We previously reported higher levels of C-C chemokine ligand (CCL) 1 in the bronchoalveolar lavage (BAL) fluid (BALF) of patients with sarcoidosis than in BALF of patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD), indicating that CCL1 might act as a marker of disease activity in sarcoidosis. Notably, less invasive sampling sources are desirable, as BAL cannot always be performed due to its inherent risk. In this study, we sought to decipher the correlation between serum levels of CCL1 and clinical characteristics of sarcoidosis. Serum samples were obtained from 44 patients with clinically confirmed sarcoidosis, 14 patients with IgG4-RD, and 14 healthy controls. The clinical and radiological findings were retrospectively evaluated. Serum levels of CCL1 were measured using a sandwich enzyme-linked immunosorbent assay. Serum levels of other 17 cytokines and chemokines were measured using a MILLIPLEX® MAP KIT and Luminex® magnetic beads. Serum levels of CCL1 were significantly higher in patients with sarcoidosis than in patients with IgG4-RD and healthy controls. Serum CCL1 was positively correlated with the degree of hilar lymph node swelling on chest computed tomography and serum levels of soluble interleukin 2 receptor. Positive correlations were also observed between serum CCL1 and total cell counts, lymphocyte counts in BALF, and serum T helper 1 mediators such as IP-10 and TNF-α in patients with sarcoidosis. Serum CCL1 levels were significantly elevated in sarcoidosis and correlated with clinical parameters of the disease. In addition, serum and BALF levels of CCL1 were positively correlated in a statistically significant manner. Although further research in this field is necessary, CCL1 might have the potential to be a reliable serological marker of disease activity in sarcoidosis.Background STW 5 is a fixed herbal combination containing extracts from nine medicinal plants bitter candytuft, greater celandine, garden angelica roots, lemon balm leaves, peppermint leaves, caraway fruits, licorice roots, chamomile flowers, and milk thistle fruit. STW 5 is a clinically proven treatment for functional dyspepsia and irritable bowel syndrome. Purpose Using a static in vitro method, we simulated oral, gastric, and small intestinal digestion and analyzed the metabolic profile changes by UHPLC-HRMS to determine the impact of oro-gastro-intestinal digestion on STW 5 constituents. Study design and methods STW 5 was incubated according to the InfoGest consensus method. Samples of each digestive phase were analyzed by UHPLC-HRMS in ESI positive and negative modes. After data processing, background subtraction, and normalization, the peak areas of detectable compounds were compared to untreated reference samples and recovery ratios were calculated to monitor the metabolic profile of STW 5 during simulated digestion. Results Although the levels of some constituents were reduced, we did not observe complete degradation of any of the constituents of STW 5 upon in vitro digestion. We did not detect any new metabolites beyond increased levels of caffeic acid and liquiritigenin due to degradation of progenitor compounds. Changes observed in intestinal bioaccessibility ratios were mainly a result of isomerization, hydrolysis, protein binding, and low water solubility. Conclusion The majority of STW 5 constituents are stable towards simulated in vitro digestion and can reach the colon to interact with gut microbiota if they remain unabsorbed in the upper intestinal tract.Background and purpose Multidrug resistance (MDR) remains the main obstacle in cancer treatment and overexpression of P-glycoprotein (P-gp) is one of the most common causes of chemoresistance. The development of novel P-gp inhibitors from natural products is a prospective strategy to combat MDR cancers. Among the natural sesquiterpene compounds, sesquiterpene pyridine alkaloids exhibit various biological properties. Therefore, in the present study, we evaluated the modulatory effects of wilforine on P-gp expression and function. The molecular mechanisms and kinetic models of wilforine-mediated P-gp inhibition were further investigated. check details Methods The human P-gp stable expression cells (ABCB1/Flp-InTM-293) and human cervical cancer cells (sensitive HeLaS3; MDR KBvin) were used. The cell viability was assessed by SRB assay. The inhibitory effect of wilforine on P-gp efflux and the underlying mechanism were evaluated by assays for calcein-AM uptake, rhodamine123 and doxorubicin efflux, ATPase activity, real-time quantitative RT-PCR, apoptosis, and cell cycle analysis. Molecular docking was performed by the docking software CDOCKER with BIOVIA Discovery Studio 4.5 (D.S. 4.5). Results We found that wilforine significantly inhibited the efflux activity of P-gp in a concentration-dependent manner. Further kinetic analysis demonstrated that wilforine significantly inhibited P-gp efflux function by competitive inhibition and stimulated the basal P-gp ATPase activity. In addition, wilforine re-sensitized MDR cancer cells to chemotherapeutic drugs. The docking model indicated that wilforine was bound to residues of P-gp such as LEU884, LYS887, THR176 and ASN172. Conclusion These results suggest a novel future therapeutic strategy for MDR cancer using wilforine as an adjuvant treatment with chemotherapy.Background Studies investigating recognition of facial expressions of emotions in Williams syndrome (WS) have reported difficulties in recognising negative expressions of emotion and a reliance on atypically developing underlying processes during task performance. Aim The aim of the study was to extend these findings to the recognition of emotions in auditory domains. Method and procedures Children and adolescents with WS, together with chronological (CA) and verbal mental age matched (VMA) typically developing (TD) comparison groups, were asked to judge expressions of happiness, sadness, anger, and fear in vocal and musical conditions. Outcomes and results Total emotion recognition scores did not differ between WS and VMA matched groups but profiles of discrimination across emotion categories were markedly different. For all groups, the accessibility of emotion category cues differed across music and speech domains. The results suggested that emotion discrimination is more strongly linked with cognitive ability in WS than in TD.check details