Adjusting Effects of Baicalin for Nuclear Factor-κB and Tumor Necrosis Factor-α on Rats With Caerulein-Induced Acute Pancreatitis

Forty Wistar rats were divided into 5 groups, including the control group, the acute pancreatitis group (AP group, induced by intraperitoneal injections of caerulein), and the AP group treated with baicalin, the AP group treated with LPS, and the AP group treated with LPS and baicalin. Pathological damage of pancreatic tissue was scored with hematoxylin and eosin (HE) staining. The mRNA expression of TNF-α was measured with semiquantitative RT-PCR, and activation of NF-κB was detected with flow cytometry assay. It was shown in the results that the expression of TNF-α mRNA, activation of NF-κB, and pathological score of AP group were all obviously higher than those of control group (P < .01). In AP group treated with LPS, further rise of these values were observed (P < .01). In the AP group treated with baicalin, activation of NF-κB decreased (P < .05), and expression of TNF-α mRNA also obviously decreased (P < .01), while pancreatic pathological damage was alleviated at the same time (P < .01); similar results were observed in AP group treated with LPS and baicalin (P < .01), which indicated that baicalin might be applied to inhibit NF-κB activating and TNF-α expressing so as to treat AP

Reconstitution of Kidney Side Population Cells after Ischemia-Reperfusion Injury by Self-Proliferation and Bone Marrow-Derived Cell Homing

The aim of this study was to examine the contribution of side population (SP) cells from kidney and bone marrow for reconstitution of kidney SP pools after ischemia-reperfusion injury (IRI). The SP and non-SP cells in kidneys following IRI were isolated and serially assessed by fluorescence-activated cell sorting. The apoptosis, proliferation, phenotype, and paracrine actions of SP cells were evaluated in vitro and in vivo. Results indicated that the SP cells from ischemic kidney were acutely depleted within one day following renal IRI and were progressively restored to baseline within 7 days after IRI, through both proliferation of remaining kidney SP cells and homing of bone marrow-derived cells to ischemic kidney. Either hypoxia or serum deprivation alone increased apoptosis of SP cells, and a combination of both further aggravated it. Furthermore, hypoxia in vivo and in vitro induced the increase in the secretion of vascular endothelial growth factor, insulin-like growth factor 1, hepatocyte growth factor, and stromal cell-derived factor-1α in kidney SP but not non-SP cells. In summary, these results suggest that following renal IRI, kidney SP cells are acutely depleted and then progressively restored to baseline levels by both self-proliferation and extrarenal source, that is, bone marrow-derived cell homing

Post-traumatic stress disorder and depressive symptoms among firefighters: a network analysis

BackgroundFirefighters, as first responders with a high risk of occupational exposure to traumatic events and heavy working stress, have a high prevalence of PTSD symptoms and depressive symptoms. But no previous studies analyzed the relationships and hierarchies of PTSD and depressive symptoms among firefighters. Network analysis is a novel and effective method for investigating the complex interactions of mental disorders at the symptom level and providing a new understanding of psychopathology. The current study was designed to characterize the PTSD and depressive symptoms network structure in the Chinese firefighters.MethodThe Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) and the Self-Rating Depression Scale (SDS) were applied to assess PTSD and depressive symptoms, respectively. The network structure of PTSD and depressive symptoms was characterized using “expected influence (EI)” and “bridge EI” as centrality indices. The Walktrap algorithm was conducted to identify communities in the PTSD and depressive symptoms network. Finally, Network accuracy and stability were examined using the Bootstrapped test and the case-dropping procedure.ResultsA total of 1,768 firefighters were enrolled in our research. Network analysis revealed that the relationship between PTSD symptoms, “Flashback” and “Avoidance,” was the strongest. “Life emptiness” was the most central symptom with the highest EI in the PTSD and depression network model. Followed by “Fatigue” and “Interest loss.” Bridge symptoms connecting PTSD and depressive symptoms in our study were “Numb,” “High alertness,” “Sad mood,” and “Compunction and blame,” successively. The data-driven community detection suggested the differences in PTSD symptoms in the clustering process. The reliability of the network was approved by both stability and accuracy tests.ConclusionTo the best of our knowledge, the current study first demonstrated the network structure of PTSD and depressive symptoms among Chinese firefighters, identifying the central and bridge symptoms. Targeting interventions to the symptoms mentioned above may effectively treat firefighters suffering from PTSD and depressive symptoms

Factors related to the length of stay for major depressive disorder patients in China: A real-world retrospective study

BackgroundAs numerous patients with depression have to be hospitalized because of various reasons, the demand far exceeds the limited bed count in the psychiatry department. Controlling the length of stay (LOS) of the patient is gradually being considered an effective method to alleviate this problem. Given the lack of statistical evidence of the LOS of patients with major depressive disorder (MDD) in China and the strain on the limited psychiatric resources, the purpose of our study was to investigate the LOS of patients with MDD among in-patient samples and to analyze related factors of the LOS in China by building a regression model.MethodThe data were exported from the electronic medical record system. A total of three categories of independent variables were enrolled in our study, namely, demographic, clinical, and biochemical. Univariate analysis and binominal regression analysis were applied comprehensively to find the factors related to the LOS among MDD samples. The discrimination accuracy of the model was evaluated by the receiver operating characteristic (ROC) analysis. ROC analysis indicated that the discrimination accuracy of our model was acceptable (AUC = 0.790, 95% CI = 0.714–0.865, P &lt; 0.001).ResultA total of 254 patients were finally brought into analysis after filtering. Regression analysis indicated that abnormal LDL was the only risk factor of long LOS (OR = 3.352, 95% CI = 1.087–10.337, P = 0.035) among all the kinds of variables. Notably, in the statistically irrelevant factors of the LOS, the category of anti-depressant drugs [serotonin–norepinephrine reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI)] prescribed to patients with MDD was not associated statistically with the LOS, which was against our initial hypothesis that the LOS of patients with MDD treated with SNRI would vary from that of the patients treated with SSRI.ConclusionUp to our knowledge, our research is the first study to show the potential factors related to the LOS from various domains, especially biochemical indexes, and the effect of drugs, among clinical patients with MDD in China. Our results could provide a theoretical reference for efficient psychiatry hospitalization management and prioritization of allocating medical resources. Future studies are required for updating independent variables which are potentially related to the LOS and verifying existing results in a larger sample

Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis

Background: Ferroptosis is a new form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxides and membrane damages. Recent studies have identified an important role for cancer cell ferroptosis in antitumor therapy. On the other hand, polyphyllin I (PPI) has been reported to exert antitumor effects on some types of cancers. However, it remains unknown whether or not PPI regulates cancer cell ferroptosis.Methods: Two types of human gastric cancer cells (AGS and MKN-45) were used to establish tumor xenograft models in nude mice that were treated with polyphyllin I (PPI) to observe tumor growth, while cells also were cultured for in vitro studies. Ferroptosis, based on the intracellular ROS/lipid ROS production and accumulation of ferrous ions, was detected using a fluorescence microscope and flow cytometer, while the expression of NRF2/FTH1 was measured using Western blotting assays.Results: Here we found that PPI inhibited the gastric cancer growth in vivo and in vitro while increasing the intracellular reactive oxygen species (ROS)/lipid peroxides and ferrous ions in the gastric cancer cells. PPI also decreased the levels of nuclear factor erythroid 2-related factor 2 (NRF2) and ferritin heavy chain 1 (FTH1) in gastric cancer cells in vitro. Moreover, liproxstain-1, an inhibitor of cell ferroptosis, mostly reversed the cell ferroptosis and tumor growth arrest induced by PPI. Finally, the effects of PPI on cancer cell ferroptosis were diminished by the overexpression of NRF2.Conclusion: For the first time, our results have demonstrated that PPI exerts its antitumor activity on the gastric cancer by, at least partially, inducing cancer cell ferroptosis via regulating NRF2/FTH1 pathway. These findings may be implicated for clinical replacement therapy of the gastric cancer

Chimeric Antigen Receptor (CAR) Treg: A Promising Approach to Inducing Immunological Tolerance

Cellular therapies with polyclonal regulatory T-cells (Tregs) in transplantation and autoimmune diseases have been carried out in both animal models and clinical trials. However, The use of large numbers of polyclonal Tregs with unknown antigen specificities has led to unwanted effects, such as systemic immunosuppression, which can be avoided via utilization of antigen-specific Tregs. Antigen-specific Tregs are also more potent in suppression than polyclonal ones. Although antigen-specific Tregs can be induced in vitro, these iTregs are usually contaminated with effector T cells during in vitro expansion. Fortunately, Tregs can be efficiently engineered with a predetermined antigen-specificity via transfection of viral vectors encoding specific T cell receptors (TCRs) or chimeric antigen receptors (CARs). Compared to Tregs engineered with TCRs (TCR-Tregs), CAR-modified Tregs (CAR-Tregs) engineered in a non-MHC restricted manner have the advantage of widespread applications, especially in transplantation and autoimmunity. CAR-Tregs also are less dependent on IL-2 than are TCR-Tregs. CAR-Tregs are promising given that they maintain stable phenotypes and functions, preferentially migrate to target sites, and exert more potent and specific immunosuppression than do polyclonal Tregs. However, there are some major hurdles that must be overcome before CAR-Tregs can be used in clinic. It is known that treatments with anti-tumor CAR-T cells cause side effects due to cytokine “storm” and neuronal cytotoxicity. It is unclear whether CAR-Tregs would also induce these adverse reactions. Moreover, antibodies specific for self- or allo-antigens must be characterized to construct antigen-specific CAR-Tregs. Selection of antigens targeted by CARs and development of specific antibodies are difficult in some disease models. Finally, CAR-Treg exhaustion may limit their efficacy in immunosuppression. Recently, innovative CAR-Treg therapies in animal models of transplantation and autoimmune diseases have been reported. In this mini-review, we have summarized recent progress of CAR-Tregs and discussed their potential applications for induction of immunological tolerance

Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models

Neuritic plaques in the brains are one of the pathological hallmarks of Alzheimer's disease (AD). Amyloid β-protein (Aβ), the central component of neuritic plaques, is derived from β-amyloid precursor protein (APP) after β- and γ-secretase cleavage. The molecular mechanism underlying the pathogenesis of AD is not yet well defined, and there has been no effective treatment for AD. Valproic acid (VPA) is one of the most widely used anticonvulsant and mood-stabilizing agents for treating epilepsy and bipolar disorder. We found that VPA decreased Aβ production by inhibiting GSK-3β–mediated γ-secretase cleavage of APP both in vitro and in vivo. VPA treatment significantly reduced neuritic plaque formation and improved memory deficits in transgenic AD model mice. We also found that early application of VPA was important for alleviating memory deficits of AD model mice. Our study suggests that VPA may be beneficial in the prevention and treatment of AD