Teadenol B as a Component of Microorganism-Fermented Tea Extract Inhibited Breast Cancers by Promoting Autophagy.

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

GWA-based pleiotropic analysis identified potential SNPs and genes related to type 2 diabetes and obesity.

Metabolic syndrome is a cluster of symptoms including excessive body fat and insulin resistance which may lead to obesity and type 2 diabetes (T2D). The physiological and pathological cross-talk between T2D and obesity is crucial and complex, meanwhile, the genetic connection between T2D and obesity is largely unknown. The purpose of this study is to identify pleiotropic SNPs and genes between these two associated conditions by applying genetic analysis incorporating pleiotropy and annotation (GPA) on two large genome-wide association studies (GWAS) data sets: a body mass index (BMI) data set containing 339,224 subjects and a T2D data set containing 110,452 subjects. In all, 5182 SNPs showed pleiotropy in both T2D and obesity. After further prioritization based on suggested local false discovery rates (FDR) by the GPA model, 2146 SNPs corresponding to 217 unique genes are significantly associated with both traits (FDR < 0.2), among which 187 are newly identified pleiotropic genes compare with original GWAS in individual traits. Subsequently, gene enrichment and pathway analyses highlighted several pleiotropic SNPs including rs849135 (FDR = 0.0002), rs2119812 (FDR = 0.0018), rs4506565 (FDR = 1.23E-08), rs1558902 (7.23E-10) and corresponding genes JAZF1, SYN2, TCF7L2, FTO which may play crucial rol5es in the etiology of both T2D and obesity. Additional evidences from expression data analysis of pleiotropic genes strongly supports that the pleiotropic genes including JAZF1 (p = 1.39E-05 and p = 2.13E-05), SYN2 (p = 5.49E-03 and p = 5.27E-04), CDKN2C (p = 1.99E-12 and p = 6.27E-11), RABGAP1 (p = 3.08E-03 and p = 7.46E-03), and UBE2E2 (p = 1.83E-04 and p = 8.22E-03) play crucial roles in both obesity and T2D pathogenesis. Pleiotropic analysis integrated with functional network identified several novel and causal SNPs and genes involved in both BMI and T2D which may be ignored in single GWAS.

Body mass index and cancer risk among Chinese patients with type 2 diabetes mellitus.

BACKGROUND: Obesity and diabetes are two risk factors for cancer. To evaluate the association of body mass index (BMI) with cancer risk in diabetic patients may improve current understanding of potential mechanisms. METHODS: A retrospective cohort study was conducted in 51,004 newly diagnosed T2DM patients derived from an electronic health record (EHR) database of Minhang district in Shanghai, China. Incident cancer cases and all-cause deaths occurred before September 30, 2015 were identified by linking with the Shanghai Cancer Registry and the Shanghai Vital Statistics. To examine the potential non-linear and linear relationships of BMI and cancer risk, Cox proportional hazard models with and without restricted cubic spline functions were used, respectively. RESULTS: A non-linear association was observed between BMI and overall cancer incidence in men younger than 60 years old (p for non-linearity = 0.009). Compared with those having BMI of 25.0 kg/m2, the cancer risk increased in those with either lower or higher BMI. In women older than 60 years old, linear dose-response relationships were observed between BMI and the risk of both overall cancer and breast cancer. As each unit increase in BMI, the overall cancer risks elevated by 3% (95%CI: 1-5%) and the breast cancer risks increased by 7% (95%CI: 1-13%). No significant association was observed between BMI and other common cancer sites. CONCLUSIONS: Our results show that the effect of BMI on cancer risk in Chinese patients with T2DM may vary by gender, age and cancer subtypes, suggesting different underlying biological mechanisms.

Cancer incidence in patients with type 2 diabetes mellitus: a population-based cohort study in Shanghai.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been suggested to increase the risk of cancers. The aim of this study was to investigate the risk of common cancers in Chinese patients with T2DM. METHODS: A population-based retrospective cohort study including 36,379 T2DM patients was conducted in Minhang District of Shanghai, China, during 2004 to 2010. All T2DM patients were enrolled from the standardized management system based on local electronic information system. Newly-diagnosed cancer cases were identified by record-linkage with the Shanghai Cancer Registry. Standardized incidence ratios (SIR) and 95% confidence interval (CI) were used to estimate the risk of cancers among T2DM patients. RESULTS: Overall crude incidence rate (CIR) of cancers was 955.21 per 105 person-years in men and 829.57 per 105 person-years in women. Increased risk of cancer was found in both gender, with an SIR being 1.28 (95% CI = 1.17-1.38) in men and 1.44 (95% CI =1.32-1.55) in women. Increased risk of colon (SIR = 1.97; 95% CI = 1.49 to 2.46), rectum (1.72; 1.23 to 2.21), prostate (2.87; 2.19 to 3.56), and bladder cancers (1.98, 1.28 to 2.68) were observed in men and elevated risk of colon (1.67; 1.25 to 2.08), breast (1.66; 1.38 to 1.95), and corpus uteri cancers (2.87; 2.03 to 3.71) were observed in women. CONCLUSIONS: Our results indicate that Chinese patients with T2DM may have an increased risk of some cancers, and the increase may vary by sub-sites of cancers.

The molecular mechanisms and potential drug targets of ferroptosis in myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI), caused by the initial interruption and subsequent restoration of coronary artery blood, results in further damage to cardiac function, affecting the prognosis of patients with acute myocardial infarction. Ferroptosis is an iron-dependent, superoxide-driven, non-apoptotic form of regulated cell death that is involved in the pathogenesis of MIRI. Ferroptosis is characterized by the accumulation of lipid peroxides (LOOH) and redox disequilibrium. Free iron ions can induce lipid oxidative stress as a substrate of the Fenton reaction and lipoxygenase (LOX) and participate in the inactivation of a variety of lipid antioxidants including CoQ10 and GPX4, destroying the redox balance and causing cell death. The metabolism of amino acid, iron, and lipids, including associated pathways, is considered as a specific hallmark of ferroptosis. This review systematically summarizes the latest research progress on the mechanisms of ferroptosis and discusses and analyzes the therapeutic approaches targeting ferroptosis to alleviate MIRI.

Ultrasound biomicroscopic imaging demonstrate thinner ciliary body thickness in eyes with angle closure.

AIM: To compare the ciliary body thickness between eyes with primary angle closure (PAC) and primary angle-closure glaucoma (PACG) with the normal eyes, and to investigate the association between ciliary body thickness and ciliary processes situation. METHODS: In this cross-sectional study, 57 patients with PAC/PACG were matched to 57 normal subjects after propensity score matching (PSM) adjusting for age and gender. All subjects underwent conventional ocular examinations and ultrasound biomicroscopy (UBM) examination, among which the patients with PAC/PACG performed the examinations one month after laser peripheral iridotomy (LPI). Quantitative parameters were measured, which included ciliary body thickness at the position of 1 mm posterior to the scleral spur (CBT1), trabecular-ciliary process distance (TCPD) and trabecular-ciliary process angle (TCA). RESULTS: Eyes with PAC/PACG presented significantly thinner CBT1, shorter TCPD and smaller TCA (P<0.001) than the normal eyes, both in comparison of the means of four quadrants and in comparisons of each quadrant. After removing images with peripheral anterior synechia (PAS), the same results were also found in comparisons between the two groups. Significant correlations were found between TCPD (R 2=0.537, P<0.001) and TCA (R 2=0.517, P<0.001) with CBT1. CONCLUSION: Eyes with PAC/PACG have thinner ciliary body thickness and more anteriorly situated ciliary processes. Thinner ciliary body thickness is associated with anterior situation of the ciliary processes.

Improved de novo chromosome-level genome assembly of the vulnerable walnut tree Juglans mandshurica reveals gene family evolution and possible genome basis of resistance to lesion nematode.

Manchurian walnut (Juglans mandshurica Maxim.) is a synonym of J. cathayensis, a diploid, vulnerable, temperate deciduous tree valued for its wood and nut. It is also valued as a rootstock for Juglans regia because of its reported tolerance of lesion nematode. Reference genomes are available for several Juglans species, our goal was to produce a de novo, chromosome-level assembly of the J. mandshurica genome. Here, we reported an improved assembly of J. mandshurica with a contig N50 size of 6.49 Mb and a scaffold N50 size of 36.1 Mb. The total genome size was 548 Mb encoding 29,032 protein coding genes which were annotated. The collinearity analysis showed that J. mandshurica and J. regia originated from a common ancestor, with both species undergoing two WGD events. A genomic comparison showed that J. mandshurica was missing 1657 genes found in J. regia, and J. mandshurica includes 2827 genes not found in of the J. regia genome. The J. mandshurica contained 1440 unique paralogues that were highly enriched for flavonoid biosynthesis, phenylpropanoid biosynthesis, and plant-pathogen interaction. Four gene families related to disease resistance notable contraction (rapidly evolving; LEA, WAK, PPR, and PR) in J. mandshurica compared to eight species. JmaPR10 and JmaPR8 contained three orthologous gene pairs with J. regia that were highly expressed in root bark. JmaPR10 is a strong candidate gene for lesion nematodes resistance in J. mandshurica. The J. mandshurica genome should be a useful resource for study of the evolution, breeding, and genetic variation in walnuts (Juglans).

Postiridotomy ultrasound biomicroscopy features in the fellow eye of Chinese patients with acute primary angle-closure and chronic primary angle-closure glaucoma.

PURPOSE: To compare the features of postiridotomy ultrasound biomicroscopy (UBM) in Chinese patients with acute primary angle-closure (aPAC) and with chronic primary angle-closure (cPAC) glaucoma. PATIENTS AND METHODS: Consecutive cases were classified into acute and chronic groups. The acute group included 77 patients with unilateral aPAC. The chronic group included 57 patients with unilateral advanced cPAC glaucoma. In both the groups, the patients' fellow eye underwent a laser iridotomy and was studied. The main outcome measures included qualitative UBM parameters such as a plateau iris, anterior iris insertion, and an anteriorly rotated ciliary process and quantitative UBM parameters such as central anterior chamber depth (ACD), basal iris thickness (IT500), and scleral ciliary process angle (SCPA). RESULTS: For the qualitative parameters, more eyes in the chronic group had a plateau iris (P=0.046), an anterior iris insertion (P=0.222), and an anteriorly rotated ciliary process (P=0.090) than those in the acute group. For the quantitative parameters, the eyes in the chronic group had a deeper ACD (P<0.001), thicker IT500 (P<0.001), and smaller SCPA (P<0.001) than those in the acute group. CONCLUSIONS: The UBM features of Chinese patients with cPAC include a more plateaued iris, a thicker basal iris, and a smaller SCPA, whereas patients with aPAC may have a shallower ACD. For Chinese patients, a nonpupillary block component may play a more important role in asymptomatic cPAC than in aPAC.

[Effect of Ferric Iron on Nitrogen Immigration and Transformation and Nitrous Oxide Emission During Simultaneous Nitrification Denitrification Process].

Effect of Fe(III) concentration on nitrogen immigration and transformation and nitrous oxide emission during the simultaneous nitrification denitrification (SND) process was investigated. Higher nitrogen removal efficiency was obtained when the Fe(III) concentration was 20 mg x L(-1), while lower nitrogen removal efficiency was observed when the Fe (III) concentration turned to 60 mg x L(-1). In addition, higher Fe(III) concentration significantly enhanced the N2O emission, as well as the N2O conversion ratio. This was mainly attributed to (1) the high concentration of nitrite accumulation during the oxic stage, which was caused by lower dehydrogenase activity at high Fe(III) concentration; (2) less PHB production during the anoxic stage, which would led to shortage of carbon source for denitrification in the following oxic stage. The results also showed that Fe(III) addition could improve the TP removal efficiency. TP removal efficiency increased with increasing Fe(III) concentration, mainly because of extra chemical reaction.

Appositional angle closure in Chinese with primary angle closure and primary angle closure glaucoma after laser peripheral iridotomy.

PURPOSE: To determine the prevalence of appositional angle closure (AAC) after laser peripheral iridotomy (LPI) in the eyes of Chinese patients with primary angle closure (PAC) and primary angle closure glaucoma (PACG) and to evaluate its pathogenesis by investigating anatomic characteristics. METHODS: This was a cross-sectional observational study. PAC and PACG subjects were consecutively enrolled after LPI. Ultrasound biomicroscopy (UBM) images, obtained in darkness, of each quadrant without peripheral anterior synechia (PAS) under gonioscopy were qualitatively assessed. Darkroom provocative test (DRPT) was also performed. RESULTS: A total of 134 eyes of 134 patients were enrolled. AAC was observed in ≥ 1 quadrant of UBM image in 85 subjects (63.4%). There were 116 randomly selected quadrants without PAS for 134 patients (86.6%). AAC existed in 38 quadrants (32.8%). Among these, plateau iris accounted for 44.7%, anteriorly inserted iris for 13.2%, thick iris for 13.2%, and anteriorly inserted iris combined with thick iris for 18.4% of the total. One hundred fifteen patients underwent DRPT and its positive rate of eyes with AAC ≥ 2 quadrants (37.5% [12 of 32 patients]) was significantly higher than those ≤ 1 quadrant (16.9% [14 of 83 patients]; P = 0.018). However, no significant differences were found between eyes with nonsynechia plateau iris ≥ 2 quadrants (36.4% [4 of 11 patients]) and those ≤ 1 quadrant (21.2% [22 of 104 patients]; P = 0.266). CONCLUSIONS: Approximately two-thirds of PAC and PACG eyes of Chinese patients after LPI had AAC. Plateau iris accounted for less than 50% of AAC. Other factors such as a thick peripheral iris and an anteriorly inserted iris also contributed to AAC. DRPT results suggested AAC might have more functional meaning than plateau iris.