Multi-Stimuli-Responsive and Cell Membrane Camouflaged Aggregation-Induced Emission Nanogels for Precise Chemo-photothermal Synergistic Therapy of Tumors.

Targeted and controllable drug release at lesion sites with the aid of visual navigation in real-time is of great significance for precise theranostics of cancers. Benefiting from the marvelous features (e.g., bright emission and phototheranostic effects in aggregates) of aggregation-induced emission (AIE) materials, constructing AIE-based multifunctional nanocarriers that act as all-arounders to integrate multimodalities for precise theranostics is highly desirable. Here, an intelligent nanoplatform (P-TN-Dox@CM) with homologous targeting, controllable drug release, and in vivo dual-modal imaging for precise chemo-photothermal synergistic therapy is proposed. AIE photothermic agent (TN) and anticancer drug (Dox) are encapsulated in thermo-/pH-responsive nanogels (PNA), and the tumor cell membranes are camouflaged onto the surface of nanogels. Active targeting can be realized through homologous effects derived from source tumor cell membranes, which advantageously elevates the specific drug delivery to tumor sites. After being engulfed into tumor cells, the nanogels exhibit a burst drug release at low pH. The near-infrared (NIR) photoinduced local hyperthermia can activate severe cytotoxicity and further accelerate drug release, thus generating enhanced synergistic chemo-photothermal therapy to thoroughly eradicate tumors. Moreover, P-TN-Dox@CM nanogels could achieve NIR-fluorescence/photothermal dual-modal imaging to monitor the dynamic distribution of therapeutics in real-time. This work highlights the great potential of smart P-TN-Dox@CM nanogels as a versatile nanoplatform to integrate multimodalities for precise chemo-photothermal synergistic therapy in combating cancers.

[Effects of soothing liver and invigorating spleen recipes on the mRNA and protein expression of TLR4 in hepatic tissues of rats with NASH].

OBJECTIVE: To research the effects of soothing liver and invigorating spleen recipes on expression of TLR4 mRNA and protein expression in hepatic tissue of rats with non-alcoholic steatohepatitis and its mechanism. METHODS: 72 male SD rats were randomly divided into 8 groups: normal group, model group, high-dose soothing liver group (receiving gavage of Chaihu Shugan Powder 9. 6 g/kg), low-dose soothing liver group (receiving gavage of Chaihu Shugan Powder 3.2 g/kg), high-dose invigorating spleen group (receiving gavage of Shen Ling Baizhu Powder 30 g/kg), low-dose invigorating spleen group (receiving gavage of Shen Ling Baizhu Powder 10 g/kg), high-dose integrated Group (receiving gavage of Chaihu Shugan Powder and Shen Ling Baizhu Powder combination recipes 39.6 g/kg), low-dose integrated Group (receiving gavage of Chaihu Shugan Powder and Shen Ling Baizhu Powder combination recipes 13.2 g/kg), 9 rats were in each group. Used high fat diet (10 mL/kg) to establish experiment model of NASH rat. At the end of the sixteenth weeks, the levels of serum lipids, liver lipids and serum aminotransferase were measured by automatic biochemical analyzer; Liver pathology was analyzed by HE and Oil red O staining; TLR4 mRNA was assayed by real-time fluorescent quantitative polymerase chain reaction (RT Q-PCR); TLR4 protein was detected by Western blot. RESULTS: Compared with normal group, the levels of TC, LDL-C in the serum, TC,TG as well as the expression of TLR4 mRNA and protein in the hepatic tissue were dramatically increased in model group (P < 0.01). Compared with the model group, the levels of serum lipids, liver lipids, the expression of TLR4 mRNA and protein in the hepatic tissue were decreased in each treatment group (P < 0.05 or P < 0.01). CONCLUSION: Soothing liver and invigorating spleen recipes can inhibit hepatic TLR4 expression, that may be one of their therapeutic mechanisms. There is much difference between high-does and low-does treatment groups in various testing items, which shows that there is does-effect relationship in intervention NASH.

Electrical stimulation promotes motor nerve regeneration selectivity regardless of end-organ connection.

Previous studies have demonstrated that end-organ deprivation after peripheral nerve injury results in targeting of regenerating nerve fibers into inappropriate pathways, which leads to poor functional recovery. Here we studied the effect of electrical stimulation on the regeneration selectivity of motor nerves after peripheral nerve injury and end-organ deprivation. We found that end-organ deprivation reduced regenerating selectivity of motor nerves, total number of regenerating motoneurons, and level of neural trophic factors in the regenerating pathways after nerve injury (p < 0.05). Electrical stimulation successfully promoted motor nerve regeneration selectivity regardless of end-organ connections (p < 0.05). This increased selectivity was accompanied by an increase in the protein level of neural trophic factors in the distal nerve stumps by 3 weeks after nerve injury (p < 0.05). There was a similar increase in the protein level of these neural trophic factors in denervated muscle. However, the RNA level of these factors decreased both in the distal nerves and in the muscle. Despite the promising effect of promoting motor nerve regeneration selectivity, electrical stimulation did not prevent motoneuron loss caused by end-organ deprivation. The present study suggests that end organs contribute to the development of selective motor nerve regeneration by increasing the neurotrophic factors in the regeneration pathways. Electrical stimulation is an efficient strategy to ameliorate the deteriorated regeneration microenvironment caused by end-organ deprivation and to promote motor nerve regeneration selectivity when end-organ connections are deprived.