ABSTRACT
OBJECTIVE: Explore the effects of Astragaloside IV and Scorpion Venom Peptide on the activity, migration, apoptosis, cell cycle, autophagy, and the expression of proteins related to the PI3K/AKT signaling pathway in prostate cancer cells. METHODS: The human prostate cancer cell lines LNCaP and PC-3 were randomly divided into blank control group, Astragaloside IV group, Scorpion Venom Peptide group, Astragaloside IV-Scorpion Venom Peptide group, and rapamycin (positive drug group). After corresponding drug treatments for 24 hours, logarithmic growth phase tumor cells were collected for testing. Cell proliferation was assessed using a Cell Counting Kit-8 (CCK-8) assay, Transwell assay, apoptosis assay, cell cycle assay, and immunofluorescence analysis were performed to detect the activity and migration capacity of prostate cancer cells in each group, as well as their effects on apoptosis, cell cycle, and the autophagy target LC3. Western blot analysis was employed to measure the protein expression levels of p-PI3K, p-Akt, p-mTOR, Beclin1, LC3, and P62. RESULTS: Compared to the blank control group, the Astragaloside IV-Scorpion Venom Peptide group exhibited a significant decrease in the activity of prostate cancer cells (P<0.05) and a reduction in the cell invasion ability (migration capacity) (P<0.05). The early apoptosis rate (LR), late apoptosis rate (UR), and total apoptosis rate all increased (P<0.05). The proportion of cells in the G1 phase increased (P<0.05), while the proportion in the G2+S phase decreased (P<0.05). The immunofluorescence expression of LC3 significantly increased (P<0.05). The expression of LC3â ¡ and Beclin1 proteins in prostate cancer cells LNCaP and PC-3 was upregulated (P<0.05), while the expression of P62, p-PI3K, p-AKT, and p-mTOR proteins was downregulated (P<0.05).Astragaloside IV-Scorpion Venom Peptide is superior to the Astragaloside IV group or Scorpion Venom Peptide group alone in inhibiting the activity and migration capacity of prostate cancer cells, suppressing cell mitosis, promoting early apoptosis, upregulating the expression level of LC3, and inhibiting the PI3K/AKT pathway while promoting autophagy (P<0.05). CONCLUSION: The mechanism by which Astragaloside IV-Scorpion Venom Peptide inhibits the proliferation and migration of prostate cancer cells, suppresses cell mitosis, promotes early apoptosis, and enhances autophagy may be related to the inhibition of the PI3K/AKT pathway.
Subject(s)
Prostatic Neoplasms , Saponins , Scorpion Venoms , Triterpenes , Humans , Male , Apoptosis , Autophagy , Beclin-1/metabolism , Cell Line, Tumor , Cell Proliferation , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Saponins/pharmacology , Scorpion Venoms/pharmacology , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Triterpenes/pharmacologyABSTRACT
Rare earth elements (REEs) are increasingly used in the high-tech sectors in the world and are therefore called burgeoning contaminants. As diffusive gradients in thin films (DGT) can be used to assess the bioavailability of inorganic matters, in this paper, we evaluated, for the first time, the ecotoxicology risks of REEs and their mixtures in river sediments of China's old industrial base by DGT. During our research, taking the Songhua River system (SRS) as an example, we detected its surficial sediments, of which the DGT-labile concentration of REEs (∑REEs) was 2.07-8.76 µg/L. As for the single toxicity, the risk quotient (RQ) values of Y at all sites were significantly greater than 1; while the values of Nd and Pr in some upstream reaches were all significantly greater than the threshold (1), indicating that these adverse effects of single REEs were not neglected. In terms of the combined toxicity of REEs mixtures, we carried out an assessment of the risks of probabilistic ecotoxicology, which showed that the SRS superficial sediments had a low probability of toxicity to aquatic organisms (0.54%).
Subject(s)
Metals, Rare Earth , Water Pollutants, Chemical , China , Environmental Monitoring , Geologic Sediments , Metals, Rare Earth/analysis , Rivers , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicityABSTRACT
Researches were reported that respiratory diseases can lead to male infertility; however, it is unclear whether there is a relationship between pulmonary fibrosis (PF) and male infertility. This study examined the influence of PF on sperm quality and its mechanisms. The key signalling pathway of male infertility caused by PF was predicted based on bioinformatics research. After modelling, we evaluated semen quality. Real-time quantitative polymerase chain reaction and Western blotting were used to measure the protein and mRNA expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylation-protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl2) in rat testicular cells. Compared with group A (48.77 ± 4.67; 59.77 ± 4.79), the sperm concentration and total sperm viability of group B (8.44 ± 1.71; 15.39 ± 3.48) showed a downward trend (p < 0.05). Western blotting showed that the protein expressions of PI3K, p-Akt and Bcl2 in the testes of group B (0.30 ± 0.06; 0.27 ± 0.05; 0.15 ± 0.03) was significantly lower than those of group A (0.71 ± 0.07; 0.72 ± 0.06; 0.50 ± 0.06) (p < 0.05). The hypoxic environment induced by PF can inhibit the expression of PI3K, p-Akt and Bcl2 protein and eventually cause dysfunctional spermatogenesis.
Subject(s)
Proto-Oncogene Proteins c-akt , Pulmonary Fibrosis , Animals , Male , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinase/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Pulmonary Fibrosis/metabolism , Rats , Semen Analysis , SpermatozoaABSTRACT
Depression and chronic prostatitis (CP) are two common diseases that affect the human population worldwide. Clinically, it has been demonstrated that andrological patients often simultaneously suffer from depression and CP. Prior investigations have established that depression acts as an independent risk factor for CP. Herein, we explored the correlation between depression and CP using bioinformatics tools and through animal experiments. The potential targets and signalling pathways involved in depression and CP were predicted using bioinformatics tool, while depression in the rat model was established through chronic restraint stress. The expression of the related proteins and mRNA was assessed by Western blotting and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Relative to those in the control rats, the protein contents of PI3K, p-Akt, and p-mTOR were lower in the model rats (p < 0.05). Similarly, the transcript levels of PI3K, Akt, and mTOR was also relatively lower in the model rats (p < 0.05). And PI3K/Akt agonists reduced inflammation in rat prostate tissue, accompanied by significant increases in the transcript and protein expression levels of PI3K, Akt, and mTOR. Thus, we proposed that depression model rats may induce CP as a result of mediation by the negative regulation of the PI3K/Akt/mTOR signalling network.
Subject(s)
Phosphatidylinositol 3-Kinases , Prostatitis , Animals , Depression/etiology , Humans , Male , Phosphatidylinositol 3-Kinases/metabolism , Prostatitis/complications , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , TOR Serine-Threonine Kinases/metabolismABSTRACT
CONTEXT: Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. OBJECTIVE: Explore mechanistic details of ABR + SV treatment against DMED. MATERIALS AND METHODS: Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 µg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. RESULTS: The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). CONCLUSION: ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.
Subject(s)
Achyranthes , Diabetes Mellitus, Experimental/drug therapy , Erectile Dysfunction/drug therapy , Network Pharmacology/methods , Plant Extracts/therapeutic use , Vaccaria , Animals , Diabetes Mellitus, Experimental/pathology , Disease Models, Animal , Erectile Dysfunction/pathology , Male , Plant Extracts/isolation & purification , Rats , Rats, Sprague-Dawley , Treatment OutcomeABSTRACT
CONTEXT: The leech and centipede granules have good curative effects on many diabetic vascular diseases, including diabetes-induced erectile dysfunction (DIED). OBJECTIVE: To explore the effect of leech and centipede on erectile function in rats with diabetes-induced erectile dysfunction and its possible mechanism. MATERIALS AND METHODS: Thirty male Sprague-Dawley DIED rats were randomly divided into the model group (Group M), low-dose group (Group DD), high-dose group (Group DG) and tadalafil group (Group T) (n = 6); diabetic rats were induced by streptozotocin. Apomorphine was used to induce diabetic erectile dysfunction. The 'leech-centipede' granules (0.15 and 0.6 g/kg) were intragastrically administered in the DD and DG groups for 8 weeks. Blood glucose, serum insulin, testosterone, cGMP levels and protein expression changes were measured in each group. RESULTS: After 8 weeks, the erectile function of rats in the DG group significantly improved (1.26 ± 0.73). Penis tissue cGMP levels were higher in the DG group (1.48 ± 0.11) than in the M group (0.58 ± 0.15). Protein and mRNA expression levels of NOS were significantly higher (0.77 ± 0.05; 0.61 ± 0.02) but those of PDE5 (0.43 ± 0.05; 0.61 ± 0.03) were lower in the DG group than in the M group (0.37 ± 0.06; 0.51 ± 0.01; 0.78 ± 0.06; 0.81 ± 0.04). CONCLUSION: The leech-centipede can improve erectile dysfunction in DIED rats by regulating the expression of cGMP, NOS, and PDE5-related molecules in the PDE5 pathway. This study provides a potential mechanism for the treatment of DIED with leech-centipede.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Erectile Dysfunction/drug therapy , Tissue Extracts/pharmacology , Animals , Blood Glucose/drug effects , Cyclic GMP/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism , Diabetes Mellitus, Experimental/complications , Erectile Dysfunction/etiology , Male , Nitric Oxide Synthase/metabolism , Penile Erection/drug effects , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , StreptozocinABSTRACT
Objective: To investigate the impact of asthma on erectile function in rats and the expressions of related proteins. METHODS: Male rats were injected intraperitoneally with ovalbumin solution to induce asthma followed by subcutaneous injection of apomorphine at 100 µg/kg into the neck, and then observed for reduced frequency or loss of penile erection. Based on the results of observation, a model of asthma-induced ED (AED) was made in 6 of the animals, and another 6 normal male rats were taken as controls. The histomorphology of the corpus cavernosum was observed by HE staining, and the mRNA and protein expressions of phosphodiesterase 5 (PDE5) and nitric oxide synthase 3 (eNOS) in the testis tissue were determined by RT-qPCR and Western blot. RESULTS: Compared with the normal controls, the rats in the AED model group showed disorderly distribution of sinusoids and decreased density of endothelial and smooth muscle cells in the corpus cavernosum. The mRNA and protein expressions of PDE5 were significantly higher (P < 0.05), while those of eNOS remarkably lower in the AED model than in the control group (P < 0.05). CONCLUSIONS: Asthma can induce ED and change the histomorphology of the corpus cavernosum in rats by affecting the expressions of PDE5 and eNOS proteins.
ABSTRACT
BACKGROUND: The current evidence on the association between obesity-associated markers and semen quality, serum reproductive hormones and lipids remains inconsistent. In this study, we tested the hypothesis that, in infertile Chinese men, body mass index (BMI) negatively correlates with sperm concentration, serum total testosterone (TT), and high-density lipoprotein cholesterol (HDL-C). The relationship between other obesity-associated markers and semen quality parameters, serum reproductive hormones, lipids and leptin were also investigated. METHODS: 181 Chinese infertile men were recruited from September 2018 to September 2019. Their obesity-associated markers, semen parameters, and serum reproductive hormones, lipids and leptin were detected. Statistical analysis was performed to assess the relationship between obesity-associated markers and semen quality, serum reproductive hormones, lipids and leptin. RESULT(S): Statistically negative correlation was found between other obesity-associated markers (e.g. waist-to-hip ratio and waist-to-height ratio) and semen parameters (e.g. sperm concentration, ratio of progressive motility and ratio of non-progressive motility), while no significant correlation was found between BMI and semen quality, serum reproductive hormones, lipids and leptin. Ratio of morphologically normal sperm was negatively correlated with serum lipids including total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), leptin and seminal superoxide dismutase. Ratio of progressive sperm, sperm concentration and ratio of morphologically normal sperm exhibited significantly lower values in overweight group than normal group. Estradiol (E2) and E2/TT were significantly higher in obese group than normal group, while TT level was significantly lower in obese group than normal group. Univariate and multivariate analysis indicated that TC was significantly associated with BMI. Serum leptin concentration was positively correlated with seminal leptin concentration in overweight and obese groups. CONCLUSION(S): No significant correlation was found between BMI and sperm concentration, serum TT and HDL-C, while other obesity-associated markers were found to negatively correlate with sperm concentration, ratio of progressive motility and ratio of non-progressive motility. Statistically significant correlations between serum reproductive hormones, lipids and leptin also existed in Chinese infertile men.
Subject(s)
Gonadal Steroid Hormones/blood , Infertility, Male/etiology , Obesity/complications , Semen Analysis , Adult , Asian People , Biomarkers/analysis , Biomarkers/metabolism , Body Mass Index , China , Cohort Studies , Humans , Infertility, Male/blood , Infertility, Male/physiopathology , Leptin/blood , Lipids/blood , Male , Middle Aged , Obesity/blood , Obesity/physiopathology , Risk Factors , Young AdultABSTRACT
OBJECTIVE: To investigate the prevalence of ED and the associated factors in infertile males. METHODS: We continuously selected 896 infertile males present at Peking Union Medical College Hospital, Dongzhimen Hospital and the Sixth Medical Center of PLA General Hospital and evaluated the erectile function of the patients using a self-designed questionnaire and IIEF-5. We analyzed the ED-associated factors by multivariate analysis. RESULTS: Based on the results of questionnaire investigation, there were 416 cases of ED in the 896 infertile males (46.43%), including 23 (2.56%) severe, 38 (4.24%) moderate, 109 (12.17%) mild-moderate and 246 (27.46%) mild cases. Multivariate analysis indicated that the prevalence rate of ED was correlated positively with obesity, hypertension and diabetes, and negatively with husband-wife affection and the frequency of sexual intercourse. CONCLUSIONS: The prevalence rate of ED is high in infertile males, mostly mild, and correlated with husband-wife affection, the frequency of sexual intercourse and some diseases.
Subject(s)
Erectile Dysfunction , Infertility, Male , Coitus , Erectile Dysfunction/epidemiology , Humans , Infertility, Male/epidemiology , Male , Penile Erection , PrevalenceABSTRACT
Objective: The study was aimed to evaluate the influences of erectile dysfunction (ED) in a rat model of stroke combined with hyperlipidemia (HLP). Methods: Male Sprague-Dawley rats were divided into control and hyperlipidemia (HLP) groups. HLP model was constructed by feeding with high-fat and cholesterol diets. Serum levels of total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG), and non-HDL were identified to check the model was success. Stroke model was established by FeCl3. ICP/MAP value was detected to evaluate the erectile function of rats. Serum level of lipoproteins and the expressions of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) were detected by ELISA. Hematoxylin-eosin (HE) staining of corpus cavernosum and measurement of penis length were utilized to assessment erectile function. Western blot was used. Results: TC, TG, LDL, and non-HDL-C in serum were up-regulated, while HDL level was attenuated. After treatment, the serum lipid level recovered. From the ICP/MAP values, the erectile function of both two treatment groups recovered. The expression of PDE5A was up-regulated, while the levels of eNOS and cGMP were suppressed after surgery. The length of penis was decreased, and corpus cavernosum was damaged following HLP and stroke. However, the erectile function was recovered after treatment. Conclusion: Stroke combined HLP caused ED through NO-cGMP-PDE5 pathway.
Subject(s)
Erectile Dysfunction , Hyperlipidemias , Stroke , Animals , Diet Therapy/methods , Disease Models, Animal , Erectile Dysfunction/blood , Erectile Dysfunction/diagnosis , Erectile Dysfunction/etiology , Erectile Dysfunction/therapy , Hyperlipidemias/blood , Hyperlipidemias/complications , Hyperlipidemias/physiopathology , Lipoproteins/blood , Male , Nitric Oxide Synthase Type III/blood , Penile Erection/physiology , Penis/pathology , Penis/physiopathology , Rats , Rats, Sprague-Dawley , Stroke/complications , Stroke/physiopathology , Vascular Endothelial Growth Factors/bloodABSTRACT
OBJECTIVE: To investigate the relationship of erectile dysfunction (ED) with psychological factors in male patients with infertility. METHODS: We conducted a questionnaire investigation among 252 male patients with infertility, which involved the general condition, results of semen routine examination, sexual life, and scores in IIEF-5, self-reported 9-item patient health questionnaire (PHQ-9) and 7-item generalized anxiety disorder scale (GAD-7). We analyzed the prevalence of ED, depression, and anxiety and their correlations among the patients in comparison with 100 fertile male controls. RESULTS: In 245 of the infertility patients, the most common symptoms of depression and anxiety were "feeling tired or no vitality" and "easily getting worried or impatient", 20.4% of them with depression disorder and 42.9% with anxiety disorder. The PHQ-9 and GAD-7 scores were significantly higher in the infertile males than in the normal fertile controls (P <0.05), and so was the incidence of ED (28.6% vs 12.4%, P <0.05), while the IIEF-5 scores were markedly lower in the former than in the latter group (P <0.01), and so were sex frequency and sexual satisfaction (P <0.05). The PHQ-9 and GAD-7 scores were remarkably higher in the infertility patients with ED than in those without (P <0.01). Logistic regression analysis showed that the level of libido and results of semen routine examination were the risk factors for depression disorder, while age, education level, disease course and experience of assisted reproduction were those for anxiety disorder. CONCLUSIONS: Male infertility patients have a poorer mental health and a higher incidence of ED than normal fertile men, and there is some interaction between psychological status and ED prevalence.
Subject(s)
Erectile Dysfunction/psychology , Infertility, Male/psychology , Anxiety/epidemiology , Depression/epidemiology , Erectile Dysfunction/epidemiology , Humans , Libido , Male , Patient Health Questionnaire , Prevalence , Risk Factors , Semen Analysis , Sexual BehaviorABSTRACT
OBJECTIVE: To evaluate the clinical efficacy and safety of Qilin Pills in the treatment of oligoasthenospermia in infertile men. METHODS: This multi-centered randomized double-blind controlled clinical trial included 216 infertile males with oligoasthenospermia, 108 in the trial group and the other 108 in the control, the former treated with Qilin Pills at the dose of 6 g tid while the latter with Wuziyanzong Pills at 6 g bid, both for 12 weeks. We examined the total sperm count, sperm motility and the count of progressively motile sperm of the patients before and at 4, 8 and 12 weeks after medication and evaluated the safety of the drug based on the adverse events and the laboratory results of blood and urine routine examinations and liver and kidney function tests. RESULTS: Compared with the baseline, the patients in the trial group showed a significant time-dependent improvement after 4, 8 and 12 weeks of medication in sperm motility (21.75% vs 27.54%, 29.04% and 32.95%, P <0.05), total sperm count (156.27 ×106 vs 177.33, 188.18 and 205.44 ×106, P <0.05), and the count of progressively motile sperm (32.08 ×106/ml vs 46.33, 50.98 and 61.10 ×106/ml, P <0.05). The three parameters above were also improved in the controls, but more significantly in the trial group (P <0.05). CONCLUSIONS: Qilin Pills can evidently improve the semen quality of oligoasthenospermia patients with no obvious adverse events.
Subject(s)
Asthenozoospermia/drug therapy , Drugs, Chinese Herbal/therapeutic use , Oligospermia/drug therapy , Capsules , Double-Blind Method , Humans , Infertility, Male/drug therapy , Male , Semen Analysis , Sperm Count , Sperm Motility , Treatment OutcomeABSTRACT
PURPOSE: Gliomas are the most common primary intracranial tumors of the central nervous system (CNS), accounting for about one third of all brain tumors. Glioblastoma multiforme (GBM) is the aggressive grade IV glioma with survival as low as 2-5% in the second year post-diagnosis, hence necessitating efficient diagnostic markers. More than 50% of the non-small cell lung cancer (NSCLC) brain metastases are solitary lesions, often difficult to differentiate from gliomas by conventional imaging diagnostics. Here, we explored the utility of measuring serum expression levels of Micro-RNAs (miRs) 221, 608 and 504 as biomarkers for differentiating primary GBMs from solitary metastatic lesions of NSCLC. METHODS: Serum expression level of miRs 221, 608 and 504 were determined in 49 GBM, 27 NSCLC brain metastasis patients, and 30 cancer-free normal controls by real time PCR using commercially available miR specific primers. Mann-Whitney U test was used to compare the expression of each miR between each group. Receiver operating characteristics (ROC) curve analysis was also carried out to determine the feasibility of using miR expression as differential diagnosis test. RESULTS: Our results indicated that serum expression of mir-221 was upregulated in GBM as well as in metastatic NSCLC patients. Although both miR-608 and 504 were specifically downregulated only in the GBM patient group, ROC curve analysis showed that only miR-504 serum expression can be utilized as reliable differential diagnosis marker (sensitivity and specificity; 100 and 88.89% respectively). CONCLUSIONS: Serum expression level of miR-504 is a reliable biomarker to be used for differentiating primary GBM from solitary brain metastasis of NSCLC.
Subject(s)
Brain Neoplasms/blood , Carcinoma, Non-Small-Cell Lung/blood , Glioblastoma/blood , Lung Neoplasms/blood , MicroRNAs/blood , Biomarkers, Tumor/blood , Brain/pathology , Brain Neoplasms/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Diagnosis, Differential , Down-Regulation/genetics , Female , Glioblastoma/genetics , Glioma/blood , Glioma/genetics , Humans , Lung Neoplasms/genetics , Male , Middle Aged , Sensitivity and Specificity , Up-Regulation/geneticsABSTRACT
BACKGROUND AND AIM: Diabetes and Urinary Tract Infections (UTIs) are both common and serious health problems. Shuangdong capsule, a Chinese patent medicine, has been used to treat these conditions. This study assesses its efficacy and mechanism in treating diabetes combined with UTIs. METHODS: We induced diabetes in rats using streptozotocin and UTIs with Escherichia coli, dividing the rats into five groups: control, model, levofloxacin, Shuangdong capsule, and levofloxacin + Shuangdong capsule. After two weeks, we measured blood glucose, insulin, infection indicators, and bladder histology. We also detected the expression of insulin receptor substrate 1 (IRS1)-phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt)-C-X-C motif chemokine ligand 2 (CXCL2) signaling pathway by Western Blot and the myeloperoxidase (MPO) levels by Enzyme-Linked Immunosorbent Assay (ELISA). Additionally, we conducted a Mendelian randomization study using genetic variants of the insulin receptor to assess its causal effect on UTI risk. RESULTS: Shuangdong capsule improved bladder pathology and infection indicators, similar to levofloxacin. It did not affect blood glucose or insulin levels. Moreover, it reversed the suppression of the IRS1-PI3K-Akt-CXCL2 pathway and MPO levels caused by UTI in diabetic rats. The Mendelian randomization study showed that increased insulin receptor expression reduced UTI risk, which was consistent with the results of the animal experiments. CONCLUSION: The Shuangdong capsule was effective in treating diabetes with UTIs. It may function by activating the IRS1-PI3K-Akt signaling pathway, thereby increasing CXCL2 and MPO levels, enhancing innate immunity, and promoting bacterial clearance. The Mendelian randomization study provided further evidence supporting the causal role of the insulin receptor in UTI prevention.
ABSTRACT
OBJECTIVE: To evaluate the clinical efficacy and safety of transperineal ultrasonic therapy for chronic prostatitis (CP) by analyzing the scores of NIH-CPSI and the results of prostate fluid routine examination. METHODS: We conducted a randomized, double-blind, multi-centered trial on 96 CP patients that met the inclusion criteria. We divided the patients into groups A (trial) and B (control) of equal number, the former treated by transperineal ultrasound, while the latter with the same machine but no ultrasound waves, 10 min a time qd alt for 2 weeks. Then we evaluated the therapeutic effect and safety by comparing the scores of NIH-CP-SI and counts of white blood cells (WBC) and lecithin corpuscles (LC) in the prostate fluid between the two groups before and after treatment. RESULTS: The total effectiveness rate was 70.83% in group A and 25% in group B (P < 0.01). The scores on prostate pain, urinary symptoms and quality of life as well as the total NIH-CPSI score were significantly improved in group A as compared with pretreatment (P < 0.05), and so were the prostate pain score and total NIH-CPSI score in group B (P < 0.05). Statistically significant differences were observed between the two groups in the scores on prostate pain and urinary symptoms and total NIH-CPSI score after treatment (P < 0.05), but not in any of the NIH-CPSI scores before treatment (P > 0.05), nor were there any significant differences in the counts of WBCs and LC either between the two groups or within each group before and after treatment (P > 0.05). Two patients experienced adverse events in group A, and 1 in group B (P > 0.05). CONCLUSION: Transperineal ultrasonic therapy is highly effective for CP, especially in relieving prostate pain. With its advantages of safety, easy operation and high acceptability, it deserves a wider clinical application.
Subject(s)
Perineum/surgery , Prostatitis/therapy , Ultrasonic Therapy/methods , Adult , Chronic Disease , Double-Blind Method , Humans , Male , Middle Aged , Treatment Outcome , Young AdultABSTRACT
Aquaculture wetlands, particularly those located within urban areas, are fragile ecosystems due to urban and aquaculture impacts. However, to date, there are no reports on the combined toxicity of heavy metal mixtures in aquatic biota in sediments from aquaculture wetlands in metropolitan areas. Thus, the characterization, bioavailability, and ecological probability risk of heavy metals were studied in the riverine/estuarine sediments of the Rongjiang River in an aquaculture wetland in Chaoshan metropolis, South China. In the study area, the average total concentrations (mg/kg) were 2.38 (Cd), 113.40 (Pb), 88.27 (Cr), 148.25 (Ni), 62.08 (Cu), 125.18 (Zn), 45,636.44 (Fe), and 797.18 (Mn), with the Cd pollution being regarded as extremely serious based on the enrichment factor (EF). There are two main sources of heavy metals in the study area; Ni, Pb, Zn, Fe and Mn are mainly from domestic waste, while Cr, Cd and Cu are possibly associated with industrial production activities. The bioavailability of most heavy metals accounted for more than 20% of the total concentration. The combined toxicity of heavy metal mixtures based on probabilistic risk assessment suggests that the surface sediments of the Rongjiang River and its estuary had a 15.71% probability of toxic effects on aquatic biota.
Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Wetlands , Ecosystem , Cadmium , Biological Availability , Lead , Water Pollutants, Chemical/analysis , Environmental Monitoring , Metals, Heavy/analysis , Aquaculture , China , Rivers , Geologic Sediments , Risk AssessmentABSTRACT
The occurrence, multi-index assessment, and sources of heavy metals in surface sediments of Zhelin Bay were investigated. Average heavy metal concentrations (mg/kg) were 81.89 (Cr), 770.76 (Mn), 16.81 (Co), 62.25 (Ni), 96.30 (Cu), 162.04 (Zn), and 73.40 (Pb), with the concentrations of studied seven heavy metals being significantly higher than their corresponding background values. Geo-accumulation index (Igeo) and pollution load index (PLI) were implemented to assess degree of heavy metal contamination. The Igeo and PLI indicated that Cr, Mn, Co, Zn, and Pb were slightly polluted, and Cu and Ni were moderately polluted in the region. Potential ecological risk index (RI) and mean possible effect level (PEL) quotient were conducted to assess ecological risk. The RI and mean PEL quotient demonstrated that surface sediments of Zhelin Bay were slight ecological risks and exhibited a 21% probability of toxicity. Principal component analysis (PCA) combined with the correlation analysis (CA) and hierarchical cluster analysis (HAC) revealed that the heavy metal contamination in Zhelin Bay might originate from three type sources.
ABSTRACT
Surface sediments from 21 stations within the Pearl River estuary (PRE) intertidal zone were sampled for heavy metal contamination analysis. Average heavy metal concentrations (mg/kg) in the PRE intertidal zone were 118.5 (Cr), 860.4 (Mn), 19.5 (Co), 72.5 (Ni), 128.1 (Cu), 198.5 (Zn), and 73.0 (Pb), with the concentrations of Mn, Co, Ni, Cu, and Zn being significantly higher than their corresponding background values. The enrichment factor (EF) and geo-accumulation index (Igeo) reveal the same contamination status, with Pb, Ni, Co, Mn, and Cu showing slight to moderate contamination. Overall, the combined heavy metal concentration in the PRE intertidal surface sediments had a 24.7 % probability of toxic effects on aquatic biota based on the joint probabilistic risk (JPR) approach. Principal component analysis (PCA) coupled with the correlation analysis (CA) revealed that the heavy metal contamination in the PRE intertidal zone might originate from natural and anthropogenic sources.
Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Rivers , Estuaries , Lead/analysis , Geologic Sediments/analysis , Environmental Monitoring , Water Pollutants, Chemical/analysis , Metals, Heavy/analysis , Risk Assessment , ChinaABSTRACT
Background: The causal relationship between hypertension, antihypertensive drugs and the risk of erectile dysfunction is still uncertain. We performed a univariable and multivariable Mendelian randomization study to investigate whether they are causally related to erectile dysfunction. Methods: Genetic variants associated with blood pressure were derived from the genome-wide association study meta-analysis of the UK Biobank and International Consortium of Blood Pressure (N = 757,601). Summary association data for hypertension were obtained from the UK Biobank (N = 463,010) and the FinnGen study (N = 356,077). The summary statistics of erectile dysfunction were obtained from the European ancestry with 223,805 subjects. The SNP instruments used to assess the effect of the protein targets of antihypertensive drugs on erectile dysfunction were obtained from previous studys. Causal effects were estimated using the univariate Mendelian randomization method (inverse variance weighted, MR-Egger, weighted median, MR-PRESSO and Wald ratios) and the multivariate Mendelian randomization method. Sensitivity analyses were implemented with the Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Results: Univariate MR found that elevated diastolic blood pressure may increase the occurrence of erectile dysfunction (odds ratio [OR] = 1.012; 95% confidence interval [CI]: 1.000-1.024; P = 0.047). Genetically predicted hypertension is also associated with ED (For the FinnGen, OR = 1.106; 95% CI: 1.027-1.191; P = 0.008. For the UK Biobank, OR = 3.832; 95% CI: 1.410-10.414; P = 0.008). However, after adjusting for systolic blood pressure, diastolic blood pressure and hypertension using multivariate Mendelian randomization, only hypertension was causally associated with ED occurrence (For the FinnGen, OR = 1.103; 95% CI: 1.018-1.195; P = 0.017. For the UK Biobank, OR = 5.037; 95% CI: 1.601-15.846; P = 0.006). We found no evidence that the use of angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and thiazide diuretic increased the risk of erectile dysfunction. Conclusions: Genetically predicted hypertension increases the risk of erectile dysfunction, but we found no causal relationship between elevated systolic/diastolic blood pressure and erectile dysfunction. We speculate that the relationship between elevated blood pressure and erectile dysfunction risk may be nonlinear. We found little evidence that antihypertensive drugs increase the risk of erectile dysfunction.
ABSTRACT
The activated sludge of a biochemical unit (WLK_OD) and an advanced denitrification unit (WLK_AD) were collected from a municipal wastewater treatment plant (WWTP), in which the TN concentration of effluent was less than 1.5 mg·L-1, and their microbial community structure and function profiles were analyzed using 16S rRNA gene high-throughput sequencing. The microorganisms in WLK_AD had lower evenness compared with that in WLK_OD, which was attributed to environmental selection. Furthermore, PCoA revealed that different incoming wastewaters had an impact on microbial community structure. At the phylum level, Proteobacteria (70.11%) was enriched in WLK_AD. At the genus level, Thauera, Flavobacterium, Hydrogenophaga, and Zoogloea served as distinct-dominant denitrifying bacteria in WLK_AD; however, Trichococcus (3.50%) and Terrimonas (1.10%) were enriched in WLK_OD. Through the comparison between groups (P<0.05), the biomarkers detected in each WWTP were different. Furthermore, the results of the co-occurrence network showed that the bacteria from module I had a higher proportion in WLK_AD; the bacteria from module II had a higher proportion in WLK_OD, and they were common microorganisms in WWTPs, implying that wastewater environments drpve the differences in the microbial community structure. Among the types of environmental parameters, the removal efficiency of COD and TN had the greatest impact on the microbial community by the RDA. The removal efficiency of COD was positively correlated with the dominant bacteria from WLK_OD, such as Saccharibacteria, Thermomarinilinea, Terrimonas, and Comamonas; the removal efficiency of TN was positively correlated with the denitrifying bacteria from WLK_AD, such as Dokdonella, Thauera, Flavobacterium, and Zoogloea. WLK_AD was enriched with Novosphingobium, Dokdonella, Thauera, and Sphingomonas, which synergistically removed TN, leading to the TN of the effluent being less than 1.5 mg·L-1. Moreover, based on the results of function prediction, WLK_AD had a higher proportion of genes that could code the denitrification enzymes.