Role of adipose-derived stem cells in healing surgically induced trauma of the rat's tunica albuginea.

Background: Injection of adipose-derived stem cells (ADSCs) into the injured tunica albuginea (TA) may prevent fibrosis, restore the balance between pro- and antifibrotic pathways, and potentially mitigate erectile dysfunction caused by abnormal TA healing. Aim: To assess the potential role of ADSC injection on structural, ultrastructural, functional, and molecular changes in surgically induced trauma of the rat's TA. Methods: Forty adult male albino Wistar rats were divided into 5 groups of 8 rats each: group 1, sham; group 2, injury to TA without treatment; group 3, injury to TA and suture repair; group 4, injury to TA and injection of ADSCs without suture repair; group 5, injury to TA followed by injection of ADSCs and suture repair. Outcomes: After 6 weeks, all groups were subjected to functional, histologic, and ultrastructural examination and molecular expression of healing growth factors. Results: The intracavernous pressure (ICP; mean ± SD) was 114 ± 2, 32 ± 2, 65 ± 2, 68 ± 2, and 111 ± 2 mm Hg in groups 1 to 5, respectively. There were significant differences in ICP between each of groups 3 to 5 and group 2 (P < .05), and groups 3 and 4 each had significant differences with group 1 (P < .05). No significant difference in ICP occurred between groups 3 and 4 (P > .05). There were significant histologic and ultrastructural alterations in tunical tissues from group 2; however, these changes were markedly less in group 5 in terms of lower levels of fibrotic changes, elastosis, and superior overall neuroendothelial expression. Groups 3 and 4 showed improved structural and ultrastructural parameters when compared with group 2. Group 5 demonstrated lower levels of transforming growth factor ß1 and basic fibroblast growth factor expression. Clinical Implications: This experimental model may encourage administration of ADSCs to prevent the deleterious effects of trauma to the TA. Strengths and Limitations: Injecting ADSCs can improve the healing process and erectile dysfunction in a rat model following TA injury, and combining ADSC injection with surgical suturing resulted in superior outcomes. The main limitation was the absence of long-term ICP measurements and a longer follow-up period that may provide further insight into the chronic phase of the healing process. Conclusion: ADSC injection may prevent structural, ultrastructural, functional, and molecular alterations in surgically induced trauma of the rat's TA and enhance the effect of tunical suturing after trauma.

Vaping, Environmental Toxicants Exposure, and Lung Cancer Risk.

Lung cancer (LC) is the second-most prevalent tumor worldwide. According to the most recent GLOBOCAN data, over 2.2 million LC cases were reported in 2020, with an estimated new death incident of 1,796,144 lung cancer cases. Genetic, lifestyle, and environmental exposure play an important role as risk factors for LC. E-cigarette, or vaping, products (EVPs) use has been dramatically increasing world-wide. There is growing concern that EVPs consumption may increase the risk of LC because EVPs contain several proven carcinogenic compounds. However, the relationship between EVPs and LC is not well established. E-cigarette contains nicotine derivatives (e.g., nitrosnornicotine, nitrosamine ketone), heavy metals (including organometal compounds), polycyclic aromatic hydrocarbons, and flavorings (aldehydes and complex organics). Several environmental toxicants have been proven to contribute to LC. Proven and plausible environmental carcinogens could be physical (ionizing and non-ionizing radiation), chemicals (such as asbestos, formaldehyde, and dioxins), and heavy metals (such as cobalt, arsenic, cadmium, chromium, and nickel). Air pollution, especially particulate matter (PM) emitted from vehicles and industrial exhausts, is linked with LC. Although extensive environmental exposure prevention policies and smoking reduction strategies have been adopted globally, the dangers remain. Combined, both EVPs and toxic environmental exposures may demonstrate significant synergistic oncogenicity. This review aims to analyze the current publications on the importance of the relationship between EVPs consumption and environmental toxicants in the pathogenesis of LC.

HSP70 Expression Signature in Renal Cell Carcinoma: A Clinical and Bioinformatic Analysis Approach.

Heat shock proteins (HSPs) are cytoprotective against stressful conditions, as in the case of cancer cell metabolism. Scientists proposed that HSP70 might be implicated in increased cancer cell survival. This study aimed to investigate the HSP70 (HSPA4) gene expression signature in patients with renal cell carcinoma (RCC) in correlation to cancer subtype, stage, grade, and recurrence, combining both clinicopathological and in silico analysis approaches. One hundred and thirty archived formalin-fixed paraffin-embedded samples, including 65 RCC tissue specimens and their paired non-cancerous tissues, were included in the study. Total RNA was extracted from each sample and analyzed using TaqMan quantitative Real-Time Polymerase Chain Reaction. Correlation and validation to the available clinicopathological data and results were executed. Upregulated HSP70 (HSPA4) gene expression was evident in RCC compared to non-cancer tissues in the studied cohort and was validated by in silico analysis. Furthermore, HSP70 expression levels showed significant positive correlations with cancer size, grade, and capsule infiltration, as well as recurrence in RCC patients. The expression levels negatively correlated with the overall survival (r = -0.87, p < 0.001). Kaplan-Meier curves showed lower survival rates in high HSP70 expressor group compared to the low expressors. In conclusion, the HSP70 expression levels are associated with poor RCC prognosis in terms of advanced grade, capsule infiltration, recurrence, and short survival.

The Anti-Rheumatic Drug, Leflunomide, Induces Nephrotoxicity in Mice via Upregulation of TGFß-Mediated p53/Smad2/3 Signaling.

Recent studies indicated renal toxicity and interstitial nephritis in patients receiving leflunomide (LEFN), but the exact mechanism is still unknown. The transforming growth factor ß (TGFß)/p53/Smad2/3 pathway crucially mediates renal fibrosis. We aimed to assess the nephrotoxic effect of LEFN in mice and the possible role of TGFß-stimulated p53/SMAD2/3 signaling. The study design involved distributing sixty male albino mice into four groups: (i) vehicle-treated mice, (ii) LEFN (2.5 mg/kg), (iii) LEFN (5 mg/kg), and (iv) LEFN (10 mg/kg). The drug was given orally every 48 h and continued for 8 weeks. Blood samples were then taken from mice for the determination of kidney function parameters. Right kidneys were used for histopathologic staining and immunohistochemistry, whereas left kidneys were frozen and used for Western blot analysis of the target proteins, p-p53 and Smad2/3. Results indicated that chronic administration of LEFN in mice resulted in a four- and nine-fold increase in serum urea and creatinine levels, respectively. Kidney specimens stained with hematoxylin and eosin or periodic acid-Schiff showed significant histopathological manifestations, such as cellular irregularity, interstitial congestion, and moderate lymphocytic inflammatory infiltrate in mice treated with LEFN. Western blotting indicated upregulation of the p-p53/Smad2/3 proteins. LEFN, especially in the highest dose (10 mg/kg), produced prominent nephrotoxicity in mice. This toxicity is mediated through stimulating fibrotic changes through TGFß-stimulated p53/Smad2/3 signaling and induction of glomerular and tubular apoptosis. An improved understanding of LEFN-induced nephrotoxicity would have great implications in the prediction, prevention, and management of leflunomide-treated rheumatic patients, and may warrant further clinical studies for following up these toxidromes.

Innovative trends and perspectives for erectile dysfunction treatment: A systematic review.

OBJECTIVE: To review contemporary knowledge concerning the innovative trends and perspectives in the treatment of erectile dysfunction (ED). METHODS: Medline was reviewed for English-language journal articles between January 2000 and March 2016, using the terms 'erectile dysfunction treatments', 'new trends' and 'perspectives'. In all, 114 original articles and 16 review articles were found to be relevant. Of the 76 cited papers that met the inclusion criteria, 51 papers had level of evidence of 1a-2b, whilst 25 had level of evidence of 3-4. Criteria included all pertinent review articles, randomised controlled trials with tight methodological design, cohort studies, and retrospective analyses. We also manually reviewed references from selected articles. RESULTS: Several interesting studies have addressed novel phosphodiesterase type 5 inhibitors (PDE5Is), orodispersible tablets, their recent chronic use, and combination with other agents. A few controlled studies have addressed herbal medicine as a sole or additional treatment for ED. Experimental studies and exciting review papers have addressed stem cells as novel players in the field of ED treatment. Other recent articles have revised the current status of low-intensity extracorporeal shockwave therapy in the field of ED. A few articles without long-term data have addressed new technologies that included: external penile support devices, penile vibrators, tissue engineering, nanotechnology, and endovascular tools for ED treatment. CONCLUSIONS: The current treatment of ED is still far from ideal. We expect to see new drugs and technologies that may revolutionise ED treatment, especially in complex cases.