Critical reviews in clinical laboratory sciences最新文献

Cancer is a major global public health problem. Epigenetic regulation, such as DNA methylation, histone modifications, and non-coding RNA (ncRNA) dysregulation, is a main driver of tumorigenesis and progression. Recent studies are suggesting that the human microbiota, commonly referred to as a "super-organ," are not only associated with tumors but play an active role in regulating the epigenetic state of the host. The aim of this review is to systematically explain the main regulatory mechanisms of the "microbiota-epigenetic-cancer regulatory axis", their heterogeneous manifestations across various tumors, and the exploration of novel diagnostic biomarkers and therapeutic strategies of this regulatory axis. Microbiota mainly drive tumor epigenetic remodeling through three levels. First, microbial metabolites (e.g., butyrate) can act as natural histone deacetylase inhibitors (HDACis), or tryptophan metabolites can directly regulate the host chromatin state by activating the aryl hydrocarbon receptor (AhR) pathway. Second, bacterial structures such as lipopolysaccharide (LPS) can induce inflammation and disease by activating inflammatory signaling pathways. Third, specific pathogens like HBV and Helicobacter pylori can hijack the host's epigenetic machinery or induce epigenetic reprogramming via virulence factors. The tumor-resident microbiota (TRM) is an emerging and important field. TRM that actively partake in the tumor microenvironment (TME) may promote immune evasion through in situ mechanisms (e.g., lactylation), thereby confirming a direct and causal role for microbes within tumors. The epigenetic therapeutic strategies based on these mechanisms are being rapidly developed, including, for example, the regulation of microbial community structure (e.g., FMT), the targeting of microbial metabolic pathways, and TRM-specific approaches and key pathways (e.g., engineered bacteria). These strategies also have great potential as biomarkers for tumor prognosis prediction and therapy response evaluation. Overall, microbes and tumor epigenetics are part of a network that brings together their metabolism, inflammation, immunity, and gene regulation. Future research will shift from exploring the correlation of the gut microbiota at the macro level to exploring TRM's causality within the TME. By using gnotobiotic mouse models, organoid co-cultures, and multiomics, we will deeply analyze the microenvironment specificity of this network and develop precision interventions targeting TRM that could transform cancer therapy.

Laboratory diagnostics of diseases have improved significantly with modern laboratory techniques offering greater accuracy, earlier detection, and opportunities for personalized diagnosis. This review highlights the key techniques used in the diagnostics of autoimmune rheumatic diseases. Detection of autoantibodies is the basis for modern laboratory diagnostics of autoimmune rheumatic diseases. Immunofluorescent analysis, enzyme-linked immunosorbent assay, chemiluminescent immunoassay, and immunoblotting are nowadays common methods for differential diagnostics, screening, and monitoring the progression of autoimmune diseases. Polymerase chain reaction methods allow the identification of genetic markers associated with autoimmune disorders, which facilitates early diagnosis. Next Generation Sequencing allows for comprehensive analysis of genetic variants, identifying novel biomarkers, and furthering our understanding of disease mechanisms. Diagnostics and treatment are now approaching personalized medicine based mainly on modern molecular discoveries. Such an approach aims to determine disease risk, tailor treatment to individual patient needs, improve safety and efficacy, and reduce treatment costs. This review covers essential laboratory techniques for diagnosing autoimmune rheumatic diseases and aims to serve as a reliable resource for clinicians, including rheumatologists, and researchers.

Loop-mediated isothermal amplification (LAMP) has emerged as a rapid and accessible alternative to traditional polymerase chain reactions (PCR) for nucleic acid amplification in research, significantly enhancing pathogen detection in infectious disease diagnostics. This review aims to bridge the gap in the literature regarding the real-world applications of LAMP assays and their potential to improve infectious disease diagnostics across various healthcare settings. We evaluated the current landscape of United States Food and Drug Administration (FDA)-authorized LAMP-based microbial tests, categorizing 30 such tests and detailing their regulatory pathways, such as 510(k) clearance and Emergency Use Authorization (EUA), particularly in response to the COVID-19 pandemic. We comprehensively examine the technical characteristics of LAMP assays, including sample collection, nucleic acid extraction, amplification processes, signal detection, device automation, and their analytical and clinical performance. We highlight the versatility of LAMP assays in diagnostic applications and their growing role in rapid infectious disease. We discuss the advantages and limitations of LAMP technology and identify future directions for its development in infectious disease diagnostics. By analyzing FDA-authorized LAMP-based microbial tests, this review aims to guide healthcare professionals and support future research and product development, ultimately improving patient care.

Several immune/inflammatory components have been associated with arthritis. The role of monocytes/macrophages in inflammatory arthritis has been explored over the last years; however, the role of other myeloid cells, such as neutrophils and dendritic cells, in driving the pathophysiology of arthritis is largely overlooked. In this article, we aim to discuss literature pointing to the role of these immune cells in inflammatory arthritis and emphasize the multiple and dynamic phenotypic roles these cells can hold either in the persistence or in the resolution of inflammation. We also highlight the interactions between neutrophils, macrophages, and/or dendritic cells in the arthritic joint space. We further discuss pathways and features that may be of importance for characterizing neutrophils and dendritic cells, the phenotype of which can be "reprogrammed" to direct the resolution of inflammation efficiently in the arthritic joint. Identifying novel and patient-tailored approaches for addressing persistent or recurrent inflammation through these cellular pathways, might address unmet needs in arthritis management. Types of arthritides discussed in this review include osteoarthritis, spondyloarthritis and rheumatoid arthritis. Brief reference to the role of these immune cells in the acute gouty inflammation is also included.

Raman spectroscopy is an important diagnostic method that extracts molecular-level information from biological specimens, with distinct potential for disease diagnoses. However, its clinical application has been limited by the challenges associated with spectral interpretation. Deep learning (DL) represents an important new approach in which selected Raman spectroscopy experiments can be automated, offering the potential for higher classification accuracy. This paper highlights recent efforts toward the integration of Raman spectroscopy and DL for medical applications and elaborates on key DL models, including Convolutional Neural Networks (CNNs), Long Short-Term Memory (LSTMs), and Generative Adversarial Networks (GANs), which can collect relevant features, denoise spectra, and provide enhanced diagnostic value from biological specimens. The use of DL in Raman spectroscopy has produced impressive results in cancer diagnosis, bacterial identification, and viral diagnostics. Therefore, this paper provides an organized introduction to explore existing DL architectures used in Raman spectroscopy, their advantages and limitations, and opportunities for clinical applications. Collectively, DL with Raman spectroscopy provides a unique approach for noninvasive and reliable diagnostics.

Over the past 60 years, preventative public health screening programs have evolved since their inception and now include newborn screening (NBS) aimed at identifying infants after birth for a number of rare, congenital, inherited diseases. Most of the conditions detected through NBS are autosomal recessive disorders or exhibit X-linked inheritance, meaning that family members of individuals with these conditions have a higher risk for being either affected or obligate heterozygotes. For example, the X-linked adrenoleukodystrophy (X-ALD) in the screening panel identifies affected newborns and asymptomatic relatives through subsequent testing. Thus, NBS becomes a gateway to family-wide prevention, through the application of reverse cascade testing (RCS). In this paper we examined the scenarios where RCS may be appropriate. Accordingly, we have identified a list of criteria assessing whether a NBS disease would benefit from RCS: (1) autosomal recessive or X-linked inheritance; (2) high carrier rates, (3) variable expressivity, (4) mild or late-onset forms; and (5) association with diagnostic delays and recent addition to the screening panel. More than one criterion usually needs to be met for a disease to benefit from RCS. We have identified a list of diseases and highlighted the potential benefits of RCS: X-ALD, Cystic Fibrosis, Sickle Cell Disease, Spinal Muscular Atrophy and Pompe disease. There are additional scenarios within NBS where disease maternal conditions (3-methylcrotonyl-CoA carboxylase deficiency and carnitine uptake deficiency) or nutritional maternal conditions (vitamin B12 deficiency) may cause a screen-positive NBS result. Whenever a maternal nutritional deficiency is a potential reason for a positive NBS, this is indicative of a non-inherited condition that may require treatment in the newborn owing to possible neurological damage and delay in normal growth in newborns with certain secondary deficiencies. For these cases RCS is recommended, as the mother's status may put her at risk for future adverse events (i.e. cardiovascular and musculoskeletal disorders, hepatic involvement, and neurodegeneration). The RCS-NBS strategy discussed in this paper offers a set of criteria against which diseases can be assessed for the potential need for RCS. Implementation of this strategy requires several considerations including educational needs, ethical issues, uptake of testing, logistics and costs for this expanded screening and counseling, and availability of appropriate specialists for ongoing management.

Circulating plasma DNA has found important applications in diverse medical fields, including prenatal testing, transplantation, and especially cancer. Many companies have developed products for detecting minimal residual disease, selecting or monitoring therapy, assessing prognosis, and confirming diagnosis. One major application is in screening asymptomatic individuals for the presence of cancer. Screening may facilitate better clinical outcomes through earlier interventions. Collectively, these technologies are widely known as "liquid biopsies". After the extraction of free DNA from the circulation, it is analyzed by various molecular techniques to explore differences between DNA originating from normal cells and cancer cells. Circulating plasma DNA originating from tumors (ctDNA) is expected to harbor the same molecular changes as tumor tissue itself. Thus, ctDNA is considered a surrogate of cancer tissue, but without the need to perform invasive biopsies to obtain it. Many new diagnostic companies have taken advantage of this new biomarker and developed technologies for screening for one or multiple cancers. We previously estimated the amount of ctDNA in circulation, which is admixed with DNA originating from normal cells. We concluded that since only a small fraction of the whole plasma (3 liters) is used for testing (3 to 4 mL), it is possible that the retrieved ctDNA may not be enough for cancer diagnosis in all patients. This problem is more acute with small tumors. Here, we mention some companies in the "liquid biopsy" arena and analyze their clinical data to establish if their tests are close to entering the clinic. We conclude from this analysis that current data do not support the use of these technologies for population screening due to many false negative and false positive results.

Post-translational modifications (PTMs) are critical regulators of protein function. Nearly two-thirds of all human proteins contain at least one PTM. These PTMs introduce covalent modifications, which modulate protein activity, location, and interactions. Further, PTMs are essential for understanding both physiological homeostasis and pathophysiology, and they play a key role in tumorigenesis and cancer development. Tumor immune evasion depends on dysregulated immune homeostasis caused by interactions between tumor cells and immune cells in the tumor microenvironment (TME). In this context, PTMs have emerged as one of the key regulators. From a pan-cancer perspective, PTMs remodel the tumor immune microenvironment through diverse mechanisms. The inability to regulate these processes is a common factor contributing to immune evasion in various cancers. It also facilitates crosstalk between tumor cells and components of TME, which in turn influences the response to immunotherapy. Because PTMs are dysregulated in cancers and can be reversed through drugs, they are attractive therapeutic targets. Small-molecule modulators of PTMs have the potential to reprogram the immune microenvironment and improve immune checkpoint blockade responses. Importantly, wide-ranging signal exchange networks between PTMs collectively increase tumoral immune phenotypic diversity and reveal new shared mechanisms of pan-cancer immune evasion. Recent studies show that the ways tumor cells change their surface proteins are driven by alterations in the tumor-immune environment. Further work could lead to strategies to treat many different cancers. Targeting PTM networks may overcome immune tolerance and significantly improve the clinical prognosis of cancer patients.

The One Health Approach recognizes the interconnectedness of human, animal, and environmental health. Emerging infectious diseases, climate change, and food/water insecurity impact all three. Global health improvement requires collaborative, holistic strategies at all levels to mitigate harmful factors and promote sustainable development. This review defines the One Health approach and illustrates its role in combating antibiotic resistance, emerging infectious diseases, and food/water insecurity. Laboratory medicine for both human and veterinary health, as well as environmental monitoring, are crucial in this context.