49 results on '"Muthusami, Sridhar"'
Search Results
2. Plumbagin as a preferential lead molecule to combat EGFR-driven matrix abundance and migration of cervical carcinoma cells
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Krishnamoorthy, Sneha, Sabanayagam, Rajalakshmi, Periyasamy, Loganayaki, Muruganantham, Bharathi, and Muthusami, Sridhar
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- 2024
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3. In vitro evaluation of p-coumaric acid and naringin combination in human epidermoid carcinoma cell line (A431)
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Velusamy, Pradeep, Muthusami, Sridhar, and Arumugam, Ramakrishnan
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- 2024
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4. Transforming growth factor-β micro-environment mediated immune cell functions in cervical cancer
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Gnanagurusamy, Jayapradha, Krishnamoorthy, Sneha, and Muthusami, Sridhar
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- 2024
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5. A comparative analysis of phyto-components on EGFR binding, viability, and migration in HPV positive ME180 and HPV negative C33A cervical cancer cells
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Sabanayagam, Rajalakshmi, Krishnamoorthy, Sneha, Anbuselvam, Mohan, Muruganantham, Bharathi, and Muthusami, Sridhar
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- 2023
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6. Fabrication and characterization of doxorubicin conjugated bimetallic gold and platinum nanoparticles for human cancer cells and its cell death mechanism
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Chinnathambi, Arunachalam, Alharbi, Sulaiman Ali, Meganathan, Velmurugan, Muthusami, Sridhar, and Arulselvan, Palanisamy
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- 2024
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7. EGCG attenuate EGF triggered matrix abundance and migration in HPV positive and HPV negative cervical cancer cells
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Sabanayagam, Rajalakshmi, Krishnamoorthy, Sneha, Gnanagurusamy, Jayapradha, Muruganatham, Bharathi, and Muthusami, Sridhar
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- 2023
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- View/download PDF
8. Plumbagin binds to epidermal growth factor receptor and mitigate the effects of epidermal growth factor micro-environment in PANC-1 cells
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Periyasamy, Loganayaki, Murugantham, Bharathi, and Muthusami, Sridhar
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- 2023
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9. Exploring the utility of FTS as a bonafide binding partner for EGFR: A potential drug target for cervical cancer
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Krishnamoorthy, Sneha, Muruganantham, Bharathi, Yu, Jae- Ran, Park, Woo- Yoon, and Muthusami, Sridhar
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- 2023
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10. Chapter 13 - Regulation of cancer stemness, cell signaling, reactive oxygen species, and microRNAs in cancer stem cells
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Chengizkhan, Gautham, Thangavelu, Sathish Kumar, Muthusami, Sridhar, Banerjee, Antara, Pathak, Surajit, Natarajan, Gopalan, Ramalingam, Satish, Queimado, Lurdes, Kumaran, R. Ileng, and Ramachandran, Ilangovan
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- 2024
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11. Chapter 11 - Pancreatic cancer stem cells and inflammation: milestones achieved and challenges ahead
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Periyasamy, Loganayaki, Krishnamoorthy, Sneha, Muruganantham, Bharathi, Ramachandran, Ilangovan, and Muthusami, Sridhar
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- 2024
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12. Chapter 12 - Stem cell aging: role of signaling pathways and microRNAs
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Muthusami, Sridhar, Mohan, Manju, Krishnamoorthy, Sneha, Kanagaraj, Palaniyandi, Kumaran, R. Ileng, Dharmarajan, Arun, Ramachandran, Ilangovan, and Bhaskaran, Natarajan
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- 2024
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13. Chapter 17 - Endocrine regulation of phospholipase as a therapeutic target for cardiovascular diseases
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Rajendran, Meenakshi Sundari, Bhaskaran, Sreenath K., Vani Raju, Manikandan, Madathil, Sri Rashmy, Muthaiya Ahalliya, Rathi, Muthusami, Sridhar, and Kannappan, Poornima
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- 2023
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14. Chapter 10 - Targeting phospholipase C using synthetic inhibitors of EGFR signaling for cancer treatment
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Krishnamoorthy, Sneha, Periyasamy, Loganayaki, Jayapradha, G., Sabanayagam, Rajalakshmi, Elango, Hemnath, Vishwanathan, M., and Muthusami, Sridhar
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- 2023
- Full Text
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15. EGF-induced expression of Fused Toes Homolog (FTS) facilitates epithelial–mesenchymal transition and promotes cell migration in ME180 cervical cancer cells
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Muthusami, Sridhar, Prabakaran, D.S., Yu, Jae-Ran, and Park, Woo-Yoon
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- 2014
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16. FTS is responsible for radiation-induced nuclear phosphorylation of EGFR and repair of DNA damage in cervical cancer cells
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Muthusami, Sridhar, Prabakaran, D. S., Yu, Jae-Ran, and Park, Woo-Yoon
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- 2015
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17. T0070907, a PPAR γ Inhibitor, Induced G2/M Arrest Enhances the Effect of Radiation in Human Cervical Cancer Cells Through Mitotic Catastrophe
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An, Zhengzhe, Muthusami, Sridhar, Yu, Jae-Ran, and Park, Woo-Yoon
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- 2014
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18. List of contributors
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Aarthi, V., Abrahamse, Heidi, Adhikary, Subhamay, Agarwal, Sparsh, Ahmed, Osama M., Allahverdi, Amir, Amalinei, Cornelia, Anbalagan, Muralidharan, Asadi, Fatemeh, Ashokkumar, Swetha, Balakrishnan, Anandan, Banerjee, Antara, Basak, Sanjay, Basalingappa, Kanthesh M., Baskaran, Ravishankar, Beyaztas, Hakan, Bhagavatheeswaran, Sambhavi, Bhasin, Nobel, Bishayee, Kausik, Bitla, Shreeja, Bozali, Kubra, Chaaudhary, Somya, Chandran, Rahul, Chatterjee, Bhaswati, Chattopadhyay, Indranil, Chengizkhan, Gautham, Chhetri, Dibyashree, Chinnadurai, Raj Kumar, Corrales, Elizabeth, Dabral, Prerna, Darko, Samuel, Das, Amitava, Dawes, McKenna, Dey, Amit, Didamson, Onyisi Christiana, Dumlu, Fatma Sena, Dutt, Shilpee, Ellis, Beanca, Garg, Khushi, Garg, Sandini, Ghosh, Amlan, Gnanasampanthapandian, Dhanavathy, Gobianand, Kuppannan, Gopan, Pournami, Gopenath, T.S., Gor, Ravi, Grigoraş, Adriana, Guler, Eray Metin, Hernandez, Erika, Huisso, Ayivi, Jayaraman, Selvaraj, Joassaint, Naphtalie, Karri, Urekha, Kathpalia, Meghavi, Kaur, Navkiran, Khan, Hafsa, Koc, Sumeyye, Krishnamoorthy, Kalaiselvi, Krishnamoorthy, Sneha, Kumar, Dinesh, Kumar, Rajappan Chandra Satish, Kumar, Subodh, Kumar, Vijay, Kumar Das, Jayanta, Kumaran, R. Ileng, M.N., Ramesh Bharadwaj, Madhumita Das, Majhi, Anjoy, Manzon, Alessandra, Morsy, Hadeer M., Moses, Leah, Munirathinam, Gnanasekar, Munuswamy-Ramanujam, Ganesh, Muruganantham, Bharathi, Muthusami, Sridhar, Narayan, Shoba, Natarajan, Aravindan, Natarajan, Gopalan, Nehru, Mohanraj, Ozkan, Beyza Nur, Palaniyandi, Kanagaraj, Palol, Varsha Virendra, Panigrahi, Ankita, Panneerselvam, Swetha, Pathak, Nishtha, Pathak, Surajit, Paul, Sandip, Paul, Solomon F.D., Periyasamy, Loganayaki, Pirsadeghi, Ali, Ponnusamy, Bhuvaneswari, Prabhu, Venkatraman, Pricope, Diana-Lavinia, Queimado, Lurdes, R., Mythreyi, Rajagopal, Ponnulakshmi, Ramachandran, Ilangovan, Ramalingam, Ravi, Ramalingam, Satish, Saha, Anwesha, Saha, Linkon, Saravanan, Suresh Kumar, Saunders, Myra, Sehgal, Rashi, Selvendiran, Karuppaiyah, Sherman, Marilyn, Shivhare, Surbhi, Singh, Bhawna, Sohani, Advait, Somasundaram, Dinesh Babu, Stella, John H., Stiffin, Rose Mary, Subramanian, Poorvi, Subramanian, Prasanth, Subramanyam, Veni, Sundaram, Jagan, Thakur, Shriya, Thakur, Suman S., Thangaraj, Kavitha R., Thangavelu, Sathish Kumar, Thomas, Amy, Varma, Saikanth, Veeraraghavan, Vishnupriya, Verma, Ranjan, Verma, Yogesh Kumar, Vijay, Amulya, Volety, Pranav, Yadav, Rahul, Yearde, Oneilia, Yousefi-Ahmadipour, Aliakbar, and Zaky, Mohamed Y.
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- 2024
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19. List of contributors
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Adhikari, Subhamay, Agraharam, Gopikrishna, Ahmadi, Amir Moghadam, Ahmed, Noha A., Ahmed, Osama M., Almoiliqy, Marwan, Arul Jothi, K.N., Asir, A. Billy, Ayoobi, Fatemeh, Bahşi, Mert, Banerjee, Antara, Basalingappa, Kanthesh M., Bhaskaran, Natarajan, Bisgin, Atil, Boga, Ibrahim, Çelenk, Alper, Chauhan, Nishtha, Chawla, Shilpa, Chopra, Tanishqua, Cyril, Rozario, Das, Alakesh, Das, Amitava, Dave, Megha, Devadarshini, P., Devi, Arikketh, Dey, Amit, Dharmarajan, Arun, Dhinekaran, Aishwarya, Di Liddo, Rosa, Ezgin, Neriman, Ghosh, Asit Ranjan, Girigoswami, Agnishwar, Girigoswami, Koyeli, Gobianand, K., Gopenath, T.S., Gottardi, Michele, Govindan, Ramajayam, Graceline, Hepzibah, Harini, Karthick, Hemarangan, J., Iffath, Aainaaz I., Iyshwarya, B.K., Jamali, Zahra, Jayaraman, Selvaraj, Jayasree, R., Kalimuthu, Senthilkumar, Kamath, Gayathri S., Kanagaraj, Palaniyandi, Kandir, Sinan, Kaya, Meltem, Keerthi, N., Krishnamoorthy, Sneha, Kulanthaivel, Langeswaran, Kumaran, K., Kumaran, R. Ileng, Lakshmi, Mallela, Lamloum, Nahed S., Latheef, Fidha, Leemon, Nikhila, Maity, Shreya, Maity, Sukhendu, Marotta, Francesco, Mathangi, Damal Chandrasekar, Mohan, Manju, Mukherjee, Raktim, Muthusami, Sridhar, Mythreyi, R., Natarajan, Pandiyan, Nidhu, A.B., Pandiyan, Radha, Panicker, Sreejith Parameswara, Panneerselvam, Swetha, Pathak, Surajit, Patni, Anjali P., Ponnusamy, Bhuvaneswari, Poomarimuthu, Maheshkumar, Pramanick, Kousik, Rajagopal, Ponnulakshmi, Rajasekaran, P.N., Ramachandran, Ilangovan, Ramachandran, Veerakumar, Ramalingam, Satish, Ramesh Bharadwaj, M.N., Sasikumar, Greeshma, Sharma, Girish, Shriya, P., Sivamani, Ganesan, Sreeshma, Bhuvanadas, Subbaraj, Gowtham Kumar, Sudhakar Bhalerao, Supriya, Thangam, C., Thanikachalam, Puvithra, Tuna, Gamze, Varshini, Murugesan Amirtha, Vasanth Kanth, T.L., Veerabathiran, Ramakrishnan, Veeraraghavan, Vishnupriya, Venkataraman, P., Vijay Murali, R.M., Vinothkumar, G., Yassin, Nour Y.S., Yousefi-Ahmadipour, Aliakbar, Yılmaz, Selda, and Zaky, Mohamed Y.
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- 2024
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20. Cissus quadrangularis augments IGF system components in human osteoblast like SaOS-2 cells
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Muthusami, Sridhar, Ramachandran, Ilangovan, Krishnamoorthy, Senthilkumar, Govindan, Ramajayam, and Narasimhan, Srinivasan
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- 2011
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21. Cordycepin increases radiosensitivity in cervical cancer cells by overriding or prolonging radiation-induced G2/M arrest
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Seong, Da Bin, Hong, Semie, Muthusami, Sridhar, Kim, Won-Dong, Yu, Jae-Ran, and Park, Woo-Yoon
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- 2016
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22. EGCG suppresses Fused Toes Homolog protein through p53 in cervical cancer cells
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Muthusami, Sridhar, Prabakaran, D. S., An, Zhengzhe, Yu, Jae-Ran, and Park, Woo-Yoon
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- 2013
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23. Chapter 14 - Cellular senescence and aging in bone
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Mohan, Manju, Muthusami, Sridhar, Selvamurugan, Nagarajan, Narasimhan, Srinivasan, Kumaran, R. Ileng, and Ramachandran, Ilangovan
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- 2021
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24. Evaluation of Anticancer Potential of Mimosa diplotricha Ethanolic Leaf Extract on N-Methyl-N-Nitroso Urea Induced Colorectal Carcinogenesis in Wistar Albino Rats.
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Madathil, Sri Rashmy, Kannappan, Poornima, Muthusami, Sridhar, Muneeswari, Perumalsamy, and Periyasamy, Loganayaki
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LABORATORY rats ,TRANSFORMING growth factors-beta ,MIMOSA ,TUMOR markers ,BIOMARKERS ,TRANSFORMING growth factors ,SOMATIC embryogenesis - Abstract
Background: Colorectal Cancer, (CRC) ranks third among global cancer incidence statistics and occupies fourth position as far as cancer related death is concerned and the aim of the study is to evaluate the therapeutic potential of Mimosa diplotricha ethanolic leaf extract in chemically induced colorectal carcinogenesis in Wistar albino rats. Materials and Methods: CRC was induced by intrarectal instillation of N-Methyl-N-Nitrosourea (MNU), 2mg per rat in 0.5ml of distilled water three times a week for five weeks. Rats were grouped as control, induced, induced and standard drug treated (15mg/kg.bw), induced and plant extract treated (in two doses 200mg/kg.bw and 400mg/kg.bw) and normal rats with respective plant extract treatment (200mg/kg.bw and 400mg/kg.bw). Treatment were carried out for 60 days followed which animals were euthanized and serum markers, oxidative stress, microbial enzymatic, histological and immunohistochemical parameters were analysed. Results: M. diplotricha was found to be effective in the down regulation of serum inflammatory and tumour markers like tumour necrosis factor alpha, transforming growth factor beta, carcinoembryogenic antigen and colon cancer specific antigen-4 levels. Oxidative stress parameters and histological data also supported the therapeutic efficacy of M. diplotricha. Expression of anti-apoptotic protein Bcl-2 was also found be downregulated in induced animals treated with M. diplotricha as evident from immunohistochemical data. Conclusion: The results of present research suggest that M. diplotricha ethanolic leaf extract showed a significant therapeutic potential against chemically induced colorectal carcinogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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25. Contributors
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Ahmed, Eman A., Ahmed, Osama M., Alam, Md Iqbal, Anand, Rahul, Anifandis, George, Anwar, Md Omair, Ayyappan, Prathapan, Bagchi, Angshuman, Belaunzarán, María Laura, Ben Bacha, Abir, Bhaskaran, Sreenath K., Biswas, Sima, Bodosa, Sidhi Soran Barman, Cai, Song, Chakraborti, Sajal, Chakraborti, Tapati, Chowdhury, Dibyapriya Roy, Dam, Somasri, Daponte, Alexandros, El-Ansary, Afaf, Fonteh, Alfred N., Ghone, Urmi, Ghosh, Mahasweta, Ghosh, Priyanka, Ghosh, Raktim, Gupta, Girdhari Lal, Hassan, Sohair Aly, Hazarika, Disha, Hösch, Natália G., Islam, Md Muzahidul, Iyshwarya, B.K., Jain, Shilpi, James, Joel, Kannappan, Poornima, Kruthica, J.G., Kumar Ebenezar, K., Leong, Vincent, Lipinski, Marta M., Ma, Rong, Madathil, Sri Rashmy, Maiti, Amit K., Malhotra, Pawan, Mandal, Amritlal, Messini, Christina I., Messinis, Ioannis E., Mohmmed, Asif, Muthaiya Ahalliya, Rathi, Muthusami, Sridhar, Niazi, Nasar Ullah Khan, Pakshir, Keyvan, Pal, Suchetana, Pingle, Tanvi, Quasimi, Huma, Rajendran, Meenakshi Sundari, Samant, Nikita Patil, Santhi Priya, S., Sarkar, Chinmoy, Sarkar, Jaganmay, Sarkar, Subhasish, Sarode, Gargi, Sarode, Sachin, Sengupta, Namrata, Shankarishan, Priyanka, Soumya, R.S., Vani Raju, Manikandan, Varghese, Mathews Valuparampil, Veerabathiran, Ramakrishnan, Wazib, Sheema, and Zambelli, Vanessa O.
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- 2023
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26. Contributors
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Ahmedi, Saiema, Arockiasamy, Prisilla, Bansal, Isha, Banudevi, Sivanantham, Bhattacharya, Sanjib, Chakraborti, Sajal, Chandralekha A.S., Chattopadhyay, Bitan Kumar, Dadmehr, Majid, Das, Simita, Delik, Anıl, Dey, Subhankar, Elango, Abinaya, Elango, Hemnath, Garg, Khushi, Giriraju, Dhananjaya, Indu, Sabapathy, Jayapradha, G., Josephinol, Savariyar, Krishnamoorthy, Sneha, Leskovac, Andreja, Mahanta, Nilkamal, Mahapatra, Manas K., Maiti, Arunima, Mandal, Chandi C., Manzoor, Nikhat, Murugan, Kumar Kalavthi, Muthusami, Sridhar, Nunia, Vandana, Panicker, Sreejith Parameswara, Pattanayakanahalli Henjarappa, Krushnamurthy, Periyasamy, Loganayaki, Petrovic, Sandra, Pourahmad, Jalal, Pugalendhi, Madhanraj Akilandeswari, Qureshi, Sameer, Radhakrishnan, Arunkumar, Raga, S.S., Rajalakshmi, Manikkam, Rana, Tanmoy, Roy, Amitava, Roy, Paromita, Ruwali, Munindra, Sabanayagam, Rajalakshmi, Sikdar, Nilabja, Soumya, V.S., Srinivasan, Sriram, Suresh, Anjana, Suresh, Surya, Ülger, Yakup, Veerabathiran, Ramakrishnan, Vijayalakshmi, Periyasamy, Vishwanathan, M., and Yousefsani, Bahareh Sadat
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- 2023
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27. A review on the role of epidermal growth factor signaling in the development, progression and treatment of cervical cancer.
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Muthusami, Sridhar, Sabanayagam, Rajalakshmi, Periyasamy, Loganayaki, Muruganantham, Bharathi, and Park, Woo Yoon
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- *
EPIDERMAL growth factor , *EPIDERMAL growth factor receptors , *CERVICAL cancer , *GROWTH factors , *PROTEIN-tyrosine kinase inhibitors - Abstract
The sub-committee constituted by the Indian Council of Medical Research (ICMR) for the management of cervical cancer (CC) detailed in the consensus document (2016) reported CC as a significant cause of morbidity and mortality in women. The incidence of an increase in CC and associated mortality in women is a major cause of cancer. To date, human papilloma viral (HPV) infection accounts for more than 99% of CC. However, there are individuals infected with HPV do not develop CC. There is a greater correlation between HPV infection and upregulation of the epidermal growth factor receptor (EGFR) signaling cascade during the initiation, sustenance, and progression of CC. Therefore, EGFR is often targeted to treat CC using tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAB). The current review analyzed the existing clinical/pre-clinical studies and the significance of EGFR abundance using the Kaplan–Meier (KM) survival plot analysis for disease-free survival (DFS) and overall survival (OS). We performed a series of bioinformatics analyses to screen the crucial role of the EGFR gene in CC. Further, different transcription factors that are dysregulated due to EGFR abundance and their relevance were determined using computational tools in this review. Endogenous microRNAs (miRNA) that undergo changes due to alterations in EGFR during CC were identified using computational database and consolidated the information obtained with the published in the area of miRNA and EGFR with special reference to the initiation, sustenance and progression of CC. The current review aims to consolidate contemporary approaches for targeting CC using EGFR and highlight the current role of miRNA and genes that are differently regulated during CC involving EGFR mutations. Potential resistance to the available EGFR therapies such as TKIs and mABs and the need for better therapies are also extensively reviewed for the development of newer therapeutic molecules with better efficacy. [ABSTRACT FROM AUTHOR]
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- 2022
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28. Ovariectomy induces oxidative stress and impairs bone antioxidant system in adult rats
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Muthusami, Sridhar, Ramachandran, Ilangovan, Muthusamy, Balaganesh, Vasudevan, Gopalakrishnan, Prabhu, Venkataraman, Subramaniam, Veni, Jagadeesan, Arunakaran, and Narasimhan, Srinivasan
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- 2005
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29. Molecular genetics involved in the pathogenesis of colorectal cancer: a review.
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MADATHIL, SRI RASHMY, KANNAPPAN, POORNIMA, MUTHUSAMI, SRIDHAR, and MUNEESWARI, PERUMALSAMY
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COLORECTAL cancer ,MOLECULAR genetics ,MICROSATELLITE repeats ,BIOLOGICAL crosstalk ,CANCER invasiveness ,BIOMARKERS - Abstract
Colorectal Cancer, (CRC) is the third most frequently diagnosed neoplasm globally and found to be a major cause of mortality in terms of gastrointestinal malignancy. Risk factors associated with CRC development include hereditary factors, age, lifestyle, defective alimentary habit and chronic gastric inflammation. Molecular genetics of CRC is highly heterogeneous and involves accumulation of genetic and epigenetic mutation. Genetic variants of CRC include Chromosomal Instability (CIN), Microsatellite Instability (MSI) and CpG Island Methylation Phenotype (CIMP) involving crosstalk between various molecular signaling pathways like Wnt/ß-catenin, PI3K/AKT pathway, NF-kB pathway etc and a consortium of genes and proteins contributing in whole process of neoplasm onset and progression. An understanding of genetic mechanism will help in developing novel biomarkers for better diagnosis and effective treatment strategies by targeting genes and molecular signaling pathways involved in evolution of carcinoma. Upgrading molecular genetics will help in developing novel approaches in targeted therapy employing monoclonal antibodies. Following review provides a basic overview of genetic mechanism involved in colorectal carcinoma. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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30. Contributors
- Author
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Akila, M., Ali, Aamina, Anbalagan, Muralidharan, Arias, Nataly, Ayala, Antonio, Balakrishnan, Anandan, Balakrishnan, Baskar, Balasubramanian, Sundaravadivel, Banerjee, Antara, Banu, L. Husaina, Barrios, Albert, Bhaskaran, Natarajan, Bhatiya, Meenu, Bhattacharyya, Sinjini, Bisgin, Atil, Bizzaro, Debora, Burra, Patrizia, Catanzaro, Roberto, Chakravarty, Shouvik, Chatterjee, Bhaswati, Das, Alakesh, Das, Sreemanti, Deka, Dikshita, Devaraj, Ezhilarasan, Devi, Arikketh, Elizabeth, K. Roshini, Girigoswami, Agnishwar, Girigoswami, Koyeli, Gopikar, A. Sai Rishika, Grajeda, Yander, He, Fang, Ileng Kumaran, R., Jain, Mayur Vilas, Jangamreddy, Jaganmohan R., Jayaraman, Selvaraj, Joseph, Joel P., Khuda-Bukhsh, Anisur Rahman, Macrin, D., Marotta, Francesco, Metkar, Sanjay Kisan, Mohan, Manju, Muthusami, Sridhar, Narasimhan, Srinivasan, Opara, Emmanuel C., Palaniyandi, Kanagaraj, Pathak, Surajit, Patni, Anjali P., Pavane, M.S., Periyasamy, Vijayalakshmi, Pervin, Shehla, Rafi, Shabana Thabassum Mohammed, Rajagopal, Ponnulakshmi, Rajasingh, Johnson, Rajendran, Vijayalakshmi, Ramachandran, Ilangovan, Ramachandran, Vinu, Ramalingam, Satish, Reddy, Sakamuri V., Russo, Francesco Paolo, Samadder, Asmita, Sambandam, Yuvaraj, Selvamurugan, Nagarajan, Sharma, Sumit, Singh, Rajan, Sittadjody, Sivanandane, Subramanyam, Deepa, Thakur, Suman S., Thangasamy, Thilakavathy, Thathapudi, Neethi Chandra, Tiwari, Mahak, and Yazdani, Azam
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- 2021
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31. Silencing of FTS increases radiosensitivity by blocking radiation-induced Notch1 activation and spheroid formation in cervical cancer cells.
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Prabakaran, D.S., Muthusami, Sridhar, Sivaraman, T., Yu, Jae-Ran, and Park, Woo-Yoon
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CERVICAL cancer , *RADIATION-sensitizing agents , *SPHEROIDAL state , *IMMUNOPRECIPITATION , *NOTCH signaling pathway - Abstract
Abstract Increasing evidence(s) suggests that cancer stem cells (CSC) in tumours contribute to radio-resistance and recurrence. Notch plays an important role in the maintenance of CSC in many cancers including cervical cancer. Previously, we have reported the role of Fused Toes Homolog (FTS) in conferring radioresistance in cervical cancer cells in vitro and human subjects. The present study investigated the regulatory role of FTS in Notch signaling and maintenance of CSC upon irradiation of cervical cancer cells. The expression of Notch1, 2, 3, cleaved Notch1 and its downstream target Hes1, and spheroid formation was increased by irradiation. Silencing of FTS prevented the radiation-induced increase in the expression of Notch signaling molecules and spheroid formation. Immunoprecipitation showed FTS binds Notch1 and Hes1. Also in silico structural analysis identified putative residues responsible for the binding between FTS and Notch1. Spheroid formation and the expression of CSC markers, Nanog, Oct4A and Sox2 were greatly reduced by combining silencing of FTS and radiation. Taken together, these results suggest that FTS is involved in the regulation of irradiation-induced Notch signaling and CSC activation and can be used as a target to increase radiosensitivity in cervical cancer. [ABSTRACT FROM AUTHOR]
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- 2019
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32. Hormonal alterations in PCOS and its influence on bone metabolism.
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Krishnan, Abhaya and Muthusami, Sridhar
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POLYCYSTIC ovary syndrome , *BONE metabolism , *DISEASES in women - Abstract
According to the World Health Organization (WHO) polycystic ovary syndrome (PCOS) occurs in 4-8% of women worldwide. The prevalence of PCOS in Indian adolescents is 12.2% according to the Indian Council of Medical Research (ICMR). The National Institute of Health has documented that it affects approximately 5 million women of reproductive age in the United States. Hormonal imbalance is the characteristic of many women with polycystic ovarian syndrome (PCOS). The influence of various endocrine changes in PCOS women and their relevance to bone remains to be documented. Hormones, which include gonadotrophin-releasing hormone (GnRH), insulin, the leutinizing/follicle-stimulating hormone (LH/FSH) ratio, androgens, estrogens, growth hormones (GH), cortisol, parathyroid hormone (PTH) and calcitonin are disturbed in PCOS women. These hormones influence bone metabolism in human subjects directly as well as indirectly. The imbalance in these hormones results in increased prevalence of osteoporosis in PCOS women. Limited evidence suggests that the drugs taken during the treatment of PCOS increase the risk of bone fracture in PCOS patients through endocrine disruption. This review is aimed at the identification of the relationship between bone mineral density and hormonal changes in PCOS subjects and identifies potential areas to study bone-related disorders in PCOS women. [ABSTRACT FROM AUTHOR]
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- 2017
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33. Cissus quadrangularis prevented the ovariectomy induced oxidative stress in the femur of adult albino rats.
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Muthusami, Sridhar, Gopalakrishnan, Vasudevan, Stanley, Jone A., Krishnamoorthy, Senthilkumar, Ilangovan, Ramachandran, Gopalakrishnan, Velliyur K., and Srinivasan, Narasimhan
- Subjects
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OXIDATIVE stress , *CISSUS , *OVARIECTOMY , *FEMUR , *LABORATORY rats , *FEMORAL artery , *LIPID peroxidation (Biology) , *PREVENTION - Abstract
The increasing evidence suggesting the role of free radicals in bone resorption and bone loss prompted us to explore whether the consumption of antioxidant rich medicinal plant C. quadrangularis modifies antioxidant status in ovariectomized rats. Methods Twenty four female adult rats, 90 days old showing regular estrous cycles were used for the present study. The animals were divided into two groups. The Group-1 rats (n = 6) were sham operated and Group-II rats were bilaterally ovariectomized (n = 18) and treated with C. quadrangularis for sixty days (100 mg/ kg body weight and 250 mg/kg body weight). After sixty days, the rats were killed, femora were dissected out, minced and homogenized in Tris-HCl buffer (pH 7.4) and the supernatant was collected and used for biochemical assays. Results Ovariectomy registered a decrease (p<0.05) in the activities of SOD, GPx, GST, ALP, collagen content and increased (p<0.05) the activities of TRAP and lipid peroxidation. Simultaneous administration of C. quadrangularis maintained the enzyme activities in ovariectomized rats. Conclusion C. quadrangularis , a natural herb may be used to treat the estrogen deficiency/menopause onset and ovariectomy induced oxidative stress. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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34. Ameliorative effect of vitamin C on hexavalent chromium-induced delay in sexual maturation and oxidative stress in developing Wistar rat ovary and uterus.
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Samuel, Jawahar B, Stanley, Jone A, Vengatesh, Ganapathy, Princess, Rajendran A, Muthusami, Sridhar, Roopha, Dailiah P, Suthagar, Esakky, Kumar, Kathiresh M, Sebastian, Maria S, and Aruldhas, Michael M
- Subjects
VITAMIN C ,HEXAVALENT chromium ,CARBOHYDRATE metabolism ,OXIDATIVE stress ,OVARIAN diseases ,UTERINE diseases ,POLLUTANTS ,LABORATORY rats - Abstract
Hexavalent chromium (CrVI) is a highly toxic metal and major environmental pollutant and is extensively used in more than 50 industries. The major route of CrVI exposure for the general population is oral intake. Chromium is considered an important nutrient responsible for carbohydrate metabolism. However, excess CrVI exposure is associated with various pathological conditions including reproductive dysfunction. CrVI can traverse the placental barrier and cause wide range of abnormalities in fetal development. Cr is transported to offspring through mother’s milk in lactating women exposed to CrVI. Therefore, the present study was carried out to determine the toxic effects of lactational CrVI exposure on ovary and uterus and the beneficial role of vitamin C in preventing/ameliorating the toxic effects of CrVI in developing female Wistar rats. Generation of oxidative stress is considered one of the plausible mechanisms behind Cr-induced cellular deteriorations. The present study evidenced a decrease in the specific activities of antioxidants, serum testosterone and progesterone and an increase in the levels of H2O2, lipid peroxidation (LPO) and follicle stimulating hormone in rats exposed to CrVI when compared to control. CrVI exposure also delayed the sexual maturation and extended the estrous cycle. Simultaneous administration of vitamin C significantly prevented the increase in LPO and enhanced the antioxidant status. These results suggest the protective effect of vitamin C against the CrVI exposure-induced toxicity and attest the significance of antioxidants in diet. [ABSTRACT FROM PUBLISHER]
- Published
- 2012
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35. Effects of Cissus quadrangularis on the proliferation, differentiation and matrix mineralization of human osteoblast like SaOS-2 cells.
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Muthusami, Sridhar, Senthilkumar, Krishnamoorthy, Vignesh, Chandragandan, Ilangovan, Ramachandran, Stanley, Jone, Selvamurugan, Nagarajan, and Srinivasan, Narasimhan
- Published
- 2011
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36. Inhibitory effects of Gracilaria edulis and Gracilaria salicornia against the MGMT and VEGFA biomarkers involved in the onset and advancement of glioblastoma using in silico and in vitro approaches.
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Vasudevan, Miji Thandaserry, Rangaraj, Kaviyaprabha, Ramesh, Ragupathi, Muthusami, Sridhar, Govindasamy, Chandramohan, Khan, Muhammad Ibrar, Arulselvan, Palanisamy, and Muruganantham, Bharathi
- Subjects
- *
EPIDERMAL growth factor receptors , *VASCULAR endothelial growth factors , *BRAIN tumors , *ROOT-mean-squares , *GENE expression , *METHYLGUANINE - Abstract
Glioblastoma (GBM), an aggressive primary brain tumor originating from glial cells, poses significant treatment challenges due to its rapid growth and invasiveness. The exact mechanisms of GBM's brain damage remain unclear. This study examines primary molecular markers commonly assessed in GBM patients, including brain‐derived neurotrophic factor (BDNF), platelet‐derived growth factor receptor A (PDGFRA), O6‐methylguanine DNA methyltransferase (MGMT), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor A (VEGFA) using computational approaches. The study revealed significant differences (
p ≤ 0.05) in PDGFRA, EGFR, and VEGFA expression rates, which are particularly interesting. Additionally, MGMT and VEGFA showed higher hazard ratios. Expression levels of MGMT and VEGFA were visualized in immune and malignant cells using single‐cell RNA datasets GSE103224 and GSE148842. From a total of 48 compounds inGracilaria edulis and 86 inGracilaria salicornia , we identified 15 compounds capable of crossing the blood‐brain barrier. Notably, 2‐tridecanone (binding affinity [BA] = −4.2 kcal/mol; root mean square deviation [RMSD] = 1.479 Å) and decanoic acid, ethyl ester (BA = −4.2 kcal/mol; RMSD = 1.702 Å) fromG. edulis interacted with MGMT via hydrogen bonds. The compound alpha‐terpineol interacted with MGMT (BA = −5.7 kcal/mol; RMSD = 0.501 Å) and VEGFA (BA = −4.7 kcal/mol; RMSD = 2.483 Å). Ethanolic and methanolic extracts fromG. edulis andG. salicornia demonstrated mild anti‐cell proliferation properties in the GBM LN‐229 cell line, suggesting potential therapeutic benefits. This study highlights the significance of molecular markers and natural compounds in understanding and potentially treating GBM. [ABSTRACT FROM AUTHOR]- Published
- 2024
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37. Zaleya decandra exerts anti-cancer activity in HCT-116 cancer cells by impairing mitochondrial activity.
- Author
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Deivasigamani, Malarvizhi, Chandrasekar, Ajay Kasivishwanathan, Muthusami, Sridhar, Kanniappan, Gopalakrishnan Velliyur, and Lakshmanan, Hariprasath
- Subjects
- *
CANCER cells , *MEMBRANE permeability (Biology) , *ACRIDINE orange , *COLON cancer , *MITOCHONDRIAL membranes , *CASPASES - Abstract
An attempt has been made to investigate the role of Zaleya decandra on the survival of HCT colon cancer cells in vitro. The cell viability and apoptosis were assessed using MTT assay and acridine orange/ethidium bromide staining, respectively. Mitrochondrial membrane permeability was assessed using rhodamine-123 staining. The activities of caspases were evaluated using ELISA kits. Treatment with Z. decandra extract increased the production of ROS in HCT cells and impaired the mitochondrial activity as evidenced by decreased reduction of tetrazolium salt and enhanced mitochondrial membrane permeability. The onset of apoptosis was evident in cells treated with the extact in acridine orange/ethidium bromide staining and was associ-ated with elevated levels of initiator and effector caspases in the conditioned medium. In conclusion, Z. decandra treatment promoted the apoptosis of HCT colon cancer cells. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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38. Pharmacophore based virtual screening for identification of effective inhibitors to combat HPV 16 E6 driven cervical cancer.
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Mohan, Anbuselvam, Krishnamoorthy, Sneha, Sabanayagam, Rajalakshmi, Schwenk, Gregory, Feng, Eric, Ji, Hai-Feng, and Muthusami, Sridhar
- Subjects
- *
CERVICAL cancer , *MEDICAL screening , *HUMAN papillomavirus , *HIGH throughput screening (Drug development) , *MOLECULAR dynamics , *PHARMACOPHORE - Abstract
Targeting HPV16 E6 has emerged as an effective drug target for the treatment/management of cervical cancer. We utilized pharmacophore-based virtual screening, molecular docking, absorption, distribution, metabolism and excretion (ADME) prediction, and molecular dynamics simulation approach for identifying potential inhibitors of HPV16 E6. Initially, we generated a ligand-based pharmacophore model based on the features of four known HPV16 E6 inhibitors (CA24, CA25, CA26, and CA27) via the PHASE module implanted in the Schrödinger suite. We constructed four-point pharmacophore features viz., three hydrogen bond acceptors (A) and one aromatic ring (R). The common pharmacophore feature further employed as a query for virtual screening against the ASINEX database via Schrödinger suite. The pharmacophore-based virtual screening filtered out top 2000 hits, based on the fitness score. We then applied the high throughput virtual screening (HTVS), standard precision (SP) and extra precision (XP). 1000 compounds were obtained from HTVS docking. Based on the glide score, they were further filtered to 500 hits by employing docking in standard precision mode. Finally, the best four hits and a negative molecule were identified using docking in XP mode. The four lead compounds and a negative molecule were then further subjected to ADME profile prediction by engaging Qikprop module. The ADME properties of the four lead molecules indicate good pharmacokinetic (PK) properties rather than the negative molecule. The binding stability of the HPV16 E6-hit complexes were investigated at a different time scale (100 ns) by using the desmond package and the results were examined using Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) and it revealed the stability of the protein-ligand complex throughout the simulation. Key residues, CYS 51 and GLN 107, also play a crucial role in enhancing the stability of the protein-ligand complex during the simulation. Furthermore, the binding free energy of the HPV16 E6-leads complexes was analyzed by prime which revealed that the ΔG bind coulomb and ΔG bind vdW interactions are crucially contributes to the binding affinity. In order to validate the computational findings, the efficacy of benzoimidazole and benzotriazole were ascertained for regulating ME180 cervical cancer cell survival, migration and ability to release MMP-2. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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39. Effect of melatonin on PCB (Aroclor 1254) induced neuronal damage and changes in Cu/Zn superoxide dismutase and glutathione peroxidase-4 mRNA expression in cerebral cortex, cerebellum and hippocampus of adult rats
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Venkataraman, Prabhu, Selvakumar, Kandaswamy, Krishnamoorthy, Gunasekaran, Muthusami, Sridhar, Rameshkumar, Radhakrishnan, Prakash, Seepan, and Arunakaran, Jagadeesan
- Subjects
- *
POLYCHLORINATED biphenyls , *MELATONIN , *OXIDATIVE stress , *NEURAL circuitry , *GLUTATHIONE , *CEREBRAL cortex , *LABORATORY rats - Abstract
Abstract: Polychlorinated biphenyls (PCBs) are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Free radicals represent a class of biologically generated species that pose a potential threat to neuronal survival. Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase-4 (GPx-4) are the key cellular antioxidant enzymes by which neurons and other cells detoxify free radicals and protect themselves from damage. Melatonin, an indoleamine plays an important role in neurodegenerative diseases as an antioxidant and neuroprotector. The aim was to carry out to investigate the effect of melatonin on PCB (Aroclor 1254) induced changes in histomorphology and Cu/Zn SOD, GPx-4 mRNA expression in selected brain regions of adult rats. Group I: rats intraperitoneally (i.p.) administered with corn oil (vehicle) for 30 days. Group II: rats injected (i.p.) with Aroclor 1254 (PCB) at 2mg/kgbw/day for 30 days. Groups III and IV: rats (i.p.) received melatonin (5 or 10mg/kgbw/day) simultaneously with PCB for 30 days. Groups V and VI: rats (i.p.) received melatonin (5 or 10mg/kgbw/day) alone for 30 days. After 30 days, rats were sacrificed and the brain regions were dissected to cerebral cortex, cerebellum and hippocampus. Activities of enzymatic antioxidants such as total SOD, Cu/Zn SOD, Mn SOD, glutathione peroxidase (GPx) were estimated. mRNA expressions of Cu/Zn SOD and GPx-4 were quantified by reverse transcriptase polymerase chain reaction (RT-PCR) method. Histological study was also observed. Specific activities of all antioxidant enzymes and mRNA expression of Cu/Zn SOD and GPx-4 were decreased in brain regions of PCB exposed animals. Neuronal damages were observed in all the brain regions. Exogenous melatonin supplementation retrieved all the parameters. These results suggest that melatonin protects PCB-induced oxidative stress and prevents neuronal damage in brain regions. [Copyright &y& Elsevier]
- Published
- 2010
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40. In vitro evaluation of p-coumaric acid and naringin combination in human epidermoid carcinoma cell line (A431).
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Velusamy P, Muthusami S, and Arumugam R
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- Humans, Quality of Life, Reactive Oxygen Species, Cell Line, Carcinoma, Squamous Cell drug therapy, Skin Neoplasms drug therapy
- Abstract
Cancer is considered most detrimental due to high mortality worldwide. Among them, skin cancers play a major part by affecting one in three cancer patients globally. About 2-3 million cancer cases were reported to be non-melanoma and melanoma skin cancers, respectively. Although chemotherapeutic drugs act on cancer cells but results in long-lasting morbidities which affects one's quality of life and also works only in the initial stage of the cancer. Hence, an idea of traditional medicine to cure the disease efficiently with less side effects was pursued by the researchers. We have assessed the combination effect of p-coumaric acid and naringin in exerting anticancer activity using A431 (epidermoid carcinoma) cells. The MTT analysis of the combination on A431 cells showed the least IC
50 concentration of 41 µg/ml which is effective than the standard drug imiquimod with IC50 concentration of 52 µg/ml. Further, flow cytometric analysis was carried out to identify the molecular mechanism behind the anticancer effects of the combination. The results revealed that the combination arrested the A431 cell cycle at S phase, induced apoptosis as indicated by more early and late apoptotic cells when compared with the control, and further altered reactive oxygen species (ROS) and mitochondrial membrane potential in A431 cells. Hence, the results suggest the potential anticancer effects of p-coumaric acid and naringin combination against the skin cancer (A431) cell line. The observed effects may be additive or synergistic effects in inducing ROS generation and apoptosis, and reducing the viability of A431 cells., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2023
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41. Screening of MMP-2 Inhibiting Phytoconstituents for the Development of Newer Pancreatic Cancer Treatment Modalities.
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Periyasamy L, Murugantham B, Sundaraj R, Krishnamoorthi S, and Muthusami S
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- Humans, Matrix Metalloproteinase 2, Molecular Docking Simulation, Early Detection of Cancer, Cell Line, Tumor, Pancreatic Neoplasms, Emodin, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms metabolism
- Abstract
Background: Pancreatic cancer metastasis is characterized by a higher incidence of morbidity and mortality. The present study attempts to identify phytocomponents with the potential to inhibit the secretion of MMP-2 by pancreatic cancer cells and ascertain the efficacy of individual components., Methods: Overall survival analysis carried out revealed reduced survival of patients with high MMP-2 expression. Data analysis from TCGA revealed increased MMP-2 expression in pancreatic cancer patients compared to adjacent normal tissues. The expression of MMP-2 was reported at different stages of pancreatic cancer (Stage I-IV). To understand the relevance of phytocomponents in binding to the catalytic site of MMP-2, molecular docking studies were performed to find the effectiveness based on Glide score/energy. To substantiate the in-silico analysis, the eight components were also tested in vitro for reducing the survival in PANC-1 cells at three different time points (24, 48, and 72 hours). Finally, zymography analysis was performed using the eight components in the PANC-1 conditioned media of treated cells to ascertain the enzymatic activity of MMP-2., Results: The obtained results suggest plumbagin, emodin, and EGCG exert potential inhibition in PANC-1 cells, among other phytocomponents tested. Therefore, as assessed using computational studies, the binding ability of plumbagin, emodin, and EGCG can be interpreted as inhibiting effects on MMP-2 activities., Conclusion: These compounds could find potential application in preventing the progression, sustenance, and metastasis of pancreatic cancer and need to be explored further using a pre-clinical model system in order to validate the efficacy, bioavailability, and safety., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2023
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42. Molecular docking analysis of estrogen receptor binding phytocomponents identified from the ethyl acetate extract of Salicornia herbacea (L) .
- Author
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Rama V, Muruganantham B, Devaki K, and Muthusami S
- Abstract
It is of interest to evaluate the secondary metabolites using high performance thin layer chromatography (HPTLC) finger printing and Gas chromatography-Mass spectroscopy (GC-MS) in S. herbacea extract. The powdered plant material extracted using different solvents were used for the qualitative analysis of alkaloids, flavonoids, terpenoids and saponins followed by HPTLC finger printing and GC-MS analysis. The components identified in the GC-MS were docked with estrogen receptor (ER) to identify the binding specificity of isolated compounds. The ethyl acetate extract of S. herbacea showed the presence of high number of secondary metabolites when compared to other solvent system. The qualitative analysis of the plant material also showed the presence of carbohydrates, protein, amino acid, phenol, flavonoids, terpenoids, glycosides, saponins and steroids. The HPTLC finger printing analysis revealed the existence of alkaloid, flavonoid, terpenoid and saponin compounds and GC-MS. GC-MS was performed to identify the phytocomponents constituents in the extract. 8 phytocompounds were identified to analyse binding with ER. The binding affinity score (-6.8 kcal/mol) and interacting ER residues (28) the phyto compound di-n-octyl phthalate showed best docking score with ER α than the standard drugs lasofoxifene, and 4-hydroxytamoxifen. The binding affinity and number of interacting ER residues was -6.9 kcal/mol; 10 and -6.2; 11, respectively. The results identified the presence of ER antagonist in S. herbacea and warrants further investigation to explore for treating ER regulated diseases., Competing Interests: We declare that we have no conflict of interest, (© 2022 Biomedical Informatics.)
- Published
- 2022
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43. Recent Developments in the Therapeutics for Endocrine Diseases.
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Sankar BR, Muthusami S, and Ilangovan R
- Subjects
- Humans, Endocrine System Diseases drug therapy
- Published
- 2022
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44. Phyto-targeting the CEMIP Expression as a Strategy to Prevent Pancreatic Cancer Metastasis.
- Author
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Periyasamy L, Muruganantham B, Park WY, and Muthusami S
- Subjects
- Cell Line, Tumor, Cell Movement physiology, Gene Expression Regulation, Neoplastic, Humans, Prognosis, Signal Transduction, Pancreatic Neoplasms, Hyaluronoglucosaminidase metabolism, Pancreatic Neoplasms genetics
- Abstract
Introduction: Metastasis of primary pancreatic cancer (PC) to adjacent or distant organs is responsible for the poor survival rate of affected individuals. Chemotherapy, radiotherapy, and immunotherapy are currently being prescribed to treat PC in addition to surgical resection. Surgical resection is the preferred treatment for PC that leads to 20% of 5-year survival, but only less than 20% of patients are eligible for surgical resection because of the poor prognosis. To improve the prognosis and clinical outcome, early diagnostic markers need to be identified, and targeting them would be of immense benefit to increase the efficiency of the treatment. Cell migration-inducing hyaluronan-binding protein (CEMIP) is identified as an important risk factor for the metastasis of various cancers, including PC. Emerging studies have pointed out the crucial role of CEMIP in the regulation of various signaling mechanisms, leading to enhanced migration and metastasis of PC., Methods: The published findings on PC metastasis, phytoconstituents, and CEMIP were retrieved from Pubmed, ScienceDirect, and Cochrane Library. Computational tools, such as gene expression profiling interactive analysis (GEPIA) and Kaplan-Meier (KM) plotter, were used to study the relationship between CEMIP expression and survival of PC individuals., Results: Gene expression analysis using the GEPIA database identified a stupendous increase in the CEMIP transcript in PC compared to adjacent normal tissues. KM plotter analysis revealed the impact of CEMIP on the overall survival (OS) and disease-free survival (DFS) among PC patients. Subsequently, several risk factors associated with PC development were screened, and their ability to regulate CEMIP gene expression was analyzed using computational tools., Conclusion: The current review is focused on gathering information regarding the regulatory role of phytocomponents in PC migration and exploring their possible impact on the CEMIP expression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2022
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45. Role of Inflammation in the Development of Colorectal Cancer.
- Author
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Muthusami S, Ramachandran IK, Babu KN, Krishnamoorthy S, Guruswamy A, Queimado L, Chaudhuri G, and Ramachandran I
- Subjects
- Animals, Cell Transformation, Neoplastic immunology, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic pathology, Colitis complications, Colitis pathology, Colorectal Neoplasms pathology, Cytokines immunology, Cytokines metabolism, Humans, Inflammation pathology, Inflammatory Bowel Diseases pathology, Colorectal Neoplasms etiology, Inflammation complications, Inflammatory Bowel Diseases complications
- Abstract
Chronic inflammation can lead to the development of many diseases, including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohnmp's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation, together with genetic and epigenetic changes, have been shown to lead to the development and progression of CRC. Various cell types present in the colon, such as enterocytes, Paneth cells, goblet cells, and macrophages, express receptors for inflammatory cytokines and respond to tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key pro-inflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of pro-inflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy) to alleviate the symptoms or treat inflammation-associated CRC by using monoclonal antibodies or aptamers to block pro-inflammatory molecules, inhibitors of tyrosine kinases in the inflammatory signaling cascade, competitive inhibitors of pro-inflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/pro-inflammatory cytokine gene expression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2021
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46. Acetogenin Extracted from Annona muricata Prevented the Actions of EGF in PA-1 Ovarian Cancer Cells.
- Author
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Periyasamy L, Muruganantham B, Deivasigamani M, Lakshmanan H, and Muthusami S
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- Acetogenins chemistry, Acetogenins isolation & purification, Cell Line, Tumor, Female, Humans, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology, Acetogenins pharmacology, Annona chemistry, Epidermal Growth Factor metabolism, Neoplasm Proteins metabolism, Ovarian Neoplasms drug therapy, Signal Transduction drug effects
- Abstract
Background: In individuals with ovarian cancer, an increase in the circulating level of the epidermal growth factor (EGF) is readily apparent. Ovarian cancer cells exhibit signaling pathway of the epidermal growth factor (EGFR) and respond to the EGF. Annona muricata (AM) has been shown to decrease ovarian cell proliferation however, role of AM in regulating EGF actions is not yet to be reported., Objective: In this study, we proposed that the fractionated compound acetogenin can inhibit the activation of EGFR-regulated signaling cascades such as MAPK7 / PI3K-Akt / mTOR / STAT upon EGF stimulation., Methods: Ethanolic extract was prepared for the whole AM plant and Thin Layer Chromatography (TLC) was performed to characterize the secondary metabolites and each fraction was assessed using kedde reagent for the presence of acetogenin. The effects of acetogenins were then tested on the survival of PA-1 ovarian cancer cells under basal and EGF stimulated conditions. To delineate the role of acetogenin in EGFR signaling cascades, the in silico docking studies were conducted., Results: The fraction of acetogenin decreased the viability of EGF induced PA-1 ovarian cancer cells that indicating the EGF inhibitory effects of acetogenin. The docking studies specifically illustrated that when the acetogenin binding with tyrosine kinase (TK) and regulatory unit (RU) which subsequently resulted in a reduction in EGF induced the survival of PA-1 ovarian cancer cells., Discussion: The vital regulatory role of acetogenin reported in this study indicate significant anticancer activities of acetogenin from AM. The in silico study of the acetogenin function predicted that it binds specifically to Asp837 (phosphor-acceptor site) of EGFR, essential for phosphorylation of substrates in the TK domain and RU which promote downstream signaling., Conclusion: Acetogenin isolated from AM effectively inhibited the survival of PA-1 ovarian cancer cells through impaired EGF signaling., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2021
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47. Regulation of MicroRNAs in Inflammation-Associated Colorectal Cancer: A Mechanistic Approach.
- Author
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Muthusami S, Ramachandran I, Krishnamoorthy S, Sambandam Y, Ramalingam S, Queimado L, Chaudhuri G, and Ramachandran IK
- Subjects
- Animals, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic pathology, Colitis complications, Colitis genetics, Colitis pathology, Colorectal Neoplasms etiology, Colorectal Neoplasms pathology, Gene Expression Regulation, Neoplastic, Humans, Inflammation complications, Inflammation genetics, Inflammation pathology, Inflammatory Bowel Diseases genetics, Inflammatory Bowel Diseases pathology, Signal Transduction genetics, Colorectal Neoplasms genetics, Inflammatory Bowel Diseases complications, MicroRNAs physiology
- Abstract
The development of colorectal cancer (CRC) is a multistage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn's disease (CD) is often regarded as the initial trigger for the development of inflammation-associated CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC, through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2021
- Full Text
- View/download PDF
48. Effect of DHT-Induced Hyperandrogenism on the Pro-Inflammatory Cytokines in a Rat Model of Polycystic Ovary Morphology.
- Author
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Krishnan A, Muthusami S, Periyasamy L, Stanley JA, Gopalakrishnan V, and Ramachandran I
- Subjects
- Animals, Disease Models, Animal, Female, Follicle Stimulating Hormone blood, Hyperandrogenism chemically induced, Insulin blood, Liver metabolism, Luteinizing Hormone blood, Polycystic Ovary Syndrome complications, Rats, Rats, Wistar, Urocortins metabolism, Cytokines blood, Dihydrotestosterone adverse effects, Hyperandrogenism metabolism, Inflammation Mediators blood, Polycystic Ovary Syndrome metabolism
- Abstract
Background and Objectives: Polycystic ovary syndrome (PCOS) is one of the most prevalent disorders among women of reproductive age. It is considered as a pro-inflammatory state with chronic low-grade inflammation, one of the key factors contributing to the pathogenesis of this disorder. Polycystic ovary is a well-established criterion for PCOS. The present investigation aimed at finding the role of hyperandrogenism, the most important feature of PCOS, in the development of this inflammatory state. To address this problem, we adopted a model system that developed polycystic ovary morphology (PCOM), which could be most effectively used in order to study the role of non-aromatizable androgen in inflammation in PCOS. Materials and Methods: Six rats were used to induce PCOM in 21-days-old female Wistar albino rats by using a pre-determined release of dihydrotestosterone (DHT), a potent non-aromatizable androgen, achieved by implanting a DHT osmotic pump, which is designed to release a daily dose of 83 μg. Results: After 90 days, the rats displayed irregular estrous cycles and multiple ovarian cysts similar to human PCOS. Elevated serum inflammatory markers such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and the presence of a necrotic lesion in the liver, osteoclast in the femur, multinucleated giant cells and lymphocytes in the ovary based on histopathological observation of DHT-treated rats clearly indicated the onset of inflammation in the hyperandrogenic state. Our results show no significant alterations in serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), insulin, and cortisol between control and hyperandrogenised rats. DHT was significantly elevated as compared to control. mRNA studies showed an increased expression level of TNF-α and IL-1β, further, the mRNA expression of urocortin 1 (Ucn-1) was stupendously elevated in the liver of hyperandrogenised rats. Conclusions: Thus, results from this study provide: (1) a good PCOM model system in order to study the inflammatory changes in PCOS aspects, (2) alteration of inflammatory markers in PCOM rats that could be either due to its direct effect or by the regulation of various inflammatory genes and markers in the liver of hyperandrogenic state suggesting the regulatory role of DHT, and (3) alteration in stress-related protein in the liver of PCOM rats.
- Published
- 2020
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49. The Functional Significance of Endocrine-immune Interactions in Health and Disease.
- Author
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Muthusami S, Vidya B, Shankar EM, Vadivelu J, Ramachandran I, Stanley JA, and Selvamurugan N
- Subjects
- Animals, Cell Communication, Cytokines genetics, Cytokines immunology, Cytokines metabolism, Dopamine genetics, Dopamine immunology, Dopamine metabolism, Endocrine System cytology, Endocrine System immunology, Endocrine System Diseases genetics, Endocrine System Diseases immunology, Endocrine System Diseases pathology, Glucocorticoids genetics, Glucocorticoids immunology, Glucocorticoids metabolism, Growth Hormone genetics, Growth Hormone immunology, Humans, Immune System cytology, Immune System immunology, Immune System Diseases genetics, Immune System Diseases immunology, Immune System Diseases pathology, Lactotrophs cytology, Lactotrophs immunology, Lactotrophs metabolism, Prolactin genetics, Prolactin immunology, Receptors, Dopamine genetics, Receptors, Dopamine immunology, Receptors, Dopamine metabolism, Somatotrophs cytology, Somatotrophs immunology, Somatotrophs metabolism, Thymocytes cytology, Thymocytes immunology, Thyroid Hormones genetics, Thyroid Hormones immunology, Thyroid Hormones metabolism, Endocrine System metabolism, Endocrine System Diseases metabolism, Growth Hormone metabolism, Immune System metabolism, Immune System Diseases metabolism, Prolactin metabolism, Thymocytes metabolism
- Abstract
Hormones are known to influence various body systems that include skeletal, cardiac, digestive, excretory, and immune systems. Emerging investigations suggest the key role played by secretions of endocrine glands in immune cell differentiation, proliferation, activation, and memory attributes of the immune system. The link between steroid hormones such as glucocorticoids and inflammation is widely known. However, the role of peptide hormones and amino acid derivatives such as growth and thyroid hormones, prolactin, dopamine, and thymopoietin in regulating the functioning of the immune system remains unclear. Here, we reviewed the findings pertinent to the functional role of hormone-immune interactions in health and disease and proposed perspective directions for translational research in the field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2020
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