Retinoic Acid Treatment Mitigates PM2.5-Induced Type 2 Inflammation: Insights into Modulation of Innate Immune Responses.

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin-CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.

Dietary probiotic Lacticaseibacillus paracasei NSMJ56 modulates gut immunity and microbiota in laying hens.

This study was performed to investigate supplementary effects of probiotic Lacticaseibacillus paracasei NSMJ56 strain on laying performance, egg quality, intestinal histology, antioxidant status, gut immunity and microbiota in laying hens. A total of ninety-six 21-wk-old Hy-Line Brown laying hens were randomly subjected to one of 2 dietary treatments: a control group fed a non-supplemented diet, or a probiotic group fed with a diet supplemented with 1 g of Lacticaseibacillus paracasei NSMJ56 (5 × 108 CFU/kg of diet). The trial lasted for 4 wk. Egg weight was increased (P < 0.05) in laying hens fed probiotic-fed diet compared with the control group. Dietary probiotics did not affect egg quality except for Haugh unit, which was improved (P < 0.05) in the probiotic-fed group. Neither jejunal histology nor cecal short-chain fatty acids were affected by dietary treatments. Dietary probiotics increased the activity of catalase compared with the control group. Flow cytometry analysis revealed that dietary probiotics elevated the CD4+ T cells, but not CD8+ T cells, in jejunal lamina propria. Based on the LEfSe analysis at the phylum and genus levels, Erysipelotrichales, Erysipelotrichia, Flintibater, Dielma, Hespellia, Coprobacter, Roseburia, Anaerotignum, and Coprococcus were enriched in the probiotic group compared with the control group. Taken together, our study showed that dietary probiotics could be used to improve some parameters associated with egg freshness and antioxidant capacity, and to partially alter T cell population and microbial community in laying hens.

Systematic review and meta-analysis of cardiac neurosis for development of clinical practice guidelines of Korean medicine.

Background: The development of clinical practice guidelines in traditional medicine requires evidence that sufficiently reflects the medical field. Cardiac neurosis is a disease that occurs because of problems in the autonomic nervous system and is characterized by symptoms of the circulatory system that are representative of autonomic dysfunction. In traditional medicine, the heart is considered to be involved in mental health problems, and cardiac neurosis is accompanied by a variety of mental symptoms. Furthermore, there is a categorized diagnosis for cardiac neurosis, and active empirical research is being conducted in China. Objective: This study aimed to systematically review and quantitatively synthesize the effects of Korean medicine treatments in patients with cardiac neurosis to develop evidence-based clinical practice guidelines for the treatment of autonomic dysfunction. Methods: Nine databases were searched for articles published before September 13, 2022. The methodological quality of the studies was assessed using the RoB tool. The primary outcomes were somatization, depression, anxiety, and effectiveness rate. The secondary outcome was the rate of adverse effects. Results: Based on a systematic literature review, 151 randomized controlled trials were selected and analyzed. For patients with cardiac neurosis, herbal medicine, combined treatment of herbal medicine and Western medicine, combined treatment of herbal medicine and acupuncture, acupuncture, and combined treatment of acupuncture and Western medicine showed better overall effects than Western medicine alone. Furthermore, the combined treatment of herbal medicine and psychotherapy and that of herbal medicine, psychotherapy, and Western medicine showed an overall better effect than the combined treatment of Western medicine and psychotherapy. Conclusion: A meta-analysis of articles revealed the effectiveness of Korean medicine treatments and verified the effectiveness of a Korean medicine treatment alone, Korean medicine combined treatment, and combined treatment of Korean medicine and Western medicine on cardiac neurosis. Limitations included the inability to verify the cause of high heterogeneity between studies and the poor quality of the included studies. Nevertheless, this systematic review and meta-analysis of cardiac neurosis showed that the disease concept of traditional medicine can also be organized based on the latest research. Future research related to traditional diseases such as these should be conducted. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022347992, identifier CRD42022347992.

Antioxidant and Anti-Inflammatory Activities of Lindera glauca Extracts.

INTRODUCTION: The current study investigated the antioxidant and anti-inflammatory effects of ethanol extracts from Lindera glauca twig (LGT) and leaf/stem (LGLS). METHODS: The antioxidant activities were measured by total content of polyphenol and flavonoid, DPPH radical scavenging, and ABTS+ radical scavenging activity. To evaluate the anti-inflammatory effect in the LPS-induced RAW 264.7 cells, protein and mRNA expression of major inflammatory factors were analyzed using Western blot analysis and RT-PCR. RESULTS: The total polyphenol content of LGT and LGLS was 88.45 ± 11.74 and 115.75 ± 7.87 GA mg/g, respectively. The total flavonoid content was 66 ± 2.89 and 74.33 ± 2.89 QE mg/g. Both LGT and LGLS showed high DPPH and ABTS+ radical scavenging activities. Neither LGT nor LGLS was cytotoxic to RAW 264.7 cells. The anti-inflammatory activities were measured by LPS-induced RAW 264.7 cells. LGT and LGLS showed inhibition of the LPS-induced production of nitric oxide (NO), inducible NO synthase, cyclooxygenase-2 at the protein and mRNA levels, as determined by Western blotting and RT-PCR, respectively. In addition, the release of tumor necrosis factor-α and interleukin-6 mRNA expression levels of these cytokines was reduced by LGT and LGLS. CONCLUSION: These results suggest that LGT and LGLS extracts have potential for use as a functional antioxidant and anti-inflammatory ingredient in cosmetic industry.

Clinical outcomes of long-term inhaled combination therapies in patients with bronchiectasis and airflow obstruction.

BACKGROUND AND OBJECTIVES: Few studies have reported which inhaled combination therapy, either bronchodilators and/or inhaled corticosteroids (ICSs), is beneficial in patients with bronchiectasis and airflow obstruction. Our study compared the efficacy and safety among different inhaled combination therapies in patients with bronchiectasis and airflow obstruction. METHODS: Our retrospective study analyzed the patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity < 0.7 and radiologically confirmed bronchiectasis in chest computed tomography between January 2005 and December 2021. The eligible patients underwent baseline and follow-up spirometric assessments. The primary endpoint was the development of a moderate-to-severe exacerbation. The secondary endpoints were the change in the annual FEV1 and the adverse events. Subgroup analyses were performed according to the blood eosinophil count (BEC). RESULTS: Among 179 patients, the ICS/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA), ICS/LABA, and LABA/LAMA groups were comprised of 58 (32.4%), 52 (29.1%), and 69 (38.5%) patients, respectively. ICS/LABA/LAMA group had a higher severity of bronchiectasis and airflow obstruction, than other groups. In the subgroup with BEC ≥ 300/uL, the risk of moderate-to-severe exacerbation was lower in the ICS/LABA/LAMA group (adjusted HR = 0.137 [95% CI = 0.034-0.553]) and the ICS/LABA group (adjusted HR = 0.196 [95% CI = 0.045-0.861]) compared with the LABA/LAMA group. The annual FEV1 decline rate was significantly worsened in the ICS/LABA group compared to the LABA/LAMA group (adjusted ß-coefficient=-197 [95% CI=-307--87]) in the subgroup with BEC < 200/uL. CONCLUSION: In patients with bronchiectasis and airflow obstruction, the use of ICS/LABA/LAMA and ICS/LABA demonstrated a reduced risk of exacerbation compared to LABA/LAMA therapy in those with BEC ≥ 300/uL. Conversely, for those with BEC < 200/uL, the use of ICS/LABA was associated with an accelerated decline in FEV1 in comparison to LABA/LAMA therapy. Further assessment of BEC is necessary as a potential biomarker for the use of ICS in patients with bronchiectasis and airflow obstruction.

Plant cell wall patterning and expansion mediated by protein-peptide-polysaccharide interaction.

Assembly of cell wall polysaccharides into specific patterns is required for plant growth. A complex of RAPID ALKALINIZATION FACTOR 4 (RALF4) and its cell wall-anchored LEUCINE-RICH REPEAT EXTENSIN 8 (LRX8)-interacting protein is crucial for cell wall integrity during pollen tube growth, but its molecular connection with the cell wall is unknown. Here, we show that LRX8-RALF4 complexes adopt a heterotetrametric configuration in vivo, displaying a dendritic distribution. The LRX8-RALF4 complex specifically interacts with demethylesterified pectins in a charge-dependent manner through RALF4's polycationic surface. The LRX8-RALF4-pectin interaction exerts a condensing effect, patterning the cell wall's polymers into a reticulated network essential for wall integrity and expansion. Our work uncovers a dual structural and signaling role for RALF4 in pollen tube growth and in the assembly of complex extracellular polymers.

Challenges and Future Trends in the Treatment of Psoriasis.

Psoriasis is a chronic inflammatory skin disorder, and current treatments include topical therapies, phototherapy, systemic immune modulators, and biologics, aiming to alleviate symptoms and improve quality of life. However, challenges persist, such as adverse effects, treatment resistance, high costs, and variability in response among individuals. The future of psoriasis treatment shows promising emerging trends. New biologic agents targeting novel pathways, such as interleukin 23 inhibitors like mirikizumab, offer enhanced efficacy. Small molecule inhibitors like RORγt inhibitors and ROCK2 inhibitors provide additional treatment options. Combination therapies, including biologics with methotrexate, may improve treatment response. Advancements in topical treatments utilizing microneedles and nanoparticle-based carriers can enhance drug delivery and improve therapeutic outcomes. Biomarkers and multi-omics technologies hold potential for personalized treatment approaches, thus aiding in diagnosis, predicting treatment response, and guiding therapeutic decisions. Collaboration among researchers, clinicians, and industry stakeholders is crucial to translating these scientific breakthroughs into clinical practice. By addressing current challenges and exploring these promising trends, we can optimize psoriasis management and improve the lives of those affected by this chronic condition.

PDZ Peptide of the ZO-1 Protein Significantly Increases UTP-Induced MUC8 Anti-Inflammatory Mucin Overproduction in Human Airway Epithelial Cells.

Mucus hyperproduction and hypersecretion are observed often in respiratory diseases. MUC8 is a glycoprotein synthesized by epithelial cells and generally expressed in the respiratory track. However, the physiological mechanism by which extracellular nucleotides induce MUC8 gene expression in human airway epithelial cells is unclear. Here, we show that UTP could induce MUC8 gene expression through P2Y2-PLCß3-Ca2+ activation. Because the full-length cDNA sequence of MUC8 has not been identified, a specific siRNA-MUC8 was designed based on the partial cDNA sequence of MUC8. siRNA-MUC8 significantly increased TNF-α production and decreased IL-1Ra production, suggesting that MUC8 may downregulate UTP/P2Y2-induced airway inflammation. Interestingly, the PDZ peptide of ZO-1 protein strongly abolished UTP-induced TNF-α production and increased IL-1Ra production and MUC8 gene expression. In addition, the PDZ peptide dramatically increased the levels of UTP-induced ZO proteins and TEER (trans-epithelial electrical resistance). These results show that the anti-inflammatory mucin MUC8 may contribute to homeostasis, and the PDZ peptide can be a novel therapeutic candidate for UTP-induced airway inflammation.

Kaempferia parviflora rhizome extract exerts anti-obesity effect in high-fat diet-induced obese C57BL/6N mice.

Kaempferia parviflora (KP) rhizome, also called black ginger, has been used as a herbal medicine for many centuries. This current study was aimed at exploring whether KP rhizome extract (KPE) had anti-obesity effects and the mechanism involved. Five-week-old C57BL/6N male mice were allocated into five groups for 8-week feeding with control diet (CD), high-fat diet (HFD), HFD + 150 mg/kg body weight (BW)/day KPE (HFD+K150), HFD + 300 mg/kg BW/day KPE (HFD+K300), and HFD + 600 mg/kg BW/day KPE (HFD+K600). KPE decreased BW, body fat mass, adipose tissue weight, adipocyte size, and serum levels of glucose, triglycerides, cholesterol, insulin, and leptin in HFD-induced obese C57BL/6N mice. KPE inhibited adipogenesis by decreasing CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase 1, ATP-citrate lyase, and fatty acid synthase mRNA expression. KPE improved lipolysis by increasing carnitine palmitoyl transferase 1 and hormone-sensitive lipase mRNA expression. These results suggest that KPE may have inhibited HFD-induced obesity by regulating several pathways involved in decreasing adipogenesis and enhancing lipolysis. Thus, the results suggest that KPE (or KP) may be applicable as an anti-obesity agent.

Comprehensive Analysis of Iron Deficiency Anemia and Its Related Disorders in Premenopausal Women Based on a Propensity Score Matching Case Control Study Using National Health Insurance Service Database in Korea.

BACKGROUND: Menorrhagia is a common cause of iron deficiency anemia (IDA) in premenopausal women. However, the effects of menorrhagia on IDA in premenopausal women have been underestimated compared to those on other IDA-related disorders (IRDs) such as gastrointestinal malignancies (GIMs). To better understand the relationship between menorrhagia and IDA in premenopausal women, we analyzed the National Health Insurance Service-National Health Information Database (NHIS-NHID). METHODS: From 2005 to 2008, data about women between the age of 20 and 59 years were extracted from the NHIS-NHID to create a propensity score-matched case (IDA) and control group. The annual incidence of IDA was calculated per age group. A 10-year follow up of the study population was determined to detect IRDs in case and control groups. We compared the risk of detection (ROD) of IRDs, including GIM and gynecological disorders associated with menorrhagia - leiomyoma of uterus (LM) and adenomyosis (AM), in the case and the control group. RESULTS: From 2005 to 2008, women diagnosed with IDA (n = 535,249) and healthy women as a control group (n = 1,070,498) were identified from the NHIS-NHID. The annual incidence of IDA was 767.4 (2005), 948.7 (2006), 981.6 (2007), and 897.7 (2008) per 100,000 women. The age distribution of IDA was similar each year; IDA was common in women aged 30-39 years (36-37%) and 40-49 years (30-32%), and its incidence was significantly decreased in women aged 50-59 years (< 10%). The ROD of IRDs were significantly higher in the IDA group than in the control group (LM: 20.8% vs. 6.9%, AM: 5.6% vs. 1.6%, and GIM: 2.6% vs. 0.7%). The corresponding hazard ratios were 3.89 (95% confidence interval [CI], 3.85-3.93) for LM, 4.99 (95% CI, 4.90-5.09) for AM, and 3.43 (95% CI, 3.32-3.55) for GIM. The ROD of the IRDs varied; the ROD of LM in the IDA group increased with age and decreased in the age group 50-59 years. AM was more frequently detected in women with IDA aged 30-39 years and less in women older than 40 years. The frequency of GIM increased with age. CONCLUSION: In this study, we found that the gynecologic disease is the main cause of IDA in premenopausal women. Gynecological evaluations should be performed more actively in the clinic to prevent and control IDA and IRDs.

Garcinia mangostana Suppresses Triacylglycerol Synthesis in Hepatocytes and Enterocytes.

Regulation of diacylglycerol acyltransferase (DGAT) and pancreatic lipase (PL) activities is important in the treatment of triacylglycerol (TG)-related metabolic diseases. Garcinia mangostana, also known as mangosteen, is a traditional medicine ingredient used in the treatment of inflammation in Southeast Asia. In this study, The ethanolic extract of G. mangostana peel inhibited human recombinant DGAT1 and DGAT2, and PL enzyme activities in vitro. The inhibitory activity of DGAT1 and DGAT2 enzymes of four representative bioactive substances in mangosteen was confirmed. In addition, G. mangostana was confirmed to suppress the serum TG levels in C57 mice by inhibiting the absorption and synthesis of TG in the gastrointestinal tract. Through this study, it was revealed that G. mangostana extract could be useful for the prevention and amelioration of TG-related metabolic diseases such as obesity and fatty liver.

Korean Red Ginseng extract attenuates alcohol-induced addictive responses and cognitive impairments by alleviating neuroinflammation.

Background: Alcohol is one of the most commonly used psychoactive drugs. Due to its addictive characteristics, many people struggle with the side effects of alcohol. Korean Red Ginseng (KRG) is a traditional herbal medicine that is widely used to treat various health problems. However, the effects and mechanisms of KRG in alcohol-induced responses remain unclear. Therefore, the purpose of this study was to investigate the effects of KRG in alcohol-induced responses. Methods: We investigated two aspects: alcohol-induced addictive responses and spatial working memory impairments. To determine the effects of KRG in alcohol-induced addictive responses, we performed conditioned place preference tests and withdrawal symptom observations. To assess the effects of KRG in alcohol-induced spatial working memory impairment, Y-maze, Barnes maze, and novel object recognition tests were performed using mice after repeated alcohol and KRG exposure. To investigate the potential mechanism of KRG activity, gas chromatography-mass spectrometry and western blot analysis were performed. Results: KRG-treated mice showed dose-dependent restoration of impaired spatial working memory following repeated alcohol exposure. Furthermore, withdrawal symptoms to alcohol were reduced in mice treated with KRG and alcohol. The PKA-CREB signaling pathway was activated after alcohol administration, which was reduced by KRG. However, the levels of inflammatory cytokines were increased by alcohol and decreased by KRG. Conclusion: Taken together, KRG may alleviate alcohol-induced spatial working memory impairments and addictive responses through anti-neuroinflammatory activity rather than through the PKA-CREB signaling pathway.

A Bioactive Compound-Loaded Zinc-Aminoclay Encapsulated, Pickering Emulsion System for Treating Acne-Inducing Microbes.

Acne is a common skin condition caused by the growth of certain bacteria. Many plant extracts have been investigated for their potential to combat acne-inducing microbes, and one such plant extract is microwave-assisted Opuntia humifusa extract (MA-OHE). The MA-OHE was loaded onto zinc-aminoclay (ZnAC) and encapsulated in a Pickering emulsion system (MA-OHE/ZnAC PE) to evaluate its therapeutic potential against acne-inducing microbes. Dynamic light scattering and scanning electron microscopy were used to characterize MA-OHE/ZnAC PE with a mean particle diameter of 353.97 nm and a PDI of 0.629. The antimicrobial effect of MA-OHE/ZnAC was evaluated against Staphylococcus aureus (S. aureus) and Cutibacterium acnes (C. acnes), which contribute to acne inflammation. The antibacterial activity of MA-OHE/ZnAC was 0.1 and 0.025 mg/mL to S. aureus and C. acnes, respectively, which were close to naturally derived antibiotics. Additionally, the cytotoxicity of MA-OHE, ZnAC, and MA-OHE/ZnAC was tested, and the results showed that they had no cytotoxic effects on cultured human keratinocytes in a range of 10-100 µg/mL. Thus, MA-OHE/ZnAC is suggested to be a promising antimicrobial agent for treating acne-inducing microbes, while MA-OHE/ZnAC PE is a potentially advantageous dermal delivery system.

Estimated dietary vitamin D intake and major vitamin D food sources of Koreans: based on the Korea National Health and Nutrition Examination Survey 2016-2019.

BACKGROUND/OBJECTIVES: The purpose of this study was to establish a database (DB) of foods containing vitamin D that were investigated in the Korea National Health and Nutrition Examination Survey (KNHANES), to estimate the dietary vitamin D intake, to evaluate the dietary adequacy of this intake, and to identify the major food sources of Koreans that contain vitamin D. SUBJECTS/METHODS: This study used data from the KNHANES 2016-2019. Individuals aged ≥ 1 year who participated in the nutrition survey (n = 28,418) were included. The dietary intake was assessed by the 24-h dietary recall method and individual dietary vitamin D intake was estimated using a newly established vitamin D DB. Dietary adequacy was evaluated by comparing the dietary intake of the participants with adequate intake (AI) as defined by Dietary Reference Intakes for Koreans (KDRIs) 2020. RESULTS: The average dietary vitamin D intake for all the subjects was 3.13 µg/d, which was 33.1% of AI. Dietary vitamin D intake was lower in rural residents, the elderly, and those with low income. The major food groups that contributed to the total dietary vitamin D intake were fish and shellfish (61.59%), eggs (17.75%), meat (8.03%), milk (4.25%), legumes (3.93%), and grains (3.84%). The top 10 individual food items that contributed to the total vitamin D intake were eggs (17.44%), squid (8.5%), eels (7.44%), salmon (5.35%), mackerel (5.27%), anchovies (4.65%), yellow croakers (4.58%), pork meat (4.47%), soymilk (4.46%), and skipjack tuna (3.80%). CONCLUSION: These results show that the mean dietary vitamin D intake of Koreans is lower than the reference AI level. Nutritional policies need to be put in place to increase the vitamin D intake of Koreans in the future. In addition, comprehensive research on all the sources of vitamin D, including intake of supplements and biosynthesis in the skin, is required.

Predicting benefit from immune checkpoint inhibitors in patients with non-small-cell lung cancer by CT-based ensemble deep learning: a retrospective study.

BACKGROUND: Only around 20-30% of patients with non-small-cell lung cancer (NCSLC) have durable benefit from immune-checkpoint inhibitors. Although tissue-based biomarkers (eg, PD-L1) are limited by suboptimal performance, tissue availability, and tumour heterogeneity, radiographic images might holistically capture the underlying cancer biology. We aimed to investigate the application of deep learning on chest CT scans to derive an imaging signature of response to immune checkpoint inhibitors and evaluate its added value in the clinical context. METHODS: In this retrospective modelling study, 976 patients with metastatic, EGFR/ALK negative NSCLC treated with immune checkpoint inhibitors at MD Anderson and Stanford were enrolled from Jan 1, 2014, to Feb 29, 2020. We built and tested an ensemble deep learning model on pretreatment CTs (Deep-CT) to predict overall survival and progression-free survival after treatment with immune checkpoint inhibitors. We also evaluated the added predictive value of the Deep-CT model in the context of existing clinicopathological and radiological metrics. FINDINGS: Our Deep-CT model demonstrated robust stratification of patient survival of the MD Anderson testing set, which was validated in the external Stanford set. The performance of the Deep-CT model remained significant on subgroup analyses stratified by PD-L1, histology, age, sex, and race. In univariate analysis, Deep-CT outperformed the conventional risk factors, including histology, smoking status, and PD-L1 expression, and remained an independent predictor after multivariate adjustment. Integrating the Deep-CT model with conventional risk factors demonstrated significantly improved prediction performance, with overall survival C-index increases from 0·70 (clinical model) to 0·75 (composite model) during testing. On the other hand, the deep learning risk scores correlated with some radiomics features, but radiomics alone could not reach the performance level of deep learning, indicating that the deep learning model effectively captured additional imaging patterns beyond known radiomics features. INTERPRETATION: This proof-of-concept study shows that automated profiling of radiographic scans through deep learning can provide orthogonal information independent of existing clinicopathological biomarkers, bringing the goal of precision immunotherapy for patients with NSCLC closer. FUNDING: National Institutes of Health, Mark Foundation Damon Runyon Foundation Physician Scientist Award, MD Anderson Strategic Initiative Development Program, MD Anderson Lung Moon Shot Program, Andrea Mugnaini, and Edward L C Smith.

Anti-inflammatory effects of Allium cepa L. peel extracts via inhibition of JAK-STAT pathway in LPS-stimulated RAW264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Allium cepa L. (A. cepa) is one of the oldest cultivated plants in the world. A. cepa has been used in traditional folk medicine to treat inflammatory disease in several regions, such as Palestine and Serbia. A. cepa peel has a higher content of flavonoids, such as quercetin, than the edible parts. These flavonoids alleviate inflammatory diseases. However, the anti-inflammatory effects of A. cepa peel extract-obtained using various extraction methods-and their underlying mechanisms require further investigation. AIM OF THE STUDY: Although research to find safe anti-inflammatory substances in various natural products has been actively conducted for many years, it is important to continue identifying potential anti-inflammatory effects in natural materials. The purpose of this study was to investigate the ethnopharmacological properties of the A. cepa peel extract, whose efficacy when obtained through different extraction methods and underlying action mechanisms is not well known. The present study specifically aimed to observe the anti-inflammatory effects of the A. cepa peel extracts obtained using various extraction methods and the related detailed mechanisms of A. cepa peel extracts in lipopolysaccharide (LPS)-induced RAW264.7 cells. MATERIALS AND METHODS: The total flavonoid content of the A. cepa peel extracts was determined the diethylene glycol colorimetric method and measured using a calibration curve prepared using quercetin as a standard solution. The antioxidant activity was evaluated using the ABTS assay, and cytotoxicity was measured using the MTT assay. NO production was measured using Griess reagent. Protein levels were measured by western blotting, and mRNA expression was measured by RT-qPCR. Secreted cytokines were analyzed using ELISA or cytokine arrays. In the GSE160086 dataset, we calculated Z-scores for individual genes of interest and displayed using a heat map. RESULTS: Of the three A. cepa peel extracts obtained using different extraction methods, the A. cepa peel 50% EtOH extract (AP50E) was the most effective at inhibiting LPS-induced nitric oxide (NO) and inducible nitric oxide synthase (iNOS). Furthermore, AP50E significantly reduced the levels of pro-inflammation cytokines interleukin (IL)-1α, IL-1ß, IL-6, and IL-27. Additionally, AP50E directly inhibited the Janus kinase-signaling transducer and activator of transcription (JAK-STAT) pathway. CONCLUSIONS: These results showed that AP50E exhibited an anti-inflammatory effect in LPS-induced RAW264.7 mouse macrophages by directly inhibiting JAK-STAT signaling. Based on these findings, we propose AP50E as a potential candidate for the development of preventive or therapeutic agents against inflammatory diseases.

Pharmacological anti-tumor effects of natural Chamaecyparis obtusa (siebold & zucc.) endl. Leaf extracts on breast cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Chamaecyparis obtusa (C. obtusa, cypress species) is a plant that grows mainly in the temperate Northern Hemisphere and has long been used as a traditional anti-inflammatory treatment in East Asia. C. obtusa contains phytoncides, flavonoids, and terpenes, which have excellent anti-cancer effects and have been reported to prevent the progression of various cancers. However, the detailed mechanisms underlying the anti-cancer effects of C. obtusa extracts are unknown. AIM OF THE STUDY: We sought to confirm the anti-cancer effects of C. obtusa leaf extracts and to reveal the mechanism of action, with the possibility of its application in the treatment or prevention of cancer. MATERIAL &METHODS: The cytotoxicity of C. obtusa leaf extracts was confirmed using an MTT assay. Intracellular changes in protein levels were measured by immunoblotting, and mRNA levels were measured with qRT-PCR. Wound healing assay and transwell migration assay were used to evaluate the metastatic potential of breast cancer cells. The extract-induced apoptosis was observed using IncuCyte Annexin V Red staining analysis. A syngeneic breast cancer mouse model was established by injecting 4T1-Luc mouse breast cancer cells into the fat pad of female BALB/c mice, and the extract was administered orally. Luciferin solution was injected intraperitoneally to assess primary tumor development and metastasis by bioluminescence. RESULTS: C. obtusa leaf extracts were extracted with boiling water, 70% EtOH, and 99% EtOH. Among the extracts, the 99% EtOH extract of C. obtusa leaf (CO99EL) most clearly inhibited the tyrosine phosphorylation of Signal Transducer and Activator of Transcription 3 (pY-STAT3) in MDA-MB-231 breast cancer cells at a concentration of 25 and 50 µg/mL. In addition, CO99EL strongly inhibited not only endogenous pY-STAT3 levels but also IL-6-induced STAT3 activation in various types of cancer cells, including breast cancer. CO99EL inhibited metastatic potential by downregulating the expression of N-cadherin, fibronectin, TWIST, MMP2, and MMP9 in MDA-MB-231 breast cancer cells. CO99EL also induced apoptotic cell death by increasing cleaved caspase-3 and decreasing anti-apoptotic proteins Bcl-2 and Bcl-xL. In an in vivo syngeneic breast cancer mouse model, 100 mg/kg CO99EL suppressed tumor growth and induced apoptosis of cancer cells. Moreover, CO99EL significantly inhibited lung metastasis from primary breast cancer. CONCLUSIONS: Our study demonstrated that 100 mg/kg CO99EL has potent anti-tumor effects against breast cancer, thus suggesting that 100 mg/kg CO99EL has potential applications in the treatment and prevention of breast cancer.

Searching for Novel Candidate Small Molecules for Ameliorating Idiopathic Pulmonary Fibrosis: a Narrative Review.

Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)-ß-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

Dietary zinc intake and sources among Koreans: findings from the Korea National Health and Nutrition Examination Survey 2016-2019.

BACKGROUND/OBJECTIVES: Zinc is an essential trace mineral which is important for the growth and development of the human body and immunological and neurological functions. Inadequate zinc intake may cause zinc deficiency with its adverse consequences. In this study, we aimed to estimate the dietary zinc intake levels and sources among Koreans. SUBJECTS/METHODS: For this secondary analysis, we obtained data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2016-2019. Individuals aged ≥ 1 yr who had completed a 24-h recall were included. The dietary zinc intake of each individual was calculated by applying data from a newly developed zinc content database to the KNHANES raw data. We also compared the extracted data with the sex-, age-specific reference values suggested in the Korean Dietary Reference Intakes 2020. The prevalence of adequate zinc intake was then evaluated by the proportion of the individuals who met the estimated average requirement (EAR). RESULTS: The mean zinc intake of Koreans aged ≥ 1 yr and adults aged ≥ 19 yrs were 10.2 and 10.4 mg/day, equivalent to 147.4% and 140.8% of the EAR, respectively. Approximately 2 in 3 Koreans met the EAR for zinc, but the zinc intake differed slightly among the different age and sex groups. In children aged 1-2 yrs, 2 out of 5 exceeded the upper level of intake, and nearly half of the younger adults (19-29 yrs) and the elders (≥ 75 yrs) did not meet the EAR. The major contributing food groups were grains (38.9%), meats (20.4%), and vegetables (11.1%). The top 5 food contributors to zinc intake were rice, beef, pork, egg, and baechu kimchi, which accounted for half of the dietary intake. CONCLUSION: The mean zinc intake among Koreans was above the recommended level, but 1 in 3 Koreans had inadequate zinc intake and some children were at risk of excessive zinc intake. Our study included zinc intake from diet only, thus to better understand zinc status, further research to include intake from dietary supplements is needed.