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risk of dysgeusia.

We aimed to investigate the effect of black mulberry and grape molasses on the prevention and treatment of oral mucositis and quality of life (QoL) in patients with head and neck cancer (HNC).

Patients treated for HNC between 2010 and 2018 in our department were divided into three groups (group 1 = control (n = 14), group 2 = grape molasses (n = 40), and group 3 = black mulberry molasses (n = 40)). Oral mucositis, pain scoring, and weight loss were evaluated weekly. The European Organization for Research and Treatment of Cancer (EORTC) General QoL Questionnaire (QLQ-C30) and EORTC Head and Neck Cancer QoL Module (QLQ-HN35) were used to evaluate QoL.

The mean body weight, scores of oral mucositis, and pain were similar among the groups throughout the treatment. Both groups 2 and 3 were associated with improved outcomes for swallowing, opening mouth, and weight loss in the EORTC HN35, and these parameters were not significantly different between groups 2 and 3. Global health score was higher in group 3 at the 6th week of RT compared to that of group 2. Both groups 2 and 3 had improved scores for role functioning, emotional and social functioning, fatigue, appetite loss, and pain throughout the treatment compared to group 1.

Both grape and black mulberry molasses improved the QoL in HNC patients. No significant difference between black mulberry and grape molasses was found with regard to the healing of oral mucositis.

Both grape and black mulberry molasses improved the QoL in HNC patients. No significant difference between black mulberry and grape molasses was found with regard to the healing of oral mucositis.Gap junctional intercellular communication (GJIC) is considered a key biological mechanism to maintain homeostasis in cell differentiation and growth. In addition, as another major signaling pathway associated with cell proliferation and differentiation, Wnt/β-catenin signaling appears to trigger several cellular responses against injury. The purpose of the present study was to investigate the effects of a known toxic agent, benzo[a]pyrene (BaP), on the regulation and interaction between GJIC and Wnt/β-catenin signaling. BaP treatment resulted in GJIC inhibition and decreases the major GJIC protein connexin 43 (Cx43) in WB-F344 rat liver epithelial cells. We also found BaP-mediated downregulation of Wnt/β-catenin signaling related to the PI3K-Akt pathway. To identify the relationship between GJIC and Wnt/β-catenin signaling, we treated WB-F344 cells with the Wnt agonist CHIR99021 and found that it inhibited GJIC while causing a significant reduction in Cx43 expression at both the mRNA and protein levels, through the repression of promoter activity. This Wnt agonist-mediated GJIC inhibition was confirmed using a small interfering RNA directed against the Wnt antagonist Dact2, indicating that Wnt/β-catenin signaling negatively regulates GJIC. Despite the inverse correlation between Wnt/β-catenin signaling and Cx43 promoter activation as indicated by downregulation of β-catenin nuclear translocation and upregulation of Cx43 promoter activation involving HNF3β, BaP treatment decreased the Cx43 protein expression, which was associated with protein degradation, possibly through protein kinase C activation. In conclusion, our results revealed the mechanism of BaP-induced inhibition of GJIC and Wnt/β-catenin signaling. More importantly, linking Wnt/β-catenin signaling to Cx protein expression will have profound implications in understanding the relationships among different major signaling pathways associated with cell proliferation and differentiation in toxicity.99mTc-DMSA is one of the most commonly used pediatric nuclear medicine imaging agents. Nevertheless, there are no pharmacokinetic (PK) models for 99mTc-DMSA in children, and currently available pediatric dose estimates for 99mTc-DMSA use pediatric S values with PK data derived from adults. Furthermore, the adult PK data were collected in the mid-70's using quantification techniques and instrumentation available at the time. Using pediatric imaging data for DMSA, we have obtained kinetic parameters for DMSA that differ from those applicable to adults.

We obtained patient data from a retrospective re-evaluation of clinically collected pediatric SPECT images of

Tc-DMSA in 54 pediatric patients from Boston's Children Hospital (BCH), ranging in age from 1 to 16 years old. These were supplemented by prospective data from twenty-three pediatric patients (age range 4 months to 6 years old).

In pediatric patients, the plateau phase in fractional kidney uptake occurs at a fractional uptake value closer to 0.3 than the value of 0.5 reported by the International Commission on Radiological Protection (ICRP) for adult patients. This leads to a 27% lower time-integrated activity coefficient in pediatric patients than in adults. Over the age range examined, no age dependency in uptake fraction at the clinical imaging time was observed. Female pediatric patients had a 17% higher fractional kidney uptake at the clinical imaging time than males (P < 0.001).

Pediatric

Tc-DMSA kinetics differ from those reported for adults and should be considered in pediatric patient dosimetry. Alternatively, the differences obtained in this study could reflect improved quantification methods and the need to re-examine DMSA kinetics in adults.

Pediatric 99mTc-DMSA kinetics differ from those reported for adults and should be considered in pediatric patient dosimetry. Alternatively, the differences obtained in this study could reflect improved quantification methods and the need to re-examine DMSA kinetics in adults.

pN3 or ypN3 stage gastric cancers (GCs) are known to have aggressive clinical behaviour. This study aimed to investigate factors affecting survival and pattern of recurrences of N3 stage GCs, treated with curative intent.

A total of 196 GC patients, operated on at the Tata Memorial Centre from 2003 to 2017 and reported as pN3 or ypN3 status on histopathology after D2 gastrectomy were included in this retrospective analysis.

On multivariate analysis, use of NACT (neoadjuvant chemotherapy) and LN ratio (≤ 0.5/> 0.5) emerged as significant predictors for long-term survival. Patients who received NACT but were still harbouring N3 nodes (ypN3; n = 102) had a worse prognosis than those operated on upfront (pN3; n = 94), with a median survival of 19 months versus 24months respectively (p = 0.003). The 5-year overall survival of the entire cohort was 16.3% (95% CI 12.8-19.8%), while 5-year disease-free survival (DFS) was 14.6% (95% CI 12.6-20%). Adjuvant chemoradiotherapy, though offered in a small number of patients (n = 38) resulted in improvement in DFS. Median DFS of adjuvant CT versus adjuvant CRT was 13months versus 23 months (p = 0.020). The commonest site of relapse was the peritoneum (49.18%) and incidence of isolatedloco-regional failure was 10.7%.

In GCs with N3 stage determined after radical D2 gastrectomy, LN ratio of > 0.5 and ypN3 status are predictors of poor prognosis. Considering the high incidence of peritoneal and loco-regional relapse in these patients, the role of more radical surgery, adjuvant chemoradiotherapy after upfront resection and intraperitoneal chemotherapy should be evaluated in prospective randomized clinical trials.

 0.5 and ypN3 status are predictors of poor prognosis. Considering the high incidence of peritoneal and loco-regional relapse in these patients, the role of more radical surgery, adjuvant chemoradiotherapy after upfront resection and intraperitoneal chemotherapy should be evaluated in prospective randomized clinical trials.The cyanobacterial non-protein amino acid α-amino-β-methylaminopropionic acid, more commonly known as BMAA, was first discovered in the seeds of the ancient gymnosperm Cycad circinalis (now Cycas micronesica Hill). BMAA was linked to the high incidence of neurological disorders on the island of Guam first reported in the 1950s. BMAA still attracts interest as a possible causative factor in amyotrophic lateral sclerosis (ALS) following the identification of ALS disease clusters associated with living in proximity to lakes with regular cyanobacterial blooms. Since its discovery, BMAA toxicity has been the subject of many in vivo and in vitro studies. A number of mechanisms of toxicity have been proposed including an agonist effect at glutamate receptors, competition with cysteine for transport system xc_ and other mechanisms capable of generating cellular oxidative stress. In addition, a wide range of studies have reported effects related to disturbances in proteostasis including endoplasmic reticulum stress and activation of the unfolded protein response. In the present studies we examine the effects of BMAA on the ubiquitin-proteasome system (UPS) and on chaperone-mediated autophagy (CMA) by measuring levels of ubiquitinated proteins and lamp2a protein levels in a differentiated neuronal cell line exposed to BMAA. The BMAA induced increases in oxidised proteins and the increase in CMA activity reported could be prevented by co-administration of L-serine but not by the two antioxidants examined. These data provide further evidence of a protective role for L-serine against the deleterious effects of BMAA.Proline metabolic reprogramming is intimately involved in cancer progression. We recently identified a critical role of PINCH-1, a cell-extracellular matrix (ECM) adhesion protein whose expression is elevated in lung adenocarcinoma, in the promotion of proline biosynthesis, fibrosis and lung adenocarcinoma growth. How PINCH-1 promotes proline biosynthesis, however, was incompletely understood. Dabrafenib solubility dmso In this study, we show that PINCH-1 promotes the expression of Δ1-pyrroline-5-carboxylate synthase (P5CS), a key enzyme that links glutamate metabolism to proline biosynthesis. Depletion of PINCH-1 from lung adenocarcinoma cells reduced the protein but not mRNA level of P5CS, resulting in down-regulation of the cellular level of P5C and cell proliferation. Treatment of the cells with protease inhibitor leupeptin effectively reversed PINCH-1 deficiency-induced reduction of the P5CS level. At the molecular level, PINCH-1, through its LIM2 domain, physically associated with P5CS in lung adenocarcinoma cells. Re-expression of wild type PINCH-1, but not that of the PINCH-1 LIM2 deletion mutant, in PINCH-1 deficient lung adenocarcinoma cells restored P5CS expression, proline biosynthesis and cell proliferation. Finally, P5CS expression, like that of PINCH-1, is elevated in human and mouse lung adenocarcinoma. Using a mouse model of lung adenocarcinoma in which PINCH-1 is conditionally ablated, we show that knockout of PINCH-1 from lung adenocarcinoma effectively reduced the P5CS level in vivo. Our results reveal an important role of PINCH-1 in the promotion of P5CS expression, which likely contributes to proline metabolic reprogramming and consequently lung adenocarcinoma progression.L-proline catabolism is emerging as a key pathway that is critical to cellular metabolism, growth, survival, and death. Proline dehydrogenase (PRODH) enzyme, which catalyzes the first step of proline catabolism, has diverse functional roles in regulating many pathophysiological processes, including apoptosis, autophagy, cell senescence, and cancer metastasis. Notably, accumulated evidence demonstrated that PRODH plays complex role in many types of cancers. In this review, we briefly introduce the function of PRODH, then its expression in different types of cancer. We next discuss the regulation of PRODH in cancer, the downstream pathways of PRODH and the therapies that are under investigation. Finally, we propose novel insights for future perspectives on the modulation of PRODH.