Global Medical Discovery features paper: Need pain relief. Think Synovia capsules by Bioparanta

Arthritis is group of conditions  which can cause pain stiffness and swelling in the joints. Arthritis can involve almost any part of the body, most often affecting the hip, spine, knee or other weight-bearing joints, but also found in the fingers and other non-weight-bearing joints. Some forms of arthritis can also affect other parts of the body. As a result of arthritis people sometime can be disabled, socially isolated and in sometimes even depress.

SYNOVIA By BioParanta which comes in an easy to swallow capsules is a unique blend of natural ingredients designed to treat wide range of conditions that is related to inflammation. Such as Arthritis, Carpal tunnel syndrome, Tendonitis, and tennis elbow. As we use our joint the cartilage mussels and tends undergo damage, with increase physical activates, sport and age, our bodies abilities to repair can’t keep up  with the damage process, this result in jointly generation giving us pain, stiffness and weakness in the joints. SYNOVIA gets to the root cause of the problem and pain which is inflammation. The active ingredient in its formula are design to reduce the inflammation of  nerves, muscles, tendons, and ligaments. SYNOVIA By BioParanta helps to strengthen the fundamental of the body while feeding the bones, ligaments and tendon specific nutrition, to create strength and mobility from the inside out.  In addition studies showed blood circulation will also be improved as well as nerve functions.

SYNOVIA By BioParanta has all natural ingredients made up of unique blend  of totally natural ingredient. The ingredients work powerfully together as a team to  reduce the inflammation, stimulate the regrowth of the cartilage tissue ,  stop the degeneration process, and bring it back healing. All the ingredients were carefully chosen for maximum effectiveness to increase absorption and utilization in a unique formulation that gives Synovia the superiority over any arthritis pain relief pill. While insuring long term safety as well as being free of side effects (it does not contain non-steroidal anti-inflammatory drugs, NSIADs).

SYNOVIA by BioParanta has natural anti- inflammatory compounds have also been added to target pain centers and restrict the inflammation that has been caused by on-going deterioration. This is a key attribute of the formula of SYNOVIA so that it supports the recovery of joints while keeping a protective response relating to ongoing wear and tear.

This innovative formula targets the trigger points to tackle the underlying cause of the pain thereby providing pain relief.Over all SYNOVIA by BioParanta is powerful, all natural trusted and highly effective formula to reduce pain and inflammation.

 

The post Need pain relief. Think Synovia capsules by Bioparanta appeared first on Global Medical Discovery.

Global Medical Discovery features paper: Different Effects of p52SHC1 and p52SHC3 on the Cell Cycle of Neurons and Neural Stem Cells

Significance Statement

Many studies clearly demonstrate the important roles of SHC1 and SHC3 in neuronal functions. However, the exact functional differences between SHC1 and SHC3, especially on the aspect of their isoforms, have not been revealed in primary neurons or neuronal precursor cells. In this study, we used

RNA interference to knock down the expression of p52SHC1and p52SHC3 in purified primary cortical neurons and neural stem cells, respectively. We also used adenovirus to overexpress p52SHC1 in primary neurons and p52SHC3 in neural stem cells to confirm their roles in neural cell cycle.

In the present study, p52SHC1 RNAi  resulted in significantly fewer percentage of G2-M phase cells in primary neural stem cells along with down-regulated cyclin A and cyclin E proteins. However, the exogenous expression of SHC1 in purified primary cortical neurons in this study did not seem to change the cell cycle distribution, although cyclin A, CDK2 and p-CDK2 were all up-regulated.

In Ning Tang and colleagues study, knockdown of p52SHC3 expression by RNAi significantly affected the cell cycle distribution and the expression levels of many cell cycle regulators. Specifically, RNAi of p52SHC3 decreased the percentage of G0/G1 phase neurons but increased the percentages of S phase and G2/M phase neurons, The changed cell cycle distribution may be caused by the changed levels of the following proteins: the upregulation of cyclin D1 which may cause reduction in the percentage of G0/G1 phase neurons; the up-regulation of cyclin E and CDK2 which may push cells to pass the G1/S boundary to enter S phase; and the up-regulation of cyclin A and CDK2 which may lead to the cells to enter G2/M phase. All these results clearly indicated that some of the neurons had reentered the cell cycle after p52SHC3 RNAi. Overexpression of exogenous p52SHC3 in neural stem cells increased the percentage of G0-G1 phase cells and decreased the percentage of G2-M phase cells by downregulating the protein levels of cyclin A, cyclin D1, and cyclin E, demonstrating a CDK2-independent cell cycle arrest.

Ning Tang and colleagues deminstrated that p52SHC1 plays an essential role in regulating cellular proliferation and p52SHC3 has crucial function in maintaining the mitotic quiescence of neurons. Controlling these domain-mediated signals could be a target in determining the fate of neural cells in the cell cycle.   

 

About The Author

Dr. Ning Tang received his Bachelor Degree in biology science from Shandong University, China, in 2003. He received his Ph. D from Institute of Basic Medical Sciences, Academy of Military Medical Sciences in 2010, majored in cell biology.

Currently, he works in Reproductive Medicine Center of Jinan Military General Hospital as an embryologist, Jinan, China. 

About The Author

Dr. Dan Lyu received her Bachelor Degree in 2005, from Chengdu Sport University, Chengdu, China. In 2008, she received her Master Degree from Hebei Medical University, Shijiazhuang, China and in 2011, she received her Ph,D from Capital Medical University, Beijing, China, majored in pain medicine.

She is now a clinical doctor in Tianjin First Central Hospital, Tianjin, China. Her research focuses on pain related neural pathological and physiological alteration. 

 

Reference

Tang N^1,2, Lyu D^1,3, Liu T¹, Chen F¹, Jing S¹, Hao T², Liu S¹. Different Effects of p52SHC1 and p52SHC3 on the Cell Cycle of Neurons and Neural Stem Cells. J Cell Physiol. 2016 ;231(1):172-80. doi: 10.1002/jcp.25069.

Show Affiliations

1 State Key Laboratory of Proteomics and, Department of Neurobiology, Institute of Basic Medical Sciences, Beijing, P. R. China.

2 Reproductive Medicine Center, Jinan Military General Hospital, Jinan, P. R. China.

3 Dan Lyu is currently working in Department of Pain Management, Tianjin First Center Hospital, Tianjin, P. R. China.  

 

Go To Journal Cell Physiology

 

 

Global Medical Discovery features paper: DNA binding activity of Ku during chemotherapeutic agent-induced early apoptosis

Significance Statement

This study analyzed the expression of the Ku protein and its DNA-binding activity during early apoptosis. In the study, Ku was neither cleaved nor degraded during early apoptosis induced by etoposide treatment. In addition, Ku was found to bind cleaved chromosomal DNA and/or nucleosomes in apoptotic cells.

The DNA-binding properties of Ku were assessed by two methods, each of which is based on electrophoresis mobility shift assay (EMSA). One commonly applied method, EMSA with 15-bp ³²P-labeled DNA probe (RI-EMSA), employs radiolabeled DNA probes. The other method, EMSA combined with western blot (WB-EMSA), employs unlabeled DNA probes followed by western blot and detection using anti-Ku antiserum. This study showed that both WB-EMSA and RI-EMSA are useful for evaluating Ku-DNA binding activity.

The significance of this work lies in its contribution to the understanding of the mechanism of interaction of Ku with DNA during apoptosis.

Figure legends:

1. RI-EMSA: Protein extract obtained from cells treated with etoposide for the duration indicated was incubated with ³²P-labeled, 15-bp dsDNA probes in the presence of closed circular DNA.
2. Western blot: Protein extract obtained from either control or etoposide-treated cells was run on a 10% SDS polyacrylamide gel under reducing conditions. Ku70 and Ku80 were detected using human polyclonal antiserum.
3. WB-EMSA: Extracts from etoposide-treated HL-60 cells were separated by 6% native PAGE, and then analyzed by western blot with polyclonal antiserum raised against Ku (lane 1). Extracts from untreated HL-60 cells were incubated with 160-bp DNA, followed by western blot (lane 2). Extracts from untreated or etoposide treated HL-60 cells were incubated with 15-bp DNA, followed by western blot (lanes 3–6).
4. Comparison of WB-EMSA to conventional RI-EMSA. The diagram of RI-EMSA is a part of Figure A, and the figure of WB-EMSA is a part of Figure C.

About The Author

Katsuya Iuchi is currently an assistant professor at the Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School. His research focuses on the mechanism of cell death and lipid peroxidation of biomembranes. Prior to joining Nippon Medical School, he was a postdoctoral fellow in the Sodeoka Live Cell Chemistry Project, ERATO, Japan Science and Technology Agency. He received his Ph.D. in chemistry from Kwansei Gakuin University, Japan in 2009.  

Journal Reference

Exp Cell Res. 2016;342(2):135-44.

Iuchi K¹, Yagura T².

Show Affiliations

1. Department of Bioscience, Faculty of Science and Technology, Kwansei Gakuin University, 2-1 Gakuin, Sanda-shi, Hyogo-ken 669-1337, Japan. Electronic address: iuchi@nms.ac.jp.
2. Department of Bioscience, Faculty of Science and Technology, Kwansei Gakuin University, 2-1 Gakuin, Sanda-shi, Hyogo-ken 669-1337, Japan.

Abstract

Ku-protein is a heterodimer composed of two subunits, and is capable of both sequence-independent and sequence-specific DNA binding. The former mode of DNA binding plays a crucial role in DNA repair. The biological role of Ku-protein during apoptosis remains unclear. Here, we show characterization of Ku-protein during apoptosis. In order to study the DNA binding properties of Ku, we used two methods for the electrophoresis mobility shift assay (EMSA). One method, RI-EMSA, which is commonly used, employed radiolabeled DNA probes. The other method, WB-EMSA, employed unlabeled DNA followed by western blot and detection with anti-Ku antiserum. In this study, Ku-DNA probe binding activity was found to dramatically decrease upon etoposide treatment, when examined by the RI-EMSA method. In addition, pre-treatment with apoptotic cell extracts inhibited Ku-DNA probe binding activity in the non-treated cell extract. The inhibitory effect of the apoptotic cell extract was reduced by DNase I treatment. WB-EMSA showed that the Ku in the apoptotic cell extract bound to fragmented endogenous DNA. Interestingly, Ku in the apoptotic cell extract purified by the Resource Q column bound 15-bp DNA in both RI-EMSA and WB-EMSA, whereas Ku in unpurified apoptotic cell extracts did not bind additional DNA. These results suggest that Ku binds cleaved chromosomal DNA and/or nucleosomes in apoptotic cells. In conclusion,Ku is intact and retains DNA binding activity in early apoptotic cells.

Copyright © 2016 Elsevier Inc. All rights reserved.

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Global Medical Discovery features paper: Identification of Palmitoylated Transitional Endoplasmic Reticulum ATPase by Proteomic Technique and Pan Antipalmitoylation Antibody

J Proteome Res. 2016 Mar 4;15(3):956-62. doi: 10.1021/acs.jproteome.5b00979.

Caiyun Fang,^† Xiaoqin Zhang,^† Lei Zhang, Xing Gao, Pengyuan Yang, and Haojie Lu^*

Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China

 

Abstract

Protein palmitoylation plays a significant role in a wide range of biological processes such as cell signal transduction, metabolism, apoptosis, and carcinogenesis. For high-throughput analysis of protein palmitoylation, approaches based on the acyl-biotin exchange or metabolic labeling of azide/alkynyl-palmitate analogs are commonly used. No palmitoylation antibody has been reported. Here, the palmitoylated proteome of human colon cancer cell lines SW480 was analyzed via a TS-6B-based method. In total, 151 putative palmitoylated sites on 92 proteins, including 100 novel sites, were identified. Except for 3 known palmitoylated transmembrane proteins, ATP1A1, ZDHHC5, and PLP2, some important proteins including kinases, ion channels, receptors, and cytoskeletal proteins were also identified, such as CLIC1, PGK1, PPIA, FKBP4, exportin-2, etc. More importantly, the pan antipalmitoylation antibody was developed and verified for the first time. Our homemade pan antipalmitoylation antiserum could differentiate well protein palmitoylation from mouse brain membrane fraction and SW480 cells, which affords a new technique for analyzing protein palmitoylation by detecting the palmitic acid moiety directly. Furthermore, the candidate protein transitional endoplasmic reticulum ATPase (VCP) identified in SW480 cells was validated to be palmitoylated by Western blotting with anti-VCP antibody and the homemade pan antipalmitoylation antibody.

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Global Medical Discovery features paper: Synthesis, antimicrobial activity of Schiff base compounds of cinnamaldehyde and amino acids

Significance Statement

Microorganism infection is a continue threat to human health. About the control the infection, using antimicrobial agent is one of the effective options. Now, natural antimicrobial agents are focused extensively because they are low-toxic and safe. Cinnamaldehyde is a natural antimicrobial substance, which is extracted from bark of  Cinnamomum genus trees. Cinnamaldehyde possesses good bioactivity and could inhibit the growing of many kinds of fungi and bacteria. Cinnamaldehyde is categorized as Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration. However, Cinnamaldehyde has several drawbacks, such as its strong odor, high volatility and water insolubility, which limited its application.

In our research, cinnamaldehyde was modified by amino acids to synthesize a new class of Schiff base compounds. Bioactivity results indicated that the Schiff base compounds remarkably inhibited the growth of the tested bacteria and fungi, and they have broad-spectrum antimicrobial activity. Compared with control compounds, i.e. Ciprofloxacin and Fluconazole, most of the Schiff base compounds exhibited better bioactivity than the two control compounds.

The key finding of this study is that, the new class of cinnamaldehyde Schiff base compounds, which could be easily synthesized, have great bioactivity, low-toxicity, low odor and good water solubility. Therefore, cinnamaldehyde Schiff base compounds were potential to be antibacterial agents or food preservatives.

Moreover, the further analysis on antimicrobial activity and chemical structure were conducted in our research. Results from the structure-activity relationship suggest that both p-Cl of benzene ring from cinnamaldehyde and the number of –COOK from amino acid salts significantly contributed to their antimicrobial activity.

Our research results provided an alternative option for exploring of new antimicrobial agents. 

About The Author

Prof. Shujun Li received her Bachelor Degree in Forest Products Chemical Processing from Northeast Forestry University, China in 1995. She received her Master Degree in 1998, also in the same major, and received her Ph. D in 2001, majored in wood science and technology.

Currently, she serves as a full Professor of Forest Products Chemical Processing Department at Northeast Forestry University, Harbin, China. Her research interests include biomass conversion and application in a high-value way. 

 

About The Author

Miss Hui Wang received her bachelor degree in 2013 from Lanzhou University of Technology, Lanzhou, China. She is now a doctoral candidate at Northeast Forestry University, and her current research is synthesis of cinnamaldehyde derivatives and its bioactivity. 

Journal Reference

Bioorg Med Chem Lett. 2016 Feb 1;26(3):809-13.

Wang H¹, Yuan H¹, Li S², Li Z¹, Jiang M¹. 

Show Affiliations

1. Key Laboratory of Bio-Based Material Science and Technology of the Ministry of Education, Northeast Forestry University, Harbin 150040, China.
2. Key Laboratory of Bio-Based Material Science and Technology of the Ministry of Education, Northeast Forestry University, Harbin 150040, China. Electronic address: lishujun@nefu.edu.cn.

Abstract

The purpose of this study was to synthesize hydrophilic cinnamaldehyde Schiff base compounds and investigate those bioactivity. A total of 24Schiff base compounds were synthesized using a simple approach with 3 cinnamaldehyde derivates and 8 amino acids as raw materials. The structures of synthesized compounds were confirmed using FTIR, (1)HNMR, HRMS purity and melting point. The antimicrobial activities of newcompounds were evaluated with fluconazole and ciprofloxacin as the control against Aspergillus niger, Penicillium citrinum, Escherichia coli and Staphylococcus aureus.

Findings show that major compounds exhibited significant bioactivity. Results from the structure-activity relationship suggest that both -p-Cl on benzene ring of cinnamaldehyde and the number of -COOK of amino acid salts significantly contributed to antimicrobialactivity.

Copyright © 2015 Elsevier Ltd. All rights reserved.

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Global Medical Discovery features paper: Inkjet-Print Micromagnet Array on Glass Slides for Immunomagnetic Enrichment of Circulating Tumor Cells

Significance Statement

To advance cancer studies and enable oncologists to make more accurate diagnosis, prognosis, and develop personalized therapies, Prof. John X.J. Zhang and Dr. Peng Chen led a team of bioengineers from the Thayer School of Engineering at Dartmouth and the University of Texas at Austin in developing an innovative system that combines inkjet-printing, microfluidic technology, and immunoassay for capturing and manipulating circulating tumor cells (CTCs). This miniaturized bio-analytical system can be further integrated with fluorescent microscope for cancer cell imaging, with fluorescent in-situ hybridization (FISH) and PCR for molecular level cancer studies. It opens up a great many possibilities to optimize cancer diagnostic and tumor management.

“This work provides a new angle, other than traditional tissue biopsy and medical imaging, to approach cancer. A fast, simple and less painful blood test may eventually provide equivalently accurate disease information about individual cancer patient in a timely manner, ” said Zhang. circulating tumor cells detach from primary tumor site, shed into the blood circulation system, and may initiate the deadly cancer metastasis process. Through efficient detection of these cells, especially at an early stage, physicians will be able to design the best diagnosis and treatment strategy for each individual cancer patient.

Immunomagnetic assay has been successfully used to separate rare circulating tumor cells from blood. However, traditional immunomagnetic assay is often limited in the low magnetic field gradient and low density of effective magnetic traps. In this work, Dr. Chen developed a novel method using inkjet-printing technology to fabricate microscale magnetic structures that can be easily deposited on an arbitrary substrate.

This inkjet-printing technology is a versatile but cost-effective approach for rapid prototyping with high accuracy and flexibility. Such microscale magnets, when placed in an external magnetic field, largely enhance the magnetic field and the attractive force applied on the target circulating tumor cells, and hence facilitates the detection. In our experiments with COLO205 (a human colorectal cancer cell line) as the separation target, the inkjet-printed micro-magnets integrated assay increased the system sensitivity by 26% compared with using normal glass slide as the substrate.

Dr. Chen’s research is focused on developing miniaturized high-performance bio-analytical systems for point-of-care and globally relevant medical diagnostic applications. “This project is to implement advanced engineering fabrication, sensing, and manipulating techniques with multiplexing immunoassay to separate these rare circulating tumor cells from whole blood.” Zhang said. “The ultimate goal is to deliver a highly sensitive, reliable, affordable, and portable cancer screening platform with high throughput. The next step – bringing the technology from lab bench to clinics is a big challenging step, but is also the most rewarding step.

This work has the potential to revolutionize cancer risk assessment, cancer management, and increase the cure rate for cancers such as breast cancer, lung cancer, and prostate cancer.” This paper is published on Annals of Biomedical Engineering (DOI: 10.1007/s10439-015-1427-z).

      

About The Author

Dr. Peng Chen received his PhD degree in Biomedical Engineering from the University of Texas at Austin. He is now working as a postdoc research associate at the Center for Applied NanoBioscience and Medicine at the University of Arizona. His research interests include (1) miniaturized microfluidic system for detection and analysis of rare circulating tumor cells (CTCs), and (2) vertical flow paper based microfluidic device as point-of-need multiplex diagnostic and surveillance tool for bio-threat detection. He has published 10 peer-reviewed journal papers and 10 conference proceedings. He now serves the editorial board of Scientific Reports (Nature publishing group). Email: pengchen@email.arizona.edu

About The Author

Prof. John Zhang, Ph.D., is a Professor at Thayer School of Engineering at Dartmouth, and a Fellow of American Institute for Medical and Biological Engineering (AIMBE). He received his Ph.D. from Stanford University, and was a Research Scientist at MIT. His key contribution is in developing miniature medical systems to improve global health, through innovations in bio-inspired nanomaterials, lab-on-chip design, and advanced nanofabrication technologies for probing complex biological networks critical to human development and diseases such as cancer. He received the Wallace Coulter Foundation Early Career Award for developing handheld microphotonic imaging scanners and microsystems for early oral cancer detection; NSF CAREER award for the invention of plasmonic scanning probes design for controlled perturbation and imaging at sub-cellular level; and DARPA Young Faculty Award for patterning plasmonic surface on MEMS for biomarker sensing applications. He has published over 120 peer reviewed papers and proceedings, presented over 45 invited seminars worldwide, and filed over 60 US and international patents. He is an alumnus of NAE Frontiers of Engineering programs, an Associate Editor for Biomedical Microdevices, IEEE/ASME Journal of Microelectromechanical Systems, and has published a textbook for undergraduates titled “Molecular Sensors and Nanodevices: Principles, Designs and Applications in Biomedical Engineering”. Email: john.zhang@dartmouth.edu

Reference

Ann Biomed Eng. 2016;44(5):1710-20.

Peng Chen¹, Yu-Yen Huang², Gauri Bhave¹, Kazunori Hoshino³, Xiaojing Zhang^4,5

Show Affiliations

¹Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.

²Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA.

³Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA.

⁴Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.

⁵Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA. john.zhang@dartmouth.edu.

We report an inkjet-printed microscale magnetic structure that can be integrated on regular glass slides for the immunomagnetic screening of rare circulating tumor cells . circulating tumor cells detach from the primary tumor site, circulate with the bloodstream, and initiate the cancer metastasis process. Therefore, a liquid biopsy in the form of capturing and analyzing circulating tumor cells may provide key information for cancer prognosis and diagnosis. Inkjet printing technology provides a non-contact, layer-by-layer and mask-less approach to deposit defined magnetic patterns on an arbitrary substrate. Such thin film patterns, when placed in an external magnetic field, significantly enhance the attractive force in the near-field close to the circulating tumor cells to facilitate the separation. We demonstrated the efficacy of the inkjet-print micromagnet array integrated immunomagnetic assay in separating COLO205 (human colorectal cancer cell line) from whole blood samples. The micromagnets increased the capture efficiency by 26% compared with using plain glass slide as the substrate.

Go To Annals of Biomedical Engineering

Global Medical Discovery features paper: Impact of patient characteristics on the clinical efficacy of mongersen (GED-0301), an oral Smad7 antisenseoligonucleotide, in active Crohn’s disease

Significance Statement

Crohn’s disease (CD) is a chronic condition characterized by segmental, transmural inflammation, which, although most common in the terminal ileum and right colon, can affect any part of the alimentary tract. In addition to the commonly observed signs and symptoms of Crohn’s disease, local complications as well as manifestations outside the digestive tract can also occur as a result of Crohn’s disease -associated inflammation, underscoring the importance of effective treatment options.

Subgroup analyses from prospective, randomised, controlled trials in patients with active Crohn’s disease have shown that patient demographics and disease characteristics such as disease duration and treatment history can impact clinical outcomes. Our retrospective study further evaluated the impact of patient baseline clinical and disease characteristics on the efficacy of mongersen, an oral, locally active Smad7 antisense oligonucleotide that targets Smad7 in the ileum and colon. In addition to the impact of human serum C-reactive protein (hsCRP) values, disease duration, and disease activity at baseline on mongersen over 10 weeks, our analysis also looked at how sex, body mass index, smoking status, history of Crohn’s disease-related intestinal resection, steroid status, and immunosuppressant use at baseline impacted treatment efficacy.

Our results showed that patients with Crohn’s Disease Activity Index (CDAI) scores ≤260 at baseline had significantly higher clinical remission rates (defined as a CDAI <150) with mongersen 40 mg/day and 160 mg/day treatment, whereas patients with CDAI scores >260 at baseline achieved clinical remission most frequently with the highest mongersen dose (160 mg/day), suggesting that greater disease activity can impact clinical benefit. Baseline disease characteristics such as hsCRP (<3 mg/L or ≥3 mg/L) and disease duration (<5 or ≥5 years) did not appear to significantly impact efficacy of mongersen treatment in our study.

About The Author

Giovanni Monteleone received his medical degree from the University Magna Graecia of Catanzaro (Italy) and completed his internship, residency, and a fellowship in gastroenterology at the same university. He joined the faculty at the University of Rome Tor Vergata in 2003, becoming an Assistant Professor of Gastroenterology, then Professor of Gastroenterology. He is the Head of Gastroenterology Unit at the Policlinico Tor Vergata in Rome. Dr. Monteleone’s basic research is mostly focused on mechanisms involved in the control of mucosal immune homeostasis and inflammatory signals that sustain and amplify pathological processes in the gastrointestinal tract. In particular, he is interested in understanding how immune cells and non-immune cells cross-talk in the gastrointestinal mucosa and which molecules mediate such an interplay. So far, these studies have contributed to delineate novel pathways of intestinal mucosal damage and paved the way for the development of anti-inflammatory compounds, which are now ready to move into the clinic. Dr. Monteleone is also interested in the immune-inflammatory networks involved in the colitis-associated colon carcinogenesis. He is author of >300 peer-reviewed articles, books, and book chapters, and serves as an editorial board member or a reviewer for several journals.

 

Journal Reference

Aliment Pharmacol Ther. 2016 ;43(6):717-24.

Monteleone G¹, Di Sabatino A², Ardizzone S³, Pallone F¹, Usiskin K⁴, Zhan X⁴, Rossiter G⁴, Neurath MF⁵. 

Show Affiliations

1. Department of Systems Medicine, University of Tor Vergata, Rome, Italy.
2. First Department of Internal Medicine, St. Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
3. Department of Surgery, “L. Sacco” University Hospital, Milan, Italy.
4. Celgene Corporation, Warren, NJ, USA.
5. Department of Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.

Abstract

BACKGROUND:

In a phase 2 study, mongersen, an oral antisense oligonucleotide targeting Smad7, was effective in inducing clinical remission in approximately 60% of patients with active Crohn’s disease (CD).

AIM:

In a post hoc analysis to evaluate those patient disease characteristics that may have influenced the efficacy and safety of mongersen therapy.

METHODS:

Patients with steroid-dependent/resistant, active Crohn’s disease were randomised to mongersen 10, 40 or 160 mg/day or placebo for 2 weeks; patients were followed for 10 weeks. Clinical remission [Crohn’s Disease Activity Index (CDAI) score <150] and clinical response (CDAI score reduction ≥100 points) were assessed at weeks 2, 4 and 12 for these subgroups: disease duration <5/≥5 years, human serum C-reactive protein (hsCRP) <3/≥3 mg/L, and CDAI at baseline ≤260/>260. Additional patient baseline and disease characteristics were explored.

RESULTS:

Clinical remission and response rates were significantly higher in patients receiving mongersen 40 and 160 mg/day but not 10 mg/day vs. placebo and independent of disease duration and hsCRP. Patients with baseline CDAI ≤260 had significantly higher remission rates with 40 and 160 mg/day. In patients with baseline CDAI >260, remission rates were statistically greater with 160 mg/day and numerically better with 40 mg/day vs. placebo. Adverse event rates were similar across treatment groups. Mongersen was safe and well tolerated.

CONCLUSIONS:

Patients with higher CDAI scores achieved clinical remission most frequently with the highest mongersen dose. Disease duration and baseline human serum C-reactive protein did not appear to significantly impact efficacy of mongersen in this study (EudraCT Number: 2011-002640-27.).

© 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Go To Aliment Pharmacol Ther