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BackgroundMild cognitive impairment (MCI) is a syndrome that disrupts an individual’s cognitive function but preserves activities of daily living. MCI is thought to be a prodromal stage of dementia, which disrupts patients’ daily lives and causes severe cognitive dysfunction. Although extensive clinical trials have attempted to slow or stop the MCI to dementia conversion, the results have been largely unsuccessful. The purpose of this study was to determine whether noninvasive electrical stimulation of MCI changes glucose metabolism.MethodsSixteen MCI patients participated in this study. We used transcranial direct current stimulation (tDCS) (2 mA/day, three times per week for 3 weeks) and assessed positron emission tomography (18 F-FDG) before and after 3 weeks of stimulation.ResultsWe showed that regular and relatively long-term use of tDCS significantly increased regional cerebral metabolism in MCI patients. Furthermore, subjective memory satisfaction and improvement of the memory strategies of participants were observed only in the real tDCS group after 3 weeks of stimulation.ConclusionOur findings suggest that neurophysiological intervention of MCI could improve glucose metabolism and transient memory function in MCI patients.

To infect definitive or paratenic hosts, metacercariae of Paragonimus westermani should excyst in the host intestine. Optimum conditions for the excystment have been known to be pH 8-9 and a temperature of 40 C. Under these conditions, excystment of P. westermani metacercariae was accelerated in the presence of 1 mM dithiothreitol (DTT). The DTT acceleration was antagonized dose-dependently by cysteine protease inhibitors of L-trans-epoxysuccinylleucylamido(4-guanidino)butane (E-64, 2-20 microM) or leupeptin (0.1-1 mM), suggesting that certain cysteine proteases of the metacercaria are involved in excystment. Protease activities were detected in excretory-secretory products (ESP) of newly excysted metacercariae. Two distinct proteases were purified by DEAE anion-exchange chromatography of the ESP. While a 27-kDa protease exhibited endodipeptidolytic activity at pH 5-8.5 and remained stable at neutral pH for 3 days, the 28-kDa enzyme was stable at pH 5-7.5, with lower activity at pH 8.5. Both proteases hydrolyzed collagen, fibronectin, and myosin within 1 hr at pH 8. These results suggest that cysteine proteases secreted by P. westermani metacercariae modulate excystment.

The use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for myocardial infarction. However, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. The expression of microRNA-210 (miR-210) is induced by hypoxia and is important for cell survival under hypoxic conditions. Hypoxia increases the levels of hypoxia inducible factor-1 (HIF-1) protein and miR-210 in human MSCs (hMSCs). miR-210 positively regulates HIF-1α activity. Furthermore, miR-210 expression is also induced by hypoxia through the regulation of HIF-1α. To investigate the effect of miR-210 on hMSC survival under hypoxic conditions, survival rates along with signaling related to cell survival were evaluated in hMSCs over-expressing miR-210 or ones that lacked HIF-1α expression. Elevated miR-210 expression increased survival rates along with Akt and ERK activity in hMSCs with hypoxia. These data demonstrated that a positive feedback loop involving miR-210 and HIF-1α was important for MSC survival under hypoxic conditions.

When immunoglobulin G (IgG) was incubated with Spirometra mansoni plerocercoid (sparganum), it was cleaved into Fab and Fc fragments. Fab/c fragments were also hydrolysed. The digestion was accelerated by dithiothreitol (DTT), indicating that cleavage of IgG heavy chain was due to a cysteine protease secreted into the medium. The responsible enzyme, of M(r) 27 (+/- 0.8) kDa, was purified by a series of thiopropyl affinity, Sephacryl S-300 HR and DEAE-anion exchange chromatographies, either from worm extracts or from excretory-secretory products (ESP). The purified, thiol-dependent protease showed an optimal activity at pH 5.7 with 0.1 M sodium acetate but was active over the pH range 4.5-8.0. Its activity was inhibited completely by 10(-5) M L-trans-epoxysuccinylleucylamido(4-guanidino) butane (E-64) and 1 mM iodoacetamide (IAA), but by only 53% using the specific cathepsin L inhibitor, Z-Phe-Phe-CHN2 (5 x 10(-5) M). Partial NH2-terminal amino acid sequence was Leu-Pro-Asp-Ser-Val-Asn-Trp-Arg-Glu-Gly-Ala-Val-Thr-Ala-Val which showed 80% homology to human cathepsin S. Immunoblot analysis showed that sera from infected patients exhibited IgE antibody reaction. It is proposed that cleavage of immunoglobulin by an excreted-secreted, cathepsin S-like, allergenic protease is a mechanism of immune evasion used by the sparganum.

Adolescence is a period of heightened vulnerability both to addictive behaviors and drug-induced brain damage. Yet, only limited information exists on the brain mechanisms underlying these adolescent-specific characteristics. Moreover, distinctions in brain correlates between predisposition to drug use and effects of drugs in adolescents are unclear. Using cortical thickness and diffusion tensor image analyses, we found greater and more widespread gray and white matter alterations, particularly affecting the frontostriatal system, in adolescent methamphetamine (MA) users compared with adult users. Among adolescent-specific gray matter alterations related to MA use, smaller cortical thickness in the orbitofrontal cortex was associated with family history of drug use. Our findings highlight that the adolescent brain, which undergoes active myelination and maturation, is more vulnerable to MA-related alterations than the adult brain. Furthermore, MA-use-related executive dysfunction was greater in adolescent MA users than in adult users. These findings may provide explanation for the severe behavioral complications and relapses that are common in adolescent-onset drug addiction. Additionally, these results may provide insights into distinguishing the neural mechanisms that underlie the predisposition to drug addiction from effects of drugs in adolescents.

Objectives: Experimental data and case reports of patients with intractable epilepsy treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN) suggest a considerable anticonvulsant effect. However, no satisfactory mechanisms of action have yet been elucidated. We investigated the putative therapeutic mechanisms of DBS from cerebral perfusion changes as measured by subtracting the SPECT image of the pre-DBS period from that of the chronic post-DBS state. Methods: Two patients who had previous resective surgery on their right frontal cortices with or without anterior callosotomy were selected for DBS of the STN. Both of them showed frequent bilateral asymmetric tonic seizures (left > right) with rare drop attacks, and 1 patient’s seizure frequency was more than 15/month during the pre-DBS period. They had both taken more than four antiepileptic agents for more than 10 years. After video-EEG monitoring, the irritative zones of the brain were delineated. The regional cerebral blood flow (rCBF) changes between the two SPECT images (pre-DBS and post-DBS after at least 6 months) were analyzed by SPECT subtraction with the volumetric MRI coregistration method using Analyze 5.0 software. Results: After chronic STN DBS (18 months, case 1; 6 months, case 2), both patients experienced markedly reduced seizure frequencies (86.7% reduction in patient 1, 88.6% in patient 2). In patient 1, the increased rCBF was observed in the right frontal areas (dorsolateral and inferior frontal area), which corresponded to the irritative zones as confirmed by previous EEG recording. Unexpectedly, there was definite hyperperfusion in the right superior and inferior temporal areas as well as rCBF increase in the right superior frontal area (SMA) in patient 2. Conclusions: We demonstrated that the cerebral perfusion increase in the irritative zones of epilepsy patients is associated with favorable seizure reduction after STN DBS in 2 cases of frontal lobe epilepsy. Although the exact mechanism remains unknown, our findings suggest that the perfusion changes after STN DBS in frontal lobe epilepsy patients are quite different from those in subjects with Parkinson’s disease. Our preliminary data suggest the clinical relevance of subtraction SPECT imaging in assessing the postprocedural outcome as well as the characteristics of SPECT perfusion patterns in other epilepsy syndromes.

The use of conditioned medium from mesenchymal stem cells may be a feasible approach for regeneration of bone defects through secretion of various components of mesenchymal stem cells such as cytokines, chemokines, and growth factors. Mesenchymal stem cells secrete and accumulate multiple factors in conditioned medium under specific physiological conditions. In this study, we investigated whether the conditioned medium collected under hypoxic condition could effectively influence bone regeneration through enhanced migration and adhesion of endogenous mesenchymal stem cells. Cell migration and adhesion abilities were increased through overexpression of intercellular adhesion molecule-1 in hypoxic conditioned medium treated group. Intercellular adhesion molecule-1 was upregulated by microRNA-221 in mesenchymal stem cells because microRNAs are key regulators of various biological functions via gene expression. To investigate the effects in vivo, evaluation of bone regeneration by computed tomography and histological assays revealed that osteogenesis was enhanced in the hypoxic conditioned medium group relative to the other groups. These results suggest that behavioral changes of endogenous mesenchymal stem cells through microRNA-221 targeted-intercellular adhesion molecule-1 expression under hypoxic conditions may be a potential treatment for patients with bone defects.