Cominho combate radicais livres e protege o DNA

Cominho

O cominho é usado extensivamente na medicina tradicional para tratar uma variedade de doenças, do vitiligo à hiperglicemia.

A planta é considerada como antiparasitária e antimicrobiana e a ciência tem repetidamente verificado sua eficácia para reduzir a febre, ou como um analgésico.

Agora, uma nova pesquisa mostra que a humilde especiaria também contém altos níveis de antioxidantes.

Radicais livres

As chamadas espécies reativas de oxigênio, mais conhecidas como radicais livres, são produzidas naturalmente, como parte dos processos metabólicos necessários à vida.

O estresse oxidativo, no entanto, é causado por uma superprodução ou sub-remoção desses radicais livres.

O estresse oxidativo está ele próprio envolvido em uma série de doenças, incluindo aterosclerose, doença degenerativa neural, inflamação, câncer e envelhecimento precoce.

Antioxidantes

Acredita-se que os antioxidantes eliminem os radicais livres, reduzam o estresse oxidativo e previnam doenças.

Os compostos fenólicos das plantas, especialmente os compostos polifenólicos, são muitas vezes considerados antioxidantes.

Um grupo de pesquisadores agora usou técnicas bioquímicas e biológicas para mostrar que as sementes do cominho (Centratherum anthelminticum (L.) Kuntze), um membro da família da margarida, representam uma rica fonte de antioxidantes fenólicos.

"Os extratos de cominho mostraram-se fortes antioxidantes nos sistemas testados. Os extratos também mostraram-se grandes doadores de elétrons e, portanto, agentes redutores, outro marcador da antioxidação," afirmam os cientistas do Central Food Technological Research Institute, na Índia.

Proteção do DNA

Nos testes biológicos, o cominho inibiu a oxidação dos lipossomas usados como modelo para a oxidação da membrana celular e ofereceu proteção total contra danos ao DNA, segundo os cientistas.

"A quantidade de fenóis que conseguimos extrair e a atividade antioxidante do cominho dependeu do método utilizado. No entanto, a atividade antioxidante do cominho está correlacionado com o teor de fenóis totais.

Por isso, uma série de compostos fenólicos dentro das sementes de cominho devem ser os responsáveis pela atividade antioxidante verificada," concluíram os cientistas.

Epigenética dá novas informações sobre o câncer de mama

Epigenética

A mais completa análise já feita das modificações epigenéticas presentes no câncer de mama revelou informações novas e importantes tanto para a detecção quanto para o tratamento da doença.

A epigenética é um termo usado para descrever alterações na molécula de DNA que afetam a forma como seu código é traduzido em proteínas.

A metilação é o principal mecanismo epigenético: um grupo metil é transferido para algumas bases de citosina do DNA. O processo é fundamental para "desligar" os genes que provocam alterações na transcrição genética.

O que controla nossos genes? Primeiro epigenoma humano está pronto

Metilação do DNA

Embora os pesquisadores já soubessem que a epigenética é importante no câncer em geral, ainda são escassas as informações sobre o seu papel especificamente para o câncer de mama.

"Nosso objetivo foi avaliar as diferenças epigenéticas entre o tecido normal e amostras do tumor primário em escala genômica, à semelhança do que tem sido feito para os padrões de expressão gênica," explicou a Dra. Sarah Dedeurwaerder, da Universidade Livre de Bruxelas, na Bélgica.

O grupo realizou um perfil completo da metilação do DNA em dois conjuntos independentes de amostras de tecidos congelados de mama: um conjunto principal de 123 amostras e um conjunto de validação, de 125 amostras.

Sub-tipos de câncer de mama

A primeira descoberta foi que dois sub-tipos importantes de câncer da mama são fortemente controlados epigeneticamente.

"Quando realizamos uma análise de agrupamento das nossas amostras com base em seus perfis de metilação do DNA, os tumores segregaram-se naturalmente em dois grupos distintos," disse a pesquisadora.

O primeiro grupo compõe-se principalmente de tumores receptor-negativos de estrogênio, e o segundo grupo de tumores receptor-positivos de estrogênio. "Isso indica que os tumores ER-negativos e ER-positivos têm perfis de metilação muito diferentes," disse ela.

Resposta aos medicamentos

A análise também revelou novas informações sobre novos sub-tipos de câncer de mama - os perfis de metilação do DNA permitem que os tumores de mama sejam classificados em mais grupos do que é feito hoje.

Isto é importante porque, hoje, pacientes classificadas no mesmo sub-grupo respondem de maneira diferente aos medicamentos - agora ficou claro que a classificação até então usada não é suficiente.

De posse de uma classificação mais precisa e mais abrangente, os médicos poderão prever melhor a resposta a cada tipo de tratamento. Futuramente, novos tratamentos poderão ser desenvolvidos para cada sub-tipo da doença.

New Nanoscale Imaging May Lead to New Treatments for Multiple Sclerosis

ScienceDaily (May 23, 2011) — Laboratory studies by chemical engineers at UC Santa Barbara may lead to new experimental methods for early detection and diagnosis -- and to possible treatments -- for pathological tissues that are precursors to multiple sclerosis and similar diseases.

These are fluorescence images of lipid domains in model (laboratory reconstituted) myelin monolayers showing coexistence of liquid-ordered (dark) and liquid-disordered (pseudo-colored) phases. Depending on the conditions (e.g., liquid-disordered (pseudo-colored) phases. Depending on the conditions (e.g., lipid composition, surface pressure, temperature), the lipid domains can exist in various shapes including striped (left) and circular (right).

Achieving a new method of nanoscopic imaging, the scientific team studied the myelin sheath, the membrane surrounding nerves that is compromised in patients with multiple sclerosis (MS).

The study is published in this week's online edition of the Proceedings of the National Academy of Sciences(PNAS).

"Myelin membranes are a class of biological membranes that are only two molecules thick, less than one millionth of a millimeter," said Jacob Israelachvili, one of the senior authors and professor of chemical engineering and of materials at UCSB. "The membranes wrap around the nerve axons to form the myelin sheath."

He explained that the way different parts of the central nervous system, including the brain, communicate with each other throughout the body is via the transmission of electric impulses, or signals, along the fibrous myelin sheaths. The sheaths act like electric cables or transmission lines.

"Defects in the molecular or structural organization of myelin membranes lead to reduced transmission efficiency," said Israelachvilli. "This results in various sensory and motor disorders or disabilities, and neurological diseases such as multiple sclerosis."

At the microscopic level and the macroscopic level, which is visible to the eye, MS is characterized by the appearance of lesions or vacuoles in the myelin, and eventually results in the complete disintegration of the myelin sheath. This progressive disintegration is called demyelination.

The researchers focused on what happens at the molecular level, commonly referred to as the nanoscopic level. This requires highly sensitive visualization and characterization techniques.

The article describes fluorescence imaging and other measurements of domains, which are small heterogeneous clusters of lipid molecules -- the main constituents of myelin membranes -- that are likely to be responsible for the formation of lesions. They did this using model molecular layers in compositions that mimic both healthy and diseased myelin membranes.

They observed differences in the appearance, size, and sensitivity to pressure, of domains in the healthy and diseased monolayers. Next, they developed a theoretical model, in terms of certain molecular properties, that appears to account quantitatively for their observations.

"The discovery and characterization of micron-sized domains that are different in healthy and diseased lipid assemblies have important implications for the way these membranes interact with each other," said Israelachvili. "And this leads to new understanding of demyelination at the molecular level."

The findings pave the way for new experimental methods for early detection, diagnosis, staging, and possible treatment of pathological tissues that are precursors to MS and other membrane-associated diseases, according to the authors.

All of the work reported in the paper was completed at UCSB, although some of the authors have moved to other institutions. In addition to Israelachvili, the other authors are Dong Woog Lee, graduate student in UCSB's Department of Chemical Engineering; Younjin Min, now a postdoctoral fellow in the Department of Chemical Engineering at the Massachusetts Institute of Engineering; Prajnaparamitra Dhar, now assistant professor in the Department of Chemical Engineering at the University of Kansas; Arun Ramachandran, now assistant professor in the Department of Chemical Engineering and Applied Chemistry at the University of Toronto; and Joseph A. Zasadzinski, now professor in the Department of Chemical Engineering and Materials Science at the University of Minnesota.

A New Program for Neural Stem Cells

ScienceDaily (May 23, 2011) — Neural stem cells can do a lot, but not everything. For example, brain and spinal cord cells are not usually generated by neural stem cells of the peripheral nervous system, and it is not possible to produce cells of the peripheral nervous system from the stem cells of the brain. However, researchers from the Max Planck Institute for Brain Research in Frankfurt and the Max Planck Institute of Immunobiology and Epigenetics in Freiburg have now succeeded in producing central nervous system cells from neural stem cells of the peripheral nervous system. They found that if peripheral stem cells are maintained under defined growth conditions, they generate oligodendrocytes, which form the myelin layer that surrounds the neurons found in the brain and spinal cord.

Transplantation of reprogrammed neural stem cells into the brains of genetically modified mice, which cannot form myelin. The stem cells develop oligodendrocytes (green), which form myelin (red)

The mammalian nervous system consists of a central (brain, spinal cord) and peripheral nervous system (e.g. nerves and sensory ganglia). Although the two systems are very closely interlinked, they differ anatomically and consist of different cell types. The cell types of the peripheral nervous system originate from precursor cells in the embryo called the neural crest. To date, it was believed that these neural crest stem cells could generate the neurons and support cells, known as glial cells, of the peripheral nervous system, but not the cells of the central nervous system.

Environmental conditions clearly determine the kind of cells into which the neural crest stem cells develop. Together with colleagues from Paris, the Freiburg- and Frankfurt-based scientists succeeded in demonstrating that, under modified conditions, these stem cells can also generate cells of the central nervous system. They exposed stem cells from the peripheral nervous system of embryonic or postnatal mice to different culture conditions. In addition to neurons, the neural crest stem cells also developed into different types of glial cells of the central nervous system, including oligodendrocytes and astrocytes. "The culture medium reprograms the neural crest stem cells in such a way that they change their identity. This worked without genetic modification of the cells," explains Hermann Rohrer from the Max Planck Institute for Brain Research.

Factors in the culture medium clearly activated a different genetic program so that cell types developed from the stem cells, which normally would not. The scientists do not yet understand the precise factors at work here. However, there are some indications that fibroblast growth factor (FGF) is involved in this transformation.

In the brains of mice at different developmental stages, the reprogrammed stem cells mainly developed into oligodendrocytes, which form the myelin layer around the neurons of the central nervous system and are, therefore, indispensable for the transmission of electrical stimuli. Transplantation experiments carried out by the researchers on genetically modified mice that do not produce myelin and have severe neurological defects proved that the new oligodendrocytes can also assume this task. "The reprogrammed stem cells can form cells of the central nervous system, and the new cells can permanently integrate into this system," says Verdon Taylor of the Max Planck Institute of Immunobiology and Epigenetics.

It is not yet clear, to what extent these basic research findings will contribute to the development of cell therapy for humans. This would require that similar stem cells are present and accessible in the peripheral nervous system of humans, and that these can be propagated and reprogrammed in culture. "At present, we only know that these stem cells in mice also have the potential to produce oligodendrocytes," says Hermann Rohrer. The scientists would now like to investigate in greater detail which molecular mechanisms are responsible for the reprogramming of the stem cells, whether neural crest stem cells also exist in the peripheral nervous system of adult mice and what kind of conditions are required to enable the reprogramming of these cells.

Human Brain's Most Ubiquitous Cell Cultivated in Lab Dish

ScienceDaily (May 23, 2011) — Pity the lowly astrocyte, the most common cell in the human nervous system. Long considered to be little more than putty in the brain and spinal cord, the star-shaped astrocyte has found new respect among neuroscientists who have begun to recognize its many functions in the brain, not to mention its role in a range of disorders of the central nervous system.

Astrocytes are star-shaped cells that are the most common cell in the human brain and have now been grown from embryonic and induced stem cells in the laboratory of UW-Madison neuroscientist Su-Chun Zhang. Once considered mere putty or glue in the brain, astrocytes are of growing interest to biomedical research as they appear to play key roles in many of the brain's basic functions, as well as neurological disorders ranging from headaches to dementia. In this picture astrocyte progenitors and immature astrocytes cluster to form an "astrosphere." The work was conducted at UW-Madison's Waisman Center.

Now, writing in the May 22 issue of the journal Nature Biotechnology, a group led by University of Wisconsin-Madison stem cell researcher Su-Chun Zhang reports it has been able to direct embryonic and induced human stem cells to become astrocytes in the lab dish.

The ability to make large, uniform batches of astrocytes, explains Zhang, opens a new avenue to more fully understanding the functional roles of the brain's most commonplace cell, as well as its involvement in a host of central nervous system disorders ranging from headaches to dementia. What's more, the ability to culture the cells gives researchers a powerful tool to devise new therapies and drugs for neurological disorders.

"Not a lot of attention has been paid to these cells because human astrocytes have been hard to get," says Zhang, a researcher at UW-Madison's Waisman Center and a professor of neuroscience in the UW-Madison School of Medicine and Public Health. "But we can make billions or trillions of them from a single stem cell."

Although astrocytes have gotten short shrift from science compared to neurons, the large filamentous cells that process and transmit information, scientists are turning their attention to the more common cells as their roles in the brain become better understood. There are a variety of astrocyte cell types and they perform such basic housekeeping tasks as helping to regulate blood flow, soaking up excess chemicals produced by interacting neurons and controlling the blood-brain barrier, a protective filter that keeps dangerous molecules from entering the brain.

Astrocytes, some studies suggest, may even play a role in human intelligence given that their volume is much greater in the human brain than any other species of animal.

"Without the astrocyte, neurons can't function," Zhang notes. "Astrocytes wrap around nerve cells to protect them and keep them healthy. They participate in virtually every function or disorder of the brain."

The ability to forge astrocytes in the lab has several potential practical outcomes, according to Zhang. They could be used as screens to identify new drugs for treating diseases of the brain, they can be used to model disease in the lab dish and, in the more distant future, it may be possible to transplant the cells to treat a variety of neurological conditions, including brain trauma, Parkinson's disease and spinal cord injury. It is possible that astrocytes prepared for clinical use could be among the first cells transplanted to intervene in a neurological condition as the motor neurons affected by the fatal amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, are swathed in astrocytes.

"With an injury or neurological condition, neurons in the brain have to work harder, and doing so they make more neurotransmitters," chemicals that in excess can be toxic to other cells in the brain, Zhang says.

"One idea is that it may be possible to rescue motor neurons by putting normal, healthy astrocytes in the brain," according to Zhang. "These cells are really useful as a therapeutic target."

The technology developed by the Wisconsin group lays a foundation to make all the different species of astrocytes. What's more, it is possible to genetically engineer them to mimic disease so that previously inaccessible neurological conditions can be studied in the lab.

In addition to Zhang, co-authors of the new Nature Biotechnology paper include Robert Krencik, Jason Weick and Zhijian Zhang, all of UW-Madison, and Yan Liu of Fudan University Shanghai Medical School. The work was supported by the ALS Foundation, the National Institute of Neurological Disorders and Stroke, the National Multiple Sclerosis Society, the Bleser Family Foundation and the Busta Family Foundation.