Statins as Secondary Preventive Agent to Limit Breast Cancer Metastatic Outgrowth.

Metastasis is a leading cause of mortality in breast cancer, as metastatic disease is often aggressive and resistant to conventional treatments. Cancer cells that spread to distant organs can enter a dormant phase for extended periods, sometimes years or decades. During this dormant phase, cancer cells avoid immune and pharmacological response.

Hepatic conditioning results in better lung endothelial cell preservation under hypoxic environment in vitro.

Background: as we look to extend lung perfusion times (EVLP) to improve preservation, the metabolic activity of the lungs will require support from other organ functions. Active functional liver support, including detoxification, synthesis, and regulation, can improve lung preservation during EVLP. This study aimed to demonstrate the effects of hepatic conditioning of the EVLP perfusate on lung endothelium, via the receptor of advanced glycation end-products (RAGE)-nuclear-factor-κB (NF-κB) signaling in vitro.

Heparanase-induced endothelial glycocalyx degradation exacerbates lung ischemia/reperfusion injury in male mice.

The endothelial glycocalyx (eGC) is a carbohydrate-rich layer on the vascular endothelium, and its damage can lead to endothelial and organ dysfunction. Heparanase (HPSE) degrades the eGC in response to cellular stress, but its role in organ dysfunction remains unclear. This study investigates HPSE's role in lung ischemia-reperfusion (I/R) injury.

LepR+ niche cell-derived AREG compromises hematopoietic stem cell maintenance under conditions of DNA repair deficiency and aging.

The cross talk between extrinsic niche-derived and intrinsic hematopoietic stem cell (HSC) factors controlling HSC maintenance remains elusive. Here, we demonstrated that amphiregulin (AREG) from bone marrow (BM) leptin receptor (LepR+) niche cells is an important factor that mediates the cross talk between the BM niche and HSCs in stem cell maintenance. Mice deficient of the DNA repair gene Brca2, specifically in LepR+ cells (LepR-Cre;Brca2fl/fl), exhibited increased frequencies of total and myeloid-biased HSCs.

Endothelial protection in lung grafts through heparanase inhibition during ex vivo lung perfusion in rats.

Background: We hypothesized that enhancing glycocalyx preservation would reduce endothelial damage in lung grafts during ex-vivo lung perfusion (EVLP) leading to better transplant outcomes. In this study, we characterized the effects of inhibiting heparanase (HPSE), an enzyme responsible for glycocalyx shedding, on lung quality during EVLP.

Methods: Human clinical EVLP perfusate from lung graft patients was utilized to identify a potential association between glycocalyx integrity in grafted lung tissue and clinical data.

Impaired Cellular and Antibody immunity after COVID-19 in Chronically Immunosuppressed Transplant Recipients.

Assessment of cellular immunity to the SARS-CoV-2 coronavirus is of great interest in chronically immunosuppressed transplant recipients (Tr), who are predisposed to infections and vaccination failures. We evaluated CD154-expressing T-cells induced by spike (S) antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. S-reactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed Tr who were sampled pre-pandemic, compared with healthy NT (p=0.

Hematopoietic stem cell regeneration through paracrine regulation of the Wnt5a/Prox1 signaling axis.

The crosstalk between the BM microenvironment (niche) and hematopoietic stem cells (HSCs) is critical for HSC regeneration. Here, we show that in mice, deletion of the Fanconi anemia (FA) genes Fanca and Fancc dampened HSC regeneration through direct effects on HSCs and indirect effects on BM niche cells. FA HSCs showed persistent upregulation of the Wnt target Prox1 in response to total body irradiation (TBI).

Persistent DNA damage and oncogenic stress-induced Trem1 promotes leukemia in mice.

The immune receptor TREM1 (Triggering receptor expressed on myeloid cells 1) is a master regulator of inflammatory response. Compelling evidence suggests important pathological roles for TREM1 in various types of solid tumors. However, the role of TREM1 in hematologic malignancies is not known.

Human Gut Microbiome: A New Frontier in Cancer Diagnostics & Therapeutics.

The field of oncology is vast and ever-growing. The present cancer therapeutics is continually exhibiting various drawbacks, which opens the door for exploring better novel therapeutic techniques. One such emerging technique is the manipulation of gut microbiota to induce a positive curative effect in the body.

Matrixmetalloproteinase Inhibitors: Promising Therapeutic Targets Against Cancer.

Background: Cancer is a wide range cellular level disease that occurs when cells go through uncontrolled division and growth. The mechanisms by which the cells undergo metastasis are complex and involve many interactions between the tumor cells and their cellular environment. Matrix metalloproteinases (MMPs) have been found to over-express at various stages of tumor progression and their inhibition using MMP inhibitors has been a subject of potential therapy against cancer.

Impaired T-cell and antibody immunity after COVID-19 infection in chronically immunosuppressed transplant recipients.

Assessment of T-cell immunity to the COVID-19 coronavirus requires reliable assays and is of great interest, given the uncertain longevity of the antibody response. Some recent reports have used immunodominant spike (S) antigenic peptides and anti-CD28 co-stimulation in varying combinations to assess T-cell immunity to SARS-CoV-2. These assays may cause T-cell hyperstimulation and could overestimate antiviral immunity in chronically immunosuppressed transplant recipients, who are predisposed to infections and vaccination failures.

Anti-inflammatory Effects of Seed Extract on Gelatinase-B (MMP-9) Regulation against Hyperglycemic Cardiomyocyte Stress.

Black berry () fruit is useful in curing diabetic complications; however, its role in diabetes-induced cardiomyopathy is not yet known. In this study, we investigated the regulation of gelatinase-B (MMP-9) by methanol seed extract (MSE) in diabetic cardiomyopathy using real-time PCR, RT-PCR, immunocytochemistry, gel diffusion assay, and substrate zymography. The regulatory effects of MSE on NF-B, TNF-, and IL-6 were also examined.

Pathophysiology, Clinical Characteristics of Diabetic Cardiomyopathy: Therapeutic Potential of Natural Polyphenols.

Diabetic cardiomyopathy (DCM) is an outcome of disturbances in metabolic activities through oxidative stress, local inflammation, and fibrosis, as well as a prime cause of fatality worldwide. Cardiovascular disorders in diabetic individuals have become a challenge in diagnosis and formulation of treatment prototype. It is necessary to have a better understanding of cellular pathophysiology that reveal the therapeutic targets and prevent the progression of cardiovascular diseases due to hyperglycemia.

Synthesis and Characterization of Sygyzium cumini Nanoparticles for Its Protective Potential in High Glucose-Induced Cardiac Stress: a Green Approach.

There exists a complex and multifactorial relationship between diabetes and cardiovascular disease. Hyperglycemia is an important factor imposing damage (glucose toxicity) on cardiac cell leading to diabetic cardiomyopathy. There are substantial clinical evidences on the adverse effects of conventional therapies in the prevention/treatment of diabetic cardiovascular complications.

An assessment of norepinephrine mediated hypertrophy to apoptosis transition in cardiac cells: a signal for cell death.

Objectives: Heart is an organ which is under a constant work load that generates numerous stress responses. Heart failure is associated with increased plasma norepinephrine (NE) and hypertrophic cell death. Within the current study we try to understand the concentration dependent molecular switch from hypertrophy to apoptosis under stress.

Protective effect of Syzygium cumini against pesticide-induced cardiotoxicity.

Pesticide-induced toxicity is a serious issue which has resulted in plethora of diseases all over the world. The organophosphate pesticide malathion has caused many incidents of poisoning such as cardiac manifestations. The present study was designed to evaluate the effect of Syzygium cumini on malathion-induced cardiotoxicity.

Cardioprotective role of Syzygium cumini against glucose-induced oxidative stress in H9C2 cardiac myocytes.

Diabetic patients are known to have an independent risk of cardiomyopathy. Hyperglycemia leads to upregulation of reactive oxygen species (ROS) that may contribute to diabetic cardiomyopathy. Thus, agents that suppress glucose-induced intracellular ROS levels can have therapeutic potential against diabetic cardiomyopathy.