Human UC-MSC-derived exosomes facilitate ovarian renovation in rats with chemotherapy-induced premature ovarian insufficiency

Premature ovarian insufficiency (POI) induced by chemotherapy is an intractable disorder with a considerable incidence that commonly results in insufficient fertility and concomitant complications in female patients. Due to limitations in the current progress in POI diagnosis and treatment, there is an urgent need to develop novel remedies to improve ovarian function and protect fertility. The ameliorative effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and exosomes derived from them in POI treatment could be a new hope for patients. Herein, we identified exosomes from hUCMSCs (hUCMSC-Exos). Then, systematic infusion of hUCMSC-Exos was accomplished via tail intravenous injection to investigate the feasibility of the treatment of rats with chemotherapy-induced POI by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS). Ovarian functions in the indicated group were evaluated, including oestrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, proliferation and apoptosis of granulosa cells (GCs), and reproductive ability testing. Furthermore, the potential influence of hUCMSC-Exos on ovarian tissues was illuminated by conducting RNA-seq and multifaceted bioinformatics analyses. POI rats with hUCMSC-Exos transplantation exhibited a decrease in follicle-stimulating hormone (FSH) and apoptosis of GCs but an increase in oestradiol (E2), anti-Müllerian hormone (AMH), and the number of ovarian follicles and foetuses in the uterus. And the immunomodulation- and cellular vitality-associated gene sets in rats had also undergone moderate changes. Our data indicated the feasibility of hUCMSC-Exos in improving ovarian function and protecting fertility in chemotherapy-induced POI rats. HUCMSC-Exos can improve the local microenvironment of ovarian tissue in POI rats by participating in immune regulation, cellular viability, inflammation regulation, fibrosis and metabolism, and other related signal pathways

Ferroptosis in Leukemia: Lessons and Challenges

Ferroptosis is a newly defined programmed cell death (PCD) process with the hallmark of the accumulation of iron-dependent lipid peroxidation, which is more immunogenic over apoptosis. Ferroptosis shows great potential as a therapeutic target against acute kidney injury (AKI), cancers, cardiovascular diseases, neurodegenerative diseases, and hepatic diseases. Accumulating evidence has highlighted that ferroptosis plays an unneglectable role in regulating the development and progression of multiple pathologies of leukemia including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). Herein, we focus on the state-of-the-art renewal in the relationship of ferroptosis with leukemia. Meanwhile, this chapter further highlights the iron, lipid and amino acid metabolism, as well as ferroptosis-based molecular mechanisms. Collectively, we summarize the contribution of ferroptosis to the pathogenesis of leukemia and discuss ferroptosis as a novel therapeutic target for different types of leukemia

Natural Killer Cells for Cancer Immunotherapy: Opportunities and Challenges

Natural killer (NK) cells are advantaged immune cells and play a pivotal role in both innate and adaptive immune responses. To date, autogenous and allogenic NK cells have been generated from a variety of origins, including perinatal blood (e.g., umbilical cord blood and placental blood), peripheral blood, and even stem cells (hematopoietic stem cells and pluripotent stem cells). NK cells function mainly via antibody-dependent cell-mediated cytotoxicity (ADCC), direct cytolytic effect, and paracrine effects (e.g., IFN-γ, GM-CSF, granzyme, and perforin). Distinguishing from the adaptive immunizing cells (e.g., T and B lymphocytes), NK cells, and chimeric antigen receptor-transduced NK (CAR-NK), cell-based cytotherapy is adequate to fulfill the biofunction of eliminating pathogenic infection, combating hematological malignancies and metastatic solid tumors, and delaying aging. In this chapter, we mainly focus on the state-of-the-art renewal of NK cell-based cytotherapy for cancer immunosurveillance and immunotherapy from the view of high-efficient in vitro preparation (e.g., candidate cell sources and ex vivo cultivation) and preclinical and clinical investigation. Furthermore, we also figure out the promising prospects and the concomitant challenges of NK cell-based remedies for cancer management in future, which will collectively benefit the development of NK cell-based cancer immunotherapy in future

Mesenchymal Stem Cell-based Cytotherapy for Osteoarthritis Management: State of the Art

Osteoarthritis (OA), a principal and challenging disorder of articular cartilage, has been regarded as the most frequent and prevalent chronic disease of degenerative joints, which is caused by multiple factors including aging, trauma, overweight, joint deformity and congenital abnormality, together with the increase in life expectancy. In spite of considerable improvements that have been obtained by conducting multidisciplinary therapies such as surgical procedures and anti-inflammatory drugs, the pathogenesis and efficacy of OA with functional losses and degeneration are still elusively complicated for ascertainment. Mesenchymal stem/stromal cells (MSCs), also termed as multipotent mesenchymal progenitor/precursor cells, skeletal stem cells, or medicinal signaling cells, are heterogeneous cell populations with hematopoietic-supporting and immunomodulatory properties, together with multilineage differentiation property. For decades, investigators have illuminated the application of the advantaged and promising sources with/without remarkable biomaterials for the treatment of recurrent and refractory disorders including OA. In this chapter, we mainly concentrate on the current progress of MSC-based cytotherapy in both preclinical study and clinical practice as well as the promising prospective and critical challenges in the field, which will conformably benefit the administration of OA in future

Dynamic model for piezotronic and piezo-phototronic devices under low and high frequency external compressive stresses (Featured)

In this work, we aim to establish a theoretical method for modelling the dynamic characteristics of piezotronics and piezo-phototronic devices. By taking the simplest piezotronic device, PN junction as an example, we combine the small signal model and the unified approach to investigate its diffusion capacitance and conductance when it is under both low and high frequency external compressive stresses. This approach is different from the traditional considerations that treat the piezopotential as a static value. Furthermore, we expand the theory into piezo-phototronic devices, e.g., a light emitting diode. The dynamic recombination rate and light emitting intensity are quantitatively calculated under different frequencies of external compressive stresses

Immunomodulation of NK Cells under Ionizing Radiation

Natural killer (NK) cells are the effector lymphocytes of the innate immune system and control many types of tumors and microbial infections. Ionizing radiation (IR) has a pronounced effect on NK cells. However, the role of NK cells in radiotherapy remains elusive. In this chapter, we summarized the direct and indirect effects of ionizing radiation on NK cells. Low doses of ionizing radiation can enhance the toxic effects of NK cells. In contrast, high doses of ionizing radiation will lead to functional impairment of NK cells. In addition, under ionizing radiation, NK cells are also modulated by other immune cells. Overall, combining NK cell therapy and radiation therapy can improve the efficacy of oncology treatment

Serum miR-195-5p Exhibits Clinical Significance in the Diagnosis of Essential Hypertension with Type 2 Diabetes Mellitus by Targeting DRD1

OBJECTIVES: Diagnosis and management of essential hypertension (EH) or type 2 diabetes mellitus (T2DM) by combining comprehensive treatment and classificatory diagnosis have been continuously improved. However, understanding the pathogenesis of EH patients with concomitant T2DM and subsequent treatment remain the major challenges owing to the lack of non-invasive biomarkers and information regarding the underlying mechanisms. METHODS: Herein, we collected 200 serum samples from EH and/or T2DM patients and healthy donors (N). Gene-expression profiling was conducted to identify candidate microRNAs with clinical significance. Then, a larger cohort of the aforementioned patients and 50 N were used to identify the correlation between the tumor suppressor miR-195-5p and EH and/or T2DM. The dual-luciferase reporter assay was used to explore the target genes of miR-195-5p. The suppressive effects of miR-195-5p on the 3′-UTR of the dopamine receptor D1 (DRD1) transcript in EH patients with concomitant T2DM were verified as well. RESULTS: Compared with that in other groups, serum miR-195-5p was highly downregulated in EH patients with concomitant T2DM. miR-195-5p overexpression efficiently suppressed DRD1 expression by binding to the two 3′-UTRs. Additionally, two single nucleotide polymorphisms, including 231T-A and 233C-G, in the miR-195-5p binding sites of the DRD1 3′-UTR were further identified. Collectively, we identified the potential clinical significance of DRD1 regulation by miR-195-5p in EH patients with concomitant T2DM. CONCLUSIONS: Our data suggested that miR-195-5p circulating in the peripheral blood served as a novel biomarker and therapeutic target for EH and T2DM, which could eventually help address major challenges during the diagnosis and treatment of EH and T2DM

Human Pluripotent Stem Cell-Derived Mesenchymal Stem Cells for Oncotherapy

Mesenchymal stem/stromal cells (MSCs) with hematopoietic-supporting and immunoregulatory properties have aroused great expectations in the field of regenerative medicine and the concomitant pathogenesis. However, many obstacles still remain before the large-scale preparation of homogeneous and standardized MSCs with high cellular vitality for clinical purposes ascribe to elusive nature and biofunction of MSCs derived from various adult and fetal sources. Current progress in human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), have highlighted the feasibility of MSC development and disease remodeling, together with robust MSC generation dispense from the inherent disadvantages of the aforementioned MSCs including ethical and pathogenic risks, donor heterogeneity and invasiveness. Herein, we review the state-of-the-art updates of advances for MSC preparation from hPSCs and multiple tissues (perinatal tissue, adult tissue) as well as tumor intervention with biomaterials, and thus propose a framework for MSCs-based oncotherapy in regenerative medicine. Collectively, we describe the landscape of in vitro generation and functional hierarchical organization of hPSC-MSCs, which will supply overwhelming new references for further dissecting MSC-based tissue engineering and disease remodeling

Advances in Natural Killer Cells and Immunotherapy for Gastric Cancer

Gastric cancer is one of the common malignant tumors in the gastrointestinal tract, and the treatment of gastric cancer includes the main ways such as radical resection, adjuvant chemotherapy, palliative care, and drug therapy; however, patients often have defects such as high recurrence rate, high treatment burden, and serious side effects, which impose a heavy burden on the economic and social construction and patients’ families. In recent years, novel gastric cancer treatment methods featuring tumor immunotherapy have provided new treatment strategies to improve the above-mentioned defects and increase the cure rate of patients. Natural killer cells (NK cells) are key components of the body’s intrinsic immune response and can participate in both the intrinsic and adaptive immune responses, exercising the functions of tumor killing, removing pathogenic microorganisms or abnormal cells and enhancing immunity, and thus have broad prospects for new drug development and clinical treatment. This article reviews the biological properties and functions of NK cells and their interrelationship with gastric cancer treatment, and provides a reference for clinical research

患者再現videoを利用したPBLテュートリアルの有用性に関する研究

研究科: 千葉大学大学院医学薬学府（先端医学薬学専攻）学位記番号: 千大院医薬博甲第医1338号博士（医学）千葉大学 = Chiba Universit