Innexin hemichannel activation by Microplitis bicoloratus ecSOD monopolymer reduces ROS.

The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus. Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro, the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy.

Immunosenescence and cancer: Opportunities and challenges.

As individuals age, cancer becomes increasingly common. This continually rising risk can be attributed to various interconnected factors that influence the body's susceptibility to cancer. Among these factors, the accumulation of senescent cells in tissues and the subsequent decline in immune cell function and proliferative potential are collectively referred to as immunosenescence. Reduced T-cell production, changes in secretory phenotypes, increased glycolysis, and the generation of reactive oxygen species are characteristics of immunosenescence that contribute to cancer susceptibility. In the tumor microenvironment, senescent immune cells may promote the growth and spread of tumors through multiple pathways, thereby affecting the effectiveness of immunotherapy. In recent years, immunosenescence has gained increasing attention due to its critical role in tumor development. However, our understanding of how immunosenescence specifically impacts cancer immunotherapy remains limited, primarily due to the underrepresentation of elderly patients in clinical trials. Furthermore, there are several age-related intervention methods, including metformin and rapamycin, which involve genetic and pharmaceutical approaches. This article aims to elucidate the defining characteristics of immunosenescence and its impact on malignant tumors and immunotherapy. We particularly focus on the future directions of cancer treatment, exploring the complex interplay between immunosenescence, cancer, and potential interventions.

Expression of Beclin1 in the colonic mucosa tissues of patients with ulcerative colitis.

To investigate the expression of Beclin1 in the colonic mucosa tissue of patients with ulcerative colitis (UC), which acts as a regulator of autophagy and might play a part in the disease progression potentially. A total of 112 patients were selected from September 2013 to November 2014, and their colonic mucosal tissues were collected as the subject of study. Among them, 75 cases were diagnosed with ulcerative colitis (UC), 37 cases were diagnosed with irritable bowel syndrome (IRS) during the same time, which was set as the control group. The mucosal tissues were processed with ELISA and IHCA to measure the expression level of Beclin1, and correlation analysis was performed to demonstrate its role in the disease progression. The expression level pf Beclin1 was significantly higher in the UC patients compared with the control group (P<0.05). Meanwhile, it's positively correlated with the severity of disease, the endoscopic classification and the pathologic staging results, which has statistical significance (P<0.05). Beclin1 was expressed at a higher level in UC patients, and correlated with the severity of the disease, indicating the abnormal regulation of autophagy in the disease progression.

Experimental study of the effect on bone metabolism and bone histomorphometry of osteoporosis rats with birdpecking and revolving moxibustion on twelve back-shu points.

The aim of the study was to explore the effect of birdpecking and revolving moxibustion on twelve back shenshu points on the bone metabolism and bone histomorphometry of osteoporosis rats. The 50 female rats of 8 months old that did not pregnant were collected and randomly divided into sham-operation group, model group, moxibustion group, moxibustion and estrogen group, and estrogen group. All the rats, except for the rats in the sham-operation group, received ovarian surgery to establish the models. After 10 days postoperatively (healing), the rats received moxibustion and estrogen therapy. According to the different groups, the rats received rat femur in vivo bone mineral density assessment at 90 days after surgery. After that, the rats were sacrificed, and then the left femoral bones were collected for bone histomorphometry test; blood was taken for bone alkaline phosphatase (BALP) testing, and urine was collected for hydroxyproline testing. The urine hydroxyproline was tested once at 24 h after ovarian surgery. At 24 h after ovarian surgery, the urine hydroxyproline in the ovariectomy group was significantly higher than that in the sham-operation group (P < 0.05), indicating that after ovarian surgery, the collagen broke down which accelerated the process of osteoporosis. After the intervention therapy with moxibustion and estrogen, the BALP, urinary hydroxyproline and femoral bone histomorphometry were comparatively analyzed, and the results showed that the intervention groups were higher than the model group (P < 0.05). But when compared with the sham-operation group, the indexes in the intervention groups were decreased, and the differences were significant (P < 0.05), indicating that intervention could only delay the incidence of osteoporosis. The Chinese traditional measure of "birdpecking and revolving moxibustion on twelve back-shu points" can effectively prevent the recession of bone metabolism of osteoporosis rats, and slow down the degeneration of bone morphology, which can be used to delay the incidence of osteoporosis.

Pathogenic analysis of Vibrio alginolyticus infection in a mouse model.

Vibrio alginolyticus is a Gram-negative halophilic bacterium and has been recognized as an opportunistic pathogen to both humans and marine animals. So far, most studies have been focused on marine animals and few reports have been aimed at mammals, including human. In this study, we first established a mouse model to understand the pathogenic mechanism of V. alginolyticus infection. After infection via intraperitoneal injection, hematological and liver function indicators were evaluated and serum interleukin (IL)-1ß and IL-6 expression were detected by ELISA. Furthermore, we compared the virulence of two V. alginolyticus strains, ATCC17749T and E0666. The results demonstrated that V. alginolyticus infection causes robust lung and liver damage and induces changes in IL-1ß, IL-6, hematological, and liver indicators. In addition, the ATCC17749T strain appeared to be more virulent than the E0666 strain. Better understanding of the pathogenic mechanism of V. alginolyticus infection should guide effective prevention and therapy for V. alginolyticus infection.