Serping1 associated with α-synuclein increase in colonic smooth muscles of MPTP-induced Parkinson's disease mice.

Patients with Parkinson's disease (PD) have gastrointestinal motility disorders, which are common non-motor symptoms. However, the reasons for these motility disorders remain unclear. Increased alpha-synuclein (α-syn) is considered an important factor in peristalsis dysfunction in colonic smooth muscles in patients with PD. In this study, the morphological changes and association between serping1 and α-syn were investigated in the colon of the 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced chronic PD model. Increased serping1 and α-syn were noted in the colon of the PD model, and decreased serping1 also induced a decrease in α-syn in C2C12 cells. Serping1 is a major regulator of physiological processes in the kallikrein-kinin system, controlling processes including inflammation and vasodilation. The kinin system also comprises bradykinin and bradykinin receptor 1. The factors related to the kallikrein-kinin system, bradykinin, and bradykinin receptor 1 were regulated by serping1 in C2C12 cells. The expression levels of bradykinin and bradykinin receptor 1, modulated by serping1 also increased in the colon of the PD model. These results suggest that the regulation of increased serping1 could alleviate Lewy-type α-synucleinopathy, a characteristic of PD. Furthermore, this study could have a positive effect on the early stages of PD progression because of the perception that α-syn in colonic tissues is present prior to the development of PD motor symptoms.

Association between Decreased SGK1 and Increased Intestinal α-Synuclein in an MPTP Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a globally common progressive neurodegenerative disease resulting from the loss of dopaminergic neurons in the brain. Increased α-synuclein (α-syn) is associated with the degeneration of dopaminergic neurons and non-motor symptoms like gastrointestinal disorders. In this study, we investigated the association between serum/glucocorticoid-related kinase 1 (SGK1) and α-syn in the colon of a PD mouse model. SGK1 and α-syn expression patterns were opposite in the surrounding colon tissue, with decreased SGK1 expression and increased α-syn expression in the PD group. Immunofluorescence analyses revealed the colocation of SGK1 and α-syn; the PD group demonstrated weaker SGK1 expression and stronger α-syn expression than the control group. Immunoblotting analysis showed that Na+/K+ pump ATPase α1 expression levels were significantly increased in the PD group. In SW480 cells with SGK1 knockdown using SGK1 siRNA, decreasing SGK1 levels corresponded with significant increases in the expression levels of α-syn and ATPase α1. These results suggest that SGK1 significantly regulates Na+/K+ pump ATPase, influencing the relationship between electrolyte balance and fecal formation in the PD mouse model. Gastrointestinal disorders are some of the major prodromal symptoms of PD. Therefore, modulating SGK1 expression could be an important strategy for controlling PD.

Association between SGK1 and α-synuclein in skeletal muscle in an MPTP-induced Parkinson's disease model.

Parkinson's disease (PD) is a neurodegenerative disease caused by loss of dopaminergic neurons in the substantia nigra and it is known to involve the accumulation of α-synuclein (α-syn), which is a neuroprotein that promotes degeneration of dopaminergic neurons. Serum/glucocorticoid-related kinase 1 (SGK1) is involved in the physiological and pathological processes in neurons. The aim of this study was to examine the relationship between SGK1 and α-syn expression in muscle tissue of a PD model and in C2C12 cells. Western blotting, immunohistochemistry, and immunofluorescence microscopy confirmed reduced SGK1 and increased α-syn expression in skeletal muscle of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice compared to the control group. To determine the relationship between SGK1 and α-syn, SGK1 small interfering RNA (siRNA) knockdown was performed in C2C12 cells, which showed that suppression of SGK1 levels resulted in increased α-syn expression. The main finding of our study is that reduction of SGK1 expression contributes to the pathogenesis of PD by increasing the expression of α-syn in skeletal muscle of MPTP-treated mice and C2C12 cells. This study confirms that decreased SGK1 induces increased α-syn expression in skeletal muscle, which suggests that maintaining SGK1 expression may improve PD symptoms.

The Effects of Serping1 siRNA in α-Synuclein Regulation in MPTP-Induced Parkinson's Disease.

Our understanding of the gastrointestinal system in the pathophysiology of Parkinson's disease (PD) has grown considerably over the last two decades. Patients with PD experience notable gastrointestinal symptoms, including constipation. In this study, the effects of knocked-down serping1, associated with the contraction and relaxation of smooth muscle and inflammation responses, by applying the serping1 siRNA were investigated in 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced PD mice in an α-syn change aspect. In the result, serping1 expression was knocked down by the treatment of serping1 siRNA, and decreased serping1 induced the decrease α-syn in the colon. Furthermore, the changes in α-syn aggregation were also examined in the brain, and alleviated α-syn aggregation was also observed in an serping1 siRNA treatment group. The results indicated that serping1 siRNA could ease synucleinopathy related to the gastrointestinal system in PD. This study also raises the possibility that serping1 siRNA could alleviate α-syn aggregation in striatum and substantia nigra regions of the brain.

Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort.

OBJECTIVE: The main aim of this study is to investigate whether acupuncture could be an effective complementary treatment for reducing the risk of macrovascular complications in diabetic patients currently taking antidiabetic medications using a nationwide population-based database. METHODS: We conducted a retrospective cohort study to assess the efficacy of acupuncture on cardiovascular complications in diabetic patients using data from patients between 40 and 79 years of age, newly diagnosed with diabetes between 2003 and 2006, found in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea. From the data, we identified 21,232 diabetic patients who were taking antidiabetic medication between 2003 and 2006. The selected patients were divided into two groups-those who received acupuncture at least three times and those who received no acupuncture (non-acupuncture) in the year following their diagnosis of diabetes. After 1:1 propensity score matching (PSM), each group had 3350 patients, and the observation ceased at the occurrence of a major adverse cardiovascular event (MACE), which was defined as either myocardial infarction, stroke, or death due to cardiovascular cause. RESULTS: After PSM, the acupuncture group had a lower incidence of MACE (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81-0.94; P = 0.0003) and all-cause mortality (HR: 0.77; 95% CI: 0.70-0.84; P < 0.0001) than the non-acupuncture group; the HRs for stroke-related mortality (HR: 0.75; 95% CI: 0.56-1.00; P = 0.0485), ischemic heart disease mortality (HR: 0.53; 95% CI: 0.34-0.84; P = 0.006) and circulatory system disease mortality (HR: 0.67; 95% CI: 0.55-0.82; P < 0.0001) were lower in the acupuncture group than in the non-acupuncture group in the secondary analysis. CONCLUSION: Our results indicate that diabetic patients receiving acupuncture treatment might have a lower risk of MACE, all-cause mortality and cardiovascular mortality. This population-based retrospective study suggests beneficial effects of acupuncture in preventing macrovascular complications associated with diabetes. These findings call for further prospective cohort or experimental studies on acupuncture treatment for cardiovascular complications of diabetes. Please cite this article as: Jung H, Won T, Kim GY, Jang J, Yeo S, Lim S. Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort. J Integr Med. 2023; 21(2): 176-183.

Acupuncture for cancer patients with nausea and vomiting: A protocol for systematic review and meta-analysis.

BACKGROUND: Nausea and vomiting are among the most common adverse effects experienced by cancer patients undergoing treatment worldwide. Their treatment with pharmacologic therapy can often be complicated by medication interactions and other unwanted side effects. The aim of this systematic review and meta-analysis protocol is to assess the effectiveness and safety of acupuncture therapy for treating nausea and vomiting in patients with cancer. METHODS: Three electronic databases and 2 clinical registry platforms will be searched from inception to May 2022: the MEDLINE via PubMed, Embase via Ovid, the Cochrane Central Register of Controlled Trials via the Cochrane Library, the World Health Organisation International Clinical Trials Registry Platform, and National Institutes of Health Clinical trials.gov. Search terms will include nausea, vomiting, cancer, and acupuncture. Two researchers will independently select studies, extract data and assess the risk of bias. The primary outcome will be the incidence of nausea and/or vomiting or other validated outcome measures. Meta-analysis will be carried out using RevMan V.5.4. The quality of evidence from randomized clinical trials will be evaluated with the Grading of Recommendations Assessment, Development and Evaluation System tool. RESULTS: The results will provide a high-quality synthesis of evidence for clinicians in the field of oncology. CONCLUSION: The conclusion is expected to provide evidence to determine whether acupuncture is an effective and safe treatment for cancer patients with nausea and vomiting.

Association Between Decreased Srpk3 Expression and Increased Substantia Nigra Alpha-Synuclein Level in an MPTP-Induced Parkinson's Disease Mouse Model.

Parkinson's disease (PD) is the second most common neurodegenerative disorder and is caused by the loss of dopaminergic neurons in the substantia nigra (SN). However, the reason for the death of dopaminergic neurons remains unclear. An increase in α-synuclein (α-syn) expression is an important factor in the pathogenesis of PD. In the current study, we investigated the association between serine/arginine-rich protein-specific kinase 3 (Srpk3) and PD in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and in SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+). Srpk3 expression was significantly downregulated, while tyrosine hydroxylase (TH) expression decreased and α-syn expression increased after 4 weeks of MPTP treatment. Dopaminergic cell reduction and α-syn expression increase were demonstrated by Srpk3 expression inhibition by siRNA in SH-SY5Y cells. Moreover, a decrease in Srpk3 expression upon siRNA treatment promoted dopaminergic cell reduction and α-syn expression increase in SH-SY5Y cells treated with MPP+ . These results suggested that Srpk3 expression decrease due to Srpk3 siRNA caused both TH level decrease and α-syn expression increase. This raises new possibilities for studying how Srpk3 controls dopaminergic cells and α-syn expression, which may be related to PD pathogenesis. Our results provide an avenue for understanding the role of Srpk3 in dopaminergic cell loss and α-syn upregulation in SN. Furthermore, this study supports a therapeutic possibility for PD in that the maintenance of Srpk3 expression inhibits dopaminergic cell reduction.

Association between Decreased ITGA7 Levels and Increased Muscle α-Synuclein in an MPTP-Induced Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN), reducing dopaminergic levels in the striatum and affecting motor control. Herein, we investigated the potential relationship between integrin α7 (ITGA7) and α-synuclein (α-syn) in the muscle of methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced mice and C2C12 cells. To characterize the pathology of PD, we examined the expression of tyrosine hydroxylase (TH) in the SN of the midbrain. Compared with the control group, MPTP-treated mice showed a significant decrease in TH expression in the SN, accompanied by a significant decrease in muscle ITGA7 expression. Compared with the control group, α-syn expression was increased in the MPTP group. Furthermore, the pattern of α-syn expression in the MPTP group was similar to the ITGA7 expression pattern in the control group (linear forms). To determine the relationship between ITGA7 and PD, we examined the expression of ITGA7 and α-syn after ITGA7 knockdown using siRNA in C2C12 cells. ITGA7 expression significantly decreased while α-syn expression significantly increased in siRNA-treated C2C12 cells. These results suggest that decreased ITGA7 muscle expression could increase α-syn expression. Moreover, α-syn accumulation, induced by decreased muscle ITGA7, might contribute to PD pathology.

Reduction of tyrosine hydroxylase expression and increase of α-synuclein in the substantia nigra in a rat model of benign prostatic hyperplasia.

Parkinson's disease (PD) occurs when dopaminergic cells in the substantia nigra (SN) region are destroyed; however, the cause of the destruction of dopamine cells has not yet been determined. This study was performed to investigate whether changes in the hormones that cause benign prostatic hyperplasia (BPH) are related to pathological changes in PD. The pathological findings were examined by observing the lesion sites related to PD in a BPH rat model. BPH was induced in rats by subcutaneous injection of testosterone propionate for 4 weeks after castration. To investigate the changes in the SN regions, tyrosine hydroxylase (TH) and α-synuclein (α-syn) expression were analyzed by western blotting. TH expression, expressed in dopaminergic cells and used as a dopaminergic cell detection marker, decreased, whereas α-syn expression increased at the SN site. These results are quite similar to the pathological changes observed in patients with PD and Parkinsonism animal models. Our results showed an increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in the SN regions in the BPH group. Additionally, a decreased expression of B-cell lymphoma protein 2 and an increased expression of B-cell lymphoma protein 2-associated X, suggesting increased apoptosis, were observed in the BPH group. These results suggest that the pathological changes associated with PD may be caused by BPH or factors related to BPH. Thus, this study has presented a new avenue for an approach related to hormonal changes as a method to determine the cause of PD, for which the exact cause is not yet known.

Decrease in ITGA7 Levels Is Associated with an Increase in α-Synuclein Levels in an MPTP-Induced Parkinson's Disease Mouse Model and SH-SY5Y Cells.

We investigated the potential association between integrin α7 (ITGA7) and alpha-synuclein (α-syn) in a methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Tyrosine hydroxylase (TH), ITGA7, and α-syn expression in the substantia nigra (SN) of the brain were observed to examine the pathological characteristics of PD. To determine the relationship between ITGA7 and PD, the expression of TH and α-syn was investigated after ITGA7 siRNA knockdown in SH-SY5Y cells. The ITGA7 microarray signal was decreased in the SN of the MPTP group, indicating reduced ITGA7 expression compared to that in the control. The expression patterns of ITGA7 in the control group and those of α-syn in the MPTP group were similar on immunohistochemical staining. Reduction in ITGA7 expression by ITGA7 siRNA administration induced a decrease in TH expression and an increase in α-syn expression in SH-SY5Y cells. The decreased expression of ITGA7 significantly decreased the expression of bcl2 and increased the bax/bcl2 ratio in SH-SY5Y cells. These results suggest that reduced ITGA7 expression may be related to increased α-syn expression and apoptosis of dopaminergic cells in an MPTP-induced PD mouse model. To the best of our knowledge, this is the first study to show an association between ITGA7 and PD.

Association of decreased triadin expression level with apoptosis of dopaminergic cells in Parkinson's disease mouse model.

BACKGROUND: Parkinson's disease (PD) represent a loss of dopaminergic neurons in the substantia nigra (SN) of the midbrain. However, its cause remains unknown and Triadin (TRDN) function in the brain is also unknown. To examine the relationship between TRDN and PD, the expression levels of protein related to PD in TRDN knockdown status were studied in the SH-SY5Y cells. Cell viability and apoptosis were assessed to examine the apoptosis effect on dopaminergic cells by decreased TRDN, and the levels of the proteins related to apoptosis were also confirmed. RESULTS: This study confirmed decreased TRDN expression level (P < 0.005) at the SN in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mouse model and identified the functional features of TRDN. Our results showed a relationship between TRDN expression and PD in that reduced TRDN level induced PD-like characteristics. Interestingly, there was TRDN expression in the regions where dopaminergic cells are in the SN, and the expression patterns of TRDN and tyrosine hydroxylase (TH) were similar. Decreased TRDN level also induced apoptotic characteristics and the Fluorescence-activated cell sorting analysis results showed that apoptosis increased (P < 0.05) as the TRDN small interfering RNA concentration increased. The cytotoxicity assay revealed that cell viability also decreased (P < 0.0005) in the same condition as that in the Fluorescence-activated cell sorting analysis. CONCLUSIONS: Decreased TRDN level could be related with the apoptotic death of dopaminergic cells at the SN in PD, and TRDN administration could give a positive effect on PD by reducing apoptotic cell death.

Association between diabetes mellitus and anemia among Korean adults according to sex: a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey (2010-2016).

BACKGROUND: There are many conflicting opinions regarding the association between anemia and diabetes mellitus (DM), and the mechanism by which DM influences anemia remains uncertain. Therefore, we aimed to investigate the association between anemia and DM in Korean adults and to analyze the risk factors for anemia among these patients according to sex. METHODS: This retrospective cross-sectional survey was conducted using data from the Korea National Health and Nutrition Examination Survey V, VI, and VII between January 2010 and December 2016. In total, 25,597 Korean adults aged ≥19 years (10,117 men, 15,480 women) were included. Patients with a fasting blood sugar level of ≥126 mg/dL or who have been diagnosed with DM were classified as the DM group. Anemia was defined as hemoglobin levels of < 13 g/dL in men and < 12 g/dL in women. Logistic regression analysis was used to adjust for demographic characteristics and lifestyle-, disease-, and health-related factors. RESULTS: Approximately 11.3% of patients had DM. The prevalence of anemia was significantly higher in the DM group than in the non-DM group. After adjusting for confounding factors, the odds of the prevalence of anemia in men were higher in the DM group than in the non-DM group (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.42-2.50, p < 0.0001). When investigated according to the serum creatinine level, the association was significantly stronger among women (OR 42.63, 95% CI 17.25-105.36, p < 0.0001) than among men (OR 6.30, 95% CI 3.08-12.90, p < 0.0001). CONCLUSIONS: We found a strong association between DM and anemia that was more prominent among men than among women. We also determined that the serum creatinine level had a greater influence on DM and anemia in women than in men.

Srpk3 Decrease Associated with Alpha-Synuclein Increase in Muscles of MPTP-Induced Parkinson's Disease Mice.

Parkinson's disease (PD) is characterized by a loss of dopaminergic cells in the substantia nigra, and its histopathological features include the presence of fibrillar aggregates of α-synuclein (α-syn), which are called Lewy bodies and Lewy neurites. Lewy pathology has been identified not only in the brain but also in various tissues, including muscles. This study aimed to investigate the link between serine/arginine-rich protein specific kinase 3 (srpk3) and α-syn in muscles in PD. We conducted experiments on the quadriceps femoris of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and the C2C12 cell line after treatment with 1-methyl-4-phenylpyridinium (MPP+) and srpk3 short interfering RNA (siRNA). Compared to the control group, the MPTP group showed significantly reduced expression of srpk3, but increased expression of α-syn. In MPP+-treated C2C12 cells, srpk3 expression gradually decreased and α-syn expression increased with the increasing MPP+ concentration. Moreover, experiments in C2C12 cells using srpk3 siRNA showed increased expressions of α-syn and phosphorylated α-syn. Our results showed that srpk3 expression could be altered by MPTP intoxication in muscles, and this change may be related to changes in α-syn expression. Furthermore, this study could contribute to advancement of research on the mechanism by which srpk3 plays a role in PD.

Efficacy of Acupuncture for Insomnia: A Systematic Review and Meta-Analysis.

Patients with insomnia frequently use acupuncture as an alternative treatment to pharmacotherapy globally. The aim of this paper is to assess the effect of acupuncture on insomnia. Seven medical databases, including MEDLINE, EMBASE, CENTRAL, CNKI, RISS, NDSL, and OASIS, were used to identify studies published through July 09, 2020. Twenty-four randomized controlled trials (RCTs) were included in this qualitative review comparing acupuncture to either pharmacotherapy or sham-acupuncture therapy. Methodological quality was assessed, using the Cochrane risk of bias (ROB). In the subsequent quantitative meta-analysis of studies comparing acupuncture versus pharmacotherapy, fifteen RCTs demonstrated that acupuncture had a significant effect on patients with insomnia as assessed by the Pittsburgh sleep quality index (PSQI) (RR: -0.74; 95% CI: -1.07 to -0.40; [Formula: see text] ¡0.0001; [Formula: see text] = 89%; [Formula: see text] = 1475). A subgroup analysis showed that there was no significant effect after weeks 1 and 2, but six studies found that acupuncture had a significant effect insomnia at week 3 (RR: -0.97; 95% CI: -1.65 to -0.28; [Formula: see text] = 0.006; [Formula: see text] = 91%; [Formula: see text] = 463) and nine studies demonstrated a significant effect at week 4 (RR: -0.70; 95% CI: -1.15 to -0.25; [Formula: see text] = 0.002; [Formula: see text] = 85%; [Formula: see text] = 594). These results suggest that insomnia patients may experience significant improvement in symptoms after more than three weeks of acupuncture treatment compared to pharmacological treatments.

Triadin Decrease Impairs the Expression of E-C Coupling Related Proteins in Muscles of MPTP-Induced Parkinson's Disease Mice.

Parkinson's disease (PD), caused by destruction of dopaminergic neurons in the brain, leads to motor symptoms like bradykinesia, tremor, and walking impairments. While most research effort focuses on changes in neuronal pathology we examined how muscle proteins were altered in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. A Ca2+ release channel complex, consisting of ryanodine receptors (RYR), triadin (TRDN), and calsequestrin (CSQ1), is important for excitation-contraction coupling in the sarcoplasmic reticulum membrane in muscles. Thus, we investigated changes in the RYR Ca2+ release channel components in PD mice model. Based on a report that TRDN deletion impairs skeletal muscle function, we also investigated how the knock-down of TRDN affects other components of the RYR channel in the PD model. In this study, the expression levels of the components of RYR channels decreased in the quadriceps femoris muscle of MPTP-induced PD mice and in C2C12 cells treated with 1-methyl-4-phenylpyridinium. We show that decreased TRDN levels decrease RYR and CSQ1 levels. These results suggest that the levels of proteins related to Ca2+ channel function decreased in this model, which could impair muscle function. We conclude that muscle function alterations could add to the bradykinesia and tremor in this model of PD.

Gene Expression of Prox-1 and Hif-1a in Primo Vessels Inside Lymph Vessels of the Rabbit.

The gene expression of Prox-1 and Hif-1a for the isolated primo vessels (PVs) and composite lymphatic vessels (LVs) containing PVs (LVs + PVs) was investigated by RNA-sequencing (Seq) and quantitative polymerase chain reaction (qRT-PCR) analysis. RNA-Seq on the passed 10 samples on RNA-QC for two experimental groups with PVs and PVs + LVs proceeded to the library construction stage automatically and analyzed differentially expressed genes (DEGs). From the real-time qRT-PCR analysis data, we found the marker genes of Prox-1 and Hif-1a were enriched and decreased in an isolated PVs compared to LVs, respectively. Based on mRNA transcriptional data, Prox-1 and Hif-1a were increased and decreased in PVs compared to LVs + PVs under lipopolysaccharide (LPS) treatment and relieved by acupuncture electric stimulation (AES), respectively. This finding indicates that high and low levels of Prox-1 and Hif-1a may be involved in the function of PVs and that pathophysiological and physiological condition could progress into inflamed lymphatic endothelial cells expanding the PV within the LV.

Effects of acupuncture on cardiovascular risks in patients with hypertension: a Korean cohort study.

OBJECTIVES: The aim of this study was to investigate the effects of acupuncture on major adverse cardiovascular events (MACE), myocardial infarction, stroke and death in hypertensive patients taking anti-hypertensives. METHODS: Using the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) database, this study identified 59,370 patients taking anti-hypertensives who had been diagnosed with hypertension between 2003 and 2006. They were divided into acupuncture and non-acupuncture groups. The follow-up period ended with the diagnosis of myocardial infarction, stroke or death. After propensity score matching (PSM), there were 18,011 patients each in the non-acupuncture and acupuncture groups. We calculated the incidence rate, hazard ratio (HR) and 95% confidence interval (CI) for MACE, myocardial infarction, stroke and death in patients with hypertension using a stratified Cox proportional hazard model. In addition, secondary outcome analyses for stroke and cardiovascular mortality were performed. RESULTS: After PSM, the HRs for MACE (0.83, 95% CI 0.80-0.86), all-cause mortality (0.73, 95% CI 0.70-0.76) and myocardial infarction (0.85, 95% CI 0.79-0.92) were significantly lower in the acupuncture group than in the non-acupuncture group. Moreover, the HRs for stroke-related mortality, hemorrhage stroke-related mortality, ischemic stroke-related mortality, ischemic heart disease-related mortality and circulatory system disease-related mortality were significantly lower in the acupuncture group than in the non-acupuncture group. CONCLUSION: This observational study with long-term follow-up extends the evidence base in support of the effectiveness of acupuncture for the management of hypertension and potentially reduce the burden of cardiovascular disease.

Association of increase in Serping1 level with dopaminergic cell reduction in an MPTP-induced Parkinson's disease mouse model.

Parkinson's disease (PD) is a progressive neurodegenerative disease, which shows distinct manifestations such as significant loss of dopaminergic neurons in the substantia nigra (SN). Gene expression was analyzed in the SN of mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), wherein downregulation of dopaminergic neurons occurred to examine the possible causes leading to the loss of dopaminergic neurons. In addition, a serine/cysteine protease inhibitor (Serping1) was studied as one of the genes that were prominently upregulated in mice chronically intoxicated with MPTP. Western blot analysis showed that, concomitant to the downregulation of dopaminergic cells, there was a substantial increase in Serping1 expression within the SN of the MPTP-induced PD mouse model. The SH-SY5Y cells were transfected with Serping1 short interfering RNA (siRNA) to evaluate the correlation between the expression of Serping1 and the loss of dopaminergic cells. Serping1 depletion elicited the upregulation of dopaminergic cells. Moreover, neuroprotective effect against dopaminergic cell loss was demonstrated upon the inhibition of Serping1 expression by siRNA in the MPP+ (1-methyl-4-phenylpyridinium)- treated SH-SY5Y cells. These results show that increased expression of Serping1 may play a critical role in dopaminergic cell death in the SN of chronic MPTP-induced PD mouse model and in SH-SY5Y cells.

Analysis and Differential Expression of Primo Genes Using RNA-Seq and qRT-PCR Experiments.

Although the existence of the primo vasculature system has been shown in many species, including mice, rats, rabbits and humans, the biological role of this system, including expression of genes and proteins, has not yet been investigated. Especially the transcriptional action by mRNA, which is required for biological action, needs to be studied in primo vasculature biology. Differentially expressed genes in both isolated primo vessels and lymphatic vessels of rabbits were analyzed by RNA sequencing experiments. Primer efficiency and RNA purity of the primo vessels under lipopolysaccharides were confirmed prior to performing real-time qRT-PCR analysis following RNA extraction. We demonstrated that FLT4 was enriched in primo vessels and that several genes, including HSPH1 and EPHB2, were highly expressed in primo vessels compared with lymphatic vessels. Our data show that almost all genes, except HSPA4, were increased or sustained in isolated primo vessels compared with lymphatic vessels (FLT4 2.58 fold, HSPH1 1.83 fold, EPHB2 1.52 fold; whereas HSPA4 decreased 0.50 fold), suggesting primo vessels as a central regulator in diverse physiology. This implies that FLT4, HSPH1, and EPHB2 in high amounts may be involved in the functional activity of primo vessels. Our experimental data show that several genes are highly enriched in primo vessels in the lymphatic vessels of the rabbit.

Acupuncture Inhibits the Increase in Alpha-Synuclein in Substantia Nigra in an MPTP- Induced Parkinsonism Mouse Model.

Parkinson's disease, a progressive neurodegenerative disease, is caused by the loss of dopaminergic neurons in the substantia nigra (SN). It is characterized by the formation of intracytoplasmic Lewy bodies that are primarily composed of the protein alpha-synuclein (α-syn), along with dystrophic neurites. Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in Parkinsonism animal models. We investigated the role of acupuncture in inhibiting the increase in α-syn expression that is related to dopaminergic cell loss in the SN in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonism mouse model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in the SN. Moreover, acupuncture stimulation attenuated the increase in α-syn in SN. Acupuncture stimulation also maintained the phosphorylated α-syn on serine 129 at levels similar to the control group. Our findings indicate that the MPTP-mediated increase in α-syn, and the acupuncture-mediated inhibition of the increase in α-syn, may be responsible for the neuroprotective effects of acupuncture in the SN following damage induced by MPTP.