فهرست مطالب
Research in Molecular Medicine
Volume:10 Issue: 4, Nov 2022
- تاریخ انتشار: 1403/01/20
- تعداد عناوین: 7
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Pages 193-204Background
Acute kidney injury (AKI) is characterized by a rapid decline in kidney function, resulting in significant morbidity and mortality. This review summarizes our knowledge of AKI risk factors, pathogenesis, prediction, diagnosis, and emerging management approaches.
MethodsA comprehensive literature search was conducted to summarize current knowledge on AKI. Five electronic databases were searched using various combinations of search terms related to AKI’s risk factors, pathogenesis, prediction, diagnosis, and management approaches. The databases included PubMed, Embase, Web of Science, CINAHL, and Cochrane Central Register of Controlled Trials. Relevant publications were limited to those written in English from 2016 to 2024, but some prior studies were included if highly seminal. Reference lists were also reviewed to find other sources. The full texts of all possibly relevant articles were assessed for inclusion. Data were extracted on study details and findings concerning AKI causes, biomarkers, prediction strategies, diagnostic techniques, treatments, and perspectives to enhance prevention and outcomes. Quality was considered during data extraction, prioritizing well-performed randomized controlled trials, systematic reviews, and large epidemiological studies. Case reports and select editorials were included to summarize specific topics. Extracted data were narratively synthesized to provide an overview of current AKI knowledge and highlight opportunities for mitigating its impact. Through searching multiple databases using applicable index terms, hand searching reference lists, screening and extracting pertinent published literature, this review aims to understand AKI complications and advance solutions from the existing evidence base.
ResultsThis review summarizes current knowledge on AKI risk mechanisms, diagnostic approaches, emerging therapies and implications of personalized medicine leveraging multi-omics for optimizing prediction and precision treatment.
ConclusionDespite progress, AKI has remained challenging. However, integrative approaches leveraging new technologies offer hope for improving AKI prevention and management.
Keywords: Acute kidney injury, Imaging modalities, Biomarker panels, Nanotechnology, Traditional medicines, Artificial intelligence -
Designing Specific Primers for Amplification and Quantitative Analysis of the GPR120 and PPARγ GenesPages 205-214Background
Designing the primer pairs is one of the most important factors in the amplification and quantitative analysis of the nucleic acid sequences of interest. Using in silico methods, the present study intends to design highly specific primers for quantitative analysis of the genes with minimum expression. To achieve this aim, we selected two candidate genes with little expression, namely, G-protein coupled receptor 120 (GPR120) and peroxisome proliferator-activated receptor-γ (PPARγ), in peripheral blood leukocytes of healthy volunteers.
MethodsPeripheral blood was collected from 30 healthy volunteers. Primers for GPR120 and PPARγ were designed using online websites (UCSC, OligoCalc, and OligoAnalyzer) and the primer designing tool (NCBI). Total RNA extraction and cDNA synthesis were done using commercially available kits based on manufacturer instructions. Finally, the melting curve analysis of GPR120 and PPARγ was assessed using the quantitative real-time PCR method.
ResultsThe in silico gene expression investigation revealed that GPR120 and PPARγ have minimal leukocyte expression. Besides, the melting curves analysis for both genes in the studied individuals showed only one melting peak, confirming the specific amplification of the desired genes.
ConclusionAltogether, the study findings indicated that we could utilize the peripheral blood sample for assessing the gene expression and amplification of omega-3 fatty acids receptors, i.e. GPR120 and PPARγ as two candidate genes with very low expression in leukocytes.
Keywords: GPR120, Omega-3 fatty acid, cDNA, PPARγ, Real-time PCR -
Pages 215-224Background
As the nicotinamide adenine dinucleotide phosphate (NADPH) is the key natural electron generator of the alive cells, investigation of the possibility of inactivation or even destruction of it by hazardous chemical molecules or ions seems to be very important.
MethodsDue to this, in this project, the behavior of NADPH in the presence of some chemical species containing Fe(II) ion, arsine, phosphoric acid, and some low weight alcohols have been investigated by using the density functional theory (DFT) method.
ResultsComparison of the results of the potential energy surface (PES) study showed that adsorption of methanol, ethanol, normal propanol, H3PO4, arsine and Fe(II) ion by NADPH release -23.19 kcal mol-1, -23.03 kcal mol-1, -23.30 kcal mol-1, -35.04 kcal mol-1, -53.03 kcal mol-1, and -161.59 kcal mol-1 energy, respectively.
ConclusionIt indicates that absorption, and even destruction of NADPH by a free Fe(II) ion is very favorable in view of thermodynamics. Somehow, such energy release could make this process irreversible. Also, the geometrical results show that during the adsorption of iron ion by the NADPH, the phosphate bridge breaks and the molecule decompose in two different parts.
Keywords: NADPH, Iron Overload, Arsine, Free Fe(II), Decomposition, Density Functional Theory -
Pages 225-233Background
The Schistosoma parasite is responsible for several overlooked tropical diseases, which cause significant economic losses in livestock. This parasite is increasingly found in the central areas of the northern provinces of Iran. To generate an effective treatment, it is crucial to understand thoroughly how the parasite’s genes work. Currently, the roles of numerous genes in these parasites are unknown, so their identification and targeting of them are challenging. Conventional techniques for assigning functions to proteins depend on the similarity of their sequences. Yet, this method does not always recognize similarities between distantly related proteins. Research has shown that taking the protein’s structure in the process of predicting its function can be helpful in pinpointing proteins whose functions are not known yet.
Materials and methodsIn our study, we utilized two advanced technologies, AlphaFold and Foldseek, to deduce the functions of theoretical proteins in the Schistosoma parasite. We accomplished this by contrasting the structure of Schistosoma proteins with those of Caenorhabditis elegans, a closely related model organism, using Foldseek to identify reciprocal best matches. Our research involved an in-depth examination of two specific predictions, evaluating evidence for functional resemblances, such as patterns of protein interactions and similarities in functional domains.
ResultsOur results indicate that one of the analyzed genes is likely involved in embryogenesis, while the other might be connected to the egg-laying process of the Schistosoma parasite.
ConclusionFunction of some hypothetical proteins can be inferred bases on their structural similarities to annotated proteins, especially proteins with a low sequence similarity to annotated proteins.
Keywords: Schistosoma, Structure, Functional Annotation, Alphafold -
Pages 235-244Background
Ankylosing spondylitis (AS) is a debilitating autoimmune disease presented by chronic inflammation of large joints and central skeleton. The role of various immune cells, including T cell subsets, has been studied in the pathogenesis of AS. Two critical transcription factors, runtrelated transcription factor 3 (RUNX3) and interferon regulatory factor 4 (IRF4), are involved in the differentiation and function of T lymphocytes. This study compared the gene expression level ofRUNX3 and IRF4 between patients with AS and healthy subjects to understand the impact of these factors in the immunopathogenesis of the disease.
MethodsThirty patients with AS and 30 age- and gender-matched healthy individuals were recruited to the study, and expression of RUNX3 and IRF4 genes was evaluated using the reverse transcription polymerase chain reaction (RT-PCR) technique in their peripheral blood.
ResultsThe expression of RUNX3 and IRF4 genes in AS patients was significantly upregulated compared to the healthy controls (P=0.03 and 0.025, respectively). In addition, there was a direct correlation between IRF4 gene expression and bath ankylosing spondylitis global score (BAS-G) (correlation coefficient=0.38, P=0.04)
ConclusionGene expression of RUNX3 and IRF4 transcription factors involved in T cells’ differentiation and function was increased in AS. These findings might have prognostic and therapeutic value.
Keywords: Ankylosing Spondylitis, Interferon Regulatory Factors 4, Quality of life, Runt-Related Transcription Factor 3 -
Pages 245-254Background
COVID-19 is a highly contagious disease that has already affected millions of people worldwide. Proinflammatory cytokines in COVID-19 infection change lipid metabolism and profile. This study investigates the association between lipid profile and inflammatory markers with the severity and outcome of COVID-19 patients referred to a teaching hospital in Mazandaran Province, Iran, during April-May and July-August 2020.
MethodsThis study was conducted on 140 patients with COVID-19 based on their clinical symptoms, imaging results, and laboratory findings. Patients were categorized as severe and non-severe groups based on the Centers for Disease Control and Prevention criteria. Blood samples (5-7 mL) were collected from patients after 12 hours of fasting. Serum triglycerides, cholesterol, highdensity lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) levels were measured using Pars Azmoon Kits (Hitachi Ltd).
ResultsOf 140 COVID-19 patients, 33.57% had severe and 66.43% had non-severe disease. Patients with severe disease had a significantly lower mean LDL serum level than those with non-severe involvement (56.39±3.62 vs 70.10±3.74 mg/dL) (P=0.023). Patients in the intensive care units had significantly lower HDL, LDL, and cholesterol serum levels than those hospitalized in other parts (P=0.006, P=0.002, and P=0.002, respectively). There was a significant negative correlation between HDL serum level and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (P=0.0001 and r=-0.482) and (P=0.01 and r=-0.258), respectively. Additionally, there was a significant correlation between cholesterol level and CRP, triglycerides, and ESR (P=0.016 and P=0.02, respectively).
ConclusionThe present study highlights the potential of lipid profiling as a cost-effective and accessible marker to assess COVID-19 severity and prognosis.
Keywords: Lipid profile, Inflammatory markers, Severity, Outcome, COVID-19 -
High Expressions of MicroRNA-143 in Patients with Methamphetamine Abuse Disorder: Case-Control StudyPages 255-262Background
Chronic drug abuse changes microRNA (miRNA) expression in the brain, which may contribute to addictive behaviors. Many miRNAs play critical roles in developing drug addiction. Methamphetamine induces various alterations in different systems by affecting gene expression, but the effects of methamphetamine on miRNA profiles need to be elucidated. This study evaluated the expression of miRNA-183 and miRNA-143 in the blood of methamphetamine abusers and controls.
MethodsIn this case-control study, the case group comprised 60 people with a methamphetamine addiction from Tabriz City, East Azerbaijan, Iran, and the control group comprised 60 healthy controls of comparable ages and ethnicities. Total RNA was extracted from peripheral blood samples, and then cDNA was synthesized. MicroRNA-183 and microRNA-143 expression levels were determined using real-time PCR.
ResultsThe results indicated that methamphetamine abusers had significantly higher blood levels of miRNA-143 than healthy controls (P<0.05); however, miRNA-183 expression was comparable between the two groups (P>0.05).
ConclusionMicroRNA-143 may play a role in the pathology of methamphetamine abuse, so it may be used as an additional method to identify people with an addiction precisely.
Keywords: Addiction, Methamphetamine, MicroRNA-183, MicroRNA-143, Biomarker