Chronic exposure to metam sodium-based pesticide in mice during adulthood elevated anxiety and depression-like behaviors: Involvement of serotoninergic depletion and gut microbiota dysbiosis.

Metam sodium-based pesticide (MS-BP) is widely used in agriculture and public health. We have previously demonstrated that maternal exposure to MS-BP resulted in sensorimotor alterations in mice offspring with long-lasting deficits including anxiety- and depression-like behaviors. Here, we project to verify whether these two neurobehavioral effects occur during adulthood following direct exposure to MS-BP and whether it results in changes in the serotoninergic system and gut microbiota. Our findings showed that chronic exposure to MS-BP increased anxiety- and depression-like behaviors, accompanied by a depletion of serotonin-like neurons within the dorsal raphe nucleus and a reduction in serotoninergic terminals in the infralimbic cortex and the basolateral amygdala. In addition, all MS-BP-exposed animals exhibited a reduced total bacterial number and diversity of gut microbiota. Taken together, our data demonstrated that MS-BP-induced behavioral changes could be related to the impairment of the serotoninergic system and gut microbiota dysbiosis.

[Epidemiological, clinical, therapeutic and evolutionary features of patients with glioblastoma: series of cases managed in the Department of Hematology-Oncology at the Mohammed VI University Hospital Center in Marrakech in 2016 and 2017]. / Caractéristiques épidémiologiques, cliniques, thérapeutiques et évolutives des patients atteints de glioblastome cérébral: série de cas pris en charge au centre d´oncohématologie du Centre Hospitalier Universitaire Mohammed VI de Marrakech en 2016 et 2017.

Glioblastoma is the most common primary malignant brain tumour. Despite advances in diagnostic and therapeutic treatments, it is still associated with poor outcome The purpose of this study of cases is to describe the epidemiological, clinical, therapeutic and evolutionary features of patients with glioblastoma admitted to the Department of Hematology-Oncology (DHO) in Marrakech in 2016 and 2017. We conducted a literature review of epidemiological, clinical, radiological, anatomopathological, therapeutic and evolutionary data from 40 patients. Glioblastoma accounted for 47.6% of treated intracranial tumours. The average age of patients was 52.4±12.3 years. Functional impotence and signs of intracranial hypertension were the main symptoms. Tumours mainly occurred in the parietal region (44%) and were large (57.5%). Aphasia was related to tumour size (p=0.042). Nine cases had glioblastomas-IDH1-wild and one case had glioblastoma-IDH1-mutant. On admission, patients had poor performance-status. This was due to a prolonged time between surgery and DHO admission (p= 0.034). Patients with sensory impairments were older (62.5±3 years) than those without sensory impairments (51.2±12 years) (p=0,045). In-patient women received chemoradiotherapy (1.5±1 month) earlier than men (2.3±1.2 months) (p=0.03). Survival was 13.6±5.3 months; it was unrelated to the time to surgery (p=0.076), the time to DHO (p=0.058), and the time to chemoradiotherapy (p=0.073). The epidemiological, clinical, radiological and evolutionary features of our sample were comparable to literature data. The molecular profiling was not systematically realized. Despite prolonged treatment times, no link to survival was detected.

Decreased AGO2 and DCR1 in PBMCs from War Veterans with PTSD leads to diminished miRNA resulting in elevated inflammation.

Chronic inflammation is a characteristic of post-traumatic stress disorder (PTSD). The initiation of inflammation and molecules involved are not yet clearly understood. Here, we provide compelling evidence that the inflammation seen in PTSD may result from the dysregulated miRNA processing pathway. Using microarray analysis with a discovery group of peripheral blood mononuclear cell (PBMC) samples from War Veterans with PTSD, we found 183 significantly downregulated miRNAs, several of which target numerous genes categorized to be pro-inflammatory in nature. This observation was further confirmed in a replicate group by including more samples. Furthermore, employing RNA-sequencing, quantitative real time PCR (qRT-PCR) and in vitro experiments, we found that Argonaute 2 (AGO2) and Dicer1 (DCR1) were downregulated in PTSD and provided convincing evidence that their downregulation affects mature miRNA generation. In addition, we noted that STAT3 transcript was reduced in PTSD and this was possibly responsible for reduced AGO2 and DCR1, which in turn affected miRNA synthesis. Furthermore, we observed that activation of CD4+ T cells or monocytes led to reduced mature miRNA availability. Finally, the inflammation seen in PTSD was associated with downregulated miRNA profile. Altogether, the current study demonstrates that the chronic inflammation seen in PTSD may be a result of dysregulated miRNA biogenesis pathway due to diminished expression of the key molecules like AGO2, DCR1 and STAT3.

Absence of tyrosinase-related protein-2/dopachrome tautomerase transcripts in PBMCs from vitiligo patients.

Tolerance is achieved by mechanisms occurring in both the thymus and periphery. Several reports have shown that presence of an antigen in the peripheral circulation results in tolerance induction. These reports imply that absence of a self-antigen can lead to induction of autoimmunity. Here, we show that tyrosinase-related protein 2 (TRP-2) transcript is not detected in the peripheral blood mononuclear cells (PBMC) of vitiligo patients but is detected in healthy controls. Our result indicates that probably due to lack of expression in the PBMC, TRP-2 is not available for induction and maintenance of peripheral tolerance in vitiligo patients. It is also reported by others that co-stimulatory molecules are required for the initiation of autoimmune diseases in experimental models. We therefore analysed the transcript levels of these costimulatory molecules in vitiligo patients and healthy controls. We observed that the transcripts of B7.2 and CD40 molecules are more or less similar in both patients and controls. We could not detect B7.1 in any of the human subjects. Thus, we conclude that the antigen presenting cells (APC) are not in an activated state and that constitutively activated APC are possibly not required for the progression of the disease once it has been initiated.