Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.

The alveolar epithelium consists of two types of cells: alveolar epithelial type Ⅱ cells (AT2) and alveolar epithelial type Ⅰ cells (AT1), which function to maintain lung compliance and gas exchange, respectively. AT2 can proliferate and differentiate into AT1 during lung development and repair, thus AT2 have been regarded very important stem cells in lung. However, impaired proliferation and differentiation of AT2 were observed in many chronic lung diseases, preventing the proper repair of alveolar and significantly impacting the life quality of patients. This review focuses on when AT2 proliferate and differentiate, and highlights the critical signaling pathways that influence these processes.

The connection between tendons and bones is called the tendon bone connection. With the continuous improvement of national sports awareness, excessive exercises and the related intensity are prone to damage the tendon bone connection. Tendon bone healing is a complex repair and healing process involving multiple factors, and good tendon bone healing is a prerequisite for its physiological function. The complexity of tendon bone structure also poses great challenges to the repair of tendon bone injuries. In recent years, researches have found that stem cells, growth factors, macrophages, and other factors are closely related to the healing process of tendon bone injuries, among which macrophages play an important role in the healing process. The authors reviewed relevant research literature in recent years and summarized the role of macrophages in tendon bone healing, in order to provide new ideas and directions for treatment strategies to promote tendon bone healing.

Objective The aim of this study was to investigate the effect of p38 on stem cell maintenance of pancreatic cancer. Methods Human pancreatic cancer cells PANC-1 were treated with different concentrations of 5-fluorouracil(5-FU)(0.5×IC50, IC50, and 2×IC50) for 24 hours, and VX-702 (p38 phosphorylation inhibitor) was added, and the cells were inoculated in 6-well culture dishes with ultra-low adhesion to observe the changes of sphere tumors. The expression levels of cyclin-dependent kinase 2(CDK2), cyclin B1 and D1, Octamer-binding transcription factor 4(OCT4), SRY-box transcription factor 2(SOX2), Nanog and p38 were measured by Western blot. The mRNA expression levels of p38, OCT4, Nanog and SOX2 were tested by RT-PCR. Cell cycle, apoptosis, and the proportion of CD44+CD133+PANC-1 cells were evaluated by flow cytometry. Results The results showed that 5-FU inhibited the formation of tumor spheres in PANC-1 cells, increased CD44+CD133+cell fragments, down-regulated the expression of OCT4, Nanog and SOX2, and inhibited the stemness maintenance of PANC-1 tumor stem cells. Phosphorylation of PANC-1 cells was inhibited by a highly selective p38 MAPK inhibitor, VX-702(p38 mitogen-activated protein kinase inhibitor), which had the same effect as 5-FU treatment. When VX-702 combined with 5-FU was used to treat PANC-1 cells, the therapeutic effect was enhanced. Conclusion p38 inhibitors decreased PANC-1 cell activity and increased cell apoptosis. p38 inhibitors inhibit the stemness maintenance of pancreatic cancer stem cells.

Liver transplantation, hepatocyte transplantation, and bioartificial liver are means of treating end-stage liver disease and acute liver failure. However, insufficient liver resources and immune rejection after transplantation, as well as a shortage of liver tissue or cell donors, are challenges faced in clinical treatment. The research progress of liver organoid technology in recent years may provide new ways to solve the above problems. Organoids are a kind of three-dimensional cell condensates formed by the self-organization of pluripotent or adult stem cells through three-dimensional culture in vitro, which can imitate the spatial structure and physiological function characteristics of the original organs, can be sub-cultured in vitro, replicated on a large scale, and have the ability of self-renewal. The emergence of organoid technology has brought new hope for providing mechanism exploration models and resolution of hepatocyte resources. In particular, induced pluripotent stem cell-derived organoids do not involve ethical concerns, and are combined with emerging technologies such as gene editing and organ chips, thereby overcoming the constraint of traditional disease research models and establishing a new platform for translational medicine. Additionally, it has expansive application prospects in building disease models, screening drugs, precision medicine, regenerative medicine, and organ transplantation. Thus, this paper summarizes the technical principles, preclinical research, and application progress and challenges of liver organoid technology.

Objective: To explore the clinical manifestations, pathogenesis, and therapeutic approaches of disseminated intravascular coagulation (DIC) associated with chimeric antigen receptor T-cell (CAR-T) therapy for B-lymphoblastic lymphoma. Methods: Retrospective collection and analysis were conducted on the clinical data of a patient with B-lymphoblastic lymphoma who received CAR-T therapy in the Hematology Department of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, in April 2020. To review the literatures, Chinese databases (CNKI, Wanfang Database) and PubMed were searched form database inception up to November 2024 using the retrieval entries "chimeric antigen receptor T-cell therapy", "CAR-T", "coagulation", "bleeding", and "thrombosis" . Results: The patient, a 32-year-old male, diagnosed with B-lymphoblastic lymphoma for over 10 months, relapsed after three cycles of chemotherapy and allogeneic hematopoietic stem cell transplantation, with bone marrow cytology indicating 20.24% abnormal phenotype B-lineage precursor cells. After CAR-T cell infusion at a dose of 4×10(6)/kg, the patient developed grade 2 cytokine release syndrome (CRS) on day 2, nasal bleeding on day 4, high fever again on day 9, with worsening coagulation parameters, DIC and persistent hypofibrinogenemia. After treatment with tocilizumab, corticosteroids to counteract CRS, and active replacement therapy such as administration of blood product and fibrinogen, the patient's CRS and coagulation abnormalities gradually improved. The patient was followed up for 16 months regularly after CAR-T therapy, with CAR-T cells sustained and minimal residual disease remained negative as assessed by bone marrow flow cytometry. Subsequently, the patient stopped taking oral immunosuppressants on his own, which aggravated rejection reaction complicated with infection. The patient and his family requested to be discharged and lost the follow-up. A total of 20 relevant English articles and 6 Chinese articles were retrieved from the literature search. Conclusion: CAR-T-associated coagulopathy occurs alongside CRS. It is characterized by hypofibrinogenemia, and is life-threatening when progressing to DIC. Anti-CRS and replacement therapies have proven to be effective treatment strategies.

To investigate the mechanism of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC) in alleviating brain injury after resuscitation in swine with cardiac arrest (CA).

Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of patients with chronic myeloid leukemia (CML), and achieving treatment-free remission (TFR) has become a new goal for these patients. Various methods of discontinuing medication are continuously being explored, with successful cessation linked to factors such as the duration of TKI treatment, the sustainability of deep molecular response (DMR), transcript type, and immunological factors. Early switching of TKI, combining other therapies, and targeting leukemia stem cells may help increase the TFR rate. This article reviews the latest research developments on the exploration of TKI cessation, factors affecting TFR, selection of patients for discontinuation, strategies to enhance TFR, and monitoring after cessation, expecting to provide reference and guidance for achieving TFR in CML patients.

Bone marrow microenvironment is the environment in which hematopoietic stem cells live, mainly composed of bone marrow stromal cells, microvessels, nerves, and cytokines secreted by stromal cells. The bone marrow microenvironment plays a crucial role in the self-renewal, directed differentiation and proliferation of hematopoietic stem cells and the regulation of proliferation, differentiation and maturation of hematopoietic cells. A class of macrophages exists in the bone marrow microenvironment, the bone marrow-resident tissue macrophages, which plays a crucial role in maintaining homeostasis in vivo, and three subpopulations of bone marrow-resident tissue macrophages have been characterized: erythroblastic island macrophages (EIMs), hematopoietic stem cell niche macrophages, and bone macrophages. This review focuses on the functions, surface markers and modeling of EIMs.

To establish an in vitro cell model simulating acute graft-versus-host disease (aGVHD) bone marrow microenvironment injury with the advantage of mouse serum of aGVHD model and explore the effect of serum of aGVHD mouse on the adipogenic differentiation ability of mesenchymal stem cells (MSCs).

To investigate the effects and underlying mechanism of ionizing radiation on the adipogenic of mesenchymal stem cells (MSCs).

To screen novel diagnostic marker or therapeutic target for multiple myeloma (MM).

Bone is a highly calcified and vascularized tissue. The vascular system plays a vital role in supporting bone growth and repair, such as the provision of nutrients, growth factors, and metabolic waste transfer. Moreover, the additional functions of the bone vasculature, such as the secretion of various factors and the regulation of bone-related signaling pathways, are essential for maintaining bone health. In the bone microenvironment, bone tissue cells play a critical role in regulating angiogenesis, including osteoblasts, bone marrow mesenchymal stem cells (BMSCs), and osteoclasts. Osteogenesis and bone angiogenesis are closely linked. The decrease in osteogenesis and bone angiogenesis caused by aging leads to osteoporosis. Long noncoding RNAs (lncRNAs) are involved in various physiological processes, including osteogenesis and angiogenesis. Recent studies have shown that lncRNAs could mediate the crosstalk between angiogenesis and osteogenesis. However, the mechanism by which lncRNAs regulate angiogenesis‒osteogenesis crosstalk remains unclear. In this review, we describe in detail the ways in which lncRNAs regulate the crosstalk between osteogenesis and angiogenesis to promote bone health, aiming to provide new directions for the study of the mechanism by which lncRNAs regulate bone metabolism.

To investigate the effect and mechanism of let-7c overexpression on the proliferation of human dental pulp stem cells (hDPSCs).

To explore the differential miRNA expression profiles and predicted target genes of mandibular bone marrow mesenchymal stem cells (MBMSCs) in a postmenopausal osteoporosis (POP) mouse model using bioinformatics methods, providing new targets for diagnosis, treatment, and prevention of POP.

This study aims to investigate the protective effect of resveratrol against liver injury in hindlimb unloading rats. Thirty 2-month-old male SD rats were randomly divided into normal group (Control), hindlimb unloading model group (Model), and hindlimb unloading+resveratrol administration group (Model+Res). The Model + Res group was injected intraperitoneally with 30 mg/kg of resveratrol, and the Control and Model groups were injected intraperitoneally with an equal volume of 0.9% NaCl. Liver tissues were collected after 28 days and analyzed for oxidative stress, inflammatory factors, energy metabolism indices, Na +-K +-ATPase and Ca 2+-Mg 2+-ATPase activity, and morphological changes were observed by hematoxylin-eosin staining. The protein expression levels of Bax, Bcl-2, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blotting. Compared with the Control group, hepatocytes in the Model group showed swelling, abnormal morphology, nuclear consolidation, and cell membrane disruption. Oxidative stress, inflammatory factor levels, hepatic glycogen accumulation, and energy metabolism were increased in the liver tissues of the Model group, while resveratrol treatment significantly reversed these changes. The results of Western blotting showed that resveratrol significantly reduced the expression of Bax and increased the expression levels of Bcl-2, and the proteins of p-PI3K/PI3K and p-AKT/AKT expression levels. It is suggested that 28 days of hindlimb unloading treatment could lead to liver tissue injury in rats, which is manifested as oxidative stress, inflammatory response, energy metabolism disorder and increased apoptosis level, and resveratrol has a certain mitigating effect on this.

To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms.

Objective: To investigate the effect of injectable adipose tissue stem cell-derived exosome-encapsulated hydrogel on the tendon healing in rats and to evaluate the temporal and spatial expressions of periphery neuropeptides at healing site. Methods: To generate the injectable exosome-encapsulated hydrogel, the methacryloylchloride solution (GelMA) and the photoinitiator were mixed first, then the exosome solution was added and oscillated together. Followed with exposing in the ultraviolet light in a wave length 405 nm for 30 seconds to form an injectable hydrogel. The Sprague Dawley (SD) rats were performed with full thickness transection and surgical repair administration of Achilles tendon to establish the animal model, including 4 groups: intact control (C group, selected the contralateral side of tendon transection with surgical repair group), tendon transection with surgical repair group (S group), tendon transection with surgical repair and hydrogel implantation group (H group) and tendon transection with surgical repair and exosome-encapsulated hydrogel group (E group). The samples were harvested on Day 7, 14 and 28 after the operation, respectively. Histopathological examination was performed with hematoxylin-eosin staining (HE staining) and immunohistochemistry staining of tenogenesis marker (Tenomodulin, TNMD), periphery neuropeptide markers (growth associated protein-43, GAP43; S100 calcium-binding protein B, S100B; neuropeptide Y, NPY; calcitonin gene-related peptide, CGRP; Substance P, SP). Morphological property was characterized with tendon length, cross-sectional area (CSA), and gastrocnemius weight ratio. Biomechanical testing was measured with maximum failure load, stiffness and tensile modulus. Results: The results of the quantitative polymerase chain reaction (qPCR) showed that the expression level of the TNMD gene in the E group was 2.12±0.43, which was significantly higher than that in the H group (1.26±0.28) and the S group (1.21±0.39) (both P<0.05). Based on the immunohistochemistry staining, the expression of GAP43 can be detected with an significant enhancement in the E group (11.20%±0.53% positive area) relative to H group (7.25%±0.22% positive area) and S group (8.68%±0.45% positive area) (both P<0.001) on day 28 post-surgery; whilst the expression of CGRP exhibited a depressed variation with a positive area of 7.62%±0.50% in E group relative to a positive area of 11.16%±1.33% in H group and a positive area of 10.16%±0.22% in S group on day 28 post-surgery, respectively (both P<0.001). Besides, the E group showed that the morphological characterization with a superior restoration of tendon length to (11.67±0.58) mm and CSA to (5.97±0.72) mm2 and biomechanical property of healed tendon with an improvement of maximum failure load to (71.06±2.48)N and tensile modulus to (9.24±1.56) MPa when compared with those in S and H groups (all P<0.01). Conclusion: Injectable Exos-encapsulated hydrogel promotes tendon healing in SD rats with enhancing temporal periphery neuropeptides expression and reducing the nerve sensitization during tendon healing.

To initially investigate the function of neuronal pentraxin 1 (NPTX1) gene on osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs).