Platelet-Rich Plasma Ameliorates Monosodium Iodoacetate-Induced Ankle Osteoarthritis in the Rat Model via Suppression of Inflammation and Oxidative Stress.

Until now, there is no treatment that cause complete cure of the chronic inflammatory and degenerative disease, osteoarthritis (OA). Moreover, the underlying mechanisms of OA development and progress are not fully elucidated, and the present pharmacological treatment alternatives are restricted and associated with adverse side effects. Thus, the present study was conducted to evaluate the role of platelet-rich plasma (PRP) in the remedy of OA in the rat model in terms of inflammation, ankle histopathological alterations, and oxidative stress. OA was induced in male Wistar rats by injection of MIA (2 mg)/50 µL isotonic saline in the right ankle joint for two successive days in each rat. After the 2nd MIA injection, the osteoarthritic rats were allocated into two groups such as the MIA group (group 2) and MIA + PRP group (group 3). The MIA + PRP group was treated with PRP (50 µL) by injection into the ankle joint of the right hind limb of each rat at days 14, 21, and 28 after the 2nd injection of MIA. The same equivalent volume of saline, as a substitute of PRP, was injected into the ankle joint of each rat of the normal control group (group 1) and MIA group (group 2) at the same tested periods. Swelling of joint, bodyweight, total leucocytes count (TLC), and morphological as well as histological changes of ankle joints were evaluated. Serum lipid peroxides (LPO), glutathione (GSH), and glutathione S-transferase (GST) levels were examined as biomarkers of oxidative stress. Serum tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and interleukin-4 (IL-4) were investigated by ELISA as biomarkers of inflammation. In addition, magnetic resonance imaging (MRI) was carried out to investigate the soft tissues in joints. The obtained results revealed that PRP reduced LPO and increased GSH and GST levels in osteoarthritic rats. Also, PRP significantly diminished serum TNF-α and IL-17 levels, while it increased IL-4 serum levels in rats with MIA-induced OA. Morphological observations, histological analysis, and MRI revealed a gradual diminishing in joint inflammation and destruction of cartilage in PRP-injected osteoarthritic rats. Based on these results, it can be suggested that PRP has antiarthritic potential in MIA-induced OA, which may be mediated via suppression of inflammation and oxidative stress.

Estimating the prevalence of autism spectrum disorder in Lebanon.

This cross-sectional survey examines the prevalence rate of Autism spectrum disorder (ASD) in 818 children (16-48 months) across all Lebanese regions. Screening was done using the revised form of the Modified-Checklist for Autism in Toddlers. Based on the total score of items failed, children were classified into 3 categories of ASD risk (low, moderate and high). Phone calls follow-up interviews and clinical assessments for diagnosis ascertainment were conducted. Given the caregivers' reluctance to participate, the prevalence rate was estimated between 49 and 513 per 10,000 with a male predominance. Our prevalence estimation, even under restrictive assumptions, is higher than elsewhere in the Arab region. Anti- stigma interventions adapted to the socio-cultural context are needed prior to future research in the field.

Transcriptomic profiling of trophoblast fusion using BeWo and JEG-3 cell lines.

In human placenta, alteration in trophoblast differentiation has a major impact on placental maintenance and integrity. However, little is known about the mechanisms that control cytotrophoblast fusion. The BeWo cell line is used to study placental function, since it forms syncytium and secretes hormones after treatment with cAMP or forskolin. In contrast, the JEG-3 cell line fails to undergo substantial fusion. Therefore, BeWo and JEG-3 cells were used to identify a set of genes responsible for trophoblast fusion. Cells were treated with forskolin for 48 h to induce fusion. RNA was extracted, hybridised to Affymetrix HuGene ST1.0 arrays and analysed using system biology. Trophoblast differentiation was evaluated by real-time PCR and immunocytochemistry analysis. Moreover, some of the identified genes were validated by real-time PCR and their functional capacity was demonstrated by western blot using phospho-specific antibodies and CRISPR/cas9 knockdown experiments. Our results identified a list of 32 altered genes in fused BeWo cells compared to JEG-3 cells after forskolin treatment. Among these genes, four were validated by RT-PCR, including salt-inducible kinase 1 (SIK1) gene which is specifically upregulated in BeWo cells upon fusion and activated after 2 min with forskolin. Moreover, silencing of SIK1 completely abolished the fusion. Finally, SIK1 was shown to be at the center of many biological and functional processes, suggesting that it might play a role in trophoblast differentiation. In conclusion, this study identified new target genes implicated in trophoblast fusion. More studies are required to investigate the role of these genes in some placental pathology.

Community cognitive interviewing to inform local adaptations of an e-mental health intervention in Lebanon.

BACKGROUND: Lebanon has a need for innovative approaches to increase access to mental health care to meet the country's current high demand. E-mental health has been included in its national mental health strategy while in parallel the World Health Organization has produced an online intervention called 'Step-by-Step' to treat symptoms of depression that is being tested in Lebanon over the coming years. AIM: The primary aim of this study is to conduct bottom-up, community-driven qualitative cognitive interviewing from a multi-stakeholder perspective to inform the cultural adaptation of an Internet-delivered mental health intervention based on behavioural activation in Lebanon. METHODS: National Mental Health Programme staff conducted a total of 11 key informant interviews with three mental health professionals, six front-line workers in primary health care centres (PHCCs) and two community members. Also, eight focus group discussions, one with seven front-line workers and seven others with a total of 66 community members (Lebanese, Syrians and Palestinians) were conducted in several PHCCs to inform the adaptation of Step-by-Step. Results were transcribed and analysed thematically by the project coordinator and two research assistants. RESULTS: Feedback generated from the cognitive interviewing mainly revolved around amending the story, illustrations and the delivery methods to ensure relevance and sensitivity to the local context. The results obtained have informed major edits to the content of Step-by-Step and also to the model of provision. Notably, the intervention was made approximately 30% shorter; it includes additional videos of content alongside the originally proposed comic book-style delivery; there is less emphasis on total inactivity as a symptom of low mood and more focus on enjoyable activities to lift mood; the story and ways to contact participants to provide support were updated in line with local gender norms; and many of the suggested or featured activities have been revised in line with suggestions from community members. CONCLUSIONS: These findings promote and advocate the use of community-driven adaptation of evidence-based psychological interventions. Some of the phenomena recorded mirror findings from other research about barriers to care seeking in the region and so changes made to the intervention should be useful in improving utility and uptake of 'Step-by-Step'.

Differential Role of Leptin and Adiponectin in Cardiovascular System.

Leptin and adiponectin are differentially expressed adipokines in obesity and cardiovascular diseases. Leptin levels are directly associated with adipose tissue mass, while adiponectin levels are downregulated in obesity. Although significantly produced by adipocytes, leptin is also produced by vascular smooth muscle cells and cardiomyocytes. Plasma leptin concentrations are elevated in cases of cardiovascular diseases, such as hypertension, congestive heart failure, and myocardial infarction. As for the event of left ventricular hypertrophy, researchers have been stirring controversy about the role of leptin in this form of cardiac remodeling. In this review, we discuss how leptin has been shown to play an antihypertrophic role in the development of left ventricular hypertrophy through in vitro experiments, population-based cross-sectional studies, and longitudinal cohort studies. Conversely, we also examine how leptin may actually promote left ventricular hypertrophy using in vitro analysis and human-based univariate and multiple linear stepwise regression analysis. On the other hand, as opposed to leptin's generally detrimental effects on the cardiovascular system, adiponectin is a cardioprotective hormone that reduces left ventricular and vascular hypertrophy, oxidative stress, and inflammation. In this review, we also highlight adiponectin signaling and its protective actions on the cardiovascular system.

Involvement of renal cytochromes P450 and arachidonic acid metabolites in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most serious complications of type I and type II diabetes. DN is characterized by hyperfiltration, hypertrophy, extracellular matrix accumulation, and proteinuria. This advances into renal fibrosis and loss of renal function. Reactive oxygen species (ROS) and TGF-beta have been implicated in the pathogenesis of diabetic nephropathy. Early stages of diabetic nephropathy are also associated with alterations in renal sodium handling as well as hypertension; both are processes linked by involvement of the arachidonic acid (AA) metabolites, 20-hydroxyeicosatetraenoic acid (20-HETE, produced by cytochrome P450-4a, (CYP4A) and epoxyeicosatrienoic acids (EETs). Indeed, metabolism of AA is increased in a rat model of diabetes. In this study, we demonstrate that rats with streptozotocin-induced diabetes of 1 month duration develop renal hypertrophy and increased fibronectin and TGF-beta1 expression/cortical levels concomitant with an increase in CYP4A expression and 20 HETE production. These results were also paralleled by an increase in reactive oxygen species (ROS) production and NADPH oxidase activity. Treatment of diabetic rats with HET0016, selective inhibitor of CYP 4A, prevented all these changes. Our results suggest that diabetes-induced induction of CYP4A and 20-HETE production could be a major pathophysiological mechanism leading to activation of ROS through an NADPH dependent pathway and TGF-beta1 thus resulting in major renal pathology. Inhibitors of 20-HETE production could thus have an important therapeutic potential in the treatment of diabetic nephropathy.

MiR-1 and miR-200 inhibit EMT via Slug-dependent and tumorigenesis via Slug-independent mechanisms.

Epithelial-mesenchymal transition (EMT) is a developmental program of signaling pathways that determine commitment to epithelial and mesenchymal phenotypes. In the prostate, EMT processes have been implicated in benign prostatic hyperplasia and prostate cancer progression. In a model of Pten- and TP53-null prostate adenocarcinoma that progresses via transforming growth factor ß-induced EMT, mesenchymal transformation is characterized by plasticity, leading to various mesenchymal lineages and the production of bone. Here we show that SLUG is a major regulator of mesenchymal differentiation. As microRNAs (miRs) are pleiotropic regulators of differentiation and tumorigenesis, we evaluated miR expression associated with tumorigenesis and EMT. Mir-1 and miR-200 were reduced with progression of prostate adenocarcinoma, and we identify Slug as one of the phylogenetically conserved targets of these miRs. We demonstrate that SLUG is a direct repressor of miR-1 and miR-200 transcription. Thus, SLUG and miR-1/miR-200 act in a self-reinforcing regulatory loop, leading to amplification of EMT. Depletion of Slug inhibited EMT during tumorigenesis, whereas forced expression of miR-1 or miR-200 inhibited both EMT and tumorigenesis in human and mouse model systems. Various miR targets were analyzed, and our findings suggest that miR-1 has roles in regulating EMT and mesenchymal differentiation through Slug and functions in tumor-suppressive programs by regulating additional targets.

[Endoscopic diverticulostomy for Zenker's diverticulum. Experience on 123 cases]. / Diverticulostomia endoscopica per diverticolo di Zenker. Esperienza su 123 casi.

AIM: To evaluate the short-term clinical outcome of the patients with Zenker 's diverticulum undergone to endoscopic esophago-diverticulostomy according to Collard. PATIENTS AND METHODS: A retrospective analysis evaluated 123 patients. The most common symptom was dysphagia, severe in 50 patients (40.6%) and moderate in 73 (59.4%), with a mean dysphagia score of 2.3 (range 0-4). Regurgitation was present in 70 cases (56.9%), with a mean score of 0.8 (range 0-2). The mean diameter of diverticula was 4.1 cm (range 2.5-10). The procedure was undertaken in 87 male and 36 female with a mean follow-up of 69.1 months (range 1-168). RESULTS: Good results were obtained in 82 patients (66.7%), and the improvement of symptoms in 24 (19.5%), data confirmed by pre versus postoperative dysphagia mean score (2.3 vs 0.4) and by regurgitation score (0.8 vs 0.2). The failures have been seen in 17 patients (13.8%). The mean time of the intervention was 18 minutes (range 15-40), while the mean length of postoperative hospital stay was 2.5 days (range 1-5), with a oral intake in first postoperative day (mean). Major complications were documented in 2 patients (1.6%), minor ones in 10 patients (6.1%), without mortality. CONCLUSION: Nowadays esophago-diverticulostomy according to Collard, based on our results and on the literature data, represent the most effective and safe technique for the patients with Zenker's diverticulum, with low rate of morbidity and mortality compared to the others surgical on endoscopic procedures.

The effect of praziquantel on the activities of some drug-metabolizing hepatic enzymes in rabbits.

The effect of oral administration of praziquantel at different dose levels on the activities of metabolizing hepatic enzymes (aminopyrine N-demethylase, aniline 4-hydroxylase and UDP-glucuronyltransferase) was studied in healthy locally bred rabbits. The pathological changes resulting from drug's toxicity were assessed histologically, by measurement of total plasma protein concentration and of the activities of the plasma enzymes sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST). No significant changes were obtained after praziquantel administration at dose levels of 40 and 800 mg/kg body weight, whereas 1600 mg/kg and 2000 mg/kg of praziquantel resulted in a significant decrease in the activities of the three drug-metabolizing hepatic enzymes under investigation in the livers of treated rabbits. All rabbits which received praziquantel at the dose rate of 2000 mg/kg died 10-20 hours following praziquantel treatment.