Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Objective:The study aimed to investigate the effects of exercise on the expression of ferroptosis-related proteins and the associated mechanisms in a post-traumatic stress disorder(PTSD)model induced by transient foot shock.Methods:Thirty-five male C57BL/6J mice(8 weeks old)were randomly divided into three groups:Control group,PTSD group,and Exe+PTSD group.PTSD model mice were established by foot-shock and PTSD behaviors were assessed using a fear conditioning box.Iron distribution areas were detected by Fe3+staining.Western Blot analysis were performed to determine the expression level of ferroptosis-related proteins in the mice.Results:Compared to the control group,the freezing time and Fe3+distribution areas in the cortex and hippocampus were significantly increased in the mice with PTSD(P＜0.05).The levels of ferroportin1(FPN1),glutathione peroxidase 4(GPX4),and brain-derived neurotrophic factor(BDNF)proteins were significantly decreased(P＜0.05),while the expression of high mobility group box 1(HMGB1)protein was significantly elevated(P＜0.05).Exercise significantly reduced freezing time and Fe3+accumulation in the cortex and hippocampus(P＜0.05),and it also up-regulated the expression of FPN1,GPX4,and BDNF proteins(P＜0.05),while down-regulating HMGB1 expression compared to the PTSD group(P＜0.05).Conclusion:This study demonstrates that PTSD induces the ferroptosis-related pathway in mice,and exercise can inhibit iron accumulation and reverse the expression of ferroptosis-related proteins induced by PTSD,there-by alleviating PTSD-like behavior in mice.

Ovarian cancer is characterized by insidious onset and poor prognosis, and among gynecological malignancies, its mortality rate ranks first, which poses a serious threat to women's health worldwide. In recent years, increasing evidence has suggested that modifiable lifestyle factors, particularly dietary factors, played important roles in the prognosis of ovarian cancer. As important nutrients, dietary fats and fatty acids can affect various vital physiological functions in human beings. However, the association of dietary fat and fatty acid intake with the prognosis of ovarian cancer remains unclear. Therefore, this review aims to analyze the existing epidemiological evidence between the two variables by searching the literature to provide dietary suggestions for ovarian cancer patients.

Epstein-Barr virus (EBV) is generally susceptible in human beings and multi-organ systems can be involved in EBV infection, such as blood, respiratory, urinary, digestive and nervous systems. EBV infection also plays an important role in the pathogenesis of related tumors, autoimmune diseases and other diseases, posing a great threat to human health. As a DNA virus, EBV can be sensed by DNA recognition receptors to trigger a series of downstream immune responses. A DNA-sensing pathway consists of DNA sensors, adaptor molecules and downstream effector signals. Double-stranded DNA sensors mainly include absent in melanoma 2-like receptors (ALRs) and cyclic GMP-AMP synthase (cGAS). Adaptors were mainly stimulator of interferon genes (STING) and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Downstream immune responses mainly involve typeⅠIFN, inflammasomes and proinflammatory cytokines. As a double-stranded DNA virus of the Herpesviridae family, EBV triggers complex innate and adaptive immune responses in the host, especially the sensing pathways mediated by a variety of DNA recognition receptors, which play a key role in host immune defense and pathogen immune evasion. This review made the DNA sensor as the clue to comprehensively summarize the progress in the activation, regulatory mechanism and clinical relevance of DNA-sensing pathways in EBV infection in recent years, aiming to achieve a better understanding of the host innate immune responses during EBV infection and provide an immunological basis for the prevention and treatment of EBV infection-related diseases.

Objective:To explore the effects of mechanical factors on the morphology of the growth plate and proximal femur development, in order to provide a mechanical basis for the mechanism of Cam lesions in femoral acetabular impingement (FAI).Methods:Using CT scan data of hip joint from adolescents, we constructed three-dimensional finite element models of normal and extended proximal femoral epiphyseal growth plates. Dynamic mechanics and position data from daily activities (walk, stand on one and two feet, go upstairs and downstairs, sit and stand up, squat and stand up) and basketball layup drills were collected from five healthy volunteers using the Vicon system. The mean values of femoral head mechanical loads and positions at peak values, movement onset, and termination were selected for finite element analysis to observe the distribution of equivalent stress, normal stress, and shear stress on the two growth plate models under different activity modes.Results:Successful construction of three-dimensional finite element models for normal and extended proximal femoral epiphyseal growth plates was achieved. Mechanical load values and spatial positions of the femoral head during daily activities and layup movements were obtained. In daily activities, peak equivalent stress values for normal and extended growth plates ranged from 1.6 to 11.0 MPa; compressive stress ranged from 1.7 to 12.0 MPa; tensile stress ranged from 0.5 to 10.0 MPa; and shear force ranged from 0.4 to 7.1 MPa. The compressive stress during walking, standing on one or both feet, going up and down stairs, sitting and standing, and squatting was concentrated in the central and lateral areas; tensile stress was concentrated in the central and medial areas; shear force was concentrated in the medial area and the anterior and posterior edges of the growth plate. During a layup, the compressive stress in the center, outer upper side, and medial edge of the growth plate of the normal model was notably concentrated, with peaks fluctuating between 5.5-19.0 MPa, 5.7-11.0 MPa, and 5.4-7.3 MPa respectively; tensile stress and shear force were concentrated at the inner and outer edges as well as in the central area, with peaks fluctuating between 3.0-24.0 MPa and 3.0-26.0 MPa respectively, these values were significantly different from those observed during daily activities. For the elongated growth plate, compressive stress was concentrated at the central and lateral edges with peaks fluctuating between 17.0-41.0 MPa and 17.0-38.0 MPa respectively; simulated shear stress and tensile stress showed significant concentration at peaks fluctuating between 4.9-34.0 MPa, also significantly different from those observed during daily activities.Conclusion:The difference in mechanical distribution between daily activities, basketball layup training, as well as between normal and extended growth plates may be the mechanical initiating factor in the development of extended growth plates and the formation of Cam lesions, it may be the mechanical initiating factor for the development of extended growth plates and the collision of Cam lesions in FAI.

Humans ; Mass Vaccination ; COVID-19 Vaccines/therapeutic use* ; COVID-19/prevention & control* ; Immunity, Herd ; Vaccination

High mobility group box 1 (HMGB1) has been reported to play an important role in experimental autoimmune encephalomyelitis (EAE). Astrocytes are important components of neurovascular units and tightly appose the endothelial cells of microvessels by their perivascular endfeet and directly regulate the functions of the blood-brain barrier. Astrocytes express more HMGB1 during EAE while the exact roles of astrocytic HMGB1 in EAE have not been well elucidated. Here, using conditional-knockout mice, we found that astrocytic HMGB1 depletion decreased morbidity, delayed the onset time, and reduced the disease score and demyelination of EAE. Meanwhile, there were fewer immune cells, especially pathogenic T cells infiltration in the central nervous system of astrocytic HMGB1 conditional-knockout EAE mice, accompanied by up-regulated expression of the tight-junction protein Claudin5 and down-regulated expression of the cell adhesion molecules ICAM1 and VCAM1 in vivo. In vitro, HMGB1 released from astrocytes decreased Claudin5 while increased ICAM1 and VCAM1 expressed by brain microvascular endothelial cells (BMECs) through TLR4 or RAGE. Taken together, our results demonstrate that HMGB1 derived from astrocytes aggravates EAE by directly influencing the immune cell infiltration-associated functions of BMECs.
Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; HMGB1 Protein/metabolism* ; Endothelial Cells/metabolism* ; Mice, Inbred C57BL ; Mice, Knockout ; Blood-Brain Barrier/metabolism*

Objective:To explore the clinical application of NanoString fluorescent barcode technology in the molecular subtyping of diffuse large B-cell lymphoma (DLBCL), and to analyze the correlation between the cell-of-origin subtype and prognosis of patients.Methods:The tumor tissue samples of 12 patients with DLBCL at the Third People's Hospital of Datong of Shanxi Province and 8 patients with DLBCL at Peking University, Health Science Center between January 2014 and December 2019 were collected. According to Hans algorithm, all patients were divided into 1 case of germinal center-derived B-cell (GCB) type and 19 cases of non-GCB type. NanoString platform was used to analyze the expression level differences of 15 genes-related to Lymph2Cx molecular subtyping of all samples at mRNA level. Hierarchical clustering was used to subgroup 20 DLBCL cases and to contrast the prognosis in different subgroups according to the subtyping.Results:NanoString fluorescent barcode technology was used to detect samples of 20 DLBCL cases and hierarchical clustering analysis was performed, and then subtyping results showed that 11 cases were GCB-like type and 9 cases were activated B cell (ABC)-like type. Based on Hans algorithm, 10 GCB-like cases were non-GCB type. According to the survival analysis, GCB-like group had a better overall survival compared with that in ABC-like group ( P=0.019). Conclusion:NanoString fluorescent barcode technology can be successfully applied to the cell-of-origin subtyping of DLBCL, and the molecular subtyping strategy can effectively predict the prognosis of patients.

Objective:To study the regulatory effect of Wumen-Yiji powder on 5-hydroxytryptamine (5-HT) signal transduction system in intestine and hypothalamus of diarrhea irritable bowel syndrome (IBS-D) model rats. Methods:Sixty male SD rats were randomly divided into blank group (10 rats) and diarrhea irritable bowel syndrome group (50 rats). The diarrhea irritable bowel syndrome group formed the diarrhea irritable bowel syndrome model after 2 weeks of senna leaf gavage and restraint stress. They were randomly divided into model group, deshute group (1.5 mg/kg), low, medium and high dose group of Wumen-Yiji San (6, 12, 24 g/kg), with 10 rats in each group. After continuous administration for 2 weeks, the contents of 5-HT in serum, colon and hypothalamus were detected by ELISA; HE staining was used to observe the pathological changes of colon in each group. The protein and mRNA levels of tryptophan hydroxylase 1 (TPH-1), serotonin receptor 3 (5-HT3R), serotonin receptor 4 (5-HT4R), serotonin transporter (SERT) in colon and hypothalamus were detected by Western blot and RT-PCR, respectively. Results:Compared with the model group, the pathological morphology of colon in each treatment group was improved. Compared with the model group, the level of 5-HT in serum and colon significantly decreased ( P<0.05), and the level of 5-HT in hypothalamus of rats in the low, medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein significantly decreased ( P<0.05), and the expression of SERT protein in the medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein in hypothalamus increased ( P<0.05), and the expression of SERT protein in the high dose group of Wumen-Yiji San significantly decreased ( P<0.05). The mRNA levels of TPH-1 (4.778 ± 0.604, 3.278 ± 0.668, 1.670 ± 0.361 vs. 6.877 ± 0.148), 5-HT3R (3.807 ± 0.463, 2.697 ± 0.455, 1.132 ± 0.136 vs. 6.322 ± 0.778), 5-HT4R (4.521 ± 0.234, 2.801 ± 0.351, 1.331 ± 0.142 vs. 6.741 ± 0.293) in colon tissue of low, medium and high dose groups of Wumen-Yiji San decreased ( P<0.05). The level of 5-HT4R mRNA (0.616 ± 0.208, 0.726 ± 0.226 vs. 0.521 ± 0.062) increased ( P<0.05), and the level of SERT mRNA (1.563 ± 1.023 vs. 2.612 ± 1.035) in medium, high dose group of Wumen-Yiji San decreased ( P<0.05). Conclusion:The result showed that Wumen-Yiji San could regulate the expression of 5-HT signaling system relating proteins and mRNA in the colon and hypothalamus of IBS-D rats within a certain dose range, so as to improve the symptoms of IBS-D.