Journal of Clinical Laboratory Analysis最新文献

Background: The infection caused by Mycobacterium tuberculosis arises from a complex interplay between the host immune system and the bacteria. Early and effective treatment of this disease is of great importance in order to prevent the emergence of drug-resistant strains. This necessitates the availability of fast and reliable diagnostic methods for managing affected cases. One reason why this study is significant is the lack of a comprehensive review in this field that thoroughly examines the importance, pathogenesis, and diagnosis of M. tuberculosis. Therefore, the aim of this review is to provide updated information on M. tuberculosis.

Methods: We investigate the virulence factors, pathogenicity, and diagnostic methods of this bacterium, alongside the clinical symptoms and interpretation of different types of tuberculosis, including cerebral, miliary, nerve, and tubercular tuberculosis.

Results: Mycobacterium tuberculosis acts as the causative agent of human tuberculosis and is regarded as one of the most adaptable human pathogens. M. tuberculosis possesses several virulence factors that help the bacterium evade mucous barriers. The rise of multidrug-resistant tuberculosis (MDR-TB) in both developing and industrialized countries emphasizes the need for rapid diagnostic methods.

Conclusions: Non-protein virulence factors play a crucial role in the pathogenicity of Mycobacterium tuberculosis (M. tuberculosis). The bacterial cell membrane contains proteins that modulate the host immune response. For instance, ESAT-6, either alone or in combination with CFP-10, reduces immune activity. While molecular techniques-such as DNA microarray, luciferase reporter assay, polymerase chain reaction (PCR), DNA and RNA probes, next-generation sequencing, and whole-genome sequencing-offer rapid, sensitive, and specific detection of M. tuberculosis, these methods are expensive and require technical expertise.

Background: Parkinson's disease (PD) is a common neurodegenerative disease. Glutamate(Glu) excitotoxicity is one of the main pathogenesis of PD. Glutaminase (Gls) is an enzyme primarily responsible for catalyzing the hydrolysis and deamidation of glutamine (Gln) to produce Glu and ammonia. Inhibiting the function of Gls may have a beneficial effect on the treatment of PD by reducing the production of Glu. The homologous gene of Gls in C. elegans is glna.

Aims: To explore the effects of glna loss on physiological and pathological phenotype of PD C. elegans, and to provide new ideas and references for the research and treatment of PD.

Materials & methods: We used PD C. elegans UA44 and QIN27 to detect development and lifespan, behavior, degeneration of dopaminergic neurons, lipid levels, ROS levels, expression levels of common amino acids.

Results: Glna loss had no significant impact on the development and lifespan of PD C. elegans. Glna loss saved part of the decline of motor function, including the head thrash frequency and the body bend frequency, and the difference was significant. There was a trend of improvement in some motor behaviors, such as the ethanol avoidance experiment, while no improvement was observed in other experiments. Glna loss slowed down the degeneration of dopaminergic neurons. Glna loss increased the lipid levels and ROS levels in C. elegans. Glna loss decreased Glu content and increased Gln content in C. elegans.

Discussion: The effect of glna loss on PD C. elegans may be the result of multiple factors, such as the tissue types of α-syn expression in C. elegans, the PD C. elegans model used, the adverse effects of glna loss on other systems, and the changes in ROS levels in C. elegans. The specific mechanisms causing these phenomena are still unclear and need to be further explored.

Conclusion: Glna loss has a certain protective effect on dopaminergic neurons in PD C. elegans, while the improvement effect on movement and behavior is limited.

Background: Hepatitis C virus (HCV) infection is a worldwide concern, causing liver damage and necessitating early detection to prevent its spread. Studies indicate that evaluating changes in biochemical and hematological parameters, which serve as suitable predictors of inflammation, can be a reasonable method for diagnosing hepatitis C infection.

Methods: This study analyzed 100 samples from high-risk patients positively identified via quantitative real-time PCR (qPCR). Anti-HCV titers, biochemical and inflammatory tests, and complete blood cell counts (CBCs) were performed for these individuals. Additionally, 100 HCV-negative individuals with normal laboratory results were selected as the control group. Receiver operating characteristic (ROC) curves were plotted to determine the cutoff values of the laboratory parameters.

Results: According to the findings, the age, average white blood cell (WBC) count, platelet-to-lymphocyte ratio (PLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP), serum glutamic-pyruvic transaminase (SGPT), and ferritin levels were significantly higher in HCV patients. On the other hand, red blood cell (RBC) counts, neutrophils, lymphocytes, hemoglobin-to-platelet ratio (HPR), and iron (Fe) levels were significantly lower in the case group compared to those in the control group (p < 0.05). Furthermore, the ROC curve analysis revealed that lymphocyte count, neutrophil count, and PLR were very strong predictors for hepatitis C infection (p < 0.0001, AUC = 1).

Conclusion: The study highlights significant biochemical and hematological differences between HCV patients and healthy subjects. These biomarkers are crucial for early diagnosis, potentially preventing liver damage and reducing HCV transmission.

Background: HER2-positive breast cancer (BC), a highly aggressive malignancy, has been treated with the targeted therapy inetetamab for metastatic cases. Inetetamab (Cipterbin) is a recently approved targeted therapy for HER2-positive metastatic BC, significantly prolonging patients' survival. Currently, there is no established biomarker to reliably predict or assess the therapeutic efficacy of inetetamab in BC patients.

Methods: This study harnesses the power of metabolomics and machine learning to uncover biomarkers for inetetamab in BC therapy. A total of 23 plasma samples from inetetamab-treated BC patients were collected and stratified into responders and nonresponders. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was utilized to analyze the metabolites in blood samples. A combination of univariate and multivariate statistical analyses was employed to identify these metabolites, and their biological functions were then ascertained by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, machine learning algorithms were employed to screen responsive biomarkers from all differentially expressed metabolites.

Results: Our finding revealed 6889 unique metabolites that were detected. Pathways like retinol metabolism, fatty acid biosynthesis, and steroid hormone biosynthesis were enriched for differentially expressed metabolites. Notably, two key metabolites associated with inetetamab response in BC were identified: FAPy-adenine and 2-Pyrocatechuic acid. There was some negative correlation between progress-free survival (PFS) and their kurtosis content.

Conclusions: In summary, the identification of these two significant differential metabolites holds promise as potential biomarkers for evaluating and predicting inetetamab treatment outcomes in BC, ultimately contributing to the diagnosis of the disease and the discovery of prognostic markers.

Background and aims: Retinitis pigmentosa (RP) is a hereditary retinal disorder that gradually leads to vision loss due to photoreceptor cell degeneration. This study aims to investigate the clinical features and genetic underpinnings of RP within a large Iranian family. Our focus centered on mutations in the NR2E3 gene, which plays a critical role in the development and maintenance of the retina.

Methods: Twenty-five family members showed symptoms of RP, and fourteen of them underwent clinical examinations conducted by geneticists and ophthalmologists. The DNA samples of five individuals diagnosed with RP from the family were subjected to whole-exome sequencing (WES) as part of the study. The candidate variant identified through WES was subsequently confirmed using bidirectional sequencing in additional family members. Additionally, in silico analysis, including molecular modeling, protein-protein docking, and molecular dynamics simulation (MD), was employed to assess potential pathogenic effects associated with the candidate variants.

Results: Ophthalmic examination revealed night blindness, which is a common symptom among affected individuals. Genetic analysis identified a homozygous missense variant (c.934G>A/p.R311Q) in NR2E3 exon 6, which co-segregates with other affected family members. Furthermore, molecular docking analysis indicated potential disruption in the binding affinity between NR2E3 and NR1D1 proteins. In-depth, molecular dynamics analysis, considering parameters such as RMSD, RMSF, and hydrogen bonding, revealed notable differences between normal and mutant protein complexes.

Conclusion: Exploring the molecular interaction between NR2E3 and NR1D1 provides new insights into the pathogenic mechanism of the p.R311Q mutation in RP.

Objective: Overweight and obesity is a risk factor for hypertension. Malignant hypertension (MHT) is the most severe form of hypertension, and thrombotic microangiopathy (TMA), one of its complications, has been linked to significant renal outcomes. However, the impact of overweight and obesity on renal prognosis in MHT patients with TMA is not well understood.

Methods: This was a prospective cohort enrolled 288 MHT patients with renal TMA from 2008 to 2023. The clinical and histopathological characteristics were recorded based on body mass index (BMI, < 25 and ≥ 25 kg/m²). The outcome was the incidence of kidney failure. The associations of BMI with kidney failure were examined in logistic regression models.

Results: Among 288 patients, 180 (62.5%) progressed to kidney failure, including 113 (68.5%) patients with BMI < 25 kg/m². Participants with obesity had higher levels of hemoglobin, estimated glomerular filtration rate and C3, but lower levels of serum creatinine and IgA nephropathy. BMI ≥ 25 kg/m² was associated with a better outcome of kidney failure in MHT patients with TMA (odd ratios [ORs]: 0.49 [95% confidence interval (CI): 0.27-0.91], p = 0.025). Male, uric acid, onion skin lesions, and global sclerosis ratio were correlated with higher risk of kidney failure; serum albumin and treatment with renin-angiotensin system blockers were related to lower risk of kidney failure.

Conclusions: In MHT patients with renal TMA, normal-weight rather than overweight was found to associate with a worse renal prognosis. Management efforts for MHT may be directed toward controlling body weight within a reasonable range for patients.

S. Salari, M. Bamorovat, I. Sharifi, and P. G. N. Almani, “Global Distribution of Treatment Resistance Genemarkers for Leishmaniasis,” Journal of Clinical Laboratory Analysis 36 (2022): e24599, https://doi.org/10.1002/jcla.24599.

In Samira Salari, Mehdi Bamorovat, Iraj Sharifi, Pooya Ghasemi Nejad Almani, “Global distribution of treatment resistance gene markers for leishmaniasis” (2022), Figure 2 was published without permission and has been removed. This does not affect the conclusions of the article.

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