Critical reviews in clinical laboratory sciences最新文献

Parkinson's disease (PD) is a neurodegenerative condition marked by the gradual depletion of dopaminergic neurons in the substantia nigra. Despite substantial strides in comprehending potential causative mechanisms, the validation of biomarkers with unequivocal evidence for routine clinical application remains elusive. Consequently, the diagnosis heavily relies on patients' clinical assessments and medical backgrounds. The imperative need for diagnostic and prognostic biomarkers arises due to the prevailing limitations of treatments, which predominantly address symptoms without modifying the disease course. This comprehensive review aims to elucidate the existing landscape of diagnostic and prognostic biomarkers for PD, drawing insights from contemporary literature.

This article comprehensively elucidates the discovery of Krebs von den Lungen-6 (KL-6), its structural features, functional mechanisms, and the current research status in various respiratory system diseases. Discovered in 1985, KL-6 was initially considered a tumor marker, but its elevated levels in interstitial lung disease (ILD) led to its recognition as a relevant serum marker for ILD. KL-6 is primarily produced by type 2 alveolar epithelial cell regeneration. Over the past 30 years since the discovery of KL-6, the number of related research papers has steadily increased annually. Following the coronavirus disease 2019 (COVID-19) pandemic, there has been a sudden surge in relevant literature. Despite KL-6's potential as a biomarker, its value in the diagnosis, treatment, and prognosis varies across different respiratory diseases, including ILD, idiopathic pulmonary fibrosis (IPF), COVID-19, and lung cancer. Therefore, as an important serum biomarker in respiratory system diseases, the value of KL-6 still requires further investigation.

Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency (PID) characterized by an impaired immunoglobulin production, in association with an increased susceptibility to infections and a diversity of clinical manifestations. This narrative review summarizes immunophenotypic abnormalities in CVID patients and their relevance for diagnosis and disease classification. A comprehensive search across four databases - PubMED, Web of Science, EMBASE and Google Scholar - yielded 170 relevant studies published between 1988 and April 31, 2023. Over the past decades, the role of immunophenotyping in CVID diagnosis has become evident by identifying "hallmark" immunophenotypic aberrancies in patient subsets, with some now integrated in the consensus diagnostic criteria. Furthermore, the role of immunophenotyping in subclassifying CVID in relation to clinical presentation and prognosis has been extensively studied. Certain immunophenotypic patterns consistently correlate with clinical manifestations and/or subsets of CVID, particularly those associated with noninfectious complications (i.e. low switched memory B cells, shifts in follicular helper T cell subsets, low naïve CD4⁺ T cells, low regulatory T cells, and expansion of CD21low B cells, often associated with autoimmunity and/or splenomegaly). Also, efforts to associate subset levels of innate immune cells, such as Natural Killer (NK) cells, invariant (i)NKT cells, innate lymphoid cells (ILCs), and dendritic cells (DCs) to CVID complications are evident albeit in a lesser degree. However, inconsistencies regarding the role of flow cytometry in classification and prognosis persist, reflecting the disease complexity, but probably also cohort variations and methodological differences between published studies. This underscores the need for collaborative efforts to integrate emerging concepts, such as standardized flow cytometry and computational tools, for a more precise CVID classification approach. Additionally, recent studies suggest a potential value of (epi)genetic-based molecular assays to this effort.

Osteoporosis and sarcopenia are both common age-related disorders that are associated with increased morbidity and mortality. Bone and muscle are metabolically very active tissues that require large amounts of energy. Bile acids (BAs), a group of liver-derived steroid compounds, are primarily known as emulsifiers that facilitate the resorption of dietary fat and lipids. In addition, they have pleiotropic metabolic functions in lipoprotein and glucose metabolism, inflammation, and intestinal bacterial growth. Through these effects, they are related to metabolic diseases, such as diabetes, hypertriglyceridemia, atherosclerosis, and nonalcoholic steatohepatitis. BAs mediate their metabolic effects through receptor dependent and receptor-independent mechanisms. Emerging evidence suggests that BAs are also involved in bone and muscle metabolism. Under normal circumstances, BAs support bone health by shifting the delicate equilibrium of bone turnover toward bone formation. In contrast, low or excessive amounts of BAs promote bone resorption. In cholestatic liver disease, BAs accumulate in the liver, reach toxic concentrations in the circulation, and thus may contribute to bone loss and muscle wasting. In addition, the measurement of BAs is in rapid evolution with modern mass spectrometry techniques that allow for the detection of a continuously growing number of BAs. This review provides a comprehensive overview of the biochemistry, physiology and measurement of bile acids. Furthermore, it summarizes the existing literature regarding their role in bone and muscle.

Natriuretic peptides (NP) play an essential role in heart failure (HF) regulation, and their measurement has improved diagnostic and prognostic accuracy. Clinical symptoms and objective measurements, such as NP levels, should be included in the HF definition to render it more reliable and consistent among observers, hospitals, and healthcare systems. BNP and NT-proBNP are reasonable surrogates for cardiac disease, and their measurement is critical to early diagnosis and risk stratification of HF patients. NPs should be measured in all patients presenting with dyspnea or other symptoms suggestive of HF to facilitate early diagnosis and risk stratification. Both BNP and NT-proBNP are currently used for guided HF management and display comparable diagnostic and prognostic accuracy. Standardized cutoffs for each NP assay are essential for data comparison. The value of NP testing is recognized at various levels, including patient empowerment and education, analytical and operational issues, clinical HF management, and cost-effectiveness.

Nucleic acids, like DNA and RNA, serve as versatile recognition elements in electrochemical biosensors, demonstrating notable efficacy in detecting various cancer biomarkers with high sensitivity and selectivity. These biosensors offer advantages such as cost-effectiveness, rapid response, ease of operation, and minimal sample preparation. This review provides a comprehensive overview of recent developments in nucleic acid-based electrochemical biosensors for cancer diagnosis, comparing them with antibody-based counterparts. Specific examples targeting key cancer biomarkers, including prostate-specific antigen, microRNA-21, and carcinoembryonic antigen, are highlighted. The discussion delves into challenges and limitations, encompassing stability, reproducibility, interference, and standardization issues. The review suggests future research directions, exploring new nucleic acid recognition elements, innovative transducer materials and designs, novel signal amplification strategies, and integration with microfluidic devices or portable instruments. Evaluating these biosensors in clinical settings using actual samples from cancer patients or healthy donors is emphasized. These sensors are sensitive and specific at detecting non-communicable and communicable disease biomarkers. DNA and RNA's self-assembly, programmability, catalytic activity, and dynamic behavior enable adaptable sensing platforms. They can increase biosensor biocompatibility, stability, signal transduction, and amplification with nanomaterials. In conclusion, nucleic acids-based electrochemical biosensors hold significant potential to enhance cancer detection and treatment through early and accurate diagnosis.

Calcium is a fundamental and integrative element and helps to ensure optimal health by regulating various physiological and pathological processes. While there is substantiated evidence confirming the beneficial effects of calcium in the treatment, management, and prevention of various health conditions, including cancer, conflicting studies are imperative to acknowledge the potential negative role of calcium supplementation. The studies on calcium supplementation showed that a specific dose can help in the maintenance of good human health, and in the control of different types of diseases, including cancer. Calcium alone and when combined with vitamin D, emerges as a promising therapeutic option for efficiently managing cancer growth, when used with chemotherapy. Combination therapy is considered a more effective approach for treating advanced types of colorectal cancer. Nevertheless, several challenges drastically influence the treatment of cancer, such as individual discrepancy, drug resistance, and stage of cancer, among others. Henceforth, novel preventive, reliable therapeutic modalities are essential to control and reduce the incidence and mortality of colorectal cancer (CRC). The calcium-sensing receptor (CaSR) plays a pivotal role in calcium homeostasis, metabolism, and regulation of oncogenesis. Numerous studies have underscored the potential of CaSR, a G protein-coupled receptor, as a potential biomarker and target for colorectal cancer prevention and treatment. The multifaceted involvement of CaSR in anti-inflammatory and anti-carcinogenic processes paves the way for its utilization in the diagnosis and management of colorectal cancer. The current review highlights the important role of supplemental calcium in overall health and disease, along with the exploration of intricate mechanisms of CaSR pathways in the management and prevention of colorectal cancer.

KIF2C/MCAK (KIF2C) is the most well-characterized member of the kinesin-13 family, which is critical in the regulation of microtubule (MT) dynamics during mitosis, as well as interphase. This systematic review briefly describes the important structural elements of KIF2C, its regulation by multiple molecular mechanisms, and its broad cellular functions. Furthermore, it systematically summarizes its oncogenic potential in malignant progression and performs a meta-analysis of its prognostic value in cancer patients. KIF2C was shown to be involved in multiple crucial cellular processes including cell migration and invasion, DNA repair, senescence induction and immune modulation, which are all known to be critical during the development of malignant tumors. Indeed, an increasing number of publications indicate that KIF2C is aberrantly expressed in multiple cancer entities. Consequently, we have highlighted its involvement in at least five hallmarks of cancer, namely: genome instability, resisting cell death, activating invasion and metastasis, avoiding immune destruction and cellular senescence. This was followed by a systematic search of KIF2C/MCAK's expression in various malignant tumor entities and its correlation with clinicopathologic features. Available data were pooled into multiple weighted meta-analyses for the correlation between KIF2C^high protein or gene expression and the overall survival in breast cancer, non-small cell lung cancer and hepatocellular carcinoma patients. Furthermore, high expression of KIF2C was correlated to disease-free survival of hepatocellular carcinoma. All meta-analyses showed poor prognosis for cancer patients with KIF2C^high expression, associated with a decreased overall survival and reduced disease-free survival, indicating KIF2C's oncogenic potential in malignant progression and as a prognostic marker. This work delineated the promising research perspective of KIF2C with modern in vivo and in vitro technologies to further decipher the function of KIF2C in malignant tumor development and progression. This might help to establish KIF2C as a biomarker for the diagnosis or evaluation of at least three cancer entities.

Extracellular vesicles (EVs) are nano-sized particles secreted by most cells. They transport different types of biomolecules (nucleic acids, proteins, and lipids) characteristic of their tissue or cellular origin that can mediate long-distance intercellular communication. In the case of cancer, EVs participate in tumor progression by modifying the tumor microenvironment, favoring immune tolerance and metastasis development. Consequently, EVs have great potential in liquid biopsy for cancer diagnosis, prognosis and follow-up. In addition, EVs could have a role in cancer treatment as a targeted drug delivery system. The intense research in the EV field has resulted in hundreds of patents and the creation of biomedical companies. However, methodological issues and heterogeneity in EV composition have hampered the advancement of EV validation trials and the development of EV-based diagnostic and therapeutic products. Consequently, only a few EV biomarkers have moved from research to clinical laboratories, such as the ExoDx Prostate IntelliScore (EPI) test, a CLIA/FDA-approved EV prostate cancer diagnostic test. In addition, the number of large-scale multicenter studies that would clearly define biomarker performance is limited. In this review, we will critically describe the different types of EVs, the methods for their enrichment and characterization, and their biological role in cancer. Then, we will specially focus on the parameters to be considered for the translation of EV biology to the clinic laboratory, the advances already made in the field of EVs related to cancer diagnosis and treatment, and the issues still pending to be solved before EVs could be used as a routine tool in oncology.