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Article ; Online: Prognostic and Clinical Implications of UNC13C expression in Hepatocellular Carcinoma Patients.

Kumar, V Bharath / Lee, Chien-Hsun / Su, Tzu-Cheng / Lin, Chia-Chieh / Mohammedsaleh, Zuhair M / Yeh, Chung-Min / Kiefer, Rudolf / Lin, Shu-Hui

International journal of medical sciences

2023 Volume 20, Issue 9, Page(s) 1235–1239

Abstract: Aberrant expression of UNC13C (Unc-13 Homolog C) has been observed during the progression of oral squamous cell carcinoma. However, the expression pattern and clinical relevance of UNC13C in Hepatocellular carcinoma (HCC) remain to be elucidated. The ... ...

Abstract	Aberrant expression of UNC13C (Unc-13 Homolog C) has been observed during the progression of oral squamous cell carcinoma. However, the expression pattern and clinical relevance of UNC13C in Hepatocellular carcinoma (HCC) remain to be elucidated. The purpose of this study is to examine UNC13C expression in HCC and explore its role in clinicopathological factor or prognosis in HCC. Two hundred and sixty-five patients diagnosed with HCC were included in the present study. The expression of UNC13C in HCC tissues was analyzed by immunohistochemistry analysis. The relationship between UNC13C protein and clinicopathological characteristics in HCC was investigated. Moreover, the high expression of UNC13C was significantly correlated with T stage, AJCC stage and overall survival rates. Cox regression analysis identified UNC13C as an independent prognostic indicator for HCC patients. UNC13C might be a prognostic biomarker and therapeutic target in HCC. Further studies with larger sample sets are needed to understand the clinical implications of UNC13C in hepatocellular carcinoma.
MeSH term(s)	Humans ; Biomarkers, Tumor/metabolism ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Squamous Cell ; Liver Neoplasms/diagnosis ; Mouth Neoplasms ; Prognosis ; Nerve Tissue Proteins/metabolism ; Membrane Proteins/metabolism
Chemical Substances	Biomarkers, Tumor ; UNC13C protein, human ; Nerve Tissue Proteins ; Membrane Proteins
Language	English
Publishing date	2023-08-06
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2151424-0
ISSN	1449-1907 ; 1449-1907
ISSN (online)	1449-1907
ISSN	1449-1907
DOI	10.7150/ijms.80488
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Article ; Online: Induction of Human Umbilical Mesenchymal Stem Cell Differentiation Into Retinal Pigment Epithelial Cells Using a Transwell-Based Co-culture System.

Chang, Yu-Hsun / Kumar, V Bharath / Wen, Yao-Tseng / Huang, Chih-Yang / Tsai, Rong-Kung / Ding, Dah-Ching

Cell transplantation

2022 Volume 31, Page(s) 9636897221085901

Abstract: There is an increasing interest in generating retinal pigment epithelial (RPE) cells from stem cells for treating degenerative eye diseases. However, whether human umbilical cord mesenchymal stem cells (HUCMSCs) can differentiate into RPE-like cells in a ...

Abstract	There is an increasing interest in generating retinal pigment epithelial (RPE) cells from stem cells for treating degenerative eye diseases. However, whether human umbilical cord mesenchymal stem cells (HUCMSCs) can differentiate into RPE-like cells in a co-culture system has not been fully understood. In this study, induction of HUCMSC differentiation into RPE-like cells was performed by co-culturing HUCMSCs and a human RPE-like cell line (ARPE19) in a transwell system and then analyzed for biomarkers using quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining technique. Moreover, the functional characterization of induced cells was carried out by examining their phagocytic and neurotrophic factor-secreting activities. Our results showed that mRNA expressions of RPE-specific markers-MITF, OTX2, RPE65, PEDF, PME17, and CRALBP-and protein markers-RPE65, CRALBP, and ZO-1-were significantly increased in HUCMSC-derived RPE-like cells. Functional characteristic studies showed that these induced cells were capable of engulfing photoreceptor outer segments and secreting brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF), which are typical functions of RPE-like cells. Overall, the study findings indicate that the morphology and proliferation of HUCMSCs can be maintained in a serum-free medium, and differentiation into RPE-like cells can be induced by simply co-culturing HUCMSCs with ARPE19 cells. Thus, the study provides fundamental information regarding the clinical-scale generation of RPE-like cells from HUCMSCs.
MeSH term(s)	Coculture Techniques ; Epithelial Cells ; Humans ; Mesenchymal Stem Cells ; Retinal Pigment Epithelium ; Retinal Pigments/metabolism
Chemical Substances	Retinal Pigments
Language	English
Publishing date	2022-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1135816-6
ISSN	1555-3892 ; 0963-6897
ISSN (online)	1555-3892
ISSN	0963-6897
DOI	10.1177/09636897221085901
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Zs.A 3556: Show issues

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Article: Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration.

Nhu, Nguyen Thanh / Xiao, Shu-Yun / Liu, Yijie / Kumar, V Bharath / Cui, Zhen-Yang / Lee, Shin-Da

Frontiers in integrative neuroscience

2022 Volume 15, Page(s) 747901

Abstract: Neural mitochondrial dysfunction, neural oxidative stress, chronic neuroinflammation, toxic protein accumulation, and neural apoptosis are common causes of neurodegeneration. Elamipretide, a small mitochondrially-targeted tetrapeptide, exhibits ... ...

Abstract	Neural mitochondrial dysfunction, neural oxidative stress, chronic neuroinflammation, toxic protein accumulation, and neural apoptosis are common causes of neurodegeneration. Elamipretide, a small mitochondrially-targeted tetrapeptide, exhibits therapeutic effects and safety in several mitochondria-related diseases. In neurodegeneration, extensive studies have shown that elamipretide enhanced mitochondrial respiration, activated neural mitochondrial biogenesis
Language	English
Publishing date	2022-01-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452962-X
ISSN	1662-5145
ISSN	1662-5145
DOI	10.3389/fnint.2021.747901
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Article: Identification and Biodegradation Potential of a Novel Strain of Kosakonia oryzae Isolated from a Polyoxyethylene Tallow Amine Paddy Soil

Nguyen, Ngoc Tuan / Pham, Thi Thanh Tra / Tran, Tuyet Nhung / Kumar, V. Bharath / Saikia, Surovi / Kiefer, Rudolf

Current microbiology. 2021 Aug., v. 78, no. 8

2021

Abstract: Polyoxyethylene tallow amine (POEA) is a nonionic surfactant added to insecticide and herbicide formulations. Experimental data have been shown the toxic effects of POEA on aquatic organisms and remain to be a serious concern. In this study, total of ... ...

Abstract	Polyoxyethylene tallow amine (POEA) is a nonionic surfactant added to insecticide and herbicide formulations. Experimental data have been shown the toxic effects of POEA on aquatic organisms and remain to be a serious concern. In this study, total of thirty-two potential bacteria that were isolated from herbicide-contaminated soil samples showed the ability to use POEA as the sole carbon and energy source. In which, a bacterial strain LA was further investigated based on the efficiency utilization of POEA and classified as Kosakonia oryzae by the 16S rRNA gene. Response surface methodology was successfully applied to understand the interaction of distinct factors on POEA degradation by LA strain. Degradation of POEA was confirmed with UV–Visible spectrophotometric analysis and HPLC analysis. The POEA utilization mechanism was explored by target gene detection and carbon source utilization. The results indicate that strain LA has the potential to serve as an in situ candidate for bioremediation polluted by POEA.
Keywords	biodegradation ; bioremediation ; carbon ; energy ; genes ; herbicides ; insecticides ; nonionic surfactants ; paddy soils ; response surface methodology ; spectral analysis ; toxicity ; ultraviolet-visible spectroscopy
Language	English
Dates of publication	2021-08
Size	p. 3173-3180.
Publishing place	Springer US
Document type	Article
ZDB-ID	134238-1
ISSN	1432-0991 ; 0343-8651
ISSN (online)	1432-0991
ISSN	0343-8651
DOI	10.1007/s00284-021-02592-9
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Article: Anticancer effects of picrasidine I on oral squamous cell carcinoma

Yang, Yuan‐Ting / Hsieh, Ming‐Ju / Chuang, Yi‐Ching / Lin, Chia‐Chieh / Lo, Yu‐Sheng / Ho, Hsin‐Yu / Kumar, V. Bharath / Ko, Jiunn‐Liang

Environmental toxicology. 2022 Mar., v. 37, no. 3

2022

Abstract: Picrasidine I is a dimeric alkaloid derived from a Southern Asian plant Picrasma quassioides and demonstrated to possess pharmacological activities, such as anti‐inflammatory and anti‐osteoclastogenic effects. However, its potential anticancer effect ... ...

Abstract	Picrasidine I is a dimeric alkaloid derived from a Southern Asian plant Picrasma quassioides and demonstrated to possess pharmacological activities, such as anti‐inflammatory and anti‐osteoclastogenic effects. However, its potential anticancer effect remains unclear. In the present study, anticancer activity of picrasidine I was assessed by treating oral squamous cell carcinoma cells with different concentrations of picrasidine I (20, 30, and 40 μM) for 24, 48, and 72 h. The findings revealed that picrasidine I reduced the cell viability in a dose‐dependent manner. Picrasidine I exerted its cytotoxic effect through arresting cell cycle at G2/M phase by downregulating cyclin A, cyclin B, CDK4, and CDK6, and inducing apoptosis in oral cancer cells. The induction of apoptosis was evidenced by increasing expression of death receptors, disruption of mitochondrial membrane potential, increased activation of PARP and caspases 3, 8, and 9, enhanced expression of proapoptotic mediators (Bak and Bim L/S), and reduced expression of antiapoptotic mediators (Bcl‐2 and Bcl‐xL). Moreover, analysis of MAPK signaling pathway revealed that picrasidine I‐mediated proapoptotic activities by downregulating JNK phosphorylation. Taken together, the study identifies picrasidine I as a potent anticancer agent that can be used as a therapeutic intervention against oral squamous cell carcinoma.
Keywords	Picrasma quassioides ; alkaloids ; antineoplastic activity ; antineoplastic agents ; apoptosis ; caspases ; cell viability ; cyclins ; cytotoxicity ; death ; dose response ; ecotoxicology ; membrane potential ; mitochondrial membrane ; mouth neoplasms ; phosphorylation ; squamous cell carcinoma ; therapeutics
Language	English
Dates of publication	2022-03
Size	p. 627-636.
Publishing place	John Wiley & Sons, Inc.
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	1463449-1
ISSN	1522-7278 ; 1520-4081
ISSN (online)	1522-7278
ISSN	1520-4081
DOI	10.1002/tox.23430
Database	NAL-Catalogue (AGRICOLA)

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Article: Increased NOTCH1 expression is associated with low survival in moderate/ poor differentiated human oral squamous cell carcinoma patients.

Mohammedsaleh, Zuhair M / Moawadh, Mamdoh S / Saleh, Fayez M / Jalal, Mohammed M / Al-Otaibi, Abdulaziz S / Saeedi, Nizar H / Baskaran, Rathinasamy / Huang, Chih-Yang / Kumar, V Bharath

Journal of Cancer

2023 Volume 14, Issue 16, Page(s) 3023–3027

Abstract: Notch deregulation has been reported in various types of cancers, including Oral squamous cell carcinomas (OSCCs). The role of Notch1 signaling in oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, NOTCH1 was aberrantly ... ...

Abstract	Notch deregulation has been reported in various types of cancers, including Oral squamous cell carcinomas (OSCCs). The role of Notch1 signaling in oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, NOTCH1 was aberrantly expressed in human oral cancer tissues compared with that in normal marginal tissues and was associated with poor prognosis. The positive Notch 1 expression was significantly associated with poor tumor differentiation status. Kaplan-Meier survival curves revealed that elevated cytoplasmic NOTCH1 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate COX proportional hazard models revealed that T N status, AJCC stage histological grade were independent prognostic factors for survival. Our result clearly demonstrates the oncogenic role of Notch1 in oral cancer and Notch1 may be a useful biomarker to target oral cancer patients.
Language	English
Publishing date	2023-09-18
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2573318-7
ISSN	1837-9664
ISSN	1837-9664
DOI	10.7150/jca.87128
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Article ; Online: 7-Epitaxol Induces Apoptosis and Autophagy in Head and Neck Squamous Cell Carcinoma through Inhibition of the ERK Pathway.

Kumar, V Bharath / Hsieh, Ming-Ju / Mahalakshmi, B / Chuang, Yi-Ching / Lin, Chia-Chieh / Lo, Yu-Sheng / Ho, Hsin-Yu / Lin, Jen-Tsun

Cells

2021 Volume 10, Issue 10

Abstract: As the main derivative of paclitaxel, 7-Epitaxol is known to a have higher stability and cytotoxicity. However, the anticancer effect of 7-Epitaxol is still unclear. The purpose of this study was to explore the anticancer effects of 7-Epitaxol in ... ...

Abstract	As the main derivative of paclitaxel, 7-Epitaxol is known to a have higher stability and cytotoxicity. However, the anticancer effect of 7-Epitaxol is still unclear. The purpose of this study was to explore the anticancer effects of 7-Epitaxol in squamous cell carcinoma of the head and neck (HNSCC). Our study findings revealed that 7-Epitaxol potently suppressed cell viability in SCC-9 and SCC-47 cells by inducing cell cycle arrest. Flow cytometry and DAPI staining demonstrated that 7-Epitaxol treatment induced cell death, mitochondrial membrane potential and chromatin condensation in OSCC cell lines. The compound regulated the proteins of extrinsic and intrinsic pathways at the highest concentration, and also increased the activation of caspases 3, 8, 9, and PARP in OSCC cell lines. Interestingly, a 7-Epitaxol-mediated induction of LC3-I/II expression and suppression of p62 expression were observed in OSCC cells lines. Furthermore, the MAPK inhibitors indicated that 7-Epitaxol induces apoptosis and autophagy marker proteins (cleaved-PARP and LC3-I/II) by reducing the phosphorylation of ERK1/2. In conclusion, these findings indicate the involvement of 7-Epitaxol in inducing apoptosis and autophagy through ERK1/2 signaling pathway, which identify 7-Epitaxol as a potent cytotoxic agent in HNSCC.
MeSH term(s)	Apoptosis/drug effects ; Autophagy/drug effects ; Caspases/metabolism ; Cell Cycle/drug effects ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Head and Neck Neoplasms/enzymology ; Head and Neck Neoplasms/pathology ; Humans ; MAP Kinase Signaling System/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; Squamous Cell Carcinoma of Head and Neck/enzymology ; Squamous Cell Carcinoma of Head and Neck/pathology ; Taxoids/chemistry ; Taxoids/pharmacology
Chemical Substances	Taxoids ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2021-10-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10102633
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Article ; Online: Identification and Biodegradation Potential of a Novel Strain of Kosakonia oryzae Isolated from a Polyoxyethylene Tallow Amine Paddy Soil.

Nguyen, Ngoc Tuan / Pham, Thi Thanh Tra / Tran, Tuyet Nhung / Kumar, V Bharath / Saikia, Surovi / Kiefer, Rudolf

Current microbiology

2021 Volume 78, Issue 8, Page(s) 3173–3180

Abstract	Polyoxyethylene tallow amine (POEA) is a nonionic surfactant added to insecticide and herbicide formulations. Experimental data have been shown the toxic effects of POEA on aquatic organisms and remain to be a serious concern. In this study, total of thirty-two potential bacteria that were isolated from herbicide-contaminated soil samples showed the ability to use POEA as the sole carbon and energy source. In which, a bacterial strain LA was further investigated based on the efficiency utilization of POEA and classified as Kosakonia oryzae by the 16S rRNA gene. Response surface methodology was successfully applied to understand the interaction of distinct factors on POEA degradation by LA strain. Degradation of POEA was confirmed with UV-Visible spectrophotometric analysis and HPLC analysis. The POEA utilization mechanism was explored by target gene detection and carbon source utilization. The results indicate that strain LA has the potential to serve as an in situ candidate for bioremediation polluted by POEA.
MeSH term(s)	Amines ; Biodegradation, Environmental ; Enterobacteriaceae ; Fats ; Polyethylene Glycols ; RNA, Ribosomal, 16S/genetics ; Soil ; Soil Microbiology ; Soil Pollutants
Chemical Substances	Amines ; Fats ; RNA, Ribosomal, 16S ; Soil ; Soil Pollutants ; Polyethylene Glycols (3WJQ0SDW1A) ; tallow (98HPY76U4W)
Language	English
Publishing date	2021-07-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	134238-1
ISSN	1432-0991 ; 0343-8651
ISSN (online)	1432-0991
ISSN	0343-8651
DOI	10.1007/s00284-021-02592-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1446: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
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Article ; Online: Anticancer effects of picrasidine I on oral squamous cell carcinoma.

Yang, Yuan-Ting / Hsieh, Ming-Ju / Chuang, Yi-Ching / Lin, Chia-Chieh / Lo, Yu-Sheng / Ho, Hsin-Yu / Kumar, V Bharath / Ko, Jiunn-Liang

Environmental toxicology

2021 Volume 37, Issue 3, Page(s) 627–636

Abstract: Picrasidine I is a dimeric alkaloid derived from a Southern Asian plant Picrasma quassioides and demonstrated to possess pharmacological activities, such as anti-inflammatory and anti-osteoclastogenic effects. However, its potential anticancer effect ... ...

Abstract	Picrasidine I is a dimeric alkaloid derived from a Southern Asian plant Picrasma quassioides and demonstrated to possess pharmacological activities, such as anti-inflammatory and anti-osteoclastogenic effects. However, its potential anticancer effect remains unclear. In the present study, anticancer activity of picrasidine I was assessed by treating oral squamous cell carcinoma cells with different concentrations of picrasidine I (20, 30, and 40 μM) for 24, 48, and 72 h. The findings revealed that picrasidine I reduced the cell viability in a dose-dependent manner. Picrasidine I exerted its cytotoxic effect through arresting cell cycle at G2/M phase by downregulating cyclin A, cyclin B, CDK4, and CDK6, and inducing apoptosis in oral cancer cells. The induction of apoptosis was evidenced by increasing expression of death receptors, disruption of mitochondrial membrane potential, increased activation of PARP and caspases 3, 8, and 9, enhanced expression of proapoptotic mediators (Bak and Bim L/S), and reduced expression of antiapoptotic mediators (Bcl-2 and Bcl-xL). Moreover, analysis of MAPK signaling pathway revealed that picrasidine I-mediated proapoptotic activities by downregulating JNK phosphorylation. Taken together, the study identifies picrasidine I as a potent anticancer agent that can be used as a therapeutic intervention against oral squamous cell carcinoma.
MeSH term(s)	Apoptosis ; Carbolines ; Carcinoma, Squamous Cell/drug therapy ; Cell Line, Tumor ; Head and Neck Neoplasms ; Humans ; Mouth Neoplasms/drug therapy ; Squamous Cell Carcinoma of Head and Neck
Chemical Substances	Carbolines ; picrasidine I
Language	English
Publishing date	2021-12-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1463449-1
ISSN	1522-7278 ; 1520-4081
ISSN (online)	1522-7278
ISSN	1520-4081
DOI	10.1002/tox.23430
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 2676: Show issues

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Article ; Online: AGR2 expression as a predictive biomarker for therapy response in esophageal squamous cell carcinoma.

Lin, Chih-Hung / Chuang, Han-Ni / Hsiao, Tzu-Hung / Kumar, V Bharath / Hsu, Chiung-Hung / Huang, Chih-Yang / Lee, Li-Wen / Mao, Chien-Lin / Ko, Jiunn-Liang / Hsu, Chung-Ping

PloS one

2022 Volume 17, Issue 11, Page(s) e0276990

Abstract: Despite multidisciplinary therapy, the prognosis is poor for esophageal squamous cell carcinoma (ESCC). In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery could provide survival benefits to some patients. Here, we ... ...

Abstract	Despite multidisciplinary therapy, the prognosis is poor for esophageal squamous cell carcinoma (ESCC). In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery could provide survival benefits to some patients. Here, we aimed to identify for tumor therapy response a biomarker based on RNA sequencing. We collected endoscopic biopsies of 32 ESCC patients, who were divided according to nCRT response, into two groups: the complete response group (n = 13) and the non-complete response group (n = 19). RNA-sequencing data showed that 464 genes were differentially expressed. Increased in non-complete response group, 4 genes increased expressions were AGR2 (anterior gradient 2), GADD45B (growth arrest and DNA damage inducible beta), PPP1R15A (protein phosphatase 1 regulatory subunit 15A) and LRG1 (leucine rich alpha-2-glycoprotein 1). The areas under the curve (AUC) of the AGR2 gene was 0.671 according to read counts of RNA-seq and therapy response of nCRT. In vitro study showed that apoptosis cell was significantly increased in the AGR2-knockdown TE-2 cell line treated with cisplatin and 5-Fluorouracil (5-FU), when compared with si-control. Results suggest that in ESCC, the AGR2 gene is a promising and predictive gene marker for the response to anti-tumor therapy.
MeSH term(s)	Humans ; Esophageal Squamous Cell Carcinoma/genetics ; Esophageal Squamous Cell Carcinoma/therapy ; Esophageal Neoplasms/therapy ; Esophageal Neoplasms/drug therapy ; Chemoradiotherapy/methods ; Neoadjuvant Therapy/methods ; Fluorouracil/pharmacology ; Fluorouracil/therapeutic use ; Biomarkers ; Esophagectomy/methods ; Mucoproteins/genetics ; Oncogene Proteins/genetics
Chemical Substances	Fluorouracil (U3P01618RT) ; Biomarkers ; AGR2 protein, human ; Mucoproteins ; Oncogene Proteins
Language	English
Publishing date	2022-11-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0276990
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