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BOSTON & LISBON, Portugal--(BUSINESS WIRE)--Proterris, Inc., a clinical-development stage company focused on therapeutic applications of low-dose carbon monoxide, and Alfama, Inc. today announced the completion of a merger of the two companies that effectively creates the world’s dominant player in the field of carbon monoxide (CO) therapies. Proterris, which has a leading position in gaseous applications of CO, has acquired Alfama’s CO releasing molecule (“CORM”) assets, arguably the most extensive in the field. In connection with the asset acquisition, Proterris has acquired all of Alfama’s subsidiaries, including Alfama Lda. located near Lisbon, Portugal, which will be renamed Proterris (Portugal) Lda. In conjunction with the merger, Proterris will also implement a collaboration with Prof. Carlos Romão of the Institute of Chemical and Biological Technology (ITQB) of the New University of Lisbon (NOVA), one of the scientific pioneers and inventors of Aflama’s CORM assets, in order to further optimize CORM candidates for a variety of indications. Proterris looks to continue advancing its own gaseous Phase 2/3 trial in delayed graft function (DGF)prior to moving one of the CORM candidates into clinical trials, which the company aims to start in the next 18-24 months. “Alfama has discovered and developed unique families of CORMs which have demonstrated very potent anti-fibrotic, anti-inflammatory and cytoprotective effects with very low toxicity potential,” said Jeffrey D. Wager, M.D., Chairman & CEO of Proterris. “Until now, achievement of such drug-like profiles for CORMs has eluded scientists and companies alike. Alfama’s CORM assets represent excellent candidates for drug development for those indications which are less amenable to therapy with CO gas. In addition, by establishing Proterris (Portugal) Lda., we are now well-positioned to pursue a variety of European partnering and fundraising activities in both the private and public sectors. This coincides very well with the Series A fundraising campaign which are launching with the closing of this merger.” Dr. Wager has designed and structured multiple cross-border life science transactions in the past, including a major Japanese spin-out involving both Asian and American investors, a European Union-based corporate venture capital fund investing in both Europe and the U.S., and a specialty pharma roll-up in Brazil involving private equity funds from both Latin America and the U.S. “The merger of Alfama with Proterris represents a very synergistic and strategic fit between two companies with common goals, and substantially enhances corporate value for both sets of shareholders,” commented Nuno Arantes-Oliveira, founding Chief Executive of Alfama. “We are very glad to make Alfama part of Proterris’ exceptional IP portfolio, an important step in our evolution towards bringing low-dose CO therapies to patients.” Celso Guedes de Carvalho, CEO of Portugal Ventures, one of Alfama’s largest shareholders, added, “This transaction demonstrates how supporting investments for the ‘long-haul’ – given the capital and time required in the biotech sector – allows breakthrough technologies to reach patients. With regard to Alfama, their story demonstrates that when the technology is truly ground-breaking and the team strong and resilient, it is worth the wait. We believe this merger, with support from Portugal Ventures, will significantly increase the international visibility of the growing Portuguese Life Science startup ecosystem.” The Proterris-Alfama proposition for CO therapy is validated by almost $23 million in funding for three Phase 2 clinical trials using low dose CO gas. The U.S. National Institutes of Health (NIH) has funded these trials over the past five years for indications covered by patents licensed from a group of top U.S. universities or written by Proterris. About Alfama Alfama is the leading company in the development of Carbon Monoxide-Releasing Molecules (CORMs) for therapy. The company has produced hundreds of CORMs and obtained exceptional results in various animal models of chronic and acute human diseases. CORMs have the potential to expand CO-based therapy to a wide range of high-value indications, can be administered orally or intravenously, and offer a very attractive therapeutic window and safety profile. After acquiring hemoCORM Ltd of London, UK, Alfama came to control a diverse set of families of patents and patent applications on CORMs which together position the company as the undisputed leader in CORM technology. Alfama was founded in Portugal and received funding from venture capital agencies such as Portugal Ventures, along with private investors from the U.S., the U.K, Spain and Portugal. The Company assembled an international team of scientific and business leaders. Its founders included Roche scientist Werner Haas, New University of Lisbon Chemistry Professor Carlos Romão, Stan Kugell, its founding Chairman, and Nuno Arantes-Oliveira, its founding CEO. About Proterris Proterris, Inc. is a clinical-development stage company focused on therapeutic applications of low-dose carbon monoxide (CO). Leveraging CO’s demonstrated anti-fibrotic, anti-inflammatory and cytoprotective properties, Proterris is initially focused on developing CO for delayed graft function (DGF) in renal transplant recipients and idiopathic pulmonary fibrosis (IPF). Other indications, including pulmonary arterial hypertension (PAH) and acute respiratory distress syndrome (ARDS), are also being developed by the National Institutes of Health (NIH). CO has broad potential to significantly impact the lives of millions of patients suffering from a wide variety of both acute and chronic diseases. Proterris was founded on the pioneering science of Proterris co-founder Augustine M.K. Choi, M.D., who is Professor of Medicine and the Stephen and Suzanne Weiss Dean at Weill Cornell Medicine and Provost for Medical Affairs at Cornell University; and David J. Pinsky, M.D., the J. Griswold Ruth M.D. & Margery Hopkins Ruth Professor of Internal Medicine, Professor of Molecular and Integrative Physiology, Chief, Cardiovascular Medicine, and Director, Cardiovascular Center of the University of Michigan. Between them, Dr.’s Choi and Pinsky have generated an extensive body of mechanistic, translational and clinical research data, as well as a broad intellectual property portfolio on the therapeutic opportunities of CO for multiple diseases. For more information, please visit www.proterris.com.


Direito R.,University of Lisbon | Lima A.,University of Lisbon | Rocha J.,University of Lisbon | Ferreira R.B.,University of Lisbon | And 8 more authors.
Journal of Nutritional Biochemistry | Year: 2017

Polyphenols from persimmon (Diospyros kaki) have demonstrated radical-scavenging and antiinflammatory activities; however, little is known about the effects of persimmon phenolics on inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Therefore, we aimed in this work to characterize the antiinflammatory and antiproliferative effects of a persimmon phenolic extract (80% acetone in water), using an in vivo model of experimental colitis and a model of cancer cell invasion. Our results show, for the first time, a beneficial effect of a persimmon phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells. Administration of persimmon phenolic extract to mice with TNBS-induced colitis led to a reduction in several functional and histological markers of colon inflammation, namely: attenuation of colon length decrease, reduction of the extent of visible injury (ulcer formation), decrease in diarrhea severity, reduced mortality rate, reduction of mucosal hemorrhage and reduction of general histological features of colon inflammation. In vitro studies also showed that persimmon phenolic extract successfully impaired cell proliferation and invasion in HT-29 cells. Further investigation showed a decreased expression of COX-2 and iNOS in the colonic tissue of colitis mice, two important mediators of intestinal inflammation, but there was no inhibition of the gelatinase MMP-9 and MMP-2 activities. Given the role of inflammatory processes in the progression of CRC and the important link between inflammation and cancer, our results highlight the potential of persimmon polyphenols as a pharmacological tool in the treatment of patients with IBD. © 2017 Elsevier Inc.


Gaspar F.B.,ITQB | Montero N.,Complutense University of Madrid | Akary E.,French National Institute for Agricultural Research | Akary E.,Agro ParisTech | And 8 more authors.
International Journal of Food Microbiology | Year: 2012

Enterococcus faecalis is a nosocomial opportunistic pathogen, but is also found in fermented food products where it plays a fundamental role in the fermentation process. Previously, we have described the non-starter E. faecalis cheese isolate QA29b as harboring virulence genes and proven to be virulent in Galleria mellonella virulence model. In this study, we further characterized this food strain concerning traits relevant for the host-pathogen relationship. QA29b was found to belong to sequence type (ST) 72, a common ST among food isolates, and thus we consider it as a good representative of food E. faecalis strains. It demonstrated high ability to form biofilms, to adhere to epithelial cells and was readily eliminated by J774.A1 macrophage cells. Despite carrying the cps locus associated with the capsular polysaccharide CPS 2 type, cps genes were not expressed, likely due to an IS. 6770 inserted in the cpsC-cpsK promoter region. This work constitutes the first study of traits important for interaction, colonization and infection in the host performed on a good representative of E. faecalis food isolates. Reported results stress the need for a reliable serotyping assay of E. faecalis, as cps genotyping may not be reliable. Overall, QA29b characterization shows that despite its virulence potential in an insect model, this food strain is readily eliminated by mammalian macrophages. Thus, fine tuned approaches combining cellular and mammalian models are needed to address and elucidate the multifactorial aspect of virulence potential associated with food isolates. © 2012 Elsevier B.V.


Courtois B.,CIRAD - Agricultural Research for Development | Greco R.,Parco Technologico Padano | Bruschi G.,Parco Technologico Padano | Frouin J.,CIRAD - Agricultural Research for Development | And 11 more authors.
Plant Genetic Resources: Characterisation and Utilisation | Year: 2011

In South Europe, rice is grown as an irrigated crop in river deltas where it plays an important role in soil desalinization. Specific varieties are needed for these tough conditions. We analyzed the genetic structure of a set of 305 varieties coming from the European Rice Germplasm Collection (ERGC) with 90 single nucleotide polymorphisms and compared it with a reference set representative of the diversity of Oryza sativa (mini-Germplasm Bank (GB)). These accessions had been characterized for their grain type and growth cycle duration. The polymorphism information contents of the ERGC were lower than those of the mini-GB, indicating a narrower genetic basis. Indeed, almost all ERGC accessions belong to the japonica group. Within the japonica group, both a dendrogram and a Bayesian clustering identified two major clusters. The first cluster encompassed tropical japonicas and American varieties from USA and Argentina characterized by long and narrow grains and medium to long duration. On a finer level, tropical japonicas appear separated from the other accessions. The second cluster is composed of European varieties mostly early or medium in duration and Asian temperate accessions, with a subgrouping based on grain format. A set of 200 accessions was composed for association mapping studies on traits such as salt tolerance. © 2011 NIAB.


Silva S.,IBET | Boross P.,ITQB | Soares R.,ITQB | Coelho A.V.,ITQB | And 3 more authors.
Acta Horticulturae | Year: 2012

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry was used to study extracts of olive seeds at different maturation stages of fruits collected in the years 2009 and 2010. For comparison purposes LC-DAD-MS/MS assays were also done. Both methodologies confirmed the presence in olive seeds of secoiridoid compounds with higher molecular mass than nüzhenide 11-methyl-oleoside such as nüzhenide di and tri (11-methyl-oleosides). 11-methyloleoside glucosides derivatives such as hexa, penta and tetra derivatives were detected in seeds of mature fruits of the year 2009 suggesting a relationship of these compounds with olives maturation stage.


Tavares S.,University of Lisbon | Vesentini D.,ITQB | Fernandes J.C.,University of Lisbon | Ferreira R.B.,University of Lisbon | And 3 more authors.
Plant Physiology and Biochemistry | Year: 2013

Grapevine (Vitis vinifera L.) is rich in phenylpropanoid compounds, namely flavonoids and stilbenes which, present in most tissues, are described as antioxidants and known to accumulate in response to biotic and abiotic stress. Grapevine is then a choice model for studying the interplay between the phenylpropanoid pathway and nutrient deficiency. Here we report the response to sulfur deficiency (-S) of flavonoids and stilbenes biosynthetic pathways in chlorophyll tissues (plantlets) and cell culture. Anthocyanins and trans-resveratrol accumulated in plantlets and trans-resveratrol glucoside in cell cultures in response to sulfur deficiency, while a significant decrease in chlorophyll was observed in -S plantlets. The up-regulation of chalcone synthase gene and the downstream flavonoid biosynthesis genes dihydroflavonol reductase and anthocyanidin synthase matched the accumulation of anthocyanins in -S V. vinifera plantlets. The mRNA level of stilbene synthase gene(s) was correlated tightly with the increase in trans-resveratrol and trans-resveratrol glucoside levels, respectively in -S plantlets and cell cultures. As a whole, the present study unveil that V. vinifera under sulfur deficiency allocates resources to the phenylpropanoid pathway, probably consecutive to inhibition of protein synthesis, which can be advantageous to resist against oxidative stress symptoms evoked by -S conditions. © 2013 Elsevier Masson SAS.


Henriques B.J.,ITQB | Olsen R.K.,Aarhus University Hospital | Bross P.,Aarhus University Hospital | Gomes C.M.,ITQB
Current Medicinal Chemistry | Year: 2010

Riboflavin, commonly known as vitamin B2, is the precursor of flavin cofactors. It is present in our typical diet, and inside the cells it is metabolized to FMN and FAD. As a result of their rather unique and flexible chemical properties these flavins are among the most important redox cofactors present in a large series of different enzymes. A problem in riboflavin metabolism or a low intake of this vitamin will have consequences on the level of FAD and FMN in the cell, resulting in disorders associated with riboflavin deficiency. In a few number of cases, riboflavin deficiency is associated with impaired oxidative folding, cell damage and impaired heme biosynthesis. More relevant are several studies referring reduced activity of enzymes such as dehydrogenases involved in oxidative reactions, respiratory complexes and enzymes from the fatty acid β-oxidation pathway. The role of this vitamin in mitochondrial metabolism, and in particular in fatty acid oxidation, will be discussed in this review. The basic aspects concerning riboflavin and flavin metabolism and deficiency will be addressed, as well as an overview of the role of the different flavoenzymes and flavin chemistry in fatty acid β-oxidation, merging clinical, cellular and biochemical perspectives. A number of recent studies shedding new light on the cellular processes and biological effects of riboflavin supplementation in metabolic disease will also be overviewed. Overall, a deeper understanding of these emerging roles of riboflavin intake is essential to design better therapies. © 2010 Bentham Science Publishers Ltd.


Rodrigues Ribeiro R.S.,INESC Porto | Queiros R.B.,INESC Porto | Ecoffet C.,CNRS Mulhouse Institute of Materials Science | Soppera O.,CNRS Mulhouse Institute of Materials Science | And 3 more authors.
Proceedings of SPIE - The International Society for Optical Engineering | Year: 2014

This work reports a new type of optical fiber tweezers based on polymeric micro-lenses. The lenses are achieved by means of an economical and fast fabrication process, using an in-fiber photo-polymerization technique. The polymerization radiation is guided towards the fiber tip creating a polymeric waveguide. The method allows tailoring the geometry of the tip by adjusting the fabrication parameters. Furthermore, more complex shapes can be fabricated by exploring modal effects at the polymerization/trapping wavelengths, which can be used for different applications such as trapping, beam shaping and patterned illumination. © 2014 SPIE.


PubMed | ITQB
Type: Journal Article | Journal: International journal of food microbiology | Year: 2012

Enterococcus faecalis is a nosocomial opportunistic pathogen, but is also found in fermented food products where it plays a fundamental role in the fermentation process. Previously, we have described the non-starter E. faecalis cheese isolate QA29b as harboring virulence genes and proven to be virulent in Galleria mellonella virulence model. In this study, we further characterized this food strain concerning traits relevant for the host-pathogen relationship. QA29b was found to belong to sequence type (ST) 72, a common ST among food isolates, and thus we consider it as a good representative of food E. faecalis strains. It demonstrated high ability to form biofilms, to adhere to epithelial cells and was readily eliminated by J774.A1 macrophage cells. Despite carrying the cps locus associated with the capsular polysaccharide CPS 2 type, cps genes were not expressed, likely due to an IS6770 inserted in the cpsC-cpsK promoter region. This work constitutes the first study of traits important for interaction, colonization and infection in the host performed on a good representative of E. faecalis food isolates. Reported results stress the need for a reliable serotyping assay of E. faecalis, as cps genotyping may not be reliable. Overall, QA29b characterization shows that despite its virulence potential in an insect model, this food strain is readily eliminated by mammalian macrophages. Thus, fine tuned approaches combining cellular and mammalian models are needed to address and elucidate the multifactorial aspect of virulence potential associated with food isolates.

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