Acta Biochimica Iranica

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

Sonia Fathi-karkan — 2024-12-10

Cancer is still a significant cause of illness and death globally, and it is therefore crucial to find new ways of improving treatment efficacy and patient outcomes. Chemotherapy has the potential to act effectively on cancer cells but also impacts normal cells, leading to serious side effects. In this review, we discuss how nanotechnology is overcoming these challenges through novel concepts to improve the specificity and efficiency of chemotherapy delivery. Through the utilization of nanocarriers (NCs), including lipid-based, polymer-based, protein-based, carbon-based, and inorganic nanosystems (for example, metallic nanoparticles, quantum dots, mesoporous silica nanoparticles, and metal-organic frameworks), as well as hybrid and responsive nanosystems, nanotechnology provides the possibility for more specific and sensitive targeted drug delivery. All these can reduce undesired side effects and enhance treatment outcomes by facilitating the potential for earlier treatment and diagnosis. Our review article presents an overview of clinical trials in progress and FDA-approved NC-based anticancer therapies, unveiling the progress in the area. Utilizing nanotechnology for cancer treatment is a significant paradigm shift, with the potential to revolutionize drug delivery, minimize side effects, and ultimately improve the lives of cancer patients. We also highlighted the challenges inherent in utilizing NCs for targeted drug delivery, alongside potential strategies to tackle these obstacles, with the ultimate goal of advancing cancer therapy and improving overall survival rates for patients.

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

Mahboobe Sattari — 2024-12-11

Non-alcoholic fatty liver disease (NAFLD) is a widespread 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 examines the mechanisms by which fisetin intervention influences NAFLD management. It emphasizes glycemic control through post-prandial 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 via enhancement of hepatic β-oxidation and reduction of lipogenesis. The anti-inflammatory effects are observed both systemically and locally within the liver. Fisetin also enhances 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 — 2024-12-18

Objectives: Oxidative stress and inflammation play important role in pathophysiology of Diabetic nephropathy (DN). Nanoparticles, including cerium oxide nanoparticles (CeO2NPs) which reduce oxidative stress and inflammation, are increasingly used in treatment of the diseases. Therefore, this study aims to assess the preventive potential of CeO2NPs' in a DN animal model by examining their effects on glucose, lipids, oxidative stress, and kidney damage markers.

Methods: Diabetes was induced in rats using streptozocin (STZ). Rats were divided into normal control (N-Cnt), diabetic control (D-Cnt), and CeO2NPs-treated groups (D-CeO2, 60 mg/kg). Fasting blood glucose (FBG) levels were measured at baseline and day 35. Also serum lipid profiles, including TC, TG, HDL-C, and LDL-C, were assessed. In kidney tissue, the activities of the antioxidant enzymes (SOD, CAT, GPx), the levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and mRNA expression of pyruvate kinase M2 (PKM2) and kidney injury molecule-1 (KIM-1) were determined.

Results: CeO2NPs treatment in D-CeO2NPs rats significantly reduced FBG and improved the lipid profile (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.

Conclusions: CeO2NPs demonstrate protective effects against DN in this rat model through ameliorating hyperglycemia, dyslipidemia, and oxidative stress, and modulating the expression of renal injury markers. These findings suggest that CeO2NPs may have therapeutic potential for DN, warranting further investigation into their mechanisms and clinical applicability.

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

Elham Esmaili — 2024-12-10

Objectives: Prostate cancer (PCa) is regarded as the most common malignancy in men, and it is associated with higher levels of prostate-specific antigen (PSA). Recently, it has been demonstrated that Glycine N-methyltransferase (GNMT) plays a critical role in sarcosine production. There is evidence that the serum levels of this enzyme changes in many malignancies, such as hepatocellular carcinoma, colorectal, and gastric cancer. In the current study, we evaluate the serum levels of GNMT in the PCa, benign prostatic hyperplasia (BPH) and healthy subjects.

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

Results: Our finding showed that PSA level was significantly higher in PCa group than BPH patients and healthy individuals. Moreover, PCa patients had higher level of GNMT as compared to the BPH patients and healthy controls, but it has not appeared significant. Serum level of GNMT enzyme was positively correlated with age in PCa group. In BPH group, the levels of GNMT was significantly correlated with PSA concentrations.

Conclusion: It seems that serum GNMT level is increased in PC patients. However, more research with a bigger sample size is needed to validate these findings.

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

Buyun Shi — 2024-12-11

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

Methods: Male Wistar rats were submitted to CLP model. The animals were grouped into the sham, sham + KMF, CLP, and CLP + KMF groups and treated with KMF (50 mg/kg, i.p). Twenty-four hours after CLP, the cytokines, NF-kB level, myeloperoxidase (MPO) activity, oxidative damage to lipids and proteins, and antioxidant enzymes activities were evaluated in the hippocampus. 10 days after sepsis induction, behavioral tests were performed to assess the cognitive damage.

Results: KMF reduced the TNF-α and IL-1β levels, MPO activity, protein level of NF-kB, and expression of TLR4 and MYD88 in the hippocampus of septic rats. KMF decreased the levels of oxidative stress parameters (MDA and protein carbonyls groups) and elevated the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). In addition, the expression level of genes involved in the anti-oxidant defense system such as nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenease-1 (HO-1) were upregulated following KMF treatment.

Conclusion: These findings indicated that KMF exhibited protective effects on the survival rate and cognitive dysfunction after sepsis by inhibiting the inflammatory responses and oxidative stress.

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

Sahereh Rouzbehan — 2024-12-10

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, yet 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 measured by Auto analyzer. 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.

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

Samaneh Mohassel Azadi — 2024-12-13

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.

Conclusions:
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.