Chellappan Praveen Rajneesh

Fu Jen Catholic University

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Yi‐No Wu

Fu Jen Catholic University

Chih‐Wei Peng

Taipei Medical University

Kuo‐Chiang Chen

Cathay General Hospital

Han‐Sun Chiang

Fu Jen Catholic University

Xiao‐Wen Tseng

Fu Jen Catholic University

Chun‐Hou Liao

Fu Jen Catholic University

Tsung-Hsun Hsieh

Chang Gung University

Hung‐Yen Chin

Taipei Medical University Hospital

Shih-Ching Chen

Taipei Medical University

Chien‐Hung Lai

Taipei Medical University Hospital

Cooperative Institutions

Fu Jen Catholic University

Taipei Medical University

Taipei Medical University Hospital

Chang Gung University

National Taiwan University

Indian Institute of Technology Kharagpur

Chang Gung Memorial Hospital

National Cheng Kung University

Cathay General Hospital

National Tsing Hua University

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Improved voiding function by deep brain stimulation in traumatic brain-injured animals with bladder dysfunctions

International Urology and Nephrology (2018)

Chellappan Praveen Rajneesh Chien‐Hung Lai Shih-Ching Chen Tsung-Hsun Hsieh Hung‐Yen Chin

Neurogenic bladder dysfunction

Nephrology

10.1007/s11255-018-2028-1

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Citations (9)

Activities of Antioxidant Enzyme and Lipid Peroxidation in Ovarian Cancer Patients

A Manimaran Chellappan Praveen Rajneesh

Ovarian cancer is the leading cause of death due to gynecological malignancies among women. The extent of free radical induced oxidative stress can be exacerbated by the decreased efficiency of antioxidant mechanisms. The present study was conducted to investigate the extent of oxidative stress and the levels of antioxidants in the circulation of ovarian cancer patients. Methods: Plasma thiobarbituric acid reactive substances (TBARS) and conjugated dienes (CD) and the levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT), vitamin C and vitamin E were estimated in the circulation of 46 ovarian cancer patients and an equal number of age-matched normal subjects as control. Results: Significantly increased concentrations of plasma TBARS and CD and significantly lowered levels of SOD, CAT, vitamin C and vitamin E were observed in ovarian cancer patients as compared with normal subjects. Conclusion: The low levels of SOD, CAT, vitamin C and vitamin E in the plasma of ovarian cancer patients may be due to their increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells. Increased levels of lipid peroxidation may be due to excessive oxidative stress caused by incessant ovulation or epithelial inflammation.

TBARS

Thiobarbituric acid

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Effects of platelet-rich plasma glue placement at the prostatectomy site on erectile function restoration and cavernous nerve preservation in a nerve-sparing prostatectomy rat model

Biomedicine & Pharmacotherapy (2023)

Chun‐Hou Liao Chee‐Jen Chang Kuo‐Chiang Chen Chellappan Praveen Rajneesh Xiao‐Wen Tseng

Despite the widespread use of nerve-sparing prostatectomy techniques, the incidence of post-operative erectile dysfunction (ED) remains high. Early intracavernous (IC) injection of platelet-rich plasma (PRP) after nerve crushing improves erectile function (EF) in rats by promoting cavernous nerve (CN) regeneration and preventing structural changes in the corpus cavernosum. However, the neuroprotective effects of the in situ application of PRP glue in rats after CN-sparing prostatectomy (CNSP) remain unclear.This study aimed to investigate the effects of PRP glue treatment on EF and CN preservation in rats after CNSP.After prostatectomy, male Sprague-Dawley rats were treated with PRP glue, IC PRP injection, or their combination. The intracavernous pressure (ICP), mean arterial pressure (MAP), and CN preservation status in the rats were evaluated after 4 weeks. Results were corroborated using histology, immunofluorescence, and transmission electron microscopy.The PRP glue-treated rats showed 100% CN preservation and significantly higher ICP responses (the ratio of maximum ICP to MAP (0.79 ± 0.09)) than the CNSP rats (the ratio of maximum ICP to MAP (0.33 ± 0.04)). PRP glue also significantly increased neurofilament-1 expression, indicating its positive effect on the CNs. Furthermore, this treatment significantly increased the expression of α-smooth muscle actin. Electron micrographs revealed that PRP glue preserved the myelinated axons and prevented atrophy of the corporal smooth muscle by maintaining the adherens junctions.These results indicate that PRP glue is a potential solution for EF preservation by neuroprotection in patients with prostate cancer who are likely to undergo nerve-sparing radical prostatectomy.

GLUE

10.1016/j.biopha.2023.114499

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Harnessing the regenerative effects of human amniotic stem cells (hAFSCs) on restoring erectile function in a bilateral cavernous nerve crush (BCNC) injury rat model

Stem Cell Research & Therapy (2024)

Chun‐Hou Liao Xiao‐Wen Tseng Chellappan Praveen Rajneesh Yu-Jen Chang Ming‐Song Tsai

Intracavernous (IC) injections of stem cells has been shown to ameliorate cavernous nerve (CN)-induced erectile dysfunction (ED). However, the regenerative effects underlying the recovery of erectile function (EF) in human amniotic fluid-derived stem cells (hAFSCs) remain unclear. In the bilateral cavernous nerve crushing (BCNC) injury rat paradigm, we sought to ascertain the effects of hAFSC treatment on EF recovery during the incipient phase. Three groups of 45 male rats were used in this study: sham (Group 1), saline IC injection after BCNC (Group 2), and hAFSC intracavernous injection (ICI) after BCNC (Group 3). hAFSCs from the fourth passage showed potential to differentiate into trilineage cells. All animals were subjected to EF analysis on the 28th day post-injection and tissues were retrieved for histopathological and immunohistochemical analyses. IC injections of hAFSC significantly improved EF parameters in BCNC-ED rats at 28 days post-injury. AFSC treatment enhanced the smooth muscle condition and increased the smooth muscle/collagen ratio, as evidenced by histological analysis. Immunohistology revealed increased expression of 𝛼-SMA andvWf in the corpus cavernosum and enhanced expression of nNOS in the dorsal penile nerve in BCNC-ED rats (p < 0.05). Western blotting showed that hAFSC treatment significantly increased α-SMA expression in the hAFSC group compared with that in the BCNC group. Electron microscopy revealed significantly elevated myelination in the CN (p < 0.05), maintenance of smooth muscle structures, and restoration of EF in BCNC-ED rats treated with hAFSC. hAFSC treatment increased EF in BCNC-ED rats at a single dose. As BCNC-ED resembles ED caused by radical prostatectomy (RP), this therapy has high potential for ED patients after RP surgery.

Regenerative Medicine

Nerve Injury

Crush injury

10.1186/s13287-024-03972-1

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Chlorogenic Acid Intravesical Therapy Changes Acute Voiding Behavior of Systemic Lipopolysaccharide Inflammation-Induced Cystitis Bladder in Mice

Toxics (2024)

Chung‐Hsin Yeh Chellappan Praveen Rajneesh Chun‐Hou Liao Wen-Chen You Kuo‐Chiang Chen

This study explores the potential efficacy of chlorogenic acid (CGA) in mitigating lipopolysaccharide (LPS)-induced cystitis in a mice model. C57BL/6J mice were divided into four groups: normal control (NC), LPS, LPS + low CGA, and LPS + high CGA. Evaluation methods included cystometrogram (CMG), histopathological, western blot, and immunohistological analysis. In the LPS group, CMG revealed abnormal voiding behavior with increased micturition pressure, voided volume (VV), and decreased voided frequency. Low CGA treatment in LPS mice demonstrated improved micturition pressure and inter-contraction intervals (ICI). However, high CGA treatment exhibited prolonged ICI and increased VV, suggesting potential adverse effects. Histological analysis of LPS-treated mice displayed bladder inflammation and interstitial edema. Low CGA treatment reduced interstitial edema and bladder inflammation, confirmed by Masson’s trichrome staining. Western blotting revealed increased cytokeratin 20 (K20) expression in the low CGA group, indicating structural abnormalities in the bladder umbrella layer after LPS administration. In conclusion, low CGA treatment positively impacted voiding behavior and decreased bladder edema and inflammation in the LPS-induced cystitis mice model, suggesting its potential as a supplement for inflammation cystitis prevention. However, high CGA treatment exhibited adverse effects, emphasizing the importance of dosage considerations in therapeutic applications.

Urination

10.3390/toxics12040239

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Insight into SLC9A3 deficiency-mediated micturition dysfunction caused by electrolyte imbalance

Biomedicine & Pharmacotherapy (2023)

Kuo‐Chiang Chen Meng‐Lin Chang Chun-Sian Lin Chellappan Praveen Rajneesh Chun‐Hou Liao

Solute carrier family nine isoform 3 (SLC9A3) is an Na+/H+ exchanger that regulates Ca2+ homeostasis. SLC9A3 is largely involved in the transepithelial absorption of Na+/H+ and frequently functions in pair with a Cl-/HCO3- exchanger.To investigate the impact and pathophysiological mechanisms of long-term SLC9A3 deficiency on lower urinary tract symptoms (LUTS) in a mouse model MATERIALS AND METHODS: Slc9a3 knockout and wild-type mice (average >6 months) were used. The effects of SLC9A3 depletion on bladder and urethral functions and effectiveness of voiding were assessed using a cystometrogram (CMG). Histology, blood electrolytes, and gene expression were also analyzed.The SLC9A3-deficient mice had smaller gross bladders than the wild-type mice. The CMG analysis revealed normal peak micturition pressure, higher threshold pressure, short intercontraction interval, less voided volume, and poor compliance in the SLC9A3-deficient mice, similar to clinical LUTS. Histological analysis revealed loose detrusor muscle and loss of transformability of the urothelium in the SLC9A3-deficient mice. Masson's trichrome analysis revealed severe collagen deposition in the detrusor muscle. Immunofluorescence staining also demonstrated a significant decrease in cytokeratins 5 and 20. Gene and protein expression analyses confirmed that SLC9A3 does not act directly on bladder tissue. Homeostasis was correlated with bladder dysfunction in the SLC9A3-deficient mice.Fibrosis and collagen deposition in the bladder of the SLC9A3-deficient mice is due to bladder inflammation because of decreased blood flow and deregulated systemic homeostasis. Long-term SLC9A3 depletion causes progressive bladder dysfunction, similar to human LUTS.Electrolyte imbalance causes SLC9A3 deficiency-mediated progressive micturition dysfunction.

Urination

Homeostasis

Pathophysiology

Masson's trichrome stain

10.1016/j.biopha.2022.114155

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Citations (2)

Cystometric Measurements in Rats with an Experimentally Induced Traumatic Brain Injury and Voiding Dysfunction: A Time-Course Study

Brain Sciences (2019)

Chellappan Praveen Rajneesh Ling-Yu Yang Shih-Ching Chen Tsung-Hsun Hsieh Hung‐Yen Chin

Traumatic brain injuries (TBIs) are a serious public health issue worldwide with increased mortality as well as severe disabilities and injuries caused by falls and road accidents. Unfortunately, there is no approved therapy for TBIs, and bladder dysfunction is a striking symptom. Accordingly, we attempted to analyze bladder dysfunction and voiding efficiency in rats with a TBI at different time-course intervals. Time-dependent analyses were scheduled from the next day until four weeks after a TBI. Experimental animals were grouped and analyzed under the above conditions. Cystometric measurements were used for this analysis and were further elaborated as external urethral sphincter electromyographic (EUS-EMG) activity and cystometrogram (CMG) measurements. Moreover, magnetic resonance imaging (MRI) studies were conducted to investigate secondary injury progression in TBI rats, and results were compared to normal control (NC) rats. Results of EUS-EMG revealed that the burst period, active period, and silent period in TBI rats were drastically reduced compared to NC rats, but they increased later and reached a stagnant phase. Likewise, in CMG measurements, bladder function, the voided volume, and voiding efficiency decreased immediately after the TBI, and other parameters like the volume threshold, inter-contraction interval, and residual volume drastically increased. Later, those levels changed, and all observed results were compared to NC rats. MRI results revealed the prevalence of cerebral edema and the progression of secondary injury. All of the above-stated results of the experiments were extensively substantiated. Thus, these innovative findings of our study model will surely pave the way for new therapeutic interventions for TBI treatment and prominently highlight their applications in the field of neuroscience in the future.

Silent period

10.3390/brainsci9110325

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New insights into CFTR modulation in reproduction: testicular microenvironment imbalance leads to over-activated caspase signalling in spermatogenesis and adversely affects fertility

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Guan‐Ru Chen Han‐Sun Chiang Shiu-Dong Chung Xiao‐Wen Tseng Chellappan Praveen Rajneesh

Abstract Cystic fibrosis transmembrane conductance regulator (CFTR) is a prominent chloride channel that governs mucous secretion in multiple organs, including the reproductive tract. According to earlier reports, defective CFTR results in infertility due to congenital bilateral absence of the vas deferens (CBAVD). However, obstruction in the vas deferens is not the only reason CFTR deficiency causes male infertility. The mechanism underlying the loss of mature sperm owing to CFTR deficiency remains elusive. This study aimed to assess the role of CFTR in spermatogenesis, for which 6- and 8-week-old male mice with Cftr +/+ , Cftr +/- , and Cftr -/- genotypes were chosen. Furthermore, we assessed the correlation between CFTR deficiency and delayed development of the reproductive system, anomalous apoptosis activation in spermatogenesis, and ionic alterations of the testis lumen. The results demonstrated that the growth of Cftr -/- mice were delayed, with underweight reproductive organs and mild hypospermatogenesis. CFTR depletion destabilizes spermatogenesis by producing abnormal sperm and triggers activation of the Bax/Bcl-2 ratio in Cftr -/- and Cftr +/- mice, causing caspase-mediated irreversible intrinsic apoptosis. Stage-specific apoptosis in germ cells targeted the sexually mature mice, and the testis microenvironment affirmed that ion concentrations influence sperm capacitation. The blood pH determines apoptosis induction, as CFTR is a bicarbonate transporter. In conclusion, Cftr -/ - mice were infertile because CFTR deficiency generated an ionic imbalance in the testis lumen, leading to Bax expression and Bcl-2 blockage, which triggered caspases or further activation of voltage-dependent anion-selective channel 1 (VDAC1). Cumulatively, cytochrome C was released due to altered mitochondrial membrane potential. Eventually, anomalous up-regulated apoptosis activation affected spermatogenesis, thus rendering the Cftr -/- male mice infertile. The results supplied new insights into CFTR modulation in reproduction: an imbalanced testicular microenvironment due to CFTR deficiency affects spermatogenesis and fertility in mice through the overactivation of spermatocyte caspase signalling, thus driving us to focus on updated treatments for CFTR deficiency-caused infertility.

Vas deferens

Chloride channel

10.1101/2022.11.16.516775

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Intracavernous injection of platelet‐rich plasma reverses erectile dysfunction of chronic cavernous nerve degeneration through reduction of prostate hyperplasia evidence from an aging‐induced erectile dysfunction rat model

The FASEB Journal (2023)

Huai‐Ching Tai Wei‐Kung Tsai Meng‐Lin Chang Chellappan Praveen Rajneesh Xiao‐Wen Tseng

Abstract Age‐induced erectile dysfunction (ED) is a convoluted medical condition, and restoring erectile function (EF) under geriatric conditions is highly complicated. Platelet‐rich plasma (PRP) treatment is an inexpensive cell‐based therapeutic strategy. We have aimed to restore EF in aged‐ED rats with PRP as a therapeutic tool. Male rats were grouped into aged and young according to age. The young rats were considered as normal control (NC) and treated with saline. Aged were further divided into 2 groups and treated with intracavernous (IC) PRP and saline. Treatment was scheduled at the 9th and 10th week for NC and 41th and 42th week for aged‐ED rats, with EF analysis scheduled on the 12th week for NC and 44th week for aged‐ED rats, respectively. Erectile response, immunofluorescence staining, and electron microscopic analyses were performed. IC PRP treatment effectively reduced prostate hyperplasia (PH). EF response indicated a significant increase in crucial EF parameters in PRP‐treated aged‐ED rats. Histological evidence denoted a rigid and restored development of tunica adventitia of the dorsal artery, decreased vacuolation of the dorsal penile nerve, and structural expansion of the epineurium. Masson's trichrome and immunostaining results affirmed an elevated expression of α‐smooth muscle actin (α‐SMA) in the corpus cavernosum (CC). Ultrastructure findings revealed that PRP effectively rejuvenated degenerating nerves, preserved endothelium and adherent junctions of corporal smooth muscle, and restored the axonal scaffolds by upregulating neurofilament‐H (NF‐H) expression. Finally, PRP enhanced neural stability by enhancing the axonal remyelination processes in aged‐ED rats. Hence, PRP treatment was proven to restore EF in aged‐ED rats, which was considered a safe, novel, cost‐effective, and hassle‐free strategy for EF restoration in geriatric patients.

Masson's trichrome stain

10.1096/fj.202201443r

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Citations (8)

List of contributors

Elsevier eBooks (2020)

Rouzbeh Abbassi Somdipta Bagchi Suman Bajracharya Manaswini Behera Udaratta Bhattacharjee

10.1016/b978-0-12-817493-7.00022-9

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