mRNA delivery in cancer immunotherapy Zhong, Yichen; Du, Shi; Dong, Yizhou
Acta pharmaceutica Sinica. B,
04/2023, Letnik:
13, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Messenger RNA (mRNA) has drawn much attention in the medical field. Through various treatment approaches including protein replacement therapies, gene editing, and cell engineering, mRNA is becoming ...a potential therapeutic strategy for cancers. However, delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular uptake. Therefore, in addition to mRNA modification, efforts have been devoted to developing nanoparticles for mRNA delivery. In this review, we introduce four categories of nanoparticle platform systems: lipid, polymer, lipid-polymer hybrid, and protein/peptide-mediated nanoparticles, together with their roles in facilitating mRNA-based cancer immunotherapies. We also highlight promising treatment regimens and their clinical translation.
mRNA has becoming a potential treatment strategy for cancer therapy. In this review, we highlight representative delivery systems of mRNA and promising treatment regimens for their clinical translation. Display omitted
Chromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers. The mechanism, however, is only partially resolved, and it is unclear if it is conserved among the four ...remodeller families. Here we use single-molecule assays to examine the mechanism of action of CHD4, which is part of the least well understood family. We demonstrate that the binding energy for CHD4-nucleosome complex formation-even in the absence of nucleotide-triggers significant conformational changes in DNA at the entry side, effectively priming the system for remodelling. During remodelling, flanking DNA enters the nucleosome in a continuous, gradual manner but exits in concerted 4-6 base-pair steps. This decoupling of entry- and exit-side translocation suggests that ATP-driven movement of entry-side DNA builds up strain inside the nucleosome that is subsequently released at the exit side by DNA expulsion. Based on our work and previous studies, we propose a mechanism for nucleosome sliding.
Adipose stem cells (ASCs) have attracted considerable attention as potential therapeutic agents due to their ability to promote tissue regeneration. However, their limited tissue repair capability ...has posed a challenge in achieving optimal therapeutic outcomes. Herein, we conceive a series of lipid nanoparticles to reprogram ASCs with durable protein secretion capacity for enhanced tissue engineering and regeneration. In vitro studies identify that the isomannide-derived lipid nanoparticles (DIM1T LNP) efficiently deliver RNAs to ASCs. Co-delivery of self-amplifying RNA (saRNA) and E3 mRNA complex (the combination of saRNA and E3 mRNA is named SEC) using DIM1T LNP modulates host immune responses against saRNAs and facilitates the durable production of proteins of interest in ASCs. The DIM1T LNP-SEC engineered ASCs (DS-ASCs) prolong expression of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 12 (CXCL12), which show superior wound healing efficacy over their wild-type and DIM1T LNP-mRNA counterparts in the diabetic cutaneous wound model. Overall, this work suggests LNPs as an effective platform to engineer ASCs with enhanced protein generation ability, expediting the development of ASCs-based cell therapies.
Abstract
Background
2019-nCoV has been spreading around the world and becoming a global concern. To prevent further widespread of 2019-nCoV, confirmed and suspected cases of COVID-19 infection are ...suggested to be kept in quarantine. However, the diagnose of COVID-19 infection is quite time-consuming and labor-intensive. To alleviate the burden on the medical staff, we have done some research on the intelligent diagnosis of COVID-19.
Methods
In this paper, we constructed a COVID-19 Diagnosis Ontology (CDO) by utilizing Protégé, which includes the basic knowledge graph of COVID-19 as well as diagnostic rules translated from Chinese government documents. Besides, SWRL rules were added into the ontology to infer intimate relationships between people, thus facilitating the efficient diagnosis of the suspected cases of COVID-19 infection. We downloaded real-case data and extracted patients’ syndromes from the descriptive text, so as to verify the accuracy of this experiment.
Results
After importing those real instances into Protégé, we demonstrated that the COVID-19 Diagnosis Ontology showed good performances to diagnose cases of COVID-19 infection automatically.
Conclusions
In conclusion, the COVID-19 Diagnosis Ontology will not only significantly reduce the manual input in the diagnosis process of COVID-19, but also uncover hidden cases and help prevent the widespread of this epidemic.
Purpose
The identification of potential kinase inhibitors plays a key role in drug discovery for treating human diseases. Currently, most existing computational methods only extract limited features ...such as sequence information from kinases and inhibitors. To further enhance the identification of kinase inhibitors, more features need to be leveraged. Hence, it is appealing to develop effective methods to aggregate feature information from multisource knowledge for predicting potential kinase inhibitors. In this paper, we propose a novel computational framework called FLMTS to improve the performance of kinase inhibitor prediction by aggregating multisource knowledge.
Method
FLMTS uses a random walk with restart (RWR) to combine multiscale information in a heterogeneous network. We used the combined information as features of compounds and kinases and input them into random forest (RF) to predict unknown compound–kinase interactions.
Results
Experimental results reveal that FLMTS obtains significant improvement over existing state-of-the-art methods. Case studies demonstrated the reliability of FLMTS, and pathway enrichment analysis demonstrated that FLMTS could also accurately predict signaling pathways in disease treatment.
Conclusion
In conclusion, our computational framework of FLMTS for improving the prediction of potential kinase inhibitors successfully aggregates feature information from multisource knowledge, yielding better prediction performance than existing state-of-the-art methods.
Graphical Abstract
Oral systemic and injectable biologic treatments are available in Australia to treat moderate to severe psoriasis.BACKGROUNDOral systemic and injectable biologic treatments are available in Australia ...to treat moderate to severe psoriasis.To examine how patients and dermatologists in Australia choose between oral and injectable treatments for psoriasis.OBJECTIVETo examine how patients and dermatologists in Australia choose between oral and injectable treatments for psoriasis.In this discrete choice experiment (DCE), adults with moderate to severe psoriasis and dermatologists were asked to choose between 2 treatments labeled by mode of administration ('oral' or 'subcutaneous injection'), each with randomly assigned levels for 9 treatment attributes. Needle fear was rated by patients.METHODSIn this discrete choice experiment (DCE), adults with moderate to severe psoriasis and dermatologists were asked to choose between 2 treatments labeled by mode of administration ('oral' or 'subcutaneous injection'), each with randomly assigned levels for 9 treatment attributes. Needle fear was rated by patients.Completed surveys from 178 patients and 43 dermatologists were included in the analysis. Symptom reduction, safety, and mode of administration were attributes found to have a significant impact on treatment choice; dosing frequency was a significant attribute for the injectable option. When treatment attributes were held equal, patients and dermatologists preferred oral versus injectable treatments for moderate disease. Patients with higher levels of needle fear were more likely to favor an oral treatment versus patients with lower levels of needle fear.RESULTSCompleted surveys from 178 patients and 43 dermatologists were included in the analysis. Symptom reduction, safety, and mode of administration were attributes found to have a significant impact on treatment choice; dosing frequency was a significant attribute for the injectable option. When treatment attributes were held equal, patients and dermatologists preferred oral versus injectable treatments for moderate disease. Patients with higher levels of needle fear were more likely to favor an oral treatment versus patients with lower levels of needle fear.Participation bias may limit the generalizability of these findings.LIMITATIONSParticipation bias may limit the generalizability of these findings.Participants preferred oral over injectable treatment for moderate psoriasis. These findings corroborate the need for efficacious oral therapies to treat the disease.CONCLUSIONParticipants preferred oral over injectable treatment for moderate psoriasis. These findings corroborate the need for efficacious oral therapies to treat the disease.
Adoptive cell therapy for cancer treatment Du, Shi; Yan, Jingyue; Xue, Yonger ...
Exploration,
August 2023, 2023-Aug, 2023-08-00, 20230801, 2023-08-01, Letnik:
3, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Adoptive cell therapy (ACT) is a rapidly growing anti‐cancer strategy that has shown promise in treating various cancer types. The concept of ACT involves activating patients’ own immune cells ex ...vivo and then transferring them back to the patients to recognize and eliminate cancer cells. Currently, the commonly used ACT includes tumor‐infiltrating lymphocytes (TILs), genetically engineered immune cells, and dendritic cells (DCs) vaccines. With the advancement of cell culture and genetic engineering techniques, ACT has been used in clinics to treat malignant hematological diseases and many new ACT‐based regimens are in different stages of clinical trials. Here, representative ACT approaches are introduced and the opportunities and challenges for clinical translation of ACT are discussed.
This perspective describes multiple types of commonly used adoptive cell therapy with an emphasis on their clinical progress. In addition, the challenges and opportunities of adoptive cell therapy for future clinical translation are described from the authors' point of view.
The real‐world treatment landscape for patients with moderate‐to‐severe psoriasis receiving systemic therapies in Japan is not well understood. This study describes the demographic and clinical ...characteristics, treatment patterns, healthcare resource utilization, and psoriasis‐associated costs in these patients. This retrospective observational study used data from the Japan Medical Data Center database between January 2016 and December 2020. Eligible patients had a confirmed diagnosis of psoriasis, ≥1 claim for a systemic treatment of interest, medical history for ≥6 months, and follow‐up data for ≥12 months. Systemic therapies comprised biologics (tumor necrosis factor and interleukin inhibitors) and oral treatments (a phosphodiesterase‐4 inhibitor, immunosuppressants, and vitamin A). Patient demographics and clinical characteristics, treatment patterns, healthcare resource utilization, and costs were evaluated. The study identified 1770 patients satisfying all inclusion criteria. The mean age was 49.0 years, with 68% of patients aged 20–54 years. Overall, 90.6% and 9.4% of patients received oral medications and biologics as index treatment, respectively. Treatment patterns, healthcare resource utilization, and costs were assessed for treatments received by ≥20 patients (n = 1730). During the 12‐month follow‐up period, 1102/1730 patients (63.7%) discontinued index treatment, of whom 9.9% switched to alternative systemic treatments. The persistence rate was ≥70% for most biologics and <50% for oral systemic treatments. All 1730 patients had ≥1 all‐cause outpatient visit (2.0 visits per person per month) and hospitalization frequency was ≤0.01 per person per month. Persistent patients incurred inflation‐adjusted costs of Japanese Yen (JPY) 88 667 per person per month. Treatment switching was associated with an increase in total cost: JPY 128 039 per person per month after switching versus JPY 117 504 before switching. This study of Japanese patients with moderate‐to‐severe psoriasis demonstrated low persistence, high discontinuation, and low rates of treatment switching with systemic therapies. Switching was associated with increased total cost. These results indicate unmet needs for new treatments.
Aiming at achieving high flexibility and safety, telerehabilitation systems and telesurgery systems often use flexible manipulators in the telerehabilitation systems. However, due to the structure of ...the flexible manipulator, it has strong model uncertainties and nonlinearity in its dynamic model which causes the difficulty of the accurate control. In order to accomplish accurate trajectory tracking of telerehabilitations systems with flexible manipulators, a bilateral controller is introduced on the basis of the sliding mode control strategy and a non-linear disturbance observer. The non-linear disturbance observer is applied to estimate the model uncertainties and external disturbance of both the master and the slave flexible manipulators in the telerehabilitation system. The asymptotic stability is analyzed by the Lyapunov function. Numerical simulations are performed and results show efficiency and effectiveness of our method.
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