Gleditsia sinensis thorns inhibit the production of NO through NF-kappaB suppression in LPS-stimulated macrophages

The thorns of Gleditsia sinensis LAM. (Leguminosae) have been used in traditional medicine for the treatment of inflammatory diseases including swelling, suppuration, carbuncle and skin diseases in China and Korea. In this study, we investigated the mechanism responsible for anti-inflammatory effects of Gleditsia sinensis thorns in RAW 264.7 macrophages. The aqueous extract of Gleditsia sinensis thorns (AEGS) inhibited LPS-induced NO secretion as well as inducible nitric oxide synthase (iNOS) expression, without affecting cell viability. Furthermore, AEGS suppressed LPS-induced NF-kappaB activation, phosphorylation and degradation of IkappaB-alpha, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). These results suggest that AEGS has the inhibitory effects on LPS-induced NO production and iNOS expression in macrophages through blockade in the phosphorylation of MAPKs, following IkappaB-alpha degradation and NF-kappaB activation.     

Fimasartan Ameliorates Deteriorations in Glucose Metabolism in a High Glucose State by Regulating Skeletal Muscle and Liver Cells

PurposeSince diabetes and hypertension frequently occur together, it is thought that these conditions may have a common pathogenesis. This study was designed to evaluate the anti-diabetic function of the anti-hypertensive drug fimasartan on C2C12 mouse skeletal muscle and HepG2 human liver cells in a high glucose state.Materials and MethodsThe anti-diabetic effects and mechanism of fimasartan were identified using Western blot, glucose uptake tests, oxygen consumption rate (OCR) analysis, adenosine 5′-triphosphate (ATP) enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining for diabetic biomarkers in C2C12 cells. Protein biomarkers for glycogenolysis and glycogenesis were evaluated by Western blotting and ELISA in HepG2 cells.ResultsThe protein levels of phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK), p-AKT, insulin receptor substrate-1 (IRS-1), and glucose transporter type 4 (Glut4) were elevated in C2C12 cells treated with fimasartan. These increases were reversed by peroxisome proliferator-activated receptor delta (PPARδ) antagonist. ATP, OCR, and glucose uptake were increased in cells treated with 200 µM fimasartan. Protein levels of glycogen phosphorylase, glucose synthase, phosphorylated glycogen synthase, and glycogen synthase kinase-3 (GSK-3) were decreased in HepG2 cells treated with fimasartan. However, these effects were reversed following the addition of the PPARδ antagonist GSK0660.ConclusionIn conclusion, fimasartan ameliorates deteriorations in glucose metabolism as a result of a high glucose state by regulating PPARδ in skeletal muscle and liver cells.     

The microbiome of lung cancer tissue and its association with pathological and clinical parameters

Lung cancer is the primary cause of cancer-related deaths worldwide. Recently, although the microbiome has emerged as the key modulator of the carcinogenesis, it has not been evaluated in lung cancer. Here, we evaluated the microbial composition of lung cancer tissues according to the histologic type and genetic mutation, compared it with that of the adjacent normal lung tissues, and investigated the association between the lung microbiome and clinical parameters. We collected lung tissue samples from 162 patients with non-small cell lung cancer (NSCLC, 162 cancer and 54 adjacent normal tissues), surgically resected between January 2018 and December 2019, and analyzed their microbiome using 16S rRNA gene amplicon sequencing, the QIIME2 pipeline, and statistical analyses. NSCLC tissues had significantly lower alpha diversity than the normal tissues, and their microbial composition differed according to the histologic type and cancer genetic mutation. The genera Romboutsia, Novosphingobium, Acinetobacter, and Prevotella were significantly overrepresented in NSCLC tissues. Alpha diversity steadily declined from a normal to a more advanced stage, and microbial compositional differences were noted along with recurrence. Stenotrophomonas was the most predominant genus in the NSCLC tissues of patients with recurrence. The pathways related to the tricarboxylic acid cycle and L-glutamate and L-glutamine biosynthesis were predominant in adenocarcinoma, whereas those related to purine and pyrimidine nucleotide degradation and formaldehyde assimilation were predominant in squamous cell carcinoma. Our findings suggest that the altered lung cancer microbial composition might be associated with cancer initiation and/or progression.     

Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing

PurposeTriple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC.MethodsA kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three non-Asian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy). The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation.ResultsThe significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort (p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset (p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort (p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets (p = 0.002 and 0.003, respectively).ConclusionComprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.     

Catechin-7-O-α-L-rhamnopyranoside can reduce α-MSH-induced melanogenesis in B16F10 melanoma cells through competitive inhibition of tyrosinase

Although melanogenesis is a defense mechanism against ultraviolet (UV)-induced skin damage, abnormally excessive melanin production causes pigmentation disorders. Tyrosinase, as a key factor for melanin synthesis, plays an important role in inducing skin pigmentation. Therefore, the inhibition of tyrosinase is crucial in preventing skin pigmentation in the cosmetics and medicine fields. However, the majority of well-known tyrosinase inhibitors have been discontinued due to toxic effects on the skin or lack of selectivity and/or stability. In this study, we evaluated possible anti-melanogenic effects of catechin-7-O-α-L-rhamnopyranoside (C7R) isolated from the stem bark of Ulmus parvifolia, to discover a new tyrosinase inhibitor that has both safety and stability. When C7R was pretreated in B16F10 melanoma cells stimulated by α-melanocyte-stimulating hormone, this compound reduced melanin accumulation and murine tyrosinase activity. In line with these results, C7R inhibits tyrosinase purified from a mushroom in vitro like kojic acid and arbutin. Furthermore, C7R exhibited a competitive inhibition on a Lineweaver-Burk plot. Next, the underlying mechanisms of the C7R-mediated tyrosinase inhibitory effect were sought through docking simulation and pharmacophore analysis between tyrosinase residues and C7R. The results of these analyses showed that C7R had binding energy of -14.5kcal/mol, and indicated that C7R interacts with tyrosinase through an aromatic ring and various hydrophobic and hydrogen bonds. Together, our results suggest that C7R can be applied as a novel natural anti-melanogenic agent that inhibits tyrosinase.     

Meditation-based intervention for obsessive-compulsive disorder: A PRISMA-compliant systematic review and meta-analysis

Background:The purpose of this study was to investigate the effects of the meditation-based intervention on obsessive-compulsive disorder (OCD).Methods:The following databases were searched up to April 2021: the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Medline (via PubMed), PsycARTICLES, 4 Korean databases (Korean Medical Database [KMbase], Koreanstudies Information Service System [KISS], National Digital Science Library [NDSL], and Oriental Medicine Advanced Searching Integrated System [OASIS]), and China National Knowledge Infrastructure (CNKI). The search terms related to meditation-based intervention and OCD were used. This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The selected articles were evaluated using the Cochrane risk of bias tool. The Review Manager (RevMan) 5.4 was used to perform the meta-analysis.Results:In all, 16 randomized controlled trials were selected. The meta-analysis showed that the group receiving the treatment combining medication and meditation-based intervention for OCD showed a more significant post-treatment improvement in Yale-Brown obsessive compulsive scale than the group receiving medication only. Compared with other non-medication interventions that are known to be effective in treating OCD, the Yale-Brown obsessive compulsive scale showed a significant improvement immediately after the meditation-based intervention. However, no significant difference was found in the follow-up monitoring data across all examined cases.Conclusion:This study was conducted to verify the effects of meditation-based intervention on OCD. The results suggested that combined treatment with medication and meditation-based intervention was more effective in treating OCD than medication alone; the positive effects of meditation-based intervention may be greater than the effects of other non-medication interventions. However, the lack of significant difference in the follow-up indicates that long-term effect of meditation-based interventions is unclear.Trial registration number:PROSPERO CRD42021244408     

Cinnamaldehyde induces autophagy-mediated cell death through ER stress and epigenetic modification in gastric cancer cells

Previous reports suggested that cinnamaldehyde(CA),the bioactive ingredient in Cinnamomum cassia,can suppress tumor growth,migratory,and invasive abilities.Howe...