Advanced Microfluidic Vascularized Tissues as Platform for the Study of Human Diseases and Drug Development.

The vascular system plays a critical role in human physiology and diseases. It is a complex subject to study using in vitro models due to its dynamic and three-dimensional microenvironment. Microfluidic technology has recently become a popular technology in various biological fields for its advantages in mimicking complex microenvironments to an extent not achievable by more conventional platforms. Microfluidic technologies can reproduce different vascular system-related structures and functions that can be utilized for drug development and human diseases studies. Herein we first review the relevant structural and functional vascular biology systems of various organ systems and then the fabrication methods to reproduce these vascular districts. We provide a thorough review of the latest achievement in vascular organ-on-chip modeling specific to lung, heart, and the brain microvasculature for drug screening and the study of human disorders.

Neuroinflammation and Its Impact on the Pathogenesis of COVID-19.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 include dry cough, difficult breathing, fever, fatigue, and may lead to pneumonia and respiratory failure. There are significant gaps in the current understanding of whether SARS-CoV-2 attacks the CNS directly or through activation of the peripheral immune system and immune cell infiltration. Although the modality of neurological impairments associated with COVID-19 has not been thoroughly investigated, the latest studies have observed that SARS-CoV-2 induces neuroinflammation and may have severe long-term consequences. Here we review the literature on possible cellular and molecular mechanisms of SARS-CoV-2 induced-neuroinflammation. Activation of the innate immune system is associated with increased cytokine levels, chemokines, and free radicals in the SARS-CoV-2-induced pathogenic response at the blood-brain barrier (BBB). BBB disruption allows immune/inflammatory cell infiltration into the CNS activating immune resident cells (such as microglia and astrocytes). This review highlights the molecular and cellular mechanisms involved in COVID-19-induced neuroinflammation, which may lead to neuronal death. A better understanding of these mechanisms will help gain substantial knowledge about the potential role of SARS-CoV-2 in neurological changes and plan possible therapeutic intervention strategies.

Molecular Mechanisms of Multi-Organ Failure in COVID-19 and Potential of Stem Cell Therapy.

As the number of confirmed cases and deaths occurring from Coronavirus disease 2019 (COVID-19) surges worldwide, health experts are striving hard to fully comprehend the extent of damage caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 primarily manifests itself in the form of severe respiratory distress, it is also known to cause systemic damage to almost all major organs and organ systems within the body. In this review, we discuss the molecular mechanisms leading to multi-organ failure seen in COVID-19 patients. We also examine the potential of stem cell therapy in treating COVID-19 multi-organ failure cases.

Cerebrovascular and Neurological Dysfunction under the Threat of COVID-19: Is There a Comorbid Role for Smoking and Vaping?

The recently discovered novel coronavirus, SARS-CoV-2 (COVID-19 virus), has brought the whole world to standstill with critical challenges, affecting both health and economic sectors worldwide. Although initially, this pandemic was associated with causing severe pulmonary and respiratory disorders, recent case studies reported the association of cerebrovascular-neurological dysfunction in COVID-19 patients, which is also life-threatening. Several SARS-CoV-2 positive case studies have been reported where there are mild or no symptoms of this virus. However, a selection of patients are suffering from large artery ischemic strokes. Although the pathophysiology of the SARS-CoV-2 virus affecting the cerebrovascular system has not been elucidated yet, researchers have identified several pathogenic mechanisms, including a role for the ACE2 receptor. Therefore, it is extremely crucial to identify the risk factors related to the progression and adverse outcome of cerebrovascular-neurological dysfunction in COVID-19 patients. Since many articles have reported the effect of smoking (tobacco and cannabis) and vaping in cerebrovascular and neurological systems, and considering that smokers are more prone to viral and bacterial infection compared to non-smokers, it is high time to explore the probable correlation of smoking in COVID-19 patients. Herein, we have reviewed the possible role of smoking and vaping on cerebrovascular and neurological dysfunction in COVID-19 patients, along with potential pathogenic mechanisms associated with it.