Clinical and laboratory characterization of cutaneous leishmaniasis in Chinese migrant workers returned from Iraq.

BACKGROUND: Imported cutaneous leishmaniasis (CL) is a growing problem with increasing global travel to endemic areas. Returned travelers with CL are easy to be misdiagnosed and mistreated due to the lack of awareness for the disease to the physicians in non-endemic region that may lead to unfavorable outcome. Our study intends to summarize the characteristics of Leishmania infection imported from Iraq, so as to help Chinese physicians diagnose and treat the disease. All CL patients were treated with intralesional injection of antimony. METHODS: The definitive diagnosis of CL is based on the parasite identification by microscopic examination directly on lesion smear or parasite culture, PCR amplification of Leishmania-specific internal transcribed spacer 1 (ITS-1). The phylogenetic analysis, the immunopathological examination and the cytokine detection were proceeded after the diagnosis. RESULTS: We have identified 25 CL cases in migrant Chinese workers returned from Iraq for the first time with L. major as the major species of infected Leishmania parasite. Clinical features of the Iraq-imported CL include the history of skin exposure to sandflies bite and the lesions mostly on the exposed limbs. More ulcerative wet lesion was observed than nodular dry lesion. PCR is not only used to detect Leishmania parasite with high sensitivity, but also to identify the species of infected parasite through sequencing the amplified Leishmania-specific ITS-1 gene. The phylogenetic analysis based on the amplified ITS-1 sequences revealed that the infected Leishmania was closed related to the species and strains endemic in Iraq. The immunopathological examination revealed the T-cell filtrated cellular immune response with less B cells and NK cells involved. The cytokine profile measured in the skin lesion also confirmed the Th1 cellular response with higher expression levels of IFN-γ, IL-6 and IL-8. The skin lesions in CL patients were healed after being treated locally with antimony. CONCLUSIONS: The clinical and parasitological features of these Chinese CL cases imported from Iraq provide useful information for the diagnosis and treatment of CL that is not commonly seen in Chinese local population.

Effect of self-acupressure on middle ear barotrauma associated with hyperbaric oxygen therapy: A nonrandomized clinical trial.

BACKGROUND: In hyperbaric oxygen therapy (HBOT), a patient is exposed to pure oxygen in a chamber. While HBOT is a long-standing and well-established treatment for a wide variety of medical conditions, one of the main complications is middle ear barotrauma (MEB), which can lead to complaints of ear discomfort, stuffiness or fullness in the ear, and difficulties in equalizing ear pressure. The aim of this study is to evaluate the efficacy of self-acupressure in preventing and reducing the degree of MEB associated with HBOT. METHODS: This is a prospective nonrandomized controlled study. A sample of 152 participants will be assigned to 2 groups in a 1:1 ratio. The participants in the control group will receive conventional Valsalva and Toynbee maneuvers, while those in the experimental group will be given additional self-acupressure therapy. The acupoints used will be TE17 (Yifeng), TE21 (Ermen), SI19 (Tinggong), and GB2 (Tinghui). The Modified Teed Classification, symptoms of MEB, and overall ear discomfort levels will be assessed. Data will be analyzed using the Chi-Squared test or t test. OBJECTIVES: This study aims to evaluate the efficacy of self-acupressure for preventing and reducing the degree of MEB associated with HBOT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04311437. Registered on 17 March, 2020.

A comparison between dexlansoprazole modified release-based and lansoprazole-based nonbismuth quadruple (concomitant) therapy for first-line Helicobacter pylori eradication: a prospective randomized trial.

PURPOSE: Steadily maintaining high intra-gastric PH is the major factor for successful Helicobacter pylori (H.pylori) eradication. It is important to search for a stronger PPI. Dexlansoprazole MR is a dual delayed release formulation PPI taken once daily which is capable of maintaining longer duration of high intra-gastric PH. It is very effective in treating gastroesophageal disease but reports on H, pylori eradication is very rare. This study sought to compare dexlansoprazole MR-based concomitant treatment and lansoprazole-based concomitant treatment in H. pylori infection and to investigate the factors that affect the eradication rates. METHODS: Two hundred two participants with H. pylori infection were included and randomly assigned to seven days of dexlansoprazole MR-based concomitant therapy (dexlansoprazole MR 60 mg once daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily; DACM group) or a seven days of lansoprazole-based concomitant therapy (lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily, and metronidazole 500 mg twice daily; LACM group). The participants were asked to perform urea breath tests eight weeks later. RESULTS: The eradication rates in the DACM group were 86.1% [95% confidence interval (CI): 77.8%-92.2%] in the ITT analysis and 90.6% (95% CI: 82.9%-95.6%) in the PP analysis, respectively, as compared with 90.1% (95% CI: 82.6%-95.2%) and 92.6% (95% CI: 85.5%-96.9%) (p=0.384 and p=0.572, respectively) in the LACM group for the same analyses. The adverse event rates were 11.5% in the DACM group and 10.2% in the LACM group (p=0.779). CONCLUSION: As a first-line H. pylori treatment regimen, dexlansoprazole MR-based concomitant therapy attained a successful eradication rate of 90%, which was non inferior to that of lansoprazole-based concomitant treatment. CLINICALTRIALSGOV IDENTIFIER: NCT03829150.

First-line Helicobacter pylori eradication rates are significantly lower in patients with than those without type 2 diabetes mellitus.

Purpose: To assess the difference of the first-line therapy for Helicobacter pylori in patients with or without type 2 diabetes (DM) and to investigate the clinical factors influencing treatment outcomes. Patients and methods: In total, 719 patients with H. pylori infection were treated with 7-day standard first-line triple therapy, of whom 182 did and 537 did not have DM. Propensity score matched at a 1:2 ratio - for age, sex and body mass index was performed for the two groups, yielding a DM group with 147 patients and a non-DM group with 249 matched controls for analysis. Urea breath test was performed 6-8 weeks after treatment. Clinical and laboratory parameters were collected for identifying factors associated with failed eradication. Results: H. Pylori was eradicated in 74.1% (95% confidence interval [CI] =66.2-81.0) of the DM group and 85.3% (95% CI =80.8-89.4) of the non-DM group (p=0.005). Of 51 gastric biopsy samples cultured for H. pylori, 41 were positive. In the DM group, the rates of resistance to amoxicillin, clarithromycin, levofloxacin, and tetracycline were 0%, 50.0%, 50.0% and 0%, respectively. In the non-DM group, the comparable proportions were 2.9%, 17.1%, 22.9%, and 0%, respectively. Univariate analysis revealed that DM (Odds ratio [OR], 1.771, 95% CI, 1.167-2.668, p=0.006), clarithromycin resistance (OR, 15.273; 95% CI, 1.687-138.269; p=0.015), and amoxicillin resistance (OR, 4.672; 95% CI, 2.431-8.979; p<0.001) were independently associated with failure to eradicate H. pylori. Multivariate analysis showed that clarithromycin resistance was the major factor independently associated with failure of eradication (OR, 25.472; 95% CI, 1.549-418.956; p=0.023). Conclusions: First-line H. pylori eradication rates in patients with DM were significantly lower than in those without DM, although neither group achieved >90% eradication.

Therapeutic effects of acupuncture plus fire needle versus acupuncture alone in lateral epicondylitis: A randomized case-control pilot study.

BACKGROUND: The aim of this study was to compare the short-term and intermediate-term efficacy of acupuncture plus fire needle therapy with that of acupuncture alone in the treatment of lateral epicondylitis (LE). METHODS: Thirty-eight patients with LE who had persisted for at least 2 months were enrolled in this prospective, assessor-blinded, randomized controlled pilot trial. Twenty-one patients were randomized to the acupuncture plus fire needle group and 17 to the acupuncture-only group. The primary outcome was the visual analog scale pain score for the previous 24 hours and the secondary outcomes were the maximum grip strength, Patient-rated Forearm Evaluation Questionnaire score, and Medical Outcomes Study 36-Item Short-form Health Survey score. The values at baseline (pretreatment), at the end of treatment, and at 3 months after treatment were used to assess the short-term and intermediate-term effects of treatment. The data were analyzed using the Chi-square test and t test. RESULTS: Within-group analyses showed better results for acupuncture plus fire needle therapy in the short term and intermediate term. Differences in the severity of pain and secondary outcomes were significant in the intermediate term in the acupuncture group. At the end of treatment, none of the differences in outcome scores were significant, except for maximum grip strength in the affected hand in the acupuncture group. No significant between-group differences in short-term or intermediate-term outcomes were observed. CONCLUSION: Acupuncture plus fire needle therapy was effective in the short term in patients seeking improvement of LE. Twelve treatments were effective for relieving pain and improving disability in the intermediate term in patients with chronic LE in both study groups. The findings of the pilot study confirm the feasibility of proceeding to a larger randomized controlled study of the longer-term effects of acupuncture plus fire needle therapy in patients with LE.

Conventional Western Treatment Associated With Chinese Herbal Medicine Ameliorates the Incidence of Head and Neck Cancer Among Patients With Esophageal Cancer.

BACKGROUND: Because of advances in medical treatment, the survival of cancer patients is prolonged. In line with the prolonged survival time of cancer the incidence of second primary cancer has increased. There is currently no effective way to prevent the occurrence of secondary primary cancer (SPC). OBJECTIVES: The aim of this study is to evaluate whether Chinese Herbal Medicine (CHM) is correlated with reduced occurrence of second primary cancer (SPC) of head and neck (H&N) in patients with esophageal cancer (EC). METHOD: We identified 15,546 patients who were diagnosed with esophageal cancer between Jan 1, 2000, and Dec 31, 2010. The patients with H&N cancer before receiving CHM were excluded. After the selection and matching process, both CHM and non-CHM cohorts each contained 850 individuals. We compared the cumulative incidence of SPC of H&N with or without CHM treatment in patients with EC by the Kaplan-Meier method. NodeXL is used to run a network analysis of CHM to examine the association between herbs and formulas. RESULTS: Compared with non-CHM users, CHM-users showed a reduced incidence rate of SPC of H&N among the patients with EC. Reduced cumulative incidence of SPC of H&N among patients with EC was noted in the CHM cohort compared to the non-CHM cohort. The most commonly used single herbs and formulas were associated with reducing SPC occurrence. CONCLUSION: We propose that CHM as an adjuvant therapy may prevent the occurrence of SPC of H&N in patients with EC.

Serum-soluble TRAIL: a potential biomarker for disease activity in myositis patients.

OBJECTIVES: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF super-family, which is involved in the regulation of immune response and pathogenesis of autoimmune diseases, including polymyositis (PM) and dermatomyositis (DM). In this study, we examined the level and origin of serum-soluble TRAIL (sTRAIL) in patients with PM and DM and analyzed its association with disease activity and clinical features. METHOD: 11 PM patients, 33 DM patients, and 20 healthy controls were enrolled in this study. Clinical features were recorded when admitted, and disease activity was evaluated by myositis disease activity assessment visual analogue scale (MYOACT). TRAIL expression in muscle tissues was detected by immunohistochemistry. Serum sTRAIL levels were measured by enzyme-linked immunosorbent assay. The expression of membrane TRAIL (mTRAIL) and its receptors, including DR4 and DR5, on circulating T cells was analyzed by flow cytometry. RESULTS: TRAIL was expressed in infiltrated inflammatory cells in muscle tissues from patients. The serum sTRAIL level was markedly increased in patients and was positively correlated with the disease activity. Serum sTRAIL was decreased after therapy in patients and was specifically higher in patients with dysphagia, but lower in patients with autoantibody Jo-1 positive. The frequency of mTRAIL and its receptors on circulating T cells from patients were significantly elevated than that from healthy controls. CONCLUSIONS: The serum sTRAIL could be a biomarker for evaluating the disease activity of PM and DM, and targeting the generation of TRAIL in T cells might be a potential approach in the treatment of PM and DM.

Alternative Therapy for Patients With Obstructive Sleep Apnea/Hypopnea Syndrome: A 1-year, Single-blind, Randomized Trial of Tui Na.

Context • Obstructive sleep apnea/hypopnea syndrome (OSAHS) is among the most prevalent of sleep-related breathing disorders. No long-term follow-up studies have documented the continued success of lifestyle changes in treatment; oral appliances have an approximate 50% success rate; compliance with continuous positive airway pressure is poor, ranging from 50% to 89%; and the success rate of upper-airway surgery is only 66.4%. Therefore, some OSAHS patients seek alternative treatments. Objectives • The study intended to examine the efficacy of traditional Chinese therapeutic massage (tui na) for patients with OSAHS. Design • The research team designed a prospective study. Setting • The study took place at the outpatient clinic of the sleep center at the Kaohsiung Chang Gung Memorial Hospital (Kaohsiung, Taiwan), an academic tertiary medical center. Participants • Participants were 31 patients with moderate to severe OSAHS. Intervention • Each participant received a tui na treatment at multiple acupoints 2 ×/wk for 10 wk for approximately 15 min/session. Outcome Measures • At baseline and 3 mo after treatment, participants completed subjective measures, including (1) quality of life using a 36-item, short-form health survey (SF-36); (2) subjective snoring intensity indicated by bed-partners using a 0-10 visual analog scale (VAS); and (3) excessive daytime sleepiness (EDS) status, using a Chinese version of the Epworth Sleepiness Scale (CESS). The research team completed objective measures, including (1) polysomnography, (2) body mass index, and (3) neck circumference. Results • Twenty patients completed the full course of treatment. The apnea/hypopnea index per hour decreased from 43.8 ± 26.9 to 37.8 ± 31.7 after the treatments, with P = .049 (paired t test). The arousal index and rapid eye movement stage of sleep improved significantly. Statistically significant improvements were observed for the SF-36 on the score for the physical component summary, for its subscale for general health, for the mental component summary, and for 2 of its subscales: vitality and mental health. The VAS and the CESS showed that snoring intensity and EDS decreased significantly, respectively. No major complications occurred. Conclusions • Tui na is a feasible and safe treatment for patients with OSAHS. It can improve the quality of life, sleep architecture, snoring intensity, and EDS in patients with moderate-to-severe OSAHS. In the future, a controlled study should be considered to further investigate the effects of tui na for OSAHS.

A new method for real-time evaluation of pepsin digestion of paraffin-embedded tissue sections, prior to fluorescence in situ hybridisation.

Fluorescence in situ hybridisation (FISH) is a molecular cytogenetic technique, which is regularly applied to formalin-fixed paraffin-embedded (FFPE) tissue sections of a variety of cancers to assess chromosomal aberrations. However, high-quality FISH requires optimal enzymatic digestion, and insufficient digestion is not noted until the hybridisation signals are evaluated in the fluorescence microscope. As a consequence, FISH results may be unreliable, and the experiment might have to be repeated. To solve this problem, we developed a new method for real-time evaluation of enzymatic tissue digestion. Termination of enzyme activity at the proper time facilitates successful hybridisation, and experiments do not have to be repeated. We first performed FISH on 20 FFPE samples, which had been pepsin digested for different times, and this revealed distinct morphological changes within the nucleus and perinuclear space that were detectable by light microscopy. These observations suggested that the presence of intact and clear bare nuclei, surrounded by a translucent perinuclear space, might serve as an indicator of adequate digestion. We developed a protocol for assessment of this indicator, based on morphological features, and applied this to a collection of 400 tissue samples, partly of breast cancer and partly of different types of lymphoma, prior to FISH. The FISH success rate was 99.5% (398/400), which was significantly higher than that of the conventional method. In all successful cases, morphological signs of adequate digestion were paralleled by easily interpretable FISH signals. This new method for the real-time assessment of digestion quality improved the success rate of FISH and in addition was simple and rapid.

Davallia bilabiata exhibits anti-angiogenic effect with modified MMP-2/TIMP-2 secretion and inhibited VEGF ligand/receptors expression in vascular endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Davallia bilabiata Hosokawa (D. bilabiata), also called GuSuiBu, is popularly used as a substitute for Drynaria fortunei J. Sm for rheumatoid and degenerative arthritis in traditional Chinese medicine. Little is known about the underlying mechanisms of anti-angiogenesis responsible for arthritis in D. bilabiata which needs to be elucidated. AIM OF THE STUDY: The present study is intended to investigate the anti-angiogenic effect of D. bilabiata associated with the modulation of matrix metalloproteinases (MMPs) and down regulation of vascular endothelial growth factor (VEGF) ligand/receptors both in vivo and in vitro. MATERIALS AND METHODS: We investigated the potential anti-angiogenic effect of D. bilabiata by the in vivo neovascularization of chick chorioallantoic membranes (CAM) assay, and the in vitro migration and matrix-induced tube formation assay using human umbilical vascular endothelial cells (HUVECs). The expressions of MMP-2, TIMP-2, RECK and VEGF/VEGFR were analyzed by real-time RT-PCR or Western blot method. RESULTS: One major compound from water extract of D. bilabiata was identified as Epicatechin 3-O-ß-D-allopyranoside. D. bilabiata was confirmed to inhibit in vivo angiogenesis by CAM assay. D. bilabiata also exhibited in vitro anti-angiogenic and anti-regrowth effects as demonstrated by tube formation assay, transwell migration assay and wound healing assay. The mRNA expressions of MMP-2, and MMP-14 were decreased. On the contrary, tissue inhibitor of metalloproteinase-2 (TIMP-2), reversion-inducing cysteine-rich protein with kazal motifs (RECK) were increased by D. bilabiata. The extracellular MMP-2 activity was found to be reduced both in vitro and in vivo by D. bilabiata as determined by gelatin zymography. Results from western blot analysis and ELISA further demonstrated the decrease of MMP-2 and increase of TIMP-2 secretion after D. bilabiata treatment. The gene expressions of VEGF-A, -B, -C, -D and VEGFR-1, -2, -3 were all inhibited by D. bilabiata. CONCLUSION: We concluded that the anti-angiogenic effect of D. bilabiata was associated with the decreased MMP-2 activity mediated by the upregulation of TIMP-2 and RECK, and the suppression of VEGF/VEGFRs expression.

Oral Vaccination with Attenuated Salmonella typhimurium-Delivered TsPmy DNA Vaccine Elicits Protective Immunity against Trichinella spiralis in BALB/c Mice.

BACKGROUND: Our previous studies showed that Trichinella spiralis paramyosin (TsPmy) is an immunomodulatory protein that inhibits complement C1q and C8/C9 to evade host complement attack. Vaccination with recombinant TsPmy protein induced protective immunity against T. spiralis larval challenge. Due to the difficulty in producing TsPmy as a soluble recombinant protein, we prepared a DNA vaccine as an alternative approach in order to elicit a robust immunity against Trichinella infection. METHODS AND FINDINGS: The full-length TsPmy coding DNA was cloned into the eukaryotic expression plasmid pVAX1, and the recombinant pVAX1/TsPmy was transformed into attenuated Salmonella typhimurium strain SL7207. Oral vaccination of mice with this attenuated Salmonella-delivered TsPmy DNA vaccine elicited a significant mucosal sIgA response in the intestine and a systemic IgG antibody response with IgG2a as the predominant subclass. Cytokine analysis also showed a significant increase in the Th1 (IFN-γ, IL-2) and Th2 (IL-4, 5, 6, 10) responses in lymphocytes from the spleen and MLNs of immunized mice upon stimulation with TsPmy protein. The expression of the homing receptors CCR9/CCR10 on antibody secreting B cells may be related to the translocation of IgA-secreted B cells to local intestinal mucosa. The mice immunized with Salmonella-delivered TsPmy DNA vaccine produced a significant 44.8% reduction in adult worm and a 46.6% reduction in muscle larvae after challenge with T. spiralis larvae. CONCLUSION: Our results demonstrated that oral vaccination with TsPmy DNA delivered by live attenuated S. typhimurium elicited a significant local IgA response and a mixed Th1/Th2 immune response that elicited a significant protection against T. spiralis infection in mice.

The Anti-Atherosclerotic Effect of Naringin Is Associated with Reduced Expressions of Cell Adhesion Molecules and Chemokines through NF-κB Pathway.

Naringin has been reported to have an anti-atherosclerosis effect but the underlying mechanism is not fully understood. The aim of this study is to investigate the impact of naringin on the TNF-α-induced expressions of cell adhesion molecules, chemokines and NF-κB signaling pathway in human umbilical vein endothelial cells (HUVECs). The experiments revealed that naringin, at concentrations without cytotoxicity, dose-dependently inhibited the adhesion of THP-1 monocytes to the TNF-α-stimulated HUVECs. The TNF-α-induced expressions of cell adhesion molecules, including VCAM-1, ICAM-1 and E-selectin, at both the mRNA and protein levels, were significantly suppressed by naringin in a dose dependent manner. In addition, the TNF-α-induced mRNA and protein levels of chemokines, including fractalkine/CX3CL1, MCP-1 and RANTES, were also reduced by naringin. Naringin significantly inhibited TNF-α-induced nuclear translocation of NF-κB, which resulted from the inhibited phosphorylation of IKKα/ß, IκB-α and NF-κB. Altogether, we proposed that naringin modulated TNF-α-induced expressions of cell adhesion molecules and chemokines through the inhibition of TNF-α-induced activation of IKK/NF-κB signaling pathway to exert the anti-atherosclerotic effect.

Partially Protective Immunity Induced by a 20 kDa Protein Secreted by Trichinella spiralis Stichocytes.

BACKGROUND: Trichinella spiralis infection induces protective immunity against re-infection in animal models. Identification of the antigens eliciting acquired immunity during infection is important for vaccine development against Trichinella infection and immunodiagnosis. METHODS AND FINDINGS: The T. spiralis adult cDNA library was immunoscreened with sera from pigs experimentally infected with 20,000 infective T. spiralis larvae. Total 43 positive clones encoding for 28 proteins were identified; one of the immunodominant proteins was 20 kDa Ts-ES-1 secreted by Trichinella stichocytes and existing in the excretory/secretory (ES) products of T. spiralis adult and muscle larval worms. Ts-ES-1 contains 172 amino acids with a typical signal peptide in the first 20 amino acids. The expression of Ts-ES-1 was detected in both the adult and muscle larval stages at the mRNA and protein expression levels. Mice immunized with recombinant Ts-ES-1 (rTs-ES-1) formulated with ISA50v2 adjuvant exhibited a significant worm reduction in both the adult worm (27%) and muscle larvae burden (42.1%) after a challenge with T. spiralis compared to the adjuvant control group (p<0.01). The rTs-ES-1-induced protection was associated with a high level of specific anti-Ts-ES-1 IgG antibodies and a Th1/Th2 mixed immune response. CONCLUSION: The newly identified rTs-ES-1 is an immunodominant protein secreted by Trichinella stichocytes during natural infection and enables to the induction of partial protective immunity in vaccinated mice against Trichinella infection. Therefore, rTs-ES-1 is a potential candidate for vaccine development against trichinellosis.

Protective effect of a prime-boost strategy with the Ts87 vaccine against Trichinella spiralis infection in mice.

Trichinellosis is a widespread zoonosis primarily caused by Trichinella spiralis. Mucosal immunity is crucial for preventing Trichinella spiralis infection. In our previous study, a DNA vaccine with the Trichinella antigen Ts87 delivered by an attenuated Salmonella typhimurium elicited partial protection against Trichinella spiralis infection in mice. In the current study, to elicit a more robust immune response and develop a potent vaccination strategy against trichinellosis, a heterologous prime-boost vaccination regimen for Ts87 was used in mice and the protective efficacy was evaluated compared to the homologous DNA prime-boost or protein prime-boost immunization alone. The results revealed that the DNA-prime/protein-boost vaccination with Ts87 induced higher levels of both humoral and cellular immune responses. The challenge results showed that mice with the DNA-prime/protein-boost vaccination displayed higher muscle larval reduction than those immunized with DNA prime-boost or protein prime-boost. The results demonstrated that mice vaccinated with Ts87 in a DNA-prime/protein-boost strategy effectively elicited a local IgA response and mixed Th1/Th2 immune response that might be responsible for improved protection against Trichinella spiralis infection.

Phyllanthus urinaria induces mitochondrial dysfunction in human osteosarcoma 143B cells associated with modulation of mitochondrial fission/fusion proteins.

Phyllanthus urinaria (P. urinaria), a widely used herbal medicine, has been reported to possess various biological characteristics including anti-inflammation, anti-virus, anti-bacteria, anti-hepatotoxicity and anti-cancer. This study provides molecular evidence associated with the dynamics and organization of mitochondria in osteosarcoma 143B cells resulted from P urinaria. Herein, P. urinaria-induced cytotoxicity and ROS associated with the inhibition of mitochondrial membrane potential were reversed by N-acetylcysteine (NAC). The endogenous antioxidant enzymes such as manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX1) were activated by P. urinaria, but not correlated to catalase. P. urinaria decreased mitochondrial respiration activity as well as respiratory chain enzymes and HIF-1α in osteosarcoma 143B cells. Additionally, both adenosine triphosphate (ATP) synthase activation and ATP production were suppressed by P. urinaria. We further investigated changes of mitochondrial dynamic in osteosarcoma 143B cells. P. urinaria indeed fragmented the mitochondrial network of osteosarcoma 143B cells. We found a significant decrease in optic atrophy type 1 (Opa1) and mitofusin 1 (Mfn1) related to fusion proteins as well as increase mitochondrial fission 1 protein (Fis1) related to fission protein. It indicated that P. urinaria modulated the mitochondrial dynamics via fusion and fission machinery. Altogether, this study offers the evidence that mitochondrial dysfunction with dynamic change is essential components for the anti-cancer mechanism elicited by P. urinaria.

The anti-atherosclerotic effect of tanshinone IIA is associated with the inhibition of TNF-α-induced VCAM-1, ICAM-1 and CX3CL1 expression.

Tanshinone IIA is one of the major diterpenes in Salvia miltiorrhiza. The inhibitory effect of Tanshinone IIA on atherosclerosis has been reported, but the underlying mechanism is not fully understood. The present study aimed to study the anti-atherosclerosis effect of Tanshinone IIA on the adhesion of monocytes to vascular endothelial cells and related mechanism. Results showed that Tanshinone IIA, at the concentrations without cytotoxic effect, dose-dependently inhibited the adhesion of THP-1 monocytes to the TNF-α-stimulated human vascular endothelial cells. The expressions of cell adhesion molecules including VCAM-1, ICAM-1 and E-selectin were induced by TNF-α in HUVECs at both the mRNA and protein levels. The mRNA and protein expressions of VCAM-1 and ICAM-1, but not E-selectin, were both significantly suppressed by Tanshinone IIA in a dose dependent manner. In addition, the TNF-α-induced mRNA expression of fractalkine/CX3CL1 and the level of soluble fractalkine were both reduced by Tanshinone IIA. We also found that Tanshinone IIA significantly inhibited TNF-α-induced nuclear translocation of NF-κB which was resulted from the inhibitory effect of Tanshinone IIA on the TNF-α-activated phosphorylation of IKKα, IKKß, IκB and NF-κB. As one of the major components of Salvia miltiorrhiza, Tanshinone IIA alone exerted more potent effect on inhibiting the adhesion of monocytes to vascular endothelial cells when compared with Salvia miltiorrhiza. All together, these results demonstrate a novel underlying mechanism for the anti-inflammatory effect of Tanshinone IIA by modulating TNF-α-induced expression of VCAM-1, ICAM-1 and fractalkine through inhibition of TNF-α-induced activation of IKK/NF-κB signaling pathway in human vascular endothelial cells.