Acta Biochimica Iranica

Investigating the Antitumor Effects of α-Lactalbumin–Oleic Acid Complexes (HAMLET and BAMLET) in Colorectal Cancer: A Systematic Perspective

Marziyeh Babazadeh — Mon, 22 Sep 2025 00:00:00 +0330

Objective: Recently, attention has turned toward naturally derived complexes such as HAMLET (Human α-lactalbumin Made Lethal to Tumor Cells) and BAMLET (Bovine α-lactalbumin Made Lethal to Tumor Cells) due to their selective cytotoxicity and promising mechanisms of action. In this study, we aimed to systematically review the effect of HAMLET and BAMLET on colorectal cancer (CRC).

Methods: PubMed, Scopus, Web of Science, and Embase were searched for studies published between 2020–2025, with one 2006 study included for its unique mechanistic insights. The search combined specific keywords and MeSH terms related to HAMLET, BAMLET, colorectal cancer, antitumor activity, and signaling pathways, using Boolean operators. After removing duplicates and applying predefined inclusion and exclusion criteria, six eligible original studies (in vitro, in vivo, and xenograft models) were included.

Results: Both HAMLET and BAMLET demonstrated cytotoxic effects against CRC cells via diverse mechanisms such as autophagy inhibition, lysosomal membrane permeabilization, mitochondrial dysfunction, and modulation of β-catenin and CK1α signaling. BAMLET notably exhibited synergistic effects with 5-fluorouracil and contributed to reduced tumor growth in murine models. HAMLET’s efficacy varied depending on KRAS/BRAF mutation status and mitochondrial resilience. Importantly, no significant toxicity was observed in healthy non-cancerous cells across the studies.

Conclusions: These findings suggest that HAMLET and BAMLET represent viable adjuncts to standard CRC therapies, offering tumor-specific mechanisms with minimal side effects. Further exploration of their molecular interactions and clinical potential could enhance combination strategies and help overcome therapeutic resistance in CRC treatment.

Recent Advances in Nanodelivery Systems for Polyphenols in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): An update

Tina Ghaffari, Arash Bahramzadeh, Reza Meshkani — Sat, 20 Sep 2025 00:00:00 +0430

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the most prevalent chronic liver disorder worldwide, closely linked to obesity, insulin resistance, and type 2 diabetes mellitus. Despite its rising global burden, there are currently no approved pharmacological therapies targeting MASLD pathogenesis directly. Polyphenolic compounds have demonstrated promising hepatoprotective, antioxidant, and anti-inflammatory properties in preclinical models; however, their poor stability, limited solubility, and low bioavailability hinder clinical translation. This review summarizes the latest advances in nano-drug delivery systems (NDDSs) designed to enhance the therapeutic potential of polyphenols in MASLD. Various nanocarrier platforms, including inorganic, lipid-based, polymeric, and hybrid nanosystems, are discussed with emphasis on their mechanisms of action, pharmacokinetic advantages, hepatocyte-targeting strategies, and translational challenges. Emerging NDDSs markedly enhance polyphenol pharmacodynamics through enhanced intestinal absorption, controlled release, and targeted hepatic accumulation. Lipid-based carriers (liposomes, solid lipid nanoparticles, nanoemulsions, and nanostructured lipid carriers) demonstrate excellent oral bioavailability and safety, whereas polymeric and inorganic systems offer multifunctional therapeutic synergy by modulating oxidative stress, lipid metabolism, and inflammatory pathways. Recent clinical evidence, including nano-micellar curcumin formulations, suggests translational feasibility and safety in MASLD patients. Nevertheless, long-term biosafety, scalability, and interindividual variability remain key challenges for clinical application. Therefore, polyphenols loaded with nanocarrier systems offer a multifaceted therapeutic approach to address the complex metabolic, inflammatory, and fibrotic processes underlying MASLD. Future research should prioritize clinical validation, mechanistic standardization, and regulatory alignment to enable the transition from preclinical innovation to precision nanomedicine in metabolic liver diseases.

Expression of PCGEM1 and lincRNA-p21 lncRNAs in breast cancer tissue

Maryam Mohammadhosseini, Nasrin Shayanfar, Roya Sharifi — Sat, 20 Sep 2025 00:00:00 +0430

Objectives: Long non-coding RNAs (lncRNAs) play critical roles in tumor development, progression, and prognosis. Prostate cancer gene expression marker 1 (PCGEM1) is an oncogenic lncRNA that inhibits apoptosis, whereas lincRNA-p21 promotes apoptosis. This study aimed to investigate the expression of these lncRNAs in breast tumor tissue and adjacent non-tumor tissue.

Methods: The expression levels of PCGEM1 and lincRNA-p21 were assessed by real-time PCR (RT-PCR) in fifty formalin-fixed, paraffin-embedded invasive ductal carcinoma breast tumor tissues and adjacent non-tumor tissues.

Results: The expression of PCGEM1 was significantly higher in tumor tissues compared to adjacent non-tumor tissues (p=0.01). ROC curve analysis indicated that the sensitivity and specificity of PCGEM1 for discriminating breast cancer were %60.87 and 70.21%, respectively, with an area under the curve (AUC) of 0.63 (p=0.01). No significant correlation was observed between PCGEM1 expression and tumor size, histological grade, or lymph node involvement. The expression of lincRNA-p21 was similar in tumor tissues and adjacent non-tumor tissues.

Conclusions: PCGEM1 may contribute to the pathogenesis of breast cancer and could serve as a diagnostic marker in breast cancer.

The Effects of two TP53 Polymorphisms on Its Expression and Folding and Association with the Pathogenesis of Polycystic Ovary Syndrome: in-silico analysis

Thu, 25 Sep 2025 00:00:00 +0330

Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial endocrinopathy characterized by various reproductive and metabolic abnormalities. The tumor suppressor p53 (TP53) plays a crucial role in cellular stress responses. Alterations in its structure or expression can influence PCOS pathogenesis. This study investigates the association of two genetic variants, rs2287499 and rs1042522, with the expression levels and folding stability of TP53 protein through in-silico analyses.

Methods: Utilizing bioinformatics tools, we examined the potential impacts of these single nucleotide polymorphisms (SNPs) on TP53 transcriptional activity, protein structure, and functional integrity.

Results: Our findings indicate that the rs2287499 variant significantly influences TP53 expression levels, while rs1042522 is associated with altered protein folding dynamics. These changes may disrupt TP53's normal regulatory functions, contributing to PCOS etiology. Furthermore, our study establishes a framework for integrating genetic variants into the understanding of TP53-mediated mechanisms in PCOS, which could pave the way for developing targeted therapeutic strategies.

Conclusion: These results underscore the importance of genetic variants in PCOS hormonal and metabolic dysregulation.

Citalopram and Physical exercise for the Prevention of Stress-Induced Dysfunction in Male Wistar Rats

Sat, 20 Sep 2025 00:00:00 +0430

Objectives: Learning is essential for nearly all aspects of human behavior and perception. Among the factors that can disrupt learning and memory, stress is particularly significant, as it interferes with cognitive functioning and overall well-being. The present study aimed to evaluate and compare the effects of citalopram, treadmill-based aerobic exercise, and swimming on learning and memory performance in male Wistar rats exposed to stress.

Methods: To assess these interventions, animals were subjected to immobility stress, moderate-intensity treadmill running, swimming exercise, or citalopram administration (10 mg/kg body weight for four weeks), as well as various combinations of these interventions under stressed and non-stressed conditions, but citalopram was assessed in the presence of stress. The Morris water maze test was used to assess cognitive performance, particularly by measuring the distance traveled to reach the hidden platform.

Results: The results revealed that stress negatively impacted learning and memory. However, both forms of exercise alleviated stress-induced cognitive impairments, with swimming showing especially beneficial effects in enhancing learning and memory among stressed rats.

Conclusion: Contrary to expectations, administration of citalopram did not prevent stress-induced cognitive dysfunction. However, the beneficial effects of both forms of exercise were evident during the acquisition phase. Notably, physical exercise—particularly swimming—may serve as a potential non-pharmacological substitute, as its cognitive effects under stress differed significantly from those of treadmill training in the presence of citalopram.

Circulating Complement C3, C4, Immunoglobulins, and hs-CRP in Women with Recurrent Implantation Failure: A Cross-Sectional Comparative Study

Rahim Rostami, Jamileh Jahanbakhsh, Shirin Salehi, Soudabeh Fallah — Mon, 22 Sep 2025 00:00:00 +0330

Objectives: Plasma levels of complement proteins C3, C4, immunoglobulins (IgGs), and C-reactive protein (CRP) are crucial in understanding recurrent implantation failure (RIF). This study aims to quantify these biomarkers and explore their clinical significance.

Methods: We conducted a cross-sectional study at Arash Hospital from December 2021 to December 2023, involving 50 women with a history of RIF after in vitro fertilization (IVF) and a control group of 50 healthy, fertile women. Serum levels of C3, C4, IgG, IgM, IgA, CRP, and hs-CRP were measured using immunoturbidimetric assays and ELISA.

Results: Plasma levels of complement components C3 and C4, IgG, IgA, CRP, and hs-CRP were significantly elevated in women with recurrent implantation failure (RIF) compared to fertile controls. A positive correlation existed between C3 and C4 in the RIF group, but no significant correlations were found for IgG, IgA, or IgM. In contrast, fertile controls showed significant associations between IgG, C3, C4, and CRP, with IgG levels also correlating with IgA. ROC curve analysis indicated strong discriminatory power for IgG, IgA, C3, and C4 (all p < 0.001). CRP AUC was 0.962, and hs-CRP AUC was 0.994, distinguishing RIF from fertile women, with CRP showing 94% sensitivity and 92% specificity at 5.3 mg/dL, and hs-CRP showing 98% sensitivity and specificity at 2.92 mg/L.

Conclusion: The findings suggested that elevated plasma levels of C3, C4, IgG, and IgA in the RIF group may be associated with the underlying mechanisms of RIF, with complement activation pathways potentially contributing to recurrent implantation failure.

Protective Effects of Encapsulated Bacillus subtilis on Oxidative Stress, Spermatogenesis, and Fertility Outcomes in Experimental Cholestasis

Mon, 22 Sep 2025 00:00:00 +0330

Objective: Probiotics such as Bacillus subtilis exhibit antioxidant and anti-inflammatory activities. However, their viability may be reduced in the gastrointestinal tract (GIT) due to acidity and enzymatic degradation. Encapsulation can improve probiotic survival and bioactivity. Probiotics have also been implicated in mitigating oxidative stress–induced reproductive toxicity. This study evaluated the effects of encapsulated B. subtilis on oxidative balance, sperm quality, and testicular histology in an experimental model of liver cholestasis.

Methods: Forty-eight male Wistar rats were randomly assigned to four groups: control, probiotic, free capsule, and encapsulated probiotic. Encapsulated B. subtilis (3 × 10⁹ CFU/day) was administered orally for one week prior to bile duct ligation (BDL) and for three weeks afterward. At the end of the experiment, rats were euthanized, and blood and testes were collected for biochemical, hormonal, and histological analyses.

Results: BDL markedly reduced sperm concentration and viability while increasing morphological abnormalities. Encapsulated B. subtilis significantly improved sperm parameters compared to free probiotics. Testicular oxidative stress, evidenced by increased protein carbonyls and total oxidant status with decreased reduced glutathione, was attenuated by encapsulated probiotics. Histological analysis revealed disrupted testicular architecture and decreased Johnson’s scores after BDL, whereas encapsulated B. subtilis restored seminiferous tubule integrity and spermatogenesis.

Conclusion: Encapsulated B. subtilis enhanced probiotic efficacy, improving sperm quality, antioxidant status, and testicular structure in cholestatic rats. These findings suggest a protective role for encapsulated probiotics in male infertility associated with oxidative stress and liver disease.

The Impact of Nasal Bone Reporting on Down Syndrome Prognosis: A Prospective Study

Sat, 20 Sep 2025 00:00:00 +0430

Objectives: Accurate prenatal screening for Down syndrome (trisomy 21) is essential for effective maternal-fetal management. The nasal bone (NB) is a critical marker in first-trimester ultrasound assessments, yet reporting inconsistencies can affect prognostic outcomes. This study aims to investigate the impact of reporting the presence or absence of the nasal bone on Down syndrome prognosis in a cohort of pregnant women.

Methods: A prospective study was conducted involving women undergoing contingent prenatal screening during the first trimester. Participants with documented present NB were classified as having unknown NB, while those with unknown reports were treated as having present NB. The risk of Down syndrome was assessed using Benetech-PRA software, and all flagged cases were monitored postpartum to evaluate outcomes.

Results: Of the fetuses assessed, only 5% were diagnosed with Down syndrome. Approximately 7.3% of sonographers reported unknown NB, which was associated with a false-positive screening rate of 16±1%. The findings indicate that NB reporting significantly influences prognostic outcomes, particularly in cases where the NB status is unclear.

Conclusion: Accurate examination and reporting of the nasal bone are critical for reliable Down syndrome prognosis. Inadequate or incorrect NB assessment can lead to misleading results and increased false-positive rates in prenatal screening, underscoring the need for standardized reporting practices in ultrasound examinations.