Mechanisms of extracellular vesicle uptake and implications for the design of cancer therapeutics.

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose-limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off-target toxicity.

Past-Year HIV Testing, Current Antiretroviral Therapy Use, and Participation in Services for People Who Inject Drugs.

Evaluating routine HIV testing and treatment and use of services for people who inject drugs (PWID) is critical to curb the ongoing HIV epidemic. We analyzed data from the 2018 National HIV Behavioral Surveillance of PWID aged 18 years or older, recruited using respondent-driven sampling and offered anonymous HIV testing after survey. We performed bivariate and multivariable analyses with log-linked Poisson regression of the generalized linear models to examine the associations between demographics and PWID service use, past-year HIV testing, and current antiretroviral therapy (ART) use.

Extracellular Vesicles in the Skin Microenvironment: Emerging Roles as Biomarkers and Therapeutic Tools in Dermatologic Health and Disease.

The recent discovery of extracellular vesicles (EVs) carrying cargo consisting of various bioactive macromolecules that can modulate the phenotype of recipient target cells has revealed an important new mechanism through which cells can signal their neighbors and regulate their microenvironment. Because EV cargo and composition correlate with the physiologic state of their cell of origin, investigations into the role of EVs in disease pathogenesis and progression have become an area of intense study. The physiologic and pathologic effects of EVs on their microenvironment are incredibly diverse and include the modulation of molecular pathways involved in angiogenesis, inflammation, wound healing, epithelial-mesenchymal transition, proliferation, and immune escape.

Understanding the Experiences of Latinx LGBTQ Texans at the Beginning of the COVID-19 Pandemic.

Marginalized communities have been disproportionately affected by COVID-19, including both racial/ethnic minority and sexual minority populations. To date, there has been little research examining the impact of the COVID-19 pandemic at the intersections of marginalized identities. Furthermore, available national data on COVID-19 outcomes may obscure our understanding of region-specific outcomes, particularly in the U.

Changes in nascent chromatin structure regulate activation of the pro-fibrotic transcriptome and myofibroblast emergence in organ fibrosis.

Cell reprogramming to a myofibroblast responsible for the pathological accumulation of extracellular matrix is fundamental to the onset of fibrosis. Here, we explored how condensed chromatin structure marked by H3K72me3 becomes modified to allow for activation of repressed genes to drive emergence of myofibroblasts. In the early stages of myofibroblast precursor cell differentiation, we discovered that H3K27me3 demethylase enzymes UTX/KDM6B creates a delay in the accumulation of H3K27me3 on nascent DNA revealing a period of decondensed chromatin structure This period of decondensed nascent chromatin structure allows for binding of pro-fibrotic transcription factor, Myocardin-related transcription factor A (MRTF-A) to nascent DNA.

Association of provider HPV vaccination training with provider assessment of HPV vaccination status and recommendation of HPV vaccination.

The delivery of strong HPV vaccine recommendations hinges on the expertise of healthcare providers (HCPs) in assessing patients' status and recommending HPV vaccination. We conducted a population-based cross-sectional study of HCPs practicing in Texas to examine the relationship between HPV vaccination training of HCPs and HPV vaccination status assessment and recommendation. Logistic regression analyses were used to assess the association between HCPs' formal training and recency of training in HPV vaccination promotion or counseling with HPV vaccination status assessment and recommendation.

Sexual Behaviors and Human Papillomavirus Vaccination in a Heterosexually Active Adult Population at Increased Risk for HIV Infection.

Human papillomavirus (HPV) is the most common sexually acquired infection in the US. Vaccination is effective against infection with high-risk HPV strains, yet HPV vaccine coverage is lower in the US than the national target. This study aimed to determine the relationship between sexual behaviors and HPV vaccination in a heterosexually active population at increased risk for HIV infection.

Associations between HIV testing and multilevel stigmas among gay men and other men who have sex with men in nine urban centers across the United States.

Background: Complex manifestation of stigma across personal, community, and structural levels and their effect on HIV outcomes are less understood than effects in isolation. Yet, multilevel approaches that jointly assesses HIV criminalization and personal sexual behavior stigma in relation to HIV testing have not been widely employed or have only focused on specific subpopulations. The current study assesses the association of three types of MSM-related sexual behavior-related stigma (family, healthcare, general social stigma) measured at both individual and site levels and the presence/absence of laws criminalizing HIV transmission with HIV testing behaviors to inform HIV surveillance and prevention efforts among HIV-negative MSM in a holistic and integrated way.

Exploring Preventive Healthcare in a High-Risk Vulnerable Population.

This study describes preventive care behaviors and explores opportunities to deliver preventive sexual healthcare to a high-risk vulnerable population. Data from the National HIV Behavioral Surveillance (NHBS) system high-risk heterosexuals (HET) cycle (2019) in Houston, Texas, was used to describe preventive care utilization and assess the relationship between healthcare utilization and sociodemographic characteristics. More than 47% reported having no usual source of healthcare, and 94.

A National Survey of Palliative Care Team Compositions.

It is unclear how well palliative care teams are staffed at US cancer centers. Our primary objective was to compare the composition of palliative care teams between National Cancer Institute (NCI)-designated cancer centers and non-NCI-designated cancer centers in 2018. We also assessed changes in team composition between 2009 and 2018.

Genital Herpes Disclosure Attitudes Among Men Who Have Sex with Men.

An abundance of literature interested in sexually transmitted infections-related disclosure attitudes among MSM (men who have sex with men) exists. However, comparatively few studies have examined these with respect to genital herpes. This cross-sectional study examined attitudes about herpes-related disclosure among Houston MSM.

Metrics of Sexual Behavior Stigma Among Cisgender Men Who Have Sex With Men in 9 Cities Across the United States.

Men who have sex with men (MSM) in the United States are stigmatized for their same-sex practices, which can lead to risky sexual behavior, potentiating risk for human immunodeficiency virus (HIV) infection. Improved measurement is necessary for accurately reporting and mitigating sexual behavior stigma. We added 13 sexual behavior stigma items to local surveys administered in 2017 at 9 sites in the Centers for Disease Control and Prevention's National HIV Behavioral Surveillance system, which uses venue-based, time-sampling procedures to survey cisgender MSM in US Census Metropolitan Statistical Areas.

Palliative medicine integration in the USA: cancer centre executives' attitudes.

Objectives: To compare cancer centre (CC) executives' attitudes towards palliative care between National Cancer Institute-designated CCs (NCI-CCs) and non-NCI-designated CCs (non-NCI-CCs) in 2018 and to examine the changes in attitudes and beliefs between 2009 and 2018.

Methods: CC chief executives at all NCI-CCs and a random sample of non-NCI-CCs were surveyed from April to August 2018. Twelve questions examined the executives' attitudes towards palliative care integration, perceived barriers and self-assessments.

Keloid disorder: Fibroblast differentiation and gene expression profile in fibrotic skin diseases.

Keloid disorder, a group of fibroproliferative skin diseases, is characterized by unremitting accumulation of the extracellular matrix (ECM) of connective tissue, primarily collagen, to develop cutaneous tumors on the predilection sites of skin. There is a strong genetic predisposition for keloid formation, and individuals of African and Asian ancestry are particularly prone. The principal cell type responsible for ECM accumulation is the myofibroblast derived from quiescent resident skin fibroblasts either through trans-differentiation or from keloid progenitor stem cells with capacity for multi-lineage differentiation and self-renewal.

miRNA- and cytokine-associated extracellular vesicles mediate squamous cell carcinomas.

Unlabelled: Exosomes, or small extracellular vesicles (sEVs), serve as intercellular messengers with key roles in normal and pathological processes. Our previous work had demonstrated that Dsg2 expression in squamous cell carcinoma (SCC) cells enhanced both sEV secretion and loading of pro-mitogenic cargo. In this study, using wild-type Dsg2 and a mutant form that is unable to be palmitoylated (Dsg2cacs), we investigated the mechanism by which Dsg2 modulates SCC tumour development and progression through sEVs.

Molecular characteristics and functional differences of anti-PM/Scl autoantibodies and two other distinct and unique supramolecular structures known as "EXOSOMES".

The term "exosome" has been applied to three distinct supramolecular entities, namely the PM/Scl autoantibodies or "RNA exosomes", transforming DNA fragments termed "DNA exosomes", and small size extracellular vesicles knows as "exosomes". Some of the molecular components of the "PM/Scl exosome complex" or "RNA exosome" are recognized by specific autoantibodies present in the serum from some Systemic Sclerosis (SSc), polymyositis (PM) and polymyositis SSc (PM/Scl) overlap syndrome patients. On the other hand, one of the most active focuses of laboratory investigation in the last decade has been the biogenesis and role of extracellular vesicles known as "exosomes".

Abrogation of transforming growth factor-β-induced tissue fibrosis in mice with a global genetic deletion of Nox4.

Excessive connective tissue deposition in skin and various internal organs is characteristic of systemic sclerosis (SSc). The profibrotic growth factor TGF-β plays a crucial role in SSc pathogenesis. The expression of NADPH oxidase 4 (NOX4), a critical mediator of oxidative stress, is potently stimulated by TGF-β.

Trametinib prevents mesothelial-mesenchymal transition and ameliorates abdominal adhesion formation.

Background: Intra-abdominal adhesions are a major cause of morbidity after abdominal or gynecologic surgery. However, knowledge about the pathogenic mechanism(s) is limited, and there are no effective treatments. Here, we investigated a mouse model of bowel adhesion formation and the effect(s) of an Federal Drug Administration-approved drug (trametinib) in preventing adhesion formation.

Existing and novel biomarkers for precision medicine in systemic sclerosis.

The discovery and validation of biomarkers resulting from technological advances in the analysis of genomic, transcriptomic, lipidomic and metabolomic pathways involved in the pathogenesis of complex human diseases have led to the development of personalized and rationally designed approaches for the clinical management of such disorders. Although some of these approaches have been applied to systemic sclerosis (SSc), an unmet need remains for validated, non-invasive biomarkers to aid in the diagnosis of SSc, as well as in the assessment of disease progression and response to therapeutic interventions. Advances in global transcriptomic technology over the past 15 years have enabled the assessment of microRNAs that circulate in the blood of patients and the analysis of the macromolecular content of a diverse group of lipid bilayer membrane-enclosed extracellular vesicles, such as exosomes and other microvesicles, which are released by all cells into the extracellular space and circulation.

Abrogation of transforming growth factor-β-induced tissue fibrosis in TBRIcaCol1a2Cre transgenic mice by the second generation tyrosine kinase inhibitor SKI-606 (Bosutinib).

Transforming growth factor-β (TGF-β) plays a crucial role in the pathogenesis of Systemic Sclerosis (SSc) and other fibrotic disorders. TGF-β-mediated c-Abl and Src kinase activation induces strong profibrotic cascade signaling. The purpose of this study was to test in vivo the antifibrotic activity of Bosutinib (SKI-606), a second generation c-Abl and Src kinase inhibitor, on TGF-β induced cutaneous and pulmonary fibrosis.

Identification of novel systemic sclerosis biomarkers employing aptamer proteomic analysis.

There is an important unmet need for clinically validated non-invasive biomarkers for SSc diagnosis, assessment of disease activity, extent of internal organ involvement, therapeutic response and prognosis. There is also an unmet need for biomarkers to accurately differentiate primary RP from recent onset RP evolving into SSc. The lack of sensitive and specific biomarkers for SSc and SSc-associated RP is a limitation for the optimal clinical management of these patients.

Desmoglein 2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes.

Extracellular vesicles (EVs) are nanoscale membrane-derived vesicles that serve as intercellular messengers carrying lipids, proteins, and genetic material. Substantial evidence has shown that cancer-derived EVs, secreted by tumor cells into the blood and other bodily fluids, play a critical role in modulating the tumor microenvironment and affecting the pathogenesis of cancer. Here we demonstrate for the first time that squamous cell carcinoma (SCC) EVs were enriched with the C-terminal fragment of desmoglein 2 (Dsg2), a desmosomal cadherin often overexpressed in malignancies.

Endothelial cell-specific activation of transforming growth factor-β signaling in mice induces cutaneous, visceral, and microvascular fibrosis.

In this study, we tested the hypothesis that constitutive endothelial cell-specific activation of TGF-β signaling induces tissue fibrosis and vasculopathy resembling the characteristic fibrotic and vascular alterations of systemic sclerosis. Transgenic mice with inducible expression of a constitutively active TGF-β receptor I specifically in endothelial cells were generated by intercrossing mice harboring a constitutively active TGF-β receptor I with a mouse strain containing the endothelial cell-specific Cdh5 gene promoter directing the tamoxifen-inducible expression of the Cre-ER cassette. Administration of tamoxifen to these mice would result in constitutive TGF-β activation and signaling confined to endothelial lineage cells.

Exosomes isolated from serum of systemic sclerosis patients display alterations in their content of profibrotic and antifibrotic microRNA and induce a profibrotic phenotype in cultured normal dermal fibroblasts.

Objectives: Exosomes are lipid bilayer-bound microvesicles containing various macromolecules including numerous microRNA (miRNA). Exosomes mediate intercellular communication by fusing and releasing their macromolecular content into target cells. Here, we analysed the content of profibrotic and antifibrotic miRNAs in exosomes isolated from the serum of systemic sclerosis (SSc) patients and tested their ability to induce a profibrotic phenotype in normal human dermal fibroblasts in vitro.