A5066398979- Mitochondrial Function and Pathology
- Alzheimer's disease research and treatments
- Autophagy in Disease and Therapy
- Cholinesterase and Neurodegenerative Diseases
- HIV Research and Treatment
- Tryptophan and brain disorders
- Sirtuins and Resveratrol in Medicine
- ATP Synthase and ATPases Research
- Surgical Sutures and Adhesives
- Calcium signaling and nucleotide metabolism
- Metabolomics and Mass Spectrometry Studies
- Biochemical Acid Research Studies
- Lung Cancer Diagnosis and Treatment
- Hernia repair and management
- Medical and Biological Sciences
- Pleural and Pulmonary Diseases
- Cardiac, Anesthesia and Surgical Outcomes
- Endometriosis Research and Treatment
- Pulmonary Hypertension Research and Treatments
- Cell death mechanisms and regulation
- Tracheal and airway disorders
- Immune Response and Inflammation
- Diverticular Disease and Complications
- Gastric Cancer Management and Outcomes
- Gastrointestinal Tumor Research and Treatment
WinnMed
2008-2025
Mayo Clinic
2014-2024
Mayo Clinic in Arizona
2001-2023
Ryazan State Medical University named after Academician I.P. Pavlov
2016-2023
Ministry of Health of the Russian Federation
2023
Mayo Clinic in Florida
2008-2009
Abstract Altered brain metabolism is associated with progression of Alzheimer’s Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture the tissue organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction visualize mitochondrial structure in from patients mouse models AD. We identified a previously unknown arrest phenotype that results elongated interconnected “mitochondria-on-a-string”...
Development of therapeutic strategies to prevent Alzheimer's Disease (AD) is great importance. We show that mild inhibition mitochondrial complex I with small molecule CP2 reduces levels amyloid beta and phospho-Tau averts cognitive decline in three animal models familial AD. Low-mass molecular dynamics simulations biochemical studies confirmed competes flavin mononucleotide for binding the redox center leading elevated AMP/ATP ratio activation AMP-activated protein kinase neurons mouse...
Autophagy is an essential catabolic process that promotes the clearance of surplus or damaged intracellular components. Loss autophagy in age-related human pathologies contributes to tissue degeneration through a poorly understood mechanism. Here, we identify evolutionarily conserved role from yeast humans preservation nicotinamide adenine dinucleotide (NAD) levels, which are critical for cell survival. In respiring mouse fibroblasts with deficiency, loss mitochondrial quality control was...
Mitochondria respond to metabolic demands of the cell and incremental damage, in part, through dynamic structural changes that include fission (fragmentation), fusion (merging distinct mitochondria), autophagic degradation (mitophagy), biogenic interactions with endoplasmic reticulum (ER). High resolution study mitochondrial functional relationships requires rapid preservation specimens reduce technical artifacts coupled quantitative assessment architecture. A practical approach for...
Autophagy is a homeostatic process critical for cellular survival, and its malfunction implicated in human diseases including neurodegeneration. Loss of autophagy contributes to cytotoxicity tissue degeneration, but the mechanistic understanding this phenomenon remains elusive. Here, we generated autophagy-deficient (ATG5−/−) embryonic stem cells (hESCs), from which established neuronal platform investigate how loss affects survival. ATG5−/− neurons exhibit basal accompanied by metabolic...
Abstract Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder without cure. Here we show that mitochondrial respiratory chain complex I an important small molecule druggable target in AD. Partial inhibition of triggers the AMP-activated protein kinase-dependent signaling network leading to neuroprotection symptomatic APP/PS1 female mice, translational model Treatment mice with inhibitor improved energy homeostasis, synaptic activity, long-term potentiation, dendritic spine...
Inhibition of mitochondrial axonal trafficking by amyloid beta (Aβ) peptides has been implicated in early pathophysiology Alzheimer's Disease (AD). Yet, it remains unclear whether the loss motility inevitably induces function, and restoration represents a valid therapeutic target. Moreover, while some investigations identify Aβ oligomers as culprit inhibition, others propose that fibrils play detrimental role. We have examined effect panel with different mutations found familial AD on...
Abstract In HIV-infected patients, concurrent infections with bacteria and viruses are known to induce HIV replication as assessed by increases in plasma RNA levels. the present study, we determined cell surface receptor molecular mechanisms of enterobacterial LPS-induced transcription. Human dermal microvessel endothelial cells (HMEC) were transfected an HIV-long terminal repeat (LTR)-luciferase construct subsequently stimulated purified bacterial LPS. Our studies demonstrate that human...
Alzheimer’s disease (AD) has no cure. Earlier, we showed that partial inhibition of mitochondrial complex I (MCI) with the small molecule CP2 induces an adaptive stress response, activating multiple neuroprotective mechanisms. Chronic treatment reduced inflammation, Aβ and pTau accumulation, improved synaptic functions, blocked neurodegeneration in symptomatic APP/PS1 mice, a translational model AD. Here, using serial block-face scanning electron microscopy (SBFSEM) three-dimensional (3D) EM...
This protocol is for the synthesis of cis-(N-(pyridin-4-ylmethyl)-2-(3-(m-tolyloxy)cyclohexyl)propan-1-amine) (c458)
This protocol is for LC-MS/MS quantification of C458. has been used to detect tissue concentrations
Abstract Despite recent approval of monoclonal antibodies that reduce amyloid (Aβ) accumulation, the development disease-modifying strategies targeting underlying mechanisms Alzheimer’s disease (AD) is urgently needed. We demonstrate mitochondrial complex I (mtCI) represents a druggable target, where its weak inhibition activates neuroprotective signaling, benefiting AD mouse models with Aβ and p-Tau pathologies. Rational design structure‒activity relationship studies yielded novel mtCI...
Impairment of autophagy leads to an accumulation misfolded proteins and damaged organelles has been implicated in plethora human diseases. Loss actively respiring cells also shown trigger metabolic collapse mediated by the depletion nicotinamide adenine dinucleotide (NAD) pools, resulting cell death. Here we found that deficit autophagy-NAD axis underpins loss viability models a neurodegenerative lysosomal storage disorder, Niemann-Pick type C1 (NPC1) disease. Defective autophagic flux NPC1...
Virus-host interactions are characterized by the selection of adaptive mechanisms which to evade pathogenic and defense mechanisms, respectively. In primary T cells infected with HIV, HIV infection up-regulates TNF-related apoptosis inducing ligand (TRAIL) death-inducing TRAIL receptors, but blockade TRAIL:TRAIL receptor interaction does not alter HIV-induced cell death. Instead, results in a novel splice variant that we call TRAIL-short (TRAIL-s), antagonizes TRAIL-R2. patients, plasma...
Human monocytes and macrophages are persistent reservoirs of human immunodeficiency virus (HIV) type-1. Persistent HIV infection these cells results in increased levels NF-kappaB the nucleus secondary to IkappaBalpha, IkappaBbeta, IkappaBepsilon degradation, a mechanism postulated regulate viral persistence. To characterize molecular mechanisms regulating HIV-mediated degradation IkappaB, we have sought identify regulatory domains IkappaBalpha targeted by infection. Using monocytic stably...
Alzheimer’s Disease (AD) has no cure. Earlier, we showed that partial inhibition of mitochondrial complex I (MCI) with small molecule CP2 induces adaptive stress response activating multiple neuroprotective mechanisms. Chronic treatment reduced inflammation, improved synaptic and functions, blocked neurodegeneration in symptomatic APP/PS1 mice, a translational model AD. Here, using serial block-face scanning electron microscopy (SBFSEM) three-dimensional (3D) EM reconstructions...
to present the results of treatment rectal foreign bodies.15-year outcomes 112 patients with bodies were analyzed.Outpatient and hospital care applied in 52 (46%) 60 (54%) cases respectively. Transanal removal was made 97 (87%) including 28 (25%) general anaesthesia. 14 (13%) underwent surgery. Colostomy performed 7 (6%) cases. We presented through laparotomy, colotomy SILS-assisted transanal approach.From clinical point view should be first all classified by their dimensions. Anamnesis...
Autophagy is an essential catabolic process that promotes clearance of surplus or damaged intracellular components 1 . As a recycling process, autophagy also important for the maintenance cellular metabolites during periods starvation 2 Loss sufficient to cause cell death in animal models and likely contribute tissue degeneration number human diseases including neurodegenerative lysosomal storage disorders 3–7 However, it remains unclear which many functions primarily underlies its role...
Novel therapeutic strategies for Alzheimer's disease (AD) are of the greatest priority given consistent failure recent clinical trials focused on Aβ or pTau. Earlier, we demonstrated that mild mitochondrial complex I inhibitor CP2 blocks neurodegeneration and cognitive decline in multiple mouse models AD. To evaluate safety humans, performed a genome-wide association study (GWAS) using 196 lymphoblastoid cell lines identified 11 SNP loci 64 mRNA expression probe sets potentially associate...
Summary Mitochondrial dynamics (fission, fusion, and the formation of nanotunnels) morphology are very sensitive to cellular environment. Mitochondria may be adversely affected by oxidative stress, changes in calcium levels, hypoxia. Investigating precise relationship between organelle structure function requires methods that can adequately preserve mitochondria while providing accurate, quantitative measurements morphological attributes. Here, we demonstrate a practical approach for...
The paper presents the results of a survey 21 patients with primary spontaneous pneumothorax using valuation techniques phenotypic criteria connective tissue dysplasia.