Characterization of ferroptosis driver gene signature in head and neck squamous cell carcinoma (HNSC).

BACKGROUND: Head and neck squamous cell carcinoma (HNSC), a prevalent malignant tumor with a low survival rate, is often accompanied by ferroptosis, which is a recently-described type ofprogrammed cell death. Investigating the significance of ferroptosis driver genes in HNSC, this study aimed to assess their diagnostic and prognostic values, as well as their impact on treatment and tumor immune function. The results of this investigation provide novel insight into using ferroptosis-related genes as molecular biomarkers as well as precise chemotherapeutic targets for the therapy of HNSC. METHODOLOGY: A detailed in silico and in vitro experiment-based methodology was adopted to achieve the goals. RESULTS: A total of 233 ferroptosis driver genes were downloaded from the FerrDB database. After comprehensively analyzing these 233 ferroptosis driver genes by various TCGA databases, RNA-sequencing (RNA-seq), and Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) techniques, TP53 (tumor protein 53), PTEN (Phosphatase and TENsin homolog deleted on chromosome 10), KRAS (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog), and HRAS (Harvey Rat sarcoma virus) were identified as differentially expressed hub genes. Interestingly, these hub genes were found to have significant (P < 0.05) variations in their mRNA and protein expressions and effects on overall survival of the HNSC patients. Moreover, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes (TP53, PTEN, KRAS, and HRAS). In addition to this, hub genes were involved in diverse oncogenic pathways. CONCLUSION: Since HNSC pathogenesis is a complex process, using ferroptosis driver hub genes (TP53, PTEN, KRAS, and HRAS) as a diagnostic and prognostic tool, and therapeutically targeting those genes through appropriate drugs could bring a milestone change in the drug discovery and management and survival in HNSC.

Association of Serum Albumin, Globulin, and Transferrin Levels in Children of Poorly Managed Celiac Disease.

Background: Celiac disease (CD) is an autoimmune genetic disorder in which gluten protein causes inflammation of the intestinal enterocytes. CD diagnosis in most cases is delayed or mistreated due to its varied clinical features. We aimed to evaluate the protein profile imbalance in different CD groups of children, which could help aid in the diagnosis and proper management of the disease. Methodology. This was a cross-sectional study with a nonrandom purposive sampling technique. All samples were taken from tertiary care hospitals of Hyderabad, Pakistan. In total, there were 175 children (age 3-15 years) divided into five equal groups (n = 35), namely, group A (control), group B (celiac diagnosed), group C (celiac-like symptoms), group D (celiac with type 1 diabetes mellitus), and group E (type 1 diabetes mellitus only). Clinical symptoms and laboratory parameters were analyzed among all the groups. Sera proteins, albumin, globulins, and transferrin levels were evaluated and compared with healthy individuals. Results: The albumin in serum of celiac groups B and C was 3.0 g/dl and 2.8 g/dl, respectively. While in diabetic patients with CD, it is 2.7 g/dl. The globulin levels were raised among all the celiac groups with typical GIT symptoms. The highest transferrin was observed in group B, celiac patients with severe anemia. Patients were not on GFD, hence had no or less recovery and had chronic symptoms of celiac. Conclusion: The misdiagnosis and poor management of celiac leads to chronic villous atrophy with imbalance in metabolic profile. Serum analysis of albumin, globulins, and transferrin may help in the diagnosis and proper management of the disease to recover the celiac symptoms.

Cholesterol pathway biomarkers are associated with neuropsychological measures in multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) is frequent in persons with multiple sclerosis (PwMS) and is linked to neurodegeneration. Cholesterol pathway biomarkers (CPB) are associated with blood-brain barrier breakdown, lesions, and neurodegeneration in multiple sclerosis (MS). CPB could influence CI. METHODS: This cross-sectional study (n = 163) included 74 relapsing-remitting MS (RR-MS), 48 progressive MS (P-MS) and 41 healthy control (HC) subjects. The assessed physical disability and cognitive measures were: Nine-hole Peg Test (NHPT), Timed 25-Foot Walk, Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test-3, and Beck Depression Inventory-Fast Screen. CPB panel included plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and the apolipoproteins (Apo), ApoA-I, ApoA-II, ApoB, ApoC-II and ApoE. Disability and cognitive measures were assessed as dependent variables in regression analyzes with age, sex, body mass index, years of education, HC vs. RR-MS vs. P-MS status, CPB, and a HC vs. RR-MS vs. P-MS status × CPB interaction term as predictors. RESULTS: SDMT was associated with the interaction terms for HDL-C (p = 0.045), ApoA-I (p = 0.032), ApoB (p = 0.032), TC/HDL-C (p = 0.013), and ApoB/ApoA-I (p = 0.008) ratios. CPB associations of SDMT were not abrogated upon adjusting for brain parenchymal volume. NHPT performance was associated with the interaction terms for TC (p = 0.047), LDL-C (p = 0.017), ApoB (p = 0.001), HDL-C (p = 0.035), ApoA-I (p = 0.032), ApoC-II (p = 0.049) and ApoE (p = 0.037), TC/HDL-C (p < 0.001), and ApoB/ApoA-I ratios (p < 0.001). CONCLUSIONS: The LDL to HDL proportion is associated with SDMT and NHPT in MS. The findings are consistent with a potential role for CPB in CI.

Human leukocyte antigen (HLA)-DQ2 and -DQ8 haplotypes in celiac, celiac with type 1 diabetic, and celiac suspected pediatric cases.

ABSTRACT: Celiac disease (CD) is an autoimmune enteropathy triggered by ingestion of gluten present in wheat, barley, and rye. Gluten along with environmental trigger starts an inflammatory reaction which results in damage to small intestine. Human leukocyte antigen (HLA)-DQA1∗05, -DQB1∗02, and -DQB1∗03:02 are the known risk alleles of CD. The diagnostic method for CD involves serological or intestinal biopsy, but genetic test could be implemented. HLA typing precludes the need for further diagnosis and it has high negative predictive value. The aim of this study was to make aware of HLA molecular typing for celiac disease among local laboratories and healthcare professionals. The prevalence and frequency distribution of HLA-DQ2 and -DQ8 haplotypes in 175 pediatric unrelated healthy controls, celiac patients, and CD with concurrent diabetes mellitus type 1 (DM1) was evaluated. The most common haplotype was DQ2 followed by DQ8. In control group only DQ2 was observed with frequency of 8.5%. In celiac patients 85.7% were DQ2, 11.4% were DQ8, and rest were DQ2/DQ8 (2.8%), and all had CD. In the group of CD with DM1, 31.4% had DQ2, 25% had DQ8, and 34% having both the haplotypes; while only 9 of these patients were suffering from CD. It was concluded that Celiac disease is frequently unrecognized by physicians, in part because of its variable clinical presentation and symptoms. Thus genetic testing for celiac disease could be an additive tool for diagnosis to exclude ambiguity.

Physicochemical Modifications and Nano Particulate Strategies for Improved Bioavailability of Poorly Water Soluble Drugs.

BACKGROUND: Bioavailability is the segment of dose that is bioavailable for its therapeutic effect on the systemic circulation without any change in its characteristics, after administration by either route. It is one of the fundamental pharmacokinetic properties of drugs. It is important because, it defines the amount of drug to be administered for its intended therapeutic effect. If drug is more bioavailable, less amount of it is required to obtain therapeutic effect. However, it is also worth mentioning that most of the newly discovered therapeutic agents have poor solubility and thus low bioavailability. OBJECTIVES: In this article, various methods including conventional and advanced, have been reviewed that could be potentially used for the enhancement of bioavailability. Moreover, the benefits and drawbacks of all the strategies are deliberated to comprehend the probable use of each method supported by latest references. METHODS: Various strategies have been developed to enhance the solubility and thus bioavailability of numerous drugs, some of which are discussed here. All these strategies involve different approaches to improve the bioavailability including physical adaptation, chemical modification and controlling particle size of the engineered particle. RESULTS: These strategies, particularly the nano-particulate systems, not only improve the bioavailability of drugs but at the same time diminish the possible toxicities of the incorporated drugs. CONCLUSION: It can be concluded that this would be a new source of information for the readers.