The role of CD4 1 cytotoxic T cells (CTLs) in hepatocellular carcinoma (HCC) remains obscure. This study characterized CD41 CTLs in HCC patients and further elucidated the associations between CD41 CTLs and HCC disease progression. In all, 547 HCC patients, 44 chronic hepatitis B (CHB) patients, 86 liver cirrhosis (LC) patients, and 88 healthy individuals were enrolled in the study. CD41 CTLs were defined by flow cytometry, immunohistochemistry, and lytic granule exocytosis assays. A multivariate analysis of prognostic factors for overall survival was performed using the Cox proportional hazards model. Circulating and liver-infiltrating CD41 CTLs were found to be significantly increased in HCC patients during early stage disease, but decreased in progressive stages of HCC. This loss of CD41 CTLs was significantly correlated with high mortality rates and reduced survival time of HCC patients. In addition, the proliferation, degranulation, and production of granzyme A, granzyme B, and perforin of CD4 1 CTLs were inhibited by the increased forkhead/winged helix transcription factor (FoxP3 1 ) regulatory T cells in these HCC patients. Further analysis showed that both circulating and tumor-infiltrating CD4
Wing dimorphism is an evolutionarily adaptive trait to maximize insect fitness under various environments, by which the population could be balanced between migration and reproduction. Most studies concern the regulatory mechanisms underlying the stimulation of wing morph in aphids, but relatively little research addresses the molecular basis of wing loss. Here, we found that the wing disc of wingless-destined pea aphids degenerated 30 h post birth by autophagic rather than apoptotic degeneration, whereas winged-destined aphids developed normally. Activation of autophagy in 1st instar nymphs reduced the proportion of winged aphids, and suppression of autophagy increased the proportion. The REPTOR2 gene associated with TOR signaling pathway was identified by RNA-seq as a differentially expressed gene between the two morphs, with higher expression in the thorax of wingless-destined aphids. Further genetic analysis indicated that REPTOR2 could be a novel gene derived from a gene duplication event exclusively in pea aphid on autosome A1 but translocated to the sex chromosome. Knockdown of REPTOR2 reduced autophagy in the wing disc and increased the proportion of winged aphids. In agreement with REPTOR's canonical negative regulatory role of TOR on autophagy, winged-destined aphids had higher TOR expression in the wing disc. Suppression of TOR activated autophagy of the wing disc and decreased the proportion of winged aphids, and vice versa. These results revealed that the TOR signaling pathway controlled degradation of the wing disc in pea aphids, and that REPTOR2 could modulate this autophagic degradation.
Oral administration is a commonly used, safe, and patient-compliant method of drug delivery. However, due to the multiple absorption barriers in the gastrointestinal tract (GIT), the oral bioavailability of many drugs is low, resulting in a limited range of applications for oral drug delivery. Nanodrug delivery systems have unique advantages in overcoming the multiple barriers to oral absorption and improving the oral bioavailability of encapsulated drugs. Metal-organic frameworks (MOFs) are composed of metal ions and organic linkers assembled by coordination chemistry. Unlike other nanomaterials, nanoscale metal-organic frameworks (nano-MOFs, NMOFs) are increasingly popular for drug delivery systems (DDSs) due to their tunable pore size and easily modified surfaces. This paper summarizes the literature on MOFs in pharmaceutics included in SCI for the past ten years. Then, the GIT structure and oral drug delivery systems are reviewed, and the advantages, challenges, and solution strategies possessed by oral drug delivery systems are discussed. Importantly, two major classes of MOFs suitable for oral drug delivery systems are summarized, and various representative MOFs as oral drug carriers are evaluated in the context of oral drug delivery systems. Finally, the challenges faced by DDSs in the development of MOFs, such as biostability, biosafety, and toxicity, are examined.
Wing dimorphism in insects is an evolutionarily adaptive trait to maximize insect fitness under various environments, by which the population could be balanced between dispersing and reproduction. Most studies concern the regulatory mechanisms underlying the stimulation of wing morph in aphids, but relatively little research addresses the molecular basis of wing loss. Here, we found that, while developing normally in winged-destined pea aphids, the wing disc in wingless-destined aphids degenerated 30-hr postbirth and that this degeneration was due to autophagy rather than apoptosis. Activation of autophagy in first instar nymphs reduced the proportion of winged aphids, and suppression of autophagy increased the proportion. REPTOR2, associated with TOR signaling pathway, was identified by RNA-seq as a differentially expressed gene between the two morphs with higher expression in the thorax of wingless-destined aphids. Further genetic analysis indicated that REPTOR2 could be a novel gene derived from a gene duplication event that occurred exclusively in pea aphids on autosome A1 but translocated to the sex chromosome. Knockdown of REPTOR2 reduced autophagy in the wing disc and increased the proportion of winged aphids. In agreement with REPTOR’s canonical negative regulatory role of TOR on autophagy, winged-destined aphids had higher TOR expression in the wing disc. Suppression of TOR activated autophagy of the wing disc and decreased the proportion of winged aphids, and vice versa. Co-suppression of TOR and REPTOR2 showed that dsREPTOR2 could mask the positive effect of dsTOR on autophagy, suggesting that REPTOR2 acted as a key regulator downstream of TOR in the signaling pathway. These results revealed that the TOR signaling pathway suppressed autophagic degradation of the wing disc in pea aphids by negatively regulating the expression of REPTOR2.
Porous polymer metal–organic frameworks (MOFs), having the characteristics of large specific surface area, high porosity, and large drug load, are used in the field of medicine. In order to explore the feasibility of MOFs to load drugs, we have made an attempt to analyze the drug loading of MOFs at the molecular level. In order to provide sufficient theoretical support for realistic research, especially in terms of adsorption sites and the adsorption capacity, we selected five MOFs, UiO‐66, UiO‐66‐NH2, UiO‐66‐COOH, UiO‐67, and UiO‐66‐NDC, with bendamustine and 5‐Fluorouracil (5‐FU) as model drugs, and applied Grand Canonical Monte Carlo (GCMC) simulation to calculate the interaction between carrier MOFs and drug molecules, adsorption sites, isothermal adsorption lines and drug loads, and compared them with real experiments. The results showed all five MOFs to have strong interaction with drug molecules, and MOFs after adsorbing drug molecules were thermally stable. The best adsorption effect on bendamustine was found to be of UiO‐66‐COOH, with a drug loading capacity of 20.94 ± 0.99%. The best adsorption effect on 5‐FU was of UiO‐66‐NDC, with a drug loading capacity of 51.23 ± 1.09%. It has been further proven that MOFs have the potential to participate in oral administration as drug carriers, and have broad prospects in the field of biomedical applications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.