Reduced S-nitrosylation of TGFβ1 elevates its binding affinity toward the receptor and promotes fibrogenic signaling in the breast.

Transforming Growth Factor β (TGFβ) is a pleiotropic cytokine closely linked to tumors. Previously, we pharmacologically inhibited basal nitric oxide (NO) production in healthy mammary glands and found that this induced precancerous progression accompanied by upregulation of TGFβ and desmoplasia. In the present study, we tested whether NO directly S-nitrosylates (forms an NO-adduct at a cysteine residue) TGFβ for inhibition, whereas reduction of NO denitrosylates TGFβ for de-repression.

Immunogenic shift of arginine metabolism triggers systemic metabolic and immunological reprogramming to prevent HER2+ breast cancer.

Arginine metabolism in tumors is often shunted into the pathway producing pro-tumor and immune suppressive polyamines (PAs), while downmodulating the alternative nitric oxide (NO) synthesis pathway. Aiming to correct arginine metabolism in tumors, arginine deprivation therapy and inhibitors of PA synthesis have been developed. Despite some therapeutic advantages, these approaches have often yielded severe side effects, making it necessary to explore an alternative strategy.

Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism.

HER2+ breast tumors have abundant immune-suppressive cells, including M2-type tumor-associated macrophages (TAMs). Although TAMs consist of the immune-stimulatory M1 type and immune-suppressive M2 type, the M1/M2-TAM ratio is reduced in immune-suppressive tumors, contributing to their immunotherapy refractoriness. M1- versus M2-TAM formation depends on differential arginine metabolism, where M1-TAMs convert arginine to nitric oxide (NO) and M2-TAMs convert arginine to polyamines (PAs).

The role of genetic polymorphisms in the sulfation of pregnenolone by human cytosolic sulfotransferase SULT2B1a.

Pregnenolone is a key intermediate in the biosynthesis of many steroid hormones and neuroprotective steroids. Sulfotransferase family cytosolic 2B member 1 (SULT2B1a) has been reported to be highly selective to sulfate pregnenolone. This study aimed to clarify the effect of missense single nucleotide polymorphisms (SNPs) of the human SULT2B1 gene on the sulfating activity of coded SULT2B1a allozymes toward Pregnenolone.

Clinical validation of an aggregate learning ratio from the neuropsychological assessment battery.

Quantifying learning deficits provides valuable information in identifying and diagnosing mild cognitive impairment and dementia. Previous research has found that a learning ratio (LR) metric, derived from the list learning test from the Neuropsychological Assessment Battery (NAB), was able to distinguish between those with normal cognition versus memory impairment. The current study furthers the NAB LR research by validating a NAB story LR, as well as an aggregate LR.

Anesthetic management for large vessel occlusion acute ischemic stroke with tandem lesions.

Background: Endovascular therapy (EVT) stands as an established and effective intervention for acute ischemic stroke in patients harboring tandem lesions (TLs). However, the optimal anesthetic strategy for EVT in TL patients remains unclear. This study aims to evaluate the impact of distinct anesthetic techniques on outcomes in acute ischemic stroke patients presenting with TLs.

Predictors of Length of Hospital Stay After Reduction of Internal Hernia in Patients With a History of Roux-en-Y Gastric Bypass.

Background: Postoperative internal hernias after Roux-en-Y gastric bypass (RYGB) have an incidence of 2%-9% and are a surgical emergency. Evidence on factors associated with length of stay (LOS) after emergent internal hernia reduction in RYGB patients is limited.

Methods: This is a retrospective review of patients who underwent internal hernia reduction after RYGB at our tertiary care center over a 5 year period from 2015 to 2020.

Extracellular Mechanical Stimuli Alters the Metastatic Progression of Prostate Cancer Cells within 3D Tissue Matrix.

This study aimed to understand extracellular mechanical stimuli's effect on prostate cancer cells' metastatic progression within a three-dimensional (3D) bone-like microenvironment. In this study, a mechanical loading platform, EQUicycler, has been employed to create physiologically relevant static and cyclic mechanical stimuli to a prostate cancer cell (PC-3)-embedded 3D tissue matrix. Three mechanical stimuli conditions were applied: control (no loading), cyclic (1% strain at 1 Hz), and static mechanical stimuli (1% strain).

The role of genetic polymorphisms in the sulfation of pregnenolone by human cytosolic sulfotransferase SULT2B1a.

Pregnenolone is a key intermediate in the biosynthesis of many steroid hormones and neuroprotective steroids. Sulfotransferase family cytosolic 2B member 1 (SULT2B1a) has been reported to be highly selective to sulfate pregnenolone. This study aimed to clarify the effect of missense single nucleotide polymorphisms (SNPs) of the human SULT2B1 gene on the sulfating activity of coded SULT2B1a allozymes toward Pregnenolone.

Potential Involvement of Sulfotransferase in the Mechanism of Lamotrigine-induced Skin Rash.

The mechanism of drug-induced skin rash is not well understood. Circumstantial evidence suggests that the covalent binding of a reactive metabolite is involved in the mechanism of most idiosyncratic drug reactions. However, there is a limited quantity of drug metabolizing enzymes in the skin, except for sulfotransferases.

A Quality Analysis of Donor Nephrectomy-Related Information on YouTube; Education or Misinformation?

Introduction: There currently remains an urgent need to increase living kidney donation to help mitigate the high demand for waitlisted kidney failure patients. Potential kidney donors can readily access social media, particularly YouTube, to gain basic knowledge about live donor nephrectomy surgical procedures. YouTube is an open-source platform where anyone can upload videos about any topic without peer review or quality control and is frequently used for disseminating health education.

Reduced S-nitrosylation of TGFβ1 elevates its binding affinity towards the receptor and promotes fibrogenic signaling in the breast.

Transforming Growth Factor β (TGFβ) is a pleiotropic cytokine closely linked to tumors. TGFβ is often elevated in precancerous breast lesions in association with epithelial-to-mesenchymal transition (EMT), indicating its contribution to precancerous progression. We previously reported that basal nitric oxide (NO) levels declined along with breast cancer progression.

Sleep apnoea, gut dysbiosis and cognitive dysfunction.

Sleep disorders are becoming increasingly common, and their distinct effects on physical and mental health require elaborate investigation. Gut dysbiosis (GD) has been reported in sleep-related disorders, but sleep apnoea is of particular significance because of its higher prevalence and chronicity. Cumulative evidence has suggested a link between sleep apnoea and GD.

How to Select an Extracellular Matrix for Wound Repair: A Comprehensive Review.

Background: An extracellular matrix (ECM) is a network of proteins and other molecules that provide support and structure to cells and tissues in the body. Since its discovery in 1930, researchers have reproduced the ECM through an array of evolving technologies, developing products that accelerate healing times, minimize scarring, and reduce pain. When selecting which ECM product to use, physicians rely on personal experience while considering wound location, type of tissue lost, exposed structures, chronicity, and even the patient's religious preferences.

Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism.

HER2+ breast tumors have abundant immune-suppressive cells, including M2-type tumor associated macrophages (TAMs). While TAMs consist of the immune-stimulatory M1-type and immune-suppressive M2-type, M1/M2-TAM ratio is reduced in immune-suppressive tumors, contributing to their immunotherapy refractoriness. M1 vs.

A comprehensive open-access database of electron backscattering coefficients for energies ranging from 0.1 keV to 15 MeV.

Purpose: The characterization of electron backscattering is essential in medical physics for accurately assessing dose deposited around inhomogeneities where backscattering alters the spatial energy distribution pattern and for determining Monte-Carlo code's ability to effectively describe electron scattering and does calculation in a target volume. Recent machine learning advances have provided physicists with powerful tools for effectively extracting information and trends from extensive experiment observations if sufficiently sizeable datasets are available for data mining. We report on the development of a publicly accessible database on electron backscattering coefficients for solid targets.

Tackling of Immunorefractory Tumors by Targeting Alternative Immune Checkpoints.

Physiologically, well known or traditional immune checkpoints (ICs), such as CTLA-4 and PD-1, are in place to promote tolerance to self-antigens and prevent generation of autoimmunity. In cancer, the ICs are effectively engaged by the tumor cells or stromal ells from the tumor microenvironment through expression of cognate ligands for the ICs present on the cell surface of CD8 T lymphocytes. The ligation of ICs on CD8 T lymphocytes triggers inhibitory signaling pathways, leading to quiescence or an exhaustion of CD8 T lymphocytes.

Novel 3D Flipwell system that models gut mucosal microenvironment for studying interactions between gut microbiota, epithelia and immunity.

Gut mucosa consists of stratified layers of microbes, semi-permeable mucus, epithelium and stroma abundant in immune cells. Although tightly regulated, interactions between gut commensals and immune cells play indispensable roles in homeostasis and cancer pathogenesis in the body. Thus, there is a critical need to develop a robust model for the gut mucosal microenvironment.

Ethnic disparities in the immune microenvironment of triple negative breast cancer and its role in therapeutic outcomes.

In 2020, newly diagnosed breast cancer (BC) cases surpassed that of lung cancer among women, making it the most common female cancer globally. In spite of recent increases in incidence rates, mortality due to BC has declined since 1989. These declines have been attributed to advancements in treatment modalities as well as increased mammography surveillance.

Utilization of the Pedicled and Free Fibula Flap for Ankle Arthrodesis.

Unlabelled: Ankle arthrodesis has become a common surgical procedure for individuals with end-stage ankle arthritis, chronic infection, and bony misalignment. Although arthrodesis is typically managed with arthrodesis in situ or realignment, reconstruction may be utilized for patients with more complicated cases that involve metatarsal defects. Our institution utilizes both the pedicled and free fibula flaps for surgical management pertaining to ankle arthrodesis.