[Mechanisms of hypoxia-induced erectile dysfunction: Advances in studies].

Hypoxia is one of the important pathophysiologic causes of ED, and the development and progression of hypoxia-induced ED can be attributed to multiple factors relating nerves, blood vessels, endocrine and various cytokines. The mechanisms of hypoxia-induced ED have not been fully clarified by now despite some advances achieved in the respects of corpus cavernosal microstructure, important signaling pathways, oxidative stress, hormone levels, autophagy and so on. This review focuses on the present status of and progress made in the studies of hypoxia-induced ED in order to provide some evidence and a direction for further researches.

Arabidopsis ADF5 promotes stomatal closure by regulating actin cytoskeleton remodeling in response to ABA and drought stress.

Stomatal movement plays an essential role in plant responses to drought stress, and the actin cytoskeleton and abscisic acid (ABA) are two important components of this process. Little is known about the mechanism underlying actin cytoskeleton remodeling and the dynamic changes occurring during stomatal movement in response to drought stress/ABA signaling. Actin-depolymerizing factors (ADFs) are conserved actin severing/depolymerizing proteins in eukaryotes, and in angiosperms ADFs have evolved actin-bundling activity. Here, we reveal that the transcriptional expression of neofunctionalized Arabidopsis ADF5 was induced by drought stress and ABA treatment. Furthermore, we demonstrated that ADF5 loss-of-function mutations increased water loss from detached leaves, reduced plant survival rates after drought stress, and delayed stomatal closure by regulating actin cytoskeleton remodeling via its F-actin-bundling activity. Biochemical assays revealed that an ABF/AREB transcription factor, DPBF3, could bind to the ADF5 promoter and activate its transcription via the ABA-responsive element core motif ACGT/C. Taken together, our findings indicate that ADF5 participates in drought stress by regulating stomatal closure, and may also serve as a potential downstream target of the drought stress/ABA signaling pathway via members of the ABF/AREB transcription factors family.

NLRP3 inhibitor combined with Yimusake improves erectile dysfunction in rats with diabetes mellitus through the attenuation of pyroptosis.

Erectile dysfunction (ED) is a prevalent complication associated with diabetes mellitus (DM), yet pharmacological treatments for diabetes-related erectile dysfunction (DMED) continue to be inadequate in clinical settings. Our previous studies have indicated that there is a close correlation between ED and pyroptosis, but the specific mechanism remains unclear. In this study, we sought to explore the therapeutic effects of DMED through the modulation of NLRP3, aiming to elucidate its potential molecular mechanisms. The DMED rat model was established via intraperitoneal injection of streptozotocin. The rats were randomly assigned to the control group, the DMED group, the Yimusake group, the MCC950 (NLRP3 inhibitor) group, and the MCC950+Yimusake group. Erectile function of rats was observed by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). HE staining was performed to observe the histopathological changes in penile; immunofluorescence was performed to measure the level of CD31 (Platelet endothelial cell adhesion molecule-1) in penile. Besides, immunohistochemistry, RT-qPCR and Western blot were performed to demonstrate the expression of NLRP3, caspase-1, IL-1ß and eNOS. After treatment with the MCC950 and Yimusake, the number of blood sinusoids and small vessels significantly reduced in penile tissue; NLRP3, caspase-1, IL-1ß proteins and mRNA expression decreased, eNOS protein and mRNA expression increased. Compare with the Y group and the MCC950 group, MCC950+Yimusake group had a more significant effect. MCC950 and Yimusake might potentially suppress pyroptosis in the penile tissue of DMED rats by modulating the NLRP3/caspase-1 pathway, thus enhancing erectile function. This discovery could offer a promising therapeutic approach for individuals with DMED.

Inhibition of the RIP3/MLKL/TRPM7 necroptotic pathway ameliorates diabetes mellitus-induced erectile dysfunction by reducing cell death, fibrosis, and inflammation.

Diabetes mellitus-induced erectile dysfunction (DMED) is a common complication in patients with diabetes mellitus. Necroptosis is regarded as a form of cell death that is intimately associated with the inflammatory response, which is not only initiated by inflammatory factors such as TNF-α, but also triggers the inflammatory cascade through the rupture of the dying cell. There is no definitive study on the role of necroptosis in the pathological process of DMED. In light of the pathological features of high inflammation levels in DMED patients, we assessed whether the necroptosis plays an important role in the course of DMED. Our study revealed that penile tissues of DMED rats showed high levels of key necroptosis factors such as receptor-interacting protein kinase 3 (RIP3), mixed-lineage kinase domain-like protein (MLKL), and transient receptor potential melatonin 7 (TRPM7). Furthermore, the inhibition of necroptosis with a receptor-interacting protein kinase 3 (RIP3) inhibitor or Yimusake (a common herbal remedy for ED) effectively rescued damage to corpus cavernosum smooth muscle cells (CCSMC) under high glucose conditions. Our findings suggest that inhibition of the RIP3/MLKL/TRPM7 necroptotic pathway could effectively ameliorate CCSMCs fibrosis and death induced by high glucose and inhibited the inflammatory response.

Exploring the application of sildenafil for high-fat diet-induced erectile dysfunction based on interleukin-18-mediated NLRP3/Caspase-1 signaling pathway.

Background: Inflammation is a key risk factor for heart disease and has also been linked to erectile dysfunction (ED). Sildenafil is a phosphodiesterase type 5 inhibitor with a strong antioxidant effect. Interleukin (IL)-18 is a proinflammatory factor. Excessive production and release of IL-18 disrupt the balance between IL-18 and IL-18 binding proteins in certain inflammatory diseases, leading to the occurrence of pathological inflammation. Aim: We evaluated the effects of sildenafil on erectile function in a rat model of high-fat diet-induced ED. Methods: Male Sprague Dawley rats (6 weeks old) were divided into 5 groups: control, ED, sildenafil, IL-18, and IL-18 + sildenafil. Subsequently, intracavernous pressure and mean arterial pressure were used to assess the erectile function of these rats. The expression of endothelial nitric oxide synthase, pyroptosis factors, and the ratio of smooth muscle cells and collagen fibers were evaluated in the serum and corpora tissue. Outcomes: Exploring the role and mechanism of sildenafil in ED through NLRP3-mediated pyroptosis pathway. Results: In comparison to the ED and IL-18 groups, there were statistically significant increases in the ratio of intracavernous pressure to mean arterial pressure, endothelial nitric oxide synthase expression, and the ratio of smooth muscle cells to collagen fibers following sildenafil intervention (P < .05). The sildenafil group and IL-18 + sildenafil group also showed statistically significant decreases the expression of NLRP3, caspase-1, and gasdermin D (P < .05). Clinical Implications: Sildenafil can improve erectile dysfunction by inhibiting inflammation. Strengths and Limitations: Strengths are that the relationship between pyroptosis and ED has been verified through in vitro and in vivo experiments. The limitation is that the conclusions drawn from animal and cells experiments need to be confirmed in clinical research. Conclusion: Sildenafil may reduce the effect of IL-18-induced inflammation in high-fat diet-induced ED rats through NLRP3/caspase-1 pyroptosis pathway.

[Study on anatomical parameters of adult lumbar intervertebral disc and endplate based on CT].

OBJECTIVE: To provide basic data for clinical application and individualized design of lumbar disc prostheses by measuring the anatomical parameters of lumbar intervertebral discs and endplates in healthy adults with CT three-dimensional reconstruction technology. METHODS: A retrospective analysis was performed on 200 males and 200 females with normal lumbar spine who were admitted to the imaging center or outpatient department of the Second Affiliated Hospital of Xinjiang Medical University from September 2019 to December 2020. The age ranged from 20 to 60 years old, with an average of (40.61±11.22) years old. The measurement segment was L1-S1 intervertebral disc, and the measurement indicators included the axial anteroposterior diameter and transverse diameter of the intervertebral disc, sagittal anterior, middle and posterior height, coronal left and right height, intervertebral space angle, and transverse and anteroposterior diameters of the upper and lower endplates of each vertebral body. RESULTS: ①In terms of gender, the anatomical parameters of L1-S1 disc axial diameter, transverse diameter, sagittal anterior, middle and posterior height, left and right coronal height and intervertebral space angle were all higher in males than in females(P<0.05), and the anatomical parameters of upper and lower endplates of L1-S1 vertebral body were higher in males than in females(P<0.001). ②In comparison of sagittal height of anterior, middle and posterior intervertebral discs, the sagittal height of L1-L5 intervertebral discs was middle-high > anterior-high > posterior-high(P<0.001), while that of L5S1 intervertebral disc was anterior-high > middle-high > posterior-high (P<0.001). ③In the comparison of left and right coronal height, there was no statistical significance in the left and right coronal height of L1-S1 disc between male and female(P>0.05). ④The L1-S1 intervertebral spaces angle between male and female increased with the increase of vertebral body segments. ⑤The anterior and posterior diameters and transverse diameters of upper and lower of L1-S1 vertebral bodies endplates were height in males than in females(P<0.001). CONCLUSION: The results suggest that gender differences should be considered in the design of adult lumbar disc prostheses. The anatomical parameters of the lumbar intervertebral disc varied with the increase of the vertebral body sequence, suggesting that different anatomical parameters of the intervertebral disc should be considered in the design of the artificial intervertebral disc, and the changes in the height of the sagittal position suggest that the design of the intervertebral disc should be wedge-shaped.