Reports of Biochemistry and Molecular Biology最新文献

Background: Lung cancer is the leading cause of cancer-related deaths worldwide, yet there has been little attention given to the correlation between the cancer transcriptome and the incidence and mortality of lung cancer across different geographic regions.

Methods: To analyze this correlation, we screened the transcriptome datasets of stage I lung adenocarcinoma (LAC) patients from the Lung Cancer Explorer and examined their correlation with the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and mortality-to-incidence ratio (MIR).

Results: The expression difference rates (DRs) of certain genes (SPARCL1, SRPX, PMP22, MSR1, BST1, AKAP12, MAOB, vimentin, serglycin, ILK, ESD, transgelin, NCOA1, and PLPP1) were significantly negatively correlated with the ASIR of female LAC. Additionally, the DR of KRT19 was significantly positively correlated with the ASIR of female LAC. Furthermore, the DRs of COL10A1, SMAD7, COL3A1, and AQP1 were significantly positively correlated with the ASMR and MIR of female LAC, while the DR of KRT15 was significantly negatively correlated with the ASMR and MIR of female LAC. In male LAC patients, the DR of RGS2 was significantly negatively correlated with the ASIR, while the DRs of SPARCL1, COX7A1, IL3RA, and ADH1B were significantly positively correlated with the ASMR and MIR. Additionally, the DR of AIMP2 was significantly negatively correlated with the ASMR and MIR.

Conclusions: Our findings suggest that the expression levels of serglycin, ILK, ESD, and PLPD1 may play a significant role in the development of LAC. This information can be valuable for identifying potential treatment targets for lung cancer.

Background: Chronic kidney disease (CKD) is a deadly progressive disorder, particularly when it progresses to end-stage renal disease (ESRD). Conventional diagnostic tools such as serum creatinine and estimated glomerular filtration rate (eGFR) often lack sensitivity for early detection of tubular injury. This study aimed to evaluate the diagnostic potential of Galectin-3 (Gal-3) and Kidney Injury Molecule-1 (KIM-1) in Iraqi patients with CKD.

Methods: This case-control study included 150 participants from Baghdad, Iraq, between August 2022 and May 2023. Participants were categorized into three groups: healthy controls (n=50), mild CKD (n=50), and severe CKD (n=50). Serum levels of Gal-3 and KIM-1 were measured using ELISA kits. Demographic, clinical, and biochemical data were collected, including age, sex, BMI, diabetes status, hypertension, and eGFR. Statistical analyses included ANOVA, Kruskal-Wallis test, and correlation analysis.

Results: Gal-3 levels were significantly higher in CKD patients compared to healthy controls, showing a progressive increase from mild to severe CKD stages (P < 0.001). It was also associated with systemic factors such as diabetes mellitus, hypertension, and obesity. In contrast, KIM-1 levels were elevated primarily in patients with advanced CKD or ESRD (P = 0.036), but no significant difference was observed between control and mild CKD groups (P = 0.149). KIM-1 did not show consistent correlations with traditional markers of renal function, suggesting its specificity for structural tubular damage rather than functional decline.

Conclusions: Our findings suggest that Gal-3 may serve as a broader biomarker reflecting both systemic inflammation and fibrosis, while KIM-1 appears to be more specific to advanced renal injury.

Background: Esophageal cancer (EC) is an aggressive gastrointestinal tumor necessitating novel prognostic, diagnostic, and therapeutic strategies. It is essential to identify important markers for diagnosing malignancy and predicting outcomes. Understanding gene functions in signaling pathways and early cancer detection are vital for reducing EC mortality. CD44 upregulation is linked to cancer stem cells (CSC), metastasis, poor prognosis, and treatment response. CD44v6, a variant of CD44, plays a pivotal role in tumor invasion and metastasis by influencing the extracellular matrix, promoting cell motility, and suppressing cancer cell apoptosis.

Methods: This study investigated CD44v6 expression in tumor and tumor-free tissues of the esophagus in 50 esophageal squamous cells carcinomas (ESCC) patients using real-time PCR. The aim was to assess its prognostic value and its correlation with tumor invasion.

Results: Significant overexpression of CD44v6 mRNA was detected in 9 out of 50 tumor specimens (18%, p = 0.0001). CD44v6 expression showed an inverse correlation with tumor cell metastasis to lymph nodes (p = 0.047). Among the 21 patients with lymph node metastasis, 5 (23%) exhibited CD44v6 overexpression. Additionally, CD44v6 expression was linked to the tumor stage (p = 0.008). Specifically, 2 out of 9 patients with stage I tumors (22.2%), 4 out of 9 with stage II tumors (44.4%), and 3 out of 9 with stage III tumors (33.3%) showed CD44v6 overexpression.

Conclusions: Our findings suggest that lower CD44v6 expression at the RNA level correlates with increased tumor invasion and more advanced stages in ESCC.

Background: Alzheimer's Disease (AD) incidence and prevalence increase every year, commonly related to neuron inflammation and degeneration conditions. Tempeh, a traditional fermented product from Indonesia, was reported to have anti-inflammatory, antioxidant, and anti-Alzheimer properties. However, anti-Alzheimer properties of tempeh peptide extracts have not been extensively examined. This research studied the effect of the extracted peptide from tempeh in preventing and delaying Alzheimer's disease.

Methods: Tempeh peptide was extracted using water maceration and quantified using HPLC and spectrophotometry. Anti-Alzheimer properties of tempeh were analyzed with Ellman's assay of anticholinesterase and in vitro gene expression analysis using LPS-induced neural Schwann cells.

Results: As a result, tempeh contained 19.27% of GABA, which is reported to have anti-Alzheimer properties, and other amino acids. Tempeh peptide extract at 12.5 µg/mL had strong inhibition activity toward acetylcholinesterase at 12.61%, and 100 µg/mL of tempeh peptide extract had 8.97% butyrylcholinesterase inhibition activity. Tempeh peptides extract also altered the expression of various genes related to Alzheimer's disease, such as TNF-α, BACE 1, Ntrk 1, BDNF 2, and APP.

Conclusions: This research proved that various peptides from tempeh have anti-Alzheimer properties.

Background: Oral and lip squamous cell carcinomas (OSCC) are malignancies among head and neck cancers. OSCC is characterized by aggressive behavior and poorer prognosis compared to other squamous cell carcinomas. Galectin-3 (Gal-3) is a multifunctional protein involved in processes such as cell proliferation, apoptosis, and metastasis. This study aims to evaluate and compare Gal-3 expression among groups to investigate its role in the biological behaviors of lip and oral SCCs.

Methods: Immunohistochemical analysis of Gal-3 was performed on OSCC and lip SCC samples, with oral and lip marginal tissues obtained as the control group. The clinicopathological parameters, including the invasive front (IF), depth of invasion (DOI), and muscular, neural, and vascular invasions, were assessed. The staining percentage, intensity, and cellular location of Gal-3 were compared between the study groups. A p-value of < 0.05 was considered statistically significant.

Results: Gal-3 staining percentages were significantly higher in the SCC groups compared to control groups (P< 0.001 for each). Staining intensity and nuclear staining were higher in OSCC than in lip SCC (P< 0.001, P< 0.010, respectively). Nuclear Gal-3 was notably associated with the presence of muscle invasion in OSCC (P=0.030). High IF status was correlated with Gal-3 expression in lip SCC (P=0.010). Staining intensity was significantly higher in OSCC samples with vascular invasion compared to those without (P= 0.016).

Conclusions: The higher Gal-3 expression and nuclear staining in OSCC may explain its aggressive nature. Gal-3 could be a diagnostic and prognostic biomarker due to its increased expression in cancerous tissues compared to normal samples.

Background: Investigating the role of glutathione S-transferase pi 1 (GSTP1) in breast cancer development and exploring genetic variations in GSTP1 that may contribute to susceptibility to the disease.

Methods: Blood samples were collected from 40 healthy control individuals and 75 breast cancer patients for genomic DNA extraction. PCR and bioinformatics analysis were used to examine the GSTP1 gene sequences.

Results: Gel electrophoresis confirmed the presence of a 433-bp amplified genetic locus with a 212C>A variation in the intron-4 region, identified as rs757152293. The Single nucleotide polymorphisms (SNP) exhibited variable distributions, with homozygous CC and heterozygous CA genotypes. Patient samples with the CA genotype were submitted to NCBI under accession numbers OL957029-OL957036, while those with the CC genotype were submitted under accession numbers OL957027-OL957034. Additionally, sequence analysis of the rs757152293 SNP in healthy individuals was submitted to NCBI under accession numbers OL957037-OL957041.

Conclusions: This study is the first to suggest a possible association between GSTP1 genetic polymorphism and breast cancer in the investigated population.

Background: Depression is one of the most common mood disorders that greatly disrupt the lives of affected individuals. Due to the numerous side effects associated with chemical antidepressants, researchers have turned their attention to natural compounds. This study investigated the effects of Morin on Reserpine-induced depression in mice.

Methods: In this study, 48 male mice were divided into six groups. The Vehicle group received normal saline, while the negative and positive control groups received Reserpine (5 mg/kg) and Reserpine (5 mg/kg) + Fluoxetine (20 mg/kg), respectively. Eighteen hours after Reserpine injection, 50, 100, and 200 mg/kg Morin were administered to treatment groups. Forced swimming test (FST), tail suspension test (TST), and light-dark box tests were done as behavioral tests. Finally, brain tissue was isolated. The activity of Superoxide Dismutase enzyme and the levels of Reduced Glutathione and Malondialdehyde in the brain were measured.

Results: Morin could significantly increase the duration of activity in FST and TST in Reserpine-treated mice. In the light and dark box tests, Morin significantly decreased the latency to the first entry to the light chamber while increasing the number of entries and total time to last in the light chamber in Reserpine-treated mice. In the brain, Morin significantly enhanced the activity of the Superoxide Dismutase enzyme and the amount of "Reduced Glutathione" while reducing the levels of Malondialdehyde.

Conclusions: The results of this study demonstrate that Morin has a dose-dependent antidepressant effect by increasing the antioxidant capacity in the brains of rats.

Background: COVID-19 is a highly contagious viral disease that primarily affects the respiratory system and occasionally the gastrointestinal system, and it was declared a pandemic in 2020. Haptoglobin is an acute-phase protein and a potent antioxidant in the body, which exerts its antioxidant effect by binding to free hemoglobin. Haptoglobin has three main variants (Hp1-1, Hp1-2, Hp2-2), each with different antioxidant capacities. The purpose of this study is to investigate frequency of the haptoglobin variants in COVID-19 patients compared to a control group.

Methods: This study was conducted on 148 COVID-19 patients and 145 healthy individuals from the Sistan and Baluchestan province. DNA was isolated from whole blood using the salt precipitation method, and the determination of haptoglobin genotypes (Hp1-1, Hp1-2, and Hp2-2) was performed using Conventional PCR.

Results: This study analyzed haptoglobin (HP) genotypes in COVID-19 patients and controls, finding no significant difference in HP variant frequencies between groups (p= 0.529). However, the HP1-2 genotype was associated with a twofold increased COVID-19 risk in men (OR=2.069, p= 0.021), and the HP1 allele significantly raised infection risk (OR= 1.62, p= 0.039). Hospitalizations and respiratory symptoms were significantly higher in COVID-19 patients (p= 0.0001 and p= 0.0176, respectively).

Conclusions: These results suggest that haptoglobin variants are not risk factors for COVID-19 infection in the overall population (both males and females). However, men with the HP1-2 genotype are 1.9 times more likely to develop COVID-19 infection compared to men with HP1-1 and HP 2-2 genotypes.

Background: The transforming growth factor beta1 (TGF-β1) signaling pathway plays a critical role in the pathogenesis of Type 2 diabetes mellitus (T2DM). Modulating this pathway may offer therapeutic benefits for managing T2DM. Chicoric acid (CA), a polyphenolic compound with reported anti-diabetic properties, has shown potential in metabolic regulation; however, its precise molecular mechanisms remain unclear. This study aimed to investigate the effects of palmitate and CA on the TGF-β1 signaling pathway in peripheral blood mononuclear cells (PBMCs) from newly diagnosed T2DM patients and healthy controls.

Methods: A total of 40 participants, including 20 newly diagnosed T2DM patients and 20 age-matched healthy individuals (40-60 years), were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and treated with palmitate and CA. The expression of TGF-β1 mRNA was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels of Smad2/3 and phosphorylated Smad2/3 (p-Smad2/3) were assessed via western blot analysis.

Results: Palmitate stimulation significantly upregulated TGF-β1 gene expression and increased p-Smad2/3 protein levels in PBMCs. However, CA treatment effectively attenuated these palmitate-induced elevations in TGF-β1 expression and p-Smad2/3 protein levels. Additionally, a positive correlation was observed between TGF-β1 expression and p-Smad2/3 protein levels.

Conclusions: These findings suggest that CA may act as an inhibitor of the TGF-β1 signaling pathway, potentially contributing to T2DM management by downregulating TGF-β1/Smad signaling. Further studies are warranted to explore its therapeutic potential in diabetes treatment.

Background: SF3B1 is a splicing factor that plays a crucial role in cancer progression and is commonly found in various types of solid cancers. However, the reports regarding the clinical implications of SF3B1 in terms of therapy response, survival, and its relationship with patients' clinicopathological features are still limited. This study aimed to assess SF3B1 expression for neoadjuvant chemotherapy response in stage III triple-negative breast cancer.

Methods: This case-control study was conducted at Prof. Dr. I.G.N.G. Ngoerah General Hospital from March to October 2021. Stage III TNBC breast cancer patients who received neoadjuvant chemotherapy were included. Variables assessed included SF3B1 expression, NAC response, and various histological and clinical parameters. Immunohistochemistry (IHC) for SF3B1 expression was performed using the avidin-biotin method. Data analysis involved univariate, bivariate (chi-square), and multivariate (logistic regression) methods using SPSS, with significance set at p ≤ 0.05.

Results: Analysis showed that high Ki-67, tumor-infiltrating lymphocytes (TILs), and SF3B1 status significantly increased the risk of chemoresistance in TNBC breast cancer (OR=6.4, 95%CI=1.20-34.19, p-value=0.017; OR=4.8, 95%CI=1.05-21.75, p-value=0.031; OR=13.5, 95%CI=1.56-116.24, p-value=0.008, respectively) No significant relationships were found with age, grading, or menopausal status. Multivariate analysis confirmed these variables independently influenced chemoresistance, with aOR=14.4, 95%CI=1.80-115.73 for Ki-67 (p-value=0.012), aOR=6.7, 95%CI=1.12-40.46 for TIL (p-value=0.037), and aOR=13.714, 95%CI=1.56-116.24 for SF3B1 (p-value=0.018).

Conclusions: High SF3B1 expression, alongside high Ki-67 and TIL levels, is potentially a prognostic marker for chemoresistance in stage III TNBC. These findings suggest that targeting SF3B1 could offer a novel therapeutic approach in TNBC patients.