Blood sphingolipid as a novel biomarker in patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Sphingolipids are signaling molecules and structural components of the axolemma and myelin sheath. Plasma sphingolipid levels may reflect disease status of neuromyelitis optica spectrum disorder (NMOSD). We aimed to examine plasma sphingolipids as disease severity biomarkers for NMOSD and compare their characteristics with those of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). METHODS: We measured plasma sphingolipids, sNfL, and sGFAP levels in NMOSD cases with anti-aquaporin-4-antibody. An unbiased approach, partial least square discriminant analysis (PLS-DA), was utilized to determine whether sphingolipid profiles differ according to the disease state of NMOSD (presence, moderate-to-severe disability [Expanded Disease Severity Scale, (EDSS) > 3.0], and relapses). RESULTS: We investigated 81 patients and 10 controls. PLS-DA models utilizing sphingolipids successfully differentiated patients with EDSS > 3.0, but failed to identify the presence of disease and relapses. Ceramide-C14-a significant contributor to differentiating EDSS > 3.0-positively correlated with EDSS, while its levels were independent of age and the presence of relapses. This characteristic was unique from those of sNfL and sGFAP, which were affected by age and relapses as well as EDSS. CONCLUSION: Plasma sphingolipids may be useful NMOSD biomarkers for disability with distinct characteristics compared to sNfL and sGFAP.

Pro-Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property.

OBJECTIVES: Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation. METHODS: This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations. RESULTS: Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45-37.31), multiple CMB (3.00, 1.34-6.71), and absence of temporopolar lesions (4.91, 2.29-10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83-35.89), multiple CMB (1.90, 1.01-3.56), and absence of temporopolar lesions (2.32, 1.08-4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations. INTERPRETATION: NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040-1054.

The Effectiveness and Safety of Chuna Manual Therapy Adjuvant to Western Medicine in Patients with Chronic Obstructive Pulmonary Disease: A Randomized, Single-Blind, Investigator-Initiated, Pilot Trial.

Recently, non-pharmacological treatments are gaining increasing importance for improving the quality of life in patients with chronic obstructive pulmonary disease (COPD). This pilot study aimed to evaluate the feasibility of conducting extensive research on Chuna manual therapy (CMT). This study investigated the effectiveness and safety of CMT adjuvant to Western medicine (WM) in patients with COPD. Forty patients with COPD were randomized into two groups in a 1:1 ratio: experimental (CMT plus WM) and control (WM only) groups. The CMT intervention was administered once a week for eight weeks. The primary outcome measured was the 6-min walk distance (6MWD). Secondary outcomes measured were: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), assessments using the modified Medical Research Council (mMRC) scale and Visual Analog Scale (VAS) for dyspnea, the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), and the EuroQoL five-dimensional questionnaire (EQ-5D). The mean differences in FEV1 (L) between Weeks 1 and 8 were statistically significant between the groups (p = 0.039). Additionally, the experimental group showed improved 6MWD, mMRC, VAS for dyspnea, CAT, SGRQ (total), and EQ-VAS scores than the control group. However, the differences between the two groups were not statistically significant. No adverse events were observed during this trial. CMT has the potential to alleviate symptoms, improve quality of life, and delay the decline in lung function in patients with COPD. The results of this pilot study could lead to large-scale clinical trials in the future.

Time Window for Induced Hypertension in Acute Small Vessel Occlusive Stroke With Early Neurological Deterioration.

BACKGROUND: Therapeutic-induced hypertension treatment (iHTN) is helpful for alleviating early neurological deterioration (END) in acute small vessel occlusive stroke. We examined the time parameters related to iHTN effectiveness in these patients. METHODS: We retrospectively reviewed patients with acute small vessel occlusive stroke who underwent iHTN for END, defined as an increase of ≥2 points in total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 point in motor items of NIHSS. The primary outcome was an early neurological improvement (ENI; a decrease of ≥2 points in total NIHSS score or ≥1 point in motor items of NIHSS), and the secondary outcome was any neurological improvement (a decrease of ≥1 point in the total NIHSS score). We conducted a multivariable logistic regression analysis, adjusting for demographics, risk factors, baseline clinical status, and intervention-related variables. We also generated a restricted cubic spline curve for the END-to-iHTN time cutoff. RESULTS: Among the 1062 patients with small vessel occlusive stroke screened between 2017 and 2021, 136 patients who received iHTN within 24 hours from END were included. The mean age was 65.1 (±12.0) years, and 61.0% were male. Sixty-five (47.8%) patients showed ENI and 77 (56.6%) patients showed any neurological improvement. END-to-iHTN time was significantly shorter in patients with ENI (150 [49-322] versus 290 [97-545] minutes; P=0.018) or any neurological improvement (150 [50-315] versus 300 [130-573] minutes; P=0.002). A 10-minute increase in the time between END and iHTN decreased the odds of achieving ENI (odds ratio, 0.984 [95% CI, 0.970-0.997]; P=0.019) or any neurological improvement (odds ratio, 0.978 [95% CI, 0.964-0.992]; P=0.002). The restricted cubic spline curve showed that the odds ratio of ENI reached its minimum at ≈3 hours. CONCLUSIONS: Among patients with small vessel occlusive stroke with END, a shorter interval between END and the initiation of iHTN was associated with increased odds of achieving neurological improvement. The efficacy of iHTN may be limited to induction within the first 3 hours of END.

Disease characteristics of idiopathic transverse myelitis with serum neuronal and astroglial damage biomarkers.

Despite its close association with CNS inflammatory demyelinating disorders (CIDDs), pathogenic characteristics of idiopathic transverse myelitis (ITM) remain largely unknown. Here, we investigated serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) in patients with ITM to unravel the disease characteristics of ITM. We prospectively recruited 70 patients with ITM, 62 with AQP4 + NMOSD and 85 with RRMS-including 31 patients with acute TM attacks-along with 30 HCs. We measured sNfL and sGFAP levels using single-molecular arrays and compared these levels per lesion volume between the disease groups during attacks. Compared to HCs, ITM patients showed higher sNfL and sGFAP during acute attacks (sNfL: p < 0.001, sGFAP: p = 0.024), while those in remission (sNfL: p = 0.944, sGFAP: p > 0.999) did not, regardless of lesion extents and presence of multiple attacks. ITM patients demonstrated lower sGFAP/volume (p = 0.011) during acute attacks and lower sGFAP (p < 0.001) in remission compared to AQP4 + NMOSD patients. These findings suggest that both neuronal and astroglial damages occur in patients with acute ITM attacks at a similar level to those with RRMS, distinct from AQP4 + NMOSD. However, active neuroinflammatory process was not remarkable during remission in this cohort.

Therapeutic Potential of Chungsangboha-tang for the Treatment of Asthma: A Review of Preclinical and Clinical Studies.

In traditional Korean medicine, Chungsangboha-tang (CSBHT) and its modified forms are used to treat various respiratory disorders, including asthma. This study aimed to identify research trends, clarify the effectiveness of CSBHT and related prescriptions, and lay a foundation for future research. We conducted a literature review using PubMed, Embase, Google Scholar, Oriental Medicine Advanced Searching Integrated System, National Digital Science Links, Korean Medical Database, Wanfang Data, and Chinese National Knowledge Infrastructure databases. We analyzed 25 studies, including 5 in vitro studies, 6 animal studies, and 14 human studies. Many studies evaluated the efficacy of CSBHT and its related prescriptions, including experimental studies on its effectiveness in asthma. The main mechanism of action involves the anti-inflammatory effect caused by the regulation of various immune cells, cytokines, and chemokines. In addition, clinical trials on asthma reported the benefits of CSBHT and its related prescriptions. However, there has been no randomized controlled study of clinical trials on the clinical effectiveness of CSBHT in asthma. Therefore, large-scale randomized controlled studies should be conducted in the future.

Rosa laevigata Attenuates Allergic Asthma Exacerbated by Water-Soluble PM by Downregulating the MAPK Pathway.

Exposure to water-soluble particulate matter (WPM) containing heavy metals can cause severe inflammatory responses and trigger and exacerbate the onset of asthma. As a follow-up study of Rosa laevigata (RL), this study analyzed the therapeutic effects and mechanisms of oral and intratracheal administration of RL and demonstrated anti-inflammatory effects in asthma models. Worse T-helper cell type 2 (Th2)-related inflammatory and pro-inflammatory responses were observed after simultaneous challenge with ovalbumin (OVA) and WPM. To establish a model of asthma exacerbated by WPM, BALB/c mice were sensitized with OVA + aluminum hydroxide and challenged with OVA + WPM. To confirm the therapeutic efficacy of RL, it was administered both orally and intratracheally. Histopathological analysis of H&E staining confirmed that oral and intratracheal administration of RL alleviated inflammatory cell infiltration in the airways aggravated by OVA + WPM. RL effectively reduced the number of inflammatory cells obtained from the bronchoalveolar lavage fluid. In addition, enzyme-linked immunosorbent assay (ELISA) and multiplex analysis of serum samples confirmed that the administration of RL reduced the levels of immuno-globulin E (IgE), Th2-related cytokines, and pro-inflammatory cytokines. Furthermore, real-time PCR analysis of lung tissue samples confirmed that the release of MUC5AC (Mucin 5AC, Oligomeric Mucus/Gel-Forming) and pro-inflammatory cytokines was reduced by RL, and western blotting confirmed that the administration of RL reduced the phosphorylation of ERK and p38 in the MAPK pathway. In conclusion, oral and intratracheal administration of RL appears to have an anti-asthmatic effect by reducing the secretion of Th2-related cytokines, pro-inflammatory cytokines, and IgE by downregulating the MAPK pathway. Thus, RL has further demonstrated potential for development as an oral and inhaled therapeutic for asthma symptoms exacerbated by WPM exposure.

Efficacy and Safety of Ojeok-San Plus Saengmaek-San for Gastroesophageal Reflux-Induced Chronic Cough: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial.

Introduction: Gastroesophageal reflux-induced chronic cough (GERC) is one of the most common etiologies of chronic cough. Despite the growing prevalence and interest in GERC, no effective treatment is currently available. In our study, we used a combination of herbal medicines, Ojeok-san (OJS) plus Saengmaek-san (SMS), for the treatment of GERC. Methods: We conducted a pilot, randomized, placebo-controlled, parallel-arm, single-center clinical trial to assess the feasibility of our study protocol, as our study is the first herbal medicine trial for GERC. All enrolled participants were randomly assigned to either the intervention or placebo group in a 1:1 ratio and were administered trial drugs three times a day for 6 weeks, with an evaluation visit performed every 2 weeks for their efficacy and safety assessment until the follow-up visit (week 8). We evaluated the severity and frequency of cough, cough-specific quality of life, airway hypersensitivity, and reflux-related gastrointestinal symptoms, as well as pattern identification, to investigate the complex mechanisms of reflux cough syndrome. Results: A total of 30 participants were enrolled, and 25 completed the study at Kyung Hee University Korean Medicine Hospital from 26 December 2018 to 31 May 2021. OJS plus SMS significantly improved the cough diary score (CDS), cough visual analog scale, Korean version of the Leicester Cough Questionnaire, Hull Airway Reflux Questionnaire, and Gastrointestinal Symptom Rating Scale after the treatment compared to the baseline. Notably, OJS plus SMS showed significant efficacy in the daytime and total CDS compared with the placebo. Only one adverse event was observed during the trial, and no serious adverse events occurred. Additionally, we achieved successful results in feasibility outcomes by exceeding the ratio of 80%. Conclusion: We confirmed the feasibility of our trial design and demonstrated the potential of OJS plus SMS in relieving the severity of cough and GI symptoms in GERC patients with safe and successful feasibility results. We anticipate that our study results will be used as the basis for further large-scale, well-designed, confirmatory trials to evaluate the safety and efficacy of OJS plus SMS in GERC. Clinical Trial Registration: [https://cris.nih.go.kr], identifier WHO International Clinical Trials Registry Platform, Clinical Research Information Service [KCT0003115].

Herbal Medicine Compared to Placebo for Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by irreversible airflow limitation. Many COPD patients use complementary and alternative modalities, including herbal medicines (HMs). This systematic review investigated the effectiveness and safety of HM in managing COPD symptoms compared to placebo. Nine electronic databases were searched to identify relevant randomized controlled trials (RCTs) up to February 12, 2021. The Cochrane risk of bias tool was used to assess the methodological qualities of the included studies. Primary outcomes were lung function parameters and exercise capacity. A meta-analysis was conducted to determine the effect size for homogeneous outcomes. Fourteen studies were included. There was low to very low quality evidence that HM significantly improved forced expiratory volume in 1 â€Šs (FEV1) (L), FEV1 (%) and 6-minute walk distance, as well as moderate quality evidence that HM significantly improved forced vital capacity (FVC) (L) compared to placebo. However, according to low quality evidence, there was no significant difference in FEV1/FVC (%) or vital capacity (L) between the groups. Low to moderate evidence suggests that HM has the potential to help improve some respiratory functions, COPD symptoms, and some aspects of quality of life in COPD patients compared to placebo. However, these findings are challenged by the poor methodological quality of the included studies, the heterogeneity of HMs used, and potential publication bias. Therefore, the findings could be significantly influenced by further larger, more rigorous RCTs on this topic. Moreover, it may also be recommended to develop standardized HMs focused on some individual herbs that are frequently used or expected to play an important role in patients with COPD, and to elucidate the underlying mechanisms.

Comparative Effectiveness of Western and Eastern Manual Therapies for Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Manual therapy (MT) is considered a promising adjuvant therapy for chronic obstructive pulmonary disease (COPD). Comparing the effectiveness among different Western and Eastern MTs being used for the management of COPD could potentially facilitate individualized management of COPD. This systematic review attempted to estimate the comparative effectiveness of Western and Eastern MTs for COPD patients using a network meta-analysis (NMA) methodology. METHODS: Nine electronic databases were comprehensively searched for relevant randomized controlled trials (RCTs) published up to February 2021. Pair-wise meta-analysis and NMA were conducted on the outcomes of COPD, which included lung function and exercise capacity. RESULTS: The NMA results from 30 included RCTs indicated that the optimal treatment for each outcome according to the surface under the cumulative ranking curve was massage, acupressure, massage, and tuina for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and 6 min walking distance, respectively. CONCLUSIONS: MTs such as massage, acupressure, and tuina have shown comparative benefits for lung function and exercise capacity in COPD. However, the methodological quality of the included studies was poor, and the head-to-head trial comparing the effects of different types of MTs for COPD patients was insufficient. Therefore, further high-quality RCTs are essential.

The effectiveness and safety of Chuna manual therapy adjuvant to Western medicine in patients with chronic obstructive pulmonary disease: Study protocol for a randomized, single-blind, investigator-initiated, pilot trial.

BACKGROUND: In chronic obstructive pulmonary disease (COPD) management, greater emphasis has been placed on symptomatic improvement and enhanced quality of life in patients. Manual therapy among respiratory rehabilitation programs has received much attention recently, with the publication of numerous studies. In South Korea, a method known as Chuna Manual Therapy (CMT) has been applied in the management of COPD patients and in clinical practice, but the clinical basis for safety and effectiveness is yet to be established. Therefore, rigorously designed randomized controlled trials are required. We aimed to evaluate the feasibility of assessing the add-on effect and safety of CMT administered with standard Western medicine therapy for the treatment of COPD. METHODS: This is a randomized, single-blind, single-center clinical pilot trial. Patients with COPD receiving standard drug therapy are randomly divided into an experimental group (n = 20) and a control group (n = 20) at a 1:1 ratio. The experimental group receives CMT adding to the standard medical therapy once a week for 8 weeks. The control group receives only the standard drug treatment. The trial is conducted with an outcome assessor and statistician blinding. The primary outcome is the 6-minute walk test. The secondary outcomes include the pulmonary function test, the Modified Medical Research Council, visual analog scale for dyspnea, COPD assessment test, quality of life using the St. George's respiratory questionnaire, EuroQOL five dimensions questionnaire, and Korean pattern identification questionnaire. Adverse events are also be evaluated. CONCLUSIONS: The results of this study will provide the feasibility of a large-scale clinical trial to establish high-quality clinical evidence of CMT for COPD. TRIAL REGISTRATION: Korean Clinical Trial Registry (http://cris.nih.go.kr; registration number: KCT0006119).

Gancaonin N from Glycyrrhiza uralensis Attenuates the Inflammatory Response by Downregulating the NF-κB/MAPK Pathway on an Acute Pneumonia In Vitro Model.

Acute pneumonia is an inflammatory disease caused by several pathogens, with symptoms such as fever and chest pain, to which children are particularly vulnerable. Gancaonin N is a prenylated isoflavone of Glycyrrhiza uralensis that has been used in the treatment of various diseases in oriental medicine. There are little data on the anti-inflammatory efficacy of Gancaonin N, and its effects and mechanisms on acute pneumonia are unknown. Therefore, this study was conducted as a preliminary analysis of the anti-inflammatory effect of Gancaonin N in lipopolysaccharide (LPS)-induced RAW264.7 cells, and to identify its preventive effect on the lung inflammatory response and the molecular mechanisms underlying it. In this study, Gancaonin N inhibited the production of NO and PGE2 in LPS-induced RAW264.7 cells and significantly reduced the expression of iNOS and COX-2 proteins at non-cytotoxic concentrations. In addition, in LPS-induced A549 cells, Gancaonin N significantly reduced the expression of COX-2 and pro-inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6. Moreover, Gancaonin N reduced MAPK signaling pathway phosphorylation and NF-κB nuclear translocation. Therefore, Gancaonin N relieved the inflammatory response by inactivating the MAPK and NF-κB signaling pathways; thus, it is a potential natural anti-inflammatory agent that can be used in the treatment of acute pneumonia.

The efficacy of manual therapy for chronic obstructive pulmonary disease: A systematic review.

BACKGROUND: Manual therapy (MT) can be beneficial in the management of chronic obstructive pulmonary disease (COPD). However, evidence of the efficacy of MT for COPD is not clear. Therefore, we aimed to review the effects of MT, including Chuna, in people diagnosed with COPD. METHODS: MEDLINE via PubMed, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Database (CNKI), KoreaMed, Korean Medical Database (KMbase), and Oriental Medicine Advanced Searching Integrated System (OASIS) were searched. Randomized controlled trials (RCTs) and crossover RCTs were included. The main inclusion criteria were COPD diagnosis (forced expiratory volume in the first second [FEV1]/forced vital capacity [FVC] < 0.70). The primary outcomes were lung function and exercise capacity. The secondary outcomes were symptoms, quality of life (QoL), and adverse event (AE)s. Studies reporting one or both of the primary outcomes were included. The Cochrane RoB 2.0 tool was used to assess the risk of bias. Data synthesis and analysis were conducted according to the trial design. RESULTS: Of the 2564 searched articles, 13 studies were included. For the primary outcomes, the effect of MT on pulmonary function and exercise capacity in COPD was partly significant but could not be confirmed due to the limited number of studies included in the subgroups. For the secondary outcomes, no definitive evidence regarding the improvement of symptoms and QoL was found, and some minor adverse effects were reported. CONCLUSIONS: There is insufficient evidence to support the role of MT in the management of COPD. High-quality studies are needed to thoroughly evaluate the effect of MT on COPD.

Effect of antiviral therapy in patients with low HBV DNA level on transarterial chemoembolization for hepatocellular carcinoma.

Antiviral therapy improves survival in patients with hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). However, the effect of antiviral therapy in patients with low-level viremia HBV-HCC receiving non-curative therapy remains unclear. We aimed to evaluate the role of antiviral therapy in patients with low-level viremia and treated with transarterial chemoembolization (TACE). This retrospective study evaluated 206 patients with HBV-HCC who underwent TACE as an initial treatment. Of those, 135 patients received antiviral therapy (antiviral group), and 71 did not (non-antiviral group). The definition of low-level viremia was an HBV DNA level <2000 IU/ml. Kaplan-Meier curves, log-rank tests and Cox regression analysis were used for statistical analyses. The median follow-up duration was 39 months (1-174 months). Overall survival (OS) did not differ between groups (P = .227). Barcelona Clinic Liver Cancer stage (BCLC), Child-Pugh (CP) class and α-fetoprotein level were independent prognostic factors for OS. Antiviral therapy (hazard ratio [HR], 0.503, P = .022) was a prognostic factor for 2-year survival. On subgroup analysis, antiviral therapy improved short-term survival in patients with BCLC stage 0 and A (P = .037) and CP class A (P = .04). In patients with low-level viremia, antiviral therapy yielded short-term survival benefits, particularly in patients with early-stage HCC.

Effectiveness and safety of herbal medicine for cancer-related fatigue in lung cancer survivors: A systematic review and meta-analysis.

Approximately half of lung cancer patients (LCP) receiving chemotherapy are experiencing cancer-related fatigue (CRF). In East Asia, herbal medicines (HMs) have been used as tonics due to their anti-fatigue effect. This systematic review evaluated the effectiveness and safety of HMs for CRF in LCP. We comprehensively searched 12 electronic medical databases to search randomized controlled trials (RCTs) and quasi-RCTs investigating HMs for CRF in LCP, published up to September 2019. The primary outcome was the fatigue severity. Secondary outcomes included patients' quality of life (QOL), activities of daily life (ADL), and incidence of adverse events. Cochrane's risk of bias tool assessed the methodological quality of included RCTs. The risk ratio or mean difference was estimated with 95% confidence intervals by performing a meta-analysis. Twelve RCTs with 861 participants were included. Compared to conventional medicine alone, HM combined with conventional medicine significantly improved fatigue level, QOL, and ADL. As monotherapy, HM significantly improved ADL compared with megestrol. No serious HM-related adverse events were reported. Limited evidence suggests that HM could be effective and safe for CRF in LCP. However, further high-quality RCTs are needed to confirm these findings owing to the small number and low methodological quality of the included studies.

Effect of Rosa laevigata on PM10-Induced Inflammatory Response of Human Lung Epithelial Cells.

Particulate matter 10 (PM10) with a diameter of less than 10 mm causes inflammation and allergic reactions in the airways and lungs, which adversely affects asthmatic patients. In this study, we examined the anti-inflammatory effects of Rosa laevigata (RL), which has been previously investigated medicinally in Korea and China for the discovery of plant-derived anti-inflammatory agents with low side effects, using a PM10-induced lung inflammatory disease model. Using MTT assay, we confirmed that in A549 cells pretreated with RL, cytotoxicity induced by PM10 (100 µg/mL) exposure was attenuated. In addition, western blotting revealed that RL suppressed the expression level of MAPK/NF-κB pathways and its downstream signal, COX-2 in PM10-induced A549 cells. Moreover, real-time PCR demonstrated that RL downregulated the mRNA expression level of inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-13, and IL-17) in PM10-induced A549 cells. Based on the results of this study, RL has been shown to relieve inflammation in the lungs due to PM10 exposure. Therefore, RL may be developed as a natural remedy for respiratory diseases caused by PM10 exposure.

A consensus guideline of herbal medicine for coronavirus disease 2019.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), which originated in Wuhan, Hubei Province, China in late December 2019, is the cause of ongoing pandemic. We analyzed the symptoms of SARS-CoV-2, a classification of the Chinese medicine dialectic and treatment regimen, and promptly enacted the recommendation of Korean medicine preparations in herbal medicine covered under domestic medical insurance benefits depending on the circumstances in our country. METHOD: The clinical practice guideline (CPG) for the treatment of SARS-CoV-2 was developed based on consensus from a group of experts. RESULTS: Two kinds of herbal medicines (HM) were recommended for the prevention of SARS-CoV-2; Youngyopaedoc-san plus Bojungikgitang, and Youngyopaedoc-san plus Saengmaek-san. Two herbal preparations were recommended for people with a history of exposure to SARS-CoV-2; Youngyopaedoc-san plus Bulhwangeumjeonggi-san, and Youngyopaedoc-san plus Bojungikgi-tang. Three herbal preparations were recommended for mildly symptomatic COVID-19 patients; Youngyopaedoc-san plus Galgunhaegui-tang was recommended for those without pneumonia with wind-warmth disease invading the lungs; Sosiho-tang plus Bulhwangeumjeonggi-san was recommended for those with dampness-heat disease in the lungs. For the recovery stage, Samchulkunbi-tang plus Saengmaek-san, or Samchulkunbi-tang plus Chungseuiki-tang was recommended. CONCLUSION: The CPG was developed to guide the use of Korean herbal medicine in the treatment of SARS-CoV-2, and it is expected that this will be the basis for providing proper treatment of similar infectious diseases in the future.

The efficacy of manual therapy (Chuna) for chronic obstructive pulmonary disease: Protocol for a systematic review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a challenging disease whose prevalence has increased over the last decades. Non-pharmacological therapies such as pulmonary rehabilitation occupy a core position in patient management. Among these therapies, manual therapy reduces symptoms and increases exercise capacity targeting musculoskeletal problems. Chuna, a traditional Korean manual therapy, has improved pulmonary disorders in clinical practice but unfortunately has not had its effects reported. This systematic review aims to evaluate the effectiveness and safety of manual therapy, focused on the use of Chuna in the management of COPD patients. METHODS: The following databases will be used in this study: MEDLINE via PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Database (CNKI), KoreaMed, Korean Medical Database (KMbase), and Oriental Medicine Advanced Searching Integrated System (OASIS). The primary outcome comprises lung function and exercise capacity. Secondary outcomes included symptoms, quality of life, and adverse events. We will include randomized controlled trials (RCTs) and crossover studies. Two independent reviewers will screen the searched studies, determine if they are suitable for inclusion, and perform data extraction. The risk of bias will be assessed using the Cochrane risk of bias tool. When appropriate, data will be pooled across studies for meta-analysis using a fixed or random effects model. When quantitative synthesis is not appropriate, the evidence will be summarized qualitatively. RESULTS: This study will provide a comprehensive review of the available evidence to assess the efficacy of Chuna for COPD patients. Results will be published in a peer-reviewed journal and disseminated electronically and in print. CONCLUSIONS: This study will provide high-quality current evidence for evaluation the efficacy of Chuna for patients with COPD. Clinicians, patients and policy makers may find this review useful in making decisions regarding the use of Chuna for patients with COPD. PROSPERO REGISTRATION NUMBER: CRD42019141150.

Efficacy and safety of Ojeok-san plus Saengmaek-san for gastroesophageal reflux-induced chronic cough: protocol for a pilot, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a major cause of chronic cough. GERD-induced chronic cough is difficult to diagnose because some patients do not complain of any gastrointestinal (GI) reflux symptoms. Although chronic cough due to GERD is highly prevalent, no effective treatment is currently available, especially for GERD-related cough without GI symptoms. Because the herbal medicines Ojeok-san and Saengmaek-san can effectively treat GERD and cough, we aim to evaluate the efficacy and safety of a combination of these components for relieving chronic cough due to GERD. METHODS/DESIGN: This is a study protocol of a randomized, double-blind, placebo-controlled, single-center pilot trial. After a 1-week run-in period, a total of 30 patients with GERD-induced chronic cough will be randomly allocated to an intervention group (n = 15) or a placebo group (n = 15). Participants will receive 5.76 g of Ojeok-san plus Saengmaek-san or a placebo three times per day for 6 weeks. The primary outcome measures, which are the frequency and severity of cough, will be recorded using a cough diary. The secondary outcome measures will include a cough visual analogue scale, the Leicester Cough Questionnaire (Korean version), the Gastrointestinal Symptom Rating Scale, the Hull Airway Reflux (hypersensitivity) Questionnaire, the Pattern Identification for Chronic Cough Questionnaire, the Pattern Identification for Gastroesophageal Reflux Disease, and safety testing. Adverse events will also be reported. DISCUSSION: This will be the first clinical trial to explore the use of herbal medicines for GERD-related chronic cough, including patients without GI reflux symptoms. This study will provide useful evidence regarding the efficacy and safety of Ojeok-san plus Saengmaek-san treatment. In addition, this trial will offer a scientific basis for the combination of herbal medicines. This study will also provide important data for conducting a larger-scale clinical trial on GERD-induced chronic cough. TRIAL REGISTRATION: This trial has been registered with Clinical Research Information Service (CRIS) of South Korea (http://cris.nih.go.kr; registration number KCT0003115). Registered August 28, 2018.

Inflammasomes and autoimmune and rheumatic diseases: A comprehensive review.

Inflammasomes are a multi-protein platform forming a part of the innate immune system. Inflammasomes are at standby status and can be activated when needed. Inflammasome activation is an important mechanism for the production of active interleukin (IL)-1ß and IL-18, which have important roles to instruct adaptive immunity. Active forms of inflammasomes trigger a series of inflammatory cascades and lead to the differentiation and polarization of naïve T cells and secretion of various cytokines, which can induce various kinds of autoimmune and rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), gout, Sjögren's syndrome, Behçet's disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and IgA vasculitis (former Henoch-Schönlein purpura ). In this review, we summarize studies published on inflammasomes and review their roles in various autoimmune diseases. Understanding of the role of inflammasomes may facilitate the diagnosis of autoimmune diseases and the development of tailored therapies in the future.