Objective To establish an acute rejection model of cervical heart transplantation in mice and evaluate the survival and dynamic rejection process post-transplantation. Methods Mice were randomly divided into sham operation group (n=10), syngeneic transplantation group (n=21), and allogeneic transplantation group (n=65). Sham operation, syngeneic cervical heart transplantation, and allogeneic cervical heart transplantation were performed respectively. The survival of recipient mice and grafts, histopathological changes of graft tissues, subpopulations of splenic lymphocytes, and expression of inflammatory factors in serum and grafts were observed. Results The survival rate and graft survival rate of the sham operation group and syngeneic transplantation group were 100% at 7 days after surgery. In the allogeneic transplantation group, 5 cases failed and died on the first day after surgery. The survival rate at 7 days after surgery was 86%, and all surviving mice had grafts that stopped beating at 7 days after surgery. The allogeneic transplantation group showed significant rejection at 7 days after surgery, accompanied by tissue damage and CD8⁺ T cell infiltration. The proportion of CD8⁺ T cells in the spleen continued to rise post-operation, while the proportion of CD4⁺ T cells showed a downward trend. The expression of interferon-γ in serum and grafts peaked at 5 days after surgery, while the expression of tumor necrosis factor-α showed no statistical significance. Conclusions Acute rejection following heart transplantation in mice intensifies between 5 to 7 days after surgery, which may be a critical time window for immunological intervention.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

Background::Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods::Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation. Results::Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI ( P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models ( P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species ( P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD). Conclusions::YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

Objective:To investigate the prevalence of albuminuria in Chinese residents aged >35 years and its potential association with cardiovascular disease (CVD).Methods:A total of 34 647 Chinese subjects aged ≥35 years were selected by stratified multi-stage random sampling from 2012 to 2015. Data were collected through questionnaires, physical examinations, and laboratory tests. Albuminuria was categorized into 3 types according to urinary albumin-to- creatinine ratio: normal (<30 mg/g), microalbuminuria (MAU, 30-300 mg/g), and macroalbuminuria (≥300 mg/g). Measurement data were expressed as xˉ±s, and t-tests were used for comparisons between indicators. Qualitative data were expressed as rate or constituent ratio, and the χ2 test or Kruskal-Wallis test was used to examine differences. Logistic regression was used for multivariate analyses. SAS 9.4 software was used for statistical analyses, and P<0.05 was considered statistically significant. Results:The prevalence of abnormal albuminuria was 19.1%; the prevalence was 17.2% for MAU and lower in males (13.8%) than females (20.1%, P<0.01). The risk of CVD was higher among subjects with MAU ( OR=1.23, 95% CI 1.12-1.35) and macroalbuminuria ( OR=1.86, 95% CI 1.50-2.32). When MAU was complicated by hypertension and diabetes mellitus, the CVD risk was 1.76 times higher. Conclusions:The prevalence of MAU is high among Chinese subjects aged 35 years and over. Those with MAU have higher CVD risk, especially those with hypertension and diabetes mellitus.

Objective To verify whether β-arrestin-2 inhibits autophagy by up-regulating PI3K/Akt signal to protect the liver from ischemia-reperfusion injury (IRI) in mice. Methods Twelve β-arrestin-2 knockout (KO) and twelve wild-type (WT) C57BL/6 mice were randomly divided into the KO+sham group, KO+IRI group, WT+sham group and WT+IRI group, six mice in each group. The mouse models with 70% liver IRI were established or sham operation was performed. Relevant experiments were carried out at 6 h after liver reperfusion or operation. The expression levels of apoptosis signal protein cleaved Caspase-3, proliferation signal protein Ki-67 and the PI3K/Akt signal protein p-Akt were detected by immunohistochemical staining. Results Immunohistochemical staining demonstrated that compared with the corresponding sham group, the positive cell count for cleaved Caspase-3, Ki-67 and p-Akt in liver tissues of mice was significantly increased in the KO+IRI and WT+IRI groups (all P < 0.01). Compared with the WT+IRI group, the positive cell count for cleaved Caspase-3 in liver tissues of mice was significantly increased, whereas the positive cell count forKi-67 and p-Akt was significantly decreased in the KO+IRI group (both P < 0.05). Conclusions β-arrestin-2 can mitigate the liver cell apoptosis and promote the repair of injury after IRI in mice. Moreover, β-arrestin-2 inhibits autophagy by up-regulating the PI3K/Akt signal to alleviate liver IRI in mice.

Platelets are small fragments of the cytoplasm and are detached from the cytoplasm of mature mega-karyocytes.They play an important role in the function of blood coagulation in humans.Recent studies have shown that in addition to participating in hemostasis,platelets play a critical role in liver regen-eration,liver inflammation,liver tumors,injury,and other liver diseases by regulating the activation of stellate cells and the interaction between Kupffer cells and sinusoidal endothelial cells.Targeting platelets and their related molecules is a promising treatment strategy in the management of liver diseases.Here,we review the role of platelets and their related molecules in the development of liver diseases and the application of targeted drugs.

Objective To investigate the changes of vital signs, serum potassium and postoperative comfort of patients treated with MECT in the treatment of low-dose rocuronium.Methods 200 patients with MECT from June 2014 to June 2016 were selected and randomly divided into two groups, and the life signs and adverse reactions were analyzed and compared.Results There was no significant difference between the experimental group and the control group in the recovery time, the recovery time and the recovery time of the pharyngeal reflex.The recovery of spontaneous respiration in the experimental group was earlier than that in the control group, and the difference was statistically significant ( P<0.05 ) .There was no significant difference between the two groups (headache, drowsiness, postoperative irritability) compared with the control group, the incidence of muscle pain in the experimental group was significantly lower than that in the control group, the difference was statistically significant (P<0.05).Conclusion Pre-injection of rocuronium can reduce the level of serum potassium, shorten the recovery time of spontaneous breathing, and reduce the incidence of postoperative muscle soreness.Compared with the conventional MECT method, it can reduce the contraindication of MECT treatment and increase the comfort of patients.