Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of ...action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell–cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies.
Article Highlights
Reactive oxygen species (ROS)-responsive nano-medicines represent an effective way of preferentially releasing prodrug at the inflammatory microenvironment and improving rheumatoid ...arthritis therapeutic efficacy.
The combination of ROS-responsive carrier nanoplatform and berberine is a potential agent for treating rheumatoid arthritis.
Rheumatoid arthritis (RA) is an autoimmune disease, which attacks human joint system and causes lifelong inflammatory condition. To date, no cure is available for RA and even the ratio of achieving remission is very low. Hence, to enhance the efficacy of RA treatment, it is essential to develop novel approaches specifically targeting pathological tissues. In this study, we discovered that RA synovial fibroblasts exhibited higher reactive oxygen species (ROS) and mitochondrial superoxide level, which were adopted to develop ROS-responsive nano-medicines in inflammatory microenvironment for enhanced RA treatment. A selenocystamine-based polymer was synthesized as a ROS-responsive carrier nanoplatform, and berberine serves as a tool drug. By assembling, ROS-responsive berberine polymeric micelles were fabricated, which remarkably increased the uptake of berberine in RA fibroblast and improved in vitro and in vivo efficacy ten times higher. Mechanistically, the anti-RA effect of micelles was blocked by the co-treatment of AMPK inhibitor or palmitic acid, indicating that the mechanism of micelles was carried out through targeting mitochondrial, suppressing lipogenesis and finally inhibiting cellular proliferation. Taken together, our ROS-responsive nano-medicines represent an effective way of preferentially releasing prodrug at the inflammatory microenvironment and improving RA therapeutic efficacy.
Background Accumulating evidence showed that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Programmed Death Ligand 1 (PD-L1) is expressed in many cancer cell ...types, while its binding partner Programmed Death 1 (PD1) is expressed in activated T cells and antigen-presenting cells. Whereas, its dysregulation in the microenvironment is poorly understood. In the present study, we confirmed that evodiamine downregulates MUC1-C, resulting in modulating PD-L1 expression in non-small cell lung cancer (NSCLC). Methods Cell viability was measured by MTT assays. Apoptosis, cell cycle and surface PD-L1 expression on NSCLC cells were analyzed by flow cytometry. The expression of MUC1-C and PD-L1 mRNA was measured by real time RT-PCR methods. Protein expression was examined in evodiamine-treated NSCLC cells using immunoblotting or immunofluorescence assays. The effects of evodiamine treatment on NSCLC sensitivity towards T cells were investigated using human peripheral blood mononuclear cells and Jurkat, apoptosis and IL-2 secretion assays. Female H1975 xenograft nude mice were used to assess the effect of evodiamine on tumorigenesis in vivo. Lewis lung carcinoma model was used to investigate the therapeutic effects of combination evodiamine and anti-PD-1 treatment. Results We showed that evodiamine significantly inhibited growth, induced apoptosis and cell cycle arrest at G2 phase of NSCLC cells. Evodiamine suppressed IFN-gamma-induced PD-L1 expression in H1975 and H1650. MUC1-C mRNA and protein expression were decreased by evodiamine in NSCLC cells as well. Evodiamine could downregulate the PD-L1 expression and diminish the apoptosis of T cells. It inhibited MUC1-C expression and potentiated CD8.sup.+ T cell effector function. Meanwhile, evodiamine showed good anti-tumor activity in H1975 tumor xenograft, which reduced tumor size. Evodiamine exhibited anti-tumor activity by elevation of CD8.sup.+ T cells in vivo in Lewis lung carcinoma model. Combination evodiamine and anti-PD-1 mAb treatment enhanced tumor growth control and survival of mice. Conclusions Evodiamine can suppress NSCLC by elevating of CD8.sup.+ T cells and downregulating of the MUC1-C/PD-L1 axis. Our findings uncover a novel mechanism of action of evodiamine and indicate that evodiamine represents a potential targeted agent suitable to be combined with immunotherapeutic approaches to treat NSCLC cancer patients. MUC1-C overexpression is common in female, non-smoker, patients with advanced-stage adenocarcinoma. Keywords: Evodiamine, PD-L1, MUC1-C, NSCLC, Immune microenvironment
Geralmente se supõe que a tradução da literatura brasileira nos primeiros anos da República Popular da China (1949-1966) foi principalmente impulsionada por forças políticas, devido às mudanças ...ideológicas oficiais e nas reformas do sistema editorial naquela época. No entanto, este argumento não leva em conta a continuidade da tradução literária antes e depois de 1949, nem considera o esforço dos tradutores naquela época em escolherem os melhores representantes da literatura brasileira e conservarem ao máximo a qualidade das obras originais. Ao analisar a tradução da literatura brasileira na China de 1919 a 1966 como um todo, com revisão especial do caso de Jorge Amado, este artigo tenta demonstrar que a publicação da literatura brasileira após 1949 seguiu o mesmo caminho da tradução da literatura das nações desfavorecidas na primeira metade do Século XX, e que tinha como objetivo de quebrar a hegemonia cultural dos países ocidentais, a fim de construir uma nova nação e uma nova literatura.
It is generally assumed that the translation of Brazilian literature in the early years of the People's Republic of China (1949-1966) was mainly driven by political forces, given the change of official ideology and the reforms of the publishing system at that time. However, this argument does not take into account the continuity of literary translation before and after 1949, nor does it consider the efforts of translators of the time to choose the best representatives of Brazilian literature and to preserve as much as possible the quality of the original works. By analyzing the translation of Brazilian literature in China from 1919 to 1966 as a whole, with special emphasis on the case of Jorge Amado, this article attempts to demonstrate that the publication of Brazilian literature after 1949 followed the same path as the translation of the literature of disadvantaged nations in the first half of the 20th Century, and that it aimed to challenge the cultural hegemony of Western countries in order to build a new nation and a new literature.
Upregulated expression of immune checkpoint molecules correlates with exhausted phenotype and impaired function of cytotoxic T cells to evade host immunity. By disrupting the interaction of PD-L1 and ...PD1, immune checkpoint inhibitors can restore immune system function against cancer cells. Growing evidence have demonstrated apigenin and luteolin, which are flavonoids abundant in common fruits and vegetables, can suppress growth and induce apoptosis of multiple types of cancer cells with their potent anti-inflammatory, antioxidant and anticancer properties. In this study, the effects and underlying mechanisms of luteolin, apigenin, and anti-PD-1 antibody combined with luteolin or apigenin on the PD-L1 expression and anti-tumorigenesis in KRAS-mutant lung cancer were investigated. Luteolin and apigenin significantly inhibited lung cancer cell growth, induced cell apoptosis, and down-regulated the IFN-γ-induced PD-L1 expression by suppressing the phosphorylation of STAT3. Both luteolin and apigenin showed potent anti-cancer activities in the H358 xenograft and Lewis lung carcinoma model in vivo, and the treatment with monoclonal PD1 antibody enhanced the infiltration of T cells into tumor tissues. Apigenin exhibited anti-tumor activity in Genetically engineered KRASLA2 mice. In conclusion, both apigenin and luteolin significantly suppressed lung cancer with KRAS mutant proliferation, and down-regulated the IFN-γ induced PD-L1 expression. Treatment with the combination of PD-1 blockade and apigenin/luteolin has a synergistic effect and might be a prospective therapeutic strategy for NSCLC with KRAS-mutant.
•Luteolin and apigenin can downregulate the PD-L1 expression in NSCLC with KRAS mutation.•The combination of apigenin or luteolin with PD-1 mAb enhanced tumor growth control and improved survival.•Apigenin but not luteolin exhibited anti-tumor activity in KRASLA2 mice.
While the printed circuit board (PCB) has been widely considered as the building block of integrated electronics, the world is switching to pursue new ways of merging integrated electronic circuits ...with textiles to create flexible and wearable devices. Herein, as an alternative for PCB, we described a non-printed integrated-circuit textile (NIT) for biomedical and theranostic application via a weaving method. All the devices are built as fibers or interlaced nodes and woven into a deformable textile integrated circuit. Built on an electrochemical gating principle, the fiber-woven-type transistors exhibit superior bending or stretching robustness, and were woven as a textile logical computing module to distinguish different emergencies. A fiber-type sweat sensor was woven with strain and light sensors fibers for simultaneously monitoring body health and the environment. With a photo-rechargeable energy textile based on a detailed power consumption analysis, the woven circuit textile is completely self-powered and capable of both wireless biomedical monitoring and early warning. The NIT could be used as a 24/7 private AI "nurse" for routine healthcare, diabetes monitoring, or emergencies such as hypoglycemia, metabolic alkalosis, and even COVID-19 patient care, a potential future on-body AI hardware and possibly a forerunner to fabric-like computers.
Lung cancer is the leading cause of cancer death due to its high degree of malignancy, rapid growth, and early metastasis. Recent studies have found that lung cancer has a high degree of ...heterogeneity which is characterized by the mixture of different tumor cell types. However, the driving genetic/epigenetic mechanism of lung cancer heterogeneity, how different types of cells interact, and the relationship between heterogeneity and drug resistance have been poorly understood. Single-cell technology can decompose high throughput sequencing information into each cell and provide single-cell information in high resolution. By using single-cell analysis, researchers can not only fully understand the molecular characteristics of different cell types in the same tissue, but also define completely new cell types. Thus, single-cell analysis has been widely utilized in systems biology, drug discovery, disease diagnosis and precision medicine. We review recent exploration of the mechanism of heterogeneity, tumor microenvironment and drug resistance in lung cancer by using single-cell analysis. We propose that the recent findings may pave new ways for the treatment strategies of lung cancer.
The self‐assembly of a rod–coil amphiphilic block copolymer (ABCP) led to Im3‾
m and Pn3‾
m polymer cubosomes and p6mm polymer hexasomes. This is the first time that these structures are observed in ...a rod–coil system. By varying the hydrophobic chain length, the initial concentration of the polymer solution, or the solubility parameter of the mixed solvent, head–tail asymmetry is adjusted to control the formation of polymer cubosomes or hexasomes. The formation mechanism of the polymer cubosomes was also studied. This research opens up a new way for further study of the bicontinuous and inverse phases in different ABCP systems.
Heads or tails? Im3‾
m and Pn3‾
m polymer cubosomes and p6mm polymer hexasomes are obtained through the self‐assembly of a rod–coil amphiphilic block copolymer in solution. Head–tail asymmetry was adjusted to control the formation of these structures, and the formation mechanism of polymer cubosomes was also studied. This research provides a new way for further study of the bicontinuous and inverse phases.
COVID-19 is associated with 5.1% mortality. Although the virological, epidemiological, clinical, and management outcome features of COVID-19 patients have been defined rapidly, the inflammatory and ...immune profiles require definition as they influence pathogenesis and clinical expression of COVID-19. Here we show lymphopenia, selective loss of CD4+ T cells, CD8+ T cells and NK cells, excessive T-cell activation and high expression of T-cell inhibitory molecules are more prominent in severe cases than in those with mild disease. CD8+ T cells in patients with severe disease express high levels of cytotoxic molecules. Histochemical studies of lung tissue from one fatality show sub-anatomical distributions of SARS-CoV-2 RNA and massive infiltration of T cells and macrophages. Thus, aberrant activation and dysregulation of CD8+ T cells occur in patients with severe COVID-19 disease, an effect that might be for pathogenesis of SARS-CoV-2 infection and indicate that immune-based targets for therapeutic interventions constitute a promising treatment for severe COVID-19 patients.
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