Reports of Biochemistry and Molecular Biology最新文献

Background: Breast cancer is the most common malignancy in women worldwide. The p16 protein is a cell cycle regulator and tumor suppressor implicated in several types of cancers. However, its relationship to breast cancer is still unknown. The present study aimed to assess the association of p16 protein expression with clinicopathological features in breast cancer.This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell.

Methods: The study enrolled 100 patients with invasive ductal carcinoma. The samples were collected before any adjuvant chemotherapy, and p16 protein expression was determined using immunohistochemistry. Clinicopathological features were obtained from the patient's medical records.

Results: Our findings demonstrated that p16 protein expression increased in estrogen receptor-positive tumor tissues (P< 0.01). However, no significant correlation was found between the p16 protein expression and the other clinicopathological features.

Conclusions: Our study demonstrated that p16 protein expression increased in ER-positive tumor tissue from patients with invasive ductal breast carcinoma. However, no correlation was found between the p16 protein expression and the other clinicopathological features.

Background: Cinnamic acid, a phenylpropanoid acid, has been investigated as a potential alternative therapy for diabetes and its complications in some studies.

Methods: In the first stage, the viability of HepG2 cells at different concentrations of glucose and CA was assessed by MTT assay. Oxidative stress markers) CAT, GPx, GSH, and MDA) were measured spectrophotometrically. After RNA extraction, the effect of different concentrations of CA on the expression of DPP4 and inflammatory factors (IL-6, NF- κB) in HepG2 cells was assessed using real-time PCR.

Results: In HepG2 cells, CA increased catalase and glutathione peroxidase activity and GSH production in a dose-dependent manner in the presence of high glucose concentrations, with the greatest effect seen at a concentration of 75 mg/ml. Also, it reduced the amount of MDA in high-glucose HepG2 cells. Furthermore, CA decreased the expression of DPP4, NF- κB, and IL-6 genes in HepG2 cells in the presence of high glucose levels.

Conclusions: The results of our study indicated that CA reduced hyperglycemia-induced complications in HepG2 cells by decreasing inflammatory gene expression, including IL-6 and NF- κB and inhibiting the expression of DPP4, and limiting oxidative stress.

Background: This study aimed to investigate the GPx-1 gene polymorphism (rs1050450), the level of oxidative stress and antioxidant parameters, and the lipid profile in an obese Kurdish population in Sulaimani, Iraq.

Methods: In a case-control study,134 obese subjects and 131 normal BMI healthy individuals participated. The GPx-1 gene polymorphism was assessed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The levels of biochemical and oxidative parameters were determined using photometric methods.

Results: The results showed that the fasting blood sugar (FBS), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in obese subjects compared to the control group. Obese individuals had significantly lower levels of high-density lipoprotein cholesterol (HDL-C) than the controls. The GPx-1 activity and total antioxidant capacity (TAC) levels were significantly elevated in the obese group compared to the control group (P=0.006, and P<0.001, respectively). No significant difference was detected in genotype and allele frequencies of GPx-1 (rs1050450) between obese and normal BMI groups. However, the presence of the GPx-1 TT genotype enhanced the risk of obesity in females by 1.93-fold (95% CI 1.04-3.58, P=0.036). In the total population, the GPx activity increased in the presence of TT compared to CC+CT and CT genotypes.

Conclusion: The study indicated that obesity is linked to significantly higher levels of FBS, TG, LDL-C, TAC, and GPx activity and lower level of HDL-C. Also, we found the GPx-1 gene polymorphism was associated with the risk of obesity in females and increased the GPx activity.

Background: The current work investigated the effect of melatonin on differentiation of adipose mesenchymal stem cells (AD-MSCs) into dopamine producing cells and its effect on autophagy process and alpha-Synuclein (α-Syn) secretion.

Methods: AD-MSCs were characterized by flow cytometry and divided into 4 groups; i) control group (AD-MSCs without any treatment), ii) M+MSCs group (MSCs treated with 1 µM melatonin for 12 days), iii) DN group (MSCs cultured in neurobasal A medium and essential neuronal growth factors for 12 days) and iv) DN+M group (MSCs cultured in neurobasal A medium and 1µM melatonin for 12 days. By the end of experiments, the dopamine and α-Syn levels using ELISA, the expression of MAP-2, m-TOR and α-Syn genes at the level of mRNA and detection of autophagosomes formation using transmission electron microscope were performed.

Results: We found that the isolated cells were MSCs due to their positivity expression for CD105 and CD90 and negativity expression for CD34 and CD45. The concentration of dopamine was significantly higher and α-Syn concentration was significantly lower in DN+M group when compared to other groups (P< 0.005). Also, this group showed the highly expression for MAP-2 gene and less expression for m-TOR and α-Syn genes (P< 0.005). Moreover, there was significantly increase in autophagosomes formation in this group than another group (P< 0.005).

Conclusions: It is concluded that the melatonin promotes the differentiation of rat AD-MSCs into dopaminergic cells via induction of autophagy process and reduction of α-Syn secretion.

Background: Background: Male infertility contributes to roughly 15% of all infertility cases in couples. The most common cause of male infertility is azoospermia, which is caused by genetic mutations. The connection between various single nucleotide polymorphisms in the PRM genes and AZF region microdeletions with male infertility has not been reported.

Methods: In this case-control study, 100 infertile males (33 with azoospermia, 48 with oligozoospermia, and 19 with severe oligozoospermia) were chosen as the study subjects, and 100 fertile males were selected. Total DNA from peripheral blood was used to amplify two sequence-tagged site markers through multiplex PCR to detect AZFc partial deletions, and SNPs in PRM1 and PRM2 were determined through PCR-RFLP. Furthermore, quantitative real-time PCR was conducted to evaluate PRM1, PRM2, and DAZ1 (found in the AZFc region) expression levels in testis tissue.

Results: The frequency of the rs779337774 SNP in the PRM2 gene in the study population had no significant differences. However, a significant association was observed between the rs737008CA genotype (P= 0.013) and the C allele (P= 0.025) as a risk factor for male infant mortality. The deletion of sY254 and sY255 was discovered in azoospermia and severe oligozoospermia patients. Furthermore, all of these genes showed considerably low expression levels. However, only DAZ1 was identified with diagnostic biomarker potential (AUC=0.742).

Conclusion: When these genes expression levels are reduced, the likelihood of spermatozoa retrieval in azoospermic individuals is elevated. Furthermore, no significant association was observed between PRM2 polymorphism and azoospermia; however, the CA genotype of PRM1 polymorphism is significantly associated with azoospermia incidence.

Background: A critical role has been known for lncRNAs in the initiation and development of cancers. Therefore, lncRNAs have been reported as the possible biomarkers in relation to the diagnosis and therapy of malignancies. This project examined the change in CYTOR lncRNA expression in human cervical cancer samples as compared with adjacent healthy ones.

Methods: We provided one hundred fifteen pairs of tumorous and adjacent healthy tissue specimens of cervical cancer patients. RNAs were isolated from tissue specimens and cDNAs were synthesized. We considered quantitative Real-time PCR (qRT-PCR) to examine the expression levels of CYTOR lncRNA. In addition, the biomarker activity of CYTOR and the associations between the lncRNA and clinicopathological characteristics were evaluated.

Results: The significant increased expression of CYTOR was obtained in cancerous samples as compared with non-cancerous ones (P< 0.0001). A significant correlation was indicated between CYTOR expression and the squamous subtype of cervical cancer (p=0.046). The receiver operating characteristic (ROC) curve-related AUC (area under the curve), specificity, and sensitivity were calculated 0.88, 81.74%, and 80%, respectively, which may introduce CYTOR as a potential biomarker.

Conclusion: CYTOR may be an effective oncogene and biomarker in cervical cancer cases given its increased expression in human cervical cancer tissues.

Background: Colorectal cancer is a heterogeneous disease that leads to metabolic disorders due to multiple upstream genetic and molecular changes and interactions. The development of new therapies, especially herbal medicines, has received much global attention. Dorema ammoniacum is a medicinal plant. Its gum is used in healing known ailments. Studying metabolome profiles based on nuclear magnetic resonance 1HNMR as a non-invasive and reproducible tool can identify metabolic changes as a reflection of intracellular fluxes, especially in drug responses. This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell.

Methods: Extraction of Dorema ammoniacum gum with hexane, chloroform, and dichloromethane organic solvents was performed. Cell inhibition growth percentage and IC₅₀ were assessed. Following treating the cells with dichloromethane extract, p53, APC, and KRAS gene expression were determined. 1HNMR spectroscopy was conducted. Eventually, systems biology software tools interpreted combined metabolites and genes simultaneously.

Results: The lowest determined IC₅₀ concentration was related to dichloromethane solvent, and the highest was hexane and chloroform. The expression of the KRAS oncogene gene decreased significantly after treatment with dichloromethane extract compared to the control group, and the expression of tumor suppressor gene p53 and APC increased significantly. Most gene-altered convergent metabolic phenotypes.

Conclusion: This study's results indicate that the dichloromethane solvent of Dorema ammoniacum gum exhibits its antitumor properties by altering the expression of genes involved in HT-29 cells and the consequent change in downstream metabolic reprogramming.

Background: Chronic kidney disease (CKD) ends mostly with renal fibrosis. The effect of CB2 receptor on renal fibrosis has been unclear. The aim of this study was to investigate the effect of CB2 receptor on renal fibrosis and the mechanisms behind it.

Methods: 50 adult male Sprague-Dawley rats were divided into 5 groups; normal, sham; rats had their ureters only manipulated, UUO; rats had their left ureters ligated, and JWH post; rats had their left ureters ligated and they received JWH 133 for 14 days, JWH pre+post; rats received JWH 133 for 14 days before and after UUO procedure. Serum creatinine and BUN were assessed together with tissue MDA, GSH, and catalase. Histopathological evaluation of the renal tissue by H&E and Masson's trichrome was done. Immunohistochemical staining for TGF-β1, AQP1, Caspase-3, LC3B and p62 was performed. AQP1 and CB2 receptors genes expression was detected by quantitative RT-PCR.

Results: UUO had caused severe damage in the renal tissue with reduction of the renal function parameter accompanied by increase in the collagen deposition with increase TGF-β1 and decrease AQP1 expression.

Conclusions: The improvement of these parameters with JWH-133 suggests an anti-fibrotic role of CB2 receptor activation through reduction of oxidative stress, apoptosis, and autophagy.

Background: Many new studies have been conducted on cellular proteins to use them as prognostic markers or in target therapy through determining the increase or decrease in their expression in the lichen planus and OSCC. LAMP3 protein is one of these proteins which has been recently considered. Thus, considering the unknown etiology of lichen planus, significance of their early diagnosis and treatment and lack of a suitable and final treatment for this disease and oral cancers, and preventing the progression of lichen planus, which can turn into OSCC, we decided to investigate the level of expression of this gene and its effect on the progression, study the connection between these two conditions and the probable factors contributing to their etiopathogenesis.

Methods: In this study, ninety-four paraffin blocks tissue samples of patients were obtained together with their demographic documents. LAMP3 expression was measured RT-qPCR method.

Results: The results show that there is not any significant difference between age and sex population of our study. in squamous cell carcinoma the amount of expression of LAMP3 was higher than lichen planus and healthy margin. Average LAMP3 Gene expression in grade III was higher than group grade I & II in which considering significant level of 5%, it is statistically significant.

Conclusions: According to the findings of this study, it can be concluded that the expression of the LAMP3 gene in SCC lesions is higher than in healthy tissue. Hence, LAMP3 gene expression can be used as a diagnostic biomarker.

Background: Colorectal cancer (CRC) is considered the third most common cancer around the world and second in terms of mortality. A significant aspect in its development is genetics. The risk of CRC and other clinicopathologic characteristics were investigated in this work in relation to the long non-coding RNA (lncRNA) MEG3 rs7158663 polymorphism, MEG3 expression, in an Egyptian population.

Methods: 160 CRC patients and 160 healthy controls were enrolled in this case-control study. The lncRNA MEG3 rs7158663 was examined using TaqMan Real-time PCR. RT-PCR was used to assess the levels of serum MEG3 expression.

Results: A significant higher expression of 'A' allele (risk allele) and A/A genotype in CRC cases vs. control subjects (P <0.001) Participants with A/A genotype had 4.8 times higher odds to exhibit CRC. Serum MEG3 gene expression was generally low in CRC patients, and it was considerably lower in those with the rs7158663 AA genotype than those with the GG genotype (P <0.001). It was found that CRC patients with the rs7158663 GA genotype had lower serum MEG3 expression levels than those with the GG genotype (P <0.001).

Conclusions: MEG3 low expression and MEG3 rs7158663 (AA) were associated with CRC risk in Egyptian patients and may serve as a diagnostic and prognostic marker for CRC patients.