Advances in biomarker sciences and technology最新文献

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.

Food poisoning related to bacterial contamination is the most common disease and cause of death nowadays in developing countries. There are many plants that have made a revolution in the field of medicine. Zygophyllum simplex (Z. simplex) is a plant that is native to Oman and it has been used since ancient times as a cure for human infectious diseases. The purpose of this study is to prepare different polarities containing plant crude extracts and evaluate their antibacterial behavior using the agar gel diffusion technique. In order to arrange their extracts via the Soxhlet extraction technique and solvent-solvent fraction technique, multi-polar solvents were used. With minor modification, the antimicrobial behaviors of the multi-polar extracts taken out were calculated by the agar gel diffusion technique. The antimicrobial action as a zone of inhibition of six different extracts at four concentrations was completed against two Gram-negative: Escherichia coli (E. coli, Code No. 683) and Klebsiella Pneumonia (K. pneumonia, Code No. 684), and three Gram-positive bacteria: Staphylococcus aureus (S. aureus, Code No. 659), Streptococcus pseudopneumonia (S. pseudopneumonia, Code No. 685), Bacillus pumilus (B. pumilus, Code No. 690). Different crude extracts showed antimicrobial activity against Gram (+ and -) bacteria at different concentrations. All extracts at different concentrations showed moderate to substantial activity against the bacterial strains of Grams (+and-) except methanol against B. pumilus. All various polarities crude extracts, ethyl acetate, DCM (dichloromethane), and water extracts at different concentrations showed the maximum activity against E coli within the range of 8–13.5 mm. The highest inhibition zone was found in DCM extract and the lowest antimicrobial activity was found in the hexane extract against different bacterial strains. So the order of DCM > butanol > water > methanol > hexane extracts preceded it. To isolate pure compounds by using column chromatography, the highest antibacterial activity DCM crude extract was chosen. The eluents were collected in a series of test tubes and a total of eight fractions were prepared based on the thin layer chromatography behavior. Similarly, the isolated eight fractions from the column were used to determine their antibacterial activity by the same agar diffusion method. The results showed that fractions number 2 and 4 gave the highest activity among the other fractions. In conclusion, the DCM extract as well as fraction numbers 2 and 4 exhibited promising activities against Gram-negative bacterial strains; therefore, the DCM extract, fraction 2, and fraction 4 could be used for the treatment of various human infectious diseases as natural antibiotics.

Breast cancer, the most predominant type of cancer reported in females, is a heterogeneous disease classified into various subcategories depending on the presence of hormone receptors. Epidemiological studies show a strong correlation between reduced 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) levels, the active component of vitamin D, and increased breast cancer risk in diverse populations. In a ligand-dependent manner, vitamin D receptor (VDR) transcriptionally modulates its target genes belonging to cell proliferation, differentiation, and apoptosis pathways, thus imparting protective function against cancer growth and progression. The coding and regulatory regions of the VDR gene contain several polymorphisms (BsmI, Fok1, Taq1, Apa1, Cdx2, poly (A), etc.) that modulate its transcription, translation, and mRNA stability. Despite this, research in this area has not yet led to many conclusions. In this review, we analyzed in a systematic way that the association of VDR allelic variants with breast cancer risk among patients from various populations. This analysis has revealed that Fok1, Bsm1, Apa1were to some extent associated with breast cancer risk, Taq1 shows no association, and Cdx2, poly(A), Tru91 gene polymorphisms may be susceptible for breast cancer development. We have highlighted the new insights of the current understanding of molecular mechanisms of the VDR gene polymorphisms related to breast cancer risk and also examined the interaction between VDR polymorphisms and steroid hormone (estrogen, progesterone, and androgen) receptors and their modifying effects on breast cancer risk, cancer severity, progression rate, and disease outcome. Therefore, with a lack of studies and inconsistent results, we recommend that further studies focus on genetic variations of the VDR gene that should be integrated with the assessment of steroid hormone receptor status in breast cancer.

Objective

Oman is a diverse habitat for various rare medicinal plants. Hyoscyamus gallagheri (H. gallagheri), locally known as Zgaf, is one of those rare plants. It is traditionally used for different ailments. This study aims to evaluate the antibacterial, antioxidant, antiulcer and antidiabetic potential of the leaves extracts of H. gallagheri.

Methods

Five extracts (hexane, chloroform, ethyl acetate, butanol, and water) were prepared and investigated for: their antibacterial potential against isolated gram (+ and -) bacteria, total antioxidant activity against DPPH (2,2 Diphenyl-1-picrylhydrazyl) and enzymatic inhibition of α-glucosidase and urease enzymes. Based on their biological potential, the chloroform and butanol extracts were fractionated by column chromatography using different polarities and proportions of organic solvents. This yielded a total of 9 chloroform and butanol fractions; their antibacterial and antioxidant potentials were investigated using the same methods.

Results

The results showed that all extracts exhibited excellent antibacterial potential against all tested bacterial strains as well as antioxidant potential, at different concentrations. The butanol extract showed the highest antibacterial, antioxidant and enzymatic activities, while the hexane and water extracts showed the least. The chloroform extract did not show any potential against urease and α-glucosidase enzymes. The butanol extract showed weak inhibitory action against α-glucosidase (^IC₅₀ = 585.76 ± 47.5 μg/ml) but the action against the urease enzyme was very good with an (IC50 = 90.3 ± 1.259 μg/ml)^.

Conclusions

Based on the obtained results, the active extract of H. gallagheri could be a valuable source of antioxidants, antibacterial, and urease inhibitory compounds.

Different biomarkers for SARS-CoV-2 have been linked to detection, diagnosis, treatment, disease progression, and development of new drugs and vaccines. The objective of this research was to evaluate various hematological, biochemicals, immunological, radiological and spirometric parameters in 20 adult patients convalescing from COVID-19 and their possible relationship with the clinical course of the disease. The frequencies of categorical variables were compared using the chi-square and Fisher's exact test. The levels of statistical significance were denoted in each figure legend. Two-dimensional clustering analysis was performed using MeV software from TIGR. The tests with P value of ≤ 0.05 were considered statistically significant. Most of the patients studied presented alterations in dissimilar laboratory, radiological and spirometric parameters, which were related to the clinical evolution of the disease. The results obtained show that certain hematological, biochemical, immunological and radiological parameters can be considered as biomarkers of sequela in adult COVID-19 patients, which allows their stratification, according to the degree of involvement or sequela, into three groups: I (mild degree of involvement or sequela), without lung lesions on computerized axial tomography (CT scan) and high values of IgG, C3 and hemoglobin, II (moderate degree of involvement or sequel), without lung lesions on CT scan, characterized by high levels of CD3+/CD4+ T lymphocytes and the rest of the variables with low values and III (severe degree of involvement or sequela), with lung lesions on CT scan and high values of erythrocyte sedimentation rate, monocytes and neutrophils, associated with lymphopenia and decreased concentrations of IgG and C3.