课程文献中心 更多>>

关键词： Laryngeal squamous cell carcinoma   Non-coding RNA   circHIPK2   miR-889-3p   MCTS1   IL-6   Tumor microenvironment  

摘要： Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck with a poor prognosis. The role of circRNAs in LSCC remains largely unknown. In this study, quantitative real-time PCR (qRTPCR), Sanger sequencing and fluorescence in situ hybridization were undertaken to detect the expression, localization, and clinical significance of circHIPK2 in LSCC tissues and TU686 and TU212 cells. The functions of circHIPK2 in LSCC were explored through proliferation analysis, EdU staining, colony formation assay, wound healing assay, and Transwell assay. The regulatory mechanisms underpinning circHIPK2, miR-889-3p, and MCTS1 were investigated using luciferase assay, Western blotting, and qRT-PCR. We found that LSCC tissues and cells demonstrated high expression of circHIPK2 that was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circHIPK2 inhibited the proliferation and migration of LSCC cells in vitro. Mechanistic studies showed that circHIPK2 competitively bound to miR-889-3p, elevated MCTS1 level, promoted IL-6 secretion, and ultimately accelerated the malignant progression of LSCC. In conclusion, an axis involving circHIPK2, miR-889-3p, MCTS1 and IL-6 regulates the malignant progression of LSCC. circHIPK2 expression may serve as a novel diagnostic and prognostic biomarker for LSCC.

关键词： IL-1 beta   Prostaglandin   Myometrium cells   Cervical stromal cells   Labor onset  

摘要： Inflammatory cytokines such as IL-1 beta and prostaglandins (PGs) are pivotal in the initiation of labor. Nevertheless, the synergistic interaction between PGs and IL-1 beta remains to be fully elucidated. Labor is defined as regular and gradually increasing uterine contractions accompanied by progressive dilation of the cervix, and descent of the fetal. This study employed Luminex to monitor alterations in inflammatory cytokine levels within myometrial tissue (n = 10) during labor compared to non-labor (n = 10) conditions. And the synergistic relationship between PGs and IL-1 beta by investigating the primary myometrium cells and cervical stromal cells culture. The results showed that the inflammatory cytokines of IL-1 beta, IL-6, IL-8 and TNF-alpha in the myometrium tissue were increased in labor group. In myometrium cells, PGF2 alpha and IL-1 beta synergistically up-regulated COX-2 mRNA, upregulated the transcription of PRA and PRB, PGF2 alpha alleviated that IL-1 beta up-regulated IL-8 mRNA. In cervical stromal cells, IL-1 beta up-regulated the COX-2 and PRB protein expression. PGE2 abated that IL-1 beta up-regulated IL-8 mRNA. PGE increased the expression of PRs, which is more pronounced with the prolonged duration. Ratio of PRA/PRB show an increased trend with IL-1 beta and PGE2 co-regulated. This study further clarified the synergistic regulatory mechanism of IL-1 beta and PGs, offering a theoretical foundation for the development of strategies aimed at labor induction and the prevention and treatment of preterm birth.

关键词： Vaccines   Bioinformatics   Immunogenic peptides   COVID 19  

摘要： Vaccines stimulate cells of the adaptive immune system, generating a protective and lasting memory, and are the main public health strategy to protect the world population from emerging pathogens such as the SARS-CoV-2 virus, responsible for millions of deaths in the recent COVID-19 pandemic. Several in-silico algorithms have facilitated the selection of antigens as vaccine candidates;however, their predictive capacity remains limited and it is necessary to continue training them, using information obtained in immunological assays. In this work, the SARS-CoV-2 proteome was sampled using a series of concatenated algorithms that allowed us to define a series of candidate viral peptides for a vaccine against SARS-CoV-2 in individuals from Colombian, whose haplotypes for HLA-I and II were incorporated as part of the algorithm. The immunogenicity of the peptides predicted with three tools or with the combination of them was evaluated and found that short peptides predicted and selected as highly immunogenic peptides were capable of expanding memory CD8 T lymphocytes with an activation phenotype. Altogether, our results outline a pipeline that combines a bioinformatic and immunological approach useful to select immunogenic epitopes from emerging pathogens as vaccine candidates tailored to the population's HLA-Haplotypes.

关键词： T lymphocytes   chlorogenic acid   interleukin-2   post-traumatic osteomyelitis   regulatory T cells  

摘要： BACKGROUND:Chlorogenic acid (CGA) exerts immunomodulatory effects by regulating the proportion of regulatory T cells (Tregs), and T-cell dysregulation is a known feature of post-traumatic osteomyelitis (PTO). This study explored the mechanism of CGA in the treatment of PTO from the perspective of T-cell immunity. METHODS:Lymphocytes isolated from rat spleens were stimulated with interleukin (IL)-2. A PTO model was established by injecting into the tibial marrow cavity of New Zealand white rabbits. PTO rabbits were treated with either CGA by gavage or lentiviral IL-2 injection. The Treg proportion was evaluated by flow cytometry. The expression of forkhead box protein 3 (), cytotoxic T lymphocyte antigen-4 (), and IL-2 was quantified by quantitative real-time polymerase chain reaction. The concentrations of tumor necrosis factor-α (TNF-α), IL-10, and IL-2 were measured using enzyme-linked immunosorbent assays. Micro-computed tomography and hematoxylin and eosin staining were performed to characterize bone destruction. The proliferation of CD4 T/CD8 T cells was evaluated by flow cytometry. RESULTS:IL-2 stimulation elevated the proportion of Tregs in rat splenic lymphocytes, upregulated , , and IL-10 expression, and decreased TNF-α expression ( < 0.05). PTO rabbits exhibited significant bone destruction and inflammatory cell infiltration in bone tissue. In the peripheral blood of PTO rabbits, the Treg proportion was elevated, with increased expressions of , , IL-10, and IL-2, reduced TNF-α expression, and increased proliferation of CD4 T/CD8 T cells. These changes were significantly reversed by CGA administration ( < 0.001). However, the reversal effects of CGA were offset by exogenous IL-2 ( < 0.001). CONCLUSION:CGA alleviates PTO by inhibiting IL-2-mediated upregulation of Tregs.

关键词： LAR   IL-6   Severe acute pancreatitis   Clinical diagnosis   Prognostic analysis   Efficacy  

摘要： To analyze the clinical value of lactate dehydrogenase to albumin ratio (LAR) and interleukin-6 (IL-6) in the early diagnosis and prognostic assessment of severe acute pancreatitis (SAP). A retrospective study was conducted on 98 cases of acute pancreatitis patients. These patients were divided into two groups based on the severity of their condition: non-SAP group (n = 68) and SAP group (n = 30). Spearman correlation analysis was utilized to investigate the correlation of LAR and IL-6 with the bedside index for severity in acute pancreatitis (BISAP). Patients in the SAP group exhibited significantly higher LAR values and IL-6 levels compared to those in the non-SAP group (P < 0.05). The APR and IL-6 of SAP patients were significantly positively correlated with BISAP scores (R = 0.758, P < 0.001) (R = 0.660, P < 0.001). The diagnostic AUC of LAR and IL-6 for SAP were 0.742 (P < 0.001) and 0.749 (P < 0.001), respectively. The Logistic regression analysis demonstrated that LAR and IL-6 were independent risk factors for SAP (P < 0.05). The levels of LAR and IL-6 in the death subgroup were significantly higher than those in the survival subgroup (P < 0.05). The diagnostic AUC of LAR and IL-6 for poor prognosis of SAP were 0.971 (P < 0.001) and 0.713 (P = 0.055), respectively. LAR was an independent risk factor for poor prognosis in SAP patients (P < 0.05). Patients with SAP may exhibit abnormally elevated levels of LAR and IL-6. LAR and IL-6 are closely associated with the severity of the patient's condition, which can be applied in the diagnosis of SAP.

关键词： Anti-HLA antibody   DSA   PBSCT   Engraftment   MFI  

摘要： Anti-human leukocyte antigen (HLA) antibodies, particularly donor-specific HLA antibodies (DSA), negatively impact engraftment in hematopoietic cell transplantation. Past studies have proposed various interventions to reduce DSA, but these were primarily from single centers and not from large-scale registry data. Therefore, we conducted a retrospective analysis of nationwide registry data to examine the effects of anti-HLA antibodies on engraftment. Evaluable patients were classified into an anti-HLA antibody-negative group (n = 3657), an anti-HLA antibody-positive group (without high DSA) (n = 137), and a high-DSA (MFI > 5000) group (n = 8). Patient characteristics differed significantly between the anti-HLA antibody-negative and anti-HLA antibody-positive groups, and the number of patients with DSA was lower than expected. Statistical analyses revealed that the anti-HLA antibody-positive group had better neutrophil engraftment than the anti-HLA antibody-negative group (94.0% vs 84.2%, p < 0.001) but worse platelet engraftment (60.3% vs 64.9%, p = 0.047). In the high DSA group, two patients received a DSA-depleting intervention. Only one patient with an MFI of 5832 (without intervention) developed primary graft failure, while the remaining seven achieved engraftment. In this study, the effect of anti-HLA antibodies remained inconclusive, and the possibility of neutrophil engraftment with high-DSA levels was confirmed.

关键词： Propolis alcoholic extract   Osteoblast   Hypoxia   Cell proliferation  

摘要： Numerous studies have demonstrated the significant role of propolis in various biological processes, including inflammation and the repair of endothelial and bone tissues. The cascade of inflammation, proliferation, and tissue remodeling characterizes the injury site. Remarkable progress has been made in the field of alternative medicine with the utilization of propolis. In this study, we specifically investigated the effects of alcoholic extract of propolis on cell adhesion, survival, remodeling, and differentiation pathways in osteoblasts. Our findings revealed the activation of survival proteins such as AKT, ERK, and phosphorylated ERK during the adhesion phase, while interleukins, specifically IL-6 and TNF, exhibited increased expression during cell differentiation. Furthermore, treatment with propolis extract led to enhanced activity of metalloproteinases (MMP9 and MMP2) and HIF-1 alpha, a crucial activator of angiogenesis and bone remodeling. It was observed that the alcoholic propolis extract stimulated cell proliferation, differentiation, and repair, with key molecules involved in these processes including pro-inflammatory factors IL-6 and TNF alpha, as well as HIF-1, MMP2, and BMP7 proteins. Collectively, these factors induced an initial state of proliferation followed by differentiation and repair. Therefore, the alcoholic extract of propolis holds promise as a potential therapeutic agent, particularly in cases involving tissue repair. Nevertheless, further comprehensive in vitro and in vivo studies targeting this area are necessary to advance our understanding.