Anti-Inflammatory Effects of Resveratrol on Human Retinal Pigment Cells and a Myopia Animal Model.

Resveratrol is a key component of red wine and other grape products. Recent studies have characterized resveratrol as a polyphenol, and shown its beneficial effects on cancer, metabolism, and infection. This study aimed to obtain insights into the biological effects of resveratrol on myopia. To this end, we examined its anti-inflammatory influence on human retinal pigment epithelium cells and in a monocular form deprivation (MFD)-induced animal model of myopia. In MFD-induced myopia, resveratrol increased collagen I level and reduced the expression levels of matrix metalloproteinase (MMP)2, transforming growth factor (TGF)-ß, and nuclear factor (NF)-κB expression levels. It also suppressed the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. Resveratrol exhibited no significant cytotoxicity in ARPE-19 cells. Downregulation of inflammatory cytokine production, and inhibition of AKT, c-Raf, Stat3, and NFκB phosphorylation were observed in ARPE-19 cells that were treated with resveratrol. In conclusion, the findings suggest that resveratrol inhibits inflammatory effects by blocking the relevant signaling pathways, to ameliorate myopia development. This may make it a natural candidate for drug development for myopia.

Diacerein Inhibits Myopia Progression through Lowering Inflammation in Retinal Pigment Epithelial Cell.

Myopia is a highly prevalent refractive disorder. We investigated the effect of diacerein on monocular form deprivation (MFD) in hamsters as a possible therapeutic intervention. Diacerein is an anthraquinone derivative drug whose active metabolite is rhein. Diacerein or atropine was applied to the MFD hamsters, and their refractive error and axial length were measured after 21 days. The refractive error (control: -0.91 ± 0.023, atropine: -0.3 ± 0.08, and diacerein: -0.27 ± 0.07 D) and axial length (control: 0.401 ± 0.017, atropine: 0.326 ± 0.017, and diacerein: 0.334 ± 0.016 mm) showed statistically significant differences between control, atropine-treated, and diacerein-treated MFD eyes. Furthermore, we determined the level of transforming growth factor-beta- (TGF-) ß1, matrix metalloproteinase- (MMP-) 2, type I collagen, interleukin- (IL-) 6, IL-8, and monocyte chemoattractant protein- (MCP-) 1 in the retina. Atropine and diacerein suppressed levels of the myopia-related TGF-ß1 and MMP-2 while increasing type I collagen expression. They also inhibited the interleukin IL-6, IL-8, and MCP-1 levels. Diacerein reduced the IL-6, IL-8, and MCP-1 expression in ARPE-19 cells. Furthermore, diacerein inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. This suggests that diacerein has a therapeutic effect on myopia and is a potential treatment option.

Amelioration of bleomycin-induced pulmonary fibrosis via TGF-ß-induced Smad and non-Smad signaling pathways in galectin-9-deficient mice and fibroblast cells.

BACKGROUND: Galectin-9 is a ß-galactoside-binding protein with two carbohydrate recognition domains. Recent studies have revealed that galectin-9 regulates cellular biological reactions and plays a pivotal role in fibrosis. The aim of this study was to determine the role of galectin-9 in the pathogenesis of bleomycin-induced systemic sclerosis (SSc). METHODS: Human galectin-9 levels in the serum of patients with SSc and mouse sera galectin-9 levels were measured by a Bio-Plex immunoassay and enzyme-linked immunosorbent assay. Lung fibrosis was induced using bleomycin in galectin-9 wild-type and knockout mice. The effects of galectin-9 on the fibrosis markers and signaling molecules in the mouse lung tissues and primary lung fibroblast cells were assessed with western blotting and quantitative polymerase chain reaction. RESULTS: Galectin-9 levels in the serum were significantly higher (9-fold) in patients compared to those of healthy individuals. Galectin-9 deficiency in mice prominently ameliorated epithelial proliferation, collagen I accumulation, and α-smooth muscle actin expression. In addition, the galectin-9 knockout mice showed reduced protein expression levels of fibrosis markers such as Smad2/3, connective tissue growth factor, and endothelin-1. Differences between the wild-type and knockout groups were also observed in the AKT, mitogen-activated protein kinase, and c-Jun N-terminal kinase signaling pathways. Galectin-9 deficiency decreased the signal activation induced by transforming growth factor-beta in mouse primary fibroblasts, which plays a critical role in fibroblast activation and aberrant catabolism of the extracellular matrix. CONCLUSIONS: Our findings suggest that lack of galectin-9 protects against bleomycin-induced SSc. Moreover, galectin-9 might be involved in regulating the progression of fibrosis in multiple pathways.

Ablation of Galectin-12 Inhibits Atherosclerosis through Enhancement of M2 Macrophage Polarization.

The formation of foam cells, which are macrophages that have engulfed oxidized low-density lipoprotein (OxLDL), constitutes the first stage in the development of atherosclerosis. Previously, we found that knocking down galectin-12, a negative regulator of lipolysis, leads to reduced secretion of monocyte chemoattractant protein-1 (MCP-1), a chemokine that plays an important role in atherosclerosis. This prompted us to study the role of galectin-12 in atherosclerosis. With that aim, we examined foam cell formation in Gal12‒/‒ murine macrophages exposed to OxLDL and acetylated LDL (AcLDL). Then, we generated an LDL receptor and galectin-12 double knockout (DKO) mice and studied the effect of galectin-12 on macrophage function and atherosclerosis. Lastly, we evaluated the role of galectin-12 in human THP-1 macrophages using a doxycycline-inducible conditional knockdown system. Galectin-12 knockout significantly inhibited foam cell formation in murine macrophages through the downregulation of cluster of differentiation 36 (CD36), and the upregulation of ATP Binding Cassette Subfamily A Member 1 (ABCA1), ATP Binding Cassette Subfamily G Member 1 (ABCG1), and scavenger receptor class B type 1 (SRB1). Consistent with this, galectin-12 knockdown inhibited foam cell formation in human macrophages. In addition, the ablation of galectin-12 promoted M2 macrophage polarization in human and murine macrophages as evidenced by the upregulation of the M2 marker genes, CD206 and CD163, and downregulation of the M1 cytokines, tumor necrosis factor α (TNF- α), interleukin-6 (IL-6), and MCP-1. Moreover, the ablation of galectin-12 decreased atherosclerosis formation in DKO mice. Based on these results, we propose galectin-12 as a potential therapeutic target for atherosclerosis.

Galectin-12 enhances inflammation by promoting M1 polarization of macrophages and reduces insulin sensitivity in adipocytes.

Galectin-12 is a member of an animal lectin family with affinity for ß-galactosides and containing consensus amino acid sequences. Here, we found that galectin-12 was expressed in macrophages and thus aimed to determine how galectin-12 affects inflammation and macrophage polarization and activation. The ablation of galectin-12 did not affect bone marrow cells to differentiate into macrophages, but reduced phagocytic activity against Escherichia coli and lowered the secretion of nitric oxide. The ablation of galectin-12 also resulted in the polarization of macrophages into the M2 direction, as indicated by increases in the levels of M2 markers, namely, resistin-like ß (FIZZ1) and chitinase 3-like 3 (Ym1), as well as a reduction in the expression levels of a number of M1 pro-inflammatory cytokines. We found that the diminished expression of pro-inflammatory cytokines in macrophages resulting from galectin-12 deletion was due to reduced activation of IKKα/ß, Akt and ERK, which in turn caused decreased activation of NF-κB and activator protein 1. The activation of STAT3 was much higher in Gal12(-/-) macrophages activated by lipopolysaccharide, which was correlated with higher levels of IL-10. Adipocytes showed higher insulin sensitivity when treated with Gal12(-/-) macrophage-conditioned media than those treated with Gal12(+/+) macrophages. We conclude galectin-12 negatively regulates macrophage polarization into the M2 population, resulting in enhanced inflammatory responses and also in turn causing decreased insulin sensitivity in adipocytes. This has implications in the treatment of a wide spectrum of metabolic disorders.

Effect of microRNA-155 on the interferon-gamma signaling pathway in biliary atresia.

MicroRNAs (miRNAs) are ~22-nucleotide long RNAs that negatively regulate gene expression and inflammatory responses in eukaryotes. The aim of this work was to evaluate the roles of miRNA (miR)-155 on the interferon-γ (IFN-γ)-induced response in biliary atresia (BA), which is the most common form of pediatric chronic liver disease and a leading indication for pediatric liver transplantation. The expression of miR-155 and the suppressor of cytokine signaling 1 (SOCS1) gene in human and mice liver tissues of BA and healthy controls was evaluated. IFN-γ-induced expression of miR-155, inflammatory cytokines and chemokines was determined in bile duct cells. A miR-155 inhibitor was used to determine the influence in the IFN-γ-induced signaling pathway by western blot analysis. A strong up-regulation of miR-155 expression was observed in BA histologic sections and mouse bile duct cells treated with IFN-γ. miR-155 down-regulated SOCS1 protein expression by targeting its mRNA. Up-regulation of miR-155 expression by IFN-γ in bile duct cells led to the activation of signal transducers and activators of transcription 1 (Stat1) and inflammatory cytokines through the Janus kinase (Jak)/Stat pathway, whereas targeted inhibition of miR-155 expression by anti-miRNA oligonucleotides significantly decreased the mRNA or protein expression levels of these inflammatory cytokines and Stat1. Overall, our results suggest that miR-155 regulates the IFN-γ signaling pathway by targeting SOCS1 expression and may be a potential target in BA therapy.

Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway.

BACKGROUND: Flavones found in plants display various biological activities, including anti-allergic, anti-viral, anti-inflammatory, anti-oxidation, and anti-tumor effects. In this study, we investigated the anti-tumor effects of flavone, apigenin and luteolin on human breast cancer cells. METHODS: The anti-cancer activity of flavone, apigenin and luteolin was investigated using the MTS assay. Apoptosis was analyzed by Hoechst 33342 staining, flow cytometry and western blot. Cell migration was determined using the culture inserts and xCELLigence real-time cell analyzer instrument equipped with a CIM-plate 16. Real-time quantitative PCR and western blot were used to determine the signaling pathway elicited by flavone, apigenin and luteolin. RESULTS: Flavone, apigenin and luteolin showed potent inhibitory effects on the proliferation of Hs578T, MDA-MB-231 and MCF-7 breast cancer cells in a concentration and time-dependent manner. The ability of flavone, apigenin and luteolin to inhibit the growth of breast cancer cells through apoptosis was confirmed by Hoechst33342 staining and the induction of sub-G1 phase of the cell cycle. Flavone, apigenin and luteolin induced forkhead box O3 (FOXO3a) expression by inhibiting Phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB)/Akt. This subsequently elevated the expression of FOXO3a target genes, including the Cyclin-dependent kinase inhibitors p21Cip1 (p21) and p27kip1 (p27), which increased the levels of activated poly(ADP) polymerase (PARP) and cytochrome c. CONCLUSION: Taken together, these data demonstrated that flavone, apigenin and luteolin induced cell cycle arrest and apoptosis in breast cancer cells through inhibiting PI3K/Akt activation and increasing FOXO3a activation, which suggest that flavone, apigenin and luteolin will be the potential leads for the preventing and treating of breast cancer.

Association of interleukin-16 polymorphisms with graves' disease in a Taiwanese population.

Graves' disease (GD) is a complex, organ-specific autoimmune disease wherein the thyroid gland becomes enlarged and overactive. During GD progression, T cells secrete interleukin-16 (IL-16) to promote inflammation, act as chemoattractants that recruit more inflammatory cells, and activate target cells to enhance the development of GD. To investigate the role of IL-16 in GD, we genotyped 474 patients with GD at 8 single-nucleotide polymorphisms (SNPs) in the IL-16 gene. The IL-16 SNP rs8028364 was found to be associated with GD when compared with the control subjects (P = 2.93 × 10⁻¹7; CG genotype: odds ratio [OR] = 0.2 [0.07, 0.59]; CC genotype: OR = 0.03 [0.01, 0.09]). The rs1131445 polymorphism was found to be associated with GD under the allelic model (P = 0.01; G allele: OR = 1.97 [1.17, 3.32]). Sliding-window haplotype analysis by the PLINK program showed that the most significant haplotype was provided by the 6-SNP haplotype window, consisting of rs7182786, rs8028364, rs12907134, rs4128767, rs4072111 and rs8031107 (P = 2.31 × 10⁻5¹). We found 2 protective haplotypes: GCAAGG (P = 8.69 × 10⁻7; OR = 0.22 [0.12, 0.41]) and AGAAGG (P = 0.0012; OR = 0.26 [0.12, 0.6]). In addition, GGGGAA (P = 0.39; OR = 2.32 [1.08, 4.99]) and GGGAGA (P = 1.18 × 10⁻5; OR = 5.54 [2.50, 12.31]) were found to be the two high-risk haplotypes. These results suggest that polymorphisms in IL-16 may be used as genetic markers for the diagnosis and prognosis of GD.

Complement decay-accelerating factor inhibits inflammation-induced myopia development.

Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-ß, IL-6, TNF-α, and IL-1ß may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-ß) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.

Genetic variation in NOS2A is associated with a sustained virological response to peginterferon plus ribavirin therapy for chronic hepatitis C in Taiwanese Chinese.

This study aimed to evaluate whether genetic polymorphisms of the inducible nitric oxide synthase (iNOS) gene NOS2A could be associated with a sustained virological response (SVR) among patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2) who were treated with peginterferon plus ribavirin (PEG-IFNα-RBV). We analyzed the associations between SVR to PEG-IFNα-RBV therapy and two single nucleotide polymorphisms (SNPs) in NOS2A. This study included Taiwanese Chinese patients infected with either HCV-1 (n = 265) or HCV-2 (n = 195) with or without a SVR. Among the NOS2A SNPs examined, the combination of genotypes A/A and A/G of rs2248814 was inversely correlated with SVR in patients infected with HCV-1 (P = 0.0048), particularly in males (P = 0.0281). This effect was not observed in patients infected with HCV-2. The AC NOS2A haplotype comprising two SNPs (rs2248814 and rs2072324) was found to be associated with SVR, and its presence may decrease the chances for a successful outcome of treatment of patients infected with HCV-1 (P = 0.0053). HCV-1 infected patients who carried the A-C diplotype will have a lower success rate of achieving a SVR (P = 0.0117). In addition, a multivariate logistic regression model for predicting a SVR revealed that the presence of the A-C diplotype interactively affected the outcome of PEG-IFNα-RBV treatment. The presence of NOS2A SNPs and the association with SVR showed that NOS2A polymorphisms may influence the therapeutic outcomes of patients infected with HCV-1 under standard of care treatment.

Using Machine Learning to Identify the Relationships between Demographic, Biochemical, and Lifestyle Parameters and Plasma Vitamin D Concentration in Healthy Premenopausal Chinese Women.

INTRODUCTION: Vitamin D plays a vital role in maintaining homeostasis and enhancing the absorption of calcium, an essential component for strengthening bones and preventing osteoporosis. There are many factors known to relate to plasma vitamin D concentration (PVDC). However, most of these studies were performed with traditional statistical methods. Nowadays, machine learning methods (Mach-L) have become new tools in medical research. In the present study, we used four Mach-L methods to explore the relationships between PVDC and demographic, biochemical, and lifestyle factors in a group of healthy premenopausal Chinese women. Our goals were as follows: (1) to evaluate and compare the predictive accuracy of Mach-L and MLR, and (2) to establish a hierarchy of the significance of the aforementioned factors related to PVDC. METHODS: Five hundred ninety-three healthy Chinese women were enrolled. In total, there were 35 variables recorded, including demographic, biochemical, and lifestyle information. The dependent variable was 25-OH vitamin D (PVDC), and all other variables were the independent variables. Multiple linear regression (MLR) was regarded as the benchmark for comparison. Four Mach-L methods were applied (random forest (RF), stochastic gradient boosting (SGB), extreme gradient boosting (XGBoost), and elastic net). Each method would produce several estimation errors. The smaller these errors were, the better the model was. RESULTS: Pearson's correlation, age, glycated hemoglobin, HDL-cholesterol, LDL-cholesterol, and hemoglobin were positively correlated to PVDC, whereas eGFR was negatively correlated to PVDC. The Mach-L methods yielded smaller estimation errors for all five parameters, which indicated that they were better methods than the MLR model. After averaging the importance percentage from the four Mach-L methods, a rank of importance could be obtained. Age was the most important factor, followed by plasma insulin level, TSH, spouse status, LDH, and ALP. CONCLUSIONS: In a healthy Chinese premenopausal cohort using four different Mach-L methods, age was found to be the most important factor related to PVDC, followed by plasma insulin level, TSH, spouse status, LDH, and ALP.

MetaMOPE: a web service for mobile phase determination and fast chromatography peaks evaluation for metabolomics.

Motivation: Liquid chromatography coupled with mass spectrometry (LC-MS) is widely used in metabolomics studies, while HILIC LC-MS is particularly suited for polar metabolites. Determining an optimized mobile phase and developing a proper liquid chromatography method tend to be laborious, time-consuming and empirical. Results: We developed a containerized web tool providing a workflow to quickly determine the optimized mobile phase by batch-evaluating chromatography peaks for metabolomics LC-MS studies. A mass chromatographic quality value, an asymmetric factor, and the local maximum intensity of the extracted ion chromatogram were calculated to determine the number of peaks and peak retention time. The optimal mobile phase can be quickly determined by selecting the mobile phase that produces the largest number of resolved peaks. Moreover, the workflow enables one to automatically process the repeats by evaluating chromatography peaks and determining the retention time of large standards. This workflow was validated with 20 chemical standards and successfully constructed a reference library of 571 metabolites for the HILIC LC-MS platform. Availability and implementation: MetaMOPE is freely available at https://metamope.cmdm.tw. Source code and installation instructions are available on GitHub: https://github.com/CMDM-Lab/MetaMOPE. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Acupuncture modulates development of myopia by reducing NLRP3 inflammasome activation via the dopamine-D1R signaling pathway.

BACKGROUND: Dopamine has been suggested to be a stop signal for eye growth and affects the development of myopia. Acupuncture is known to increase dopamine secretion and is widely used to treat myopia clinically. OBJECTIVE: The aim of this study was to determine if acupuncture inhibits myopia progression in form deprived Syrian hamsters by inducing rises in dopamine content that in turn suppress inflammasome activation. METHODS: Acupuncture was applied at LI4 and Taiyang every other day for 21 days. The levels of molecules associated with the dopamine signaling pathway, inflammatory signaling pathway and inflammasome activation were determined. A dopamine agonist (apomorphine) was used to evaluate if activation of the dopaminergic signaling pathway suppresses myopia progression by inhibiting inflammasome activation in primary retinal pigment epithelial (RPE) cells. A dopamine receptor 1 (D1R) inhibitor (SCH39166) was also administered to the hamsters. RESULTS: Acupuncture inhibited myopia development by increasing dopamine levels and activating the D1R signaling pathway. Furthermore, we also demonstrated that nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome activation was inhibited by activation of the D1R signaling pathway. CONCLUSION: Our findings suggest that acupuncture inhibits myopia development by suppressing inflammation, which is initiated by activation of the dopamine-D1R signaling pathway.

Determination of trace indium in urine after preconcentration with a chelating-resin-packed minicolumn.

A simple and rapid chelating-resin-packed column has been developed for preconcentration of trace indium in biological samples. A large-sized urine sample was pumped through a minicolumn at a flow rate of 1.0 mL/min by using a peristaltic pump, and the eluents were analyzed using graphite furnace atomic absorption spectrometry (GFAAS). Four commercially available chelating resins including Chelex-100, Amberlite IRC-50, Duolite GT-73, and Celite 545-AW were studied for evaluating the indium sorption performance. Several parameters, such as pH, resin amount, eluent volume, eluent flow rate, and the volume of sample, were investigated and optimized. A 100-200 mL of the sample was loaded into a column containing 1.2 g of wet Chelex-100 and subjected to the ion-exchange procedure. The retained analytes were eluted with 5.0 mL of 0.1 M HNO(3) and quantified by GFAAS. The correlation coefficient in the range 10-250 ng/mL was of 0.9994. The limit of detection of the proposed method was 2.75 ng/mL. The method developed was successfully applied to analysis of spiked urine samples with good recoveries of 93-103% (n = 6) and reproducibility (relative standard deviation < 4.9%). The accuracy of procedure was confirmed by indium determination in spiked certified reference materials.

Rhein induces apoptosis in human breast cancer cells.

Human breast cancers cells overexpressing HER2/neu are more aggressive tumors with poor prognosis, and resistance to chemotherapy. This study investigates antiproliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2) and control vector MCF-7 (MCF-7/VEC) cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells.

A study of students' learning perceptions and behaviors in remote STEM programming education.

In recent years, STEM education has developed students' fundamental subject knowledge, and has allowed students to integrate STEM cross-domain knowledge. Universities emphasize innovative thinking, practice and application, problem-solving, and teamwork to nurture students while learning STEM cross-domain knowledge development in remote STEM program education. When students take online STEM programs, they may encounter unanswered questions and may give up on trying to solve them. Therefore, this study proposed a problem-based learning approach with an online programming system integrated into an online STEM programming course. To help students solve the past programming assignments, the assignments were simplified, decomposed, and reorganized. The teacher guided the students to understand the STEM programming problems and taught them to use appropriate problem-solving skills to motivate them to complete the STEM programming assignments. The experiment was conducted with students in an online STEM programming course at a university in northern Taiwan. In the experimental activities, we used a problem-based learning approach for the online STEM programming activity. The problem-based learning method can be divided into four steps, namely stating the problem, understanding the problem, developing a solution plan, and executing the plan, reflecting, and debugging. This study used a problem-based learning approach and an online programming system integrated into a STEM programming curriculum to explore the differences in students' perceptions of STEM learning, learning outcomes, and learning behaviors. The experimental results found a significant difference between students' prior knowledge and learning outcomes. Students showed significant gains in learning the STEM programming content using the problem-based learning approach and the online programming system. In the analysis of their STEM learning perceptions, we found that there were significant differences in students' responses for each dimension. This shows that using the problem-based learning approach with the online programming system helped students learn the course content. The analysis of students' behaviors in answering the STEM programming assignments indicated that some students had the habit of taking notes. This helped them to easily associate and integrate STEM cross-domain knowledge with what they had learned in the online course, and enhanced their ability to implement STEM programs. In addition, students could take the initiative and focus on repeatedly watching the teacher solve the material in the online course. Students could try different solving plans to pass the code validation of the STEM programming assignments. This revealed that students wanted to complete the STEM programming assignments to achieve good learning performance.

RSDB: A rare skin disease database to link drugs with potential drug targets for rare skin diseases.

Rare skin diseases include more than 800 diseases affecting more than 6.8 million patients worldwide. However, only 100 drugs have been developed for treating rare skin diseases in the past 38 years. To investigate potential treatments through drug repurposing for rare skin diseases, it is necessary to have a well-organized database to link all known disease causes, mechanisms, and related information to accelerate the process. Drug repurposing provides less expensive and faster potential options to develop treatments for known diseases. In this work, we designed and constructed a rare skin disease database (RSDB) as a disease-centered information depository to facilitate repurposing drug candidates for rare skin diseases. We collected and integrated associated genes, chemicals, and phenotypes into a network connected by pairwise relationships between different components for rare skin diseases. The RSDB covers 891 rare skin diseases defined by the Orphanet and GARD databases. The organized network for each rare skin disease comprises associated genes, phenotypes, and chemicals with the corresponding connections. The RSDB is available at https://rsdb.cmdm.tw .

Fallopia Japonica and Prunella vulgaris inhibit myopia progression by suppressing AKT and NFκB mediated inflammatory reactions.

BACKGROUND: The increased global incidence of myopia requires the establishment of therapeutic approaches. This study aimed to investigate the effect of Fallopia Japonica (FJ) and Prunella vulgaris (PV) extract on myopia caused by monocular form deprivation (MFD). METHODS: We used human retinal pigment epithelial cell to study the molecular mechanisms on how FJ extract (FJE) and PV extract (PVE) lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia. RESULTS: FJE + PVE reduced IL-6, IL-8, and TNF-α expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-α expression levels in RPE cells treated with IL-6 and TNF-α. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-α. They also inhibited myopia-related transforming growth factor-beta (TGF)-ß1, matrix metalloproteinase (MMP)-2, and NF-κB expression while increasing type I collagen expression. CONCLUSIONS: Overall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.

In vivo and in vitro evidence for growth hormone-like bioactivity of Rhizoma Anemarrhenae extract.

Certain herbs used in traditional Chinese medicine may produce a growth-enhancing effect by promoting the secretion of growth hormone (GH) by the pituitary gland or mimicking the function of GH. In this study, we aimed to identify herbs that could serve as GH alternatives. A reporter gene assay for GH was developed, and 100 different herbal extracts were assayed. We found that Rhizoma Anemarrhenae (RA) water extracts exhibited transactivation activities that stimulate the activation of signal transducer and activator of transcription 5 (STAT5). The growth-promoting effect of RA in NB2-11 cells was inhibited by co-treatment with GH receptor (GHR)-Fc fusion protein. Unlike GH, RA extracts did not enhance the growth of B16F10 melanoma cells. The activation of the Janus kinase 2-STAT5 signaling pathway was confirmed in both NB2-11 cells and WI-38 human normal lung fibroblasts; the activation was inhibited by co-treatment with GHR-Fc fusion protein. Docking analysis of the active ingredients of RA, including mangiferin, neomangiferin, isomangiferin, anemarsaponin E, 7-O-methylmangiferin, officinalisinin I, timosaponin BII, timosaponin AI, and timosaponin AIII, using SWISSDOCK indicated a direct interaction of these compounds with GHR. The growth-promoting effects and activation of STAT5 were also confirmed. Moreover, we found that RA extract significantly increased the height of the tibial growth plate and stimulated the production of insulin-like growth factor 1 in the serum, liver, and muscle tissues. Our findings provide evidence that herbal extracts, particularly, RA extracts, can promote growth by mimicking GH bioactivity.

(4Z)-4-[(2,6-Diisopropyl-anilino)(phen-yl)methyl-idene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one.

In the title compound, C(29)H(31)N(3)O, the three terminal benzene rings are oriented at dihedral angles of 20.7 (3), 65.8 (3) and 72.6 (3)° with respect to the central pyrazolone ring. Intra-molecular N-H⋯O hydrogen bonding occurs between the imine and carbonyl groups. Inter-molecular C-H⋯π inter-actions are present in the crystal structure.