Molecular Diagnosis & Therapy最新文献

{"title":"The Complement System and C4b-Binding Protein: A Focus on the Promise of C4BPα as a Biomarker to Predict Clopidogrel Resistance.","authors":"Hong-Guang Xie, Li-Ping Jiang, Ting Tai, Jin-Zi Ji, Qiong-Yu Mi","doi":"10.1007/s40291-023-00691-w","DOIUrl":"10.1007/s40291-023-00691-w","url":null,"abstract":"<p><p>The complement system plays a dual role in the body, either as a first-line defense barrier when balanced between activation and inhibition or as a potential driver of complement-associated injury or diseases when unbalanced or over-activated. C4b-binding protein (C4BP) was the first circulating complement regulatory protein identified and it functions as an important complement inhibitor. C4BP can suppress the over-activation of complement components and prevent the complement system from attacking the host cells through the binding of complement cleavage products C4b and C3b, working in concert as a cofactor for factor I in the degradation of C4b and C3b, and consequently preventing or reducing the assembly of C3 convertase and C5 convertase, respectively. C4BP, particularly C4BP α-chain (C4BPα), exerts its unique inhibitory effects on complement activation and opsonization, systemic inflammation, and platelet activation and aggregation. It has long been acknowledged that crosstalk or interplay exists between the complement system and platelets. Our unpublished preliminary data suggest that circulating C4BPα exerts its antiplatelet effects through inhibition of both complement activity levels and complement-induced platelet reactivity. Plasma C4BPα levels appear to be significantly higher in patients sensitive to, rather than resistant to, clopidogrel, and we suggest that a plasma C4BPα measurement could be used to predict clopidogrel resistance in the clinical settings.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"189-199"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139522185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Fluid Biomarkers for Diagnosis and Prognosis in Children with Mild Traumatic Brain Injury: A Systematic Review.","authors":"Armaan K Malhotra, Kentaro Ide, Zaid Salaheen, Quenby Mahood, Jessie Cunningham, Jamie Hutchison, Anne-Marie Guerguerian","doi":"10.1007/s40291-023-00685-8","DOIUrl":"10.1007/s40291-023-00685-8","url":null,"abstract":"<p><strong>Background and objective: </strong>Fluid biomarkers have the potential to improve the accuracy of diagnosis and prognosis in children with mild traumatic brain injury. Our primary objective was to assess the diagnostic and prognostic utility of acute blood and fluid biomarkers in children with mild traumatic brain injury.</p><p><strong>Methods: </strong>We performed a systematic review of the published literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Fluid biomarker studies assessing pediatric mild traumatic brain injury diagnosis or prognosis were included if blood or fluids were sampled within 24 h of injury.</p><p><strong>Results: </strong>Thirty-two studies involving 4743 patients were included comprising 25 diagnostic studies and ten prognostic studies with three studies assessing both diagnosis and prognosis. Sixteen of the 25 diagnostic studies reported the area under the receiver operating characteristic curve (AUC) for predicting abnormal computed tomography scans of the head; S100 calcium binding protein B (S100B, N = 6 studies, AUC range 0.67-1.00), glial fibrillary acidic protein (N = 5, AUC range 0.41-0.85), ubiquitin C-terminal hydrolase (N = 3, AUC 0.59 and 0.83), neuron specific enolase (N = 1, AUC 0.99), total tau (N = 1, AUC 0.65), and interleukin-6 (N = 1, AUC 0.61). In four of the ten prognostic studies, increased acute serum S100B levels, tumor necrosis factor-α, or interleukin-8 were associated with post-concussive symptoms or fatigue from 3 to 12 months post-injury.</p><p><strong>Conclusions: </strong>The largest amount of evidence supported the potential use of S100B, glial fibrillary acidic protein, and UCH-L1, but there was mixed accuracy for diagnosis and prognostication for all biomarkers in pediatric mTBI.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"169-187"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138832644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling Emerging Anal Cancer Clinical Biomarkers from Current Immuno-Oncogenomics Advances.","authors":"Soledad Iseas, Golubicki Mariano, Louis Gros, Nabil Baba-Hamed, Vincent De Parades, Julien Adam, Eric Raymond, Martin Carlos Abba","doi":"10.1007/s40291-023-00692-9","DOIUrl":"10.1007/s40291-023-00692-9","url":null,"abstract":"<p><p>Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk human papillomavirus (HPV) and is currently one of the fastest-growing causes of cancer incidence and mortality in developed countries. Although next-generation sequencing technologies (NGS) have revolutionized cancer and immuno-genomic research in various tumor types, a limited amount of clinical research has been developed to investigate the expression and the functional characterization of genomic data in ASCC. Herein, we comprehensively assess recent advancements in \"omics\" research, including a systematic analysis of genome-based studies, aiming to identify the most relevant ASCC cancer driver gene expressions and their associated signaling pathways. We also highlight the most significant biomarkers associated with anal cancer progression, gene expression of potential diagnostic biomarkers, expression of therapeutic drug targets, and emerging treatment opportunities. This review stresses the urgent need for developing target-specific therapies in ASCC. By illuminating the molecular characteristics and drug-target expression in ASCC, this study aims to provide insights for the development of precision medicine in anal cancer.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"201-214"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta‑Analysis\".","authors":"Wei Han, Li-Zhou Shi, Yu-Wei Zhang, Hao-Nan Wang","doi":"10.1007/s40291-024-00700-6","DOIUrl":"10.1007/s40291-024-00700-6","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"237-238"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADORA3: A Key Player in the Pathogenesis of Intracranial Aneurysms and a Potential Diagnostic Biomarker.","authors":"Rui-Ting Hu, Hao-Wei Deng, Wen-Bin Teng, Shao-Dan Zhou, Zi-Ming Ye, Zi-Mei Dong, Chao Qin","doi":"10.1007/s40291-024-00694-1","DOIUrl":"10.1007/s40291-024-00694-1","url":null,"abstract":"<p><strong>Background: </strong>The effects of genes on the development of intracranial aneurysms (IAs) remain to be elucidated, and reliable blood biomarkers for diagnosing IAs are yet to be established. This study aimed to identify genes associated with IAs pathogenesis and explore their diagnostic value by analyzing IAs datasets, conducting vascular smooth muscle cells (VSMC) experiments, and performing blood detection.</p><p><strong>Methods: </strong>IAs datasets were collected and the differentially expressed genes were analyzed. The selected genes were validated in external datasets. Autophagy was induced in VSMC and the effect of selected genes was determined. The diagnostic value of selected gene on the IAs were explored using area under curve (AUC) analysis using IAs plasma samples.</p><p><strong>Results: </strong>Analysis of 61 samples (32 controls and 29 IAs tissues) revealed a significant increase in expression of ADORA3 compared with normal tissues using empirical Bayes methods of \"limma\" package; this was further validated by two external datasets. Additionally, induction of autophagy in VSMC lead to upregulation of ADORA3. Conversely, silencing ADORA3 suppressed VSMC proliferation and autophagy. Furthermore, analysis of an IAs blood sample dataset and clinical plasma samples demonstrated increased ADORA3 expression in patients with IA compared with normal subjects. The diagnostic value of blood ADORA3 expression in IAs was moderate when analyzing clinical samples (AUC: 0.756). Combining ADORA3 with IL2RB or CCR7 further enhanced the diagnostic ability for IAs, with the AUC value over 0.83.</p><p><strong>Conclusions: </strong>High expression of ADORA3 is associated with IAs pathogenesis, likely through its promotion of VSMC autophagy. Furthermore, blood ADORA3 levels have the potential to serve as an auxiliary diagnostic biomarker for IAs.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"225-235"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139718009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chimeric Genes Causing 11β-Hydroxylase Deficiency: Implications in Clinical and Molecular Diagnosis.","authors":"Paola Concolino","doi":"10.1007/s40291-024-00697-y","DOIUrl":"10.1007/s40291-024-00697-y","url":null,"abstract":"<p><p>Deficiency of 11β-hydroxylase (11β-OHD) is the second most common cause of congenital adrenal hyperplasia (CAH), accounting for 0.2-8% of all cases. The disease is transmitted as an autosomal recessive trait and the underlying genetic causes of 11β-OHD are primarily small pathogenic variants affecting the CYP11B1 gene coding the 11β-hydroxylase enzyme. However, special events complicate the molecular diagnosis of 11β-OHD such as an unequal crossing over between the CYP11B2 (coding aldosterone synthase enzyme) and CYP11B1 genes. The resulting allele contains a hybrid gene, with a CYP11B2 5'-end and a CYP11B1 3'-end, where the CYP11B1 gene is under the control of the CYP11B2 promoter and thus not responding to the adrenocorticotropin (ACTH) but to angiotensin II and K⁺. This leads a reduction of cortisol production in 11β-OHD. In particular, CYP11B2/CYP11B1 chimeric genes can be distinguished into two groups depending on the breakpoint site: chimeras with breakpoint after the exon 5 of CYP11B2 preserve the aldosterone synthase activity, the others with breakpoint before exon 5 lose this function. In the last case, a more severe phenotype is expected. The aim of this review was to explore the setting of CYP11B2/CYP11B1 chimeras in 11β-OHD, performing a careful review of clinical literature cases.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"215-224"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clostridium Bacteria: Harnessing Tumour Necrosis for Targeted Gene Delivery","authors":"Jan Theys, Adam V. Patterson, Alexandra M. Mowday","doi":"10.1007/s40291-024-00695-0","DOIUrl":"https://doi.org/10.1007/s40291-024-00695-0","url":null,"abstract":"<p>Necrosis is a common feature of solid tumours that offers a unique opportunity for targeted cancer therapy as it is absent from normal healthy tissues. Tumour necrosis provides an ideal environment for germination of the anaerobic bacterium <i>Clostridium</i> from endospores, resulting in tumour-specific colonisation. Two main species, <i>Clostridium novyi</i>-NT and <i>Clostridium sporogenes</i>, are at the forefront of this therapy, showing promise in preclinical models. However, anti-tumour activity is modest when used as a single agent, encouraging development of <i>Clostridium</i> as a tumour-selective gene delivery system. Various methods, such as allele-coupled exchange and CRISPR–cas9 technology, can facilitate the genetic modification of <i>Clostridium</i>, allowing chromosomal integration of transgenes to ensure long-term stability of expression. Strains of <i>Clostridium</i> can be engineered to express prodrug-activating enzymes, resulting in the generation of active drug selectively in the tumour microenvironment (a concept termed <i>Clostridium</i>-directed enzyme prodrug therapy). More recently, <i>Clostridium</i> strains have been investigated in the context of cancer immunotherapy, either in combination with immune checkpoint inhibitors or with engineered strains expressing immunomodulatory molecules such as IL-2 and TNF-α. Localised expression of these molecules using tumour-targeting <i>Clostridium</i> strains has the potential to improve delivery and reduce systemic toxicity. In summary, <i>Clostridium</i> species represent a promising platform for cancer therapy, with potential for localised gene delivery and immunomodulation selectively within the tumour microenvironment. The ongoing clinical progress being made with <i>C. novyi</i>-NT, in addition to developments in genetic modification techniques and non-invasive imaging capabilities, are expected to further progress <i>Clostridium</i> as an option for cancer treatment.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139664011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Ability of Serum Amino Acid Levels to Differentiate Fibromyalgia Patients from Healthy Subjects.","authors":"Alma Rus, José Alberto López-Sánchez, José Manuel Martínez-Martos, María Jesús Ramírez-Expósito, Francisco Molina, María Correa-Rodríguez, María Encarnación Aguilar-Ferrándiz","doi":"10.1007/s40291-023-00677-8","DOIUrl":"10.1007/s40291-023-00677-8","url":null,"abstract":"<p><strong>Background: </strong>Fibromyalgia is a complex illness to diagnose and treat.</p><p><strong>Objectives: </strong>To evaluate a broad range of circulating free amino acid (AA) levels in fibromyalgia patients as well as the ability of the AAs to differentiate fibromyalgia patients from healthy subjects.</p><p><strong>Design: </strong>We carried out a case-control study to evaluate AA levels in 62 patients with fibromyalgia and 78 healthy subjects. This study adheres to the STROBE guidelines.</p><p><strong>Methods: </strong>AAs content was assayed by HPLC in serum samples. The predictive value of AA levels in fibromyalgia was determined by receiver operating characteristic (ROC) curve and forward binary logistic regression analyses.</p><p><strong>Results: </strong>Fibromyalgia patients showed higher serum levels of aspartic acid, glutamic acid, aminoadipic acid, asparagine, histidine, 3-methyl-histidine, 5-methyl-histidine, glycine, threonine, taurine, tyrosine, valine, methionine, isoleucine, phenylalanine, leucine, ornithine, lysine, branched chain AAs (BCAAs), large neutral AAs, essential AAs (EAAs), non-essential AAs (NEAAs), basic AAs, EAAs/NEAAs ratio, phenylalanine/tyrosine ratio, and global arginine bioavailability ratio than the controls. Serum alanine levels were lower in patients than in controls. According to ROC analysis, most of these AAs may be good markers for differentiating individuals with fibromyalgia from healthy subjects. Results of logistic regression showed that the combination of glutamic acid, histidine, and alanine had the greatest predictive ability to diagnose fibromyalgia.</p><p><strong>Conclusions: </strong>Our results show an imbalance in serum levels of most AAs in patients with fibromyalgia, which suggest a metabolic disturbance. The determination of serum levels of these AAs may aid in the diagnosis of fibromyalgia, in combination with clinical data of the patient.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"113-128"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41240334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saliva Collection Methods Among Children and Adolescents: A Scoping Review.","authors":"Juliette M H Fey, Floris J Bikker, Daniela Hesse","doi":"10.1007/s40291-023-00684-9","DOIUrl":"10.1007/s40291-023-00684-9","url":null,"abstract":"<p><strong>Objective: </strong>Saliva can be used for screening and diagnostic purposes. Although multiple saliva collection methods are available, their use in children can be limited due to lack of cooperation, developmental stage, and age. The aim of this scoping review was to comprehensively appraise the different methods of saliva collection among both children and adolescents by assessing the available scientific literature.</p><p><strong>Methods: </strong>A literature search was performed using the databases PubMed, Embase, and Web of Science. Eligible studies on saliva collection methods among children and adolescents were included for this review.</p><p><strong>Results: </strong>The literature search identified 249 eligible articles, of which 205 had a cross-sectional study design. Four distinct saliva collection methods have surfaced: the drooling method, the absorption method, the spitting method, and the suction method. Among infants or children under the age of 6 years, the suction and absorption methods were most preferred. The drooling and spitting methods were only applicable among children above the age of 3 years. When children were not willing to cooperate, the absorption method was most feasible. In adolescents and older children, no specific method was found to be preferred over another method.</p><p><strong>Conclusion: </strong>Overall, saliva collection is well tolerated by children and adolescents, with the absorption and suction methods being preferred with young and uncooperative children.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"15-26"},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10786738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72211623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Recent Advancements in Nanomaterials: A Promising Way to Manage Neurodegenerative Disorders.","authors":"Thuy Trang Nguyen, Phuong-Trang Nguyen-Thi, Thi Hong Anh Nguyen, Thanh-Tam Ho, Nguyen-Minh-An Tran, Toi Van Vo, Giau Van Vo","doi":"10.1007/s40291-023-00682-x","DOIUrl":"10.1007/s40291-023-00682-x","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"131"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50163433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}