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This study aimed to identify the association between cardiopulmonary exercise and neurological activation by measuring dictation accuracy and the extent of spatial perception.First of all, the body composition of subjects was analyzed to verify their physical abnormality. The subjects were given treadmill exercise using modified Bruce protocol. Before and after the treadmill exercise, a spatial perception test and dictation task with auditory and visual stimulation were carried out to identify the changes in neurological activation.The scores of spatial perception after treadmill exercise were higher than those before treadmill exercise (p0.05). In addition, the speed of the post-treadmill dictation task with visual stimulation was significantly increased compared to that of the pre-treadmill dictation task (p0.05). However, the accuracy of the post-treadmill dictation task with visual stimulation was significantly decreased compared to that of the pre-treadmill dictation task (p0.05).In this study, it was shown that spatial perception and speed of visual dictation were increased after treadmill exercise. These results suggest that cardiovascular fitness exercise increases spatial perception and typing speed by facilitating neurological activation.

Recently, there has been growing interest in exosomal biomarkers for their active targeting and specificity for delivering their cargos (proteins, lipids, nucleic acids) from the parent cell to the recipient cell. Currently, the clinical diagnosis of Parkinson's disease (PD) is mainly based on a clinician's neuropsychological examination and motor symptoms (e.g., bradykinesia, rigidity, postural instability, and resting tremor). However, this diagnosis method is not accurate due to overlapping criteria of other neurodegenerative diseases. Exosomes are differentially expressed in PD and a combination of types and contents of exosomes might be used as a biomarker in PD. Here, we systematically reviewed and meta-analyzed exosomal contents, types and sources of exosomes, method of isolation, and protein quantification tools to determine the optimum exosome-related attributes for PD diagnosis. Pubmed, Embase, and ISI Web of Science were searched for relevant studies. 25 studies were included in the meta-analysis. The Ratio of Mean (RoM) with 95% confidence intervals (CI) was calculated to estimate the effect size. Biomarker performances were rated by random-effects meta-analysis with the Restricted Maximum Likelihood (REML) method. The study protocol is available at PROSPERO (CRD42022331885). Exosomal α-synuclein (α-Syn) was significantly altered in PD patients from healthy controls [RoM = 1.67, 95% CI (0.99 to 2.35); p = 0.00] followed by tau [RoM = 1.33, 95% CI (0.79 to 1.87); p = 0.00], PS-129 [RoM = 0.97, 95% CI (0.54 to 1.40); p = 0.00], and DJ-1/PARK7 [RoM = 0.93, 95% CI (0.64 to 1.21); p = 0.00]. Central nervous system derived L1CAM exosome [RoM = 1.24, 95% CI (1.04 to 1.45); p = 0.00] from either plasma [RoM = 1.35, 95% CI (1.09 to 1.61); p = 0.00]; or serum [RoM = 1.47, 95% CI (1.05 to 1.90); p = 0.00] has been found the optimum type of exosome. The exosome isolation by ExoQuick [RoM = 1.16, 95% CI (0.89 to 1.43); p = 0.00] and protein quantification method by ELISA [RoM = 1.28, 95% CI (1.15 to 1.41); p = 0.00] has been found the optimum isolation and quantification method, respectively for PD diagnosis. This meta-analysis suggests that α-Syn in L1CAM exosome derived from blood, isolated by ExoQuick kit, and quantified by ELISA can be used for PD diagnosis.

Toll-like receptor (TLR) agonist polyinosinic-polycytidylic acid (poly I:C) exerts neuroprotective effects against cerebral ischemia (CI), but concrete evidence supporting its exact mechanism of action is unclear.We evaluated the neuroprotective role of poly I:C by assessing CI indicators such as brain infarct volume (BIV), neurological deficit score (N.S.), and signaling pathway proteins. Moreover, we performed a narrative review to illustrate the mechanism of action of TLRs and their role in CI. Our search identified 164 articles and 10 met the inclusion criterion.Poly I:C reduces BIV and N.S. (p = 0.00 and p = 0.03). Interestingly, both pre- and post-conditioning decrease BIV (preC p = 0.04 and postC p = 0.00) and N.S. (preC p = 0.03 and postC p = 0.00). Furthermore, poly I:C upregulates TLR3 [SMD = 0.64; CIs (0.56, 0.72); p = 0.00], downregulates nuclear factor-κB (NF-κB) [SMD = -1.78; CIs (-2.67, -0.88); p = 0.0)], and tumor necrosis factor alpha (TNF-α) [SMD = -16.83; CIs (-22.63, -11.02); p = 0.00].We showed that poly I:C is neuroprotective and acts via the TLR3/NF-κB/TNF-α pathway. Our review indicated that suppressing TLR 2/4 may illicit neuroprotection against CI. Further research on simultaneous activation of TLR3 with poly I:C and suppression of TLR 2/4 might open new vistas for the development of therapeutics against CI.

Integrins are heterodimeric transmembrane receptors that mediate a variety of biological function and plays a critical role in osteoarthritis (OA) pathogenesis, which may provide new targets for the development of OA therapies. However, the roles of integrins in different stages of OA remain elusive.This study aimed to synthesize all published preclinical evidence on the roles of integrin receptors in different stages of OA to identify the potential target for drug development in alleviating OA pathogenesis.Major electronic databases were used to identify related original articles. The methodological quality of all included studies was appraised using the SYRCLE risk of bias tool. We used the generic inverse variance with random effects model to calculate standardized mean differences (SMDs) and 95% confidence interval (CI).Seventeen studies were included in this systematic review. Integrin α5β1 activation increases the histopathological score both in early [SMD, 6.39; 95%CI (2.90, 9.87); p = 0.0003] and late [SMD, 3.41; 95%CI (2.44, 4.38); p 0.00001] stage of OA. Integrin α5β1 also increased the core catabolic factors like MMP-3, IL-1β, and TNF-α. Interestingly, the inactivation of α5β1 integrin did not change the histopathological score (p = 0.84). Similarly, β1 integrin notably increased histopathological score at both stages of OA [early; SMD, 7.13; 95%CI (2.01, 12.24); p = 0.006]; [late; SMD, 10.25; 95%CI (5.11, 15.39); p 0.0001], and increased the MMP-13 levels. However, integrin β1 was upregulated at the early stage and downregulated at the late stage of OA. Furthermore, α2β1 integrin significantly increased histopathological score [SMD, 3.14; 95%CI (2.18, 4.10); p 0.00001] and MMP-13 [SMD, 2.24; 95%CI (0.07, 4.41); p = 0.04]. Deactivating integrin α1β1 increased histopathological score in late [SMD, 1.53; 95%CI (0.80, 2.26); p 0.0001], but not in early [SMD, 0.90; 95%CI (-1.65, 3.45); p = 0.49] stage of OA.This study provides evidence that α5β1, α2β1, and α1β1 integrin might be the potential target for future drug development in alleviating OA pathogenesis. Further work is required to establish our findings through activating/deactivating these receptors in different stages of OA.

Tryptophan and melatonin are pleiotropic molecules, each capable of influencing several cellular, biochemical, and physiological responses. Therefore, sensitive detection of tryptophan and melatonin in pharmaceutical and human samples is crucial for human well-being. Mass spectrometry, high-performance liquid chromatography, and capillary electrophoresis are common methods for both tryptophan and melatonin analysis; however, these methods require copious amounts of time, money, and manpower. Novel electrochemical and optical detection tools have been subjects of intensive research due to their ability to offer a better signal-to-noise ratio, high specificity, ultra-sensitivity, and wide dynamic range. Recently, researchers have designed sensitive and selective electrochemical and optical platforms by using new surface modifications, microfabrication techniques, and the decoration of diverse nanomaterials with unique properties for the detection of tryptophan and melatonin. However, there is a scarcity of review articles addressing the recent developments in the electrochemical and optical detection of tryptophan and melatonin. Here, we provide a critical and objective review of high-sensitivity tryptophan and melatonin sensors that have been developed over the past six years (2015 onwards). We review the principles, performance, and limitations of these sensors. We also address critical aspects of sensitivity and selectivity, limit and range of detection, fabrication process and time, durability, and biocompatibility. Finally, we discuss challenges related to tryptophan and melatonin detection and present future outlooks.

Cerebral hypoxia-ischemia (CHI) causes brain aging, neurological disorders, cognitive decline, motor function impairment, and mortality. Inhibiting death-associated protein kinase 1 (DAPK1) has shown therapeutic potential against CHI, but several reports contradict its protective function, mechanism of activation, and signal transduction. Here, we systematically reviewed the role and the activation mechanism of DAPK1, and quantitatively assess the efficacy of DAPK1 inhibition (DI) methods in neuroprotection, following a CHI in animal models. Embase and PubMed were searched for relevant studies. Overall, 13 studies met the inclusion criteria, and the SYRCLE Risk of bias tool (RoB) tool was used to assess RoB. StataSE 16 was used for meta-analysis and network meta-analysis (NMA). Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated to estimate the effect size. DI was associated with the reduction of brain infarct volume (BIV) [SMD = -1.70, 95% CI (-2.10, -1.30); p = 0.00], neurological score (N.S.), neuronal degeneration, with no change in the level of in cell death [SMD = -0.83, 95% CI (-2.00, 0.35); p = 0.17], indicating the protective role of DI against CHI. No differences were found in DAPK1 mRNA and protein levels [SMD = 0.50, 95% CI (-0.05, 1.04); p = 0.07] {single-study driven; upregulated after exclusion (p = 0.01, I

Extensive burns result in a local wound response and distant-organ injury (DOI) caused by oxidative-stress and inflammation. Melatonin (MT) shows promise in alleviating oxidative-stress and inflammation, but its role in thermal injury is largely unexplored. The present systematic review and meta-analysis were designed to assess the effects of MT on oxidative-stress and inflammatory markers against severe burn-induced DOI. Mean difference (MD)/standard mean difference (SMD) with 95% confidence interval (CI) were estimated using fixed-effect/random-effects models. Eighteen experimental studies met the inclusion criteria. Compared with the control group, MT significantly decreased the levels of malondialdehyde (SMD, −1.03; 95% CI, −1.30, −0.76, p < 0.00001) and 4-hydroxynonenal (MD, −1.06; 95% CI, −1.57, −0.56, p < 0.0001). Additionally, MT increased the levels of glutathione (SMD, 1.94; 95% CI, 1.27, 2.61, p < 0.00001) and superoxide-dismutase (SMD, 0.76; 95% CI, 0.08, 1.45, p = 0.03). Finally, MT significantly decreased the levels of tumor necrosis factor-α (SMD, −1.34; 95% CI, −1.92 to −0.77; p < 0.00001) and C-reactive protein (MD, −12.67; 95% CI, −16.72 to −8.62; p < 0.00001). Meta-analysis indicates that severe burn followed by immediate MT (10 mg/kg) intervention shows significant beneficial effects after 24-h against DOI by regulating oxidative-stress and the inflammatory response.

Endogenous melatonin levels are inversely associated with age and cognitive deficits. Although melatonin can improve psychopathological behavior disturbances in clinical trials, whether melatonin may also enhance cognitive function remains elusive. This study examined cognitive outcomes from randomized trials of melatonin treatment for Alzheimer's disease (AD), insomnia, and healthy-subjects. Twenty-two studies met the inclusion criteria (AD = 9, insomnia = 2, healthy-subjects = 11). AD patients receiving12 weeks of melatonin treatment improved mini-mental state examination (MMSE) score [MD: 1.82 (1.01; 2.63) p 0.0001]. Importantly, melatonin significantly improved MMSE score in mild stage of AD [MD: 1.89 (0.96; 2.82) p 0.0001]. In healthy-subjects, although daytime melatonin treatment notably decreased in accuracy by correct responses [SMD: -0.74 (-1.03; -0.45) p 0.00001], the reaction-time score on different stimuli (p = 0.37) did not increased. Additionally, by pooling of short-term, spatial, and visual memory scores, melatonin did not reduce memory function (p = 0.08). Meta-analysis of MMSE score suggested that melatonin is effective in treatment for mild stage of AD. Additionally, we propose that melatonin may be preferable to traditional hypnotics in management of insomnia.

In research on cognitive function, the use of experimental animals is essential for the study of human cognitive processes and mechanisms. Furthermore, non-human primates are necessary for understanding higher cognitive functions in humans. However, there are few cognitive function tests available for non-human primates, Thus, we modified a finger maze test for application to non-human primates. In this study, we assessed learning and memory in 12 adult rhesus monkeys using a finger maze test that was developed to assess cognitive functions in captive non-human primates. The monkeys were trained with moving rewards indicating the correct direction, which allowed the monkeys to obtain the reward. Following training, subjects completed a learning trial and a memory trial two months later. Although the time required for training varied among the monkeys, 11 out of 12 monkeys completed the training and achieved a high success rate in the learning trial as well as in the memory trial conducted 2 months later. This is the first study to apply the finger maze test to adult rhesus monkeys. The finger maze test enabled us to assess learning and memory in several adult rhesus monkeys simultaneously.

In the last few decades, there has been notable progress in understanding the molecular and cellular basis of the complex process involved in cancer. In this context, tumor-promoting inflammation, dysregulation of apoptotic signaling, tissue invasion and metastasis, and cancer microenvironment have recently attracted interest from researchers. Irisin is a hormone released by muscles during exercise and it directly acts on key functional cells involving energy metabolism and homeostasis. Recently, many studies have reported the anticancer effect of irisin against different types of cancer. Translation of these findings to clinical practice for the diagnosis and treatment of several types of cancer is urgently required. In this review, we summarized preclinical and clinical studies on the anticancer effects of irisin in various types of cancer, and also discussed the mechanisms activated by irisin to suppress cancer pathogenesis. We further discussed the serum level of irisin related to different types of cancer to understand more clearly the association between irisin concentration and tumor burden. This review may serve as a solid foundation for researchers and physicians to support basic and clinical studies on irisin as a promising strategy for early diagnosis and treatment of a various types of cancers.

// Yunkyung Hong 1,2,3,4 , Hyunsoo Kim 2 , Seunghoon Lee 1,2,3,4 , Yunho Jin 2,3,4 , Jeonghyun Choi 2,3,4 , Sang-Rae Lee 5 , Kyu-Tae Chang 5 and Yonggeun Hong 1,2,3,4 1 Department of Physical Therapy, College of Biomedical Science & Engineering, Inje University, Gimhae, Korea 2 Department of Rehabilitation Science, Graduate School of Inje University, Gimhae, Korea 3 Biohealth Products Research Center (BPRC), Inje University, Gimhae, Korea 4 Ubiquitous Healthcare & Anti-aging Research Center (u-HARC), Inje University, Gimhae, Korea 5 National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Korea Correspondence to: Yonggeun Hong, email: // Kyu-Tae Chang, email: // Keywords : osteoarthritis, metabolic homeostasis, melatonin, exercise, circadian clock Received : November 01, 2016 Accepted : May 12, 2017 Published : July 16, 2017 Abstract Here, we show the role of melatonin combined with or without exercise as a determinant of multicellular behavior in osteoarthritis. We address the relationship between the molecular components governing local circadian clock and changes in the osteoarthritic musculoskeletal axis. Melatonin was injected subcutaneously in animals with advanced knee osteoarthritis (OA) for 4 weeks. Concurrently, moderate treadmill exercise was applied for 30 min/day. Morphometric, histological, and gene/protein-level analyses were performed in the cartilage, synovium, bone, and gastrocnemius muscle. Primary cultured chondrocytes repeatedly exposed to TNF-α were used in an in vitro study. The symptoms of OA include gait disturbance, osteophyte formation, and abnormal metabolism of the extracellular matrix (ECM) of the cartilage. Low-level expression of clock genes was accompanied by aberrant changes in cartilage specimens.Nanomolar doses of melatonin restored the expression of clock-controlled genes and corrected the abnormal chondrocyte phenotype. Melatonin combined with or without exercise prevented periarticular muscle damage as well as cartilage degeneration. But prolonged melatonin administration promoted the proteolytic cleavage of RANKL protein in the synovium, leading to severe subchondral bone erosion. These musculoskeletal changes apparently occurred via the regulation of molecular clock components, suggesting a role of melatonin as a switch-like regulator for the OA phenotype.

Physical exercise has long been recommended as a treatment for osteoarthritis (OA), though its effects vary based on the exercise protocol. Here, we examined whether environmental lighting conditions influence the anti-inflammatory benefits of exercise in a rat model of OA. Moderate-intensity treadmill exercise (Ex) was performed for six weeks under a 12:12 h light/dark (L/D) cycle, and compared against rats housed in a 24 h continuous light (L/L) environment. L/L conditions were associated with serological changes shortly after OA induction, which exacerbated the inflammatory microenvironment in the joint. Differentiation capacity was also impaired in bone precursor cells isolated from normal rats maintained under L/L conditions, despite elevated inflammatory responses. Exercise training under L/L conditions led to increased corticosterone levels in the blood, which exacerbated the progression of cartilaginous and synovial lesions. Osteoporotic phenomena were also observed in exercise-trained rats maintained under L/L conditions, along with inflammation-induced catabolism in the gastrocnemius muscle. Aberrant light/dark cycle conditions were also found to be associated with suppression of splenic Cry1 expression in exercise-trained rats, leading to dysregulation of immune responses. Taken together, these data suggest that lighting condition may be an important environmental factor influencing the exercise-induced benefits on OA.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is accompanied by social deficits, repetitive and restricted interests, and altered brain development. The majority of ASD patients suffer not only from ASD itself but also from its neuropsychiatric comorbidities. Alterations in brain structure, synaptic development, and misregulation of neuroinflammation are considered risk factors for ASD and neuropsychiatric comorbidities. Electroencephalography has been developed to quantitatively explore effects of these neuronal changes of the brain in ASD. The pineal neurohormone melatonin is able to contribute to neural development. Also, this hormone has an inflammation-regulatory role and acts as a circadian key regulator to normalize sleep. These functions of melatonin may play crucial roles in the alleviation of ASD and its neuropsychiatric comorbidities. In this context, this article focuses on the presumable role of melatonin and suggests that this hormone could be a therapeutic agent for ASD and its related neuropsychiatric disorders.

Osteoarthritis (OA), the most common form of arthritis, may be triggered by improper secretion of circadian clock-regulated hormones, such as melatonin, thyroid-stimulating hormone (TSH), or cortisol. The imbalance of these hormones alters the expression of pro-inflammatory cytokines and cartilage degenerative enzymes in articular cartilage, resulting in cartilage erosion, synovial inflammation, and osteophyte formation, the major hallmarks of OA. In this review, we summarize the effects of circadian melatonin, TSH, and cortisol on OA, focusing on how different levels of these hormones affect OA pathogenesis and recovery with respect to the circadian clock. We also highlight the effects of melatonin, TSH, and cortisol at different concentrations both in vivo and in vitro, which may help to elucidate the relationship between circadian hormones and OA.

[Purpose] The purpose of the present review is to discuss recent published articles in the understanding of efficacy of interventional exercise on autistic Fragile X syndrome (FXS) with special emphasis on its significance in clinical application in patients. [Methods] This review article was identified scientifically and/or clinically relevant articles from PubMed that directly/indirectly met the inclusion criteria. [Results] Mutation of fragile X mental retardation 1 (fmr1) gene on the X chromosome is related with loss of fragile X mental retardation protein (FMRP) that affecting physiological and behavioral abnormalities. Autistic FXS individuals exhibit disturbed sleep and altered circadian behavior. Although the underlying molecular mechanisms are not been fully explored, interventional exercise in autistic FXS has been clinically used for the treatment of physiological and behavioral abnormalities as well as psychiatric disorder in autistic FXS. [Conclusion] This review describes beneficial efficacy of interventional exercise and its controversy in patients with autistic FXS. This review also provides interventional strategies for clinicians and scientists that the way of neurophysiological approaches according to the level of physical and behavioral abnormalities.