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Chondroitin sulfate (CS) is a potential candidate for colon-specific drug carriers. However, the readily water-soluble nature limits its application as a solid-state drug-delivery vehicle. In this study, the CS formation of a polyelectrolyte complex (PEC) with Ca2+ (CS-Ca) was adapted to retain CS in a solid form for use in a drug-delivery system. Pre-treated CS with poly(ethylene glycol) diglycidyl ether (EX-810) followed by complexation with Ca2+ was also tested (CS-Ca-EX). Diclofenac sodium was used as a drug probe to evaluate the performance of the drug-release behavior of the complexes. The amount of diclofenac sodium released was higher in simulated intestinal fluid (SIF) than in simulated gastric fluid (SGF) due to the anionic groups on CS or the higher solubility of drug itself in PBS. The release profile of diclofenac sodium from CS-Ca-EX was most notably sustained when compared to other groups. Enzymatic degradation by chondroitinase ABC of CS, CS-Ca and CS-Ca-EX exhibited a similar degradation mechanism and GPC revealed the dissolution rate of CS from the three matrix types was, in decreasing order: CS, CS-Ca, CS-Ca-EX. The synergy of the anti-inflammatory activity of diclofenac sodium in CS-based complexes was evaluated using the carrageenan-induced edema rat test. The percentage of swelling was lower for all experimental groups as compared to the control, untreated group. The anti-inflammatory activity of diclofenac in the CS matrix gradually increased up to 9 h but CS-Ca or CS-Ca-EX matrices showed less potency than the CS matrix in reducing inflammation.

Pyroptosis or cellular inflammatory necrosis is a programmed cell death kind. Accumulating evidence shows that pyroptosis plays a crucial role in the invasion, metastasis, and proliferation of tumor cells, thus affecting the prognosis of tumors and therapeutic effects. Prostate cancer (PCa), a common malignancy among men, is associated with inflammation. Pathophysiological effects of pyroptosis on tumor development and progression, as well as the mediation of PCa, are known, but its effects on the potential prognosis for PCa warrant in-depth investigation. Herein, we built a risk model of six pyroptosis-related genes and verified their predictive abilities for prognostic and therapeutic effects. Higher risk scores indicated a higher probability of biochemical recurrence (BCR), higher immune infiltration, and worsened clinicopathological features. To derive scientific and reliable predictions for BCR in patients having PCa, the findings of the current study were verified in the Gene Expression Omnibus (GEO) cohort following evaluation in The Cancer Genome Atlas (TCGA) dataset. Additionally, after evaluating the six genes in the model, ZDHHC1 was found to be an important component. Its antitumor role was further assessed through in vivo and in vitro experiments, and its promoting effect on pyroptosis was further evaluated and verified. The above results provided a new perspective for further studies on pyroptosis and its clinical utility for PCa.

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Purpose To develop a novel combination therapy for high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT), namely, intra-arterial chemotherapy (IAC) plus BCG immunotherapy, and to compare the feasibility and safety of the two therapies. Materials and methods A retrospective study was conducted on the data of 119 patients who were diagnosed with high-risk NMIBC and underwent TURBT in the past five years. Those who did not complete the treatment were excluded, and the remaining 98 patients were divided into two groups: both groups received intravesical BCG immunotherapy, while the BCG+IAC group received 4 courses of extra intra-arterial chemotherapy. Clinical and follow-up data were processed using statistical software.Result The recurrence rate was 22.2% in the BCG+IAC group and 35.8% in the BCG group, whereas the progression rates were 8.9% and 24.5%, respectively. In the Kaplan-Meier plot, a statistically significant difference was observed with respect to recurrence-free survival (p=0.025), as well as the progression-free survival of the two groups was similar (p=0.019). 22.2% of the patients with adverse effects of IAC and 79.6% of patients suffered from adverse reactions to BCG immunotherapy, and most of the adverse effects were mild and tolerable. Univariate and multivariate analysis indicated that multifocal and treatment were independent risk factors for recurrence, while the history of recurrence and treatment were independent risk factors for progression.Conclusion IAC could be a promising auxiliary treatment for BCG immunotherapy in decreasing the recurrence and progression rate of high-risk NMIBC with little additional toxicity.Date of registration:10th, April 23, 2022. TRN: ChiCTR2200058555, retrospectively registered