ETHNOPHARMACOLOGICAL RELEVANCE: Ayurveda has its unique perceptions and resultant methodologies for defining and treating human diseases. Fumigation therapy is one of the several treatment methods described in Ayurveda whereby fumes produced from defined drug formulations are inhaled by patients. This therapeutic procedure offers promising research opportunities from phytochemical and ethnopharmacological viewpoints, however, it remains under-noticed.
PURPOSE: Telomeres are specialized DNA-protein complexes found at the ends of eukaryotic chromosomes. In normal somatic cells these become shorter with each cell division and appear to control their replicative lifespan. However almost all tumours show activation of the enzyme telomerase, a specialised reverse transcriptase/DNA polymerase, that can add new telomeric repeats to the ends of chromosomes and this appears to be a key factor in the cell immortalization process.
Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. SMA is caused by loss of functional survival motor neuron 1 (SMN1), resulting in death of spinal motor neurons. Current therapeutic research focuses on modulating the expression of a partially functioning copy gene, SMN2, which is retained in SMA patients. However, a treatment strategy that improves the SMA phenotype by slowing or reversing the skeletal muscle atrophy may also be beneficial. Myostatin, a member of the TGF-beta super-family, is a potent negative regulator of skeletal muscle mass.
Translational Research: The Journal of Laboratory and Clinical Medicine
Silent information regulator 2 (Sir2/Sirt1), a member of the sirtuin family of class III histone deacetylases, has been implicated extensively in lifespan extension and is a prominent drug target in antiaging medicine. The mammalian Sirt1 has multiple targets, which include histones, transcription factors, and other molecules that collectively modulate energy metabolism, stress response, and cell/tissue survival. Several of Sirt1's substrates regulate key metabolic processes, and Sirt1 activation may underlie the lifespan prolonging effect of caloric restriction.
Nutrient-deprivation autophagy factor-1 (NAF-1) (synonyms: Cisd2, Eris, Miner1, and Noxp70) is a [2Fe-2S] cluster protein immune-detected both in endoplasmic reticulum (ER) and mitochondrial outer membrane. It was implicated in human pathology (Wolfram Syndrome 2) and in BCL-2 mediated antagonization of Beclin 1-dependent autophagy and depression of ER calcium stores. To gain insights about NAF-1 functions, we investigated the biochemical properties of its 2Fe-2S cluster and sensitivity of those properties to small molecules.
Numerous mutations increase lifespan in diverse organisms from worms to mammals. Most genes that affect longevity encode components of the target of rapamycin (TOR) pathway, thus revealing potential targets for pharmacological intervention. I propose that one target, TOR itself, stands out, simply because its inhibitor (rapamycin) is a non-toxic, well-tolerated drug that is suitable for everyday oral administration.
A critical requirement for research using model organisms is a well-defined and consistent diet. There is currently no complete chemically defined (holidic) diet available for Drosophila melanogaster. We describe a holidic medium that is equal in performance to an oligidic diet optimized for adult fecundity and lifespan. This holidic diet supports development over multiple generations but at a reduced rate. Over 7 years of experiments, the holidic diet yielded more consistent experimental outcomes than did oligidic food for egg laying by females.
The first- and second-generation antipsychotic drugs have become mainstay drug treatment for schizophrenia. However, patients who receive antipsychotic drugs differ with respect to treatment response and drug-induced adverse events. The biological predictors of treatment response are being researched worldwide, with emphasis on molecular genetic predictors of treatment response. Because of the rapid and exciting developments in the field, we reviewed the recent studies of the molecular genetic basis of treatment response in schizophrenia.
Epigenetics is a mechanism that regulates gene expression not depending on the underlying DNA sequence, but on the chemical modifications of DNA and histone proteins. Defects in the factors involved in epigenetic regulation cause congenital neurodevelopmental diseases, and thus, epigenetic regulation is essential for normal brain development. Besides these intrinsic defects, it is becoming increasingly apparent that extrinsic factors, such as insufficient nutrition, psychiatric drugs, and mental stress, also alter epigenetic regulation.