It has been well documented that chronic stress can induce atherosclerotic changes, however, the underlying mechanisms is yet to be established. In this regard, this study aimed to elucidate the relation between hypothalamic-pituitary adrenal-axis (HPA-axis), toll-like receptors (TLRs), as well as M1/M2 macrophage ratio and pre-atherosclerotic changes in social isolation stress (SIS) in mice. We used small interfering RNA against the glucocorticoid receptor (GR) to evaluate the relation between HPA-axis and TLRs. C57BL/6J mice were subjected to SIS and RT-PCR, ELISA, flow cytometry, and immunohistochemistry were used to assess the relations between pre-atherosclerotic changes and TLRs, macrophage polarization, pro-inflammatory cytokines, and cell adhesion molecules in aortic tissue. We used TAK-242 (0.3 mg/kg, intraperitoneally), a selective antagonist of TLR4, as a possible prophylactic treatment for atherosclerotic changes induced by SIS. We observed that isolated animals had higher serum concentration of corticosterone and higher body weight in comparison to normal animals. In isolated animals, results of in vitro study showed that knocking-down of the GR in bone marrow–derived monocytes significantly decreased the expression of TLR4. In vivo study suggested higher expression of TLR4 on circulating monocytes and higher M1/M2 ratio in aortic samples. Pathological study showed a mild pre-atherosclerotic change in isolated animals. Finally, we observed that treating animals with TAK-242 could significantly inhibit the pre-atherosclerotic changes. SIS can possibly increase the risk of atherosclerosis through inducing abnormal HPA-axis activity and subsequently lead to TLR4 up-regulation, vascular inflammation, high M1/M2 ratio in intima. Thus, TLR4 inhibitors might be a novel treatment to decrease the risk of atherosclerosis induced by chronic stress.

Cancer is one of the most critical human challenges which endangers many people’s lives every year with enormous direct and indirect costs worldwide. Unfortunately, despite many advanced treatments used in cancer clinics today, the treatments are deficiently encumbered with many side effects often encountered by clinicians while deploying general methods such as chemotherapy, radiotherapy, surgery, or a combination thereof. Due to their low clinical efficacy, numerous side effects, higher economic costs, and relatively poor acceptance by patients, researchers are striving to find better alternatives for treating this life-threatening complication. As a result, Metal nanoparticles (Metal NPs) have been developed for nearly 2 decades due to their important therapeutic properties. Nanoparticles are quite close in size to biological molecules and can easily penetrate into the cell, so one of the goals of nanotechnology is to mount molecules and drugs on nanoparticles and transfer them to the cell. These NPs are effective as multifunctional nanoplatforms for cancer treatment. They have an advantage over routine drugs in delivering anticancer drugs to a specific location. However, targeting cancer sites while performing anti-cancer treatment can be effective in improving the disease and reducing its complications. Among these, the usage of these nanoparticles (NPs) in photodynamic therapy and sonodynamic therapy are notable. Herein, this review is aimed at investigating the effect and appliances of Metal NPs in the modulation tumor microenvironment which bodes well for the utilization of vast and emerging nanomaterial resources.

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Background: It has been well documented that social isolation stress (SIS) can accelerate the formation of atherosclerotic plaque through inflammation. In this regard, this study aimed to elucidate the relation between HPA-axis, toll-like receptors (TLRs), as well as M1/M2 macrophage ratio and atherosclerosis in socially isolated (SI) animals.Methods: We used small interfering RNA (siRNA) against the glucocorticoid receptor (GR) to evaluate the relation between HPA-axis and TLRs. RT-PCR, ELISA, flow cytometry, and immunohistochemistry were used to assess any relation between atherosclerosis and TLRs, M1/M2 ratio, pro-inflammatory cytokines, and cell adhesion molecules in aortic tissue. Finally, we used TAK-242 (0.3 mg/kg, intraperitoneally), a selective antagonist of TLR4, as a possible prophylactic agent in formation of atherosclerotic plaque in-vivo.Results: We observed that SI animals had higher serum concentration of corticosterone and higher body weight in comparison to normal animals. In SI animals, results of in-vitro study showed that knocking-down of the GR in bone marrow–derived monocytes significantly decreased the expression of TLR4. In-vivo study suggested higher expression of TLR4 on circulating monocytes and higher M1/M2 ratio in aortic samples. Pathological study showed a mild formation of pre-atherosclerotic changes in SI animals. Finally, we observed that treating animals with TAK-242 could significantly inhibit the formation of pre-atherosclerotic changes.Conclusion: SIS can possibly increase the risk of atherosclerosis through over-activating HPA-axis and subsequently led to TLR4 up-regulation, tissue inflammation, high M1/M2 ratio in endothelium. Thus, TLR4 inhibitors might be a novel treatment to reduce the risk of atherosclerosis-induced by chronic stress.