Redox System and Oxidative Stress-Targeted Therapeutic Approaches in Bladder Cancer.

Bladder cancer (BCa) is the most common genitourinary malignancy, with a high global incidence and recurrence rate that is paired with an increasing caregiver burden and higher financial cost, in addition to increasing morbidity and mortality worldwide. Histologically, BCa is categorized into non-muscle invasive, muscle invasive, and metastatic BCa, on the basis of which the therapeutic strategy is determined. Despite all innovations and recent advances in BCa research, conventional therapies such as chemotherapy, immunotherapy, radiotherapy, and surgery fall short in the complete management of this important malignancy. Besides this worrying trend, the molecular basis of BCa development also remains poorly understood. Burgeoning evidence from experimental and clinical studies suggests that oxidative stress resulting from an imbalance between reactive oxygen species (ROS) generation and the body's antioxidant production plays an integral role in BCa development and progression. Hence, ROS-induced oxidative stress-related pathways are currently under investigation as potential therapeutic targets of BCa. This review focuses on our current understanding regarding ROS-associated pathways in BCa pathogenesis and progression, as well as on antioxidants as potential adjuvants to conventional BCa therapy.

Pre-Treatment of Transplant Donors with Hydrogen Sulfide to Protect against Warm and Cold Ischemia-Reperfusion Injury in Kidney and Other Transplantable Solid Organs.

Ischemia-reperfusion injury (IRI), a pathological condition resulting from prolonged cessation and subsequent restoration of blood flow to a tissue, is an inevitable consequence of solid organ transplantation. Current organ preservation strategies, such as static cold storage (SCS), are aimed at reducing IRI. However, prolonged SCS exacerbates IRI. Recent research has examined pre-treatment approaches to more effectively attenuate IRI. Hydrogen sulfide (H2S), the third established member of a family of gaseous signaling molecules, has been shown to target the pathophysiology of IRI and thus appears to be a viable candidate that can overcome the transplant surgeon's enemy. This review discusses pre-treatment of renal grafts and other transplantable organs with H2S to mitigate transplantation-induced IRI in animal models of transplantation. In addition, ethical principles of pre-treatment and potential applications of H2S pre-treatment in the prevention of other IRI-associated conditions are discussed.

A pilot study evaluating the effects of concussion on the ability to form cognitive maps for spatial orientation in adolescent hockey players.

OBJECTIVE: In this pilot study, we investigated the impact of a sport-related concussion (SRC) on the ability to form cognitive maps, mental representations of the environment that are critical for spatial orientation and navigation. PARTICIPANTS: We recruited 18 adolescent hockey players suffering from a SRC, and 19 age, sex and handedness-matched hockey players with no history of concussion. MAIN MEASURE: We asked participants to perform the Spatial Configuration Task (SCT), a computerized tool used to quantitatively measure the ability of the individuals to form cognitive maps. RESULTS: We found that athletes with a concussion performed significantly worse than controls on the SCT (F(1,34) = 5.82, p =.021, [Formula: see text] = -0.72), confirming a negative effect of a SRC on the ability to form cognitive maps. We found no significant difference between groups in average response time, and no significant correlation between participants' performance at the SCT and reported symptoms of concussion as rated on the Sport Concussion Assessment Tool (SCAT5). CONCLUSIONS: Consistent with the integrity of extended neural networks required for effective spatial orientation and navigation, the findings of our pilot study provide preliminary evidence suggesting that a SRC may affect the ability to familiarize with a spatial surrounding and orient within it.

Ventral-Dorsal Functional Contribution of the Posterior Cingulate Cortex in Human Spatial Orientation: A Meta-Analysis.

The retrosplenial cortex has long been implicated in human spatial orientation and navigation. However, neural activity peaks labeled "retrosplenial cortex" in human neuroimaging studies investigating spatial orientation often lie significantly outside of the retrosplenial cortex proper. This has led to a large and anatomically heterogenous region being ascribed numerous roles in spatial orientation and navigation. Here, we performed a meta-analysis of functional Magnetic Resonance Imaging (fMRI) investigations of spatial orientation and navigation and have identified a ventral-dorsal functional specialization within the posterior cingulate for spatial encoding vs. spatial recall. Generally, ventral portions of the posterior cingulate cortex were more likely to be activated by spatial encoding, i.e., passive viewing of scenes or active navigation without a demand to respond, perform a spatial computation, or localize oneself in the environment. Conversely, dorsal portions of the posterior cingulate cortex were more likely to be activated by cognitive demands to recall spatial information or to produce judgments of distance or direction to non-visible locations or landmarks. The greatly varying resting-state functional connectivity profiles of the ventral (centroids at MNI -22, -60, 6 and 20, -56, 6) and dorsal (centroid at MNI 4, -60, 28) posterior cingulate regions identified in the meta-analysis supported the conclusion that these regions, which would commonly be labeled as "retrosplenial cortex," should be more appropriately referred to as distinct subregions of the posterior cingulate cortex. We suggest that future studies investigating the role of the retrosplenial and posterior cingulate cortex in spatial tasks carefully localize activity in the context of these identifiable subregions.