Reports of Biochemistry and Molecular Biology最新文献

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: 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.

Background: Preeclampsia (PE) is a hypertensive disorder in pregnancy affecting multiple organ systems. This study hypothesized that oxidative stress and inflammatory responses contribute to the pathogenesis of Preeclampsia, and that selenium and N-acetylcysteine (NAC) could mitigate these effects.

Methods: The study was initiated after approval from the Institutional Animal Ethics Committee. Twenty-four female Wistar rats were divided equally into four groups. Group I served as controls, while Groups II, III, and IV received Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) to induce hypertension from day 10 to 20 of gestation. Additionally, Group III received selenium (240 μg/kg/day) and Group IV received NAC (160 mg/kg). On day 20, Blood Pressure (BP) monitoring and urine protein estimation were carried out to assess hypertension and proteinuria, while blood samples were collected to measure malondialdehyde (MDA) and interleukin-6 (IL-6) levels, as markers of oxidative stress and inflammation, respectively. Statistical analysis was performed using GraphPad Prism 10.2.

Results: Selenium improved L-NAME-induced hypertension (Mean BP 107.63±5.22 mmHg vs 140.9±8.38 mmHg in disease control (DC) and proteinuria (65.5±4.09 vs 140.2±11.85 mg/day in DC) and significantly reduced the inflammatory response (IL-6 23.4±1.06 vs 50.63±3.35 pg/mL in DC) but had little effect on oxidative stress (MDA 0.21±0.02 vs 0.24±0.02 nmol/mL in DC). NAC did not lower BP (Mean BP 129.33±7.96 mmHg) but significantly reduced proteinuria (92.7±6.37mg/day), IL-6 levels (18.24±0.42 pg/mL), and oxidative stress (MDA 0.16±0.01 nmol/mL).

Conclusions: These findings suggest that selenium and NAC play distinct protective roles in the pathophysiology of preeclampsia, potentially offering synergistic effects for cardiovascular and kidney health in hypertensive pregnancies.

Background: Apelin is a naturally produced ligand for G protein-linked receptors derived from a 77-amino acid pre-propeptide. The effect of apelin on the development of cardiovascular diseases and the relationship between the apelin gene and the apelin receptor.

Methods: The case-control study included 100 participants of people suffering from cardiovascular diseases. Samples were collected from patients hospitalized at the Nasiriyah Heart Center between November 10, 2023, and February 15, 2024. The study also included 50 healthy people who did not suffer from cardiovascular disease. The lipid profile was measured by spectrophotometer, and the Apelin level was measured by enzyme-linked immunosorbent assay. Four single nucleotide polymorphisms for Apelin (APLN) and Apelin receptor (APLNR) were chosen, and Sanger sequencing was used to genotype them accurately.

Results: The findings indicated that there was no statistically significant difference in age between the two groups. Upon comparing the age demographics of the two groups in the study, the results indicated a lack of statistical significance in the levels of APLN or the lipid profile, despite the case group exhibiting markedly elevated Apelin and lipid levels compared to the control group. After multiple test adjustments (P < 0.05), neither the APLN rs2235310T allele nor the APLNR rs9943582 allele demonstrated an association with an elevated risk of coronary heart disease.

Conclusions: The investigation revealed no significant age variations or genetic correlations associated with CHD risk. However, rather than age or genetic differences, elevated apelin and cholesterol levels in the case group indicate these factors as primary contributors to cardiovascular risk.

Background: Arsenic (As), a toxic metalloid present in drinking water, is one of the environmental pollutants associated with diabetes in humans. Vanillic acid (VA), a bioactive compound derived from plants has various medicinal activities.

Methods: This study was conducted on NMRI male mice for 8 weeks. forty mice were randomly divided into control group, As group (50 ppm), VA (100 mg/kg) group, and two groups receiving As (50 ppm) and VA with doses of 50 mg/kg and 100 mg/kg. After 56 days of the study, the mice were fasted overnight and on day 57, fasting blood glucose was measured, and glucose tolerance test was performed. On day 59, mice were euthanized and serum factors, markers of oxidative stress, tumor necrosis factor-α (TNF-α), and expression nuclear factor kappa B (NF-κB) and Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) proteins were measured.

Results: The As significantly increased fasting blood sugar, the activity level of liver function enzymes, thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), TNF-α, and NF-κB expression. Furthermore, As decreased hepatic total thiol (TT) and activity levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and expression of PPARγ. VA decreased the altered liver enzymes, hyperglycemia, NO, TBARS, TNF-α and the expression of NF-κB. Furthermore, increased the hepatic activity of the CAT, SOD, and GPx, TT and the expression of PPARγ.

Conclusions: The administration of VA at doses of 50 and 100 mg/kg demonstrated significant mitigation of the toxic effects induced by As on the liver.

Background: Hospitalized Coronavirus Disease 2019 (COVID-19) patients are at a higher risk of bacterial and fungal infections. Procalcitonin is an inflammatory marker that has been suggested for distinguishing between bacterial and viral infections that predicting bacterial co-infection in COVID-19 and serving as a helpful indicator for determining the severity of the illness. This study aimed to evaluate procalcitonin levels and antimicrobial resistance (AMR) among microbial co-infections in hospitalized COVID-19 patients.

Methods: Clinical and microbiological data were obtained from the medical records of 100 COVID-19 patients.

Results: COVID-19 patients with bacterial infections had a 55% mortality rate. The majority of microbial cultures were detected in blood (49%), sputum (44%), and urine (7%). Among the isolates, 57.7% were Gram-negative bacteria, 31.7% were Gram-positive bacteria, 6.7% were mixed isolates, and 3.8% were fungal isolates. The predominant Gram-negative isolates were Klebsiella pneumoniae (37.2%), Acinetobacter baumannii (20.2%), and Streptococcus pneumoniae (14.4%). Candida albicans (2.9%) was the most commonly isolated fungal pathogen, followed by Aspergillus spp. (1%). Most of the isolates showed high resistance to broad-spectrum antibiotics. Gram-negative bacteria were detected in 29% of COVID-19 patients who died, Gram-positive bacteria in 20%, and mixed bacteria in 6%. The majority of surviving patients had procalcitonin levels below 0.25 ng/mL, whereas non- survivors had higher levels.

Conclusions: Secondary microbial infections in COVID-19 patients remain a critical concern during the pandemic. Additionally, multidrug-resistant organisms are an increasing challenge. In hospitalized COVID-19 patients, baseline procalcitonin levels were associated with patient outcomes and bacterial coinfection.