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New findings in rodents and human brain shed light on the mechanisms of major depressive disorder (MDD), uncovering over-expression of MKP-1 (mitogen-activated protein kinase [MAPK] phosphatase-1)...and identifying a new therapeutic target. MKP-1, also known as dual-specificity phosphatase-1 (DUSP1), is a member of a family of proteins that dephosphorylate both threonine and tyrosine residues and thereby serves as a key negative regulator of the MAPK cascade4, a major signaling pathway involved in neuronal plasticity, function and survival This study identifies MKP-1 as a key factor in MDD pathophysiology, and as a new target for therapeutic interventions.f Here we use whole-genome expression profiling of postmortem tissue and show significantly increased expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1, encoded by DUSP1, but hereafter called MKP-1) in the hippocampal subfields of subjects with MDD compared to matched controls. MKP-1, also known as dual-specificity phosphatase-1 (DUSP1), is a member of a family of proteins that dephosphorylate both threonine and tyrosine residues and thereby serves as a key negative regulator of the MAPK cascade4, a major signaling pathway involved in neuronal plasticity, function and survival. We tested the role of altered MKP-1 expression in rat and mouse models of depression and found that increased hippocampal MKP-1 expression, as a result of stress or viral-mediated gene transfer, causes depressive behaviors. Conversely, chronic antidepressant treatment normalizes stress-induced MKP-1 expression and behavior, and mice lacking MKP-1 are resilient to stress. These postmortem and preclinical studies identify MKP-1 as a key factor in MDD pathophysiology and as a new target for therapeutic interventions.

"Hop up on the table, Honey." mThat's how an x-ray technician addressed my 89-year-old mother-in-law in 2001, when we took her for knee x-rays. Mom, who had advanced osteoporosis and arthritis as well as confusion and heart problems, had long since given up hopping. When it became obvious that she needed assistance, the technician grabbed her arm -- as if pulling on another sore appendage would magically raise the rest of her onto the table. It didn't. This incident has become our personal mantra for expressing what is wrong with America's health care system. Having helped our four parents during their final years and having both had cancer ourselves as well as other medical problems, we have had experiences with five nursing homes, two personal care facilities and a half dozen hospitals. We've lost count of the doctors, drugstores and health insurance plans. All of us have had health insurance, though some policies were better than others. Nonetheless, we have experienced incident after incident demonstrating the waste, ignorance and apathy which is rampant in the system. Unable to list them all, I have been heretofore reluctant to write about a handful of them lest the reader be persuaded that the problem is with only that hospital, only that nursing home or only that doctor. There is, however, an increasing crisis of confusion, mismanagement and ill-preparedness which is at the core of our healthcare system. We are all familiar at least with the trend line if not the specifics for healthcare costs. According to WhiteHouse.gov, "The United States spends over $2.2 trillion on health care each year-almost $8,000 per person." That's sixteen percent of the economy. Healthcare costs are projected to increase to almost twenty percent ($4 trillion a year) by 2017. Meanwhile forty-six million Americans are without health insurance (14,000 more each day), premiums and co-pays are rising and more reasons are used to refuse coverage both to those willing to pay and thos

"Hop up on the table, Honey." mThat's how an x-ray technician addressed my 89-year-old mother-in-law in 2001, when we took her for knee x-rays. Mom, who had advanced osteoporosis and arthritis as well as confusion and heart problems, had long since given up hopping. When it became obvious that she needed assistance, the technician grabbed her arm -- as if pulling on another sore appendage would magically raise the rest of her onto the table. It didn't. This incident has become our personal mantra for expressing what is wrong with America's health care system. Having helped our four parents during their final years and having both had cancer ourselves as well as other medical problems, we have had experiences with five nursing homes, two personal care facilities and a half dozen hospitals. We've lost count of the doctors, drugstores and health insurance plans. All of us have had health insurance, though some policies were better than others. Nonetheless, we have experienced incident after incident demonstrating the waste, ignorance and apathy which is rampant in the system. Unable to list them all, I have been heretofore reluctant to write about a handful of them lest the reader be persuaded that the problem is with only that hospital, only that nursing home or only that doctor. There is, however, an increasing crisis of confusion, mismanagement and ill-preparedness which is at the core of our healthcare system. We are all familiar at least with the trend line if not the specifics for healthcare costs. According to WhiteHouse.gov, "The United States spends over $2.2 trillion on health care each year-almost $8,000 per person." That's sixteen percent of the economy. Healthcare costs are projected to increase to almost twenty percent ($4 trillion a year) by 2017. Meanwhile forty-six million Americans are without health insurance (14,000 more each day), premiums and co-pays are rising and more reasons are used to refuse coverage both to those willing to pay and thos

Mice fed fish oil and curcumin showed a significantly reduced tumor volume, 25% (P < 0.04) and 43% (P < 0.005), respectively, and importantly, a combination of curcumin and fish oil diet showed > 72% (P < 0.0001) tumor volume reduction. Expression and activity of iNOS, COX-2, and 5-LOX are downregulated, and p21 is upregulated in tumor xenograft fed curcumin combined with fish oil diet when compared to individual diets. The preceding results evidence for the first time that curcumin combined with omega-3 fatty acids provide synergistic pancreatic tumor inhibitory properties. \n\nPrevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids.\nSwamy MV, Citineni B, Patlolla JM, Mohammed A, Zhang Y, Rao CV. \nNutr Cancer. 2008;60 Suppl 1:81-9. \nPMID: 19003584

The precise mechanism of the anti-tumor effect of imiquimod in BCC is not known. It has been postulated that ultraviolet radiation induces mutations in the tumor-suppressor genes and alters the immuno-surveillance, so that tumor cells escape from cytotoxic T cells and apoptosis.[1] Th-2 cytokines, that downregulate tumor surveillance, are raised in BCC.[1],[5] Imiquimod acts on toll-like receptor-7 (TLR-7) present on dendritic cells, macrophages and monocytes and induces expression of interferons, Th-1 cytokines (IL-1, IL-6, IL-10 and IL-12), tumor necrosis factor-a and G-CSF, thereby counteracting Th2 cytokines and promoting tumor surveillance.[1],[5] It also enhances the activity of natural killer cells and epidermal Langerhans' cells. The tumor regression is achieved probably by induction of Fas receptors on the tumor cells resulting in their apoptosis.[10]

The cellular and extracellular matrix accumulations that comprise the lesions of atherosclerosis are driven by local release of cytokines at sites of predilection for lesion formation, and by the specific attraction and activation of cells expressing rece

It was concluded that omega-3 fatty acid could inhibit the proliferation of pancreatic cancer cell line SW1990 cells and promote their apoptosis. The down-regulation of the cyclin E expression by omega-3 fatty acid might be one of the mechanisms for its anti-tumor effect on pancreatic cancer. \n\nModulatory effects of EPA and DHA on proliferation and apoptosis of pancreatic cancer cells.\nZhang W, Long Y, Zhang J, Wang C.\nJ Huazhong Univ Sci Technolog Med Sci. 2007 Oct;27(5):547-50.\nPMID: 18060632

Study provides the first evidence of a direct relationship between the depression of protein synthesis in skeletal muscle by PIF and Ang II, through activation of PKR, and eIF2{alpha} phosphorylation, and the enhanced degradation of the myofibrillar protein myosin, through activation of NF-{kappa}B resulting in an increased expression and activity of the ubiquitin-proteasome proteolytic pathway. This suggests that agents that target PKR may be effective in the treatment of muscle atrophy in cancer cachexia or other wasting conditions.

"new research demonstrates that ingested vitamin D is immunosuppressive and that low blood levels of vitamin D may be actually a result of the disease process. Supplementation may make the disease worse. "

This article discusses new Duke University research showing a highly significant correlation (p = 0.007) between higher vitamin D intake and MRI brain lesions (http://www.fasebj.org/cgi/content/meeting_abstract/21/6/A1072), as well as the potential for lesion reversal. These lesions have been associated with cognitive impairment, stroke, psychiatric disorders and mortality. This article also discusses the levels of vitamin D and calcium needed to avoid osteoporosis and vascular calcification in the light of new research on blockage of the vitamin D receptor due to bacterial products and elevated 25D.

Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some patients with asthma, supporting the idea that the n-3 PUFA in fish oil are anti-inflammatory. There are indications that inclusion of n-3 PUFA in enteral and parenteral formulas might be beneficial to patients in intensive care or post-surgery.