PROTECTIVE EFFECTS OF CISTANCHES HERBA AQUEOUS EXTRACT ON CISPLATIN-INDUCED PREMATURE OVARIAN FAILURE IN MICE

Background: Chemotherapeutic treatment of premenopausal women has been linked to premature ovarian failure (POF). Cistanches Herba (CH) is a commonly used male impotence and female infertility treatment in China; however, whether CH protects ovaries from chemotherapeutic drug-induced POF remains unclear. In this study, we investigated the protective effects of CH in a mouse model of chemotherapeutic drug-induced POF. Materials and Methods: We administered low- and high-concentration CH to cisplatin-induced POF mice for 2 weeks and determined body and ovarian weights, as well as serum follicle-stimulating hormone (FSH) and estradiol concentrations, to evaluate ovarian function. In addition, we evaluated the protective mechanisms of CH by detecting the levels of apoptosis-related proteins and evaluating markers of mitochondrial function. Results: In POF mice, we observed reduced body and ovarian weights; elevated serum FSH and attenuated estradiol concentrations; apoptosis of ovarian granulosa with concomitant changes in apoptosis-related proteins (including caspase-3, poly adenosine diphosphate-ribose polymerase, Bcl-2, and Bax); and mitochondrial dysfunction, such as a reduction in mitochondrial numbers, destruction of ultrastructural morphology, decrease in ATPase activity, and decreases in mitochondrial membrane potential and mitofusin-2 (a mitochondria dynamin-like GTPase). Significantly, CH reversed, to an extent, functional and morphologic injuries and ovarian tissue apoptosis by up-regulating the level of Mfn2 and the ratio of Bcl-2/Bax. Furthermore, CH reduced cisplatin-induced mitochondrial dysfunction in ovarian tissues. Conclusion: The present findings showed that CH inhibited cisplatin-induced POF through interactions between Mfn2 and Bcl-2/Bax proteins and, possibly, by up-regulation of Mfn2 expression. Ultimately, CH protects ovarian tissues from cisplatin-induced apoptosis

Phosphorylation by Aurora B Converts MgcRacGAP to a RhoGAP during Cytokinesis

AbstractCell division is finely controlled by various molecules including small G proteins and kinases/phosphatases. Among these, Aurora B, RhoA, and the GAP MgcRacGAP have been implicated in cytokinesis, but their underlying mechanisms of action have remained unclear. Here, we show that MgcRacGAP colocalizes with Aurora B and RhoA, but not Rac1/Cdc42, at the midbody. We also report that Aurora B phosphorylates MgcRacGAP on serine residues and that this modification induces latent GAP activity toward RhoA in vitro. Expression of a kinase-defective mutant of Aurora B disrupts cytokinesis and inhibits phosphorylation of MgcRacGAP at Ser387, but not its localization to the midbody. Overexpression of a phosphorylation-deficient MgcRacGAP-S387A mutant, but not phosphorylation-mimic MgcRacGAP-S387D mutant, arrests cytokinesis at a late stage and induces polyploidy. Together, these findings indicate that during cytokinesis, MgcRacGAP, previously known as a GAP for Rac/Cdc42, is functionally converted to a RhoGAP through phosphorylation by Aurora B

PD-1 blockade and radiotherapy combination for advanced Epstein-Barr virus-associated intrahepatic cholangiocarcinoma: a case report and literature review

Advanced intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of biliary epithelial cells, known for its extremely unfavorable prognosis. In the absence of intervention, patients typically survive for less than 5 months. Current guidelines from the Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) recommend chemotherapy-based systemic therapy as the standard treatment for advanced ICC. However, the first-line regimen, consisting of gemcitabine in combination with cisplatin, generally results in a median survival of approximately one year, which is considered suboptimal. Significant progress has been made in radiotherapy techniques, molecular diagnostics, and tumor immune microenvironments. The integration of immune and radiation therapies has revolutionized treatment strategies for cholangiocarcinoma. Moreover, combined therapeutic regimens have shown promising results in improving survival rates among patients with advanced ICC. In this study, we present a case report of a 70-year-old male patient diagnosed with stage IV ICC, featuring metastases to the retroperitoneal, left adrenal, and left supraclavicular lymph nodes. The patient exhibited a high tumor mutational load, significant microsatellite instability, and hyper-expression of PD-L1 (90%), along with positive Epstein-Barr virus-encoded RNA (EBER). Pembrolizumab, a programmed cell death 1 (PD-1) inhibitor, was administered in conjunction with radiotherapy. As a result, considerable shrinkage and inactivation of the primary foci were observed, accompanied by the disappearance of metastases. Ultimately, the patient achieved complete remission and maintained progression-free survival for 41 months following the initial treatment. To the best of our knowledge, this represents the longest case of complete remission using a combination of immunotherapy and radiotherapy as a first-line regimen for the high tumor mutational load, microsatellite instability, and PD-L1 expression (90%) subtype of Epstein-Barr virus-associated ICC (EBVaICC). These findings suggest that the combination of PD-1 inhibitors with radiotherapy may serve as a promising therapeutic strategy for treating this particular cancer subtype

A simulation study on the measurement of D0-D0bar mixing parameter y at BES-III

We established a method on measuring the \dzdzb mixing parameter $y$ for BESIII experiment at the BEPCII $e^+e^-$ collider. In this method, the doubly tagged $\psi(3770) \to D^0 \overline{D^0}$ events, with one $D$ decays to CP-eigenstates and the other $D$ decays semileptonically, are used to reconstruct the signals. Since this analysis requires good $e/\pi$ separation, a likelihood approach, which combines the $dE/dx$, time of flight and the electromagnetic shower detectors information, is used for particle identification. We estimate the sensitivity of the measurement of $y$ to be 0.007 based on a $20fb^{-1}$ fully simulated MC sample.Comment: 6 pages, 7 figure

In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection

Dengue virus (DENV) infection can lead to a complex spectrum of clinical outcomes, ranging from asymptomatic infection to life-threatening severe dengue. The reasons for thus drastically varying manifestations of the disease remain an enigma. Herein, we reported an original discovery of the synergistic effect between preexisting Epstein–Barr virus (EBV) infection and DENV superinfection in vitro and of a strong correlation of these two viruses in the clinical samples from dengue patients. We showed that (I) DENV-2 infection of an EBV-positive cell line (EBV + Akata cell) reactivated EBV, and it could be blocked by wortmannin treatment. (II) Examination of human peripheral blood mononuclear cell (PBMC) samples from dengue patients revealed significantly elevated cell-associated EBV DNA copy number at the time of hospitalization vs. at the time of disease recovery in most individuals. (III) EBV infection promoted DENV propagation in both EBV-hosting B cells and indirectly in THP-1 cells, supported by the following evidence: (A) EBV + Akata cells were more permissive to DENV-2 infection compared with Akata cells harboring no EBV virus (EBV- Akata cells). (B) Low-molecular weight fraction secreted from EBV + Akata cells could enhance DENV-2 propagation in monocytic THP-1 cells. (C) While reactivation of EBV in EBV + Akata cells further increased DENV-2 yield from this cell line, pharmacological inhibition of EBV replication by acyclovir had the opposite effect. To our knowledge, this is the first investigation demonstrating a positive correlation between EBV and DENV in vitro and in human biospecimens

Transcriptional regulation of macrophages in heart failure

Adverse cardiac remodeling after acute myocardial infarction is the most important pathological mechanism of heart failure and remains a major problem in clinical practice. Cardiac macrophages, derived from tissue resident macrophages and circulating monocyte, undergo significant phenotypic and functional changes following cardiac injury and play crucial roles in inflammatory response and tissue repair response. Currently, numerous studies indicate that epigenetic regulatory factors and transcription factors can regulate the transcription of inflammatory and reparative genes and timely conversion of inflammatory macrophages into reparative macrophages and then alleviate cardiac remodeling. Accordingly, targeting transcriptional regulation of macrophages may be a promising option for heart failure treatment. In this review, we not only summarize the origin and function of cardiac macrophages, but more importantly, describe the transcriptional regulation of macrophages in heart failure, aiming to provide a potential therapeutic target for heart failure