Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders.

Neuroinflammatory and neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood. These disorders show dysregulated neuroimmune and inflammatory responses, including activation of neurons, glial cells, and neurovascular unit damage associated with excessive release of proinflammatory cytokines, chemokines, neurotoxic mediators, and infiltration of peripheral immune cells into the brain, as well as entry of inflammatory mediators through damaged neurovascular endothelial cells, blood-brain barrier and tight junction proteins. Activation of glial cells and immune cells leads to the release of many inflammatory and neurotoxic molecules that cause neuroinflammation and neurodegeneration. Gulf War Illness (GWI) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic disorders that are also associated with neuroimmune dysfunctions. Currently, there are no effective disease-modifying therapeutic options available for these diseases. Human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, endothelial cells and pericytes are currently used for many disease models for drug discovery. This review highlights certain recent trends in neuroinflammatory responses and iPSC-derived brain cell applications in neuroinflammatory disorders.

Artichoke as a melanoma growth inhibitor.

Melanoma is the most lethal malignancy in skin cancers. About 97,610 new cases of melanoma are projected to occur in the United States (US) in 2023. Artichoke is a very popular plant widely consumed in the US due to its nutrition. In recent years, it has been shown that artichoke shows powerful anti-cancer effects on cancers such as breast cancer, colon cancer, liver cancer, and leukemia. However, there is little known about its effect on melanoma. This study was designed to investigate if artichoke extract (AE) has any direct effect on the growth of melanoma. Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the effects AE has on cell survival, proliferation, and apoptosis of the widely studied melanoma cell line HTB-72. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. The percentage of colonies of HTB-72 melanoma cells decreased significantly after treated with AE. This was paralleled with the decrease in the optic density (OD) value of cancer cells after treatment with AE. This was further supported by the decreased expression of PCNA mRNA after treated with AE. Furthermore, the cellular caspase-3 activity increased after treated with AE. The anti-proliferative effect of AE on melanoma cells correlated with increased p21, p27, and decreased CDK4. The pro-apoptotic effect of AE on melanoma cells correlated with decreased survivin. Artichoke inhibits growth of melanoma by inhibition of proliferation and promotion of apoptosis. Such a study might be helpful to develop a new promising treatment for melanoma.

COVID-19 and Long COVID: Disruption of the Neurovascular Unit, Blood-Brain Barrier, and Tight Junctions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), could affect brain structure and function. SARS-CoV-2 can enter the brain through different routes, including the olfactory, trigeminal, and vagus nerves, and through blood and immunocytes. SARS-CoV-2 may also enter the brain from the peripheral blood through a disrupted blood-brain barrier (BBB). The neurovascular unit in the brain, composed of neurons, astrocytes, endothelial cells, and pericytes, protects brain parenchyma by regulating the entry of substances from the blood. The endothelial cells, pericytes, and astrocytes highly express angiotensin converting enzyme 2 (ACE2), indicating that the BBB can be disturbed by SARS-CoV-2 and lead to derangements of tight junction and adherens junction proteins. This leads to increased BBB permeability, leakage of blood components, and movement of immune cells into the brain parenchyma. SARS-CoV-2 may also cross microvascular endothelial cells through an ACE2 receptor-associated pathway. The exact mechanism of BBB dysregulation in COVID-19/neuro-COVID is not clearly known, nor is the development of long COVID. Various blood biomarkers could indicate disease severity and neurologic complications in COVID-19 and help objectively diagnose those developing long COVID. This review highlights the importance of neurovascular and BBB disruption, as well as some potentially useful biomarkers in COVID-19, and long COVID/neuro-COVID.