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Metabolic alteration drives renal cell carcinoma (RCC) development, while the impact of melatonin (MLT), a neurohormone secreted during darkness, on RCC cell growth and underlying mechanisms remains unclear. We detected concentration of metabolites through metabolomic analyses using UPLC-MS/MS, and the oxygen consumption rate was determined using the Seahorse Extracellular Flux analyzer. We observed that MLT effectively inhibited RCC cell growth both in vitro and in vivo. Additionally, MLT increased ROS levels, suppressed antioxidant enzyme activity, and induced apoptosis. Furthermore, MLT treatment upregulated key TCA cycle metabolites while reducing aerobic glycolysis products, leading to higher oxygen consumption rate, ATP production, and membrane potential. Moreover, MLT treatment suppressed phosphorylation of Akt, mTOR, and p70 S6 Kinase as well as the expression of HIF-1α/VEGFA in RCC cells; these effects were reversed by NAC (ROS inhibitors). Conversely, MLT synergistically inhibited cell growth with sunitinib and counteracted the Warburg effect induced by sunitinib in RCC cells. In conclusion, our results indicate that MLT treatment reverses the Warburg effect and promotes intracellular ROS production, which leads to the suppression of Akt/mTOR/S6K signaling pathway, induction of cell apoptosis, and synergistically inhibition of cell growth with sunitinib in RCC cells. Overall, this study provides new insights into the mechanisms underlying anti-tumor effect of MLT in RCC cells, and suggests that MLT might be a promising therapeutic for RCC. [ABSTRACT FROM AUTHOR]

Sesquiterpenes are a large variety of terpene natural products, widely existing in plants, fungi, marine organisms, insects, and microbes. Value-added sesquiterpenes are extensively used in industries such as: food, drugs, fragrances, and fuels. With an increase in market demands and the price of sesquiterpenes, the biosynthesis of sesquiterpenes by microbial fermentation methods from renewable feedstocks is acquiring increasing attention. Synthetic biology provides robust tools of sesquiterpene production in microorganisms. This review presents a summary of metabolic engineering strategies on the hosts and pathway engineering for sesquiterpene production. Advances in synthetic biology provide new strategies on the creation of desired hosts for sesquiterpene production. Especially, metabolic engineering strategies for the production of sesquiterpenes such as: amorphadiene, farnesene, bisabolene, and caryophyllene are emphasized in: Escherichia coli, Saccharomyces cerevisiae, and other microorganisms. Challenges and future perspectives of the bioprocess for translating sesquiterpene production into practical industrial work are also discussed. [ABSTRACT FROM AUTHOR]

Diffuse large B cell lymphoma is one of the predominant histological subtypes of primary gastric lymphomas. Factors that contribute to precise stratification and guide the treatment of this disease are still not well understood. We analyzed 73 primary gastric diffuse large B cell lymphoma patients retrospectively, and found that patients characterized by late stage, multiple localization, B symptoms, lower serum albumin level and elevated LDH level had a shorter overall survival through Univariate Cox regression analysis. Multivariate Cox regression analysis demonstrated that ALB ≤ 35g/L, staging ≥ IIE and multiple sites localization were independent adverse prognostic factors. Significantly, in 35 patients who received endoscopy at diagnosis, Kaplan–Meier analyses indicated that patients with large (≥3 cm) and deep lesions (≥11 mm) had an inferior OS (p =.01 and.039). These findings implicated that tumor size and depth are two indicators of prognosis under ultrasonography. Further randomized studies with large number of cases are needed. [ABSTRACT FROM AUTHOR]

In China, reports on the epidemiology of adenocarcinomas of the nasal cavity and paranasal sinuses are limited. This study aimed to describe the experience of a single institution in China in treating these malignant tumours. We conducted a retrospective chart review of patients with adenocarcinoma of the nasal cavity and paranasal sinuses admitted between January 2019 and December 2021. Tumour staging was based on the American Joint Committee on Cancer, 8th edition, for sinonasal malignancies. The series included 10 men and 4 women (mean age, 54.5 [range, 14–80] years). Epistaxis and nasal obstruction were the most common clinical manifestations in 10 (71.4%) patients. Ten (71.4%) had stage T4 disease at diagnosis, but no patient had lymph node or distant metastasis. The posterosuperior septum (100.0%) and middle turbinate (92.8%) were the two sites most vulnerable to tumour invasion. All patients underwent endoscopic resection as the initial treatment; one patient died. In China, these malignancies are related to exposure to certain substances; however, diagnosis can be delayed. Endoscopic resection is a suitable treatment option for adenocarcinomas of the nasal cavity and paranasal sinuses. [ABSTRACT FROM AUTHOR]

This article is concerned with the prediction problems in linear mixed models (LMM). Both biased predictors and restricted predictors are introduced. It was found that the mean square error matrix (MSEM) of a predictor strongly depends on the MSEM of corresponding estimator of the fixed effects and precise formulas are obtained. As an application, we propose three new predictors to improve the best linear unbiased predictor (BLUP). The performance of the new predictors can be examined easily with the help of vast literature on the linear regression models (LM). We also illustrate our findings with a Monte Carlo simulation and a numerical example. [ABSTRACT FROM PUBLISHER]

Objectives:Our aim was to retrospectively investigate the data from our institute the response rate and outcome in patients with primary mediastinal B-cell lymphoma (PMBL) who received the rituximab in combination with CHOP (RCHOP) followed by autologous stem cell transplantation (ASCT) or RCHOP followed by involved field radiation therapy (IFRT). Methods:Sixty five patients with PMBL received RCHOP as first-line chemotherapy between January 2005 and December 2010. Forty of the 65 patients completed the planned subsequent IFRT after initial chemotherapy. Thirteen of the 65 patients received the front-line ASCT after RCHOP. Twelve patients received RCHOP alone. Results:Thirty two of the 40 patients who received the RCHOP followed by IFRT have complete remission (CR) or CRu (CR/unconfirmed). All patients have CR or CRu after the ASCT. The progression free survival (PFS) and the estimated overall survival (OS) rate at 5 years for 32 CR/CRu patients in the RCHOP followed by IFRT group were 57 and 65%, respectively, as compared to RCHOP/ASCT group who were 94 and 100%, respectively. Twelve patients who received RCHOP alone had the same PFS and OS rate as the 40 patients who received RCHOP/IFRT (5-year PFS:62 vs. 65%,p = 0.068; 5-year OS:57 vs. 67%,p = 0.058). For all 65 patients, the age-adjusted international prognostic index (aaIPI) score remained the only predictor of a worse outcome. Conclusion:The PFS and OS rate of RCHOP/IFRT were found to be unsatisfied. RCHOP/ASCT showed a satisfactory PFS and OS rate. [ABSTRACT FROM PUBLISHER]