Lead is a known toxicant that has been implicated in encephalopathy in children and may affect the gastrointestinal and hematopoietic and other systems in adults. In fact, lead has been shown to compete with calcium for entry into the synaptosome and induce toxic effects. The aim of the current study was to evaluate the cytotoxic and genotoxic effects of lead by using lymphocytes from human peripheral blood in vitro. The LC50 for lead nitrate as determined by Trypan blue dye exclusion technique was found to be 3.14 mM. Chromosomal aberration frequency at sublethal doses (1/10 of LC50) as determined by examining the metaphase chromosomes (karyotyping) did not show significant aberrations except for some aneuploidy and about 2-4% gaps, breaks (3-4%), and about 5% satellite associations. However, significant DNA damage was determined by SCGE (Comet assay). The comet tail length proportionately increased with increasing lead nitrate concentration. Thus, Pb can induce single-strand DNA breaks, possibly by competing with metal binding sites.
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http://dx.doi.org/10.1080/01480540500408739 | DOI Listing |
Sci Rep
December 2024
Department of Psychiatry and Behavioral Sciences and Weill Center for Neurosciences, University of California, San Francisco, CA, 94107, USA.
Telomere attrition is a hallmark of biological aging, contributing to cellular replicative senescence. However, few studies have examined the determinants of telomere attrition in vivo in humans. Mitochondrial Health Index (MHI), a composite marker integrating mitochondrial energy-transformation capacity and content, may be one important mediator of telomere attrition, as it could impact telomerase activity, a direct regulator of telomere maintenance.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Vascular Surgery, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
Adverse aortic remodeling increases the risk of aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) and affects the overall prognosis of aortic dissection (AD). It is imperative to delve into the exploration of prognostic indicators to streamline the identification of individuals at elevated risk for postoperative AAEs, and therapeutic targets to optimize the efficacy of TEVAR for patients with AD. Here, we perform proteomic and single-cell transcriptomic analyses of peripheral blood and aortic lesions, respectively, from patients with AD and healthy subjects.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4 T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL.
View Article and Find Full Text PDFHere we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.
View Article and Find Full Text PDFElife
December 2024
Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Psoriasis is a multifactorial disorder mediated by IL-17-producing T cells, involving immune cells and skin-constituting cells. Semaphorin 4A (Sema4A), an immune semaphorin, is known to take part in T helper type 1/17 differentiation and activation. However, Sema4A is also crucial for maintaining peripheral tissue homeostasis and its involvement in skin remains unknown.
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