Next-generation biological vector platforms for in vivo delivery of genome editing agents.

CRISPR-based genome editing holds promise for addressing genetic disease, infectious disease, and cancer and has rapidly advanced from primary research to clinical trials in recent years. However, the lack of safe and potent in vivo delivery methods for CRISPR components has limited most ongoing clinical trials to ex vivo gene therapy. Effective CRISPR in vivo genome editing necessitates an effective vehicle ensuring target cell transduction while minimizing off-target effects, toxicity, and immune reactions.

Advanced Glycation End Products as a Potential Target for Restructuring the Ovarian Cancer Microenvironment: A Pilot Study.

Ovarian cancer is the sixth leading cause of cancer-related death in women, and both occurrence and mortality are increased in women over the age of 60. There are documented age-related changes in the ovarian cancer microenvironment that have been shown to create a permissive metastatic niche, including the formation of advanced glycation end products, or AGEs, that form crosslinks between collagen molecules. Small molecules that disrupt AGEs, known as AGE breakers, have been examined in other diseases, but their efficacy in ovarian cancer has not been evaluated.

Another Wrinkle with Age: Aged Collagen and Intra-peritoneal Metastasis of Ovarian Cancer.

Background: Age is the most significant risk factor for ovarian cancer (OvCa), the deadliest gynecologic malignancy. Metastasizing OvCa cells adhere to the omentum, a peritoneal structure rich in collagen, adipocytes, and immune cells. Ultrastructural changes in the omentum and the omental collagen matrix with aging have not been evaluated.

An Optogenetic Tool to Raise Intracellular pH in Single Cells and Drive Localized Membrane Dynamics.

Intracellular pH (pHi) dynamics are critical for regulating normal cell physiology. For example, transient increases in pHi (7.2-7.

Synthesis and mannosidase inhibitory profile of a small library of aminocyclitols from shikimic acid-derived scaffolds.

A short synthetic route to a small library of aminocyclitols 14·HCl-19·HCl has been elaborated from the common shikimic acid-derived scaffolds 20 and 21. The developed strategy features three oxidative processes ‒ ozonolysis, dihydroxylation and epoxidation ‒ as the key transformations. The stereochemistry of the newly created stereocentres was confirmed either via crystallographic analysis or by means of NOESY experiments conducted on advanced intermediates.

Mitochondrial stress and activation of PI3K and Akt survival pathway in bladder ischemia.

Purpose: Detrusor overactivity contributes to bothersome constellation of lower urinary tract symptoms (LUTS) in men and women as they age. However, the underlying mechanisms of non-obstructive detrusor overactivity and LUTS remain largely unknown. Growing evidence suggests that ischemia may be an independent factor in the development of non-obstructive bladder dysfunction.

Short-term outcomes of the new intragastric balloon End-Ball for treatment of obesity.

Introduction: Intragastric balloons (IGBs) have been successfully used to treat obesity for the last 18 years. These balloons are made of different materials and filled with either air or saline. It seems that balloons filled with saline result in more effective weight loss, but are associated with worse tolerance after implantation.

Corrigendum: Correction of title spelling. Progressive changes in detrusor function and micturition patterns with chronic bladder ischemia.

[This corrects the article on p. 249 in vol. 57.

Progressive changes in detrusor function and micturition patterns with chronic bladder ischemia.

Purpose: Lower urinary tract symptoms (LUTS) are bothersome constellation of voiding symptoms in men and women as they age. Multiple factors and comorbidities are attributed to this problem but underlying mechanisms of nonobstructive nonneurogenic detrusor overactivity, detrusor underactivity and LUTS remain largely unknown. Our goal was to characterize detrusor function and voiding patterns in relation to muscarinic receptors expression, nerve fiber density, and neural ultrastructure in chronic bladder ischemia.

Effects of ischemia and oxidative stress on bladder purinoceptors expression.

Objective: To study the effects of chronic ischemia on bladder purinoceptors. A close correlation between bladder ischemia and lower urinary tract symptoms has been reported. Purinoceptors contribute to important aspects of bladder function including sensation, neural signaling, and voiding contraction.

Neural regulation of sexual function in men.

Male sexual response is controlled by a series of neurally mediated phenomena regulating libido, motivation, arousal and genital responses such as penile erection and ejaculation. These neural events that occur in a hormonally defined milieu involve different neurophysiological, neurochemical, and neuropsychological parameters controlled by central mechanisms, spinal reflexes and peripheral nervous system. Epidemiologic studies have suggested the high prevalence of male sexual dysfunction worldwide with significant impact on the quality of life of patients suffering from this problem.

Mechanisms of Lower Urinary Tract Symptoms in Pelvic Ischemia.

The etiology of lower urinary tract symptoms is poorly understood. The pathophysiology of detrusor instability, voiding dysfunction and pelvic pain in patients with non-obstructed bladder remains highly controversial. In the male, most cases of lower urinary tract symptoms are attributed to bladder outlet obstruction due to benign prostatic hyperplasia.

Molecular reactions and ultrastructural damage in the chronically ischemic bladder.

Purpose: Clinical and basic research data suggest that pelvic ischemia may contribute to bladder overactivity. We characterized the molecular and ultrastructural reactions of the chronically ischemic bladder.

Materials And Method: A model of pelvic ischemia was developed by creating iliohypogastric/pudendal arterial atherosclerosis in rabbits.

Human bladder smooth muscle cell damage in disturbed oxygen tension.

Objective: To characterize human bladder smooth muscle cell reactions to disturbed oxygen tension. Clinical studies have shown a close correlation between bladder ischemia and lower urinary tract symptoms in elderly patients.

Materials And Methods: Confluent cultured human bladder smooth muscle cells were incubated under normoxia, continuous hypoxia, and oxidative stress (hypoxia/reoxygenation) conditions using a computerized oxycycler system.

Prostate-specific antigen/solvent interaction analysis: a preliminary evaluation of a new assay concept for detecting prostate cancer using urinary samples.

Objective: To provide preliminary clinical performance evaluation of a novel prostate cancer (CaP) assay, prostate-specific antigen/solvent interaction analysis (PSA/SIA) that focused on changes to the structure of PSA.

Methods: Two-hundred twenty-two men undergoing prostate biopsy for accepted clinical criteria at 3 sites (University Hospitals Case Medical Center in Cleveland, Cleveland Clinic, and Veterans Administration Boston Healthcare System) were enrolled in institutional review board-approved study. Before transrectal ultrasound-guided biopsy, patients received digital rectal examination with systematic prostate massage followed by collection of urine.

Neurologic factors in female sexual function and dysfunction.

Sexual dysfunction affects both men and women, involving organic disorders, psychological problems, or both. Overall, the state of our knowledge is less advanced regarding female sexual physiology in comparison with male sexual function. Female sexual dysfunction has received little clinical and basic research attention and remains a largely untapped field in medicine.

Dietary antioxidants improve arteriogenic erectile dysfunction.

Most cases of erectile dysfunction (ED) are associated with oxidative stress risk factors such as diabetes mellitus, smoking, hypercholesterolaemia and hypertension. Our goal was to search for markers of oxidative stress in arteriogenic ED and examine the protective role of dietary antioxidants. Atherosclerosis-induced ED was developed in rabbits by balloon de-endothelialization of the iliac arteries.

Oxidative modification of mitochondrial integrity and nerve fiber density in the ischemic overactive bladder.

Purpose: To our knowledge the mechanism of neurodegeneration in the overactive bladder remains unknown. We examined mitochondrial integrity and searched for markers of oxidative neural injury in the ischemic overactive bladder.

Materials And Methods: A rabbit model of overactive bladder was developed by inducing moderate pelvic ischemia.

Frequent long-distance gene flow in a rare temperate forest tree (Sorbus domestica) at the landscape scale.

Precise empirical data on current gene flow by pollen, both with respect to distance and abundance, is crucial to understand whether habitat fragments are functionally connected. Based on a large-scale inventory ( approximately 100 km(2)) in which all individuals of a naturally scattered forest tree (Sorbus domestica) were mapped, we inferred current gene flow by pollen using genetic paternity analysis. We detected an extensive network of effective pollen transfer.

Oxidative stress and neurodegeneration in penile ischaemia.

Objective: To seek markers of oxidative stress and examine neural structural integrity in chronic penile ischaemia using a rabbit model of arteriogenic erectile dysfunction (ED), as the role of ischaemia in penile neuropathy and the oxidative mechanism of neurodegeneration in ED remains unknown.

Materials And Methods: A rabbit model of atherosclerosis-induced ED was developed by partial balloon de-endothelialization of the iliac arteries. After 10 weeks, intracavernosal blood flow and erectile function in the arteriogenic ED group were compared with age-matched controls.

Hiatal hernia and Barrett's oesophagus impact on symptoms occurrence and complications.

Unlabelled: The aim of the study was to evaluate the influence of sliding hiatal hernia over the Barrett's oesophagus, including symptoms rate and complications.

Methods: A total of 520 (4.6%) cases of Barrett's oesophagus were found out of 18.

Electrogastrography in patients with Roux-en-Y reconstruction after previous Billroth gastrectomy.

Background/aims: The aim of this prospective study was to characterize gastric myoelectrical activity in patients with Roux-en-Y reconstruction after previous Billroth gastrectomy.

Methodology: Thirteen patients entered the study (6 men and 7 women, aged 35-57). The mean time from Roux-en-Y reconstruction to electrogastrography (EGG) recording was 5 years.

Effects of ischemia on tachykinin-containing nerves and neurokinin receptors in the rabbit bladder.

Objectives: Our previous studies showed marked changes in efferent nerve structure and reactivity in the ischemic bladder. The goal of this study was to examine the effects of bladder ischemia on tachykinin (TK) containing sensory nerves and neurokinin receptors (NKR) in a rabbit model.

Methods: We recorded bladder blood flow and spontaneous contractions in treated animals at week 8 after the induction of iliac arteries atherosclerosis and in age-matched controls.

Oxidative stress and neurodegeneration in the ischemic overactive bladder.

Purpose: The central and peripheral nervous systems are highly sensitive to ischemia and oxidative stress. We searched for markers of oxidative injury and examined neural density in the rabbit ischemic overactive bladder.

Materials And Methods: Blood flow and oxygenation were recorded during cystometrogram in overactive and control rabbit bladders at weeks 8 and 16 after the induction of ischemia.