Electrochemical bromocyclization enables 3,5-diversification of heterocyclic indolines.

Electrophilic bromocyclization reactions are widely used as key steps in the synthesis of diverse functionalized tetrahydrofuroindolines and hexahydropyrroloindolines. However, the direct dibromination variants of these reactions for the synthesis of 3,5-dibromoindolines remain undeveloped. Here, we report a protonic-acid-promoted electrooxidative protocol for the dearomative C3,C5-dibromocyclizations of tryptophol and tryptamine derivatives.

Copper-Catalyzed Aerobic Selective Oxidation of Tetrahydrocarbolines.

We report a safe and convenient open-flask copper-catalyzed selective oxidation/functionalization methodology for tetrahydrocarbolines and tetrahydro-β-carbolines that employs atmospheric O as the terminal oxidant. The system is applicable to oxidative rearrangement of tetrahydro-β-carbolines, tetrahydrocarboline oxidation to α-alkoxy carbazoles and spirooxindoles, and Witkop oxidation. Mechanistic experiments indicated that a single-electron oxidation process is responsible for the tunable selectivity control.

Copper-Catalyzed Cyclization/Dimerization of Tryptamines with O/Air as the Sole Oxidant: Direct Access to Complex Bispyrrolidino[2,3-]indoline.

The first transition metal catalytic one-step synthesis of the 3a, 3a'-bispyrrolidino [2,3-] indoline scaffold via tandem cyclization/dimerization of tryptamines has been realized with the environmentally friendly O/air as the sole oxidant. Different from the traditional direct oxidation of indole "N-H" group by excess amount of metal salts, a copper-catalyzed oxidative cyclization reaction is developed for the formation of the radical pyrrolidinoindoline intermediate in the current strategy. The robustness and practicality of this methodology is demonstrated by the step-economic, divergent total synthesis of natural products (±)-folicanthine and -folicanthine.

Life history tradeoffs in humans: increased life expectancy with sperm count reduction.

Although not without controversy, as a general trend, the human sperm count is declining world-wide. One major reason for such a decline is an increase in the human life-span.  According to the life history tradeoff theory, fecundity is inversely related to the lifespan; the longer the lifespan, the lower the fecundity.

Combined use of alcohol in conventional chemical-induced mouse liver cancer model improves the simulation of clinical characteristics of human hepatocellular carcinoma.

Liver cancer is the one of most common types of cancer and the 2nd cause of cancer-associated mortalities worldwide. Establishing appropriate animal models of liver cancer is essential for basic and translational studies. The present study evaluated the effects of the combined use of alcohol with a conventional chemical-induced mouse liver cancer model.

Metastasis-Associated Protein 1 Deficiency Results in Compromised Pulmonary Alveolar Capillary Angiogenesis in Mice.

BACKGROUND The aim of this study was to investigate the effects of metastasis-associated protein 1 (MTA1) deficiency during angiogenesis of pulmonary alveolar capillaries in mice and to determine the molecular mechanisms involved. MATERIAL AND METHODS The expressions of MTA1, CD34, vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), and HIF-1α were analyzed in the lungs of MTA1-knockout (KO) and wild-type mice at embryonic day 18.5 and 2 months by quantitative PCR, immunoblotting, and immunohistochemistry.

Life history tradeoffs of pathogens and the treatment principle of antibiogenesis.

There are no eternal individual lives so life continues by relaying with reproduction. Consequently, lifespan and fecundity are two essential genetic traits of life. The life history tradeoffs theory holds that there is an inverse relationship between lifespan and fecundity.

Differential distribution of immune cells in breast invasive carcinoma vs. breast carcinoma and its significance in interpretation of immune surveillance.

Immune surveillance is a highly controversial subject in both the field of immunology and cancer biology. On one hand, in spite of extensive studies, there is no cancer specific antigens identified. Yet, the organisms do exert immune response to tumors.

Epithelial-mesenchymal transition as strategic microenvironment mimicry for cancer cell survival and immune escape?

Epithelial-mesenchymal transition (EMT) is the phenotypic transition of epithelial cells to mesenchymal cells characterized by loss of epithelial markers, loss of intercellular adherence and acquirement of mesenchymal cell markers and increased locomotive ability. EMT is widely considered to be a gene regulated process necessary for cancer metastasis. Yet it is a highly controversial issue.

Structure, expression and functions of MTA genes.

Metastatic associated proteins (MTA) are integrators of upstream regulatory signals with the ability to act as master coregulators for modifying gene transcriptional activity. The MTA family includes three genes and multiple alternatively spliced variants. The MTA proteins neither have their own enzymatic activity nor have been shown to directly interact with DNA.

Reasons for cancer metastasis: A holistic perspective.

Over several years, scientists investigating cancer have focused their efforts on elucidating the mechanisms underlying cancer metastasis, with the aim of finding a way to inhibit this process. These mechanisms, however, only explain the process of cancer metastasis, but do not explain why cancer would metastasize in the first place. Cancer metastasizes due to several factors, namely attack by the immune system, lack of oxygen and necessary nutrients, large amounts of lactic acid produced by glycolysis and increased cell death.

MTA1--a stress response protein: a master regulator of gene expression and cancer cell behavior.

Gene mutation's role in initiating carcinogenesis has been controversial, but it is consensually accepted that both carcinogenesis and cancer metastasis are gene-regulated processes. MTA1, a metastasis-associated protein, has been extensively researched, especially regarding its role in cancer metastasis. In this review, I try to elucidate MTA1's role in both carcinogenesis and metastasis from a different angle.

Resistance to apoptosis should not be taken as a hallmark of cancer.

In the research community, resistance to apoptosis is often considered a hallmark of cancer. However, pathologists who diagnose cancer via microscope often see the opposite. Indeed, increased apoptosis and mitosis are usually observed simultaneously in cancerous lesions.

Central role of cellular senescence in TSLP-induced airway remodeling in asthma.

Background: Airway remodeling is a repair process that occurs after injury resulting in increased airway hyper-responsiveness in asthma. Thymic stromal lymphopoietin (TSLP), a vital cytokine, plays a critical role in orchestrating, perpetuating and amplifying the inflammatory response in asthma. TSLP is also a critical factor in airway remodeling in asthma.

c-Myc-mediated epigenetic silencing of MicroRNA-101 contributes to dysregulation of multiple pathways in hepatocellular carcinoma.

Unlabelled: The MYC oncogene is overexpressed in hepatocellular carcinoma (HCC) and has been associated with widespread microRNA (miRNA) repression; however, the underlying mechanisms are largely unknown. Here, we report that the c-Myc oncogenic transcription factor physically interacts with enhancer of zeste homolog 2 (EZH2), a core enzymatic unit of polycomb repressive complex 2 (PRC2). Furthermore, miR-101, an important tumor-suppressive miRNA in human hepatocarcinomas, is epigenetically repressed by PRC2 complex in a c-Myc-mediated manner.

Invasive cancers are not necessarily from preformed in situ tumours - an alternative way of carcinogenesis from misplaced stem cells.

Cancers are thought to be the result of accumulated gene mutations in cells. Carcinomas, which are cancers arising from epithelial tissues usually go through several stages of development: atypical hyperplasia, carcinoma in situ and then invasive carcinoma, which might further metastasize. However, we think that the present pathological data are enough to prove that there might be an alternative way of carcinogenesis.

MTA1 promotes STAT3 transcription and pulmonary metastasis in breast cancer.

Overexpression of the prometastatic chromatin modifier protein metastasis tumor antigen 1 (MTA1) in human cancer contributes to tumor aggressiveness, but the role of endogenous MTA1 in cancer has not been explored. Here, we report the effects of selective genetic depletion of MTA1 in a physiologically relevant spontaneous mouse model of breast cancer pulmonary metastasis. We found that MTA1 acts as a mandatory modifier of breast-to-lung metastasis without effects on primary tumor formation.

Apoptosis drives cancer cells proliferate and metastasize.

Cancer has been considered to be the result of accumulated gene mutations, which result in uncontrolled cell proliferations for a long time. Cancers are also regarded to be capable of immune evasion. Furthermore, resistance to apoptosis was recognized as an important trait of cancer in the last score of years.

TBX2 expression is regulated by PAX3 in the melanocyte lineage.

The paired box homeotic gene 3 (PAX3) is a crucial regulator for the maintenance of melanocytic progenitor cells and has a poorly defined role in melanoma. To understand how PAX3 affects melanocyte and melanoma proliferation, we identified potential PAX3 downstream targets through gene expression profiling. Here, we identify T-box 2 (TBX2), a key developmental regulator of cell identity and an antisenescence factor in melanoma, as a directly regulated PAX3 target.

[Expression and potential role of metastasis-associated protein 1 in the induced carcinogenesis of mouse liver].

Aim: To establish a hepatocellular carcinoma model of BALB/c mouse and to study the expression and potential role of metastasis-associated protein 1 (MTA1) in the carcinogenesis process.

Methods: Normal adult male BALB/c mice were induced by the combined dimethylnitrosamine (DEN)/carbon tetrachloride (CCl(4);)/alcohol for 150 d. The morphological changes in liver cells and the expression of MTA1 in the liver lesions were observed by HE and immunohistochemical stainings, respectively.

HER2 interacts with CD44 to up-regulate CXCR4 via epigenetic silencing of microRNA-139 in gastric cancer cells.

Background & Aims: Human epidermal growth factor receptor 2 (HER2) (neu/ERBB2) is overexpressed on many types of cancer cells, including gastric cancer cells; HER2 overexpression has been associated with metastasis and poor prognosis. We investigated the mechanisms by which HER2 regulates cell migration and invasion.

Methods: HER2 expression or activity was reduced in gastric cancer cell lines using small interfering RNAs or the monoclonal antibody, trastuzumab.

Notch1 expression, which is related to p65 Status, is an independent predictor of prognosis in colorectal cancer.

Purpose: Notch1 has been proven to be aberrantly expressed in colorectal cancer and related to tumor differentiation status. However, few previous studies concentrated on the predictive role of Notch1 expression on the overall survival of patients with colorectal cancer. This study explored expression of Notch1 and its relationship with p65 and prognosis in colorectal cancer.

[Observation on therapeutic alliance with UDCA and glucocorticoids in AIH-PBC overlap syndrome].

Objective: To observe the efficacy of ursodeoxycholic acid (UDCA) combined with glucocorticoids in the treatment of autoimmune hepatitis-primary biliary cirrhosis (AIH-PBC) overlap syndrome.

Methods: 19 patients with AIH-PBC overlap syndrome were divided randomly into two groups: initiate combined group and initiate UDCA-monotherapy group. Biochemical responses and pathological features before and after treatment were analyzed retrospectively with student's t test, Wilcoxon rank sum test and Fisher's exact method.

[Comparison between two diagnostic criteria for PBC-AIH overlap syndrome].

Not Abstract.

[A two-year follow-up study on the efficacy of ursodeoxycholic acid on primary biliary cirrhosis in different stages].

Objective: To assess the therapeutic effect of primary biliary cirrhosis(PBC) in different stages with ursodeoxycholic acid (UDCA).

Methods: 91 patients with PBC were divided into 4 periods based on levels of liver test and symptoms. Clinical manifestations, biochemical changes and pathological changes were observed for 2 years on UDCA therapy.