Exercise, Neuroprotective Exerkines, and Parkinson's Disease: A Narrative Review.

Parkinson's disease (PD) is a prevalent neurodegenerative disease in which treatment often includes an exercise regimen. Exercise is neuroprotective in animal models of PD, and, more recently, human clinical studies have verified exercise's disease-modifying effect. Aerobic exercise and resistance training improve many of PD's motor and non-motor symptoms, while neuromotor therapy and stretching/flexibility exercises positively contribute to the quality of life in people with PD.

Suggestions on leading an academic research laboratory group.

This commentary is about running an academic research laboratory group, including some reflections, memories, and tips on effectively managing such a group of scientists focused on one's research. The author's academic career has spanned from 1982 to 2022, including postdoctoral research associate through the rank of professor with tenure. Currently, the author is in the final year of 3 years of phased retirement.

Role of SARS-CoV-2 in Modifying Neurodegenerative Processes in Parkinson's Disease: A Narrative Review.

The COVID-19 pandemic, caused by SARS-CoV-2, continues to impact global health regarding both morbidity and mortality. Although SARS-CoV-2 primarily causes acute respiratory distress syndrome (ARDS), the virus interacts with and influences other organs and tissues, including blood vessel endothelium, heart, gastrointestinal tract, and brain. We are learning much about the pathophysiology of SARS-CoV-2 infection; however, we are just beginning to study and understand the long-term and chronic health consequences.

PRIME Immunology: Self-directed Introduction to Medical School Immunology.

Introduction: Medical students find immunology difficult to understand and relate to clinically and are often frustrated by the amount of detailed material. We created PRIME Immunology: Preview or Review of Important Material for Everyone: (i) video modules, (ii) Instagram site, and (iii) vocabulary files called Immunology Language.

Methods: The self-paced modules introduced key topics in immunology for students to complete prior to their instructional block.

Golf as a Physical Activity to Potentially Reduce the Risk of Falls in Older Adults with Parkinson's Disease.

Advanced age is associated with an increased risk for falls in aging adults. Older adults are also more likely to be diagnosed with Parkinson's disease (PD), with advanced age as the most significant risk factor. PD is a neurodegenerative disorder with four Cardinal motor symptoms: rigidity, bradykinesia, postural instability, and tremor.

Treatment Options for Motor and Non-Motor Symptoms of Parkinson's Disease.

Parkinson's disease (PD) usually presents in older adults and typically has both motor and non-motor dysfunctions. PD is a progressive neurodegenerative disorder resulting from dopaminergic neuronal cell loss in the mid-brain substantia nigra pars compacta region. Outlined here is an integrative medicine and health strategy that highlights five treatment options for people with Parkinson's (PwP): rehabilitate, therapy, restorative, maintenance, and surgery.

Potential Role of Vitamin D in the Elderly to Resist COVID-19 and to Slow Progression of Parkinson's Disease.

While we are still learning more about COVID-19, caused by the novel SARS-CoV-2 virus, finding alternative and already available methods to reduce the risk and severity of the disease is paramount. One such option is vitamin D, in the form of vitamin D (cholecalciferol) supplementation, due to its potential antiviral properties. It has become apparent that older individuals have a greater risk of developing severe COVID-19, and compared to younger adults, the elderly have lower levels of vitamin D due to a variety of biological and behavioral factors.

Synergy between plasminogen activator inhibitor-1, α-synuclein, and neuroinflammation in Parkinson's disease.

Parkinson's disease (PD) is a progressive degenerative nervous system disorder and is the second most common neurodegenerative disorder in the elderly population. The disease originates from the loss of dopamine-producing neurons in the substantia nigra in the brain, resulting in unregulated activity of the basal ganglia. Αlpha-synuclein (α-syn) is a protein found to aggregate in the substantia nigra region of patients with PD, forming Lewy Body inclusions; its aggregation may contribute to neuronal cell death in PD.

Protease-Activated Receptor 1 Contributes to Angiotensin II-Induced Cardiovascular Remodeling and Inflammation.

Background: Angiotensin II (Ang II) plays an important role in cardiovascular disease. It also leads to the activation of coagulation. The coagulation protease thrombin induces cellular responses by activating protease-activated receptor 1 (PAR-1).

Employing Demand-Based Volumetric Forecasting to Identify Potential for and Roles of Devices in Scale-Up of Medical Male Circumcision in Zambia and Zimbabwe.

Introduction: Devices for male circumcision (MC) are becoming available in 14 priority countries where MC is being implemented for HIV prevention. Understanding potential impact on demand for services is one important programmatic consideration because countries determine whether to scale up devices within MC programs.

Methods: A population-based survey measuring willingness to undergo MC, assuming availability of surgical MC and 3 devices, was conducted among 1250 uncircumcised men, ages 10-49 years in Zambia and 1000 uncircumcised men, ages 13-49 years in Zimbabwe.

Emerging pathophysiological roles for fibrinolysis.

Purpose Of Review: The fibrinolytic system plays a key role in the regulation of hemostasis and thrombosis; however, it also has multiple pleiotropic effects. In this review, we examine the studies that investigated the role of the plasminogen activator system and its inhibitors outside the context of clot lysis.

Recent Findings: Activators of plasminogen, plasminogen receptors, and inhibitors of plasminogen activation all play a role in the proliferation, migration, and metastasis of tumor cells in many cancer types and may serve as prognostic and diagnostic markers.

Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer.

Cancer patients often have an activated clotting system and are at increased risk for venous thrombosis. In the present study, we analyzed tissue factor (TF) expression in 4 different human pancreatic tumor cell lines for the purpose of producing derivative tumors in vivo. We found that 2 of the lines expressed TF and released TF-positive microparticles (MPs) into the culture medium.

Mature breast adipocytes promote breast cancer cell motility.

Adipocytes express substances involved in both normal physiology and pathological processes. One such adipocyte protein is the Serpin (serine protease inhibitor) plasminogen activator inhibitor-1 (PAI-1). PAI-1 functions to inhibit urokinase type plasminogen activator (uPA) though PAI-1 itself is also implicated in breast cancer progression.

A high affinity, antidote-controllable prothrombin and thrombin-binding RNA aptamer inhibits thrombin generation and thrombin activity.

Background: The conversion of prothrombin to thrombin is one of two non-duplicated enzymatic reactions during coagulation. Thrombin has long been considered an optimal anticoagulant target because it plays a crucial role in fibrin clot formation by catalyzing the cleavage of fibrinogen, upstream coagulation cofactors and platelet receptors. Although a number of anti-thrombin therapeutics exist, it is challenging to use them clinically due to their propensity to induce bleeding.

Peroxisome Proliferator-Activated Receptor-γ Ligands Alter Breast Cancer Cell Motility through Modulation of the Plasminogen Activator System.

We investigated peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands effect on cell motility and the plasminogen activator system using normal MCF-10A and malignant MCF-10CA1 cell lines. Ciglitazone reduced both wound-induced migration and chemotaxis. However, the effect was not reversed with pretreatment of cells with the PPAR-γ-specific antagonist GW9662.

Serpin-glycosaminoglycan interactions.

Serpins (serine protease inhibitors) have traditionally been grouped together based on structural homology. They share common structural features of primary sequence, but not all serpins require binding to cofactors in order to achieve maximal protease inhibition. In order to obtain physiologically relevant rates of inhibition of target proteases, some serpins utilize the unbranched sulfated polysaccharide chains known as glycosaminoglycans (GAGs) to enhance inhibition.

Heparin cofactor II: discovery, properties, and role in controlling vascular homeostasis.

Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) found in high concentrations in human plasma. Despite its discovery >30 years ago, its physiological function is still poorly understood. It is known to inhibit thrombin, the predominant coagulation protease, and HCII-thrombin complexes have been found in plasma, yet it is thought to contribute little to normal hemostasis.

Regulation of thrombin-induced plasminogen activator inhibitor-1 in 4T1 murine breast cancer cells.

Protease-activated receptor-1 (PAR-1) and PAR-2 are overexpressed in cancer cells and activation of these receptors contributes to malignancy. We have recently shown that thrombin activates PAR-1, which induces transactivation of PAR-2, resulting in increased plasminogen activator inhibitor-1 (PAI-1) expression in 4T1 murine mammary adenocarcinoma cells. Our goal was to analyze the signal transduction pathways that regulate thrombin-induced PAI-1 expression.

Causal relationship between hyperfibrinogenemia, thrombosis, and resistance to thrombolysis in mice.

Epidemiologic studies have correlated elevated plasma fibrinogen (hyperfibrinogenemia) with risk of cardiovascular disease and arterial and venous thrombosis. However, it is unknown whether hyperfibrinogenemia is merely a biomarker of the proinflammatory disease state or is a causative mechanism in the etiology. We raised plasma fibrinogen levels in mice via intravenous infusion and induced thrombosis by ferric chloride application to the carotid artery (high shear) or saphenous vein (lower shear); hyperfibrinogenemia significantly shortened the time to occlusion in both models.

Overexpression of the cell cycle inhibitor p16INK4a promotes a prothrombotic phenotype following vascular injury in mice.

Objective: Age-associated cellular senescence is thought to promote vascular dysfunction. p16(INK4a) is a cell cycle inhibitor that promotes senescence and is upregulated during normal aging. In this study, we examine the contribution of p16(INK4a) overexpression to venous thrombosis.

Protease-activated receptors mediate crosstalk between coagulation and fibrinolysis.

The coagulation and fibrinolytic systems contribute to malignancy by increasing angiogenesis, tumor growth, tumor invasion, and tumor metastasis. Oncogenic transformation increases the expression of tissue factor (TF) that results in local generation of coagulation proteases and activation of protease-activated receptor (PAR)-1 and PAR-2. We compared the PAR-dependent expression of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI)-1 in 2 murine mammary adencocarcinoma cell lines: metastatic 4T1 cells and nonmetastatic 67NR cells.