The Rhyothemis princeps Brain Externalization Project

  Role of the Heme Oxygenase 1 In Modulating Inflammation After Insect Bites, uploaded 22 Sept. 2021 - presenter not identified 10:20 feral dogs as reservoirs for Leishmania 11:554 bite site microenvironment - vector gut microbiome, parasite derived exosomes 12:35 diagram of skin, immune cells 15:42 study aims 19:38 HO-1 production is a universal host skin response to blood feeding (hematophagous) arthropods 20:25 poking with needle does not provoke same response 22:51 Anophelese gambiae did not promote significant ischemic hemorrhage in tissue, but still increased HO-1 production in skin 31:01 inflammatory monocytes could be involved in erythrophagocytosis; in response to heat can differentiation into iron recycling macrophages 34:50 in situ confocal imaging of erythrophagocytosis in skin 36:16 HO-1 expressed both in cytopplasm and in nucleus 40:50 HO-1 promotes disease tolerance and reduces pathology, does not affect parasite replication or parasite load 41:37

A recent flare up of fibrocystic breast symptoms had me wondering if use of cold packs has any effect on breast cancer (BC) risk. Cold packs are often recommended for mastalgia (breast pain) from fibrocystic breast disease, mastitis, engorgement due to breast feeding cessation, and post breast cancer surgery. Whole body cold exposure has been found to increase tumor growth and metastasis in mice: https://www.medicalnewstoday.com/articles/269266 T-cell function is diminished at colder temperature leading to reduced anti-tumor immune responses. The article notes implications for standard research practice of housing mice at relatively colder temperatures - another thing to add to the list of problems in current practices.  (Could cold acclimation be used to promote tolerance in autoimmunity and atopy? Another topic for another day.) The mice were subjected to whole body cold exposure  - not spot treatment. It is conceivable that reducing acute inflammation through localized cold exposure

 There are a number of research programs that study interventions for increasing lifespan and healthspan in animals (dogs, mice, flies, nematode worms) with the aim of finding successful interventions that could be translated to humans. The Dog Aging Project enrolls companion dogs in observational and interventional studies on aging; it seems a worthwhile endeavor even if treatments are not applicable to humans as improving the lifespan and healthspan of dogs is worthwhile for its own sake. To date, however, there has not been a similar project for cats - or has there?  I watch a lot of cat videos and came upon one that reported ultra-longevity in a number of cats apparently achieved through diet and lifestyle interventions implemented by their human companion, Jake Perry. It seems strange that I learned about this from a cat video rather than through all the longevity-related media I consume. https://youtu.be/CXGCJeH4e-w?t=32   An article by Christina Couch published in Atlas Obscura

Marine collagen peptides have antioxidant properties.  Characterization and Antioxidant Activity of Collagen, Gelatin, and the Derived Peptides from Yellowfin Tuna (Thunnus albacares) Skin [2020] - https://pubmed.ncbi.nlm.nih.gov/32023998/  Functional and bioactive properties of collagen and gelatin from alternative sources: A review [2011] - https://www.sciencedirect.com/science/article/pii/S0268005X11000427 "The exact mechanism underlying the antioxidant activity of peptides is not fully understood, but various studies have shown that they are lipid peroxidation inhibitors, free radical scavengers and transition metal ion chelators. According to some studies, gelatin peptides could inhibit lipid peroxidation more efficiently than antioxidative peptides derived from many other protein sources ...   .. peptides isolated from hoki skin gelatin were capable of enhancing the expression of antioxidative enzymes such as glutathione peroxidase, catalase and superoxide dismutas

Yesterday I watched two introductory videos on the ubiquitin-proteasome system - very important in autoimmunity, aging, cancer and neurodegeneration. Alfred Goldberg, Functions of the proteasome, R&D Systems,  recorded February 4, 2016:  Index: 9:30 start of presentation 13:20 ubiquitin-proteasome pathway summary slide - ATP required 15:22 antigen presentation - 1% of product peptides are taken up by ER and displayed in cell surface by MHC class I molecules - proteasome allows immune system to screen intracellular space for abnormal proteins (pathogen or cancer) 23:16 multiple ATP dependent steps in proteasome function 38:00 Bortezmib - proteasome inhibitor, inhibits NF-kB, does not cross BBB, induces apoptosis 40:33 Endoplasmic-reticulum-associated protein degradation (ERAD) pathway is unusually activated in multiple myeloma cells ; proteasome inhibition results in increased ER stress and triggers UPR, further UPR activation triggers apoptosis 42:30 proteasome inhib

Protein aggregates in nematode worm gonads set off the mitochondrial unfolded protein response (UPRmt) that propagates throughout the organism via Wnt signalling, causing changes in mitochondrial function and potentially increasing protein aggregation in distal tissues. It is not known if this happens in mammals. advances.sciencemag.org/con... This news might not be such a big deal as it has already been reported that Wnt signalling is altered in post-menopausal women due to loss of estrogen and rates of neurodegeneration increase after menopause. However, it would be interesting to know whether in mammals insults (possibly caused by infection) to the ovaries earlier in life (and testes?) may propagate the UPRmt throughout the body.  ~ If UPRmt is meant to counter stress and clean up misfolded proteins, then why would increasing it be bad?  It may actually be good, but there have been conflicting findings, which are reviewed here: The mitochondrial unfolded protein response

Returning to my quest to understand the mechanisms of chronic nausea and vomiting, I revisited mirtazapine for cats. The main reason cats are prescribed Mirtz is for nausea and vomiting (NV) from azotemia or uremia due to chronic kidney disease, which older cats are prone to suffer. So which uremic toxins are implicated in NV?  Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA).  ~ SDMA has been found to be lower in women with ME/CFS: https://www.frontiersin.org/articles/10.3389/fmed.2021.642710/full hmmm ... so I guess this is not a cause of nausea in ME/CFS ... more on related metabolic pathways in ME/CFS: http://followmeindenmark.blogspot.com/2019/03/polyamines-5-methylthioadenosine-and.html  ~ database entry on SDMA: https://hmdb.ca/metabolites/HMDB0003334  "Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. This seems to be mediated by the direct binding or inhibition by uremic toxins of

 I don't even have time today to post links to references and  hope I can find them again at some point in future ... {update 2021-07-18 - I'm working on it} A commenter on YT that I had previously discussed how methionine restriction can actually cause an increase in homocysteine levels asked me what I thought about the apparent paradox - since methionine restriction (MR) lengthens lifespan, but high homocysteine / hyperhomocysteinemia (HHcy) should cause an increase in mortality from CVD (and other things). In lab animals HHcy is induced by feeding excess met and restricting B12, folate and B6. But low met decreases CBS activity, which can also cause HHcy. Chronic HHcy can cause hypermethylation of the CBS gene, reducing its expression. I'm guessing that's why clinical trials to lower Hcy with vitamin B6 etc. don't necessarily result in improvement in cardiovascular health - CBS is still not working and H2S signalling is still impaired. Maybe not the case, though,

  A brief review on how statins could be used to treat immune thrombocytopenia (ITP), an autoimmune disease: Nazy and Cuker (2018) - Statins for high cholesterol … and for low platelets? - https://doi.org/10.1182/blood-2018-01-824888 "Megakaryocytes in ITP patients show impaired maturation and signs of degradation due to defects in the megakaryocytes and their environment. 7   Among the cells in the BM [bone marrow] niche implicated in supporting megakaryopoiesis and thrombopoiesis are the BM EPCs [endothelial progenitor cells], ... Treatments that induce platelet production by enhancing the BM microenvironment could be beneficial for corticosteroid-resistant ITP. Atorvastatin is a widely used drug for the treatment of primary hypercholesterolemia and mixed dyslipidemia by inhibiting 3-hydroxy-3methyl-glutaryl-coenzyme A reductase. Among its activities, it is known to improve the mobilization and function of EPCs. Recently, Shi et al showed the effectiveness of atorvasta

Two mind-blowing articles on the effects of geomagnetic field fluctuations on human health, published in highly ranked peer-reviewed journals. Otsuka et al. (2019) Anti-aging effects of long-term space missions, estimated by heart rate variability  https://www.nature.com/articles/s41598-019-45387-6 "Exposure to variable magnetic fields in space resulted in an increase in several HRV endpoints, suggesting that aging may also be slowed down in astronauts in space, as it was for Caenorhabditis elegans 18 . By contrast, our previous 1998–2000 studies (during solar cycle 23) in a subarctic area indicated that magnetic storms, which involved larger magnetic disturbances than those observed during ISS01 and ISS02, suppressed HRV indices in 19 clinically healthy subjects 24 . The decrease in HRV was statistically validated for TF (−18.6%, P = 0.00009), primarily contributed to by VLF (−21.9%, P < 0.000001) in conjunction with ULF (−15.5%, P = 0.00865) and LF (−14.2%, P = 0.001

Modern Healthspan released a video on an article that reports that shikimic acid reduced markers of  UV light induced cellular senescence in cultured dermal fibroblasts, increased SIRT1 activity and restored proteostasis . As MH suggests in the video, these findings could have much broader implications. Video: https://youtu.be/m_qaZSsFiT8 Research article:  Martinez-Gutierrez et al. (2021) https://www.aging-us.com/article/203010/text "SA reverted misfolded protein accumulation upon senescence, an effect that was abrogated by EX-527. Consistently, SA induced an increase in the levels of the chaperone BiP, resulting in a downregulation of unfolded protein response (UPR) signaling and UPR-dependent autophagy, avoiding their abnormal hyperactivation during senescence. SA did not directly activate SIRT1 in vitro, suggesting that SIRT1 is a downstream effector of SA signaling specifically in the response to cellular senescence. Our study not only uncovers a shikimic acid/SIRT1 signaling

Yesterday Lifespan.io reported on a finding by Wen et al. (2021) that vibration at 90 Hz reduced cellular senescence in bone marrow mesenchymal stem cells; from the news article's conclusion: https://www.lifespan.io/news/vibration-reduces-cellular-senescence-in-the-bones-of-rats/ "Further, while maintaining bone density is crucial to extending healthspan, vibration does not seem to be a great candidate as an anti-aging therapy. One of the greatest advantages of a longevity-based approach is its application to all the tissues in the body, and while the authors of this study did not investigate the effect of vibration on other organs, it seems logical that these effects would apply only to bone tissue."  Original research article: https://www.aging-us.com/article/202907/text  However - https://pubmed.ncbi.nlm.nih.gov/16364518/ “Longstanding evidence that bone formation and resorption are required for the development of haemopoietic marrow strongly suggests that ost