Aging is the greatest risk factor for late-onset Alzheimer's disease (LOAD), which accounts for >95% of Alzheimer's disease (AD) cases. The mechanism underlying the aging-related susceptibility to ...LOAD is unknown. Cellular senescence, a state of permanent cell growth arrest, is believed to contribute importantly to aging and aging-related diseases, including AD. Senescent astrocytes, microglia, endothelial cells, and neurons have been detected in the brain of AD patients and AD animal models. Removing senescent cells genetically or pharmacologically ameliorates β-amyloid (Aβ) peptide and tau-protein-induced neuropathologies, and improves memory in AD model mice, suggesting a pivotal role of cellular senescence in AD pathophysiology. Nonetheless, although accumulated evidence supports the role of cellular senescence in aging and AD, the mechanisms that promote cell senescence and how senescent cells contribute to AD neuropathophysiology remain largely unknown. This review summarizes recent advances in this field. We believe that the removal of senescent cells represents a promising approach toward the effective treatment of aging-related diseases, such as AD.
It is common that different crystal facets in metal and metal oxide nanocrystals display different catalytic performances, whereas such phenomena have been rarely documented in metal–organic ...frameworks (MOFs). Herein, we demonstrate for the first time that a nickel metal–organic layer (MOL) exposing rich (100) crystal facets (Ni‐MOL‐100) shows a much higher photocatalytic CO2‐to‐CO activity than the one exposing rich (010) crystal facets (Ni‐MOL‐010) and its bulky counterpart (bulky Ni‐MOF), with a catalytic activity up to 2.5 and 4.6 times more active than Ni‐MOL‐010 and bulky Ni‐MOF, respectively. Theoretical studies reveal that the two coordinatively unsaturated NiII ions with a close distance of 3.50 Å on the surface of Ni‐MOL‐100 enables synergistic catalysis, leading to more favorable energetics in CO2 reduction than that of Ni‐MOL‐010.
Crystal‐facet‐dependent catalytic performance for CO2 reduction has been observed in Ni‐based 2D MOLs. Ni‐MOL‐100 displays much higher catalytic activity than Ni‐MOL‐010, benefiting from the synergistic catalysis between two adjacent Ni sites in Ni‐MOL‐100.
Lactobacillus-derived exosomes, small extracellular vesicles released by bacteria, have emerged as a promising area of research in recent years. These exosomes possess a unique structural and ...functional diversity that allows them to regulate the immune response and promote gut health. The isolation and purification of these exosomes are crucial for their effective use as a therapeutic agent. Several isolation and purification methods have been developed, including differential ultracentrifugation, density gradient centrifugation, and size-exclusion chromatography. Lactobacillus-derived exosomes have been demonstrated to have therapeutic potential in various diseases, such as inflammatory bowel disease, liver disease, and neurological disorders. Moreover, they have been shown to serve as effective carriers for drug delivery. Genetic engineering of these exosomes has also shown promise in enhancing their therapeutic potential. Overall, Lactobacillus-derived exosomes represent a promising area of research for the development of novel therapeutics for immunomodulation, gut health, and drug delivery.
We report in this paper a solar eruptive event, in which a vertical current sheet (VCS) is observed in the wake of an erupting flux rope in the Solar Dynamic Observatory (SDO)/Atmospheric Imaging ...Assembly (AIA) 131 Å passband. The VCS is first detected following the impulsive acceleration of the erupting flux rope but prior to the onset of a non-thermal hard X-ray (HXR)/microwave burst, with plasma blobs moving upwards at speeds up to 1400 km s−1 along the sheet. The timing suggests that the VCS with plasma blobs might not be the primary accelerator for non-thermal electrons emitting HXRs/microwaves. The initial, slow acceleration of the erupting structure is associated with the slow elevation of a thermal looptop HXR source and the subsequent, impulsive acceleration is associated with the downward motion of the looptop source. We find that the plasma blobs moving downwards within the VCS into the cusp region and the flare loops retracting from the cusp region make a continuous process, with the former apparently initiating the latter, which provides a 3D perspective on reconnections at the VCS. We also identify a dark void moving within the VCS towards the flare arcade, which suggests that dark voids in supra-arcade downflows are of the same origin as plasma blobs within the VCS.
It is widely accepted that β-amyloid oligomers (Aβos) play a key role in the progression of Alzheimer's disease (AD) by inducing neuron damage and cognitive impairment, but Aβos are highly ...heterogeneous in their size, structure and cytotoxicity, making the corresponding studies tough to carry out. Nevertheless, a number of studies have recently made remarkable progress in the describing the characteristics and pathogenicity of Aβos. We here review the mechanisms by which Aβos exert their neuropathogenesis for AD progression, including receptor binding, cell membrane destruction, mitochondrial damage, Ca
homeostasis dysregulation and tau pathological induction. We also summarize the characteristics and pathogenicity such as the size, morphology and cytotoxicity of dimers, trimers, Aβ*56 and spherical oligomers, and suggest that Aβos may play a different role at different phases of AD pathogenesis, resulting in differential consequences on neuronal synaptotoxicity and survival. It is warranted to investigate the temporal sequence of Aβos in AD human brain and examine the relationship between different Aβos and cognitive impairment.
Idiopathic pulmonary fibrosis (IPF) is a progressive fatal lung disorder with an unknown etiology and very limited therapeutic options. The incidence and severity of IPF increase with advanced age, ...suggesting that aging is a major risk factor for IPF. The mechanism underlying the aging-related susceptibility to IPF, however, remains unclear. Cellular senescence, a permanent arrest of cell growth, has been increasingly recognized as an important contributor to aging and aging-related diseases, including IPF. Senescent cells have been identified in IPF lungs and in experimental lung fibrosis models. Removal of senescent cells pharmacologically or genetically improves lung function and reverses pulmonary fibrosis induced by different stimuli in experimental fibrosis models. Treatment with senolytic drugs also improves clinical symptoms in IPF patients. These intriguing findings suggest that cellular senescence contributes importantly to the pathogenesis of fibrotic lung diseases and targeting senescent cells may represent a novel approach for the treatment of fibrotic lung disorders. In this mini review, we summarize the recent advance in the field regarding the role of cellular senescence in fibrotic lung diseases, with a focus on IPF.
•Cellular senescence is a pathological feature of IPF lung and is evident in experimental lung fibrosis models.•Various types of lung cells, including alveolar epithelial cells and fibroblasts, undergo senescence in fibrotic lungs•Different mechanisms are involved in lung cell senescence: genetic, epigenetic, oxidative stress, and inflammation•Targeting senescent cells may be effective for the treatment of fibrotic lung disease.
Despite the tremendous efforts made in the past decades, severe side/toxic effects and poor bioavailability still represent the main challenges that hinder the clinical translation of drug molecules. ...This has turned the attention of investigators towards drug delivery vehicles that provide a localized and controlled drug delivery. Molecularly imprinted polymers (MIPs) as novel and versatile drug delivery vehicles have been widely studied in recent years due to the advantages of selective recognition, enhanced drug loading, sustained release, and robustness in harsh conditions. This review highlights the design and development of strategies undertaken for MIPs used as drug delivery vehicles involving different drug delivery mechanisms, such as rate-programmed, stimuli-responsive and active targeting, published during the course of the past five years.
Metal sulfonate frameworks offer unique properties and enormous potential for proton conduction. This review summarizes the recent progress in this topical field, including sulfonic acid coordinated ...MOFs, sulfate groups encapsulated MOFs and the composite membranes with these MOFs and so on. In-depth disscusses of the relationship of structures and proton conducting properties on such MOFs are presented.
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•Proton conductive metal sulfonate frameworks were reviewed.•MOFs are classified and described according to the type of organic ligands.•Proton conductivity and conducting mechanism were discussed.•The future development trend of such MOFs is prospected.
Since the easy-to-design and customization of structures, guest accessibility of cavities, and functional tunability, MOFs have evolved into a burgeoning type of proton conductors. The sulfonic acid groups in MOFs can not only be used as proton sources but also can be involved in the formation of hydrogen bonds within the frameworks, which is extremely conducive to the efficient transfer of protons. In this review, recent advances of proton conductive sulfonate-based MOFs are provided covering sulfonic acid coordinated MOFs, MOFs encapsulated sulfate groups and the composite membrane contained these MOFs and so on. In-depth discussion of the relationship of structures and proton conducting properties on such MOFs is presented. Perspectives on the opportunities and challenges are proposed and highlighted.
Summary
Senescence of alveolar type 2 (ATII) cells, progenitors of the alveolar epithelium, is implicated in the pathogeneses of idiopathic pulmonary fibrosis (IPF), an aging‐related progressive ...fatal lung disorder with unknown etiology. The mechanism underlying ATII cell senescence in fibrotic lung diseases, however, remains poorly understood. In this study, we report that ATII cells in IPF lungs express higher levels of serpine 1, also known as plasminogen activator inhibitor 1 (PAI‐1), and cell senescence markers p21 and p16, compared to ATII cells in control lungs. Silencing PAI‐1 or inhibition of PAI‐1 activity in cultured rat ATII (L2) cells leads to decreases in p53 serine 18 phosphorylation (p53S18P), p53 and p21 protein expressions; an increase in retinoblastoma protein phosphorylation (ppRb); and a reduction in the sensitivity to bleomycin‐ and doxorubicin‐induced senescence. Silencing p53, on the other hand, abrogates PAI‐1 protein‐stimulated p21 expression and cell senescence. In vivo studies, using ATII cell‐specific PAI‐1 conditional knockout mouse model generated recently in this laboratory, further support the role of PAI‐1 in the activation of p53‐p21‐Rb cell cycle repression pathway, ATII cell senescence, and lung fibrosis induced by bleomycin. This study reveals a novel function of PAI‐1 in regulation of cell cycle and suggests that elevation of PAI‐1 contributes importantly to ATII cell senescence in fibrotic lung diseases.
Lipid metabolism and cancer Bian, Xueli; Liu, Rui; Meng, Ying ...
The Journal of experimental medicine,
2021-Jan-04, Letnik:
218, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for biological membranes, and ...signaling molecules needed for proliferation, survival, invasion, metastasis, and response to the tumor microenvironment impact and cancer therapy. Here, we summarize and discuss current knowledge about the advances made in understanding the regulation of lipid metabolism in cancer cells and introduce different approaches that have been clinically used to disrupt lipid metabolism in cancer therapy.
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