Analysis of IDH and EGFR as biomarkers in glioblastoma multiforme: A case-control study.

Background: Glioblastoma multiforme (GBM) is a very aggressive primary central nervous system (CNS) tumor with limited therapeutic options and poor prognosis. This study aimed to analyze the association between single nucleotide polymorphisms (SNPs), including IDH1 rs121913500C > T, IDH2 rs11540478G > A, and EGFR rs1468727C > T, and their association on the risk and overall survival of GBM patients in Jordan. Methods: Using a case-control study design involving 63 GBM patients and 226 healthy controls was conducted at King Abdullah University Hospital in Jordan. DNA extraction was performed using formalin-fixed and paraffin-embedded tissue for GBM samples and blood samples for controls. SNPs analysis was performed using the Sequenom iPLEX assay sequencing technique. Survival outcomes were assessed using Cox models and hazard ratios (HR), and single-cell RNA (scRNA) analysis was performed from GSE70630. Results: The study showed a significant association between genotype frequency in GBM cases and controls for specific SNPs, including IDH1 rs121913500C > T, and EGFR rs1468727C > T. The G/G genotype of rs11540478 (IDH2) was associated with better prognostic outcomes in GBM patients. The scRNA analysis demonstrated the differential expression of IDH1, IDH2, and EGFR in GBM, with enrichment in central carbon metabolism in cancer. Conclusion: Our findings suggest that SNPs, particularly in IDH1 and IDH2 genes and EGFR, may serve as diagnostic and prognostic biomarkers for GBM. While the study underscores the clinical relevance of these genetic variants, further investigations with larger and more diverse populations are essential to validate and extend these associations.

The impact of IDH and NAT2 gene polymorphisms in acute myeloid leukemia risk and overall survival in an Arab population: A case-control study.

Acute myeloid leukemia (AML) is a malignancy of the myeloid cells due to the clonal and malignant proliferation of blast cells. The etiology of AML is complex and involves environmental and genetic factors. Such genetic aberrations include FLT3, DNMT3, IDH1, IDH2, NAT2, and WT. In this study, we analyzed the relationship between five, not previously studied in any Arab population, single nucleotide polymorphisms (SNPs) and the risk and overall survival of AML in Jordanian patients. The SNPs are NAT2 (rs1799930 and rs1799931), IDH1 (rs121913500), and IDH2 (rs121913502 and rs1057519736). A total number of 30 AML patients and 225 healthy controls were included in this study. Females comprised 50% (n = 15) and 65.3% (n = 147) of patients and controls, respectively. For AML patients (case group) Genomic DNA was extracted from formalin-fixed paraffin-embedded tissues and from peripheral blood samples for the control subjects group. Genotyping of the genetic polymorphisms was conducted using a sequencing protocol. Our study indicates that NAT2 rs1799930 SNP had a statistically significant difference in genotype frequency between cases and controls (p = 0.023) while IDH mutations did not correlate with the risk and survival of AML in the Jordanian population. These results were also similar in the TCGA-LAML cohorts with the notable exception of the rare NAT2 mutation. A larger cohort study is needed to further investigate our results.

Integrative analysis of gene expression and DNA methylation to identify biomarkers of non-genital warts induced by low-risk human papillomaviruses infection.

Background: Human papillomaviruses have been shown to dysregulate the gene expression and DNA methylation profiles of their host cells over the course of infection. However, there is a lack of information on the impact of low-risk HPV infection and wart formation on host cell's expression and methylation patterns. Therefore, the objective of this study is to analyse the genome and methylome of common warts using an integrative approach. Methods: In the present study, gene expression (GSE136347) and methylation (GSE213888) datasets of common warts were obtained from the GEO database. Identification of the differentially expressed and differentially methylated genes was carried out using the RnBeads R package and the edgeR Bioconductor package. Next, functional annotation of the identified genes was obtained using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Network construction and analyses of the gene-gene, protein-protein, and signaling interactions of the differentially expressed and differentially methylated genes was performed using the GeneMANIA web interface, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the Signaling Network Open Resource 2.0 (SIGNOR 2.0), respectively. Lastly, significant hub genes were identified using the Cytoscape application CytoHubba. Results: A total of 276 genes were identified as differentially expressed and differentially methylated in common warts, with 52% being upregulated and hypermethylated. Functional enrichment analysis identified extracellular components as the most enriched annotations, while network analyses identified ELN, ITGB1, TIMP1, MMP2, LGALS3, COL1A1 and ANPEP as significant hub genes. Conclusions: To the best knowledge of the authors, this is the first integrative study to be carried out on non-genital warts induced by low-risk HPV types. Future studies are required to re-validate the findings in larger populations using alternative approaches.

Genotoxicity of nedaplatin in cultured lymphocytes: modulation by vitamin E.

Nedaplatin is a chemotherapeutic agent used widely in cancer therapy. Nedaplatin has been shown to cause DNA damage to cells via the induction of oxidative stress. Vitamin E (Vit E) has an anti-mutagenic activity that can protect cells from DNA damaging agents. The objective of this study is to examine the genotoxic and cytotoxic effects of nedaplatin in human cultured lymphocytes. In addition, modulation of such effects by Vit E was also examined. The frequencies of sister chromatid exchange (SCE) and chromosomal aberrations (CAs) were used as an indicator for genotoxicity. The mitotic and proliferative indices were used to examine the cytotoxic effects of nedaplatin. The results showed that nedaplatin significantly elevated SCE and CA frequencies in human lymphocytes (p Ë‚ 0.01). The increases in the frequencies of SCE and CA caused by nedaplatin were lowered by pretreatment treatment with Vit E (p < 0.05). Nedaplatin significantly lowered mitotic index but Vit E pretreatment did not modulate this effect. These results suggest that Vit E has the potential to ameliorate the genotoxicity of nedaplatin in cultured lymphocytes.

Network analysis of long non-coding RNA expression profiles in common warts.

Background: Long non-coding RNAs (lncRNAs) have been the subject of considerable attention in recent years due to their role in gene regulation. However, the function of lncRNAs remains poorly understood, especially in the context of infection with low-risk human papillomaviruses (HPVs). To further understanding on this issue, we investigated lncRNA expression in HPV-induced common warts. Methods: A publicly available high-throughput sequencing dataset for common warts was downloaded from the Gene Expression Omnibus (GEO). lncRNA profiles were generated using the NetworkAnalyst 3.0 workflow, and a list of differentially expressed (DE) lncRNAs in common warts was identified and inputted into the ENCODE, RegNetwork, DisGeNet, and miRNet platforms. Results: A total of 54 lncRNAs were revealed to be significantly dysregulated in common warts. Of these 54 lncRNAs, 24 and 30 were upregulated and downregulated, respectively. The most significantly differentially expressed lncRNAs in common warts included the CERNA2, LINC02159, SH3PXD2A-AS1, and UNC5B-AS1 genes. Conclusion: The current findings suggest that HPV-induced warts impact the host lncRNA transcriptome. To the best of our knowledge, the present study is the first to explore the impact of low-risk HPV infection on lncRNA expression profiles.

RAD51-UTR haplotype genetic polymorphisms and susceptibility to breast cancer in women from Jordanian population.

BACKGROUND: Genetic predisposition to breast cancer (BC) has been extensively explored to achieve an enhanced understanding of the biology of BC. Targeting candidate genes to screen different genetic variants such as RAD51 gene that plays a critical role in DNA repair pathways including the double-strand break repair system is an important task. AIM: To study several single nucleotide polymorphisms (SNPs) within RAD51-UTR gene and to find their relationship with BC risk and prognosis among Jordanian females. MATERIALS AND METHODS: In this case-control study, DNA sequencing technique was used to screen SNPs within the untranslated region (UTR) of RAD51 in 206 cases and 185 controls and the resulting data were statistically analyzed using different types of genetic analyses. Patients' clinical and pathological features were obtained from their medical records to perform genotype-phenotype association analysis. RESULTS: Our findings show a significant association between both SNPs rs528590644, rs1801320 and BC risk (p = 0.016). We estimated the correlation between many of BC prognostic factors and BC risk, and we found an association between rs1801321 and age at first menstruation (p = 0.032) in addition to a strong correlation between age at BC diagnosis and rs1801320 (p = 0.008). CONCLUSION: RAD51-UTR polymorphisms may be involved in BC development and progression.

Influence of CYP4F2, ApoE, and CYP2A6 gene polymorphisms on the variability of Warfarin dosage requirements and susceptibility to cardiovascular disease in Jordan.

Cardiovascular diseases are among the leading causes of death worldwide. Many of those diseases require treatment with warfarin, an anticoagulant that has a large high inter and intra-variability in the required doses. The aim of this study is to find if there are any associations between rs2108622 of CYP4F2, rs7412 and rs405509 of ApoE, and rs1801272 of CYP2A6, and CVD and warfarin dose variability. The selected genes and their polymorphisms are involved in many GWAS associated with cardiovascular disease and variability in warfarin treatment. The study sample consisted of 212 Jordanian Cardiovascular patients and 213 healthy controls. DNA was extracted and the Mass ARRAY™ system was used to genotype four selected SNPs within three genes (CYP4F2, ApoE, and CYP2A6). Only one out of the four selected SNPs (ApoE rs7412 SNP) was found to be associated with the risk of cardiovascular disease. Also, this SNP showed significant differences in warfarin initial doses. CYP2A6 rs1801272 SNP was found to be associated with warfarin sensitivity during the initiation phase of therapy and with warfarin responsiveness and INR measurement during the stabilization phase of therapy. This study improves the current understanding of the high inter and intra-variabilities in response to warfarin, including the variety of dosing requirements and the susceptibility to cardiovascular disease in the Jordanian Arab population. Further study on a larger sample and in different ethnic groups could help in improving our understanding of warfarin's pharmacogenetics and its application in personalized medicine.

Genetic susceptibility of opioid receptor genes polymorphism to drug addiction: A candidate-gene association study.

BACKGROUND: Like other complex diseases including drug addiction, genetic factors can interfere with the disease. In this study, three opioid genes (OPRM1, OPRD1, and OPRK1) were examined for an association with drug addiction among Jordanian males. METHODS: The study involved 498 addicts, in addition to 496 healthy controls and all from Arab descent. RESULTS: The findings in this study showed that rs1799971 of the OPRM1 gene was in association with drug addiction for both alleles and genotypes with P-values = 0.002 and 0.01, respectively. In addition, a significant association between the dominant model (A/A vs G/A-G/G) of rs1799971 (OPRM1) and drug addiction (P-value = 0.003, OR = 1.59 (1.17-2.15)) was detected. Moreover, a genetic haplotype (AGGGCGACCCC) of theOPRM1 gene revealed a significant association with drug addiction (P-value = 0.01, OR = 1.56 (1.15-2.12)). We also found that the age of addicts, smoking, and marital status with genetic variants within OPRM1, OPRD1, and OPRK1 genes may be implicated in drug addiction risk. CONCLUSION: We propose that rs1799971 of the OPRM1gene is a genetic risk factor for drug addiction among Jordanian males.

Global gene methylation profiling of common warts caused by human papillomaviruses infection.

Infection with the human papillomaviruses (HPV) often involves the epigenetic modification of the host genome. Despite its prevalence among the population, host genome methylation in HPV-induced warts is not clearly understood. In this study, genome-wide methylation profiling was carried out on paired healthy skin and wart samples in order to investigate the effects that benign HPV infection has on gene methylation status. To overcome this gap in knowledge, paired wart (n = 12) and normal skin (n = 12) samples were obtained from Arab males in order to perform DNA extraction and subsequent genome-wide methylation profiling on the Infinium Methylation EPIC Bead Chip microarray. Analysis of differential methylation revealed a clear pattern of discrimination between the wart and normal skin samples. In warts, the most differentially methylated (DM) genes included long non-coding RNAs (AC005884, AL049646.2, AC126121.2, AP001790.1, and AC107959.3), microRNAs (MIR374B, MIR596, MIR1255B1, MIR26B, and MIR196A2),snoRNAs (SNORD114-22, SNORD70, and SNORD114-31), pseudogenes (AC069366.1, RNU4ATAC11P, AC120057.1, NANOGP3, AC106038.2, TPT1P2, SDC4P, PKMP3, and VN2R3P), and protein-coding genes (AREG, GJB2, C12orf71, AC020909.2, S100A8, ZBED2, FABP7, and CYSLTR1). In addition, pathway analysis revealed that, among the most differentially methylated genes, STAT5A, RARA, MEF2D, MAP3K8, and THRA were the common regulators. It can be observed that HPV-induced warts involve a clear and unique epigenetic alteration to the host genome.

Association of CYP2C19, TNF-α, NOD1, NOD2, and PPARγ polymorphisms with peptic ulcer disease enhanced by Helicobacter pylori infection.

OBJECTIVES: To assess the correlation between a number of genetic variations of CYP2C19, TNF-α, NOD1, NOD2, and PPARγ genes with the severity of Helicobacter pylori (H. pylori) infections and peptic ulcers (PU). METHODS: A retrospective cross-sectional design was used in this study. Formalin-fixed paraffin-embedded (FFPE) tissue was used to extract genomic DNA that was collected from Jordanian patients who visited endoscopy clinics between 2014 to 2018 at the King Abdullah University Hospital (KAUH), Irbid, Jordan. Genotyping of the studied single nucleotide polymorphisms (SNPs) were applied using the sequencing protocol. Results:  A total of 251 patients (mean age: 42.12 ± 16.09 years) and healthy controls (mean age: 52.76 ± 19.45 years) were enrolled in this study. This study showed no significant association between patients and the studied polymorphisms except for rs2075820 of the NOD1 (p=0.0046). It is hypothesized that the heterozygous genotype (TC); 44.8% in patients versus 61.3% in controls has a decreased risk of peptic ulcers (OR:  0.49). The alleles frequency association was insignificant in all studied SNPs with a p-value more than 0.05. CONCLUSION: This study provided evidence regarding the association of the rs2075820 with H. pylori infections. The other studied SNPs were not statistically significant.

Clavulanic Acid in the Scope of Helicobacter pylori Treatment: A Literature Review and Beyond.

BACKGROUND: Helicobacter pylori (H. pylori) infection is the most common cause of peptic ulcer disease and it can be associated with many complications, including malignancies. In clinical practice, some clinicians may use Clavulanic Acid (CA) in combination with amoxicillin or other beta-lactams as an addition to the standard treatment regimens. This practice may be done by habitual mistake, non-evidence based hypothetical assumptions, or by prescribing it as an alternative treatment. This review aims to expose the effect of CA against H. pylori infection and to review the possible mechanisms that may contribute to that effect. METHODS: A PubMed and Google Scholar literature search was obtained on both pre-clinical and clinical studies related to CA and H. pylori infection. RESULTS: Available clinical studies showed improvement in the eradication of H. pylori by about 10- 20% when CA was added to the treatment regimens. This effect for CA could be related to several mechanisms including inhibition of H. pylori growth by binding to Penicillin-Binding Proteins (PBPs), the transformation of H. pylori from the active filamentous form into coccoidal form, induction of the release of dopamine, modulation of immunological response towards H. pylori infection and its relationship with other microbiota. Randomized-controlled studies on patients with resistance to H. pylori are needed. Moreover, in vitro studies to evaluate the mechanisms by which CA may influence H. pylori are warranted. CONCLUSION: The presented literature suggests potential avenues for the use of CA in the management of peptic ulcer disease and H. pylori infection.

The Associations of Common Genetic Susceptibility Variants with Breast Cancer in Jordanian Arabs: A Case-Control Study.

OBJECTIVE: In Jordan, breast cancer (BC) affects a substantial proportion of Jordanian women, highlighting the need for studies to be carried out regarding the genetic component of the disease. The aim of the present study was to investigate the interaction between BC risk and prognosis and polymorphisms in genes (ATM, CASP8, FGFR2, FN1, IGF1, LSP1, MAP3K, MMP7, and RHOC) that were chosen for this study previously reported as having a role in the disease. MATERIALS AND METHODS: Blood samples were collected from 242 BC patients and 231 disease-free volunteers recruited from the Jordanian population. DNA was extracted from blood and each sample was sent to the Australian Genome Research Facility for genotyping. RESULTS: The rs1219648 SNP of the FGFR2 gene was the only investigated variant to show any direct association with BC in Jordanian women (p-value = 0.04). However, the CASP8rs6760993 SNP was found to be significantly associated with BC (p-value = 0.04) when using the dominant model. Other gene polymorphisms showed varying levels of association between some investigated SNPs and different BC risk and prognostic factors. CONCLUSION: Despite reports to the contrary in other populations, most of the investigated genes and their respective SNPs did not show any significant association with BC in Jordanian women. Our results underline the need for independent BC research to be carried out in the Jordanian population to decipher the genetic basis of the disease.
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LTA, LEP, and TNF-a Gene Polymorphisms are Associated with Susceptibility and Overall Survival of Diffuse Large B-Cell lymphoma in an Arab Population: A Case-Control Study.

OBJECTIVE: In this study, we aimed to explore the relationship between five selected proinflammatory and immune-mediated genes (TNF rs1800629G>A, rs361525G>A, rs1799964T>C, LTA rs1800683G>A, rs909253A>G, TNFAIP8 rs1042541C>T, LEPR rs1327118G>C, and LEP rs2167270G>A) and the risk and overall survival of DLBCL patients within the Jordanian Arab population. METHODS: One hundred twenty-five patients (125) diagnosed with DLBCL at the King Abdullah University Hospital (KAUH) between 2013 and 2018 and 238 healthy cancer-free control subjects with similar geographic and ethnic backgrounds to the patients were included in the study. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissues of the subjects and from peripheral blood samples of the controls. The Sequenom MassARRAY® sequencer system (iPLEX GOLD) was used. The analyses included assessments of population variability and survival. RESULTS: Our study showed significant differences in the distribution of the studied polymorphisms of DLBCL between the patients and controls for TNF rs1800629G>A, LTA rs909253 G>A and LEP rs2167270 G>A. TNF rs1800629G>A (p = 0.01), in which the G allele harbors a higher risk of DLBCL (GG and GA genotypes when compared with AA genotype) (p = 0.044). The LTA rs909253 A>G polymorphism is associated with a higher risk of DLBCL in the allelic model (p = .004).  LEP rs2167270 G>A polymorphism is associated with a decreased risk of DLBCL in the recessive mode models (p = .03). Subjects with the dominant model for TNF-a rs1799964 (TT genotype in comparison with the combined TT/TC genotype) and patients with the homozygous genotype (GG) of rs361525 have better overall survival rates. CONCLUSION: Our results confirmed the diversity and the heterogeneity of the disease. Although the study has a limitation because of its relatively small size, it clearly emphasizes the significance of ancestry and genetic composition as the determinants of DLBCL risk and behavior.
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Possible mechanisms for the renoprotective effects of date palm fruits and seeds extracts against renal ischemia/reperfusion injury in rats.

PURPOSE: This work investigates the possible renoprotective effects of date palm fruits and seeds extract against renal ischemia and their underlying mechanisms. METHODS: 108-Sprague Dawle male rats were randomly allocated into 6 equal groups differently receiving aqueous or methanolic fruit and seed extracts. Assay of serum creatinine, BUN and TNF-α, morphological examination of the left kidney, markers of the redox state (MDA, CAT, and GSH), the expression of TNFα and Nrf2 genes at the level of mRNA, the expression of caspase-3 and TGF-ß proteins by immunohistochemistry were performed. RESULTS: 45-min renal I/R caused significant deterioration of kidney functions (increase in serum creatinine and BUN) and morphology (P < 0.001) and significant reduction in CAT activity and GSH levels with significant increase in serum TNF-α and MDA concentration and the expression of Nrf2, caspase-3, TNF-α, and TGF-ß in kidney tissues. Pre-treatment with either date palm fruit or seed extracts significantly improved kidney functions and morphology (P ≤ 0.001) with a significant increase in the expression of Nrf2 and CAT activity, and GSH concentration and a reduction in serum TNF-α and expression of caspase-3, TNF-α, and TGF-ß (P < 0.001). CONCLUSIONS: Administration of date palm extracts exhibited a renoprotective effect against renal I/R injury.This renoprotective action might be due to their antioxidants, anti-apoptotic and anti-inflammatory actions. Moreover, aqueous fruit extracts offered powerful renoprotective effect than aqueous seed extracts, and aqueous fruit and seed extracts were generally more effective than methanolic extracts.

The Impact of the Genetic Polymorphism in DNA Repair Pathways on Increased Risk of Glioblastoma Multiforme in the Arab Jordanian Population: A Case-Control Study.

INTRODUCTION: Among the Jordanian population, brain tumors are the tenth most common type of cancers in both males and females, comprising 2.8% of all newly diagnosed neoplasms. Diffuse gliomas are the most prevalent and the most aggressive primary brain tumors in adults. The incidence of diffuse gliomas varies among different populations; this variation is partially linked to genetic polymorphisms. The purpose of the study is to examine the association between (BRCA1 rs799917G>A, rs1799966T>C, EXO1 rs1047840G>A, EME1 rs12450550T>C, ERCC2 rs13181T>G, rs1799793C>T, and XRCC1 rs1799782G>A) DNA repair gene polymorphisms and glioblastoma multiforme (GBM) susceptibility, and survival in the Jordanian Arab population. METHODS: Eighty-four patients diagnosed with glioblastoma multiforme at the King Abdullah University Hospital (KAUH) between 2013 and 2018 and 225 healthy cancer-free control subjects with similar geographic and ethnic backgrounds to the patients were included in the study. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissues of the subjects. The Sequenom MassARRAY® sequencer system (iPLEX GOLD) was used. The analyses included assessments of population variability and survival. RESULTS: This study is the first to address the relationship between BRCA1 rs1799966 and rs799917 SNP, and the risk of GBM among the Arab Jordanian population. The findings of the study show that BRCA1 rs799917 is associated with decreased risk of GBM in the recessive model (AA vs G/G-A/G: OR, 0.46, 95% CI, 0.26-0.82, p=0.01) and the same SNP is associated with increased risk of GBM in the overdominant model (AG vs G/G-A/A: OR, 1.72, 95% CI, 1.02-2.89, p=0.04).

Identification of Differentially Methylated CpG Sites in Fibroblasts from Keloid Scars.

As a part of an abnormal healing process of dermal injuries and irritation, keloid scars arise on the skin as benign fibroproliferative tumors. Although the etiology of keloid scarring remains unsettled, considerable recent evidence suggested that keloidogenesis may be driven by epigenetic changes, particularly, DNA methylation. Therefore, genome-wide scanning of methylated cytosine-phosphoguanine (CpG) sites in extracted DNA from 12 keloid scar fibroblasts (KF) and 12 control skin fibroblasts (CF) (six normal skin fibroblasts and six normotrophic fibroblasts) was conducted using the Illumina Human Methylation 450K BeadChip in two replicates for each sample. Comparing KF and CF used a Linear Models for Microarray Data (Limma) model revealed 100,000 differentially methylated (DM) CpG sites, 20,695 of which were found to be hypomethylated and 79,305 were hypermethylated. The top DM CpG sites were associated with TNKS2, FAM45B, LOC723972, GAS7, RHBDD2 and CAMKK1. Subsequently, the most functionally enriched genes with the top 100 DM CpG sites were significantly (p ≤ 0.05) associated with SH2 domain binding, regulation of transcription, DNA-templated, nucleus, positive regulation of protein targeting to mitochondrion, nucleoplasm, Swr1 complex, histone exchange, and cellular response to organic substance. In addition, NLK, CAMKK1, LPAR2, CASP1, and NHS showed to be the most common regulators in the signaling network analysis. Taken together, these findings shed light on the methylation status of keloids that could be implicated in the underlying mechanism of keloid scars formation and remission.

Genome-wide identification of methylated CpG sites in nongenital cutaneous warts.

BACKGROUND: Low-risk HPV infection has not been the subject of epigenetic investigation. The present study was carried out in order to investigate the methylation status of CpG sites in non-genital cutaneous warts. METHODS: Genomic DNA was extracted from 24 paired epidermal samples of warts and normal skin. DNA samples were bisulfite converted and underwent genome-wide methylation profiling using the Infinium MethylationEPIC BeadChip Kit. RESULTS: From a total of 844,234 CpG sites, 56,960 and 43,040 CpG sites were found to be hypo- and hypermethylated, respectively, in non-genital cutaneous warts. The most differentially methylated CpG sites in warts were located within the C10orf26, FAM83H-AS1, ZNF644, LINC00702, GSAP, STAT5A, HDAC4, NCALD, and EXOC4 genes. CONCLUSION: Non-genital cutaneous warts exhibit a unique CpG methylation signature.

Secreted Factors from Keloid Keratinocytes Modulate Collagen Deposition by Fibroblasts from Normal and Fibrotic Tissue: A Pilot Study.

Interactions between keratinocytes and fibroblasts in the skin layers are crucial in normal tissue development, wound healing, and scarring. This study has investigated the role of keloid keratinocytes in regulating collagen production by primary fibroblasts in vitro. Keloid cells were obtained from removed patients' tissue whereas normal skin cells were discarded tissue obtained from elective surgery procedures. Fibroblasts and keratinocytes were isolated, cultured, and a transwell co-culture system were used to investigate the effect of keratinocytes on collagen production using a 'scar-in-a-jar' model. Keloid fibroblasts produced significantly more collagen than normal skin fibroblasts in monoculture at the RNA, secreted protein, and stable fibrillar protein level. When keloid keratinocytes were added to normal skin fibroblasts, expression of collagen was significantly upregulated in most samples, but when added to keloid fibroblasts, collagen I production was significantly reduced. Interestingly, keloid keratinocytes appear to decrease collagen production by keloid fibroblasts. This suggests that signaling in both keratinocytes and fibroblasts is disrupted in keloid pathology.

Application of Gas Chromatography-Mass Spectrometry for the Identification and Quantitation of Three Common Synthetic Cannabinoids in Seized Materials from the Jordanian Market.

Synthetic cannabinoids (SCs) were developed to mimic the effects of Δ9-tetrahydrocannabinol on humans. SCs were distributed in the form of herbal blends, with smoking being the main method of consumption. These synthetic compounds have a wide range of physical, behavioral, and harmful effects on the body. However, this study aimed to identify and quantify three common SCs including AB-FUBINACA, AB-CHMINACA, and XLR-11 in the seized materials from the Jordanian market by gas chromatography coupled with mass spectrometry (GC-MS). A liquid-liquid extraction sample preparation technique was applied to 100 different seized samples obtained from the Anti-Narcotics Department of Public Security in a period between 2017 and 2018. Profiling of the seized samples revealed different distributions of the targeted SCs in the obtained samples. Upon quantitation, concentrations of these SCs varied greatly within and among the samples. The use of GC-MS analysis provided a powerful technique in the detection and identification of SCs. This study revealed the current and trends of SC use in the Jordanian illicit substance market, which was previously unclear. Future studies are required to explore new SCs and their influence in different biological samples.

Transcriptome analysis of HPV-induced warts and healthy skin in humans.

BACKGROUND: The human papillomaviruses (HPV) are a group of viruses that, depending on the strain, can cause cancer or the formation of benign growths known as warts. Scarce information exists with regard to the genetic nature of non-genital cutaneous warts induced by the human papillomavirus (HPV). METHODS: The main purpose of this study is to investigate the differences between the gene expression profiles of common warts and healthy skin in HPV-positive individuals by RNA sequencing on the Illumina HiSeq 2500. After obtaining shave biopsies of common warts and healthy skin from twelve Arab males, we were able to analyze the transcriptomes of 24 paired cases and controls. RESULTS: Common warts were found to possess a highly significant and unique molecular signature. Many of the most up-regulated (KRT16, EPGN, and ABCG4) and down-regulated genes (C15orf59, CYB561A3, and FCGRT) in warts were the subject of little investigation in the published literature. Moreover, the top 500 differentially expressed genes were found to be associated with immune and autoimmune pathways, such as the neutrophil degranulation, toll-like receptor 7/8 (TLR 7/8) cascade, toll-like receptor 9 (TLR9) cascade, and toll-like receptor 10 (TLR10) pathways, among others. CONCLUSIONS: Our findings are particularly important because they serve as the most comprehensive to date with regard to the modulation of human skin gene expression by HPV infection.