Study on the targeted regulation of Scutellaria baicalensis leaf on glutamine-glutamate metabolism and glutathione synthesis in the liver of d-gal ageing rats.

OBJECTIVES: Scutellaria baicalensis leaf (SLE), the above-ground part of the traditional Chinese medicine Scutellaria baicalensis Georgi, is rich in resources and contains a large number of flavonoids with anti-inflammatory, antioxidant and neuroprotective functions. The present study evaluated the ameliorative effects and related mechanisms of SLE on d-gal-induced ageing rats, providing a theoretical basis for the exploitation of SLE. METHODS: This experiment investigated the mechanism of SLE for anti-ageing by non-targeted metabonomics technology combined with targeted quantitative analysis and molecular biology technology. KEY FINDINGS: Non-targeted metabonomics analysis showed that 39 different metabolites were screened out. Among them, 38 metabolites were regulated by SLE (0.4 g/kg), and 33 metabolites were regulated by SLE (0.8 g/kg). Through enrichment analysis, glutamine-glutamate metabolic pathway was identified as the key metabolic pathway. Subsequently, the results of targeted quantitative and biochemical analysis displayed that the contents of key metabolites and the activities of enzymes in glutamine-glutamate metabolic pathway and glutathione synthesis could be regulated by SLE. Furthermore, the results of Western blotting indicated that SLE significantly modulated the expression of Nrf2, GCLC, GCLM, HO-1, and NQO1 proteins. CONCLUSION: To sum up, the anti-ageing mechanism of SLE was related to glutamine-glutamate metabolism pathway and Nrf2 signalling pathway.

Long non-coding RNA MAFG-AS1 promotes proliferation and metastasis of breast cancer by modulating STC2 pathway.

Breast cancer is the most common cancer worldwide. A number of studies proposed that long non-coding RNA plays an essential role in the regulation of invasion and metastasis of various forms of malignancy, including lung cancer, gastric cancer, and bladder cancer. In this study, a long non-coding RNA(LncRNA) MAFG-AS1 was explored in detail to understand the significance in the etiology of breast cancer. The results indicated that expression of LncRNA MAFG-AS1 in the breast cancer tissues was significantly higher than the adjacent normal breast tissues and elevated expression level of LncRNA MAFG-AS1 was correlated to the larger tumor size, negative expression of ER, PR and lymph node metastasis. The potency of breast cancer proliferation, invasion, and metastasis was inhibited in the absence of LncRNA MAFG-AS1. Mechanically, LncRNA MAFG-AS1 was mainly located in the cytoplasm. The downstream target gene of LncRNA MAFG-AS1 was STC2 which might promote cell proliferation and metastasis in breast cancer and this study provides a new potential therapeutic target for breast cancer.

Synthetic MRI with quantitative mappings for identifying receptor status, proliferation rate, and molecular subtypes of breast cancer.

OBJECTIVE: To investigate whether quantitative parameters of synthetic magnetic resonance imaging (MRI) can be used to differentiate among receptor status, proliferation rate, and molecular subtypes in patients with breast cancer. MATERIALS AND METHODS: This retrospective study included patients with suspicious breast lesions who underwent breast MR examinations (including synthetic MRI) from May 2019 to Oct 2020. Quantitative parameters of synthetic MRI, including T1, T2, and proton density (PD) in the breast lesions before and after (T1-Gd, T2-Gd, and PD-Gd) contrast agent injection were obtained. The Wilcoxon rank sum was utilized to analyze the differences between the parameters and receptor status, proliferation rate, Luminal A/B, TN, and HER2-enriched. The Spearman's rank correlation test was used to analyze association between parameters among five molecular subtypes. RESULTS: 115 patients who met the inclusion criteria were included. Quantitative T1, T2, PD, and T2-Gd can be used as imaging biomarkers for the different receptor status and proliferation rate of breast cancer. Among them, T2 and T2-Gd were significantly different in the molecular subtypes (P = 0.000 and P = 0.006, respectively) and can further differentiate luminal A/B breast cancers from non-luminal subtypes (P = 0.005 and P = 0.015, respectively). T1 and T2 were significantly different between triple negative (TN) and non-TN breast cancers (P = 0.004 and P = 0.024, respectively). T2 and T2-Gd values were lower for luminal A/B tumors (79.5 ms and 68.00 ms, respectively) and higher for non-luminal tumors (84.00 ms and 75.00 ms, respectively). T1 and T2 values were higher for TN tumors (1.54 × 103ms and 84.00 ms, respectively) and lower for non-TN tumors (1.39 × 103 ms and 80.00 ms, respectively). CONCLUSION: Quantitative parameters derived from synthetic MRI mappings may provide a non-invasive biomarker for discriminating receptor status, proliferation rate, and molecular subtypes in patients with breast cancer.

Clinicopathological and molecular genomic features of monomorphic epitheliotropic intestinal T-cell lymphoma in the Chinese population: a study of 20 cases.

BACKGROUND: Monomorphic epitheliotropic T-cell lymphoma (MEITL) is an aggressive non-Hodgkin lymphoma with a high fatality rate. This study was aimed to explore the clinicopathological and molecular genetic features of MEITL in the Chinese population. METHODS: A retrospective analysis was performed based on the clinical manifestations and pathological features of 20 Chinese MEITL. 9 cases with paired diseased-normal tissues were also analyzed for molecular information by whole-exome sequencing. RESULTS: There were 14 men and 6 women with a median age of 58.5 (28-81) years. 17(17/20) lesions were located in the jejunum or ileum; 13(13/20) cases had ulcers or perforations. Microscopically, except for 1(1/20) case of pleomorphic cells, the monomorphic, middle-sized tumor cells infiltrating into the intestinal epithelial and peripheral intestinal mucosa recess could be seen in the other 19 cases. Immunohistochemistry showed that most of the tumor cells in MEITL were positive for CD3(20/20), CD8(17/20), CD43(19/20), and CD56(15/20), but negative for CD5(20/20). The most frequently mutated genes of these Chinese cases were STAT5B (4/9) and TP53 (4/9), not SETD2(2/9). JAK3 mutations (3/9) were also detected with a high mutated frequency. We demonstrated that mutations of JAK-STAT pathway-related genes and the amplification of Chromosome 9q appeared at the same time in most cases(5/9). CONCLUSIONS: The clinicopathological features were consistent with that in previous western studies, but a special case with pleomorphic cells was found in this study. The co-occurrence of JAK-STAT pathway-related gene mutations and the amplification of Chr9q is a molecular feature of MEITL.

The long noncoding RNA TINCR promotes breast cancer cell proliferation and migration by regulating OAS1.

Breast cancer is the leading cause of cancer-related death in women around the world. It is urgently needed to identify genes associated with tumorigenesis and prognosis, as well as to elucidate the molecular mechanisms underlying the oncogenic process. Long noncoding RNAs (lncRNAs) are widely involved in the pathological and physiological processes of organisms and play an important role as oncogenes or tumor suppressor genes, affecting the development and progression of tumors. In this study, we focused on terminal differentiation-induced non-coding RNA (TINCR) (GeneID:257000) and explore its role in the pathogenesis of breast cancer. The results showed that TINCR was increased in breast cancer tissue, and high expression level of TINCR was associated with older age, larger tumor size, and advanced TNM stage. High level of TINCR can promote proliferation and metastasis of breast cancer cells, while downregulation of TINCR induces G1-G0 arrest and apoptosis. Mechanismly, TINCR can bind to staufen1 (STAU1) and then guide STAU1 (GeneID:6780) to bind to OAS1 mRNA (NM_016816.4) to mediate its stability. Thus low level of OAS1(GeneID:4938) can lead to cell proliferation and migration. This result elucidates a new mechanism for TINCR in breast cancer development and provides a survival indicator and potential therapeutic target for breast cancer patients.