Histology-resolved proteomics reveals distinct tumor and stromal profiles in low- and high-grade prostate cancer.

Background: Prostate cancer is one of the most frequently diagnosed cancers in men. Prostate tumor staging and disease aggressiveness are evaluated based on the Gleason scoring system, which is further used to direct clinical intervention. The Gleason scoring system provides an estimate of tumor aggressiveness through quantitation of the serum level of prostate specific antigen (PSA) and histologic assessment of Grade Group, determined by the Gleason Grade of the tumor specimen.

In situ profiling reveals metabolic alterations in the tumor microenvironment of ovarian cancer after chemotherapy.

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm.

Brain proteomic atlas of alcohol use disorder in adult males.

Alcohol use disorder (AUD) affects transcriptomic, epigenetic and proteomic expression in several organs, including the brain. There has not been a comprehensive analysis of altered protein abundance focusing on the multiple brain regions that undergo neuroadaptations occurring in AUD. We performed a quantitative proteomic analysis using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of human postmortem tissue from brain regions that play key roles in the development and maintenance of AUD, the amygdala (AMG), hippocampus (HIPP), hypothalamus (HYP), nucleus accumbens (NAc), prefrontal cortex (PFC) and ventral tegmental area (VTA).

Repurposing alagebrium for diabetic foot ulcer healing: Impact on AGEs/NFκB/NOX1 signaling.

Background: Diabetic foot ulcer (DFU) is a common diabetic complication associated with disability and reduced quality of life. Available therapeutics are not sufficient to combat the spread of DFU. Here we aim to investigate the impact of alagebrium, an advanced glycation end product (AGE)-crosslink breaker, on the healing of DFU.

Classification of High-Grade Serous Ovarian Cancer Using Tumor Morphologic Characteristics.

Importance: Despite similar histologic appearance among high-grade serous ovarian cancers (HGSOCs), clinical observations suggest vast differences in gross appearance. There is currently no systematic framework by which to classify HGSOCs according to their gross morphologic characteristics.

Objective: To develop and characterize a gross morphologic classification system for HGSOC.

Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens.

Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by laser microdissection from thin sections across spatially separated levels of ten high-grade serous ovarian carcinomas (HGSOCs) and analyzed by mass spectrometry, reverse phase protein arrays, and RNA sequencing. Unsupervised analyses of protein abundance data revealed independent clustering of an enriched stroma and enriched tumor epithelium, with whole tumor tissue clustering driven by overall tumor "purity." Comparing these data to previously defined prognostic HGSOC molecular subtypes revealed protein and transcript expression from tumor epithelium correlated with the differentiated subtype, whereas stromal proteins (and transcripts) correlated with the mesenchymal subtype.

Rutin and orlistat produce antitumor effects via antioxidant and apoptotic actions.

Cancer is a broad term used to describe a large number of diseases characterized by uncontrolled cell proliferation that leads to tumor production. Cancer is associated with mutations in genes controlling proliferation and apoptosis, oxidative stress, fatty acid synthase (FAS) expression, and other mechanisms. Currently, most antineoplastic drugs have severe adverse effects and new effective and safe drugs are needed.

Effectiveness of arginase inhibitors against experimentally induced stroke.

Stroke is a lethal disease, but it disables more than it kills. Stroke is the second leading cause of death and the most frequent cause of permanent disability in adults worldwide, with 90% of survivors having residual deficits. The pathophysiology of stroke is complex and involves a strong inflammatory response associated with oxidative stress and activation of several proteolytic enzymes.

Anticancer activity of salicin and fenofibrate.

Cancer refers to a disorder of cell proliferation that leads to tumor production. Cancer is usually treated by surgery, chemotherapeutic drugs, and radiation. Despite the presence of many anticancer drugs, cancer is still an uncontrolled disease and is a major cause of death worldwide.

Impact of Exposure to Fenitrothion on Vital Organs in Rats.

This study was designed to investigate the impact of oral administration of fenitrothion (10 mg/kg) on liver, kidney, brain, and lung function in rats. The effect was studied on days 7, 14, 21, 28, and 42. Our results have shown deterioration in liver function as evidenced by the elevation in serum ALT, AST, ALP, and bilirubin and reduction in albumin and hepatic glycogen.

Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats.

Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis.

Pentoxifylline abrogates cardiotoxicity induced by the administration of a single high dose or multiple low doses of doxorubicin in rats.

Doxorubicin (DOX) possesses a broad-spectrum antineoplastic activity; however, its clinical application is impeded by cardiotoxicity. This study aimed to investigate the protective effect of pentoxifylline (PXF), which possesses antioxidant and anti-inflammatory properties against cardiotoxicity induced by a single high dose (15 mg/kg, i.p.

Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats.

Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs) is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE), AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues.

Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice.

Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg) against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg).

Nalbuphine could decrease the rewarding effect induced by tramadol in mice while enhancing its antinociceptive activity.

Nalbuphine, a kappa-opioid agonist and mu-opioid partial agonist, has been used as an analgesic or an adjuvant with morphine to attenuate the development of morphine dependence and rewarding effect. In this study, we investigated the effect of nalbuphine on tramadol rewarding effect and antinociception. Using the conditioned place preference (CPP) paradigm in mice, we demonstrated that co-administration of nalbuphine (7mg/kg, s.

Modulation of diabetes and dyslipidemia in diabetic insulin-resistant rats by mangiferin: role of adiponectin and TNF-α.

Mangiferin, present in Mangifera indica bark, was reported to produce hypoglycemic and antidiabetic activity in an animal model of genetic type 2 diabetes and in streptozotocin diabetic rats. Its effect on diabetic insulin-resistant animals has not been investigated. The current work aimed to explore the effect of mangiferin on diabetic insulin-resistant rat model.

Insights in the mechanism underlying the protective effect of α-lipoic acid against acetaminophen-hepatotoxicity.

Acetaminophen (APAP) is one of the most widely used analgesic antipyretic drugs and is a major cause of acute liver failure at overdose. The aim of this study is to investigate the possible protective effect of α-lipoic acid (α-LA, 20 or 100 mg/kg administered simultaneously or after 1.5 h) against APAP-induced hepatotoxicity in rats.

Candesartan and glycyrrhizin ameliorate ischemic brain damage through downregulation of the TLR signaling cascade.

Stroke is the second leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. The final outcome of stroke is determined not only by the volume of the ischemic core, but also by the extent of secondary brain damage inflicted to penumbral tissues by brain swelling, impaired microcirculation, and inflammation. The only drug approved for the treatment ischemic stroke is recombinant tissue plasminogen activator (rt-PA).

Inhibition of TNF-α protects against hepatic ischemia-reperfusion injury in rats via NF-κB dependent pathway.

Hepatic ischemia-reperfusion injury (I/R) is a serious health problem associated with liver transplantation, resection surgery, and various types of shock especially hemorrhagic shock. In the present investigation, the effect of inhibition of tumor necrosis factor-alpha (TNF-α) using pentoxifylline or infliximab against hepatic I/R injury induced in rats by 45-min ischemia and 1-h reperfusion was studied. It was observed that both pentoxifylline and infliximab-treated groups showed a significantly lower extent and severity of liver injury.

Pannexins in ischemia-induced neurodegeneration.

Pannexin 1 (Px1, Panx1) and pannexin 2 (Px2, Panx2) form large-pore nonselective channels in the plasma membrane of cells and were suggested to play a role in the pathophysiology of cerebral ischemia. To directly test a potential contribution of pannexins in ischemia-related mechanisms, we performed experiments in Px1(-/-), Px2(-/-), and Px1(-/-)Px2(-/-) knockout mice. IL-1β release, channel function in astrocytes, and cortical spreading depolarization were not altered in Px1(-/-)Px2(-/-) mice, indicating that, in contrast to previous concepts, these processes occur normally in the absence of pannexin channels.

NF-kappaB induces PGE2-synthesizing enzymes in neurons.

The transcription factor NF-kappaB is activated in neurons and promotes neuronal death in cerebral ischemia. Its target genes include cytosolic phospholipase A-2 (cPLA-2), cyclooxygenase-2 (COX-2), and microsomal prostaglandin E(2) synthase-1 (mPGES-1), three genes that are involved in the synthesis of prostaglandin E(2) (PGE(2)). In our study, oxygen glucose deprivation (OGD), an in vitro model of cerebral ischemia, activated NF-kappaB activity in primary cortical neurons.

The HMGB1 receptor RAGE mediates ischemic brain damage.

In ischemic stroke, the necrotic core is surrounded by a zone of inflammation, in which delayed cell death aggravates the initial insult. Here, we provide evidence that the receptor for advanced glycation end products (RAGE) functions as a sensor of necrotic cell death and contributes to inflammation and ischemic brain damage. The RAGE ligand high mobility group box 1 (HMGB1) was elevated in serum of stroke patients and was released from ischemic brain tissue in a mouse model of cerebral ischemia.