Corais servirão de base para pílulas de proteção solar

Corais contra o Sol

Cientistas esperam utilizar o sistema de defesa natural dos corais contra os nocivos raios ultravioleta do Sol (UV) para produzir uma pílula de proteção solar para consumo humano.

Uma equipe da universidade King's College, de Londres, visitou a Grande Barreira de Corais da Austrália para desvendar os processos genéticos e bioquímicos por trás do dom inato destes animais.

Ao estudar algumas amostras da espécie ameaçada de coral Acropora, os cientistas acreditam poder reproduzir em laboratório os principais componentes responsáveis pela proteção solar.

Testes com pele humana devem começar em breve.

Loção de coral

Antes de criar uma versão em forma de comprimido, a equipe, liderada pelo professor Paul Long, pretende testar uma loção contendo os mesmos componentes encontrados no coral.

Para fazer isso, os pesquisadores vão copiar o código genético usado pelos corais para criar os componentes e colocá-los, em laboratório, dentro de bactérias que podem se reproduzir rapidamente, a fim de proporcionar uma produção em grande escala.

"Nós não poderíamos e não quereríamos usar o coral em si, já que ele é uma espécie ameaçada", disse Paul Long.

Corais e algas

Segundo o professor, se sabe há algum tempo que os corais e algumas algas podem proteger-se dos raios UV em climas tropicais ao produzir seus próprios filtros solares, mas, até agora, eles não sabiam como isto ocorria.

"O que nós descobrimos é que as algas que existem dentro dos corais produzem um componente que acreditamos ser transportado para o coral, que então o transforma em um protetor solar, tanto para benefício próprio quanto da alga", afirma Long.

"Isto não só os protege dos danos dos raios UV, mas notamos que os peixes que se alimentam do coral também se beneficiam dessa proteção solar, então isto é claramente passado na cadeia alimentar."

Isto pode ocasionar, em algum momento, que as pessoas possam desenvolver uma proteção solar interior para sua pele e seus olhos ao tomar um comprimido contendo esses componentes.

Loção anti-UV

Mas, por enquanto, a equipe de Long está concentrando seus esforços em uma loção.

"Assim que nós recriarmos os componentes, poderemos colocá-los em uma loção e testá-la em pedaços de pele descartados depois de cirurgias plásticas", diz Long.

"Nós não saberemos quanta proteção solar (a loção) poderá dar até que estejamos realizando testes", afirma. "Mas há a necessidade de melhores protetores solares."

Outro objetivo de longo prazo do estudo, financiado pelo Conselho de Pesquisa em Ciências Biotecnológicas e Biológicas britânico, é observar se os processos também podem ser usados para desenvolver a agricultura sustentável nos países em desenvolvimento.

Os componentes naturais de proteção solar encontrados nos corais podem ser usados para produzir lavouras tolerantes aos raios UV, capazes de suportar a violência do Sol em climas tropicais.

Descoberta sobre parasita pode gerar vacina contra malária

Químico crucial

Cientistas descobriram que um único composto químico é crucial para o efeito infeccioso da malária.

Ao investigar a biologia do parasita da malária, o grupo da Universidade da Califórnia (EUA) descobriu que esse composto é responsável pela capacidade de sobrevivência e reprodução do parasita na corrente sanguínea humana.

A descoberta dá aos pesquisadores uma ferramenta poderosa para o desenvolvimento de novos medicamentos para tratar a malária, que infecta milhões de pessoas todos os anos em todo o mundo, matando sobretudo crianças.

Vacina contra malária

O trabalho pode gerar imediatamente uma potencial nova vacina contra a malária, na forma de uma versão enfraquecida do parasita.

Essa versão foi desenvolvida artificialmente em laboratório, suprida com o químico que ela precisa para viver, mas simultaneamente tratada com drogas para destruir sua capacidade de produzir esse químico por contra própria.

O objetivo dos pesquisadores é aplicar essa forma atenuada do parasita para dar aos pacientes uma resistência ao patógeno natural. Para isso, eles planejam solicitar autorização para iniciar os testes em humanos.

Já está em testes uma outra vacina contra a malária. que atua sobre o sistema imunológico humano.

Sumiço do mosquito da malária

Várias abordagens têm sido tentadas nas últimas décadas em busca da erradicação da malária, mas a doença persiste em vários países.

Um fato intrigante, detectado recentemente, é que os mosquitos da malária estão desaparecendo misteriosamente na África, com uma queda drástica no número de infecções.

Embora pareça ser uma boa notícia, os cientistas temem que a doença volte reforçada nos próximos anos.

Vírus ataca e destrói câncer infantil

Sarcomas de tecidos moles

Cientistas da Universidade de Yale, nos Estados Unidos, estão estudando um vírus da mesma família do vírus da raiva para combater um tipo de câncer encontrado principalmente em crianças e adultos jovens.

Sarcomas de tecidos moles são cânceres que se desenvolvem em tecidos que conectam, dão suporte ou circundam outras estruturas e órgãos do corpo.

Músculos, tendões, tecidos fibrosos, gordura, vasos sanguíneos, nervos e tecidos sinoviais são exemplos de tecidos moles.

Embora relativamente raros em adultos, esses sarcomas representam aproximadamente 15% das neoplasias malignas pediátricas e resultam em morte em aproximadamente um terço dos pacientes até cinco anos depois do diagnóstico.

Vírus oncolítico

O vírus da estomatite vesicular (VSV) é um rabdovírus, que é a mesma família de vírus como o da raiva. Ele causa uma doença semelhante à febre aftosa em bovinos.

Uma pesquisa recente descobriu que o vírus também é oncolítico, o que significa que ele procura e destrói tumores cancerígenos.

Estudos anteriores também já demonstraram que o VSV é promissor no tratamento de tumores cerebrais em camundongos.

Neste estudo, os pesquisadores investigaram o potencial do VSV e de uma versão oncoliticamente melhorada do vírus da estomatite vesicular (VSV-rp30a) para efetivamente alvejar e matar 13 sarcomas diferentes.

Agente oncolítico

As duas linhagens do vírus efetivamente infectaram e mataram 12 dos 13 sarcomas.

A resistência do sarcoma sobrevivente foi finalmente superada com um pré-tratamento com compostos que antagonizam a sinalização interferon.

Adicionalmente, os cientistas analisaram a capacidade do VSV-rp30a para infectar e evitar o crescimento de tumores.

"Uma única injeção intravenosa do VSV-rp30a infectou seletivamente todos os sarcomas subcutâneos humanos testados em camundongos e impediu o crescimento de tumores que cresceriam 11 vezes [se não tratados]," escrevem os pesquisadores.

"No geral, achamos que a eficácia potencial do VSV como um agente oncolítico estende-se a tumores mesodérmicos não-hematológicos e que a resistência invulgarmente forte à oncólise do VSV pode ser superada com atenuadores de interferon," concluem.

New HIV Vaccine Approach Targets Desirable Immune Cells

ScienceDaily (Sep. 1, 2011) — Researchers at Duke University Medical Center, Beth Israel Deaconess Medical Center and Harvard Medical School have demonstrated an approach to HIV vaccine design that uses an altered form of HIV's outer coating or envelope protein.

The researchers showed that they could design HIV envelopes that could bind better to immature B cell receptors to create an enhanced immune response in an animal model. Immature B cells are the targets of vaccines, and when strongly targeted, they produce strong vaccine responses. The work of the Duke team was to improve on the ability of the HIV envelope to target immature B cells of the immune system.

"This is first step towards a new way of making vaccines against HIV: targeting immature immune cells and attempting to drive a pathway of events that rarely occur," said Barton Haynes, M.D., co-senior author and director of the national Center for HIV-AIDS Vaccine Immunology (CHAVI) laboratory and Frederic M. Hanes Professor of Medicine and Immunology at Duke University School of Medicine. "This avenue of research provides additional evidence about why some of the earlier, traditional vaccine approaches for HIV may not have been successful."

The study was published in the Sept. 1 issue of PLoS Pathogens.

Handcrafting vaccines that will stimulate different stages of the pathway toward immunity looks to be important, Haynes said. A vaccine usually uses a part of the virus (like part of its outer coating) or a harmless form of the virus to create a strong immune response against the virus.

This new work is the first time researchers have made an HIV envelope that binds better to precursor antibodies and also stimulates better immunity, compared with a natural envelope, in primates.

Hua-Xin Liao, M.D., Ph.D., a professor of medicine in the Duke Human Vaccine Institute (DHVI) and co-senior author, created the altered HIV outer coats. "Roadblocks thrown up by HIV have plagued HIV vaccine development," Liao said. "HIV hides its Achilles' heels of vulnerability on its outer coat by covering them with sugars. This covering is the result of virus mutations as the virus became resistant to antibodies."

The researchers found that the sugars on the natural HIV envelope prevented the envelope from binding to the immature B cell receptors that scientists want to trigger with a vaccine. So human and animal B cells fail to make antibodies against the HIV envelope's vulnerable spots when natural HIV envelope is injected as a vaccine candidate, even though these viral envelopes are the target of protective, neutralizing antibodies.

"We found that when you remove the sugars from the envelope proteins, you can create an envelope that targets those immature B cell receptors," said Haynes, who is also director of the DHVI.

"After the initial results, we completed a study in primates, which are similar to humans in terms of their genetics and their immune systems," Haynes said. "When they were given the HIV outer coat with many of the sugars removed, this sugar-depleted envelope bound better to the immature B cell receptors and stimulated antibodies better, which is a first step in the HIV-1 envelope activating an immature B cell target that previously it could not target."

Dimiter Dimitrov at the National Cancer Institute has previously shown that the natural HIV envelope protein frequently does not target immature B cells.

"The importance of this new finding is that it not only provides evidence for our hypothesis, but also for the first time it has identified envelope-based immunogens capable of binding to putative antibody germline predecessors that correlated with enhanced immunogenicity in animals," Dimitrov said.

Investigators have found that pathways for inducing the "right" kind of antibodies may be blocked or are unusual and are not routinely followed by HIV envelope-induced antibodies. John Mascola, Peter Kwong and colleagues at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID) have shown that very complex, broadly neutralizing B cell maturation pathways may require targeting early B cell receptors.

"This is an important step forward," said Nelson Michael, director of the Military HIV Research Program at the Walter Reed Army Institute of Research. "The observation that improving envelope immunogen binding to immature B cell receptors can improve immunogenicity provides new hope for design of strategies for inducing difficult-to-induce neutralizing antibodies."

Norman Letvin, a professor of medicine in immunology at Harvard, performed the envelope immunizations in rhesus macaques. "These new envelope immunogens are the first step towards driving immature B cells through new pathways to make HIV-protective antibodies," Letvin said.

Other authors include Ben-Jiang Ma, S. Cindy Bowman, Laura L. Sutherland, Richard M. Scearce, Xiaozhi Lu and Munir Alam of DHVI (Alam is also with the Duke Department of Medicine); Georgia D. Tomaras of DHVI, and the Duke Departments of Surgery and Immunology; Thomas B. Kepler of the Duke Center for Computational Immunology; Eden P. Go and Heather Desaire of the Department of Chemistry at the University of Kansas; and Sampa Santra of the Beth Israel Deaconess Medical Center, Harvard Medical School.

The work was supported by the NIAID, part of the National Institutes of Health, through a grant to the Center for HIV/AIDS Vaccine Immunology (CHAVI). The study also was funded by the Bill & Melinda Gates Foundation through a Collaboration for HIV Vaccine Discovery grant.

How White Blood Cell Promotes Growth and Spread of Cancer

ScienceDaily (Sep. 1, 2011) — Scientists at The Scripps Research Institute have shown that a particular white blood cell plays a direct role in the development and spread of cancerous tumors. Their work sheds new light on the development of the disease and points toward novel strategies for treating early-stage cancers.
The study was published in September 2011 print issue of theAmerican Journal of Pathology.

Scripps Research Professor James Quigley, Staff Scientist Elena Deryugina, and colleagues had previously demonstrated that white blood cells known as neutrophils -- bone marrow-derived cells that function as "first responders" at sites of acute inflammation -- promote the growth of new blood vessels in normal, healthy tissue.

The team has now tied these cells to the induction and growth of new blood vessels in malignant tumors and to the spread of tumor cells through those newly formed vessels. The scientists have also uncovered some of the mechanisms underpinning this process -- which could be interrupted by properly targeted drugs.

Potent and Uninhibited

The Scripps Research team has been particularly interested in neutrophils, in part because several studies have demonstrated a link between elevated neutrophil levels and high rates of tumor invasion among cancer patients. Mounting evidence has also indicated that neutrophils play a particularly important role during the early stages of tumor development.

"During tumor development, neutrophils appear to be one of the first inflammatory cell types on the scene," said Deryugina, who spearheaded the new study.

The researchers have been especially interested in the blood vessel-forming or "angiogenic," powers of neutrophils, which stem from a special enzyme they produce known as MMP-9 (matrix metalloproteinase type 9). The enzyme is, in fact, synthesized by a number of different types of white blood cells and has long been linked to tumor development. But the particular form synthesized by neutrophils is especially potent, in part because it does not come bound up with the natural inhibitory regulating agents that other cells supply.

Whereas other types of white blood cells only manufacture the enzyme later and invariably deliver it in combination with one of its natural inhibitors, neutrophils come loaded with pre-synthesized MMP-9 in a form that is unencumbered.

Making the Case

In a series of cleverly designed experiments, Quigley, Deryugina, and colleagues established a link between neutrophils, their MMP-9, and the growth and spread of tumors.

The scientists alternately raised and lowered the quantity of neutrophils allowed to flow into two different kinds of early-stage tumors, which had been transplanted into chicken embryos and mice. They also introduced several different versions of the enzyme, sometimes combining it with dampening agents, sometimes not.

By observing the subsequent decrease and increase in the formation of new blood vessels, the Scripps Research team was able to establish that the unique form of the enzyme delivered by neutrophils was directly responsible for heightening the growth of new blood vessels in the tumors. Just as importantly, they were able to determine that the newly formed blood vessels served as "escape routes" or conduits for the spread of tumor cells beyond their initial location.

First, the scientists established that the most aggressive tumors -- that is, the ones that were able to most quickly penetrate the surrounding blood vessels and spread to different areas -- depended on their ability to attract large numbers of neutrophils.

The researchers then proceeded to spur the growth of new blood vessels in even relatively nonaggressive tumors by supplying additional quantities of neutrophil-derived enzyme. They also blocked the formation of new vessels with the anti-inflammatory drug ibuprofen and then restored, or "rescued," angiogenesis by pumping in additional enzyme.

Quigley and Deryugina also drastically reduced the influx of neutrophils by neutralizing IL-8 (interleukin 8), the chemical attractant that draws neutrophils to sites of inflammation. Blood vessel formation declined correspondingly, as did the penetration of vessels by tumor cells, clearly linking neutrophils to the development and spread of two different, but highly aggressive, forms of cancer. To further strengthen that link, the researchers again reversed the decline with an infusion of neutrophil-derived enzyme.

"By dampening neutrophil influx into tumors, we dampen angiogenesis, but we also dampen metastasis," Quigley said. "And when we rescue angiogenesis, we also rescue the high metastatic rate of the tumors."

Significantly, only the unregulated, uninhibited version of the enzyme provided by neutrophils reversed the dampening effect caused by reducing inflammation or cutting off the flow of neutrophils. No such rescue occurred when the enzyme was combined with its natural inhibiting agents -- the same molecules that accompany the enzyme when it is delivered by other kinds of white blood cells.

Intriguing Possibilities

The scientists note that the study suggests tumors that engender a strong inflammatory response may be particularly amenable to early-stage treatment by drugs that specifically target neutrophils, whether that means inhibiting the enzyme they deliver or simply preventing them from showing up in the first place.

"It might be best to combat tumor angiogenesis earlier rather than later," Quigley said, adding that "more specifically directed anti-neutrophil agents might be better suited than a general anti-inflammatory." The Quigley lab continues to investigate.

Support for this study came from the National Institutes of Health, Scripps Translational Science Institute, the Max Kade Foundation, and the National Cancer Institute.

Medicinal Chemists Modify Sea Bacteria Byproduct for Use as Potential Cancer Drug

ScienceDaily (Sep. 1, 2011) — University of Florida researchers have modified a toxic chemical produced by tiny marine microbes and successfully deployed it against laboratory models of colon cancer.

Writing August 31 in ACS Medicinal Chemistry Letters, UF medicinal chemists describe how they took a generally lethal byproduct of marine cyanobacteria and made it more specifically toxic -- to cancer cells.

When the scientists gave low doses of the compound to mice with a form of colon cancer, they found that it inhibited tumor growth without the overall poisonous effect of the natural product. Even at relatively high doses, the agent was effective and safe.

"Sometimes nature needs a helping human hand to further optimize these products of evolution to treat human diseases," said Hendrik Luesch, Ph.D., an associate professor of medicinal chemistry at UF's College of Pharmacy. "Based on what we learned about apratoxins' mechanism of action, we knew this compound class had great potential for use in anticancer therapies; however, the natural product itself is too toxic to become a therapeutic."

The researchers synthesized several apratoxin compounds that were similar to the original except for slight differences in composition, designing one that proved to be extremely potent against the cancer cells in cultures and in mice, but without the overwhelming toxicity.

The compound acts as a single agent to reduce levels of two types of proteins that are targeted by cancer research labs around the world -- growth factors, and enzymes called tyrosine kinases, which act as receptors for the growth factors.

Known as apratoxin S4, the compound strips colon cancer cells of their ability to both secrete and use naturally occurring factors that fuel growth -- something that Luesch, postdoctoral chemist Oi-Yen Chen, Ph.D., and assistant scientist Yanxia Liu, Ph.D., say is a powerful "one-two punch" against mushrooming populations of cancer cells.

The trio describes apratoxin's dual action for the first time in the current publication, although Luesch presented early findings in May at the New York Academy of Sciences.

"This is an extremely interesting discovery that may have the potential to lead to a novel drug, but an extraordinary amount of additional research is needed before we will know. We can hope," said David J. Newman, D.Phil., chief of the National Cancer Institute's Natural Products Branch, who was not involved in the research. "Luesch has found a novel compound and a novel mechanism of action that stops the secretion of the receptor and the growth factor -- as far as I am aware, this mechanism has only been shown in apratoxin at this time. If nothing else, he has shown us a new way to kill tumor cells and has revealed a new chemistry, and those are important steps."

Apratoxin is produced by cyanobacteria, microbes that have evolved toxins to fend off predators and cope with harsh conditions in a marine environment. Collectively known as blue-green algae -- a misnomer because the single-celled organisms are not algae or members of the plant kingdom -- a wide variety of cyanobacteria species exists in both sea and freshwater environments.

Like plants, cyanobacteria convert sunlight into energy through a process known as photosynthesis. But where plants exclusively use a green pigment called chlorophyll to capture light to make food, cyanobacteria also use a bluish pigment called phycocyanin.

In addition, cyanobacteria have the unique ability to use respiration as well as photosynthesis to acquire energy, making these organisms tiny chemical factories capable of producing many as-yet unidentified molecules that may be useful for health applications.

"Marine cyanobacteria produce a huge diversity of compounds," said Luesch, who is also a member of the UF Shands Cancer Center. "About half of anticancer drugs are based on natural products. All but a couple of them are derived from terrestrial organisms, yet more than 70 percent of the Earth is covered by oceans, which presumably contain a number of therapeutic molecules with potentially novel biological activities. When we studied the biological effects of apratoxin, we predicted it would be particularly useful against colon cancer if we could engineer it to be more selective."

Chen synthesized the apratoxins, while Liu carried out the biology and pharmacology experiments. More lab work is required before a drug based on apratoxin can be tested in patients with colon cancer, but Luesch believes apratoxin S4 is the first candidate to show the needed tumor selectivity, antitumor effects and potency to be effective. The UF Research Opportunity Fund and the Bankhead-Coley Cancer Research Program supported the study.

Faster Diagnostics Through Cheap, Ultra-Portable Blood Testing

ScienceDaily (Sep. 1, 2011) — Blood tests are important diagnostic tools. They accurately tease-out vanishingly small concentrations of proteins and other molecules that help give a picture of overall health or signal the presence of specific diseases. Current testing procedures, however, are expensive and time-consuming, while sophisticated test equipment is bulky and difficult to transport.

Illustration of the Surface Plasmon Resonance (SPR) system for selective blood protein sensing. Detection and monitoring is achieved through measuring the degree of reflected light from a disposable functionalized SPR microfluidic chip. The measured reflectance signal is directly related to the conditions for excitation of surface plasmons at the gold surface caused by the degree of thrombin binding.

Now, a team of researchers from the University of Toledo in Ohio has addressed all these drawbacks by developing a low-cost, portable technique that is able to quickly and reliably detect specific proteins in a sample of human blood. This innovative technique, described in the Sept. 1 issue of the Optical Society's (OSA) open-access journalBiomedical Optics Express, could help in a wide range of medical sensing applications, including diagnosing diseases like cancer and diabetes long before clinical symptoms arise.

"The detection and measurement of specific blood proteins can have a huge impact on numerous applications in medical diagnostic sensing," says Brent D. Cameron with the department of bioengineering at the University of Toledo, one of the paper's authors. "This method has the potential to provide similar functionality of large and costly clinical instrumentation currently used to identify and quantify blood proteins for a fraction of current costs."

Human blood contains literally thousands of different proteins. Many are essential for the day-to-day mechanics of life. Others are formed only in response to certain diseases. Knowing which protein is the hallmark of an illness and singling it out of a blood sample leads to earlier diagnosis and more effective treatment. An example of this is the prostate-specific antigen (PSA), which is now routinely tested for to help detect prostate cancer and other prostate abnormalities in men.

In this new system, the researchers borrowed a trick from nature, using artificially created molecules called aptamers to latch on to free-floating proteins in the blood. Aptamers are custom-made and commercially available short strands of nucleic acid. In some ways, they mimic the natural behavior of antibodies found in the body because they connect to one type of molecule, and only one type. Specific aptamers can be used to search for target compounds ranging from small molecules -- such as drugs and dyes -- to complex biological molecules such as enzymes, peptides, and proteins.

Aptamers, however, have advantages over antibodies in clinical testing. They are able to tolerate a wide range of pH (acid and base environments) and salt concentrations. They have high heat stability, are easily synthesized, and cost efficient.

For their demonstration, the researchers chose thrombin and thrombin-binding aptamers. Thrombin is a naturally occurring protein in humans that plays a role in clotting.

The researchers affixed the aptamers to a sensor surface, in this case a glass slide coated with a nanoscale layer of gold. As the blood sample is applied to the testing surface, the aptamer and their corresponding proteins latched together.

The next step is to actually determine if the couples pairing was successful. To make this detection, the researchers used a real-time optical sensing technique known as Surface Plasmon Resonance (SPR). A surface plasmon is a "virtual particle," created by the wave-motion of electrons on the surface of the sensor. If the protein is present and has bound to the aptamer, conditions for which resonance will occur at the gold layer will change. This resonance change is detected through a simple reflectance technique that is coupled to a linear detector.

"By monitoring these conditions, we can quantify the amount of the target protein that is present; even at very low concentrations," says Cameron. "This approach is very robust in that unique aptamers for almost any given protein can be identified. This makes the technique very specific and adaptable for any given application." The approach also requires less-bulky optics, which is the key to the portability aspect of the design.

Aptamer sensors, according to the researchers, are also capable of being reversibly denatured, meaning they can easily release their target molecules, which makes them perfect receptors for biosensing applications.

"The advantage of this surface plasmon sensor," says Cameron, "is that it enabled us to demonstrate low sample consumption, high sensitivity, and fast response time." The direct detection of blood proteins in this manner can benefit a number of scientific and clinical applications, such as monitoring diabetes, drug research, environmental monitoring, and cancer diagnosis.

For commercial use in medical diagnostics, according to Cameron, the technology is three to five years away, pending FDA procedures and filings. "The time frame is very dependent on the target application area. We are currently in the procedure of determining suitable aptamers for a range of target proteins for both diabetic and cancer-related applications," he says.