Extracellular Vesicles Derived From Stem Cells in Intervertebral Disc Degeneration

Intervertebral disc degeneration (IVDD) is the leading cause of low back pain related to degradation of cartilaginous tissues, mainly resulting from oxidative stress, cell apoptosis, and extracellular matrix degradation. Extracellular vesicles (EVs) exist in all bodily fluids and can be produced by all types of cells. Stem cell-derived EVs (SC-EVs), which are the main paracrine components of stem cells, have gained significant attention in the field of regenerative medicine. Over the past years, accumulating evidence indicates the therapeutic and diagnostic potentials of EVs in IVDD. The main mechanisms involve the induction of regenerative phenotypes, apoptosis alleviation, and immune modulation. In addition, the efficiency of SC-EVs can be enhanced by choosing appropriate donor cells and cell phenotypes, optimizing cell culture conditions, or engineering EVs to deliver drugs and targeting molecules. Given the importance and novelty of SC-EVs, we give an overview of SC-EVs and discuss the roles of SC-EVs in IVDD.

Emerging Molecular Markers Towards Potential Diagnostic Panels for Lupus

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease which can affect various tissues and organs, posing significant challenges for clinical diagnosis and treatment. The etiology of SLE is highly complex with contributions from environmental factors, stochastic factors as well as genetic susceptibility. The current criteria for diagnosing SLE is based primarily on a combination of clinical presentations and traditional lab testing. However, these tests have suboptimal sensitivity and specificity. They are unable to indicate disease cause or guide physicians in decision-making for treatment. Therefore, there is an urgent need to develop a more accurate and robust tool for effective clinical management and drug development in lupus patients. It is fortunate that the emerging Omics have empowered scientists in the discovery and identification of potential novel biomarkers of SLE, especially the markers from blood, urine, cerebrospinal fluids (CSF), and other bodily fluids. However, many of these markers have not been carefully validated for clinical use. In addition, it is apparent that individual biomarkers lack sensitivity or specificity. This review summarizes the sensitivity, specificity and diagnostic value of emerging biomarkers from recent studies, and discusses the potential of these markers in the development of biomarker panel based diagnostics or disease monitoring system in SLE.

The necessity for carnivore experimentation in predicting the next zoonotic disease epidemic

Zoonoses are human infections or diseases caused by disease spillover from vertebrate animals to people [1]. Spillover is the movement of pathogens from their normal host to a novel species [2]; this can occur through bodily fluids, bites, food, water, or contact with surfaces where infected animals have travelled [3]. Although some zoonoses remain established within populations and primarily affect only one person per spillover (classified as enzootic zoonoses—e.g., rabies), others can be transmitted between people and result in localized, or even global outbreaks [4]. Zoonoses account for over 60% of infectious diseases in humans [4] and can be caused by viruses, parasites, bacteria, or fungi. Of these, viral zoonoses prove to be of greatest detriment to the public on a widespread scale, as they are responsible for numerous epidemics and pandemics, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the novel coronavirus (COVID-19) [5-7]. Research has also been conducted on different taxonomic orders of species, such as Carnivora — placental animals which obtain nutrients from flesh — and their viral spillover risk [11].

On patients who explode: surviving petrifying psychotherapeutic experiences

Although most of our patients will enter the consulting room quite quietly, often in a depressive state, having contained their sadistic impulses, a tiny fraction of those with whom we work will attack us in a variety of chilling ways. In this article, the author describes in detail two particularly terrifying clinical experiences in which a patient either threatened to kill him or actually sullied his consulting room with bodily fluids. Drawing upon his psychotherapeutic encounters not only with intellectually disabled patients and forensic patients but, also, with those who presented as ordinary “normal-neurotics”, the author considers the phenomenology of these “bomb”-like explosions and explains how he attempted to maintain a classical psychoanalytical focus of understanding, which consisted of a careful scrutiny of the countertransference and a firm commitment to the interpretation of unconscious material, whilst under attack. Furthermore, he examines the essential role of speaking with experienced colleagues who will provide essential supervision or assistance during these challenging chapters of clinical practice. The author also considers the many ways in which “bombs” can be hurled not only by the more obviously dangerous or disturbed individuals but, also, with surprising frequency, by those with no criminal history whatsoever, who, upon first encounter, often present as reasonably healthy.

New Insights Into the Regulatory Roles of Extracellular Vesicles in Tumor Angiogenesis and Their Clinical Implications

Angiogenesis is required for tumor growth and development. Extracellular vesicles (EVs) are important signaling entities that mediate communication between diverse types of cells and regulate various cell biological processes, including angiogenesis. Recently, emerging evidence has suggested that tumor-derived EVs play essential roles in tumor progression by regulating angiogenesis. Thousands of molecules are carried by EVs, and the two major types of biomolecules, noncoding RNAs (ncRNAs) and proteins, are transported between cells and regulate physiological and pathological functions in recipient cells. Understanding the regulation of EVs and their cargoes in tumor angiogenesis has become increasingly important. In this review, we summarize the effects of tumor-derived EVs and their cargoes, especially ncRNAs and proteins, on tumor angiogenesis and their mechanisms, and we highlight the clinical implications of EVs in bodily fluids as biomarkers and as diagnostic, prognostic, and therapeutic targets in cancer patients.

Possibility of Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) through Wastewater in Developing Countries

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was detected in Wuhan, China. The clinical manifestation of COVID-19 varies from asymptomatic to severe infection. The World Health Organization has reported over 248 million cases and more than 5 million deaths worldwide due to COVID-19. Additionally, developing countries are still struggling to achieve the rapid diagnosis of suspected cases to break the chain of transmission of COVID-19. There may be undiagnosed or missing cases in these countries. Various studies have reported that the SARS-CoV-2 can be discharged in the stool and other bodily fluids. Moreover, it is possible that SARS-CoV-2 can be transmitted in the environment via municipal wastewater. In developing countries, such as Nepal, the molecular-based diagnosis of SARS-CoV-2 for the entire population is not practical owing to insufficient diagnostic material and budgetary constraints. Wastewater-based epidemiology (WBE) is a promising public health surveillance tool for the early warning of disease outbreaks and the understanding the prevalence of viruses for the development of intervention measures. This study highlights the importance of the utilization of WBE as an alternative tool for the mass detection of SARS-CoV-2 RNA in wastewater.

Multiplexed Profiling of Extracellular Vesicles for Biomarker Development

Extracellular vesicles (EVs) are cell-derived membranous particles that play a crucial role in molecular trafficking, intercellular transport and the egress of unwanted proteins. They have been implicated in many diseases including cancer and neurodegeneration. EVs are detected in all bodily fluids, and their protein and nucleic acid content offers a means of assessing the status of the cells from which they originated. As such, they provide opportunities in biomarker discovery for diagnosis, prognosis or the stratification of diseases as well as an objective monitoring of therapies. The simultaneous assaying of multiple EV-derived markers will be required for an impactful practical application, and multiplexing platforms have evolved with the potential to achieve this. Herein, we provide a comprehensive overview of the currently available multiplexing platforms for EV analysis, with a primary focus on miniaturized and integrated devices that offer potential step changes in analytical power, throughput and consistency.