BackgroundEnterovirus 71 (EV71) infection can lead to a rapidly progressing, life-threatening, and severe neurological disease in young children, including the development of human hand, foot, and mouth disease (HFMD). This study aims to further characterize the specific immunological features in EV71–mediated HFMD patients presenting with differing degrees of disease severity.MethodologyComprehensive cytokine and chemokine expression were broadly evaluated by cytokine antibody array in EV71–infected patients hospitalized for HFMD compared to Coxsackievirus A16-infected patients and age-matched healthy controls. More detailed analysis using Luminex-based cytokine bead array was performed in EV71–infected patients stratified into diverse clinic outcomes. Additionally, immune cell frequencies in peripheral blood and EV71–specific antibodies in plasma were also examined.Principal FindingsExpression of several cytokines and chemokines were significantly increased in plasma from EV71–infected patients compared to healthy controls, which further indicated that: (1) GM-CSF, MIP-1β, IL-2, IL-33, and IL-23 secretion was elevated in patients who rapidly developed disease and presented with uncomplicated neurological damage; (2) G-CSF and MCP-1 were distinguishably secreted in EV71 infected very severe patients presenting with acute respiratory failure; (3) IP-10, MCP-1, IL-6, IL-8, and G-CSF levels were much higher in cerebrospinal fluid than in plasma from patients with neurological damage; (4) FACS analysis revealed that the frequency of CD19+HLADR+ mature B cells dynamically changed over time during the course of hospitalization and was accompanied by dramatically increased EV71–specific antibodies. Our data provide a panoramic view of specific immune mediator and cellular immune responses of HFMD and may provide useful immunological profiles for monitoring the progress of EV71–induced fatal neurological symptoms with acute respiratory failure.

Background Despite great efforts to improve diagnosis and treatment, tuberculosis (TB) remains a major health problem worldwide, especially in developing countries. Lack of concrete immune markers is still the obstacle to properly evaluate active TB. Therefore, identification of more validated biomarkers and phenotypic signatures is imperative. In particular, T cell-related biomarkers are more significant. Methodology To understand the nature of CD4 + T cell-derived signatures involved in infection and disease development, we examined and analyzed whole genome expression profiles of purified CD4 + T cells from healthy individuals (HD), two distinct populations with latent infection (with low or high IFN-γ levels, LTB L /LTB H ) and untreated TB patients. Following, we validated the expression profiles of genes in the peripheral CD4 + T cells from each group and examined secretion levels of distinct cytokines in serum and pleural effusion. Principal Findings Our bio-informatic analyses indicate that the two latent populations and clinical TB patients possess distinct CD4 + T cell gene expression profiles. Furthermore, The mRNA and protein expression levels of B cell activating factor (BAFF), which belongs to the TNF family, and a proliferation-inducing ligand (APRIL) were markedly up-regulated at the disease stage. In particular, the dramatic enhancement of BAFF and APRIL in the pleural effusion of patients with tuberculosis pleurisy suggests that these proteins may present disease status. In addition, we found that the BAFF/APRIL system was closely related to the Th1 immune response. Our study delineates previously unreported roles of BAFF and APRIL in the development of tuberculosis, and these findings have implications for the diagnosis of the disease. Our study also identifies a number of transcriptional signatures in CD4 + T cells that have the potential to be utilized as diagnostic and prognostic tools to combat the tuberculosis epidemic.

BackgroundIFN-γ is presently the only soluble immunological marker used to help diagnose latent Mycobacterium tuberculosis (M.tb) infection. However, IFN-γ is not available to distinguish latent from active TB infection. Moreover, extrapulmonary tuberculosis, such as tuberculous pleurisy, cannot be properly diagnosed by IFN-γ release assay. As a result, other disease- or infection-related immunological biomarkers that would be more effective need to be screened and identified.MethodologyA panel of 41 soluble immunological molecules (17 cytokines and 24 chemokines) was tested using Luminex liquid array-based multiplexed immunoassays. Samples, including plasma and pleural effusions, from healthy donors (HD, n = 12) or patients with latent tuberculosis infection (LTBI, n = 20), pulmonary tuberculosis (TB, n = 12), tuberculous pleurisy (TP, n = 15) or lung cancer (LC, n = 15) were collected and screened for soluble markers. Peripheral blood mononuclear cells (PBMCs) and pleural fluid mononuclear cells (PFMCs) were also isolated to investigate antigen-specific immune factors.Principal FindingsFor the 41 examined factors, our results indicated that three patterns were closely associated with infection and disease. (1) Significantly elevated plasma levels of IL-2, IP-10, CXCL11 and CXCL12 were present in both patients with tuberculosis and in a sub-group participant with latent tuberculosis infection who showed a higher level of IFN-γ producing cells by ELISPOT assay compared with other latently infected individuals. (2) IL-6 and IL-9 were only significantly increased in plasma from active TB patients, and the two factors were consistently highly secreted after M.tb antigen stimulation. (3) When patients developed tuberculous pleurisy, CCL1, CCL21 and IL-6 were specifically increased in the pleural effusions. In particular, these three factors were consistently highly secreted by pleural fluid mononuclear cells following M.tb-specific antigen stimulation. In conclusion, our data imply that the specific secretion of soluble immunological factors, in addition to IFN-γ, may be used to evaluate M.tb infection and tuberculosis disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. Although the exact causes of AD have not yet been fully elucidated, cholinergic dysfunction, mitochondrial damage, oxidative stress and neuroinflammation have been recognized as influential factors. Current drugs that are designed to address only a single target are unable to mitigate or prevent the progression of this complicated disease, so new disease-modifying drugs are urgently needed. Chinese herbs with thousand years of effective usage might be a good source for potential drugs. Gardenia jasminoides J. Ellis (Fructus Gardenia) is a common traditional Chinese medicine with tranquilizing effects, which is an important component of widely-used traditional Chinese medicine for dementia. GJ-4 is crocin richments extracted from Gardenia jasminoides J. Ellis. In our study, we attempted to observe the effects of GJ-4 on learning and memory injury induced by amyloid-[Formula: see text] 25-35 (A[Formula: see text] injection in mice. Treatment with GJ-4 dose-dependently enhanced the memory and cognition ability of A[Formula: see text]-injected mice. Preliminary mechanistic studies revealed the protective effect of GJ-4 was related to its protection of neurons and cholinergic dysfunction. The mechanistic results also indicated that GJ-4 could enhance antioxidant capacity and attenuate neuroinflammation. Our results implied that GJ-4 might be a promising drug to improve cognitive and memory impairment, with multiple targets.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.

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BackgroundTo investigate the surgical methods and clinical results of robot-assisted laparoscopic antegrade inguinal lymphadenectomy.MethodsA retrospective study was performed on clinical data from 19 patients with penile cancer admitted from March 2013 to October 2017. Among them, nine patients underwent robot-assisted laparoscopic antegrade inguinal lymphadenectomy (robot-assisted group) and 10 patients underwent open inguinal lymphadenectomy (open group). In the robot-assisted group, preoperative preparation, patient position, robot placement, design of operating channel and establishment of operating space are described. Key surgical procedures and techniques are also summarized. In addition, the number of lymph nodes removed, postoperative complications and follow-up in both groups were statistically analyzed.ResultsFor the 9 patients in the robot-assisted group, surgery was successfully accomplished at 17 sides without intraoperative conversion to open surgery. The surgery time for each side was 45~90 min using laparoscope with an average of 68.5 ± 13.69 min/side. The intraoperative blood loss was estimated to be < 10 ml/side, and the number of removed lymph nodes was not significantly different from that of the open group (12 ± 4.2/side vs.11 ± 5.8/side, P = 0.84). There were no postoperative complications such as skin necrosis, delayed wound healing and cellulitis in the robot-assisted group. Skin-related complications occurred in 9 (45%) of the 20 sides in the open group. During a median follow-up of 25 months in robot-assisted group and 52.5 mouths in open group, was not significantly different there were no statistical differences in recurrence-free survival between the groups (75% vs 60%, p = 0.536).ConclusionRobot-assisted laparoscopic antegrade inguinal lymphadenectomy achieved the desired surgical outcomes with fewer intraoperative and postoperative complications. The robotic arms of the surgical system were placed between the lower limbs of each patient. There was no need to re-position the robotic arms during bilateral inguinal lymphadenectomy. This simplified the procedure and reduced the use of trocars. If necessary, pelvic lymphadenectomy could be performed simultaneously using the original trocar position.

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