Lipidomic and proteomic insights from extracellular vesicles in the postmortem dorsolateral prefrontal cortex reveal substance use disorder-induced brain changes.

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to reactive astrogliosis and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD.

Rigorous Process for Isolation of Gut-Derived Extracellular Vesicles (EVs) and the Effect on Latent HIV.

The human gastrointestinal (GI) track host trillions of microorganisms that secrete molecules, including extracellular vesicles (EVs) and extracellular condensates (ECs) that may affect physiological and patho-physiological activities in the host. However, efficient protocols for the isolation of pure and functional GI-derived EVs|ECs is lacking. Here, we describe the use of high-resolution particle purification liquid chromatography (PPLC) gradient-bead-column integrated with polyvinylpolypyrrolidone (PVPP)-mediated extraction of impurities to isolate EVs from colonic content (ColEVs).

Rigorous process for isolation of gut-derived extracellular vesicles and the effect on latent HIV.

Aim: Extracellular particles (EPs) are produced/secreted by cells from all domains of life and are present in all body fluids, brain, and gut. EPs consist of extracellular vesicles (EVs) made up of exosomes, microvesicles, and other membranous vesicles; and extracellular condensates (ECs) that are non-membranous carriers of lipid-protein-nucleic acid aggregates. The purity of EVs|ECs, which ultimately depends on the isolation method used to obtain them is critical, particularly EVs|ECs from the gastrointestinal (GI) tract that is colonized by a huge number of enteric bacteria.

Lipidomic and Proteomic Insights from Extracellular Vesicles in Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes.

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to glial activation and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD.

Alterations in Abundance and Compartmentalization of miRNAs in Blood Plasma Extracellular Vesicles and Extracellular Condensates during HIV/SIV Infection and Its Modulation by Antiretroviral Therapy (ART) and Delta-9-Tetrahydrocannabinol (Δ-THC).

In this follow-up study, we investigated the abundance and compartmentalization of blood plasma extracellular miRNA (exmiRNA) into lipid-based carriers-blood plasma extracellular vesicles (EVs) and non-lipid-based carriers-extracellular condensates (ECs) during SIV infection. We also assessed how combination antiretroviral therapy (cART), administered in conjunction with phytocannabinoid delta-9-tetrahydrocannabinol (THC), altered the abundance and compartmentalization of exmiRNAs in the EVs and ECs of SIV-infected rhesus macaques (RMs). Unlike cellular miRNAs, exmiRNAs in blood plasma may serve as minimally invasive disease indicators because they are readily detected in stable forms.

SIV Infection Regulates Compartmentalization of Circulating Blood Plasma miRNAs within Extracellular Vesicles (EVs) and Extracellular Condensates (ECs) and Decreases EV-Associated miRNA-128.

: This is Manuscript 1 of a two-part Manuscript of the same series. Here, we present findings from our first set of studies on the abundance and compartmentalization of blood plasma extracellular microRNAs (exmiRNAs) into extracellular particles, including blood plasma extracellular vesicles (EVs) and extracellular condensates (ECs) in the setting of untreated HIV/SIV infection. The goals of the study presented in this Manuscript 1 are to (i) assess the abundance and compartmentalization of exmiRNAs in EVs versus ECs in the healthy uninfected state, and (ii) evaluate how SIV infection may affect exmiRNA abundance and compartmentalization in these particles.

SARS-CoV-2: big seroprevalence data from Pakistan-is herd immunity at hand?

Purpose: Seroprevalence surveys from different countries have reported SARS CoV-2 antibodies below 20% even in the most adversely affected areas and herd immunity cannot be predicted till more than half of the population gets the disease. The purpose of this survey was to estimate the magnitude of community-based spread of the infection, associated immunity, and the future prospects and proximity to a 'herd community'.

Methods: The study was undertaken as a cluster randomized, cross-sectional countrywide survey.

BST-2 promotes survival in circulation and pulmonary metastatic seeding of breast cancer cells.

Bone marrow stromal antigen 2 (BST-2) mediates various facets of cancer progression and metastasis. Here, we show that BST-2 is linked to poor survival in invasive breast cancer patients as its expression positively correlates with disease severity. However, the mechanisms that drive the pro-metastatic functions of BST-2 are not fully understood.

Structural determinant of BST-2-mediated regulation of breast cancer cell motility: a role for cytoplasmic tail tyrosine residues.

There is now irrefutable evidence that overexpression of the innate immunity protein-BST-2, in breast cancer cells is implicated in tumor growth and progression. The cellular mechanisms that control BST-2-mediated effect in tumor progression involve enhancement of cancer cell motility-migration/invasion. However, the distinct structural elements of BST-2 that mediate breast cancer cell motility remain unknown.

Prevalence of EBV, HPV and MMTV in Pakistani breast cancer patients: A possible etiological role of viruses in breast cancer.

Background: Breast cancer being a multifactorial disease, the role of infectious agent in development of disease is of great interest. The high incidence of breast cancer around the world has woken the interest in a viral etiology of breast cancer. Despite decades of research, no etiologic factor(s) for human breast cancer has been known and the quest for a contributing cause has all but been abandoned during the past years.

Detection and identification of mouse mammary tumor virus-like DNA sequences in blood and breast tissues of breast cancer patients.

Mouse mammary tumor virus (MMTV) is a well-known cause of mammary tumors in mice transmitted as endogenous proviruses or exogenously as infectious virions. The hypothesis that a retrovirus homologous to MMTV is involved in human breast cancers has resulted in renewed interest in the etiology of human breast cancer. Therefore, the detection of MMTV-like exogenous sequences in 30-40 % of invasive breast cancer has increased attention towards this hypothesis.