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4. Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

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Steinmetz, Jaimie D, Seeher, Katrin Maria, Schiess, Nicoline, Nichols, Emma, Cao, Bochen, Servili, Chiara, Cavallera, Vanessa, Cousin, Ewerton, Hagins, Hailey, Moberg, Madeline E, Mehlman, Max L, Abate, Yohannes Habtegiorgis, Abbas, Jaffar, Abbasi, Madineh Akram, Abbasian, Mohammadreza, Abbastabar, Hedayat, Abdelmasseh, Michael, Abdollahi, Mohammad, Abdollahi, Mozhan, Abdollahifar, Mohammad-Amin, Abd-Rabu, Rami, Abdulah, Deldar Morad, Abdullahi, Auwal, Abedi, Aidin, Abedi, Vida, Abeldańo Zuńiga, Roberto Ariel, Abidi, Hassan, Abiodun, Olumide, Aboagye, Richard Gyan, Abolhassani, Hassan, Aboyans, Victor, Abrha, Woldu Aberhe, Abualhasan, Ahmed, Abu-Gharbieh, Eman, Aburuz, Salahdein, Adamu, Lawan Hassan, Addo, Isaac Yeboah, Adebayo, Oladimeji M, Adekanmbi, Victor, Adekiya, Tayo Alex, Adikusuma, Wirawan, Adnani, Qorinah Estiningtyas Sakilah, Adra, Saryia, Afework, Tsion, Afolabi, Aanuoluwapo Adeyimika, Afraz, Ali, Afzal, Saira, Aghamiri, Shahin, Agodi, Antonella, Agyemang-Duah, Williams, Ahinkorah, Bright Opoku, Ahmad, Aqeel, Ahmad, Danish, Ahmad, Sajjad, Ahmadzade, Amir Mahmoud, Ahmed, Ali, Ahmed, Ayman, Ahmed, Haroon, Ahmed, Jivan Qasim, Ahmed, Luai A, Ahmed, Muktar Beshir, Ahmed, Syed Anees, Ajami, Marjan, Aji, Budi, Ajumobi, Olufemi, Akade, Seyed Esma'il, Akbari, Morteza, Akbarialiabad, Hossein, Akhlaghi, Shiva, Akinosoglou, Karolina, Akinyemi, Rufus Olusola, Akonde, Maxwell, Al Hasan, Syed Mahfuz, Alahdab, Fares, AL-Ahdal, Tareq Mohammed Ali, Al-amer, Rasmieh Mustafa, Albashtawy, Mohammed, AlBataineh, Mohammad T, Aldawsari, Khalifah A, Alemi, Hediyeh, Alemi, Sharifullah, Algammal, Abdelazeem M, Al-Gheethi, Adel Ali Saeed, Alhalaiqa, Fadwa Alhalaiqa Naji, Alhassan, Robert Kaba, Ali, Abid, Ali, Endale Alemayehu, Ali, Liaqat, Ali, Mohammed Usman, Ali, Musa Mohammed, Ali, Rafat, Ali, Shahid, Ali, Syed Shujait Shujait, Ali, Zahid, Alif, Sheikh Mohammad, Alimohamadi, Yousef, Aliyi, Ahmednur Adem, Aljofan, Mohamad, Aljunid, Syed Mohamed, Alladi, Suvarna, Almazan, Joseph Uy, Almustanyir, Sami, Al-Omari, Basem, Alqahtani, Jaber S, Alqasmi, Ibrahim, Alqutaibi, Ahmed Yaseen, Al-Shahi Salman, Rustam, Altaany, Zaid, Al-Tawfiq, Jaffar A, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Al-Worafi, Yaser Mohammed, Aly, Hany, Aly, Safwat, Alzoubi, Karem H, Amani, Reza, Amindarolzarbi, Alireza, Amiri, Sohrab, Amirzade-Iranaq, Mohammad Hosein, Amu, Hubert, Amugsi, Dickson A, Amusa, Ganiyu Adeniyi, Amzat, Jimoh, Ancuceanu, Robert, Anderlini, Deanna, Anderson, David B, Andrei, Catalina Liliana, Androudi, Sofia, Angappan, Dhanalakshmi, Angesom, Teklit W, Anil, Abhishek, Ansari-Moghaddam, Alireza, Anwer, Razique, Arafat, Mosab, Aravkin, Aleksandr Y, Areda, Demelash, Ariffin, Hany, Arifin, Hidayat, Arkew, Mesay, Ärnlöv, Johan, Arooj, Mahwish, Artamonov, Anton A, Artanti, Kurnia Dwi, Aruleba, Raphael Taiwo, Asadi-Pooya, Ali A, Asena, Tilahun Ferede, Asghari-Jafarabadi, Mohammad, Ashraf, Muhammad, Ashraf, Tahira, Atalell, Kendalem Asmare, Athari, Seyyed Shamsadin, Atinafu, Bantalem Tilaye Tilaye, Atorkey, Prince, Atout, Maha Moh'd Wahbi, Atreya, Alok, Aujayeb, Avinash, Avan, Abolfazl, Ayala Quintanilla, Beatriz Paulina, Ayatollahi, Haleh, Ayinde, Olatunde O, Ayyoubzadeh, Seyed Mohammad, Azadnajafabad, Sina, Azizi, Zahra, Azizian, Khalil, Azzam, Ahmed Y, Babaei, Mahsa, Badar, Muhammad, Badiye, Ashish D, Baghdadi, Soroush, Bagherieh, Sara, Bai, Ruhai, Baig, Atif Amin, Balakrishnan, Senthilkumar, Balalla, Shivanthi, Baltatu, Ovidiu Constantin, Banach, Maciej, Bandyopadhyay, Soham, Banerjee, Indrajit, Baran, Mehmet Firat, Barboza, Miguel A, Barchitta, Martina, Bardhan, Mainak, Barker-Collo, Suzanne Lyn, Bärnighausen, Till Winfried, Barrow, Amadou, Bashash, Davood, Bashiri, Hamideh, Bashiru, Hameed Akande, Basiru, Afisu, Basso, João Diogo, Basu, Sanjay, Batiha, Abdul-Monim Mohammad, Batra, Kavita, Baune, Bernhard T, Bedi, Neeraj, Begde, Ahmet, Begum, Tahmina, Behnam, Babak, Behnoush, Amir Hossein, Beiranvand, Maryam, Béjot, Yannick, Bekele, Alehegn, Belete, Melaku Ashagrie, Belgaumi, Uzma Iqbal, Bemanalizadeh, Maryam, Bender, Rose G, Benfor, Bright, Bennett, Derrick A, Bensenor, Isabela M, Berice, Betyna, Bettencourt, Paulo J G, Beyene, Kebede A, Bhadra, Abhishek, Bhagat, Devidas S, Bhangdia, Kayleigh, Bhardwaj, Nikha, Bhardwaj, Pankaj, Bhargava, Ashish, Bhaskar, Sonu, Bhat, Ajay Nagesh, Bhat, Vivek, Bhatti, Gurjit Kaur, Bhatti, Jasvinder Singh, Bhatti, Rajbir, Bijani, Ali, Bikbov, Boris, Bilalaga, Mariah Malak, Biswas, Atanu, Bitaraf, Saeid, Bitra, Veera R, Bjørge, Tone, Bodolica, Virginia, Bodunrin, Aadam Olalekan, Boloor, Archith, Braithwaite, Dejana, Brayne, Carol, Brenner, Hermann, Briko, Andrey, Bringas Vega, Maria L, Brown, Julie, Budke, Christine M, Buonsenso, Danilo, Burkart, Katrin, Burns, Richard A, Bustanji, Yasser, Butt, Muhammad Hammad, Butt, Nadeem Shafique, Butt, Zahid A, Cabral, Lucas Scotta, Caetano dos Santos, Florentino Luciano, Calina, Daniela, Campos-Nonato, Ismael R, Cao, Chao, Carabin, Hélène, Cárdenas, Rosario, Carreras, Giulia, Carvalho, Andre F, Castańeda-Orjuela, Carlos A, Casulli, Adriano, Catalá-López, Ferrán, Catapano, Alberico L, Caye, Arthur, Cegolon, Luca, Cenderadewi, Muthia, Cerin, Ester, Chacón-Uscamaita, Pamela R, Chan, Jeffrey Shi Kai, Chanie, Gashaw Sisay, Charan, Jaykaran, Chattu, Vijay Kumar, Chekol Abebe, Endeshaw, Chen, Hui, Chen, Jianqi, Chi, Gerald, Chichagi, Fatemeh, Chidambaram, Saravana Babu, Chimoriya, Ritesh, Ching, Patrick R, Chitheer, Abdulaal, Chong, Yuen Yu, Chopra, Hitesh, Choudhari, Sonali Gajanan, Chowdhury, Enayet Karim, Chowdhury, Rajiv, Christensen, Hanne, Chu, Dinh-Toi, Chukwu, Isaac Sunday, Chung, Eric, Coberly, Kaleb, Columbus, Alyssa, Comachio, Josielli, Conde, Joao, Cortesi, Paolo Angelo, Costa, Vera Marisa, Couto, Rosa A S, Criqui, Michael H, Cruz-Martins, Natália, Dabbagh Ohadi, Mohammad Amin, Dadana, Sriharsha, Dadras, Omid, Dai, Xiaochen, Dai, Zhaoli, D'Amico, Emanuele, Danawi, Hadi A, Dandona, Lalit, Dandona, Rakhi, Darwish, Amira Hamed, Das, Saswati, Das, Subasish, Dascalu, Ana Maria, Dash, Nihar Ranjan, Dashti, Mohsen, De la Hoz, Fernando Pio, de la Torre-Luque, Alejandro, De Leo, Diego, Dean, Frances E, Dehghan, Amin, Dehghan, Azizallah, Dejene, Hiwot, Demant, Daniel, Demetriades, Andreas K, Demissie, Solomon, Deng, Xinlei, Desai, Hardik Dineshbhai, Devanbu, Vinoth Gnana Chellaiyan, Dhama, Kuldeep, Dharmaratne, Samath Dhamminda, Dhimal, Meghnath, Dias da Silva, Diana, Diaz, Daniel, Dibas, Mahmoud, Ding, Delaney D, Dinu, Monica, Dirac, M Ashworth, Diress, Mengistie, Do, Thanh Chi, Do, Thao Huynh Phuong, Doan, Khanh Duy Khanh, Dodangeh, Milad, Doheim, Mohamed Fahmy, Dokova, Klara Georgieva, Dongarwar, Deepa, Dsouza, Haneil Larson, Dube, John, Duraisamy, Senbagam, Durojaiye, Oyewole Christopher, Dutta, Sulagna, Dziedzic, Arkadiusz Marian, Edinur, Hisham Atan, Eissazade, Negin, Ekholuenetale, Michael, Ekundayo, Temitope Cyrus, El Nahas, Nevine, El Sayed, Iman, Elahi Najafi, Mohammad Amin, Elbarazi, Iffat, Elemam, Noha Mousaad, Elgar, Frank J, Elgendy, Islam Y, Elhabashy, Hala Rashad, Elhadi, Muhammed, Elilo, Legesse Tesfaye, Ellenbogen, Richard G, Elmeligy, Omar Abdelsadek Abdou, Elmonem, Mohamed A, Elshaer, Mohammed, Elsohaby, Ibrahim, Emamverdi, Mehdi, Emeto, Theophilus I, Endres, Matthias, Esezobor, Christopher Imokhuede, Eskandarieh, Sharareh, Fadaei, Abdolmajid, Fagbamigbe, Adeniyi Francis, Fahim, Ayesha, Faramarzi, Ali, Fares, Jawad, Farjoud Kouhanjani, Mohsen, Faro, Andre, Farzadfar, Farshad, Fatehizadeh, Ali, Fathi, Mobina, Fathi, Saeid, Fatima, Syeda Anum Fatima, Feizkhah, Alireza, Fereshtehnejad, Seyed-Mohammad, Ferrari, Alize J, Ferreira, Nuno, Fetensa, Getahun, Firouraghi, Neda, Fischer, Florian, Fonseca, Ana Catarina, Force, Lisa M, Fornari, Arianna, Foroutan, Behzad, Fukumoto, Takeshi, Gadanya, Muktar A, Gaidhane, Abhay Motiramji, Galali, Yaseen, Galehdar, Nasrin, Gan, Quan, Gandhi, Aravind P, Ganesan, Balasankar, Gardner, William M, Garg, Naval, Gau, Shuo-Yan, Gautam, Rupesh K, Gebre, Teshome, Gebrehiwot, Mesfin, Gebremeskel, Gebreamlak Gebremedhn, Gebreslassie, Haftay Gebremedhin, Getacher, Lemma, Ghaderi Yazdi, Bardiya, Ghadirian, Fataneh, Ghaffarpasand, Fariborz, Ghanbari, Reza, Ghasemi, MohammadReza, Ghazy, Ramy Mohamed, Ghimire, Sailaja, Gholami, Ali, Gholamrezanezhad, Ali, Ghotbi, Elena, Ghozy, Sherief, Gialluisi, Alessandro, Gill, Paramjit Singh, Glasstetter, Logan M, Gnedovskaya, Elena V, Golchin, Ali, Golechha, Mahaveer, Goleij, Pouya, Golinelli, Davide, Gomes-Neto, Mansueto, Goulart, Alessandra C, Goyal, Anmol, Gray, Richard J, Grivna, Michal, Guadie, Habtamu Alganeh, Guan, Bin, Guarducci, Giovanni, Guicciardi, Stefano, Gunawardane, Damitha Asanga, Guo, Hanbing, Gupta, Bhawna, Gupta, Rajeev, Gupta, Sapna, Gupta, Veer Bala, Gupta, Vivek Kumar, Gutiérrez, Reyna Alma, Habibzadeh, Farrokh, Hachinski, Vladimir, Haddadi, Rasool, Hadei, Mostafa, Hadi, Najah R, Haep, Nils, Haile, Teklehaimanot Gereziher, Haj-Mirzaian, Arvin, Hall, Brian J, Halwani, Rabih, Hameed, Sajid, Hamiduzzaman, Mohammad, Hammoud, Ahmad, Han, Hannah, Hanifi, Nasrin, Hankey, Graeme J, Hannan, Md. Abdul, Hao, Junwei, Harapan, Harapan, Hareru, Habtamu Endashaw, Hargono, Arief, Harlianto, Netanja I., Haro, Josep Maria, Hartman, Nicholas Nathaniel, Hasaballah, Ahmed I., Hasan, Faizul, Hasani, Hamidreza, Hasanian, Mohammad, Hassan, Amr, Hassan, Shoaib, Hassanipour, Soheil, Hassankhani, Hadi, Hassen, Mohammed Bheser, Haubold, Johannes, Hay, Simon I, Hayat, Khezar, Hegazy, Mohamed I, Heidari, Golnaz, Heidari, Mohammad, Heidari-Soureshjani, Reza, Hesami, Hamed, Hezam, Kamal, Hiraike, Yuta, Hoffman, Howard J, Holla, Ramesh, Hopf, Kathleen Pillsbury, Horita, Nobuyuki, Hossain, Md Mahbub, Hossain, Md. Belal, Hossain, Sahadat, Hosseinzadeh, Hassan, Hosseinzadeh, Mehdi, Hostiuc, Sorin, Hu, Chengxi, Huang, Junjie, Huda, Md. Nazmul, Hussain, Javid, Hussein, Nawfal R, Huynh, Hong-Han, Hwang, Bing-Fang, Ibitoye, Segun Emmanuel, Ilaghi, Mehran, Ilesanmi, Olayinka Stephen, Ilic, Irena M, Ilic, Milena D, Immurana, Mustapha, Iravanpour, Farideh, Islam, Sheikh Mohammed Shariful, Ismail, Faisal, Iso, Hiroyasu, Isola, Gaetano, Iwagami, Masao, Iwu, Chidozie C D, Iyer, Mahalaxmi, Jaan, Ali, Jacob, Louis, Jadidi-Niaragh, Farhad, Jafari, Mahboobeh, Jafarinia, Morteza, Jafarzadeh, Abdollah, Jahankhani, Kasra, Jahanmehr, Nader, Jahrami, Haitham, Jaiswal, Abhishek, Jakovljevic, Mihajlo, Jamora, Roland Dominic G, Jana, Somnath, Javadi, Nilofer, Javed, Saad, Javeed, Saad, Jayapal, Sathish Kumar, Jayaram, Shubha, Jiang, Heng, Johnson, Catherine Owens, Johnson, Walter D, Jokar, Mohammad, Jonas, Jost B, Joseph, Abel, Joseph, Nitin, Joshua, Charity Ehimwenma, Jürisson, Mikk, Kabir, Ali, Kabir, Zubair, Kabito, Gebisa Guyasa, Kadashetti, Vidya, Kafi, Fatemeh, Kalani, Rizwan, Kalantar, Farnaz, Kaliyadan, Feroze, Kamath, Ashwin, Kamath, Sagarika, Kanchan, Tanuj, Kandel, Amit, Kandel, Himal, Kanmodi, Kehinde Kazeem, Karajizadeh, Mehrdad, Karami, Jafar, Karanth, Shama D, Karaye, Ibraheem M, Karch, André, Karimi, Aliasghar, Karimi, Hanie, Karimi Behnagh, Arman, Kasraei, Hengameh, Kassebaum, Nicholas J, Kauppila, Joonas H, Kaur, Harkiran, Kaur, Navjot, Kayode, Gbenga A, Kazemi, Foad, Keikavoosi-Arani, Leila, Keller, Cathleen, Keykhaei, Mohammad, Khadembashiri, Mohammad Amin, Khader, Yousef Saleh, Khafaie, Morteza Abdullatif, Khajuria, Himanshu, Khalaji, Amirmohammad, Khamesipour, Faham, Khammarnia, Mohammad, Khan, Maseer, Khan, Moien AB, Khan, Yusra H, Khan Suheb, Mahammed Ziauddin, Khanmohammadi, Shaghayegh, Khanna, Tripti, Khatab, Khaled, Khatatbeh, Haitham, Khatatbeh, Moawiah Mohammad, Khateri, Sorour, Khatib, Mahalaqua Nazli, Khayat Kashani, Hamid Reza, Khonji, Mohammad Saeid, khorashadizadeh, Fatemeh, Khormali, Moein, Khubchandani, Jagdish, Kian, Saeid, Kim, Grace, Kim, Jihee, Kim, Min Seo, Kim, Yun Jin, Kimokoti, Ruth W, Kisa, Adnan, Kisa, Sezer, Kivimäki, Mika, Kochhar, Sonali, Kolahi, Ali-Asghar, Koly, Kamrun Nahar, Kompani, Farzad, Koroshetz, Walter J, Kosen, Soewarta, Kourosh Arami, Masoumeh, Koyanagi, Ai, Kravchenko, Michael A, Krishan, Kewal, Krishnamoorthy, Vijay, Kuate Defo, Barthelemy, Kuddus, Md Abdul, Kumar, Ashish, Kumar, G Anil, Kumar, Manasi, Kumar, Nithin, Kumsa, Netsanet Bogale, Kundu, Satyajit, Kurniasari, Maria Dyah, Kusuma, Dian, Kuttikkattu, Ambily, Kyu, Hmwe Hmwe, La Vecchia, Carlo, Ladan, Muhammad Awwal, Lahariya, Chandrakant, Laksono, Tri, Lal, Dharmesh Kumar, Lallukka, Tea, Lám, Judit, Lami, Faris Hasan, Landires, Iván, Langguth, Berthold, Lasrado, Savita, Latief, Kamaluddin, Latifinaibin, Kaveh, Lau, Kathryn Mei-Ming, Laurens, Matthew B, Lawal, Basira Kankia, Le, Long Khanh Dao, Le, Thao Thi Thu, Ledda, Caterina, Lee, Munjae, Lee, Sang-woong, Lee, Seung Won, Lee, Wei-Chen, Lee, Yo Han, Leonardi, Matilde, Lerango, Temesgen L, Li, Ming-Chieh, Li, Wei, Ligade, Virendra S, Lim, Stephen S, Linehan, Christine, Liu, Chaojie, Liu, Jue, Liu, Wei, Lo, Chun-Han, Lo, Warren David, Lobo, Stany W, Logroscino, Giancarlo, Lopes, Graciliana, Lopukhov, Platon D, Lorenzovici, László, Lorkowski, Stefan, Loureiro, Joana A, Lubinda, Jailos, Lucchetti, Giancarlo, Lutzky Saute, Ricardo, Ma, Zheng Feei, Mabrok, Mahmoud, Machoy, Monika, Madadizadeh, Farzan, Magdy Abd El Razek, Mohammed, Maghazachi, Azzam A, Maghbouli, Nastaran, Mahjoub, Soleiman, Mahmoudi, Morteza, Majeed, Azeem, Malagón-Rojas, Jeadran N., Malakan Rad, Elaheh, Malhotra, Kashish, Malik, Ahmad Azam, Malik, Iram, Mallhi, Tauqeer Hussain, Malta, Deborah Carvalho, Manilal, Aseer, Mansouri, Vahid, Mansournia, Mohammad Ali, Marasini, Bishnu P, Marateb, Hamid Reza, Maroufi, Seyed Farzad, Martinez-Raga, Jose, Martini, Santi, Martins-Melo, Francisco Rogerlândio, Martorell, Miquel, März, Winfried, Marzo, Roy Rillera, Massano, João, Mathangasinghe, Yasith, Mathews, Elezebeth, Maude, Richard James, Maugeri, Andrea, Maulik, Pallab K, Mayeli, Mahsa, Mazaheri, Maryam, McAlinden, Colm, McGrath, John J, Meena, Jitendra Kumar, Mehndiratta, Man Mohan, Mendez-Lopez, Max Alberto Mendez, Mendoza, Walter, Mendoza-Cano, Oliver, Menezes, Ritesh G, Merati, Mohsen, Meretoja, Atte, Merkin, Alexander, Mersha, Abera M, Mestrovic, Tomislav, Mi, Tianyue, Miazgowski, Tomasz, Michalek, Irmina Maria, Mihretie, Ephrem Tesfaye, Minh, Le Huu Nhat, Mirfakhraie, Reza, Mirica, Andreea, Mirrakhimov, Erkin M, Mirzaei, Mehdi, Misganaw, Awoke, Misra, Sanjeev, Mithra, Prasanna, Mizana, Biru Abdissa, Mohamadkhani, Ashraf, Mohamed, Nouh Saad, Mohammadi, Esmaeil, Mohammadi, Hiwa, Mohammadi, Shadieh, Mohammadi, Soheil, Mohammadshahi, Marita, Mohammed, Mustapha, Mohammed, Salahuddin, Mohammed, Shafiu, Mohan, Syam, Mojiri-forushani, Hoda, Moka, Nagabhishek, Mokdad, Ali H, Molinaro, Sabrina, Möller, Holger, Monasta, Lorenzo, Moniruzzaman, Md, Montazeri, Fateme, Moradi, Maryam, Moradi, Yousef, Moradi-Lakeh, Maziar, Moraga, Paula, Morovatdar, Negar, Morrison, Shane Douglas, Mosapour, Abbas, Mosser, Jonathan F, Mossialos, Elias, Motaghinejad, Majid, Mousavi, Parsa, Mousavi, Seyed Ehsan, Mubarik, Sumaira, Muccioli, Lorenzo, Mughal, Faraz, Mukoro, George Duke, Mulita, Admir, Mulita, Francesk, Musaigwa, Fungai, Mustafa, Ahmad, Mustafa, Ghulam, Muthu, Sathish, Nagarajan, Ahamarshan Jayaraman, Naghavi, Pirouz, Naik, Ganesh R, Nainu, Firzan, Nair, Tapas Sadasivan, Najmuldeen, Hastyar Hama Rashid, Nakhostin Ansari, Noureddin, Nambi, Gopal, Namdar Areshtanab, Hossein, Nargus, Shumaila, Nascimento, Bruno Ramos, Naser, Abdallah Y, Nashwan, Abdulqadir J J, Nasoori, Hadis, Nasreldein, Ahmed, Natto, Zuhair S, Nauman, Javaid, Nayak, Biswa Prakash, Nazri-Panjaki, Athare, Negaresh, Mohammad, Negash, Hadush, Negoi, Ionut, Negoi, Ruxandra Irina, Negru, Serban Mircea, Nejadghaderi, Seyed Aria, Nematollahi, Mohammad Hadi, Nesbit, Olivia D, Newton, Charles Richard James, Nguyen, Dang H, Nguyen, Hau Thi Hien, Nguyen, Hien Quang, Nguyen, Ngoc-Trinh Thi, Nguyen, Phat Tuan, Nguyen, Van Thanh, Niazi, Robina Khan, Nikolouzakis, Taxiarchis Konstantinos, Niranjan, Vikram, Nnyanzi, Lawrence Achilles, Noman, Efaq Ali, Noroozi, Nafise, Norrving, Bo, Noubiap, Jean Jacques, Nri-Ezedi, Chisom Adaobi, Ntaios, George, Nuńez-Samudio, Virginia, Nurrika, Dieta, Oancea, Bogdan, Odetokun, Ismail A, O'Donnell, Martin James, Ogunsakin, Ropo Ebenezer, Oguta, James Odhiambo, Oh, In-Hwan, Okati-Aliabad, Hassan, Okeke, Sylvester Reuben, Okekunle, Akinkunmi Paul, Okonji, Osaretin Christabel, Okwute, Patrick Godwin, Olagunju, Andrew T, Olaiya, Muideen Tunbosun, Olana, Matifan Dereje, Olatubi, Matthew Idowu, Oliveira, Gláucia Maria Moraes, Olufadewa, Isaac Iyinoluwa, Olusanya, Bolajoko Olubukunola, Omar Bali, Ahmed, Ong, Sokking, Onwujekwe, Obinna E, Ordak, Michal, Orji, Aislyn U, Ortega-Altamirano, Doris V, Osuagwu, Uchechukwu Levi, Otstavnov, Nikita, Otstavnov, Stanislav S, Ouyahia, Amel, Owolabi, Mayowa O, P A, Mahesh Padukudru, Pacheco-Barrios, Kevin, Padubidri, Jagadish Rao, Pal, Pramod Kumar, Palange, Padmavali Nanaji, Palladino, Claudia, Palladino, Raffaele, Palma-Alvarez, Raul Felipe, Pan, Feng, Panagiotakos, Demosthenes, Panda-Jonas, Songhomitra, Pandey, Anamika, Pandey, Ashok, Pandian, Jeyaraj Durai, Pangaribuan, Helena Ullyartha, Pantazopoulos, Ioannis, Pardhan, Shahina, Parija, Pragyan Paramita, Parikh, Romil R, Park, Seoyeon, Parthasarathi, Ashwaghosha, Pashaei, Ava, Patel, Jay, Patil, Shankargouda, Patoulias, Dimitrios, Pawar, Shrikant, Pedersini, Paolo, Pensato, Umberto, Pereira, David M, Pereira, Jeevan, Pereira, Maria Odete, Peres, Mario F P, Perico, Norberto, Perna, Simone, Petcu, Ionela-Roxana, Petermann-Rocha, Fanny Emily, Pham, Hoang Tran, Phillips, Michael R, Pinilla-Monsalve, Gabriel D, Piradov, Michael A, Plotnikov, Evgenii, Poddighe, Dimitri, Polat, Burcu, Poluru, Ramesh, Pond, Constance Dimity, Poudel, Govinda Raj, Pouramini, Alireza, Pourbagher-Shahri, Ali Mohammad, Pourfridoni, Mohammad, Pourtaheri, Naeimeh, Prakash, Peralam Yegneswaran, Prakash, Sanjay, Prakash, V, Prates, Elton Junio Sady, Pritchett, Natalie, Purnobasuki, Hery, Qasim, Nameer Hashim, Qattea, Ibrahim, Qian, Gangzhen, Radhakrishnan, Venkatraman, Raee, Pourya, Raeisi Shahraki, Hadi, Rafique, Ibrar, Raggi, Alberto, Raghav, Pankaja Raghav, Rahati, Meghdad M, Rahim, Fakher, Rahimi, Zahra, Rahimifard, Mahban, Rahman, Md Obaidur, Rahman, Mohammad Hifz Ur, Rahman, Mosiur, Rahman, Muhammad Aziz, Rahmani, Amir Masoud, Rahmani, Shayan, Rahmani Youshanlouei, Hamed, Rahmati, Masoud, Raj Moolambally, Sheetal, Rajabpour-Sanati, Ali, Ramadan, Hazem, Ramasamy, Shakthi Kumaran, Ramasubramani, Premkumar, Ramazanu, Sheena, Rancic, Nemanja, Rao, Indu Ramachandra, Rao, Sowmya J, Rapaka, Deepthi, Rashedi, Vahid, Rashid, Ahmed Mustafa, Rashidi, Mohammad-Mahdi, Rashidi Alavijeh, Mehran, Rasouli-Saravani, Ashkan, Rawaf, Salman, Razo, Christian, Redwan, Elrashdy Moustafa Mohamed, Rekabi Bana, Atefe, Remuzzi, Giuseppe, Rezaei, Nazila, Rezaei, Negar, Rezaei, Nima, Rezaeian, Mohsen, Rhee, Taeho Gregory, Riad, Abanoub, Robinson, Stephen R, Rodrigues, Mónica, Rodriguez, Jefferson Antonio Buendia, Roever, Leonardo, Rogowski, Emma L B, Romoli, Michele, Ronfani, Luca, Roy, Priyanka, Roy Pramanik, Koushik, Rubagotti, Enrico, Ruiz, Milagros A, Russ, Tom C, S Sunnerhagen, Katharina, Saad, Aly M A, Saadatian, Zahra, Saber, Korosh, SaberiKamarposhti, Morteza, Sacco, Simona, Saddik, Basema, Sadeghi, Erfan, Sadeghian, Saeid, Saeed, Umar, Saeed, Usman, Safdarian, Mahdi, Safi, Sher Zaman, Sagar, Rajesh, Sagoe, Dominic, Saheb Sharif-Askari, Fatemeh, Saheb Sharif-Askari, Narjes, Sahebkar, Amirhossein, Sahoo, Soumya Swaroop, Sahraian, Mohammad Ali, Sajedi, Seyed Aidin, Sakshaug, Joseph W, Saleh, Mohamed A, Salehi Omran, Hossein, Salem, Marwa Rashad, Salimi, Sohrab, Samadi Kafil, Hossein, Samadzadeh, Sara, Samargandy, Saad, Samodra, Yoseph Leonardo, Samuel, Vijaya Paul, Samy, Abdallah M, Sanadgol, Nima, Sanjeev, Rama Krishna, Sanmarchi, Francesco, Santomauro, Damian Francesco, Santri, Ichtiarini Nurullita, Santric-Milicevic, Milena M, Saravanan, Aswini, Sarveazad, Arash, Satpathy, Maheswar, Saylan, Mete, Sayyah, Mehdi, Scarmeas, Nikolaos, Schlaich, Markus P, Schuermans, Art, Schwarzinger, Michaël, Schwebel, David C, Selvaraj, Siddharthan, Sendekie, Ashenafi Kibret, Sengupta, Pallav, Senthilkumaran, Subramanian, Serban, Dragos, Sergindo, Mihretu Tagesse, Sethi, Yashendra, SeyedAlinaghi, SeyedAhmad, Seylani, Allen, Shabani, Mohammad, Shabany, Maryam, Shafie, Mahan, Shahabi, Saeed, Shahbandi, Ataollah, Shahid, Samiah, Shahraki-Sanavi, Fariba, Shahsavari, Hamid R, Shahwan, Moyad Jamal, Shaikh, Masood Ali, Shaji, KS, Sham, Sunder, Shama, Adisu Tafari T, Shamim, Muhammad Aaqib, Shams-Beyranvand, Mehran, Shamsi, Mohammad Anas, Shanawaz, Mohd, Sharath, Medha, Sharfaei, Sadaf, Sharifan, Amin, Sharma, Manoj, Sharma, Rajesh, Shashamo, Bereket Beyene, Shayan, Maryam, Sheikhi, Rahim Ali, Shekhar, Shashank, Shen, Jiabin, Shenoy, Suchitra M, Shetty, Pavanchand H, Shiferaw, Desalegn Shiferaw, Shigematsu, Mika, Shiri, Rahman, Shittu, Aminu, Shivakumar, K M, Shokri, Fereshteh, Shool, Sina, Shorofi, Seyed Afshin, Shrestha, Sunil, Siankam Tankwanchi, Akhenaten Benjamin, Siddig, Emmanuel Edwar, Sigfusdottir, Inga Dora, Silva, João Pedro, Silva, Luís Manuel Lopes Rodrigues, Sinaei, Ehsan, Singh, Balbir Bagicha, Singh, Garima, Singh, Paramdeep, Singh, Surjit, Sirota, Sarah Brooke, Sivakumar, Shravan, Sohag, Abdullah Al Mamun, Solanki, Ranjan, Soleimani, Hamidreza, Solikhah, Solikhah, Solomon, Yerukneh, Solomon, Yonatan, Song, Suhang, Song, Yimeng, Sotoudeh, Houman, Spartalis, Michael, Stark, Benjamin A, Starnes, Joseph R, Starodubova, Antonina V, Stein, Dan J, Steiner, Timothy J, Stovner, Lars Jacob, Suleman, Muhammad, Suliankatchi Abdulkader, Rizwan, Sultana, Abida, Sun, Jing, Sunkersing, David, Sunny, Angel, Susianti, Hani, Swain, Chandan Kumar, Szeto, Mindy D, Tabarés-Seisdedos, Rafael, Tabatabaei, Seyyed Mohammad, Tabatabai, Shima, Tabish, Mohammad, Taheri, Majid, Tahvildari, Azin, Tajbakhsh, Ardeshir, Tampa, Mircea, Tamuzi, Jacques JL Lukenze, Tan, Ker-Kan, Tang, Haosu, Tareke, Minale, Tarigan, Ingan Ukur, Tat, Nathan Y, Tat, Vivian Y, Tavakoli Oliaee, Razieh, Tavangar, Seyed Mohammad, Tavasol, Arian, Tefera, Yibekal Manaye, Tehrani-Banihashemi, Arash, Temesgen, Worku Animaw, Temsah, Mohamad-Hani, Teramoto, Masayuki, Tesfaye, Amensisa Hailu, Tesfaye, Edosa Geta, Tesler, Riki, Thakali, Ocean, Thangaraju, Pugazhenthan, Thapa, Rajshree, Thapar, Rekha, Thomas, Nikhil Kenny, Thrift, Amanda G, Ticoalu, Jansje Henny Vera, Tillawi, Tala, Toghroli, Razie, Tonelli, Marcello, Tovani-Palone, Marcos Roberto, Traini, Eugenio, Tran, Nghia Minh, Tran, Ngoc-Ha, Tran, Phu Van, Tromans, Samuel Joseph, Truelsen, Thomas Clement, Truyen, Thien Tan Tri Tai, Tsatsakis, Aristidis, Tsegay, Guesh Mebrahtom, Tsermpini, Evangelia Eirini, Tualeka, Abdul Rohim, Tufa, Derara Girma, Ubah, Chukwudi S, Udoakang, Aniefiok John, Ulhaq, Inam, Umair, Muhammad, Umakanthan, Srikanth, Umapathi, Krishna Kishore, Unim, Brigid, Unnikrishnan, Bhaskaran, Vaithinathan, Asokan Govindaraj, Vakilian, Alireza, Valadan Tahbaz, Sahel, Valizadeh, Rohollah, Van den Eynde, Jef, Vart, Priya, Varthya, Shoban Babu, Vasankari, Tommi Juhani, Vaziri, Siavash, Vellingiri, Balachandar, Venketasubramanian, Narayanaswamy, Verras, Georgios-Ioannis, Vervoort, Dominique, Villafańe, Jorge Hugo, Villani, Leonardo, Vinueza Veloz, Andres Fernando, Viskadourou, Maria, Vladimirov, Sergey Konstantinovitch, Vlassov, Vasily, Volovat, Simona Ruxandra, Vu, Loc Tri, Vujcic, Isidora S, Wagaye, Birhanu, Waheed, Yasir, Wahood, Waseem, Walde, Mandaras Tariku, Wang, Fang, Wang, Shu, Wang, Yanzhong, Wang, Yuan-Pang, Waqas, Muhammad, Waris, Abdul, Weerakoon, Kosala Gayan, Weintraub, Robert G, Weldemariam, Abrha Hailay, Westerman, Ronny, Whisnant, Joanna L, Wickramasinghe, Dakshitha Praneeth, Wickramasinghe, Nuwan Darshana, Willekens, Barbara, Wilner, Lauren B, Winkler, Andrea Sylvia, Wolfe, Charles D A, Wu, Ai-Min, Wulf Hanson, Sarah, Xu, Suowen, Xu, Xiaoyue, Yadollahpour, Ali, Yaghoubi, Sajad, Yahya, Galal, Yamagishi, Kazumasa, Yang, Lin, Yano, Yuichiro, Yao, Yao, Yehualashet, Sisay Shewasinad, Yeshaneh, Alex, Yesiltepe, Metin, Yi, Siyan, Yiğit, Arzu, Yiğit, Vahit, Yon, Dong Keon, Yonemoto, Naohiro, You, Yuyi, Younis, Mustafa Z, Yu, Chuanhua, Yusuf, Hadiza, Zadey, Siddhesh, Zahedi, Mohammad, Zakham, Fathiah, Zaki, Nazar, Zali, Alireza, Zamagni, Giulia, Zand, Ramin, Zandieh, Ghazal G Z, Zangiabadian, Moein, Zarghami, Amin, Zastrozhin, Mikhail Sergeevich, Zeariya, Mohammed G M, Zegeye, Zelalem Banjaw, Zeukeng, Francis, Zhai, Chunxia, Zhang, Chen, Zhang, Haijun, Zhang, Yunquan, Zhang, Zhi-Jiang, Zhao, Hanqing, Zhao, Yang, Zheng, Peng, Zhou, Hengxing, Zhu, Bin, Zhumagaliuly, Abzal, Zielińska, Magdalena, Zikarg, Yossef Teshome, Zoladl, Mohammad, Murray, Christopher J L, Ong, Kanyin Liane, Feigin, Valery L, Vos, Theo, and Dua, Tarun

Published
2024
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8. The PI3K/Akt signaling axis and type 2 diabetes mellitus (T2DM): From mechanistic insights into possible therapeutic targets.

Author

Taheri, Rana, Mokhtari, Yazdan, Yousefi, Amir‐Mohammad, and Bashash, Davood

Subjects
PI3K/AKT pathway, TYPE 2 diabetes, METABOLIC regulation, DRUG target, PHOSPHATIDYLINOSITOL 3-kinases, ADIPOSE tissues, PHOSPHOINOSITIDES, PANCREATIC beta cells
Abstract

Type 2 diabetes mellitus (T2DM) is an immensely debilitating chronic disease that progressively undermines the well‐being of various bodily organs and, indeed, most patients succumb to the disease due to post‐T2DM complications. Although there is evidence supporting the activation of the phosphoinositide 3‐kinase (PI3K)/Akt signaling pathway by insulin, which is essential in regulating glucose metabolism and insulin resistance, the significance of this pathway in T2DM has only been explored in a few studies. The current review aims to unravel the mechanisms by which different classes of PI3Ks control the metabolism of glucose; and also to discuss the original data obtained from international research laboratories on this topic. We also summarized the role of the PI3K/Akt signaling axis in target tissues spanning from the skeletal muscle to the adipose tissue and liver. Furthermore, inquiries regarding the impact of disrupting this axis on insulin function and the development of insulin resistance have been addressed. We also provide a general overview of the association of impaired PI3K/Akt signaling pathways in the pathogenesis of the most prevalent diabetes‐related complications. The last section provides a special focus on the therapeutic potential of this axis by outlining the latest advances in active compounds that alleviate diabetes via modulation of the PI3K/Akt pathway. Finally, we comment on the future research aspects in which the field of T2DM therapies using PI3K modulators might be developed. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Royal jelly induces ROS-mediated apoptosis in acute lymphoblastic leukemia (ALL)-derived Nalm-6 cells: Shedding light on novel therapeutic approaches for ALL.

Author

Yazdanparast, Somayeh, Bashash, Davood, Bahrami, Amirsalar Nikkhah, Ghorbani, Mohammad, Izadirad, Mehrdad, Bakhtiyaridovvombaygi, Mehdi, Hasanpour, Seyede Zahra, and Gharehbaghian, Ahmad

Subjects
*ROYAL jelly, *LYMPHOBLASTIC leukemia, *ACUTE leukemia, *THERAPEUTICS, *APOPTOSIS
Abstract

Objective(s): Until recently, a conventional chemotherapy regimen for Acute lymphoblastic leukemia (ALL) is considered an efficient therapeutic method in children. However, suboptimal long-term survival rates in adults, disease relapse, and drug-induced toxicities require novel therapeutic agents for ALL treatments. Today, natural products with pharmacological benefits play a significant role in treating different cancers. Among the most valued natural products, honey bees’ royal jelly (RJ) is one of the most appreciated which has revealed anti-tumor activity against different human cancers. This study aimed to evaluate anti-leukemic properties and the molecular mechanisms of RJ cytotoxicity on ALL-derived Nalm-6 cells. Materials and Methods: The metabolic activity was measured by MTT assay. Apoptosis, cell distribution in the cell cycle, and intracellular reactive oxygen species (ROS) level were investigated using flow cytometry analysis. Moreover, quantitative real-time PCR (qRT-PCR) was performed to scrutinize the expression of various regulatory genes. Results: RJ significantly decreased the viability of Nalm-6 cells but had no cytotoxic effect on normal cells. In addition, RJ induced ROS-mediated apoptosis by up-regulating pro-apoptotic genes while decreasing anti-apoptotic gene expression. The results outlined that ROS-dependent up-regulation of FOXO4 and Sirt1 inhibits the cells’ transition to the S phase of the cell cycle through p21 upregulation. The qRT-PCR analysis of autophagy-related gene expression also demonstrated that RJ induced BECN1 mediated autophagy in Naml-6 cells. Conclusion: Taken together, this study showed that RJ can be utilized as a potent natural substance to induce ALL cells’ programmed cell death. However, further studies are required to examine this compound’s pharmaceutical application. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Immune landscape of hepatocellular carcinoma: From dysregulation of the immune responses to the potential immunotherapies.

Author

Pourbagheri‐Sigaroodi, Atieh, Momeny, Majid, Rezaei, Nima, Fallah, Fatemeh, and Bashash, Davood

Subjects
TREATMENT effectiveness, MYELOID-derived suppressor cells, IMMUNE response, KILLER cells, REGULATORY T cells, HEPATOCELLULAR carcinoma
Abstract

Hepatocellular carcinoma (HCC) presents a considerable global health burden due to its late diagnosis and high morbidity. The liver's specific anatomical and physiological features expose it to various antigens, requiring precise immune regulation. To the best of our knowledge, this is the first time that a comprehensive overview of the interactions between the immune system and gut microbiota in the development of HCC, as well as the relevant therapeutic approaches are discussed. Dysregulation of immune compartments within the liver microenvironment drives HCC pathogenesis, characterized by elevated regulatory cells such as regulatory T cells (Tregs), myeloid‐derived suppressor cells, and M2 macrophages as well as suppressive molecules, alongside reduced number of effector cells like T cells, natural killer cells, and M1 macrophages. Dysbiosis of gut microbiota also contributes to HCC by disrupting intestinal barrier integrity and triggering overactivated immune responses. Immunotherapy approaches, particularly immune checkpoint inhibitors, have exhibited promise in HCC management, yet adoptive cell therapy and cancer vaccination research are in the early steps with relatively less favorable outcomes. Further understanding of immune dysregulation, gut microbiota involvement, and therapeutic combination strategies are essential for advancing precision immunotherapy in HCC. Significance statement: Hepatocellular carcinoma (HCC) presents a considerable global health burden due to its late diagnosis and high morbidity. The liver's specific anatomical and physiological features expose it to various antigens, requiring precise immune regulation. Dysregulation of immune compartments within the liver microenvironment drives HCC pathogenesis, characterized by elevated regulatory cells such as Tregs, myeloid‐derived suppressor cells, and M2 macrophages. This review article provides a comprehensive overview of the key immunological features of the liver and the intricate interactions between the immune system and HCC. It takes a close look at the roles of innate and adaptive immune effector cells, as well as the immunosuppressive regulatory immune cells, in shaping the tumor microenvironment. Importantly, it explores the crosstalk between the gut microbiome and the liver immune response, underscoring the importance of this gut‐liver axis in HCC pathogenesis. Furthermore, the article examines the emerging applications of immunotherapy, including immune checkpoint inhibitors, adoptive cell therapy, and therapeutic cancer vaccination, in the treatment of HCC. This knowledge is essential for advancing our understanding of the complex interplay between the immune system and liver cancer, and for developing more effective immunotherapeutic strategies to improve clinical outcomes for HCC patients. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Unleashing the Impact of Exosomes Derived from Human Placental Mesenchymal Stem Cells (hPMSCs) on U-266 Myeloma Cell Line.

Author

Saghchy Khorasani, Ayda Baghery, Soufizomorrod, Mina, and Bashash, Davood

Subjects
PLASMA cell leukemia, MESENCHYMAL stem cells, PLASMA cells, CELL cycle, CANCER cells
Abstract

Multiple myeloma (MM) is a malignancy of plasma cells, terminally differentiated B cells, with complications like hypercalcemia, renal failure, anemia, and bone disease, which are also known as CRAB criteria. MM develops from monoclonal gammopathy of unknown significance (MGUS), a pre-malignant plasma cell dyscrasia. Over some time, MGUS has the potential to progress into smoldering multiple myeloma (SMM), which can evolve into MM. MM rarely progresses into plasma cell leukemia (PCL), a condition in which malignant plasma cells no longer stay in the bone marrow niche and circulate in the peripheral blood. In MM, various soluble factors play important roles, and interleukin-6 has different vital roles. Interleukin-6, an inflammatory cytokine, has significant roles in the growth, survival, angiogenesis, metastasis, and apoptosis resistance in MM. Interleukin-6 is produced and secreted by both autocrine from myeloma cells and paracrine from bone marrow stromal cells. To tackle MM, various therapeutic approaches were applied over many years, and according to the results, most patients with MM can respond well to first-line treatment. However, the majority of patients may relapse as conventional treatment may not be curative. So, there is an urgent need for novel cell-based and cell-free therapeutic strategies, such as mesenchymal stem cell-based therapies and their products to offer new therapeutic strategies for MM. Materials and Methods: In the present study, we investigated the impacts of exosomes derived from human placental mesenchymal stem cells (hPMSCs) on apoptosis and interleukin-6 expression in a myeloma cell line, U-266, for the first time. hPMSCs were isolated from the human placenta and cultured in a DMEM medium. After characterizing the cells and acknowledging their identity, they underwent several passages and their supernatant was collected to harvest exosomes. The exosomes were isolated by ultracentrifugation and characterized by DLS and TEM, and their concentration was measured by BCA protein assay. U266 cells were treated with different concentrations of exosomes and then MTT and annexin/propidium iodide flow cytometry tests were performed to evaluate cell viability. Afterward, a real-time PCR test was performed to evaluate interleukin-6 gene expression. Results: According to our findings, treatment of U-266 cells with hPMSCS-derived exosomes led to the preservation of myeloma cells without changes in their cell cycle. Surprisingly, treatments did not hinder the expression of interleukin-6 in the myeloma cells. Conclusion: In MM patients, interleukin-6 pl ays different roles, and it is a desirable target to design new therapeutic strategies. To evaluate the effects of new therapeutic strategies, we designed and performed our study to estimate the effects of cell-free therapeutic strategy. In the present study, the impacts of hPMSCS-derived exosomes on the viability of MM cells and interleukin-6 gene expression were evaluated. The results showed that hPMSCS-derived exosomes resulted in the perseverance of myeloma cells without changes in the cell cycle. Furthermore, the interleukin-6 gene expression level showed no significant change. [ABSTRACT FROM AUTHOR]

Published
2024

16. Gaillardin exerts potent antileukemic effects on HL‐60 cells and intensifies arsenic trioxide cytotoxicity: Providing new insight into sesquiterpene lactones in leukaemia treatment.

Author

Noormohamadi, Hanieh, Hamzeloo‐Moghadam, Maryam, Bashash, Davood, Kargar, Maryam, Izadirad, Mehrdad, Hasanpour, Seyedeh Zahra, and Gharehbaghian, Ahmad

Subjects
ARSENIC trioxide, SESQUITERPENE lactones, ACUTE promyelocytic leukemia, CYTOTOXINS, LEUKEMIA, REACTIVE oxygen species, TERPENES
Abstract

The use of all‐trans retinoic acid and arsenic trioxide resulted in favourable therapeutic responses in standard‐risk acute promyelocytic leukaemia (APL) patients. However, resistance to these agents has made treating the high‐risk subgroup more problematic, and possible side effects limit their clinical dosages. Numerous studies have proven the cytotoxic properties of Gaillardin, one of the Inula oculus‐christi‐derived sesquiterpene lactones. Due to the adverse effects of arsenic trioxide on the high‐risk subgroup of APL patients, we aimed to assess the cytotoxic effect of Gaillardin on HL‐60 cells as a single or combined‐form approach. The results of the trypan blue and MTT assays outlined the potent cytotoxic properties of Gaillardin. The flow cytometric analysis and the mRNA expression levels revealed that Gaillardin attenuated the proliferative capacity of HL‐60 cells through cell cycle arrest and induced apoptosis via reactive oxygen species generation. Moreover, the results of synergistic experiments indicated that this sesquiterpene lactone sensitizes HL‐60 cells to the cytotoxic effects of arsenic trioxide. Taken together, the findings of the present investigation highlighted the antileukemic characteristics of Gaillardin by inducing G1 cell cycle arrest and triggering apoptosis. Gaillardin acts as an antileukemic metabolite against HL‐60 cells and this study provides new insight into treating APL patients, especially in the high‐risk subgroup. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Construction of immune-related gene pairs signature to predict the overall survival of multiple myeloma patients based on whole bone marrow gene expression profiling.

Author

Jafari-Raddani, Farideh, Davoodi-Moghaddam, Zeinab, and Bashash, Davood

Abstract

Multiple myeloma (MM) is a plasma cell dyscrasia that is characterized by the uncontrolled proliferation of malignant PCs in the bone marrow. Due to immunotherapy, attention has returned to the immune system in MM, and it appears necessary to identify biomarkers in this area. In this study, we created a prognostic model for MM using immune-related gene pairs (IRGPs), with the advantage that it is not affected by technical bias. After retrieving microarray data of MM patients, bioinformatics analyses like COX regression and least absolute shrinkage and selection operator (LASSO) were used to construct the signature. Then its prognostic value is assessed via time-dependent receiver operating characteristic (ROC) and the Kaplan–Meier (KM) analysis. We also used XCELL to examine the status of immune cell infiltration among MM patients. 6-IRGP signatures were developed and proved to predict MM prognosis with a P-value of 0.001 in the KM analysis. Moreover, the risk score was significantly associated with clinicopathological characteristics and was an independent prognostic factor. Of note, the combination of age and β2-microglobulin with risk score could improve the accuracy of determining patients’ prognosis with the values of the area under the curve (AUC) of 0.73 in 5 years ROC curves. Our model was also associated with the distribution of immune cells. This novel signature, either alone or in combination with age and β2-microglobulin, showed a good prognostic predictive value and might be used to guide the management of MM patients in clinical practice. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Prognostic Significance of Circulating and Disseminated Tumor Cells in Breast Cancer Patients before and after Adjuvant Chemotherapy.

Author

Ghaffari, Parisa, Yousefi, Meysam, Aznab, Mozaffar, Khazan, Negar, Yaghmaie, Marjan, Bashash, Davood, Vaezi, Mohammad, Ghavamzadeh, Ardeshir, and Ghaffari, Seyed Hamidollah

Subjects
*ADJUVANT chemotherapy, *TREFOIL factors, *CARCINOEMBRYONIC antigen, *POLYMERASE chain reaction, *GENE expression
Abstract

Objective: Despite the advances in treatment, breast cancer (BC) remains a major cause of death in women. This study aims to evaluate the prognostic significance of detecting circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in paired peripheral blood (PB) and bone marrow (BM) samples obtained both before and after adjuvant chemotherapy from patients with operable BC. Materials and Methods: In this experimental study, from 160 patients with primary BC, we collected 160 PB and BM samples before and we could be able to collect PB and BM samples from 100 of them after adjuvant chemotherapy. The expression level of cytokeratin 19 (CK19), carcinoembryonic antigen (CEA), mammaglobin 1 (MGB1), mucin 2 (MUC2) and trefoil factor 1 (TFF1) mRNAs in the PB/BM samples were analyzed by quantitative real-time polymerase chain reaction (PCR). Results: Multivariate Cox regression analyses indicated that the detection of CK19 mRNA-positive CTCs/DTCs either before or after adjuvant chemotherapy was an independent factor for prognosis associated with decreased disease-free survival (DFS). Patients with tumor cells detected in both PB and BM and patients with persistent detection of tumor cells before and after chemotherapy had worse outcomes compared to those with tumor cells detected in one or neither of the compartments. Conclusion: This study suggests that the detection of CK19 mRNA-positive CTCs/DTCs either before or after adjuvant chemotherapy could be an independent predictor of DFS in operable BC patients. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Monkeypox (Mpox) vs. Innate immune responses: Insights into evasion mechanisms and potential therapeutic strategies.

Author

Pashazadeh Azari P, Rezaei Zadeh Rukerd M, Charostad J, Bashash D, Farsiu N, Behzadi S, Mahdieh Khoshnazar S, Heydari S, and Nakhaie M

Abstract

Orthopoxviruses, a group of zoonotic viral infections, have emerged as a significant health emergency and global concern, particularly exemplified by the re-emergence of monkeypox (Mpox). Effectively addressing these viral infections necessitates a comprehensive understanding of the intricate interplay between the viruses and the host's immune response. In this review, we aim to elucidate the multifaceted aspects of innate immunity in the context of orthopoxviruses, with a specific focus on monkeypox virus (MPXV). We provide an in-depth analysis of the roles of key innate immune cells, including natural killer (NK) cells, dendritic cells (DCs), and granulocytes, in the host defense against MPXV. Furthermore, we explore the interferon (IFN) response, highlighting the involvement of toll-like receptors (TLRs) and cytosolic DNA/RNA sensors in detecting and responding to the viral presence. This review also examines the complement system's contribution to the immune response and provides a detailed analysis of the immune evasion strategies employed by MPXV to evade host defenses. Additionally, we discuss current prevention and treatment strategies for Mpox, including pre-exposure (PrEP) and post-exposure (PoEP) prophylaxis, supportive treatments, antivirals, and vaccinia immune globulin (VIG)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Published
2024
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20. Unleashing the Impact of Exosomes Derived from Human Placental Mesenchymal Stem Cells (hPMSCs) on U-266 Myeloma Cell Line.

Author

Baghery Saghchy Khorasani A, Soufizomorrod M, and Bashash D

Abstract

Multiple myeloma (MM) is a malignancy of plasma cells, terminally differentiated B cells, with complications like hypercalcemia, renal failure, anemia, and bone disease, which are also known as CRAB criteria. MM develops from monoclonal gammopathy of unknown significance (MGUS), a pre-malignant plasma cell dyscrasia. Over some time, MGUS has the potential to progress into smoldering multiple myeloma (SMM), which can evolve into MM. MM rarely progresses into plasma cell leukemia (PCL), a condition in which malignant plasma cells no longer stay in the bone marrow niche and circulate in the peripheral blood. In MM, various soluble factors play important roles, and interleukin-6 has different vital roles.  Interleukin-6, an inflammatory cytokine, has significant roles in the growth, survival, angiogenesis, metastasis, and apoptosis resistance in MM. Interleukin-6 is produced and secreted by both autocrine from myeloma cells and paracrine from bone marrow stromal cells. To tackle MM, various therapeutic approaches were applied over many years, and according to the results, most patients with MM can respond well to first-line treatment. However, the majority of patients may relapse as conventional treatment may not be curative. So, there is an urgent need for novel cell-based and cell-free therapeutic strategies, such as mesenchymal stem cell-based therapies and their products to offer new therapeutic strategies for MM. Materials and Methods: In the present study, we investigated the impacts of exosomes derived from human placental mesenchymal stem cells (hPMSCs) on apoptosis and interleukin-6 expression in a myeloma cell line, U-266, for the first time. hPMSCs were isolated from the human placenta and cultured in a DMEM medium. After characterizing the cells and acknowledging their identity, they underwent several passages and their supernatant was collected to harvest exosomes. The exosomes were isolated by ultracentrifugation and characterized by DLS and TEM, and their concentration was measured by BCA protein assay. U266 cells were treated with different concentrations of exosomes and then MTT and annexin/propidium iodide flow cytometry tests were performed to evaluate cell viability. Afterward, a real-time PCR test was performed to evaluate interleukin-6 gene expression. Results: According to our findings, treatment of U-266 cells with hPMSCS-derived exosomes led to the preservation of myeloma cells without changes in their cell cycle. Surprisingly, treatments did not hinder the expression of interleukin-6 in the myeloma cells. Conclusion: In MM patients, interleukin-6 pl ays different roles, and it is a desirable target to design new therapeutic strategies. To evaluate the effects of new therapeutic strategies, we designed and performed our study to estimate the effects of cell-free therapeutic strategy.  In the present study, the impacts of hPMSCS-derived exosomes on the viability of MM cells and interleukin-6 gene expression were evaluated. The results showed that hPMSCS-derived exosomes resulted in the perseverance of myeloma cells without changes in the cell cycle.  Furthermore, the interleukin-6 gene expression level showed no significant change., Competing Interests: The authors declared that there is no conflict of interests., (Copyright © 2024 Tehran University of Medical Sciences.)

Published
2024
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