Gender differences are present in many diseases and are especially prevalent in cardiovascular disease. Males tend to suffer from myocardial infarctions earlier than females, and a woman's risk of cardiovascular disease increases after menopause, suggesting a cardio‐protective role of estrogen. However, hormone replacement therapy did not decrease the risk of cardiovascular disease in post‐menopausal women; thus, other mechanisms may be involved besides estrogen. Oxidative stress plays an important role in the development of cardiovascular diseases such as coronary artery disease. Gender is also associated with differences in oxidative stress. Under physiological conditions, females appear to be less susceptible to oxidative stress. This may be due to the antioxidant properties of estrogen, gender differences in NADPH‐oxidase activity or other mechanism(s) yet to be defined. This review strives to discuss gender differences in general terms followed by a more detailed examination of gender differences with oxidative stress and various associated diseases and the possible mechanisms underlying these differences.

Multidrug resistance is a major challenge to cancer chemotherapy. The multidrug resistance phenotype is associated with the overexpression of the adenosine triphosphate (ATP)-driven transmembrane efflux pumps in cancer cells. Here, we report a lipid membrane-coated silica-carbon (LSC) hybrid nanoparticle that targets mitochondria through pyruvate, to specifically produce reactive oxygen species (ROS) in mitochondria under near-infrared (NIR) laser irradiation. The ROS can oxidize the NADH into NAD+ to reduce the amount of ATP available for the efflux pumps. The treatment with LSC nanoparticles and NIR laser irradiation also reduces the expression and increases the intracellular distribution of the efflux pumps. Consequently, multidrug-resistant cancer cells lose their multidrug resistance capability for at least 5 days, creating a therapeutic window for chemotherapy. Our in vivo data show that the drug-laden LSC nanoparticles in combination with NIR laser treatment can effectively inhibit the growth of multidrug-resistant tumors with no evident systemic toxicity.

Development of high-fidelity 3D models to recapitulate the tumor microenvironment is essential for studying tumor biology and discovering anticancer drugs. Here we report a method to engineer the 3D microenvironment of human tumor, by encapsulating cancer cells in the core of microcapsules with a hydrogel shell for miniaturized 3D culture to obtain avascular microtumors first. The microtumors are then used as the building blocks for assembling with endothelial cells and other stromal cells to create macroscale 3D vascularized tumor. Cells in the engineered 3D microenvironment can yield significantly larger tumors in vivo than 2D-cultured cancer cells. Furthermore, the 3D vascularized tumors are 4.7 and 139.5 times more resistant to doxorubicin hydrochloride (a commonly used chemotherapy drug) than avascular microtumors and 2D-cultured cancer cells, respectively. Moreover, this high drug resistance of the 3D vascularized tumors can be overcome by using nanoparticle-mediated drug delivery. The high-fidelity 3D tumor model may be valuable for studying the effect of microenvironment on tumor progression, invasion, and metastasis, and for developing effective therapeutic strategy to fight against cancer.

Circular RNAs (circRNAs), one kind of noncoding RNAs, can interact with miRNA and transcription factors to regulate gene expression. However, little is known on which circRNA is crucial for the pathogenesis of hepatocellular carcinoma (HCC). CircRNA expression profile was analyzed by a microarray. Regulatory gene targets were predicted by bioinformatics analysis and validated by luciferase assay. Their expression was determined by qRT-PCR and Western blotting. DNA methylation was determined by methylation-specific PCR. Gene knockdown and overexpression were mediated by lentivirus-mediated shRNA and transfection with plasmids for cDNA expression, respectively. MTT assay, wound-healing assay, transwell invasion assay, and flow cytometry were used to determine malignant behaviors of HCC cells. HCC xenograft mouse model was used to determine the in vivo effects of circRNA-5692. CircRNA-5692 expression was downregulated in HCC tissues, and circRNA-5692 overexpression attenuated the malignant behaviors of HCC cells. Bioinformatics predicted that circRNA-5692 interacted with miR-328-5p, which targeted the DAB2IP mRNA. Actually, miR-328-5p promoted the malignant behaviors of HCC cells, while DAB2IP had opposite effects. Moreover, circRNA-5692 overexpression inhibited the growth of xenograft HCC tumors in vivo by decreasing miR-328-5p expression to enhance DAB2IP expression. In conclusion, the circRNA-5692–miR-328-5p–DAB2IP regulatory pathway inhibits the progression of HCC. Our findings may provide potential new targets for the diagnosis and therapy of HCC.