Non-enzymatic glycation and aggregation of camel immunoglobulins induce breast cancer cell proliferation.

Glycation of biomolecules results in the formation of advanced glycation end products (AGEs). Immunoglobulin G (IgG) has been implicated in the progression of various diseases, including diabetes and cancer. This study purified three IgG subclasses (IgG1, IgG2, and IgG3) from Camelus dromedarius colostrum using ammonium sulfate fractionation and chromatographic procedures. SDS-PAGE was performed to confirm the purity and molecular weight of the IgG subclasses. Several biochemical and biophysical techniques were employed to study the effect of glycation on camel IgG using methylglyoxal (MGO), a dicarbonyl sugar. Early glycation measurement showed an increase in the fructosamine content by ~four-fold in IgG2, ~two-fold in IgG3, and a slight rise in IgG1. AGEs were observed in all classes of IgGs with maximum hyperchromicity (96.6%) in IgG2. Furthermore, glycation-induced oxidation of IgGs led to an increase in carbonyl content and loss of -SH groups. Among subclass, IgG2 showed the highest (39.7%) increase in carbonyl content accompanied by 82.5% decrease in -SH groups. Far UV-CD analysis illustrated perturbation of ß-sheet structure during glycation reaction with MGO. Moreover, glycation of IgG proceeds to various conformational states like aggregation and increased hydrophobicity. In addition, the cytotoxicity assay (MTT) illustrated the proliferation of breast cancer cells (MCF-7) with IgG2 treatment.

Metabolic Alteration of MCF-7 Cells upon Indirect Exposure to E. coli Secretome: A Model of Studying the Microbiota Effect on Human Breast Tissue.

According to studies, the microbiome may contribute to the emergence and spread of breast cancer. E. coli is one of the Enterobacteriaceae family recently found to be present as part of the breast tissue microbiota. In this study, we focused on the effect of E. coli secretome free of cells on MCF-7 metabolism. Liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to study the E. coli secretome and its role in MCF-7 intra- and extracellular metabolites. A comparison was made between secretome-exposed cells and unexposed controls. Our analysis revealed significant alterations in 31 intracellular and 55 extracellular metabolites following secretome exposure. Several metabolic pathways, including lactate, aminoacyl-tRNA biosynthesis, purine metabolism, and energy metabolism, were found to be dysregulated upon E. coli secretome exposure. E. coli can alter the breast cancer cells' metabolism through its secretome which disrupts key metabolic pathways of MCF-7 cells. These microbial metabolites from the secretome hold promise as biomarkers of drug resistance or innovative approaches for cancer treatment, either as standalone therapies or in combination with other medicines.

CFTR protein quantification as a cystic fibrosis diagnostic biomarker in dried blood spots using multiple reaction monitoring tandem mass spectrometry.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel found on the apical surface of epithelial cells in the airway and gastrointestinal tract. A mutation in the CFTR protein is responsible for developing cystic fibrosis (CF) disease. Therefore, circulating CFTR protein could be a promising biomarker of CF disease. Multiple methodological challenges are associated with CF's available diagnostic and screening methods, such as low specificity and potential false discovery rate, mainly for ethnic groups whose CFTR mutations are not covered in the mutation panels. Herein, we have developed an absolute quantification (AQUA) method based on two CFTR signature peptides (SPs). A liquid chromatography-tandem spectrometry (LC-MS/MS) method in multiple reaction monitoring (MRM) mode (MRM transitions 1168.90 > 85.929 and 707.19 > 85.93 of SP1 and SP2, respectively) enabled the accurate quantification of CFTR protein in a dried blood spot (DBS). The method was validated successfully based on international guidelines in terms of signal linearity, precision (within-run CV 3.37-8.54%; between-run CV 5.15-11.06% for the selected SPs), and accuracy (within-run 93.4-105.59%; between-run 97.45-103.28% for the selected SPs). The level of soluble CFTR protein was evaluated as a potential biomarker for CF using patients (n = 39) and healthy controls (n = 30), were found to be in CF patients lower than controls. For instant, the level of signature peptide 1 (SP1) was 2.09 ± 0.55 nM, 68.77 ± 1.40 nM in CF patients compared to Ctrl, respectively; p < 0.0001. This study is the first to report CFTR levels in DBS using signature peptides by LC-MS/MS as a diagnostic marker for CF. The receiver operating characteristic (ROC) for CFTR SP1 and SP2 showed a significant area under the curves (AUC) 0.7714 (99% CI, p < 0.0001), and 0.8234 (99% CI, p < 0.0001), respectively. The presented MRM method provides a highly specific and sensitive approach to CFTR quantification in a DBS and could be applied in CF screening.

Elucidating the role of hypoxia-inducible factor in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic multifactorial disease, provocative, and degenerative autoimmune condition that impacts millions of individuals around the globe. As a result of this understanding, anti-inflammatory drugs have been created, perhaps widely effective (like steroids) and highly specialized methods (including anti-TNF antibody) using biological therapies (including TNF inhibitors). Despite this, the connections between inflammatory response, articular development, and intracellular responsiveness to changes in oxygen concentration are undervalued in rheumatoid arthritis. Hypoxia, or a lack of oxygen, is thought to cause enhanced synovial angiogenesis in RA, which is mediated by some of the hypoxia-inducible factors like vascular endothelial growth factor (VEGF). Substantial genetic alterations occur when the HIF regulatory factors signaling cycle is activated, allowing organelles, tissues, and species to acclimatize to decreasing oxygen saturation. The most well-characterized hypoxia-responsive transcripts are the angiogenic stimulant VEGF, whose production is greatly elevated by hypoxia in several types of cells, especially RA synovium fibroblasts. Blocking vascular endothelial growth factors has been demonstrated to be helpful in murine models of rheumatism, indicating how hypoxia could trigger the angiogenesis process, resulting in the progression of RA. These mechanisms highlight the intimate affiliation amongst hypoxia, angiogenesis, and inflammation in rheumatoid arthritis. This review will look at how hypoxia activates molecular pathways and how other pathways involving inflammatory signals develop and sustain synovitis in rheumatoid arthritis.

Awareness Level of Cancer Risk Factors and Warning Signs and Cancer Campaign Attendance behavior among Saudi Adults in a Tertiary Hospital in Riyadh.

OBJECTIVE: To estimate the awareness level of Saudi adults about the risk factors and warning signs of cancer and observe the association of different determinants with cancer Knowledge in Riyadh city. METHODS: A cross-sectional study carried out on 390 Saudis in the outpatient clinics of King Khalid University Hospital (KKUH), Riyadh. Data was collected using a validated Arabic questionnaire. Data was analyzed using SPSS software. RESULTS: The overall awareness of the participants was limited, as the mean score of the overall cancer knowledge was 49.2%. Most of the correctly answered questions were on general cancer knowledge and not about risk factors or warnings signs. The only risk factors identified by most participants were smoking, alcohol, air pollution and genetic factors. Important risk factors such as physical inactivity, low dietary fibers and obesity were not well known. Despite Hepatitis B virus infection (HBV) being endemic in the kingdom, only 30% identified it as a risk factor. Apart from "A Thickening or a lump in breast or other organs", < 50% of participants recognized alarming warning signs such as unexplained weight loss, unusual bleeding, and change in bowel habits. Females were more inclined to attend cancer awareness campaigns. Though people who reported attendance of cancer awareness campaigns surprisingly did not achieve a significantly higher overall knowledge score. CONCLUSION: The public lacks knowledge of well-established cancer risk factors and warning signs, despite recent advances in the medical field. Results suggest that current strategies to educate the public need to be revised.
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Metabolomics Profiling of Cystic Renal Disease towards Biomarker Discovery.

Cystic renal disease (CRD) comprises a heterogeneous group of genetic and acquired disorders. The cystic lesions are detected through imaging, either incidentally or after symptoms develop, due to an underlying disease process. In this study, we aim to study the metabolomic profiles of CRD patients for potential disease-specific biomarkers using unlabeled and labeled metabolomics using low and high-resolution mass spectrometry (MS), respectively. Dried-blood spot (DBS) and serum samples, collected from CRD patients and healthy controls, were analyzed using the unlabeled and labeled method. The metabolomics profiles for both sets of samples and groups were collected, and their data were processed using the lab's standard protocol. The univariate analysis showed (FDR p < 0.05 and fold change 2) was significant to show a group of potential biomarkers for CRD discovery, including uridine diphosphate, cystine-5-diphosphate, and morpholine. Several pathways were involved in CRD patients based on the metabolic profile, including aminoacyl-tRNA biosynthesis, purine and pyrimidine, glutathione, TCA cycle, and some amino acid metabolism (alanine, aspartate and glutamate, arginine and tryptophan), which have the most impact. In conclusion, early CRD detection and treatment is possible using a metabolomics approach that targets alanine, aspartate, and glutamate pathway metabolites.

Awareness of cardiovascular disease associated risk factors among Saudis in Riyadh City.

OBJECTIVE: The aim of this study was to estimate the awareness of Saudi population in Riyadh regarding cardiovascular diseases (CVDs) and their risk factors. METHODS: This was a cross-sectional study that used self-administered questionnaires conducted in universities, primary care centers, and electronic copies distributed in social media websites. RESULTS: Overall, 47.1% of the respondents had a good awareness of CVD and associated risk factors. However, awareness of the symptoms of stroke and heart attack was low. Pulmonary embolism and deep vein thrombosis were the most commonly identified types of CVD, with 39.2% aware of these conditions. The most well-known symptom of heart attack was shortness of breath (known by 54.4% of the respondents). In relation to stroke, the most commonly recognized symptom was "sudden dizziness, trouble walking, or loss of balance" (45.4%). Respondents' awareness of CVD risk factors was moderate. The most common factors-identified by over two-thirds of participants-were unhealthy diet, smoking, dyslipidemia, and physical inactivity. Independent predictors of good CVD awareness were age 35-44 years, living in the north of Riyadh and following a healthy diet. CONCLUSIONS: The awareness of CVD and associated risk factors is insufficient among Saudis in Riyadh City. This study emphasizes the necessity for effective education to increase the awareness about CVD in Saudi Arabia. High awareness may lead to early recognition of the risk factors and lead to early implementation of primary prevention which the cornerstone of family medicine practice.