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Yu-Hua Lin
Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City 231, Taiwan

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Journal article
Published: 19 November 2020 in Biomedicines
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Septins (SEPTs) are highly conserved GTP-binding proteins and the fourth component of the cytoskeleton. Polymerized SEPTs participate in the modulation of various cellular processes, such as cytokinesis, cell polarity, and membrane dynamics, through their interactions with microtubules, actin, and other cellular components. The main objective of this study was to dissect the molecular pathological mechanism of SEPT14 mutation-induced sperm head defects. To identify SEPT14 interactors, co-immunoprecipitation (co-IP) and nano-liquid chromatography-mass spectrometry/mass spectrometry were applied. Immunostaining showed that SEPT14 was significantly localized to the manchette structure. The SEPT14 interactors were identified and classified as (1) SEPT-, (2) microtubule-, (3) actin-, and (4) sperm structure-related proteins. One interactor, ACTN4, an actin-holding protein, was selected for further study. Co-IP experiments showed that SEPT14 interacts with ACTN4 in a male germ cell line. SEPT14 also co-localized with ACTN4 in the perinuclear and manchette regions of the sperm head in early elongating spermatids. In the cell model, mutated SEPT14 disturbed the localization pattern of ACTN4. In a clinical aspect, sperm with mutant SEPT14, SEPT14A123T (p.Ala123Thr), and SEPT14I333T (p.Ile333Thr), have mislocalized and fragmented ACTN4 signals. Sperm head defects in donors with SEPT14 mutations are caused by disruption of the functions of ACTN4 and actin during sperm head formation.

ACS Style

Yu-Hua Lin; Chia-Yen Huang; Chih-Chun Ke; Ya-Yun Wang; Tsung-Hsuan Lai; Hsuan-Che Liu; Wei-Chi Ku; Chying-Chyuan Chan; Ying-Hung Lin. ACTN4 Mediates SEPT14 Mutation-Induced Sperm Head Defects. Biomedicines 2020, 8, 518 .

AMA Style

Yu-Hua Lin, Chia-Yen Huang, Chih-Chun Ke, Ya-Yun Wang, Tsung-Hsuan Lai, Hsuan-Che Liu, Wei-Chi Ku, Chying-Chyuan Chan, Ying-Hung Lin. ACTN4 Mediates SEPT14 Mutation-Induced Sperm Head Defects. Biomedicines. 2020; 8 (11):518.

Chicago/Turabian Style

Yu-Hua Lin; Chia-Yen Huang; Chih-Chun Ke; Ya-Yun Wang; Tsung-Hsuan Lai; Hsuan-Che Liu; Wei-Chi Ku; Chying-Chyuan Chan; Ying-Hung Lin. 2020. "ACTN4 Mediates SEPT14 Mutation-Induced Sperm Head Defects." Biomedicines 8, no. 11: 518.

Biotechnology
Published: 25 September 2020 in PLOS Genetics
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Approximately 2–15% of couples experience infertility, and around half of these cases are attributed to male infertility. We previously identified TBC1D21 as a sterility-related RabGAP gene derived from infertile men. However, the in vivo function of TBC1D21 in male fertility remains unclear. Here, we show that loss of Tbc1d21 in mice resulted in male infertility, characterized by defects in sperm tail structure and diminished sperm motility. The mitochondria of the sperm-tail had an abnormal irregular arrangement, abnormal diameter, and structural defects. Moreover, the axoneme structure of sperm tails was severely disturbed. Several TBC1D21 interactors were selected via proteomic analysis and functional grouping. Two of the candidate interactors, a subunit protein of translocase in the outer membrane of mitochondria (TOMM20) and an inner arm component of the sperm tail axoneme (Dynein Heavy chain 7, DNAH7), confirmed in vivo physical co-localization with TBC1D21. In addition, TOMM20 and DNAH7 detached and dispersed outside the axoneme in Tbc1d21-deficient sperm, instead of aligning with the axoneme. From a clinical perspective, the transcript levels of TBC1D21 in sperm from teratozoospermia cases were significantly reduced when compared with those in normozoospermia. We concluded that TBC1D21 is critical for mitochondrial and axoneme development of mammalian sperm. Male sterility affects one in seven couples, and around half of these are the result of male factor disorders. The common conditions of male infertility cases include reduced sperm motility, low sperm account, and spermatozoa with abnormal morphology. We previously identified TBC1D21 as a sterility-related RabGAP gene from infertile men. However, the in vivo function of TBC1D21 in male fertility remains untested. Here, we created Tbc1d21 knockout mice. The knockout males were completely sterile, and had sperm-tail and mitochondria defects. Two interactors of TBC1D21, TOMM20, and DNAH7, may account for the irregular and defective patterns observed in Tbc1d21-/- mouse sperm tails. From a clinical perspective, TBC1D21 transcripts are reduced in sperm from patients exhibiting teratozoospermia. Our results indicate that TBC1D21 plays a critical role in the formation of intact mitochondria, and structure of mammalian sperm.

ACS Style

Ya-Yun Wang; Chih-Chun Ke; Yen-Lin Chen; Yu-Hua Lin; I-Shing Yu; Wei-Chi Ku; Moira K. O’Bryan; Ying-Hung Lin. Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice. PLOS Genetics 2020, 16, e1009020 .

AMA Style

Ya-Yun Wang, Chih-Chun Ke, Yen-Lin Chen, Yu-Hua Lin, I-Shing Yu, Wei-Chi Ku, Moira K. O’Bryan, Ying-Hung Lin. Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice. PLOS Genetics. 2020; 16 (9):e1009020.

Chicago/Turabian Style

Ya-Yun Wang; Chih-Chun Ke; Yen-Lin Chen; Yu-Hua Lin; I-Shing Yu; Wei-Chi Ku; Moira K. O’Bryan; Ying-Hung Lin. 2020. "Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice." PLOS Genetics 16, no. 9: e1009020.

Review
Published: 18 February 2020 in Toxins
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Intravesical botulinum toxin (BoNT) injection is effective in reducing urgency and urinary incontinence. It temporarily inhibits the detrusor muscle contraction by blocking the release of acetylcholine (Ach) from the preganglionic and postganglionic nerves in the efferent nerves. BoNT-A also blocks ATP release from purinergic efferent nerves in the detrusor muscle. In afferent nerves, BoNT-A injection markedly reduces the urothelial ATP release and increases nitric oxide (NO) release from the urothelium. BoNT-A injection in the urethra or bladder has been developed in the past few decades as the treatment method for detrusor sphincter dyssyndergia, incontinence due to neurogenic or idiopathic detrusor overactivity, sensory disorders, including bladder hypersensitivity, overactive bladder, and interstitial cystitis/chronic pelvic pain syndrome. Although the FDA only approved BoNT-A injection treatment for neurogenic detrusor overactivity and for refractory overactive bladder, emerging clinical trials have demonstrated the benefits of BoNT-A treatment in functional urological disorders. Cautious selection of patients and urodynamic evaluation for confirmation of diagnosis are crucial to maximize the successful outcomes of BoNT-A treatment.

ACS Style

Yu-Hua Lin; Bing-Juin Chiang; Chun-Hou Liao. Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders. Toxins 2020, 12, 129 .

AMA Style

Yu-Hua Lin, Bing-Juin Chiang, Chun-Hou Liao. Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders. Toxins. 2020; 12 (2):129.

Chicago/Turabian Style

Yu-Hua Lin; Bing-Juin Chiang; Chun-Hou Liao. 2020. "Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders." Toxins 12, no. 2: 129.

Randomized controlled trial
Published: 07 October 2019 in PLOS ONE
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We aim to examine the trend in the use of antimuscarinics and off-label alpha-adrenergic blockers for treatment of lower urinary tract symptoms (LUTS) in a Taiwanese Women Cohort between 2007 and 2012. This population-based National Health Insurance Research Database (NHIRD) was used to examine the trends in the use of antimuscarinics or off-label alpha-adrenergic blockers in Taiwan. A sample of 1,000,000 individuals randomly drawn from the whole population of 23 million individuals who were registered in the NHI in 2005. From 2007 through 2012, women aged over 18 years whose claim record contained prescriptions of either of the two drugs for treatment of any of the LUTS-related diagnoses were identified and analyzed. The annual usage of the two drug classes were calculated by defined daily dose (DDD). From 2007-2012, there was a 0.80 fold (69676.8 to 125104.3) increase in DDD of antimuscarinics in our cohort. The overall healthcare seeking prevalence of LUTS was 7.33% in 2007 and 12.38% in 2012, in a rising trend. The prevalence of antimuscarinics-treated LUTS in our cohort increased from 2.53 in 2007 to 3.41 per 1000 women in 2012. The prevalence of LUTS treated by antimuscarinics increased especially for those older than 60 years during the study period. This 6-year observational study provided the epidemiologic information of clinically significant LUTS of Asian female population. Moreover, there was a rising trend in the use of antimuscarinics and off-label alpha-adrenergic blockers in the population-based cohort.

ACS Style

Yu-Hua Lin; Wei-Yi Huang; Chi-Chih (Clare) Chang; Yu-Fen Chen; Ling-Ying Wu; Hong-Chiang Chang; Kuo-How Huang. Trends in the use of antimuscarinics and alpha-adrenergic blockers in women with lower urinary tract symptoms in Taiwan: A nationwide, population-based study, 2007-2012. PLOS ONE 2019, 14, e0220615 .

AMA Style

Yu-Hua Lin, Wei-Yi Huang, Chi-Chih (Clare) Chang, Yu-Fen Chen, Ling-Ying Wu, Hong-Chiang Chang, Kuo-How Huang. Trends in the use of antimuscarinics and alpha-adrenergic blockers in women with lower urinary tract symptoms in Taiwan: A nationwide, population-based study, 2007-2012. PLOS ONE. 2019; 14 (10):e0220615.

Chicago/Turabian Style

Yu-Hua Lin; Wei-Yi Huang; Chi-Chih (Clare) Chang; Yu-Fen Chen; Ling-Ying Wu; Hong-Chiang Chang; Kuo-How Huang. 2019. "Trends in the use of antimuscarinics and alpha-adrenergic blockers in women with lower urinary tract symptoms in Taiwan: A nationwide, population-based study, 2007-2012." PLOS ONE 14, no. 10: e0220615.

Journal article
Published: 01 September 2017 in Urological Science
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Objective: The aim of this study was to report our preliminary experience of the treatment with mirabegron and to identify the predictors of a successful treatment with mirabegron in overactive bladder (OAB) patients. Materials and methods: Between October 2015 and February 2016, 234 consecutive patients (167 men and 67 women; mean age: 65.6 years; standard deviation: 16.3) diagnosed with OAB and receiving mirabegron monotherapy were enrolled retrospectively. Four weeks after mirabegron treatment, a global response assessment (GRA) was performed for all patients and analyses were performed to identify possible predictors of successful mirabegron treatment (defined as GRA ≥ 1). Mirabegron was intended being given for at least 12 weeks. Adverse events (AEs) and reasons for discontinuing mirabegron were recorded between 4 and 12 weeks of following-up. Results: The rate of successful mirabegron treatment (GRA ≥ 1) was 70.5%. The proportion of patients with a successful response was significantly higher in men than in women (75.3% vs. 60.5%, p = 0.022). The success rates as well as the percentage of older patients between groups with or without diabetes, hypertension, nocturia, urge incontinence, or prior anticholinergic treatment were not significantly different. Multivariable analysis showed that male sex was a significant independent predictor (p < 0.05) for successful treatment. The overall rate of AEs was 3.8%, including five cases with hypertension (2.1%) and three with severe voiding difficulty (1.3%). A total of 136 patients (58%) were administered mirabegron for more than 12 weeks. The reasons for discontinuing mirabegron included symptom improvement (17%), loss to follow-up (13%), poor treatment efficacy (8%), and side effects (4%). Conclusions: The success rate of mirabegron treatment for OAB patients was high and the rate of overall AEs was low. Although only 58% patients continued mirabegron at 12 weeks, most patients (17%) discontinued the treatment because of reduction in symptoms. Male sex showed better response to mirabegron treatment

ACS Style

Tsai-Feng Chen; Hsu-Che Huang; Yu-Hua Lin; Chun-Hou Liao; Bing-Juin Chiang. Preliminary experience and possible predictors of successful mirabegron treatment for overactive bladder. Urological Science 2017, 28, 162 -165.

AMA Style

Tsai-Feng Chen, Hsu-Che Huang, Yu-Hua Lin, Chun-Hou Liao, Bing-Juin Chiang. Preliminary experience and possible predictors of successful mirabegron treatment for overactive bladder. Urological Science. 2017; 28 (3):162-165.

Chicago/Turabian Style

Tsai-Feng Chen; Hsu-Che Huang; Yu-Hua Lin; Chun-Hou Liao; Bing-Juin Chiang. 2017. "Preliminary experience and possible predictors of successful mirabegron treatment for overactive bladder." Urological Science 28, no. 3: 162-165.