Increased Oxidative Stress and Decreased Sirtuin-3 and FOXO3 Expression Following Carotid Artery Intimal Injury in Hyperlipidemic Yucatan Microswine.

Hypercholesterolemia is a major risk factor for atherosclerosis as oxidized-low-density lipoproteins (ox-LDL) contribute to the formation of foam cells and inflammation. Increased immune cell infiltration and oxidative stress induce instability of a plaque. Rupture of the unstable plaque precipitates adverse ischemic events. Since reactive oxygen species (ROS) play a critical role in plaque formation and vulnerability, regulating ROS generation may have therapeutic potential. Sirtuins, specifically sirtuin-3 (SIRT3), are antigenic molecules that can reduce oxidative stress by reducing mitochondrial ROS production through epigenetic modulation. Lack of SIRT3 expression is associated with dysregulation of ROS and endothelial function following high-fat high-cholesterol diet. SIRT3 deacetylates FOXO3a (Forkhead transcription factor O subfamily member 3a) and protects mitochondria against oxidative stress which can lead to even further protective anti-oxidizing properties. This study was designed to investigate the association between hyperlipidemia, intimal injury, chronic inflammation, and the expression of NAD-dependent deacetylase SIRT-3, FOXO3, antioxidant genes, and oxidative stress in carotid arteries of hypercholesterolemic Yucatan microswine. We found that intimal injury in hypercholesterolemic state led to increased expression of oxidative stress, inflammation, neointimal hyperplasia, and plaque size and vulnerability, while decreasing anti-oxidative regulatory genes and mediators. The findings suggest that targeting the SIRT3-FOXO3a-oxidative stress pathway will have therapeutic significance.

A Review of Hematological Complications and Treatment in COVID-19.

COVID-19, caused by SARS-CoV-2, and its variants have spread rapidly across the globe in the past few years, resulting in millions of deaths worldwide. Hematological diseases and complications associated with COVID-19 severely impact the mortality and morbidity rates of patients; therefore, there is a need for oversight on what pharmaceutical therapies are prescribed to hematologically at-risk patients. Thrombocytopenia, hemoglobinemia, leukopenia, and leukocytosis are all seen at increased rates in patients infected with COVID-19 and become more prominent in patients with severe COVID-19. Further, COVID-19 therapeutics may be associated with hematological complications, and this became more important in immunocompromised patients with hematological conditions as they are at higher risk of hematological complications after treatment. Thus, it is important to understand and treat COVID-19 patients with underlying hematological conditions with caution. Hematological changes during COVID-19 infection and treatment are important because they may serve as biomarkers as well as to evaluate the treatment response, which will help in changing treatment strategies. In this literature review, we discuss the hematological complications associated with COVID-19, the mechanisms, treatment groups, and adverse effects of commonly used COVID-19 therapies, followed by the hematological adverse events that could arise due to therapeutic agents used in COVID-19.

Biomarkers to monitor the prognosis, disease severity, and treatment efficacy in coronary artery disease.

INTRODUCTION: Coronary Artery Disease (CAD) is a prevalent condition characterized by the presence of atherosclerotic plaques in the coronary arteries of the heart. The global burden of CAD has increased significantly over the years, resulting in millions of deaths annually and making it the leading health-care expenditure and cause of mortality in developed countries. The lack of cost-effective strategies for monitoring the prognosis of CAD warrants a pressing need for accurate and efficient markers to assess disease severity and progression for both reducing health-care costs and improving patient outcomes. AREA COVERED: To effectively monitor CAD, prognostic biomarkers and imaging techniques play a vital role in risk-stratified patients during acute treatment and over time. However, with over 1,000 potential markers of interest, it is crucial to identify the key markers with substantial utility in monitoring CAD progression and evaluating therapeutic interventions. This review focuses on identifying and highlighting the most relevant markers for monitoring CAD prognosis and disease severity. We searched for relevant literature using PubMed and Google Scholar. EXPERT OPINION: By utilizing the markers discussed, health-care providers can improve patient care, optimize treatment plans, and ultimately reduce health-care costs associated with CAD management.

Coronary artery disease is a narrowing or blockage of coronary arteries due to the formation of plaque. The main risk factors are inflammation, aging, high cholesterol, shear stress, obesity, and smoking. Narrowing of the arteries results in decreased blood supply (nutrient and oxygen) to the tissue precipitating ischemia presented as angina or myocardial infarction. During ischemic events, there occurs a change in the expression of various molecular and cellular components and increased expressions of many of these factors have been used as biomarkers to diagnose the pathology. Myoglobin, fatty acid-binding proteins, and glycogen phosphorylase isoenzyme BB are early biomarkers, troponin-T and troponin-I are late biomarkers, while creatine kinase-myocardial band is a biomarker in the first 10­12 h for the diagnosis of AMI. However, there is a need for a panel of biomarkers that can help in the prediction, prognosis, and diagnosis of disease progression (atherosclerosis), pre-ischemic and ischemic events, and post-MI periods to design the treatment strategies in a specific and sensitive manner. There is a need for cost-effective sensitive biomarkers that can prevent progression, risk stratify, predict, diagnose, and prevent MI in a timely manner. In this comprehensive review, we discuss the key markers of substantial utility for monitoring coronary artery disease progression and the efficacy of therapeutic intervention among various markers of interest.

Adverse Hematological Effects of COVID-19 Vaccination and Pathomechanisms of Low Acquired Immunity in Patients with Hematological Malignancies.

The SARS-CoV-2 virus and the COVID-19 pandemic have spread across the world and severely impacted patients living with hematological conditions. Immunocompromised patients experience rapidly progressing symptoms following COVID-19 infection and are at high risk of death. In efforts to protect the vulnerable population, vaccination efforts have increased exponentially in the past 2 years. Although COVID-19 vaccination is safe and effective, mild to moderate side effects such as headache, fatigue, and soreness at the injection site have been reported. In addition, there are reports of rare side effects, including anaphylaxis, thrombosis with thrombocytopenia syndrome, Guillain-Barré Syndrome, myocarditis, and pericarditis after vaccination. Further, hematological abnormalities and a very low and transient response in patients with hematological conditions after vaccination raise concerns. The objective of this review is to first briefly discuss the hematological adverse effects associated with COVID-19 infection in general populations followed by critically analyzing the side effects and pathomechanisms of COVID-19 vaccination in immunocompromised patients with hematological and solid malignancies. We reviewed the published literature, with a focus on hematological abnormalities associated with COVID-19 infection followed by the hematological side effects of COVID-19 vaccination, and the mechanisms by which complications can occur. We extend this discussion to include the viability of vaccination efforts within immune-compromised patients. The primary aim is to provide clinicians with critical hematologic information on COVID-19 vaccination so that they can make informed decisions on how to protect their at-risk patients. The secondary goal is to clarify the adverse hematological effects associated with infection and vaccination within the general population to support continued vaccination within this group. There is a clear need to protect patients with hematological conditions from infection and modulate vaccine programs and procedures for these patients.

Mitochondrial Biogenesis as a Therapeutic Target for Rotator Cuff Tendon Tears.

Rotator Cuff Injuries (RCI) are highly prevalent and characterized by shoulder pain, restricted shoulder movement, and difficulty with overhead activity, radiating pain in the deltoid muscle, and atrophy of the rotator cuff muscles. Increasing age, hand dominance, smoking, hypertension, hyperlipidemia, and obesity are common risk factors. Chronic inflammation plays a critical role in the underlying pathogenesis. RCI accounts for massive healthcare expenditure costing about $15,000 per repair, and over 4.5 million physician visits per year, however, there is still no therapeutic target to improve clinical outcomes. Mitochondrial biogenesis in response to inflammatory stimuli supports increased cellular energy requirements, cell proliferation, and differentiation. This suggests that mitochondrial biogenesis may play a role in healing RCI by serving as a protective factor against free oxygen species and promoting homeostasis within the rotator cuff. There is evidence highlighting the potential therapeutic benefits of mitochondrial biogenesis in various inflammatory diseases, but no study explored the role of mitochondrial biogenesis in rotator cuff tears. Since hypercholesterolemia is a risk factor for RCI, we investigated the effects of hypercholesterolemia on the expression of PGC-1α, a marker of mitochondrial biogenesis, in rotator cuff muscle. The findings revealed an increased gene and protein expression of inflammatory mediators and PGC-1α, suggesting enhanced inflammation and increased mitochondrial biogenesis due to hypercholesterolemia. Additional studies are warranted to further investigate the chronic effect of hyperlipidemia induced RCI to elucidate the cause of insufficient mitochondrial biogenesis unable to protect the rotator cuff and the therapeutic effect of promoting mitochondrial biogenesis.

Rotator Cuff Health, Pathology, and Repair in the Perspective of Hyperlipidemia.

Rotator Cuff Injuries (RCI) are prevalent cause of shoulder pain affecting over 20% of the population in the USA. Surgical repair of the torn rotator cuff helps in relieving the pressure on the rotator cuff tendon and from symptoms, however tendon-to-bone healing after rotator cuff surgery still has a high failure rate. Hyperlipidemia has been strongly associated with RCI although the cellular and molecular mechanisms are largely unknown. The focus of this critical review is to further explore the role of hyperlipidemia in RCI and rotator cuff tissue repair to determine its implication as a risk factor for tears, repair, and retears. A literature review was conducted to elucidate the role of hyperlipidemia as an inflammatory mediator and catalyst for structural instability within the shoulder. The results from various studies were critically reviewed to summarize the relationship between hyperlipidemia and rotator cuff pathology. Hyperlipidemia induces LDL-particle entrapment within the dense regular collagen of rotator cuff tendons resulting in foam cell aggregation and macrophage recruitment. Subsequent inflammatory pathways including the JAK2/STAT3 pathway and NLRP3 inflammasome pathway led to persistent inflammation and Extracellular Matrix (ECM) degradation within the rotator cuff. While arthroscopic repair remains the most common treatment modality, nonsurgical treatment including statins, vitamin D, and targeting miRNA are also of therapeutic benefit. Hyperlipidemia interferes with arthroscopic repairs by inducing inflammation and stiffness within tendons and increases the risk of retears. Most notably, targeting underlying mechanisms influencing inflammation has large therapeutic value as a novel treatment strategy for the management of rotator cuff pathology.

Influence of Riparian Habitat and Ground Covers on Threecornered Alfalfa Hopper (Hemiptera: Membracidae) Populations in Vineyards.

Grapevine red blotch virus (GRBV) is the causal agent of grapevine red blotch disease, which affects wine grapes and leads to reduced crop yield and quality. While some virus spread can be attributed to the propagation of infected plant material, a greenhouse assay recently demonstrated that the threecornered alfalfa hopper (Membracidae: Spissistilus festinus Say) can transmit GRBV between grapevines. While S. festinus is not considered an economic pest of wine grapes, this species is present in California vineyards and their feeding can cause petiole girdling. Recent surveys have noted a correlation between S. festinus populations and GRBV-positive vines in vineyard areas adjacent to riparian habitat. Here, S. festinus populations were monitored over a 2-yr period at multiple vineyard sites adjacent to riparian habitats. At each site, insects were sampled from ground covers and the vine canopy at the vineyard edge and interior, and vines in both locations were evaluated for petiole girdling. Results indicate that there was no difference in abundance of S. festinus at the vineyard edge and interior. Populations in the vine canopy were highest in the late spring and early summer, and this was followed by the appearance of petiole girdling, indicating a key period of potential GRBV transmission. Furthermore, activity in the vine canopy appears to be amplified when the quality of ground covers is reduced as the season progresses. That said, overall populations of S. festinus were relatively low and additional work is needed to characterize the timing and efficiency of transmission under field conditions.