The effect of Dunaliella tertiolecta supplementation on diet-induced obesity in UCP1-deficient mice.

We previously demonstrated that dietary supplementation with Dunaliella tertiolecta (DT) increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) and improves diet-induced obesity (DIO) in C57BL/6 J mice at thermoneutrality (30 °C). Here, we investigated whether DT improves DIO in a thermoneutral UCP1-deficient (KO) animal. KO mice were fed a high-fat diet supplemented with DT for 12 weeks. Compared to control group without DT, body weight was significantly reduced in DT group with no difference in food intake. Dunaliella tertiolecta-supplemented mice exhibited lower adiposity and well-maintained multilocular morphology in BAT, in which a significant increase in gene expression of PR domain containing 16 was detected in DT group compared to control group. Moreover, increase in UCP2 level and/or decrease in ribosomal protein S6 phosphorylation were detected in adipose tissues of DT group relative to control group. These results suggest that DT supplementation improves DIO by stimulating UCP1-independent energy dissipation at thermoneutrality.

Relationship between health literacy and attitudes toward acupuncture: A web-based cross-sectional survey with a panel of Japanese residents.

The relationship between health literacy of Japanese people, their attitudes toward acupuncture, and their behavior in choosing this therapy is currently unclear. Therefore, for this study, we conducted a web-based survey to address this unknown relationship. A questionnaire comprising four categories (health status, health literacy, previous acupuncture experience, and attitudes toward acupuncture) was administered to 1,600 Japanese participants. For this study, we performed cross-tabulation and path analysis to examine the relationship between each questionnaire item. The mean score of participants' health literacy was 3.41 (SD = 0.74), and older, educated, female participants tended to have higher health literacy. The respondents perceived acupuncture to be effective for chronic low back pain, tension-type headache, and knee pain due to osteoarthritis (40.0%, 38.7%, and 21.8%, respectively). Contrastingly, acupuncture was perceived as far less effective for postoperative nausea/vomiting and prostatitis symptoms (8.3% and 8.7%, respectively). Of the total study respondents, 34.4% reported that they would try acupuncture only if recommended by clinical practice guidelines, and 35.6% agreed that acupuncture is safe. The path analysis showed that attitudes toward acupuncture were significantly influenced by the participants' health literacy, number of information sources, and previous acupuncture experience. However, it was also found that experience with acupuncture was not directly associated with health literacy. Although the Japanese population with higher health literacy is more likely to perceive acupuncture positively, they do not necessarily have sufficient relevant knowledge of the clinical evidence. Therefore, their decision to receive acupuncture may be more dependent on personal narratives rather than clinical evidence. Thus, future challenges lie in individual education of the population on how to choose a reliable health information source, and organizational efforts to provide more reliable health information.

Trends and quality of randomized controlled trials on acupuncture conducted in Japan by decade from the 1960s to the 2010s: a systematic review.

BACKGROUND: More new randomized controlled trials (RCTs) on acupuncture have been published in Japan since our last updated systematic review (2010). This systematic review aimed to evaluate the quality of RCTs on acupuncture conducted in Japan and understand the decade-wise changes in the methodological characteristics of the relevant RCTs. METHODS: The literature search was performed using Ichushi Web, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and our team's compilation of relevant papers. We included full-length papers reporting RCTs that examined the clinical effects of acupuncture on patients in Japan published in or before 2019. We assessed the risk of bias (RoB), sample size, control setting, negative trial reporting, informed consent, ethics approval, trial registration, and adverse event reporting. RESULTS: A total of 99 articles reporting 108 eligible RCTs were identified. The number of RCTs published in each decade was 1, 6, 9, 5, 40, and 47 in the 1960s, 1970s, 1980s, 1990s, 2000s, and 2010s, respectively. Quality assessment using the Cochrane RoB tool revealed that "sequence generation" improved in and after 1990 (73%-80% of RCTs were rated as "low") and "blinding of outcome assessors" slightly improved in and after the 2000s (40%-50% judged as "low"). However, "high" or "unclear" remained the dominant grades in other domains. Clinical trial registration and adverse events were reported only in 9% and 28% of the included RCTs even in the 2010s, respectively. A different acupuncture method or different point selection (e.g., deep vs. shallow insertion) was the most dominant control setting before 1990, while sham (or "placebo") needling and/or sham acupoints became the most dominant in the 2000s. The proportion of RCTs with positive results was 80% in the 2000s and 69% in the 2010s. CONCLUSIONS: The quality of RCTs on acupuncture conducted in Japan did not appear to have improved over the decades except for "sequence generation." While the culture of submitting negative trial reports was prevalent in the Japanese acupuncture research milieu as late as the 1990s, the overall quality of the relevant trials needs to be further improved.

Quality assessment of Japanese clinical practice guidelines including recommendations for acupuncture.

Background: The quality of clinical practice guidelines (CPGs) should be extensively evaluated. This study aimed to evaluate Japanese CPGs that include recommendations for acupuncture. Methods: In a literature search, CPGs including recommendations for acupuncture published in Japan until October 2021 were sought. We assessed (1) whether the CPGs were developed in accordance with the Grading Recommendations Assessment, Development and Evaluation (GRADE) system, (2) the quality of the CPGs using the Appraisal of Guidelines for Research and Evaluation (AGREE) II, and (3) whether the strength of the recommendations for acupuncture was consistent with each CPG's predefined procedure. Results: Seventeen CPGs including 23 recommendations in total were identified and assessed. (1) Three CPGs were in accordance with the GRADE system. (2) The mean score of overall assessment using AGREE II was 4.5 on a 7-point Likert scale. The mean domain scores were 77% for domain 1 (scope and purpose), 54% for domain 2 (stakeholder involvement), 48% for domain 3 (rigor of development), 78% for domain 4 (clarity of presentation), 20% for domain 5 (applicability), and 51% for domain 6 (editorial independence). (3) The strength of the recommendations for acupuncture in two CPGs was judged to be underestimated. Some of the CPGs contained elementary problems that were not considered in AGREE II. Conclusion: The methodological quality of Japanese CPGs including recommendations for acupuncture was not necessarily high. Since technical issues exist in each field of therapy, the respective experts should be involved in developing and reviewing CPGs to disseminate accurate health information.

Dietary Supplementation with Dunaliella Tertiolecta Prevents Whitening of Brown Fat and Controls Diet-Induced Obesity at Thermoneutrality in Mice.

We investigated the effect of evodiamine-containing microalga Dunaliella tertiolecta (DT) on the prevention of diet-induced obesity in a thermoneutral C57BL/6J male (30 °C). It attenuates the activity of brown adipose tissue (BAT), which accelerates diet-induced obesity. Nine-week-old mice were fed a high-fat diet supplemented with 10 g (Low group) or 25 g (High group) DT powder per kg food for 12 weeks. Compared to control mice without DT supplementation, body weight gain was significantly reduced in the High group with no difference in food intake. Tissue analyses indicated maintenance of multilocular morphology in BAT and reduced fat deposition in liver in DT-supplemented mice. Molecular analysis showed a significant decrease in mammalian target of rapamycin-ribosomal S6 protein kinase signaling pathway in white adipose tissue and upregulation in mRNA expression of brown fat-associated genes including fibroblast growth factor-21 (Fgf21) and uncoupling protein 1 (Ucp1) in BAT in the High group compared to the control. In the experiments using C3H10T1/2 adipocytes, DT extract upregulated mRNA expression of brown fat-associated genes in dose-dependent and time-dependent manners, accompanied by a significant increase in secreted FGF21 levels. Our data show the ability of DT as a nutraceutical to prevent brown fat attenuation and diet-induced obesity in vivo.

A Multicenter Prospective Survey of Adverse Events Associated with Acupuncture and Moxibustion in Japan.

Background: There have been only a few prospective surveys on adverse events (AEs) in Japanese-style acupuncture practice, and these surveys were conducted only in a single college acupuncture clinic. Objective: The goal of this research was to assess the safety of acupuncture and moxibustion performed in educational facilities in Japan. Materials and Methods: This was a multicenter prospective survey, using paper reporting forms. It was conducted in eight acupuncture clinics affiliated with educational institutions. The subjects were outpatients attending the clinics. The main outcome measure was the number of reported adverse events. The study was conducted for 5-7 months at each facility between October 2014 and June 2015. Participating acupuncture practitioners were instructed to self-report AEs observed during and after treatment; patients were interviewed upon treatment completion. For returning patients, treatment was preceded by an interview survey regarding the AEs identified after the previous treatment session. A specialized 4-sheet questionnaire was used. Results: Two hundred and thirty-two acupuncture practitioners participated, 2180 patients received treatment, and there were 14,039 sessions, overall. In total, 847 (6.03%) AEs were reported. The most common AEs included subcutaneous bleeding and hematomas (370, 2.64%), followed by discomfort (109, 0.78%) and residual pain at insertion points (94, 0.67%). No infections or serious AEs were reported. Conclusions: Acupuncture and moxibustion performed in educational facilities in Japan were safe because most of the AEs reported were mild and transient. However, the risk cannot be defined definitely because the survey sample size was too small.

Traditional medicine in china, Korea, and Japan: a brief introduction and comparison.

Background and Purpose. Traditional medicine (TM) has been widely used in China (including the Taiwan region), Korea, and Japan. The purposes of this paper are to summarize the basic data on TM systems in these three countries and to compare them in terms of overall policy, education, and insurance. Methods. Government websites, national statistics, and authoritative papers from each country were fully searched. Further data were gathered by TM experts from each country. Results. China and Korea showed similar patterns in TM systems, whereas Japan showed different patterns. In China and Korea, TM was practiced in a dual system with conventional medicine (CM), and TM education was 6-year training programs on average for TM doctors, and acupuncture, moxibustion, and cupping were completely insured. Whereas, CM was dominant in Japan, and TM was practiced by each health care worker who has received different TM education respectively, and main TM therapies were partially insured. Conclusions. TM was developed similarly or somewhat differently based on differences in cultural background and national policies in East Asia. We cautiously propose that this study could contribute to the development of TM and also be used for reference in complementary and alternative medicine systems.

Evodiamine inhibits adipogenesis via the EGFR-PKCalpha-ERK signaling pathway.

The molecular mechanism of the anti-adipogenic effect of evodiamine (which has several capsaicin-like pharmacological actions) was investigated. The evodiamine effect was not blocked by the specific TRPV1 antagonist capsazepine in 3T3-L1 preadipocytes, whereas its effect was greatly curtailed by inhibitors of protein kinase C (PKC) and epidermal growth factor receptor (EGFR). Signal analyses showed that evodiamine stimulated the phosphorylation of EGFR, PKCalpha, and ERK, all of which were reduced by an EGFR inhibitor. Silencing experiments of EGFR mRNA supported the involvement of these signaling molecules in the inhibitory effect of evodiamine. An unidentified mechanism whereby evodiamine inhibits adipogenesis via the EGFR-PKCalpha-ERK signaling pathway was revealed.

Safety of acupuncture practice in Japan: patient reactions, therapist negligence and error reduction strategies.

Evidence-based approach on the safety of acupuncture had been lagging behind both in the West and the East, but reliable data based on some prospective surveys were published after the late 1990s. In the present article, we, focusing on 'Japanese acupuncture', review relevant case reports and prospective surveys on adverse events in Japan, assess the safety of acupuncture practice in this country, and suggest a strategy for reducing the therapists' error. Based on the prospective surveys, it seems reasonable to suppose that serious adverse events are rare in standard practice by adequately trained acupuncturists, regardless of countries or modes of practice. Almost all of adverse reactions commonly seen in acupuncture practice-such as fatigue, drowsiness, aggravation, minor bleeding, pain on insertion and subcutaneous hemorrhage-are mild and transient, although we should be cautious of secondary injury following drowsiness and needle fainting. After demonstrating that acupuncture is inherently safe, we have been focusing on how to reduce the risk of negligence in Japan, as well as educating acupuncturists more about safe depth of insertion and infection control. Incident reporting and feedback system is a useful strategy for reducing therapist errors such as forgotten needles. For the benefit of acupuncture patients in Japan, it is important to establish mandatory postgraduate clinical training and continued education system.

Evodiamine improves diet-induced obesity in a uncoupling protein-1-independent manner: involvement of antiadipogenic mechanism and extracellularly regulated kinase/mitogen-activated protein kinase signaling.

Evodiamine is an alkaloidal compound with antiobesity effects that have been thought to be due to uncoupling protein-1 (UCP1) thermogenesis similar to the effects of capsaicin, but the underlying mechanisms are poorly understood. To clarify the mechanisms, we first examined whether the antiobesity effect of evodiamine could be attributed to the involvement of UCP1. When UCP1-knockout mice were fed a high-fat diet with 0.03% evodiamine (wt/wt) for 2 months, the increases in body weight, adiposity, and the serum levels of leptin and insulin were reduced in a manner indistinguishable from control mice fed a high-fat diet with evodiamine, suggesting that evodiamine triggered a UCP1-independent mechanism to prevent diet-induced obesity. By using preadipocyte cultures, we found that evodiamine, but not capsaicin, increased phosphorylation of ERK/MAPK, reduced the expression of transcription factors such as peroxisome proliferator-activated receptor-gamma, and strongly inhibited adipocyte differentiation. Evodiamine treatment also reduced insulin-stimulated phosphorylation of Akt, a crucial regulator of adipocyte differentiation; and the reduction of phosphorylated-Akt and augmentation of phosphorylated ERK were reversed by blockade of the MAPK kinase/MAPK signaling pathway, restoring adipogenesis in the cultures. The changes in ERK and Akt phosphorylation levels were also observed in white adipose tissues of UCP1-knockout mice fed the evodiamine diet. These findings suggest that evodiamine has a potential to prevent the development of diet-induced obesity in part by inhibiting adipocyte differentiation through ERK activation and its negative cross talk with the insulin signaling pathway.

Factors that influence the applicability of sham needle in acupuncture trials: two randomized, single-blind, crossover trials with acupuncture-experienced subjects.

OBJECTIVES: In recent years the retractable type of sham needle has been anticipated to be a possible solution for masking patients in acupuncture research. However, this needle has been intended mainly for acupuncture-naïve subjects. The authors' goal in this study was to assess the validity of the retractable type of sham needle. METHODS: The authors conducted two randomized, single-blind, crossover trials with acupuncture-experienced subjects. Different acupuncture points were used in each trial (a LI-4 trial and a BL-23 trial). The subjects received two sessions of different stimulations in each trial. A Park Sham Needle was used in one session, a genuine acupuncture needle in the other. RESULTS: In the LI-4 trial, all of the 21 subjects (100%) felt penetration with the genuine needle, but only 7 of the 20 subjects (35%) felt a similar sensation with the sham needle (P=0.0002). Fifteen of the 21 subjects (71%) felt a dull sensation with the genuine needle, but only 4 of the 20 subjects (20%) felt a similar sensation with the sham needle (P=0.01). In the BL-23 trial, 14 of the 20 subjects (70%) felt penetration with the genuine needle and 10 of the 20 subjects (50%) felt "penetration" with the sham needle (P=0.39). Eight of the 20 subjects (40%) felt a dull sensation with the genuine needle and 2 of the 20 subjects (10%) did with the sham needle (P=0.109). CONCLUSIONS: Potential factors that influence the applicability of "placebo" needling include not only inter-tester variability but also the patient's knowledge and experience of acupuncture, acupuncture point selection, the visual impact of needling, and so on.

Randomised controlled trial comparing the effectiveness of electroacupuncture and TENS for low back pain: a preliminary study for a pragmatic trial.

The objective of this study was to compare the effectiveness of electroacupuncture and TENS for low back pain when the electroacupuncture is applied in a clinically realistic manner. The study was designed as an evaluator-blinded randomised controlled trial (RCT). The study was performed at the Tsukuba College of Technology Clinic in Japan. Twenty subjects, who suffered from low back pain (LBP) without sciatica, were recruited, using leaflets in Tsukuba city. Subjects were allocated to either an electroacupuncture (EA) group (10 patients) or a transcutaneous electrical nerve stimulation (TENS) group (10 patients). The procedure for EA was in accordance with standard practice at our clinic. The main outcome measures were a pain relief scale (100 mm visual analogue scale: VAS) and a LBP score recommended by the Japanese Orthopaedic Association (JOA Score). Mean VAS value during the 2-weeks experimental period of the EA group was significantly smaller than that of the TENS group (65 mm vs 86 mm; 95% CI, 4.126 - 37.953). JOA Score in the EA group improved significantly while that in the TENS group showed no change. Although some placebo effect may be included, EA appeared more useful than TENS in the short-term effect on low back pain. We suggest that more realistic acupuncture interventions based on standard practice should be employed in pragmatic RCTs.