Sirtuins such as SIRT1 are conserved protein NAD(+)-dependent deacylases and thus their function is intrinsically linked to cellular metabolism. Over the past two decades, accumulating evidence has indicated that sirtuins are not only important energy status sensors but also protect cells against metabolic stresses. Sirtuins regulate the aging process and are themselves regulated by diet and environmental stress. The versatile functions of sirtuins including, more specifically, SIRT1 are supported by their diverse cellular location allowing cells to sense changes in energy levels in the nucleus, cytoplasm, and mitochondrion. SIRT1 plays a critical role in metabolic health by deacetylating many target proteins in numerous tissues, including liver, muscle, adipose tissue, heart, and endothelium. This sirtuin also exerts important systemic effects via the hypothalamus. This review will cover these topics and suggest that strategies to maintain sirtuin activity may be on the horizon to forestall diseases of aging.

/pdf/sirt1-and-other-sirtuins-in-metabolism-14osjdyabq.pdf

SIRT1 and other sirtuins in metabolism.

SIRT1 and other sirtuins in metabolism

Naturally occurring cancers in pet dogs and humans share many features, including histological appearance, tumour genetics, molecular targets, biological behaviour and response to conventional therapies. Studying dogs with cancer is likely to provide a valuable perspective that is distinct from that generated by the study of human or rodent cancers alone. The value of this opportunity has been increasingly recognized in the field of cancer research for the identification of cancer-associated genes, the study of environmental risk factors, understanding tumour biology and progression, and, perhaps most importantly, the evaluation and development of novel cancer therapeutics.

Translation of new cancer treatments from pet dogs to humans.

Tumors of the Skin and Soft Tissues

Histone posttranslational modifications represent a versatile set of epigenetic marks involved not only in dynamic cellular processes, such as transcription and DNA repair, but also in the stable maintenance of repressive chromatin. In this article, we review many of the key and newly identified histone modifications known to be deregulated in cancer and how this impacts function. The latter part of the article addresses the challenges and current status of the epigenetic drug development process as it applies to cancer therapeutics.

/pdf/histone-modifications-and-cancer-w2boj1xl6t.pdf

Histone Modifications and Cancer.

The standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of live Mycobacterium bovis BCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as Mycobacterium brumae, and/or different vehicles for mycobacteria delivery, such as an olive oil (OO)-in-water emulsion. While it has been established that BCG treatment activates the immune system, the immune effects of altering the mycobacterium and/or the preparation remain unknown. In an orthotopic murine BC model, local immune responses were assessed by measuring immune cells into the bladder and macromolecules in the urine by flow cytometry and multiplexing, respectively. Systemic immune responses were analyzed by quantifying sera anti-mycobacteria antibody levels and recall responses of ex vivo splenocytes cultured with mycobacteria antigens. In both BCG- and M. brumae-treated mice, T, NK, and NKT cell infiltration in the bladder was significantly increased. Notably, T cell infiltration was enhanced in OO-in-water emulsified mycobacteria-treated mice, and urine IL-6 and KC concentrations were elevated. Furthermore, mycobacteria treatment augmented IgG antibody production and splenocyte proliferation, especially in mice receiving OO-in-water emulsified mycobacteria. Our data demonstrate that intravesical mycobacterial treatment triggers local and systemic immune responses, which are most significant when OO-in-water emulsified mycobacteria are used.

/pdf/intravesical-mycobacterium-brumae-triggers-both-local-and-3al0mqe8ge.pdf

Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice.

https://www.mdpi.com/2076-393X/8/2/198/pdf

Mycolicibacterium brumae Is a Safe and Non-Toxic Immunomodulatory Agent for Cancer Treatment

Diabetic neuropathy is one of the most frequent complications in diabetes but there are no treatments beyond glucose control, due in part to the lack of an appropriate animal model to assess an effective therapy. This study was undertaken to characterize the degenerative and regenerative responses of peripheral nerves after induced sciatic nerve damage in transgenic rat insulin I promoter / human interferon beta (RIP/IFNbeta) mice made diabetic with a low dose of streptozotocin (STZ) as an animal model of diabetic complications. In vivo, histological and immunohistological studies of cutaneous and sciatic nerves were performed after left sciatic crush. Functional tests, cutaneous innervation, and sciatic nerve evaluation showed pronounced neurological reduction in all groups 2 weeks after crush. All animals showed a gradual recovery but this was markedly slower in diabetic animals in comparison with normoglycemic animals. The delay in regeneration in diabetic RIP/IFNbeta mice resulted in an increase in active Schwann cells and regenerating neurites 8 weeks after surgery. These findings indicate that diabetic-RIP/IFNbeta animals mimic human diabetic neuropathy. Moreover, when these animals are submitted to nerve crush they have substantial deficits in nerve regrowth, similar to that observed in diabetic patients. When wildtype animals were treated with the same dose of STZ, no differences were observed with respect to nontreated animals, indicating that low doses of STZ and the transgene are not implicated in development of the degenerative and regenerative events observed in our study. All these findings indicate that RIP/IFNbeta transgenic mice are a good model for diabetic neuropathy.

Diabetic neuropathy: Electrophysiological and morphological study of peripheral nerve degeneration and regeneration in transgenic mice that express IFNβ in β cells

PROTOTHECOSIS is an opportunistic disease caused by the unicellular achlorophyllic algae Prototheca , which is found in a wide variety of sources such as tree sap, lakes, marine waters, faeces or soil (Huerre and others 1993). Protothecosis is a rare infection in human beings that can cause olecranon bursitis, cutaneous or systemic signs (Lass-Florl and Mayr 2007). The most commonly affected domestic animals are cattle, which develop mastitis (Cheville and others 1984); dogs, which can show cutaneous and disseminated forms (Sudman and others 1973, Tyler and others 1980, Merideth and others 1982, Migaki and others 1982, Perez and others 1997, Strunck and others 2004, Pressler and others 2005, Stenner and others 2007, Salvadori and others 2008); cats, which mainly develop a cutaneous form (Dillberger and others 1988); and, rarely, goats (Macedo and others 2008).

In dogs, the most common presentation is the disseminated form, which causes gastrointestinal, ophthalmic, urinary and neurological signs. In most cases, haemorrhagic diarrhoea due to colitis is the first clinical sign, suggesting a gastroenteric route of infection (Stenner and others 2007), while haematogenous-lymphatic dissemination occurs later during the course of the disease. To the authors' knowledge, canine protothecosis affecting the brain without involvement of other organs has not been previously described.

A two-year-old, male boxer was presented to the Veterinary Medical Teaching Hospital of the Autonomous University of Barcelona, with a seven-day history of anorexia, frequent coughing, mild depression and generalised pain that did not respond to NSAID treatment. Physical examination showed a body temperature of 38°C, and swelling of the right submandibular lymph node. Neurological examination showed diffuse paraspinal hyperaesthesia, more severe in the cervical region, and mild mental depression, which was attributed to severe pain due to the meningitis. The animal demonstrated pain both, spontaneously …

Protothecal pyogranulomatous meningoencephalitis in a dog without evidence of disseminated infection

A case of a dwarf hamster with two progressively growing nodules on the right fore limb is described. These were excised following ineffective medical treatment and were submitted for histopathological examination, which revealed bacterial pseudomycetoma in both nodules. To the authors' knowledge this is the first reported case of bacterial pseudomycetoma in a dwarf hamster.

R.M. Rabanal

Papers

Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice.

Mycolicibacterium brumae Is a Safe and Non-Toxic Immunomodulatory Agent for Cancer Treatment

Diabetic neuropathy: Electrophysiological and morphological study of peripheral nerve degeneration and regeneration in transgenic mice that express IFNβ in β cells

Protothecal pyogranulomatous meningoencephalitis in a dog without evidence of disseminated infection

Bacterial pseudomycetoma in dwarf hamster, Phodopus sungorus