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.

Comprehensive stability analysis of 13 ß-lactams and ß-lactamase inhibitors in in vitro media, and novel supplement dosing strategy to mitigate thermal drug degradation.

Non-clinical antibiotic development relies on in vitro susceptibility and infection model studies. Validating the achievement of the targeted drug concentrations is essential to avoid under-estimation of drug effects and over-estimation of resistance emergence. While certain ß-lactams (e.g., imipenem) and ß-lactamase inhibitors (BLIs; clavulanic acid) are believed to be relatively unstable, limited tangible data on their stability in commonly used in vitro media are known. We aimed to determine the thermal stability of 10 ß-lactams and 3 BLIs via LC-MS/MS in cation-adjusted Mueller Hinton broth at 25 and 36°C as well as agar at 4 and 37°C, and in water at -20, 4, and 25°C. Supplement dosing algorithms were developed to achieve broth concentrations close to their target over 24 h. During incubation in broth (pH 7.25)/agar, degradation half-lives were 16.9/21.8 h for imipenem, 20.7/31.6 h for biapenem, 29.0 h for clavulanic acid (studied in broth only), 23.1/71.6 h for cefsulodin, 40.6/57.9 h for doripenem, 46.5/64.6 h for meropenem, 50.8/97.7 h for cefepime, 61.5/99.5 h for piperacillin, and >120 h for all other compounds. Broth stability decreased at higher pH. All drugs were ≥90% stable for 72 h in agar at 4°C. Degradation half-lives in water at 25°C were >200 h for all drugs except imipenem (14.7 h, at 1,000 mg/L) and doripenem (59.5 h). One imipenem supplement dose allowed concentrations to stay within ±31% of their target concentration. This study provides comprehensive stability data on ß-lactams and BLIs in relevant in vitro media using LC-MS/MS. Future studies are warranted applying these data to antimicrobial susceptibility testing and assessing the impact of ß-lactamase-related degradation.

Vitamin D Reduces GABA-Positive Astrocytes in the 5xFAD Mouse Model of Alzheimer's Disease.

Background: Vitamin D has neuroprotective and immunomodulating functions that may impact glial cell function in the brain. Previously, we reported molecular and behavioral changes caused by deficiency and supplementation of vitamin D in an Alzheimer's disease (AD) mouse model. Recent studies have highlighted reactive astrocytes as a new therapeutic target for AD treatment. However, the mechanisms underlying the therapeutic effects of vitamin D on the glial cells of AD remain unclear. Objective: To investigate the potential association between vitamin D deficiency/supplementation and the pathological progression of AD, including amyloid-ß (Aß) pathology and reactive astrogliosis. Methods: Transgenic hemizygous 5XFAD male mice were subjected to different dietary interventions and intraperitoneal vitamin D injections to examine the effects of vitamin D deficiency and supplementation on AD. Brain tissue was then analyzed using immunohistochemistry for Aß plaques, microglia, and astrocytes, with quantifications performed via ImageJ software. Results: Our results demonstrated that vitamin D deficiency exacerbated Aß plaque formation and increased GABA-positive reactive astrocytes in AD model mice, while vitamin D supplementation ameliorated these effects, leading to a reduction in Aß plaques and GABA-positive astrocytes. Conclusions: Our findings highlight the significant impact of vitamin D status on Aß pathology and reactive astrogliosis, underscoring its potential role in the prevention and treatment of AD. This study provides the first in vivo evidence of the association between vitamin D and reactive astrogliosis in AD model mice, indicating the potential for targeting vitamin D levels as a novel therapeutic approach for AD.

The effect of sham acupuncture can differ depending on the points needled in knee osteoarthritis: A systematic review and network meta-analysis.

Objective: In sham acupuncture-controlled acupuncture clinical trials, although sham acupuncture techniques are different from those of verum acupuncture, the same acupuncture points are often used for verum and sham acupuncture, raising the question of whether sham acupuncture is an appropriate placebo. We aimed to examine the effects of sham and verum acupuncture according to the points needled (same or different between verum and sham acupuncture) in knee osteoarthritis. Methods: Ten databases were searched to find randomized controlled clinical trials (RCTs) assessing the effects of verum acupuncture with sham acupuncture or waiting lists on knee osteoarthritis. Sham acupuncture was classified as using the same acupuncture points as those in verum acupuncture (SATV) or using sham points (SATS). A frequentist network meta-analysis (NMA) was conducted, and the certainty of evidence was evaluated. Results: A total of 10 RCTs involving 1628 participants were included. Verum acupuncture was significantly superior to SATS but not different from SATV in terms of pain reduction. Additionally, SATV was significantly superior to the waiting list. For physical function, no difference were found between verum acupuncture, SATV, and SATS. The certainty of evidence was low to moderate. Conclusion: For knee osteoarthritis, the pain reduction effect of acupuncture may differ according to the needling points of sham acupuncture, and the control group should be established according to the specific aim of the study design and treatment mechanism.

Selenium reduction of ubiquinone via SQOR suppresses ferroptosis.

The canonical biological function of selenium is in the production of selenocysteine residues of selenoproteins, and this forms the basis for its role as an essential antioxidant and cytoprotective micronutrient. Here we demonstrate that, via its metabolic intermediate hydrogen selenide, selenium reduces ubiquinone in the mitochondria through catalysis by sulfide quinone oxidoreductase. Through this mechanism, selenium rapidly protects against lipid peroxidation and ferroptosis in a timescale that precedes selenoprotein production, doing so even when selenoprotein production has been eliminated. Our findings identify a regulatory mechanism against ferroptosis that implicates sulfide quinone oxidoreductase and expands our understanding of selenium in biology.

Pyromeconic acid-enriched Erigeron annuus water extract as a cosmetic ingredient for itch relief and anti-inflammatory activity.

Erigeron annuus (EA), traditionally used to treat disorders such as diabetes and enteritis, contains a variety of chemicals, including caffeic acid, flavonoids, and coumarins, providing antifungal and antioxidative benefits. However, the ingredients of each part of the EA vary widely, and there are few reports on the functionality of water extracts in skin inflammation and barrier protection. We assessed the therapeutic properties of the extract of EA without roots (EEA) and its primary ingredient, pyromeconic acid (PA), focusing on their antihistamine, anti-inflammatory, and antioxidative capabilities using HMC-1(human mast cells) and human keratinocytes (HaCaT cells). Our findings revealed that histamine secretion, which is closely related to itching, was notably reduced in HMC-1 cells following pretreatment with EEA (0.1% and 0.2%) and PA (corresponding concentration, 4.7 of 9.4 µg/mL). Similarly, they led to a marked decrease in the levels of pro-inflammatory cytokines, including IL-1ß, IL-8, IL-6, and IFN-γ. Furthermore, EA and PA enhanced antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), reduced malondialdehyde (MDA) production, and showed reactive oxygen species (ROS) scavenging activity in HaCaT cells. Moreover, at the molecular level, elevated levels of the pro-inflammatory cytokines IL-1ß, IL-6, TARC, and MDC induced by TNF-α/IFN-γ in HaCaT cells were mitigated by treatment with EEA and PA. We also revealed the protective effects of EEA and PA against SDS-induced skin barrier dysfunction in HaCaT cells by enhancing the expression of barrier-related proteins. Using NanoString technology, a comprehensive analysis of gene expression changes indicated significant modulation of autoimmune and inflammatory genes by EEA and PA. In summary, this study suggests that EEA and the corresponding concentration of PA as an active ingredient have functional cosmetic applications to alleviate itching and improve skin health.

Supporting Life Adjustment in Patients With Lung Cancer Through a Comprehensive Care Program: Protocol for a Controlled Before-and-After Trial.

BACKGROUND: Lung cancer diagnosis affects an individual's quality of life as well as physical and emotional functioning. Information on survivorship care tends to be introduced at the end of treatment, but early intervention may affect posttreatment adjustment. However, to the best of our knowledge, no study has explored the effect of early information intervention on the return to work, family, and societal roles of lung cancer survivors. OBJECTIVE: We report the study protocol of a comprehensive care prehabilitation intervention designed to facilitate lung cancer survivors' psychological adjustment after treatment. METHODS: A comprehensive care program was developed based on a literature review and a qualitative study of patients with lung cancer and health professionals. The Lung Cancer Comprehensive Care Program consists of educational videos and follow-up visits by a family medicine physician. To prevent contamination, the control group received routine education, whereas the intervention group received routine care and intervention. Both groups completed questionnaires before surgery (T0) and at 1-month (T1), 6-month (T2), and 1-year (T3) follow-up visits after surgery. The primary outcome was survivors' psychological adjustment to cancer 6 months after pulmonary resection. RESULTS: The historical control group (n=441) was recruited from September 8, 2021, to April 20, 2022, and the intervention group (n=350) was recruited from April 22, 2022, to October 17, 2022. All statistical analyses will be performed upon completion of the study. CONCLUSIONS: This study examined the effectiveness of an intervention that provided general and tailored informational support to lung cancer survivors, ranging from before to the end of treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05078918; https://clinicaltrials.gov/ct2/show/NCT05078918. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54707.

Anti-Wrinkle and Skin Moisture Efficacy of 7-MEGATM: A Randomized, Double-Blind, Placebo Comparative Clinical Trial.

7-MEGATM is a food product made from purified Alaska pollack fish oil containing palmitoleic acid (16:1), commonly referred to as omega-7. We sought to quantitatively evaluate whether this substance inhibits skin aging. A total of 101 middle-aged females were randomly allocated to the intervention (N = 50) or placebo group (N = 51). Each participant was advised to take either 500 mg of 7-MEGATM or a placebo twice daily for 12 weeks. The primary outcomes were the degree of improvement in wrinkles and the degree of moisture filling after consumption for 12 weeks compared to baseline. The secondary outcomes were improvement in skin wrinkles; moisture changes at 4 and 8 weeks from baseline; changes in transdermal water loss, skin elasticity, the melanin index, the erythema index, and the Global Photo Damage Score. We found a significant improvement in skin wrinkles and elasticity at 12 weeks in the 7-MEGATM-consuming group compared to that in the placebo group; skin moisture, elasticity, and the melanin index were also improved. No supplement-related adverse reactions were observed and 7-MEGATM was identified as safe. 7-MEGATM was effective for human skin function in terms of wrinkles, moisture, elasticity, and melanin production and may be useful as a skin nutritional supplement.

Uncovering the colorectal cancer immunotherapeutic potential: Evening primrose (Oenothera biennis) root extract and its active compound oenothein B targeting the PD-1/PD-L1 blockade.

BACKGROUND: The emergence of immune checkpoint inhibitors, a novel class of immunotherapy drugs, represents a major breakthrough in cancer immunotherapy, substantially improving patient survival post-treatment. Blocking programmed death-ligand 1 (PD-L1) and programmed death protein-1 (PD-1) has demonstrated promising clinical results in various human cancer types. The US FDA has recently permitted only monoclonal antibody (mAb)-based PD-L1 or PD-1 blockers. Although these antibodies exhibit high antitumor efficacy, their size- and affinity-induced side effects limit their applicability. PURPOSE: As small-molecule-based PD-1/PD-L1 blockers capable of reducing the side effects of antibody therapies are needed, this study focuses on exploring natural ingredient-based small molecules that can target hPD-L1/PD-1 using herbal medicines and their components. METHODS: The antitumor potential of evening primrose (Oenothera biennis) root extract (EPRE), a globally utilized traditional herbal medicine, folk remedy, and functional food, was explored. A coculture system was established using human PD-L1-expressed murine MC38 cells (hPD-L1-MC38s) and CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) expressing humanized PD-1. The in vivo experiments utilized a colorectal cancer (CRC) C57BL/6 J mouse model bearing MC38 cells expressing humanized PD-L1 and PD-1 proteins. RESULTS: EPRE and its active compound oenothein B effectively hindered the molecular interaction between hPD-L1 and hPD-1. EPRE stimulated tumor-specific T lymphocytes of a hPD-L1/PD-1 CRC mice. This action resulted in the elevated infiltration of cytotoxic CD8+T lymphocytes and subsequent tumor growth reduction. Moreover, the combined therapy of oenothein B, a PD-1/PD-L1 blocker, and FOLFOX (5-fluorouracil plus oxaliplatin) cooperatively suppressed hPD-L1-MC38s growth in the ex vivo model through activated CD8+ TIL antitumor immune response. Oenothein B exhibited a high binding affinity for hPD-L1 and hPD-1. We believe that this study is the first to uncover the inhibitory effects of EPRE and its component, oenothein B, on PD-1/PD-L1 interactions. CONCLUSION: This study identified a promising small-molecule candidate from natural products that blocks the hPD-L1/PD-1 signaling pathway. These findings emphasize the potential of EPRE and oenothein B as effective anticancer drugs.

Iridoid Glycosides and Coumarin Glycoside Derivatives from the Roots of Nymphoides peltata and Their In Vitro Wound Healing Properties.

Nymphoides peltata has been used as a medicinal herb in traditional medicines to treat strangury, polyuria, and swelling. The phytochemical investigation of the MeOH extract of N. peltata roots led to the isolation of three iridoid glycosides and three coumarin glycoside derivatives, which were characterized as menthiafolin (1), threoninosecologanin (2), callicoside C (3), and scopolin (4), as well as two undescribed peltatamarins A (5) and B (6). The chemical structures of the undescribed compounds were determined by analyzing their 1 dimensional (D) and 2D nuclear magnetic resonance (NMR) spectra and using high-resolution (HR)-electrospray ionization mass spectroscopy (ESI-MS), along with the chemical reaction of acid hydrolysis. The wound healing activities of the isolated compounds 1-6 were evaluated using a HaCaT cell scratch test. Among the isolates, scopolin (4) and peltatamarin A (5) promoted HaCaT cell migration over scratch wounds, and compound 5 was the most effective. Furthermore, compound 5 significantly promoted cell migration without adversely affecting cell proliferation, even when treated at a high dose (100 µM). Our results demonstrate that peltatamarin A (5), isolated from N. peltata roots, has the potential for wound healing effects.

Safety and Efficacy Assessment of Red Ginseng Oil (RXGIN) in Men with Lower Urinary Tract Symptoms in a Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of red ginseng oil (RXGIN) in men with lower urinary tract symptoms. MATERIALS AND METHODS: Men aged between 40 and 75 years with a total International Prostate Symptom Score (IPSS) of 8 to 19 points were recruited from April 2020 to December 2020. Subjects were randomly assigned to either the RXGIN group or the control group in a 1:1 ratio and received either RXGIN or placebo daily for 12 weeks. For the primary outcome, changes in IPSS scores at 6 and 12 weeks from baseline were analyzed. The secondary outcomes were changes in International Index of Erectile Function (IIEF), maximum urinary flow rate, and post-void residual volume at weeks 6 and 12 compared to baseline. Urine analysis and blood tests were additionally performed for safety assessment. RESULTS: A total of 88 subjects (RXGIN group, 46; control group, 42) completed the study. The total IPSS and IPSS subscores (residual urine sensation, frequency, intermittency, urgency, weak stream, straining, nocturia, and quality of life) were significantly improved in the RXGIN group compared to the control group at weeks 6 and 12. Total IIEF and sexual desire were significantly improved in the RXGIN group at week 6 and week 12, respectively, but there were no significant changes in the level of serum testosterone or dihydrotestosterone. The serum prostate-specific antigen showed significant decrease at weeks 12. No serious adverse events leading to discontinuation of the study drug were observed in the RXGIN group. CONCLUSIONS: Red ginseng oil (RXGIN) appears to be safe and effective in improving lower urinary tract symptoms in men and may also improve some aspects of sexual function.

3‴-O-Foliamenthoyl-Rutin, a New Flavonoid Glycoside from the Roots of Nymphoides peltata.

Nymphoides peltata (Menyanthaceae) has been used as a medicinal herb in traditional medicines to treat conditions such as strangury, polyuria, swelling, and as a diuretic and antipyretic. In our ongoing research to discover novel structural and/or biological natural products in natural resources, five flavonoids, quercetin (1), quercitrin (2), isoquercetin (3), quercetin-3-O-vicianoside (4), and rutin (5), as well as a new flavonoid glycoside, 3‴-O-foliamenthoyl-rutin (6), were isolated from the MeOH extract of N. peltata roots. The chemical structure of the new compound (6) was determined by analyzing 1D and 2D NMR spectra and high-resolution (HR) electrospray ionization mass spectroscopy (ESIMS), along with a chemical reaction. The wound-healing activities of the isolated compounds (1-6) were evaluated using a HaCaT cell scratch test. Among the isolates, isoquercetin (3), quercetin-3-O-vicianoside (4), and 3‴-O-foliamenthoyl-rutin (6) promoted HaCaT cell migration over scratch wounds, with compound 4 being the most effective. Our findings provide experimental data supporting the potential of quercetin-3-O-vicianoside (4) as a wound-healing agent.

Different Outcomes According to Needling Point Location Used in Sham Acupuncture for Cancer-Related Pain: A Systematic Review and Network Meta-Analysis.

Numerous acupuncture studies have been conducted on cancer-related pain; however, its efficacy compared to sham acupuncture remains controversial. We confirmed whether the outcome of acupuncture differs according to the needling points of sham acupuncture for cancer-related pain. We searched 10 databases on 23 May 2023 to screen acupuncture trials using sham acupuncture or waiting list as controls for cancer-related pain. Sham acupuncture was classified into two types, depending on whether the needling was applied at the same locations as verum acupuncture (SATV) or not (SATS). A network meta-analysis (NMA) was performed on the basis of a frequentist approach to assess pain severity. Eight studies (n = 574 participants) were included in the review, seven of which (n = 527 participants) were included in the NMA. The pain severity was not significantly different between SATV and verum acupuncture, but verum acupuncture significantly improved pain severity compared to SATS. The risk of bias affecting the comparisons between the verum and sham acupuncture was generally low. Previous acupuncture trials for cancer-related pain showed differing outcomes of sham and verum acupuncture, depending on the needling points of sham acupuncture. The application of SATV cannot be considered a true placebo, which leads to an underestimation of the efficacy of verum acupuncture.

Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts.

Complement component 3 (C3) deficiency has recently been known as a cause of constipation, without studies on the therapeutic efficacy. To evaluate the therapeutic agents against C3-deficiency-induced constipation, improvements in the constipation-related parameters and the associated molecular mechanisms were examined in FVB/N-C3em1Hlee/Korl knockout (C3 KO) mice treated with uridine (Urd) and the aqueous extract of Liriope platyphylla L. (AEtLP) with laxative activity. The stool parameters and gastrointestinal (GI) transit were increased in Urd- and AEtLP-treated C3 KO mice compared with the vehicle (Veh)-treated C3 KO mice. Urd and AEtLP treatment improved the histological structure, junctional complexes of the intestinal epithelial barrier (IEB), mucin secretion ability, and water retention capacity. Also, an improvement in the composition of neuronal cells, the regulation of excitatory function mediated via the 5-hydroxytryptamine (5-HT) receptors and muscarinic acetylcholine receptors (mAChRs), and the regulation of the inhibitory function mediated via the neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) were detected in the enteric nervous system (ENS) of Urd- and AEtLP-treated C3 KO mice. Therefore, the results of the present study suggest that C3-deficiency-induced constipation can improve with treatment with Urd and AEtLP via the regulation of the mucin secretion ability, water retention capacity, and ENS function.

Universal selective transfer printing via micro-vacuum force.

Transfer printing of inorganic thin-film semiconductors has attracted considerable attention to realize high-performance soft electronics on unusual substrates. However, conventional transfer technologies including elastomeric transfer printing, laser-assisted transfer, and electrostatic transfer still have challenging issues such as stamp reusability, additional adhesives, and device damage. Here, a micro-vacuum assisted selective transfer is reported to assemble micro-sized inorganic semiconductors onto unconventional substrates. 20 µm-sized micro-hole arrays are formed via laser-induced etching technology on a glass substrate. The vacuum controllable module, consisting of a laser-drilled glass and hard-polydimethylsiloxane micro-channels, enables selective modulation of micro-vacuum suction force on microchip arrays. Ultrahigh adhesion switchability of 3.364 × 106, accomplished by pressure control during the micro-vacuum transfer procedure, facilitates the pick-up and release of thin-film semiconductors without additional adhesives and chip damage. Heterogeneous integration of III-V materials and silicon is demonstrated by assembling microchips with diverse shapes and sizes from different mother wafers on the same plane. Multiple selective transfers are implemented by independent pressure control of two separate vacuum channels with a high transfer yield of 98.06%. Finally, flexible micro light-emitting diodes and transistors with uniform electrical/optical properties are fabricated via micro-vacuum assisted selective transfer.

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.

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.

The Genome of the Korean Island-Originated Perilla citriodora 'Jeju17' Sheds Light on Its Environmental Adaptation and Fatty Acid and Lipid Production Pathways.

Perilla is a key component of Korean food. It contains several plant-specialized metabolites that provide medical benefits. In response to an increased interest in healthy supplement food from the public, people are focusing on the properties of Perilla. Nevertheless, unlike rice and soybeans, there are few studies based on molecular genetics on Perilla, so it is difficult to systematically study the molecular breed. The wild Perilla, Perilla citriodora 'Jeju17', was identified a decade ago on the Korean island of Jeju. Using short-reads, long-reads, and Hi-C, a chromosome-scale genome spanning 676 Mbp, with high contiguity, was assembled. Aligning the 'Jeju17' genome to the 'PC002' Chinese species revealed significant collinearity with respect to the total length. A total of 31,769 coding sequences were predicted, among which 3331 were 'Jeju17'-specific. Gene enrichment of the species-specific gene repertoire highlighted environment adaptation, fatty acid metabolism, and plant-specialized metabolite biosynthesis. Using a homology-based approach, genes involved in fatty acid and lipid triacylglycerol biosynthesis were identified. A total of 22 fatty acid desaturases were found and comprehensively characterized. Expression of the FAD genes in 'Jeju17' was examined at the seed level, and hormone signaling factors were identified. The results showed that the expression of FAD genes in 'Jeju17' at the seed level was high 25 days after flowering, and their responses of hormones and stress were mainly associated with hormone signal transduction and abiotic stress via cis-elements patterns. This study presents a chromosome-level genome assembly of P. citriodora 'Jeju17', the first wild Perilla to be sequenced from the Korean island of Jeju. The analyses provided can be useful in designing ALA-enhanced Perilla genotypes in the future.

Anti-Wrinkling Effect of 3,4,5-tri-O-caffeoylquinic Acid from the Roots of Nymphoides peltata through MAPK/AP-1, NF-κB, and Nrf2 Signaling in UVB-Irradiated HaCaT Cells.

Nymphoides peltata has been widely used pharmacologically in traditional Chinese medicine to treat heat strangury and polyuria. The aim of this study was to isolate the bioactive components from N. peltata and evaluate their potential use as antioxidant and anti-wrinkle agents. Phytochemical investigation of the methanolic extract of N. peltata roots led to the isolation of 15 compounds (1-15), which were structurally determined as α-spinasterol (1), 3-O-ß-D-glucopyranosyl-oleanolic acid 28-O-ß-D-glucuronopyranoside (2), 4-hydroxybenzoic acid (3), protocatechuic acid (4), vanillic acid (5), p-coumaric acid (6), caffeic acid (7), ferulic acid (8), neochlorogenic acid (neo-CQA) (9), chlorogenic acid (CQA) (10), cryptochlorogenic acid (crypto-CQA) (11), isochlorogenic acid B (3,4-DCQA) (12), isochlorogenic acid A (3,5-DCQA) (13), isochlorogenic acid C (4,5-DCQA) (14), and 3,4,5-tri-O-caffeoylquinic acid (TCQA) (15). Of these 15 compounds, compound 2 was a new oleanane saponin, the chemical structure of which was characterized by 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data and high-resolution electrospray ionization mass spectrometry (HRESIMS), as well as chemical reaction. Biological evaluation of the isolated compounds revealed that 3,4,5-tri-O-caffeoylquinic acid (TCQA) significantly improved Nrf2 levels in an Nrf2-ARE reporter HaCaT cell screening assay. TCQA was found to potently inhibit the Nrf2/HO-1 pathway and to possess strong anti-wrinkle activity by modulating the MAPK/NF-κB/AP-1 signaling pathway and thus inhibiting MMP-1 synthesis in HaCaT cells exposed to UVB. Our results suggest that TCQA isolated from N. peltata might be useful for developing effective antioxidant and anti-wrinkle agents.

Inhibitory Activity of Natural cis-Khellactone on Soluble Epoxide Hydrolase and Proinflammatory Cytokine Production in Lipopolysaccharides-Stimulated RAW264.7 Cells.

The pursuit of anti-inflammatory agents has led to intensive research on the inhibition of soluble epoxide hydrolase (sEH) and cytokine production using medicinal plants. In this study, we evaluated the efficacy of cis-khellactone, a compound isolated for the first time from the roots of Peucedanum japonicum. The compound was found to be a competitive inhibitor of sEH, exhibiting an IC50 value of 3.1 ± 2.5 µM and ki value of 3.5 µM. Molecular docking and dynamics simulations illustrated the binding pose of (-)cis-khellactone within the active site of sEH. The results suggest that binding of the inhibitor to the enzyme is largely dependent on the Trp336-Gln384 loop within the active site. Further, cis-khellactone was found to inhibit pro-inflammatory cytokines, including NO, iNOS, IL-1ß, and IL-4. These findings affirm that cis-khellactone could serve as a natural therapeutic candidate for the treatment of inflammation.