The Effects of Spirulina maxima Extract on Memory Improvement in Those with Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Spirulina maxima is a marine microalga that has been promoted worldwide as a super food. This study was conducted to evaluate its ability to improve memory in the older adults using Spirulina maxima 70% ethanol extract (SM70EE). This randomized, double-blind, placebo-controlled clinical trial comprised 80 volunteers recruited from Jeonbuk National University Hospital in Jeonju, Republic of Korea, who were randomly assigned to two groups. The participants received either 1 g/day of SM70EE or a placebo without otherwise changing their diet or physical activity. The participants were examined at baseline and after a 12-week interval to determine whether there were changes in their results for visual learning, visual working memory, and verbal learning tests from the Korean version of the Montreal Cognitive Assessment, brain-derived neurotrophic factor and beta-amyloid levels, and total antioxidant capacity. Compared to the placebo group, the treatment group showed a significant improvement in visual learning and visual working memory test results and enhanced vocabulary. SM70EE use was shown to improve memory, with no adverse effects. Its efficacy in alleviating Alzheimer's disease symptoms was verified for the first time through this clinical trial. SM70EE could play a role in the management of patients with dementia. This trial is registered with registration number of clinical research information service (CRIS: KCT0006161).

DNA barcoding and morphological identification of spiny lobsters in South Korean waters: a new record of Panulirus longipes and Panulirus homarus homarus.

To date, 19 species of spiny lobsters from the genus Panulirus have been discovered, of which only P. japonicus, P. penicilatus, P. stimpsoni, and P. versicolor have been documented in South Korean waters. In this study, we aimed to identify and update the current list of spiny lobster species that inhabit South Korean waters based on the morphological features and the phylogenetic profile of cytochrome oxidase I (COI) of mitochondrial DNA (mtDNA). Spiny lobsters were collected from the southern and eastern coasts of Jeju Island, South Korea. Phylogenetic analyses were performed using neighbor-joining (NJ), maximum likelihood (ML), and Bayesian inference (BI) methods. The ML tree was used to determine the spiny lobster lineages, thereby clustering the 17 specimens collected in this study into clades A, B, C, and D, which were reciprocally monophyletic with P. japonicus, P. homarus homarus, P. longipes, and P. stimpsoni, respectively. These clades were also supported by morphological examinations. Interestingly, morphological variations, including the connected pleural and transverse groove at the third abdominal somite, were observed in four specimens that were genetically confirmed as P. japonicus. This finding is novel within the P. japonicus taxonomical reports. Additionally, this study updates the documentation of spiny lobsters inhabiting South Korean waters as P. longipes and P. homarus homarus were recorded for the first time in this region.

Dysfunctional energy metabolisms in fibromyalgia compared with healthy subjects.

This study aimed to investigate the levels of creatine (Cr) metabolites in the anterior cingulate cortex (ACC), thalamus, and insula of patients with fibromyalgia (FM) using proton magnetic resonance spectroscopy (MRS). The levels of Cr and phosphocreatine (PCr) relative to total Cr (tCr), which includes Cr and PCr, in the ACC, thalamus, and insula were determined using MRS in 12 patients with FM and in 13 healthy controls. The FM group had lower levels of PCr/tCr in the ACC and right insula compared to healthy controls. There was a negative correlation between Cr/tCr in the ACC and total pain levels (McGill Pain Questionnaire-Total; r = -0.579, p = 0.049) and between Cr/tCr in the left insula and affective pain levels (McGill Pain Questionnaire-Affective; r = -0.638, p = 0.047) in patients with FM. In addition, there were negative correlations between stress levels (Stress Response Inventory) and Cr/tCr in the right (r = -0.780, p = 0.005) and left thalamus (r = -0.740, p = 0.006), as well as in the right insula (r = -0.631, p = 0.028) in patients with FM. There were negative correlations between symptom levels of post-traumatic stress disorder (PTSD; PTSD checklist) and Cr/tCr in the right (r = -0.783, p = 0.004) and left thalamus (r = -0.642, p = 0.024) of patients with FM. These findings are paramount to understanding the decisive pathologies related to brain energy metabolism in patients with FM.

Spirulina maxima Derived Pectin Nanoparticles Enhance the Immunomodulation, Stress Tolerance, and Wound Healing in Zebrafish.

In this study, Spirulina maxima derived pectin nanoparticles (SmPNPs) were synthesized and multiple biological effects were investigated using in vitro and in vivo models. SmPNPs were not toxic to Raw 264.7 cells and zebrafish embryos up to 1 mg/mL and 200 µg/mL, respectively. SmPNPs upregulated Il 10, Cat, Sod 2, Def 1, Def 2, and Muc 1 in Raw 264.7 cells and tlr2, tlr4b, tlr5b, il1ß, tnfα, cxcl8a, cxcl18b, ccl34a.4, ccl34b.4, muc5.1, muc5.2, muc5.3, hamp, cstd, hsp70, cat, and sod1 in the larvae and adult zebrafish, suggesting immunomodulatory activity. Exposure of larvae to SmPNPs followed by challenge with pathogenic bacterium Aeromonas hydrophila resulted a two-fold reduction of reactive oxygen species, indicating reduced oxidative stress compared to that in the control group. The cumulative percent survival of larvae exposed to SmPNPs (50 µg/mL) and adults fed diet supplemented with SmPNPs (4%) was 53.3% and 76.7%, respectively. Topical application of SmPNPs on adult zebrafish showed a higher wound healing percentage (48.9%) compared to that in the vehicle treated group (38.8%). Upregulated wound healing markers (tgfß1, timp2b, mmp9, tnfα, il1ß,ccl34a.4, and ccl34b.4), enhanced wound closure, and restored pigmentation indicated wound healing properties of SmPNPs. Overall, results uncover the multiple bioactivities of SmPNPs, which could be a promising biocompatible candidate for broad range of aquatic and human therapies.

Spirulina maxima derived marine pectin promotes the in vitro and in vivo regeneration and wound healing in zebrafish.

Purified bioactive components of marine algae have shown great pharmaceutical and biomedical potential, including wound healing activity. However, the activity of Spirulina maxima is the least documented with regard to wound healing potential. In the present study, we investigated the regenerative and wound healing activities of a Spirulina (Arthrospira) maxima based pectin (SmP) using in vitro human dermal fibroblasts (HDFs) and in vivo zebrafish model. SmP treated (12.5-50 µg/mL) HDFs showed increased cell proliferation by 20-40% compared to the untreated HDFs. Moreover, in vitro wound healing results in HDFs demonstrated that SmP decreased the open wound area % in concentration-dependent manner at 12.5 (32%) and 25 µg/mL (12%) compared to the control (44%). Further, zebrafish larvae displayed a greater fin regenerated area in the SmP exposed group at 25 (0.48 mm2) and 50 µg/mL (0.51 mm2), whereas the untreated group had the lowest regenerated area (0.40 mm2) at 3 days post amputation. However, fin regeneration was significantly (P < 0.001) higher only in the SmP treated group at 50 µg/mL. Furthermore, the open skin wound healing % in adult zebrafish was significantly higher (P < 0.05) after topical application (600 µg/fish) of SmP (46%) compared to the control (38%). Upregulation of genes such as tgfß1, timp2b, mmp9, tnf-α, and il-1ß, and chemokines such as cxcl18b, ccl34a.4, and ccl34b.4, in the muscle and kidney tissues of SmP treated fish compared to the respective control group was demonstrated using qRT-PCR. Histological analysis results further supported the rapid epidermal growth and tissue remodeling in SmP treated fish, suggesting that SmP exerts positive effects associated with wound healing. Therefore, SmP can be considered a potential regenerative and wound healing agent.

Long-term beneficial effects of an online mind-body training program on stress and psychological outcomes in female healthcare providers: A non-randomized controlled study.

Mind-body training (MBT) programs are effective interventions for relieving stress and improving psychological capabilities. To expand our previous study which demonstrated the short-term effects of an 8-week online MBT program, the present study investigated whether those short-term effects persist up to a month after the end of the intervention.Among previous participants, 56 (64%) participated in this follow-up study, 25 in the MBT group and 31 in the control group. Outcome measures included the stress response, emotional intelligence, resilience, coping strategies, positive and negative affect, and anger expression of both groups at baseline, at 8 weeks (right after the training or waiting period), and at 12 weeks (a month after the training or waiting period).The MBT group showed a greater decrease in stress response at 8 weeks, and this reduction remained a month after the end of the intervention. The effect of MBT on resilience and effective coping strategies was also significant at 8 weeks and remained constant a month later. However, the improvement to emotional intelligence and negative affect did not persist a month after training.These findings suggest that the beneficial short-term effects of MBT may last beyond the training period even without continuous practice, but the retention of these benefits seems to depend on the outcome variables. Through a convenient, affordable, and easily accessible online format, MBT may provide cost-effective solutions for employees at worksites.

Marine Microalgae, Spirulina maxima-Derived Modified Pectin and Modified Pectin Nanoparticles Modulate the Gut Microbiota and Trigger Immune Responses in Mice.

This study evaluated the modulation of gut microbiota, immune responses, and gut morphometry in C57BL/6 mice, upon oral administration of S. maxima-derived modified pectin (SmP, 7.5 mg/mL) and pectin nanoparticles (SmPNPs; 7.5 mg/mL). Metagenomics analysis was conducted using fecal samples, and mice duodenum and jejunum were used for analyzing the immune response and gut morphometry, respectively. The results of metagenomics analysis revealed that the abundance of Bacteroidetes in the gut increased in response to both modified SmP and SmPNPs (75%) as compared with that in the control group (66%), while that of Firmicutes decreased in (20%) as compared with that in the control group (30%). The mRNA levels of mucin, antimicrobial peptide, and antiviral and gut permeability-related genes in the duodenum were significantly (p < 0.05) upregulated (> 2-fold) upon modified SmP and SmPNPs feeding. Protein level of intestinal alkaline phosphatase was increased (1.9-fold) in the duodenum of modified SmPNPs feeding, evidenced by significantly increased goblet cell density (0.5 ± 0.03 cells/1000 µm2) and villi height (352 ± 10 µm). Our results suggest that both modified SmP and SmPNPs have the potential to modulate gut microbial community, enhance the expression of immune related genes, and improve gut morphology.

Characterization of ionic cross-linked composite foams with different blend ratios of alginate/pectin on the synergistic effects for wound dressing application.

Alginate and pectin have been widely employed together in various industrial and biomedical applications due to their synergistic interaction. Although alginate and pectin have been used as composite materials in films, gels, and particles, research characterizing their properties in foams is scarce. Thus, in the present study, we fabricated alginate-pectin composite foams with different blending ratios (9:1, 7:3, and 5:5) using calcium ion cross-linking and characterized their properties. It was found that the G' values of rehydrated alginate-pectin 9:1 foam was higher than those of the other rehydrated foams in the rheological behavior. In addition, higher pectin levels in the composite foams led to more water being absorbed during swelling tests and the higher release of BSA in drug-release testing. In indirect and direct cytotoxicity testing, none of the foams exhibited cell cytotoxicity for fibroblast and keratinocyte cells. These results suggest that controlling the pectin content in alginate-pectin foams is key to adjusting their mechanical properties, water absorption, and drug-release ability. In addition, alginate-pectin composite foams are promising candidates for use in wound-dressing applications.

Disruption of Homeostasis Based on the Right and Left Hemisphere in Patients with Complex Regional Pain Syndrome.

OBJECTIVE: Although the clinical features and pathophysiology of complex regional pain syndrome (CRPS) have been studied in the peripheral and central nervous systems, few plausible pathological interactions are known among the metabolites in these systems. Thus, the purpose of this study was to investigate abnormal relationships and interactions between peripheral metabolites and central neurometabolites in patients with CRPS. METHODS: Various metabolites and molecules were measured in the peripheral blood, and central neurometabolites in the right and left thalamus using proton magnetic resonance spectroscopy in 12 patients with CRPS and 11 healthy controls. Interactions between peripheral metabolites in blood and central neurometabolites in the right and left thalamus were also investigated. RESULTS: The interactions between peripheral and central metabolites were different in the right and left hemispheres of healthy subjects, suggesting the presence of right hemisphere-dependent energy homeostasis and left hemisphere-dependent acid-base homeostasis that enables effective functioning. The interactions between central and peripheral metabolites in CRPS patients were distinct from those in healthy individuals, supporting the possibility of abnormal interactions and disrupted homeostasis between peripheral and central metabolites, which may result from neuroinflammation and immune system dysfunction. CONCLUSION: To the authors' knowledge, this is the first report describing abnormal metabolic dysfunction and disrupted homeostasis in interactions between metabolites of the peripheral and central nervous systems in CRPS. The approach used to uncover hidden pathophysiologies will improve understanding of how chronic pain can disrupt homeostasis in interactions between two systems and how alternative metabolites can be activated to recover and compensate for pathological dysfunctions in patients with CRPS.

Novel pectin isolated from Spirulina maxima enhances the disease resistance and immune responses in zebrafish against Edwardsiella piscicida and Aeromonas hydrophila.

In this study, we demonstrate the enhanced disease resistance and positive immunomodulation of novel pectin isolated from Spirulina maxima (SmP) in zebrafish model. Zebrafish larvae exposed to SmP had significantly (p < 0.05) higher cumulative percent survival (CPS) at 25 (44.0%) and 50 µg/mL (67.0%) against Edwardsiella piscicida compared to the control. However, upon Aeromonas hydrophila challenge, SmP exposed larvae at 50 µg/mL had slightly higher CPS (33.3%) compared to control group (26.7%). SmP supplemented zebrafish exhibited the higher CPS against E. piscicida (93.3%) and A. hydrophila (60.0%) during the early stage of post-infection (<18 hpi). qRT-PCR results demonstrated that exposing (larvae) and feeding (adults) of SmP, drive the modulation of a wide array of immune response genes. In SmP exposed larvae, up-regulation of the antimicrobial enzyme (lyz: 3.5-fold), mucin (muc5.1: 2.84, muc5.2: 2.11 and muc5.3: 2.40-fold), pro-inflammatory cytokines (il1ß: 1.79-fold) and anti-oxidants (cat: 2.87 and sod1: 1.82-fold) were identified. In SmP fed adult zebrafish (gut) showed >2-fold induced pro-inflammatory cytokine (il1ß) and chemokines (cxcl18b, ccl34a.4 and ccl34b.4). Overall results confirmed the positive modulation of innate immune responses in larval stage and it could be the main reason for developing disease resistance against E. piscicida and A. hydrophila. Thus, non-toxic, natural and biodegradable SmP could be considered as the potential immunomodulatory agent for sustainable aquaculture.

Brain education-based meditation for patients with hypertension and/or type 2 diabetes: A pilot randomized controlled trial.

BACKGROUND: Hypertension and type 2 diabetes are chronic diseases, which generally require lifetime care. Meditation and yoga can be complementary to pharmacological therapies according to the scientific evidences so far. Brain education-based meditation (BEM) is a technique, which has been known to change brain structure, psychology, and physiology of healthy adult participants. This randomized, nonblinded pilot trial aimed to examine whether BEM affects the conditions of patients with hypertension and/or type 2 diabetes compared with health education classes. METHODS: We randomly allocated 48 patients with hypertension and/or type 2 diabetes to BEM (n = 24) or health education (n = 24) classes in the Ulsan Junggu Public Health Center in Korea, where the classes were run during the same period and explored the impact of 8-week practice on the serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, gamma glutamyl transpeptidase, creatinine, high-density lipoprotein cholesterol, and low-density lipoprotein (LDL) cholesterol. Total RNA was extracted to examine inflammatory gene expressions from the whole blood using PAXgene blood RNA System. In addition, self-reports on mental/physical health were evaluated. The Student's t test, chi-squared test, and analysis of covariance were used for statistical analysis. RESULTS: The number of people who participated until the completion of the study was 14 in the control and 21 in the BEM group. After 8 weeks, LDL cholesterol level was significantly decreased in the BEM group after the intervention (13.82 mg/dL reduction, P < .05), while it was not significantly altered in the control group. The expression of inflammatory genes was significantly reduced after 8 weeks of the BEM training (0.3-, 0.5-, and 0.2-fold change for NFKB2, RELA, and IL1B, respectively, all P < .05). In the item analysis of mental/physical health self-reports, a significant improvement was confirmed as follows: increases in focus, confidence, relaxation, and happiness; decreases in fatigue, anger, and loneliness (all P < .05). There were no important adverse events or side-effects by BEM intervention. CONCLUSION: Compared to health education, BEM helps lower LDL cholesterol level and the inflammatory gene expression in the patients with hypertension and/or type 2 diabetes. Moreover, BEM induces positive effects on the self-reported mental/physical states, warranting further study.

Differences in Functional Connectivity of the Insula Between Brain Wave Vibration in Meditators and Non-meditators.

The majority of meditation involves focusing attention on internal events or sensations and becoming aware of emotions. The insula cortex, through a functional connection with the prefrontal cortex and other brain regions, plays a key role in integrating external sensory information with internal bodily state signals and emotional awareness. The purpose of this exploratory study was to examine the resting-state functional connectivity of the insula with other brain regions in meditation practitioners and control subjects. Thirty-five Brain Wave Vibration meditation practitioners and 33 controls without meditation experience were included in this study. All subjects underwent 4.68-min resting-state functional scanning runs using magnetic resonance imaging. The anterior and posterior insulae were chosen as seed regions for the functional connectivity map. Meditation practitioners showed significantly greater insula-related functional connectivity in the thalamus, caudate, middle frontal gyrus, and superior temporal gyrus than did controls. Control subjects demonstrated greater functional connectivity with the posterior insula in the parahippocampal gyrus. Our findings suggest that the practice of Brain Wave Vibration meditation may be associated with functional differences in regions related to focused attention, executive control, and emotional awareness and regulation.

In-Depth Relationships between Emotional Intelligence and Personality Traits in Meditation Practitioners.

OBJECTIVE: Meditation can elicit trait-like changes in psychological and social styles, as well as enhancement of emotional regulatory capacity. We investigated the relation between personality traits and emotional intelligence in meditation practitioners. METHODS: Seventy-two long-term practitioners of mind-body training (MBT) and 62 healthy comparative individuals participated in the study. The participants completed emotional intelligence questionnaires and the Myers-Briggs Type Indicator (MBTI). RESULTS: The MBT group revealed higher scores on all five emotional intelligence factors than did those in the control group, such as emotional awareness and expression, empathy, emotional thinking, emotional application, and emotional regulation (all p≤0.001). MBT practitioners also had higher scores on the intuition of perceiving function (t =-2.635, p =0.010) and on the feeling of the judging function (t =-3.340, p =0.001) of the MBTI compared with those in the control group. Only the MBT group showed a robust relationship with every factor of emotional intelligence and MBTI-defined intuitive styles, indicating that higher scores of emotional intelligence were related to higher scores for intuition. CONCLUSION: Emotional intelligence of meditation practitioners showed notable relationships with some features of personality trait. In-depth associations between emotional intelligence and personality traits would help to foster psychological functions in meditation practitioners.

Effects of an Online Imagery-Based Treatment Program in Patients with Workplace-Related Posttraumatic Stress Disorder: A Pilot Study.

OBJECTIVE: We developed easily accessible imagery-based treatment program for patients with post-traumatic stress disorder (PTSD) related to workplace accidents and investigated the effects of the program on various PTSD related symptoms. METHODS: The program was based on an online platform and consisted of eight 15-min sessions that included script-guided imagery and supportive music. Thirty-five patients with workplace-related PTSD participated in this program 4 days per week for 4 weeks. Its effects were examined using self-report questionnaires before and after the take-home online treatment sessions. RESULTS: After completing the 4-week treatment program, patients showed significant improvements in depressed mood (t=3.642, p=0.001) based on the Patient Health Questionnaire-9 (PHQ-9), anxiety (t=3.198, p=0.003) based on the Generalized Anxiety Disorder seven-item (GAD-7) scale, and PTSD symptoms (t=5.363, p<0.001) based on the Posttraumatic Stress Disorder Check List (PCL). In particular, patients with adverse childhood experiences exhibited a greater degree of relief related to anxiety and PTSD symptoms than those without adverse childhood experiences. CONCLUSION: The present. RESULTS: demonstrated that the relatively short online imagery-based treatment program developed for this study had beneficial effects for patients with workplace-related PTSD.

Effects of an Online Mind-Body Training Program on the Default Mode Network: An EEG Functional Connectivity Study.

Online mind-body training (MBT) programs can improve the psychological capabilities of practitioners. Although there has been a lot of effort to understand the neural mechanisms underlying the therapeutic effects of meditation, little is known about changes in electroencephalographic (EEG) functional connectivity that accompany mind-body training. The present study aimed to investigate how an online MBT program alters EEG functional connectivity in the default mode network (DMN). We assessed a group of healthcare providers, including 14 females who participated in the 4-week MBT program and 15 females who underwent a 4-week of waiting period. EEG data and information about psychological states were obtained at baseline and 4 weeks. The result was that the intervention group showed significant reductions in anxiety and trait anger that were accompanied by increased global DMN network strengths in the theta and alpha (but not beta and delta) frequency bands; these changes were not observed in the control group. Other variables including state anger, positive and negative affect, and self-esteem have not been changed over time in both groups. These findings suggest that practicing the mind-body training could have a relevance to the functional differences in network related to stress and anxiety reaction.

Aberrant interactions of peripheral measures and neurometabolites with lipids in complex regional pain syndrome using magnetic resonance spectroscopy: A pilot study.

Background The aim of this study was to assess peripheral measures and central metabolites associated with lipids using magnetic resonance spectroscopy. Results Twelve patients with complex regional pain syndrome (CRPS) and 11 healthy controls participated. Using magnetic resonance spectroscopy, we measured the levels of lipid 13a (Lip13a) and lipid 09 (Lip09) relative to total creatine (tCr) levels in the right and left thalamus. We found negative correlations of Lip13a/tCr in the right thalamus with red blood cells or neutrophils, but a positive correlation between Lip13a/tCr and lymphocytes in the controls. We found negative correlations between Lip09/tCr and peripheral pH or platelets in the controls. There were positive correlations between Lip09a/tCr and myo-inositol/tCr, between Lip13a/tCr and N-acetylaspartate (NAA)/tCr, and between Lip09/tCr and NAA/tCr in healthy controls. On the other hand, there were positive correlations between Lip13a/tCr and Lip09/tCr and urine pH in CRPS patients. There were significant correlations between Lip13a/tCr or Lip09/tCr and different peripheral measures depending on the side of the thalamus (right or left) in CRPS patients. Conclusion This is the first report indicating that abnormal interactions of Lip13a and Lip09 in the thalamus with peripheral measures and central metabolites may mediate the complex pathophysiological mechanisms underlying CRPS.

Effect of Fermented Spirulina maxima Extract on Cognitive-Enhancing Activities in Mice with Scopolamine-Induced Dementia.

This work provides the first demonstration that Spirulina maxima extract fermented with the lactic acid bacterium Lactobacillus planetarium HY-08 has the ability to ameliorate scopolamine-induced memory impairment in mice. The fermented extract exhibited good cognitive-enhancing activities, as demonstrated through Morris water maze and passive avoidance experiments: in these tests, the mice administered the fermented extract at a dose of 400 mg/kg exhibited an escape latency time and a latency time of 88.5 and 76.0 sec, respectively, whereas those administered donepezil, which was used as a positive control, showed an escape latency time and a latency time of 81.3 and 83.3 sec, respectively. However, an extract of 200 mg/kg was considered economically feasible for maintaining relatively high memory-improving activities because only a slight difference in activities was found between 200 and 400 mg/kg. The study also provides the first demonstration that ß-carotene, one of the major bioactive substances in S. maxima, has memory-enhancing activity. A detailed analysis of the mechanism for the cognitive-enhancing activities of the fermented extract revealed that the fermented extract effectively increased the phosphorylation of both extracellular signal-regulated kinases (p-ERK) and p-cAMP response element-binding protein (p-CREB) and sequentially upregulated the expression of brain-derived neurotrophic factor (BDNF), whose signaling pathway responds to a reduction in oxidative stress in the brain. The results indicate that the improved efficacy of the fermented extract was likely due to the synergistic effects of ß-carotene and other bioactive substances. Therefore, it can be concluded that the fermented extract exerts memory-improving effects in the hippocampus of scopolamine-treated mice through an initial increase in ERK signaling and a sequential induction of the expression of p-CREB and BDNF, and these effects are related to the antioxidant activities of ß-carotene and other components.

Cellular properties of the fermented microalgae Pavlova lutheri and its isolated active peptide in osteoblastic differentiation of MG­63 cells.

Fermented microalgae Pavlova lutheri (P. lutheri), the product of Hansenula polymorpha fermentation, exhibited an increase in alkaline phosphatase (ALP) activity in MG­63 osteoblastic cells when compared to that of non­fermented P. lutheri. Fractionation of the fermented P. lutheri resulted in identification of the active peptide [peptide of P. lutheri fermentation (PPLF)] with the sequence of EPQWFL. PPLF significantly increased ALP release from MG­63 cells and mineralization in a dose­dependent manner. In addition, the intracellular levels of ALP and osteocalcin (OCN) proteins were augmented by PPLF treatment. To identify the molecular mechanism underlying the effect of PPLF on osteoblastic differentiation, the phosphorylation levels of the mitogen­activated protein kinases, p38, extracellular signal­regulated kinases 1/2 and Jun, and nuclear factor (NF)­κB were determined following PPLF treatment and the differences in expression were analyzed using p38 and NF­κB selective inhibitors. These results concluded that PPLF from fermented P. lutheri induced osteoblastic differentiation by increasing ALP and OCN release in MG­63 cells via the p38/p65 signaling pathway, indicating that PPLF supplement may be effective for therapeutic application in the field of bone health.

Spirulina maxima Extract Ameliorates Learning and Memory Impairments via Inhibiting GSK-3ß Phosphorylation Induced by Intracerebroventricular Injection of Amyloid-ß 1-42 in Mice.

Spirulina maxima, a microalga containing high levels of protein and many polyphenols, including chlorophyll a and C-phycocyanin, has antioxidant and anti-inflammatory therapeutic effects. However, the mechanisms where by Spirulina maxima ameliorates cognitive disorders induced by amyloid-ß 1-42 (Aß1-42) are not fully understood. In this study, we investigated whether a 70% ethanol extract of Spirulina maxima (SM70EE) ameliorated cognitive impairments induced by an intracerebroventricular injection of Aß1-42 in mice. SM70EE increased the step-through latency time in the passive avoidance test and decreased the escape latency time in the Morris water maze test in Aß1-42-injected mice. SM70EE reduced hippocampal Aß1-42 levels and inhibited amyloid precursor protein processing-associated factors in Aß1-42-injected mice. Additionally, acetylcholinesterase activity was suppressed by SM70EE in Aß1-42-injected mice. Hippocampal glutathione levels were examined to determine the effects of SM70EE on oxidative stress in Aß1-42-injected mice. SM70EE increased the levels of glutathione and its associated factors that were reduced in Aß1-42-injected mice. SM70EE also promoted activation of the brain-derived neurotrophic factor/phosphatidylinositol-3 kinase/serine/threonine protein kinase signaling pathway and inhibited glycogen synthase kinase-3ß phosphorylation. These findings suggested that SM70EE ameliorated Aß1-42-induced cognitive impairments by inhibiting the increased phosphorylation of glycogen synthase kinase-3ß caused by intracerebroventricular injection of Aß1-42 in mice.

[11C]-(R)-PK11195 positron emission tomography in patients with complex regional pain syndrome: A pilot study.

Complex regional pain syndrome (CRPS) is characterized by severe and chronic pain, but the pathophysiology of this disease are not clearly understood. The primary aim of our case-control study was to explore neuroinflammation in patients with CRPS using positron emission tomography (PET), with an 18-kDa translocator protein specific radioligand [C]-(R)-PK11195. [C]-(R)-PK11195 PET scans were acquired for 11 patients with CRPS (30-55 years) and 12 control subjects (30-52 years). Parametric image of distribution volume ratio (DVR) for each participant was generated by applying a relative equilibrium-based graphical analysis. The DVR of [C]-(R)-PK11195 in the caudate nucleus (t(21) = -3.209, P = 0.004), putamen (t(21) = -2.492, P = 0.022), nucleus accumbens (t(21) = -2.218, P = 0.040), and thalamus (t(21) = -2.395, P = 0.026) were significantly higher in CRPS patients than in healthy controls. Those of globus pallidus (t(21) = -2.045, P = 0.054) tended to be higher in CRPS patients than in healthy controls. In patients with CRPS, there was a positive correlation between the DVR of [C]-(R)-PK11195 in the caudate nucleus and the pain score, the visual analog scale (r = 0.661, P = 0.026, R = 0.408) and affective subscales of McGill Pain Questionnaire (r = 0.604, P = 0.049, R = 0.364). We demonstrated that neuroinflammation of CRPS patients in basal ganglia. Our results suggest that microglial pathology can be an important pathophysiology of CRPS. Association between the level of caudate nucleus and pain severity indicated that neuroinflammation in this region might play a key role. These results may be essential for developing effective medical treatments.