Novel drug therapy of acute hepatic failure induced in rats by a combination of tadalafil and Lepidium sativum.

BACKGROUND: Hepatocyte death and a systemic inflammatory response are the outcome of a complex chain of events mediated by numerous inflammatory cells and chemical mediators. The point of this study was to find out if tadalafil and/or Lepidium sativum (L. sativum) could help people who have been exposed to carbon tetrachloride (CCL4) and are experiencing acute moderate liver failure. This was especially true when the two were used together. METHOD AND MATERIALS: To cause mild liver failure 24 h before sacrifice, a single oral dosage of CCL4 (2.5 mL/kg b.w.) (50% in olive oil) was utilized. Furthermore, immunohistochemical expression of nuclear factor kappa B (NF-κB) as well as histological abnormalities were performed on liver tissue. RESULTS: The results showed that tadalafil and/or L. sativum, especially in combination, performed well to cure acute mild liver failure caused by CCL4. This was demonstrated by a decrease in NF-κB expression in the liver tissue and an improvement in organ damage markers observed in the blood and liver tissues. Furthermore, such therapy reduced interleukin1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) levels in the liver tissue. It's worth noting that the tested combination resulted in greater liver improvement. CONCLUSIONS: According to the findings, tadalafil and L. sativum, particularly in combination, have the ability to protect the liver from the negative effects of CCL4 exposure. Because of its capacity to improve liver function, restore redox equilibrium, and decrease inflammatory mediators, it is a prospective option for mitigating the negative effects of common environmental pollutants such as CCL4.

Comparison of the effect of hyperbaric oxygen therapy and tadalafil daily use on erectile function: a prospective, double controlled study.

PURPOSE: Erectile dysfunction (ED) is a worldwide health problem. Oral phosphodiesterase type 5 inhibitors (PDE5I) are used in its first-line treatment. This study aimed to compare the effects of hyperbaric oxygen (HBO) treatment with PDE5I treatment and determine the patient-dependent factors affecting the efficacy of the HBO treatment and duration of action of HBO treatment. METHODS: Adult male patients who presented to the HBO unit for HBO treatment with non-urological indications and had ED based on the International Index for Erectile Function (IIEF-5) constituted the target population of this study. Participants were given HBO treatment (Group 1), no treatment (Group 2), or daily oral tadalafil 5 mg treatment (Group 3). The treatment duration was 1 month. Patients were assessed by IIEF-5 both initially and after the completion of 1 month. RESULTS: There were significant increases in the mean IIEF-5 scores of the patients in Group 1 and Group 3 (p < 0.001, p < 0.001). However, there was no significant improvement in Group 2 (p = 0.496). Also, the post-treatment IIEF-5 scores of Group 1 and Group 3 were significantly higher than Group 2 (p < 0.001). There was no significant difference between the IIEF-5 scores and ∆IIEF-5 values of Group 1 and Group 3 (p = 0.166, p = 0.093). Evaluation regarding comorbidities revealed that patients with the peripheral vascular disease did not improve with HBO treatment (p = 0.285). CONCLUSION: HBO can improve erectile functions, and it can be a reasonable alternative for patients who cannot use PDE5Is due to comorbidities or treatment side effects.

Analytical methods for the detection and characterization of unapproved phosphodiesterase type 5 inhibitors (PDE-5i) used in adulteration of dietary supplements- a review.

This article is an up-to-date review of 112 unapproved phosphodiesterase type 5 inhibitors (PDE-5i) found as adulterants in sexual enhancement dietary supplements and other products from 2003 to July 2023. Seventy-five of these unapproved PDE-5i are analogues of sildenafil (67%), followed by 26 analogues of tadalafil (23%), 9 analogues of vardenafil (8%) and 2 other type of compounds (2%). The products have been formulated in various packaging, primarily in capsule, tablet, and powder forms. Common screening techniques allowing detection of such analogues include high performance or ultra-high performance liquid chromatography in tandem with ultra-violet detector (HPLC-UV or UPLC-UV) (50%) and thin-layer chromatography in tandem with ultra-violet detection (TLC-UV) (7%). Screening by mass spectrometry (MS) is relatively less common with the use of single-, triple-quadrupole or time-of-flight (TOF) mass spectrometers (9%). Meanwhile, the combined detection by UV-MS has been recorded at 10% usage. Screening by proton nuclear magnetic resonance spectroscopy (NMR) (11%) has also been applied. For compound characterization, i.e. structural elucidation, NMR spectroscopy has been preferred (100 out of 112 compounds), followed by high-resolution mass spectrometry (HRMS) (74 out of 112 compounds) and Fourier-transform infrared spectroscopy (FTIR) (44 out of 112 compounds). Over the past two decades, analytical technology has been evolving with enhanced sensitivity and resolution. Despite this, structural elucidation of the new emerging analogues in adulterated dietary supplements remains a challenge, especially when the analogues involve complex structural modification. Therefore, the above-mentioned techniques may not be adequate to characterize the analogues. Additional work involving chiroptical methods, two-dimensional (2D) NMR experiments and X-ray crystallography are likely to be required in the future.

[Dumai moxibustion combined with low-dose tadalafil for erectile dysfunction: Evaluation of therapeutic effect].

OBJECTIVE: To investigate the clinical effect of dumai (governor meridian) moxibustion combined with low-dose tadalafil in the treatment of ED with decline of vital gate fire. METHODS: We enrolled in this study 130 ED patients with decline of vital gate fire who met the inclusion criteria and equally randomized them into a control and an experimental group, the former treated with low-dose tadalafil tablets at 5 mg once a day while the latter by dumai moxibustion once a week in addition, all for 4 weeks. Of the total number of subjects, 62 in the control group and 63 in the experimental group completed the experiment. We recorded the scores on IIEF-5, Erection Quality Scale (EQS), Erection Hardness Scale (EHS), TCM symptoms and Treatment Satisfaction Scale (TSS) as well as the penile hemodynamic parameters peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) before and after treatment and compared them between the two groups. RESULTS: The total response rate was significantly higher in the experimental group than in the control (87.30% vs 66.13%, P < 0.05). IIEF-5, EQS, EHS and TSS scores, PSV and RI were markedly increased while TCM symptoms and EDV remarkably decreased in both groups after treatment (P < 0.05), even more significantly in the experimental than in the control group (P < 0.05). CONCLUSION: Dumai moxibustion combined with low-dose tadalafil can improve erectile function, increase penile blood flow velocity and alleviate clinical symptoms in ED patients with decline of vital gate fire, with definite clinical effect and safety.

Determination of Phosphodiesterase Type-5 Inhibitors (PDE-5) in Dietary Supplements.

This study proposed a high-performance thin-layer chromatography (HPTLC) screening method to detect phosphodiesterase 5 (PDE-5) inhibitors as possible adulterant agents in various dietary supplements. Chromatographic analysis was performed on silica gel 60F254 plates using a mixture of ethyl acetate:toluene:methanol:ammonia in a volume ratio of 50:30:20:0.5 as a mobile phase. The system provided compact spots and symmetrical peaks of sildenafil and tadalafil with retardation factor values of 0.55 and 0.90, respectively. The analysis of products purchased from the internet or specialized stores demonstrated the presence of sildenafil, tadalafil, or both compounds in 73.3% of products, highlighting inadequacies and inconsistencies in the labeling, as all dietary supplements were declared to be natural. The results were confirmed using ultra-high-performance liquid chromatography coupled with a positive electrospray ionization high-resolution tandem mass spectrometry (UHPLC-HRMS-MS) method. Furthermore, in some samples, vardenafil and various analogs of PDE-5 inhibitors were detected using a non-target HRMS-MS approach. The results of the quantitative analysis revealed similar findings between the two methods, with adulterant quantities found to be similar to or higher than those in approved medicinal products. This study demonstrated that the HPTLC method is a suitable and economical method for screening PDE-5 inhibitors as adulterants in dietary supplements intended for sexual activity enhancement.

Sildenafil Vs. Tadalafil for The Treatment of Benign Prostatic Hyperplasia: A Single-arm Self-controlled Clinical Trial.

PURPOSE: To compare the efficacy and adverse events of sildenafil monotherapy for benign prostatic hyperplasia (BPH) with its FDA-approved counterpart, tadalafil. MATERIALS AND METHODS: In this single-arm self-controlled clinical trial, 33 patients were enrolled. All patients underwent a 6-week treatment with sildenafil, followed by a 4-week washout period and finally a 6-week treatment with tadalafil. Patients were examined on each appointment and post-void residual (PVR) urine, International Prostate Symptom Score (IPSS) and Quality of life index (IPSS-QoL index) were recorded subsequently. Efficacy of each drug regimen was then evaluated by comparing these outcome parameters. RESULTS: Both sildenafil and tadalafil were shown to improve PVR (both p < .001), IPSS (both p < .001) and IPSS- QoL index (both p < .001) significantly. Sildenafil was more effective than tadalafil in reducing PVR (mean difference (95%CI) = 9.91% (4.11, 15.72), p < .001) and ameliorating IPSS-QoL index (mean difference (95%CI) = 19.3% (4.47, 34.41), p = .027). Moreover, although not significant, sildenafil reduced IPSS more than tadalafil (mean difference (95%CI) = 3.33% (-0.22, 6.87), p = .065). Concurrent erectile dysfunction did not affect responsiveness to therapy with either sildenafil or tadalafil but age was inversely related to post-treatment IPSS in both sildenafil (B = 0.21 (0.04, 0.37), p = .015) and tadalafil (B = 0.14 (0.02, 0.26), p = .021) regimens with a more prominent role in responsiveness to sildenafil (ß = 0.31) compared to tadalafil (ß = 0.19). CONCLUSION: Considering the significantly better improvement of PVR and IPSS-Qol index with sildenafil, this drug can be nominated as a suitable alternative for tadalafil as a BPH treatment, especially in younger patients who don't have any contraindications.

Isolation and characterization of a novel tadalafil analogue adulterant, N-cyclohexyl nortadalafil, in a dietary supplement.

A novel tadalafil analogue was detected during routine screening of dietary supplements suspected to be adulterated with an erectile dysfunction drug(s) by using ultra-high-performance liquid chromatography coupled to Quadrupole-Exactive Orbitrap mass spectrometry (UPLC­Q­Exactive Orbitrap/MS). The MS2 spectrum of the compound was highly similar to that of tadalafil within the range of < 300 m/z. The UV spectrum of the compound was almost identical to that of tadalafil. The analogue was purified by semi-preparative HPLC and structurally elucidated by FT-IR, MS and NMR analysis. The analogue was finally determined as N-cyclohexyl nortadalafil, featuring the cyclohexyl group instead of the N-methyl group on the piperazinedione ring of tadalafil.

Development of a detector tube for screening tadalafil and its analogues in adulterated sexual enhancement products.

Sexual enhancement products adulterated with phosphodiesterase 5 inhibitors (PDE-5i) pose a serious public health concern. Tadalafil and its analogues (Tds) are PDE-5i frequently detected as adulterants. In this study, a Td detector tube for the rapid detection of Tds was developed based on the color change reaction between sulfuric acid and Tds. The specificity of this test method was evaluated using 13 Tds, all of which elicited positive results. Additionally, 30 commonly found adulterants in dietary supplements, 11 active pharmaceutical ingredients of psychotropic drugs and 18 food ingredients were tested and obtained no false-positive results, except levomepromazine. The test tube accurately detected the presence or absence of Tds in 54 commercially available products. The visual detection limit was 2-50 and 5-20 µg/ml for Tds and tadalafil-spiked samples with matrix, respectively. The applicability of the developed detector tube to a semiquantitative test using digital image analyses were investigated using red, green, and blue color values. The results of the recovery test suggested that the tube test was affected by the dark-colored matrix. The results of semiquantitative analyses of tadalafil for five marketed products were consistent with the liquid chromatographic quantification results, except for the blue value. The detector tube developed in this study can facilitate with the rapid screening of Tds in adulterated sexual enhancement products.

[To evaluate the efficacy of Yishen Tongluo decoction combined with low-dose tadalafil in the treatment of diabetic erectile dysfunction with kidney deficiency and blood stasis syndrome].

OBJECTIVE: To observe the clinical efficacy of the combined treatment of Yishen Tongluo formula and low-dose tadalafil in diabetic erectile dysfunction. METHODS: A total of 80 patients with diabetic erectile dysfunction were randomly divided into two groups. The control group given tadalafil treatment, observation group in the control group given Yishen Tongluo Formula on the basis of treatment. The treatment period was 8 weeks. Erectile function were observed before and after treatment in the two groups patients-5 international questionnaire (IIEF - 5) score, erection quality scale (EQS) score, erectile hardness (EHS) score, TCM syndrome integral, content of serum homocysteine (HCY), endothelial function index ï¼»serum levels of prostaglandin I2 (PGI2)ï¼½ and endothelin (ET) content, a The changes of nitrogen oxide (NO), glucose and lipid metabolism indexes ï¼»triglyceride (TC), total cholesterol (TG)ï¼½ and oxidative stress related factors ï¼»total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px)ï¼½ were evaluated, and the clinical efficacy of the two groups was evaluated. RESULTS: In terms of overall efficacy rate, the observation group (79.4%) outperformed that of the control (48.7%, P< 0.01).After treatment, the IIEF-5 score, EQS score, EHS score, and serum levels of PGI2, NO, T-AOC and GSH-Px were higher than those before treatment in the two groups (P< 0.05). The TCM syndrome score and serum HCY, ET-1, TC and TG were lower than those before treatment (P< 0.05), and the comparison group's consequence was comparatively worse than the group under observation (P< 0.01). CONCLUSIONS: Yishen Tongluo Formula can dramatically enhance the erectile dysfunction andimprovement of glucose-lipid metabolism when adopted in together with low-dose tadalafil.

[Effect of functional acupoint electrical stimulation combined with tadalafil on erectile dysfunction in middle-aged and elderly patients].

OBJECTIVE: To investigate the application effect of functional acupoint electrical stimulation combined with tadara irregular administration in middle-aged and elderly patients with erectile dysfunction (ED), and to provide reference for clinical treatment. METHODS: A total of 40 middle-aged and elderly patients with ED admitted to the pelvic floor Center of our hospital from March 2021 to March 2023 were randomly divided into two groups with 20 cases in each group.The control group was treated with tadalafil regularly, and the observation group was treated with functional acupoint electrical stimulation on the basis of this treatment. The total course of treatment was 6 weeks.The clinical efficacy of the two groups was compared. The therapeutic efficacy was evaluated by the International Erectile Function Index (IIEF-5), penile hardness score (EHS), serum total testosterone (TT) level, sexual satisfaction scale (SS) and pelvic floor electromyography, and the occurrence of adverse events was recorded. RESULTS: The total effective rate of the observation group was significantly higher than that of the control group (90% vs 70%, P < 0.05). After 6 weeks of treatment, both groups showed improvements in IIEF-5, EHS, SS, and TT compared to before treatment (P < 0.01). However, the improvement in the observation group was significantly better than that in the control groupï¼»IIEF-5: (22.13±2.11) vs (19.69±2.04), EHS: (3.68±0.47) vs (2.89±0.60), SS: (77.41±7.59) vs (70.32±7.28), TT: (13.43±3.89) nmol/L vs (8.85±3.02) nmol/L, all P < 0.01ï¼½; There were no significant changes in pelvic floor muscle electromyography values in the control group before and after treatment (P > 0.05), while in the observation group, pelvic floor muscle electromyography values (PFMV) in the pre-resting phase, fast muscle (Type II muscle) phase, slow muscle (Type I muscle) phase, endurance testing phase, and post-resting phase all improved compared to before treatment and were superior to the control group (P < 0.05). CONCLUSION: Functional acupoint electrical stimulation combined with tadara irregular administration can improve the therapeutic effect of middle-aged and elderly patients with ED, improve pelvic floor function, safe and reliable.

Clinical study of comprehensive TCM therapy in the treatment of damp and hot stasis erectile dysfunction.

BACKGROUND: The dilemma of male sexual dysfunction has been the focus of the whole society. Erectile dysfunction (ED) is one of the common sexual dysfunctions, and traditional Chinese medicine therapy has shown potential benefits in the treatment of ED. Comprehensive therapy of traditional Chinese medicine (CTTCM) is a comprehensive application of Chinese medicine therapy for auxiliary intervention. Through preliminary clinical observations, we found that CTTCM is simple, safe, and has good efficacy; however, there is a lack of rigorous clinical trials to support its application. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of CTTCM for patients with ED of damp-heat stasis type, and to provide evidence for the clinical application of CTTCM and the construction of a traditional Chinese medicine andrology rehabilitation system. METHODS: In this randomized controlled study, 108 eligible patients were assigned 1:1 to the CTTCM group or the tadalafil group. The treatment period was 8 weeks and the follow-up period was 8 weeks. The primary outcome will be the International Erectile Function Score and traditional Chinese medicine Syndrome Score. Secondary outcomes will include the Erection Quality Score, Patient Health Questionnaire-9, and the 7-item Generalized Anxiety Scale. Safety results will include electrocardiogram, blood tests (including blood, liver and kidney function), urine and stool. International Erectile Function Score-5, traditional Chinese medicine Syndrome Score, Erectile Quality Score, Patient Health Questionnaire-9, 7-item Generalized Anxiety Scale and all Safety outcomes will be conducted at baseline, 2th, 4th, 6th, and 8th week. Follow-up results will be assessed at 8th week after 8 weeks' treatment. DISCUSSION: This study will provide preliminary evidence for the efficacy and safety of traditional Chinese medicine integrated therapy in the treatment of damp-heat stasis ED. In addition, it also provides a basis for the clinical application of Chinese medicine comprehensive therapy and the construction of Chinese medicine andrology rehabilitation system. TRIAL REGISTRATION: Chinese clinical trial registration identifier, ChiCTR2200062016, registered on July 19, 2022.

Screening and Determination of Synthetic PDE-5 Inhibitors in Adulterated Sexual Enhancement Supplements.

This paper reports an important investigation and quantification of adulteration of sexual enhancement supplements with prescription medicines available in United Arab Emirates (UAE): tadalafil, sildenafil and vardenafil. A total of 158 sexual enhancement supplements were collected and analyzed in the current study. The samples were screened using REVERSE-phase liquid chromatography tandem high-resolution mass spectrometry/mass spectrometry (RP-HPLC-MS/MS). Of all sexual enhancements, 12.7% (95% CI: 7.4-18) contained undeclared sildenafil, 3.8% (95% CI: 0.78-6.81) contained undeclared tadalafil and 1.9% (95% CI: 0.25-4.05) contained undeclared vardenafil. Of all sexual enhancement supplements, 13.9% (95% CI: 8.5-19.4) contained significant concentrations of sildenafil, tadalafil or vardenafil. While the study found relatively low levels of undeclared pharmaceutical ingredients in the sexual enhancement dietary supplements available on the UAE market, it is likely that patients with ED tend to consume multiple such supplements daily, thereby exposing themselves to highly elevated cumulative levels.

Detection of 94 PDE-5is and Their Analogs Including N-Desmethylthiosildenafil in Various Formulations of Dietary Supplements and Food Samples Using HPLC and LC-Q-TOF/MS.

Consumption of foods and dietary supplements (DS) adulterated with unprescribed or non-permitted phosphodiesterase-5 inhibitors (PDE-5i) and their analogs can cause serious risk to human health. This study aims to analyze 93 PDE-5i and their analogs present in adulterated foods and DS using an established and validated method involving high-performance liquid chromatography (HPLC). The method was validated in solid and liquid samples, resulting in a limit of detection and quantitation of 0.03-0.5 and 0.08-1.6 µg/mL, respectively. Using the validated method, a total of 404 samples were screened. It was found that 32% of 404 samples were illegally adulterated with PDE-5i and their analogs; moreover, 16.9% of the adulterated samples were found to contain more than three compounds. HPLC-quadrupole-time-of-flight (TOF)/mass spectrometry (MS) analysis was conducted on all the samples to confirm the detected compounds accurately based on fragmentation ion patterns. In addition, sildenafil and tadalafil were detected from the capsule shells of DS unusually. Subsequently, the detected compounds were identified and quantified using HPLC at concentrations ranging from 0.007 to 370.0 mg/g. NMR analysis was carried out to confirm the accurate chemical structure of a compound found during the TOF/MS analysis, which did not match with the 93 reference standards.; it was identified to be N-desmethylthiosildenafil. In this study, various PDE-5i compounds and their analogs were detected from low to high concentrations in a sample. Therefore, the study sheds light on the misuse of PDE-5i and their analogs in consumable products, which pose a severe threat to public health.

HPLC/Fluorescence-Diode Array Detection for Rapid and Reliable Determination of Illegal Synthetic Drugs in Male Sexual Herbal and Honey Remedies: Comparative Study with UFLC-MS.

BACKGROUND: Nutraceuticals (NTCs), as honey and tablets with herbal extract are subjected to adulteration. OBJECTIVE: For NTCs claimed to enhance sexual performance, synthetic drugs (sildenafil, tadalafil, avanafil, vardenafil, and dapoxetine) are common adulterants, so they were selected to be simultaneously analyzed in the current study. Natural aphrodisiacs (icariin and yohimbine) are claimed to be present in many fake NTCs, so they were also included in the study. METHODS: In order to achieve the target of the current study, three liquid chromatographic methods with different unique detectors were developed and validated. RESULTS: High performance liquid chromatography (HPLC) with fluorescence detection enables rapid and reliable determination of natively fluorescent yohimbine, tadalafil vardenafil, and dapoxetine and it is the first report to analyze these compounds as adulterants in counterfeit NTC. Although the diode-array detector (DAD) enables the analysis of the seven adulterants, the fluorescence detector (FLD) shows better sensitivity and selectivity with lower LOQs and LODs. On the other hand, ultra-fast liquid chromatography-mass spectrometry (UFLC-MS) offers the advantages of peak identity confirmation, and it is of comparable sensitivity and selectivity to HPLC-FLD. CONCLUSION: One or more of these synthetic drugs were found in the analyzed NTCs while natural aphrodisiacs were absent. HIGHLIGHTS: Aphrodisiac nutraceuticals, NTCs, were analyzed for adulterants: five aphrodisiac synthetic drugs (adulterants) and two natural claimed aphrodisiacs. UFLC-MS and HPLC-DAD/FLD were compared for illicit NTCs analysis; all NTCs show the presence of synthetic aphrodisiacs and the absence of natural ones.

Adjuvant daily therapy with L-arginine 2,500 mg and tadalafil 5 mg increases efficacy and duration of benefits of low-intensity extracorporeal shock wave therapy for erectile dysfunction: A prospective, randomized, single-blinded study with 1-year follow-up.

PURPOSE: To investigate a therapeutic protocol for erectile dysfunction (ED) based on the combination of low-intensity extracorporeal shock wave therapy (Li-ESWT), tadalafil, and L-arginine. MATERIALS AND METHODS: Recruited patients completed the International Index of Erectile Function erectile function domain (IIEF-EF) and the Erection Hardness Score (EHS) questionnaires at baseline and were randomly assigned in two groups: A (treatment group) and B (control group). Men in both groups received six weekly applications of Li-ESWT. Group A was prescribed adjuvant oral therapy with tadalafil 5 mg and L-arginine 2,500 mg. Follow-up visits were scheduled 1, 6, and 12 months after the last Li-ESWT application. At each follow-up visit, the IIEF-EF and EHS questionnaires were administered again. The main outcome measures were the changes from baseline to every follow-up visit in IIEF-EF and EHS scores. RESULTS: The mean IIEF-EF score in group A was 16.0±4.0, 24.8±3.4, 23.3±4.6, and 21.6±5.5 at baseline, 1, 6, and 12 months of follow-up, respectively, whereas in group B the mean IIEF-EF score was 16.5±4.1, 22.7±4.2, 21.5±4.5, and 19.5±4.9, respectively. We reported an increase in the mean EHS score in group A from 2.07±0.72 at baseline to 3.39±0.59, 3.17±0.67, and 2.98±0.72 at 1, 6, and 12 months, respectively, and in group B from 2.12±0.80 at baseline to 3.07±0.78 and 2.95±0.76 at 1 and 6 months, respectively. CONCLUSIONS: Adjuvant daily therapy with L-arginine 2,500 mg and tadalafil 5 mg was safe and effective in increasing the efficacy and the duration of benefits of Li-ESWT.

[Efficacy of leech powder on hyperlipidaemia-associated erectile dysfunction in male rats].

OBJECTIVE: To investigate the therapeutic effect of the Chinese medicine leech powder (LP) on hyperlipidaemia-associated ED (HLED) in male rats. METHODS: We randomly divided 50 eight-week-old male SD rats into five groups, blank control, HLED model control, tadalafil and low- and high-dose leech powder. After establishment of the HLED model by high-fat diet, we treated the rats in the latter three groups by intragastric administration of tadalafil at 5 mg/kg/d, LP at 0.3 g/kg/d and LP at 1.8 g/kg/d, respectively, all for 4 weeks. We examined the erectile function of the rats by mating experiment, apomorphine assay, and measurement of intracavernosal pressure (ICP) and mean arterial pressure (MAP), obtained the levels of blood glucose, lipid, serum total superoxide dismutase (SOD), malondialdehyde (MDA) and oxidized low-density lipoprotein (ox-LDL), observed the pathological changes in the rat liver and penile tissue by HE staining, and determined the expressions of NF-κB, MCP-1 and PDE5A in penile tissue by Western blot. RESULTS: Compared with the HLED model controls, all the rats in the tadalafil and LP intervention groups showed significantly improved erectile function (P < 0.05), increased erection frequency, ICPmax and ICPmax/MAP ratio, even more significantly in the LP groups; the levels of LDL, TC and TG were remarkably decreased in the three treatment groups (P < 0.05), most significantly in the low-dose LP group; the content of SOD was markedly increased while those of MDA and ox-LDL decreased after intervention (P < 0.05). The results of Western blot revealed that the expressions of NF-κB and MCP-1 in the testis tissue was down-regulated in the tadalafil and high-dose LP groups while that of PDE5A up-regulated in the tadalafil and low-dose LP groups. CONCLUSION: Leech powder can improve erectile function in male rats with hyperlipidaemia-associated ED by reducing blood lipid levels and oxidative stress, which may related to the NF-κB signaling pathway.

Supramolecular Tadalafil Nanovaccine for Cancer Immunotherapy by Alleviating Myeloid-Derived Suppressor Cells and Heightening Immunogenicity.

Tumor-induced immune suppression mediated by myeloid-derived suppressor cells (MDSCs) and insufficient immunogenicity are two major factors for the poor overall response rate to the immune checkpoint blockade (ICB). Here, a tumor microenvironment responsive nanoprodrug (FIT nanoparticles) is presented for co-delivering tadalafil (TAD) and indocyanine green (ICG) photosensitizer to simultaneously targeting intratumor MDSCs and amplifying tumor immunogenicity. The resulting nanoprodrug shows high drug loading (nearly 100%), tumor-specific release, and robust therapeutic efficacy by virtue of promoting immunogenic cell death (ICD) induction and alleviation of MDSCs for augmenting the photothermal immunotherapy. In an in vivo colon tumor model, the released TAD in the tumor can effectively ameliorate MDSCs immunosuppressive activity, while the photosensitizer ICG is capable of inducing ICD to promote sufficient dendritic cells maturation and T cell infiltration. The results reported here may provide a superior candidate of adjuvants for strengthening immune response and ICB efficacy.

[Effect of Shanhaidan Granules combined with tadalafil on erectile dysfunction: A multi-center clinical trial].

OBJECTIVE: To observe the clinical effect and safety of Shanhaidan Granules (SHDG) combined with tadalafil tablets (TT) in the treatment of ED. METHODS: In this open multi-center case-control clinical trial, we enrolled 247 ED patients according to the designed criteria, and treated them orally with SHDG at 10 g per time tid (n = 74), TT at 5 mg per time bid (n = 52), or SHDG + TT at the above doses (n = 121), all for 8 weeks. Before and after medication, we recorded the IIEF-6, erection hardness scores (EHS), traditional Chinese medicine syndromes (TCMS) scores, penile cavernous blood flow parameters and adverse reactions, and compared them between the 3 groups of patients. RESULTS: After 8 weeks of treatment, all the patients showed significantly increased IIEF-6, EHS and TCMS scores in comparison with the baseline (P < 0.05). The total effectiveness rates in the SHDG, TT and SHDG + TT groups were 60.8%, 67.3% and 69.4% respectively based on the IIEF-6 scores, remarkably higher in the TT and SHDG + TT groups than in the SHDG group (P < 0.05), and 40.5%, 32.7% and 63.6% respectively according to the TCMS scores, markedly higher in the SHDG and SHDG + TT groups than in the TT group (P < 0.05). Single-center data manifested significantly increased peak systolic velocity (PSV) of the penile artery in the SHDG + TT and TT groups (P < 0.05). The improvement values of relevant parameters were remarkably higher in the SHDG + TT group than in the TT and SHDG groups, so were IIEF-6 scores in the TT than in the SHDG group, and TCM syndromes in the SHDG than in the TT group. No medication-related adverse events were found in any of patients after treatment, except for some mild side effects including muscle soreness and gastrointestinal reactions in a few cases, all soon relieved, none with abnormalities in blood and urine routine tests or hepatic and renal function indicators. CONCLUSIONS: Shanhaidan Granules combined with tadalafil can significantly improve the erectile function and reduce TCM syndromes in ED patients, and therefore can be applied effectively and safely in clinical practice./.