The programmed cell death protein 1 (PD-1) pathway has received considerable attention due to its role in eliciting the immune checkpoint response of T cells, resulting in tumor cells capable of evading immune surveillance and being highly refractory to conventional chemotherapy. Application of anti-PD-1/PD-L1 antibodies as checkpoint inhibitors is rapidly becoming a promising therapeutic approach in treating tumors, and some of them have successfully been commercialized in the past few years. However, not all patients show complete responses and adverse events have been noted, suggesting a better understanding of PD-1 pathway mediated immunosuppression is needed to predict patient response and improve treatment efficacy. Here, we review the progresses on the studies of the mechanistic role of PD-1 pathway in the tumor immune evasion, recent clinical development and commercialization of PD-1 pathway inhibitors, the toxicities associated with PD-1 blockade observed in clinical trials as well as how to improve therapeutic efficacy and safety of cancer immunotherapy.
Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibroblast-like cells that can differentiate into cells of multiple lineages, such as chondrocytes, osteoblasts, adipocytes, myoblasts, and others. These multipotent MSCs can be found in nearly all tissues but mostly located in perivascular niches, playing a significant role in tissue repair and regeneration. Additionally, MSCs interact with immune cells both in innate and adaptive immune systems, modulating immune responses and enabling immunosuppression and tolerance induction. Understanding the biology of MSCs and their roles in clinical treatment is crucial for developing MSCbased cellular therapy for a variety of pathological conditions. Here, we review the progress in the study on the mechanisms underlying the immunomodulatory and regenerative effects of MSCs; update the medical translation of MSCs, focusing on the registration trials leading to regulatory approvals; and discuss how to improve therapeutic efficacy and safety of MSC applications for future.
This paper provides a brief review on the advanced shape memory technology (ASMT) with a focus on polymeric materials. In addition to introducing the concept and fundamentals of the ASMT, the potential applications of the ASMT either alone or integrated with an existing mature technique (such as, 3D printing, quick response (QR) code, lenticular lens) and phenomena (e.g., wrinkling and stress-enhanced swelling effect) in product design, manufacturing, and recycling are demonstrated. It is concluded that the ASMT is indeed able to provide a range of powerful approaches to reshape part of the life cycle or the whole life cycle of products.
Dermatophytes are the most common cause of onychomycosis, counting for 90% fungal nail infection. Although dermatophyte pathogens are normally susceptible to antifungal agents, onychomycosis often results in refractory chronic disease, and the formation of biofilms frequently underlines the inadequate responses and resistance to standard antifungal treatment. Numerous
in vitro
and
in vivo
antimicrobial photodynamic therapy (aPDT) studies have shown biofilm eradication or substantial reduction, however, such investigation has not yet been expanded to the biofilms of dermatophytes involved in onychomycosis. To shed a light on the potential application of aPDT in the clinic management of onychomycosis, in particular with the manifestation of dermatophytoma, we investigated photodynamic effects on the viabilities and the drug susceptibilities of the biofilm of dermatophytes
in vitro
. Here, methylene blue at the concentration of 8, 16, and 32 μg/ml applied as photosensitizing agent and LED (635 ± 10 nm, 60 J/cm
2
) as light source were employed against six strains of
Trichophyton rubrum
, ten strains of
Trichophyton mentagrophytes
and three strains of
Microsporum gypseum
isolated from clinical specimens. Our results indicated highly efficient photodynamic inhibition, exhibiting CFU (colony forming unit) reduction up to 4.6 log
10
, 4.3 log
10
, and 4.7 log
10
against the biofilms formed by
T. rubrum, T. mentagrophytes
, and
M. gypseum
, respectively. Subjected biofilms displayed considerable decreases in SMICs (sessile minimum inhibitory concentrations) to multiple antifungal agents when compared with untreated groups, indicating the biofilms of dermatophytes became more susceptible to conventional antifungal drugs after aPDT. Additionally, the obliteration of biofilm after aPDT could be observed as shattered and ruptured structures being evident in SEM (Scanning Electron Microscopy) images. These findings suggest that aPDT is an attractive alternative treatment holding great promise for combating recalcitrant onychomycosis associated with the biofilm formation.
AbstractAfter a short discussion of various shape memory related phenomena and the basic working mechanisms behind the shape memory effect (SME) in polymeric shape memory materials (SMMs), standard techniques and procedures to characterize these types of materials are reviewed in details (including the concerns in the selection of testing methods and parameters). Although the focus of this paper is on the heating-responsive SME, important issues in the chemo-responsive SME are addressed. Furthermore, some other shape memory related phenomena, such as various kinds of temperature memory effect (TME), and multiple-SME etc., and optimization of the shape memory performance of a shape memory polymer (SMP) via tailoring the programming parameters are included.
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