MedNexus
2022年 · 第05卷第02期
MedNexus
Vaccines are one of the biggest successes in modern history and are particularly important in light of the multiple ongoing epidemics. Recently, vaccines have protected peoples’ health and lives around the world during the coronavirus disease 2019 pandemic. Different types of vaccines have their own characteristics and advantages and are used in the context of different epidemics. Responses to vaccination are also different, and can include adverse reactions and absent responses. These individual differences are thought to be influenced by host genes. In this review, we first discuss vaccine types and characteristics. Second, we discuss different responses to vaccination, primarily focusing on the association between genetic variation and inter-individual differences.
Hereditary spastic paraplegia type 56 (SPG56-HSP) is a rare autosomal recessive disorder caused by loss of function mutations in CYP2U1, leading to an early-onset limbs spasticity, often complicated by additional neurological or extra-neurological manifestations. Given its low prevalence, the molecular bases underlying SPG56-HSP are still poorly understood, and effective treatment options are still lacking. Recently, through the generation and characterization of the SPG56-HSP mouse model, we were able to take few important steps forward in expanding our knowledge of the molecular background underlying this complex disease. Leveraging the Cyp2u1-/- mouse model we were able to identify several new diagnostics biomarkers (vitamin B2, coenzyme Q, neopterin, and interferon-alpha), as well as to highlight the key role played by the folate pathway in SPG56-HSP pathogenesis, providing a potential treatment option. In this review, we discuss the major role played by the Cyp2u1-/- model in dissecting clinical and biological aspects of the disease, opening the way to a series of new research paths ranging from clinical trials, biomarker testing, and to the expansion of the underlying genetic and molecular, emphasizing how basic mouse model characterization could contribute to advance research in the context of rare disorders.
An increasing body of evidence supports the hypothesis that atherosclerosis is caused by multiple factors and mechanisms. A better understanding of the contribution of hypertriglyceridemia or oleic acid to the pathogenesis of atherosclerosis would significantly increase our ability to successfully treat these diseases. We propose that oleic acid promotes atherosclerosis via multiple pathophysiological mechanisms. Here we suggest that (1) atherosclerosis may develop through multiple pathophysiological mechanisms and that this may be a common feature of human diseases; (2) diseases may be the consequence of natural selection or the interaction of internal and external factors; (3) diseases should be recognized with "biological diversity," and that this concept should be introduced into medical education, clinical treatment, drug research and development, and medical research. The work reported here will benefit a new generation of medical trainees and promote the development of the relevant medical fields.
Most patients with advanced lung cancer have a poor prognosis. Recent studies have identified TRIM59 as a novel molecule that serves as a prognostic factor for the progression of non-small cell lung cancer. In the present study, we investigated the role of TRIM59 in predicting the prognosis of lung adenocarcinoma (LUAD) as well as the correlation between TRIM59 expression and immune infiltrates.
We analyzed TRIM59 expression in normal and tumor tissues based on RNA-sequencing datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Forty-seven cases of LUAD tissues and their matching adjacent tissues were collected, and TRIM59 expression in tissue samples was demonstrated by immunohistochemistry. All tissue specimens were obtained under the approval of the Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (approval No. IR2019001101; approved on April 3, 2019). The immune cell scores were calculated using the CIBERSORT database. The Tumor Immune Estimation Resource database was used to analyze the correlation between TRIM59 and immune cell activities.
TRIM59 was up-regulated in most cancer types. High TRIM59 expression predicted a worse prognosis in patients with LUAD (overall survival, P= 0.00096; disease-specific survival, P= 0.00056; disease-free interval, P= 0.0009; progression-free interval, P= 0.0012). Moreover, TRIM59 was highly expressed in patients with LUAD who had a poorer prognosis. TRIM59 also showed a significant correlation with the ESTIMATE score (P = 0.04) and stromal score (P = 0.005) in patients with LUAD. Notably, a significant correlation between TRIM59 and the tumor mutation burden was found in LUAD but in no other cancer types (P < 0.001). Further investigation showed that TRIM59 had a significant correlation with gene markers on neutrophils and dendritic cells.
TRIM59 is a potential prognosticator in LUAD and may be correlated with immune cell identification, immune cell infiltration, and immunotherapy checkpoints in LUAD.
The aim of this work was to explore the feasibility of in vivo and non-invasive monitoring of deuterium/hydrogen (2H/1H) exchange at the metabolic level upon exposure to heavy water (2H2O).
The healthy female mice were randomly assigned to two groups after day 0 when both mice received standard drinking water. The treated mouse was fed with 2H2O (80%, v/v) and the control mouse fed with standard drinking water (H2O) over next 13 days. Real-time mass spectrometric analysis of volatile metabolism emitted through breathing and the skin was performed on days 1, 2, 3, 10, 12, and 13. Animal experiment was approved by the Laboratory Animal Ethics Committee of Jinan University (approval No. 20161117163322) on October 29, 2021.
We observed a replacement of 1H by 2H in 52 mass spectral features (60 2H/1H isotopologue pairs) for the mouse fed with 2H2O, but not for the control mouse. These included pyruvic acid and lactic acid, lysine and methyl-lysine as well as short-chain fatty acids comprising acetic acid, propionic acid, butyric acid and valeric acid.
Secondary electrospray ionization-high resolution mass spectrometry allows monitoring in vivo2H-incorporation of metabolites in a non-invasive and real-time setup and opens new opportunities to use 2H tracing to extend current metabolic studies, especially those with a focus on anaerobic glycolysis, lysine methylation and gut microbiome via monitoring of short-chain fatty acids.
Only a few studies have investigated the development trends in spatial working memory and attention among a large sample of primary school students over a wide range of ages, while the efficiency of learning and memory processes is fundamental to academic performance, particularly for children, who are in a key developmental stage when their life opportunities can be altered. We aimed to explore how the spatial working memory and attention of primary school children are affected by grade, academic performance, and sex.
In this cross-sectional observational study, students (144 boys, 139 girls, 6-13 years old) were recruited from Experimental Primary School Affiliated to Shanghai Jiao Tong University in Shanghai, China in 2018. The study protocol was reviewed and approved by the Bio-Ethics Board of the Bio-X Institutes, Shanghai Jiao Tong University. Based on a simple Spatial Working Memory and Attention Test on Paired Symbols test, we evaluate 283 participants’ working memory and attention ability.
Attention and working memory performance were enhanced as a positive function of grade in primary school children, and students who showed better academic achievement also performed better on the working memory task. However, attention and working memory performance were not affected by sex.
Attention and working memory performance of primary school students develop with grade and corresponds to Better academic performance. Attention and working memory ability do not differ significantly between boys and girls.
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