In Situ Tumor Vaccination with Calcium-Linked Degradable Coacervate Nanocomplex Co-Delivering Photosensitizer and TLR7/8 Agonist to Trigger Effective Anti-Tumor Immune Responses.

In situ anti-tumor vaccination is an attractive type of cancer immunotherapy which relies on the effectiveness of dendritic cells (DCs) to engulf tumor antigens, become activated, and present antigens to T cells in lymphoid tissue. Here, a multifunctional nanocomplex based on calcium crosslinked polyaspartic acid conjugated to either a toll-like receptor (TLR)7/8 agonist or a photosensitizer is reported. Intratumoral administration of the nanocomplex followed by laser irradiation induces cell killing and hence generation of a pool of tumor-associated antigens, with concomitant promotion of DCs maturation and expansion of T cells in tumor-draining lymph nodes. Suppression of tumor growth is observed both at the primary site and at the distal site, thereby hinting at successful induction of an adaptive anti-tumor response. This strategy holds promise for therapeutic application in a pre-operative and post-operative setting to leverage to mutanome of the patient's own tumor to mount immunological memory to clear residual tumor cells and metastasis.

Valproate decreases vitamin D levels in pediatric patients with epilepsy.

PURPOSE: To compare Vitamin D (Vit D) levels in children with epilepsy on valproate monotherapy with healthy controls. METHODS: A meta-analysis performed on articles identified from PubMed and Web of Science online databases evaluated using National Institute of Health National Heart, Lung, and Blood Institute Study Quality Assessment Tools. Subgroup analyses and publication bias assessments were also performed. RESULTS: Eleven publications were eligible based on inclusion/exclusion criteria for the meta-analysis. Results noted a decrease in the mean Vit D level in children with epilepsy on valproate monotherapy compared with healthy children with a Standard Mean Difference = -0.313 [-0.457, -0.169]. Cumulative meta-analysis showed progressive negative effect of valproate therapy on Vit D levels across time. Other antiepileptic medications caused a similar effect on Vit D status. There was no evidence of publication bias in the analyses. Type of study design and country of origin introduced heterogeneities into the meta-analyses. CONCLUSION: This meta-analysis provides evidence that long-term therapy with valproate causes a decrease in Vit D levels in children. Therefore, in children with a seizure disorder on long-term valproate therapy, 25-OH-Vit D levels should be monitored and appropriate supplementation implemented if levels are deficient.

Valproic Acid and the Liver Injury in Patients with Epilepsy: An Update.

BACKGROUND: Valproic acid (VPA) as a widely used primary medication in the treatment of epilepsy is associated with reversible or irreversible hepatotoxicity. Long-term VPA therapy is also related to increased risk for the development of non-alcoholic fatty liver disease (NAFLD). In this review, metabolic elimination pathways of VPA in the liver and underlying mechanisms of VPA-induced hepatotoxicity are discussed. METHODS: We searched in PubMed for manuscripts published in English, combining terms such as "Valproic acid", "hepatotoxicity", "liver injury", and "mechanisms". The data of screened papers were analyzed and summarized. RESULTS: The formation of VPA reactive metabolites, inhibition of fatty acid ß-oxidation, excessive oxidative stress and genetic variants of some enzymes, such as CPS1, POLG, GSTs, SOD2, UGTs and CYPs genes, have been reported to be associated with VPA hepatotoxicity. Furthermore, carnitine supplementation and antioxidants administration proved to be positive treatment strategies for VPA-induced hepatotoxicity. CONCLUSION: Therapeutic drug monitoring (TDM) and routine liver biochemistry monitoring during VPA-therapy, as well as genotype screening for certain patients before VPA administration, could improve the safety profile of this antiepileptic drug.

Modified dachengqi tang improves decreased gastrointestinal motility in postoperative esophageal cancer patients.

OBJECTIVE: To investigate the clinical effects of modified dachengqi tang (DCQT) on promoting gastrointestinal motility in post-operative esophageal cancer patients. METHODS: Sixty postoperative esophageal cancer patients were enrolled and randomly assigned to the modified treatment group or the control group (30 patients in each group). Patients in the treatment group were given DCQT made from decocted herbs and administered via nasojejunal tube at a dosage of 150 mL. Gastrointestinal motility was assessed by recording time for recovery of bowel sounds, flatus, defecation, and the total amount of gastric drainage during the first three postoperative days. Plasma motilin (MTL) and vasoactive intestinal peptide (VIP) were measured one hour before and three days after surgery. RESULTS: Compared with the control group, the times to first bowel sound, flatus, and defecation were significantly shorter and there was less gastric drainage in the treatment group (P < 0.01, P < 0.01, P < 0.01, and P < 0.05, respectively). In the treatment group, postoperative plasma MTL was significantly higher (P < 0.01) and VIP was significantly lower than those in the control group (P < 0.05). There was no difference found in either MTL or VIP from before to after operation in the treatment group (P > 0.05). MTL was significantly lower and VIP was higher postoperatively in the control group, compared to before surgery (P < 0.01). CONCLUSION: Modified DCQT effectively improved decreased gastrointestinal motility in postoperative esophageal cancer patients by increasing MTL and reducing VIP.