Discovery medicine最新文献

Objective: IKBKB-interacting protein (IKBIP) has rarely been reported in tumor research. This study aimed to evaluate IKBIP role in tumor progression. mRNA (messenger ribonucleic acid) expression, clinical characteristics and predictive values of IKBIP were assessed.

Methods: R package "clusterProfiler" was used to examine the potential mechanisms in which IKBIP may involve. Immune cell infiltration and its correlation with IKBIP was also analyzed. We further evaluated IKBIP influence on drug resistance.

Results: It was found that IKBIP was overexpressed and related to poorer survival in most types of tumors. IKBIP expression was strongly related to immunosuppressive cells in the TCGA (The Cancer Genome Atlas) pan-cancer samples. These immunosuppressive cells included tumor-related macrophages, tumor-related fibroblasts, and regulatory T cells. Moreover, immunosuppressive genes and immune checkpoints were positively related to IKBIP expression in several tumor types. Furthermore, patients with IKBIP overexpressed did not respond to most anti-cancer medications. It was also found that compared to control group, the number of invasive cells is four times that of IKBIP overexpression group, and the number of clone forming cells is six times that of IKBIP overexpression group. IKBIP overexpression promoted colon cancer cells invasiveness and clonogenesis by Transwell assay and colon formation assay.

Conclusions: According to current findings, IKBIP is a probable oncogene and predictive marker for most of tumor types. High IKBIP expression is associated with tumor immunosuppression.

Purpose: Although numerous studies have revealed that various long-non coding RNA (lncRNA) are implicated in multiple myeloma (MM) regulation, MM lncRNA profile and novel functional lncRNAs in MM need to be elucidated.

Methods: Herein, lncRNAs and mRNAs (messenger ribonucleic acids) patterns in MM were evaluated using RNA-sequencing (RNAseq). Differentially expressed (DE) genes were defined and a complex regulatory network based on validation and predication was shaped.

Results: LncRNA-seq data analysis identified 539 DE lncRNAs and RP11-1100L3.8 was the most up-regulated known lncRNA. Subsequently, the upregulation and clinical RP11-1100L3.8 utilization value was verified in an expanded cohort. Based on the results of Cis nearby-targets and co-expression analysis, 1 correlation pair RP11-1100L3.8-nuclear receptor subfamily 4 group A member 1 (NR4A1) was defined. It is worth noting that NR4A1 is one of the top 5 significantly up-regulated DE mRNAs in MM patients. Moreover, it was found that NR4A1 overexpression is associated with poor prognosis in MM patients, making it suitable as biomarker. Additionally, spearman correlation analysis revealed the positive association between RP11-1100L3.8 and NR4A1 in MM patients. Furthermore, the dominant NR4A1 interacted genes were predicated and it was found that the genes containing NR4A1 were remarkably enriched in phosphatidylinositol 3-kinase (PI3K)-AKT (protein kinase B) signaling pathway. In addition, in vitro experiment suggested that RP11-1100L3.8 downregulation decreased NR4A1 expression in U266 and RPMI 8226 MM cells. RP11-1100L3.8 inhibition declined proliferation and promoted apoptosis in MM cells, which were rescued by NR4A1 overexpression. Moreover, it was found that RP11-1100L3.8 inhibition impeded PI3K and AKT phosphorylation and rapamycin mammalian target in MM cells, which was rescued by NR4A1 overexpression.

Conclusions: This study identifies RP11-1100L3.8 as a potential MM biomarker, and it may be involved in MM pathophysiology by regulating NR4A1-mediated PI3K-AKT signaling pathway. This study provides a novel biomarker candidate for MM therapy.

Background: Long non-coding RNA (lncRNA) AP000695.2 (ENSG00000248538) expresses abnormally in various malignancies, what shows its role as oncogene. However, it has not been extensively studied in gastric cancer. The aim of the current study was to explore the clinical value of AP000695.2 to prognose gastric cancer.

Methods: The cancer genome atlas (TCGA) and the gene expression profiling interactive analysis (GEPIA) online tool were used to analyze AP000695.2 expression pattern, diagnostic and prognostic role in gastric cancer. Kaplan-Meier and Cox regression analyses were used to assess survival in patients with gastric cancer. Receiver operating curve (ROC) analysis was used to assess AP000695.2 diagnostic capacity. Nomograms were created to predict overall survival (OS) and progression free survival (PFS).

Results: LncRNA AP000695.2 was abnormally upregulated in 19 types of malignancy, including gastric cancer. Survival analysis indicated that high expression of AP000695.2 was associated with poor survival of gastric cancer. Multivariate Cox regression analysis verified the independent prognostic value of AP000695.2 to predict OS (HR (hazard ratio): 1.104, 95% CI (confidence interval): 1.035-1.178, p = 0.003) and PFS (HR: 1.170, 95% CI: 1.090-1.256, p < 0.001). ROC analysis indicated a favorable AP000695.2 diagnostic capacity (area under the curve (AUC) = 0.890). Nomograms were also constructed for OS and PFS based on AP000695.2 expression-related risk score. Additionally, AP000695.2 was found to be positively associated with tumor-infiltrating immune cells, including classically activated (M1) macrophages, neutrophils, alternatively activated (M2) macrophages, and natural killer (NK) cells.

Conclusions: It was observed that AP000695.2 can be used as a novel biomarker to diagnose or predict survival of gastric patient.

A subset of renal tumors (5-8%) are associated with syndromes such as von Hippel-Lindau (VHL) syndrome, Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex (TSC), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), and BRCA1 associated protein (BAP1) tumor predisposition syndrome, succinate dehydrogenase RCC (SDHB/C/D). These syndromes have their specific defined genetic alterations and associated extrarenal manifestations. Due to varying histopathology and aggressiveness of the tumors amongst these syndromes, the management strategies can range from active surveillance to upfront surgical resection. This review delineates specific characteristics of the most common familial renal cancer syndromes and discusses current management strategies.

Population-based estimates of the differences -in metastatic pattern, incidence, and prognosis of breast cancer patients by histologic grade at breast cancer diagnosis are lacking. Patients with breast cancer and metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Multivariable logistic and Cox regression were performed to determine the effect of histologic grade on the presence of metastases at diagnosis and all-cause mortality. We identified a population-based sample of adult patients diagnosed with invasive breast cancer between 2010 and 2015 for whom the presence or absence of metastases was known. We depicted the landscape of metastatic pattern of breast cancer histologic grade that the percentage of bone metastasis was decreasing with higher histologic grade, while the percentages of lung and brain metastasis were increasing. Higher histologic grade was associated with a greater incidence of all metastatic lesions. Median durations of survival with distant metastasis were 41 months (Grade I), 34 months (Grade II), 21 months (Grade III), 13 months (Grade IV), and 16 months (unknown histologic grade). Grade III and unknown histologic grade represent the most common part of patients with metastatic disease, but not for breast cancer patients without metastasis. In multivariate analysis, Grade II, III, IV, and unknown histologic grade were associated with significantly greater odds of patients with metastatic disease to any distant site, compared with Grade I, but not to bone. Grade III was associated with increased all-cause mortality among patients having metastases to any sites, bone, brain, liver, and lung compared with Grade I, but not Grade II and Grade IV. Breast cancer histologic grades are associated with distinct patterns of metastatic spread and notable differences in survival.

COVID-19 infection can cause damage to various systems, such as cardiovascular, respiratory, and neurological, both during the course of the disease and in the period after recovery, caused by the effects of so-called "Long COVID." Cardiovascular complications caused by COVID-19 infection are not yet fully understood and characterized. Cardiovascular complications caused by COVID-19 include pericarditis, myocarditis, dysrhythmias, ischemic and non-ischemic heart disease, and thromboembolic disease. The pathophysiological and molecular mechanisms of cardiovascular damage caused by SARS-CoV-2 are still being studied. More severe COVID-19 cases with the multisystem inflammatory syndrome (MIS) have frequent involvement of cardiovascular damage. In addition, recent evidence shows that months later, individuals who have had a COVID-19 infection may be at a greater risk of suffering heart disease than individuals who have not had the infection. In this brief literature review, we summarize the current evidence in the literature on cardiovascular damage caused by COVID-19, during the period of infection and in the long COVID, and possible concomitant risk factors, which may play an important role.

Based on the abundant published literature, here we expand the understanding of cardiovascular diseases in a framework already presented in previous articles. In this context, some unique distinguishing features of vascular lesions are explained. A rationale for the role of apolipoprotein apoB100 is presented. It is hypothesized that K⊂ATP⊂ channels and their control by blood pH are behind the development of coronary artery spasm and cardiomyocyte death. Finally, the main cardiovascular risks are explained within the proposed framework.

Background: Studies have suggested that age and the serum total cholesterol (TC) concentration are independent risk factors for cardiovascular disease (CVD) in patients with familial hypercholesterolemia (FH); however, the relationship between age and TC in patients with FH is unclear. We aimed to investigate the correlation between age and TC in patients with FH.

Methods: In this study, 103 patients with FH and 106 non-FH controls were recruited from 2004 to 2017. Spearman and partial correlation analyses, as well as multiple regression analyses, were used to evaluate the relationship between TC and age.

Results: There were no significant differences in age, gender, or BMI between the FH group and the control group (p > 0.05). Family history of CVD, TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), lipoprotein (a) (Lp[a]), and non-HDL-C levels were significantly higher in patients with FH compared with the controls (p < 0.01). Additionally, the serum TC levels for ages ≥ 50 years were significantly higher than those for ages < 50 years (p < 0.05) in FH patients. In both Spearman and partial correlation analyses, age was found to be significantly correlated with serum TC (p < 0.001) in the FH group but not in the control group, which was confirmed by further multiple linear regression analyses and logistic regression analyses.

Conclusions: Age is an independent factor influencing serum TC level in patients with FH, and it is necessary to conduct early screening and early intervention.

Pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC), has a mortality rate that is among the highest. The single therapy option that has the potential to be curative for the illness is surgery, which is generally accepted as being the only effective treatment available. This is because most pancreatic tumors are intractable to chemotherapy. Because of the severe nature of the illness that these tumors cause, only around twenty percent of these tumors can be surgically removed when the first symptoms appear. This is due to the harm that these tumors cause. Since surgery in late-stage cases does not usually offer benefits, here we shed light on the molecular mechanisms of the most aggressive pancreatic tumors that are highly resistant to drugs. We also describe two latest novel treatment approaches that are used to combat this fierce tumor: targeting exosome-mediated tumor-enhancement mechanisms and radiation therapy in combination with adverse effect-mitigating agents. Effective treatments for pancreatic cancer are needed to meet this urgent medical need.

Pernicious anemia (PA) is an autoimmune disease characterized by cobalamin deficiency (CD) due to immune-mediated chronic atrophic gastritis (CAG). CD results from poor absorption of dietary cobalamin from the terminal ileum, triggered by positive intrinsic factor (IF) antibodies. It is the most common cause of CD worldwide. Despite advances in understanding biochemistry and pathogenesis of PA, its diagnosis can be extremely challenging as the disease may present with hematological as well as nonhematological manifestations and also because of unreliable serum cobalamin assays. Nonhematological manifestations may present in a patient with PA even in the absence of hematological findings. Herein, an overview of common and uncommon nonhematological manifestations of PA is discussed.