Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression.

Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.

Potential role of acupuncture in the treatment of Parkinson's disease: A narrative review.

Background: The prevalence of Parkinson's disease (PD) has grown rapidly compared to that of other neurological disorders. Acupuncture has been used to address the complex symptoms of PD. Recently, similarities in the mechanisms of action between acupuncture and neuromodulation have received considerable attention. This review aims to summarize the evidence regarding these similarities to suggest potential role of acupuncture in the treatment of PD. Methods: The literature from two electronic databases, PubMed and Google Scholar, was searched using the search terms 'Acupuncture', 'Parkinson's disease', 'Vagus nerve stimulation', and 'Brain functional connectivity'. We then explored the evidence for the effectiveness of acupuncture in PD and evaluated the evidence for similarities in the mechanisms of action between acupuncture and neuromodulation. Results: Data suggests that acupuncture treatment is effective for PD symptoms by modulating inflammation and brain functional connectivity (BFC). These acupuncture effects have been shown to be similar to neuromodulation in controlling inflammation and BFC. Based on the shared mechanisms of action, potential acupuncture mechanisms that may ameliorate a wide range of PD symptoms include but are not limited to (1) vagal activation of the anti-inflammatory pathway and (2) BFC enhancement. Conclusion: The development of acupuncture strategies based on shared mechanisms with neuromodulation will provide new treatment options for patients with PD as personalized neuromodulating therapies. Further studies are needed to gather scientific evidence for optimizing parameters in PD patients.

Comparison of pharmacogenomic information for drug approvals provided by the national regulatory agencies in Korea, Europe, Japan, and the United States.

Pharmacogenomics, which is defined as the study of changes in the properties of DNA and RNA associated with drug response, enables the prediction of the efficacy and adverse effects of drugs based on patients' specific genetic mutations. For the safe and effective use of drugs, it is important that pharmacogenomic information is easily accessible to clinical experts and patients. Therefore, we examined the pharmacogenomic information provided on drug labels in Korea, Europe, Japan, and the United States (US). The selection of drugs that include pharmacogenomic information was based on the drug list that includes genetic information from the Korea Ministry of Food and Drug Safety (MFDS) and US Food and Drug Administration (FDA) websites. Drug labels were retrieved from the sites of MFDS, FDA, European Medicines Agency, and Japanese Pharmaceuticals and Medical Devices Agency. Drugs were classified as per the Anatomical Therapeutic Chemical code, and the biomarkers, labeling sections, and necessity of genetic tests were determined. In total, 348 drugs were selected from 380 drugs with available pharmacogenomic information in Korea and the US after applying the inclusion and exclusion criteria. Of these drugs, 137, 324, 169, and 126 were with pharmacogenomics information in Korea, the US, Europe, and Japan, respectively. The most commonly represented drug class was antineoplastic and immunomodulating agents. Regarding the classification as per the mentioned biomarkers, the cytochrome P450 enzyme was the most frequently mentioned information, and the targeted anticancer drugs most commonly required genetic biomarker testing. The reasons for differences in drug labeling information based on country include differences in mutant alleles according to ethnicity, frequencies at which drug lists are updated, and pharmacogenomics-related guidelines. Clinical experts must continuously strive to identify and report mutations that can explain drug efficacy or side effects for safe drug use.

Acupuncture Regulates Symptoms of Parkinson's Disease via Brain Neural Activity and Functional Connectivity in Mice.

Parkinson's disease (PD) is a multilayered progressive brain disease characterized by motor dysfunction and a variety of other symptoms. Although acupuncture has been used to ameliorate various symptoms of neurodegenerative disorders, including PD, the underlying mechanisms are unclear. Here, we investigated the mechanism of acupuncture by revealing the effects of acupuncture treatment on brain neural responses and its functional connectivity in an animal model of PD. We observed that destruction of neuronal network between many brain regions in PD mice were reversed by acupuncture. Using machine learning analysis, we found that the key region associated with the improvement of abnormal behaviors might be related to the neural activity of M1, suggesting that the changes of c-Fos in M1 could predict the improvement of motor function induced by acupuncture treatment. In addition, acupuncture treatment was shown to significantly normalize the brain neural activity not only in M1 but also in other brain regions related to motor behavior (striatum, substantia nigra pars compacta, and globus pallidus) and non-motor symptoms (hippocampus, lateral hypothalamus, and solitary tract) of PD. Taken together, our results demonstrate that acupuncture treatment might improve the PD symptoms by normalizing the brain functional connectivity in PD mice model and provide new insights that enhance our current understanding of acupuncture mechanisms for non-motor symptoms.

The Role of Skin Mast Cells in Acupuncture Induced Analgesia in Animals: A Preclinical Systematic Review and Meta-analysis.

While mast cells (MCs) are previously well-known as a pathological indicator of pain, their role in alleviating pain is recently emerged in acupuncture research. Thus, this study systematically reviews the role of MC in acupuncture analgesia. Animal studies on MC changes associated with the acupuncture analgesia were searched in PubMed and EMBASE. The MC number, degranulation ratio and pain threshold changes were collected as outcome measures for meta-analyses. Twenty studies were included with 13 suitable for meta-analysis, most with a moderate risk of bias. A significant MC degranulation after acupuncture was indicated in the normal and was significantly higher in the pain model. In the subgroup analysis by acupuncture type, manual (MA) and electrical (EA, each P < .00001) but not sham acupuncture had significant MC degranulation. Meta-regression revealed the linear proportionality between MC degranulation and acupuncture-induced analgesia (P < .001), which was found essential in MA (P < .00001), but not in EA (P = .45). MC mediators, such as adenosine and histamine, are involved in its mechanism. Taken together, skin MC is an essential factor for acupuncture-induced analgesia, which reveals a new aspect of MC as a pain alleviator. However, its molecular mechanism requires further study. PERSPECTIVE: This systematic review synthesizes data from studies that examined the contribution of skin MC in acupuncture analgesia. Current reports suggest a new role for skin MC and its mediators in pain alleviation and explain a peripheral mechanism of acupuncture analgesia, with suggesting the need of further studies to confirm these findings.

Acupuncture alleviates chronic pain and comorbid conditions in a mouse model of neuropathic pain: the involvement of DNA methylation in the prefrontal cortex.

ABSTRACT: Chronic pain reduces life quality and is an important clinical problem associated with emotional and cognitive dysfunction. Epigenetic regulation of DNA methylation is involved in the induction of abnormal behaviors and pathological gene expression. We examined whether acupuncture can restore epigenetic changes caused by chronic pain, and identified the underlying mechanisms in neuropathic pain mice. Acupuncture treatment for 6 months (3 days/week) improved mechanical/cold allodynia and the emotional/cognitive dysfunction caused by left partial sciatic nerve ligation (PSNL)-induced neuropathic pain. The effects of acupuncture were associated with global DNA methylation recovery in the prefrontal cortex (PFC). Analysis of DNA methylation patterns in PFC indicated that 1364 overlapping genes among 4442 and 4416 methylated genes in the PSNL vs sham and PSNL vs acupuncture points groups, respectively, were highly associated with the DNA methylation process. Acupuncture restored the reduced expression of 5-methylcytosine, methyl-cytosine-phospho-guanine binding protein 2, and DNA methyltransferase family enzymes induced by PSNL in PFC. Methylation levels of Nr4a1 and Chkb associated with mitochondrial dysfunction were decreased in PFC of the PSNL mice, and increased by acupuncture. By contrast, high expression of Nr4a1 and Chkb mRNA in PSNL mice decreased after acupuncture. We also found that acupuncture inhibited the expression of Ras pathway-related genes such as Rasgrp1 and Rassf1. Finally, the expression of Nr4a1, Rasgrp1, Rassf1, and Chkb mRNA increased in the neuronal cells treated with Mecp2 small interfering RNA. These results suggest that acupuncture can relieve chronic pain-induced comorbid conditions by altering DNA methylation of Nr4a1, Rasgrp1, Rassf1, and Chkb in the PFC.

Intranasal Administration of Melanin-Concentrating Hormone Reduces Stress-Induced Anxiety- and Depressive-Like Behaviors in Rodents.

Major depressive disorder is a complex neuropsychiatric disorder with few treatment options. Non-targeted antidepressants have low efficacy and can induce series of side effects. While a neuropeptide, melanin-concentrating hormone (MCH), is known to exhibit regulator of affective state, no study to date has assessed the anti-depressive effects of MCH in a stress-induced depression model. This study aimed to evaluate the pharmacological effects of intranasal administration of MCH on depression-related behavior in stressed rats and mice. Using a number of behavioral tests, we found that MCH treatment significantly decreased anxiety- and depressive-like behaviors induced by stress. Notably, the effects of MCH were equivalent to those of fluoxetine. MCH treatment also restored the activity of the mammalian target of rapamycin (mTOR) signaling pathway and normalized the levels of synaptic proteins, including postsynaptic density 95, glutamate receptor 1, and synapsin 1, which were all downregulated by stress. Interestingly, the protective effects of MCH were blocked by the mTOR inhibitor, rapamycin. These results suggest that MCH exhibits antidepressant properties by modulating the mTOR pathway. Altogether, this study provides an insight into the molecular mechanisms involved in the antidepressant-like effects of MCH, thereby paving the way for the future clinical application of MCH.

Acupuncture inhibits neuroinflammation and gut microbial dysbiosis in a mouse model of Parkinson's disease.

Growing evidences show that gut microbiota is associated with the pathogenesis of Parkinson's disease (PD) and the gut-brain axis can be promising target for the development of the therapeutic strategies for PD. Acupuncture has been used to improve brain functions and inflammation in neurological disorders such as PD, and to recover the gastrointestinal dysfunctions in various gastrointestinal disorders. Thus, we investigated whether acupuncture could improve Parkinsonism and gut microbial dysbiosis induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. First, we observed that acupuncture treatment at acupoints GB34 and ST36 could improve motor functions and comorbid anxiety in PD mice. Next, we found that acupuncture increased the levels of dopaminergic fibers and neurons in the striatum and the substantia nigra, respectively. Acupuncture also restored the overexpression of microglia and astrocyte as well as conversion of Bax and Bcl-2 expression in both the striatum and the substantia nigra, indicating that inflammatory responses and apoptosis were blocked by acupuncture. Additionally, via 16S rRNA sequence analysis, we observed that the relative abundance of 18 genera were changed in acupuncture-treated mice compared to the PD mice. Of them, Butyricimonas, Holdemania, Frisingicoccus, Gracilibacter, Phocea, and Aestuariispira showed significant correlations with anxiety as well as motor functions. Furthermore, the predicted functional analyses showed that acupuncture restored the physiology functions such as glutathione metabolism, methane metabolism, and PD pathway. In conclusion, we suggest that the effects of acupuncture on the enhanced motor function and the protection of the dopaminergic neurons may be associated with the regulation of the gut microbial dysbiosis and thus the inhibition of the neuroinflammation in the PD mice.

Muscovite nanoparticles mitigate neuropathic pain by modulating the inflammatory response and neuroglial activation in the spinal cord.

Despite numerous efforts to overcome neuropathic pain, various pharmacological drugs often fail to meet the needs and have many side effects. Muscovite is an aluminosilicate mineral that has been reported to have an anti-inflammatory effect, but the efficacy of muscovite for neuropathic pain has not been investigated. Here, we assessed whether muscovite nanoparticles can reduce the symptoms of pain by controlling the inflammatory process observed in neuropathic pain. The analgesic effects of muscovite nanoparticles were explored using partial sciatic nerve ligation model of neuropathic pain, in which one-third to one-half of the nerve trifurcation of the sciatic nerve was tightly tied to the dorsal side. Muscovite nanoparticles (4 mg/100 µL) was given intramuscularly to evaluate its effects on neuropathic pain (3 days per week for 4 weeks). The results showed that the muscovite nanoparticle injections significantly alleviated partial sciatic nerve ligation-induced mechanical and cold allodynia. In the spinal cord, the muscovite nanoparticle injections exhibited inhibitory effects on astrocyte and microglia activation and reduced the expression of pro-inflammatory cytokines, such as interleukin-1ß, tumor necrosis factor-α, interleiukin-6 and monocyte chemoattractant protein-1, which were upregulated in the partial sciatic nerve ligation model. Moreover, the muscovite nanoparticle injections resulted in a decrease in activating transcription factor 3, a neuronal injury marker, in the sciatic nerve. These results suggest that the analgesic effects of muscovite nanoparticle on partial sciatic nerve ligation-induced neuropathic pain may result from inhibiting activation of astrocytes and microglia as well as pro-inflammatory cytokines. We propose that muscovite nanoparticle is a potential anti-nociceptive candidate for neuropathic pain. All experimental protocols in this study were approved by the Institutional Animal Ethics Committee (IACUC) at Dongguk University, South Korea (approval No. 2017-022-1) on September 28, 2017.

Atopic dermatitis induces anxiety- and depressive-like behaviors with concomitant neuronal adaptations in brain reward circuits in mice.

Clinically, it has been reported that atopic dermatitis (AD) has been linked with negative emotional problems such as depression and anxiety, thereby reducing the quality of life, but little is known about the molecular mechanism that underlies AD-associated emotional impairments. We sought to determine whether AD could induce anxiety- and depressive-like symptoms in mice and to identify pertinent signaling changes in brain reward circuitry. AD-like lesions were induced by the repeated intradermal application of MC903 into the cheek of the mouse. We assessed dermatitis severity with scratching behavior, histopathological changes, anxiety- and depressive-like behaviors using the elevated plus maze, open field and tail suspension tests, and serum corticosterone levels. In the nucleus accumbens (NAc), dorsal striatum (DS) and ventral tegmental area (VTA), protein levels of dopamine- and plasticity-related signaling molecules were determined by Western immunoblotting assay. Intradermal administration of MC903 into mouse cheek provoked a strong hind limb scratching behavior as well as the robust skin inflammation with epidermal thickening. MC903-treated mice also displayed markedly increased anxiety- and depressive-like behaviors, along with elevated serum corticosterone levels. Under these conditions, enhanced cAMP response element binding protein (CREB) and dopamine and cAMP-regulated phosphoprotein, 32 kDa (DARPP32) phosphorylation, significantly higher brain-derived neurotrophic factor (BDNF) and ΔFosB, but reduced tyrosine hydroxylase (TH) and dopamine D1 receptor (D1R) protein expression were found in the NAc, DS and VTA. Striatal BDNF, phospho-DARPP32 and phospho-CREB levels were significantly associated with the levels of depressive-like behavior in these mice. Taken together, these findings demonstrate that AD-like skin lesion elicits anxiety- and depressive-like phenotypes that are associated with neuroplasticity-related changes in reward circuitry, providing a better understanding of AD-associated emotional impairments.

Physiological impact of nanoporous acupuncture needles: Laser Doppler perfusion imaging in healthy volunteers.

BACKGROUND: Recently, porous acupuncture (PA), which is anodized to increase its surface area for higher stimulation intensity, was developed and showed significantly improved therapeutic effects with more comfort as compared with original acupuncture (OA) in vivo. However, the impact of PA on the change of local blood flow as well as its efficacy and acceptability has not yet been confirmed in a clinical trial. In a randomized, controlled crossover clinical trial, we investigated the effects of PA on the change in local blood flow using laser Doppler perfusion imaging and considered the sensation of pain intensity and discomfort severity using a visual analogue scale (VAS) to explore its physiological impact and the possibility of PA in clinical use. METHODS: Twenty-one healthy participants were randomly treated with PA or OA on one side of Zusanli (ST36) and each participant served as his or her own control. Baseline local blood flow and galvanic skin response (GSR) were obtained for 5 min and acupuncture interventions were subsequently performed. Next, local blood flow and GSR were subsequently obtained for 10 min after insertion, 10 min after manipulation, and 5 min after the withdrawal of acupuncture. At the end of the experiment, participants were asked to indicate the sensation of pain intensity at each session of insertion, retention, manipulation, and withdrawal as well as the overall pain intensity and discomfort severity. RESULTS: PA significantly increased the local blood flow as compared with OA and there was no significant difference in GSR between patients treated with PA versus OA in each phase of insertion and manipulation. No significant difference in pain intensity or discomfort severity was found during manipulation, retention, or withdrawal of acupuncture. CONCLUSIONS: These results indicate that PA increases local blood flow, which can be closely related to the observed enhanced performance, without any associated discomfort or pain, suggesting its applicability in clinical practice.

Effects of Combined Treatment with Acupuncture and Chunggan Formula in a Mouse Model of Parkinson's Disease.

Parkinson's disease is the second most common neurodegenerative disease. Patients with Parkinson's disease can be treated with a combination of acupuncture and herbal medicine, but studies on the synergistic effects of the combined treatment have not yet been conducted. Thus, we subjected an MPTP-induced Parkinson's disease mouse model to the combined treatment. We used acupoint GB34 for acupuncture and modified Chunggantang (KD5040) as the herbal medicine, as they have been reported to be effective in Parkinson's disease. We investigated the suboptimal dose of KD5040 and then used this dose in the combined treatment. The results showed that the combined treatment had a synergistic effect on improvements in abnormal motor function and neurodegeneration compared with the use of acupuncture or herbal medicine alone. The combined treatment also had a neuroprotective effect via the PI3K/AKT and MAPK/ERK signaling pathways. These findings suggest that the combined treatment with acupuncture and KD5040 can help improve the symptoms of Parkinson's disease.

Acupuncture Improves Comorbid Cognitive Impairments Induced by Neuropathic Pain in Mice.

Growing evidence indicates that neuropathic pain is frequently accompanied by cognitive impairments, which aggravate the quality of life of chronic pain patients. Here, we investigated whether acupuncture treatments can improve cognitive dysfunction as well as allodynia induced by neuropathic pain in mice. One week after the left partial sciatic nerve ligation (PSNL), acupuncture treatments on the acupoints GB30-GB34 (AP1), HT7-GV20 (AP2), or control points (CP) were performed for 4 weeks. Notably, the significant attenuations of mechanical allodynia and cognitive impairment were observed in the AP1 group, but not in PSNL, AP2, or CP groups. A random decision forest classifier based on the pain and cognitive functions displayed that the acupuncture group was clearly segregated from the other groups. We also demonstrated that acupuncture restored the reduced field excitatory post-synaptic potentials and was able to elevate the expression levels of glutamate receptors (NR2B and GluR1) in the hippocampus. Moreover, the expressions of Ca2+/calmodulin-dependent protein kinase II and synaptic proteins (pPSD-95 and pSyn-1) were enhanced by acupuncture treatment. These results suggest that acupuncture can enhance hippocampal long-term action through the regulation of the synaptic efficacy and that acupuncture may provide a viable option for managing both pain and cognitive functions associated with chronic neuropathic pain.

Augmented Mechanical Forces of the Surface-Modified Nanoporous Acupuncture Needles Elicit Enhanced Analgesic Effects.

Over the past several decades, clinical studies have shown significant analgesic effects of acupuncture. The efficacy of acupuncture treatment has improved with the recent development of nanoporous needles (PN), which are produced by modifying the needle surface using nanotechnology. Herein, we showed that PN at acupoint ST36 produces prolonged analgesic effects in an inflammatory pain model; the analgesic effects of PN acupuncture were sustained over 2 h, while those using a conventional needle (CN) lasted only 30 min. In addition, the PN showed greater therapeutic effects than CN after 10 acupuncture treatments once per day for 10 days. We explored how the porous surface of the PN contributes to changes in local tissue, which may in turn result in enhanced analgesic effects. We showed that the PN has greater rotational torque and pulling force than the CN, particularly at acupoints ST36 and LI11, situated on thick muscle layers. Additionally, in ex vivo experiments, the PN showed greater winding of subcutaneous connective tissues and muscle layers. Our results suggest that local mechanical forces are augmented by the PN and its nanoporous surface, contributing to the enhanced and prolonged analgesic effects of PN acupuncture.

Acupuncture modulates stress response by the mTOR signaling pathway in a rat post-traumatic stress disorder model.

Post-traumatic stress disorder (PTSD) is a psychiatric disease that can form following exposure to a traumatic event. Acupuncture has been proposed as a beneficial treatment for PTSD, but the underlying mechanisms remain unclear. The present study investigated whether acupuncture improves depression- and anxiety-like behaviors induced using a single prolonged stress (SPS) as a PTSD rat model. In addition, we investigated whether the effects were mediated by increased mTOR activity and its downstream signaling components, which contribute to protein synthesis required for synaptic plasticity in the hippocampus. We found that acupuncture at HT8 significantly alleviated both depression- and anxiety-like behaviors induced by SPS in rats, as assessed by the forced swimming, elevated plus maze, and open field tests; this alleviation was blocked by rapamycin. The effects of acupuncture were equivalent to those exerted by fluoxetine. Acupuncture regulated protein translation in the mTOR signaling pathway and enhanced the activation of synaptic proteins, PSD95, Syn1, and GluR1 in the hippocampus. These results suggest that acupuncture exerts antidepressant and anxiolytic effects on PTSD-related symptoms by increasing protein synthesis required for synaptic plasticity via the mTOR pathway in the hippocampus. Acupuncture may be a promising treatment for patients with PTSD and play a role as an alternative PTSD treatment.

Novel analgesic effects of melanin-concentrating hormone on persistent neuropathic and inflammatory pain in mice.

The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons in the lateral hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, indicating the involvements of many physiological functions, but the role in pain has yet to be determined. In this study, we found that pMCH-/- mice showed lower baseline pain thresholds to mechanical and thermal stimuli than did pMCH+/+ mice, and the time to reach the maximum hyperalgesic response was also significantly earlier in both inflammatory and neuropathic pain. To examine its pharmacological properties, MCH was administered intranasally into mice, and results indicated that MCH treatment significantly increased mechanical and thermal pain thresholds in both pain models. Antagonist challenges with naltrexone (opioid receptor antagonist) and AM251 (cannabinoid 1 receptor antagonist) reversed the analgesic effects of MCH in both pain models, suggesting the involvement of opioid and cannabinoid systems. MCH treatment also increased the expression and activation of CB1R in the medial prefrontal cortex and dorsolateral- and ventrolateral periaqueductal grey. The MCH1R antagonist abolished the effects induced by MCH. This is the first study to suggest novel analgesic actions of MCH, which holds great promise for the application of MCH in the therapy of pain-related diseases.

What intrinsic factors influence responsiveness to acupuncture in pain?: a review of pre-clinical studies that used responder analysis.

BACKGROUND: Not many studies have investigated individual sensitivity to acupuncture. To explore the intrinsic factors related to individual responses to acupuncture, we reviewed published pre-clinical studies using responder analysis on pain. METHODS: We searched the PubMed and EMBASE databases to June 2015. We included pre-clinical reports describing responders and non-responders to anti-nociceptive and analgesic effects of acupuncture in animal study. We identified the potential intrinsic factors which might be related with the response to acupuncture. RESULTS: Totally, 216 potentially relevant articles were retrieved and 14 studies met our inclusion criteria. Rat (n = 1348) and rabbit (n = 56) were used, and only electroacupuncture (EA) was applied as an intervention. Results showed that high levels of cholecystokinin-8 and receptors were associated with poor responsiveness to EA. Endogenous opioids including ß-endorphin and met-enkephalin, descending inhibitory norepinephrine and serotonin system, and hypothalamic 5'-AMP-activated protein kinase seemed to be associated with high-level responses. Spinal levels of neurotransmitters and pro-inflammatory cytokines were also differentially expressed depending on the EA sensitiveness. In the central nervous system, hypothalamus, periaqueductal grey, pituitary gland, and spinal cord were suggested to be involved in the EA responsiveness. Identified individual variations did not seem to be accidental, as the responsiveness to EA was replicated over time. However, methodological issues such as reproducibility, cut-off criteria, and clinical relevance need to be further elaborated. CONCLUSION: Our study suggests that the identification of the biological factors differentiating responders from non-responders is necessary and it may aid in understanding how acupuncture modulates pain.

Novel Neuroprotective Effects of Melanin-Concentrating Hormone in Parkinson's Disease.

Acupuncture has shown the therapeutic effect on various neurodegenerative disorders including Parkinson's disease (PD). While investigating the neuroprotective mechanism of acupuncture, we firstly found the novel function of melanin-concentrating hormone (MCH) as a potent neuroprotective candidate. Here, we explored whether hypothalamic MCH mediates the neuroprotective action of acupuncture. In addition, we aimed at evaluating the neuroprotective effects of MCH and elucidating underlying mechanism in vitro and in vivo PD models. First, we tested whether hypothalamic MCH mediates the neuroprotective effects of acupuncture by challenging MCH-R1 antagonist (i.p.) in mice PD model. We also investigated whether MCH has a beneficial role in dopaminergic neuronal protection in vitro primary midbrain and human neuronal cultures and in vivo MPTP-induced, Pitx3-/-, and A53T mutant mice PD models. Transcriptomics followed by quantitative PCR and western blot analyses were performed to reveal the neuroprotective mechanism of MCH. We first found that hypothalamic MCH biosynthesis was directly activated by acupuncture treatment and that administration of an MCH-R1 antagonist reverses the neuroprotective effects of acupuncture. A novel finding is that MCH showed a beneficial role in dopaminergic neuron protection via downstream pathways related to neuronal survival. This is the first study to suggest the novel neuroprotective action of MCH as well as the involvement of hypothalamic MCH in the acupuncture effects in PD, which holds great promise for the application of MCH in the therapy of neurodegenerative diseases.

A Selective Encryption Algorithm Based on AES for Medical Information.

OBJECTIVES: The transmission of medical information is currently a daily routine. Medical information needs efficient, robust and secure encryption modes, but cryptography is primarily a computationally intensive process. Towards this direction, we design a selective encryption scheme for critical data transmission. METHODS: We expand the advandced encrytion stanard (AES)-Rijndael with five criteria: the first is the compression of plain data, the second is the variable size of the block, the third is the selectable round, the fourth is the optimization of software implementation and the fifth is the selective function of the whole routine. We have tested our selective encryption scheme by C(++) and it was compiled with Code::Blocks using a MinGW GCC compiler. RESULTS: The experimental results showed that our selective encryption scheme achieves a faster execution speed of encryption/decryption. In future work, we intend to use resource optimization to enhance the round operations, such as SubByte/InvSubByte, by exploiting similarities between encryption and decryption. CONCLUSIONS: As encryption schemes become more widely used, the concept of hardware and software co-design is also a growing new area of interest.

Purification and characterization of a new anticoagulant protein, PP27, from placenta.

It has long been known that water extracts of placenta hominis (Jahage in Korean) are effective for treating immunological and vascular diseases and is a major constituent of traditional oriental medicines. We report herein on the isolation and purification of a new type of anticoagulant protein, PP27, from human placenta. PP27 ran as a single band on SDS-PAGE with a molecular mass (Mr) of 27 kDa under denaturing conditions and chromatography on a calibrated Sepharose 4B column indicated a molecular mass of 23 kDa, a value that is similar to those of other PP4 enzymes reported to date. The isoelectric point of PP27 was pI 5.2. PP27, at doses higher than 10 microg/ml, inhibited platelet activating factor (PAF)-induced platelet activation in a dose-dependent manner. The protein was found to inhibit the coagulation time in a concentration-dependent manner. PP27, which acts as a vascular anticoagulant of annexin type, inhibits the blood clotting process by virtue of its binding of essential lipids, which is dependent on the presence of Ca2+ ions. In the presence of Ca2+ ions, PP27 combines with platelet membranes and neutralizes their procoagulant effect. Coagulation, triggered by the addition of thromboplastin/lipid mixtures, is extinguished by PP27.