Endoplasmic Reticulum (ER) Stress and Unfolded Protein Response (UPR) in Mammalian Oocyte Maturation and Preimplantation Embryo Development.

Mammalian oocytes and early embryos derived from in vitro production are highly susceptible to a variety of cellular stresses. During oocyte maturation and preimplantation embryo development, functional proteins must be folded properly in the endoplasmic reticulum (ER) to maintain oocyte and embryo development. However, some adverse factors negatively impact ER functions and protein synthesis, resulting in the activation of ER stress and unfolded protein response (UPR) signaling pathways. ER stress and UPR signaling have been identified in mammalian oocytes and embryos produced in vitro, suggesting that modulation of ER stress and UPR signaling play very important roles in oocyte maturation and the development of preimplantation embryos. In this review, we briefly describe the current state of knowledge regarding ER stress, UPR signaling pathways, and their roles and mechanisms in mammalian (excluding human) oocyte maturation and preimplantation embryo development.

Effect of oocyte chromatin status in porcine follicles on the embryo development in vitro.

OBJECTIVE: The main goal of this study was to provide a morphological indicator that could be used to select high-quality oocytes of appropriate meiotic and developmental capabilities in pig. The higher quality of immature oocytes, the higher success rates of in vitro maturation (IVM) and in vitro fertilization (IVF). Thus, prior to the IVM culture, it is important to characterize oocytes morphologically and biochemically in order to assess their quality. Two of the largest indicators of oocyte quality are the presence of cumulus cells and status of chromatin. To investigate the effects of porcine oocyte chromatin configurations on the developmental capacity of blastocysts, we assessed oocyte chromatin status according to follicle size and measured the developmental potency of blastocysts. METHODS: To sort by follicle size, we divided the oocytes into three groups (less than 1 mm, 1 to 3 mm, and more than 3 mm in diameter). To assess chromatin configuration, the oocytes were assessed for their stages (surrounded nucleolus [SN] germinal vesicle [GV], non-surrounded nucleolus [NSN] GV, GV breakdown, metaphase I [MI], pro-metaphase II [proMII], and metaphase II [MII]) at different maturation times (22, 44, and 66 h). To assess the development rate, oocytes of each follicle size were subjected to parthenogenetic activation for further development. Finally, GV oocytes were grouped by their chromatin configuration (SN, SN/NSN, and NSN) and their global transcriptional levels were measured. RESULTS: SN GV oocytes were more suitable for IVF than NSN GV oocytes. Moreover, oocytes collected from the larger follicles had a greater distribution of SN GV oocytes and a higher developmental capacity during IVM, reaching MII more quickly and developing more often to blastocysts. CONCLUSION: Porcine oocytes with high-level meiotic and developmental capacity were identified by analyzing the relationship between follicle size and chromatin configuration. The porcine oocytes from large follicles had a significantly higher SN status in which the transcription level was low and could be better in the degree of meiotic progression and developmental capacity.

Liver enzyme abnormalities of inpatients with rheumatic diseases: A 10-year retrospective study in a Korean medicine hospital.

Herbal medicines have been used as a treatment option for rheumatic disease (RD), but they often produce liver enzyme abnormality. This study examines the incidence of herb-induced liver injury (HILI) and the relationship between risk factors and liver enzyme abnormality (LEA) in inpatients with RD. HILI was analyzed using the Roussel Uclaf causality assessment method liver injury criteria and causality assessment. Multivariable analysis was performed to assess the relationship between patient characteristics and LEA in RD. The features of LEA were also examined in each RD. Among 352 patients included in this study, 105 patients showed LEA on admission, of which 6 had fulfilled the Roussel Uclaf causality assessment method criteria. The incidence risks of LEA and HILI were 12.55% and 0.58%, respectively. Multivariable analysis showed that LEA on admission and occasional use of alcohol could be risk factors for LEA on follow-up. In an additional analysis with each RD, all rheumatoid arthritis patients with LEA were taking nonsteroidal anti-inflammatory drugs, steroids, and disease-modifying antirheumatic drugs, and 4 out of 5 gout patients with LEA were taking steroids. The use of herbal medicine in RD is relatively safe. However, regular monitoring of liver enzyme tests and examination of alcohol consumption are required.

Hemodynamic changes caused by acupuncture in healthy volunteers: a prospective, single-arm exploratory clinical study.

BACKGROUND: Radial pressure pulse wave (RPPW) examination has been a key diagnostic component of traditional Chinese medicine. The objective of this study was to investigate the changes in RPPW along with various hemodynamic variables after acupuncture stimulation and to examine the validity of pulse diagnosis as a modern diagnostic tool. METHODS: We conducted acupuncture stimulation at both ST36 acupuncture points in 25 healthy volunteers. We simultaneously assessed the RPPW by pulse tonometry; heart rate variability (HRV) by electrocardiogram; photoplethysmogram (PPG) signals, respiration rate, peripheral blood flow velocity and arterial depth by ultrasonography; and cardiac output by impedance cardiography, before, during and after a session of acupuncture stimulation. RESULTS: We observed consistent patterns of increased spectral energy at low frequency (<10 Hz) and pulse power using RPPW examination and in the amplitude and systolic area of the PPG signal during the entire acupuncture session. The low- and high-frequency domains of HRV increased and decreased, respectively, during the acupuncture session. The peripheral blood velocity rose shortly after needle insertion, reached a maximum in the middle of the session and decreased afterwards. The augmentation index (AIX) and pulse transit time (PTT) obtained from RPPW did not change significantly. CONCLUSION: Acupuncture stimulation at ST36 in healthy subjects increased the peripheral pulse amplitudes (pressure pulse wave (PPW) and PPG), blood flow velocity (ultrasonography) and sympathetic nerve activity (HRV). The lack of changes in the AIX and PTT suggests that the increased pulse amplitudes and blood flow velocity may result from increased cardiac output. TRIAL REGISTRATION: Clinical Research Information Service ( KCT0001663 ).

Acupuncture and related interventions for symptoms of chronic kidney disease.

BACKGROUND: People living with chronic kidney disease (CKD) experience a range of symptoms and often have complex comorbidities. Many pharmacological interventions for people with CKD have known risks of adverse events. Acupuncture is widely used for symptom management in patients with chronic diseases and in other palliative care settings. However, the safety and efficacy of acupuncture for people with CKD remains largely unknown. OBJECTIVES: We aimed to evaluate the benefits and harms of acupuncture, electro-acupuncture, acupressure, moxibustion and other acupuncture-related interventions (alone or combined with other acupuncture-related interventions) for symptoms of CKD. In particular, we planned to compare acupuncture and related interventions with conventional medicine, active non-pharmacological interventions, and routine care for symptoms of CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 28 January 2016 through contact with the Information Specialist using search terms relevant to this review. We also searched Korean medical databases (including Korean Studies Information, DBPIA, Korea Institute of Science and Technology Information, Research Information Centre for Health Database, KoreaMed, the National Assembly Library) and Chinese databases (including the China Academic Journal). SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that investigated the effects of acupuncture and related point-stimulation interventions with or without needle penetration that involved six sessions or more in adults with CKD stage 3 to 5, regardless of the language and type of publication. We excluded studies that used herbal medicine or co-interventions administered unequally among the study groups. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed risk of bias. We calculated the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) for dichotomous outcomes. Primary outcomes were changes in pain and depression, and occurrence of serious of adverse events. MAIN RESULTS: We included 24 studies that involved a total of 1787 participants. Studies reported on various types of acupuncture and related interventions including manual acupuncture and acupressure, ear acupressure, transcutaneous electrical acupuncture point stimulation, far-infrared radiation on acupuncture points and indirect moxibustion. CKD stages included pre-dialysis stage 3 or 4 and end-stage kidney disease on either haemodialysis or peritoneal dialysis.None of the included studies assessed pain outcomes, nor formally addressed occurrence of serious adverse events, although three studies reported three participant deaths and three hospitalisations as reasons for attrition. Three studies reported minor acupuncture-related harms; the remainder did not report if those events occurred.All studies were assessed at high or unclear risk of bias in terms of allocation concealment. Seventeen studies reported outcomes measured for only two months.There was very low quality of evidence that compared with routine care, manual acupressure reduced scores of the Beck Depression Inventory score (scale from 0 to 63) (3 studies, 128 participants: MD -4.29, 95% CI -7.48 to -1.11, I(2) = 0%), the revised Piper Fatigue Scale (scale from 0 to 10) (3 studies, 128 participants: MD -1.19, 95% CI -1.77 to -0.60, I(2) = 0%), and the Pittsburgh Sleep Quality Index (scale from 0 to 21) (4 studies, 180 participants: MD -2.46, 95% CI -4.23 to -0.69, I(2) = 50%).We were unable to perform further meta-analyses because of the paucity of data and problems with clinical heterogeneity, such as different interventions, comparisons and timing of outcome measurements. AUTHORS' CONCLUSIONS: There was very low quality of evidence of the short-term effects of manual acupressure as an adjuvant intervention for fatigue, depression, sleep disturbance and uraemic pruritus in patients undergoing regular haemodialysis. The paucity of evidence indicates that there is little evidence of the effects of other types of acupuncture for other outcomes, including pain, in patients with other stages of CKD. Overall high or unclear risk of bias distorts the validity of the reported benefit of acupuncture and makes the estimated effects uncertain. The incomplete reporting of acupuncture-related harm does not permit us to assess the safety of acupuncture and related interventions. Future studies should investigate the effects and safety of acupuncture for pain and other common symptoms in patients with CKD and those undergoing dialysis.

Lysophosphatidic acid improves porcine oocyte maturation and embryo development in vitro.

Lysophosphatidic acid (LPA), a member of the phospholipid autacoid family, is present in human follicular fluid. The aim of the present study was to compare the developmental competence of porcine embryos created via in vitro fertilization (IVF) and parthenogenetic activation (PA) in culture medium supplemented with LPA, in comparison with a control group. The effects of LPA on porcine oocyte maturation and pre-implantation embryonic development were also examined. Addition of 10 µM LPA to the oocyte maturation medium significantly increased the proportion of oocytes reaching metaphase I (MI) or metaphase II (MII), and enhanced embryonic developmental potential. When present during oocyte maturation, LPA significantly increased the abundance of phosphorylated ERK1/2 in MI and MII oocytes, showing that LPA enhanced nuclear maturation via activation of the mitogen-activated protein kinase (MAPK) pathway. In addition, Cyclin B1 levels were elevated in MI- and MII-stage oocytes, suggesting that LPA plays a role in both nuclear and cytoplasmic maturation of oocytes. After fertilization, the frequency of polyspermy in embryos obtained using LPA-treated oocytes was less than that in the control group. Further, blastocyst formation and blastocyst cell number were enhanced and apoptosis was reduced upon LPA treatment of embryos created either by IVF and PA. LPA treatment of blastocysts derived by IVF or PA resulted in increased expression of the anti-apoptotic BCL2L1 gene while reducing expression of the pro-apoptotic genes BAX and CASP3. Together, our data indicate that LPA supplementation improves porcine oocyte maturation and subsequent in vitro development of pre-implantation embryos.

Effects of sorbitol on porcine oocyte maturation and embryo development in vitro.

In the present study, a porcine system was supplemented with sorbitol during in vitro maturation (IVM) or in vitro culture (IVC), and the effects of sorbitol on oocyte maturation and embryonic development following parthenogenetic activation were assessed. Porcine immature oocytes were treated with different concentrations of sorbitol during IVM, and the resultant metaphase II stage oocytes were activated and cultured in porcine zygote medium-3 (PZM-3) for 7 days. No significant difference was observed in cumulus expansion and the nuclear maturation between the control and sorbitol-treated groups, with the exception of the 100 mM group, which showed significantly decreased nuclear maturation and cumulus expansion. There was no significant difference in the intracellular reactive oxygen species (ROS) levels between oocytes matured with 10 or 20 mM sorbitol and control groups, but 50 and 100 mM groups had significantly higher ROS levels than other groups. The 20 mM group showed significant increases in intracellular glutathione and subsequent blastocyst formation rates following parthenogenetic activation compared with the other groups. During IVC, supplementation with sorbitol significantly reduced blastocyst formation and increased the apoptotic index compared with the control. The apoptotic index of blastocysts from the sorbitol-treated group for entire culture period was significantly higher than those of the partially sorbitol-exposed groups. Based on these findings, it can be concluded that the addition of a low concentration of sorbitol (20 mM) during IVM of porcine oocytes benefits subsequent blastocyst development and improves embryo quality, whereas sorbitol supplement during IVC has a negative effect on blastocyst formation.

The standardized BHH10 extract, a combination of Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, reverses bone mass and metabolism in a rat model of postmenopausal osteoporosis.

Jasin-hwan-gagambang (BHH10), a modified prescription of Jasin-hwan, contains Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, and it has been traditionally used to treat osteoporosis and other inflammatory diseases. In this study, we systematically investigated the protective effects of BHH10 in ovariectomy (OVX)-induced rats. Sprague-Dawley rats were randomly divided into sham and OVX subgroups. The rats in the OVX group were treated with vehicle, BHH10, alendronate (ALN), and 17ß-estradiol (E2). BHH10 treatment significantly inhibited OVX-induced increases in body weight and uterus atrophy. In addition, it significantly increased the bone mineral density (BMD) and prevented a decrease in trabecular bone volume, connectivity density, trabecular number, thickness, and separation at the total femur and femur neck. The OVX rats showed significant decreases in the serum levels of calcium and phosphorous and significant increases in the serum levels of cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, osteocalcin, C-telopeptide type 1 collagen, and bone morphogenetic protein-2. These changes were significantly reduced to near sham levels by administration of BHH10 to OVX rats. BHH10-treated rats had a greater bone mass, a better structural architecture of the bone, and higher levels of biochemical markers of the bone than did the ALN-treated or E2-treated rats. These results suggest that BHH10 reverses osteoporosis in OVX rats by stimulating bone formation or regulating bone resorption and is not associated with toxicity.

Distinct roles of ROCK1 and ROCK2 during development of porcine preimplantation embryos.

Cell-to-cell contact mediated by cell adhesion is fundamental to the compaction process that ensures blastocyst quality during embryonic development. In this study, we first showed that Rho-associated coiled-coil protein kinases (ROCK1 and ROCK2) were expressed both in porcine oocytes and IVF preimplantation embryos, playing different roles in oocytes maturation and embryo development. The amount of mRNA encoding ROCK1 and the protein concentration clearly increased between the eight-cell and morula stages, but decreased significantly when blastocysts were formed. Conversely, ROCK2 was more abundant in the blastocyst compared with other embryonic stages. Moreover, immunostaining showed that ROCK1 protein distribution changed as the embryo progressed through cleavage and compaction to the morula stage. Initially, the protein was predominantly associated with the plasma membrane but later became cytoplasmic. By contrast, ROCK2 protein was localized in both the cytoplasm and the spindle rotation region during oocyte meiosis, but in the cytoplasm and nucleus as the embryo developed. In addition, ROCK2 was present in the trophectoderm cells of the blastocyst. Treatment with 15 µM Y27632, a specific inhibitor of ROCKs, completely blocked further development of early four-cell stage embryos. Moreover, we did not detect the expression of ROCK1 but did detect ROCK2 expression in blastocysts. Moreover, lysophosphatidic acid an activator of ROCKs significantly improved the rates of blastocyst formation. These data demonstrate that ROCKs are required for embryo development to the blastocyst stage. Together, our results indicate that ROCK1 and ROCK2 may exert different biological functions during the regulation of compaction and in ensuring development of porcine preimplantation embryos to the blastocyst stage.

Formononetin attenuates osteoclastogenesis via suppressing the RANKL-induced activation of NF-κB, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 signaling pathway.

Formononetin (1), a plant-derived phytoestrogen, possesses bone protective properties. To address the potential therapeutic efficacy and mechanism of action of 1, we investigated its antiosteoclastogenic activity and its effect on nuclear factor-kappaB ligand (RANKL)-induced bone-marrow-derived macrophages (BMMs). Compound 1 markedly inhibited RANKL-induced osteoclast differentiation in the absence of cytotoxicity, by regulating the expression of osteoprotegerin (OPG) and RANKL in BMMs and in cocultured osteoblasts. Compound 1 significantly inhibited RANKL-induced tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) in a concentration-dependent manner. These effects were accompanied by a decrease in RANKL-induced activation of the NF-κB p65 subunit, degradation of inhibitor κBα (IκBα), induction of NF-κB, and phosphorylation of AKT, extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). NF-κB siRNA suppressed AKT, ERK, JNK, and p38 MAPK phosphorylation. Furthermore, 1 significantly suppressed c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), key transcription factors during osteoclastogenesis. SP600125, a specific inhibitor of JNK, reduced RANKL-induced expression of phospho-c-Jun, c-Fos, and NFATc1 and inhibited osteoclast formation. These results suggested that 1 acted as an antiresorption agent by blocking osteoclast activation.

The effectiveness and safety of moxibustion for treating cancer-related fatigue: a systematic review and meta-analyses.

PURPOSE: Among cancer patients, cancer-related fatigue (CRF) is one of the most common symptoms and adversely affects physical ability and quality of life even several years after treatment. This study aims to evaluate the current evidence for moxibustion in patients with CRF. METHODS: Eighteen databases were searched from their inception to April 2013. All randomized controlled trials (RCTs) of moxibustion for treating CRF without language restriction were considered for inclusion. The risk of bias and reporting quality of each study were assessed using the Cochrane risk of bias tool, Consolidated Standards of Reporting Trials (CONSORT), and Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Risk ratio (RR) or mean difference (MD) was used to measure the treatment effect with 95 % confidence intervals (CIs) in a random effects model. RESULTS: Four RCTs with a total of 374 subjects were included for the review. These four studies compared moxibustion plus routine care with routine care alone. Most studies were determined to have a moderate to high risk of bias with low reporting quality. An indirect moxa stick was used in two studies, an indirect ginger cake-separated moxa was used in one study, and in one remaining study, both moxibustion methods were used. Meta-analysis showed the favorable effects of moxibustion on the response rate (RR, 1.73; 95 % CI, 1.29 to 2.32; p=.0003; heterogeneity, I (2)=15 %, p=.32). Burning with a mild blister after moxibustion was reported in one study. CONCLUSIONS: Because of a high risk of bias and low reporting quality of the studies included in this review, it is difficult to draw the conclusion that moxibustion is an effective and safe treatment for patients with CRF. Further rigorous research will be necessary to evaluate whether moxibustion has beneficial effects on CRF. TRIAL REGISTRATION: PROSPERO. Unique identifier: CRD42013004501.

Acupuncture for treating acute ankle sprains in adults.

BACKGROUND: An acute ankle sprain is a sudden-onset injury of one or more of the ankle ligaments. It is one of the most common musculoskeletal injuries in the general population as well as in athletes. In some countries, such as China and Korea, acupuncture is frequently used in the treatment of ankle sprains, either as a single treatment or a secondary intervention accompanied by standard medical treatment. OBJECTIVES: To assess the effects (benefits and harms) of acupuncture for the treatment of ankle sprains in adults. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (May 2013), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 4), MEDLINE (1948 to May week 2 2013), EMBASE (1980 to May week 2 2013), China National Knowledge Infrastructure databases (1994 to August week 4 2013), the Cumulative Index to Nursing and Allied Health Literature (1937 to May 2013), the Allied and Complementary Medicine Database (1985 to May 2013), Science Links Japan (1996 to August week 4 2013), several Korean medical databases (August week 4 2013), the World Health Organization International Clinical Trials Registry Platform (August week 4 2013), the bibliographic references of included trials and conference proceedings. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials involving adults with acute ankle sprains. We included all types of acupuncture practices, such as needle acupuncture, electroacupuncture, laser acupuncture, pharmacoacupuncture, non-penetrating acupuncture point stimulation (e.g. acupressure and magnets) and moxibustion. Acupuncture could be compared with control (no treatment or placebo) or another standard non-surgical intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed trial eligibility, assessed risk of bias and extracted data from the included trials. We calculated risk ratios (RRs) for dichotomous outcomes and mean differences for continuous outcomes. We conducted meta-analyses using the fixed-effect method or, where appropriate, the random-effects method, and used 95% confidence intervals (CI) throughout. MAIN RESULTS: We included a total of 20 heterogeneous studies (2012 participants with acute ankle sprains); three of which included more than one comparison. Seventeen trials were conducted in China. All of the studies had a high risk of bias due to lack of blinding. The results may also have been affected by selection bias, particularly as five studies were quasi-randomised controlled trials and 12 studies gave no information on their method of randomisation. Of our three prespecified primary outcomes, only cure rate was reported by the majority of studies. No study reported on patient-reported assessment of function and only one reported on adverse events (in which three participants receiving a control intervention experienced skin problems from over-the-counter Chinese herbal patches). The other 19 studies did not record or report on adverse events. We assessed the quality of evidence for cure rates as very low for all comparisons, which means we are very uncertain about the reliability of any of the estimates.The single study comparing acupuncture treatment with no treatment found acupuncture to be more effective with regard to cure rate at five days (31/31 versus 1/30; RR 20.34, 95% CI 4.27 to 96.68). Acupuncture plus another standard treatment versus that standard treatment alone was tested in eight studies; with cure rate data available for seven. Most of these studies reported higher cure rates in the acupuncture plus another standard treatment group than in the standard treatment alone group. However, while the results of an exploratory meta-analysis of cure rate data from eight trials testing acupuncture versus no acupuncture tended to favour acupuncture, the results were very inconsistent across the studies and the estimated effect was very imprecise (383/396 versus 272/355; RR 1.32, 95% CI 0.95 to 1.84; P value = 0.1; I(2) = 98%).Fourteen studies compared acupuncture with a variety of other non-surgical treatments, such as Chinese drug patches, hot and cold water, ice packs, oral Chinese herbal medicine and elastic bandage. Some studies found in favour of acupuncture, some in favour of the other treatment and some found a lack of evidence for a difference between the two interventions under test. The results of an exploratory meta-analysis of cure rate data from 11 trials testing acupuncture versus another non-surgical intervention tended to slightly favour acupuncture, but these were not statistically significant and the data were very heterogeneous (404/509 versus 416/497; RR 1.07, 95% CI 0.94 to 1.22; P value = 0.30; I(2) = 92%). AUTHORS' CONCLUSIONS: The currently available evidence from a very heterogeneous group of randomised and quasi-randomised controlled trials evaluating the effects of acupuncture for the treatment of acute ankle sprains does not provide reliable support for either the effectiveness or safety of acupuncture treatments, alone or in combination with other non-surgical interventions; or in comparison with other non-surgical interventions. Future rigorous randomised clinical trials with larger sample sizes will be necessary to establish robust clinical evidence concerning the effectiveness and safety of acupuncture treatment for acute ankle sprains.

Arginine enhances osteoblastogenesis and inhibits adipogenesis through the regulation of Wnt and NFATc signaling in human mesenchymal stem cells.

Arginine, an α-amino acid, has been reported to exert beneficial effects that ameliorate health problems and prevent excessive fat deposition. In this study, we investigated whether the activation of cell signaling by arginine can induce osteogenic differentiation and modulate excessive adipogenic differentiation in human mesenchymal stem cells (MSCs). Arginine potently induced the expression of type Iα1 collagen, osteocalcin, and ALP in a dose-dependent manner without causing cytotoxicity. Arginine significantly increased the mRNA expression of the osteogenic transcription factors runt-related transcription factor 2 (Runx2), DIx5, and osterix. Furthermore, arginine demonstrated its antiadipogenicity by decreasing adipocyte formation and triglyceride (TG) content in MSCs and inhibiting the mRNA expression of the adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and fatty acid binding protein 4 (Fabp4). This effect was associated with increased expression of Wnt5a, and nuclear factor of activated T-cells (NFATc), and was abrogated by antagonists of Wnt and NFATc, which indicated a role of Wnt and NFATc signaling in the switch from adipogenesis to osteoblastogenesis induced by arginine. In conclusion, this is the first report of the dual action of arginine in promoting osteogenesis and inhibiting adipocyte formation through involving Wnt5a and NFATc signaling pathway.

Firefighters' medical use and Korean Medicine experience in Korea: A qualitative study protocol.

INTRODUCTION: Firefighters, compared to other occupational groups, are exposed more frequently in their working environment not only to physical issues, such as musculoskeletal disease, respiratory disease, and burns but also to mental health issues, such as PTSD and depression. Specifically, Korean firefighters experience significantly higher rates of work-related injuries compared to those in other countries. Recent statistics from the Korea National Fire Agency indicate a steady increase in the number of firefighting work-related injuries. However, there is a shortage of measures in place to address these issues. This study aims to investigate the health needs, overall healthcare usage, and unmet needs of firefighters in Korea. We also aim to investigate, through in-depth interviews, perceptions and hindering factors for integrative medicine approaches to fulfilling unmet needs. METHOD: This study was conducted in accordance with the consolidated criteria for reporting qualitative research. Convenience and snowball sampling methods will be used to recruit firefighters to participate in the study, and interviews will be conducted using a semi-structured interview guide. The data will be analyzed in four stages using the qualitative analysis method of Krippendorff. DISCUSSION: In this study, we examine the state of health issues and healthcare usage among Korean firefighters and investigate their perceptions of and needs for integrative medicine. In this way, we aim to explore how integrative medicine and Korean medicine approaches could improve and assist healthcare services for firefighters. Furthermore, our findings will provide policymakers and healthcare providers with the necessary basic information to develop integrative medicine systems suited to firefighters.

The reporting quality of acupuncture-related traumatic adverse events: a systematic review of case studies in Korea.

BACKGROUND: Acupuncture is known for a harmless treatment when administered by well-trained clinicians. However, multiple case reports of traumatic adverse events (AEs) related to acupuncture treatments continue to be published in literature. In this review, we evaluated the reporting quality and conducted causality assessments of case studies that have reported acupuncture-related traumatic AEs in Korea. METHODS: Eight databases were searched from their inception to January 2024. Only Korean case studies that reported traumatic AEs following acupuncture procedures were included without any language restrictions. Reporting quality was evaluated based on patient characteristics, AEs, and acupuncture practice. Causality was assessed using the modified WHO-UMC causality criteria. RESULTS: Twenty-eight studies were included from a total of 1,154 identified studies. The quality of reporting in the included studies was low overall. While the descriptions of patient characteristics and AEs were relatively well detailed, most information on acupuncture practice was not reported at all. During the causality assessment, only three (10.7%) studies were judged to be "certain". Twelve (42.9%) studies were "unassessable" because they inadequately described the information necessary for decision-making. It was practically difficult to establish the causality between acupuncture and AEs, as well as the appropriateness of acupuncture practice. CONCLUSIONS: Insufficient and inappropriate reporting was observed in most case studies reporting acupuncture-related traumatic AEs in Korea. To overcome these limitations, we have suggested tentative guidelines in the form of a set of items that should be reported by future authors who plan to publish case studies on acupuncture-related traumatic AEs in a clinical setting.

Moxibustion for treating knee osteoarthritis: study protocol of a multicentre randomised controlled trial.

BACKGROUND: The treatment of knee osteoarthritis, which is a major cause of disability among the elderly, is typically selected from multidisciplinary options, including complementary and alternative medicine. Moxibustion has been used in the treatment of knee osteoarthritis in Korea to reduce pain and improve physical activity. However, there is no sufficient evidence of its effectiveness, and it cannot therefore be widely recommended for treating knee osteoarthritis. We designed a randomised controlled clinical trial to evaluate the effectiveness, safety, cost-effectiveness, and qualitative characteristics of moxibustion treatment of knee osteoarthritis compared to usual care. METHODS/DESIGNS: This is a protocol for a multicentre, pragmatic, randomised, assessor-blinded, controlled, parallel-group study. A total of 212 participants will be assigned to the moxibustion group (n = 106) and the usual care group (n = 106) at 4 clinical research centres. The participants assigned to the moxibustion group will receive moxibustion treatment of the affected knee(s) at 6 standard acupuncture points (ST36, ST35, ST34, SP9, Ex-LE04, and SP10) 3 times per week for 4 weeks (a total of 12 sessions). Participants in the usual care group will not receive moxibustion treatment during the study period. Follow-up will be performed on the 5th and 13th weeks after random allocation. Both groups will be allowed to use any type of treatment, including surgery, conventional medication, physical treatment, acupuncture, herbal medicine, over-the-counter drugs, and other active treatments. Educational material that explains knee osteoarthritis, the current management options, and self-exercise will be provided to each group. The global scale of the Korean Western Ontario and McMaster Osteoarthritis Index (K-WOMAC) will be the primary outcome measurement used in this study. Other subscales (pain, stiffness, and function) of the K-WOMAC, the Short-Form 36v2 Health Survey, the Beck Depression Inventory, the Physical Function test, Patient Global Assessment, and the Pain Numerical Rating Scale will be used as outcome variables to evaluate the effectiveness of moxibustion. Safety will be assessed at every visit. In addition, an economic evaluation and a qualitative study will be conducted as a mixed-methods approach. DISCUSSION: This trial may contribute to developing evidence for the effectiveness and safety of moxibustion for treating knee osteoarthritis. TRIAL REGISTRATION NUMBER: KCT0000130.

Anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan from Myristica fragrans.

Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes. The inhibition of platelet function is beneficial for the treatment and prevention of these diseases. In this study, we investigated the anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan (EATN), a neolignan isolated from Myristica fragrans, using human platelets. EATN preferentially inhibited thrombin- and platelet-activating factor (PAF)-induced platelet aggregation without affecting platelet damage in a concentration-dependent manner with IC50 values of 3.2 ± 0.4 and 3.4 ± 0.3 µM, respectively. However, much higher concentrations of EATN were required to inhibit platelet aggregation induced by arachidonic acid. EATN also inhibited thrombin-induced serotonin and ATP release, and thromboxane B2 formation in human platelets. Moreover, EATN caused an increase in cyclic AMP (cAMP) levels and attenuated intracellular Ca(2+) mobilization in thrombin-activated human platelets. Therefore, we conclude that the inhibitory mechanism of EATN on platelet aggregation may increase cAMP levels and subsequently inhibit intracellular Ca(2+) mobilization by interfering with a common signaling pathway rather than by directly inhibiting the binding of thrombin or PAF to their receptors. This is the first report of the anti-platelet activity of EATN isolated from M. fragrans.

Publication status and reporting quality of case reports on acupuncture-related adverse events: A systematic reviews of case studies.

Introduction: Case reports on acupuncture-related adverse events (AEs) have been consistently published in the literature. This review aims to assess the current publication status of case reports on acupuncture-related AEs and evaluate their reporting quality in order to identify areas for improvement. Methods: This study is a systematic review (SR) of case reports. Studies describing cases for acupuncture-related AEs between 2010 and 2023 (until July) were searched in PubMed, Embase, and local databases (China and Korea), as well as by hand-searching references included in published relevant SRs. A bibliometric analysis was conducted to examine the publication trends of the included literature. The appropriateness of the acupuncture described in the cases, the causality assessment between AEs and acupuncture treatment, and the presence of necessary items from the CAse REport guidelines (CARE) checklist were narratively analyzed. Results: A total of 169 case reports were included in this review. Over the past decade, an average of 12 case reports on acupuncture-related AEs were published annually. However, only 38.2% of the articles provided sufficient information to determine the appropriateness of the acupuncture treatment used in the reported cases, and considerable numbers of the included case reports did not suggest enough information for the assessment of a causal relationship. The majority of cases did not report the timeline (n = 164), patient perspectives (n = 157), and informed consent (n = 121) items from the CARE checklist. Discussion: Acupuncture-related AEs persist in being frequently reported in the literature. Nonetheless, the information concerning acupuncture and causality assessment within these publications is still found to be insufficient. The development of reporting guidelines for future case reports on acupuncture-related AEs is anticipated to promote an academic environment conducive to more comprehensive reporting.

Efficacy and safety of acupuncture treatment for fatigue after COVID-19 infection: study protocol for a pilot randomized sham-controlled trial.

Background: As the coronavirus disease 2019 (COVID-19) pandemic has spread globally, its sequelae, called Long COVID, have persisted, troubling patients worldwide. Although fatigue is known to be the most frequent among Long COVID symptoms, its mechanism and treatment have not been clearly demonstrated. In 2022, we conducted a preliminary prospective case series and found that acupuncture and moxibustion were feasible interventions for fatigue. This study is a pilot patient-assessor-blinded randomized sham-controlled trial to evaluate the efficacy and safety of acupuncture treatment for patients with fatigue that has persisted for at least 4 weeks after recovery from COVID-19. Methods: Thirty patients will be recruited and randomly assigned to either the acupuncture or sham acupuncture treatment groups. Treatment will be conducted thrice a week for both groups during 4 weeks. The primary outcome will be the efficacy and safety of acupuncture, including numeric rating scale (NRS), brief fatigue inventory (BFI), fatigue severity scale (FSS), and adverse event evaluation. Secondary outcomes will be evaluation of improvement in the comorbid symptoms of fatigue and feasibility variables. Outcome variables will be assessed before treatment, 4 weeks after treatment, and 8 weeks after treatment completion. Discussion: The results of this study will be used to clarify the efficacy and safety of acupuncture treatment for persistent fatigue in patients with Long COVID. Additionally, the feasibility of the study design was validated to provide evidence for future full-scale randomized controlled trials.Clinical trial registration: identifier: KCT0008656 https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24785&search_page=L.