Effects of the hook of Uncaria rhynchophylla on neurotoxicity in the 6-hydroxydopamine model of Parkinson's disease

Ethnopharmacological relevance

While the hook of Uncaria rhynchophylla (URH) is a traditional herb used in northeast Asia for the treatment of Parkinson's disease (PD)-like symptoms such as tremor, it has not been experimentally evaluated in a PD model.

Aim of the study

We investigated the effects of URH on 6-hydroxydapamine (6-OHDA)-induced neurotoxicity in in vitro and in vivo models of PD.

Materials and methods

The cell viability, anti-oxidative activity, and anti-apoptotic activity of a water extract of URH (URE) were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, reactive oxygen species (ROS), total glutathione (GSH), and caspase-3 assays in PC12 cells stressed by 6-OHDA. We also investigated the behavioral recovery and dopaminergic neuron protection of URE using an apomorphine-induced rotation test and tyrosine hydroxylase immunohistochemistry in the hemi-parkinsonian rat model of the unilateral 6-OHDA lesion of the medial forebrain bundle.

Results

In PC12 cells, URE significantly reduced cell death and the generation of ROS, increased GSH levels, and inhibited caspase-3 activity induced by 6-OHDA. In 6-OHDA-lesioned rats, posttreatment with URE (5 mg/kg/day for 14 days) significantly reduced apomorphine-induced rotation, and it lowered dopaminergic neuronal loss in substantia nigra pars compacta.

Conclusions

URE possesses neuroprotective activity against 6-OHDA-induced toxicity through anti-oxidative and anti-apoptotic activities in PD models.     

In vitro anti‐adhesive activity of green tea extract against pathogen adhesion

Camellia sinensis polysaccharide has been reported to possess anti‐adhesive activity against pathogens. The present study was designed to investigate whether hot water extracts obtained from green tea leaves might inhibit pathogen adhesion to human or mouse cell lines. Green tea extract‐4 (CSI‐4) with the maximum yield of 4% (w/v) is composed of a major proportion of carbohydrates containing 40% uronic acids, but lack of catechins. It showed strong inhibitory activities against hemagglutination mediated by pathogens Helicobacter pylori, Propionibacterium acnes and Staphylococcus aureus with the minimum inhibitory concentrations of 0.01‐0.5 mg/mL. CSI‐4 further demonstrated an inhibitory effect on the adhesion of these pathogens to host cell lines with the IC₅₀ values (50% inhibition of adhesion) of 0.14–2.3 mg/mL. It exhibited the highest activity against P. acnes, but no inhibitory effects were observed against Lactobacillus acidophilus, Bifidobacterium bifidum, Escherichia coli, or Staphylococcus epidermidis. Our results suggest that CSI‐4 may exert a selective anti‐adhesive effect against certain pathogenic bacteria with no adverse effects against beneficial or commensal bacteria. Copyright © 2008 John Wiley & Sons, Ltd.     

Effect of Training with Whole Body Vibration on the Sitting Balance of Stroke Patients

[Purpose] The purpose of this study was to determine the effects of task-oriented training with whole body vibration (WBV) on the sitting balance of stroke patients. [Subjects] The subjects were 30 stroke patients who were randomly divided into experimental (n₁=15) and control (n₂=15) groups. [Methods] Subjects in both groups received general training five times per week. Subjects in the experimental group practiced an additional task-oriented training program with WBV, which was performed for 15 minutes, five times per week, for four weeks. The center of pressure (COP) path length and average velocity were used to assess subjects static sitting balance, and the Modified Functional Reach Test (MFRT) was used to assess their dynamic sitting balance. The paired t-test was performed to test the significance of differences between before and after the intervention. The independent t-test was conducted to test the significance of differences between the groups. [Results] Following the intervention, the experimental group showed a significant change in MFRT. [Conclusion] The results of this study suggest that task-oriented training with WBV is feasible and efficacious for stroke patients.Key words: Balance, Stroke, Whole body vibration     

Effects of Aquatic Backward Locomotion Exercise and Progressive Resistance Exercise on Lumbar Extension Strength in Patients Who Have Undergone Lumbar Diskectomy

Kim Y-S, Park J, Shim JK. Effects of aquatic backward locomotion exercise and progressive resistance exercise on lumbar extension strength in patients who have undergone lumbar diskectomy.

Objective

To compare the effects of aquatic backward locomotion exercise and progressive resistance exercise with a machine on lumbar extension strength in patients who have undergone diskectomy for a lumbar disk herniation.

Design

Prospective comparative study.

Setting

Department of Kinesiology at a state university.

Participants

Male patients (N=30) with disk herniation at spinal levels L3 to S1 completed this study as subjects.

Intervention

After the diskectomy for a lumbar disk herniation, all patients had 6 weeks of rest time. At the end of the rest period, the aquatic backward locomotion exercise and progressive resistance exercise groups, respectively, started first 6 weeks of underwater training and lumbar extension training twice per week. After completion of the first 6-week training, subjects participated in a second 6-week training. After the whole 12-week training, subjects had no training for 6 weeks (detraining) and a follow-up 6-week training (retraining). The control (CON) group did not undergo any training.

Main Outcome Measures

For each test, maximum voluntary isometric lumbar extension strength was measured in 7 trunk positions (72°, 60°, 48°, 36°, 24°, 12°, and 0° of the trunk angle).

Results

The progressive resistance exercise and aquatic backward locomotion exercise groups showed increases in lumbar extension strength after the first 6-week training, although they were not statistically different from the CON group. After a second 6-week training, the progressive resistance exercise and aquatic backward locomotion exercise groups showed statistically significant increases in their strength levels as compared with the CON group. After the detraining period, the strength levels of the progressive resistance exercise and aquatic backward locomotion exercise groups did not statistically differ from the CON group. After the retraining period, the progressive resistance exercise and aquatic backward locomotion exercise groups showed increases in their strength levels, which were different from that of the CON group.

Conclusions

The results obtained suggested that the aquatic backward locomotion exercise is as beneficial as progressive resistance exercise for improving lumbar extension strength in patients after lumbar diskectomy surgery.     

Effects of bee venom on the maturation of murine dendritic cells stimulated by LPS

Aim of study

This study was performed to elicit the effectiveness of bee venom (BV), a traditional immunosuppressive Korean acupuncture agent, on the maturation of dendrtic cells (DCs).

Materials and methods

Immature dendritic cells (iDCs) were generated from mouse bone marrow cells with GM-CSF. After 10 days of initial differentiation, DCs were activated with lipopolysaccharides (LPS) for another 48h in the presence or absence of BV. Surface molecule analysis, intracytoplasmic staining of cytokines, FITC-conjugated antigen uptake, and transwell migration assays were conducted with iDCs and activated DCs.

Results

Up-regulation of costimulatory molecules, typical of mature DCs (mDCs) was inhibited by addition of BV. Pro-inflammatory cytokines were also found to be reduced with BV treatment in LPS-stimulated DC. A decrease in antigen uptake upon the maturation of DC was reversed in low dose BV treated mDC. In addition, BV treated mDC demonstrated reduced directional migration in response to CCL21, a lymphoid chemokine which directs mDC.

Conclusions

BV may have a therapeutic effect an on abnormally activated immune status, such as autoimmune rheumatoid arthritis, through an immune-modulatory effect on DC.     

Cumulative Recurrence Rate and Risk Factors for Recurrent Abdominal Wall Endometriosis after Surgical Treatment in a Single Institution

PurposeThis study aimed to evaluate the cumulative recurrence rate and risk factors for recurrent abdominal wall endometriosis (AWE) after surgical treatment.Materials and MethodsA retrospective cohort study was conducted at a single gynecological surgery center between January 2004 and December 2020. Patients who were surgically treated and followed up for at least 6 months after surgery were selected.ResultsEighteen patients with pathologically diagnosed AWE were included in this study. The median follow-up duration was 22.5 months (range, 6–106). The median age was 37 years (range, 22–48), and 33.3% of the patients were nulliparous. Among the patients included in our study, 55.6% complained of a mass with cyclic pain, and 27.8% had a palpable mass. In addition, 22.2% of patients experienced recurrence with 17.5±9.7 months of mean time to recurrence. The cumulative recurrence rates at 24 and 60 months after surgical treatment of AWE were 23.8% and 39.1%, respectively. There were no statistically significant risk factors for the recurrence of AWE, including postoperative medical treatment.ConclusionThe recurrence rate of AWE appears to be correlated with the follow-up duration. There was no statistically significant risk factor for the recurrence of AWE. Unlike ovarian endometriosis, postoperative hormonal treatment does not seem to lower the recurrence of AWE. The findings of the current study may help healthcare providers in counselling and managing patients with AWE.     

Cell membrane and nuclear expression of programmed death ligand-1 in prostate needle biopsy tissue in prostate cancer patients undergoing primary radiation therapy

BackgroundProgrammed death ligand-1 (PD-L1) expression in cancer is often associated with cancer aggressiveness and responsiveness to treatment with PD-1 pathway inhibitors. We conducted a systematic study on the expression of membranous PD-L1 (mPD-L1) and nuclear PD-1-L1 (nPD-L1) in prostate needle biopsy specimens of prostate cancer patients who underwent primary radiotherapy and analyzed the association between PD-L1 expression and clinicopathological characteristics and prognosis of patients.MethodA total of 971 cancer-containing prostate needle biopsy cores from 172 patients were immunohistochemically stained with anti-PD-L1 antibody. The association of PD-L1 expression with Gleason score and tumor volume percentage was evaluated for each biopsy core. Total of 171 patients were divided according to mPD-L1 or nPD-L1 expression, and clinicopathological characteristics were compared between the positive and negative groups. The prognostic significance of mPD-L1, nPD-L1 and common prognostic factors were analyzed in terms of biochemical recurrence.ResultTotal of 15% and 46% of biopsy cores were stained positive for mPD-L1 and nPD-L1, respectively. There was a positive correlation between Gleason score and mPD-L1 and a negative correlation between Gleason score and nPD-L1. Between mPD-L1 and nPD-L1, there was no significant correlation. There was intraindividual heterogeneity in PD-L1 expression among different Gleason scores. For mPD-L1, only pretreatment PSA was significantly higher in the positive group than in the negative, but not Gleason score and T stage. For nPD-L1, Gleason score and T stage were significantly higher in the positive group than in the negative. Both mPD-L1 and nPD-L1 expression were not predictive of BCR-free survival in univariate and multivariate analyses.ConclusionsOur results suggest that PD-1 pathway inhibitor may be a potential therapeutic option in high risk prostate cancer patients as early as neoadjuvant setting. The novel discovery of PD-L1 expression in the nucleus of PC should be subjected to further research.     

Polycythemia is associated with bone loss and reduced osteoblast activity in mice

Summary

Increased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity in a mouse model of PV and another mouse of polycythemia and elevated circulating erythropoietin (EPO). Our results are important for patients with PV or those treated with recombinant EPO (rEPO).

Introduction

PV and other myeloproliferative syndromes have been recently associated with an increased risk for fractures. However, the presence of osteoporosis in these patients has not been well documented. EPO, a hormone primarily known to stimulate erythropoiesis, has been shown recently to regulate bone homeostasis in mice. The aim of this study was to examine the bone phenotype of a mouse model of PV and compare it to that of animals with polycythemia caused by elevated circulating EPO.

Methods

Bone mass and remodeling were evaluated by micro-computed tomography and histomorphometry. The JAK2^V617F knock-in mouse, a model of human PV, manifests polycythemia and low circulating EPO levels. Results from this mouse were compared to wild type (wt) controls and the tg6 transgenic mouse that shows polycythemia caused by increased constitutive expression of EPO.

Results

Compared to wt, both JAK2^V617F and tg6 mice had a decrease in trabecular bone mass. Tg6 mice showed an additional modest decrease in cortical thickness and cortical bone volume per tissue volume (P?<?0.01) suggesting a more severe bone phenotype than JAK2^V617F. Decreased osteoblast numbers and bone formation along with normal osteoclast numbers and activity were found in both mice.

Conclusions

This study indicates that PV is associated with low bone mass and decreased osteoblast activity in mice. Our results support future studies of osteoporosis in affected humans. Polycythemia caused by chronically elevated circulating EPO also results in bone loss, and implications on patients treated with rEPO should be evaluated.