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The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines

Background Curcumin is a naturally occurring phenolic compound shown to have a wide variety of antitumor activities; however, it does not attain sufficient blood levels to do so when ingested. Using structure-based design, a novel compound, FLLL32, was generated from curcumin. FLLL32 possesses superior biochemical properties and more specifically targets STAT3, a transcription...

A Modified Sagittal Spine Postural Classification and Its Relationship to Deformities and Spinal Mobility in a Chinese Osteoporotic Population

Background Abnormal posture and spinal mobility have been demonstrated to cause functional impairment in the quality of life, especially in the postmenopausal osteoporotic population. Most of the literature studies focus on either thoracic kyphosis or lumbar lordosis, but not on the change of the entire spinal alignment. Very few articles reported the spinal alignment of Chinese...

Squalene Synthase As a Target for Chagas Disease Therapeutics

Trypanosomatid parasites are the causative agents of many neglected tropical diseases and there is currently considerable interest in targeting endogenous sterol biosynthesis in these organisms as a route to the development of novel anti-infective drugs. Here, we report the first x-ray crystallographic structures of the enzyme squalene synthase (SQS) from a trypanosomatid...

A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells

Background Targeting Signal Transducer and Activator of Transcription 3 (STAT3) signaling is an attractive therapeutic approach for most types of human cancers with constitutively activated STAT3. A novel small molecular STAT3 inhibitor, FLLL32 was specifically designed from dietary agent, curcumin to inhibit constitutive STAT3 signaling in multiple myeloma, glioblastoma, liver...

Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis

Computational approaches have promised to organize collections of functional genomics data into testable predictions of gene and protein involvement in biological processes and pathways. However, few such predictions have been experimentally validated on a large scale, leaving many bioinformatic methods unproven and underutilized in the biology community. Further, it remains...

Exploring the functional landscape of gene expression: directed search of large microarray compendia

Motivation: The increasing availability of gene expression microarray technology has resulted in the publication of thousands of microarray gene expression datasets investigating various biological conditions. This vast repository is still underutilized due to the lack of methods for fast, accurate exploration of the entire compendium. Results: We have collected Saccharomyces...

Progression and regression of incident cervical HPV 6, 11, 16 and 18 infections in young women

Background We describe type-specific progression, regression and persistence of incident human papillomavirus (HPV)-6-11-16 and -18 infections, along with type distribution in cervical intra-epithelial neoplasia (CIN) lesions. Methods The study population consisted of 16–23 year-old women undergoing Pap testing and cervical swab polymerase chain reaction testing for HPV DNA at...

Persistence of Type-Specific Human Papillomavirus Infection and Increased Long-term Risk of Cervical Cancer

Hui-Chi Chen Mark Schiffman Ching-Yu Lin Mei-Hung Pan San-Lin You Li-Chung Chuang Chang-Yao Hsieh Kai-Li Liaw Ann W. Hsing Chien-Jen Chen for the CBCSP-HPV Study Group Methods Human papillomavirus ... the study; the collection, analysis, or interpretation of the data; neither the writing of the article, and the decision to submit the article for publication. Kai-Li Liaw holds stock in Merck and

Persistence of Type-Specific Human Papillomavirus Infection and Increased Long-term Risk of Cervical Cancer

, analysis, or interpretation of the data; neither the writing of the article, and the decision to submit the article for publication. Kai-Li Liaw holds stock in Merck and Company, Inc, the maker of Gardasil

Somatic microindels in human cancer: the insertions are highly error-prone and derive from nearby but not adjacent sense and antisense templates

Somatic microindels (microdeletions with microinsertions) have been studied in normal mouse tissues using the Big Blue lacI transgenic mutation detection system. Here we analyze microindels in human cancers using an endogenous and transcribed gene, the TP53 gene. Microindel frequency, the enhancement of 1–2 microindels and other features are generally similar to that observed in...

A HIV-1 heterosexual transmission chain in Guangzhou, China: a molecular epidemiological study

Background We conducted molecular analyses to confirm four clustering HIV-1 infections (Patient A, B, C & D) in Guangzhou, China. These cases were identified by epidemiological investigation and suspected to acquire the infection through a common heterosexual transmission chain. Methods Env C2V3V4 region, gag p17/p24 junction and partial pol gene of HIV-1 genome from serum...

New structural analogues of curcumin exhibit potent growth suppressive activity in human colorectal carcinoma cells

Background Colorectal carcinoma is one of the major causes of morbidity and mortality in the Western World. Novel therapeutic approaches are needed for colorectal carcinoma. Curcumin, the active component and yellow pigment of turmeric, has been reported to have several anti-cancer activities including anti-proliferation, anti-invasion, and anti-angiogenesis. Clinical trials have...

Characterization of STAT3 activation and expression in canine and human osteosarcoma

Background Dysregulation of signal transducer and activator of transcription 3 (STAT3) has been implicated as a key participant in tumor cell survival, proliferation, and metastasis and is often correlated with a more malignant tumor phenotype. STAT3 phosphorylation has been demonstrated in a subset of human osteosarcoma (OSA) tissues and cell lines. OSA in the canine population...

Visualization methods for statistical analysis of microarray clusters

Background The most common method of identifying groups of functionally related genes in microarray data is to apply a clustering algorithm. However, it is impossible to determine which clustering algorithm is most appropriate to apply, and it is difficult to verify the results of any algorithm due to the lack of a gold-standard. Appropriate data visualization tools can aid this...

The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity

computational modeling to interact with the SH2 domain of STAT3 [16] and inhibit STAT3 homodimerization (unpublished observations, Dr. Pui-Kai Li, The Ohio State University). One analog, termed FLLL32, was

A Dominant X-Linked QTL Regulating Pubertal Timing in Mice Found by Whole Genome Scanning and Modified Interval-Specific Congenic Strain Analysis

Background Pubertal timing in mammals is triggered by reactivation of the hypothalamic-pituitary-gonadal (HPG) axis and modulated by both genetic and environmental factors. Strain-dependent differences in vaginal opening among inbred mouse strains suggest that genetic background contribute significantly to the puberty timing, although the exact mechanism remains unknown...

A PILOT STUDY OF ALCOHOL EXPOSURE AND PHARMACOKINETICS IN WOMEN WITH OR WITHOUT CHILDREN WITH FETAL ALCOHOL SYNDROME

Aims: To determine the alcohol exposure and pharmacokinetics of alcohol in a group of women who had given birth to children with FAS, compared with women who had not given birth to FAS children. Methods: 10 women who had given birth to FAS children (FAS mothers) and 20 Controls were studied to determine how they metabolize alcohol in a single limited-access quasi-experimental...

Cholera toxin B subunit binding to an antigen-presenting cell directly co-stimulates cytokine production from a T cell clone

Cholera toxin (CT) is a powerful immunomodulator with strong adjuvant activity. Much of this activity is retained by the binding component alone, cholera toxin B subunit (CTB). Little is known about the mechanism of the immunomodulatory activity of CTB. In this study, both CT and CTB were found to dramatically enhance IL-4 production from a T cell clone stimulated with antigen...

The Burden of Genital Warts: A Study of Nearly 70,000 Women from the General Female Population in the 4 Nordic Countries

Objective. To asses the burden and correlates of genital warts in women. Methods. We conducted a population-based cross-sectional study in 69,147 women (18–45 years of age) randomly chosen from the general population in Denmark, Iceland, Norway, and Sweden. Information on clinically diagnosed genital warts and lifestyle habits was collected using a questionnaire. Results. Overall...

Neuroscience Networks: Data-sharing in an Information Age

States of America. Thomas R. Insel is the director of the National Insti- tute of Mental Health. Nora D. Volkow is the director of the National Institute on Drug Abuse. Ting-Kai Li is the director of the