Mitochondria are considered the power house of cells where ATP is generated for cellular metabolism, and they also act as a crucial regulator of the intrinsic apoptosis pathway. During ATP synthesis, reactive oxygen species (ROS) are produced as secondary products. Overproduction of ROS can promote mitochondrial DNA mutation, dysfunction and depolarization of the mitochondrial membrane, ultimately resulting in cell death. Therefore, the destruction of mitochondria would be an effective therapeutic approach to kill malignant tumors. Herein, we formulated a PEGylated α-TOS polymeric micellar system loaded with 10-hydroxycamptothecin (HCPT) drug to inhibit the nuclear topoisomerase I enzyme and disrupt the mitochondrial membrane to induce apoptosis. In addition, tumor-penetrating CRGDK peptide-functionalized TPGS specifically bound to the Nrp-1 receptor to facilitate higher cell uptake of polymeric micelles by tumor cells. Experimental studies confirmed that HCPT-loaded and peptide-functionalized TPGS-TOS micelles (HLPFTTM) showed an enhanced anti-cancer effect in A549 cancer cells.
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http://dx.doi.org/10.1016/j.ijpharm.2018.05.074 | DOI Listing |
Front Cell Infect Microbiol
February 2025
Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
This review article discusses the role of vascular endothelial growth factor A (VEGF-A) in the pathogenesis of SARS-CoV-2 and HIV infection, both conditions being renowned for their impact on the vascular endothelium. The processes involved in vascular homeostasis and angiogenesis are reviewed briefly before exploring the interplay between hypoxia, VEGF-A, neuropilin-1 (NRP-1), and inflammatory pathways. We then focus on SARS-CoV-2 infection and show how the binding of the viral pathogen to the angiotensin-converting enzyme 2 receptor, as well as to NRP-1, leads to elevated levels of VEGF-A and consequences such as coagulation, vascular dysfunction, and inflammation.
View Article and Find Full Text PDFRes Sq
January 2025
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, USA 75390.
Background: Although Amyloid-beta and Tau are the hallmarks of Alzheimer's Disease (AD), other protein pathways such as endothelial dysfunction may be involved and may precede cognitive symptoms. Our objective was to characterize the cerebrospinal fluid (CSF) proteomic profiles focusing on cardiometabolic-related protein pathways in individuals on the AD spectrum.
Methods: We performed CSF and plasma-targeted proteomics (276 proteins) from 354 participants of the Brain Stress Hypertension and Aging Program (BSHARP), of which 8% had preclinical AD, and 24% had MCI due to AD.
Mol Pharm
February 2025
Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-based Medicine, Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 Wenhua West Road, Jinan 250012, China.
Numerous diseases, such as diabetic retinopathy and age-related macular degeneration, can lead to retinal neovascularization, which can seriously impair the visual function and potentially result in blindness. The presence of the blood-retina barrier makes it challenging for ocularly administered drugs to penetrate physiological barriers and reach the ocular posterior segments, including the retina and choroid. Herein, we developed an innovative bifunctional peptide, Tat-C-RP7, which exhibits excellent penetration capabilities and antiangiogenic properties aimed at treating retinal neovascularization diseases.
View Article and Find Full Text PDFHum Cell
December 2024
Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Jiangxi Hospital, National Reginal Center for Neurological Disease, Honggutan District, No.266 Fenghe North Avenue, Nanchang, 330038, Jiangxi, China.
Acute injury and secondary injury caused by traumatic brain injury (TBI) seriously threaten the health of patients. The purpose of this study was to investigate the role of β-Asarone in TBI-induced neuroinflammation and injury. In this work, the effects of β-Asarone on nerve injury and neuronal apoptosis were investigated in mice with TBI by controlled cortical impingement.
View Article and Find Full Text PDFCancer Res
March 2025
School of Pharmacy, Institutes of Biomedical Sciences, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
T cells within the tumor microenvironment frequently exhibit dysfunctional characteristics that compromise their ability to elicit both innate and therapeutic-induced immune responses. Regulators of immune dysfunction represent therapeutic targets to activate antitumor immunity. In this study, we identified semaphorin 3G (SEMA3G) as a key regulator of immune responses in cancer.
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