BackgroundIntrauterine adhesion (IUA) is a common uterine cavity disease which can be caused by mechanical damage that may eventually lead to infertility and pregnancy abnormalities. Since the effect of therapeutic drugs appears disappointing, cell therapy has emerged as an alternative choice for endometrium regeneration. The aim of this study is to investigate whether the combination of hydrogel Pluronic F-127 (PF-127), Vitamin C (Vc), and a bone marrow stromal cell (BMSC) mixture could be a feasible strategy to improve the endometrial regeneration in a mechanical damage model of IUA in rats.MethodsFirstly, PF-127 cytotoxicity and the effect of Vc was tested in vitro using the Annexin V/propidium iodide (PI) apoptosis test, cell count kit (CCK) growth test, and enzyme-linked immunosorbent assay (ELISA). For the establishment of the rat IUA model, a 2-mm transverse incision in the uterus was prepared at the upper end, and 1.5- to 2.0-cm endometrial damage was scraped. Rats were randomly assigned to five groups to investigate the combined strategy on IUA uterine regeneration: a sham group, an IUA control group, an IUA BMSC encapsulated in PF-127 plus Vc group, an IUA BMSC plus Vc group, and an IUA PF-127 plus Vc group. A cell mixture was injected into the uterine horn while making the IUA model. Eight weeks after cell transplantation, the rats were sacrificed and the uterine was dissected for analysis. Endometrial thickness, gland number, fibrosis area, and the expression of marker proteins for endometrial membrane were examined by hematoxylin and eosin staining, Masson’s staining, and immunohistochemistry.ResultsVc promoted the survival and health of PF-127-encapsulated BMSCs in vitro. When this combination was transplanted in vivo, the endometrium showed better restoration as the endometrium membrane became thicker and had more glands and less fibrosis areas. The expression of cytokeratin, von Willebrand Factor (vWF), was also restored. The proinflammatory cytokine interleukin-1β (IL-1β) was significantly lower compared with the control group.ConclusionsVc alleviates the cytotoxic effect of PF-127 and promotes cell survival and growth in rat BMSC encapsulation. Thus, a cell therapy strategy containing biomaterial scaffold, BMSCs and the modulatory factor Vc promotes the restoration of damaged IUA endometrium.

This study aimed to investigate the effects of estrogen in combination with aspirin and intrauterine balloon on the uterine endometrial repair and reproductive prognosis in patients after surgery for severe intrauterine adhesion (sIUA). We prospectively recruited 114 patients with sIUA. Intrauterine device (IUD) was placed and oral estrogen was administered after surgery. Patients were divided into control group and aspirin group. In addition, patients in aspirin group were subdivided into nonballoon group and balloon group. Results showed that, after therapy, the increase in endometrial thickness of aspirin groups was superior to control group (P < 0.05). The scores of intrauterine adhesion and menstruation were significantly improved in balloon group as compared to nonballoon group and control group, and significant differences were also observed between nonballoon group and control group (P < 0.05). Of 97 patients, 44.3% became pregnant after surgery, the live birth rate was 27.8%, and the miscarriage rate was 37.2%, but there were no significant differences among three groups (P > 0.05). Thus, aspirin may promote the uterine endometrial growth and repair after surgery for sIUA, and IUD in combination with intrauterine balloon may reduce the recurrence of intrauterine adhesion, but their effect on the reproductive prognosis is required to be further studied.

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Alzheimer’s disease (AD) is the most common cause of dementia and is characterized by the deposition of extracellular aggregates of amyloid-β (Aβ), the formation of intraneuronal tau neurofibrillary tangles and microglial activation-mediated neuroinflammation. One of the key molecules involved in microglial activation is galectin-3 (Gal-3). In recent years, extensive studies have dissected the mechanisms by which Gal-3 modulates microglial activation, impacting Aβ deposition, in both animal models and human studies. In this review article, we focus on the emerging role of Gal-3 in biology and pathobiology, including its origin, its functions in regulating microglial activation and neuroinflammation, and its emergence as a biomarker in AD and other neurodegenerative diseases. These aspects are important to elucidate the involvement of Gal-3 in AD pathogenesis and may provide novel insights into the use of Gal-3 for AD diagnosis and therapy.

Objective: To study the effect of chronic endometritis (CE) diagnosed by CD138 immunohistochemical (IHC) staining on endometrial fibrosis and reproductive prognosis in patients with moderate or severe intrauterine adhesions (IUAs). Design: Prospective cohort study (Canadian Task Force classification II-2). Setting: University-affiliated hospital. Patient(s): One hundred sixty-seven women with moderate to severe IUAs. Intervention(s): Transcervical resection of adhesions (TCRA) and endometrial biopsy were performed in all patients. According to results of IHC staining with anti-syndecan-1 antibodies to identify CD138 cells, participants were classified into two groups: 78 patients with CE (CE group) and 89 women without CE (NCE group). IHC staining for fibrosis markers transforming growth factor beta 1, antifibrosis markers matrix metalloproteinase 9, and endometrial receptivity marker integrin alpha v beta 3 was later applied to all tissue samples. Main Outcome Measure(s): Endometrial fibrosis, endometrial receptivity, and reproductive prognosis. Result(s): CE diagnosed by CD138 IHC staining has a high incidence, 46%, in moderate and severe IUAs. In the CE group, the expression of transforming growth factor beta 1 was higher than that in the NCE group, and the expression of matrix metalloproteinase 9 and alpha v beta 3 was lower than that in the NCE group. The pregnancy rate and live birth rate in the NCE group were higher than those in the CE group (42.7% vs. 31.5%, 26.9% vs. 17.9%). Conclusion(s): CE may affect the endometrial fibrosis homeostasis in IUAs. Women with CE were more likely to experience recurrence of adhesions and had poorer reproductive outcomes.

Background Mesenchymal stem cells (MSCs) have exerted their brilliant potential to promote heart repair following myocardial infarction. However, low survival rate of MSCs after transplantation due to harsh conditions with hypoxic and ischemic stress limits their therapeutic efficiency in treating cardiac dysfunction. ELABELA (ELA) serves as a peptide hormone which has been proved to facilitate cell growth, survival, and pluripotency in human embryonic stem cells. Although ELA works as an endogenous ligand of a G protein-coupled receptor APJ (Apelin receptor, APLNR), whether APJ is an essential signal for the function of ELA remains elusive. The effect of ELA on apoptosis of MSCs is still vague. Objective We studied the role of ELABELA (ELA) treatment on the anti-apoptosis of MSCs in hypoxic/ischemic (H/I) conditions which mimic the impaired myocardial microenvironment and explored the possible mechanisms in vitro. Methods MSCs were obtained from donated rats weighing between 80~120 g. MSCs were exposed to serum-free and hypoxic (1% O2) environments for 24 h, which mimics hypoxic/ischemic damage in vivo, using serum-containing normoxic conditions (20% O2) as a negative control. MSCs that were exposed to H/I injury with ELA processing were treated by 5 μM of ELA. Cell viability and apoptosis of MSCs were evaluated by CCK8 and flow cytometry, respectively. Mitochondrial function of MSCs was also assessed according to mitochondrial membrane potential (MMP) and ATP content. The protein expression of key kinases of the PI3K/AKT and ERK1/2 signaling pathways involving t-AKT, p-AKT, t-ERK1/2, and p-ERK1/2, as well as apoptosis-related protein expression of Bcl-2, Bax, and cleaved Caspase 3, were monitored by Western blot. Results We found that ELA treatment of H/I-induced MSCs improved overall cell viability, enhanced Bcl/Bax expression, and decreased Caspase 3 activity. ELA inhibited H/I-induced mitochondrial dysfunction by increasing ATP concentration and suppressing the loss of mitochondrial transmembrane potential. However, this anti-apoptotic property of ELA was restrained in APJ-silenced MSCs. Additionally, ELA treatment induced the phosphorylation of AKT and ERK, while the blockade of PI3K/AKT and ERK1/2 pathways with respective inhibitors, LY294002 and U0126, suppressed the action of ELA. Conclusion ELA positively affected on the survival of MSCs and exhibited anti-apoptotic characteristics when exposed to hypoxic/ischemic condition in vitro. Also, the function of ELA was correlated with the APJ receptor, reduced mitochondrial damage, and activation of the PI3K/AKT and ERK1/2 signal axes.

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Therapeutic Level II. See page 128 for a complete description of levels of evidence.