Maintained particulate integrity of soy protein nanoparticles during gastrointestinal digestion via genipin crosslinking enhancing stability and bioavailability of curcumin.

Poor stability during gastrointestinal digestion is a major challenge for the applications of protein-based nanoparticles as oral delivery systems. In this work, genipin was used to crosslink the partially enzymatic hydrolyzed soy protein nanoparticles, aiming to improve their performance in gastrointestinal tract as delivery carrier. Results showed that the obtained genipin-crosslinked soy protein nanoparticles (GSPNPs) were still spherically monodisperse with a diameter around 60 nm. Encapsulation with GSPNPs significantly improved the solubility of curcumin (Cur) and its stability against UV light as well as long-term storage. Compared to those un-crosslinked nanoparticles, particles crosslinked by genipin had a more compact structure less sensitive to ionic effect and digestive enzymes, showing enhanced digestion stability. The well-maintained nanoparticulate structure of GSPNPs further contributed to the enhanced bioaccessibility and facilitated absorption by epithelial cells. Furthermore, in vivo experiment on rats showed that Cur encapsulated in GSPNPs exhibited a slowed down and sustained absorption manner with an 8.11-fold improvement in its bioavailability. These suggested that GSPNPs could be a promising nanocarrier to enhance the bioavailability of functional factors.

Formation of mucus-permeable nanoparticles from soy protein isolate by partial enzymatic hydrolysis coupled with thermal and pH-shifting treatment.

Modulating the size and surface charge of nanocarriers provides an efficacious strategy to enhance bioavailability of encapsulated cargos through increased mucus penetration. In this study, mucus-permHeable soy protein nanoparticles (SPNPs) were successfully fabricated via gastrointestinal proteolysis coupled with heating and pH-shifting treatment. Results showed that treatment at 65 °C and 75 °C after proteolysis induced the assembly of α, ά, and ß subunits, forming a relatively loose structure. This facilitated further assembly upon pH-shifting, forming smaller-sized and less electronegative nanoparticles, which showed enhanced mucus permeability. However, treatment at 85 °C and 95 °C promoted stronger hydrophobic interactions and induced disulfide bond cross-linking between B and ß subunits, forming compact macro-aggregates with high ß-sheet structure. These larger-sized aggregates were less influenced by pH-shifting treatment, demonstrating limited mucus diffusion. This study provides a potential alternative to fabricate mucus-permeable nanoparticles, and established a relationship between protein subunit assembly behavior and its mucus permeability.

Immune checkpoint inhibitors for treatment of small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Small cell lung cancer (SCLC) is a very aggressive and proliferative disease, with little progress being having made for its treatment in decades. Our goal was to evaluate the effect of immune checkpoint inhibitors (ICIs) and identify optimal first-line interventions for the treatment of SCLC. METHODS: A systematic literature search of the Cochrane Library, PubMed and oncology conference proceedings were conducted. Randomized trials evaluating ICIs for SCLC were included. We use the risk of bias tool in RevMan 5.3 to assess the quality of studies. We used Stata version 15.0 to carry out data direct comparison and R version 4.0.2 to conduct the Bayesian network analysis. RESULTS: A total of 16 relevant clinical trials comprising 4,476 patients were included. We found the magnitude of efficacy for ICIs as first-line therapy conferred a statistically significant benefit in overall survival (OS) and progression-free survival compared to chemotherapy alone. The results were 0.82 (95% CI, 0.76-0.89, P<0.001) and 0.80 (95% CI, 0.74-0.86, P<0.001). For objective response rate (ORR), the result (1.13, 95% CI, 0.97-1.31, P=0.109) was not significant. In the second-line and maintenance treatment, no additional benefit was observed. With regard to safety, results showed that for all grades of AEs and grades 3-4 AEs, the pooled results were 1.36 (95% CI: 0.50-3.70; P=0.543) and 1.35 (95% CI: 0.58-3.15; P=0.484) respectively. In addition, the indirect comparison results showed that nivolumab combined with chemotherapy led to the most significant improvement in OS, while durvalumab combined with chemotherapy was a more efficacious therapy for improving ORR compared with the other interventions; the probability were the best treatments was 73.93% and 81% respectively. DISCUSSION: Our results showed ICIs combined with etoposide and platinum-based drugs as first-line treatment of SCLC have benefits for patients and there was no evidence of a significant difference in efficacy among the different ICI drugs used for the first-line therapy. As for toxicity, the ICIs did not increase the frequency AEs for patients. However, as some studies are ongoing and the full data have still not been reported, our conclusions may not be completely representative.

lncRNA TUG1 Expression in NSCLC and Its Clinical Significance.

BACKGROUND: This study was aimed at exploring the expression of lncRNA TUG1 in non-small cell lung cancer (NSCLC) and analyzing the correlations between TUG1 expression and an NSCLC patient's clinical and pathological parameters and prognosis. METHODS: This study included 132 NSCLC patients who were admitted between January 2012 and May 2013 in our hospital. Expression levels of TUG1 expression in the resected cancer tissue and normal adjacent tissue (NAT) were assessed using the ISH and RT-qPCR assays to analyze the correlations between TUG1 expression in NSCLC tissue and an NSCLC patient's clinical and pathological parameters and prognosis. RESULTS: Compared to NAT, NSCLC tissue has a lower expression level of TUG1. The TUG1 expression further decreases as NSCLC progressed to a later stage, indicating a statistically significant difference (p < 0.01 or p < 0.001). High TUG1 expression is not strongly associated with age, gender, smoking history, or the degree of differentiation of NSCLC (p > 0.05) but exhibits close correlations with tumor size, TNM stage, and lymph node metastasis (p < 0.05). Patients with a higher level of TUG1 expression have a higher survival rate and a longer survival time than those with lower TUG1 expression. The inter-group differences were statistically significant (p < 0.05). CONCLUSION: Considering TUG1 presence in the development and progression of NSCLC, hopefully, it can be used as a tumor marker in the diagnostic workup of patients with NSCLC.

A novel Pickering emulsion system as the carrier of tocopheryl acetate for its application in cosmetics.

Pickering emulsion (PE) stabilized by bio-compatible polymer nanoparticles (NPs) was first developed for the encapsulation of lipophilic tocopheryl acetate (TA) for its application in cosmetics. The poly(lactide-co-glycolide) (PLGA)/poly(styrene-co-4-styrene-sulfonate) (PSS) NPs were prepared by solvent displacement, and then they were used as emulsifier particles to fabricate TA-encapsulated PE. It was found that the TA encapsulation efficiency was >98%. Scanning electron microscope analysis showed that the obtained PE exhibited 'shell' structure. The PE droplets had spherical shape with diameter around 2 µm and good dispersibility as evidenced by laser scanning confocal microscope. In addition, the PE was stable at the pH range of 4.29-7.07 which was compatible to skin pH. Meanwhile, the PE also showed good storage stability since there was no obvious change in its diameter, PDI and TA retention after storage at 4 °C for 30 days. The DPPH method confirmed that TA retained its antioxidation in the PE preparation process. Moreover, an improved UV irradiation stability was observed for the TA after being encapsulated in the PE. The results of cytotoxicity test suggested that the PE was compatible to the Hacat cell line (human immortalized keratinocytes). And there is negligible influence in the cellular uptake of TA after its encapsulation in the PE. However, the cellular antioxidant activity (CAA) of encapsulated TA presented a significant increase from 1.32 to 1.56 µM quercetin equivalent/mg·mL-1. Hence, the prepared PE was promising as the carrier of TA for its cosmetic application.

Advances in research of angiogenesis inhibitors combined with immune checkpoint inhibitors in the treatment of malignant tumors / 中国肿瘤生物治疗杂志

@#肿瘤的生长需要血管的生成，不同于正常的血管，异常的肿瘤血管通过改变肿瘤微环境来抑制机体的免疫功能，从而 使肿瘤发生免疫逃逸。抗血管生成治疗可以使肿瘤血管正常化，进而改善机体的免疫功能。免疫检查点抑制剂通过改变肿瘤微 环境，不仅可以提高机体的免疫功能，同时也可以促进肿瘤血管的正常化。本文综述了抗血管生成治疗联合免疫检查点抑制剂 治疗恶性肿瘤的理论依据以及相关的临床数据，为恶性肿瘤的治疗提供更多的治疗策略。