Microglia-derived exosomal ciRS-7 mediates IL-17A effect of promoting neurodegeneration via miR-7 and SNCA targets in an experimental Parkinson's disease.

Parkinson' s disease (PD) is a chronic neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra (SN). Our research has demonstrated that the levels of interleukin (IL)-17A are elevated in the SN of rodent models of PD, and that IL-17A accelerates neurodegeneration in PD depending on microglial activation. Furthermore, existing studies indicate that exosomes released by activated microglia may play a significant role as mediators of neurodegeneration in PD.

The Proteomics of T-Cell and Early T-Cell Precursor (ETP) Acute Lymphocytic Leukemia: Prognostic Patterns in Adult and Pediatric-ETP ALL.

Background: The 5-year overall survival (OS) rates of T-cell lymphocytic leukemia (T-ALL) are better for children (>90%) compared to adults (~57%). The early T-cell precursor (ETP) T-ALL subtype is prognostically unfavorable in adults, but less significant in pediatric T-ALL, and the diagnosis and prognosis of "near"-ETP is controversial. We compared protein and RNA expression patterns in pediatric and adult T-ALL to identify prognostic subgroups, and to further characterize ETP and near-ETP T-ALL in both age groups.

Encapsulation of lycopene in Pickering emulsion stabilized by complexes of whey protein isolate fibrils and sodium alginate: Physicochemical property, structural characterization and in vitro digestion property.

In present study, whey protein isolate fibrils and sodium alginate complexes (WPIFs-SA) were prepared and further used to stabilize Pickering emulsions for lycopene delivery. The optimal interaction between WPIFs and SA occurred at pH 3.0, with a mass ratio of 2:1.

Reverse Phase Proteomic Array Profiling of Asparagine Synthetase Expression in Newly Diagnosed Acute Myeloid Leukemia.

Asparaginase-based therapy is a cornerstone in acute lymphoblastic leukemia (ALL) treatment, capitalizing on the methylation status of the asparagine synthetase (ASNS) gene, which renders ALL cells reliant on extracellular asparagine. Contrastingly, ASNS expression in acute myeloid leukemia (AML) has not been thoroughly investigated, despite studies suggesting that AML with chromosome 7/7q deletions might have reduced ASNS levels. Here, we leverage reverse phase protein arrays to measure ASNS expression in 810 AML patients and assess its impact on outcomes.

Chromatin Profiles Are Prognostic of Clinical Response to Bortezomib-Containing Chemotherapy in Pediatric Acute Myeloid Leukemia: Results from the COG AAML1031 Trial.

The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children's Oncology Group phase 3 trial AAML1031 (NCT01371981). Proteasome inhibition influences the chromatin landscape and proteostasis, and we hypothesized that baseline proteomic analysis of histone- and chromatin-modifying enzymes (HMEs) would identify AML subgroups that benefitted from bortezomib addition. A proteomic profile of 483 patients treated with AAML1031 chemotherapy was generated using a reverse-phase protein array.

Development and characterization of hydrogel-in-oleogel (bigel) systems and their application as a butter replacer for bread making.

Background: Butter has been widely used in bakery products and it contains high level of saturated fats. However, excessive consumption of saturated fats would increase the risk of chronic disease. This study was to fabricate water-in-oil (W/O) type bigels as butter replacers to improve the quality attributes of breads.

Co-encapsulation of collagen peptide and astaxanthin in W/O/W double emulsions-filled alginate hydrogel beads: Fabrication, characterization and digestion behaviors.

The double emulsions-filled hydrogel beads delivery systems with controlled lipolysis and sustained-release property of co-encapsulated bioactive substances will be highly desired. Herein, the water-in-oil-in-water emulsion with gelled inner water phase and oil phase (W/O/W) filled hydrogel beads as a novel co-delivery system were developed with varied concentrations of rice bran wax and W/O emulsions to achieve effectively controlled release of lipolysis and nutraceuticals. Interestingly, the gelation of oil phase triggered by rice bran wax could enhance the storage stability of W/O/W emulsions due to the enhanced viscoelastic property.

Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children's Oncology Group.

Purpose: The endoplasmic reticulum (ER) is the major site of protein synthesis and folding in the cell. ER-associated degradation (ERAD) and unfolded protein response (UPR) are the main mechanisms of ER-mediated cell stress adaptation. Targeting the cell stress response is a promising therapeutic approach in acute myeloid leukemia (AML).

Dopamine D2 receptor on CD4 T cells is protective against inflammatory responses and signs in a mouse model of rheumatoid arthritis.

Background: Dopamine is a neurotransmitter and has been found to regulate lymphocytes by acting on dopamine receptors (DRs). CD4 T cells express all the five subtypes of DRs, D1R to D5R. Although CD4 T cells have been involved in pathogenesis of rheumatoid arthritis (RA), roles of DRs expressed on these cells in RA are poorly understood.

DNA Damage Response-Related Proteins Are Prognostic for Outcome in Both Adult and Pediatric Acute Myelogenous Leukemia Patients: Samples from Adults and from Children Enrolled in a Children's Oncology Group Study.

The survival of malignant leukemic cells is dependent on DNA damage repair (DDR) signaling. Reverse Phase Protein Array (RPPA) data sets were assembled using diagnostic samples from 810 adult and 500 pediatric acute myelogenous leukemia (AML) patients and were probed with 412 and 296 strictly validated antibodies, respectively, including those detecting the expression of proteins directly involved in DDR. Unbiased hierarchical clustering identified strong recurrent DDR protein expression patterns in both adult and pediatric AML.

Prognostication of DNA Damage Response Protein Expression Patterns in Chronic Lymphocytic Leukemia.

Proteomic DNA Damage Repair (DDR) expression patterns in Chronic Lymphocytic Leukemia were characterized by quantifying and clustering 24 total and phosphorylated DDR proteins. Overall, three protein expression patterns (C1-C3) were identified and were associated as an independent predictor of distinct patient overall survival outcomes. Patients within clusters C1 and C2 had poorer survival outcomes and responses to fludarabine, cyclophosphamide, and rituxan chemotherapy compared to patients within cluster C3.

Reverse Phase Protein Array Profiling Identifies Recurrent Protein Expression Patterns of DNA Damage-Related Proteins across Acute and Chronic Leukemia: Samples from Adults and the Children's Oncology Group.

DNA damage response (DNADR) recognition and repair (DDR) pathways affect carcinogenesis and therapy responsiveness in cancers, including leukemia. We measured protein expression levels of 16 DNADR and DDR proteins using the Reverse Phase Protein Array methodology in acute myeloid (AML) ( = 1310), T-cell acute lymphoblastic leukemia (T-ALL) ( = 361) and chronic lymphocytic leukemia (CLL) ( = 795) cases. Clustering analysis identified five protein expression clusters; three were unique compared to normal CD34+ cells.

Activation of β2-adrenergic Receptor Alleviates Collagen-induced Arthritis by Ameliorating Th17/Treg Imbalance.

Background: Recent research in our laboratory shows that CD4+ T cells express the β2 adrenergic receptor (β2-AR), and the sympathetic neurotransmitter norepinephrine regulates the function of T cells via β2-AR signaling. However, the immunoregulatory effect of β2-AR and its related mechanisms on rheumatoid arthritis is unknown.

Objective: To explore the effects of β2-AR in collagen-induced arthritis (CIA) on the imbalance of T helper (Th) 17/ regulatory T (Treg) cells.

Pomelo peel derived nanocellulose as Pickering stabilizers: Fabrication of Pickering emulsions and their potential as sustained-release delivery systems for lycopene.

Two kinds of nanocellulose (cellulose nanofibrils (CNFs) and cellulose nanocrystals (CNCs) were synthesized from pomelo peels via a facile approach of TEMPO oxidation and sulfuric acid treatment respectively. The FTIR results illustrated that hemicelluloses and lignin were completely removed from the pomelo peel cellulose substrate. The obtained CNFs and CNCs possessed a uniform morphology and nanoscale particle size.

Protein profiling by reverse phase protein array (RPPA) in classical hairy cell leukemia (HCL) and HCL-variant.

Classical hairy cell leukemia (HCL-c) and HCL variant (HCL-v) are recognized as separate entities with HCL-v having significantly shorter overall survival. Proteomic studies, shown to be prognostic in various forms of leukemia, have not been performed in HCL. We performed reverse phase protein array-based protein profiling with 384 antibodies in HCL-c ( = 12), HCL-v ( = 4), and normal B-cells ( = 5) samples.

Recent Advances in Hepatocellular Carcinoma Treatment with Radionuclides.

As the third leading cause of cancer death worldwide, hepatocellular carcinoma (HCC) is characterized by late detection, difficult diagnosis and treatment, rapid progression, and poor prognosis. Current treatments for liver cancer include surgical resection, radiofrequency ablation, liver transplantation, chemotherapy, external radiation therapy, and internal radionuclide therapy. Radionuclide therapy is the use of high-energy radiation emitted by radionuclides to eradicate tumor cells, thus achieving the therapeutic effect.

Interleukin 17A deficiency alleviates neuroinflammation and cognitive impairment in an experimental model of diabetic encephalopathy.

Interleukin 17A (IL-17A) was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications. However, the role of IL-17A in diabetic encephalopathy remains poorly understood. In this study, we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a mice with spontaneously diabetic Ins2 (Akita) mice.

Proteomic profiling based classification of CLL provides prognostication for modern therapy and identifies novel therapeutic targets.

Protein expression for 384 total and post-translationally modified proteins was assessed in 871 CLL and MSBL patients and was integrated with clinical data to identify strategies for improving diagnostics and therapy, making this the largest CLL proteomics study to date. Proteomics identified six recurrent signatures that were highly prognostic of survival and time to first or second treatment at three levels: individual proteins, when grouped into 40 functionally related groups (PFGs), and systemically in signatures (SGs). A novel SG characterized by hairy cell leukemia like proteomics but poor therapy response was discovered.

Clinical relevance of proteomic profiling in pediatric acute myeloid leukemia: a Children's Oncology Group study.

Pediatric acute myeloid leukemia (AML) remains a fatal disease for at least 30% of patients, stressing the need for improved therapies and better risk stratification. As proteins are the unifying feature of (epi)genetic and environmental alterations, and are often targeted by novel chemotherapeutic agents, we studied the proteomic landscape of pediatric AML. Protein expression and activation levels were measured in 500 bulk leukemic patients' samples and 30 control CD34+ cell samples, using reverse phase protein arrays with 296 strictly validated antibodies.

Bortezomib is significantly beneficial for de novo pediatric AML patients with low phosphorylation of the NF-κB subunit RelA.

Purpose: The addition of the proteasome inhibitor (PI) bortezomib to standard chemotherapy (ADE: cytarabine [Ara-C], daunorubicin, and etoposide) did not improve overall outcome of pediatric AML patients in the Children's Oncology Group AAML1031 phase 3 randomized clinical trial (AAML1031) . Bortezomib prevents protein degradation, including RelA via the intracellular NF-kB pathway. In this study, we hypothesized that subgroups of pediatric AML patients benefitting from standard therapy plus bortezomib (ADEB) could be identified based on pre-treatment RelA expression and phosphorylation status.

RPPA-based proteomics recognizes distinct epigenetic signatures in chronic lymphocytic leukemia with clinical consequences.

The chronic lymphocytic leukemia (CLL) armamentarium has evolved significantly, with novel therapies that inhibit Bruton Tyrosine Kinase, PI3K delta and/or the BCL2 protein improving outcomes. Still, the clinical course of CLL patients is highly variable and most previously recognized prognostic features lack the capacity to predict response to modern treatments indicating the need for new prognostic markers. In this study, we identified four epigenetically distinct proteomic signatures of a large cohort of CLL and related diseases derived samples (n = 871) using reverse phase protein array technology.

Decoupling Lineage-Associated Genes in Acute Myeloid Leukemia Reveals Inflammatory and Metabolic Signatures Associated With Outcomes.

Acute myeloid leukemia (AML) is a heterogeneous disease with variable responses to therapy. Cytogenetic and genomic features are used to classify AML patients into prognostic and treatment groups. However, these molecular characteristics harbor significant patient-to-patient variability and do not fully account for AML heterogeneity.

Dopamine receptor D2 on CD4 T cells is protective against neuroinflammation and neurodegeneration in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease. Recently, neuroinflammation driven by CD4 T cells has been involved in PD pathophysiology. Human and murine lymphocytes express all the five subtypes of dopamine receptors (DRs), DRD1 to DRD5.

Intervention of Tyrosine Hydroxylase Expression Alters Joint Inflammation and Th17/Treg Imbalance in Collagen-Induced Arthritis.

Background/aims: Neuroendocrine dysregulation has been associated with rheumatoid arthritis (RA). Tyrosine hydroxylase (TH), a rate-limiting enzyme for synthesis of neuroendocrine hormones such as epinephrine, is also expressed in T lymphocytes and regulates balance between helper T (Th) 17 cells and regulatory T (Treg) cells. Herein, we aimed to show that TH expression in joints alleviates joint inflammation and Th17/Treg imbalance in collagen-induced arthritis (CIA), an animal model of RA, and these effects may be implemented by the mechanism of epinephrine action on α1-adrenoreceptor (α1-AR) in T cells.