A J-aggregated nanoporphyrin overcoming phototoxic side effects in superior phototherapy with two-pronged effects.

Phototherapy has been a promising therapeutic modality for pathological tissue due to its spatiotemporal selectivity and non-invasive characteristics. However, as a core component of phototherapy, a single photosensitizer (PS) nanoplatform integrating excellent therapeutic efficiency and minimal side effects remains an urgent but unmet need. Here, we construct a J-aggregated nano-porphyrin termed MTE based on the self-assembly of methyl-pheophorbide a derivative MPa-TEG (MT) and natural polyphenolic compound epigallocatechin gallate (EGCG). Due to the synergistic interaction between similar large π-conjugated structural EGCG and MT, MTE with small and uniform size is obtained by effectively hindering Ostwald ripening of MT. Noteworthily, MTE not only effectively avoids the inadvertent side effects of phototoxicity during transport thank to the ability of reactive oxygen species (ROS) scavenging, but also achieves two-pathway augmented superior phototherapy: (1) enhancing photodynamic therapy (PDT) via inhibiting the expression of anti-apoptosis protein surviving; (2) achieving adjuvant mild-temperature laser interstitial thermal therapy (LITT) via reducing the tumor thermoresistance on account that MTE inhibits the overexpression of HSP 70 and HSP 90. This research not only offers a facile strategy to construct multicomponent nanoplatforms but also provides a new pathway for efficient and low-toxicity phototherapy, which is beneficial to the future clinical application.

Application of a novel machine learning framework for predicting non-metastatic prostate cancer-specific mortality in men using the Surveillance, Epidemiology, and End Results (SEER) database.

BACKGROUND: Accurate prognostication is crucial in treatment decisions made for men diagnosed with non-metastatic prostate cancer. Current models rely on prespecified variables, which limits their performance. We aimed to investigate a novel machine learning approach to develop an improved prognostic model for predicting 10-year prostate cancer-specific mortality and compare its performance with existing validated models. METHODS: We derived and tested a machine learning-based model using Survival Quilts, an algorithm that automatically selects and tunes ensembles of survival models using clinicopathological variables. Our study involved a US population-based cohort of 171 942 men diagnosed with non-metastatic prostate cancer between Jan 1, 2000, and Dec 31, 2016, from the prospectively maintained Surveillance, Epidemiology, and End Results (SEER) Program. The primary outcome was prediction of 10-year prostate cancer-specific mortality. Model discrimination was assessed using the concordance index (c-index), and calibration was assessed using Brier scores. The Survival Quilts model was compared with nine other prognostic models in clinical use, and decision curve analysis was done. FINDINGS: 647 151 men with prostate cancer were enrolled into the SEER database, of whom 171 942 were included in this study. Discrimination improved with greater granularity, and multivariable models outperformed tier-based models. The Survival Quilts model showed good discrimination (c-index 0·829, 95% CI 0·820-0·838) for 10-year prostate cancer-specific mortality, which was similar to the top-ranked multivariable models: PREDICT Prostate (0·820, 0·811-0·829) and Memorial Sloan Kettering Cancer Center (MSKCC) nomogram (0·787, 0·776-0·798). All three multivariable models showed good calibration with low Brier scores (Survival Quilts 0·036, 95% CI 0·035-0·037; PREDICT Prostate 0·036, 0·035-0·037; MSKCC 0·037, 0·035-0·039). Of the tier-based systems, the Cancer of the Prostate Risk Assessment model (c-index 0·782, 95% CI 0·771-0·793) and Cambridge Prognostic Groups model (0·779, 0·767-0·791) showed higher discrimination for predicting 10-year prostate cancer-specific mortality. c-indices for models from the National Comprehensive Cancer Care Network, Genitourinary Radiation Oncologists of Canada, American Urological Association, European Association of Urology, and National Institute for Health and Care Excellence ranged from 0·711 (0·701-0·721) to 0·761 (0·750-0·772). Discrimination for the Survival Quilts model was maintained when stratified by age and ethnicity. Decision curve analysis showed an incremental net benefit from the Survival Quilts model compared with the MSKCC and PREDICT Prostate models currently used in practice. INTERPRETATION: A novel machine learning-based approach produced a prognostic model, Survival Quilts, with discrimination for 10-year prostate cancer-specific mortality similar to the top-ranked prognostic models, using only standard clinicopathological variables. Future integration of additional data will likely improve model performance and accuracy for personalised prognostics. FUNDING: None.

The Preventive Effect of Parotid Gland Massage on Salivary Gland Dysfunction During High-Dose Radioactive Iodine Therapy for Differentiated Thyroid Cancer: A Randomized Clinical Trial.

PURPOSE: To evaluate the preventive effect of parotid gland (PG) massage for PG damage during the I therapy, we prospectively investigated the serum amylase value and salivary gland scintigraphy (SGS) after I therapy. MATERIALS AND METHODS: One hundred patients with thyroidectomized differentiated thyroid cancer who underwent high-dose I therapy were enrolled in the clinical trial and randomized into 2 groups (PG massage group and nonmassage group). The serum amylase value was obtained before and 24 hours after I therapy, and the SGSs were also taken just before and at 8 months after the I therapy. Change in serum amylase value and SGS was compared between PG massage and nonmassage groups. RESULTS: The difference value of serum amylase was significantly lower in PG massage group than in nonmassage group (P = 0.0052). Worsening of PG function on SGS was observed in 43 (45.3%) of the 95 patients. The incidence rate of PG abnormality on F/U SGS was significantly lower in PG massage group than in nonmassage group (odds ratio, 0.3704; P = 0.0195). In the multiple regression analysis, PG massage significantly affected the abnormality on the 8-month F/U SGS (rpartial = -0.2741, P = 0.0090) after adjusting for clinical variables (age, sex, TNM stage, TSH preparation methods for the I therapy, and I dose). CONCLUSIONS: PG gland massage significantly reduced the incidence rates of salivary gland dysfunction on the 8-month F/U SGS and the level of the serological marker of salivary gland destruction after I therapy. Therefore, PG gland massage could alleviate salivary gland damage related to I therapy.

Assessment of the safety and efficacy of an attenuated live vaccine based on highly virulent genotype 2b porcine epidemic diarrhea virus in nursing piglets.

We have previously reported the generation of the attenuated KNU-141112-S DEL5/ORF3 virus by continuous propagation of highly virulent G2b porcine epidemic diarrhea virus (PEDV) in Vero cells. The present study aimed to assess the safety of S DEL5/ORF3 and to evaluate its effectiveness as a live vaccine for prime-booster vaccinations. Reversion to virulence experiments revealed that the S DEL5/ORF3 strain retains its attenuated phenotype and genetic stability after five successive passages in susceptible piglets. Pregnant sows were primed orally with an S DEL5/ORF3 live vaccine and boosted intramuscularly twice with a commercial killed vaccine at 2-week intervals prior to parturition. This sow vaccination regimen completely protected nursing piglets against virulent G2b challenge, as evidenced by the increase in survival rate from 0% to 100% and the significant reduction in diarrhea intensity, including the amount and duration of PEDV fecal shedding. In addition, despite a 2-3 day period of weight loss in piglets from vaccinated sows after challenge, their daily weight gain was recovered at 7 days post-challenge and became similar to that of unchallenged pigs from unvaccinated sows over the course of the experiment. Furthermore, strong antibody responses to PEDV were verified in the sera and colostrum of immunized sows with the prime-boost treatment and their offspring. Altogether, our data demonstrated that the attenuated S DEL5/ORF3 strain guarantees the safety to host animals with no reversion to virulence and is suitable as an effective primary live vaccine providing durable maternal lactogenic immunity for passive piglet protection.

Effects of oral administration of different dosages of carvacrol essential oils on intestinal barrier function in broilers.

Essential oils are widely used in the pharmaceutical, food and cosmetic industries, and many plant essential oils have shown that they have positive effects on broilers nutrition. This experiment was conducted to study the effects of orally administered different dosages of carvacrol essential oils on intestinal barrier function in broiler chickens. A total of eighty 28-day-old (1.28 ± 0.15 kg) ROSS 308 broilers were randomly allocated to four groups of 20 replicates each, with one chicken per replicate per cage, and all were fed with the same diet. Four experimental groups were orally administered 0, 200, 300 or 400 µl carvacrol essential oils at 18:00 hr every day during the 2-week experimental period. As a result of which, the gene expression of the occludin, claudin-1, claudin-5, ZO-1 and ZO-2 in intestinal mucosa of small intestine (p < 0.05) and the goblet cell content in small intestine epithelium (p < 0.05) were significantly increased; test subjects with 300 or 400 µl carvacrol essential oils reduced the microbial counts of Salmonella spp. and Escherichia coli in the intestines (p < 0.05); Essential oils administration also significantly increased activity of the sucrase (p < 0.05) and lactase (p < 0.05) in intestinal mucosa. In conclusion, the carvacrol essential oils have positive effects on growth performance and intestinal barriers function of broilers; those effects may be related to the dosage, as administration of 300 or 400 µl was more effective than that of 200 µl.

Sasa quelpaertensis Nakai extract suppresses porcine reproductive and respiratory syndrome virus replication and modulates virus-induced cytokine production.

Although Sasa quelpaertensis Nakai, a dwarf bamboo, is known to exert a variety of beneficial effects on health, its antiviral effect remains to be elucidated. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating viral pathogens of swine and has a substantial economic impact on the global pork industry. Therefore, the present study was conducted to determine whether Sasa quelpaertensis Nakai extract (SQE) inhibits PRRSV infection in cultured porcine alveolar macrophages (PAMs). Our results demonstrated that SQE treatment suppressed the replication of PRRSV in a dose-dependent manner. The antiviral activity of SQE on PRRSV replication was found to be primarily exerted at early times postinfection. Treatment with SQE resulted in marked reduction of viral genomic and subgenomic RNA synthesis, viral protein expression, and progeny virus production. Notably, pro-inflammatory cytokine production in PAM cells infected with PRRSV was shown to be modulated in the presence of SQE. Taken together, our data indicate that SQE has potential as a therapeutic agent against PRRSV.