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News Article | May 17, 2017
Site: www.biosciencetechnology.com

Researchers from the Gladstone Institutes have discovered that newly-developed cancer drugs may also provide a treatment option for heart failure patients. Heart failure is the leading cause of mortality, hospitalization and healthcare costs in the U.S. Even though there are currently-approved drugs on the market, the five-year mortality rate after diagnosis is close to 40 percent. The new agent, which was successfully tested in mice and human heart cell lines, is a drug-like small molecule called JQ1.  It is part of a class of compounds called BET bromodomain inhibitors, which act by blocking a protein known as BRD4. Drugs derived from JQ1 are currently being investigated in early human cancer trials, but researchers including senior author Saptarsi Haldar, M.D., an associate investigator at Gladstone, decided to look at this target for heart failure. “We recognized that there may be some shared features of cancer pathogenesis and heart failure pathobiology – namely the “dependence” on transcriptional signaling to sustain a pathological state,” Haldar told Bioscience Technology. This is particularly interesting, Haldar said, because it means in contrast to many cancer drugs, which are toxic to the heart, that BET inhibitors may actually be a special class of drugs that have both anti-cancer and cardioprotective properties. BET bromodomains are a good target because they directly influence heart failure. “BET bromodomains are key signaling molecules in the nucleus that trigger excessive induction of a broad program of stress-response genes during heart failure,” Haldar explained. “Many of these genes are involved in fibrosis and inflammation, processes which are detrimental to the heart if they are overactive or go on for too long.” Unlike current heart failure drugs, such as beta blockers and ACE-inhibitors, which generally block stress hormones at the cell surface, BET bromodomain inhibitors dampen down the stress responses at the final convergence point for stress signals – at the level of gene transcription in the nucleus. Previous work found that JQ1 could prevent heart failure in mouse models when administered at the onset of the disease, however the current study shows that JQ1 can successfully treat severe, pre-established heart failure by inhibiting inflammation and scarring of the heart tissue, or fibrosis. Mice were given a dose of 50 mg/kg/day, late in the disease process when robust, pre-existing pathology was already present. “In mouse models, we found that JQ1 improved all hallmark features of heart failure,” Haldar, also an associate professor in the Department of Medicine at the University of California, San Francisco, said. “Improved pumping function, less cardiac enlargement, and less scar tissue deposition (fibrosis).” Next they used induced pluripotent stem cells (iPSCs), derived from adult human skin cells to create heart cell known as cardiomyocytes, to test the drug in cell culture. “We showed that JQ1 suppressed key features of pathological stress responses in these human cells, including inflammation and fibrosis causing pathways,” Haldar said. “Findings which strongly paralleled our animal studies.” The team, including co-first author Qiming Duan, M.D., Ph.D., postdoctoral scholar in Haldar’s lab, did not observe any weight loss or lethargy in mice, but human studies in cancer are underway to define what the side effect profile in humans will look like, Haldar noted. A drop in platelet counts is one effect that has been seen in phase 1 cancer trials, he added. “While potent drugs like BET inhibitors will certainly have on-target side effects, it is our hope that a tractable therapeutic window can be established for heart disease,” Haldar said. JQ1 also did not block normal “physiologic” cardiac growth during endurance exercise training in mice, supporting its tolerability. The next step will be to perform more preclinical studies, including testing BET inhibitor drugs in large animal models of heart failure, according to Haldar.  The team’s contemplation of a potential first-in-human study in the cardiac space will be guided by the ongoing results of Phase 1 and 2 cancer trials, he noted. Sarah McMahon, a UCSF graduate student in Haldar’s lab was co-first author on the paper. The findings were published in Science Translational Medicine.


News Article | May 19, 2017
Site: www.chromatographytechniques.com

Researchers from Cedars Sinai Medical Center have developed a new technique that, if successful in humans, could replace traditional bone grafts for mending nonhealing limb fractures. The new method, which combines, microbubbles, ultrasound, and gene and stem cell therapies, effectively healed severely broken bones in a study in pigs. In the U.S., approximately 100,000 bones fail to heal correctly, and more than 2 million bone grafts are performed around the globe each year. Bone grafts bridge gaps between the edges of a fracture that are too big for the bone to heal on its own.  There are two kinds of bone grafts: autologous, where bone is taken from the patient’s own body, or allogeneic, where it is taken from a tissue bank. However, both have drawbacks. Autografts, which are considered the current gold standard, are not always available in the volume required, may cause prolonged pain because of the second surgical site, and entail risk of infection and more time spent in the hospital, Gadi Pelled, Ph.D., DMD, assistant professor of surgery at Cedars-Sinai and the study’s co-senior author explained in an interview with Bioscience Technology. “Allografts are readily available from tissue banks, but have a low capacity to form new bone and integrate with the patient’s bones,” he said. “They also have the risk of immune rejection and disease transmission.” Hence, there is a large unmet need in skeleton repair. For the new study, researchers built a scaffold made of collagen, which is a protein the body uses to build bones.  It was implanted at the site of the bone break in laboratory pigs for two weeks, during which it “attracted" stem cells from adjacent bone marrow to populate the injury site, principal investigator and co-senior author of the study Dan Gazit, Ph.D. DMD, co-director of the Skeletal Regeneration and Stem Cell Therapy program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute told Bioscience Technology. Next they injected microbubbles combined with genetic material called a plasmid, which is a short circular strand of DNA that codes for a protein known to induce new bone formation. The DNA can’t enter the cells on its own, so ultrasound pulses and microbubbles facilitate the DNA entry across the cell membrane in a process called sonoporation, Gazit said. “The ultrasound waves cause the microbubbles to oscillate, i.e. inflate and deflate,” Gazit explained. “The oscillation pulls gently on the cell membrane leading to the opening of tiny pores, which shut down very quickly, through which the DNA enters the cells.” The technique promoted total bone healing and the leg fracture was mended in all of the animals within eight weeks after surgery.  Expression of the introduced gene was undetectable after 10 days, and the bone grown in fracture had comparable strength to those produced by surgical bone grafts. “This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal’s own stem cells can effectively be used to treat nonhealing bone fractures,” Pelled said in a statement. “It addresses a major orthopedic unmet need and offers new possibilities for clinical translation.” Zulma Gazit, Ph.D., co-director of the Skeletal Regeneration and Stem Cell Program in the Depart of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute and co-author of the study, told Bioscience Technology that the team hopes the technique will translate into humans, and they are actively working towards that goal. “If our technique is successful, bone grafts would not be needed for these types of bone loss cases,” she said. “In addition, we see great promise in the technology for the regeneration and repair of other tissues such as muscle ligaments and more. Wherever stem cells can be recruited and the regeneration factor (gene) is known, the system may be beneficial.” Up next the team is planning to perform comprehensive research to address any concern about the safety of the technology prior to human trials. “We are just at the beginning of a revolution in orthopedics,” Dan Gazit said in a statement. “We’re combining an engineering approach with a biological approach to advance regenerative engineering, which we believe is the future of medicine.” The findings were detailed in a paper published May 17 in Science Translational Medicine.


The present invention relates to inventive novel industrialized method for preparing purified extract containing more abundant active ingredients such as catalpol derivatives from the extract of Pseudolysimachion rotundum var subintegrum than that prepared by the conventional preparation method disclosed in the prior art and the therapeutics or functional health food comprising the purified extract for treating and preventing inflammatory, allergic or asthmatic disease. The purified extract showed more potent anti-inflammatory, anti-allergy and anti-asthma activity than that prepared by the conventional preparation method disclosed in the prior art through various in vivo tests such as inhibition test on the reproduction of eosinophil, the release of immunoglobulin and inflammatory chemokines in plasma and bronchoalveolar fluid as well as the suppression of airway hyperresponsiveness and goblet cell hyperplasia in a OVA-sensitized/challenged mouse model.


News Article | May 8, 2017
Site: www.biosciencetechnology.com

Helen Torley, M.B, Ch.B., came across an interesting statistic last year. Out of the 44 publicly traded biotech companies in the thriving life science hub of San Diego, there was only one female CEO: her. The report, released in 2016 by UK-based executive recruitment firm Liftstream, found that only 2 percent of biotech companies in San Diego have a female CEO, while the national average is between 7 and 9 percent. Since taking the reins as CEO of Halozyme Therapeutics three years ago, Torley knew from first-hand experience that the gender balance was skewed, as she was often one of only a few women among 50 men at CEO networking events. However to find out that the numbers were quite so low was “certainly a surprise,” she told Bioscience Technology. That trend in biotech is not exclusive to the CEO role, though. A new study this year from Liftstream of 177 biotechs that went public from 2012 through 2015 found that women held only 10 percent of board positions. One positive note was that nearly 58 percent of the studied boards had a woman on them, which is up from 48 percent reported in Lifstream’s 2014 survey. The new report also found that gender diversity at the leadership level is associated with business advantages. Companies that had at least one female board member saw an average share price increase of 19 percent, while those with all-male board members showed a 9 percent decrease. So why are women being underrepresented in the top levels of biotech organizations? Torley, who has become more interested in and vocal about this topic since seeing recent statistics, broke this question down into three parts: When it comes to the first factor, Torley does not think it is a matter of under training. “If you look at the graduates of all the major business schools, 40 percent of Columbia, Harvard, MIT are women,” she said. “So certainly we’re getting business-trained women.” The same goes for the percentage of women graduating with STEM degrees, which is rising all the time, Torley, who first started out as a physician training in rheumatology, said. As for the pipeline of women, Torley referenced a 2016 McKinsey & Company study about the state of women in corporate America. “What we see is that women, in general, are less likely to be promoted, less likely to get developmental opportunities, and less likely to have meaningful interactions with senior management or have a sponsor for their career,” she said. The concept of sponsorship, which will be discussed later, is very important to Torley. Women drop off at every promotional level, according the McKinsey report, with the percentage getting lower and lower at each higher rung of the corporate ladder. For first time CEO’s, the majority come from what in biotech is called a line function position, where they’re in a role such as the head or VP of a business unit, Torley said. At senior levels, studies show that women often shift from line to staff roles, such as in human resources or finance. By the time they reach the SVP level, women hold only 20 percent of line roles, which hurts their chances of getting a CEO position, the McKinsey report found. “So women are not moving up the chain and being given the types of jobs you need to have to prepare you to be a CEO,” Torley said. While Torley said women are obviously making progress in getting to higher levels, she noted there is certainly data to suggest an unconscious bias can be at play during the selection process where companies don’t develop a diverse candidate pool or choose a male over a female. Also, from her own experience, though not while at Halozyme, she said she has seen unconscious bias at play and been in “plenty of discussions” where a promotion is on the table and people in the room discussing candidates would say things like ‘well she won’t be able to move she’s got young children’ or ‘I know her husband and he’s got a great job so they won’t move,’ or even worry that a female candidate could become pregnant. It’s very important that filters aren’t on, and companies should understand that in today’s world work life balance issues are just as important for males as females, she noted. The good news, Torley said, is that all of these issues can be addressed with attention and effort. “It’s a multifactorial situation, and there’s room for improvement at every step.” One important aspect of career development that many women lack is a sponsor.  Women tend to have mentors, which are great and can give advice and guidance, but as a general rule, Torley said, mentors are not in a position to specifically advance a woman’s career. In contrast, men tend to have a network that includes sponsorship—a person who is actively engaged in helping them find jobs and provide opportunities. It is only in retrospect that Torley realized how important sponsors were to her success and advancement, and that she was extremely fortunate to have numerous ones as her career progressed. For example, when she was up for a big promotion early in her career as a rheumatologist, she admits she may not have been the most scientifically qualified but the head consultant sponsored her to be the person he wanted in that role. Then, when she moved to Novartis to head up ongoing phase 3 studies, she wanted to switch from the medical side of the company to marketing and business. She tried for a year, but no one listened to her until a new head of marketing came in. When Torley asked to be moved, he decided to take a chance on her and the next day she found herself heading up a launch. Later, Torley had the same experience at Amgen, where she was working on the rheumatoid arthritis drug Enbrel. The head of sales and marketing came into her office and asked if she wanted to head up a business unit, and that opportunity helped her make the difficult transition to enter into a line leadership function that helped prepare her for her future as a CEO. Torley credits having these sponsors who were willing to take a chance on her. “I was probably at 80 percent of the qualifications, but they said ‘I think she’s got the potential, let me sponsor her in this role, support her and help her to be successful.” Unfortunately, women don’t have sponsors as often as men.


The present invention relates to novel pterocarpan compound or pharmaceutically acceptable salt thereof and a composition for the prevention or treatment of metabolic disease or complications thereof comprising the same as an active ingredient. The novel pterocarpan compound of the present invention isolated from soybean leaves inhibits -glucosidase activity and hACAT activity, and suppresses LDL-oxidation efficiently. Therefore, the compound of the present invention not only can be effectively used for the prevention or treatment of metabolic disease or complications thereof but also can be effectively used as an anti-oxidative composition owing to its excellent anti-oxidative activity.


Patent
Bioscience Technology | Date: 2013-09-16

Provided are a complex microbial flora, an application thereof in preparing a textile fabric, a cellulose for use as an additive, and a biological bacterial solution pulp, and a method for using the complex microbial flora. The complex microbial flora comprises Bacillus sp. of deposit number CGMCC No. 5971, Rheinheimera tangshanensis of deposit number CGMCC No. 5972, Acinetobacter Iwoffi of deposit number CGMCC No. 5973, Pseudomonas fluorescens of deposit number CGMCC No. 5974, and Wickerhamomyces anomalus of deposit number CGMCC No. 5975. The method provided comprises: formulation of a bacterial solution, processing of raw materials, and preparation or pulping of the fiber. In one embodiment, the invention generally includes at least one Bacillus. Sp. under CGMCC Deposit No. 5971 alone or in the presence of other microorganisms as a complex microbial flora, and their applications thereof.


Patent
Bioscience Technology | Date: 2013-09-16

Provided are a complex microbial flora, an application thereof in preparing a textile fabric, a cellulose for use as an additive, and a biological bacterial solution pulp, and a method for using the complex microbial flora. The complex microbial flora comprises Bacillus sp. of deposit number CGMCC No. 5971, Rheinheimera tangshanensis of deposit number CGMCC No. 5972, Acinetobacter Iwoffii of deposit number CGMCC No. 5973, Pseudomonas fluorescens of deposit number CGMCC No. 5974, and Wickerhamomyces anomalus of deposit number CGMCC No. 5975. The method provided comprises: formulation of a bacterial solution, processing of raw materials, and preparation or pulping of the fiber. In one embodiment, the invention generally includes at least one Wickerhamomyces anomalus of deposit number CGMCC No. 5975, either alone or in the presence of other microorganisms as a complex microbial flora, and their applications thereof.


Patent
Bioscience Technology | Date: 2013-09-16

Provided are a complex microbial flora, an application thereof in preparing a textile fabric, a cellulose for use as an additive, and a biological bacterial solution pulp, and a method for using the complex microbial flora. The complex microbial flora comprises Bacillus sp. of deposit number CGMCC No. 5971, Rheinheimera tangshanensis of deposit number CGMCC No. 5972, Acinetobacter lwoffii of deposit number CGMCC No. 5973, Pseudomonas fluorescens of deposit number CGMCC No. 5974, and Wickerhamomyces anomalus of deposit number CGMCC No. 5975. The method provided comprises: formulation of a bacterial solution, processing of raw materials, and preparation or pulping of the fiber. In one embodiment, the invention generally includes at least one Pseudomonas fluorescens of deposit number CGMCC No. 5974, either alone or in the presence of other microorganisms as a complex microbial flora, and their applications thereof.


Patent
Bioscience Technology | Date: 2013-09-16

Provided are a complex microbial flora, an application thereof in preparing a textile fabric, a cellulose for use as an additive, and a biological bacterial solution pulp, and a method for using the complex microbial flora. The complex microbial flora comprises Bacillus sp. of deposit number CGMCC No. 5971, Rheinheimera tangshanensis of deposit number CGMCC No. 5972, Acinetobacter lwoffii of deposit number CGMCC No. 5973, Pseudomonas fluorescens of deposit number CGMCC No. 5974, and Wickerhamomyces anomalus of deposit number CGMCC No. 5975. The method provided comprises: formulation of a bacterial solution, processing of raw materials, and preparation or pulping of the fiber. In one embodiment, the invention generally includes at least one Rheinheimera tangshanensis of deposit number CGMCC No. 5972, either alone or in the presence of other microorganisms as a complex microbial flora, and their applications thereof.


Patent
Bioscience Technology | Date: 2013-09-16

Provided are a complex microbial flora, an application thereof in preparing a textile fabric, a cellulose for use as an additive, and a biological bacterial solution pulp, and a method for using the complex microbial flora. The complex microbial flora comprises Bacillus sp. of deposit number CGMCC No. 5971, Rheinheimera tangshanensis of deposit number CGMCC No. 5972, Acinetobacter lwoffii of deposit number CGMCC No. 5973, Pseudomonas fluorescens of deposit number CGMCC No. 5974, and Wickerhamomyces anomalus of deposit number CGMCC No. 5975. The method provided comprises: formulation of a bacterial solution, processing of raw materials, and preparation or pulping of the fiber. In one embodiment, the invention generally includes at least one Acinetobacter lwoffii of deposit number CGMCC No. 5973, either alone or in the presence of other microorganisms as a complex microbial flora, and their applications thereof.

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