Acta Biochimica Iranica

Breaking Barriers in Cancer Treatment: An updated review on Clinical Translation of Novel Nanocarrier Systems

Sun, 13 Jul 2025 07:59:36 +0000

Cancer remains a significant cause of illness and death globally, and it is therefore crucialto find new ways to improve treatment efficacy and patient outcomes. Chemotherapy hasthe potential to act effectively on cancer cells but also impacts normal cells, leading toserious side effects. In this review, we discuss how nanotechnology is overcoming thesechallenges through novel concepts aimed at improving the specificity and efficiency ofchemotherapy delivery. Through the utilization of nanocarriers (NCs), including lipid-based, polymer-based, protein-based, carbon-based, and inorganic nanosystems (suchas metallic nanoparticles, quantum dots, mesoporous silica nanoparticles, and metal-organic frameworks), as well as hybrid and responsive nanosystems, nanotechnologyenables more specific and sensitive targeted drug delivery. All of these approaches canreduce undesired side effects and enhance treatment outcomes by facilitating the potentialfor earlier treatment and diagnosis. Our review article presents an overview of ongoingclinical trials and FDA-approved NC-based anticancer therapies, unveiling progress inthe field. Utilizing nanotechnology for cancer treatment represents a significant paradigmshift, with the potential to revolutionize drug delivery, minimize side effects, andultimately improve the lives of cancer patients. We also highlight the challenges inherentin utilizing NCs for targeted drug delivery, alongside potential strategies to tackle theseobstacles, with the ultimate goal of advancing cancer therapy and improving overallsurvival rates for patients.

Fisetin as a Promising Agent in Non-Alcoholic Fatty Liver Disease: Insights into Pathogenic Mechanisms and Therapeutic Potential

Tue, 15 Jul 2025 07:55:52 +0000

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver condition characterized by fat accumulation in the liver, with its development involving intricate processes such as inflammation, oxidative damage, and lipid metabolism disturbances. Current treatment options are limited, emphasizing the need for multi-targeted approaches that can simultaneously address these pathogenic pathways to improve liver health. This review synthesizes current evidence on how fisetin impacts molecular pathways relevant to NAFLD. It focuses on its effects in reducing inflammation, oxidative stress, and lipid accumulation, based on experimental and clinical studies examining gene expression, enzyme activity, and signaling pathways involved in hepatic steatosis and injury. This review also explores the mechanisms by which fisetin intervention influences NAFLD management, highlighting its role in glycemic control through postprandial glucose reduction, mitigation of insulin resistance, improvements in pancreatic insulin secretion, and suppression of hepatic gluconeogenesis and glycogenolysis. Additionally, fisetin exerts plasma lipid-lowering effects by enhancing hepatic β-oxidation and reducing lipogenesis. Its anti-inflammatory effects are observed both systemically and locally within the liver. Fisetin also strengthens antioxidant defenses by activating antioxidant enzymes, reducing superoxide levels, chelating metal ions, and scavenging free radicals. Furthermore, fisetin modulates endoplasmic reticulum (ER) stress and promotes autophagy, contributing to the amelioration of NAFLD pathology. Taken together, fisetin exhibits a promising hepatoprotective profile and may serve as a beneficial natural supplement for liver health. Its potential benefits in reducing liver steatosis and supporting NAFLD management, combined with its minimal side effects, make it an attractive candidate for further exploration as a complementary therapy

Cerium Oxide Nanoparticles Attenuate Diabetic Nephropathy in Rats by Reducing Oxidative Stress, Improving Dyslipidemia, and Modulating PKM2 and KIM-1

Jamal Amri, Abolfazl Emadi, Narjes Rezaei, Zahra Salemi — Tue, 15 Jul 2025 07:59:33 +0000

Objectives: Oxidative stress and inflammation play important roles in the pathophysiology of diabetic nephropathy (DN). Nanoparticles, including cerium oxide nanoparticles (CeO₂NPs), which reduce oxidative stress and inflammation, are increasingly utilized in disease treatment. This study aims to assess the preventive potential of CeO₂NPs in a DN animal model by examining their effects on glucose levels, lipid profiles, oxidative stress, and kidney damage markers.

Methods: Diabetes was induced in rats using streptozotocin (STZ). Rats were divided into three groups: normal control (N-Cnt), diabetic control (D-Cnt), and CeO₂NP- treated (D-CeO₂, 60 mg/kg) groups. Fasting blood glucose (FBG) levels were measured at baseline and on day 35. Additionally, serum lipid profiles (total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)) were assessed. In kidney tissue, activities of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)), levels of malondialdehyde (MDA) and total antioxidant capacity (TAC), as well as mRNA expression of pyruvate kinase M2 (PKM2 ) and kidney injury molecule-1 (KIM-1) were analyzed.

Results: CeO₂NP treatment in D-CeO₂ rats significantly reduced FBG and improved lipid profiles (decreased TC, TG, LDL-C; increased HDL-C, P < 0.05). CeO₂NPs also attenuated oxidative stress (increased SOD, CAT, GPx, TAC; reduced MDA, P < 0.05) and downregulated PKM2 and KIM-1 mRNA expression (P < 0.05) compared to D-Cnt rats.

Conclusion: CeO₂NPs demonstrate protective effects against DN in this rat model by ameliorating hyperglycemia, dyslipidemia, oxidative stress, and renal injury marker expression. These findings suggest that CeO₂NPs may possess therapeutic potential for DN, warranting further investigation into their mechanisms and clinical applicability.

Serum Carcinoembryonic Antigen (CEA) and Tumor Characteristics Correlate with UBE2Q1 Protein Expression in Colorectal Cancer Patients

Tue, 15 Jul 2025 08:02:26 +0000

Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, ranking third in men and second in women. The ubiquitin-conjugating enzyme UBE2Q1 has been reported to be overexpressed in colorectal tumors; however, its role in CRC pathogenesis and prognosis remains unclear. Carcinoembryonic antigen (CEA) is a well-established biomarker elevated in CRC, used to monitor treatment response and disease progression. This study aimed to investigate the association between UBE2Q1 gene expression and CRC prognosis by evaluating its correlation with serum CEA levels.

Methods: In this cross-sectional study, 48 CRC patients undergoing surgery at Faghihi Hospital, Shiraz University of Medical Sciences, were analyzed. Tumor and adjacent normal tissues were collected for UBE2Q1 expression analysis via Western blotting. Concurrently, serum CEA concentrations were measured using ELISA, and liver function tests were assessed using an autoanalyzer. Clinical and pathological data, including tumor size, lymph node involvement, and liver function tests, were also recorded.

Results: The cohort had a mean age of 57.2 ± 14.6 years, with equal gender distribution. Mean serum CEA was 2.35 ± 3.45 ng/mL, and UBE2Q1 expression was 5.80 ± 12.39 arbitrary units. Tumor size averaged 29.17 ± 46.13 cm²; 21.4% had lymph node metastasis, and 70% exhibited well-differentiated pathology. Tumors were predominantly located in the rectum (35.7%) and colon (33.3%). A significant positive correlation was observed between serum CEA levels and UBE2Q1 expression (Spearman’s ρ = 0.38, p < 0.05). UBE2Q1 expression also correlated significantly with alkaline phosphatase and AST liver enzymes (p < 0.05). No significant associations were found between UBE2Q1 expression and age, sex, or histopathological features, while serum CEA correlated with pathological differentiation.

Conclusion: UBE2Q1 protein expression is positively associated with serum CEA levels and certain liver function markers, suggesting its potential utility as a prognostic biomarker in CRC. Further studies are warranted to elucidate its mechanistic role and clinical applicability.

The protective effects and underlying mechanisms of Kaempferol on sepsis associated cognitive impairment in rats

Buyun Shi, Ming Chen, Hui Xu — Tue, 15 Jul 2025 08:07:10 +0000

Objectives: The neuroprotective effects of Kaempferol (KMF) have been previously reported; however, its possible effects on sepsis-associated encephalopathy remain unclear. This study aimed to investigate the effects and underlying mechanisms of KMF on cognitive impairment in a cecal ligation and puncture (CLP)-induced sepsis model.

Methods: Male Wistar rats were subjected to the CLP model. The animals were divided into four groups: sham, sham + KMF, CLP, and CLP + KMF, and treated with KMF (50 mg/kg, i.p.). Twenty-four hours after CLP, the levels of cytokines, NF-κB, myeloperoxidase (MPO) activity, oxidative damage to lipids and proteins, and antioxidant enzyme activities were evaluated in the hippocampus. Ten days after sepsis induction, behavioral tests were conducted to assess cognitive damage.

Results: KMF reduced TNF-α and IL-1β levels, MPO activity, NF-κB protein levels, and the expression of TLR4 and MYD88 in the hippocampus of septic rats. KMF decreased oxidative stress parameters (MDA and protein carbonyl groups) and increased the activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Additionally, the expression of genes involved in the antioxidant defense system, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), was upregulated following KMF treatment.

Conclusion: These findings indicate that KMF exerts protective effects on survival rate and cognitive dysfunction after sepsis by inhibiting inflammatory responses and oxidative stress

Comparison of the serum level of glycine N-methyl transferase (GNMT) enzyme in prostate cancer, benign prostatic hyperplasi and healthy subjects

Tue, 15 Jul 2025 08:10:50 +0000

Objectives: Prostate cancer (PCa) is the most common malignancy in men and is associated with elevated levels of prostate-specific antigen (PSA). Recently, Glycine N-methyltransferase (GNMT) has been recognized for its critical role in sarcosine production. Evidence suggests that serum GNMT levels fluctuate in various malignancies, including hepatocellular carcinoma, colorectal cancer, and gastric cancer. The current study evaluates serum GNMT levels in PCa, benign prostatic hyperplasia (BPH), and healthy subjects.

Methods: Serum samples were obtained from 85 adult males (29 PCa patients, 28 BPH patients, and 28 healthy participants) referred to Shahid Beheshti Hospital, Babol, and Shahid Hasheminejad Hospital, Tehran.

Results: Our findings revealed that PSA levels were significantly higher in the PCa group compared to BPH patients and healthy individuals. Additionally, PCa patients exhibited higher GNMT levels compared to BPH patients and healthy controls, though this difference was not statistically significant. Serum GNMT levels were positively correlated with age in the PCa group. In the BPH group, GNMT levels were significantly correlated with PSA concentrations.

Conclusion: Serum GNMT levels appear to be elevated in PCa patients; however, further research with a larger sample size is necessary to validate these findings

Expression Patterns of SIRT1, SIRT3, and TFAM in Adipose Tissue: Associations with Adiposity Indices and Insulin Resistance in Women

Tue, 15 Jul 2025 08:15:11 +0000

Objectives: Obesity is linked to metabolic dysfunction, with mitochondrial regulators such as SIRT1, SIRT3, and TFAM playing key roles in adipose tissue health. This study examined the expression of these genes in subcutaneous and visceral adipose tissues of obese and normal-weight women, and their associations with adiposity indices and insulin resistance.

Methods: Forty-six women (22 obese, 24 normal-weight) were enrolled. Anthropometric, metabolic, and biochemical parameters were measured. mRNA levels of SIRT1, SIRT3, and TFAM were assessed in adipose tissue samples using quantitative real-time PCR.

Results: Obese women had significantly higher adiposity indices and insulin resistance markers. SIRT1 expression in subcutaneous adipose tissue and SIRT3 expression in visceral adipose tissue were lower in obese women compared to controls. SIRT1 and SIRT3 transcript levels showed significant inverse correlations with several adiposity indices and insulin resistance measures. TFAM expression did not differ significantly between groups but was inversely associated with metabolic risk factors in visceral fat.

Conclusion: Reduced SIRT1 and SIRT3 expression in adipose tissue is associated with greater adiposity and insulin resistance in obese women, suggesting a potential role for these genes in obesity-related metabolic disturbances.