To investigate the effects of rat amniotic mesenchymal stem cells (R-AMSCs) on blood glucose and pancreatic tissue in type 1 diabetes (T1D) model rats.

Amniotic mesenchymal stem cells (AMSCs) were isolated from the placentas of pregnant rats at 17-19 days of gestation. Flow cytometry was used to detect the expressions of stem cell surface markers (CD29, CD34, CD45, CD73), immunofluorescence was performed to identify vimentin expression, and trilineage differentiation (osteogenic, adipogenic, chondrogenic) was induced to evaluate the multipotency. Twenty-four adult male SD rats were randomly divided into three groups (n = 8 per group), which named control, T1D (model), and T1D + R-AMSCs (intervention) respectively. The T1D model was established by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg). One week after successful modeling, the rats in intervention group were received tail vein injections of 5 × 10⁶ R-AMSCs (once per week for 3 weeks), while the control and model groups received equal volumes of PBS. 2 weeks after the intervention, blood and pancreatic tissue were collected after anesthesia with isoflurane. The expression levels of blood glucose, serum insulin and C-peptide, the pathological changes of pancreatic tissue, as well as the expression levels of mRNA and protein of Neurogenin 3 (Ngn3) and pancreatic and duodenal homeobox 1 (PDX-1) were measured to evaluate the therapeutic effects of R-AMSCs. The differences among multiple groups were compared with ANOVA test, and the LSD-t test was used for pairwise comparisons between groups. Repeated measures design quantitative data were analyzed using repeated measures design analysis of variance, and pairwise comparisons were conducted using Bonferroni post hoc tests.

R-AMSCs were successfully isolated using enzymatic digestion. Flow cytometry, immunofluorescence (vimentin-positive), and trilineage differentiation confirmed their stem cell characteristics. Blood glucose levels were significantly lower in the intervention group compared to the model group (P < 0.05). Compared with the control group, the level of serum insulin [ (5.48 ± 1.51) vs (11.18 ± 2.42) mU/L] and C-peptide levels in model group were decreased significantly [ (149.88 ± 14.19) vs (199.35 ± 22.10) pg/mL] (P < 0.05). In contrast, the levels of serum insulin [ (7.67 ± 1.33) vs (5.48 ± 1.51) mU/L] and C-peptide levels [ (176.04 ± 17.88) vs (149.88 ± 14.19) pg/mL] in the intervention group were significant higher compared to the model group (P < 0.05). HE staining of pancreatic tissue showed that the pancreatic morphologtical structure and insulin expression in the intervention group were improved compared to the model group. Compared with the control group, the expression level of Ngn3 mRNA (0.57 ± 0.15 vs 1.00 ± 0.18), protein (0.80 ± 0.04 vs 1.11 ± 0.08) as well as PDX mRNA (0.47 ± 0.08 vs 1.00 ± 0.11), protein (0.84 ± 0.13 vs 1.19 ± 0.06), mRNA and protein were significant lower than those in model group (all P < 0.05). Compared with the model group, the expression levels of Ngn3 mRNA (0.87 ± 0.06 vs 0.57 ± 0.15) and protein (1.03 ± 0.11 vs 0.80 ± 0.04), as well as PDX-1 mRNA (0.71 ± 0.14 vs 0.47 ± 0.08) and protein (1.12 ± 0.11 vs 0.84 ± 0.13) in the intervention group were increased (all P < 0.05) .

Three weeks of R-AMSCs treatment could reduce the blood glucose levels effectively, improve the pathological morphology of the pancreas, and up-regulate the expression of key pancreatic transcription factors (Ngn3 and PDX-1) as well as serum insulin and C-peptide levels in T1D model rats, indicating a potential therapeutic effect of R-AMSCs on T1D.

Establish the mouse models of acute graft-versus-host disease (aGVHD) after H-2 haploidentical (haplo-HSCT) and MHC incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT) and observe the pathological changes of different organs after HSCT, laying a foundation for mechanism research.

By administering the recipient mice with a dose of 8 Gy dose of ⁶⁰Coγ rays as the pretreatment protocol, using male C57BL/6 (H-2K^b) as the donor mice and female BALB /C (H-2K^d) as the recipient mice, 200 μL of suspension of bone marrow cells (5 × 10⁶/ mouse) and spleen monocytes (1 × 10⁷/ mouse) was reinfused via the tail vein within 2 hours to construct an animal model of aGVHD after allo-HSCT with MHC mismatch. Under the same pretreatment conditions, male C57BL/6 (H-2K^b) was used as the donor mouse and female[C57BL/6 × BALB/C]F1 (H-2K ^b/d) was used as the recipient mouse, and 200 μL of bone marrow cells (5 × 10⁶/ mouse) and spleen monocytes (1 × 10⁷/ mouse) were infused back into the tail vein within 2 hours to construct an animal model of aGVHD after haplo-HSCT. The two recipients were divided into TBI group, TBI plus allo-HSCT group (aGVHD model group). The two groups were given healthy mice of the same age as controls. The survival rate, clinical score and body mass changes of mice were observed, the pathological changes of organs (lungs, liver, spleen, kidneys, skin and intestines) were observed by HE staining. Data analysis was conducted using the independent samples t-test for inter-group comparisons. One-way analysis of variance was used for comparison between multiple groups, and LSD-t test was used for pairwise comparison between groups.

Compared with the healthy control group, the survival rate and body weight in both two aGVHD groups were decreased significantly, while the clinical score were increased (6.18 ± 0.23 vs 0, 5.14 ± 0.38 vs 0), and the pathological damage of organs was severe (P < 0.01). The mice in two TBI groups showed a decreased in appetite and activity, but did not have typical aGVHD manifestations. Compared with the TBI group, the clinical score of the aGVHD group was significantly higher (6.18 ± 0.23 vs 1.82 ± 0.11, 5.14 ± 0.38 vs 1.45 ± 0.23). Compared with the mice in the MHC-incompatible aGVHD group, the pathological observation of mice in the aGVHD group after haplo-HSCT showed that the organ damage was mild, the difference in kidney and skin were statistically significant (3.67 ± 0.32 vs 2.60 ± 0.25, 7.50 ± 0.38 vs 6.00 ± 0.32), while the difference in lung, liver, spleen and intestines was not statistically significant, and the survival time of mice in the aGVHD group was prolonged after haplo-HSCT.

Using TBI as the pretreatment regimen, C57BL/6 (H-2^b) as the donor mouse, BALB/C and CB6F1 (H-2^b/d) as the recipient mouse, the aGVHD model could be stably constructed, and the immune rejection and organ damage were more severe in MHC incompatible HSCT compared with haplo-HSCT.

Phenyl-modified mesoporous silica nanoparticles (PMSN) -loaded immunomodulator Resiquimod (R848) was prepared to investigate whether PMSN-R848 could repolarize M2-type macrophages to M1-type.

Mesoporous silica (MSN) was prepared by calcination, Phenyltriethoxysilane (PhTES) was added to modify MSN with phenyl and loaded with R848 to obtain PMSN-R848 nanoparticles. The drug loading efficiency of R848 on PMSN was calculated by measuring the R848 standard curve using an enzyme-linked immunosorbent assay (ELISA) reader. The structure of PMSN and PMSN-R848 was observed by transmission electron microscopy. The cytotoxicity of PMSN-R848 was assessed via the CCK-8 assay. Fluorescence electron microscopy (FEM) was employed to detect the colocalization of PMSN-R848 with macrophage lysosomes. Flow cytometry was performed to determine whether PMSN-R848 could repolarize macrophages. One-way analysis of variance was used for comparison between multiple groups, and LSD-t test was used for pairwise comparison between groups.

The drug loading rate of PMSN loaded with R848 was (36.97 ± 5.80) %, the PMSN transmission electron microscope showed a spherical structure with pores, adsorbed particles could be seen on the surface of the spherical structure of PMSN-R848, PMSN-R848 was non-cytotoxic and could be well localized in macrophage lysosomes, and M2 macrophages were repolarized to the M1 phenotype after co-incubation with PMSN-R848.

The PMSN loaded with R848 could effectively repolarize M2 macrophages to M1.

To investigate the targeting relationship between LncRNA Plasmacytoma Variant Translocation 1 (PVT1) and miR-145-5p, and its effects on H₂O₂-induced apoptosis and oxidative stress in H9C2 cardiomyocytes.

Serum samples were collected from patients with acute myocardial infarction (AMI) (AMI group) and healthy individuals (control group). RT-qPCR were used to detect the expression levels of PVT1 and miR-145-5p. H9C2 cardiomyocytes were cultured and divided into NC group, H₂O₂ group, H₂O₂+si-NC group, H₂O₂+si-PVT1 group, H₂O₂+si-PVT1+anti-miR-NC group, and H₂O₂+si-PVT1+anti-miR-145-5p group. RT-qPCR was used to detect the expression levels of PVT1 and miR-145-5p in H9C2 of each group. CCK-8 and immunofluorescence were used to detect the proliferation ability of H9C2 cells in each group. Flow cytometry, AO/EB staining, and Caspase-3 activity were used to assess apoptosis of H9C2 cells in each group. The DCFH-DA probe method and reagent kit were used to measure the oxidative stress of H9C2 cells in each group. In addition, dual luciferase activity and RIP assay were used to detect the targeting relationship between PVT1 and miR-145-5p in H9C2 cells. One-way analysis of variance was used for comparisons among multiple groups, and SNK-q test was used for pairwise comparisons between groups. Pearson correlation analysis was used to examine the correlations between variables.

Compared to the control group, the expression level of PVT1 was significantly up regulated (1.80 ± 0.58 vs 1.08 ± 0.34, P < 0.05) in AMI patients, while the expression level of miR-145-5p was significantly downregulated (0.52 ± 0.16 vs 1.02 ± 0.32, P < 0.05), and the expression of PVT1 and miR-145-5p were negatively correlated (r = -0.612, P < 0.05). PVT1 is primarily localized in the cytoplasm. Compared to the NC group, H₂O₂ treatment could significantly up-regulated the expression of PVT1 (2.35 ± 0.49 vs 1.01 ± 0.08, P < 0.05), cell apoptosis rate[ (32.16 ± 5.06) %vs (5.16 ± 0.45) %, P < 0.05], AO/EB apoptosis rate[ (40.24 ± 6.16) %vs (6.49 ± 0.97) %, P < 0.05], Caspase-3 activity [ (70.54 ± 9.16) vs (15.98 ± 1.69) U/mL, P < 0.05]and enhance the oxidative stress levels, including a significant increase in ROS fluorescence intensity (423.87 ± 45.16 vs 98.33 ± 11.36, P < 0.05), LDH activity[ (375.69 ± 30.16) vs (132.56 ± 18.63) U/L, P < 0.05], and MDAcontent [ (16.98 ± 2.36) vs (3.69 ± 0.51) nmol/mL, P < 0.05]. Conversely, H₂O₂ treatment significantly inhibited miR-145-5p expression (0.25 ± 0.04 vs 1.04 ± 0.06, P < 0.05) and cell proliferation capacity, specifically manifested as decreased OD value (0.34 ± 0.06 vs 0.83 ± 0.09, P < 0.05) and Ki67 positive rate [ (21.09 ± 4.03) % vs (68.96 ± 8.65) %, P < 0.05]. Knocking down PVT1 (H₂O₂+si-PVT1 group) reversed the effects induced by H₂O₂ (all P < 0.05). In contrast, inhibiting miR-145-5p (H₂O₂+si-PVT1+anti-miR-145-5p group) partially counteracted the protective effect conferred by PVT1 knockdown, thereby re-aggravating apoptosis and oxidative stress, and suppressing proliferation (all P < 0.05). Dual-luciferase and RIP assays confirmed that PVT1 can directly target and bind to miR-145-5p (P < 0.05) .

PVT1 promotes H₂O₂-induced apoptosis and oxidative stress in H9C2 cardiomyocytes by targeting and negatively regulating miR-145-5p.

Diabetes is a metabolic disease characterized by persistently high blood glucose levels due to insufficient insulin secretion or impaired insulin effects. Among the current treatment options, insulinrequires frequent injection, which seriously reduces the quality in life of patients; although pancreatic transplantation may cure the disease, the scarcity of donors and potential risk of strong immune rejection pose significant challenges. To overcome these obstacles, an increasing number of studies have focused on transplanting insulin-producing islet cells encapsulated in hydrogels for the treatment of diabetes. Therefore, this review summarizes the relevant strategies for using hydrogel-encapsulated islet cells in the cellular therapy of diabetes and elaborates in detail from four aspects: cell sources, material selection, encapsulation methods, and current challenges. Finally, the development prospects of islet encapsulation technology are also discussed.

In recent years, immunotherapy has made remarkable advances in cancer treatment, with adoptive cellular immunotherapy gaining increasing attention in both solid and hematologic malignancies. Tumor-infiltrating lymphocytes (TIL), identified after lymphokine-activated killer cells, represent a novel population of immune-active cells that exhibit strong specificity and efficacy without the need for extensive interleukin-2 (IL-2) induction. This review summarizes the biological characteristics of TIL, highlights the challenges associated with their clinical application, examines recent advances in both solid and hematologic malignancies, and outlines potential future directions in the field.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) have shown significant potential in the field of neural injury repair due to their high proliferation capacity, low immunogenicity and easy accessibility. It has been demonstrated that hUC-MSCs can effectively attenuate neural functional damage through multiple pathways, such as promoting neural differentiation, exerting paracrine effects and regulating the immune microenvironment. This article aims to review the latest research progress and potential mechanisms of hUC-MSCs in the treatment of neurological diseases, and to prospect their future clinical application prospects, providing new ideas for the development of neural regenerative medicine.

Sepsis is a life-threatening organ dysfunction syndrome caused by dysregulation of the host's response to infection, characterized by high morbidity and mortality. The liver is a key metabolic and immune organ in the progression of sepsis, and sepsis-associated liver injury (SALI) is an independent predictor of mortality in sepsis patients. Hepatic dysfunction can severely impair their prognosis, and alleviating SALI is crucial for reducing the mortality of sepsis patients. The pathogenesis of SALI is complex, and pyroptosis, as a pro-inflammatory form of programmed cell death, plays a key role in it. Pyroptosis is regulated through classical (NLRP3-caspase-1-GSDMD) and non-classical (caspase-4/5/11-GSDMD) pathways. The pyroptosis of different cell types in the liver, such as hepatocytes, hepatic macrophages, and neutrophils, can participate in the process of SALI through mechanisms such as inflammation amplification and microcirculatory disturbance. At present, some existing hepatoprotective drugs in clinical practice have been proven to have anti-pyroptotic effects. Some natural compounds, synthetic drugs, endogenous active molecules, and stem cell therapy can also alleviate SALI by regulating pyroptosis pathways. In conclusion, pyroptosis is a key mechanism of SALI, and in-depth exploration of its regulatory mechanisms and intervention drugs can provide new strategies for the precise prevention and treatment of SALI.