Peripheral Rho-associated protein kinase activation mediates acupuncture analgesia.

Background: Acupuncture has been proven effective for various types of pain, and peripheral molecular signals around acupuncture-treated areas have been suggested to contribute to the analgesic effects of acupuncture. However, the underlying mechanism from these peripheral molecular signals to central ones remains unclear. The purpose of this study was to investigate whether peripheral Rho-associated protein kinase (ROCK) activation induced by acupuncture treatment mediates acupuncture analgesia, and also to investigate the relationship between ROCK activation and extracellular signal-regulated kinase (ERK), which has previously been proven to mediate acupuncture analgesia and other related molecular changes during acupuncture. Methods: Acupuncture was treated at the bilateral GB34 acupoints of C57BL/6 mice, after which changes in ROCK activation and the location of its expression in the skin were analyzed. To verify the role of ROCK in acupuncture analgesia, we administrated ROCK inhibitor Y-27632 (0.3 µg/ul) into the skin before acupuncture treatment with formalin and complete Freund adjuvant (CFA) induced pain models, then the nociceptive responses were analyzed. Results: Acupuncture treatment produced ROCK2 activation in the skin after 30 and 60 min, and the histological analyses revealed that ROCK2 was activated in the fibroblast of the dermis. The acupuncture-induced ROCK2 expression was significantly attenuated by the ERK inhibitor, whereas phospho-ERK expression was not inhibited by ROCK inhibitor. In both the formalin- and CFA-induced mouse pain models, acupuncture analgesia was blocked by ROCK inhibitor administration. Conclusion: Acupuncture treatment-induced ROCK2 expression is a downstream effector of phospho-ERK in the skin and plays a crucial role in acupuncture analgesia.

A survey on the real-world clinical utilization of a traditional acupuncture in Republic of Korea: Sa-am acupuncture.

OBJECTIVE: This study investigated the clinical details and usage of Sa-am acupuncture in Korean medicine clinics and explored how practicing Korean medicine doctors (KMDs) think about Sa-am acupuncture. METHODS: We conducted a questionnaire-based survey of KMDs who utilize Sa-am acupuncture in their practice. The study comprehensively investigated issues related to clinical application of Sa-am acupuncture, needling techniques used during treatment, training methods, and directions for its future improvement. RESULTS: We analyzed 572 responses. An average of 50% of the patients visiting Korean medicine clinics were receiving Sa-am acupuncture. The most prevalent indication for Sa-am acupuncture use was digestive disorders. The patients' appetite level and digestive function were most frequently used indicators for selecting acupuncture points. Regarding prescription compositions, Jung-Gyuk formulas were more frequently used than Seung-Gyuk formulas. Inserting the needle along the flow of the channel or against the flow of the channel was most popular. The acupuncture style most frequently used in combination with Sa-am acupuncture was Ashi point acupuncture. Strengths of Sa-am acupuncture included its versatility, easy application, and good outcomes. Limitations included the lack of rigorous education and training programs, difficulty in applying the principles for beginners, and insufficient clinical research evidence. CONCLUSION: In clinics where Sa-am acupuncture is available, KMDs were providing Sa-am acupuncture to about half of their patients. Practitioners were not using all of the tonification and sedation techniques which may be due to time constraints or simply a lack of necessity. Sa-am acupuncture demonstrated high utility in clinical practice and high satisfaction based on the efficacy and safety. More training programs and high-quality research are needed to help expand the use of Sa-am acupuncture. Please cite this article as: Park JY, Lee YS, Park HJ, Lee SK, Lee JW, Kim SY. A survey on the real-world clinical utilization of a traditional acupuncture in Republic of Korea: Sa-am acupuncture. J Integr Med. 2024; 22(5): 570-578.

Driving Under the Influence of Alcohol in People With Major Depressive Episodes and Alcohol Use Disorder.

OBJECTIVES: Alcohol use disorder (AUD) and depression are the most commonly reported psychiatric comorbid conditions. We examined trends in the past-year prevalence of driving under the influence of alcohol (DUIA) among people with major depressive episodes (MDE), AUD, or both in the United States. METHODS: We analyzed 543,573 individuals aged 18 years or older from the 2005 to 2019 National Surveys on Drug Use and Health (NSDUH). Multivariate logistic regression models were applied to examine the adjusted past-year prevalence of DUIA. To assess trends in DUIA over time, average annual percent change (AAPC) was calculated. RESULTS: From 2005 to 2019, DUIA prevalence among US adults with MDE declined significantly from 18.1% to 9.4% (AAPC = -4.9). Decreasing trends in DUIA were also observed among those with AUD (from 55.4% to 37.8%, AAPC = -3.0) and among those with co-occurring MDE and AUD (from 58.3% to 38.8%, AAPC = -3.1). Compared to those with no MDE or AUD, individuals with AUD and those with co-occurring MDE and AUD had significantly lower AAPCs across all examined sociodemographic subgroups except Non-Hispanic Other and those without a high school diploma. CONCLUSIONS: From 2005 to 2019, DUIA prevalence declined significantly with varying rates of decrease across different diagnostic and sociodemographic groups. Focused public health efforts are needed to engage high-risk groups that have shown a tendency toward less expedient reductions in DUIA.

Secondhand smoke exposure and asthma status among adolescents: Findings from the 2019-2020 California Student Tobacco Survey.

Background and objectives: Secondhand tobacco smoke is associated with worsening asthma symptoms among children. However, the relationship between secondhand marijuana smoke and asthma symptoms among youth has not been examined. This study compares the prevalence of secondhand tobacco and marijuana smoke exposure, overall and by asthma status, among middle and high school students. Methods: The study assessed participants of the 2019-2020 California Student Tobacco Survey: a large, cross-sectional random sample of 8th, 10th, and 12th graders (N = 158,937). Descriptive analyses examined exposure to combustible tobacco and marijuana secondhand smoke by students' asthma status and sociodemographic characteristics. Results: More students with asthma were exposed to combustible tobacco secondhand smoke (13.4 %) and marijuana secondhand smoke (12.0 %) than students without asthma (10.9 % and 9.3 %, respectively). The prevalence of secondhand marijuana smoke exposure was higher among 12th grade students (12.2 %) while the prevalence of secondhand tobacco smoke exposure was higher among 8th grade students (13.4 %) and those who lived in rural locations (15.4 %). Conclusions: California students are exposed to marijuana secondhand smoke at similar proportions to combustible tobacco secondhand smoke and more students with asthma are exposed to marijuana secondhand smoke. These results expand the public health issue of secondhand smoke exposure among children with asthma by highlighting the need to examine marijuana secondhand smoke. Given the rapid shift in marijuana laws across the US, exposure to secondhand marijuana smoke is likely to increase. Therefore, vulnerable populations, such as children with asthma, should be prioritized for interventions that aim to alleviate secondhand marijuana exposure.

Peripheral mast cells derive the effects of acupuncture in Parkinson's disease.

This research investigates the peripheral mechanisms of acupuncture in treating Parkinson's disease (PD), a progressive neurodegenerative disorder marked by motor impairments. While the central mechanisms of acupuncture have been extensively studied, our focus lies in the peripheral mechanisms at the acupoints, the sites of acupuncture signal initiation. Employing a PD model, we analyzed the local responses to acupuncture stimulation at these points. Our key finding was a significant elevation in both the number and activity of mast cells (MCs) in the peripheral tissues following acupuncture. Intriguingly, pre-treatment with an MC stabilizer diminished the acupuncture's therapeutic effects on PD symptoms. Similarly, local anesthesia with lidocaine at the acupoints attenuated the symptom improvement typically observed with acupuncture. Meanwhile, the augmentation of MC activity induced by acupuncture was significantly impeded by cromolyn, an MC stabilizer, but remained unaffected by lidocaine. This finding suggests that MC activity is a more upstream regulator of acupuncture effects compared to nerve conduction. This study provides groundbreaking insights into the initiation and transmission of acupuncture signals, highlighting the significant role of peripheral MC modulation in PD treatment.

Exploring the potential effect of electroacupuncture on cardiovascular function and lipid profiles in spontaneously hypertensive rats.

Background: Investigating the effects of electroacupuncture (EA) treatment on cardiovascular function and aortic lipid profiles in spontaneously hypertensive rats (SHR) constitutes the foundational focus of this study. The overarching goal is to comprehensively elucidate the alterations brought about by EA treatment and to assess its potential as an alternative therapy for hypertension. Methods: Consecutive EA treatments were administered to SHR, and the effects on systolic blood pressure, cardiac function, and hypertension-related neuronal signals were assessed. Aortic lipid profiles in vehicle-treated SHR and EA-treated SHR groups were analyzed using mass spectrometry-based lipid profiling. Additionally, the expression of Cers2 and GNPAT, enzymes involved in the synthesis of specific aortic lipids, was examined. Results: The study demonstrated that consecutive EA treatments restored systolic blood pressure, improved cardiovascular function, and normalized hypertension-related neuronal signals in SHR. Analysis of the aortic lipid profiles revealed distinct differences between the vehicle-treated SHR group and the EA-treated SHR group. Specifically, EA treatment significantly altered the levels of aortic sphingomyelin and phospholipids, including very long-chain fatty acyl-ceramides and ether phosphatidylcholines. These changes in aortic lipid profiles correlated significantly with systolic blood pressure and cardiac function indicators. Furthermore, EA treatment significantly altered the expression of Cers2 and GNPAT. Conclusions: The findings suggest that EA may influence cardiovascular functions and aortic lipid profiles in SHR.

Designing a Placebo Microneedle Stamp: Modeling and Validation in a Clinical Control Trial.

Recently, several clinical studies have been conducted using microneedles (MNs), and various devices have been developed. This study aimed to propose and confirm the feasibility of a placebo control for activating MN clinical research. A 0.5 mm MN stamp with 42 needles was used as a treatment intervention, and a placebo stamp with four acupressure-type needles that did not penetrate was proposed and designed as a control for comparison. First, to check whether the placebo stamp did not invade the skin and to set an appropriate level of pressure to be provided during skin stimulation, two participants were stimulated with five different forces on the forearm, and then the skin was dyed. Secondly, to evaluate the validity of the placebo control group, a blinded study between the MN and placebo stamps was performed on 15 participants. We confirmed that the placebo stamp did not penetrate the skin at any intensity or location. Both types of stamps reported relatively low pain levels, but the MN stamp induced higher pain compared to the placebo stamp. Based on the speculation regarding the type of intervention received, the MN stamp was successfully blinded (random guess), whereas the placebo stamp was unblinded. However, according to a subgroup analysis, it was confirmed that the group with low skin sensitivity was completely blind. Blinding the placebo MN stamp had limited success in participants with low skin sensitivity. Future research on suitable placebo controls, considering the variations in MN stamp length and needle count, is warranted.

The vital role of exercise and nutrition in COVID-19 rehabilitation: synergizing strength.

Since the outset of the COVID-19 pandemic, the global healthcare community has faced the challenge of understanding and addressing the ongoing and multi-faceted SARS-CoV-2 infection outcomes. As millions of individuals worldwide continue to navigate the complexities of post-hospitalization recovery, reinfection rates, and the increasing prevalence of Long-COVID symptoms, comprehensive COVID-19 rehabilitation strategies are greatly needed. Previous studies have highlighted the potential synergy between exercise and nutrition, suggesting that their integration into patient rehabilitation programs may yield improved clinical outcomes for survivors of COVID-19. Our group aimed to consolidate existing knowledge following the implementation of patient, intervention, comparison, and outcome (PICO) search strategies on the distinct and combined impacts of exercise and nutrition interventions in facilitating the recovery of COVID-19 patients following hospitalization, with a specific focus on their implications for both public health and clinical practice. The incorporation of targeted nutritional strategies alongside exercise-based programs may expedite patient recovery, ultimately promoting independence in performing activities of daily living (ADLs). Nonetheless, an imperative for expanded scientific inquiry remains, particularly in the realm of combined interventions. This mini-review underscores the compelling prospects offered by an amalgamated approach, advocating for the seamless integration of exercise and nutrition as integral components of post-hospitalization COVID-19 rehabilitation. The pursuit of a comprehensive understanding of the synergistic effects and effectiveness of exercise and nutrition stands as a crucial objective in advancing patient care and refining recovery strategies in the wake of this enduring global health crisis.

Warm needle acupuncture for osteoarthritis: A systematic review and meta-analysis.

BACKGROUND: Warm needle acupuncture (WA) is considered a potential intervention in the treatment of osteoarthritis (OA). PURPOSE: To systematically evaluate the clinical efficacy and safety of WA in the treatment of OA. STUDY DESIGN: Systematic review and meta-analysis METHODS: Fourteen databases were searched from their inception until May 2022. Randomized controlled trials (RCTs) of WA for treating OA were identified. Study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation program were used to assess all included RCTs. RESULTS: A total of 66 RCTs met the inclusion criteria for this review. Most of the included studies had an unclear risk of bias, and the certainty of the evidence was very low. Twenty-four RCTs compared the effects of WA with those of oral drug therapies. Meta-analysis showed superior effects of WA for the total effective rate (risk ratio (RR): 1.22, 95% confidence interval (CI): 1.17 to 1.27, I2 = 26%, p < 0.001, 24 studies, n = 2278), pain, and function. Eight RCTs compared the effects of WA+drug therapy, and meta-analysis showed favorable effects for the total effective rate (RR: 1.27, 95% CI: 1.18 to 1.35, I2 =0%, p < 0.001, 8 studies, n = 646). Eight RCTs compared the effects of WA and intra-articular sodium hyaluronate (IASH) injection on OA and found equivalent effects of WA on the symptoms of OA. Twenty-eight RCTs compared the effects of WA+IASH injection with those of IASH injection, and meta-analysis showed superior effects of WA+IASH in terms of the total effective rate (RR: 1.15, 95% CI: 1.11 to 1.19, I2 =27.3%, p < 0.001, 25 studies, n = 2208), pain, and function. None of the RCTs reported serious adverse events. CONCLUSIONS: WA may have some distinct advantages in the treatment of OA. However, well-designed RCTs with larger sample sizes are needed.

Scoping review of the medicinal effects of Eupolyphaga sinensis Walker and the underlying mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Eupolyphaga sinensis Walker (ES) is an insect widely used in traditional East Asian medicine known to exhibit clinical effects on various pathological conditions. Overall, ES is a useful medicinal insect that can treat various diseases, including cancer and immune diseases. However, further mechanistic studies based on its therapeutic effects in clinical settings are required. AIM OF THE STUDY: We aimed to evaluate the current research landscape and diseases associated with ES to synthesize the clinical value of ES based on the associated diseases and underlying therapeutic mechanisms. MATERIALS AND METHODS: Embase and PubMed databases were searched for experimental studies that evaluated the therapeutic efficacy or underlying mechanisms of ES until May 2021. The evidence for each study was summarized using a narrative synthesis approach. Studies on extracted or dried whole ES and ES-derived compounds were quantitatively analyzed by year and disease type. Meanwhile, the overall research trend was confirmed for studies on ES-containing prescriptions by visualizing the disease type analysis. RESULTS: A total of 151 studies were identified, of which 51 were included in our review. There were 14 studies on extracted or dried whole ES, 15 on ES-derived compounds, and 22 on ES-containing prescriptions. ES was most commonly used for cancer-related diseases, followed by those related to endocrine function and immunity. ES regulates the cell cycle, tumor suppressor genes and proteins, immune-related biomarkers, and antioxidant molecules. CONCLUSIONS: Overall, ES is a beneficial medicinal insect that can treat various diseases, including cancer and immune diseases. However, further mechanistic studies based on its therapeutic effects in clinical settings are required.

Changes of local microenvironment and systemic immunity after acupuncture stimulation during inflammation: A literature review of animal studies.

An increasing number of studies have demonstrated the underlying mechanisms by which acupuncture therapy mediates both local and systemic immunomodulation. However, the connection between alterations in the local microenvironment and the resulting change in systemic immunity remains unclear. In this review, we focus on cell-specific changes in local immune responses following acupuncture stimulation and their link to systemic immune modulation. We have gathered the most recent evidence for chemo- and mechano-reactive changes in endothelial cells, neutrophils, macrophages, and mast cells in response to acupuncture. Local signaling is then related to the activation of systemic neuro-immunity including the cholinergic, adrenal, and splenic nervous systems and pain-related neuromodulation. This review aims to serve as a reference for further research in this field.

In-home cannabis smoking more prevalent than in-home tobacco smoking among 2019 Global Drug Survey respondents.

PURPOSE OF THE RESEARCH: Early evidence from studies of home smoking policies suggests that in-home cannabis smoking is more often allowed than in-home tobacco smoking, but there are not yet data on whether cannabis is more often smoked in the home compared to tobacco, or whether in-home cannabis and tobacco smoking differs by usage status. Using cross-sectional data from over 100,000 sentinel drug users from 17 countries, we compared cannabis and tobacco smoking in the homes of Global Drug Survey 2019 respondents who currently used cannabis only, tobacco only, both tobacco and cannabis, or neither. PRINCIPAL RESULTS: Complete data on cannabis and tobacco use and in-home smoking were available for 107,272 adults (average age = 30 ± 12, 34% women, countries with the three highest response rates; Germany = 32%, USA = 10%, New Zealand = 9%). In total, 53.6% and 50.6% of respondents reported past-year cannabis and tobacco smoking in their home respectively. Stratifying respondents into current cannabis-only users, tobacco-only users, dual users, and non-users, past-year in-home cannabis smoking was more prevalent (78.8%) among cannabis-only users than was in-home tobacco smoking (67.9%) among tobacco-only users. Among dual users, past-year in-home cannabis smoking (82.8%; 95%CI = 80%-86%) was higher than in-home tobacco smoking (75.9%; 95%CI = 69%-81%; p < 0.001). In-home cannabis and tobacco smoking was similar among non-users (20.2% and 20.5%, respectively). MAJOR CONCLUSIONS: Past-year in-home cannabis smoking was more prevalent than tobacco smoking in the homes of participants who used cannabis and/or tobacco, supporting our speculation that in-home cannabis smoking might be more socially acceptable than in-home tobacco smoking.

Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression, pain, and fatigue behaviors and its underlying mechanisms. Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression, pain, and fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal hypersensitivity, and fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and transforming growth factor ß (TGF-ß) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased tyrosine hydroxylase (TH) expression and the levels of dopamine and serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related mRNA expression in the spleen and liver. In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-ß expression in the brain, as well as anti-inflammatory and anti-oxidant mechanisms in internal organs.

A scoping review on biomedical journal peer review guides for reviewers.

BACKGROUND: Peer review is widely used in academic fields to assess a manuscript's significance and to improve its quality for publication. This scoping review will assess existing peer review guidelines and/or checklists intended for reviewers of biomedical journals and provide an overview on the review guidelines. METHODS: PubMed, Embase, and Allied and Complementary Medicine (AMED) databases were searched for review guidelines from the date of inception until February 19, 2021. There was no date restriction nor article type restriction. In addition to the database search, websites of journal publishers and non-publishers were additionally hand-searched. RESULTS: Of 14,633 database publication records and 24 website records, 65 publications and 14 websites met inclusion criteria for the review (78 records in total). From the included records, a total of 1,811 checklist items were identified. The items related to Methods, Results, and Discussion were found to be the highly discussed in reviewer guidelines. CONCLUSION: This review identified existing literature on peer review guidelines and provided an overview of the current state of peer review guides. Review guidelines were varying by journals and publishers. This calls for more research to determine the need to use uniform review standards for transparent and standardized peer review. PROTOCOL REGISTRATION: The protocol for this study has been registered at Research Registry (www.researchregistry.com): reviewregistry881.

Peripheral ERK modulates acupuncture-induced brain neural activity and its functional connectivity.

Acupuncture has been widely used as a therapeutic intervention, and the brain network plays a crucial role in its neural mechanism. This study aimed to investigate the acupuncture mechanism from peripheral to central by identifying how the peripheral molecular signals induced by acupuncture affect the brain neural responses and its functional connectivity. We confirmed that peripheral ERK activation by acupuncture plays a role in initiating acupuncture-induced peripheral proteomic changes in mice. The brain neural activities in the neocortex, hippocampus, thalamus, hypothalamus, periaqueductal grey, and nucleus of the solitary tract (Sol) were significantly changed after acupuncture, and these were altered by peripheral MEK/MAPK inhibition. The arcuate nucleus and lateral hypothalamus were the most affected by acupuncture and peripheral MEK/MAPK inhibition. The hypothalamic area was the most contributing brain region in contrast task PLS analysis. Acupuncture provoked extensive changes in brain functional connectivity, and the posterior hypothalamus showed the highest betweenness centrality after acupuncture. After brain hub identification, the Sol and cingulate cortex were selected as hub regions that reflect both degree and betweenness centrality after acupuncture. These results suggest that acupuncture activates brain functional connectivity and that peripheral ERK induced by acupuncture plays a role in initiating brain neural activation and its functional connectivity.

Lipidomics reveals that acupuncture modulates the lipid metabolism and inflammatory interaction in a mouse model of depression.

Depression is a serious disease that has considerable impact on lipid metabolism and inflammatory responses. Recent studies have shown that leptin, which is well known as a mediator of energy homeostasis and is a cytokine in inflammatory response, plays an important role in depression. Acupuncture is widely used to treat depression; however, the underlying mechanisms and the effect of acupuncture on depression remain poorly understood. In this study, we utilized the chronic restraint stress (CRS) induced depression model and acupuncture treatment was performed at KI10, LR8, LU8, LR4 (AP) or non-acupoint (NP). Then, lipidomics was applied to investigate the effects of acupuncture on lipid metabolism and analyze leptin signals in the brain and changes of immune markers. Acupuncture treatment at AP improved depression-like behavior in an open-field test, forced swimming test, and marble burying test. Concurrently, CRS mice treated with AP acupuncture (CRS + AP) had significantly lower levels of aspartate aminotransaminase (AST, liver injury markers) and exhibited different lipid patterns in liver lipidomic profiles. In particular, triglycerides (TGs) contributed the change of lipid patterns. Compared to the CRS mice, TGs with relatively high degrees of unsaturated fatty acids increased in the CRS + AP mice, but did not change in CRS mice treated with NP acupuncture (CRS + NP). The levels of leptin in plasma and leptin receptor positive cells in the brain (hypothalamus and hippocampus) decreased and increased, respectively, in the CRS + AP mice, while opposite patterns were exhibited in the CRS and CRS + NP mice. These results indicated that acupuncture treatment at AP attenuated leptin insensitivity in CRS mice. Additionally, expression of pro-inflammatory cytokines such as interleukin-1 beta and tumor necrosis factor-alpha were decreased in the spleen, plasma, and liver of CRS + AP mice, which was one of results of alleviation of leptin resistance. In conclusion, these results show that AP acupuncture treatment effectively alleviated the depression-like behavior, affected immune responses, and altered hepatic lipid metabolism through the attenuation of leptin insensitivity.

The Current Status of Clinical Research Involving Microneedles: A Systematic Review.

In recent years, a number of clinical trials have been published on the efficacy and safety of drug delivery using microneedles (MNs). This review aims to systematically summarize and analyze the current evidence including the clinical effect and safety of MNs. Three electronic databases, including PubMed, were used to search the literature for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that evaluated the therapeutic efficacy of MNs from their inception to 28 June 2018. Data were extracted according to the characteristics of study subjects; disorder, types, and details of the intervention (MNs) and control groups; outcome measurements; effectiveness; and incidence of adverse events (AEs). Overall, 31 RCTs and seven CCTs met the inclusion criteria. Although MNs were commonly used in skin-related studies, evaluating the effects of MNs was difficult because many studies did not provide adequate comparison values between groups. For osteoporosis treatment, vaccine, and insulin delivery studies, MNs were comparable to or more effective than the gold standard. Regarding the safety of MNs, most AEs reported in each study were minor (grade 1 or 2). A well-designed RCT is necessary to clearly evaluate the effectiveness of MNs in the future.

Muscovite nanoparticles mitigate neuropathic pain by modulating the inflammatory response and neuroglial activation in the spinal cord.

Despite numerous efforts to overcome neuropathic pain, various pharmacological drugs often fail to meet the needs and have many side effects. Muscovite is an aluminosilicate mineral that has been reported to have an anti-inflammatory effect, but the efficacy of muscovite for neuropathic pain has not been investigated. Here, we assessed whether muscovite nanoparticles can reduce the symptoms of pain by controlling the inflammatory process observed in neuropathic pain. The analgesic effects of muscovite nanoparticles were explored using partial sciatic nerve ligation model of neuropathic pain, in which one-third to one-half of the nerve trifurcation of the sciatic nerve was tightly tied to the dorsal side. Muscovite nanoparticles (4 mg/100 µL) was given intramuscularly to evaluate its effects on neuropathic pain (3 days per week for 4 weeks). The results showed that the muscovite nanoparticle injections significantly alleviated partial sciatic nerve ligation-induced mechanical and cold allodynia. In the spinal cord, the muscovite nanoparticle injections exhibited inhibitory effects on astrocyte and microglia activation and reduced the expression of pro-inflammatory cytokines, such as interleukin-1ß, tumor necrosis factor-α, interleiukin-6 and monocyte chemoattractant protein-1, which were upregulated in the partial sciatic nerve ligation model. Moreover, the muscovite nanoparticle injections resulted in a decrease in activating transcription factor 3, a neuronal injury marker, in the sciatic nerve. These results suggest that the analgesic effects of muscovite nanoparticle on partial sciatic nerve ligation-induced neuropathic pain may result from inhibiting activation of astrocytes and microglia as well as pro-inflammatory cytokines. We propose that muscovite nanoparticle is a potential anti-nociceptive candidate for neuropathic pain. All experimental protocols in this study were approved by the Institutional Animal Ethics Committee (IACUC) at Dongguk University, South Korea (approval No. 2017-022-1) on September 28, 2017.

Anti-Inflammatory Effects of Modified Buyang Huanwu Decoction.

METHODS: A cytotoxicity assay for BHD was performed using the MTT assay. Following treatment with BHD, mBHD-1, and mBHD-2 in the presence of lipopolysaccharide (LPS), nitric oxide (NO) secretion was detected in cell supernatants using a NO detection kit. The expression of proinflammatory mediators was detected using RT-PCR and western blotting. To verify the mechanism of mBHD, specific inhibitors of JNK (SP600125) or p38 (SB203580) were used for co-treatment with mBHD, and then the changes in NO and nitric oxide synthase (iNOS) were measured. RESULTS: Both mBHD-1 and mBHD-2 showed greater anti-inflammatory effects than BHD. Both mBHD-1 and mBHD-2 inhibited NO secretion and decreased the expression of IL-1ß, IL-6, TNF-α, and iNOS. Treatment with a p38 inhibitor and a JNK inhibitor in mBHD-1- and mBHD-2-treated cells resulted in inhibition of NO and iNOS. CONCLUSION: We provided the first experimental evidence that mBHD may be a more useful anti-inflammatory than BHD. High concentrations or long-term use of BHD may be harmful to inflammatory status. Therefore, the length of treatment and concentration should be considered depending on the targeted disease.