1. Place animal in induction chamber and anesthetize the mouse and ensure sedation. 2. Once the animal is sedated, move it to a nose cone for hair removal using cream. Only apply cream to the area of the chest that will be utilized for imaging. Once the hair is removed, wipe area with wet gauze to ensure all hair is removed. 3. Move the animal to the imaging platform and tape its paws to the ECG lead plates and insert rectal probe. Body temperature should be maintained at 36-37°C. During imaging, reduce anesthesia to maintain proper heart rate. If the animal shows signs of being awake, use a higher concentration of anesthetic.

人唾液天疱疮抗原的纯化

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities. Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.

/pdf/natural-products-in-drug-discovery-advances-and-4axj6y2vp0.pdf

Natural products in drug discovery: advances and opportunities.

Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes a reduction of antioxidants, which in turn produce an oxidation–reduction imbalance in organisms. Paucity of the antioxidant system generates oxidative-stress, characterized by elevated levels of reactive species (oxygen, hydroxyl free radical, and so on). Mitochondria play a key role in ATP supply to cells via oxidative phosphorylation, as well as synthesis of essential biological molecules. Various redox reactions catalyzed by enzymes take place in the oxidative phosphorylation process. An inefficient oxidative phosphorylation may generate reactive oxygen species (ROS), leading to mitochondrial dysfunction. Mitochondrial redox metabolism, phospholipid metabolism, and proteolytic pathways are found to be the major and potential source of free radicals. A lower concentration of ROS is essential for normal cellular signaling, whereas the higher concentration and long-time exposure of ROS cause damage to cellular macromolecules such as DNA, lipids and proteins, ultimately resulting in necrosis and apoptotic cell death. Normal and proper functioning of the central nervous system (CNS) is entirely dependent on the chemical integrity of brain. It is well established that the brain consumes a large amount of oxygen and is highly rich in lipid content, becoming prone to oxidative stress. A high consumption of oxygen leads to excessive production of ROS. Apart from this, the neuronal membranes are found to be rich in polyunsaturated fatty acids, which are highly susceptible to ROS. Various neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), among others, can be the result of biochemical alteration (due to oxidative stress) in bimolecular components. There is a need to understand the processes and role of oxidative stress in neurodegenerative diseases. This review is an effort towards improving our understanding of the pivotal role played by OS in neurodegenerative disorders.

https://www.mdpi.com/1420-3049/24/8/1583/pdf

Oxidative Stress: A Key Modulator in Neurodegenerative Diseases.

The autonomic nervous system.

Growing interest in workplace spirituality has led to the development of a new paradigm in organizational science Theoretical assumptions abound as to how workplace spirituality might enhance organizational performance, most postulating a significant positive impact Here, that body of research has been reviewed and analyzed, and a resultant values framework for workplace spirituality is introduced, providing the groundwork for empirical testing A discussion of the factors and assumptions involved for future research are outlined

A Values Framework for Measuring the Impact of Workplace Spirituality on Organizational Performance

Aim: The aim of this article is to review the current literature on the therapeutic uses and efficacy of Triphala. Herbal remedies are among the most ancient medicines used in traditional systems of healthcare such as Ayurveda. Triphala, a well-recognized and highly efficacious polyherbal Ayurvedic medicine consisting of fruits of the plant species Emblica officinalis (Amalaki), Terminalia bellerica (Bibhitaki), and Terminalia chebula (Haritaki), is a cornerstone of gastrointestinal and rejuvenative treatment. Methods: A search of the PubMed database was conducted. Results: In addition, numerous additional therapeutic uses described both in the Ayurvedic medical literature and anecdotally are being validated scientifically. In addition to laxative action, Triphala research has found the formula to be potentially effective for several clinical uses such as appetite stimulation, reduction of hyperacidity, antioxidant, anti-inflammatory, immunomodulating, antibacterial, antimutagenic, adaptogenic, h...

/pdf/therapeutic-uses-of-triphala-in-ayurvedic-medicine-4mvdzb6xb5.pdf

Therapeutic Uses of Triphala in Ayurvedic Medicine

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ), intracellular neurofibrillary tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques) not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2) performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of polymerized microtubules, their binding to MAP-tau, and molecular dynamics involved in cognition. Further, our theory supports novel AD therapeutic strategies targeting intra-neuronal zinc homeostasis and microtubule dynamics to prevent neurodegeneration and cognitive decline.

/pdf/the-zinc-dyshomeostasis-hypothesis-of-alzheimer-s-disease-muaykmqyyg.pdf

The zinc dyshomeostasis hypothesis of alzheimer's disease

Quantum Healing : Exploring the Frontiers of Mind/Body Medicine

Spirituality and gratitude are associated with well-being. Few if any studies have examined the role of gratitude in heart failure (HF) patients or whether it is a mechanism through which spirituality may exert its beneficial effects on physical and mental health in this clinical population. This study examined associations between gratitude, spiritual well-being, sleep, mood, fatigue, cardiac-specific selfefficacy, and inflammation in 186 men and women with Stage B asymptomatic HF (age 66.5 years 10). In correlational analysis, gratitude was associated with better sleep (r .25, p .01), less depressed mood (r .41, p .01), less fatigue (r .46, p .01), and better self-efficacy to maintain cardiac function (r .42, p .01). Patients expressing more gratitude also had lower levels of inflammatory biomarkers (r .17, p .05). We further explored relationships among these variables by examining a putative pathway to determine whether spirituality exerts its beneficial effects through gratitude. We found that gratitude fully mediated the relationship between spiritual well-being and sleep quality (z 2.35, SE .03, p .02) and also the relationship between spiritual well-being and depressed mood (z 4.00, SE .075, p .001). Gratitude also partially mediated the relationships between spiritual well-being and fatigue (z 3.85, SE .18, p .001) and between spiritual well-being and self-efficacy (z 2.91, SE .04, p .003). In sum, we report that gratitude and spiritual well-being are related to better mood and sleep, less fatigue, and more self-efficacy, and that gratitude fully or partially mediates the beneficial effects of spiritual well-being on these endpoints. Efforts to increase gratitude may be a treatment for improving well-being in HF patients’ lives and be of potential clinical value.

/pdf/the-role-of-gratitude-in-spiritual-well-being-in-dmrtzdbx8y.pdf

Deepak Chopra

Papers

Therapeutic Uses of Triphala in Ayurvedic Medicine

The zinc dyshomeostasis hypothesis of alzheimer's disease

Quantum Healing : Exploring the Frontiers of Mind/Body Medicine

The Role of Gratitude in Spiritual Well-being in Asymptomatic Heart Failure Patients.

The embodied mind: A review on functional genomic and neurological correlates of mind-body therapies.