Advances in biomarker sciences and technology最新文献

The use of UCH-L1 detection with point-of-care (POC) assay alone has not been characterized for clinical use. This study compares the accuracies of POC UCH-L1 and Neuron-Specific Enolase (NSE) Elecsys® levels for identifying TBI patients with structural abnormalities on neuroimaging.

The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Phase 1 Cohort, enrolled 1375 TBI patients (GCS 3–15) presenting to one of 18 US Level I trauma centers within 24 h of injury who had an admission head CT; blood samples were collected, along with 122 orthopedic and 209 healthy controls. The TBI cohort consisted of 810 CT-negative (CT-) and 549 CT-positive (CT+) subjects. Of the CT- subjects who had MRIs, 121 were MRI-positive (MRI+) and 333 were MRI-negative (MRI-). UCH-L1 POC showed best diagnostic performance for CT + versus CT-, 0–8 h post-injury with an AUC of 0·779 [0·708–0.850] when compared to the 0–25 h interval, with an AUC of 0.684 [0.655–0.712]. NSE assay has an AUC of 0.695 [0.619–0.770] for the 0–8 h interval and 0.634 [0.603–0.665] for the 0–25 h interval. During the first 8 after injury, POC UCH-L1 outperforms NSE in identifying TBI patients with structural abnormalities on neuroimaging.

Background

A mutant P53 protein plays such a crucial role in ovarian cancer, and natural compounds have been known to be effective in treating cancer. The current study was conducted to discover new mutant P53 modulators in plants used for medicinal purposes. The mutant p53 3D structure was built using homology modeling, while its active binding domain was predicted using Findsitecom2.0. Docking studies were conducted with ligands derived from bioactive components of seven different plants and mutant p53 binding sites. Autodocking programs, including Discovery Studio and PyRx, were used to obtain the docking protein and its intricate visual representation. Gemcitabine and thiotepa were the reference drugs. Acute RAT toxicity and Pharmacokinetic properties were utilized in Gusar and SWISSADME, respectively, to narrow down the hit compounds to those with the highest binding affinities. Using the density functional theory (DFT) method, the electronic properties of the bioactive constituents were determined. 15 of the 50 bioactive phytochemicals displayed superior mutant p53 binding energies compared to Gemcitabine and Thioteba (−5.4 and −3.5 binding scores, respectively). Considering acute toxicity predictions and pharmacokinetics, 10-hydroxycamptothecin, irinotecan, morusin, and rubitecan were the four major compounds with low toxicity. DFT calculations uncovered regions susceptible to nucleophilic and electrophilic assaults. The study sought to identify potential drug candidates for modulating mutant P53 in ovarian cancer treatment.

The physiologic and irreversible process of ageing is accompanied by a wide range of structural and functional shifts at multiple different levels. It is also suggested that variations in the blood concentrations of metabolites, hormones, and micronutrients may play a role in the ageing process. Recently, Singh et al. ^1,2 investigated a study on Taurine shortage as a driver and biomarker of ageing and its impact on a healthy lifespan.² They further proposed that functional abnormalities in numerous organs associated with age-related illnesses have been linked to early-life Taurine insufficiency. Taurine deficiency in the elderly and the possible benefits of Taurine supplements One of the reasons for decreasing Taurine concentration is the loss of endogenous synthesis, which may contribute to the decrease in Taurine levels seen in the elderly. While it was previously believed that the liver was responsible for most Taurine synthesis in humans, new research suggests that other organs or common intermediates may play a larger role. The authors experimented with and analysed a life-span examination of various organisms, for example, mice to assess the impacts of Taurine supplementation. They also analysed after the administration of oral Taurine supplementation in conjunction with other interventions using multi-omics data sets (RNA sequencing, metabolomics etc.) across different species.

Earlier, a study conducted by the Indian Council of Medical Research – National Institute of Occupational Health (ICMR-NIOH), India, evidenced that CC16 may be used as a proxy marker and screening tool for early detection and progression of silica-induced lung damage. Once CC16 indicates early silicosis, it needs to be confirmed by chest radiography. Next, ICMR-NIOH and ICMR-National Institute of Virology (ICMR-NIV) jointly developed a semi-quantitative and point-of-care CC16 detection kit using lateral flow immune chromatography. The said test can be done from one drop of blood collected through a finger prick. All trained peripheral healthcare workers can screen the silica dust-exposed workers periodically, under the national silicosis control program. Once early silicosis is detected, their sputum may be examined periodically by CB-NAAT/True-NAT for early detection of silicotuberculosis. The serum CC-16 detection kit is the first of its kind for early detection of silicosis through periodic screening, which is approved by the Indian Council of Medical Research, Ministry of Health, Govt. of India. Unless silicosis is controlled, elimination of TB appears to be difficult in India as there is a huge burden of silicosis including sub-radiological silicosis in India and considering the fact that silicosis is a stronger risk factor for lung tuberculosis due to its progressive declining effect of lung immunity. Since occupational silica dust exposure facilitates progressive fibrosis of lung tissue, a clinical trial using metformin may be the need of the day as animal experiments have already shown metformin's anti-fibroblastic effect in silica-induced animals.

Type-2 diabetes mellitus (T2DM), the predominant form of diabetes in adults, is a co-morbid condition that exacerbates the severity of many other diseases, including cardiovascular disease, obesity, dyslipidemia, hypertension, and cancer. Among these, cancer is particularly concerning due to elevated mortality rates and a distinct lack of cost-effective therapeutic interventions. Identifying novel biomarkers for improved early cancer detection is imperative. Therefore, an integrated bioinformatics analysis was conducted to elucidate the co-morbid relationship between T2DM and five different types of cancer, namely bladder (BLCA), breast (BRCA), colon (CRC), liver (HCC), and prostate cancer (PRAD) and identification of novel biomarkers for early cancer detection in individuals with T2DM. A significant comorbid relationship was observed among T2DM, BLCA, and BRCA through gene expression and pathway enrichment analysis, while a moderate association was observed for between T2DM, and PRAD. Notably, we identified 18 significant hub proteins in the context of cancer and T2DM, along with 16 transcription factors and 5 miRNAs. Among these, the hub proteins ESR1, PIK3CA, GNAI1, ERBB2, NR3C1, SNCA, TGFBR2, as well as the micro RNAs hsa-mir-335–5p, hsa-mir-16–5p, and hsa-mir-93–5p hold promise for understanding the comorbidities of T2DM and cancers; and could serve as valuable disease biomarkers for clinical diagnosis and prognosis. This study, centred on bioinformatics analysis for biomarker identification in comorbidities, paves the way for future research encompassing wet lab experimentation and translational studies. These endeavours are poised to validate and facilitate the integration of these findings into the realm of personalized medicine.

Background

Omicron and its subvariants have become the predominant SARS-CoV-2 variants worldwide. The Omicron’s basic reproduction number (R0) has been close to 20 or higher. However, it is not known what caused such an extremely high R0 and whether Omicron’s intrinsic gene-gene interactions are different from earlier variants.

Objective

Find Omicron’s intrinsic gene-gene interactions and an explanation for the extremely high R0 Omicron infection.

Methods

Max-linear competing logistic regression classifier.

Results

We found that Omicron’s intrinsic gene-gene interactions jumped away from earlier SARS-CoV-2 variants which can be fully described by a miniature set of genes reported in our earlier work. We found that the gene PTAFR (Platelet Activating Factor Receptor) is highly correlated with Omicron variants, and so is the gene CCNI (Cyclin I), which is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog. The combination of PTAFR and CCNI can lead to a 100% accuracy of differentiating Omicron COVID-19 infection and COVID-19 negative.

Conclusions

We hypothesize that Omicron variants were potentially jumped from COVID-19-infected animals back to humans. In addition, there are also several other two-gene interactions, besides PTAFR and CCNI, that lead to 100% accuracy. Such observations can explain Omicron's fast-spread reproduction capability as either of those two-gene interactions can lead to COVID-19 infection, i.e., multiplication of R0s leads to a much higher R0. At the genomic level, PTAFR, CCNI, and several other genes identified in this work rise to Omicron druggable targets and antiviral drugs besides the existing antiviral drugs.

Tumor heterogeneity and lack of pre-operative diagnostic biomarkers are key topics in the field of renal cell carcinoma (RCC) identification. Clear cell RCC (ccRCC) is an aggressive cancer subtype which accounts for most RCC related deaths. The capacity to monitor changes at a molecular or biochemical level using two-dimensional (2D) correlated magnetic resonance spectroscopy of human kidney cancer biopsies, offers an insight into how ccRCC differs from other kidney cancer subtypes (termed here, non-ccRCC). Using this technology, two new spectral assignments, isovalerylglycine and α-ketobutyrate, were elevated in the potentially aggressive ccRCC cancer subtype. The crosspeak at F2: 0.95 ppm, F1: 2.05 ppm was assigned to isovalerylglycine and the diagonal resonance at 2.77 ppm to α-ketobutyrate. Isovalerylglycine, an amino acid leucine catabolite, was 55% higher (p = 0.004) and α-ketobutyrate 108% higher (p < 0.001) in ccRCC compared with non-ccRCC tissue biopsies. They were also elevated compared with non-cancer kidney. The increase in α-ketobutyrate in ccRCC compared with non-ccRCC also provides further insight into the role of homocysteine metabolism in kidney cancer. These biomarkers provide metabolic insight that could have future diagnostic or clinical value. They may help develop a spectral signature that, preoperatively, improves distinction between life-threatening ccRCC, non-ccRCC and non-cancer kidney.

Astrocytoma and oligodendroglioma are primary brain tumors classified as gliomas. Because there is difference in the prognostic significance of the extent of resection between IDH-mutant astrocytoma and oligodendroglioma, intraoperative differential diagnosis between them provides important information for optimal extent of resection. Although the characteristics of genetic mutations and chromosomal aberrations in both tumors have been reported, there is no molecular diagnostic methods that is able to be used quickly and simply for differentiate the two tumors. Therefore, we aimed to search for biomarker candidates for differentiating them with metabolome analysis using liquid chromatography/tandem mass spectrometry and develop a molecular diagnostic method based on quantitative analysis.

We searched for peaks that differed in two types of gliomas using global metabolomics. Next, we identified five biomarker candidates as hypoxanthine, inosine, cystine, proline and uric acid, respectively. Next, we developed an LC/MS/MS analytical method for five biomarker candidates and quantified them in brain tumors. Cystine had significantly lower amounts in astrocytomas than in oligodendrogliomas. We developed two prediction models for differentiation of the two gliomas and validated them using the separated two dataset. The logistic regression model with only cystine provided the best prediction performance. It was suggested that mass spectrometric analysis of cystine in surgery might be useful for differentiating astrocytoma and oligodendroglioma with 91.7% positive prediction value and 80.0% specificity whereas negative predictive value and sensitivity was lesser than 70%, so that further exploration for unknown metabolite is mandatory.