查看更多>>摘要：? 2022 Elsevier B.V.Atherosclerosis (AS) is a chronic inflammatory lesion of the arterial vessel wall caused by a variety of complex factors. Furthermore, it is a major cause of cardiovascular disease and a leading cause of death. Circular RNAs (circRNAs) are a new family of endogenous non-coding RNAs with unique covalently closed loops that have sparked interest due to their unique characteristics and potential diagnostic and therapeutic applications in various diseases. A growing number of studies have shown that circRNAs can be used as biomarkers for the diagnosis and treatment of AS. In this article, we review the biogenesis, classification as well as functions of circRNA and summarize the research on circRNA as a diagnostic biomarker for AS. Finally, we describe the regulatory capacity of circRNA in AS pathogenesis through its pathogenesis and demonstrate the potential therapeutic role of circRNA for AS.
查看更多>>摘要：? 2022 The AuthorsMutations in RET have been found in multiple diseases including isolated and associated congenital anomalies. Here, we report a case presented with disparate phenotypes in each pregnancy but caused by the same novel mutation. Whole-exome sequencing (WES) was performed on the proband/abortion product-parental trio and a novel missense variant in RET (chr10:43615610C > G; c.2689C > G; p.Arg897Gly) was identified. The mother was a low-level somatic carrier of this new mutation, with 17.3% in blood, 19.1% in oral mucous membrane, and 15.7% in urine by droplet digital polymerase chain reaction (dd PCR). Our finding not only broadens the mutation spectrum of RET but also gives supportive genetic counseling and timely guidance on fertility choices.
查看更多>>摘要：? 2022 Elsevier B.V.Glycated hemoglobin (HbA1c) assays are currently utilized to monitor patients with diabetes mellitus type 2 (T2DM). These assays employ various methods, some of which are more prone to interference than others. Commonly recognized causes of interference include hemoglobin variants and conditions that result in reduced red blood cell survival such as hemolytic anemia and certain medications. Enzymatic assays represent one of the predominant methods for HbA1c testing for practical reasons. Herein, we describe a potentially novel interference in an enzymatic HbA1c assay by neoplastic lymphocytes in a patient with chronic lymphocytic leukemia. We hypothesize that the marked number of neoplastic lymphocytes are interfering in the enzymatic steps inherent to this assay, resulting in a discordantly low HbA1c result. Awareness of this possibility and further investigation into the precise mechanism by which this interference is occurring are warranted.
查看更多>>摘要：? 2022 Elsevier B.V.Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic disease characterized by disorders of sex development, commonly caused by mutations of the androgen receptor (AR) gene. Herein, we identified a novel hemizygous mutation (c.2118T > A, p. Asn706Lys) of AR resulting in complete androgen insensitivity syndrome (CAIS) in twins. This missense mutation contributed to significantly decreased mRNA transcription and protein expression. In addition, structure model analysis showed that Asn706Lys resulted in loss of hydrogen bond with Asp891 and reduced protein stability. Furthermore, the mutant AR failed to bind to ligand due to the loss of hydrogen bond with dihydrotestosterone (DHT). This disrupted the translocation of AR protein from cytoplasm to nucleus after hormone stimulation. Our findings firstly demonstrated the novel mutation of c.2118T > A in AR directly caused CAIS. This contributed to expanding the AR mutational spectrum and revealed the pathogenic mechanism of AIS, as well as facilitating precise diagnosis and genetic counseling.
查看更多>>摘要：? 2022 Elsevier B.V.Background and aims: The potential of disease-modifying therapies for Alzheimer's disease has greatly stimulated interest in the development of minimally invasive testing for early identification of at-risk individuals. Accordingly, identification of blood-based biomarkers is paramount. The recent discovery of plasma phosphorylated at threonine217 (p-tau217) may provide a turning point in Alzheimer's disease detection. This systematic review aims to evaluate the available evidence on the use of plasma p-tau217 as a marker to predict Alzheimer's disease and to monitor disease progression. Material and methods: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Study quality was assessed using the QUADAS-2 tool. In total, 676 publications were identified, of which 16 were in accordance with the pre-defined eligibility criteria. Results: Current evidence shows that plasma p-tau217 is a sensitive maker of the clinical manifestation and progression of Alzheimer‘s disease and of pathological changes associated with this condition, including amyloid accumulation, tau burden, brain atrophy and physical degradation. Moreover, given that plasma p-tau217 does not predict such changes in patients with other neurodegenerative disorders, plasma p-tau217 is also specific to Alzheimer's disease. Conclusion: More large, diverse community studies are needed to harmonize plasma p-tau217 measurements and to determine widely applicable diagnostic cut-off values.
查看更多>>摘要：? 2022 Elsevier B.V.Background and aims: Hereditary anemia (HA) encloses a wide group of rare inherited disorders with clinical and hematologic overlaps that complicate diagnosis. Materials and methods: A 48-gene panel was developed to diagnose HA by Next Generation Sequencing (NGS) in a large cohort of 165 patients from 160 unrelated families. Results: Patients were divided in: A) patients who had a suspicion of a specific type of HA (n = 109), and B) patients who had a suspicion of HA but with no clear type (n = 56). Diagnostic performance was 83.5% in group A and a change of the initial diagnosis occurred in 11% of these patients. In group B, 35.7% of patients achieved a genetic diagnosis. NGS identified 6 cases of xerocytosis, 6 of pyruvate kinase (PK) deficiency, 4 of G6PD, and 1 case of phytosterolemia with no initial suspicion of these pathologies, which is clinically relevant since they have specific treatment. Five patients were found to carry variants associated to two different pathologies (4 of them combining a metabolic deficiency and a membrane defect), and 44 new variants were identified in 41 patients. Conclusion: The use of NGS is a sensitive technique to diagnose HA and it shows better performance when patients are better characterized.
查看更多>>摘要：? 2022Background: Bartter syndrome is an inherited renal tubular disorder that is characterized by hypokalemic, hypochloremic metabolic alkalosis in which the primary defect is a deficiency of transporters involved in sodium chloride reabsorption. Bartter syndrome type 1 is caused by SLC12A1 mutations. Methods: The patients were from two unrelated non-consanguineous Chinese families. Both patients presented with intrauterine growth retardation, premature delivery, failure to thrive, polyuria and metabolic alkalosis. Whole-exome sequencing was used to identify the causative gene. Results: Exome sequencing identified three novel SLC12A1 mutations in our patients. And we found the two patients had significantly different outcomes when they were two years of age. Moreover, we identified four novel variants of SLC12A1 that were likely to be pathogenic, from our in-house database. A review of the whole-exome sequencing data of patient 1 lead to her brother being genetically diagnosed with pulmonary alveolar microlithiasis, which was caused by compound heterozygous SLC34A2 variations. Conclusion: We reported two children from one family who were affected by different rare conditions. This study expanded the mutation spectra of the SLC12A1 and SLC34A2 genes. We showed the important role of early genetic testing for disease diagnosis and emphasized the importance of standardized treatment and management.
查看更多>>摘要：? 2022 The AuthorsBackground: Pathological abdominal adhesions can cause bowel obstructions. A history of appendectomy (appy) increases patient rehospitalization risk directly related to adhesions. To potentially identify strategies for adhesion treatment, we characterized reactive ascites (rA) collected during appy or adhesiolysis for small bowel obstruction (SBO). Methods: This is a non-randomized, prospective observational study recruiting patients with non-perforated appendicitis or SBO from three Level 1 trauma centers in the United States. rA were analyzed via liquid chromatography-mass spectrometry (LC-MS) (n = 31), bead-based quantification cytokines and chemokines (n = 32) and soluble receptors (n = 30), and LC-MS metabolomics (n = 18). Results: LC-MS showed that samples contained albumin, apolipoprotein A1, and transthyretin and that metabolites increased in SBO vs appy rA were biomarkers of oxidative stress. Multi-plex analyses showed levels of 17 cytokines/chemokines and 6 soluble receptors were significantly different in appy vs SBO rA. Top increased proteins in appy compared to SBO rA by 20.14-, 11.53-, and 8.18-fold were granulocyte-colony stimulating factor, C-X-C motif chemokine ligand 10, and interleukin-10, respectively. Conclusions: These data further define pro- and anti-inflammatory mediators and metabolites that may drive formation or perpetuate chronic abdominal adhesions. Future research is to further explore whether attenuation of these factors may decrease pathologic adhesion formation.
查看更多>>摘要：? 2022 Elsevier B.V.Overproduction of the reactive oxygen, nitrogen, and chlorine species by the immune systems during chronic infection and inflammation can cause structural and functional changes of cellular proteins. The high abundance of hemoglobin in blood makes hemoglobin adducts suitable biomarkers for assessing the damage of these reactive species in the body. In this study, a total of 23 types and sites of modification in human hemoglobin were simultaneously analyzed, including monooxygenation of histidine, tyrosine, methionine, and aspartate, conversion of histidine to aspartate and hydroxyaspartate, as well as chlorination and nitration of tyrosine residues. Hemoglobin was isolated from the blood of the study subjects, digested into peptides, and the extents of these modifications were quantified relative to their parent peptides using nanoflow liquid chromatography nanoelectrospray ionization tandem mass spectrometry under selected reaction monitoring (nanoLC ? NSI-MS/MS-SRM). The extents of monooxygenation at β-His-77 and β-Tyr-130, chlorination at α-Tyr-24 and β-Tyr-130, and nitrosylation at α-Tyr-24 were elevated in gastric cancer patients. Conversely, conversion of histidine to aspartate at α-His-20, α-His-50, β-His-2, β-His-143, and monooxygenation at β-His-143 were decreased in gastric cancer patients. The areas under the receiver operating characteristics (AUC of ROC) curve of these ten types and sites of hemoglobin modifications were between 0.7644 and 0.9644. The ratio of conversion of histidine to hydroxyaspartate versus conversion of histidine to aspartate was significantly higher in gastric cancer patients at α-His-20, α-His-50, and β-His-143 (p < 0.05) with AUC of ROC ranging between 0.7689 and 0.9178. To our knowledge, this is the first report of simultaneous measurement of multiple types of oxidative and advanced oxidative hemoglobin modifications in gastric cancer patients. The results revealed elevated levels of oxidative stress-induced protein damage in gastric cancer patients and the potential of using these modifications of hemoglobin as biomarkers for evaluation of oxidative stress in one drop of blood.
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