Journal of Medical Biochemistry最新文献

Background: Diabetic Kidney Disease (DKD) is a significant challenge in healthcare. However, there are currently no reliable biomarkers for renal impairment diagnosis, prognosis, or staging in DKD patients. CircRNAs and microRNAs have emerged as noninvasive and efficient biomarkers.

Methods: We explored Cannabinoid receptor 1 (CNR1), C reactive protein (CRP), hsa_circ_ 0000146 and 0000072, and hsa-miR-21 and 495 as diagnostic biomarkers in DKD. The serum concentrations of CRP and CNR1 were measured using ELISA. Rt-qPCR was used to evaluate the expression levels of CNR1, circRNAs, and miRNAs in 55 controls, 55 type 2 diabetes mellitus patients, and 55 DKD patients. Their diagnostic value was determined by their ROC curve. KEGG pathway was used to predict the functional mechanism of the circRNA's target genes.

Results: DKD patients exhibited a significant increase in CRP and CNR1 levels and the expression of miR-21 and 495. The expression levels of circ_0000146 and 0000072 decreased in DKD patients. ROC analysis revealed that circRNAs and miRNAs alone or CNR1 and CRP have significant diagnostic potential. The functional prediction results showed the involvement of hsa_circ_0000146 and 0000072 in various pathways that regulate DKD.

Conclusions: Therefore, the examined circRNAs and miRNAs may represent a novel noninvasive biomarker for diagnosing and staging DKD.

Background: Breast cancer (BC) is the primary cause of mortality due to cancer in females around the world. Fetuin-A is known to increase metastases over signals and peroxisomes related with growing. Receptor activator of nuclear factor-kB ligand (RANKL) takes part in cell adhesion, and RANKL inhibition is used in the management of cancer. We aimed to examine the relationship between serum fetuin-A, RANKL levels, other laboratory parameters and clinical findings in women diagnosed with early stage BC, in our population.

Methods: Women having early stage BC (n=117) met our study inclusion criteria as they had no any anti-cancer therapy before. Thirty-seven healthy women controls were also confirmed with breast examination and ultrasonography and/or mammography according to their ages. Serum samples were stored at -80°C and analysed via ELISA.

Results: Median age of the patients was 53 (range: 57-86) while it was 47 (range: 23-74) in the healthy group. Patients had lower high-density lipoprotein levels (p=0.002) and higher neutrophil counts (p=0.014). Fetuin-A and RANKL levels did not differ between the groups (p=0.116 and p=0.439, respectively) but RANKL leves were found to be lower in the favorable histological subtypes (p=0.04).

Conclusions: In this study, we found no correlation between serum fetuin-A levels and clinical findings in patients diagnosed with early stage BC. However, RANKL levels are found to be lower in subgroups with favorable histopathologic subtypes such as tubular, papillary and mucinous BC and there was statistically significant difference.

Background: To uncover the diagnostic potential of peripheral blood microRNA-200b (miRNA-200b) in renal interstitial injury in diabetic nephropathy (DN) patients.

Methods: A total of 50 diabetes subjects, 50 mild DN subjects, 50 moderate-severe DN subjects and 50 healthy subjects were included. Peripheral blood level of miRNA-200b in every subject was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Serum levels of renal function indicators were determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile, relative levels of fibrosis damage indicators were examined by chemiluminescent immunoassay. Diagnostic potentials of miRNA200b in diabetes, mild DN and moderate-severe DN were assessed by depicting receiver operating characteristic (ROC) curves.

Results: Peripheral blood level of miRNA-200b was higher in DN subjects than diabetes subjects without vascular complications, especially moderate-severe DN patients. Peripheral blood level of miRNA-200b in DN subjects was negatively correlated to relative levels of serum creatinine, urinary nitrogen, cystatin, TGF-b, CIV and PCIII. ROC curves demonstrated diagnostic potentials of miRNA-200b in mild and moderate-severe DN.

Conclusions: Peripheral blood level of miRNA-200b is closely linked to the degree of renal interstitial injury in DN patients. MiRNA-200b may be a vital indicator in predicting the development of DN.

Background: The purpose of the current research was to investigate the biological roles of LINC00467 in inducing melanoma deterioration.

Methods: Differential level of LINC00467 in melanoma tissues and its prognostic value were analyzed in GEPIA, which were further confirmed in clinical samples we collected. Regulatory effects of LINC00467 on proliferation, migration and invasion capacities of A375 and SKMEL1 cell lines were examined by a series of functional experiments. Potential downstream targets of LINC00467 were identified through dual-luciferase reporter assay, and their synergistic role in melanoma process was finally explored by rescue experiments.

Results: LINC00467 was up-regulated in melanoma samples, but it did not have a prognostic potential in melanoma. LINC00467 has the capacities to stimulate proliferation, migration and invasion of A375 and SKMEL1 cell lines. The feedback loop LINC00467/miR-485-5p/PAK1 was identified, which was responsible for inducing melanoma deterioration.

Conclusions: LINC00467 stimulates proliferation, migration and invasion capacities of melanoma via targeting miR-485-5p to upregulate PAK1, which provides potential targets for treatment of melanoma.

Background: Given the fact that the studies that examined oxidative stress in relation to obesity that included late adolescents are scarce and show inconclusive results we aimed to investigate a wide spectrum of nitro-oxidative stress biomarkers i.e., malondialdehyde (MDA), xanthine oxidase (XO), xanthine oxidoreductase (XOD), xanthine dehydrogenase (XDH), advanced oxidation protein products (AOPP) and nitric oxide products (NOx), as well as an antioxidative enzyme, i.e., catalase (CAT) in relation with obesity in the cohort of adolescent girls ages between 16 and 19 years old.

Methods: A total of 59 teenage girls were included in this cross-sectional study. Binary logistic regression analysis was performed to examine possible associations between biochemical and nitro-oxidative stress markers and body mass index (BMI).

Results: There were not significant differences between oxidative stress markers between normal weight and overweight/obese girls (i.e., AOPP, XOD, XO, XDH) and CAT, except for MDA (p<0.001) and NOx (p=0.010) concentrations which were significantly higher in overweight/obese adolescent girls. Positive associations were evident between BMI and high sensitivity C-reactive protein (hsCRP) (OR=2.495), BMI and uric acid (OR=1.024) and BMI and MDA (OR=1.062). Multivariable binary regression analysis demonstrated significant independent associations of BMI and hsCRP (OR=2.150) and BMI and MDA (OR=1.105). Even 76.3% of the variation in BMI could be explained with this Model.

Conclusions: Inflammation (as measured with hsCRP) and oxidative stress (as determined with MDA) independently correlated with BMI in teenage girls.

Background: Inaccurate test results may be a reason why vitamin D deficiency is seen as a common problem worldwide. Interferences from the sample matrix during testing are the most important factors in measurement errors. In this study, the relationship between triglycerides and total cholesterol levels and vitamin D levels in Turkey was investigated.

Methods: The 25-hydroxyvitamin D test results and lipid test results studied in Turkey in 2021 were compared. Data were obtained from the Ministry of Health National Health Database. Simultaneously, 25-hydroxyvitamin D, triglyceride, and total cholesterol levels were studied, and 1,135,644 test results were taken as the basis.

Results: In the group of patients with total cholesterol levels between 0-10.33 mmol/L, the proportion of patients below 20 mg/L ranged from 56.8% to 61.8%. In the patient group with cholesterol between 10.36-259 mmol/L, the rate of patients with less than 20 mg/L was between 70.8-100%, while the rate of patients with cholesterol above 100 mg/L was 0%. The mean 25-hydroxyvitamin D level was 20.1 mg/L in the patient group with a total cholesterol level between 0-10.33 mmol/L, and 16 mg/L in the patient group with a cholesterol level above 10.36 mmol/L. The mean 25-hydroxyvitamin D level was 20.11 mg/L in the patient group with triglycerides 0-10.16 mmol/L, and the 25-hydroxyvitamin D level was 12.28 mg/L in the patient group with triglycerides 10.17-113 mmol/L. The proportion of patients with vitamin D levels above 100 mg/L was found to be 0% in the group of patients with triglycerides above 10.17-113 mmol/L.

Conclusions: According to this study, there is a risk of toxicity when administering vitamin D therapy in patients with high cholesterol and triglycerides levels. This study is the first of this size in the literature. High triglycerides and cholesterol levels can cause inaccurate measurement of vitamin D levels, so care should be taken when evaluating these tests.

Background: To explore the role of LncFEZF1-AS1 in renal cell carcinoma (RCC) tissues and cells, and the possible molecular mechanism.

Methods: Expressions of LncFEZF1-AS1 in RCC tissues and adjacent ones were detected. The association of LncFEZF1-AS1 level with clinical data of RCC patients was also analyzed. Besides, the differential expressions of LncFEZF1-AS1 in a variety of RCC cell lines were also determined. Then the LncFEZF1-AS1 knockdown model was constructed in RCC cell line to further determine the influences of LncFEZF1-AS1 on the proliferative ability and migration of RCC cells through CCK8 and Transwell experiments. Furthermore, luciferase reporter gene experiment were used to validate the combination of LncFEZF1-AS1 to ETNK1.

Results: Results suggested that expression of LncFEZF1-AS1 was noticeably higher in RCC tumor tissues and the RCC cells. Clinical pathological data analysis also suggested that high LncFEZF1-AS1 expression was in correlation with the pathological stage and the incidence of distant metastasis in RCC patients, and the poor overall survival rate. In vitro experiments demonstrated that knocking down of LncFEZF1-AS1 markedly repressed the proliferation and migration of RCC cell lines. Bioinformatics suggested that LncFEZF1-AS1 can interact with the downstream target gene ETNK1, which was confirmed by the luciferase reporter gene experiments. Western Blot results revealed that knocking down of LncFEZF1-AS1 markedly enhanced ETNK1. qRT-PCR analysis indicated that ETNK1 level was under-expressed in RCC tissues and in negative correlation with LncFEZF1-AS1. Further experiments suggested that knockdown of ETNK1 partially reversed the inhibitory effects of LncFEZF1-AS1 silencing on the proliferative and migrative abilities of RCC cells.

Conclusions: LncFEZF1-AS1 could facilitation the proliferative and migration of RCC cells by regulating the expression of ETNK1. Therefore, FEZF1-AS1 might function as a cancer-promoting factor and possible new therapeutic target for RCC.

Background: To clarify if a2-macroglobulin (α2M) has an antioxidative effect during the progression of the intervertebral disc degeneration (IVDD).

Methods: The content of α2M and reactive oxygen species (ROS) were measured to compare mildly and severely degenerated human nucleus pulposus (NP) tissue by immunohistochemistry, mass spectrometry, and enzyme-linked immunosorbent assay (ELISA). Additionally, exogenic α2M was used to culture severely degenerated NP tissue in vitro. The effects of α2M on hypochlorite (HOCl)-treated NP cells were evaluated, containing antioxidative enzymes, ROS level, collagen II, and aggrecan expression, MMP3/13, and ADAMTS4/5.

Results: ROS level increased in severely degenerated NP, accompanying with a decreased α2M content. Supplement of α2M could decrease the ROS level of cultured NP in vitro, meanwhile, the MMP13 and ADAMTS4 expression were also reduced. It was found that treatment of HOCl resulted in oxidative damage to NP cells and decreased α2M expression in a dose and time-dependent manner. Furthermore, exogenic α2M stimulation reversed the HOCl-triggered ROS accumulation. The promotion of SOD1/2, CAT, GPX1, collagen II, and aggrecan, and suppression of MMP3/13, ADAMTS4/5 expression caused by α2M were also observed.

Conclusions: Our study indicates that α2M has an antioxidative ability in degenerated NP cells by promoting the antioxidative enzyme production.

Background: The study aimed to estimate lidocaine (LID) pharmacokinetic parameter values in patients with impaired liver function, level of correlation between the pharmacokinetic parameters and Child-Pugh class and change in pharmacokinetic parameters after liver tumor resection compared to the preoperative value.

Methods: Patients with impaired liver function were subject to the LID test 1 day prior to, 3 and 7 days after the intervention. LID was administered in single i.v. dose of 1 mg/kg. Blood samples were collected at 15, 30 and 90 minutes after drug administration. Non-compartmental analysis was applied for calculating the pharmacokinetic parameters.

Results: The study included 17 patients with the diagnosis of cirrhosis and 41 patients with liver tumor. In both groups of patients, the values of the coefficients of correlation show the best correlation between clearance (CL) and Child-Pugh score (-0.693, p<0.005) over other pharmacokinetic parameters. The results indicate worsening hepatic function on 3rd day after operation in comparison to the values of LID CL prior to operation (mean LID CL for patients with Child-Pugh class A are 25.91 L/h, 41.59 L/h, respectively; while for B class are 16.89 L/h, 22.65 L/h, respectively). On day 7th, the values of LID CL (mean value for patients with Child-Pugh class A and B are 40.98 L/h and 21.46 L/h, respectively) are increased in comparison to 3rd day after.

Conclusions: LID pharmacokinetic parameters consequently changed according to the severity of liver impairment, assessed by Child-Pugh score. Values of LID CL and volume of distribution (Vd) coupled with standard biochemical parameters may be used for preoperative assessment of liver function and monitoring of its postoperative recovery.