0,84, P <0,0001. Conclusion: Il y a eu une amélioration de l'EIQ après la mise en œuvre du FDP. Ainsi, la nécessité d'une formation active et d'un recyclage de la faculté pour un meilleur QEI ne peut pas être surestimée.

Prevalence of active epilepsy, lifetime epilepsy prevalence, and burden of epilepsy in Sub-Saharan Africa from meta-analysis of door-to-door population-based surveys.

BACKGROUND: There is marked variation in the prevalence of epilepsy across Sub-Saharan Africa (SSA). In order to accurately estimate the clinical and public health impacts of epilepsy in the region, robust and reliable epidemiological data are required for appropriate estimation of logistical, economical, and social impacts of epilepsy including policy formulation and intervention in the region. OBJECTIVE: We sought to evaluate the prevalence of active epilepsy (AE) and lifetime epilepsy prevalence in SSA using available data collected at community level. METHODS: We carefully searched online databases and identified the required articles using prespecified criteria. Random-effects model (REM) was used to estimate the active and lifetime prevalence from data generated from studies in SSA.. The burden of epilepsy, in terms of the number of people with the disease, was also obtained. Heterogeneity in the analysis was further explored using subgroup analysis and meta-regression techniques. RESULT: A total of 39 and 12 community-based door-to-door surveys addressing AE and lifetime epilepsy, respectively, from different countries of SSA met the inclusion criteria for the study. Random-effects model estimates of overall prevalence of epilepsy were 9 per 1000 persons (95% confidence interval (CI): 8.0-9.9 per 1000 persons) for AE and 16 per 1000 persons (95% CI: 12.3-19.7 per 1000 persons) for lifetime epilepsy. The prevalence was highest in the Central Africa subregion with 30.2 per 1000 persons (95% CI: 6.2 to 66.7 per 1000 persons). The prevalence of AE in the rural settlement was twice that of the urban settlements. About 9,596,551 (95% CI: 8,530,267-10,556,206) people with AE and 17,060,535 (95% CI: 13,115,286-21,005,784) people with lifetime epilepsy live in SSA. CONCLUSION: This study estimates the active (9/1000) and lifetime (16/1000) epilepsy with a remarkable burden of the disease in SSA. However, the prevalence, which is higher in the rural setting, varies within the subregion of SSA.

Some Strychnos spinosa (Loganiaceae) leaf extracts and fractions have good antimicrobial activities and low cytotoxicities.

BACKGROUND: Strychnos spinosa Lam. is a deciduous tree used in traditional medicine to treat infectious diseases. This study is designed to determine the antimicrobial, antioxidant and cytotoxic activities of extracts and fractions from leaves of S. spinosa. METHODS: Extracts were obtained by maceration with acetone, methanol and dichloromethane/methanol (1/1) while fractions were prepared by liquid-liquid fractionation of the acetone extract. A broth serial microdilution method with tetrazolium violet as growth indicator was used to determine the minimum inhibitory concentration (MIC) against fungi, Gram-positive and Gram-negative bacteria. The antioxidant activity was determined using free-radical-scavenging assays, and the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide reduction assay was used to determine cytotoxicity. RESULTS: Four extracts and five fractions had good to weak antimicrobial activity with MICs ranging from 0.04 to >1.25 mg/ml against both fungi and bacteria. The chloroform and ethyl acetate fractions had an MIC of 0.08 mg/ml against Aspergillus fumigatus. The n-butanol fraction had an MIC of 0.04 mg/ml against Cryptococcus neoformans. The hexane and chloroform fractions had an MIC of 0.08 mg/ml against Staphylococcus aureus. The antioxidant activities were much lower than that of the positive controls. Except for the alkaloid extract, all the extracts and fractions had free-radical-scavenging activity (IC50 ranging from 33.66 to 314.30 µg/ml). The cytotoxicity on Vero cells was reasonable to low with LC50 values ranging between 30.56 and 689.39 µg/ml. CONCLUSION: The acetone extract and the chloroform fraction had the highest antibacterial activity. By solvent-solvent fractionation it was possible to increase the activity against A. fumigatus and to decrease the cytotoxicity leading to a potentially useful product to protect animals against aspergillosis. Our results therefore support the use of S. spinosa leaves in traditional medicine to treat infectious diseases.