Impact of Sodium Thiosulfate on Prevention of Nephrotoxicities in HIPEC: An Ancillary Evaluation of Cisplatin-Induced Toxicities in Ovarian Cancer.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC) but is associated with renal toxicity. Sodium thiosulfate (ST) is used for nephroprotection for HIPEC with cisplatin, but standard HIPEC practices vary. METHODS: A prospective, nonrandomized, clinical trial evaluated safety outcomes of HIPEC with cisplatin 75 mg/m2 during cytoreductive surgery (CRS) in patients with EOC (n = 34) and endometrial cancer (n = 6). Twenty-one patients received no ST (nST), and 19 received ST. Adverse events (AEs) were reported according to CTCAE v.5.0. Serum creatinine (Cr) was collected preoperatively and postoperatively (Days 5-8). Progression-free survival (PFS) was followed. Normal peritoneum was biopsied before and after HIPEC for whole transcriptomic sequencing to identify RNAseq signatures correlating with AEs. RESULTS: Forty patients had HIPEC at the time of interval or secondary CRS. Renal toxicities in the nST group were 33% any grade AE and 9% grade 3 AEs. The ST group demonstrated no renal AEs. Median postoperative Cr in the nST group was 1.1 mg/dL and 0.5 mg/dL in the ST group (p = 0.0001). Median change in Cr from preoperative to postoperative levels were + 53% (nST) compared with - 9.6% (ST) (p = 0.003). PFS did not differ between the ST and nST groups in primary or recurrent EOC patients. Renal AEs were associated with downregulation of metabolic pathways and upregulation of immune pathways. CONCLUSIONS: ST significantly reduces acute renal toxicity associated with HIPEC with cisplatin in ovarian cancer patients. As nephrotoxicity is high in HIPEC with cisplatin, nephroprotective agents should be considered.

Plant phenotype relationship corpus for biomedical relationships between plants and phenotypes.

Medicinal plants have demonstrated therapeutic potential for applicability for a wide range of observable characteristics in the human body, known as "phenotype," and have been considered favorably in clinical treatment. With an ever increasing interest in plants, many researchers have attempted to extract meaningful information by identifying relationships between plants and phenotypes from the existing literature. Although natural language processing (NLP) aims to extract useful information from unstructured textual data, there is no appropriate corpus available to train and evaluate the NLP model for plants and phenotypes. Therefore, in the present study, we have presented the plant-phenotype relationship (PPR) corpus, a high-quality resource that supports the development of various NLP fields; it includes information derived from 600 PubMed abstracts corresponding to 5,668 plant and 11,282 phenotype entities, and demonstrates a total of 9,709 relationships. We have also described benchmark results through named entity recognition and relation extraction systems to verify the quality of our data and to show the significant performance of NLP tasks in the PPR test set.

A New Surface Charge Neutralizing Nano-Adjuvant to Potentiate Polymyxins in Killing Mcr-1 Mediated Drug-Resistant Escherichia coli.

Resistance to polymyxins when treating multidrug-resistant (MDR) Gram-negative bacterial infections limit therapeutic options. Here, we report the synthesis of a nickel (Ni) doped Zinc oxide (NZO) combined with black phosphorus (BP) (NZB) nanocomposite and its synergistic action with polymyxin B (PolB) against polymyxin-resistant Escherichia coli harboring mobilized colistin resistance (mcr-1) gene. NZB and PolB combination therapy expressed a specific and strong synergy against Mcr-1 expressing E. coli cells. The underlying mechanism of the synergy is the charge neutralization of the E. coli cell surface by NZB, resulting in a more feasible incorporation of PolB to E. coli. The synergistic concentration of NZB with PolB was proved biocompatible. Thus, the NZB is the first biocompatible nano-adjuvant to polymyxins against polymyxin-resistant E. coli cells, recognizing the physical status of bacteria instead of known adjuvants targeting cellular gene products. Therefore, NZB has the potential to revive polymyxins as leading last-resort antibiotics to combat polymyxin-resistant Gram-negative bacterial infections.

Multifunctional N-P-doped carbon dots for regulation of apoptosis and autophagy in B16F10 melanoma cancer cells and in vitro imaging applications.

Rationale: The present study reports the multifunctional anticancer activity against B16F10 melanoma cancer cells and the bioimaging ability of fluorescent nitrogen-phosphorous-doped carbon dots (NPCDs). Methods: The NPCDs were synthesized using a single-step, thermal treatment and were characterized by TEM, XPS, fluorescence and UV-Vis spectroscopy, and FTIR analysis. The anticancer efficacy of NPCDs was confirmed by using cell viability assay, morphological evaluation, fluorescent live-dead cell assay, mitochondrial potential assay, ROS production, RT-PCR, western-blot analysis, siRNA transfection, and cellular bioimaging ability. Results: The NPCDs inhibited the proliferation of B16F10 melanoma cancer cells after 24 h of treatment and induced apoptosis, as confirmed by the presence of fragmented nuclei, reduced mitochondrial membrane potential, and elevated levels of reactive oxygen species. The NPCDs treatment further elevated the levels of pro-apoptotic factors and down-regulated the level of Bcl2 (B-cell lymphoma 2) that weakened the mitochondrial membrane, and activated proteases such as caspases. Treatment with NPCDs also resulted in dose-dependent cell cycle arrest, as indicated by reduced cyclin-dependent kinase (CDK)-2, -4, and -6 protein levels and an enhanced level of p21. More importantly, the NPCDs induced the activation of autophagy by upregulating the protein expression levels of LC3-II and ATG-5 (autophagy-related-5) and by downregulating p62 level, validated by knockdown of ATG-5. Additionally, owing to their excellent luminescence property, these NPCDs were also applicable in cellular bioimaging, as evidenced by the microscopic fluorescence imaging of B16F10 melanoma cells. Conclusion: Based on these findings, we conclude that our newly synthesized NPCDs induced cell cycle arrest, autophagy, and apoptosis in B16F10 melanoma cells and presented good cellular bioimaging capability.

Effects of contralateral electroacupuncture on brain function: a double-blind, randomized, pilot clinical trial.

OBJECTIVES: The aim of this study was to ascertain the effects of contralateral acupuncture on brain function using blind-spot mapping. DESIGN AND PARTICIPANTS: Forty (40) healthy volunteers in whom the right-side blind spot was larger than the left-side one-which indicates lower left-brain function-were randomly assigned into the following two groups in which electroacupuncture was applied to: (1) the contralateral ST36 acupuncture point (right side), and (2) the ipsilateral ST36 acupuncture point (left side). OUTCOME MEASURE: Blind-spot perimetry length was the outcome measure. RESULTS: Electroacupuncture to the contralateral side decreased the blind-spot perimetry length by 5.0 (-9.3 to 0.9) [median (interquartile range, IQR)], whereas that to the ipsilateral side increased the length by 4.5 (-3.7 to 7.8) [median, IQR]. There was significant difference in this length between the two groups (p < 0.05). CONCLUSIONS: These results suggest that electroacupuncture application increased or decreased the brain function- as assessed by changes to the blind spot-depending on the treatment side: Contralateral-side treatment has a better effect than ipsilateral-side treatment on brain function. However, further randomized studies that include both right- and left-side-enlarged subjects with a sham needle are needed to convincingly show the effects of contralateral acupuncture on brain function.

Protective effects of Korean herbal remedy against oxidative stress in cardiomyocytes.

Ondamtanggagambang (ODG) has been used as a prescription for psychological anxiety and depression in Korean medicine. In this study, we found that ODG have protective effects against oxidative stress in cardiomyocytes. Pretreatment with ODG extract prevented H2O2 and ZnCl2-induced cell damage in H9c2 cardiomyocytes, whereas simultaneous treatment of ODG extract did not. The protective effect of ODG extract on oxidative stress-induced damage was suppressed significantly by heme oxygenase (HO) inhibitors, zinc protoporphyrin-IX (ZnPP-IX, p < 0.01) and tin protoporphyrin-IX (SnPP-IX, p < 0.01) in H9c2 cells. ODG stimulation of cells strongly induced the expression of HO-1 protein. Taken together, it is suggested that ODG-induced expression of HO-1 may have a beneficial role in cardiomyocytes under oxidative stress.