Bacille Calmette-Guerin (BCG) vaccination is widely practiced around the world to protect against the mycobacterial infection tuberculosis. BCG is also effective against the pathogenic mycobacteria that cause leprosy and Buruli’s ulcer. BCG is part of the standard of care for bladder cancer where, when given as an intravesicular irrigant, BCG acts as an immunomodulating agent and lessens the risk of recurrence. Mycobacterium avium ss. paratuberculosis (MAP) causes a fatal enteritis of ruminant animals and is the putative cause of Crohn’s disease of humans. MAP has been associated with an increasingly long list of inflammatory/autoimmune diseases: Crohn’s, sarcoidosis, Blau syndrome, Hashimoto’s thyroiditis, autoimmune diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis, lupus and Parkinson’s disease. Epidemiologic evidence points to BCG providing a “heterologous” protective effect on assorted autoimmune diseases; studies using BCG vaccination for T1D and MS have shown benefit in these diseases. This article proposes that the positive response to BCG in T1D and MS is due to a mitigating action of BCG upon MAP. Other autoimmune diseases, having a concomitant genetic risk for mycobacterial infection as well as cross-reacting antibodies against mycobacterial heat shock protein 65 (HSP65), could reasonably be considered to respond to BCG vaccination. The rare autoimmune disease, relapsing polychondritis, is one such disease and is offered as an example. Recent studies suggesting a protective role for BCG in Alzheimer’s disease are also explored. BCG-induced energy shift from oxidative phosphorylation to aerobic glycolysis provides the immunomodulating boost to the immune response and also mitigates mycobacterial infection-this cellular mechanism unifies the impact of BCG on the disparate diseases of this article
The really dangerous American fascist… is the man who wants to do in the United States in an American way what Hitler did in Germany in a Prussian way. The American fascist would prefer not to use violence. His method is to poison the channels of public information. With a fascist the problem is never how best to present the truth to the public but how best to use the news to deceive the public into giving the fascist and his group more money or more power… They claim to be super-patriots, but they would destroy every liberty guaranteed by the Constitution. They demand free enterprise, but are the spokesmen for monopoly and vested interest. Their final objective, toward which all their deceit is directed, is to capture political power so that, using the power of the state and the power of the market simultaneously, they may keep the common man in eternal subjection.
~quoted in the New York Times, April 9, 1944
Henry A. Wallace
[**Biochemical Pharmacology**][Biochemical Pharmacology]
Available online 10 February 201
Aging is accompanied by progressive declines in skeletal muscle mass and strength and impaired regenerative capacity, predisposing older adults to debilitating age-related muscle deteriorations and severe morbidity. Muscle stem cells (muSCs) that proliferate, differentiate to fusion-competent myoblasts, and facilitate muscle regeneration are increasingly dysfunctional upon aging, impairing muscle recovery after injury. While regulators of muSC activity can offer novel therapeutics to improve recovery and reduce morbidity among aged adults, there are no known muSC regenerative small molecule therapeutics. We recently developed small molecule inhibitors of nicotinamide N-methyltransferase (NNMT), an enzyme overexpressed with aging in skeletal muscles and linked to impairment of the NAD\\+ salvage pathway, dysregulated sirtuin 1 activity, and increased muSC senescence. We hypothesized that NNMT inhibitor (NNMTi) treatment will rescue age-related deficits in muSC activity to promote superior regeneration post-injury in aging muscle. 24-month old mice were treated with saline (control), and low and high dose NNMTi (5 and 10 mg/kg) for 1-week post-injury, or control and high dose NNMTi for 3-weeks post-injury. All mice underwent an acute muscle injury (barium chloride injection) locally to the tibialis anterior (TA) muscle, and received 5-ethynyl-2’-deoxyuridine systemically to analyze muSC activity. *In vivo*contractile function measurements were conducted on the injured TA muscle and tissues collected for ex-vivo analyses, including myofiber cross-sectional area (CSA) measurements to assess muscle recovery. Results revealed that muscle stem cell proliferation and subsequent fusion were elevated in NNMTi-treated mice, supporting nearly 2-fold greater CSA and shifts in fiber size distribution to greater proportions of larger sized myofibers and fewer smaller sized fibers in NNMTi-treated mice compared to controls. Prolonged NNMTi treatment post-injury further augmented myofiber regeneration evinced by increasingly larger fiber CSA. Importantly, improved muSC activity translated not only to larger myofibers after injury but also to greater contractile function, with the peak torque of the TA increased by ∼70% in NNMTi-treated mice compared to controls. Similar results were recapitulated *in vitro* with C2C12 myoblasts, where NNMTi treatment promoted and enhanced myoblast differentiation with supporting changes in the cellular NAD\\+/NADH redox states. Taken together, these results provide the first clear evidence that NNMT inhibitors constitute a viable pharmacological approach to enhance aged muscle regeneration by rescuing muSC function, supporting the development of NNMTi as novel mechanism-of-action therapeutic to improve skeletal muscle regenerative capacity and functional recovery after musculoskeletal injury in older adults
[Biochemical Pharmacology]: https://www.sciencedirect.com/science/journal/00062952
[In Press_ Accepted]: https://www.sciencedirect.com/science/journal/aip/00062952
There is no question that in 3 months time we will have not one but several vaccines fid the new coronavirus virus outbreak. Several companies produced vaccines for SARS and at least one company for MERS. However, none of these efforts have resulted in a vaccine available to the public. This time it is abundantly clear that a vaccine should be made available vaccine to provide population wide herd immunity not only for this virus but also cross protection against future coronavirus outbreaks. I suggest a mass vaccination campaign sponsored by the government with a vaccine provided at cost.
China Quarantines 11 Million Residents Due To Coronavirus Outbreak
The United States recognizing the seriousness of the coronvirus outbreak has awarded contracts for the development of a vaccine. The quickest vaccine development platforms are the Mrna system of Moderna and the DNA vaccine system of Invio
The CDC describes both the nature of coronavirus and the outbreak in China as follows:
“Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases, says the CDC. Coronaviruses that infect animals can also evolve and become a human coronavirus. The best-known human coronaviruses are Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). Outbreaks of a Novel Coronavirus (nCoV), now known as 2019-nCoV, are causing pneumonia-related infections in various counties in 2020
As of January 26, 2020, there are no approved antiviral medications to treat or vaccines to prevent the 2019-nCoV virus in the USA, says the Centers for Disease Control and Prevention (CDC).
The WHO China Country Office was informed of cases of pneumonia of unknown etiology (cause) detected in Wuhan City, Hubei Province of China on December 31, 2019. A novel coronavirus (2019-nCoV) was identified as the causative virus by Chinese authorities”
The WHO has declared a country wide emergency in China and is monitoring the situation regarding the need for a pandemic world wide emergency should the virus spread within other countries.
Transcripts of human endogenous retrovirus K are expressed in most breast cancers (BCs). Yellow fever vaccine 17D (YFV) expresses a protein with a closely homologous epitope. Cross-reactive immunity could hypothetically inhibit BC growth at least in women aged around 50 years at diagnosis, in whom the prognosis of BC was found to be better than that in women younger or older. A cohort of 12 804 women who received YFV in the Veneto Region, Italy, was divided into two subcohorts according to age at vaccination and followed up through the Veneto Tumor Registry. The time since vaccination until cancer incidence was categorized (≤1.9; 2-3.9; 4-5.9; 6-7.9; 8-10.9; ≥11 years) and, using the lowest class as a reference, the incidence rate ratio for BC with a 95% confidence interval and P-value was estimated by Poisson regression in each time since vaccination class, adjusting for age and calendar period. In 3140 women vaccinated at 40-54 years of age, YFV administration resulted in a protective effect of long duration slowly fading over time with a U-shaped pattern of response. Overall, BC risk was reduced by about 50% (incidence rate ratio=0.46; 95% confidence interval=0.26-0.83; P=0.009) 2 years after vaccination. Cross-reactive antigens could not be the mechanism because no protection was observed in women vaccinated before 40 or after 54 years of age. BC cells in a microscopic stage of disease can be destroyed or severely damaged by YFV if BC is not very aggressive. To prove that treatment is truly effective, a placebo-controlled double-blind trial should be conducted.