Influence of patient-clinician relationship style on acupuncture outcomes in functional dyspepsia: A multi-site randomized controlled trial in Korea.

INTRODUCTION: Research suggests that a warm and empathic "patient-centered" patient-clinician relationship produces better clinical outcomes when compared with a more neutral "disease-centered" relationship. Acupuncturists performed both styles of therapy for patients with functional dyspepsia in Korea. METHODS: The present randomized controlled trial assigned patients (n = 73) to identical acupuncture treatment with either patient-centered augmented care or disease-centered limited care. The Korean version of the Nepean Dyspepsia Index (NDI-K) was the primary outcome measure. Secondary outcome measures included Consultation And Relational Empathy (CARE) scale. RESULTS: Both groups showed improvement in NDI-K. Patient-centered augmented acupuncture produced less effective symptom improvement compared to disease-centered limited acupuncture (NDI-K sum score and frequency; P = 0.008 and P = 0.037 respectively). CARE scores were higher for the augmented versus limited group (P = 0.001), supporting the fidelity of the experimentally controlled patient/clinician relationship. There were no significant differences between the groups in any of other secondary outcomes. CONCLUSION: Patients demonstrated greater improvement following acupuncture conducted with a more neutral, "disease-centered" style of relationship. This result is counter to similar research conducted in Western countries and suggests that cultural factors can significantly shape optimum styles of acupuncture therapy. PRACTICE IMPLICATIONS: Clinicians should consider cultural differences when applying acupuncture therapy.

Ligand-based magnetic extraction and safety assessment of zinc oxide nanoparticles in food products.

Zinc oxide (ZnO) is a zinc supplement widely used in health products and is approved by the FDA as Generally Regarded as Safe (GRAS). However, concerns have arisen regarding the potential health effects of nanoscale ZnO, as its reactivity differs from that of its bulk form. This has led to the need for an efficient method to extract ZnO from food products without altering its physicochemical properties, where conventional methods have proven to be inadequate. This study introduces an innovative approach using starch magnetic particles (SMPs) functionalized with a 12-amino acid peptide modified with five lysines (ZBP), that has specific affinity to ZnO. ZBP@SMPs effectively and rapidly extract intact ZnO from food products, achieving recovery efficiencies ranging from 60% to 90%, all while maintaining its morphology and crystallinity. The diameter of ZnO particles recovered from six commercial food products ranged from 25 to 500 nm, with 33% falling below 100 nm, highlighting the need for a size-dependent toxicity study. However, cytotoxicity assessment on human intestinal Caco-2 cells shows all ZnO samples affects cell proliferation and membrane integrity in a dose-dependent manner due to partial dissolution. This study contributes to understanding the safety of ZnO-containing food products and highlights potential health implications associated with their consumption.

Anti-Cancer Effects of a New Herbal Medicine PSY by Inhibiting the STAT3 Signaling Pathway in Colorectal Cancer Cells and Its Phytochemical Analysis.

Colorectal cancer (CRC) is an inflammation-associated common cancer worldwide. Paejang-san and Mori Cortex Radicis have been traditionally used for treating intestinal inflammatory diseases in Korea and China. In the present study, we developed a new herbal formula as an alternative to CRC treatments, which is composed of two main components of Paejangsan (Patriniae Radix (Paejang in Korean) and Coix Seed (Yiyiin in Korean)), and Mori Cortex Radicis (Sangbekpi in Korean) based on the addition and subtraction theory in traditional medicine, hence the name PSY, and explored the potential therapeutic effects of the new formula PSY in human CRC cells by analyzing viability, cell cycle and apoptosis. We found that PSY ethanol extract (EtOH-Ex), but not water extract, significantly suppressed the viability of human CRC cells, and synergistically decreased the cell proliferation compared to each treatment of Patriniae Radix and Coix Seed extract (PY) or Mori Cortex Radicis extract (S), suggesting the combination of PY and S in a 10-to-3 ratio for the formula PSY. PSY EtOH-Ex in the combination ratio reduced cell viability but induced cell cycle arrest at the G2/M and sub-G1 phases as well as apoptosis in CRC cells. In addition, the experimental results of Western blotting, immunofluorescence staining and reporter assays showed that PSY also inhibited STAT3 by reducing its phosphorylation and nuclear localization, which resulted in lowering STAT3-mediated transcriptional activation. In addition, PSY regulated upstream signaling molecules of STAT3 by inactivating JAK2 and Src and increasing SHP1. Moreover, the chemical profiles of PSY from UPLC-ESI-QTOF MS/MS analysis revealed 38 phytochemicals, including seven organic acids, eight iridoids, two lignans, twelve prenylflavonoids, eight fatty acids, and one carbohydrate. Furthermore, 21 potentially bioactive compounds were highly enriched in the PSY EtOH-Ex compared to the water extract. Together, these results indicate that PSY suppresses the proliferation of CRC cells by inhibiting the STAT3 signaling pathway, suggesting PSY as a potential therapeutic agent for treating CRC and 21 EtOH-Ex-enriched phytochemicals as anti-cancer drug candidates which may act by inhibiting STAT3.

Effect of multimodal intervention care on cachexia in patients with advanced cancer compared to conventional management (MIRACLE): an open-label, parallel, randomized, phase 2 trial.

BACKGROUND: Cancer cachexia (CC) is a multifactorial process characterized by progressive weight loss, muscle mass, and fat tissue wasting, which adversely affects the quality of life and survival of patients with advanced stages of cancer. CC has a complex and multifactorial pathophysiology, and there is no established standard treatment. Therefore, it is often irreversible and a single treatment modality is unlikely to suppress its progression. We are conducting a randomized trial to investigate the efficacy and safety of a multimodal intervention compared to the best supportive care for patients who received palliative chemotherapy. METHODS: Patients with lung or gastrointestinal cancers undergoing palliative chemotherapy are eligible. Patients are randomized into a multimodal intervention care (MIC) arm versus a conventional palliative care (CPC) arm. MIC includes ibuprofen, omega-3-fatty acid, oral nutritional supplement, weekly physical, psychiatric assessment, nutritional counseling, and complementary and alternative medicine. CPC includes basic nutritional counseling and megestrol acetate as needed (i.e., anorexia ≥ grade 2). All interventions are performed for 12 weeks per subject. The co-primary outcomes are change (kg) in total lean body mass and handgrip strength (kg) from the baseline. A total of 112 patients will be assigned to the two arms (56 in each group). DISCUSSION: The purpose of this study is to evaluate the effect of MIC in preventing or alleviating CC in patients who underwent palliative chemotherapy. As there is no established single treatment for CC, it is expected that the results of this clinical trial will provide new insights to significantly improve the quality of life of patients with cancer. Considering the complex mechanisms of cachexia, the effect of MIC rather than a single specific drug is more promising. In this study, we did not overly restrict the type of cancer or chemotherapy. Therefore, we attempted to measure the effects of complex interventions while preserving clinical situations. Thus, it is expected that the results of this study can be applied effectively to real-world practice. TRIAL REGISTRATION: This clinical trial was registered in the Clinical Research Information Service (KCT0004967), Korean Clinical Trial Registry on April 27, 2020, and ClinicalTrial.gov (NCT04907864) on June 1, 2021.

Assessment of metabolic risks for non-communicable diseases using Sasang constitution: a protocol for a systematic review and meta-analysis.

BACKGROUND: Sasang constitutional medicine (SCM), which categorizes humans into four Sasang types according to their constitution-specific characteristics, has been identified as being useful in predicting metabolic risks and preventing non-communicable diseases (NCDs). However, no systematic review has evaluated this relationship previously. This study protocol describes a method for evaluating the association between Sasang constitution and the metabolic risk factors for NCDs. METHODS: The following nine academic databases will be used as data sources for entries: Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Web of Science, and six Korean databases. All cohort, case-control, and cross-sectional studies that were published by December 2021 and could explain the association between Sasang constitution and metabolic risk factors for NCDs will be considered eligible. Two independent researchers will select studies, extract data, assess quality of studies, and qualitatively evaluate clinical evidence, subsequently. The quality assessment will be evaluated using the Newcastle-Ottawa Scale, with modifications if necessary. Quantitative data will be synthesized as a random-effects model, if applicable. The strength of clinical evidence will be performed applying the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) or GRADE-Confidence in Evidence from Reviews of Qualitative research approach. DISCUSSION: This study will contribute to helping clinicians and health authorities detect any relevant metabolic risks that patients may have, based on systematic clinical evidence. TRIAL REGISTRATION: Review Registry Unique Identifying Number: reviewregistry1213.

Effect of Acupuncture on Delayed Emesis for the Patients Who Received High-Emetogenic Chemotherapy with Standard Antiemetic Prophylaxis (KHMC-HO-01): An Open-Label, Randomized Study.

Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most important issues associated with chemotherapy. The additional or synergistic effect of acupuncture on CINV remains controversial. Methods: Patients were randomized into either the group that received standard antiemetics with acupuncture (Arm A) or standard antiemetics only (Arm C). Acupuncture with manual stimulation was applied at eight predefined points and was started before the first cycle of chemotherapy on the first day and two additional sessions were administered on the second day of chemotherapy. Acute and delayed CINV was assessed using the Rhodes Index of Nausea, Vomiting, and Retching (RINVR) and the MASCC Antiemesis Tool (MAT). The primary outcome was the delayed nausea score assessed using the RINVR. Results: Overall, 42 patients were included. In the delay phase, the severity of delayed nausea was slightly lower without significance in Arm A than in Arm C (5.35 vs. 5.98, p = 0.3011). Similarly, patients in Arm A reported less severe vomiting than those in Arm C (0.75 vs. 1.25, p = 0.3064). Delayed nausea and vomiting assessed by the MAT showed significant relief with acupuncture compared to standard antiemesis alone. In terms of acute emesis, there was no significant difference between the two arms according to either scoring method. Conclusions: Delayed nausea after HEC tended to decrease with acupuncture using the RINVR score, though it was also not significant. With the MAT assessment, delayed emesis (nausea and vomiting) was significantly improved with acupuncture, suggesting a promising effect of acupuncture. This trial is registered with KCT0006477.

Could nutrient supplements provide additional glycemic control in diabetes management? A systematic review and meta-analysis of randomized controlled trials of as an add-on nutritional supplementation therapy.

This systematic review and meta-analysis assessed the antidiabetic effect of pharmaconutrients as an add-on in type 2 diabetes mellitus patients by pooling data from currently available randomized controlled trials (RCTs). Data sources included the PubMed and EMBASE, Cochrane Central Register of Controlled Trials. RCTs reporting changes in glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), or homeostasis model assessment of insulin resistance (HOMA-IR) levels following add-on pharmaconutritional therapies for T2DM patients consuming antidiabetic drugs were targeted. Using random-effects meta-analyses, we identified pharmaconutrients with effects on glycemic outcomes. Heterogeneity among studies was presented using I2 values. Among 9537 articles, 119 RCTs with nine pharmaconutrients (chromium; coenzyme Q10; omega-3 fatty acids; vitamins C, D, and E; alpha-lipoic acid; selenium; and zinc) were included. Chromium (HbA1c, FBG, and HOMA-IR), coenzyme Q10 (HbA1c and FBG), vitamin C (HbA1c and FBG), and vitamin E (HbA1c and HOMA-IR) significantly improved glycemic control. Baseline HbA1c level and study duration influenced the effects of chromium and vitamin E on HbA1c level. Sensitivity analyses did not modify the pooled effects of pharmaconutrients on glycemic control. Administration of chromium, coenzyme Q10, and vitamins C and E for T2DM significantly improved glycemic control. This study has been registered in PROSPERO (CRD42018115229).

Mapping thalamocortical functional connectivity with large-scale brain networks in patients with first-episode psychosis.

Abnormal thalamocortical networks involving specific thalamic nuclei have been implicated in schizophrenia pathophysiology. While comparable topography of anatomical and functional connectivity abnormalities has been reported in patients across illness stages, previous functional studies have been confined to anatomical pathways of thalamocortical networks. To address this issue, we incorporated large-scale brain network dynamics into examining thalamocortical functional connectivity. Forty patients with first-episode psychosis and forty healthy controls underwent T1-weighted and resting-state functional magnetic resonance imaging. Independent component analysis of voxelwise thalamic functional connectivity maps parcellated the cortex into thalamus-related networks, and thalamic subdivisions associated with these networks were delineated. Functional connectivity of (1) networks with the thalamus and (2) thalamic subdivision seeds were examined. In patients, functional connectivity of the salience network with the thalamus was decreased and localized to the ventrolateral (VL) and ventroposterior (VP) thalamus, while that of a network comprising the cerebellum, temporal and parietal regions was increased and localized to the mediodorsal (MD) thalamus. In patients, thalamic subdivision encompassing the VL and VP thalamus demonstrated hypoconnectivity and that encompassing the MD and pulvinar regions demonstrated hyperconnectivity. Our results extend the implications of disrupted thalamocortical networks involving specific thalamic nuclei to dysfunctional large-scale brain network dynamics in schizophrenia pathophysiology.

Comparison of the Efficacy and Safety of Atorvastatin 40 mg/ω-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Randomized, Double-blind Phase III Study.

PURPOSE: Residual cardiovascular risk in patients with hypertriglyceridemia, despite optimal low-density lipoprotein cholesterol levels being achieved with intensive statin treatment, is a global health issue. The purpose of this study was to investigate the efficacy and tolerability of treatment with a combination of high-dose atorvastatin/Ω-3 fatty acid compared to atorvastatin + placebo in patients with hypertriglyceridemia who did not respond to statin treatment. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, patients who had residual hypertriglyceridemia after a 4-week run-in period of atorvastatin treatment were randomly assigned to receive UI-018 (fixed-dose combination atorvastatin/Ω-3 fatty acid 40 mg/4 g) or atorvastatin 40 mg + placebo (control). The primary efficacy end points were the percentage change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) level at the end of treatment and the adverse events recorded during treatment. A secondary end point was the percentage change from baseline in triglyceride level. FINDINGS: After 8 weeks of treatment, the percentage changes from baseline in non-HDL-C (-4.4% vs +0.6%; p = 0.02) and triglycerides (-18.5% vs +0.9%; p < 0.01) were significantly greater in the UI-018 group (n = 101) than in the control group (n = 99). These changes were present in subgroups of advanced age (≥65 years), status (body mass index ≥25 kg/m2), or without diabetes. The prevalences of adverse events did not differ between the 2 treatment groups. IMPLICATIONS: In patients with residual hypertriglyceridemia despite receiving statin treatment, a combination of high-dose atorvastatin/Ω-3 fatty acid was associated with a greater reduction of triglyceride and non-HDL-C compared with atorvastatin + placebo, without significant adverse events.

Intact thalamic microstructure in asymptomatic relatives of schizophrenia patients with high genetic loading.

BACKGROUND: Disrupted thalamic connectivity system, which encompasses the deficits in the thalamus and thalamocortical connectivity, is regarded to contribute to the pathophysiology of schizophrenia. Recent reports suggest the possible genetic contribution to the disrupted thalamo-prefrontal connectivity, however, research on elucidating thalamic connectivity system components, specifically the thalamic nuclei, associated with the genetic predisposition to schizophrenia has been limited. Here, we investigated the genetic aspects of thalamic nuclei-specific microstructural integrities in schizophrenia. METHODS: A total of 34 asymptomatic relatives of schizophrenia patients with high genetic loading and 33 healthy control subjects underwent diffusion tensor imaging, diffusion kurtosis imaging, and T1-weighted magnetic resonance imaging. The thalamus was segmented via a connectivity-based segmentation method using the region-of-interest masks. The microstructural integrity of each thalamic nucleus, measured by averages of the diffusion kurtosis values, was then compared between the groups. RESULTS: The volumetric and mean kurtosis values of the thalamic nuclei were intact in asymptomatic relatives of schizophrenia patients with high genetic loading. CONCLUSIONS: Our results revealed that, in the thalamic connectivity system, the genetics may hold different weights of effects on different components, and that more is given on the thalamo-prefrontal connectivity than on the thalamus. Further, the current results may add further evidence to the current literature that thalamic nuclei microstructural abnormalities present in psychosis may have state marker characteristics.

Rectal perforations caused by cleansing enemas in chronically constipated patients: Two case reports.

Constipation is a common disease that is frequently treated with cleansing enemas. Enemas are considered as effective and in some cases may cause serious adverse events. Iatrogenic perforations due to enemas lead to adverse outcomes in elderly patients with a poor general condition. Perforation remains an infrequent and rarely reported complication. In this work, we describe the cases of two patients with rectal perforation caused by a cleansing enema. The first patient had rectal perforation that led to a para-rectal abscess and the second patient had generalized peritonitis caused by rectal perforation.

Inhibitory effects of Cheongsangbangpoong-tang on both inflammatory acne lesion and facial heat in patients with acne vulgaris: A double-blinded randomized controlled trial.

OBJECTIVES: To investigate the inhibitory effects of an herbal formulation of Cheongsangbangpoong-tang (CBT) on inflammatory acne lesions as the control of the 'Heat' pattern. DESIGN: A single center study. Randomized, placebo-controlled, parallel group, double-blind trial SETTING: Fifty-six subjects, who had more than 10 acne inflammatory lesions each, were randomly allocated into the CBT or placebo groups and took 5 g CBT extract (CBT group) or 5 g placebo extract (control group), respectively, three times a day for 8 weeks. Pattern identification, change of the inflammatory and non-inflammatory acne lesions, temperature of the facial points, serum cortisol level, serum dehydroepiandrosterone-sulfate level, number rating scale, investigator global assessment (IGA), and severity score on the Korean acne grading system were measured. MAIN OUTCOME MEASURE: mean change of the inflammatory acne lesions. RESULTS: After CBT/placebo administration, the percentage count of inflammatory lesions in subjects was significantly reduced in the CBT group when compared with the control group. The other outcomes showed no significant difference between the two groups. On pattern identification, subjects with the Wind-Heat pattern (, WHP) and Disharmony of the thoroughfare and conception vessels pattern (, DTCVP) tended show better effect than those with other patterns. CONCLUSIONS: CBT is a potential therapeutic agent for the treatment of acne vulgaris, linked to inhibition of inflammatory lesions and facial heat. TRIAL REGISTRATION: CRiS (Clinical Research Information Service, Republic of Korea), KCT0001468. Registered 06 May 2015.

Disturbed thalamocortical connectivity in unaffected relatives of schizophrenia patients with a high genetic loading.

OBJECTIVES: Alterations in thalamocortical anatomical connectivity, specifically the connection between the orbitofrontal cortex and thalamus, have been frequently reported in schizophrenia and are suggested to contribute to the pathophysiology of schizophrenia. The connectivity of the thalamocortical white matter in unaffected relatives of schizophrenia patients was compared to that of healthy controls. METHODS: The unaffected relative group was defined as asymptomatic family members who had at least one first-degree relative with schizophrenia and one or more other affected first- to third-degree relatives. A total of 35 unaffected relatives and 34 healthy controls underwent diffusion-weighted and T1-weighted magnetic resonance imaging to examine the white matter connectivity between the thalamus and orbitofrontal cortex using probabilistic tractography. RESULTS: After controlling for age and sex, the unaffected relatives exhibited significantly reduced fractional anisotropy values for the left thalamo-orbitofrontal tract compared to that of healthy controls, F(1, 65) = 6.93, p = 0.011, effect size partial η2 = 0.10. However, there was no association between the Genetic Liability Score and fractional anisotropy in the left thalamo-orbitofrontal tracts. CONCLUSION: Our findings in the unaffected relatives of schizophrenia patients, which are in line with the alterations reported in schizophrenia, first-episode psychosis and clinical high risk for psychosis, highlight a possible genetic contribution to the proposed biomarker of altered thalamocortical connectivity.

Arctiin is a pharmacological inhibitor of STAT3 phosphorylation at tyrosine 705 residue and potentiates bortezomib-induced apoptotic and anti-angiogenic effects in human multiple myeloma cells.

BACKGROUND: Arctiin is a main component from the fruits of Arctium lappa L., that can be prescribed for cold or flu in East Asian countries; it has also been found to exert chemopreventive actions against various tumor cells. HYPOTHESIS: In view of this evidence, we examined arctiin for its ability to trigger apoptosis and inhibit the activation of signal transducer and activator of transcription 3 (STAT3) in human multiple myeloma (MM) cells. METHODS: We evaluated the effect of arctiin on STAT3 signaling cascades and its regulated functional responses in MM cells. RESULTS: Arctiin effectively blocked the constitutive activation of STAT3 phosphorylation in the residue of tyrosine 705. Arctiin also abrogated the constitutive activation of Src phosphorylation and Janus-activated kinases (JAKs) 1/2. Furthermore, it was found that arctiin treatment clearly enhanced the mRNA and protein levels of protein tyrosine phosphatase ε (PTPε), and the silencing of PTPε caused a reversal of the arctiin-induced PTPε expression and the blockadge of STAT3 phosphorylation. Interestingly, arctiin could not repress IL-6-induced STAT3 activation in serum-starved U266 cells and when arctiin was incubated with a complete culture medium in RPMI 8226 and MM.1S cells. Arctiin suppressed cell proliferation, accumulated cells in the G2/M cell-cycle phase, and induced apoptosis within U266 cells, although the knockdown of PTPε prevented PARP cleavage and caspase-3 activation induced by the arctiin. In addition, arctiin exerted cytotoxicity in MM cells, but did not do so in peripheral blood mononuclear cells. Arctiin down-modulated diverse oncogenic gene products regulated by STAT3, although the induction of apoptosis by arctiin was abrogated upon transfection with pMXs-STAT3C in mouse embryonic fibroblast (MEF) cells. Arctiin also potentiated bortezomib-induced antitumor effects in U266 cells. CONCLUSION: On the whole, our results indicate that arctiin is a potentially new inhibitor of constitutive STAT3 activation through the induction of PTPε in MM, cells and therefore has great value in treating various tumors sheltering constitutively activated STAT3.

Development of in vitro three-dimensional co-culture system for metabolic syndrome therapeutic agents.

AIMS: There are many obstacles to overcome in the development of new drugs for metabolic diseases, including efficacy and toxicity problems in later stages of drug development. To overcome these problems and predict efficacy and toxicity in early stages, we constructed a new model of insulin resistance in terms of communication between 3T3-L1 adipocytes and RAW264.7 macrophages by three-dimensional (3D) culture. RESULTS: In this study, results focused on the functional resemblance between 3D co-culture of adipocytes and macrophages and adipose tissue in diabetic mice. The 3D mono-culture preadipocytes showed good cell viability and induced cell differentiation to adipocytes, without cell confluence or cell-cell contact and interaction. The 3D co-cultured preadipocytes with RAW264.7 macrophages induced greater insulin resistance than two-dimensional and 3D mono-cultured adipocytes. Additionally, we demonstrated that 3D co-culture model had functional metabolic similarity to adipose tissue in diabetic mice. We utilized this 3D co-culture system to screen PPARγ antagonists that might have potential as therapeutic agents for diabetes as demonstrated by an in vivo assay. CONCLUSION: This in vitro 3D co-culture system could serve as a next-generation platform to accelerate the development of therapeutics for metabolic diseases.

Thalamo-cortical system involving higher-order nuclei in patients with first-episode psychosis.

Based on the piling reports of disruptions in the thalamus of patients with schizophrenia, the alteration in the thalamo-cortical system has been regarded as the core pathophysiology. As the thalamus is composed of distinctive nuclei with different cytoarchitecture and cortical connections, nuclei specific investigations have been actively conducted in post-mortem studies. In addition, the importance of early changes has been highlighted, which in turn has led to investigations of the thalamo-cortical system using non-invasive neuroimaging methods. From this perspective, the early structural changes in the thalamo-cortical system, such as the thalamo-cortical connection and nuclei specific microstructural changes (which are coherent with findings from post-mortem methods) will be briefly discussed. The main findings, which are the reduced thalamo-prefrontal connection and reduced microstructural complexity in the higher-order nuclei detected in first-episode psychosis patients, suggest the occurrence of early alterations within and between the communication hub of the brain and cortex. These findings suggest not only directions for further studies for unveiling the thalamo-cortical system related pathophysiology, but also the possibility of using the reduced microstructural complexity in the higher order nucleus as a biomarker for schizophrenia. [BMB Reports 2018; 51(9): 427-428].

Identification and metabolite profiling of alkaloids in aerial parts of Papaver rhoeas by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

Papaver plants can produce diverse bioactive alkaloids. Papaver rhoeas Linnaeus (common poppy or corn poppy) is an annual flowering medicinal plant used for treating cough, sleep disorder, and as a sedative, pain reliever, and food. It contains various powerful alkaloids like rhoeadine, benzylisoquinoline, and proaporphine. To investigate and identify alkaloids in the aerial parts of P. rhoeas, samples were collected at different growth stages and analyzed using liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. A liquid chromatography with mass spectrometry method was developed for the identification and metabolite profiling of alkaloids for P. rhoeas by comparing with Papaver somniferum. Eighteen alkaloids involved in benzylisoquinoline alkaloid biosynthesis were used to optimize the liquid chromatography gradient and mass spectrometry conditions. Fifty-five alkaloids, including protoberberine, benzylisoquinoline, aporphine, benzophenanthridine, and rhoeadine-type alkaloids, were identified authentically or tentatively by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry in samples taken during various growth stages. Rhoeadine alkaloids were observed only in P. rhoeas samples, and codeine and morphine were tentatively identified in P. somniferum. The liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry method can be a powerful tool for the identification of diverse metabolites in the genus Papaver. These results may help understand the biosynthesis of alkaloids in P. rhoeas and evaluate the quality of this plant for possible medicinal applications.

Influence of the patient-practitioner interaction context on acupuncture outcomes in functional dyspepsia: study protocol for a multicenter randomized controlled trial.

BACKGROUND: In the treatment of functional dyspepsia, the placebo effect has been reported to be high, and the influence of the patient-practitioner relationship may be a major component of this effect. The specific and non-specific effects of acupuncture cannot be easily distinguished, and the patient-practitioner relationship may influence the total therapeutic effect in clinical practice. There have been no studies that investigate the influence of patient-practitioner relationship on acupuncture treatment for patients with functional dyspepsia. METHODS: Patients with postprandial distress syndrome, a functional dyspepsia subtype, will be recruited at three hospitals (two in Korea and one in USA) for an international, multi-center, randomized, patient/assessor-blinded, clinical trial. The total anticipated sample size is 88. The participants will be randomly allocated into two groups: an augmented interaction group and a limited interaction group. Acupuncture, with total 12 acupoints, will be performed twice weekly for 4 weeks in both groups. Trained practitioners will provide an "augmented" or "limited" interaction context, as determined by random allocation. The primary outcome measure is the proportion of responders, the proportion of participants who answer "yes" to more than half of the adequate relief questions during the study. Secondary outcome measures include questionnaires for quality of life and symptoms of dyspepsia, and maximum tolerable volume of nutrient drink test. Data will be collected at baseline and following 4 weeks of acupuncture. DISCUSSION: This study will evaluate the influence of the patient-practitioner interaction on clinical effects of acupuncture in patients with functional dyspepsia. TRIAL REGISTRATION: CRIS Identifier: ( KCT0002229 ).

Effects of herbal medicine for dysmenorrhea treatment on accompanied acne vulgaris: a study protocol for a randomized controlled trial.

BACKGROUND: The incidence of preadolescent acne among women is increasing. Acne deteriorates the quality of life; conventional treatment options are limited and have not been effective against acne, particularly acne associated with menstruation. Despite evidence that acne associated with menstruation abnormalities naturally improves when menstruation recovers to normal, there have only been few studies on the effects of dysmenorrhea treatment on acne. Therefore- we designed this study to assess the effects of gyejibokryung-hwan (GBH) and dangguijagyag-san (DJS), which are widely used in dysmenorrhea treatment, on acne associated with menstruation cycle. METHODS: This is a protocol for a randomized, double-blind, parallel-group, placebo-controlled and multicenter trial. One hundred and sixteen participants with dysmenorrhea accompanied by acne vulgaris will be recruited at three centers and randomized into two groups, the herbal treatment group and placebo group. The participants will receive GBH or DJS based on pattern identification or placebo granules thrice daily for 8 weeks, with an 8-week follow up. The primary outcome will be the mean percentage change in the count of inflammatory acne lesions. The secondary outcomes would be based on dysmenorrhea numeric rating scale, verbal multidimensional scoring system for dysmenorrhea, acne numeric rating scale, investigator's static global assessment scale of facial acne vulgaris, and safety testing. Adverse events will also be reported. DISCUSSION: The effects of GBH or DJS used in dysmenorrhea treatment on acne associated with the menstrual cycle will be evaluated. The findings of this trial will provide evidence regarding the effect of herbal medicine in improving acne vulgaris associated with menstruation in women. TRIAL REGISTRATION: Korean Clinical Trial Registry ( http://cris.nih.go.kr ; registration number: KCT0002259). Date of registration: March 10, 2017.

Supercritical Fluid Extraction of Citrus iyo Hort. ex Tanaka Pericarp Inhibits Growth and Induces Apoptosis Through Abrogation of STAT3 Regulated Gene Products in Human Prostate Cancer Xenograft Mouse Model.

Activation of signal transducer and activator of transcription 3 (STAT3) is well known to play a major role in the cell growth, survival, proliferation, metastasis, and angiogenesis of various cancer cells. Most of the citrus species offer large quantities of phytochemicals that have beneficial effects attributed to their chemical components. Our study was carried out to evaluate the anticancer effects of the pericarp of Iyokan ( Citrus iyo Hort. ex Tanaka), locally known as yeagam in Korea, through modulation of the STAT3 signaling pathway in both tumor cells and a nude mice model. The effect of supercritical extracts of yeagam peel (SEYG) on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was examined. The in vivo effect of SEYG on the growth of DU145 human prostate xenograft tumors in athymic nu/nu male mice was also investigated. We found SEYG exerted substantial inhibitory effect on STAT3 activation in human prostate cancer DU145 cells as compared to other tumor cells analyzed. SEYG inhibited proliferation and downregulated the expression of various STAT3-regulated gene products such as bcl-2, bcl-xL, survivin, IAP-1/2, cyclin D1, cyclin E, COX-2, VEGF, and MMP-9. This correlated with an increase in apoptosis as indicated by an increase in the expression of p53 and p21 proteins, the sub-G1 arrest, and caspase-3-induced PARP cleavage. When administered intraperitoneally, SEYG reduced the growth of DU145 human prostate xenograft tumors through downmodulation of STAT3 activation in athymic nu/nu male mice. Overall, these results suggest that SEYG extract has the potential source of STAT3 inhibitors that may have a potential in chemoprevention of human prostate cancer cells.