As we age, our risk for neurological disorders increases. It is part of life. Why do some people live past 100 years of age and never lose an ounce of brainpower or memory, and others can develop Alzheimer’s disease (AD) in their 50s? We may never know. However, we know a lot and are learning more all the time.
Each disease has a pathway for development. Almost everyone starts with chronic low-level inflammation that grows over time. Oxidative stress results from untreated inflammation, and then a whole world of disease development can occur – depending on the specific disease. When we know that a particular molecule or compound effectively blocks a pathway, that regimen is adopted and refined to address that disease.
Fisetin and Alzheimer’s disease (AD)
https://content.iospress.com/articles/brain-plasticity/bpl200104. This article is lengthy and contains valuable information on fisetin and other neurological disorders – Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis (ALS), ischemic and hemorrhagic stroke, and traumatic brain injury (TBI). This article will concentrate on fisetin and AD.
First, we must know a bit more about fisetin before going into the pathways of AD and what fisetin can do. Fisetin is an antioxidant that increases glutathione (GSH), a reduced molecule because it is an electron donor that can act as an antioxidant. It also maintains mitochondrial function when oxidative stress levels increase. Fisetin has anti-inflammatory traits that inhibit the 5-lipoxygenase protein enzyme (5LO), which is key to treating AD. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689181/
Fisetin and AD Pathways
Fisetin effectively shuts down and prevents the development of AD pathways in preclinical trials. Anti-inflammatory and oxidative stress are two common pathways for AD to grow in brain tissue. Fisetin consistently prevented cognitive function loss in laboratory animals. Synaptic proteins were maintained at functional levels, and markers of inflammation were reduced. In addition, multiple markers of oxidative stress and lipid peroxidation were noticeably reduced.
Reducing lipid peroxidation is critical in controlling the advancement of AD. Peroxidation of lipids causes changes in membrane permeability and fluidity that impact mitochondria function in the brain. It also alters and inhibits other metabolic processes. https://www.frontiersin.org/research-topics/1269/impact-of-lipid-peroxidation-on-the-physiology-and-pathophysiology-of-cell-membranes
Fisetin also activated the ERK pathway. An extracellular-signal-regulated kinase (ERK) is one pathway the brain uses for signaling and memory. ERK regulates many aspects of cellular function – proliferation, cycle regulation, differentiation, tissue formation, and cell apoptosis (cellular suicide – a normal function over time). https://www.spandidos-publications.com/10.3892/etm.2020.8454
Fisetin also has a proven role in neurotrophic factor production. BDNF (brain-derived neurotrophic factor) is critical for the brain’s nervous system to develop and function properly. BDNF promotes cell survival and differentiation needed in different brain cells. https://www.frontiersin.org/articles/10.3389/fncel.2019.00363/full
5LO (5-lipoxygenase) modulates oxidation and inflammation. The 5LO pathway in AD promotes increases in inflammation in the brain. 5LO and arachidonic acid are interwoven and affect the development of beta-amyloid plaques and tau tangles. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294160/ and https://www.frontiersin.org/articles/10.3389/fncel.2014.00436/full
Conclusion
Fisetin was one of around 30 flavonoids studied as a neuroprotective compound that can prevent a specific type of cell death. Typically, cellular death is termed apoptosis. However, in this case, fisetin stopped ferroptosis (formerly known as oxytosis).
This flavonoid, fisetin, is being clinically evaluated in multiple studies to determine the effectiveness at various dose levels and in conjunction with other compounds – quercetin, isorhamnetin, and luteolin.
Double-blind, randomized, placebo-controlled clinical trials in China are evaluating fisetin and ischemic stroke recovery. There are no clinical trials in the United States currently evaluating fisetin in neurological disorders. The most significant amount of fisetin is found in strawberries. So, would it hurt to add a few more strawberries to your diet? I think not!
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Understanding the complex world of chronometers
Understanding COSC Certification and Its Importance in Horology
COSC Accreditation and its Stringent Standards
Controle Officiel Suisse des Chronometres, or the Controle Officiel Suisse des Chronometres, is the authorized Swiss testing agency that attests to the precision and precision of wristwatches. COSC validation is a sign of superior craftsmanship and trustworthiness in timekeeping. Not all watch brands seek COSC accreditation, such as Hublot, which instead sticks to its proprietary demanding standards with mechanisms like the UNICO, achieving similar precision.
The Science of Precision Chronometry
The core system of a mechanized watch involves the mainspring, which supplies energy as it unwinds. This system, however, can be prone to external elements that may influence its precision. COSC-validated mechanisms undergo strict testing—over 15 days in various circumstances (5 positions, three temperatures)—to ensure their resilience and reliability. The tests measure:
Typical daily rate precision between -4 and +6 seconds.
Mean variation, maximum variation rates, and impacts of thermal changes.
Why COSC Accreditation Matters
For watch fans and connoisseurs, a COSC-validated watch isn’t just a piece of technology but a demonstration to enduring quality and accuracy. It represents a watch that:
Offers exceptional dependability and accuracy.
Ensures guarantee of quality across the complete design of the timepiece.
Is apt to retain its worth more effectively, making it a wise investment.
Well-known Timepiece Brands
Several renowned manufacturers prioritize COSC certification for their timepieces, including Rolex, Omega, Breitling, and Longines, among others. Longines, for instance, offers collections like the Record and Soul, which highlight COSC-certified movements equipped with innovative substances like silicon equilibrium suspensions to boost durability and performance.
Historical Context and the Evolution of Chronometers
The notion of the chronometer originates back to the requirement for precise timekeeping for navigational at sea, emphasized by John Harrison’s work in the eighteenth cent. Since the official foundation of COSC in 1973, the certification has become a standard for evaluating the accuracy of high-end watches, continuing a legacy of superiority in horology.
Conclusion
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Understanding COSC Validation and Its Importance in Watchmaking
COSC Certification and its Rigorous Criteria
Controle Officiel Suisse des Chronometres, or the Controle Officiel Suisse des Chronometres, is the official Switzerland testing agency that attests to the precision and precision of timepieces. COSC accreditation is a sign of superior craftsmanship and dependability in chronometry. Not all timepiece brands pursue COSC validation, such as Hublot, which instead adheres to its own demanding criteria with movements like the UNICO, attaining equivalent precision.
The Art of Exact Timekeeping
The core system of a mechanical watch involves the mainspring, which provides energy as it loosens. This mechanism, however, can be vulnerable to environmental factors that may impact its precision. COSC-accredited movements undergo rigorous testing—over fifteen days in various circumstances (5 positions, three temperatures)—to ensure their resilience and dependability. The tests measure:
Mean daily rate accuracy between -4 and +6 seconds.
Mean variation, maximum variation levels, and effects of temperature variations.
Why COSC Validation Matters
For watch aficionados and connoisseurs, a COSC-validated timepiece isn’t just a piece of tech but a demonstration to lasting quality and accuracy. It symbolizes a timepiece that:
Offers excellent dependability and accuracy.
Ensures assurance of quality across the whole construction of the watch.
Is likely to hold its worth more effectively, making it a wise choice.
Popular Timepiece Brands
Several well-known brands prioritize COSC validation for their watches, including Rolex, Omega, Breitling, and Longines, among others. Longines, for instance, presents collections like the Archive and Soul, which highlight COSC-certified mechanisms equipped with advanced substances like silicon balance suspensions to boost durability and efficiency.
Historical Background and the Evolution of Timepieces
The concept of the chronometer originates back to the requirement for exact timekeeping for navigation at sea, highlighted by John Harrison’s work in the 18th century. Since the official establishment of Controle Officiel Suisse des Chronometres in 1973, the validation has become a standard for judging the precision of luxury timepieces, maintaining a legacy of superiority in horology.
Conclusion
Owning a COSC-accredited timepiece is more than an visual selection; it’s a dedication to quality and precision. For those valuing precision above all, the COSC validation offers tranquility of mind, ensuring that each accredited watch will operate dependably under various conditions. Whether for individual contentment or as an investment decision, COSC-certified timepieces stand out in the world of horology, carrying on a legacy of precise chronometry.