Chagas disease is a chronic infection caused by an intracellular protozoan parasite. Chronic chagasic patients (CCPs) have dysfunctional CD8 T cells that are characterized by impaired cytokine production, high coexpression of inhibitory receptors, and advanced cellular differentiation. Most patients diagnosed in the chronic phase of Chagas disease already exhibit heart involvement, and there is no vaccination that protects against the disease. Antiparasitic treatment is controversial as to its indication for this stage of the disease. There is a lack of biological markers to evaluate the effectiveness of antiparasitic treatment, and little is known about the effect of the treatment on CD8 T cells. Thus, the aim of the current study was to analyze the early effects of antiparasitic treatment on CD8 T cells from CCPs with asymptomatic clinical forms of disease. To evaluate the CD8 T cell subsets, expression of inhibitory receptors, and functionality of T cells in CCPs, PBMCs were isolated. The results showed that treatment of CCPs with the asymptomatic form of the disease induces an increase in the frequency of CD8 central memory T cells and terminal effector T cells, a decrease in the coexpression of inhibitory receptors, an improved Ag-specific CD8 T cell response exhibited by the individual production of IFN-γ or IL-2, and a multifunctional CD8 T cell profile of up to four functions (IFN-γIL-2PerforinGranzyme B). These findings suggest that, in CCPs, antiparasitic treatment improved the quality of Ag-specific CD8 T cell responses associated with a decrease in inhibitory receptor coexpression, which could serve as biomarkers for monitoring the effectiveness of antiparasitic treatment.
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http://dx.doi.org/10.4049/jimmunol.1602095 | DOI Listing |
Nat Commun
January 2025
School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen, China.
Hypoxic tumors present a significant challenge in cancer therapy due to their ability to adaptation in low-oxygen environments, which supports tumor survival and resistance to treatment. Enhanced mitophagy, the selective degradation of mitochondria by autophagy, is a crucial mechanism that helps sustain cellular homeostasis in hypoxic tumors. In this study, we develop an azocalix[4]arene-modified supramolecular albumin nanoparticle, that co-delivers hydroxychloroquine and a mitochondria-targeting photosensitizer, designed to induce cascaded oxidative stress by regulating mitophagy for the treatment of hypoxic tumors.
View Article and Find Full Text PDFBiomed Chromatogr
February 2025
Guangdong Provincial key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China.
Praziquantel (PZQ) is the most effective treatment for schistosomiasis, commonly administered as a racemic mixture of the two enantiomers. Despite many reports on the pharmacokinetics of PZQ, the stereoselective pharmacokinetics of PZQ and its major metabolite 4-hydroxypraziquantel (4-OH-PZQ) remain poorly understood in goats. In this study, the chiral LC-MS/MS method was further optimized for separating and quantifying PZQ, trans-4-OH-PZQ, and cis-4-OH-PZQ and their enantiomers and then applied for the molecular pharmacokinetics of three analytes in black goat plasma.
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January 2025
The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.
Background: N6-methyladenosine (m6A) is one of the most conserved internal RNA modifications, which has been implicated in many biological processes, such as apoptosis and proliferation. Wilms tumor 1-associating protein (WTAP), as a key component of m6A methylation, is a nuclear protein that has been associated with the regulation of proliferation and apoptosis. Rheumatoid arthritis (RA), a systemic, infiltrating autoimmune disease, is characterized by synovial hyperplasia.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
School of Life Science, Nanchang University, Nanchang 330031, China.
Abamectin is an insecticide, miticide and nematicide that has been extensively used in agriculture for many years. The excessive use of abamectin inevitably pollutes water and soil and might even cause adverse effects on aquatic biota. However, it is currently unclear how abamectin exposure causes neurotoxicity in aquatic organisms.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Health Sciences, Institute of Research for Food Safety and Health (IRC-FSH), University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.
In this manuscript, the effects of two extracts from were tested: (a) an extract titrated to 49.7% of andrographolide and obtained from leaves of the plant: (b) the pure andrographolide titrated to 99%. The extracts were dissolved in 1-butanol and tested on tumor lines (MCF7 and SH-SY5Y) and the non-tumor line (Huvec) to understand the effects on cell proliferation.
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