BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t...BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.展开更多
Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(...Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of paninhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynaminrelated protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.展开更多
The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger ...The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase (AC) system and the cGMP/guanylate cyclase (GC) system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide (NO) leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil's actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assisted reproductive technology (ART) programs. In the future PDE5 inhibitors might serve as adjunct therapeutical agents for the alleviation of male infertility.展开更多
Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats...Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed. Results: Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P 〈 0.01); DHT concentrations of group D rats were significantly decreased (P 〈 0.01 ) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion: These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.展开更多
Virion infectivity factor(Vif) is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G(h-APOBEC3G) is a cytidine deaminase only expre...Virion infectivity factor(Vif) is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G(h-APOBEC3G) is a cytidine deaminase only expressed in "nonpermissive" cells and exhibits virus suppressive activity. With the aid of a Cullin-5 E3 ligase, Vif induces h-APOBEC3G degradation and with the destruction of this ligase, Vif is functionally inactive. Therefore, it is expected that blocking this E3 pathway would be a new therapeutic strategy against HIV-1 infection. In this article, the authors' took sequence alignment of the N-termini of Cullin-5 and three other members of the Cullin protein family, respectively. A set of small peptides has been synthesized based on the sequence comparison results and possible Vif-Cullin-5 interaction domains. Moreover, it has been demonstrated that several peptides can reduce virus infectivity in "nonpermissive" cells with a dose-responsive manner, but not in "permissive" cells. The results also indicate that the loss of viral infectivity may be because of the increase of APOBEC3G amount in the peptide-treated cells. It is concluded that peptides derived from Cullin-5 can block the APOBEC3G degradation induced by Vif and suppress HIV-1 infectivity. Therefore this study starts a novel strategy for the development of a new HIV-1 inhibitor.展开更多
Aim: To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 (PDE5) inhibitor, on penile erection in obese rats. Meth...Aim: To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 (PDE5) inhibitor, on penile erection in obese rats. Methods: The rats were fed a high-energy diet for 12 weeks and divided into three groups: an obesity-resistant (OR) control group, an obesity-prone (OP) control group, and an OP-DA-8159 treatment (DA-8159) group. The electrostimulation-induced erectile responses were measured in all groups. The body weight, plasma cholesterol, triglyceride and glucose levels were also measured. Results: In the OP control group, the maximum intracavernous pressure (ICP) and ICP/blood pressure (ICP/BP) ratio after electric stimulation were significantly lower than those in OR control group. The corresponding area under the curve (AUC) of the ICP/BP ratio, the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group, but this difference was not significant. The body weight gain, plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159, a significant increase in the maximum ICP and the ICP/BP ratio were observed. The corresponding AUCs in the DA-8159 group were also higher than those in the two control groups. Furthermore, the detumescence time was significantly prolonged after treatment with DA-8159. Conclusion: These results demon- strate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction (ED) can be improved by the treatment with DA-8159, indicating DA-8159 might be a treatment option for ED associated with obesity.展开更多
5α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies reported that preoperative 5α-RI had impact on i...5α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies reported that preoperative 5α-RI had impact on intraoperative haemorrhage during surgery for BPH, but it was still in controversial. So, we conducted a systematic review of the effects and mechanisms of 5α-RIs on intraoperative bleeding for BPH. MEDLINE, EMBASE, the Cochrane Controlled Trail Register of Controlled Trials and the reference lists of retrieved studies were searched in the analysis. Sixteen publications involving 15 different randomized controlled trials (RCTs) and a total of 1156 patients were used in the analysis, including 10 RCTs for finasteride and five RCTs for dutasteride. We found that preoperative finasteride treatment decreases microvessel density (MVD) in resected prostate specimens. Total blood loss, blood loss per gram of resected prostate tissue and decreases in haemoglobin were all greatly reduced in the finasteride group as compared to controls. Dutasteride appeared to have no effect on bleeding. This meta-analysis shows that preoperative finasteride treatment could decrease intraoperative haemorrhage during surgery for BPH. Preoperative dutasteride had no effect on intraoperative haemorrhage, but further high-qualitv prospective studies are still needed to confirm this observation.展开更多
Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead ...Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead to complications including acute urinary retention(AUR)and the need for BPH-related surgery.Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone(DHT),which is formed from testosterone under the influence of 5-alpha reductase.Thus,5-alpha reductase inhibitors(5-ARIs)effectively reduce the serum and intraprostatic concentration of DHT,causing an involution of prostate tissue.Two 5-ARIs are currently available for the treatment of BPHdfinasteride and dutasteride.Both have been demonstrated to decrease prostate volume,improve LUTS and urinary flow rates,which ultimately reduces the risk of AUR and BPH-related surgery.Therefore,either alone or in combination with other BPH medications,5-ARIs are a mainstay of BPH management.展开更多
文摘BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82103208,and 82002948)the Guangdong Basic and Applied Basic Research Foundation(Grant Nos.:2022A1515220212,and 2023A1515030115)+1 种基金National Key R&D Program of China(Grant No.:2020YFE0202200)Jinan University National College Students'Innovation and Entrepreneurship Training Program(Program No.:202110559085).
文摘Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of paninhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynaminrelated protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.
文摘The aim of this review study is to elucidate the effects that phosphodiesterase 5 (PDE5) inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase (AC) system and the cGMP/guanylate cyclase (GC) system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide (NO) leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil's actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assisted reproductive technology (ART) programs. In the future PDE5 inhibitors might serve as adjunct therapeutical agents for the alleviation of male infertility.
基金Acknowledgment This study was support by Natural Science Foundation of Shanghai, China (No. 06ZR14137).
文摘Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed. Results: Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P 〈 0.01); DHT concentrations of group D rats were significantly decreased (P 〈 0.01 ) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion: These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.
基金the National Natural Science Foundation of China(No.30570363)Distinguished Young Scholars Fund of Jilin Province, China(No.20050112)the New Century Excellent Talents
文摘Virion infectivity factor(Vif) is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G(h-APOBEC3G) is a cytidine deaminase only expressed in "nonpermissive" cells and exhibits virus suppressive activity. With the aid of a Cullin-5 E3 ligase, Vif induces h-APOBEC3G degradation and with the destruction of this ligase, Vif is functionally inactive. Therefore, it is expected that blocking this E3 pathway would be a new therapeutic strategy against HIV-1 infection. In this article, the authors' took sequence alignment of the N-termini of Cullin-5 and three other members of the Cullin protein family, respectively. A set of small peptides has been synthesized based on the sequence comparison results and possible Vif-Cullin-5 interaction domains. Moreover, it has been demonstrated that several peptides can reduce virus infectivity in "nonpermissive" cells with a dose-responsive manner, but not in "permissive" cells. The results also indicate that the loss of viral infectivity may be because of the increase of APOBEC3G amount in the peptide-treated cells. It is concluded that peptides derived from Cullin-5 can block the APOBEC3G degradation induced by Vif and suppress HIV-1 infectivity. Therefore this study starts a novel strategy for the development of a new HIV-1 inhibitor.
文摘Aim: To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 (PDE5) inhibitor, on penile erection in obese rats. Methods: The rats were fed a high-energy diet for 12 weeks and divided into three groups: an obesity-resistant (OR) control group, an obesity-prone (OP) control group, and an OP-DA-8159 treatment (DA-8159) group. The electrostimulation-induced erectile responses were measured in all groups. The body weight, plasma cholesterol, triglyceride and glucose levels were also measured. Results: In the OP control group, the maximum intracavernous pressure (ICP) and ICP/blood pressure (ICP/BP) ratio after electric stimulation were significantly lower than those in OR control group. The corresponding area under the curve (AUC) of the ICP/BP ratio, the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group, but this difference was not significant. The body weight gain, plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159, a significant increase in the maximum ICP and the ICP/BP ratio were observed. The corresponding AUCs in the DA-8159 group were also higher than those in the two control groups. Furthermore, the detumescence time was significantly prolonged after treatment with DA-8159. Conclusion: These results demon- strate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction (ED) can be improved by the treatment with DA-8159, indicating DA-8159 might be a treatment option for ED associated with obesity.
文摘5α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies reported that preoperative 5α-RI had impact on intraoperative haemorrhage during surgery for BPH, but it was still in controversial. So, we conducted a systematic review of the effects and mechanisms of 5α-RIs on intraoperative bleeding for BPH. MEDLINE, EMBASE, the Cochrane Controlled Trail Register of Controlled Trials and the reference lists of retrieved studies were searched in the analysis. Sixteen publications involving 15 different randomized controlled trials (RCTs) and a total of 1156 patients were used in the analysis, including 10 RCTs for finasteride and five RCTs for dutasteride. We found that preoperative finasteride treatment decreases microvessel density (MVD) in resected prostate specimens. Total blood loss, blood loss per gram of resected prostate tissue and decreases in haemoglobin were all greatly reduced in the finasteride group as compared to controls. Dutasteride appeared to have no effect on bleeding. This meta-analysis shows that preoperative finasteride treatment could decrease intraoperative haemorrhage during surgery for BPH. Preoperative dutasteride had no effect on intraoperative haemorrhage, but further high-qualitv prospective studies are still needed to confirm this observation.
文摘Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead to complications including acute urinary retention(AUR)and the need for BPH-related surgery.Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone(DHT),which is formed from testosterone under the influence of 5-alpha reductase.Thus,5-alpha reductase inhibitors(5-ARIs)effectively reduce the serum and intraprostatic concentration of DHT,causing an involution of prostate tissue.Two 5-ARIs are currently available for the treatment of BPHdfinasteride and dutasteride.Both have been demonstrated to decrease prostate volume,improve LUTS and urinary flow rates,which ultimately reduces the risk of AUR and BPH-related surgery.Therefore,either alone or in combination with other BPH medications,5-ARIs are a mainstay of BPH management.