Revealing the mechanism of ethyl acetate extracts of Semen Impatientis against prostate cancer based on network pharmacology and transcriptomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Prostate cancer (PCa) is the most common malignancy of the male genitourinary system and currently lacks effective treatment. Semen Impatientis, the dried ripe seed of Impatiens balsamina L., is described by the Chinese Pharmacopoeia as a traditional Chinese medicine (TCM) and is used in clinical practice to treat tumors, abdominal masses, etc. In our previous study, the ethyl acetate extracts of Semen Impatientis (EAESI) was demonstrated to be the most effective extract against PCa among various extracts. However, the biological effects of EAESI against PCa in vivo and the specific antitumor mechanisms involved remain unknown. AIM OF THE STUDY: In this study, we aimed to investigate the antitumor effect of EAESI on PCa in vitro and in vivo by performing network pharmacology analysis, transcriptomic analysis, and experiments to explore and verify the underlying mechanisms involved. MATERIALS AND METHODS: The antitumor effect of EAESI on PCa in vitro and in vivo was investigated via CCK-8, EdU, flow cytometry, and wound healing assays and xenograft tumor models. Network pharmacology analysis and transcriptomic analysis were employed to explore the underlying mechanism of EAESI against PCa. Activating transcription factor 3 (ATF3) and androgen receptor (AR) were confirmed to be the targets of EAESI against PCa by RT‒qPCR, western blotting, and rescue assays. In addition, the interaction between ATF3 and AR was assessed by coimmunoprecipitation, immunofluorescence, and nuclear-cytoplasmic separation assays. RESULTS: EAESI decreased cell viability, inhibited cell proliferation and migration, and induced apoptosis in AR+ and AR- PCa cells. Moreover, EAESI suppressed the growth of xenograft tumors in vivo. Network pharmacology analysis revealed that the hub targets of EAESI against PCa included AR, AKT1, TP53, and CCND1. Transcriptomic analysis indicated that activating transcription factor 3 (ATF3) was the most likely critical target of EAESI. EAESI downregulated AR expression and decreased the transcriptional activity of AR through ATF3 in AR+ PCa cells; and EAESI promoted the expression of ATF3 and exerted its antitumor effect via ATF3 in AR+ and AR- PCa cells. CONCLUSIONS: EAESI exerts good antitumor effects on PCa both in vitro and in vivo, and ATF3 and AR are the critical targets through which EAESI exerts antitumor effects on AR+ and AR- PCa cells.

Compound K is a potential clinical anticancer agent in prostate cancer by arresting cell cycle.

BACKGROUND: Ginsenosides, phenolic compounds, and polysaccharides are the bioactive constituents of Panax ginseng Meyer. Compound K (CK) is a secondary ginsenoside with better bioavailability. It is also a promising anticancer agent. PURPOSE: We aimed to evaluate the effect of CK on prostate cancer (PCa) and its potential mechanisms. STUDY DESIGN: The proliferation, migration and cell cycle of PCa cells after CK treatment were assessed in various PCa cell lines. Docetaxel was used as a positive control drug. Unlike other published studies, the potential mechanisms of CK (50 µM) were investigated by an unbiased global transcriptome sequencing in the current study. METHODS: Key CK related genes (CRGs) with prognostic significance were identified and verified by bioinformatic methods using data from the TCGA dataset and GSE21034 dataset. The role of CDK1 in the effect of CK treatment on PCa cells was investigated by overexpression of CDK1. RESULTS: CK inhibited the proliferation and migration of PCa cells at concentrations (less than 25 µM) without obvious cytotoxicity. Five key CRGs with prognostic significance were identified, including CCNA2, CCNB2, CCNE2, CDK1, and PKMYT1, which are involved in cell cycle pathways. CK inhibited the expression of these 5 genes and the cell cycle of PCa cells. According to the results of bioinformatic analysis, the expression of the five key CRGs was strongly associated with poor prognosis and advanced pathological stage and grade of PCa. In addition, CK could restore androgen sensitivity in castration-resistant PCa cells, probably by inhibiting the expression of CDK1. After CDK1 overexpression, the inhibition of proliferation and migration of PCa cells by CK was decreased. The inhibition on the phosphorylation of AKT by CK was also reduced. CONCLUSION: CK can inhibit PCa cells, and the mechanisms may be associated with the inhibition of cell cycle pathways through CDK1. CK is also a potential clinical anticancer agent for treating PCa.

Paeonol ameliorates diabetic erectile dysfunction by inhibiting HMGB1/RAGE/NF-kB pathway.

BACKGROUND: The management of diabetes mellitus-induced erectile dysfunction (DMED) is progressively becoming tricky due to the surge in the number of patients and the poor efficiency of phosphodiesterase type 5 inhibitors in DMED. Paeonol (Pae), as a traditional Chinese medicine, has been more and more widely used in the treatment of diabetic complications. However, whether Pae could be a potential therapeutic drug of DMED needs to be further evaluated. OBJECTIVES: To investigate the pharmacological effect and possible mechanism of Pae in the treatment of DMED. METHODS: Intraperitoneal streptozotocin injection and an apomorphine test were used to construct the model of DMED. Seventeen DMED rats were divided into two groups: DMED group (n = 8) and DMED+Pae group (Pae; 100 mg/kg/d; oral administration; n = 9). In addition, there were still 10 normal age-matched male rats as control group. Four weeks later, the cavernous nerve electric stimulation was carried out to measure the erectile response. Moreover, the corpus cavernosum smooth muscle cells (CCSMCs) were primarily isolated and exposed to high glucose (HG) stimulation, Pae treatment and glycyrrhizin (GL; the selective inhibitor of HMGB1). After an incubation for 1 week, the CCSMCs were harvested for detection. RESULTS: The impairment of erectile function was observed in DMED rats compared with control samples, accompanied by the upregulation of HMGB1/RAGE/NF-κB Pathway. The lower nitric oxide and cGMP level and the higher level of inflammation, fibrosis, and apoptosis were also observed in DMED rats. It showed contrast that Pae treatment could improve the erectile function, as well as histologic alteration and related molecular changes. In addition, Pae could downregulate the HMGB1/RAGE/NF-κB pathway to regulate the apoptosis and inflammation levels of CCSMCs in high-glucose conditions, which is similar to the results of GL treatment. CONCLUSION: Pae alleviated ED in DMED rats, likely by inhibiting HMGB1/RAGE/NF-κB Pathway, inflammatory, apoptosis, and fibrotic activity, and moderating endothelial dysfunction. Our study provide evidence for a potential new therapy for DMED.

Molecular pathogenesis and treatment of cavernous nerve injury-induced erectile dysfunction: A narrative review.

Introduction: Erectile dysfunction (ED) is a common complication after radical prostatectomy (RP), and it seriously affects the quality of life in patients and their partners. The primary trigger of postoperative ED is surgical injury to the cavernous nerves that control penile erection and run along the anterolateral aspect of the prostate. Despite the introduction and ongoing innovation of nerve-sparing techniques, a significant number of patients still suffer from moderate cavernous nerve injury (CNI), which is thought to be transient and reversible. Therefore, early postoperative penile rehabilitation therapy may salvage patients' erectile function by promoting cavernous nerve regeneration and preventing penile structural alterations. Aims: To present a comprehensive overview of the current molecular pathogenesis of CNI-induced ED, as well as novel therapeutic strategies and their potential mechanisms. Methods: A literature search was performed using PubMed. Search terms included erectile dysfunction, cavernous nerve injury, pathogenesis, pathway, and treatment. Results: The NOS/NO pathway, oxidative stress-related pathway, RhoA/ROCK pathway, transforming growth factor-ß (TGF-ß), sonic hedgehog (Shh), and hydrogen sulfide (H2S) are involved in the molecular pathogenesis of CNI-induced ED. Multiple neurotrophins, including brain-derived nerve growth factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and neurturin (NTN), were found to promote cavernous nerve regeneration. Emerging therapeutic approaches can be roughly summarized into four categories, namely small molecule and drug, stem cell-based therapy (SCT), micro-energy therapy and platelet-rich plasma (PRP) therapy. Conclusion: These pathways collectively lead to the irreversible damage to the penile structure after CNI. The combined early rehabilitation strategies of promoting upstream nerve regeneration and recovering abnormal molecular signals of downstream penis are presumed to save patients' erectile function after RP. In future studies, the cross-talk between these molecular pathways needs to be further clarified, and the questions of how denervation injury induces the molecular alterations in the penis also need to be addressed.

GPX4 Alleviates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting Ferroptosis.

Pharmacological therapy of diabetes mellitus-induced erectile dysfunction (DMED) is intractable owig to the poor response to phosphodiesterase type 5 inhibitors (PDE5i). The surge in the number of diabetic patients makes it extremely urgent to find a novel therapy for DMED. Ferroptosis is a recently discovered form of cell death evoked by lipid peroxidation and is related to several diabetic complications. GPX4, an important phospholipid hydroperoxidase, can alleviate ferroptosis and maintain redox balance via reducing lipid peroxides. However, whether GPX4 can be a prospective target of DMED needs to be determined. Fifty rats were randomly divided into control group, DMED group, DMED + negative control group (DMED + NC group), DMED + low-dose group (1 × 106 infectious units), and DMED + high-dose group (2 × 106 infectious units). Erectile function was assessed 4 weeks after intracavernous injection of GPX4 or negative control lentivirus. The penile shafts were collected for subsequent molecular biological and histological analysis. The results demonstrated that erectile function of the rats in DMED and DMED + NC groups was extremely impaired and was improved in a dose-dependent manner with GPX4 lentivirus (GPX4-LV) injection. Additionally, upregulation of the ACSL4-LPCAT3-LOX pathway, iron overload, oxidative stress, fibrosis, and decreased endothelial and smooth muscle cell numbers were observed in the corpus cavernosum of DMED group. Meanwhile, the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway was inhibited, and the Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway was promoted in DMED rats. The above histologic alterations and related molecular changes were alleviated after GPX4-LV injection. The results revealed that GPX4 improved erectile function by modulating ferroptosis during DMED progression. This finding is of paramount significance in deciphering the molecular mechanism of hyperglycemia-induced ferroptosis, thereby providing a prospective target for preventing the development of DMED.

Deciphering the myth of icariin and synthetic derivatives in improving erectile function from a molecular biology perspective: a narrative review.

Background and Objective: Although epimedium herb (EH) has been widely used in ancient Chinese medicine to enhance sexual activity, its pharmacological mechanism is not clear. Modern studies have shown that epimedium herb is rich in icariin (ICA, a flavonoid compound), and 91.2% of icariin is converted to icariside II (ICA II) by hydrolytic enzymes in intestinal bacteria after oral administration. YS-10 is a synthetic derivative of icariside II. The aim of this review was to summarize the contemporary evidence regarding the pharmacokinetics, therapeutic properties, and molecular biological mechanisms of ICA and some ICA derivatives for erectile dysfunction therapy. Methods: A detailed search was conducted in the PubMed database using keywords and phrases, such as "icariin" AND "erectile dysfunction", "icariside II" AND "erectile dysfunction". The publication time is limited to last 20 years. Articles had to be published in peer reviewed journals. Key Content and Findings: ICA and its some derivatives showed the specific inhibition on phosphodiesterase type 5 (PDE5) and the promotion of testosterone synthesis. In addition, by regulating various reliable evidence of signaling pathways such as PI3K/AKT, TGFß1/Smad2, p38/MAPK, Wnt and secretion of various cytokines, ICA and ICA derivatives can activate endogenous stem cells (ESCs) leading to endothelial cell and smooth muscle cell proliferation, nerve regeneration and fibrosis inhibition, repair pathological changes in penile tissue and improve erectile function. Conclusions: ICA and some of its derivatives could be a potential treatment for restoring spontaneous erections. In addition ICA and his derivatives may also be valuable as a regenerative medicine approach for other diseases, but more clinical and basic researches with high quality and large samples are recommended.

Sodium bicarbonate reduces the cooked hardness of lotus rhizome via side chain rearrangement and pectin degradation.

In this study, 0.1% (W/V) sodium bicarbonate (SB) solution was used to soften lotus rhizome, and the mechanism was characterized by monoclonal antibodies labeling (mAbs) and atomic force microscopy (AFM). The results showed that the cell wall of lotus rhizome was disintegrated under SB treatment. In addition, the mAbs results revealed that low-esterified homogalacturonan (HG) at the tricellular junction was degraded, the rearrangement of Ara and the interaction between Gal and cellulose may be related to the texture changes. Compared with distilled water treatment, SB treatment reduced the relative content of pectin from 34.1% to 19.1% while increased that of cellulose from 65.9% to 80.9%. AFM results revealed that the height of CSF skeleton decreased from about 32 nm to 1.5 nm. These results clearly demonstrate that cooking with 0.1% SB can soften lotus rhizome through degradation of pectin and arrangement of side chains of rhamnogalacturonan-Ⅰ (RG-Ⅰ).

Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways.

BACKGROUND: The population with diabetes mellitus-induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas. OBJECTIVES: To evaluate the therapeutic effect and potential mechanism of berberine on the erectile function of diabetic rats. MATERIALS AND METHODS: Fifty male Sprague-Dawley rats were randomly grouped, and 42 rats were injected intraperitoneally with streptozotocin to establish a diabetes model. Erectile dysfunction rats were screened out through the apomorphine test and randomly divided into the diabetes mellitus and berberine groups, and these animals were administered berberine (200 mg/kg/day) and normal saline by gavage for 4 weeks. Primary corpus cavernous smooth muscle cells from healthy rats were cultured and treated with berberine. RESULTS: Fasting blood glucose in the diabetes mellitus group was significantly increased, while berberine showed no significant effect on glucose. Erectile function was obviously impaired in the diabetes mellitus group, and berberine administration partially rescued this impairment. The expression of sphingosine kinase 1, S1PR2, and sphingosine-1-phosphate in the diabetes mellitus group was increased. Berberine partially inhibited the expression of sphingosine kinase 1 and S1PR2, but the decrease in sphingosine-1-phosphate was not significant. Moreover, mitogen-activated protein kinase pathway factor expression was upregulated and eNOS activity was decreased in the diabetes mellitus group. Berberine treatment could partially reverse these alterations. Severe fibrosis and apoptosis were detected in diabetic rats, accompanied by higher expression of TGFß1, collagen I/IV, Bax/Bcl-2, and caspase 3 than in the other groups. However, supplementation with berberine inhibited the expression of these proteins and attenuated fibrosis and apoptosis. CONCLUSIONS: Berberine ameliorated erectile dysfunction in rats with diabetes mellitus, possibly by improving endothelial function and inhibiting apoptosis and fibrosis by suppressing the sphingosine kinase 1/sphingosine-1-phosphate/S1PR2 and mitogen-activated protein kinase pathways.

NOX1/4 Inhibitor GKT-137831 Improves Erectile Function in Diabetic Rats by ROS Reduction and Endothelial Nitric Oxide Synthase Reconstitution.

BACKGROUND: Previous studies have shown that oxidative stress contributes to hyperglycemia-induced erectile dysfunction. A preferential direct inhibitor of NOX1 and NOX4, GKT-137831, exhibited a strong anti­oxidative role via blockade of reactive oxygen species (ROS) generation in endothelial cells, but whether GKT-137831 could improve erectile function was not clear. AIM: Our study was designed to investigate the effect of NOX1/4 inhibition on improving diabetic erectile dysfunction (ED) in rats. METHODS: We used streptozotocin to induce type 1 diabetes mellitus (DM) in 32 male Sprague Dawley (SD) rats (8 weeks old). Eight weeks later, type 1 diabetes mellitus-induced erectile dysfunction (DMED) in rats was confirmed using an apomorphine test. Our study consisted of 3 groups: (i) nondiabetic control group (n = 8), (ii) DMED + vehicle group (DMED group; n = 8), and (iii) DMED + GKT-137831 group (n = 9); GKT-137831 was given as a once-daily intraperitoneal injection for 4 weeks. Cavernous nerve electrostimulation was used to evaluate erectile function. Western blot, ELISA, immunohistochemistry, and immunofluorescence were used to measure expression of specific proteins, and DHE fluorescent probe was performed to detect ROS level. OUTCOMES: Intracavernous pressure (ICP), nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway, oxidative stress level, inflammatory response, corporal autophagy, and apoptosis were measured. RESULTS: Erectile function in the DMED group was significantly impaired compared to the nondiabetic control group, whereas this impairment was improved with GKT-137831 treatment by 70%. Similarly, endothelial function and overactivated oxidative stress in the corpus cavernosum (CC) of the DMED + GKT-137831 group were improved. The DMED group showed serious inflammatory responses and excessive autophagy, which were inhibited by GKT-137831 treatment in the DMED + GKT-137831 group. CLINICAL TRANSLATION: Our study showed improvement in erectile function with GKT-137831 in a diabetic rat ED model. STRENGTH AND LIMITATIONS: This study suggested for the first time that GKT-137831, an NOX1/4 inhibitor undergoing clinical trials, is effective in improving erectile function in rats with type 1 DMED. However, we only investigated GKT-137831 treatment of streptozotocin-induced type 1 diabetic rats, and therapeutic evidence in other types of diabetes is lacking. CONCLUSION: GKT-137831 improves erectile function by 70% in type 1 DMED rats and constitutes a promising compound for the treatment of type 1 DMED, likely by inhibition of overactivated oxidative stress, down-regulation of proinflammatory factors, and amelioration of excessive autophagy and endothelial function. B Zhou, Y Chen, H Yuan, et al. NOX1/4 Inhibitor GKT-137831 Improves Erectile Function in Diabetic Rats by ROS Reduction and Endothelial Nitric Oxide Synthase Reconstitution. J Sex Med 2021;18:1970-1983.

[Changes of histology and ultrastructure of otopoint "Stomach" area in rabbits with chronic gastritis].

OBJECTIVE: To observe the histological and ultrastructural changes of the otopoint "Stomach" (MA-IC) area in chronic gastritis rabbits so as to provide a foundation for auricular acupoint diagnosis and treatment. METHODS: A total of 20 New Zealand rabbits (half male and half female) were randomly and equally divided into control and model groups. The chronic gastritis model was established by gavage of 5% sodium salicylate each day for 5 weeks, while the rabbits of the control group received gavage of clear water at the same volume. Morphological changes of the tissues of gastric mucosa, otopoint "Stomach" and auricular control point were observed under light microscope after staining with hematoxylin-eosin (H.E.), and given scores (0-3 points) according to the levels of inflammatory cells. The ultrastructural changes of the otopoint "Stomach" tissue were observed under transmission electronic microscope (TEM). RESULTS: H.E. staining revealed smoothness of the gastric smooth muscle with no or a few of inflammatory cells in the control group, and appearance of gastric mucosal hemorrhage and erosion, slightly disordered epithelial glands and infiltration of a large number of lymphocytes in the mucosal layer with some clustered lymphocyte aggregation foci in the model group. The pathological score of gastric mucous in the model group was significantly higher than that in the control group (P<0.01). Under light microscope, no obvious changes were observed in the skin of the otopoint "Stomach" of the control group and the control point of the model group, whereas hyperplasia and abscission in the epidermic cuticle and spinous layer and basal layer, dermal tissue and inflammatory cell infiltration were observed in the otopoint "Stomach" of the model group. Results of TEM observation showed no significant changes in the ultrastructure of the otopoint "Stomach" in the control group, and swollen and vacuolated epidermal keratinocyte mitochondria, reduced keratin filament aggregation, widened local cell space, unclear desmosome structure, activation of the dermal fibroblasts, and an increase of the myelinated nerve mitochondria in the "Stomach" region in the model group. CONCLUSION: The otopoint "Stomach" tissue has structural damage and hyperplasia in chronic gastritis rabbits, suggesting a special correlation between the otopoint "Stomach" and gastric tissue, hence, providing a morphological basis for otopoint diagnosis and treatment.

Systematic Review and Meta-Analysis of the Association between Vitamin D Status and Lower Urinary Tract Symptoms.

PURPOSE: Cumulative studies have shown that vitamin D may be associated with lower urinary tract symptoms but the findings have been inconsistent. The aim of this study was to systematically evaluate the relationship between vitamin D and lower urinary tract symptoms. MATERIALS AND METHODS: The PubMed®, Scopus® and Embase™ databases were searched for articles up to June 2020. A meta-analysis was conducted to evaluate the effects of vitamin D insufficiency or intake on lower urinary tract symptoms. A qualitative description summarized vitamin D intervention for treating lower urinary tract symptoms. Sensitivity analysis was conducted to examine heterogeneity and the robustness of the results. RESULTS: A total of 23 studies including 86,332 participants were analyzed in our study. Vitamin D insufficiency was associated with a 1.37-fold to 2.06-fold increased likelihood of having lower urinary tract symptoms, and patients with lower urinary tract symptoms had significantly lower levels of vitamin D. Furthermore, vitamin D intake was significantly associated with an 11% reduction in the risk of lower urinary tract symptoms. In the subgroup analysis, the effects of vitamin D insufficiency on the risk of lower urinary tract symptoms were notably observed in nonAsians, females and patients with urinary incontinence. CONCLUSIONS: Consistent results indicated that vitamin D insufficiency was a crucial risk factor for lower urinary tract symptoms and that vitamin D supplementation showed promising effects on these symptoms. It would be of great guiding significance to consider vitamin D status when treating lower urinary tract symptoms.

Acute EPA-induced learning and memory impairment in mice is prevented by DHA.

Eicosapentaenoic acid (EPA), an omega-3 fatty acid, has been widely used to prevent cardiovascular disease (CVD) and treat brain diseases alone or in combination with docosahexaenoic acid (DHA). However, the impact of EPA and DHA supplementation on normal cognitive function and the molecular targets of EPA and DHA are still unknown. We show that acute administration of EPA impairs learning and memory and hippocampal LTP in adult and prepubescent mice. Similar deficits are duplicated by endogenously elevating EPA in the hippocampus in the transgenic fat-1 mouse. Furthermore, the damaging effects of EPA are mediated through enhancing GABAergic transmission via the 5-HT6R. Interestingly, DHA can prevent EPA-induced impairments at a ratio of EPA to DHA similar to that in marine fish oil via the 5-HT2CR. We conclude that EPA exhibits an unexpected detrimental impact on cognitive functions, suggesting that caution must be exercised in omega-3 fatty acid supplementation and the combination of EPA and DHA at a natural ratio is critical for learning and memory and synaptic plasticity.

Liraglutide Ameliorates Erectile Dysfunction via Regulating Oxidative Stress, the RhoA/ROCK Pathway and Autophagy in Diabetes Mellitus.

BACKGROUND: Erectile dysfunction (ED) occurs more frequently and causes a worse response to the first-line therapies in diabetics compared with nondiabetic men. Corpus cavernosum vascular dysfunction plays a pivotal role in the occurrence of diabetes mellitus ED (DMED). The aim of this study was to investigate the protective effects of glucagon-like peptide-1 (GLP-1) analog liraglutide on ED and explore the underlying mechanisms in vivo and in vitro. METHODS: Type 1 diabetes was induced in rats by streptozotocin, and the apomorphine test was for screening the DMED model in diabetic rats. Then they were randomly treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. Erectile function was assessed by cavernous nerve electrostimulation. The corpus cavernosum was used for further study. In vitro, effects of liraglutide were evaluated by primary corpus cavernosum smooth muscle cells (CCSMCs) exposed to low or high glucose (HG)-containing medium with or without liraglutide and GLP-1 receptor (GLP-1R) inhibitor. Western blotting, fluorescent probe, immunohistochemistry, and relevant assay kits were performed to measure the levels of target proteins. RESULTS: Administration of liraglutide did not significantly affect plasma glucose and body weights in diabetic rats, but improved erectile function, reduced levels of NADPH oxidases and ROS production, downregulated expression of Ras homolog gene family (RhoA) and Rho-associated protein kinase (ROCK) 2 in the DMED group dramatically. The liraglutide treatment promoted autophagy further and restored expression of GLP-1R in the DMED group. Besides, cultured CCSMCs with liraglutide exhibited a lower level of oxidative stress accompanied by inhibition of the RhoA/ROCK pathway and a higher level of autophagy compared with HG treatment. These beneficial effects of liraglutide effectively reversed by GLP-1R inhibitor. CONCLUSION: Liraglutide exerts protective effects on ED associated with the regulation of smooth muscle dysfunction, oxidative stress and autophagy, independently of a glucose- lowering effect. It provides new insight into the extrapancreatic actions of liraglutide and preclinical evidence for a potential treatment for DMED.

The Effect of Tai Chi for Improving Sleep Quality: A Systematic Review and Meta-analysis.

BACKGROUND: Sleep quality is a major concern around the world, yet currently there are no recognized non-pharmacological treatments. A systematic review and meta-analysis investigated Tai Chi's effect on patients with sleep complaints, both those with insomnia and those with other conditions. METHODS: 4 English language databases (MEDLINE, EMBASE, PsycINFO, and CENTRAL) and 4 Chinese databases (CNKI, CBM, VIP, and Wanfang Data) were searched from database inception through June 23, 2019. Searches were conducted in both English and Chinese language. Meta-analysis by mean difference (MD) and 95% confidence interval (CI) was performed with RevMan 5.3. Risk of bias for each study was accounted for according to the Cochrane Handbook. RESULTS: Twenty randomized controlled studies from five countries covering 1,703 patients were included and divided into two control groups. Tai Chi had a significant effect on the Pittsburgh Sleep Quality Index (PSQI) compared with non-treatment and active treatment groups. Moreover, the articles were divided into groups according to Tai Chi styles. Both 24-form Yang-style Tai Chi and 8-form Yang-style Tai Chi had significant effects on PSQI. LIMITATIONS: One limitation of our work was that there were some forms of insomnia for which conclusions could not be drawn. Also, no relationship between efficacy and any of the factors could be elucidated. CONCLUSIONS: Compared with non-therapeutic and other active treatments, Tai Chi has a positive effect on improving sleep quality. In-depth analysis showed that 24-form and 8-form Yang style Tai Chi have significant positive effects on sleep quality, as assessed by PSQI.

Glycyrrhizin Prevents Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke with Delayed Thrombolysis Through Targeting Peroxynitrite-Mediated HMGB1 Signaling.

Peroxynitrite (ONOO-) and high mobility group box 1 protein (HMGB1) are important cytotoxic factors contributing to cerebral ischemia-reperfusion injury. However, the roles of ONOO- in mediating HMGB1 expression and its impacts on hemorrhagic transformation (HT) in ischemic brain injury with delayed t-PA treatment remain unclear. In the present study, we tested the hypothesis that ONOO- could directly mediate the activation and release of HMGB1 in ischemic brains with delayed t-PA treatment. With clinical studies, we found that plasma nitrotyrosine (NT, a surrogate marker of ONOO-) was positively correlated with HMGB1 level in acute ischemic stroke patients. Hemorrhagic transformation and t-PA-treated ischemic stroke patients had increased levels of nitrotyrosine and HMGB1 in plasma. In animal experiments, we found that FeTmPyP, a representative ONOO- decomposition catalyst (PDC), significantly reduced the expression of HMGB1 and its receptor TLR2, and inhibited MMP-9 activation, preserved collagen IV and tight junction claudin-5 in ischemic rat brains with delayed t-PA treatment. ONOO- donor SIN-1 directly induced expression of HMGB1 and its receptor TLR2 in naive rat brains in vivo and induced HMGB1 in brain microvascular endothelial b.End3 cells in vitro. Those results suggest that ONOO- could activate HMGB1/TLR2/MMP-9 signaling. We then addressed whether glycyrrhizin, a natural HMGB1 inhibitor, could inhibit ONOO- production and the antioxidant properties of glycyrrhizin contribute to the inhibition of HMGB1 and the neuroprotective effects on attenuating hemorrhagic transformation in ischemic stroke with delayed t-PA treatment. Glycyrrhizin treatment downregulated the expressions of NADPH oxidase p47 phox and p67 phox and iNOS, inhibited superoxide and ONOO- production, reduced the expression of HMGB1, TLR2, MMP-9, preserved type IV collagen and claudin-5 in ischemic brains. Furthermore, glycyrrhizin significantly decreased the mortality rate, attenuated hemorrhagic transformation, brain swelling, blood-brain barrier damage, neuronal apoptosis, and improved neurological outcomes in the ischemic stroke rat model with delayed t-PA treatment. In conclusion, peroxynitrite-mediated HMGB1/TLR2 signaling contributes to hemorrhagic transformation, and glycyrrhizin could be a potential adjuvant therapy to attenuate hemorrhagic transformation, possibly through inhibiting the ONOO-/HMGB1/TLR2 signaling cascades.

[Clinical research of auricular gold-needle therapy in treatment of chronic fatigue syndrome of qi deficiency constitution].

OBJECTIVE: To observe the clinical therapeutic effects of auricular gold-needle therapy on chronic fatigue syndrome of qi deficiency constitution and explore its potential mechanism. METHODS: A total of 120 patients were randomized into an auricular gold-needle therapy group, an auricular point pressure therapy group and a Chinese herb group, 40 cases in each one. Additionally, a health control group (40 cases) was set up, without any intervention. In the auricular gold-needle therapy group, the gold needle was used to stimulate the auricular points on one side and the cowherb seed pressure therapy on the other side. In the auricular point pressure therapy group, the cowherb seed pressure therapy was adopted only on one side. The auricular points were shen (CO10), xin (CO15), fei (CO14), pizhixia (AT4), etc. in the two groups. The auricular points on both sides were used alternatively. The treatment was given once a week, 4 treatments as one course and the consecutive 3 courses of treatment were required. In the Chinese herb group, buzhong yiqi wan was prescribed for oral administration, 6 g, twice a day, the medication for 1 month was as one session and the consecutive 3 sessions of medication were required. Before and after treatment, separately, the clinical symptom score, the levels of the serum immunoglobulins, i.e. IgA, IgG and IgM were observed in the patients of the three groups. The therapeutic effects were evaluated in the three groups. RESULTS: The total effective rate was 90.0% (36/40) in the auricular gold-needle therapy group, better than 80.0% (32/40) in the auricular point pressure therapy group and 82.5% (33/40) in the Chinese herb group (both P<0.05). Before treatment, the clinical symptom scores of the patients in the three groups were obviously higher than the health control group (all P<0.001). After treatment, the symptom scores were all reduced as compared the scores before treatment in the three groups (all P<0.001) and the symptom scores in the auricular gold-needle therapy group were better than the auricular point pressure therapy group and the Chinese herb group (both P<0.01). Before treatment, the levels of serum IgA, IgG and IgM of the patients in the three groups were lower than the health control group (all P<0.001). The levels were all improved after treatment in the three groups (all P<0.01), and the levels in the auricular gold-needle therapy group was better than the auricular point pressure therapy group and the Chinese herb group (all P<0.05). CONCLUSION: The auricular gold-needle therapy achieves the significant therapeutic effects on chronic fatigue syndrome of qi deficiency constitution and its mechanism is probably related to the regulation of immune function.

Standardized Auricular Therapy for Patients with Different Constitutions and Suboptimal Health: A Retrospective Study.

Objective: According to the guideline for preventive treatment in Traditional Chinese Medicine (TCM), this study examined the efficacy of standardized auricular therapy for patients with different constitutions who had suboptimal health. To prevent the occurrence and development of diseases, it is necessary to find new positive and feasible methods. Materials and Methods: A retrospective study of standardized auricular therapy for patients with different constitutions who had suboptimal health was conducted. The study included 176 patients with Qi Deficiency, Yang Deficiency, Yin Deficiency, Qi Stagnation, Phlegm Dampness, Blood Stasis, Damp-Heat, and Special Constitution. As the patients underwent treatment, they were examined with a weekly test for changes in symptoms for 4 weeks. Results: Using statistical analysis, the efficacy rate of treatment for patients with Yang deficiency was 83.90%. Other constitutional efficacy rates were: Yin Deficiency, 84.62%; Qi Deficiency, 75.00%; Qi Stagnation, 92.31%; Phlegm-Dampness, 82.69%; Damp-Heat, 84.84%; Blood Stasis, 71.43%; and Special Endowment, 83.33%. Conclusions: Standardized auricular therapy has curative effects on patients with a variety of constitutions and who have suboptimal health. This therapy can not only balance the constitutions of patients with suboptimal health but also can play an important role in the field of prevention and health-promoting medicine.

Traditional Chinese medical therapy for erectile dysfunction.

Traditional Chinese medicine (TCM), including acupuncture and Chinese herbs, is used as an alternative therapy to increase the curative effect for erectile dysfunction (ED). A large number of studies have been conducted to investigate the effect and mechanism of TCM for treating ED. The therapeutic effect of acupuncture on ED is still controversial at present. However, some Chinese herbs exhibited satisfying outcomes and they might improve erectile function by activating nitric oxide synthase (NOS)-cyclic guanosine monophosphate (cGMP) pathway, increasing cyclic adenosine monophosphate (cAMP) expression, elevating testosterone level, reducing intracellular Ca2+ concentration, down-regulating transforming growth factor ß1 (TGFß1)/Smad2 signaling pathway, or ameliorating the oxidative stress.

Ethyl Acetate Extracts of Semen Impatientis Inhibit Proliferation and Induce Apoptosis of Human Prostate Cancer Cell Lines through AKT/ERK Pathways.

Objective. To investigate the inhibitory effect of ethyl acetate extracts of Impatiens balsamina L. on prostate cancer cells. Methods. Impatiens balsamina L. was extracted to get water, ethanol, oil ether, ethyl acetate, and butanol extracts. CCK-8 assay was used to detect the inhibitory effect. Apoptosis rates and cell cycle distribution were detected by flow cytometry. Transwell assay was performed to test the ability of migration. The expressions of Bcl-2, Bax, cleaved-caspase-3, p-ERK, ERK, p-AKT, AKT, cyclin D1, cyclin E, and MMP2 were detected by Western blot. Results. Ethyl acetate extracts had the strongest inhibitory effect. After being treated with different concentrations of ethyl acetate extracts, the percentage of G0/G1 phase increased significantly, cyclin D1 and cyclin E expression decreased, apoptosis rate was significantly higher, and the ability of migration of PC-3 and RV1 was inhibited significantly. Western blot showed that the expressions of Bcl-2, p-ERK, and p-AKT were significantly decreased, but the expressions of Bax and caspase-3 cleavage were increased. Conclusions. Impatiens balsamina L. inhibited the proliferation of human prostate cancer cells; ethyl acetate extracts have the strongest effect. It could inhibit cell proliferation and migration, cause G1 phase arrest, and induce apoptosis probably through inhibition of the AKT and ERK pathways.

Local anesthesia for transrectal ultrasound-guided biopsy of the prostate: A meta-analysis.

A meta-analysis was performed to evaluate the efficacy of local anesthesia in alleviating pain during prostate biopsy. We searched relevant articles in PubMed and Embase. The included studies should be randomized controlled trials (RCT) using local anesthesia to alleviate pain during biopsy, which was recorded by a pain scale. Analgesic efficacy of different local anesthesia techniques were analyzed, including intrarectal local anesthesia (IRLA), periprostatic nerve block (PNB), pelvic plexus block (PPB) and intraprostatic local anesthesia (IPLA). We included 46 RCTs. PNB significantly reduced pain score compared with placebo (-1.27 [95% confidence interval [95% CI] -1.72, -0.82]) or no injection (-1.01 [95% CI -1.2, -0.82]). IRLA with prilocaine-lidocaine cream could also reduced pain (-0.45 [95% CI -0.76, -0.15]), while the IRLA with lidocaine gel was not effective (-0.1 [95% CI -0.24, 0.04]). PNB lateral to the neurovascular bundle had better analgesic effect than at prostate apex (P = 0.02). Combination use of PPB and IRLA considerably alleviated pain of patients compared with the combination of PNB and IRLA (-1.32 [95% CI -1.59, -1.06]). In conclusion, local anesthesia could alleviate patients' pain during the prostate biopsy. PNB was not so effective as PPB.