Role of bone marrow-derived mesenchymal stem cells in a rat model of severe acute pancreatitis

AIM:To investigate the role and potential mechanisms of bone marrow mesenchymal stem cells(MSCs) in severe acute peritonitis(SAP).METHODS:Pancreatic acinar cells from Sprague Dawley rats were randomly divided into three groups:nonsodium deoxycholate(SDOC) group(non-SODC group),SDOC group,and a MSCs intervention group(i.e.,a co-culture system of MSCs and pancreatic acinar cells + SDOC).The cell survival rate,the concentration of malonaldehyde(MDA),the density of superoxide dismutase(SOD),serum amylase(AMS) secretion rate and lactate dehydrogenase(LDH) leakage rate were detected at various time points.In a separate study,Sprague Dawley rats were randomly divided into either an SAP group or an SAP + MSCs group.Serum AMS,MDA and SOD,interleukin(IL)-6,IL-10,and tumor necrosis factor(TNF)-α levels,intestinal mucosa injury scores and proliferating cells of small intestinal mucosa were measured at various time points after injecting either MSCs or saline into rats.In both studies,the protective effect of MSCs was evaluated.RESULTS:In vitro,The cell survival rate of pancreatic acinar cells and the density of SOD were significantly reduced,and the concentration of MDA,AMS secretion rate and LDH leakage rate were significantly increased in the SDOC group compared with the MSCs intervention group and the Non-SDOC group at each time point.In vivo,Serum AMS,IL-6,TNF-α and MAD level in the SAP + MSCs group were lower than the SAP group;however serum IL-10 level was higher than the SAP group.Serum SOD level was higher than the SAP group at each time point,whereas a significant betweengroup difference in SOD level was only noted after 24 h.Intestinal mucosa injury scores was significantly reduced and the proliferating cells of small intestinal mucosa became obvious after injecting MSCs.CONCLUSION:MSCs can effectively relieve injury to pancreatic acinar cells and small intestinal epithelium,promote the proliferation of enteric epithelium and repair of the mucosa,attenuate systemic inflammation in rats with SAP.

高吸附电化学纤维传感器用于实时、准确检测颅内一氧化氮

电化学一氧化氮传感器能够实时监测颅内一氧化氮浓度,对于了解大脑中一氧化氮的功能至关重要.然而,在大脑中使用的传统刚性传感电极面临着灵敏度低和植入后神经炎症引起一氧化氮浓度异常的问题.在这里,我们报道了一种结合物理和化学吸附能力、具有高灵敏度和准确性的电化学一氧化氮传感器.其对一氧化氮的物理和化学吸附能力分别来自于电极的高比表面积和丰富的羧基官能团.此外,柔软的电极可以与脑组织的力学性能相匹配,实现了一个高度适应的电极/组织界面.由此设计的颅内一氧化氮传感器表现出迄今为止所报道文献中最高的灵敏度,为3245 pA nmol^(-1)L,检测限为0.1 nmol L^(-1).电极在植入后未观察到显著的炎症反应以及过量的一氧化氮表达,提高了检测的准确性.该传感器成功捕捉了大脑中的一氧化氮波动,并实现了对多个脑区的同时检测,促进了对大脑中一氧化氮生理病理作用的研究.

肱骨头坏死的疾病特点及诊疗情况

肱骨头坏死是临床上常见的骨坏死之一。肱骨头的血供主要来源于旋肱前动脉和旋肱后动脉。由多因素导致的肱骨头血液供应受损,进而发生局部缺血时,肱骨头就会出现骨坏死。肱骨头坏死的病因可分为创伤性和非创伤性两大类,常见的创伤性因素有:骨折、脱位、肩部手术等;非创伤性因素有:糖皮质激素、血红蛋白病、沉箱病、戈谢病、吸烟、酗酒、系统性免疫病等。肱骨头坏死的主要症状是肩关节疼痛、活动受限。由于疾病早期通常无症状或症状较轻,不能引起患者重视,从而延误诊治。因此在临床工作中碰到高风险患者时,医务工作者要提高警惕,避免漏诊、误诊。肱骨头坏死可根据患者病史、临床表现、影像学检查来诊断。影像学检查是疾病分期的依据,疾病分期对治疗具有指导作用。早期肱骨头坏死可通过保守治疗取得较好效果,而晚期多需要手术治疗。无论采用何种治疗方法,其目的均是缓解疼痛、改善患肢功能。

Kruppel-like factor 10 protects against acute viral myocarditis by negatively regulating cardiac MCP-1 expression

Viral myocarditis(VMC)is a cardiac disease associated with myocardial inflammation and injury induced by virus infection.Cardiomyocytes have recently been regarded as key players in eliciting and modulating inflammation within the myocardium.Kruppel-like factor 10(KLF10)is a crucial regulator of various pathological processes and plays different roles in a variety of diseases.However,its role in VMC induced by coxsackievirus B3(CVB3)infection remains unknown.In this study,we report that cardiac KLF10 confers enhanced protection against viral myocarditis.We found that KLF10 expression was downregulated upon CVB3 infection.KLF10 deficiency enhanced cardiac viral replication and aggravated VMC progress.Bone marrow chimera experiments indicated that KLF10 expression in nonhematopoietic cells was involved in the pathogenesis of VMC.We further identified MCP-1 as a novel target of KLF10 in cardiomyocytes,and KLF10 cooperated with histone deacetylase 1(HDAC1)to negatively regulate MCP-1 expression by binding its promoter,leading to activation of MCP-1 transcription and recruitment of Ly6C^(high) monocytes/macrophages into the myocardium.This novel mechanism of MCP-1 regulation by KLF10 might provide new insights into the pathogenesis of VMC and a potential therapeutic target for VMC.

Tertiary lymphoid structures as unique constructions associated with the organization,education,and function of tumor-infiltrating immunocytes

Tertiary lymphoid structures(TLSs)are formations at sites with persistent inflammatory stimulation,including tumors.These ectopic lymphoid organs mainly consist of chemo-attracting B cells,T cells,and supporting dendritic cells(DCs).Mature TLSs exhibit functional organization for the optimal development and collaboration of adaptive immune response,delivering an augmented effect on the tumor microenvironment(TME).The description of the positive correlation between TLSs and tumor prognosis is reliable only under a certain condition involving the localization and maturation of TLSs.Emerging evidence suggests that underlying mechanisms of the anti-tumor effect of TLSs pave the way for novel immunotherapies.Several approaches have been developed to take advantage of intratumoral TLSs,either by combining it with therapeutic agents or by inducing the neogenesis of TLSs.

Quantitative conditions for time evolution in terms of the von Neumann equation

The adiabatic theorem describes the time evolution of the pure state and gives an adiabatic approximate solution to the Schr ¨odinger equation by choosing a single eigenstate of the Hamiltonian as the initial state. In quantum systems, states are divided into pure states(unite vectors) and mixed states(density matrices, i.e., positive operators with trace one). Accordingly, mixed states have their own corresponding time evolution, which is described by the von Neumann equation. In this paper, we discuss the quantitative conditions for the time evolution of mixed states in terms of the von Neumann equation. First, we introduce the definitions for uniformly slowly evolving and δ-uniformly slowly evolving with respect to mixed states, then we present a necessary and sufficient condition for the Hamiltonian of the system to be uniformly slowly evolving and we obtain some upper bounds for the adiabatic approximate error. Lastly, we illustrate our results in an example.

Transcriptional regulation of the immune checkpoints PD-1 and CTLA-4

Immunotherapy targeting immune checkpoints(ICs)has revolutionized the field of cancer treatment.ICs are a group of proteins that provide stimulatory or inhibitory signals to regulate T-cell activation,tolerance,and exhaustion.To date,some immune checkpoint inhibitors(ICIs)targeting TIM-3,LAG-3,TIGIT,and VISTA are under investigation for their clinical applications.However,only ICIs against CTLA-4,PD-1,and PD-L1 are approved by the FDA and widely used as first-line or second-line treatments for multiple cancer types.CTLA-4 and PD-1 are coinhibitory receptors that are mainly expressed by T cells.

The DDB1-DCAF2 complex is essential for B cell development because it regulates cell cycle progression

B cell development in the bone marrow is critical for producing numerous B cells that play an essential role in the adaptive immune response.B cells develop from common lymphoid progenitors(CLPs),which then differentiate through a series of stages,which include prepro-B cells,pro-B cells,pre-B cells,immature B cells,and mature B cells.