Central nervous system (CNS) diseases are the leading cause of morbidity and mortality; their treatment, however, remains constrained by the blood-brain barrier (BBB) that impedes the access of most therapeutics to the brain. A CNS delivery platform for protein therapeutics, which is achieved by encapsulating the proteins within nanocapsules that contain choline and acetylcholine analogues, is reported herein. Mediated by nicotinic acetylcholine receptors and choline transporters, such nanocapsules can effectively penetrate the BBB and deliver the therapeutics to the CNS, as demonstrated in mice and non-human primates. This universal platform, in general, enables the delivery of any protein therapeutics of interest to the brain, opening a new avenue for the treatment of CNS diseases.
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http://dx.doi.org/10.1002/adma.201807557 | DOI Listing |
Elife
January 2025
Department of Molecular and Cell Biology, Berkeley, United States.
Type II nuclear receptors (T2NRs) require heterodimerization with a common partner, the retinoid X receptor (RXR), to bind cognate DNA recognition sites in chromatin. Based on previous biochemical and overexpression studies, binding of T2NRs to chromatin is proposed to be regulated by competition for a limiting pool of the core RXR subunit. However, this mechanism has not yet been tested for endogenous proteins in live cells.
View Article and Find Full Text PDFGenet Mol Biol
January 2025
University of KwaZulu-Natal, Howard College, College of Health Sciences, School of Laboratory Medicine and Medical Sciences, Department of Medical Biochemistry, Durban, South Africa.
Methylenetetrahydrofolate reductase (MTHFR) gene is involved in homocysteine and folic acid metabolism. Tumour suppressor protein TP53 gene maintains cellular and genetic integrity. To date, no studies associated the MTHFR C677T rs1801133 and TP53 Pro72Arg rs1042522 with CRP levels and methotrexate (a folic acid antagonist) treatment outcomes in psoriatic arthritis (PsA) patients.
View Article and Find Full Text PDFJ Cancer Res Ther
December 2024
Department of Medical Ultrasound, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
Introduction: Cancer cachexia (CC) is characterized by weight loss with specifically reduced skeletal muscles and adipose tissues in patients with late-stage cancer. Dihydroartemisinin (DHA), an effective antimalarial derivative of artemisinin, has been demonstrated to have anti-inflammatory and antitumor properties.
Materials And Methods: This study examined the effects of DHA on the Lewis lung carcinoma (LLC)-induced CC mouse model.
Diabetes
January 2025
Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Diabetes is a major risk factor for cardiovascular disease, but the molecular mechanisms underlying diabetic vasculopathy have been elusive. Here we report that inositol hexakisphosphate kinase 1 (IP6K1) mediates hyperglycemia-induced endothelial senescence by rewiring the liver kinase B1 (LKB1) signaling from activating the adenosine monophosphate-activated protein kinase (AMPK) pathway to the p53 pathway. We found that hyperglycemia upregulated IP6K1, which disrupts the Hsp/Hsc70 and carboxyl terminus of Hsc70-interacting protein (CHIP)-mediated LKB1 degradation, leading to increased expression levels of LKB1.
View Article and Find Full Text PDFMol Divers
January 2025
Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases Ministry of Education, Jiangxi Province Key Laboratory of Biomaterials and Biofabrication for Tissue Engineering, Gannan Medical University, Ganzhou, 341000, Jiangxi, China.
Identifying drug-target binding affinity (DTA) plays a critical role in early-stage drug discovery. Despite the availability of various existing methods, there are still two limitations. Firstly, sequence-based methods often extract features from fixed length protein sequences, requiring truncation or padding, which can result in information loss or the introduction of unwanted noise.
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