Recent studies have revealed a significant relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), both of which commonly affect middle-aged and older men. These conditions share underlying causes, particularly endothelial dysfunction, atherosclerosis, and chronic pelvic ischemia (CPI). This study investigated the therapeutic potential of LDD175, a large-conductance Ca 2+ -activated K + channel (BKCa channel) opener, in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats. Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet. We assessed erectile and voiding functions by measuring intracavernosal pressure (ICP) and intraurethral pressure (IUP), respectively, after nerve stimulation. We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms. This study evaluated the effectiveness of LDD175 compared to standard treatments, such as sildenafil for ED and tamsulosin for LUTS. Therefore, the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP. Analysis revealed elevated levels of hypoxia-inducible factor-1α, transforming growth factor-β1 and β2 in cavernous tissue, and increased α1A-adrenoceptor expression in prostate tissue. LDD175 administration showed promising results, with dose-dependent improvements in ICP and IUP, and therapeutic effects comparable to those of established treatments. Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS, opening new possibilities for clinical application in the treatment of these interconnected conditions.
Male ; Animals ; Erectile Dysfunction/etiology* ; Rats, Sprague-Dawley ; Lower Urinary Tract Symptoms/etiology* ; Ischemia/drug therapy* ; Rats ; Tamsulosin ; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects* ; Sildenafil Citrate/therapeutic use* ; Penis/blood supply* ; Disease Models, Animal ; Transforming Growth Factor beta1/metabolism* ; Pelvis/blood supply* ; Prostate/metabolism* ; Sulfonamides/therapeutic use* ; Large-Conductance Calcium-Activated Potassium Channels/agonists*

OBJECTIVE: To clarify the role of concentrated growth factors (CGF) in the treatment of periodontal cement defects using calcium phosphate cement (CPC) with self-curing properties. METHODS: Thirty-six intrabony defects were randomly divided into two groups. The experimental group received CGF+CPC treatment (n=18), while the control group received CPC treatment alone (n=18). The probing depth, clinical attachment loss, and hard tissue filling as measured by cone beam CT (CBCT) were evaluated at baseline and 1 year postoperatively in both groups, and the levels of major growth factors in CGF and serum were compared [platelet-derived growth factor-BB (PDGF-BB), transforming growth factor-β1 (TGF-β1), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF)]. RESULTS: At baseline, there were no statistically significant differences in probing depth, clinical attachment loss and CBCT measurements between the two groups (P>0.05). At 1 year postoperatively, significant improvements were observed in parameters mentioned above in both groups (P < 0.05). The CGF+CPC group seemed more effective compared with the CPC group in reduction of probing depth [(4.5±1.3) mm vs. (3.2±1.1) mm] and clinical attachment gain [(3.8±0.9) mm vs. (2.0±0.5) mm, P < 0.05]. Compared with the group treated with CPC alone, the hard tissue filling degree shown by CBCT in the CGF+CPC group was significantly increased [the reduction of the depth of the intrabony defects was (3.9±1.2) mm vs. (2.1±0.7) mm, respectively, P < 0.01]. At 1 year post-operatively, the volume of the intrabony defects shown by CBCT in the CGF+CPC group was reduced by (0.031 8±0.004 1) mL, which was significantly more than that in the CPC group [(0.019 7±0.001 2) mL, P < 0.05]. In addition, the concentration of the main growth factors (PDGF-BB, TGF-β1, IGF-1, and VEGF) in CGF were higher than those in serum (P < 0.001). CONCLUSION After 1 year of follow-up, the results of the present study indicated that CGF could significantly improve the clinical and radiological effects of CPC on the treatment of periodontal intrabony defects.
Humans ; Calcium Phosphates/therapeutic use* ; Male ; Female ; Bone Cements/therapeutic use* ; Middle Aged ; Cone-Beam Computed Tomography ; Alveolar Bone Loss/therapy* ; Becaplermin ; Adult ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins/therapeutic use* ; Proto-Oncogene Proteins c-sis/blood* ; Transforming Growth Factor beta1/blood* ; Vascular Endothelial Growth Factor A/blood*

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus, which is characterized in renal tubulointerstitial fibrosis (TIF). The current study was designed to investigate the protective effect of Jujuboside A (Ju A) on TIF in type 2 diabetes (T2DM) mice, and explore its underlying anti-fibrosis mechanism. A mouse T2DM model was established using high fat diet (HFD) feeding combined with intraperitoneal injection of streptozotocin (STZ). Then, diabetic mice were treated with Ju A (10, 20 and 40 mg·kg^-1·d^-1, i.g.) for 12 weeks. Results showed that administration of Ju A not only down-regulated fasting blood glucose (FBG) levels, but also improved hyperlipidemia and renal function in diabetic mice. Moreover, the reduced ECM accumulation was observed in the renal cortex of Ju A treated diabetic mice, while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs). Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1 (YY1) in the renal cortex of diabetic mice, and reduced the levels of transforming growth factor-β1 (TGF-β1) in the serum and renal cortex of Ju A treated mice. According to invitro studies, the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose (HG) cultured HK-2 cells. Taken together, these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Type 2/drug therapy* ; Diabetic Nephropathies/metabolism* ; Fibrosis ; Mice ; Saponins ; Signal Transduction ; Streptozocin ; Transforming Growth Factor beta1/metabolism*

OBJECTIVE: To analyze the influence of serum levels of transforming growth factor-β1 (TGF-β1) and epidermal growth factor receptor (EGFR) on the therapeutic effect of high-dose cytarabine (HD-AraC) in patients with acute myeloid leukemia (AML). METHODS: 98 patients with AML treated in our hospital from January 2019 to June 2020 were selected as the research subjects, all patients were treated with HD-AraC for 1 course of treatment every week. The effect of 2 groups were evaluated during after one course of treatment and divided into effective group and ineffective group, statistical table of baseline data was designed, the baseline data of 2 groups were counted in detail, the baseline data and serum levels of TGF-β1 and EGFR of 2 groups were compared, Logistic regression analysis was used to examine the relationship between the levels of serum TGF-β1, EGFR and the therapeutic effect of HD-AraC in patients with AML, the value of serum TGF-β1 and EGFR levels in predicting the therapeutic effect of HD-AraC in AML patients was analyzed based on ROC curve and decision curve. RESULTS: After 1 course of treatment, among the 98 patients, 26 cases had complete remission, 38 cases had partially remission and 34 cases no remission, the total effective rate was 65.31% (64/98); after comparing data of 2 groups, Logistic regression analysis showed that the overexpression of serum EGFR before treatment might be a risk factor for the ineffective treatment of HD-AraC in AML patients (OR>1, P<0.05), overexpression of serum TGF-β1 before treatment might be a protective factor for the ineffective treatment of HD-AraC in AML patients (OR<1, P<0.05); the ROC curve results showed that the AUC of serum EGFR and TGF-β1 before treatment in predicting the risk of ineffective HD-AraC treatment in AML patients were >0.70, which had certain predictive value. The decision curve results showed that in the threshold range of 0.15-044, the prediction model combined with serum EGFR and TGF-β1 levels in predicting the net benefit rate of HD-AraC treatment in AML patients was better than that of serum EGFR or serum TGF-β1 alone. CONCLUSION The levels of serum TGF-β1 and EGFR affect the therapeutic effect of HD-AraC in patients with AML and increase the risk of ineffective treatment, serum TGF-β1 and EGFR can be used to predict the risk of ineffective HD-AraC treatment in AML patients, and the combined prediction of net benefit rate is higher.
Cytarabine/therapeutic use* ; ErbB Receptors/blood* ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Remission Induction ; Transforming Growth Factor beta1/blood*

OBJECTIVETo investigate the percentages of peripheral blood γδ T cells and regulatory T cells (Treg) and the expression of associated cytokines, interleukin 17 (IL-17) and transforming growth factor-β1 (TGF-β1), in infants with human cytomegalovirus (HCMV) infection.

METHODSTwenty-two infants with HCMV infection (HCMV group) and 22 healthy infants who underwent physical examination (control group) were enrolled in this study. The percentages of peripheral blood γδ T cells and Treg cells were determined by flow cytometry. The levels of IL-17 and TGF-β1 in plasma were measured using ELISA.

RESULTSCompared with the control group, the HCMV group had significantly higher percentage of γδ T cells and IL-17 level (P<0.01) and significantly lower percentage of Treg cells and TGF-β1 level (P<0.01). In the HCMV group, the percentage of γδ T cells was negatively correlated with the percentage of Treg cells and TGF-β1 level (P<0.05), but positively correlated with IL-17 level (P<0.05); the percentage of Treg cells was positively correlated with TGF-β1 level (P<0.05), but negatively correlated with IL-17 level (P<0.05); there was no correlation between IL-17 level and TGF-β1 level (P>0.05).

CONCLUSIONSThere is an imbalance between γδ T cells and Treg cells in the peripheral blood of infants with HCMV infection, and γδ T cells may be involved in the secretion of IL-17.

Cytokines ; blood ; Cytomegalovirus Infections ; immunology ; Female ; Humans ; Infant ; Interleukin-17 ; blood ; Male ; Receptors, Antigen, T-Cell, gamma-delta ; analysis ; T-Lymphocytes, Regulatory ; immunology ; Transforming Growth Factor beta1 ; blood

Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L were selected for experiments. The DN rats were treated with Taxus chinensis orally (0.32, 0.64, and 1.28 g·kg) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway.
Albumins ; Animals ; Blood Glucose ; metabolism ; Creatinine ; blood ; Diabetic Nephropathies ; blood ; drug therapy ; genetics ; urine ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; metabolism ; Male ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Smad Proteins ; genetics ; metabolism ; Taxus ; chemistry ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo explore the mechanism of the protective effects of Panax notoginseng saponins (PNS) on kidney in diabetic rats.

METHODSDiabetic rat model was obtained by intravenous injection of alloxan, and the rats were divided into model, PNS-100 mg/(kg day) and PNS-200 mg/(kg day) groups, 10 each. Another 10 rats injected with saline were served as control. Periodic acid-Schiff staining and immunological histological chemistry were used to observe histomorphology and tissue expression of bone morphogenetic protein-7 (BMP-7). Silent information regulator 1 (SIRT1) was silenced in rat mesangial cells by RNA interference. The mRNA expressions of SIRT-1, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor β1 (TGF-β1) and plasminogen activator inhibitor-1 (PAI-1) were analyzed by reverse transcription polymerase chain reaction. The protein expressions of SIRT1 and the acetylation of nuclear factor κB (NF-κB) P65 were determined by western blotting. The concentration of MCP-1, TGF-β1 and malondialdehyde (MDA) in culture supernatant were detected by enzyme-linked immuno sorbent assay. The activity of superoxide dismutase (SOD) was detected by the classical method of nitrogen and blue four.

RESULTSIn diabetic model rats, PNS could not only reduce blood glucose and lipid (P<0.01), but also increase protein level of BMP-7 and inhibit PAI-1 expression for suppressing fibrosis of the kidney. In rat mesangial cells, PNS could up-regulate the expression of SIRT1 (P<0.01) and in turn suppress the transcription of TGF-β1 (P<0.05) and MCP-1 (P<0.05). PNS could also reverse the increased acetylation of NF-κB p65 by high glucose. In addition, redox regulation factor MDA was down-regulated (P<0.05) and SOD was up-regulated (P<0.01), which were both induced by SIRT1 up-regulation.

CONCLUSIONSPNS could protect kidney from diabetes with the possible mechanism of up-regulating SIRT1, therefore inhibiting inflammation through decreasing the induction of inflammatory cytokines and TGF-β1, as well as activating antioxidant proteins.

Acetylation ; drug effects ; Animals ; Antioxidants ; metabolism ; Blood Glucose ; metabolism ; Bone Morphogenetic Protein 7 ; metabolism ; Chemokine CCL2 ; metabolism ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; genetics ; physiopathology ; Gene Knockdown Techniques ; Immunohistochemistry ; Kidney ; drug effects ; pathology ; Kidney Function Tests ; Lipids ; blood ; Male ; Malondialdehyde ; metabolism ; Mesangial Cells ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Panax notoginseng ; chemistry ; Plasminogen Activator Inhibitor 1 ; genetics ; metabolism ; Protective Agents ; pharmacology ; therapeutic use ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; therapeutic use ; Sirtuin 1 ; genetics ; Superoxide Dismutase ; metabolism ; Transcription Factor RelA ; metabolism ; Transcription, Genetic ; drug effects ; Transforming Growth Factor beta1 ; metabolism ; Up-Regulation ; drug effects

OBJECTIVETo explore the dynamic changes of transforming growth factor-α (TGF-α) and transforming growth factor-β1 (TGF-β1) of liver cirrhosis induced by multiple pathogenic factors in rats.

METHODSAnimals in the cirrhosis group were fed a mixture of maize flour, lard, cholesterol and alcohol plus subcutaneously injection with carbon tetrachloride (CCl₄), the CCl₄(0.5 ml/100 g · w) was injected at the first day of experiment and the 40% CCl₄oil solution (0.3 ml /100 g · w) was injected at an interval of three days. The thirty-six male SD rats were randomly divided into liver cirrhosis group of the 4th, 6th and 8 th week, and normal control group of the 4th, 6th and 8th week. The contents of alanine transferase (ALT), endotoxin, tumor necrosis factor-α (TNF-α) and homocysteine (Hcy) in plasma were evaluated. Histopathological changes of the liver were observed under microscope with the staining of HE. The expressions of TGF-α and TGF-β1 were analyzed by the method of immunohistochemistry.

RESULTSCompared with the corresponding normal control group, the levels of ALT, endotoxin, TNF-α and Hcy in plasma were gradually significantly increased in liver cirrhosis group of the 4th, 6th and 8th week (P < 0.05); the expression of TGF-α in the liver tissues was significantly increased at the 4th week (P < 0.05); the expression of TGF-β1 in the liver tissues was gradually significantly increased in every model group (P < 0.05).

CONCLUSIONIn the formation process of cirrhosis, the expression of TGF-α was increased in liver of cirrhosis group at the 4th week, and later it was suppressed; the expression of TGF-β1 was continuously increased. The characteristic dynamic changes of TGF-α and TGF-β1 might be related to sustained endotoxemia, the high level of TNF-α and hyperhomocysteinemia.

Alanine Transaminase ; blood ; Animals ; Carbon Tetrachloride ; Endotoxins ; blood ; Homocysteine ; blood ; Liver Cirrhosis ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor alpha ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; Tumor Necrosis Factor-alpha ; blood ; metabolism

OBJECTIVETo investigate ORMDL3 polymorphisms in children with asthma in Hunan, China, and to determine the relationship between ORMDL3 polymorphisms and serum osteopontin (OPN) and transforming growth factor-β1 (TGF-β1) levels.

METHODSPeripheral blood samples were collected in children with asthma (n=98; astma group) or without asthma (n=30; control group) from Hunan, China. The asthma group was subdivided into atopic (n=62) and non-atopic (n=36) subgroups. Single nucleotide polymorphism (SNP) analysis was performed, and serum OPN and TGF-β1 levels were measured.

RESULTSThere were no significant differences in genotype and allele frequencies of rs7216389 of the ORMDL3 gene between the asthma and control groups. The serum level of OPN in the asthma group was significantly higher than in the control group (P<0.05). Both the atopic and non-atopic subgroups showed increased serum levels of OPN compared with the control group (P<0.05). The serum level of TGF-β1 in the atopic subgroup was significantly higher than in the control group (P<0.05). The serum levels of OPN and TGF-β1 showed no significant differences in asthmatic children with different genotypes. The serum levels of OPN and TGF-β1 were in a positive linear correlation in the asthma group (r=0.620; P<0.01) and its two subgroups (r=0.734, 0.649 respectively; P<0.01).

CONCLUSIONSIn children from Hunan, China, the SNP (rs7216389) of ORMDL3 is not related to asthma susceptibility. OPN and TGF-β1 may be involved in the development of asthma, and they are in a positive linear correlation. The SNP (rs7216389) of ORMDL3 does not influence the expression of OPN and TGF-β1, suggesting that it may not be associated with airway remodeling.

Airway Remodeling ; Asthma ; blood ; genetics ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Membrane Proteins ; genetics ; Osteopontin ; blood ; Polymorphism, Single Nucleotide ; Transforming Growth Factor beta1 ; blood

OBJECTIVETo observe the dynamic changes of Th17/Treg balance in patients following surgical intervention for intracranial aneurysm rupture.

METHODSThe percentage of Th cells and the intracellular IL-17 level, Treg cell percentage and transforming growth factor -β1 (TGF-β1) levels were examined in 73 patients with rupture of aneurysms before and at 24 h, 72 h and 1 week after operation, with 62 patients with unruptured aneurysms and 65 healthy volunteers as the control. The correlations among the immune cells, cytokines and clinical characteristics of the patients (NIHSS, ADL and hospitalization stay) were analyzed.

RESULTSTh17 percentage and intracellular IL-17 levels were significantly higher in the patients with ruptured and unruptured aneurysms than in the healthy volunteers, and were significantly higher in patients with ruptured aneurysms than in those with unruptured aneurysms. Treg cell percentage and TGF-β1 level were significantly lower in patients with aneurysms than in the healthy volunteers, and were lower in patients with ruptured aneurysms than in those with uruptured aneurysms (P<0.05). Patients with intracranial aneurysm rupture showed significantly increased Th17 cell percentage and IL-17 level but significantly lowered Treg cell percentage and TGF-β1 at 24 h following the surgery (P<0.05); these changes were reversed significantly at 72 h and 1 week after the surgery. Th17 cell percentage and IL-17 level were positively correlated with NIHSS and the length of postoperative hospital stay but inversely correlated with ADL; Treg cell percentage and TGF-β1 were inversely correlated with NIHSS and hospital stay but positively with ADL (P<0.05).

CONCLUSIONIn patients with intracranial aneurysms, the systemic immune inflammatory response is highlighted by excessive Th17 cells and insufficient Treg cells, which are closely related with the outcomes of the patients following surgical intervention. Evaluation of Th17/Treg balance and the cytokine levels can help to assess the prognosis of patients with aneurysm rupture.

Aneurysm, Ruptured ; immunology ; Flow Cytometry ; Humans ; Interleukin-17 ; blood ; Intracranial Aneurysm ; immunology ; Postoperative Period ; Prognosis ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology ; Transforming Growth Factor beta1 ; blood