Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.

SiO_(2) Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO_(2)-induced cardiac injury using a mouse model.Methods Male C57BL/6 mice were intratracheally instilled with SiO_(2) to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed.Results SiO_(2) altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO_(2)-induced mitochondrial damage and myocardial injury.SiO_(2) inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO.Conclusion Iron overload-induced ferroptosis contributes to SiO_(2)-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO_(2) cardiotoxicity,potentially via modulation of the Nrf2 pathway.

Effects of Curcumin on Neuroinflammation and the Nrf2/HO-1 Pathway in Rat Brains Following Gas Explosion

Gas explosions,a major occupational hazard in China’s coal industry,endanger the lives and health of miners.These explosions cause a specific type of traumatic brain injury with complex mechanisms,leading to disability and death.A study by Zhao et al.using magnetic resonance imaging on 49 gas explosion survivors revealed significant damage to brain regions like the hippocampus and cerebral cortex.

Association among Serum Organochlorine Pesticide Residues, Glutathione S-Transferase M1 Genetic Polymorphism and Female Breast Cancer

Background: The purpose of this study was to evaluate the association among serum organochlorine pesticide residues, glutathione S-transferase M1 genetic polymorphism and female breast cancer. Methods: A 1:1 matched case-control study of 140 newly diagnosed breast cancer patients and 140 non-cancer female patients who consulted the five largest hospitals in the Tangshan city from September 2006 to October 2007. Results: The result showed higher risk of breast cancer among subjects with higher levels of serum DDT and HCH residue, the OR was 3.18 (95%CI, 1.11 - 9.07) and 5.02 (95%CI, 1.64 - 16.56).The value of ORe associated with single environmental factor DDT high residues, and ORg associated with single GSTM1 deletion genotype were respectively 3.86 (1.20 - 12.47) and 1.34 (0.36 - 5.08). The OReg associated with combined action of two factors was 5.59 (1.63 - 18.90), and the value of interaction parameters (γ) equaled 1.24. The value of ORe associated with single environmental factor HCH higher residue and ORg associated with single GSTM1 deletion genotype were respectively 2.73 (0.84 - 8.87) and 1.48 (0.49 - 4.60). The value of OReg associated with combined action of two factors was 3.87 (1.18 - 12.68), and γ equaled 1.38. Conclusion: The results indicated that breast cancer occurrence was the combined result of environmental and genetic factors. The concurrent action of GSTM1 deletion genotype and DDT/HCH enhanced the risk of breast cancer.