Small extracellular vesicles from menstrual blood-derived mesenchymal stem cells (MenSCs) as a novel therapeutic impetus in regenerative medicine.

Menstrual blood-derived mesenchymal stem cells (MenSCs) have great potential in regenerative medicine. MenSC has received increasing attention owing to its impressive therapeutic effects in both preclinical and clinical trials. However, the study of MenSC-derived small extracellular vesicles (EVs) is still in its initial stages, in contrast to some common MSC sources (e.g., bone marrow, umbilical cord, and adipose tissue). We describe the basic characteristics and biological functions of MenSC-derived small EVs. We also demonstrate the therapeutic potential of small EVs in fulminant hepatic failure, myocardial infarction, pulmonary fibrosis, prostate cancer, cutaneous wound, type-1 diabetes mellitus, aged fertility, and potential diseases. Subsequently, novel hotspots with respect to MenSC EV-based therapy are proposed to overcome current challenges. While complexities regarding the therapeutic potential of MenSC EVs continue to be unraveled, advances are rapidly emerging in both basic science and clinical medicine. MenSC EV-based treatment has great potential for treating a series of diseases as a novel therapeutic strategy in regenerative medicine.

The progress and challenge of anti-PD-1/PD-L1 immunotherapy in treating non-small cell lung cancer.

The use of programmed cell-death protein 1 (PD-1)/programmed cell-death ligand 1 (PD-L1) inhibitors is the standard therapy for the first-line or second-line treatment of patients with non-small-cell lung cancer (NSCLC). In contrast to current traditional treatments such as chemotherapy or radiotherapy, anti-PD-1 and anti-PD-L1 treatments can directly attenuate tumour-mediated exhaustion and effectively modulate the host anti-tumour immune response in vivo. In addition, compared with traditional therapy, PD-1/PD-L1 inhibitor monotherapy can significantly prolong survival without obvious side effects in the treatment of advanced NSCLC. Ideally, several biomarkers could be used to monitor the safety and effectiveness of anti-PD-1 and anti-PD-L1 treatments; however, the current lack of optimal prognostic markers remains a widespread limitation and challenge for further clinical applications, as does the possibility of immune-related adverse events and drug resistance. In this review, we aimed to summarise the latest progress in anti-PD-1/anti-PD-L1 treatment of advanced NSCLC, worldwide, including in China. An exploration of underlying biomarker identification and future challenges will be discussed in this article to facilitate translational studies in cancer immunotherapy.

Chimeric antigen receptor (CAR)-T-cell therapy in non-small-cell lung cancer (NSCLC): current status and future perspectives.

There has been a rapid progress in developing genetically engineered T cells in recent years both in basic and clinical cancer studies. Chimeric antigen receptor (CAR)-T cells exert an immune response against various cancers, including the non-small-cell lung cancer (NSCLC). As novel agents of immunotherapy, CAR-T cells show great promise for NSCLC. However, targeting specific antigens in NSCLC with engineered CAR-T cells is complicated because of a lack of tumor-specific antigens, the immunosuppressive tumor microenvironment, low levels of infiltration of CAR-T cells into tumor tissue, and tumor antigen escape. Meanwhile, the clinical application of CAR-T cells remains limited due to the cases of on-target/off-tumor and neurological toxicity, as well as cytokine release syndrome. Hence, optimal CAR-T-cell design against NSCLC is urgently needed. In this review, we describe the basic structure and generation of CAR-T cells and summarize the common tumor-associated antigens targeted in clinical trials on CAR-T-cell therapy for NSCLC, as well as point out current challenges and novel strategies. Although many obstacles remain, the new/next generation of CARs show much promise. Taken together, research on CAR-T cells for the treatment of NSCLC is underway and has yielded promising preliminary results both in basic and pre-clinical medicine. More pre-clinical experiments and clinical trials are, therefore, warranted.

Oxidative CaMKII as a potential target for inflammatory disease (Review).

CaMKII is a calcium­activated kinase, proved to be modulated by oxidation. Currently, the oxidative activation of CaMKII exists in several models of asthma, chronic rhinosinusitis with nasal polyps, cardiovascular disease, diabetes mellitus, acute ischemic stroke and cancer. Oxidized CaMKII (ox­CaMKII) may be important in several of these diseases. The present review examines the mechanism underlying the oxidative activation of CaMKII and summarizes the current findings associated with the function of ox­CaMKII in inflammatory diseases. Taken together, the findings of this review aim to improve current understanding of the function of ox­CaMKII and provide novel insights for future research.

Interleukin-13 +2044 G/A and +1923C/T polymorphisms are associated with asthma susceptibility in Asians: A meta-analysis.

A number of studies have reported that the interleukin 13 (IL-13) gene is associated with asthma susceptibility. However, the reported relationships between the +2044G/A and +1923C/T polymorphisms and asthma susceptibility are inconsistent, especially in Asian adults and children with atopic status. Meta-analysis was used to analyze combined data.The +2044G/A and +1923C/T polymorphisms were investigated using data from 18 and 11 studies, respectively. The results suggested that there was an association between asthma and the IL-13 +2044G/A polymorphisms: odds ratio (OR) 1.34, 95% confidence interval (CI) 1.03-1.75 for AA versus GG + GA and +1923C/T; OR 1.50, 95% CI 1.26-1.78 for TT versus CC; and OR 1.15, 95% CI 1.10-1.21 for TC versus CC. The subgroup meta-analysis demonstrated that IL-13 +2044G/A polymorphisms are associated with asthma: OR 1.47, 95% CI 1.06-2.04 for AA versus GG + GA and +1923C/T; OR 1.70, 95% CI 1.26-2.30 for TT versus CC; and OR 1.27, 95% CI 1.03-1.56 for TC versus CC. In particular, IL-13 +2044G/A polymorphisms are specifically associated with Asian ethnicity in both adults and children with atopic status. However, the 1923C/T polymorphisms were not significantly associated with age group or atopic status within the Asian subgroups. Further investigation using larger samples and meta-analysis is required. No publication bias was detected.This meta-analysis indicates that the IL13 +2044G/A and +1923C/T polymorphisms are risk factors for asthma, especially among Asians.