Novel Strategies For Diagnosis Research Articles

Odontogenic Maxillary Sinusitis Microbiology Compared With Chronic Rhinosinusitis: A Meta-Analysis.

Subtypes of sinusitis have different symptoms and prognoses due to different pathogens. Odontogenic maxillary sinusitis (OMS) mainly occurs unilaterally and is different from chronic rhinosinusitis (CRS) usually occurring bilaterally in terms of clinical characteristics. However, comprehensive microbiological comparisons between OMS and CRS have never been systematically conducted and most comparisons are methodologically biased. This study aims to provide a comprehensive analysis of the microbiology associated with OMS and CRS through a meta-analysis approach in order to provide evidence for differential diagnosis of OMS and CRS from a microbiological perspective. The databases PubMed and CNKI were searched from their inception to July 2023. A random-effects model was employed to derive the pooled prevalence estimates of the identified bacterial species or genera. The 17 represented studies included 6 concerning OMS, 12 concerning CRS, and 4 concerning normal sinus, yielding 191, 610, and 92 samples, respectively. Though not statistically significant, the prevalence of Peptostreptococcus and Prevotella was generally higher in OMS compared to CRS. Notably, Fusobacterium was identified as the only genus with a significantly higher prevalence in OMS compared to CRS. Fusobacterium was significantly more prevalent in OMS compared with CRS, while Staphylococcus aureus was more prevalent in CRS than in OMS. Such differences in bacterial profile may partly explain the distinct pathology observed and contribute to the development of novel strategies for diagnosis and therapeutic interventions in OMS.

Anxiety and depressive personality disorders in the modern world

The study's significance lies in the multitude of challenges facing individuals today, such as the COVID-19 pandemic, military conflicts like the war in Ukraine, and the escalating rates of cancer morbidity and mortality. These factors contribute to the onset of anxiety and depressive disorders, disrupting various aspects of individuals' mental functioning and social interactions. Addressing these disorders effectively necessitates a comprehensive approach, combining pharmacological interventions with psychotherapeutic strategies under the guidance of specialized professionals. In this regard, the study is aimed at identifying aspects and features of the development of psychological problems and personality disorders in the modern world filled with various stressors. The leading methods of studying this problem are analysis, synthesis, induction, deduction, comparison, experiment and systematisation of approaches that will help determine a wide range of mental disorders. Theoretical methods were used to analyze the literature and summarize theoretical material on anxiety and depressive disorders. Diagnostic methods were used to assess the psychological state of the study population. The study examines significant clinical syndromes and vegetative disorders that disrupt normal lifestyle, hinder daily activities, and impede professional growth. It evaluates the roles of psychologists, psychiatrists, and social workers in assisting individuals with anxiety disorders. It outlines preventive measures for anxiety and depression, while also delving into various types of anxiety disorders. The research proposes diverse methods to prevent emotional anxiety and instability. It underscores the importance of devising novel strategies for diagnosis and therapy, emphasizing a comprehensive approach involving psychotherapeutic support, medical intervention, and adaptive behavioral techniques. The findings of the study hold both practical and theoretical significance for professionals in psychology, psychiatry, psychoanalysis, and sociology who provide support for individuals with anxiety and depressive disorders. Furthermore, the insights provided may be pertinent to researchers and scholars investigating the psychological well-being of contemporary society amidst adverse external circumstances.

Galectin-3 and Severity of Liver Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease.

Metabolic dysfunction-associated Fatty Liver Disease (MAFLD) is a chronic liver disease characterized by the accumulation of fat in the liver and hepatic steatosis, which can progress to critical conditions, including Metabolic dysfunction-associated Steatohepatitis (MASH), liver fibrosis, hepatic cirrhosis, and hepatocellular carcinoma. Galectin-3, a member of the galectin family of proteins, has been involved in cascades that are responsible for the pathogenesis and progression of liver fibrosis in MAFLD. This review summarizes the present understanding of the role of galectin-3 in the severity of MAFLD and its associated liver fibrosis. The article assesses the underlying role of galectin-3-mediated fibrogenesis, including the triggering of hepatic stellate cells, the regulation of extracellular degradation, and the modulation of immune reactions and responses. It also highlights the assessments of the potential diagnostic and therapeutic implications of galectin-3 in liver fibrosis during MAFLD. Overall, this review provides insights into the multifaceted interaction between galectin-3 and liver fibrosis in MAFLD, which could lead to the development of novel strategies for diagnosis and treatment of this prevalent liver disease.

Endothelial dysfunction of syphilis: Pathogenesis.

Treponema pallidum is the causative factor of syphilis, a sexually transmitted disease (STD) characterized by perivascular infiltration of inflammatory cells, vascular leakage, swelling and proliferation of endothelial cells (ECs). The endothelium lining blood and lymphatic vessels is a key barrier separating body fluids from host tissues and is a major target of T. pallidum. In this review, we focus on how T. pallidum establish intimate interactions with ECs, triggering endothelial dysfunction such as endothelial inflammation, abnormal repairment and damage of ECs. In addition, we summarize that migration and invasion of T. pallidum across vascular ECs may occur through two pathways. These two mechanisms of transendothelial migration are paracellular and cholesterol-dependent, respectively. Herein, clarifying the relationship between T. pallidum and endothelial dysfunction is of great significance to provide novel strategies for diagnosis and prevention of syphilis, and has a great potential prospect of clinical application.

Higher Expression of Human Endogenous Retrovirus-K was Observed in Peripheral B Lymphocytes of Leukemia and Lymphoma Patients.

Hematological malignant tumors (HMTs) are serious diseases that threaten human health and life with high mortality. Therefore, it is necessary to develop novel strategies for diagnosis and treatment. Human endogenous retroviruses (HERVs) have recently attracted increasing attention as potential targets for cancer diagnosis and therapy. In this study, we explored the association between HERV-K expression levels and HMTs development. Clinical data and peripheral blood samples were collected from 236 leukemia, 384 lymphoma patients, and 69 healthy controls. Quantitative polymerase chain reaction was used to detect the expression of HERV-K gag, pol, and env genes in peripheral blood mononuclear cells or different cell subpopulations. Differently expressed HERV-K genes were further tested by using deep sequencing method, and further analyzed with gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. B cell- and T cell-related cytokines in patients were also detected by enzyme-linked immunosorbent assay (ELISA). The results showed that the expression levels of the HERV-K gag, pol, and env genes in patients were significantly higher than in healthy controls. There was a correlation between the expression level of HERV-K and the clinicopathological parameters of leukemia patients. HERV-K expression was increased in the B lymphocytes of leukemia and lymphoma patients, but not in the T cells or neutrophils. The GO and KEGG analyses showed that abnormal expression of the HERV-K locus in patients affected immune regulation. The analysis of cytokines proved that the B cell-related cytokines, including interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon-gamma, were significantly decreased in patients, while the T cell-related cytokines, including IL-3, IL-12, and TNF-β, were not significantly changed. In conclusion, HERV-K genes might participate in the occurrence and development of leukemia and lymphoma, and might be biomarkers for the detection or evaluation of leukemia and lymphoma.

Seminal plasma untargeted metabolomic and lipidomic profiling for the identification of a novel panel of biomarkers and therapeutic targets related to male infertility.

Male infertility occurs approximately in about 50% of all infertility cases and represents a serious concern worldwide. Traditional semen analysis alone is insufficient to diagnose male infertility. Over the past two decades, advances in omics technologies have led to the widespread application of metabolomics profiling as a valuable diagnostic tool for various diseases and disorders. Seminal plasma represents a rich and easily accessible source of metabolites surrounding spermatozoa, a milieu that provides several indispensable nutrients to sustain sperm motility and fertilization. Changes of metabolic profiles in seminal plasma reflect male reproductive tract disorders. Here, we performed seminal plasma metabolomics and lipidomics profiling to identify a new pattern of biomarkers of male infertility. Seminal plasma samples from unfertile subjects (n = 31) and fertile controls (n = 19) were analyzed using an untargeted metabolomics/lipidomics integrated approach, based on Ultra-High-Pressure Liquid Chromatography-tandem Mass Spectrometry. Partial Least Squares-Discriminant Analysis showed a distinct separation between healthy fertile men and infertile subjects. Among the 15 selected candidate biomarkers based on Variable Importance in Projection scores, phosphatidylethanolamine (PE) (18:1; 18:1) resulted with the highest score. In total, 40 molecular species showed statistically significant variations between fertile and infertile men. Heat-map and volcano plot analysis indicated that acylcarnitines, phosphatidylserine (PS) (40:2) and lactate were decreased, while PE (18:1; 18:1), Phosphatidic acid (PA) (O-19:2; 18:1), Lysophosphatidylethanolamine (LPE) (O-16:1) and Phosphatidylcholine (PC) (O-16:2; 18:1)-CH3 were increased in the infertile group. The present study is the first one to analyze the metabolomics/lipidomics dysregulation in seminal plasma between fertile and infertile individuals regardless of sub-infertility condition. Association of several metabolites/lipids dysregulation with male infertility reinforced data of previous studies performed with different approaches. In particular, we confirmed significantly decreased levels of PS and carnitines in infertile patients as well as the positive correlation with sperm motility and morphology. If validated on a larger prospective cohort, the metabolite biomarkers of infertility in seminal plasma we identified in the present study might inform novel strategies for diagnosis and interventions to overcome male infertility.

The Siderophore Ferricrocin Mediates Iron Acquisition in Aspergillus fumigatus.

The opportunistic fungal pathogen Aspergillus fumigatus utilizes two high-affinity iron uptake mechanisms, termed reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA). The latter has been shown to be crucial for virulence of this fungus and is a target for development of novel strategies for diagnosis and treatment of fungal infections. So far, research on SIA in this mold focused mainly on the hyphal stage, revealing the importance of extracellular fusarinine-type siderophores in iron acquisition as well as of the siderophore ferricrocin in intracellular iron handling. The current study aimed to characterize iron acquisition during germination. High expression of genes involved in biosynthesis and uptake of ferricrocin in conidia and during germination, independent of iron availability, suggested a role of ferricrocin in iron acquisition during germination. In agreement, (i) bioassays indicated secretion of ferricrocin during growth on solid media during both iron sufficiency and limitation, (ii) ferricrocin was identified in the supernatant of conidia germinating in liquid media during both iron sufficiency and limitation, (iii) in contrast to mutants lacking all siderophores, mutants synthesizing ferricrocin but lacking fusarinine-type siderophores were able to grow under iron limitation in the absence of RIA, and (iv) genetic inactivation of the ferricrocin transporter Sit1 decreased germination in the absence of RIA. Taken together, this study revealed that ferricrocin has not only an intracellular role but also functions as an extracellular siderophore to support iron acquisition. The iron availability-independent ferricrocin secretion and uptake during early germination indicate developmental, rather than iron regulation. IMPORTANCE Aspergillus fumigatus is one of the most common airborne fungal pathogens for humans. Low-molecular-mass iron chelators, termed siderophores, have been shown to play a central role in iron homeostasis and, consequently, virulence of this mold. Previous studies demonstrated the crucial role of secreted fusarinine-type siderophores, such as triacetylfusarinine C, in iron acquisition, as well as of the ferrichrome-type siderophore ferricrocin in intracellular iron storage and transport. Here, we demonstrate that ferricrocin is also secreted to mediate iron acquisition during germination together with reductive iron assimilation. During early germination, ferricrocin secretion and uptake were not repressed by iron availability, indicating developmental regulation of this iron acquisition system in this growth phase.

Understanding the Interactions of Guanine Quadruplexes with Peptides as Novel Strategies for Diagnosis or Tuning Biological Functions.

Guanine quadruplexes (G4s) are nucleic acid structures exhibiting a complex structural behavior and exerting crucial biological functions in both cells and viruses. The specific interactions of peptides with G4s, as well as an understanding of the factors driving the specific recognition are important for the rational design of both therapeutic and diagnostic agents. In this review, we examine the most important studies dealing with the interactions between G4s and peptides, highlighting the strengths and limitations of current analytic approaches. We also show how the combined use of high-level molecular simulation techniques and experimental spectroscopy is the best avenue to design specifically tuned and selective peptides, thus leading to the control of important biological functions.

Interleukin-34 promotes the proliferation and epithelial-mesenchymal transition of gastric cancer cells.

BACKGROUNDInterleukin (IL)-34 is a pro-inflammatory cytokine involved in tumor development. The role of IL-34 in the proliferation and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) remains to be investigated.AIMTo investigate whether and how IL-34 affects the proliferation of GC cells and EMT.METHODSUsing immunohistochemical staining, the expression of IL-34 protein was detected in 60 paired GC and normal paracancerous tissues and the relationship between IL-34 and clinicopathological factors was analyzed. The expression of IL-34 mRNA and protein in normal gastric epithelial cell lines and GC was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Stable IL-34 knockdown and overexpression in AGS cell lines were established by lentiviral infection and validated by qRT-PCR and western blotting. The cholecystokinin-8 assay, clone formation assay, cell scratch assay, and transwell system were used to detect GC cell proliferation, clone formation, migration, and invasion capacity, respectively. The effects of IL-34 on the growth of GC transplant tumors were assessed using a subcutaneous transplant tumor assay in nude mice. The effects of IL-34 on the expression level of EMT-associated proteins in AGS cells were examined by western blotting.RESULTSExpression of IL-34 protein and mRNA was higher in GC cell lines than in GES-1 cells. Compared to matched normal paraneoplastic tissues, the expression of IL-34 protein was higher in 60 GC tissues, which was correlated with tumor size, T-stage, N-stage, tumor, node and metastasis stage, and degree of differentiation. Knockdown of IL-34 expression inhibited the proliferation, clone formation, migration, and invasion of AGS cells, while overexpression of IL-34 promoted cell proliferation, clone formation, migration, and invasion. Furthermore, the reduction of IL-34 promoted the expression of E-cadherin in AGS cells but inhibited the expression of vimentin and N-cadherin. Overexpression of IL-34 inhibited E-cadherin expression but promoted expression of vimentin and N-cadherin in AGS cells. Overexpression of IL-34 promoted the growth of subcutaneous transplanted tumors in nude mice.CONCLUSIONIL-34 expression is increased in GC tissues and cell lines compared to normal gastric tissues or cell lines. In GC cells, IL-34 promoted proliferation, clone formation, migration, and invasion by regulating EMT-related protein expression cells. Interference with IL-34 may represent a novel strategy for diagnosis and targeted therapy of GC.

A metabolism-relevant signature as a predictor for prognosis and therapeutic response in pancreatic cancer.

Although several altered metabolic genes have been identified to be involved in the tumorigenesis and advance of pancreatic cancer (PC), their prognostic values remained unclear. The purpose of this study was to explore new targets and establish a metabolic signature to predict prognosis and chemotherapy response for optimal individualized treatment. The expression data of PC patients from two independent cohorts and metabolism-related genes from KEGG were utilized and analyzed for the establishment of the signature via lasso regression. Then, the differentially expressed candidate genes were further confirmed via online data mining platform and qRT-PCR of clinical specimens. Then, the analyses of gene set enrichment, mutation, and chemotherapeutic response were performed via R package. As results showed, 109 differentially expressed metabolic genes were screened out in PC. Then a metabolism-related five-gene signature comprising B3GNT3, BCAT1, KYNU, LDHA, and TYMS was constructed and showed excellent ability for predicting survival. A novel nomogram coordinating the metabolic signature and other independent prognostic parameters was developed and showed better predictive power in predicting survival. In addition, this metabolic signature was significantly involved in the activation of multiple oncological pathways and regulation of the tumor immune microenvironment. The patients with high risk scores had higher tumor mutation burdens and were prone to be more sensitive to chemotherapy. In summary, our work identified a new metabolic signature and established a superior prognostic nomogram which may supply more indications to explore novel strategies for diagnosis and treatment.

Porous Au@Pt nanoparticles with superior peroxidase-like activity for colorimetric detection of spike protein of SARS-CoV-2

The development of colorimetric assays for rapid and accurate diagnosis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of practical importance for point-of-care (POC) testing. Here we report the colorimetric detection of spike (S1) protein of SARS-CoV-2 based on excellent peroxidase-like activity of Au@Pt nanoparticles, with merits of rapidness, easy operation, and high sensitivity. The Au@Pt NPs were fabricated by a facile seed-mediated growth approach, in which spherical Au NPs were premade as seeds, followed by the Pt growth on Au seeds, producing uniform, monodispersed and porous Au@Pt core–shell NPs. The as-obtained Au@Pt NPs showed a remarkable enhancement in the peroxidase-mimic catalysis, which well abided by the typical Michaelis-Menten theory. The enhanced catalysis of Au@Pt NPs was ascribed to the porous nanostructure and formed electron-rich Pt shells, which enabled the catalytic pathway to switch from hydroxyl radical generation to electron transfer process. On a basis of these findings, a colorimetric assay of spike (S1) protein of SARS-CoV-2 was established, with a linear detection range of 10–100 ng mL−1 of protein concentration and a low limit of detection (LOD) of 11 ng mL−1. The work presents a novel strategy for diagnosis of COVID-19 based on metallic nanozyme-catalysis.

Clinical features and Outcomes of Cryptococcemia patients with and without HIV infection.

The effects of cryptococcemia on patient outcomes in those with or without HIV remain unclear. One hundred and seventy-nine cryptococcemia patients were enrolled in this retrospective study. Demographic characteristics, blood test results and outcome were compared between the two groups. The diagnosis time of Cryptococcus infection was 2.0(0-6.0) days for HIV-infected patients, 5.0 (1.5-8.0) days for HIV-uninfected patients (p=.008), 2.0 (1.0-6.0) days for cryptococcal meningitis (CM) patients and 6.0 (5.0-8.0) days for non-CM patients (p<.001). HIV infection [adjusted odds ratio (AOR) (95% confidence interval): 6.0(2.3-15.9)], CRP<15mg/L [AOR:3.7(1.7-8.1)) and haemoglobin>110g/L [AOR:2.5(1.2-5.4)] were risk factors for CM development. Forty-six (25.7%) patients died within 90days. ICU stay [AOR:2.8(1.1-7.1)], hypoalbuminemia [AOR:2.7(1.4-5.3)], no anti-cryptococcal treatment [AOR:4.7(1.9-11.7)] and altered consciousness [AOR:2.4(1.0-5.5)] were independent risk factors for 90-day mortality in all patients. HIV infection did not increase the 90-day mortality of cryptococcemia patients when anti-Cryptococcus treatment was available. Non-Amphotericin B treatment [AOR:3.4(1.0-11.2)] was associated with 90-day mortality in HIV-infected patients, but age≥50.0years old [AOR:2.7(1.0-2.9)], predisposing disease [AOR:4.1(1.2-14.2)] and altered consciousness [AOR:3.7(1.1-12.9)] were associated with 90-day mortality in HIV-uninfected patients who accepted anti-Cryptococcus treatment. HIV infection increased the incidence of CM rather than mortality in cryptococcemia patients. The predictive model was completely divergent in HIV-infected and HIV-uninfected patients, suggesting that novel strategies for diagnosis and treatment algorithms are urgently needed.

Myosin Heavy Chain-Associated RNA Transcripts Promotes Gastric Cancer Progression Through the miR-4529-5p/ROCK2 Axis

Characterization of genetic aberrations provides novel strategies for diagnosis and treatment of gastric cancer. Accumulating evidence has shown the involvement of long non-coding RNA (lncRNA) in the pathology of gastric cancer, especially in proliferation and metastasis. The aim of this study was to delineate the role of myosin heavy chain-associated RNA transcripts (MHRT), a heart-specific lncRNA, in gastric cancer and to understand the correlation between MHRT, miR-4529-5p, and ROCK2. To study expression level of MHRT, clinical gastric cancer samples, gastric cancer cell lines, adjacent normal tissues, and gastric epithelial cell lines were used. Additionally, apoptosis, proliferation, and invasion of gastric cancer cells were studied with or without downregulation of MHRT and miR-4529-5p. We identified that MHRT was ectopically expressed in gastric cancer tissues and cell lines. Interestingly, similar to the anti-apoptotic role of MHRT in cardiomyocytes, our data illustrated that MHRT inhibits apoptosis of gastric cancer cells. Moreover, we found that MHRT promotes proliferation and invasion of gastric cancer cells in vitro. Importantly, our data revealed that MHRT regulates the expression of miR-4529-5p via direct binding. Additionally, functional experiments illustrated that miR-4529-5p is particularly responsible for MHRT-mediated regulation of apoptosis. Besides, ROCK2 was identified as a downstream target of miR-4529-5p. Additionally, upregulated MHRT promotes the expression of ROCK2 by inhibiting miR-4529-5p. Our data illustrated a MHRT/miR-4529-5p/ROCK2 regulatory axis that contributes to the tumorigenesis of gastric cancer and provided potential therapeutic targets for precise gastric cancer treatment.

Emerging therapeutic potential of group 2 innate lymphoid cells in acute kidney injury.

Acute kidney injury (AKI) remains a global challenge and, despite the availability of dialysis and transplantation, can be fatal. Those that survive an AKI are at increased risk of developing chronic kidney disease and end stage renal failure. Understanding the fundamental mechanisms underpinning the pathophysiology of AKI is critical for developing novel strategies for diagnosis and treatment. A growing body of evidence indicates that amplifying type 2 immunity may have therapeutic potential in kidney injury and disease. Of particular interest are the recently described subset of innate immune cells, termed group 2 innate lymphoid cells (ILCs). Group 2 ILCs are crucial tissue-resident immune cells that maintain homeostasis and regulate tissue repair at multiple organ sites, including the kidney. They are critical mediators of type 2 immune responses following infection and injury. The existing literature suggests that activation of group 2 ILCs and production of a local type 2 immune milieu is protective against renal injury and associated pathology. In this review, we describe the emerging role for group 2 ILCs in renal homeostasis and repair. We provide an in-depth discussion of the most recent literature that use preclinical models of AKI and assess the therapeutic effect of modulating group 2 ILC function. We debate the potential for targeting these cells as novel cellular therapies in AKI and discuss the implications for future studies and translation. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Abstract 12834: Increased Plasma Serotonin and Circulating microRNA-1914 Reflect Oxidative Stress and Play Crucial Roles in Atherosclerosis

Introduction: Serotonin, synthesized from enterochromaffin cells, modulates vascular tonus and thrombus formation, and mediates development of atherosclerotic plaque. Oxidative stress is involved in vascular inflammation and progression of atherosclerosis. Hypothesis: We hypothesized that plasma serotonin plays a crucial role in increasing oxidative stress and aimed to identify the circulating microRNA(s) associated with serotonin ratio for coronary artery disease (CAD). Methods: Blood was sampled from 120 outpatients with cardiovascular risk factors but without a history of previous cardiovascular events. Serotonin levels both in platelet poor plasma (PPP) and whole blood (WB) were measured with HPLC, and the ratio of serotonin in PPP to that in WB (PPP/WB) was used as an index of platelet activation. For assessment of oxidative stress, serum levels of derivative reactive oxygen metabolites (d-ROM) were measured. Total RNA was isolated from subjects who were scheduled for coronary angiography with suspicion of CAD and a microRNA array analysis was performed. The expression levels of microRNAs were scaled by global normalization. Results: Serotonin levels in both PPP and PPP/WB ratio were significantly correlated with the d-ROM levels. Among enrolled patients, 25 subjects were diagnosed as having CAD. The levels of the PPP/WB ratio of serotonin, d-ROM, and CRP were significantly higher in subjects with CAD than in those without CAD. Logistic regression analysis performed with endpoint of having CAD revealed that the PPP/WB ratio of serotonin was independently associated with CAD. In subjects with CAD, 5 increased microRNAs and 30 decreased microRNAs were identified among more than 2000 microRNAs as compared to those without CAD. Among candidate microRNAs, expression of microRNA-1914 showed significant inverse correlation with PPP/WB ratio (r=-0.61, P&lt;0.05) and d-ROM levels (r=-0.63, P&lt;0.05). Conclusions: A significant association among platelet activation assessed by PPP and PPP/WB ratio and oxidative stress assessed by d-ROM, was detected in individuals with cardiovascular risk factors. Targeting serotonin-oxidative stress axis, and circulating microRNA-1914 may serve as novel strategy for diagnosis of atherosclerotic CAD.

Abstract 4223: Novel strategy for diagnosis of solid tumors by visualization of fusion transcripts

Abstract The discovery of chromosomal translocations as one major cause of cancers has led to the introduction of numerous diagnostic techniques to detect these chromosomal abnormalities. Chromosomal banding, DNA fluorescence in situ hybridization (DNA FISH), and RT PCR are all techniques used for the diagnosis of cancers. Despite the advancement these techniques have brought to the field, they are primarily optimized for the detection of blood cancers and are not very efficient for the detection of solid tumors which are very heterogeneous. One such cancer, Ewing's sarcoma (ES), is a prevalent pediatric, bone and soft tissue tumor that is caused by a chromosomal translocation between Ewing's sarcoma breakpoint region 1 (EWSR1) on chromosome 22 and various members of the ETS protein family. The most common fusion partner, in 85% of cases, is Friend leukemia integration 1 (FLI1) on chromosome 11 which leads to the formation of the fused EWS/FLI1 gene that codes for an aberrant transcription factor. However, even within this single translocation there are multiple breakpoint-fusion scenarios that can occur which results in heterogeneity and increases the chances of a faulty diagnosis with standard techniques. Considering the diversity that exists within the molecular abnormalities that result in Ewing's sarcoma and other solid tumors, there is a need for an alternative and more robust method of detection. The technique of single molecule fluorescence in situ hybridization (smFISH) has been modified by our group to target the EWS/FLI1 transcript that results from the chromosomal fusion; this new technique is referred to as “Fusion FISH”. In Fusion FISH, two differently labeled probe sets are designed to target each half of the EWS/FLI1 fusion transcript. A co-localization of the two probe sets indicates the presence of the EWS/FLI1 translocation and a positive test for Ewing's sarcoma. Preliminary data has established the success of Fusion FISH in detecting both type 1 and type 2 translocations in several Ewing's sarcoma cell lines. The fusion transcript is expressed at similar levels in all cell lines and clearly distinct from the signal of wild type EWS and FLI1 mRNA. Additional studies will examine this new technique in other solid cancers, patient tumor samples, and for validation of additional relevant mRNA biomarkers. Citation Format: Fatu Badiane Markey, Mona Batish. Novel strategy for diagnosis of solid tumors by visualization of fusion transcripts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4223.

Involvement of Non-coding RNAs in the Signaling Pathways of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common diagnosed cancers worldwide. The metastasis and development of resistance to anti-cancer treatment are major challenges in the treatment of CRC. Understanding mechanisms underpinning the pathogenesis is therefore critical in developing novel agents for CRC treatments. A large number of evidence has demonstrated that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs have functional roles in both the physiological and pathological processes by regulating the expression of their target genes. These molecules are engaged in the pathobiology of neoplastic diseases and are targets for the diagnosis, prognosis and therapy of a variety of cancers, including CRC. In this regard, ncRNAs have emerged as one of the hallmarks of CRC pathogenesis and they also play key roles in metastasis, drug resistance and the stemness of CRC stem cell by regulating various signaling networks. Therefore, a better understanding the ncRNAs involved in the signaling pathways of CRC may lead to the development of novel strategy for diagnosis, prognosis and treatment of CRC. In this chapter, we summarize the latest findings on ncRNAs, with a focus on miRNAs and lncRNAs involving in signaling networks and in the regulation of pathogenic signaling pathways in CRC.

Pythiosis: An endemic fatal infectious disease

Pythiosis is a life threatening infectious disease of humans and animals living in tropical and subtropical areas of the world. The causative agent is the fungus-like microorganism Pythium insidiosum , which is a member of the oomycetes. Most of the pathogenic oomycetes infect plants, several infect animals, and P. insidiosum is capable of infecting humans. Pythiosis in animals has been increasingly found worldwide, while the disease state in humans has been mostly reported in Thailand. Pythiosis has high rate of morbidity and mortality. Patients usually come with clinical features associated with an infection of eye (called ocular pythiosis, which presents with cornea ulcer or keratitis) or arteries (called vascular pythiosis, which presents with claudication and gangrenous ulcer at leg). Diagnosis of pythiosis can be difficult and delayed. Conventional antifungal drugs are not effective against P. insidiosum . Main treatment option for most patients with pythiosis is radical excision of infected organs. In advanced case, death is a final outcome. Information on the disease and its causative agent is limited. It is apparent that more needs to be done in the way of basic and applied research to provide insights into the disease, and thereby lead to the discovery of novel strategies for diagnosis and infection control, such as, better diagnostic assays, new antimicrobial agents, and vaccines. This talk will present update information on the disease, including biology of P. insidiosum , and diagnosis and treatment of pythiosis.

Increased plasma microRNA and CD133/CK18-positive cancer cells in the pleural fluid of a pancreatic cancer patient with liver and pleural metastases and correlation with chemoresistance

We report a case of notably increased plasma levels of microRNA (miR)-21, miR-25, miR-103 and miR-151 in a pancreatic cancer patient with liver and pleural metastases. CD45-coated immunomagnetic beads detected an enrichment of malignant cancer cells in the pleural fluid, and CD133(+)CK18(+) cancer cells were identified. Using computer tomography (CT) combined with cancer cells stained in the pleural fluid, a previously healthy 60-year-old male was diagnosed with pancreatic cancer with multiple liver tumor metastases. Cancer antigen 19-9 (CA19-9), alkaline phosphatase (ALP) and γ-glutamate-transpeptidase (γ-GT) were notably increased in the serum, and carcinoembryonic antigen (CEA) was increased in the pleural fluid. The patient succumbed to the disease three months following standard chemotherapy. The increased levels of plasma miR-21, miR-25, miR-103 and miR-151, as well as the identification of CD133(+)CK18(+) cells in the pleural fluid of a pancreatic cancer patient with liver metastases, may regulate the molecular mechanisms involved in chemoresistance. The patient was insensitive to chemotherapy and succumbed 3 months later. Full elucidation of the molecular and pathological features of pancreatic cancer may be a novel strategy for diagnosis and tailored therapy.

Epigenetic inheritance of disease and disease risk.

Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations. This review examines the challenging possibility that epigenetic changes induced by environmental factors can contribute to some of the inheritance of disease and disease risk. This concept has immense implications for the understanding of biological functions and disease etiology, and provides potential novel strategies for diagnosis and treatment. Examples of epigenetic inheritance relevant to human disease, such as the detrimental effects of traumatic stress or drug/toxic exposure on brain functions, are reviewed. Different possible routes of transmission of epigenetic information involving the germline or germline-independent transfer are discussed, and different mechanisms for the maintenance and transmission of epigenetic information like chromatin remodeling and small noncoding RNAs are considered. Future research directions and remaining major challenges in this field are also outlined. Finally, the adaptive value of epigenetic inheritance, and the cost and benefit of allowing acquired epigenetic marks to persist across generations is critically evaluated.