Breast adipose tissue-derived extracellular vesicles from obese women alter tumor cell metabolism.

Breast adipose tissue is an important contributor to the obesity-breast cancer link. Extracellular vesicles (EVs) are nanosized particles containing selective cargo, such as miRNAs, that act locally or circulate to distant sites to modulate target cell functions. Here, we find that long-term education of breast cancer cells with EVs obtained from breast adipose tissue of women who are overweight or obese (O-EVs) results in increased proliferation. RNA-seq analysis of O-EV-educated cells demonstrates increased expression of genes involved in oxidative phosphorylation, such as ATP synthase and NADH: ubiquinone oxidoreductase. O-EVs increase respiratory complex protein expression, mitochondrial density, and mitochondrial respiration in tumor cells. The mitochondrial complex I inhibitor metformin reverses O-EV-induced cell proliferation. Several miRNAs-miR-155-5p, miR-10a-3p, and miR-30a-3p-which promote mitochondrial respiration and proliferation, are enriched in O-EVs relative to EVs from lean women. O-EV-induced proliferation and mitochondrial activity are associated with stimulation of the Akt/mTOR/P70S6K pathway, and are reversed upon silencing of P70S6K. This study reveals a new facet of the obesity-breast cancer link with human breast adipose tissue-derived EVs causing metabolic reprogramming of breast cancer cells.

Cardiovascular and haematological events post COVID-19 vaccination: A systematic review.

Since COVID-19 took a strong hold around the globe causing considerable morbidity and mortality, a lot of effort was dedicated to manufacturing effective vaccines against SARS-CoV-2. Many questions have since been raised surrounding the safety of the vaccines, and a lot of media attention to certain side effects. This caused a state of vaccine hesitancy that may prove problematic in the global effort to control the virus. This review was undertaken with the aim of putting together all the reported cardiovascular and haematological events post COVID-19 vaccination in published literature and to suggest possible mechanisms to explain these rare phenomena.

A Closer Look into Gastrointestinal Bleeding in Heart Failure Patients.

BACKGROUND: The frequency and risk factors for gastrointestinal bleed (GIB) in patients with heart failure with reduced ejection fraction (HFrEF) have not been extensively researched. OBJECTIVE: We aim to assess the frequency of GIB in this subset of patients and identify potential risk factors for bleeding. This study will evaluate the frequency of commonly used antiplatelet and anticoagulation agents in the HFrEF population, as well as look at some of the endoscopic features of the GIB. METHODS: A retrospective cohort analysis of 670 patients admitted between November 2021 to August 2023 to a single urban, tertiary teaching institution with acute HFrEF ICD-10 codes. Upper or lower GIB (hematemesis, coffee ground emesis, melena or hematochezia during admission) was identified on a manual chart review. Patients with GIB were defined as our cases. No GIB was defined as our controls. Sub analysis included comparing the use of anticoagulant and antiplatelet between the cohort. Independent t test assessed statistical differences in the case and control groups RESULTS: Out of the 670 patients, 134 (20%) were identified with GIB. The cases were older than the controls (median age 77 vs. 70 years) (p = 0.001), had a lower hemoglobin (9 g/dL vs. 12 g/dL) (p =<0.05), and had higher BNP levels (7,938 pg/ml vs. 6472 pg/ml) (IQR: 3,239, 23,701) (p =<0.01). Among the anticoagulant users, 64% of cases were on an anticoagulant compared to 42% of the controls (p<0.05). Among the antiplatelet users, 68% of the controls were on one or more antiplatelet agents, compared to 52% in the controls (p = 0.01). When combining AC and AP treatment, there was no statistical difference between cases and controls. Ninety-three (69%) patients from cases had cross-sectional imaging with only 23 (25%) showing abnormal findings which included diverticulosis, colitis, and GI masses. When comparing upper endoscopy findings, the presence of esophageal diseases (esophagitis and esophageal varices) and gastric/duodenal diseases (gastritis, gastric ulcer, duodenal ulcer and AVM) were significantly higher in cases compared to controls (p < 0.05). In addition to the colonoscopy findings, polyps and diverticulosis were more prevalent in the cases compared to the controls (p = 0.01). CONCLUSION: Heart failure patients are at risk of developing GIB. Age and high BNP on admission are risk factors for GIB, the higher the BNP levels the higher risk of GIB. Anticoagulant and antiplatelet use are associated with a higher risk of bleeding. However, the addition of dual antiplatelet therapy or concurrent antiplatelet and anticoagulation does not increase the risk of GIB. Some of the most common upper endoscopy findings include esophagitis/gastritis and esophageal/gastric ulcer. In terms of colonoscopy, findings include colonic mass, diverticulosis and hemorrhoids.

Breast adipose tissue-derived extracellular vesicles from women with obesity stimulate mitochondrial-induced dysregulated tumor cell metabolism.

Breast adipose tissue is an important contributor to the obesity-breast cancer link. Dysregulated cell metabolism is now an accepted hallmark of cancer. Extracellular vesicles (EVs) are nanosized particles containing selective cargo, such as miRNAs, that act locally or circulate to distant sites to modulate target cell functions. Here, we found that long-term education of breast cancer cells (MCF7, T47D) with EVs from breast adipose tissue of women who are overweight or obese (O-EVs) leads to sustained increased proliferative potential. RNA-Seq of O-EV-educated cells demonstrates increased expression of genes, such as ATP synthase and NADH: ubiquinone oxidoreductase, involved in oxidative phosphorylation. O-EVs increase respiratory complex protein expression, mitochondrial density, and mitochondrial respiration in tumor cells. Mitochondrial complex I inhibitor, metformin, reverses O-EV-induced cell proliferation. Several miRNAs, miR-155-5p, miR-10a-3p, and miR-30a-3p, which promote mitochondrial respiration and proliferation, are enriched in O-EVs relative to EVs from lean women. O-EV-induced proliferation and mitochondrial activity are associated with stimulation of the Akt/mTOR/P70S6K pathway, and are reversed upon silencing of P70S6K. This study reveals a new facet of the obesity-breast cancer link with human breast adipose tissue-derived EVs causing the metabolic reprogramming of ER+ breast cancer cells.

Cancer Patients and the COVID-19 Vaccines: Considerations and Challenges.

Few guidelines exist for COVID-19 vaccination amongst cancer patients, fostering uncertainty regarding the immunogenicity, safety, and effects of cancer therapies on vaccination, which this review aims to address. A literature review was conducted to include the latest articles covering the immunogenicity and safety of COVID-19 vaccination in patients with solid and hematologic cancers receiving various treatments. Lower seropositivity following vaccination was associated with malignancy (compared to the general population), and hematologic malignancy (compared to solid cancers). Patients receiving active cancer therapy (unspecified), chemotherapy, radiotherapy, and immunosuppressants generally demonstrated lower seropositivity compared to healthy controls; though checkpoint inhibition, endocrine therapy, and cyclin dependent kinase inhibition did not appear to affect seropositivity. Vaccination appeared safe and well-tolerated in patients with current or past cancer and those undergoing treatment. Adverse events were comparable to the general population, but inflammatory lymphadenopathy following vaccination was commonly reported and may be mistaken for malignant etiology. Additionally, radiation recall phenomenon was sporadically reported in patients who had received radiotherapy. Overall, while seropositivity rates were decreased, cancer patients showed capacity to generate safe and effective immune responses to COVID-19 vaccination, thus vaccination should be encouraged and hesitancy should be addressed in this population.

Neurological Immune-Related Adverse Events After COVID-19 Vaccination: A Systematic Review.

The coronavirus disease 2019 (COVID-19) pandemic has affected millions of individuals worldwide. The global scientific effort to design an effective vaccine against this virus has led to the development of several vaccine candidates. The expedited rollout of these vaccines has created some public distrust regarding the safety of these new vaccines. This review compiles clinical data from reports of diagnosed immune-related neurological events that have occurred after COVID-19 vaccine administration with the exception of those secondary to hematological abnormalities. A systematic literature search was performed, using several databases, to identify reports of postvaccination adverse neurological events. The search resulted in 18 studies that met our criteria. These studies included 61 patients who had received COVID-19 vaccines and experienced at least 1 neurological adverse effect. The most common neurological event was facial nerve palsy (50% of all events). Other less frequently reported events included the reactivation of herpes zoster, Guillain-Barre syndrome, other demyelinating diseases, and neuropathy. The underlying mechanism was hypothesized to be related to vaccine-induced type 1 interferon production leading to decreased tolerance of the myelin sheath antigens. Other hypotheses include vaccine-induced transient lymphopenia and immune dysregulation. Most of the reported events were time limited and resolved spontaneously. Given the rarity of reported neurological events compared to the total number of vaccines administered, and the similarity in the incidence of events between COVID-19 vaccines and other more common vaccines, there is little evidence to support a causal relationship between COVID-19 vaccines and adverse neurological events.