Postconditioning has been shown to protect the mouse brain from ischemic injury. However, the neuroprotective mechanisms of postconditioning remain elusive. We have found that toll-like receptor 5 (TLR5) plays an integral role in postconditioning-induced neuroprotection through Akt/nuclear factor kappa B (NF-κB) activation in cerebral ischemia. Compared to animals that received 30 min of transient middle cerebral artery occlusion (tMCAO) group, animals that also underwent postconditioning showed a significant reduction of up to 60.51% in infarct volume. Postconditioning increased phospho-Akt (p-Akt) levels and NF-κB translocation to the nucleus as early as 1 h after tMCAO and oxygen-glucose deprivation. Furthermore, inhibition of Akt by Akt inhibitor IV decreased NF-κB promoter activity after postconditioning. Immunoprecipitation showed that interactions between TLR5, MyD88, and p-Akt were increased from postconditioning both in vivo and in vitro. Similar to postconditioning, flagellin, an agonist of TLR5, increased NF-κB nuclear translocation and Akt phosphorylation. Our results suggest that postconditioning has neuroprotective effects by activating NF-κB and Akt survival pathways via TLR5 after cerebral ischemia. Additionally, the TLR5 agonist flagellin can simulate the neuroprotective mechanism of postconditioning in cerebral ischemia.
Animals ; Brain ; Brain Ischemia* ; Flagellin ; Immunoprecipitation ; In Vitro Techniques ; Infarction, Middle Cerebral Artery ; Mice* ; Neuroprotection ; Neuroprotective Agents ; NF-kappa B ; Phosphorylation ; Toll-Like Receptor 5

OBJECTIVE: To determine which ultrasonographic measurement can be used as an indicator reflecting the severity of carpal tunnel syndrome (CTS), by comparing electrodiagnostic results with ultrasonographic measurements in females. Many previous studies have tried to reveal that the ultrasonography (US) can possibility be used for diagnosis and severity of CTS. However, the criteria are different by gender. Thus far, there have been many efforts towards providing patients with a CTS diagnosis and severity prediction using US, but studies' results are still unclear due to lack of data on gender differences. METHODS: We collected data from 54 female patients. We classified the severity of CTS according to electrodiagnostic results. Ultrasonographic measurements included proximal and distal cross-sectional areas of the median nerve and carpal tunnel. RESULTS: The severity by electrodiagnostic results statistically correlated to the proximal cross-sectional area (CSA) of the median nerve and carpal tunnel. However, there was no relationship between the proximal and distal nerve/tunnel indexes and the severity by electrodiagnostic results. CONCLUSION: In female patients with CTS, the proximal CSAs of the median nerve and carpal tunnel increase. They correlate with the severity by electrodiagnostic findings. The CSA of the proximal median nerve could be particularly used as a predictor of the severity of CTS in female patients. However, the nerve/tunnel index is constant, irrespective of the severity of CTS.
Carpal Tunnel Syndrome* ; Diagnosis ; Electrodiagnosis ; Female* ; Humans ; Median Nerve ; Ultrasonography

The elucidation of the molecular mechanisms underlying the differentiation and proliferation of human adipose tissue-derived stromal cells (hADSCs) represents a critical step in the development of hADSCs-based cellular therapies. To examine the role of the microRNA-103a-3p (miR-103a-3p) in hADSCs functions, miR-103a-3p mimics were transfected into hADSCs in order to overexpress miR-103a-3p. Osteogenic differentiation was induced for 14 days in an osetogenic differentiation medium and assessed by using an Alizarin Red S stain. The regulation of the expression of CDK6 (cyclin-dependent kinase 6), a predicted target of miR-103a-3p, was determined by western blot, real-time PCR and luciferase reporter assays. Overexpression of miR-103a-3p inhibited the proliferation and osteogenic differentiation of hADSCs. In addition, it downregulated protein and mRNA levels of predicted target of miR-103a-3p (CDK6 and DICER1). In contrast, inhibition of miR-103a-3p with 2'O methyl antisense RNA increased the proliferation and osteogenic differentiation of hADSCs. The luciferase reporter activity of the construct containing the miR-103a-3p target site within the CDK6 and DICER1 3'-untranslated regions was lower in miR-103a-3p-transfected hADSCs than in control miRNA-transfected hADSCs. RNA interference-mediated downregulation of CDK6 and DICER1 in hADSCs inhibited their proliferation and osteogenic differentiation. The results of the current study indicate that miR-103a-3p regulates the osteogenic differentiation of hADSCs and proliferation of hADSCs by direct targeting of CDK6 and DICER1 partly. These findings further elucidate the molecular mechanisms governing the differentiation and proliferation of hADSCs.
Adipose Tissue/*cytology ; Cell Differentiation ; *Cell Proliferation ; Cells, Cultured ; Cyclin-Dependent Kinase 6/genetics ; DEAD-box RNA Helicases/genetics ; *Gene Expression Regulation ; Humans ; MicroRNAs/genetics/*metabolism ; *Osteogenesis ; Ribonuclease III/genetics ; Stromal Cells/cytology/metabolism

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8⁺ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.
Animals ; Autoimmunity ; Child ; Child, Orphaned ; Friends ; Humans ; Inflammation ; Interleukin-17 ; Killer Cells, Natural ; Lymphocytes ; Mice ; T-Lymphocytes ; Th17 Cells ; Tumor Microenvironment

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8⁺ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i.c.v.) administration of ex-4 or ex9-39. Oxygen-glucose deprivation was also induced in primary neurons, bEnd.3 cells, and BV-2. Ischemia-reperfusion injury reduced expression of GLP-1R. Additionally, higher oxidative stress in SOD2 KO mice decreased expression of GLP-1R. Downregulation of GLP-1R by ischemic injury was 70% restored by GLP-1R agonist, ex-4, which resulted in significant reduction of infarct volume. Levels of intracellular cyclic AMP, a second messenger of GLP-1R, were also increased by 2.7-fold as a result of high GLP-1R expression. Moreover, our results showed that ex-4 attenuated pro-inflammatory cyclooxygenase-2 (COX-2) and prostaglandin E₂ after MCAO. C-Jun NH₂ terminal kinase (JNK) signaling, which stimulates activation of COX-2, was 36% inhibited by i.c.v. injection of ex-4 at 24 h. Islet-brain 1 (IB1), a scaffold regulator of JNK, was 1.7-fold increased by ex-4. GLP-1R activation by ex-4 resulted in reduction of COX-2 through increasing IB1 expression, resulting in anti-inflammatory neuroprotection during stroke. Our study suggests that the anti-inflammatory action of GLP-1 could be used as a new strategy for the treatment of neuroinflammation after stroke accompanied by hyperglycemia.
Animals ; Brain Ischemia ; Cyclic AMP ; Cyclooxygenase 2 ; Diabetes Mellitus, Type 2 ; Down-Regulation ; Glucagon* ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Hyperglycemia ; Infarction, Middle Cerebral Artery ; Insulin ; Mice ; Neurons ; Neuroprotection ; Neuroprotective Agents ; Oxidative Stress ; Phosphotransferases ; Rats ; Reperfusion Injury ; Second Messenger Systems ; Stroke*

The aim of this study was to evaluate and compare the reorganization of corticospinal pathways innervating upper extremity muscles in patients with spastic hemiplegic cerebral palsy (CP). Thirty-2 patients (17 male, 15 female) with spastic hemiplegic CP were enrolled. The average age (mean ± standard deviation) was 7.5 ± 4.6 (range: 2–17) years. Transcranial magnetic stimulation (TMS) was applied to the unaffected and affected motor cortices in turn, and bilateral electromyographic recordings were made from the first dorsal interossei (FDI), the biceps brachii (BB), and the deltoid muscles during rest. The onset latency, central motor conduction time, and peak-to-peak amplitude of motor evoked potentials (MEPs) were measured for each muscle bilaterally. Whilst TMS of both affected and unaffected hemispheres elicited contralateral MEPs in all muscles, the number of MEPs evoked from the affected hemisphere was less than from the unaffected hemisphere for FDI and BB. TMS responses to stimulation of the affected side showed prolonged latency and reduced amplitude. The amplitudes of MEPs increased with age whereas the latencies were relatively constant. These results suggest that the corticospinal pathways to the proximal and distal muscles of the upper extremity undergo sequential maturation and reorganization patterns.
Cerebral Palsy ; Child ; Deltoid Muscle ; Evoked Potentials, Motor ; Humans ; Male ; Muscle Spasticity ; Muscles ; Pyramidal Tracts ; Transcranial Magnetic Stimulation ; Upper Extremity

Kennedy’s disease (KD) or bulbospinal muscular atrophy is an uncommon x-linked recessive genetic disorder. Its diagnosis is challenging due to its wide array of clinical manifestations and difficulty distinguishing it from other motor neuron diseases.Thus, diagnosis is confirmed through DNA testing. 52-year-old male patient presented to the hospital with chronic low back pain (LBP) and muscle weakness. The patient had mild weakness in some proximal muscles, increased deep tendon reflex.Lumbar spine magnetic resonance imaging (MRI) showed degenerative changes. Motor nerve conduction test results showed close to the normal. Sensory nerve conduction test results showed decreased latency and amplitude in most nerves. Needle electromyography revealed fasciculation potentials, diffuse fibrillation potentials, and positive sharp waves were detected. Thus, molecular genetic testing was performed. Consequently, KD was diagnosed. These results suggest the importance of detailed history taking and neurological examination even for patients with chronic LBP to rule out severe diseases.

Objective: To determine the effects of an integrated training device for strength and balance on extremity muscle strength, postural balance, and cognition in older adults using a combination with various rehabilitation training games, in which balance, strength, and cognitive training were configured in a single device. Methods: This prospective study included 20 healthy participants aged 65–85 years. Participants trained for 30 minutes daily, 3 days weekly, for 6 weeks with an integrated training device for strength and balance (SBT-120; Man&Tel Inc., Gumi, Korea). Main outcomes were measured using the Korean Mini-Mental State Examination (K-MMSE), Korean version of the Montreal Cognitive Assessment (K-MoCA), Timed Up and Go Test (TUG), Functional Reach Test (FRT), Berg Balance Scale (BBS), and Manual Muscle Test. Measurements were taken at three time points: T0 (pretreatment), T1 (immediately after treatment), and T2 (4 weeks after treatment). Results: All 20 patients completed the training, and TUG, FRT, and BBS scores significantly improved at T1 and T2 compared to T0. Mean TUG scores decreased by 0.99±2.00 at T1 and 1.05±1.55 at T2 compared to T0. Mean FRT scores increased by 6.13±4.26 at T1 and 6.75±4.79 at T2 compared to T0. BBS scores increased by 0.60±0.94 at T1 and 0.45±1.15 at T2 compared to T0. Moreover, muscle strength and cognition (K-MMSE and K-MoCA scores) increased after training. Conclusion Our findings suggest that an integrated training device for strength and balance can be a safe and useful tool for older adults.

We measured the difference of sitting pressure between the affected and unaffected sides (DSPAU) using sitting pressure measured with a force platform to identify sitting imbalance. The aim of this study is to investigate the relations between sitting balance and functional status or parameters according to characteristics stroke patients. We examine changes in DSPAU and functional assessment before and after a 3 week of rehabilitation in hemiplegic stroke patients (n = 73). These pre- and post-treatment data according to stroke characteristics, and correlations between the DSPAU and functional scales were analyzed. The DSPAU was greater in the non-ambulatory group compared to the ambulatory group, in patients who scored lower in the Medical Research Council (MRC) scores, and in patients whose the MRC scores for the lower limbs were lower than of the upper limbs. We observed that a decrease in the DSPAU was associated with an improvement in functional assessment parameters following rehabilitation. Further, changes in DSPAU were significantly correlated to the Modified Barthel Index. We observed that a decrease in DSPAU was associated with an improvement in functional parameters following rehabilitation. In conclusion, repeated measurements of sitting balance using DSPAU may be helpful to predict motor and functional recovery in stroke patient with hemiplegia.