Rôle de la PKC delta dans la fonction plaquettaire en réponse à la thrombine via le récepteur GPIb alpha

La famille des protéines kinases C (PKC) est essentielle pour la fonction plaquettaire en réponse à la thrombine qui signale et active les plaquettes via les proteases activated receptors (PAR-1 et PAR-4) et le GPIbα. Ces derniers constituent les récepteurs de moyenne/faible et de hautes affinités pour la thrombine, respectivement. L’isoforme PKCδ régule positivement ou négativement la fonction des plaquettes tout dépendamment de la nature du stimulus. Cependant, son importance dans la fonction plaquettaire en réponse à la thrombine en aval de la GPIbα reste inconnue. L’objectif principal de ce projet de doctorat était de déterminer l'implication de l'axe thrombine/GPIbα/PKCδ dans la fonction plaquettaire et d’évaluer le rôle de cet axe dans la régulation de la thrombose. Dans les plaquettes humaines, le prétraitement avec l'inhibiteur spécifique de la PKCδ δ(V1-1)TAT, a significativement potentialisé l'activation et l’agrégation des plaquettes en réponse à de faibles concentrations de α-thrombine, mais pas en réponse à la γ-thrombine ou aux agonistes des PARs. Ce phénomène de potentialisation a été associé à une sécrétion accrue de granules, de génération de thromboxane A2 (TXA2) et une phosphorylation de la PKCδ sur la Tyr311, qui ont toutes été prévenues par l’inhibition spécifique du GPIbα à l’aide d’un anticorps monoclonal bloquant. En outre, l'inhibition de la p38 MAPK, ERK1/2 et le TXA2 a inversé ce processus de potentialisation. Les plaquettes murines déficientes en PKCδ étaient aussi plus réactives à la thrombine et ont montré une augmentation significative de l'agrégation, alors qu’une étude menée in vivo chez la souris PKCδ- /- a montré, suite à une stimulation par α-thrombine, une réaction thrombotique accrue caractérisée par une diminution significative du temps de saignement ainsi qu’une formation de thrombo-embolies pulmonaires. En bloquant le GPIbα, ces effets ont été renversés. Cette étude ouvre de nouvelles perspectives quant au rôle de la PKCδ dans les plaquettes en aval de GPIbα, où elle régule négativement la fonction plaquettaire en réponse à la thrombine. Ainsi, l'axe thrombine/GPIbα/PKCδ dans les plaquettes pourrait représenter un régulateur critique de la fonction plaquettaire et l'hémostase, et le dysfonctionnement de cette voie pourrait conduire à des événements thrombotiques.The protein kinase C (PKC) family is essential for platelet function in response to thrombin, which signals and activates platelets via protease-activated receptors (PARs) and GPIbα, the low/medium and high affinity receptors in human platelets, respectively. PKCδ positively and negatively regulates platelet function depending on the nature of the stimulus. However, its importance in platelet function in response to thrombin downstream of GPIbα remains unknown. Here, we aimed to determine the involvement of the thrombin/GPIbα/PKCδ axis in platelet function and investigate the relevance of this axis in regulating thrombosis. In human platelets, pre-treatment with the specific PKCδ inhibitor δ(V1-1)TAT significantly potentiated platelet activation and aggregation in response to a priming concentration of α-thrombin, but not to γ-thrombin or PAR agonists. This potentiation process was associated with enhanced granule secretion, TXA2 generation and PKCδ phosphorylation on Tyr311, all of which were prevented by GPIbα blockade. Moreover, inhibition of p38 MAPK, Erk1/2 and TXA2 reverses this potentiation process. Platelets from PKCδ-/- mice show increased aggregation, whereas PKCδ-/- mice exhibit significantly decreased in vivo tail bleeding times and exacerbated pulmonary thrombo-emboli in response to α-thrombin. Blockade of GPIbα protects PKCδ-/- mice from these effects. This study adds new insights into the role of PKCδ in platelets downstream of GPIbα, where it negatively regulates platelet function in response to thrombin. Thus, the thrombin/GPIbα/PKCδ axis in platelets may represent a critical regulator of platelet function and hemostasis, and dysfunction of this pathway could lead to adverse thrombotic events

The Impact of Electronic Sales Channels on Customers Response of Convenience Products Outlets Stores

Purpose: The current study sought to determine the effect of electronic sales channels on customer response to appropriate product outlet stores.   Theoretical framework: With the development of modern means of communication and technologies that have proven effective and efficient, the online shopping system has evolved to be an important resource in the field of electronic commerce. Therefore, in recent times, the issue of customer response has become a sensitive issue for companies, especially in light of the intense competition in the business environment.   Design/methodology/approach: The study used the descriptive analytical approach, and the administrative survey was designed to access the data. The study population consisted of (10) major electronic sales outlets located in the city of Irbid, and a random sample of a total of (400) respondents was used. To analyze the data, this study used modern systems, which is the statistical program (SPSS).   Findings: The results of the study indicate the positive impact of electronic sales channels on customer response.   Research, Practical & Social implications: The study recommended the need, and most importantly, to recommend the adoption of a diversity strategy in e-mail so that companies can access more widespread applications, which increases the interest of the customer and thus is reflected in his purchase decision.   Originality/value: Despite the scientific contribution that was evident in this study, we still need more future studies related to electronic sales channels about customer response in other dimensions such as purchasing decisions, sales and marketing performance, customer trust, and customer intention in different commercial and marketing environments

Total phenolic and flavonoid contents of Mentha spicata leaves aqueous extracts in different regions of Algeria and their antioxidant, and antidiabetic activities

Purpose: To evaluate the total phenolic and flavonoid contents of Mentha spicata (MS) leaves aqueous extracts obtained from different regions (El-Oued, Tebessa and El-Tarf) of Algeria, as well as their in vitro antioxidant and antidiabetic activities. Methods: Aqueous extracts were obtained from the air-dried leaves of MS by maceration followed by filtration and evaporation using a rotary evaporator. Folin-Ciocalteu and Aluminium chloride colorimetric techniques were used to determine the total phenolic and flavonoid contents, respectively. The radical DPPH, ABTS, and FRAP tests were used to determine their antioxidant activities, while the in vitro inhibition percentages of α-amylase and α-glucosidase enzymes were used to assess the anti-diabetic activity. Results: The El-Oued's extract exhibited the highest total phenolic content (108.94 mg GAE/g dry extract (DE)), while the highest total flavonoid content (0.039 mg QE/g DE) was found in El-Tarf's extract. The radical DPPH and FRAP scavenging activity of the El-Oued extract exhibited the highest inhibition activities (IC50 = 102.5 and 289.5 μg/mL), respectively, while the ABTS inhibition activity of the El-Tarf extract exhibited a maximum IC50 value of 111 ± 2.8 μg/mL. The MS extract of the El-Oued region had the highest α-amylase and α-glucosidase enzyme activities with IC50 values of 121.4 and 216.9 μg/mL, respectively. Conclusion: The leaves of Mentha spicata exhibit high phenolic and flavonoid contents, along with significant antioxidant and antidiabetic properties. This study reveals that Mentha spicata flavonoid and phenolic contents as well as other properties vary by region

Warm stratification combined with organic manure application enhances seed germination and improves Cycas revoluta growth and development

Cycas revoluta (Sago palm) is one of the widespread ornamental plant, used as an indoor and outdoor plant. Seed propagation is extremely hard and time consuming, given the physical dormancy imposed by hard coat. The use of warm stratification improves seed germination by prompting embryos development. As mean to gain more insight on the beneficial effect of warm treatment on seed germination, histological analysis of warm stratified and untreated embryos was conducted. Our results revealed that warm treatment accelerated embryos development, resulting in a rapid differentiation of embryos’ tissues. α-amylase, GA3 and ABA quantification showed that warm stratified embryos accumulated higher and lower amounts of α-amylase and ABA respectively compared to untreated embryos. Regarding plant development, our results showed that organic manures significantly improved Cycas revoluta growth and development. The best response was recorded with the application of sheep manure. Indeed, sheep manure addition increased plant height, the number of leaves per plant, stip length and width by nearby 188% and 61%, 36% and 17% respectively. In roots, the presence of nodules had been recorded in the three applied treatments and more importantly in the presence of sheep manure. At the physiological level, sheep manure supplementation improved photosynthetic apparatus and nitrogen content in leaves (by 75%), thereby explaining the growth promotion. Taken together, these results underlined the beneficial effect of organic manure on Cycas revoluta growth and development and proposed a new strategy to improve plant growth and development with the use of sheep manure as organic amendment

RAPID IMPLEMENTATION OF REAL-TIME REVERSE-TRANSCRIPTION POLYMERASE CHAIN REACTION (REAL-TIME RT-PCR) ASSAY FOR THE DETECTION OF SARS-COV-2 IN A MOROCCAN HOSPITAL

Background: The main challenge faced in the African countries was to implement efficient molecular diagnostic facilities and start Covid-19 diagnosis as fast as possible to handle the rapid and unpredictable rise of cases. Materials, Methods and Results: We describe our experience in implementing a molecular biology unit at Sheikh Zaïd International University Hospital in Rabat, with a delay as short as one week, and starting real-time RT-PCR assay for the detection of SARS-Cov-2 infection, since the outbreak widened in Morocco in mid-March, 2020. Conclusion: The challenges encountered in the first period of Covid-19 pandemic are still present. This work aims to give an example of a rapid and adaptive response in order to maintain our diagnosis ability for Covid-19 and for other pathogen

Paraneoplastic cerebellar degeneration as a presentation of breast cancer – a case report and review of the literature

Paraneoplastic cerebellar degeneration is part of a rare spectrum of neurological syndromes whereby gynaecological, lung or breast cancers present primarily with neurological manifestations. The presence of onconeural antibodies and PET scanning help in the challenging diagnosis of these conditions but despite the treatment of the primary cancer, the prognosis for the neurological symptoms is poor

Right atrial thrombus, junctional tachycardia, and critical lower limb ischemia: three rare complications of severe acute respiratory syndrome coronavirus 2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can engender multi-system inflammatory syndrome. Its main symptoms are cardiovascular and thromboembolic problems that can develop into severe complications. The present case is about a 55-year-old patient who was admitted for critical ischemia of the right lower limb and necrosis of the right forefoot. The patient was infected with coronavirus disease 2019 (COVID-19) one month before her admission. The patient also has cardiovascular risks including type 2 diabetes and hypertension. The performance of ultrasounds revealed a thrombus in the right atrium and the pulmonary artery, and arteriography detected an occlusion of the right popliteal joint for which she had an endovascular recanalization and amputation of the right forefoot. This case highlights that SARS-CoV-2 infection could be considered a serious cardiovascular disease requiring cardiovascular explorations to initiate hospital management and avoid severe complications

Natural bioactive compounds targeting DNA methyltransferase enzymes in cancer: Mechanisms insights and efficiencies

The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i.e. their abnormal expression or activity, can result in the repression or overactivation of gene expression. Consequently, this can generate cellular dysregulation leading to instability and tumor development. Several reports highlighted the involvement of DNMTs in human cancers. The inhibition or activation of DNMTs is a promising therapeutic approach in many human cancers. In the present work, we provide a comprehensive and critical summary of natural bioactive molecules as primary inhibitors of DNMTs in human cancers. The active compounds hold the potential to be developed as anti-cancer epidrugs targeting DNMTs