Roles for mesenchymal stem cells as medicinal signaling cells

Understanding the in vivo identity and function of mesenchymal stem cells (MSCs) is vital to fully exploiting their therapeutic potential. New data are emerging that demonstrate previously undescribed roles of MSCs in vivo. Understanding the behavior of MSCs in vivo is crucial as recent results suggest these additional roles enable MSCs to function as medicinal signaling cells. This medicinal signaling activity is in addition to the contribution of MSCs to the maintenance of the stem cell niche and homeostasis.

There is increasing evidence that not all cells described as MSCs share the same properties. Most MSCs reside in a perivascular location and have some functionalities in common with those of the pericytes and adventitial cells located around the microvasculature and larger vessels, respectively. 

Here we focus on the characteristics of MSCs that have been demonstrated to be similar to those of pericytes located around the microvasculature, defined as perivascular MSCs (pMSCs). Although we focus here on pMSCs, it is important to bear in mind that pericytes are found in many types of blood vessels, and that not all pericytes are thought to be MSCs.

Read more: Roles for mesenchymal stem cells as medicinal signaling cells

Source: NatureReviews

Hepatocellular carcinoma

Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. 

Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies — resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate- and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches.

Read more: Hepatocellular carcinom

Source: NatureReviews

Autistic people have higher gene mutations but lesser risk to cancer

While people with autism have more cancer-related gene mutations, they are at lower risk for developing the disease. This is the conclusion of a new study by researchers from the University of Iowa.

Autism is a developmental disorder characterized by problems with social interaction, communication and repetitive behaviors.

In the US, it is estimated that 1 in 68 children have autism, most of whom are boys.

Study leader Dr. Benjamin Darbro, of the University of Iowa Carver College of Medicine, notes that the finding of a genetic link between autism and cancer is not a new discovery; previous research has established that the conditions share risk genes.

Read more: Autistic people have higher gene mutations but lesser risk to cancer

Autism patients have more mutations in cancer-related genes, but they are at lower risk of developing
cancer than those without autism.

Source: medicalnewstoday

Gastritis: Facts, Causes, Diagnosis and Treatment

Gastritis is the inflammation of the stomach lining, which can have a multitude of causes.

The condition can be an acute (sudden onset, short-term) or chronic (persistent, long-term) issue that increases the risk of other conditions such as stomach ulcers, bleeding or cancer.

Facts about gastritis.

• Gastritis can increase the risk of other gastrointestinal conditions such as stomach ulcers and cancer
• People with gastritis typically report that their abdominal pain is located in the upper center of the abdomen
• Gastritis can also cause pain in the upper left portion of the stomach radiating to the back
• Pain caused by gastritis is often described as sharp, stabbing or burning
• Treatment of gastritis depends on the factors that caused the illness along with whether the disease is acute or chronic.

Causes of gastritis

Gastritis occurs when the protective mucus lining of the stomach is weakened. When this happens, the digestive juices in the stomach can damage and inflame the walls of the stomach.

Read more: Gastritis: Facts, Causes, Diagnosis and Treatment

Gastritis occurs when the mucus lining of the stomach is weakened, enabling the digestive juices
to damage the stomach wall.

Source: steptohealth

Novel Use of Insulin-Producing Beta Cells

While not having love handles in the first place would probably be an ideal situation, scientists at the Swiss Federal Institute of Technology (ETH) in Zurich have found an exciting new use for the cells that reside in the undesirable flabby tissue—creating pancreatic beta cells. The ETH researchers extracted stem cells from a 50-year-old test subject's fatty tissue and reprogrammed them into mature, insulin-producing beta cells.

The findings from this study were published recently in Nature Communications in an article entitled “A Programmable Synthetic Lineage-Control Network That Differentiates Human IPSCs into Glucose-Sensitive Insulin-Secreting Beta-Like Cells.”

The investigators added a highly complex synthetic network of genes to the stem cells to recreate precisely the key growth factors involved in this maturation process. Central to the process were the growth factors Ngn3, Pdx1, and MafA; the researchers found that concentrations of these factors change during the differentiation process.

Read more: Novel Use of Insulin-Producing Beta Cells

The diagram shows the dynamics of the most important growth factors during differentiation of
human induced pluripotent stem cells to beta-like cells.

Source: ETH Zurich

Essentials of MEDICAL PHARMACOLOGY 7e

Medical pharmacology is a unique synthesis of basic pharmacology with clinical pharmacology and pharmacotherapeutics. The subject is highly dynamic. Developments are occurring both in defining molecular targets for drug action and finding targeted drugs, as well as in accruing credible evidence regarding the impact of different treatment modalities on therapeutic outcomes. These efforts have begun to crystallize into evidence based medicine and clear cut therapeutic guidelines. The present edition endeavours to amalgamate the developments with the core content of the subject.

While the primary theme of the book outlined in the preface to the first edition is maintained, the successive editions have become more descriptive and more comprehensive. In preparing this edition, all chapters have been revisited and extensively updated. Latest therapeutic guidelines from authoritative sources like WHO, British National Formulary, National Formulary of India, as well as from eminent professional bodies have been incorporated, especially in areas like hypertension, dyslipidaemias, acute coronary syndromes, surgical prophylaxis, tuberculosis (including MDR-TB), MAC-infection, leprosy, HIV-AIDS, malaria, kala-azar, etc. Recent innovations have been highlighted, notably in antidiabetic drugs, psychopharmacological agents, antiplatelet drugs, treatment of inflammatory bowel disease, drugs affecting renin-angiotensin system, anticoagulants, antiviral (including anti-HIV) drugs, targeted anticancer drugs, etc…

Hardcover: 1002 pages

Publisher: Jaypee Brothers Medical Pub; 7 edition (July 2013)

Language: English

ISBN-10: 9350259370

ISBN-13: 978-9350259375

Product Dimensions: 2 x 7 x 9.5 inches

Shipping Weight: 4.6 pounds

Download here: 1, Essential of MEDICAL PHARMACOLOGY 7e;
                           2, Google Drive

Source: Medsouls Medical Books

Being Too Nice Can be Depressive!

There is such a thing as being too nice, too giving and too caring. To overcome depression you must stop the habit of bending over to gain people’s approval. I know, it’s easier said than done. But no one said it’d be easy.

Those who are affected by depression tend to be people-pleasers. And yet, ironically, quite often their actions are viewed by others as selfish and self-centered. For over three decades I believed in that crap myself. I believed I was selfish and self-involved. I was convinced I had nothing to offer. I also thought that it didn’t matter what I thought. That my opinion was less important than anyone else’s. It seemed as if I was always living someone else’s life.

Finally, after two major brain seizures caused by a suicide attempt, I stopped living someone else’s life and looked deep within…

Someone Else’s Life

I was the child who was “too young to understand things” and therefore to make decisions. My life was run by the grown ups, who weren’t able to see the serious damage caused by the primitive belief such as; “children should be seen but not heard.” Then later, I became an young adult, clinging to any guy who’d find anything whatsoever appealing in me.

Read more: Being Too Nice Can be Depressive!

Source: WakeupWorld

A Journal Editor's Tips to a Good Reviewer

Peer review is one of the foundations of science. To have research scrutinized, criticized, and evaluated by other experts in the field helps to make sure that a study is well-designed, appropriately analyzed, and well-documented. It helps to make sure that other scholars can readily understand, appreciate, and build upon that work.

Of course, peer review is not perfect. Flawed studies are published, and peer reviewers may miss critical problems or errors in particular studies. Reviewers often do not have the time, nor the inclination, to dig deeply into a study’s methods, or assumptions, or supporting materials, in order to find errors or flaws in a research paper.

Even though peer review is not perfect, as a journal editor I rely heavily on the evaluations and advice provided by peer reviewers. We spend a great deal of time trying to find the right reviewers for each and every paper that we put through the peer review process, and an equally large amount of time reading, evaluating, and putting into appropriate context the responses that we receive from our reviewers.

What is ironic, however, is that despite the importance of peer review in science, it’s not a skill that we typically directly address in our graduate programs, nor in our professional societies. I’m not aware of graduate seminars in “how to be a good peer reviewer”, nor are there materials easily available for scholars to reference when they are asked to undertake a particular peer review task for a journal.

Read more: A Journal Editor's Tips to a Good Reviewer

Source: OUPblog

Parasitic worms help gut flora to prevent Crohn’s disease

The parasitic worms that lurk in some people’s intestines may be revolting, but they seem to forestall Crohn’s disease and other types of inflammatory bowel disease (IBD). A new study might explain how, revealing that the worms enable beneficial microbes in the intestines to outcompete bacteria that promote inflammation. The results could lead to new ways of treating gut diseases by mimicking the effects of the parasites.

“It’s a beautifully done paper,” says immunologist Joel Weinstock of Tufts University in Boston, who wasn’t connected to the work. “It had not been previously shown that one of the mechanisms [of IBD] is through changes in the intestinal flora.”

In people with IBD, inflammation in the digestive tract results in symptoms such as diarrhea and bleeding and can sometimes lead to intestinal obstructions or other severe complications. Because parasitic worms, or helminths, can be harmful, they appear to be unlikely allies against these diseases. “They are called parasites for a reason,” says immunologist Ken Cadwell of the New York University School of Medicine in New York City, a co-author on the new study. However, IBD is rare in parts of the world where helminths are prevalent, and it is surging in more developed countries, where few people now carry the intestinal intruders. That difference suggests, researchers say, that they are protective.

Read more: Parasitic worms help gut flora to prevent Crohn’s disease

Parasites like this whipworm might protect us from Crohn’s disease by altering our intestinal bacteria.

Source: CNRI/Science

Novel Genomic Analysis of Immune Cell Infiltration in Colorectal Cancer

The past several years have seen some exciting results for cancer immunotherapy. However, there remains a fundamental lack of understanding of immune system recognition in various cancers. Many large-scale sequencing efforts have added to our collective knowledge base, but too many of these studies have been deficient in comprehensive epidemiological and demographic information.

Now, researchers at the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard report on their findings from a new study, which found that colorectal cancers festooned with tumor-related proteins called neoantigens were likely to be saturated with disease-fighting white blood cells, mainly lymphocytes.

Using several data sets from patients in two large health-tracking studies, the Nurses' Health Study and the Health Professionals Follow-up Study, investigators performed whole-exome sequencing on colorectal tumor samples from 619 patients—itemizing each DNA base that specifies how cell proteins are to be constructed. This information was merged with data from tests of the immune system's response to the tumors and with patient clinical data, including length of survival.

Read more: Novel Genomic Analysis of Immune Cell Infiltration in Colorectal Cancer

Through whole-exome sequencing of colorectal tumors, researchers were able to identify additional driver

genes that correlate high neoantigen load with increased lymphocytic infiltration and improved survival.

Source: Giannakis et al., 2016, Cell Reports 15, 1–9