Pathobiology Research
Year:2025 | Volume:28 | Issue:2|Papers Count:8

Heart failure (HF) is associated with several systemic complications that require combination therapies. Considering the type and clinical manifestations of HF, several types of medications are used to overcome some harmful activated compensatory mechanisms. Angiotensin receptor–neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs) and sodium–glucose cotransporter 2 (SGLT2) inhibitors alongside with other classes like diuretics, vasodilators and/or positive inotropic agents constitute the medication basket for patients with heart failure. Polypharmacy with different classes of drugs increases the risk of drug-drug interactions during treatment. One of the main issues in these interactions is the risk of electrolyte abnormalities, especially regarding the potassium level, which would be so threatening. This mini review focused on specific aspects of drug-drug interactions that might occur during treatment and how they can be life-threatening.

Introduction: Colorectal cancer (CRC) is one of the leading cancers, following skin, breast, and stomach cancers. This study aimed to investigate the relationship between mutations in axin1 and axin2 in association with CRC. Methods: Our study contains 147 fresh frozen samples from CRC patients, 25 normal samples, and 3 cell lines, including HT29, SW480, and CACO-2. The chosen SNPs from databases are placed in exon 5 of axin1, in exon 2 of axin1, and in exon 7 of axin2. By PCR-RFLP method, mutated samples were identified and sequenced. Results: The results showed that mutations in the single-nucleotide polymorphism (SNP) in axin2 were observed in 1 out of 147 patient samples (0.68%). In the three sequences examined in axin2 (exon 7), mutations in SNP with rs79024445 at A2052C were observed. Statistical analysis of clinical and pathological data of patients showed a significant relationship between the tumor size factor and grade of cancer (P=0.016) as well as the degree of tumor diffusion to the lymph nodes factor with a grade of cancer (P=0.001). Conclusion: The multi-factorial nature of cancer, the high genetic diversity of the Iranian population, and the limited statistical population could affect these outcomes. The observed mutations in each sample can also indicate the importance of personalized medicine in studying diseases

Abstract: Objective: Despite the availability of effective vaccines and antiviral treatments, influenza remains a significant cause of hospitalizations and mortality globally. This study aimed to evaluate the epidemiological characteristics, clinical manifestations, and outcomes of patients diagnosed with seasonal influenza in two referral centers in northeastern Iran. Methods: This retrospective cross-sectional study analyzed data from 58 patients with a mean age of 45 who tested positive for seasonal influenza via PCR. These patients were hospitalized at Imam Reza and Qaem hospitals between 2009 and 2017. Data were collected using a standardized checklist and analyzed using SPSS software version 23. Non-normally distributed data were assessed using the Mann-Whitney test, while qualitative variables were compared using the Chi-square test, with Fisher's exact test applied when necessary. Results: Among the 58 influenza-infected patients, 37 (67.2%) survived, 18 (32.7%) died, and 6 (10.9%) were discharged at their own request. Influenza A subtypes identified included H1N1 (15.7%) and H3N2 (23.6%), with 60.5% remaining untyped. Antiviral drug administration did not significantly correlate with hospital mortality. However, initiating antiviral treatment within the first 48 hours did influence mortality outcomes. Patient age, influenza virus type, and subtype showed no significant relationship with hospital mortality. Conclusion: The study highlights concerning clinical outcomes and hospital mortality rates among patients diagnosed with seasonal influenza. Given the preventable nature of influenza and the challenges in managing these patients, there is an urgent need to enhance physician awareness, particularly among specialists. Emphasizing timely diagnostic and therapeutic interventions is critical, especially during peak influenza seasons.

Introduction: Opioid Use Disorder (OUD) is a chronic neuropsychiatric condition driven by persistent neuroadaptive changes in reward, motivation, and stress-related circuits. While opioid receptors are central to OUD, the broader role of G protein-coupled receptors (GPCRs) in opioid-induced neuroplasticity remains underexplored. This study systematically characterizes GPCR dysregulation in OUD to identify potential pharmacological targets. Methods: We performed transcriptomic analysis of RNA sequencing (RNA-seq) datasets from addiction-related brain regions, including the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (GSE174409), Brodmann area 9 (GSE182321), and central amygdala (GSE194368). A curated set of ~900 GPCR genes was analyzed for differentially expressed genes (DEG), principal component analysis (PCA), and hierarchical clustering. Drug-targetable GPCRs were identified via DrugBank and ChEMBL, and their behavioral and stress-related roles were determined. Protein-protein interaction (PPI) networks were constructed using STRING. Results: We identified 58 GPCRs consistently dysregulated across brain regions, reflecting common molecular adaptations in OUD. PCA revealed a clear separation between OUD and control groups, indicating distinct receptor remodeling. Hierarchical clustering identified functional subgroups, including drug-targetable GPCRs and orphan GPCRs. Notably, 17 GPCRs—including DRD1, DRD3, DRD4, HTR1A, HTR2A, OXTR, and CNR1—are involved in behavioral regulation and addiction vulnerability. Network analysis highlighted key receptor hubs, suggesting novel therapeutic targets. Conclusion: The present study provides a receptor-centric framework for drug repurposing and precision medicine in OUD. Integrating transcriptomic and pharmacological data, we highlight GPCRs with translational potential. Further validation through functional assays and single-cell studies is warranted.

Introduction: This experimental in-vitro and in-vivo parallel-group study aimed to investigate the ZNF521 overexpression effects on the glioblastoma cell line (U87MG) behavior in vitro and the therapeutic potential of U87MG cells that were overexpressed by ZNF521 (U87-ZNF521) in functional recovery of spinal cord injury (SCI) in rats. Methods: ZNF521-IRES-GFP was introduced into U87MG cells and maintained in the neural inductive medium for over 3 weeks. The GFAP, ITGA6, PAX6, NES, SOX1, TUBB3, and OLIG2 gene expressions were analyzed. The SCI rats were split into three groups, with 10 rats each (30 rats in total). Then, U87-ZNF521 cells were transplanted, and the Basso-Beattie-Bresnahan scale and footprint analysis were used to evaluate the rats’ locomotor capacity. Results: ZNF521 overexpression induced morphological changes and aggregated formation in U87MG cells, with a 26% transfection rate. Significant upregulation of PAX6, TUBB3, and OLIG2 and decreasing SOX1 were observed, while GFAP, ITGA6, and NES showed non-significant changes compared to the control group. In SCI rats, U87-ZNF521 exhibited substantial recovery in hindlimb motor coordination and weight support. Moreover, gait analysis revealed increased step length, stride angle, and step width in U87-ZNF521 rats during a five-week treatment. However, no significant improvement was observed with plantar application. Conclusion: ZNF521 overexpression in the U87MG suggests its potential to differentiate into neural progenitors. Additionally, these neural progenitors improved motor function in SCI rats. ZNF521 can be a potential therapy for promoting recovery in glioblastoma and SCIs, highlighting its role as a promising target for further exploration in neural regeneration strategies.

Introduction: Disruption of inflammatory profile in the presence of obesity and overweight is associated with reduced insulin action in target cells. In the present study, the effect of aerobic training on insulin resistance is evaluated with an emphasis on possible changes in adropin and fetuin-A in overweight women. Methods: For this purpose, 24 overweight adult females (26 ≤ BMI ≤ 30) were randomly assigned into experimental (n=12) or control (n=12) groups. The experimental group underwent an 8-week aerobic training of 3 sessions weekly, and the control group did not participate in the training. 24 hours before and 48 hours after exercise training, fasting blood sample was taken to measure serum levels of adropin, fetuin-A and insulin resistance in the 2 groups. Data were compared between the two groups by independent and paired sample t test at a significance level of less than 0.5 percent. Results: No significant difference was observed in all variables between groups at baseline (p < 0.05). Aerobic training resulted in significant increase in serum adropin (p = 0.001) and decrease in Fetuin-A (p = 0.001) and insulin resistance (p = 0.019) in experimental groups. All variables remained without change in control group (p < 0.05) Conclusion: The improvement in insulin resistance following aerobic training may be attributed to a decrease in fetuin-A and an increase in adropin in response to this type of exercise. However, further studies are needed to understand the underlying mechanisms responsible for these changes.

M2 macrophages and their exosome-derived products have therapeutic potential in regenerative medicine. M2 macrophages, characterized by their anti-inflammatory and tissue-repair functions, play pivotal roles in immune modulation, wound healing, and disease resolution. M2 macrophage-derived exosomes can modulate inflammatory responses, promote angiogenesis, and stimulate stem cell activity. The review systematically examines their roles in diverse preclinical models, including diabetic fractures, periodontitis, neurodegenerative diseases, myocardial infarction, and chronic wounds. It addresses progress in bioengineering, such as combining M2-derived exosomes with biomaterials and scaffolds to improve targeted delivery and regenerative results. Although they show great potential, obstacles like exosome diversity, restricted scalability, and the need for standardized isolation techniques are recognized as hindrances to clinical application. This review distinguishes M2 macrophage-derived exosomes as a promising acellular tool for personalized therapeutic applications and tissue repair by synthesizing existing literature and identifying promising directions for future research. It emphasizes the need for ongoing research to overcome technical and regulatory barriers to their successful translation to the clinical setting

Introduction: Anxiety disorders involve altered brain circuit dynamics, but the neural mechanisms underlying olfactory-prefrontal interactions during anxiety remain unclear. Beta oscillations are implicated in long-range neural communication and emotional processing, but their specific role in anxiety remains underexplored. Methods: I recorded simultaneous local field potentials (LFPs) from the olfactory bulb (OB) and prefrontal cortex (PFC) in male Wistar rats during anxiety-provoking behavioral tests, including the Elevated Plus Maze (EPM) and Open Field (OF). Functional connectivity was assessed through beta-band (13–30 Hz) synchronization using cross-correlation and power correlation analyses. Results: Behavioral tests revealed a significant increase in beta-frequency synchronization between OB and PFC during anxiogenic conditions compared to resting states. Notably, enhanced functional coupling was observed specifically in anxiogenic zones—the open arms of the EPM and the center area of the OF. These effects suggest an intensity-dependent increase in OB-PFC interaction associated with anxiety states. Conclusion: My findings identify beta-band OB-PFC synchronization as a novel electrophysiological marker of anxiety, providing insight into sensory-executive integration during threat processing. This enhanced connectivity may contribute to the neural circuitry underlying anxiety and represents a potential target for therapeutic intervention.