The concept of cell death has been expanded beyond apoptosis and necrosis to additional forms, including necroptosis, pyroptosis, autophagy, and ferroptosis. These cell death modalities play a critical role in all aspects of life, which are noteworthy for their diverse roles in diseases. Atherosclerosis (AS) and vascular calcification (VC) are major causes for the high morbidity and mortality of cardiovascular disease. Despite considerable advances in understanding the signaling pathways associated with AS and VC, the exact molecular basis remains obscure. In the article, we review the molecular mechanisms that mediate cell death and its implications for AS and VC. A better understanding of the mechanisms underlying cell death in AS and VC may drive the development of promising therapeutic strategies.
Purpose: As a main rate-limiting subunit of the 2-oxoglutarate dehydrogenase multienzyme complex, oxoglutarate dehydrogenase like (OGDHL) is involved in the tricarboxylic acid cycle, and frequently downregulated in human carcinoma and suppresses tumor growth. However, little is known about the role of OGDHL in human cancer, especially pancreatic cancer. Our goal is to study the underlying mechanism and define a novel signaling pathway controlled by OGDHL modulating pancreatic cancer progression. Experimental Design: The expression and functional analysis of OGDHL, miR-214, and TWIST1 in human pancreatic cancer tissues, cell lines, and xenograft tumor model were investigated. The correlations between OGDHL and those markers were analyzed. Results: OGDHL was downregulated in human pancreatic cancer and predicted poor prognosis. OGDHL overexpression inhibited migration and invasion of pancreatic cancer cells and suppressed pancreatic cancer tumor growth. OGDHL was shown to be negatively regulated by miR-214. TWIST1 upregulation induced miR-214 expression in pancreatic cancer. OGDHL suppressed TWIST1 expression through promoting ubiquitin-mediated proteasomal degradation of HIF1a and regulating AKT pathways. A combination of OGDHL downregulation and TWIST1 and miR-214 overexpression predicted worse prognosis in patients with pancreatic cancer. Conclusions: We demonstrated the prognostic value of OGDHL, miR-214, and TWIST1 in pancreatic cancer, and elucidated a novel pathway in OGDHL-regulated inhibition of pancreatic cancer tumorigenesis and metastasis. These findings may lead to new targeted therapy for pancreatic cancer through regulating OGDHL, miR-214, and TWIST1.
Peptides are strings of approximately 2–50 amino acids, which have gained huge attention for theranostic applications in cancer research due to their various advantages including better biosafety, customizability, convenient process of synthesis, targeting ability via recognizing biological receptors on cancer cells, and better ability to penetrate cell membranes. The conjugation of peptides to the various nano delivery systems (NDS) has been found to provide an added benefit toward targeted delivery for cancer therapy. Moreover, the simultaneous delivery of peptide-conjugated NDS and nano probes has shown potential for the diagnosis of the malignant progression of cancer. In this review, various barriers hindering the targeting capacity of NDS are addressed, and various approaches for conjugating peptides and NDS have been discussed. Moreover, major peptide-based functionalized NDS targeting cancer-specific receptors have been considered, including the conjugation of peptides with extracellular vesicles, which are biological nanovesicles with promising ability for therapy and the diagnosis of cancer.
Traditional antibacterial procedures are getting inefficient
due
to the emergence of antimicrobial resistance, which makes alternative
treatments in urgent demand. However, the selectivity toward infectious
bacteria is still challenging. Herein, by taking advantage of the
self-directed capture of infectious bacteria by macrophages, we developed
a strategy to realize precise in vivo antibacterial
photodynamic therapy (APDT) through adoptive photosensitizer-loaded
macrophage transfer. TTD with strong reactive oxygen species (ROS)
production and bright fluorescence was first synthesized and was subsequently
formulated into TTD nanoparticles for lysosome targeting. TTD-loaded
macrophages (TLMs) were constructed by direct incubation of TTD nanoparticles
with macrophages, in which the TTD was localized in the lysosomes
to meet the captured bacteria in the phagolysosomes. The TLMs could
precisely capture and eradicate bacteria while being activated toward
the proinflammatory and antibacterial M1 phenotype upon light illumination.
More importantly, after subcutaneous injection, TLMs could effectively
inhibit bacteria in the infected tissue through APDT, leading to good
tissue recovery from severe bacterial infection. Overall, the engineered
cell-based therapeutic approach shows great potential in the treatment
of severe bacterial infectious diseases.
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