Activation of TRPV1 by capsaicin-loaded CaCO3 nanoparticle for tumor-specific therapy.

Capsaicin is a natural non-toxic small molecular organic substance, which is often used clinically to reduce inflammation and pain. Here, we report an acid-responsive CaCO3 nanoparticle loaded with capsaicin that can specifically activate TRPV1 channels and trigger tumor calcium ion therapy. The excellent acid responsiveness of calcium carbonate enables it to precisely target the tumor sites. The released capsaicin can specifically activate TRPV1 channel, overloading the intracellular calcium ion concentration and causing cell apoptosis, which provides a new safer and cheaper treatment. We proved that the naturalness and non-toxicity of capsaicin make the CaCO3@CAP nanoparticles have excellent biocompatibility, which has good development prospects and clinical application potential.

Safety analysis of early oral feeding after esophagectomy in patients complicated with diabetes.

OBJECTIVE: To evaluate the safety of early oral feeding in patients with type II diabetes after radical resection of esophageal carcinoma. METHODS: The clinical data of 121 patients with type II diabetes who underwent radical resection of esophageal carcinoma in the department of cardiothoracic surgery of Jinling Hospital from January 2016 to December 2018 were retrospectively analyzed. According to the median time (7 days) of the first oral feeding after surgery, the patients were divided into early oral feeding group (EOF, feeding within 7 days after surgery, 67 cases) and late oral feeding group (LOF, feeding after 7 days, 54 cases). Postoperative blood glucose level, incidence of complications, nutritional and immune indexes, inflammatory indexes, normalized T12-SMA (the postoperative/preoperative ratio of vertical spinal muscle cross-sectional area at the 12th thoracic vertebra level) and QLQ-C30 (Quality Of Life Questionnaire) scores were recorded and compared in the two groups. RESULTS: There was no statistical difference in preoperative nutritional index and postoperative complication rates between the EOF and LOF group (p > 0.05). The postoperative nutritional index (ALB, PA, TRF, Hb) and immune index (IgA, IgG, IgM) of the EOF group were higher than those of the LOF group (p < 0.05), and the inflammatory indicators (CRP, IL-6) of the EOF group were significantly lower than those of the LOF group (p < 0.05). Moreover, postoperative T12-SMA variation and QLQ-C30 scores of the EOF group were higher than those in LOF group (p < 0.05). CONCLUSIONS: Early oral feeding is safe and feasible for patients with type II diabetes after radical resection of esophageal cancer, and it can improve short-term nutritional status and postoperative life quality of the patients.

Identification and Validation of a Potent Multi-lncRNA Molecular Model for Predicting Gastric Cancer Prognosis.

Gastric cancer (GC) remains the third deadliest malignancy in China. Despite the current understanding that the long noncoding RNAs (lncRNAs) play a pivotal function in the growth and progression of cancer, their prognostic value in GC remains unclear. Therefore, we aimed to construct a polymolecular prediction model by employing a competing endogenous RNA (ceRNA) network signature obtained by integrated bioinformatics analysis to evaluate patient prognosis in GC. Overall, 1,464 mRNAs, 14,376 lncRNAs, and 73 microRNAs (miRNAs) were found to be differentially expressed in GC. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these differentially expressed RNAs were mostly enriched in neuroactive ligand-receptor interaction, chemical carcinogenesis, epidermis development, and digestion, which were correlated with GC. A ceRNA network consisting of four lncRNAs, 21 miRNAs, and 12 mRNAs were constructed. We identified four lncRNAs (lnc00473, H19, AC079160.1, and AC093866.1) as prognostic biomarkers, and their levels were quantified by qRT-PCR in cancer and adjacent noncancerous tissue specimens. Univariable and multivariable Cox regression analyses suggested statistically significant differences in age, stage, radiotherapy, and risk score groups, which were independent predictors of prognosis. A risk prediction model was created to test whether lncRNAs could be used as an independent risk predictor of GC or not. These novel lncRNAs' signature independently predicted overall survival in GC (p < 0.001). Taken together, this study identified a ceRNA and protein-protein interaction networks that significantly affect GC, which could be valuable for GC diagnosis and therapy.

Light-Induced Caspase-3-Responsive Chimeric Peptide for Effective PDT/Chemo Combination Therapy with Good Compatibility.

Activated doxorubicin (DOX) often has severe systemic toxicity and side effects due to its inability to distinguish tumor cells from normal cells, which seriously affects the prognosis of patients. Here, we synthesized an inactivated a DOX prodrug that could be selectively activated by a light-induced caspase-3 enzyme in the tumor site. In the absence of light, this uniformly dispersed nanoparticle avoided the unnecessary toxicity under physiological conditions. Upon the laser irradiating to the tumor area of interest, the nanoparticles can produce a large amount of reactive oxygen species (ROS) to induce cell apoptosis and activate caspase-3 enzyme to release DOX selectively. Meanwhile, the produced ROS can also combine with activated DOX to cause more potent tumor damage. The experiments demonstrated that the light can effectively activate DOX drug through a series of cascade events and the subsequent synergistic therapy both in vitro and in vivo. This strategy achieved excellent therapeutic outcomes and minimal adverse effects, which should significantly improve the dilemma of traditional chemotherapy.

Reasonably retard O2 consumption through a photoactivity conversion nanocomposite for oxygenated photodynamic therapy.

Photodynamic therapy (PDT) brings excellent treatment outcome while also causing poor tumor microenvironment and prognosis due to the uncontrolled oxygen consumption. To solve this issue, a novel PDT strategy, oxygenated PDT (maintain the tumor oxygenation before and after PDT) was carried out by a tumor and apoptosis responsive photoactivity conversion nanocomposite (MPPa-DP). Under physiological conditions, this nanocomposite has a low photoactivity. While at H2O2-rich tumor microenvironment, the nanocomposite could react with overexpressed H2O2 to produce O2 and release high photoactivity chimeric peptide PPa-DP for oxygenated tumor and PDT. Importantly, when the PDT mediates cell apoptosis, the photoactivity of PPa-DP be effectively quenched and the O2 consumption appeared retard, which avoided further consumption of residual O2 on apoptotic cells. In vitro and vivo studies revealed that this nanocomposite could efficiently change photoactivity, reasonable control O2 consumption and increase residual O2 content of tumor after PDT.

Theoretical investigations on oxidative stability of solvents and oxidative decomposition mechanism of ethylene carbonate for lithium ion battery use.

The electrochemical oxidative stability of solvent molecules used for lithium ion battery, ethylene carbonate (EC), propylene carbonate, dimethyl carbonate, diethyl carbonate, and ethyl methyl carbonate in the forms of simple molecule and coordination with anion PF(6)(-), is compared by using density functional theory at the level of B3LYP/6-311++G (d, p) in gas phase. EC is found to be the most stable against oxidation in its simple molecule. However, due to its highest dielectric constant among all the solvent molecules, EC coordinates with PF(6)(-) most strongly and reaches cathode most easily, resulting in its preferential oxidation on cathode. Detailed oxidative decomposition mechanism of EC is investigated using the same level. Radical cation EC(*+) is generated after one electron oxidation reaction of EC and there are five possible pathways for the decomposition of EC(*+) forming CO(2), CO, and various radical cations. The formation of CO is more difficult than CO(2) during the initial decomposition of EC(*+) due to the high activation energy. The radical cations are reduced and terminated by gaining one electron from anode or solvent molecules, forming aldehyde and oligomers of alkyl carbonates including 2-methyl-1,3-dioxolane, 1,3,6-trioxocan-2-one, 1,4,6,9-tetraoxaspiro[4.4]nonane, and 1,4,6,8,11-pentaoxaspiro[4.6]undecan-7-one. The calculation in this paper gives a detailed explanation on the experimental findings that have been reported in literatures and clarifies the mechanism on the oxidative decomposition of EC.