Analysis of Chromatin Accessibility Changes Induced by BMMC Recognition of Foot-and-Mouth Disease Virus-like Particles through ATAC-seq.

Mast cells can recognize foot-and-mouth disease virus-like particles (FMDV-VLPs) via mannose receptors (MRs) to produce differentially expressed cytokines. The regulatory role of chromatin accessibility in this process is unclear. Bone marrow-derived mast cells (BMMCs) were cultured, and an assay of transposase-accessible chromatin sequencing (ATAC-seq) was applied to demonstrate the regulation of chromatin accessibility in response to the BMMCs' recognition of FMDV-VLPs. A pathway enrichment analysis showed that peaks associated with the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), and other signaling pathways, especially the NF-κB pathway, were involved in the BMMCs' recognition of VLPs. Moreover, transcription factors including SP1, NRF1, AP1, GATA3, microphthalmia-associated transcription factor (MITF), and NF-κB-p65 may bind to the motifs with altered chromatin accessibility to regulate gene transcription. Furthermore, the expression of NF-κB, interleukin (IL)-9, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the BMMCs of the VLP group increased compared with that of the BMMCs in the control group, whereas the expression of IL-10 did not differ significantly between groups. After inhibiting the MRs, the expression of NF-κB, IL-9, TNF-α, and IFN-γ decreased significantly, whereas the expression of IL-10 increased. The expression of MAPK and IL-6 showed no significant change after MR inhibition. This study demonstrated that MRs expressed on BMMCs can affect the NF-κB pathway by changing chromatin accessibility to regulate the transcription of specific cytokines, ultimately leading to the differential expression of cytokines. These data provide a theoretical basis and new ideas for the development of a novel vaccine for FMD.

Histone acetylation regulates BMMCs recognition of foot-and-mouth disease virus-like particles.

Foot-and-mouth disease (FMD) is one of the most economically and socially devastating diseases affecting animal agriculture worldwide. Foot-and-mouth disease virus (FMDV) virus-like particles (VLPs) have been widely studied as a candidate vaccine. Mast cells (MCs) are highly versatile innate immunity cells that perform various functions in regulating innate and adaptive immune responses. Recently, we found that MCs can recognize recombinant FMDV VP1-VP4 protein to produce various cytokines with differential expression, suggesting that this may be epigenetically regulated. In this study, we evaluated the effect of trichostatin A (TSA), a histone deacetylase inhibitor, on bone marrow-derived mast cells (BMMCs) recognition of FMDV-VLPs in vitro. BMMCs can recognize FMDV-VLPs via mannose receptors (MRs) and resulted in enhanced expression and secretion of tumour necrosis factor α (TNF-α) and interleukin (IL)-13. Nevertheless, BMMCs recognition of FMDV-VLPs to secrete IL-6 was irrelevant to MRs, and MRs may play a negative regulation for IL-10 secretion. Pre-treatment with TSA caused decreased expression of IL-6, TNF-α and IL-13, and increased expression of IL-10. Furthermore, the expression of nuclear factor-kappa B (NF-κB) was supressed in TSA treated BMMCs, suggesting histone acetylation may alter NF-κB expression to influence the TNF-α and IL-13 secretion. Pre-treatment with TSA had no influence on the expression of microphthalmia-associated transcription factor (MITF) and GATA-2. These data therefore suggest that altered histone acetylation regulates the immune responses induced by BMMCs recognition of FMDV-VLPs, providing an understanding and theory basis for the prevention and control of FMD based MCs.

B cell memory responses induced by foot-and-mouth disease virus-like particles in BALB/c mice.

A challenging but critical question is that new foot-and-mouth disease (FMD) vaccines should be to induce B cell memory to provide antibodies for long-term protection. The maintenance of B cell memory is dependent on long-lived plasma cells (LLPCs) and memory B cells. We developed a chimeric FMDV virus-like particles (FMDV-VLPs), fusing VP1-VP4 into HBcAg. In our study, we investigated if or how long B cell memory was induced by FMDV-VLPs in mice. The data showed that FMDV-VLPs can induce memory humoral responses with a high level of total IgG1, IgG2a, IgA, and FMDV-specific IgG antibodies in serum. The persistence of antibody levels in serum could depend on LLPCs. The proportion of LLPCs in CD19+ cells in bone marrow exhibited a dynamic trend with two peaks at 28 days post-immunization (dpi) and 72 dpi, respectively. Additionally, the proportion of memory B cells in CD19+ cells in the spleen increased significantly both at 7 days post primary immunization and at 7 days post -boost immunization. Of note, LLPCs together with memory B cells contribute to the production of FMDV-specific IgG and IgG1. The changes of LLPCs and memory B cells may be related to TNF-α, IL-6 and, CXCL12. Taken together, FMDV-VLPs could induce B cells memory responses. A further understanding of the mechanisms that FMDV-VLPs how we can manipulate the induction and maintenance of memory B cells and LLPCs will promote vaccine design and likely address several challenges to develop FMDV new vaccines in the future.

Underlying Causes and Co-existence of Malnutrition and Infections: An Exceedingly Common Death Risk in Cancer.

In nutrition science, malnutrition is a state of imbalance between intake and the needs of the organism, leading to metabolic changes, impaired physiological functions, and weight loss. Regardless of the countless efforts being taken and researched for years, the burden of malnutrition is still alarming and considered a significant agent of mortality across the globe. Around 45% of 12 million children deaths (0-5 years old) annually are due to malnutrition, mostly from developing countries. Malnutrition develops associations with other infections and leads to substantial clinical outcomes, such as mortality, more visits to hospitals, poor quality of life and physical frailty, and socioeconomic issues. Here, in this review, we intend to provide an overview of the current burden, underlying risk factors, and co-existence of malnutrition and other infections, such as cancer. Following the rising concern of the vicious interplay of malnutrition and other medical illnesses, we believed that this narrative review would highlight the need to re-make and re-define the future strategies by giving comprehensive and sustainable programs to alleviate poverty and combat the rampant infectious diseases and those nutrition-related health problems. Furthermore, the study also raises the concern for hospitalized malnourished cancer patients as it is crucially important to knowledge the caregiver healthcare staff for early interventions of providing nutritional support to delay or prevent the onset of malnutrition.

Large Transmission Clusters of HIV-1 Main Genotypes Among HIV-1 Individuals Before Antiretroviral Therapy in the Hebei Province, China.

In recent 10 years, the sexual contact transmission has led to the consecutive upsurge of HIV in Hebei. Especially, the risk behaviors such as homosexual contact in Hebei have presented challenges for HIV prevention and treatment efforts. In this study, we found that 98.9% of subjects attributed their HIV-1 infections to sexual contact, and men who have sex with men (MSM) accounted for 77.5%. CRF01_AE (49.6%), CRF07_BC (29.7%), and subtype B (13.0%) were three main genotypes. AE_cluster 1 (73 cases), AE_cluster 2 (62 cases), and 1 large 07_BC cluster (75 cases) were identified, and only closely clustered with MSM sequences from Beijing. Further, all of HIV-1-resistant strains were circulating in transmission clusters. Particularly, 76.5% of subjects resistant to drugs were circulating in above three large transmission clusters associated with MSM from Beijing. Our study proved that the busy movement of MSM between Beijing and Hebei could meet conveniently, which might result in the bidirectional exchange of HIV-1 strains between Beijing and Hebei. As the most frequent genotypes, large transmission clusters associated with CRF01_AE and CRF07_BC have become one of the main factors resulting in the rapid increase of HIV in Hebei. Therefore, the enhanced surveillance for HIV should be planned early among the floating population traveling between Beijing and Hebei. Hebei should construct the cooperative mechanism for HIV prevention and control together with Beijing.

Effects of comprehensive rehabilitation training in combination with multi-mode analgesia on body function recovery after tumor-type knee replacement.

OBJECTIVE: To discuss the significance of comprehensive rehabilitation training combined with multimodal analgesia (MMA) for the early knee function recovery of patients with knee bone tumor who underwent prosthesis replacement operation. METHODS: Sixty patients with knee bone tumor who underwent prosthesis replacement operation were selected and randomly divided into two groups according to rehabilitation training and postoperative analgesic methods, namely, observation group and control group, 30 cases in each group. The control group was treated with symptomatic treatment (drugs were given based on pain before and after surgery) and continuous passive motion (CPM) functional training, while the observation group was treated with comprehensive rehabilitation training combined with MMA. The compliance of patients in the two groups was compared and the first-time off-bed activity time was recorded. Recovery conditions of wounds were observed, and recovery conditions of limb functions after operations were evaluated. RESULTS: The compliance of patients in the observation group was significantly higher than that in the control group, and the difference was statistically significant (P<0.05). The first-time off-bed activity time of patients of the observation group was earlier than that of the control group. The wound recovery condition of the observation group 7 days after operation was better compared to that of the control group, and the difference between two groups two weeks after operation was not statistically significant. The Hospital for special surgery knee (HSS) score and evaluation result of range of motion (ROM) of knees of the observation group were both better than those of the control group in different periods after operation, and the differences were statistically significant (P<0.05). CONCLUSION: Comprehensive rehabilitation training combined with MMA can improve the compliance of patients and help patients off bed earlier, and remarkably promote the early recovery of knee functions; hence it deserves to be promoted clinically.