Isolation of amylase regulators from the leaves of <i>Ixeridium dentatum</i>

Two new compounds, one sesquiterpene lactone (1) and one phenylethanoid tautomer (2), together with eleven known compounds (3–13) were isolated from the leaves of Ixeridium dentatum. Their structures were determined by extensive spectroscopic methods, including 1D-, 2D-NMR, and mass spectrometry. All compounds were evaluated for their amylase secretion activity in human salivary gland cells after treatment in 40 mM of high glucose. All compounds showed increased amylase secretion activity. Moreover, previously undescribed compounds (1–2), luteolin 7-O-β-D-glucopyranoside (10), quercimeritrin (11), and quercetin 3-O-β-D-xylopyranoside (13) exhibited significant amylase activity, which is comparable to the positive control.</p

Supplementary methods and Supplementary FigS1-6 from c-MYC Drives Breast Cancer Metastasis to the Brain, but Promotes Synthetic Lethality with TRAIL

S1. Elevated c-MYC activity in MCF7-BrM promotes brain metastasis (related to Fig 1) S2. C-MYC regulates tumor sphere circularity and invasiveness in a HA-collagen matrix (related to Fig 2) S3. c-MYC-mediated recruitment of RAW cells (related to Fig 3) S4. qRT-PCR analysis of c-MYC-regulated genes (related to Fig 4) S5. Association of c-MYC and MYC-BrMFS with BrMFS in the MSK82 dataset (related to Fig 5) S6. BrM-BCCs exhibit elevated TRAIL sensitivity (related to Fig 6)</p

Supplementary Data S1 from Oncogenic KRAS Sensitizes Lung Adenocarcinoma to GSK-J4–Induced Metabolic and Oxidative Stress

list of genes regulated from RNA sequencing analysis</p

Supplementary Tables S1 and S2, supplementary figures S1-S7, legends, and methods from Oncogenic KRAS Sensitizes Lung Adenocarcinoma to GSK-J4–Induced Metabolic and Oxidative Stress

Supplementary Table S1. Protein-protein interaction enrichment analysis of GSK-J4-induced genes in sensitive lines; Supplementary Table S2. Mutation status of several oncogenes and tumor suppressor genes in GSK-J4-sensitive and resistant lines. Supplementary Figure S1. GSK-J4 segregates LuAC cell lines into the "sensitive" and "resistant" groups via targeting KDM6B; Supplementary Figure S2. Effects of GSK-J4 on cell cycle and apoptosis of the GSK-J4-sensitive and resistant LuAC lines; Supplementary Figure S3. GSK-J4 affects expression of specific gene sets in sensitive LuAC cell lines; Supplementary Figure S4. Chromatin and gene expression analysis of GSK-J4-regulated genes in various LuAC; Supplementary Figure S5. GSK-J4 induces the ATF4 pathway in sensitive LuAC lines but ATF4 knockdown does not affect GSK-J4 sensitivity; Supplementary Figure S6. GSK-J4 induces oxidative and metabolic stress in the sensitive LuAC lines; Supplementary Figure S7. Oncogenic KRAS sensitizes LuAC and PDAC cell lines to GSK-J4. Supplementary materials and methods include materials, colony formation assay, animal studies, RNA extraction from subcutaneous tumor samples, quantification of ROS upon KRAS knockdown, generation of overexpression cell lines, motif analysis, genome-wide ChIP-seq analysis, qRT-PCR, western blotting, apoptosis analysis, cell viability assay, genome-wide RNA-seq analysis, overexpression constructs, oligo sequences for siRNAs.</p

Supplementary Data S2 from Oncogenic KRAS Sensitizes Lung Adenocarcinoma to GSK-J4–Induced Metabolic and Oxidative Stress

GO analysis of GSK-J4 downregulated genes</p

Supplementary Data S3 from Oncogenic KRAS Sensitizes Lung Adenocarcinoma to GSK-J4–Induced Metabolic and Oxidative Stress

GO analysis of GSK-J4-upregulated genes</p

PET Imaging of Innate Immune Activation Using ¹¹C Radiotracers Targeting GPR84

Chronic innate immune activation is a key hallmark of many neurological diseases and is known to result in the upregulation of GPR84 in myeloid cells (macrophages, microglia, and monocytes). As such, GPR84 can potentially serve as a sensor of proinflammatory innate immune responses. To assess the utility of GPR84 as an imaging biomarker, we synthesized 11C-MGX-10S and 11C-MGX-11S via carbon-11 alkylation for use as positron emission tomography (PET) tracers targeting this receptor. In vitro experiments demonstrated significantly higher binding of both radiotracers to hGPR84-HEK293 cells than that of parental control HEK293 cells. Co-incubation with the GPR84 antagonist GLPG1205 reduced the binding of both radiotracers by >90%, demonstrating their high specificity for GPR84 in vitro. In vivo assessment of each radiotracer via PET imaging of healthy mice illustrated the superior brain uptake and pharmacokinetics of 11C-MGX-10S compared to 11C-MGX-11S. Subsequent use of 11C-MGX-10S to image a well-established mouse model of systemic and neuro-inflammation revealed a high PET signal in affected tissues, including the brain, liver, lung, and spleen. In vivo specificity of 11C-MGX-10S for GPR84 was confirmed by the administration of GLPG1205 followed by radiotracer injection. When compared with 11C-DPA-713an existing radiotracer used to image innate immune activation in clinical research studies11C-MGX-10S has multiple advantages, including its higher binding signal in inflamed tissues in the CNS and periphery and low background signal in healthy saline-treated subjects. The pronounced uptake of 11C-MGX-10S during inflammation, its high specificity for GPR84, and suitable pharmacokinetics strongly support further investigation of 11C-MGX-10S for imaging GPR84-positive myeloid cells associated with innate immune activation in animal models of inflammatory diseases and human neuropathology

PET Imaging of Innate Immune Activation Using ¹¹C Radiotracers Targeting GPR84

Chronic innate immune activation is a key hallmark of many neurological diseases and is known to result in the upregulation of GPR84 in myeloid cells (macrophages, microglia, and monocytes). As such, GPR84 can potentially serve as a sensor of proinflammatory innate immune responses. To assess the utility of GPR84 as an imaging biomarker, we synthesized 11C-MGX-10S and 11C-MGX-11S via carbon-11 alkylation for use as positron emission tomography (PET) tracers targeting this receptor. In vitro experiments demonstrated significantly higher binding of both radiotracers to hGPR84-HEK293 cells than that of parental control HEK293 cells. Co-incubation with the GPR84 antagonist GLPG1205 reduced the binding of both radiotracers by >90%, demonstrating their high specificity for GPR84 in vitro. In vivo assessment of each radiotracer via PET imaging of healthy mice illustrated the superior brain uptake and pharmacokinetics of 11C-MGX-10S compared to 11C-MGX-11S. Subsequent use of 11C-MGX-10S to image a well-established mouse model of systemic and neuro-inflammation revealed a high PET signal in affected tissues, including the brain, liver, lung, and spleen. In vivo specificity of 11C-MGX-10S for GPR84 was confirmed by the administration of GLPG1205 followed by radiotracer injection. When compared with 11C-DPA-713an existing radiotracer used to image innate immune activation in clinical research studies11C-MGX-10S has multiple advantages, including its higher binding signal in inflamed tissues in the CNS and periphery and low background signal in healthy saline-treated subjects. The pronounced uptake of 11C-MGX-10S during inflammation, its high specificity for GPR84, and suitable pharmacokinetics strongly support further investigation of 11C-MGX-10S for imaging GPR84-positive myeloid cells associated with innate immune activation in animal models of inflammatory diseases and human neuropathology

PET Imaging of Innate Immune Activation Using ¹¹C Radiotracers Targeting GPR84

Chronic innate immune activation is a key hallmark of many neurological diseases and is known to result in the upregulation of GPR84 in myeloid cells (macrophages, microglia, and monocytes). As such, GPR84 can potentially serve as a sensor of proinflammatory innate immune responses. To assess the utility of GPR84 as an imaging biomarker, we synthesized 11C-MGX-10S and 11C-MGX-11S via carbon-11 alkylation for use as positron emission tomography (PET) tracers targeting this receptor. In vitro experiments demonstrated significantly higher binding of both radiotracers to hGPR84-HEK293 cells than that of parental control HEK293 cells. Co-incubation with the GPR84 antagonist GLPG1205 reduced the binding of both radiotracers by >90%, demonstrating their high specificity for GPR84 in vitro. In vivo assessment of each radiotracer via PET imaging of healthy mice illustrated the superior brain uptake and pharmacokinetics of 11C-MGX-10S compared to 11C-MGX-11S. Subsequent use of 11C-MGX-10S to image a well-established mouse model of systemic and neuro-inflammation revealed a high PET signal in affected tissues, including the brain, liver, lung, and spleen. In vivo specificity of 11C-MGX-10S for GPR84 was confirmed by the administration of GLPG1205 followed by radiotracer injection. When compared with 11C-DPA-713an existing radiotracer used to image innate immune activation in clinical research studies11C-MGX-10S has multiple advantages, including its higher binding signal in inflamed tissues in the CNS and periphery and low background signal in healthy saline-treated subjects. The pronounced uptake of 11C-MGX-10S during inflammation, its high specificity for GPR84, and suitable pharmacokinetics strongly support further investigation of 11C-MGX-10S for imaging GPR84-positive myeloid cells associated with innate immune activation in animal models of inflammatory diseases and human neuropathology

PET Imaging of Innate Immune Activation Using ¹¹C Radiotracers Targeting GPR84

Chronic innate immune activation is a key hallmark of many neurological diseases and is known to result in the upregulation of GPR84 in myeloid cells (macrophages, microglia, and monocytes). As such, GPR84 can potentially serve as a sensor of proinflammatory innate immune responses. To assess the utility of GPR84 as an imaging biomarker, we synthesized 11C-MGX-10S and 11C-MGX-11S via carbon-11 alkylation for use as positron emission tomography (PET) tracers targeting this receptor. In vitro experiments demonstrated significantly higher binding of both radiotracers to hGPR84-HEK293 cells than that of parental control HEK293 cells. Co-incubation with the GPR84 antagonist GLPG1205 reduced the binding of both radiotracers by >90%, demonstrating their high specificity for GPR84 in vitro. In vivo assessment of each radiotracer via PET imaging of healthy mice illustrated the superior brain uptake and pharmacokinetics of 11C-MGX-10S compared to 11C-MGX-11S. Subsequent use of 11C-MGX-10S to image a well-established mouse model of systemic and neuro-inflammation revealed a high PET signal in affected tissues, including the brain, liver, lung, and spleen. In vivo specificity of 11C-MGX-10S for GPR84 was confirmed by the administration of GLPG1205 followed by radiotracer injection. When compared with 11C-DPA-713an existing radiotracer used to image innate immune activation in clinical research studies11C-MGX-10S has multiple advantages, including its higher binding signal in inflamed tissues in the CNS and periphery and low background signal in healthy saline-treated subjects. The pronounced uptake of 11C-MGX-10S during inflammation, its high specificity for GPR84, and suitable pharmacokinetics strongly support further investigation of 11C-MGX-10S for imaging GPR84-positive myeloid cells associated with innate immune activation in animal models of inflammatory diseases and human neuropathology