intracavernous-pressure-recording-cavernous-nerve-injury-rat

Intracavernous Pressure Recording in a Cavernous Nerve Injury Rat Model

The bilateral cavernous nerve (CN) injury rat model has been extensively used to simulate clinical cavernous nerve injury associated with erectile ...

The Fifth Affiliated Hospital of Sun Yat-sen University

The Fifth Affiliated Hospital, Sun Yat-sen University

The role of TDRG1 in tumorigenesis and the progression of seminoma, as well as its role in regulating chemosensitivity of seminoma to cisplatin through the PI3K/Akt/mTOR signaling pathway, has been previously defined. However, the detailed mechanism underlying TDRG1 expression and concomitant chemoresistance conditions are unknown. Furthermore, it has been reported that non-protein-coding RNAs play an important role in a variety of vital processes including cellular chemosensitivity. However, the role of non-protein-coding RNAs in regulating the chemosensitivity of seminoma remains unknown. In this study, using microarray analysis, we found that long non-coding RNA H19 was upregulated while miRNA-106b-5p was downregulated in an established cisplatin-resistant TCam-2 cell line. Moreover, H19 acts as a miRNA-106b-5p sponge and thus impairs the function of miRNA-106b-5p on its target gene, TDRG1. Based on these findings, we propose that H19 promotes the expression of TDRG1 by sequestering miRNA-106b-5p and uses this mechanism to facilitate cell survival in cisplatin-based chemotherapeutic conditions. These findings elucidate the mechanisms, at least partially, applied to deregulate TDRG1 and cisplatin sensitivity, and may provide new therapeutic possibilities for chemoresistant seminoma.

Long non-coding RNA H19 promotes TDRG1 expression and cisplatin resistance by sequestering miRNA-106b-5p in seminoma.

Bladder urothelial carcinoma (BUC) is one of the most common urological malignancies. Our previous study found that adenosine A2b receptor (A2bR) was upregulated in BUC tissues and cells. In the present study, we investigated the effect of MRS1754 (a selective A2bR antagonist) on cell proliferation and migration in two well-studied invasive urothelial cell carcinoma lines EJ and T24. Our results showed that MRS1754 reduced BUC cell proliferation and induced a G0/G1 phase cell-cycle arrest. Next, MRS1754 inhibited cell migration and Bay60-6583 (a selective A2bR agonist) treatment could reverse the inhibitory effect of MRS1754 on BUC cells migration. Furthermore, our results showed MRS1754 treatment downregulated the protein levels of p-P38, p-JNK, and phospho-extracellular signal-regulated kinase (p-ERK). These findings suggest that MRS1754 can inhibit progression of BUC via mitogen-activated protein kinase (MAPK) pathway and indicate the therapeutic potential of A2B antagonists in BUC.

MRS1754 inhibits proliferation and migration of bladder urothelial carcinoma by regulating mitogen-activated protein kinase pathway.

A new platinum(II) complex, [Pt(ClClQ)(DMSO)Cl] (1), utilizing 6,7-dichloro-5,8-quinolinedione (ClClQ) as a ligand, has been synthesized and fully characterized. Single-crystal X-ray diffraction and other spectroscopic and analytical methods revealed that the coordination geometry of Pt(II) in complex 1 can also be described as a four-coordinated square planar geometry. The aim of the study was to explore the in vitro anticancer properties of complex 1. Our studies showed that complex 1 can regulate the viability of testicular seminoma cells in vitro, including cell proliferation and apoptosis. We further observed negative regulation by complex 1 of the expression levels of the key elements in the phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK3β) pathway, including phosphorylated phosphoinositide-3 kinase (p-PI3K), phosphorylated protein kinase B(p-Akt) and phosphorylated glycogen synthase kinase-3β (p-GSK3β). Moreover, the negative effect of complex 1 was reversed by LiCl, a GSK3β-specific inhibitor of the PI3K signaling pathway. Meanwhile, the levels of Bcl2 associated death promoter (Bad), cytochrome c, active-caspase-3 and active-caspase-9 increased significantly. In conclusion, we observed that complex 1 can regulate the viability of testicular seminoma cells through the PI3K/Akt/GSK3β signaling pathway and the mitochondria-mediated apoptotic pathway in vitro, and thus, complex 1 may have potential for use as a drug in the treatment of testicular germ cell tumors.

Synthesis of a novel platinum(II) complex with 6,7-dichloro-5,8-quinolinedione and the study of its antitumor mechanism in testicular seminoma.

To investigate the possibility and mechanism of microenergy acoustic pulses (MAP) for activating tissue resident stem/progenitor cells within pelvic and urethral muscle and possible mechanism.

The effects of microenergy acoustic pulses on animal model of obesity-associated stress urinary incontinence. Part 2: In situ activation of pelvic floor and urethral striated muscle progenitor cells.

We previously identified testis developmental related gene 1 (TDRG1), a gene implicated in proliferation of TCam-2 seminoma cells. Recent evidence has revealed that autophagy influences the chemosensitivity of cancer cells to chemotherapy. However, whether TDRG1 protein regulates autophagy in seminoma cells and influences their sensitivity to cis-dichlorodiammine platinum (CDDP) remains unknown. In this study, we used TCam-2 cells and male athymic BALB/c nude mice with xenografts of TCam-2 cells to investigate autophagy, cell viability, apoptosis and the p110β/Rab5/Vps34 (PI3-kinase Class III) pathway under the conditions of TDRG1 overexpression or knockdown and with or without CDDP treatment. We found that TDRG1 upregulation promoted autophagy in both TCam-2 cells and seminoma xenografts via p110β/Rab5/Vps34 activation. Inhibition of autophagy reduced cell viability and promoted apoptosis during CDDP treatment of TCam-2 cells. Similarly, TDRG1 knockdown inhibited autophagy, reduced cell viability and promoted apoptosis during CDDP treatment of TCam-2 cells. TDRG1 knockdown inhibited tumour growth and promoted apoptosis in TCam-2 cell xenografts, whereas TDRG1 overexpression had the opposite effect. According to these results, we propose that high expression of TDRG1 promotes autophagy through the p110β/Rab5/Vps34 pathway in TCam-2 cells. TDRG1 overexpression promotes autophagy and leads to CDDP resistance, whereas TDRG1 knockdown inhibits autophagy and promotes chemosensitivity to CDDP both in vivo and in vitro. This study has uncovered a novel role of TDRG1 in reducing chemoresistance during CDDP treatment and provides potential therapeutic strategies for the treatment of human seminoma.

Testis developmental related gene 1 regulates the chemosensitivity of seminoma TCam-2 cells to cisplatin via autophagy.

Metformin, a drug used to treat type 2 diabetes, has gained attention for its multiple therapeutic applications. However, little is known about its effects on human sperm function at therapeutically relevant concentration.

In vitro exposure to metformin activates human spermatozoa at therapeutically relevant concentrations.

Testicular germ cell tumours (TGCTs) rank as the most common malignancy in men aged 20-34 years, and seminomas are the most type of TGCTs. As a crucial anti-tumour agent with explicit toxicity, cisplatin may render resistance through intertwined mechanisms, even in disease entities with high curative ratio, such as seminoma. Previously, we established cisplatin-resistant seminoma TCam-2 (TCam-2/CDDP) cells and showed that epigenetic regulations, such as non-coding RNA (ncRNA) interactions, might orchestrate cell fate decisions in the cisplatin treatment context in seminoma. N6-methyladenosine (m6A) is the most prevalent internal modification in mRNA. In the present study, we assessed cisplatin resistance in seminoma from the perspective of m A, another manner of epigenetic modification. The global m A enrichment of TCam-2 and TCam-2/CDDP was depicted. Then, we elucidated whether transcription factor-activating enhancer-binding protein 2C (TFAP2C) was functionally m A-modified by methyltransferase-like protein 3 (METTL3), which acted as an m A 'writer', and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which acted as an m A 'reader'. Enhanced stability of TFAP2C mRNA promoted seminoma cell survival under cisplatin treatment burden probably through up-regulation of DNA repair-related genes. Hopefully, this study will help improve our understanding of the subtleties of the tumour cellular coping strategy in response to chemotherapy. Targeting factors that are involved in m A methylation may be an effective strategy for circumventing cisplatin resistance in seminoma.

METTL3 potentiates resistance to cisplatin through m A modification of TFAP2C in seminoma.

Is there an association between the human testis-specific gene, testis developmental related gene 1 (TDRG1) and human sperm motility?

Testis developmental related gene 1 (TDRG1) encodes a progressive motility-associated protein in human spermatozoa.

To date, few studies have evaluated the role of peripheral blood T lymphocyte subsets in patients with clear cell renal cell carcinoma (ccRCC). Here we measured the levels of peripheral blood T lymphocyte subsets and evaluated its prognostic value in ccRCC.

Prognostic value of peripheral blood T lymphocyte subsets in clear cell renal cell carcinoma.

Our previous work shows Autophagy enhanced resistance to cisplatin in seminoma. The expression of the N6-methyladenosine (m6A) methyltransferases METTL3 was significantly increased in the cisplatin-resistant TCam-2 cell line of seminoma. We aimed to investigate the role of m6A methylation in autophagy and the chemosensitivity of seminoma cells.

The m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting ATG5 in seminoma.

There are many Western reports on factors influencing coital frequency among men. However, no articles could be found about the factors influencing sexual activity among Chinese men.

Article	Year
Long non-coding RNA H19 promotes TDRG1 expression and cisplatin resistance by sequestering miRNA-106b-5p in seminoma. Cancer medicine\| PubMed ID: 30430771	2018
MRS1754 inhibits proliferation and migration of bladder urothelial carcinoma by regulating mitogen-activated protein kinase pathway. Journal of cellular physiology\| PubMed ID: 30565699	2019
Synthesis of a novel platinum(II) complex with 6,7-dichloro-5,8-quinolinedione and the study of its antitumor mechanism in testicular seminoma. Journal of inorganic biochemistry\| PubMed ID: 31055215	2019
The effects of microenergy acoustic pulses on animal model of obesity-associated stress urinary incontinence. Part 2: In situ activation of pelvic floor and urethral striated muscle progenit... Neurourology and urodynamics\| PubMed ID: 31452249	2019
Testis developmental related gene 1 regulates the chemosensitivity of seminoma TCam-2 cells to cisplatin via autophagy. Journal of cellular and molecular medicine\| PubMed ID: 31496041	2019
In vitro exposure to metformin activates human spermatozoa at therapeutically relevant concentrations. Andrology\| PubMed ID: 31944615	2020
METTL3 potentiates resistance to cisplatin through m A modification of TFAP2C in seminoma. Journal of cellular and molecular medicine\| PubMed ID: 32857912	2020
Testis developmental related gene 1 (TDRG1) encodes a progressive motility-associated protein in human spermatozoa. Human reproduction (Oxford, England)\| PubMed ID: 33279973	2021
Prognostic value of peripheral blood T lymphocyte subsets in clear cell renal cell carcinoma. Translational andrology and urology\| PubMed ID: 33532321	2021
The m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting ATG5 in seminoma. Translational andrology and urology\| PubMed ID: 33968659	2021
What Influences Coital Frequency Among Chinese Men?: A Cross-Sectional Study. Sexual medicine\| PubMed ID: 34090240	2021

Yuxin Tang

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