Search

Author(s): Shokoufeh Moezzi [sup.1] , Majid Ghoshuni [sup.1] , Mahdi Amiri [sup.2] Author Affiliations: (1) grid.411768.d, 0000 0004 1756 1744, Department of Biomedical Engineering, Mashhad Branch, Islamic Azad University, , [...], The main goal of this paper is to present a biomarker using Event Related Potentials (ERPs) to assess the impact of Transcranial Direct Current Stimulation (tDCS) on brain activity during an attentional task. 13 participants (6 males, mean age 24.53 ± 4.5), participated in this study. tDCS was used to stimulate Dorso Lateral Prefrontal Cortex (DLPFC) for 5 consecutive days. Immediately before and after the tDCS sessions, the participants performed an Integrated Visual and Auditory-Adult Edition (IVA-AE) task while behavioral and neurophysiological responses were measured. As a result, tDCS led to a significant improvement in reaction time and an increase in visual P600 amplitude (p < 0.05). Also, the percent changes of P600 amplitude during visual target stimulation was significantly correlated with the percent changes of reaction time to visual targets (p = 0.007, r = -0.704). Consequently, tDCS applied over the DLPFC modulates executive function especially in visual attention during the IVA-AE task.

Background: The rapid advancement of digital technology and information has revolutionized teaching approaches, and evidence retrieval in medical academic settings, highlighting the necessity for adequate digital literacy (DL) among students. This research assessed DL and its components within the medical science student population. Methods: Comprehensive searching was done using the Web of Science, Scopus, Embase, and PubMed databases. Meta-analysis was conducted using CMA V.3.3. Results: Out of the 6773 identified articles, 54 studies were selected for the final synthesis. DL in medical science students has improved over the past two decades. However, there were differences in the components of DL, with computer literacy ranking the highest and search literacy ranking the lowest. Results of the meta-analysis showed that most students were skilled in using Word Processing (78%) and Presentation (68%) software, while fewer were skilled in using Spreadsheets (49%) and Email (34%). Conclusion: Medical science students have made progress in DL but there is still a gap in achieving expected competency. The COVID-19 pandemic has pushed the adoption of digital technologies for online learning, benefiting DL. This experience should guide educational practices, emphasizing online and blended learning, and integrating ICT courses into the medical science curriculum. [ABSTRACT FROM AUTHOR]

NBCn1 (SLC4A7) is one of the two major Na+-HCO3− cotransporters in the human colonic epithelium, expressed predominantly in the highly proliferating colonocytes at the cryptal base. Increased NBCn1 expression levels are reported in tumors, including colorectal cancer. The study explores its importance for maintenance of the intracellular pH (pHi), as well as the proliferative, adhesive, and migratory behavior of the self-differentiating Caco2BBe colonic tumor cell line. In the self-differentiating Caco2BBe cells, NBCn1 mRNA was highly expressed from the proliferative stage until full differentiation. The downregulation of NBCn1 expression by RNA interference affected proliferation and differentiation and decreased intracellular pH (pHi) of the cells in correlation with the degree of knockdown. In addition, a disturbed cell adhesion and reduced migratory speed were associated with NBCn1 knockdown. Murine colonic Nbcn1–/– enteroids also displayed reduced proliferative activity. In the migrating Caco2BBe cells, NBCn1 was found at the leading edge and in colocalization with the focal adhesion markers vinculin and paxillin, which suggests that NBCn1 is involved in the establishment of cell-matrix adhesion. Our data highlight the physiological significance of NBCn1 in modulating epithelial pH homeostasis and cell-matrix interactions in the proliferative region of the colonic epithelium and unravel the molecular mechanism behind pathological overexpression of this transporter in human colorectal cancers. NEW & NOTEWORTHY: The transporter NBCn1 plays a central role in maintaining homeostasis within Caco2BBe colonic epithelial cells through its regulation of intracellular pH, matrix adhesion, migration, and proliferation. These observations yield valuable insights into the molecular mechanism of the aberrant upregulation of this transporter in human colorectal cancers. [ABSTRACT FROM AUTHOR]

Cation and anion transport in the colonocyte apical membrane is highly spatially organized along the cryptal axis. Because of lack of experimental accessibility, information about the functionality of ion transporters in the colonocyte apical membrane in the lower part of the crypt is scarce. The aim of this study was to establish an in vitro model of the colonic lower crypt compartment, which expresses the transit amplifying/progenitor (TA/PE) cells, with accessibility of the apical membrane for functional study of lower crypt-expressed Na+/H+ exchangers (NHEs). Colonic crypts and myofibroblasts were isolated from human transverse colonic biopsies, expanded as three-dimensional (3D) colonoids and myofibroblast monolayers, and characterized. Filter-grown colonic myofibroblast–colonic epithelial cell (CM-CE) cocultures (myofibroblasts on the bottom of the transwell and colonocytes on the filter) were established. The expression pattern for ion transport/junctional/stem cell markers of the CM-CE monolayers was compared with that of nondifferentiated (EM) and differentiated (DM) colonoid monolayers. Fluorometric pHi measurements were performed to characterize apical NHEs. CM-CE cocultures displayed a rapid increase in transepithelial electrical resistance (TEER), paralleled by downregulation of claudin-2. They maintained proliferative activity and an expression pattern resembling TA/PE cells. The CM-CE monolayers displayed high apical Na+/H+ exchange activity, mediated to >80% by NHE2. Human colonoid–myofibroblast cocultures allow the study of ion transporters that are expressed in the apical membrane of the nondifferentiated colonocytes of the cryptal neck region. The NHE2 isoform is the predominant apical Na+/H+ exchanger in this epithelial compartment. [ABSTRACT FROM AUTHOR]

Up to now, numerous randomized controlled trials (RCTs) have examined various drugs as possible treatments for Coronavirus Disease 2019 (COVID-19), but the results were diverse and occasionally even inconsistent with each other. To this point,we performed a systematic review and meta-analysis to assess the comparative effectiveness of pharmacological agents in published RCTs. A literature search was performed using PubMed, SCOPUS, EMBASE, and Web of Science databases. RCTs evaluating mortality and the average length of hospital stay to standard of care (SOC)/placebo/control were included. RCTs mainly were classified into five categories of drugs, including anti-inflammatory, antiviral, antiparasitic, antibody and antibiotics. Meta-analysis was done on 5 drugs classes and sub-group meta-analysis was done on single drugs and moderate or severe stage of disease. Mortality and the average length of hospital stay of COVID-19 patients were significantly reduced with anti-inflammatory drugs (odds ratio [OR]: 0.77, 95% confidence interval [CI]: 0.69 to 0.85, P<0.00001, and mean difference [MD]: −1.41, CI:-1.75 to −1.07, P<0.00001, respectively) compared to SOC/control/placebo. Furthermore, antiparasitic was associated with reduced length of hospital stay (MD: −0.65, CI: −1.26 to −0.03, P<0.05) in comparison to SOC/placebo/control. However, no effectiveness was found in other pharmacological interventions. [ABSTRACT FROM AUTHOR]

Although graphene oxide (GO) nanosheets are widely used in different fields, the mechanism of their toxicity remains relatively unknown. NMR-based metabolomics was used to study in vivo time and dose-dependent toxicity of GO nanosheets in mice. Sixty serum samples from mice in four different time intervals including 24 and 72 h and 7 and 21 days after injection of 0-, 1-, and 10-mg/kg b.w. were analyzed based on 1HNMR spectra of each sample and multivariate methods. In comparison with the control group, 12 changed metabolites were identified in GO nanosheettreated mice groups. These metabolites are involved in steroid hormone biosynthesis and steroid biosynthesis pathways. It was seen that the time factor is more important than the dose factor and the groups were separated in a time direction, completely. We found that GO nanosheets has toxicity and can affect steroidal hormones. However, this study shows that after 21 days, the treated groups regardless of their GO nanosheet dose are very close to the control group. This means that in one step exposure to GO nanosheets, their toxicity diminished after 21 days. [ABSTRACT FROM AUTHOR]

Intestinal NaCl, HCO3-, and fluid absorption are strongly dependent on apical Na+/H+ exchange. The intestine expresses three presumably apical sodium-hydrogen exchanger (NHE) isoforms: NHE2, NHE3, and NHE8. We addressed the role of NHE8 [solute carrier 9A8 (SLC9A8)] and its interplay with NHE2 (SLC9A2) in luminal proton extrusion during acute and chronic enterocyte acidosis and studied the differential effects of NHE8 and NHE2 on enterocyte proliferation. In contrast to NHE3, which was upregulated in differentiated versus undifferentiated colonoids, the expression of NHE2 and NHE8 remained constant during differentiation of colonoids and Caco2Bbe cells. Heterogeneously expressed Flag-tagged rat (r)Nhe8 and human (h)NHE8 translocated to the apical membrane of Caco2Bbe cells. rNhe8 and hNHE8, when expressed in NHE-deficient PS120 fibroblasts showed higher sensitivity to HOE642 compared to NHE2. Lentiviral shRNA knockdown of endogenous NHE2 in Caco2Bbe cells (C2Bbe/shNHE2) resulted in a decreased steady-state intracellular pH (pHi), an increased NHE8 mRNA expression, and augmented NHE8-mediated apical NHE activity. Lentiviral shRNA knockdown of endogenous NHE8 in Caco2Bbe cells (C2Bbe/shNHE8) resulted in a decreased steady-state pHi as well, accompanied by decreased NHE2 mRNA expression and activity, which together contributed to reduced apical NHE activity in the NHE8-knockdown cells. Chronic acidosis increased NHE8 but not NHE2 mRNA expression. Alterations in NHE2 and NHE8 expression/activity affected proliferation, with C2Bbe/shNHE2 cells having lower and C2Bbe/shNHE8 having higher proliferative capacity, accompanied by amplified ERK1/2 signaling pathway and increased EGFR expression in the latter cell line. Thus, both Na+/H+ exchangers have distinct functions during cellular homeostasis by triggering different signaling pathways to regulate cellular proliferation and pHi control. [ABSTRACT FROM AUTHOR]