Proteomic analysis of APOEε4 carriers implicates lipid metabolism, complement and lymphocyte signaling in cognitive resilience.

Background: Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late onset Alzheimer's disease (AD). This case-cohort study used targeted plasma biomarkers and large-scale proteomics to examine the biological mechanisms that allow some APOEε4 carriers to maintain normal cognitive functioning in older adulthood.

Methods: APOEε4 carriers and APOEε3 homozygotes enrolled in the Women's Health Initiative Memory Study (WHIMS) from 1996 to 1999 were classified as resilient if they remained cognitively unimpaired beyond age 80, and as non-resilient if they developed cognitive impairment before or at age 80.

Plasma proteome-wide analysis of cerebral small vessel disease identifies novel biomarkers and disease pathways.

Cerebral small vessel disease (SVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although conditions such as hypertension are known to contribute to SVD, little is known about the diverse set of subclinical biological processes and molecular mediators that may also influence the development and progression of SVD. To better understand the mechanisms underlying SVD and to identify novel SVD biomarkers, we used a large-scale proteomic platform to relate 4,877 plasma proteins to MRI-defined SVD characteristics within 1,508 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort.

A plasma proteomic signature links secretome of senescent monocytes to aging- and obesity-related clinical outcomes in humans.

Cellular senescence increases with age and contributes to age-related declines and pathologies. We identified circulating biomarkers of senescence associated with diverse clinical traits in humans to facilitate future non-invasive assessment of individual senescence burden and efficacy testing of novel senotherapeutics. Using a novel nanoparticle-based proteomic workflow, we profiled the senescence-associated secretory phenotype (SASP) in monocytes and examined these proteins in plasma samples (N = 1060) from the Baltimore Longitudinal Study of Aging (BLSA).

A real world analysis of secondary BRAF variations after targeted therapy resistance in driver gene positive NSCLC.

Secondary BRAF variations have been identified as a mechanism of resistance to tyrosine kinase inhibitors (TKIs) in patients with driver gene-positive NSCLC. Nevertheless, there is still a lack of consensus regarding the characteristics and subsequent treatment strategies for these patients. We retrospectively reviewed the medical records of patients with driver gene-positive NSCLC who received TKIs therapy at Zhejiang Cancer Hospital between May 2016 and December 2023.

Efficacy of immunotherapy in fusion-positive NSCLC: A meta-analysis.

Background: The Rearranged during Transfection () gene represents a rare driver mutation in non-small cell lung cancer (NSCLC) occurring in only 1 %-2 % of cases, with implications in targeted carcinogenesis. Despite the significant efficacy demonstrated by immunotherapy in advanced NSCLC with wild-type driver genes, its validation in fusion-positive patients is yet to be established.

Objectives: This meta-analysis aims to systematically evaluate the effectiveness of immunotherapy in patients with fusion-positive NSCLC.

Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline.

Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe.

Role of immunotherapy in pulmonary sarcomatoid carcinoma: review of current approaches and related biomarkers.

Pulmonary sarcomatoid carcinoma (PSC), a rare subtype of non-small cell lung cancer, is highly malignant and has a poor prognosis. Treatments for PSC are presently limited. Traditional treatments provide fewer benefits to PSC patients and are associated with early recurrence and metastasis.

Evaluating for Correlations between Specific Metabolites in Patients Receiving First-Line or Second-Line Immunotherapy for Metastatic or Recurrent NSCLC: An Exploratory Study Based on Two Cohorts.

Immune checkpoint inhibitors (ICI) have displayed impressive clinical efficacy in the context of non-small cell lung cancer (NSCLC). However, most patients do not achieve long-term survival. Minimally invasive collected samples are attracting significant interest as new fields of biomarker study, and metabolomics is one of these growing fields.

Antegrade flexible ureteroscopy-assisted percutaneous nephrolithotomy for staghorn calculi: a prospective randomized controlled study.

The aim is to compare the efficacy and safety between single percutaneous nephrolithotomy (sPNL) and antegrade flexible ureteroscopy-assisted percutaneous nephrolithotomy (aPNL) for the treatment of staghorn calculi. A prospective randomized controlled study was conducted at the Second Hospital of Tianjin Medical University. A total of 160 eligible patients were included, with 81 in the sPNL group and 79 in the aPNL group.

Identification of Clinically Relevant Brain Endothelial Cell Biomarkers in Plasma.

Background: Proteins expressed by brain endothelial cells (BECs), the primary cell type of the blood-brain barrier, may serve as sensitive plasma biomarkers for neurological and neurovascular conditions, including cerebral small vessel disease.

Methods: Using data from the BLSA (Baltimore Longitudinal Study of Aging; n=886; 2009-2020), BEC-enriched proteins were identified among 7268 plasma proteins (measured with SomaScanv4.1) using an automated annotation algorithm that filtered endothelial cell transcripts followed by cross-referencing with BEC-specific transcripts reported in single-cell RNA-sequencing studies.

Proteomic Indicators of Health Predict Alzheimer's Disease Biomarker Levels and Dementia Risk.

Objective: Few studies have comprehensively examined how health and disease risk influence Alzheimer's disease (AD) biomarkers. The present study examined the association of 14 protein-based health indicators with plasma and neuroimaging biomarkers of AD and neurodegeneration.

Methods: In 706 cognitively normal adults, we examined whether 14 protein-based health indices (ie, SomaSignal® tests) were associated with concurrently measured plasma-based biomarkers of AD pathology (amyloid-β [Aβ] , tau phosphorylated at threonine-181 [pTau-181]), neuronal injury (neurofilament light chain [NfL]), and reactive astrogliosis (glial fibrillary acidic protein [GFAP]), brain volume, and cortical Aβ and tau.

Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life.

A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer's disease (AD) and related dementias. However, there is limited understanding of the peripheral biological mechanisms relevant in the earliest phases of the disease. Here, we used a large-scale proteomics platform to examine the association of 4877 plasma proteins with 25-year dementia risk in 10,981 middle-aged adults.

Serum cytokine analysis in a cohort of advanced non-small cell lung cancer treated with PD-1 inhibitors reveals predictive markers of CXCL12.

Background: The circulating predictive factors for the outcomes of advanced non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs) remain elusive. We aimed to assess the predictive value of circulating cytokines for outcomes.

Methods: Serum samples of 102 advanced-stage NSCLC patients who underwent immunotherapy were collected at baseline.

Plasma proteins related to inflammatory diet predict future cognitive impairment.

Dysregulation of the immune system and dietary patterns that increase inflammation can increase the risk for cognitive decline, but the mechanisms by which inflammatory nutritional habits may affect the development of cognitive impairment in aging are not well understood. To determine whether plasma proteins linked to inflammatory diet predict future cognitive impairment, we applied high-throughput proteomic assays to plasma samples from a subset (n = 1528) of Women's Health Initiative Memory Study (WHIMS) participants (mean [SD] baseline age, 71.3 [SD 3.

Association of liver disease with brain volume loss, cognitive decline, and plasma neurodegenerative disease biomarkers.

Although liver dysfunction has been implicated in Alzheimer's disease (AD), it remains unknown how liver disease may influence the trajectory of brain and cognitive changes in older adults. We related self-reported liver disease to longitudinal measures of brain structure and cognition, as well as baseline measures of plasma AD/neurodegeneration biomarkers in the Baltimore Longitudinal Study of Aging. Liver disease was identified using ICD-9 classification codes.

Herpes Viruses in the Baltimore Longitudinal Study of Aging: Associations With Brain Volumes, Cognitive Performance, and Plasma Biomarkers.

Background And Objectives: Although an infectious etiology of Alzheimer disease (AD) has received renewed attention with a particular focus on herpes viruses, the longitudinal effects of symptomatic herpes virus (sHHV) infection on brain structure and cognition remain poorly understood, as does the effect of sHHV on AD/neurodegeneration biomarkers.

Methods: We used a longitudinal, community-based cohort to characterize the association of sHHV diagnoses with changes in 3 T MRI brain volume and cognitive performance. In addition, we related sHHV to cross-sectional differences in plasma biomarkers of AD (β-amyloid [Aβ]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neurodegeneration (neurofilament light [NfL]).

Zinc finger protein 277 is an intestinal transit-amplifying cell marker and colon cancer oncogene.

Sustained proliferative signaling and resisting cell death are hallmarks of cancer. Zinc finger protein 277 (ZNF277; murine Zfp277), a transcription factor regulating cellular senescence, is overexpressed in colon cancer, but its actions in intestinal homeostasis and neoplasia are unclear. Using human and murine intestine, human colon cancer cells, and ApcMin/+ mice with dysregulated β-catenin signaling and exuberant intestinal neoplasia, we explored the actions of ZNF277/Zfp277 and defined the underlying mechanisms.

Farnesoid X receptor represses matrix metalloproteinase 7 expression, revealing this regulatory axis as a promising therapeutic target in colon cancer.

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of bile acid-activated transcription factors and an important regulator of cell proliferation, apoptosis, and Wnt signaling. Down-regulated expression of FXR plays an important role in some malignancies such as colon cancer, and in rodent models of intestinal neoplasia, FXR knockout increases the size and number of colon tumors. These previous observations implicate FXR as a tumor suppressor, but the underlying molecular mechanisms are unclear.

Cholinergic muscarinic receptor activation augments murine intestinal epithelial cell proliferation and tumorigenesis.

Background: Previously, we showed that M3 muscarinic receptor (M3R; gene name Chrm3) deficiency attenuates murine intestinal neoplasia, supporting the hypothesis that muscarinic receptors play an important role in intestinal tumorigenesis.

Methods: To test this hypothesis, in the present study we treated mice with bethanechol, a non-selective muscarinic receptor agonist without nicotinic receptor activity, and examined its effects on azoxymethane (AOM)-induced colon neoplasia. Mice were provided with drinking water containing 400 μg/mL bethanechol chloride or water without additions (control) for a total of 20 weeks, a period that included the initial 6 weeks when mice received intraperitoneal injections of AOM.

Src-mediated cross-talk between farnesoid X and epidermal growth factor receptors inhibits human intestinal cell proliferation and tumorigenesis.

Besides its essential role in controlling bile acid and lipid metabolism, the farnesoid X receptor (FXR) protects against intestinal tumorigenesis by promoting apoptosis and inhibiting cell proliferation. However, the mechanisms underlying these anti-proliferative actions of FXR remain to be elucidated. In the present study, we examined the effects of FXR activation (FXR overexpression and treatment with an FXR agonist GW4064) and inactivation (treatment with FXR siRNA and an FXR antagonist guggulsterone) on colon cancer cell proliferation in vitro using human colon cancer cell lines (H508, SNU-C4 and HT-29) and in vivo using xenografts in nude mice.

Src-mediated aryl hydrocarbon and epidermal growth factor receptor cross talk stimulates colon cancer cell proliferation.

The aryl hydrocarbon receptor (AhR) mediates many toxic effects of environmental pollutants. AhR also interacts with multiple growth factor-driven signaling pathways. In the course of examining effects of growth factors on proliferation of human colon cancer cells, we identified cross talk between AhR and the epidermal growth factor receptor (EGFR).