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Background: Pain is the major cause of disability in disc induced lumbosacral radiculopathy (LSR) and is related to neurotrophins mainly brain derived neurotrophic factor (BDNF). However, to our knowledge evaluating serum BDNF in disc induced LSR has not been reported before. This study was done to investigate serum BDNF in LSR patients and its relation to pain severity and functional disability., Methods: This case-control study included 40 disc induced LSR patients and 40 age and sex matched healthy subjects. All patients were subjected to neurological examination, electrophysiological evaluation, pain severity assessment using numerical rating scale (NRS) and functional disability assessment using Modified Oswestry Low Back Pain Disability Index (ODI) and Maine-Seattle Back Questionnaire (MSBQ). According to Douleur neuropathique 4 (DN4) questionnaire, patients were divided into those with neuropathic pain and those with non-neuropathic pain. Serum BDNF was measured by enzyme-linked immunosorbent assay in all participants., Results: Serum BDNF was significantly higher in LSR patients than in healthy controls (U=272.5, P<0.001). Moreover, serum BDNF was significantly higher in those with neuropathic pain compared to those with non-neuropathic pain (U=35, P=0.03). Serum BDNF had a significant positive correlation with NRS score among those with acute pain (r s= 0.537, P=0.026), however there was no significant correlation among those with chronic pain. Furthermore, BDNF had no significant correlation with modified ODI and MSBQ., Conclusion: Increased serum BDNF may be associated with neuropathic pain and acute pain severity in disc induced LSR. However, it may not be related to chronic pain severity or functional disability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: HER2-positive breast cancer occurs in 15-20% of breast cancer patients and is characterized by poor prognosis. Trastuzumab is considered the key drug for treatment of HER2-positive breast cancer patients. It improves patient survival; however, resistance to trastuzumab remains a challenge in HER2-positive breast cancer patients. Therefore, the prediction of response to trastuzumab is crucial to choose optimal treatment regimens. The aim of the study was to identify genetic variants that could predict response to anti-HER2-targeted therapy (trastuzumab) using next-generation sequencing., Method: Genetic variants in the hotspot regions of 17 genes were studied in 24 Formalin-Fixed Paraffin-Embedded (FFPE) samples using Ion S5 next-generation sequencing system. FFPE samples were collected from HER2‑positive breast cancer patients previously treated with anti‑HER2‑targeted treatment (Trastuzumab). Patients were divided into two groups; trastuzumab-sensitive group and trastuzumab-resistant group based on their response to targeted therapy., Results: We identified 29 genetic variants in nine genes that only occurred in trastuzumab-resistant patients and could be associated with resistance to targeted therapy including TP53, ATM, RB1, MLH1, SMARCB1, SMO, GNAS, CDH1, and VHL. Four variants out of these 29 variants were repeated in more than one patient; two variants in TP53, one variant in ATM gene, and the last variant in RB1 gene. In addition, three genes were found to be mutated only in resistant patients; MLH1, SMARCB1 and SMO genes. Moreover, one novel allele (c.407A > G, p. Gln136Arg) was detected within exon 4 of TP53 gene in one resistant patient., Conclusion: NGS sequencing is a useful tool to detect genetic variants that could predict response to trastuzumab therapy., (© 2023. The Author(s).)

Background: Most cases of lung cancer are diagnosed at advanced stage. Detection of genetic and epigenetic markers in cell-free DNA (cfDNA) is a promising tool for the diagnosis of lung cancer at an early stage. The aim of this study was to identify non-invasive diagnostic markers in cell free DNA (cfDNA) for non-small cell lung cancer (NSCLC) as it is the most common type of lung cancer., Methods: We investigated the cfDNA HOXA9 gene promotor methylation by pyrosequencing. Copy number variation of SOX2 and HV2 genes were detected by real-time PCR in cfDNA extracted from plasma samples of 25 newly diagnosed NSCLC patients and 25 age and sex matched controls., Results: Methylation level of HOXA9 was significantly higher in NSCLC patients than controls (p > 0.001). SOX2 showed significantly higher CNV and HV2 showed lower CNV in patients than controls (p > 0.001, p = 0.001 respectively). Receiver Operating Characteristic (ROC) curve analysis for HOXA9 methylation, SOX2 CNV and HV2 CNV showed a discrimination power of 79.4%, 80% and 77.5% respectively and the area under the curve for the combined analysis of the three genes was 0.958 with 88% sensitivity and 100% specificity., Conclusions: In this study, we suggest a potentially diagnostic panel that may help in detection of lung cancer with high sensitivity and specificity using cell free DNA. This Panel included HOXA9 gene methylation and the CNV of SOX2 and HV2 genes., (© 2023. The Author(s).)

To date, the genes associated with susceptibility to Atopic Eczema (AE) are mainly implicated in immunity, inflammation, and maintenance of skin barrier. Little is known about the possible relationship between genes modulating Extra-Cellular Matrix (ECM) and AE etiopathogenesis. In this regard, the primary objective of the present study has been the investigation of susceptibility biomarkers localized within genes encoding collagen proteins. Several studies have shown that polymorphisms within the genes encoding such proteins may generate abnormal connective tissues, making them more susceptible to mechanical stress, loss of epidermal integrity, and aging. We therefore decided to investigate three polymorphisms located in COL6A5, COL8A1 , and COL10A1 as potential susceptibility biomarkers for AE in a cohort of 1470 subjects of Mediterranean origin. The genes of interest have been selected considering that the ECM and immune/inflammatory response are strongly dysregulated in AE and other complex disorders. The study confirmed that the susceptibility to AE depends on a complex interaction between latitude, geographical localization, and the differential distribution of genetic variants among populations exposed to similar environmental factors.

Background: H19 is one of the long non-coding RNAs (LncRNA) that is related to the progression of many diseases including cancers. This work was carried out to study the level of the long non-coding RNA; H19, in plasma of patients with gastric cancer (GC) and to assess its significance in their clinical management., Methods: Sixty-two participants were enrolled in the present study. The first group included 32 GC patients. The second group was formed of 30 age and sex matched healthy volunteers serving as a control group. Plasma samples were used to assess H19 gene expression using real-time quantitative PCR technique., Results: H19 expression was up-regulated and closely related to TNM cancer stages in GC patients. Using Receiver Operating Characteristic (ROC) curve analysis, a cutoff level of 0.5 was set for H19 expression to diagnose GC cases achieving a sensitivity of 68.75%, specificity of 56.67%, positive predictive value (PPV) 62.86% and negative predictive value (NPV) 62.96% with an area under the curve (AUC) of 72.4%. Combined use of Carcinoembryonic Antigen (CEA) and H19 level in GC diagnosis was evaluated using ROC curve revealing improvement in performance with an area under the curve of 80.4%., Conclusions: Up-regulation of H19 is closely associated with gastric cancer displaying progressive up-regulation in advanced stages of the disease implementing its role as a potential non-invasive diagnostic biomarker in gastric cancer and as a novel tool in gastric cancer management with better performance achieved on using both CEA and H19 simultaneously., (© 2016 Wiley Periodicals, Inc.)

Background: Chronic kidney disease (CKD) is characterized by progressive irreversible deterioration of renal functions. Advanced stages of CKD are associated with oxidative stress due to the imbalance between oxidant production and antioxidant defense mechanisms. Survival of patients with end stage renal diseases is maintained on variable forms of renal replacement therapies (RRT) which include peritoneal dialysis, hemodialysis, and sometimes renal transplantation. In humans, Nuclear Respiratory Factor 1 (NRF-1) gene encodes for a transcription factor that, together with the transcriptional co-activator encoded by Peroxisome Proliferator activated Receptor Gamma coactivator 1 Alpha (PGC1-a) gene, stimulates the expression of a broad set of nuclear genes (as COX6C) which are involved in mitochondrial biogenesis and functions. As mitochondria are considered a major source of reactive oxidant species, the objective of the present study was to assess mitochondrial oxidative dysregulation occurring in chronic kidney disease patients undergoing hemodialysis employing NRF-1 and COX6C genes' expression as an indicator of mitochondrial oxidative metabolism., Methods: Forty-nine chronic kidney disease patients undergoing intermittent hemodialysis were included in the present study. A group of thirty-three age- and gender- matched healthy volunteers served as a control group. Assessment of expression of NRF-1 and COX6C genes was performed using quantitative real-time PCR technique., Results: NRF-1 and COX6C expression showed a statistically significant difference between both studied groups being down-regulated in CKD patients. In addition, malondialdehyde (MDA) levels were higher in patients on hemodialysis indicating lipid peroxidation. A negative correlation was detected between MDA level and expression of both NRF-1 and COX6C genes., Conclusions: Chronic kidney disease patients undergoing hemodialysis might be subjected to potential mitochondrial oxidative dysregulation with subsequent possible vascular and tissue injury.

Background: Replication of hepatitis B virus (HBV) in the absence of a detectable hepatitis B surface antigen (HBsAg) and occasionally other HBV serologic markers has been called occult hepatitis B infection. As the presence of OBI represents a possible threat to those on hemodialysis, being a high risk group, this study was carried out to investigate the prevalence of OBI in a cohort of Egyptian patients maintained on hemodialysis and to evaluate the protocol of HBV detection in the Alexandria Main University Hospital dialysis unit., Methods: Patients enrolled in the study included ninety three HBs-Ag negative Egyptian patients maintained on hemodialysis. Liver function tests, serological HBV markers, HCV antibodies, and quantification of HBV viral DNA titer were assayed for all participants in the study., Results: Twenty five individuals were HBV DNA-positive, representing 26.8% of the tested patients. As regards HBV DNA-positive cases, eighteen (72%) patients were HCV-Ab positive. Three patients (12%) were positive to both anti-HBc and anti-HBs and only one patient (4%) was negative to both antibodies. Fifteen patients (60%) were positive to anti-HBc only, while 6 patients (24%) were positive to anti-HBs only., Conclusions: OBI is relatively common in Egyptian dialysis patients at the Alexandria Main University Hospital dialysis unit, and it might be a possible mechanism of transmission of HBV infection between them. The protocol implemented in the Alexandria Main University Hospital dialysis unit for detection of HBV positive patients should be refined to screening with sensitive PCR-based assays for all dialysis patients regardless of biochemical or serological findings.

microRNA146a (miRNA) expression profiles are likely to become important diagnostic and prognostic tools in many disease aspects. This work aimed to study the expression of miRNA146a in lupus patients with and without renal complications and to assess its association with disease activity. Patients enrolled in the study included 52 females affected by systemic lupus erythematosus (SLE) and another 60 females with lupus nephritis (LN). Forty-eight age-matched healthy females were enrolled as a control group. miRNA146a expression was assessed using real-time PCR. In SLE patients, miRNA146a was underexpressed as compared to healthy controls and lower levels were detected among lupus patients with renal affection. In addition, miRNA146a expression was low and serum Interferon-α (IFN-α) level was high in patients with active lupus as compared to those with inactive disease. miRNA146a expression was inversely correlated to serum IFN-α level and to anti ds-DNA titer in the three studied groups. In conclusion, miRNA146a might be implicated in lupus pathogenesis. Moreover, miRNA146a expression correlates negatively to lupus activity and LN, whereas serum IFN-α has a direct correlation to both disease activity and nephritis; hence, both miRNA146a expression and serum IFN-α could be potentially important diagnostic biomarkers and potential novel strategies for therapeutic interventions, which may possibly be implied to enhance the sensitivity and specificity for the prediction of flares and prognosis in SLE patients., (© 2012 Wiley Periodicals, Inc.)

Aim: This study evaluates the use of cell-free fetal DNA in the plasma of RhD-negative women for noninvasive early detection of fetal RhD status and gender., Method: Ninety RhD-negative pregnant women were enrolled in the study. Amplification by real-time polymerase chain reaction (PCR) of RhD gene sequences and SRY gene sequence for the diagnosis of fetal RhD and sex was performed., Results: Among 90 RhD-negative women, according to phenotypic diagnosis, there were 61 RhD-positive and 29 RhD-negative fetuses. Also, 37 were males and 53 were females. In the first trimester, the sensitivity and the diagnostic accuracy of real-time PCR for Rh genotyping were 93.5% and 91.1%, increasing to 100% and 97.78%, respectively, in the second trimester. With regard to fetal sex determination, in the first trimester, PCR results had a sensitivity of 95.2% and a diagnostic accuracy of 97.8%, both increasing to 100% in the second trimester., Conclusion: The use of cell-free fetal DNA in prenatal noninvasive early detection of fetal RhD status and gender by real-time PCR is highly sensitive and accurate as early as the 11th week of gestation for RhD status and the 7th week of gestation for fetal sex.