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Category: biotech/medical – Page 35

A Review of How the Heart Ages

The European Heart Journal has published a review of what happens to the human heart as it ages, noting the cellular effects of mitochondrial dysfunction and cellular senescence along with more visible changes such as hypertrophy and fibrosis.

A constantly working organ

The reviewers begin this paper by noting the constant work of the heart, as it must unceasingly pump blood for us to be able to live. Unfortunately, this organ is well-known to fail with age; while only roughly 1% of people under 55 suffer heart failure, it occurs in over 10% of people over 70 [1].

Dendritic cell immunotherapy induces anti-tumor effect in a transgenic mouse model of pancreatic ductal adenocarcinoma

The promise of dendritic cell (DC)-based immunotherapy has been established by two decades of translational research. However, long-term benefits of DC vaccination are reported in only scattered patients with pancreatic ductal adenocarcinoma (PDAC). Here we optimize DC vaccination and evaluate its safety and antitumor efficacy in the genetically engineered PDAC model (KrasLSL-G12D p53LSL-R172H Pdx-1-Cre (KPC mice)). KPC transgenic mice and orthotopic models using KPC cell lines were treated with DC vaccine via an intraperitoneal route. Tumor growth and microenvironment were dynamically monitored by magnetic resonance imaging (MRI). Histological analysis and flow cytometry were used to evaluate tumor-directed T cell immunity of these mice. DC vaccine via intraperitoneal injection suppressed tumor progression (P = 0.030) and significantly prolonged survival time (P = 0.028) in KPC mice. Vaccinated KPC mice displayed an increased antitumor T cell response indicated by a higher IFN-γ production (P = 0.016) and tumor-specific cytotoxicity (P = 0.027). Particularly, the mean apparent diffusion coefficient (ADC) values of KPC tumor calculated from diffusion weighted MRI (DW-MRI) were significantly higher in DC vaccine group than that in control group (P < 0.001). More interestingly, we observed that ADC positively correlated with fibrosis in KPC tumor (R2 = 0.463, P = 0.015). Our study demonstrated that the immunization with our improved DC vaccine can elicit a strong tumor-specific immune response and tumor suppression in PDAC.

A new model for alveolar macrophage-Mycobacterium tuberculosis (TB) interactions!

A new model for alveolar macrophage–Mycobacterium tuberculosis (TB) interactions!

https://doi.org/10.1172/jci.insight.

Michael S. Glickman & team establish a stem cell–derived lung alveolar macrophage model to reveal itaconate functions differently between human macrophage types in the host defense against Mtb:

The figure: Brightfield and stained images of two macrophage populations.

1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

2Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine, New York, New York, USA.

Continue reading “A new model for alveolar macrophage-Mycobacterium tuberculosis (TB) interactions!” | >

Study suggests one common amino acid may affect how long men live

A large new study suggests that higher levels of a common amino acid called tyrosine may be linked to a shorter lifespan in men.

The research, published recently in the journal Aging, examined whether blood levels of two amino acids, phenylalanine and tyrosine, were connected to how long people live.

Amino acids are building blocks of protein. They are found in protein-rich foods such as milk, eggs and meat, and are also sold as dietary supplements.

Insulin resistance prediction from wearables and routine blood biomarkers

A machine-learning model that integrates data from wearable devices (such as smartwatches) with blood biomarkers and demographic data can predict whether someone has insulin resistance, enabling timely lifestyle interventions to prevent progression to type 2 diabetes.

Clinical Heterogeneity and Candidate Biomarkers in POLG-Related Mitochondrial Disease

POLG-related disorders demonstrate extensive clinical variability with no consistent genotype-phenotype correlation. GDF15 and NF-L may serve as useful, though nonspecific, biomarkers of mitochondrial and neuroaxonal dysfunction, respectively.

Background and Objectives.

End Point–Based Threshold for the Ambulatory Arterial Stiffness Index

RESEARCH ARTICLE: End Point–Based Threshold for the Ambulatory Arterial Stiffness Index @jasta49 @melgarejo1024 @neurociencias @PPBoggia

BACKGROUND: The ambulatory arterial stiffness index (AASI) is increasingly used in clinical research and practice. This individual-participant meta-analysis aims to consolidate the prognostic accuracy of AASI in the general population and to derive an end point–based AASI risk threshold. METHODS: In 12 558 individuals enrolled in 14 population studies (48.8% women; mean age, 59.3 years), AASI was derived by regressing 24-hour diastolic on systolic blood pressure (mm Hg/mm Hg). Using Cox regression, the risk-carrying AASI threshold was established by examining stepwise increasing AASI levels and by determining the AASI level, yielding a 10-year risk similar to an office systolic pressure of 140 mm Hg. RESULTS: Over 10.7 years (median), 3,027 all-cause deaths and 2,183 cardiovascular end points occurred.

Pearls & Oy-sters: Using Susceptibility-Based Imaging in Highly Active Late-Onset Multiple Sclerosis

Central vein sign and paramagnetic rim lesions can aid in an earlier diagnosis of late-onset multiple sclerosis and may circumvent the need for biopsy. Learn more in this Pearls & Oy-sters article.

CSF analysis revealed lymphocytic pleocytosis (41 total nucleated cells [normal 0–5/μL], 98% lymphocytes) and an elevated protein of 89 mg/dL (normal, 0–35 mg/dL) without hypoglycorrhachia. CSF kappa free light chains (KFLC) and IgG index were not elevated, and CSF-specific oligoclonal bands (OCBs) were absent. CSF cytology and flow cytometry were negative for malignancy. Extensive neural antibody testing was negative including serum aquaporin-4-immunoglobulin G, myelin oligodendrocyte glycoprotein-immunoglobulin G, and CSF glial fibrillary acidic protein antibody. Extensive rheumatological and infectious testing was also negative. Neurofilament light chain was elevated to 188 pg/mL (normal ≤19 pg/mL for age 60–65 years). Whole body PET was negative, and optical coherence tomography was normal.

Owing to concerns for neurosarcoidosis, lymphoma, or vasculitis, a percutaneous stereotactic biopsy of a right occipital lesion was performed. Pathology revealed a demarcated CD68/163+ macrophage-rich lesion with myelin loss, relative axonal preservation, and a CD3+ predominant lymphocytic infiltrate with rare CD20+ B cells, consistent with active demyelination (Figure 2). She initiated a 5-day course of high-dose oral prednisone (1,250 mg daily) followed by a taper. Within 2 days of treatment, she experienced mild improvement in dysarthria and ataxia, although her EDSS score remained 6 on discharge.

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