Effects of transcranial direct current stimulation on the glutamatergic pathway in the male rat hippocampus after experimental focal cerebral ischemia.

This study aimed to assess the focal cerebral ischemia-induced changes in learning and memory together with glutamatergic pathway in rats and the effects of treatment of the animals with transcranial Direct Current Stimulation (tDCS). One hundred male rats were divided into five groups as sham, tDCS, Ischemia/Reperfusion (IR), IR + tDCS, and IR + E-tDCS groups. Learning, memory, and locomotor activity functions were evaluated by behavioral experiments in rats. Glutamate and glutamine levels, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptor (AMPAR1), N-Methyl-D-Aspartate receptors (NMDAR1 and NMDAR2A), vesicular glutamate transporter-1 (VGLUT-1), and excitatory amino acid transporters (EAAT1-3) mRNA expressions in hippocampus tissues were measured. Ischemic areas were analyzed by TTC staining. The increase was observed in IR + tDCS, and IR + E-tDCS groups compared to the IR group while a significant decrease was observed in IR group compared to the sham in the locomotor activity, learning, and memory tests. While glutamate and glutamine levels, AMPAR1, NMDAR1, NMDAR2A, VGLUT1, and EAAT1 mRNA expressions were significantly higher in IR group compared to the sham group, it was found to be significantly lower in IR + tDCS and IR + E-tDCS groups compared to the IR group. EAAT2 and EAAT3 mRNA expressions were significantly higher in IR + tDCS and IR + E-tDCS groups compared to the IR group. Ischemic areas were significantly decreased in IR + tDCS and IR + E-tDCS groups compared to the IR group. Current results suggest that tDCS application after ischemia improves learning and memory disorders and these effects of tDCS may be provided through transporters that regulate glutamate levels.

The clinical utility of the LENT score in patients with malignant pleural mesothelioma.

Introduction: In malignant pleural mesothelioma (MPM), useful tools are needed to predict survival. Thus, we aimed to evaluate the LENT score, and demonstrate the performance of the LENT score in predicting survival in patients with MPM. Materials and Methods: This was a retrospective, observational single-center study. Sixty-nine patients diagnosed with MPM who had pleural effusion (March 2009-December 2020) were divided into groups according to their LENT score and compared. Median survivals were estimated and compared according to the LENT score and parameters of the LENT score. Result: Fifty-four patients were in the low-LENT score group, 15 patients were in the moderate-LENT score group, and there were no patients in the highLENT score group. The two groups had similar characteristics in terms of age, gender, and histological subtype distribution. There were no patients with ECOG-PS 0 in the moderate-LENT score group. Serum neutrophil-tolymphocyte ratio (NLR), pleural lactate dehydrogenase (LDH), patients with serum NLR> 9, and patients with pleural LDH> 1500 were significantly higher in the moderate-LENT score group (p= 0.002, 0.001, <0.01, <0.01, respectively). Fifty patients had died during a median follow-up of 38.6 ± 6.5 (95% CI= 25.84-51.41) months. The median survival for all patients was 28.63 ± 3.2 (95% CI= 22.33-34.92) months, higher than the original study. It was 30.97 ± 2 months in the low-LENT score group, and 20.7 ± 3.4 months in the moderate-LENT score group (p= 0.98). The median survival for patients with pleural LDH<1500 was significantly higher than for patients with pleural LDH> 1500 (p= 0.006) (30.97 vs. 16.73 months), while ECOG-PS (0 vs. 1) and NLR (<9 vs. >9) showed no differences. Conclusions: The survival in our resultant groups was higher than those reported in the original study, and the LENT score had no discriminatory ability for predicting survival in patients with MPM. We nevertheless believe that before reaching more definite conclusions, further large-scale multicenter prospective studies are needed to better define the clinical utility of the LENT score.

Effects of amnion derived mesenchymal stem cells on fibrosis in a 5/6 nephrectomy model in rats.

Chronic kidney disease (CKD) is characterized by disruption of the glomerulus, tubule and vascular structures by renal fibrosis. Mesenchymal stem cells (MSC) ameliorate CKD. We investigated the effects of human amnion derived MSC (hAMSC) on fibrosis using expression of transforming growth factor beta (TGF-ß), collagen type I (COL-1) and bone morphogenetic protein (BMP-7). We also investigated levels of urinary creatinine and nitrogen in CKD. We used a 5/6 nephrectomy (5/6 Nx) induced CKD model. We used 36 rats in six groups of six animals: sham group, 5/6 Nx group, 15 days after 5/6 Nx (5/6 Nx + 15) group, 30 days after 5/6 Nx (5/6 Nx + 30) group, transfer of hAMSC 15 days after 5/6 Nx (5/6 Nx + hAMSC + 15) group and transfer of hAMSC 30 days after 5/6 Nx (5/6 Nx + hAMSC + 30) group. We isolated 106 hAMSC from the amnion and transplanted them via the rat tail vein into the 5/6 Nx + hAMSC + 15 and 5/6 Nx + hAMSC + 30 groups. We measured the expression of BMP-7, COL-1 and TGF-ß using western blot and immunohistochemistry, and their gene expressions were analyzed by quantitative real time PCR. TGF-ß and COL-1 protein, and gene expressions were increased in the 5/6 Nx +30 group compared to the 5/6 Nx + hAMSC + 30 group. Conversely, both protein and gene expression of BMP-7 was increased in 5/6 Nx + hAMSC + 30 group compared to the 5/6 Nx groups. Increased TGF-ß together with decreased BMP-7 expression may cause fibrosis by epithelial-mesenchymal transition due to chronic renal injury. Increased COL-1 levels cause accumulation of extracellular matrix in CKD. Levels of urea, creatinine and nitrogen were increased significantly in 5/6 Nx + 15 and 5/6 Nx + 30 groups compared to the hAMSC groups. We found that hAMSC ameliorate CKD.