Cellular and Molecular Biology

Molecular cloning and characterization of heat-responsive LcOPR1, a gene encoding oxophytodienoic acid reductase in lentil

2024-06-04T16:50:56+02:00

Improving crop plants using biotechnological implications is a promising and modern approach compared to traditional methods. High-temperature exposure to the reproductive stage induces flower abortion and declines grain filling performance, leading to smaller grain production and low yield in lentil and other legumes. Thus, cloning effective candidate genes and their implication in temperature stress tolerance in lentil (Lens culinaris Medik.) using biotechnological tools is highly demandable. The 12-oxophytodienoic acid reductases (OPRs) are flavin mononucleotide-dependent oxidoreductases with vital roles in plants. They are members of the old yellow enzyme (OYE) family. These enzymes are involved in the octadecanoid pathway, which contributes to jasmonic acid biosynthesis and is essential in plant stress responses. Lentil is one of the vital legume crops affected by the temperature fluctuations caused by global warming. Therefore, in this study, the LcOPR1 gene was successfully cloned and isolated from lentils using RT-PCR to evaluate its functional responses in lentil under heat stress. The bioinformatics analysis revealed that the full-length cDNA of LcOPR1 was 1303 bp, containing an 1134 bp open reading frames (ORFs), encoding 377 amino acids with a predicted molecular weight of 41.63 and a theoretical isoelectric point of 5.61. Bioinformatics analyses revealed that the deduced LcOPR1 possesses considerable homology with other plant 12-oxophytodienoic acid reductases (OPRs). Phylogenetic tree analysis showed that LcOPR1 has an evolutionary relationship with other OPRs in different plant species of subgroup I, containing enzymes that are not required for jasmonic acid biosynthesis. The expression analysis of LcOPR1 indicated that this gene is upregulated in response to the heat-stress condition and during recovery in lentil. This study finding might be helpful to plant breeders and biotechnologists in LcOPR1 engineering and/or plant breeding programs in revealing the biological functions of LcOPR1 in lentils and the possibility of enhancing heat stress tolerance by overexpressing LcOPR1 in lentil and other legume plants under high temperature.

Mitofusin 1 and 2 overexpression reduces AβO-mediated ER stress and apoptosis in N2a APPswe cells

2024-06-04T16:57:15+02:00

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and amyloid beta oligomers (AβO), which are pathological markers of AD, are known to be highly toxic. AβO increase mitochondrial dysfunction, which is accompanied by a decrease in mitochondrial fusion. Although mitofusin (Mfn) 1 and Mfn2 are mitochondrial fusion proteins, Mfn2 is known to regulate endoplasmic reticulum (ER) function, as it is located in the ER. Several studies have shown that AβO exacerbates ER stress, however, the exact mechanism requires further elucidation. In this study, we used mouse neuroblastoma cells stably overexpressing the amyloid precursor protein (APP) with the Swedish mutation (N2a APPswe cells) to investigate the role of Mfn in ER stress. Our results revealed that amyloid beta (Aβ) caused cellular toxicity in N2a APPswe cells, upregulated ER stress-related proteins, and promoted ER expansion. The AβO-mediated ER stress was reduced when Mfn1 and Mfn2 were overexpressed. Moreover, Mfn1 and Mfn2 overexpressed resulted in reduced apoptosis of N2a APPswe cells. In conclusion, our results indicate that both Mfn1 and Mfn2 reduce ER stress and apoptosis. Our data provide a foundation for future studies on the roles of Mfn1 and Mfn2 in the molecular mechanisms underlying AβO-mediated ER stress and the pathogenesis of AD.

Unraveling the molecular regulation of biofilm underlying effect of chronic disease medications

2024-06-04T17:01:12+02:00

A biofilm is a complex microbial structure that promotes the progression of persistent infections, particularly in nosocomial settings via indwelling medical devices. Conventional antibiotics are often ineffective treatments for biofilms; hence, it is crucial to investigate or design non-antibiotic antibiofilm compounds that can successfully reduce and eradicate biofilm-related infections. This study was an attempt to repurpose chronic disease medications of the antihypertensive and antilipidemic drug classes, including candesartan cilexetil (CC) and ursodeoxycholic acid (UDCA), respectively, to be used as antibiofilm agents against the two infectious pathogens Staphylococcus aureus and Enterococcus faecalis. Crystal violet (CV) staining assay was used to evaluate the antibiofilm activity of the drugs. Real-time polymerase chain reaction (RT-PCR) was performed to determine the transcription levels of the biofilm-related genes (icaA and icaR in S. aureus and fsrC and gelE in E. faecalis) following treatment with different concentrations of CC and UDCA. we found that a concentration of greater than 1.5 µg/ml of CC significantly (p < 0.005) inhibited the biofilm formation of both bacterial isolates, and a concentration of greater than 50 µg/ml of UDCA significantly (p < 0.005) inhibited the biofilm formation of both bacterial isolates. Interestingly, the mRNA expression levels of biofilm-related genes were decreased in the two bacterial isolates at concentrations that were lower than the human pharmaceutical daily doses.

Dual protection of aqueous garlic extract biomolecules against hemolysis and its oxidation products in preventing inflammation

2024-06-04T17:07:00+02:00

Garlic (Allium sativum) is recognized as functional food, rich in bioactive compounds that can combat diseases associated with oxidative stress. This study aims to investigate the protective potential of aqueous garlic extract against hemolysis and oxidation. Despite being caused by membrane fragility, hemolysis can lead to inflammation through the oxidation of its products, and in some cases, even exacerbate it in certain pathological contexts. Supplementation with antioxidant molecules can improves oxidative status, in this study, we selected garlic, an excellent functional food, and targeted its effects using aqueous extract and pure molecules. The aqueous garlic extract was prepared under safe conditions and subjected to toxicity on human neutrophils and red blood cells before experimentation. The results indicate that aqueous garlic extract significantly reduces hemolysis with a maximum protection of 98. 74 ± 1. 08 % at a concentration of 5μg/ml. Additionally, experiments were conducted with pure compounds found in garlic such as quercetin, gallic acid, and caffeic acid. The outcomes show that quercetin reduces hemolysis of RBC with a maximum protection of 88. 8 ± 2. 89 % at 20 µM followed by caffeic acid and gallic acid. The action mechanism of the extract was tested on human neutrophil cells, the extract significantly reduced luminol-amplified chemiluminescence of PMA-stimulated neutrophils up to 50 % at 10 µg/ml in addition to its ability to directly scavenge hydrogen peroxide. Our results suggest that aqueous garlic extract exerts promising anti-inflammatory activity in vitro. Through its dual protection against hemolysis and Ros production, garlic may indirectly prevent inflammation reducing the oxidation of hemolysis products. These abilities make garlic aqueous extract promising candidate for improving cardiovascular health, reducing oxidative stress and modulating immunity.

Oxidative stress and galectin-3 levels during skin grafting after hand injury: gender differences

2024-06-04T17:09:05+02:00

The study included 40 patients of both genders who underwent skin transplantation after a hand injury. The study aims to evaluate the oxidative stress parameters in patients’ blood and serum levels of galectin-3 in order to investigate gender differences pre- and post- skin transplantation. The results of the study suggest a significant increase in superoxide anion radical levels, catalase activity, and reduced glutathione levels in females before skin transplantation. The surgical treatment caused significant increase in superoxide anion radical and hydrogen peroxide levels as prooxidants in males, while superoxide dismutase and catalase activity were also increased 7 days after the procedure. In females, superoxide anion radical and TBARS levels increased after surgical procedure as well as the activity of catalase. Regarding galectin-3 levels, a significant interaction between gender and time was observed (gender×time; p=0.000). Correlation analysis of different oxidative stress markers with gal-3 revealed the existence of a significant negative correlation of superoxide anion radical, catalase, and reduced glutathione with gal-3, but only in female patients. It can be concluded that OS as well as galectin-3 play important roles at least in the first 7 days of the postoperative period.

Pulsatillic acid as a potential inhibitor of protein kinase C-alpha in non-small cell lung cancer

2024-06-04T17:22:44+02:00

Non-small cell lung cancer (NSCLC) is a global health concern with a significant impact on morbidity and mortality. Small molecule inhibitors targeting genetic mutations like EGFR and ALK have shown promise in NSCLC treatment. This study focuses on Protein Kinase C-alpha (PKCα), implicated in NSCLC pathogenesis. Overexpression of PKCα correlates with advanced disease stages. Preclinical studies suggest its inhibition can suppress NSCLC cell growth. The research employs molecular docking to identify Pulsatillic acid (PA) as a potential PKCα inhibitor. ADMET predictions support PA's candidacy and PASS analysis and Swiss Target Prediction reveal its biological properties. Fluorescence-based binding assays demonstrate PA's inhibitory potency on PKCα, aligning with molecular docking findings. Cytotoxicity assays show PA's minimal impact on HEK-293 cell viability, with an IC50 of 21.03 μM in A549 cells. mRNA expression analysis in A549 cells indicates PA's potential inhibitory effect on PKCα. In conclusion, this study highlights that PA may emerge as a promising therapeutic candidate for NSCLC, emphasizing the need for further research, validation, and exploration of its translational potential. The study contributes valuable insights into NSCLC treatment strategies, emphasizing the significance of targeting PKCα.

Exploring the In Vitro and In Vivo Therapeutic Efficacy of Juniperus oxycedrus Cade Oil: Antioxidant, Anti-inflammatory, and Anti-asthmatic Effects in an Allergic Asthma Model

2024-06-04T17:28:40+02:00

This investigation aimed to explore the antioxidant, anti-inflammatory effects of Cade oil and its efficacy within a Wistar allergic asthma model. The antioxidant activity was assessed through various in vitro tests using chain-breaking antioxidant effects (radical scavenging and reducing abilities assays). In vivo experiments involved Wistar rats categorized into four groups: negative control group, Ovalbumin-sensitised/challenged group, Cade oil-treated group, and Ovalbumin-sensitised/challenged Cade oil-treated group. These experiments aimed to evaluate oxidative stress parameters in the lungs and erythrocytes. The results indicated that the Cade oil exhibited significant antioxidant capabilities, evidenced by its radical scavenging activity against DPPH, ABTS, and Galvinoxyl radicals, with IC₅₀ values ranging from 21.92 to 24.44 µg/mL. Besides, the reducing abilities methods showed A_0,5value ranging from 11.51 to 30.40 µg/mL for reducing power, Cupric ion reducing antioxidant capacity, and O-phenanthroline assays. Additionally, the IC₅₀ value for β-carotene scavenging was found to be (8.2 ± 0.25 µg/ml). Analysis revealed high levels of polyphenols and flavonoids in Cade oil, indicating rich polyphenol (275.21 ± 3.14 mg GAE/g DW) and flavonoid (28.23 ± 1.91 µg QE/mg) content. In vivo findings highlighted Cade oil's efficacy in reducing inflammatory cell recruitment, enhancing antioxidant status, reducing lipid peroxidation, and improving histopathological alterations within the allergic asthma model. These results demonstrated that Cade oil has a potent antioxidant, anti-inflammatory, and anti-asthmatic properties, suggesting its potential therapeutic application in asthma treatment.

Network preservation analysis to identify transcriptional biomarkers related to flowering in Crocus sativus

2024-06-04T17:32:34+02:00

Crocus sativus L. is known as an ornamental geophyte and a source of valuable spice and secondary metabolites. Network preservation module analysis is one of the best approaches to revealing special features of different conditions. It can determine patterns of divergence and conservation between transcriptome data. Herein, we explored the regulatory genes of the flowering process by RNA-Seq data containing flowering and non-flowering samples in gene expression profiles. Persevered module analysis revealed three significant non-persevered modules related to the flowering process, namely pink, green, and blue. Several hub genes associated with non-preserved modules such as PIA1, NAC90, ALY3, Sus3, MYB31, ARF5/MP, MYB31, HD-ZIP, SEP3d, OR_B, AGL6a, bZIP(TGA1) and GRAS were identified. These candidate genes can be considered key diagnostic biomarkers for the flowering process. Here, we also compared two approaches, WGCNA and NetRep for module preservation analysis. The results of these methods were consistent with non-preserved modules. NetRep was a faster (11 times) and more efficient (run more than 10000 permutations for each comparison) method than WGCNA module preservation. Differential expression genes (DEGs) screening showed that many hub genes were downregulated in non-flowering than flowering samples. Our finding revealed regulatory mechanisms of the flowering process in C. sativus as can be developed transcriptional biomarkers which could pave the way for promoting saffron yield via flowering induction.

MiR-3195 inhibits non-small cell lung cancer malignant behaviors along with cisplatin resistance through targeting PFKFB4

2024-06-04T17:34:42+02:00

Chemotherapy presents the main therapy of non-small cell lung cancer (NSCLC). Nevertheless, cisplatin-based therapy can be limited by drug resistance. MicroRNA (miRNA) possesses a vital regulatory function in modulating the progression as well as cisplatin resistance of NSCLC, but how miR-3195 influences NSCLC is obscure. In this work, it was discovered that miR-3195 presented definite down-regulation in NSCLC cells. Gain-of function assays revealed that overexpressing miR-3195 hindered NSCLC cell proliferation together with migration whereas induced cell apoptosis. Mechanically, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) presented the target gene of miR-3195 and was high-expressed in NSCLC cells. The repressive impacts of overexpressing miR-3195 on NSCLC cells malignant behaviors were reversed via PFKFB4 elevation. Additionally, elevated miR-3195 expression reduced cisplatin resistance of NSCLC both in vitro as well as in vivo. PFKFB4 elevation could offset the reduced cisplatin resistance caused by miR-3195 overexpression in NSCLC cells. In conclusion, this work clarified miR-3195 repressed NSCLC cell proliferation, migration, as well as cisplatin resistance by modulating PFKFB4. Our study might provide a promising clue to promote the anti-tumor effects of chemotherapy.

Hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway–based ulcer-healing mechanism of Astragalus Aqueous extract in diabetic foot rats

2024-06-04T17:53:40+02:00

The main objective of this work was to investigate the mechanism of Astragalus aqueous extract ulcer healing in diabetic foot model rats through the hypoxia-inducible factor 1-alpha (HIF-1ɑ)/vascular endothelial growth factor (VEGF) signalling pathway. Fifty specific-pathogen-free male Sprague Dawley rats were divided into blank (A), model control (B), Astragalus extract (C) and mupirocin (D) treatment groups. Group A received a regular diet, whereas the other groups received a high-fat/high-sugar diet and intraperitoneal streptozotocin injections to induce diabetes. Diabetic foot ulcers were created via skin excision. Subsequently, ulcers were debrided daily. Groups B, C and D received wet saline gauze, wet gauze with Astragalus extract and gauze with mupirocin, respectively, on the affected area. Group A received no treatment. After 14 days, the rats were assessed for ulcer healing and general condition. Immunohistochemistry was used to detect HIF-1ɑ and VEGF levels in the dorsalis pedis artery, and ELISA was used to determine serum IL-6 and CRP levels. The results revealed that Groups C and D had significantly faster ulcer healing compared with Group B (p < 0.01), and ulcer healing was faster in Group C than in Group D (p < 0.01). Group C exhibited notably higher HIF-1ɑ and VEGF protein expression levels compared with Groups B and D (p < 0.01). IL-6 and CRP expression levels in Groups C and D were significantly lower than those in Group B (p < 0.01). In summary, Astragalus aqueous extract effectively treats diabetic foot ulcers by up-regulating HIF-1ɑ and VEGF expression, activating the HIF-1ɑ/VEGF pathway, improving local tissue ischaemia and hypoxia, promoting collateral circulation and enhancing dorsalis pedis artery formation, thereby accelerating ulcer repair in diabetic rats.

Circ_0006220 (circ-TADA2A) accelerates prostate cancer cell malignant behaviors through miR-520f-3p/CDCA7 axis

2024-06-04T17:56:19+02:00

Prostate cancer (PCa) belongs to a prevailing neoplasm globally. Circular RNAs (circRNAs) are critical regulators in various tumors, but the role of circRNAs in PCa is obscure. In this research, a circRNA derived from the TADA2A gene (hsa_circ_0006220) was high-expressed in PCa tissues along with cell lines. Elevated Circ-0006220 expression was also related to PCa poor prognosis. Besides, circ-0006220 accelerated PCa cells malignant behaviors in vitro; it also promoted PCa tumor growth together with metastasis in vivo. Moreover, circ-0006220 competed with the Cell Division Cycle Associated 7 (CDCA7) for binding to miR-520f-3p. Circ-0006220 sponged miR-520f-3p to regulate CDCA7 expression, thereby promoting PCa cell proliferation, migration, invasion, along with metastasis. All above data suggested that circ-0006220 may be a worthy target for PCa therapeutics.

Bioinformatics analysis of high-intensity intermittent exercise for prevention of myocardial infarction

2024-06-04T17:57:46+02:00

The mechanism of target interaction involving high-intensity interval training (HIIT) in improving prognosis of myocardial infarction (MI) remains unclear. This study aimed to establish a visual network of "HIIT-target-disease" by referring to the methods of pharmacological disease and drug bioinformatic analysis, to explore the potential targets, and key targets and predict the potential biological mechanism of high-intensity intermittent exercise in preventing and treating myocardial infarction. Public data resources such as OMIM, NCBI and GeneCards were used to find potential targets of high-intensity intermittent exercise and myocardial infarction. Key targets of overlap between exercise and disease were determined according to the Relevance score values analyzed by GeneCards. The visual network diagram of "HIIT - Multi-target-disease" was constructed by Cytoscape. A total of 4820 disease targets and 528 high-intensity intermittent exercise targets were screened out, and 444 overlapped targets were obtained, including 425 protein targets. Five core protein targets were selected: IL10, PPARA, TNF, IL6, and STAT3. It may pass PI3K-AKT signaling pathway, Insulin resistance pathway, T-cell signaling pathway, TNF signaling pathway, and JAX-STAT signaling pathway and other pathways play a role. Our study comprehensively elucidated the potential targets, key targets and molecular mechanisms of high-intensity intermittent exercise in improving the prognosis of myocardial infarction, and proved that high-intensity intermittent exercise can act on multiple targets and multiple pathways to play a good preventive and therapeutic effect on myocardial infarction, providing scientific theoretical basis for revealing the mechanism of high-intensity intermittent exercise in the prevention and treatment of cardiovascular disease.

Goosecoid promotes pancreatic adenocarcinoma metastasis through TGF-β signaling

2024-06-04T17:59:29+02:00

Goosecoid (GSC), translated from a homeobox gene, is a protein that participates in metastasis of various cancers. Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies associated with a poor diagnosis and prognosis. To develop new treatment target or biomarker for PAAD, this study intended to assess the effects and the molecular mechanism of GSC on PAAD metastasis. The expressive discrepancy of GSC in PAAD and normal tissues/cells was compared by both the quantitative PCR and western blot. The effects of GSC silencing and GSC over-expression on PAAD cells and TGF-β signaling were proved by wound-healing assay, cell counting kit-8, Transwell assay and western blot. From the results, GSC mRNA and protein levels were enriched in PAAD cancer tissues and cells. GSC silencing prohibited metastasis of PAAD cells including the ability to invade, migrate and epithelial-mesenchymal transition (EMT), whereas GSC upregulation stimulated these cells behaviors above. GSC silencing reversed the effects on cellular processes induced by activation of the TGF-β pathway. Furthermore, silencing of GSC postponed tumor growth in xenograft model. In summary, GSC was abundantly expressed in PAAD, which activated the TGF-β pathway to enhance cell metastasis and tumor development.

Genetic and morphological diversity of introduced cultivars of almonds (Prunus amygdalus L.) in Bosnia and Herzegovina

2024-06-04T18:01:46+02:00

The main morphological and genetic characterization of seven introduced almond cultivars in Bosnia & Herzegovina was conducted. The almond cultivars included three from Italy (Tuono, Genco, Supernova), two from France (Ferragnes and Ferraduel), and two from the USA (Texas and Nonpareil). Genetic characterization was utilized by using 10 microsatellite markers, with nine markers from Prunus persicae and one from Prunus armeniaca. The results of genetic characterization revealed an average of 5.40 alleles per primer per locus. The average number of effective alleles for the 10 SSR loci of introduced cultivars was 3.92. The Shannon Information Index averaged 1.41. The observed heterozygosity (Ho) and expected heterozygosity (He) averaged 0.53 and 0.69, respectively. Morphological analyses of the fruit of introduced almond cultivars in Bosnia & Herzegovina indicated favorable agroecological conditions for their cultivation and spread. The results suggest that these introduced almond cultivars could be utilized in breeding programs to enhance the genetic diversity of the local almond population in Bosnia & Herzegovina.

Evaluation of serum ferritin level and hepatitis b and hepatitis c viral infection in chronic hemodialysis patients

2024-06-04T18:04:59+02:00

The most popular treatment for end-stage renal illness is hemodialysis (HD). The study aimed to assess serum ferritin levels and their connection to Epoetin alfa resistance, along with exploring the link between hepatitis C virus, iron overload, and the prevalence of hepatitis C and B infections in chronic HD patients. This was a descriptive-analytical study conducted on 50 Patients with chronic kidney disease (CKD) who were on regular HD in the dialysis unit of Ibin Sina Teaching Hospital in Mosul City, Iraq. Out of 50 patients, 26 (52%) tested positive for Hepatitis C Virus (HCV) Antibody, 10 (20%) for Hepatitis B surface Antigen (HBsAg), and 14 (28%) tested negative for both. Higher serum iron and ferritin levels were found in HCV antibody-positive patients (p < 0.05). Despite Epoetin alfa treatment, patients with elevated ferritin levels exhibited lower Hemoglobin (HB) and Packed Cell Volume (p < 0.05). Non-diabetics exhibited significantly higher serum ferritin, Hemoglobin, Blood urea, and serum creatinine than diabetics (p < 0.05). A noteworthy association was seen between the quantity of blood transfusions and elevated levels of serum ferritin and total serum iron (p < 0.05). Most HD patients were anemic, with Hepatitis B and C prevalent. The main CKD causes were diabetes and hypertension. HCV-positive patients often showed mild to moderate iron overload, and high serum ferritin was linked to poor Epoetin alfa response. Dialysis can elevate blood urea, ferritin, and creatinine, worsening anemia. High ferritin levels may hinder response to Epoetin alfa and iron replacement. Excessive blood transfusions can lead to iron overload and inhibit erythropoiesis. Maintaining HB at 110-120 g/l improves quality of life and reduces anemia-related risks.

Huangbaiye Tuji combined with Longdan Xiegan Decoction for anal cryptitis: Analysis of clinical efficacy and its influence on disease recurrence

2024-06-04T18:06:19+02:00

Given the rising incidence of anal cryptitis (AC) in recent years, it is of great significance to find an effective and safe treatment scheme to ensure the healthy life of patients. In this study, we explored the clinical efficacy of Huangbaiye Tuji combined with Longdan Xiegan Decoction (LDXGD) for AC and observed changes in patients' cellular immune function, which can provide a new reference for future treatment of AC. By comparison, we found that compared with Huangbaiye Tuji treatment alone, its combination with LDXGD had better clinical efficacy and high safety, contributing to more significant relief of inflammatory reaction and oxidative stress. In terms of immune function, the patients' humoral and cellular immunity were more effectively enhanced after the combination therapy. According to these results, it is recommended to use Huangbaiye Tuji combined with LDXGD in the treatment of AC.

Diagnostic efficacy of SEPT9 and PAX5 gene methylation in gastrointestinal cancer and precancerous lesions

2024-06-04T18:10:03+02:00

To assess the diagnostic efficacy of SEPT9 along with PAX5 gene methylation detection in gastrointestinal cancer and precancerous lesions, the peripheral blood of 62 patients with gastric cancer (GC) and 60 patients with no evidence of disease (as the control group) were retrospectively collected. The methylation rates of PAX5 and SEPT9 gene promoters in blood samples of GC group were detected by PCR. At the same time, the differences in methylation rates of genes in the two groups were compared, and the predictive value of plasma methylation PAX5 and SEPT9 in GC was evaluated by receiver operating characteristic (ROC) curve. We found that there were 41 cases of methylated PAX5 gene promoter region and 39 cases of methylated SEPT9 gene promoter region in GC group. The control group contained 14 cases of PAX5 gene promoter methylation and 12 cases of RNF¹80 gene promoter methylation. The occurrence of PAX5 promoter methylation was correlated with age of GC patients. There were statistically significant differences in mSEPT9 gene in patients with different TNM stages. Kaplan-Meier survival curve analysis revealed that the three-year overall survival rate of GC patients with PAX5 methylation was lower than that of GC patients without PAX5 methylation. No significant difference was discovered in 3-year overall survival rate between GC patients with SEPT9 methylation and those without SEPT9 methylation. Combined detection could not improve the diagnostic value of GC, but could promote diagnosis sensitivity. In summary, the risk of PAX5 and SEPT9 gene methylation in GC patients presents higher when compared with healthy people. PAX5 gene methylation is closely related to age, while SEPT9 is closely related to tumor TNM stage, and PAX5 gene methylation can decrease the survival rate of GC patients. Detection of PAX5 gene methylation level can assist in evaluating the prognosis of GC patients.

Heterozygous variants in transmembrane channel-like 1 gene cause autosomal recessive nonsyndromic hearing loss

2024-06-04T18:11:37+02:00

Autosomal recessive non-syndromic hearing loss (ARNSHL) can cause severe or very severe pre-speech hearing loss. Transmembrane channel-like 1 (TMC1) gene is the sixth deafness gene discovered, but the precise extent of its protein structure and function is unknown. First, history collection, audiology examination and imaging examination were performed on the proband and his family members. Peripheral blood of proband and family members was collected, genomic DNA was extracted, exon high-throughput sequencing technology was used to detect the deafness gene mutation of the proband, and Sanger sequencing was performed to verify the TMC1 gene of the proband's parents. The proband was born with hearing impairment, normal tympanic function, inability to induce acoustic reflex in both ears (acoustic reflex threshold is 100 dBHL), and severe sensorineural deafness. One of his sisters has severe sensorineural hearing loss, and neither his parents nor his other sister is hearing impaired. High-throughput sequencing of the proband identified mutations at c.741+3_741+6delAAGT (splicing) and c.884C>T (p.A295V) of the TMC1 gene, two of which were heterozygous mutations. Sanger sequencing confirmed that the c.884C > T mutation was inherited from the mother, while the c.741+3_741+6delAAGT mutation was derived from the father. Prediction of amino acid function suggested that both mutations were pathogenic mutations. In conclusion, we found a new pathogenic complex heterozygous mutation of the TMC1 gene, which enriched the mutation spectrum of the TMC1 gene and provided a basis for genetic counseling and prenatal diagnosis of ARNSHL.

99mTc-HYNIC-Annexin V detection of apoptosis in the rabbit model of liver cancer

2024-06-04T18:19:30+02:00

To investigate the feasibility of detection of apoptosis in vivo by ^99mTc-HYNIC-Annexin V, Annexin V was labeled with ^99mTc through HYNIC. 18 New Zealand rabbits implanted VX-2 were randomly divided into control (n = 8) and paclitaxel (PAC, n = 10) groups, given 2 mL/kg of normal saline or 2.4 mg/kg of PAC intravenously. The liver tumor imaging was detected by SPECT through intravenous injection of ^99mTc-HYNIC-Annexin V before treatment, 24 hours and 48 hours after treatment respectively. Tumor radioactive count proportion to non-tumor sites was calculated. When the last imaging was finished, the rabbits were sacrificed. The tumor was taken out and divided into two pieces, one for TUNEL immunohistochemical analysis and the other for flow cytometry (FCM). We found that the rate of Annexin V labeled with ^99mTc through HYNIC was more than 95%, and radiochemical purity was above 95%. The SPECT showed that two groups had no significant tumor imaging before the treatment. There is no significant tumor imaging in control group, while the PAC group 24 h and 48 h after treatment showed significant accumulation. The Tumor/non-Tumor (T/NT) in PAC group at 24 h and 48 h after chemotherapy was significantly different from that in the control group and PAC group prior to treatment. There was no significant difference between 24 h and 48 h in PAC group. The TUNEL-positive cells detected by immunohistochemistry and apoptotic rate detected by FCM in PAC group were significant different from those in control group. The T/NT was significantly correlated to TUNEL-positive cells and apoptotic rate of the tumor. PAC can induce apoptosis of rabbit VX-2 liver cancer cells. 24-48 h after paclitaxel chemotherapy is a window time for apoptosis detection. Apoptotic cells in vivo can be detected by SPECT through ^99mTc-HYNIC-Annexin V.

Transcription factor DDIT3 is a potential driver in pancreatic cancer

2024-06-04T18:21:04+02:00

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and aggressive tumor that affects the digestive tract, leading to high mortality and poor survival rates. The purpose of the present study was to evaluate the expression levels of DNA damage-inducible transcript 3 (DDIT3) in pancreatic cancer and to investigate its effects in in vitro and in vivo experiments. Bioinformatics analysis indicated that DDIT3 expression was higher in pancreatic cancer tumor tissues and associated with a poor prognosis. Positive or strong positive DDIT3 expression was observed in PDAC, and no or weak expression was observed in normal pancreatic tissues. It was also highly expressed in PDAC cells, while being expressed at lower levels in normal pancreatic ductal epithelial cells. Transfection of short hairpin RNA targeting the DDIT3 gene reduced the proliferation, migration and invasion of PANC-1 cells. In vivo, in an in situ implantation tumor model with Pan02 cells, the size and weight of the tumors were reduced in the DDIT3 knockdown Pan02 cell-implanted group. These data suggested that DDIT3 represents a novel predictive biomarker for the potential treatment of patients presenting with PDAC.

Cytogenetic study of Meriz goat breeds in Iraqi Kurdistan region

2024-06-04T18:23:20+02:00

Goats are considered the leading farm animal that has a substantial role in the agricultural sector in the Kurdistan Region of Iraq. No cytological examination has been carried out on them. This experiment aims to identify the Karyotype of the local breeds of domestic goats. This experiment was conducted on the Karyotype and prepared the ideogram of Meriz goats. The determination of the relative length and centromeric index arm ratio of the chromosomes in the breed was achieved by the production of karyotypes. A total of (30)Meriz goats, consisting of (10) males and (20) females, were selected to collect blood samples for a short-term lymphocyte culture. The diploid chromosome count was observed to be (60), consisting of (29) pairs of acrocentric autosomes and one pair of allosomes, specifically the X and Y chromosomes. The acrocentric nature of the X-chromosome and the sub-metacentric nature of the Y-chromosome were identified through scientific investigation. The study observed a variation in the relative length of autosomal chromosomes in Meriz goats, with females ranging from 4.49% to 1.89% and males ranging from (4.53%) to (1.75%). The X-chromosome had a relative length of 3.96 in females, while the Y-chromosome displayed a relative length of (5.05). The findings of this karyological investigation suggest that the chromosomal composition seen in the Meriz goats under examination was within the expected range of normalcy. It is recommended that more cytogenetic analyses be conducted at the population level in order to identify individuals within the Meriz breed population who possesses numerical and/or structural chromosome abnormalities. This research is crucial for enhancing the efficiency of production and reproduction in this breed.

Linggui Zhugan decoction as a potential medicine for neuroprotection in Alzheimer's Disease via AMPK pathway

2024-06-04T18:26:32+02:00

Alzheimer's disease (AD) is a degenerative dementia illness that causes atrophy of the temporal and frontal lobes of the cerebral cortex. Linggui Zhugan (LGZG), a classic Chinese herbal formula, was initially recognized as a safe and effective treatment of cardiovascular diseases for long history. This study intended to assess the effects and the molecular mechanism of LGZG on AD progress. C57BL/6 mice were divided into six groups: normal mice, amyloid precursor protein/presenilin 1 (APP/PS1) mice (model group), positive control group (model mice treated with donepezil), high, medium and low LGZG group (model mice treated with 7g/kg/d, 3.5g/kg/d or 1.75g/kg/d LGZG respectively). Water maze results showed that the escape latency and path length of high and medium LGZG groups declined compared to the model mice, the decline degree was dose-dependent. The hippocampal slices of six groups were analyzed by Nissl-staining, Perls’ iron staining and immunofluorescence assay. The results indicated LGZG could restore morphological anomalies and alleviate iron deposition of AD mice, and the GXP4 positive cells increased significantly. The MDA, Fe2⁺and GSH were measured by biochemical testing, whose results illustrated that LGZG could normalize MDA, Fe2⁺and GSH levels in AD model compared to un-treated APP/PS1 model. The higher dose of LGZG the mice received, the more intensive effects on those levels of molecules. Western blot results showed that LGZG could affect NeuN, AMPK, p53, SLC7A11 and GPX4 levels in the hippocampus of AD model, which was all proteins related to AMPK pathway. In conclusion, LGZG has a neuroprotective effect on AD through AMPK pathway by alleviating oxidative stress and ferroptosis.

CRISPR-Cas9 Mediated AGO2 Knockout inhibits tumorigenesis in human colorectal cancer cells

2024-06-04T18:52:45+02:00

AGO2 plays a vital role in small RNA-guided gene silencing, which has been implied in the tumorigenesis of different types of tumors. Fundamentally, increased expression of AGO2 protein is associated with cancer progression and metastasis. This study aims to investigate the molecular mechanism by which AGO2 promotes tumorigenesis in colorectal cancer (CRC). Databases were used to analyze the expression levels of AGO2 in CRC and confirmed by a quantitative reverse transcriptase-PCR (qRT-PCR) assay in CRC tissues and normal adjacent tissues collected from 25 CRC patients. CRISPR/Cas9-mediated genome editing was used to knockout the AGO2 in HCT116 cells as a model system for colorectal cancers. The cell proliferation, migration and invasion ability of HCT116 cells were detected by CCK-8 assay, Wound scratch assay and Transwell assay. Moreover, the quantities of miRNA binding with AGO2 were detected by RNA-Binding Protein Immunoprecipitation (RIP-Assay). We demonstrated that AGO2 was aberrantly high-expressed in 25 matched-tissue pairs of colorectal cancer and para-carcinoma tissue. The following functional experiments verified that knockout of AGO2 suppressed cell proliferation, migration and tumorigenesis to hamper the aggressiveness of CRC. Our study also suggests a possible link between AGO2 and miRNA in RISC. AGO2 was elevated in CRC and knockout of AGO2 suppressed proliferation and tumorigenicity of CRC cells. Moreover, RISC formation and the function of miRNAs are also subject to AGO2. AGO2 may be a meaningful target for CRC therapy.

Idebenone protects the kidneys of rats with renovascular arterial hypertension by inhibiting oxidative stress and apoptosis

2024-07-28T19:00:04+02:00

Here, the protective effect of antioxidant Idebenone (IDB) on renovascular hypertension was studied. The two-kidney one-clip (2K-1C) model of renal hypertension was established. The rats were divided into 3 groups: sham-operation group, 2K-1C renal hypertensive rats’ model group and model treated with IDB group. The mean arterial blood pressure (MBP) of rats was measured and pathological condition of kidney was observed by H&E staining. The change of renal damage biomarkers (Cre, BUN, urine proteins), inflammatory factors (IL-6, IL-1β and TNF-α), oxidative stress ratio and key factors (MDA, SOD and CAT) were assessed by kits. The apoptosis key proteins (BAD, BAX, Caspase9, GSK-3β) were detected via Western blot. The 2K-1C model of renal hypertension was established. IDB reduced the MBP, Cre, BUN, urine proteins and improved the pathological condition of 2K-1C kidney. IDB restrained the inflammation factors (IL-6, IL-1β and TNF-α) and oxidative stress in kidney of renal hypertensive rats’ model. Besides, IDB suppressed the expression of apoptosis key factors (BAD, BAX, Caspase9, GSK-3β) in kidney of renal hypertensive rats’ model. IDB protects the kidneys of rats with renovascular arterial hypertension by inhibiting inflammation, oxidative stress, and apoptosis. These findings might provide medication guidance for IDB in renovascular arterial hypertension.

The role of remifentanil in regulating mitochondrial autophagy in osteoclasts was investigated based on PINK1/Parkin pathway

2024-06-05T07:39:15+02:00

This study aimed to explore the regulatory effect of remifentanil-mediated mitochondrial autophagy on osteoclast formation and further investigate its mechanism. Macrophage cell line RAW264.7 was taken and induced to differentiate into mature osteoclasts using nuclear factor kB receptor activating factor ligand (RANKL). The cell model was treated with different concentrations of remifentanil or down-regulated expression of mitochondrial autophagy-related gene PINK1. The survival, death and ROS production of osteoclasts were detected by CCK8 kit and flow cytometry, MMP level was detected by JC-1 method, mitochondrial morphology and autophagy were observed by transmission electron microscopy, and mitochondrial autophagy-related protein expression was detected by Western blot. The number of osteoclasts in the remifentanil-treated group was significantly reduced compared to the control group, accompanied by a reduction in reactive oxygen species (ROS) and mitochondrial membrane potential levels (MMP). Further results showed that remifentanil could significantly up-regulate the activity of PINK1/Parkin pathway, promote the occurrence of mitochondrial autophagy, and damaged mitochondria, and inhibit the formation of osteoclasts. Remifentanil successfully inhibited osteoclast formation by regulating mitochondrial autophagy mediated by PINK1/Parkin pathway. The results of this study revealed that remifentanil plays an important role in the physiology and pathology of osteoclasts, which may provide new ideas and strategies for the clinical treatment of remifentanil in tibial fractures.

Expression and prognostic analysis of PFKFB4 in oral squamous cell carcinoma

2024-06-04T18:59:04+02:00

Fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a crucial enzyme in the glycolysis pathway, possessing both kinase and phosphatase capabilities. Although it has emerged as an important oncogene in various cancer types, its function in oral squamous cell carcinoma (OSCC) is still not well understood. In our research, PFKFB4 expression was assessed via immunohistochemical (IHC) staining of tissue microarrays and OSCC patient specimens. The transcriptional expression of PFKFB4 in OSCC was analyzed by utilizing The Cancer Genome Atlas (TCGA) dataset. Correlation between PFKFB4 expression and clinicopathological features was examined using the χ2 test. Prognostic investigation of PFKFB4 was conducted via Kaplan-Meier and Cox analyses. PFKFB4 levels were notably elevated in OSCC samples in comparison to adjacent normal tissues (P < 0.001). Elevated PFKFB4 expression was associated with higher histologic grade (P = 0.0438), higher T stage (P = 0.031), and more advanced clinical stage (P = 0.0063). The ROC curve demonstrated the diagnostic potential of PFKFB4 (AUC = 0.827). Increased levels of PFKFB4 were linked to decreased overall survival (OS) (P = 0.04), poorer disease-specific survival (DSS) (P = 0.04), and shorter progression-free interval (PFI) (P < 0.001). PFKFB4 expression was identified as an independent risk factor for OS based on Cox regression analysis [hazard ratio (HR) = 1.517, P = 0.044)]. An OS nomogram was constructed with a concordance index of 0.690. Our findings reveal that upregulated PFKFB4 expression in OSCC tissues could serve as a potential prognostic biomarker.

The fibroblast heterogeneity across keloid, normal and tumor samples from single-cell resolution

2024-07-28T19:09:16+02:00

Keloids are defined as a benign dermal fibroproliferative disorder, with excessive fibroblast proliferation, and excessive overproduction of collagen. Although the heterogeneity during keloid development has been extensively studied, the heterogeneity across different skin states is still unclear. So, a global comparison across skin states is needed. In this study, we collected samples from 5 states of skin, including melanoma, cutaneous squamous cell carcinoma, keloid skin, scar skin, and healthy control samples. The heterogeneity of cell types and subtypes was analyzed and compared across 5 states, and we observed significant differences among them. Our results showed a cancer-like fibroblast, which is not in normal samples, may play an important role in antigen processing and presentation. We also noticed that the mesenchymal fibroblast increased in keloid samples, which highly expressed POSTN. And POSTN may participate in epithelial-mesenchymal transition and collagen overexpression to promote keloid growth. These findings help to understand the alteration among different skin states and provide potential genetic basis for keloid therapies.

Effect of ethyl pyruvate on human esophageal squamous cell carcinoma transplanted tumors in nude mice

2024-06-04T19:10:06+02:00

The objective of this study was to investigate the impact of ethyl pyruvate (EP), an HMGB1 inhibitor, on ESCC cells both in vitro and in vivo. The viability of ESCC cells was assessed using the MTT method to evaluate the correlation between EP and cell viability. A scratch test was used to investigate the relationship between EP and cell migration and invasion. The effects of EP on tumor growth and survival in cancerous nude mice were examined using a tumor formation model. Immunohistochemical staining was performed to evaluate the expression levels of HMGB1, TLR4, and MyD88 in tumor tissues. EP, an anti-HMGB1 inhibitor, inhibited ESCC cell proliferation and metastasis in vitro and in vivo. Furthermore, compared with the control treatment, EP improved the activity, diet, and drinking behaviour of nude mice; inhibited tumour growth; and led to lower protein expression levels of HMGB1, TLR4, and MyD88. EP has the potential to regulate the HMGB1/TLR4-MyD88 signaling pathway, thereby inhibiting the proliferation and metastasis of ESCC, suppressing tumor growth, improving quality of life, and serving as an effective drug for ESCC treatment.

Prenatal methamphetamine hydrochloride exposure downregulates miRNA-151-3p and CACNA1C in testis rats’ offspring

2024-06-04T19:12:18+02:00

Due to the widespread use of methamphetamine (METH) among reproductive-aged women, the effects of intrauterine exposure to METH need to be investigated, as previous studies on this topic have been limited. The goal of this study is to examine the influence of two regulatory genes (miRNA-151-3p and CACNA1C) on the intrauterine life of mice exposed to METH. Pregnant mice received doses of 2 and 5 mg/kg of METH and saline from day 10 of pregnancy until the end. Their offspring were then evaluated for miRNA-151-3p and CACNA1C gene expression levels using real-time PCR. The findings indicated that exposure to METH reduced the expression levels of both miRNA-151-3p and CACNA1C genes in offspring compared to the control group (p≤0.001). In conclusion, intrauterine exposure to METH leads to a decrease in expression levels of both miRNA-151-3p and CACNA1C genes, potentially disrupting regulatory pathways involving these genes and having an impact on male reproductive health.

Pan-cancer analysis of TMEM45A and exploration of its prognostic value and mechanism in gastric cancer

2024-07-28T19:19:33+02:00

Cancer is a major category of diseases that need to be addressed urgently, bringing a huge burden to the world. Gastric cancer (GC) is a frequent malignant tumor of the digestive system with the highest incidence and mortality rate among all tumors. The purpose of this study was to explore the mechanism of action of TMEM45A in pan-cancer and gastric cancer. First, GEO and TCGA database were employed to analyze the expression of TMEM45A in GC patients. Then, we determined the association between TMEM45A expression and survival of GC patients using the Kaplan-Meier Plotter database and TCGA database and verified the accuracy of TMEM45A in predicting prognosis. Next, we analyzed the effect of CTHRC expression on TIICs in GC tissues. A prognostic model was constructed using immunomodulatory genes associated with TMEM45A. The specificity and accuracy of the model were verified. TMEM45A expression was markedly higher in GC tissue than in normal tissue. GC patients with TMEM45A overexpression had a poor prognosis. The AUC value of 5-year survival on the ROC curve was 0.705, indicating that TMEM45A is a reliable prognostic factor and can be used as a clinicopathological indicator alone to predict patient prognosis. Three high-risk immunomodulatory genes (CXCR4 and TGFB1) and one low-risk immunomodulatory gene (PDCD1) were obtained using both univariate and multivariate COX methods. These three immunomodulatory molecules were used to construct prognostic models. GC patients with TMEM45A overexpression have a poor prognosis and are associated with immune cell infiltration. Hence, TMEM45A is a fairly reliable independent prognostic marker.

Genome editing in K562 cells suggests a functional role for the XmnI Gg polymorphism: a widely used genetic marker in β-thalassemia and sickle cell disease patients

2024-06-04T19:15:08+02:00

The XmnI Gg -158 C/T polymorphism has been widely associated with fetal hemoglobin (HbF) levels, the severity of disease, and the response to the drug hydroxyurea (HU) in both β-thalassemia (β-thal) and sickle cell disease (SCD) patients. However, the functional significance of this single nucleotide polymorphism (SNP) remains unclear. To gain insight, green fluorescence protein (GFP) cassettes harboring the XmnI C or T alleles in their left homology arms (i.e. Gg promoters) were knocked into the Gg gene(s) of K562 cells via CRISPR/Cas9. Subsequently, the GFP fluorescence levels were compared in the ensuing cell populations and isolated clones. In both instances, median fluorescence intensities (MFI) of the knockin cells having the inserted XmnI T allele were higher than those having the XmnI C allele. Our results suggest that the XmnI T allele can increase Gg expression in K562 cells. The possible functional significance of the XmnI Gg -158 C/T polymorphism provides a rationale for the aforementioned associations. Furthermore, the XmnI polymorphism as a functional SNP substantiates its importance as a prognostic marker.

Enhancing rooting tobacco (Nicotiana tabacum) plant by loaded indole-3-butyric acid in alginate/chitosan nanocapsule

2024-06-04T19:17:16+02:00

Recently, nanocarriers have been utilized for encapsulating and sustained release of agrochemicals specifically auxins. Due to their potential applications such as increased bioavailability and improved crop yield and nutritional quality. Herein, the efficacy of alginate/chitosan nanocapsules as a nanocarrier for the hormone indole-3-butyric acid (IBA) loading and its effect on rooting tobacco plants has been carried out in the present study. The average particle size of IBA-alginate/chitosan nanocapsules was measured by Dynamic light scattering analysis at 321 nm. Scanning electron microscope studies revealed the spherical shape of nanoparticles with an average size of 97 nm. The average particle size of IBA-alginate/chitosan nanocapsules was measured by Dynamic light scattering analysis at 321 nm. The characteristic peaks of IBA on alginate/chitosan nanocapsules were identified by Fourier transform infrared spectroscopic analysis. Also, high efficiency (35%) of IBA hormone loading was observed. The findings indicated that the concentration of 3 mgL^-1 of IBA-alginate/chitosan nanocapsules has the highest efficiency in increasing the rooting in tobacco (Nicotiana tabacum) plants compared to other treatments. According to our results, we can introduce alginate/chitosan nanocapsules as an efficient nanocarrier in IBA hormone transfer applications and their use in agriculture.

Engineering erucic acid biosynthesis in camelina (Camelina sativa) via FAE1 gene cloning and antisense technology

2024-07-28T20:07:12+02:00

Oil seeds now make up the world's second-largest food source after cereals. In recent years, the medicinal- oil plant Camelina sativa has attracted much attention for its high levels of unsaturated fatty acids and low levels of saturated fatty acids as well as its resistance to abiotic stresses. Improvement of oil quality is considered an important trait in this plant. Erucic acid is one of the fatty acids affecting the quality of camelina oil. Altering the fatty acid composition in camelina oil through genetic manipulation requires the identification, isolation, and cloning of genes involved in fatty acid biosynthesis. The Fatty Acid Elongase 1 (FAE1) gene encodes the enzyme β-ketoacyl CoA synthase (KCS), a crucial enzyme in the biosynthesis of erucic acid. In this study, the isolation and cloning of the FAE1 gene from Camelina sativa were conducted to construct an antisense structure. The molecular homology modeling of DFAE1 proteins using the SWISS-MODEL server on ExPASy led to the generation of the 3D structures of FAE1 and DFAE1 proteins. The GMQE values of 0.44 for FAE1 and 0.08 for DFAE1 suggest high accuracy in the structural estimation of these genes. The fragments were isolated from the DNA source of the genomic Soheil cultivar with an erucic acid content of about 3% (in matured seeds) using PCR. After cloning the FAE1 gene into the Bluescript II SK+ vector and sequencing, the resulting fragments were utilized to construct the antisense structure in the pBI121 plant expression vector. The approved antisense structure was introduced into the Camelina plant using the Agrobacterium-mediated method, with optimization of tissue culture and gene transfer conditions. This approach holds potential to advance our knowledge of fat biosynthesis, leading to potential improvements in oil quality in Camelina sativa.

Association of XRCC2 with breast cancer, a multi-omics analysis at genomic, transcriptomic, and epigenomic level

2024-07-28T20:12:41+02:00

One of the main causes of cancer-related mortality for women worldwide is breast cancer (BC). The XRCC2 gene, essential for DNA repair, has been implicated in cancer susceptibility. This study aims to evaluate the association between XRCC2 and BC risk. The study was conducted at Zheen International Hospital in Erbil, Iraq, between 2021 and 2024 with a total of 88 samples, including 44 paired normal and cancer tissue samples. Mutation analysis was performed using Next-Generation Sequencing, coupled with in silico tools for variant impact prediction. Expression levels were assessed through RT-PCR, and methylation status was determined using methylation-sensitive restriction enzyme digestion PCR. The study identified seven inherited germline variants in the XRCC2 gene, with five of these mutations being Uncertain Significance, one being Likely Pathogenic, and one being Likely benign. RNA purity was found high with mean A260/280 ratios of 1.986 ± 0.097 in normal (N) and 1.963 ± 0.092 in tumor (T) samples. Tumor samples exhibited a higher RNA concentration (78.56 ± 40.87 ng/µL) than normal samples (71.44 ± 40.79 ng/µL). XRCC2 gene expression was significantly upregulated in tumor tissue, with marked increases in patients aged 40-55 and >56 years and in higher cancer grades (II and III) and invasive ductal carcinoma (p-values ranging from <0.0001 to 0.0392). DNA methylation rates in tumor tissues were low (7%), suggesting limited regulation by methylation. The study suggests that XRCC2 can be classified as an oncogene and that its structural investigation by targeted NGS and expression evaluation can be used as a potential biomarker in BC.

Epigenetics modification among vitrified oocytes and early embryos derived from them: a narrative review

2024-06-04T17:03:57+02:00

Vitrification has important application in assisted reproductive technology (ART) and this technique has been widely used in the cryopreservation of oocytes and embryos. However, due to susceptibility of epigenetic modifications to environmental changes induced by cryopreservation procedures, there are concerns about the potential epigenetic consequences of oocyte and embryo vitrification. This review comprehensively summarized the effect of cryopreservation—especially the vitrification method in ART-on oocytes and embryos. Various studies have reported changes in different aspects of genomic status which directly affect the quality of fertilized embryos. The objective of this review is to assess existing literature on the epigenetic modifications that occur in vitrified oocytes and early embryos resulting from oocyte vitrification, including DNA modifications, RNA methylation, histone modification and microRNAs related to ART.

Predictive significance of the blood eosinophilia for chronic sinusitis with nasal polyp recurrence: A systematic review and meta-analysis

2024-06-04T18:49:18+02:00

Chronic sinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition characterized by recurring nasal polyps, often necessitating repeated interventions. Blood eosinophilia has emerged as a potential biomarker for predicting disease recurrence. The present study aims to assess the predictive significance of blood eosinophilia for the recurrence of nasal polyps. To accomplish this objective, we employed the appropriate search keywords to explore international databases such as Web of Science, PubMed, Embase, and Scopus. Through this process, we extracted scholarly articles that assessed the prognostic value of blood eosinophilia in the recurrence of nasal polyps. The statistical software STATA (version 15) was employed, along with random and fixed-effects models, to appraise the compiled data. Nine articles met inclusion criteria, with a total sample size of 1279 individuals (569 recurrent polyp individuals and 710 non-recurrent polyp individuals). Cumulative Odds ratio analysis revealed that CRSwNP is associated with high blood eosinophile percentage compared to the non-CRSwNP group (p=0.01, OR=1.26, 95%Cl (1.15,1.36). The cut-off value of blood eosinophil percentage (>0.78) had relatively good, and statistically significant predictive potential. No significant publication bias was observed for the included studies. Our findings indicate that the utilization of blood eosinophils holds significant predictive value and can serve as a valuable tool for detecting recurrence in patients with CRSwNP. Based on the outcomes of our comprehensive analysis, we propose a threshold of >0.78 as a reliable indicator for assessing the probability of recurrence in CRSwNP patients.