Browsing by Author "Bharat B. Aggarwal"

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Chronic diseases, inflammation, and spices: How are they linked?
(BioMed Central Ltd., 2018) Ajaikumar B. Kunnumakkara; Bethsebie L. Sailo; Kishore Banik; Choudhary Harsha; Sahdeo Prasad; Subash Chandra Gupta; Alok Chandra Bharti; Bharat B. Aggarwal
Extensive research within the last several decades has revealed that the major risk factors for most chronic diseases are infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and diet. It is now well established that these factors induce chronic diseases through induction of inflammation. However, inflammation could be either acute or chronic. Acute inflammation persists for a short duration and is the host defense against infections and allergens, whereas the chronic inflammation persists for a long time and leads to many chronic diseases including cancer, cardiovascular diseases, neurodegenerative diseases, respiratory diseases, etc. Numerous lines of evidence suggest that the aforementioned risk factors induced cancer through chronic inflammation. First, transcription factors NF-ΚB and STAT3 that regulate expression of inflammatory gene products, have been found to be constitutively active in most cancers; second, chronic inflammation such as pancreatitis, prostatitis, hepatitis etc. leads to cancers; third, activation of NF-ΚB and STAT3 leads to cancer cell proliferation, survival, invasion, angiogenesis and metastasis; fourth, activation of NF-ΚB and STAT3 leads to resistance to chemotherapy and radiation, and hypoxia and acidic conditions activate these transcription factors. Therefore, targeting these pathways may provide opportunities for both prevention and treatment of cancer and other chronic diseases. We will discuss in this review the potential of various dietary agents such as spices and its components in the suppression of inflammatory pathways and their roles in the prevention and therapy of cancer and other chronic diseases. In fact, epidemiological studies do indicate that cancer incidence in countries such as India where spices are consumed daily is much lower (94/100,000) than those where spices are not consumed such as United States (318/100,000), suggesting the potential role of spices in cancer prevention. © 2018 The Author(s).
COVID-19, cytokines, inflammation, and spices: How are they related?
(Elsevier Inc., 2021) Ajaikumar B. Kunnumakkara; Varsha Rana; Dey Parama; Kishore Banik; Sosmitha Girisa; Sahu Henamayee; Krishan Kumar Thakur; Uma Dutta; Prachi Garodia; Subash C. Gupta; Bharat B. Aggarwal
Background: Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-19 associated deaths (as of January 15, 2021; https://www.worldometers.info/coronavirus/) in the USA is high (1199/million) as compared to countries like India (110/million). Although the reason behind this is not clear, spices may have some role in explaining this difference. Spices and herbs are used in different traditional medicines, especially in countries such as India to treat various chronic diseases due to their potent antioxidant and anti-inflammatory properties. Aim: To evaluate the literature available on the anti-inflammatory properties of spices which might prove beneficial in the prevention and treatment of COVID-19 associated cytokine storm. Method: A detailed literature search has been conducted on PubMed for collecting information pertaining to the COVID-19; the history, origin, key structural features, and mechanism of infection of SARS-CoV-2; the repurposed drugs in use for the management of COVID-19, and the anti-inflammatory role of spices to combat COVID-19 associated cytokine storm. Key findings: The literature search resulted in numerous in vitro, in vivo and clinical trials that have reported the potency of spices to exert anti-inflammatory effects by regulating crucial molecular targets for inflammation. Significance: As spices are derived from Mother Nature and are inexpensive, they are relatively safer to consume. Therefore, their anti-inflammatory property can be exploited to combat the cytokine storm in COVID-19 patients. This review thus focuses on the current knowledge on the role of spices for the treatment of COVID-19 through suppression of inflammation-linked cytokine storm. © 2021 Elsevier Inc.
Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials
(Academic Press, 2016) Amirhossein Sahebkar; Arrigo F.G. Cicero; Luis E. Simental-Mendía; Bharat B. Aggarwal; Subash C. Gupta
Background Tumor necrosis factor-α (TNF-α) is a key inflammatory mediator and its reduction is a therapeutic target in several inflammatory diseases. Curcumin, a bioactive polyphenol from turmeric, has been shown in several preclinical studies to block TNF-α effectively. However, clinical evidence has not been fully conclusive. Objective The aim of the present meta-analysis was to evaluate the efficacy of curcumin supplementation on circulating levels of TNF-α in randomized controlled trials (RCTs). Methods The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases by up to September 21, 2015, to identify RCTs investigating the impact of curcumin on circulating TNF-α concentration. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Meta-regression and leave-one-out sensitivity analyses were performed to assess the modifiers of treatment response. Results Eight RCTs comprising nine treatment arms were finally selected for the meta-analysis. There was a significant reduction of circulating TNF-α concentrations following curcumin supplementation (WMD: -4.69 pg/mL, 95% CI: -7.10, -2.28, p < 0.001). This effect size was robust in sensitivity analysis. Meta-regression did not suggest any significant association between the circulating TNF-α-lowering effects of curcumin with either dose or duration (slope: 0.197; 95% CI: -1.73, 2.12; p = 0.841) of treatment. Conclusion This meta-analysis of RCTs suggested a significant effect of curcumin in lowering circulating TNF-α concentration. © 2016 Elsevier Ltd. All rights reserved.
Curcumin mediates anticancer effects by modulating multiple cell signaling pathways
(Portland Press Ltd, 2017) Ajaikumar B. Kunnumakkara; Devivasha Bordoloi; Choudhary Harsha; Kishore Banik; Subash C. Gupta; Bharat B. Aggarwal
Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170].Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s).
Curcumin, the Holistic Avant-Garde
(Elsevier Inc., 2017) Subash C. Gupta; Ajaikumar B. Kunnumakkara; Bharat B. Aggarwal
Curcumin is a polyphenol derived from the rhizomes of the turmeric (golden spice) that has been used in Ayurveda and traditional Chinese medicine since ancient times. Curcumin is a highly pleiotropic molecule; its safety and efficacy has been demonstrated in cell-based studies and in animal models. The pharmacokinetics, safety, and efficacy of curcumin have also been studied in humans for a wide range of diseases. Curcumin has been used either as a single agent or in combination with other agents. Modern science has delineated the molecular basis for the pleiotropic activities of curcumin. The pleiotropic activities of curcumin originate from its ability to modulate signaling pathways either by direct binding to molecules or in an indirect manner. Considering curcumin's multitargeting nature and its efficacy against multiple human diseases, polyphenol appears to represent a holistic medicine pointing to the entire human body. In this chapter, we discuss the reported activities of curcumin at molecular, cellular, and human levels. © 2017 Elsevier Inc. All rights reserved.
Dietary nutraceuticals as backbone for bone health
(Elsevier Inc., 2018) Manoj K. Pandey; Subash C. Gupta; Deepkamal Karelia; Patrick J. Gilhooley; Mehdi Shakibaei; Bharat B. Aggarwal
Bone loss or osteoporosis, is a slow-progressing disease that results from dysregulation of pro-inflammatory cytokines. The FDA has approved number of drugs for bone loss prevention, nonetheless all are expensive and have multiple side effects. The nutraceuticals identified from dietary agents such as butein, cardamonin, coronarin D curcumin, diosgenin, embelin, gambogic acid, genistein, plumbagin, quercetin, reseveratrol, zerumbone and more, can modulate cell signaling pathways and reverse/slow down osteoporosis. Most of these nutraceuticals are inexpensive; show no side effect while still possessing anti-inflammatory properties. This review provides various mechanisms of osteoporosis and how nutraceuticals can potentially prevent the bone loss. © 2018
Googling the guggul (Commiphora and Boswellia) for prevention of chronic diseases
(Frontiers Media S.A., 2018) Ajaikumar B. Kunnumakkara; Kishore Banik; Devivasha Bordoloi; Choudhary Harsha; Bethsebie L. Sailo; Ganesan Padmavathi; Nand K. Roy; Subash C. Gupta; Bharat B. Aggarwal
Extensive research during last 2 decades has revealed that most drugs discovered today, although costs billions of dollars for discovery, and yet they are highly ineffective in their clinical response. For instance, the European Medicines Agency has approved 68 anti-cancer drugs, and out of which 39 has reached the market level with no indication of increased survival nor betterment of quality of life. Even when drugs did improve survival rate compared to available treatment strategies, most of these were found to be clinically insignificant. This is a fundamental problem with modern drug discovery which is based on thinking that most chronic diseases are caused by alteration of a single gene and thus most therapies are single gene-targeted therapies. However, extensive research has revealed that most chronic diseases are caused by multiple gene products. Although most drugs designed by man are mono-targeted therapies, however, those designed by "mother nature" and have been used for thousands of years, are "multi-targeted" therapies. In this review, we examine two agents that have been around for thousands of years, namely "guggul" from Commiphora and Boswellia. Although we are all familiar with the search engine "google," this is another type of "guggul" that has been used for centuries and being explored for its various biological activities. The current review summarizes the traditional uses, chemistry, in vitro and in vivo biological activities, molecular targets, and clinical trials performed with these agents. © 2018 Kunnumakkara, Banik, Bordoloi, Harsha, Sailo, Padmavathi, Roy, Gupta and Aggarwal.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1
(Taylor and Francis Ltd., 2021) Daniel J. Klionsky; Amal Kamal Abdel-Aziz; Sara Abdelfatah; Mahmoud Abdellatif; Asghar Abdoli; Steffen Abel; Hagai Abeliovich; Marie H. Abildgaard; Yakubu Princely Abudu; Abraham Acevedo-Arozena; Iannis E. Adamopoulos; Khosrow Adeli; Timon E. Adolph; Annagrazia Adornetto; Elma Aflaki; Galila Agam; Anupam Agarwal; Bharat B. Aggarwal; Maria Agnello; Patrizia Agostinis; Javed N. Agrewala; Alexander Agrotis; Patricia V. Aguilar; S. Tariq Ahmad; Zubair M. Ahmed; Ulises Ahumada-Castro; Sonja Aits; Shu Aizawa; Yunus Akkoc; Tonia Akoumianaki; Hafize Aysin Akpinar; Ahmed M. Al-Abd; Lina Al-Akra; Abeer Al-Gharaibeh; Moulay A. Alaoui-Jamali; Simon Alberti; Elísabet Alcocer-Gómez; Cristiano Alessandri; Muhammad Ali; M. Abdul Alim Al-Bari; Saeb Aliwaini; Javad Alizadeh; Eugènia Almacellas; Alexandru Almasan; Alicia Alonso; Guillermo D. Alonso; Nihal Altan-Bonnet; Dario C. Altieri; Élida M. C. Álvarez; Sara Alves; Cristine Alves da Costa; Mazen M. Alzaharna; Marialaura Amadio; Consuelo Amantini; Cristina Amaral; Susanna Ambrosio; Amal O. Amer; Veena Ammanathan; Zhenyi An; Stig U. Andersen; Shaida A. Andrabi; Magaiver Andrade-Silva; Allen M. Andres; Sabrina Angelini; David Ann; Uche C. Anozie; Mohammad Y. Ansari; Pedro Antas; Adam Antebi; Zuriñe Antón; Tahira Anwar; Lionel Apetoh; Nadezda Apostolova; Toshiyuki Araki; Yasuhiro Araki; Kohei Arasaki; Wagner L. Araújo; Jun Araya; Catherine Arden; Maria-Angeles Arévalo; Sandro Arguelles; Esperanza Arias; Jyothi Arikkath; Hirokazu Arimoto; Aileen R. Ariosa; Darius Armstrong-James; Laetitia Arnauné-Pelloquin; Angeles Aroca; Daniela S. Arroyo; Ivica Arsov; Rubén Artero; Dalia Maria Lucia Asaro; Michael Aschner; Milad Ashrafizadeh; Osnat Ashur-Fabian; Atanas G. Atanasov; Alicia K. Au; Patrick Auberger; Holger W. Auner; Laure Aurelian; Riccardo Autelli; Laura Avagliano; Yenniffer Ávalos; Sanja Aveic; Célia Alexandra Aveleira; Tamar Avin-Wittenberg; Yucel Aydin; Scott Ayton; Srinivas Ayyadevara; Maria Azzopardi; Misuzu Baba; Jonathan M. Backer; Steven K. Backues; Dong-Hun Bae; Ok-Nam Bae; Soo Han Bae; Eric H. Baehrecke; Ahruem Baek; Seung-Hoon Baek; Sung Hee Baek; Giacinto Bagetta; Agnieszka Bagniewska-Zadworna; Hua Bai; Jie Bai; Xiyuan Bai; Yidong Bai; Nandadulal Bairagi; Shounak Baksi; Teresa Balbi; Cosima T. Baldari; Walter Balduini; Andrea Ballabio; Maria Ballester; Salma Balazadeh; Rena Balzan; Rina Bandopadhyay; Sreeparna Banerjee; Sulagna Banerjee; Ágnes Bánréti; Yan Bao; Mauricio S. Baptista; Alessandra Baracca; Cristiana Barbati; Ariadna Bargiela; Daniela Barilà; Peter G. Barlow; Sami J. Barmada; Esther Barreiro; George E. Barreto; Jiri Bartek; Bonnie Bartel; Alberto Bartolome; Gaurav R. Barve; Suresh H. Basagoudanavar; Diane C. Bassham; Robert C. Bast; Alakananda Basu; Henri Batoko; Isabella Batten; Etienne E. Baulieu; Bradley L. Baumgarner; Jagadeesh Bayry; Rupert Beale; Isabelle Beau; Florian Beaumatin; Luiz R.G. Bechara; George R. Beck; Michael F. Beers; Jakob Begun; Christian Behrends; Georg M.N. Behrens; Roberto Bei; Eloy Bejarano; Shai Bel; Christian Behl; Amine Belaid; Naïma Belgareh-Touzé; Cristina Bellarosa; Francesca Belleudi; Melissa Belló Pérez; Raquel Bello-Morales; Jackeline Soares de Oliveira Beltran; Sebastián Beltran; Doris Mangiaracina Benbrook; Mykolas Bendorius; Bruno A. Benitez; Irene Benito-Cuesta; Julien Bensalem; Martin W. Berchtold; Sabina Berezowska; Daniele Bergamaschi; Matteo Bergami; Andreas Bergmann; Laura Berliocchi; Clarisse Berlioz-Torrent; Amélie Bernard; Lionel Berthoux; Cagri G. Besirli; Sebastien Besteiro; Virginie M. Betin; Rudi Beyaert; Jelena S. Bezbradica; Kiran Bhaskar; Ingrid Bhatia-Kissova; Resham Bhattacharya; Sujoy Bhattacharya; Shalmoli Bhattacharyya; Md. Shenuarin Bhuiyan; Sujit Kumar Bhutia; Lanrong Bi; Xiaolin Bi; Trevor J. Biden; Krikor Bijian; Viktor A. Billes; Nadine Binart; Claudia Bincoletto; Asa B. Birgisdottir; Geir Bjorkoy; Gonzalo Blanco; Ana Blas-Garcia; Janusz Blasiak; Robert Blomgran; Klas Blomgren; Janice S. Blum; Emilio Boada-Romero; Mirta Boban; Kathleen Boesze-Battaglia; Philippe Boeuf; Barry Boland; Pascale Bomont; Paolo Bonaldo; Srinivasa Reddy Bonam; Laura Bonfili; Juan S. Bonifacino; Brian A. Boone; Martin D. Bootman; Matteo Bordi; Christoph Borner; Beat C. Bornhauser; Gautam Borthakur; Jürgen Bosch; Santanu Bose; Luis M. Botana; Juan Botas; Chantal M. Boulanger; Michael E. Boulton; Mathieu Bourdenx; Benjamin Bourgeois; Nollaig M. Bourke; Guilhem Bousquet; Patricia Boya; Peter V. Bozhkov; Luiz H. M. Bozi; Tolga O. Bozkurt; Doug E. Brackney; Christian H. Brandts; Ralf J. Braun; Gerhard H. Braus; Roberto Bravo-Sagua; José M. Bravo-San Pedro; Patrick Brest; Marie-Agnès Bringer; Alfredo Briones-Herrera; V. Courtney Broaddus; Peter Brodersen; Jeffrey L. Brodsky; Steven L. Brody; Paola G. Bronson; Jeff M. Bronstein; Carolyn N. Brown; Rhoderick E. Brown; Patricia C. Brum; John H. Brumell; Nicola Brunetti-Pierri; Daniele Bruno; Robert J. Bryson-Richardson; Cecilia Bucci; Carmen Buchrieser; Marta Bueno; Laura Elisa Buitrago-Molina; Simone Buraschi; Shilpa Buch; J. Ross Buchan; Erin M. Buckingham; Hikmet Budak; Mauricio Budini; Geert Bultynck; Florin Burada; Joseph R. Burgoyne; M. Isabel Burón; Victor Bustos; Sabrina Büttner; Elena Butturini; Aaron Byrd; Isabel Cabas; Sandra Cabrera-Benitez; Ken Cadwell; Jingjing Cai; Lu Cai; Qian Cai; Montserrat Cairó; Jose A. Calbet; Guy A. Caldwell; Kim A. Caldwell; Jarrod A. Call; Riccardo Calvani; Ana C. Calvo; Miguel Calvo-Rubio Barrera; Niels OS Camara; Jacques H. Camonis; Nadine Camougrand; Michelangelo Campanella; Edward M. Campbell; François-Xavier Campbell-Valois; Silvia Campello; Ilaria Campesi; Juliane C. Campos; Olivier Camuzard; Jorge Cancino; Danilo Candido de Almeida; Laura Canesi; Isabella Caniggia; Barbara Canonico; Carles Cantí; Bin Cao; Michele Caraglia; Beatriz Caramés; Evie H. Carchman; Elena Cardenal-Muñoz; Cesar Cardenas; Luis Cardenas; Sandra M. Cardoso; Jennifer S. Carew; Georges F. Carle; Gillian Carleton; Silvia Carloni; Didac Carmona-Gutierrez; Leticia A. Carneiro; Oliana Carnevali; Julian M. Carosi; Serena Carra; Alice Carrier; Lucie Carrier; Bernadette Carroll; A. Brent Carter; Andreia Neves Carvalho; Magali Casanova; Caty Casas; Josefina Casas; Chiara Cassioli; Eliseo F. Castillo; Karen Castillo; Sonia Castillo-Lluva; Francesca Castoldi; Marco Castori; Ariel F. Castro; Margarida Castro-Caldas; Javier Castro-Hernandez; Susana Castro-Obregon; Sergio D. Catz; Claudia Cavadas; Federica Cavaliere; Gabriella Cavallini; Maria Cavinato; Maria L. Cayuela; Paula Cebollada Rica; Valentina Cecarini; Francesco Cecconi; Marzanna Cechowska-Pasko; Simone Cenci; Victòria Ceperuelo-Mallafré; João J. Cerqueira; Janete M. Cerutti; Davide Cervia; Vildan Bozok Cetintas; Silvia Cetrullo; Han-Jung Chae; Andrei S. Chagin; Chee-Yin Chai; Gopal Chakrabarti; Oishee Chakrabarti; Tapas Chakraborty; Trinad Chakraborty; Mounia Chami; Georgios Chamilos; David W. Chan; Edmond Y. W. Chan; Edward D. Chan; H.Y. Edwin Chan; Helen H. Chan; Hung Chan; Matthew T.V. Chan; Yau Sang Chan; Partha K. Chandra; Chih-Peng Chang; Chunmei Chang; Hao-Chun Chang; Kai Chang; Jie Chao; Tracey Chapman; Nicolas Charlet-Berguerand; Samrat Chatterjee; Shail K. Chaube; Anu Chaudhary; Santosh Chauhan; Edward Chaum; Frédéric Checler; Michael E. Cheetham; Chang-Shi Chen; Guang-Chao Chen; Jian-Fu Chen; Liam L. Chen; Leilei Chen; Lin Chen; Mingliang Chen; Mu-Kuan Chen; Ning Chen; Quan Chen; Ruey-Hwa Chen; Shi Chen; Wei Chen; Weiqiang Chen; Xin-Ming Chen; Xiong-Wen Chen; Xu Chen; Yan Chen; Ye-Guang Chen; Yingyu Chen; Yongqiang Chen; Yu-Jen Chen; Yue-Qin Chen; Zhefan Stephen Chen; Zhi Chen; Zhi-Hua Chen; Zhijian J. Chen; Zhixiang Chen; Hanhua Cheng; Jun Cheng; Shi-Yuan Cheng; Wei Cheng; Xiaodong Cheng; Xiu-Tang Cheng; Yiyun Cheng; Zhiyong Cheng; Zhong Chen; Heesun Cheong; Jit Kong Cheong; Boris V. Chernyak; Sara Cherry; Chi Fai Randy Cheung; Chun Hei Antonio Cheung; King-Ho Cheung; Eric Chevet; Richard J. Chi; Alan Kwok Shing Chiang; Ferdinando Chiaradonna; Roberto Chiarelli; Mario Chiariello; Nathalia Chica; Susanna Chiocca; Mario Chiong; Shih-Hwa Chiou; Abhilash I. Chiramel; Valerio Chiurchiù; Dong-Hyung Cho; Seong-Kyu Choe; Augustine M.K. Choi; Mary E. Choi; Kamalika Roy Choudhury; Norman S. Chow; Charleen T. Chu; Jason P. Chua; John Jia En Chua; Hyewon Chung; Kin Pan Chung; Seockhoon Chung; So-Hyang Chung; Yuen-Li Chung; Valentina Cianfanelli; Iwona A. Ciechomska; Mariana Cifuentes; Laura Cinque; Sebahattin Cirak; Mara Cirone; Michael J. Clague; Robert Clarke; Emilio Clementi; Eliana M. Coccia; Patrice Codogno; Ehud Cohen; Mickael M. Cohen; Tania Colasanti; Fiorella Colasuonno; Robert A. Colbert; Anna Colell; Miodrag Čolić; Nuria S. Coll; Mark O. Collins; María I. Colombo; Daniel A. Colón-Ramos; Lydie Combaret; Sergio Comincini; Márcia R. Cominetti; Antonella Consiglio; Andrea Conte; Fabrizio Conti; Viorica Raluca Contu; Mark R. Cookson; Kevin M. Coombs; Isabelle Coppens; Maria Tiziana Corasaniti; Dale P. Corkery; Nils Cordes; Katia Cortese; Maria do Carmo Costa; Sarah Costantino; Paola Costelli; Ana Coto-Montes; Peter J. Crack; Jose L. Crespo; Alfredo Criollo; Valeria Crippa; Riccardo Cristofani; Tamas Csizmadia; Antonio Cuadrado; Bing Cui; Jun Cui; Yixian Cui; Yong Cui; Emmanuel Culetto; Andrea C. Cumino; Andrey V. Cybulsky; Mark J. Czaja; Stanislaw J. Czuczwar; Stefania D’Adamo; Marcello D’Amelio; Daniela D’Arcangelo; Andrew C. D’Lugos; Gabriella D’Orazi; James A. da Silva; Hormos Salimi Dafsari; Ruben K. Dagda; Yasin Dagdas; Maria Daglia; Xiaoxia Dai; Yun Dai; Yuyuan Dai; Jessica Dal Col; Paul Dalhaimer; Luisa Dalla Valle; Tobias Dallenga; Guillaume Dalmasso; Markus Damme; Ilaria Dando; Nico P. Dantuma; April L. Darling; Hiranmoy Das; Srinivasan Dasarathy; Santosh K. Dasari; Srikanta Dash; Oliver Daumke; Adrian N. Dauphinee; Jeffrey S. Davies; Valeria A. Dávila; Roger J. Davis; Tanja Davis; Sharadha Dayalan Naidu; Francesca De Amicis; Karolien De Bosscher; Francesca De Felice; Lucia De Franceschi; Chiara De Leonibus; Mayara G. de Mattos Barbosa; Guido R.Y. De Meyer; Angelo De Milito; Cosimo De Nunzio; Clara De Palma; Mauro De Santi; Claudio De Virgilio; Daniela De Zio; Jayanta Debnath; Brian J. DeBosch; Jean-Paul Decuypere; Mark A. Deehan; Gianluca Deflorian; James DeGregori; Benjamin Dehay; Gabriel Del Rio; Joe R. Delaney; Lea M. D. Delbridge; Elizabeth Delorme-Axford; M. Victoria Delpino; Francesca Demarchi; Vilma Dembitz; Nicholas D. Demers; Hongbin Deng; Zhiqiang Deng; Joern Dengjel; Paul Dent; Donna Denton; Melvin L. DePamphilis; Channing J. Der; Vojo Deretic; Albert Descoteaux; Laura Devis; Sushil Devkota; Olivier Devuyst; Grant Dewson; Mahendiran Dharmasivam; Rohan Dhiman; Diego di Bernardo; Manlio Di Cristina; Fabio Di Domenico; Pietro Di Fazio; Alessio Di Fonzo; Giovanni Di Guardo; Gianni M. Di Guglielmo; Luca Di Leo; Chiara Di Malta; Alessia Di Nardo; Martina Di Rienzo; Federica Di Sano; George Diallinas; Jiajie Diao; Guillermo Diaz-Araya; Inés Díaz-Laviada; Jared M. Dickinson; Marc Diederich; Mélanie Dieudé; Ivan Dikic; Shiping Ding; Wen-Xing Ding; Luciana Dini; Jelena Dinić; Miroslav Dinic; Albena T. Dinkova-Kostova; Marc S. Dionne; Jörg H.W. Distler; Abhinav Diwan; Ian M.C. Dixon; Mojgan Djavaheri-Mergny; Ina Dobrinski; Oxana Dobrovinskaya; Radek Dobrowolski; Renwick C.J. Dobson; Jelena Đokić; Serap Dokmeci Emre; Massimo Donadelli; Bo Dong; Xiaonan Dong; Zhiwu Dong; Gerald W. Dorn II; Volker Dotsch; Huan Dou; Juan Dou; Moataz Dowaidar; Sami Dridi; Liat Drucker; Ailian Du; Caigan Du; Guangwei Du; Hai-Ning Du; Li-Lin Du; André du Toit; Shao-Bin Duan; Xiaoqiong Duan; Sónia P. Duarte; Anna Dubrovska; Elaine A. Dunlop; Nicolas Dupont; Raúl V. Durán; Bilikere S. Dwarakanath; Sergey A. Dyshlovoy; Darius Ebrahimi-Fakhari; Leopold Eckhart; Charles L. Edelstein; Thomas Efferth; Eftekhar Eftekharpour; Ludwig Eichinger; Nabil Eid; Tobias Eisenberg; N. Tony Eissa; Sanaa Eissa; Miriam Ejarque; Abdeljabar El Andaloussi; Nazira El-Hage; Shahenda El-Naggar; Anna Maria Eleuteri; Eman S. El-Shafey; Mohamed Elgendy; Aristides G. Eliopoulos; María M. Elizalde; Philip M. Elks; Hans-Peter Elsasser; Eslam S. Elsherbiny; Brooke M. Emerling; N. C. Tolga Emre; Christina H. Eng; Nikolai Engedal; Anna-Mart Engelbrecht; Agnete S.T. Engelsen; Jorrit M. Enserink; Ricardo Escalante; Audrey Esclatine; Mafalda Escobar-Henriques; Eeva-Liisa Eskelinen; Lucile Espert; Makandjou-Ola Eusebio; Gemma Fabrias; Cinzia Fabrizi; Antonio Facchiano; Francesco Facchiano; Bengt Fadeel; Claudio Fader; Alex C. Faesen; W. Douglas Fairlie; Alberto Falcó; Bjorn H. Falkenburger; Daping Fan; Jie Fan; Yanbo Fan; Evandro F. Fang; Yanshan Fang; Yognqi Fang; Manolis Fanto; Tamar Farfel-Becker; Mathias Faure; Gholamreza Fazeli; Anthony O. Fedele; Arthur M. Feldman; Du Feng; Jiachun Feng; Lifeng Feng; Yibin Feng; Yuchen Feng; Wei Feng; Thais Fenz Araujo; Thomas A. Ferguson; Álvaro F. Fernández; Jose C. Fernandez-Checa; Sonia Fernández-Veledo; Alisdair R. Fernie; Anthony W. Ferrante; Alessandra Ferraresi; Merari F. Ferrari; Julio C.B. Ferreira; Susan Ferro-Novick; Antonio Figueras; Riccardo Filadi; Nicoletta Filigheddu; Eduardo Filippi-Chiela; Giuseppe Filomeni; Gian Maria Fimia; Vittorio Fineschi; Francesca Finetti; Steven Finkbeiner; Edward A. Fisher; Paul B. Fisher; Flavio Flamigni; Steven J. Fliesler; Trude H. Flo; Ida Florance; Oliver Florey; Tullio Florio; Erika Fodor; Carlo Follo; Edward A. Fon; Antonella Forlino; Francesco Fornai; Paola Fortini; Anna Fracassi; Alessandro Fraldi; Brunella Franco; Rodrigo Franco; Flavia Franconi; Lisa B. Frankel; Scott L. Friedman; Leopold F. Fröhlich; Gema Frühbeck; Jose M. Fuentes; Yukio Fujiki; Naonobu Fujita; Yuuki Fujiwara; Mitsunori Fukuda; Simone Fulda; Luc Furic; Norihiko Furuya; Carmela Fusco; Michaela U. Gack; Lidia Gaffke; Sehamuddin Galadari; Alessia Galasso; Maria F. Galindo; Sachith Gallolu Kankanamalage; Lorenzo Galluzzi; Vincent Galy; Noor Gammoh; Boyi Gan; Ian G. Ganley; Feng Gao; Hui Gao; Minghui Gao; Ping Gao; Shou-Jiang Gao; Wentao Gao; Xiaobo Gao; Ana Garcera; Maria Noé Garcia; Verónica E. Garcia; Francisco García-Del Portillo; Vega Garcia-Escudero; Aracely Garcia-Garcia; Marina Garcia-Macia; Diana García-Moreno; Carmen Garcia-Ruiz; Patricia García-Sanz; Abhishek D. Garg; Ricardo Gargini; Tina Garofalo; Robert F. Garry; Nils C. Gassen; Damian Gatica; Liang Ge; Wanzhong Ge; Ruth Geiss-Friedlander; Cecilia Gelfi; Pascal Genschik; Ian E. Gentle; Valeria Gerbino; Christoph Gerhardt; Kyla Germain; Marc Germain; David A. Gewirtz; Elham Ghasemipour Afshar; Saeid Ghavami; Alessandra Ghigo; Manosij Ghosh; Georgios Giamas; Claudia Giampietri; Alexandra Giatromanolaki; Gary E. Gibson; Spencer B. Gibson; Vanessa Ginet; Edward Giniger; Carlotta Giorgi; Henrique Girao; Stephen E. Girardin; Mridhula Giridharan; Sandy Giuliano; Cecilia Giulivi; Sylvie Giuriato; Julien Giustiniani; Alexander Gluschko; Veit Goder; Alexander Goginashvili; Jakub Golab; David C. Goldstone; Anna Golebiewska; Luciana R. Gomes; Rodrigo Gomez; Rubén Gómez-Sánchez; Maria Catalina Gomez-Puerto; Raquel Gomez-Sintes; Qingqiu Gong; Felix M. Goni; Javier González-Gallego; Tomas Gonzalez-Hernandez; Rosa A. Gonzalez-Polo; Jose A. Gonzalez-Reyes; Patricia González-Rodríguez; Ing Swie Goping; Marina S. Gorbatyuk; Nikolai V. Gorbunov; Kıvanç Görgülü; Roxana M. Gorojod; Sharon M. Gorski; Sandro Goruppi; Cecilia Gotor; Roberta A. Gottlieb; Illana Gozes; Devrim Gozuacik; Martin Graef; Markus H. Gräler; Veronica Granatiero; Daniel Grasso; Joshua P. Gray; Douglas R. Green; Alexander Greenhough; Stephen L. Gregory; Edward F. Griffin; Mark W. Grinstaff; Frederic Gros; Charles Grose; Angelina S. Gross; Florian Gruber; Paolo Grumati; Tilman Grune; Xueyan Gu; Jun-Lin Guan; Carlos M. Guardia; Kishore Guda; Flora Guerra; Consuelo Guerri; Prasun Guha; Carlos Guillén; Shashi Gujar; Anna Gukovskaya; Ilya Gukovsky; Jan Gunst; Andreas Günther; Anyonya R. Guntur; Chuanyong Guo; Chun Guo; Hongqing Guo; Lian-Wang Guo; Ming Guo; Pawan Gupta; Shashi Kumar Gupta; Swapnil Gupta; Veer Bala Gupta; Vivek Gupta; Asa B. Gustafsson; David D. Gutterman; Ranjitha H.B; Annakaisa Haapasalo; James E. Haber; Aleksandra Hać; Shinji Hadano; Anders J. Hafrén; Mansour Haidar; Belinda S. Hall; Gunnel Halldén; Anne Hamacher-Brady; Andrea Hamann; Maho Hamasaki; Weidong Han; Malene Hansen; Phyllis I. Hanson; Zijian Hao; Masaru Harada; Ljubica Harhaji-Trajkovic; Nirmala Hariharan; Nigil Haroon; James Harris; Takafumi Hasegawa; Noor Hasima Nagoor; Jeffrey A. Haspel; Volker Haucke; Wayne D. Hawkins; Bruce A. Hay; Cole M. Haynes; Soren B. Hayrabedyan; Thomas S. Hays; Congcong He; Qin He; Rong-Rong He; You-Wen He; Yu-Ying He; Yasser Heakal; Alexander M. Heberle; J. Fielding Hejtmancik; Gudmundur Vignir Helgason; Vanessa Henkel; Marc Herb; Alexander Hergovich; Anna Herman-Antosiewicz; Agustín Hernández; Carlos Hernandez; Sergio Hernandez-Diaz; Virginia Hernandez-Gea; Amaury Herpin; Judit Herreros; Javier H. Hervás; Daniel Hesselson; Claudio Hetz; Volker T. Heussler; Yujiro Higuchi; Sabine Hilfiker; Joseph A. Hill; William S. Hlavacek; Emmanuel A. Ho; Idy H.T. Ho; Philip Wing-Lok Ho; Shu-Leong Ho; Wan Yun Ho; G. Aaron Hobbs; Mark Hochstrasser; Peter H.M. Hoet; Daniel Hofius; Paul Hofman; Annika Höhn; Carina I. Holmberg; Jose R. Hombrebueno; Chang-Won Hong Yi-Ren Hong; Lora V. Hooper; Thorsten Hoppe; Rastislav Horos; Yujin Hoshida; I-Lun Hsin; Hsin-Yun Hsu; Bing Hu; Dong Hu; Li-Fang Hu; Ming Chang Hu; Ronggui Hu; Wei Hu; Yu-Chen Hu; Zhuo-Wei Hu; Fang Hua; Jinlian Hua; Yingqi Hua; Chongmin Huan; Canhua Huang; Chuanshu Huang; Chuanxin Huang; Chunling Huang; Haishan Huang; Kun Huang; Michael L.H. Huang; Rui Huang; Shan Huang; Tianzhi Huang; Xing Huang; Yuxiang Jack Huang; Tobias B. Huber; Virginie Hubert
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field. © 2020 Informa UK Limited, trading as Taylor & Francis Group.
Inflammation, a Double-Edge Sword for Cancer and Other Age-Related Diseases
(Frontiers Media S.A., 2018) Subash Chandra Gupta; Ajaikumar B. Kunnumakkara; Sadhna Aggarwal; Bharat B. Aggarwal
Increasing evidence from diverse sources during the past several years has indicated that long-term, low level, chronic inflammation mediates several chronic diseases including cancer, arthritis, obesity, diabetes, cardiovascular diseases, and neurological diseases. The inflammatory molecules and transcription factors, adhesion molecules, AP-1, chemokines, C-reactive protein (CRP), cyclooxygenase (COX)-2, interleukins (ILs), 5-lipooxygenase (5-LOX), matrix metalloproteinases (MMPs), nuclear factor (NF)-kB, signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) are molecular links between inflammation and chronic diseases. Thus, suppression of inflammatory molecules could be potential strategy for the prevention and therapy of chronic diseases. The currently available drugs against chronic diseases are highly expensive, minimally effective and produce several side effects when taken for long period of time. The focus of this review is to discuss the potential of nutraceuticals derived from “Mother Nature” such as apigenin, catechins, curcumin, ellagic acid, emodin, epigallocatechin gallate, escin, fisetin, flavopiridol, genistein, isoliquiritigenin, kaempferol, mangostin, morin, myricetin, naringenin, resveratrol, silymarin, vitexin, and xanthohumol in suppression of these inflammatory pathways. Thus, these nutraceuticals offer potential in preventing or delaying the onset of chronic diseases. We provide evidence for the potential of these nutraceuticals from pre-clinical and clinical studies. © Copyright © 2018 Gupta, Kunnumakkara, Aggarwal and Aggarwal.
Inflammation, nf-κb, and chronic diseases: How are they linked?
(Begell House Inc., 2020) Ajaikumar B. Kunnumakkara; Bano Shabnam; Sosmitha Girisa; Choudhary Harsha; Kishore Banik; Th. Babita Devi; Ruplekha Choudhury; Henamayee Sahu; Dey Parama; Bethsebie L. Sailo; Krishan Kumar Thakur; Subash C. Gupta; Bharat B. Aggarwal
Most chronic diseases, caused by lifestyle factors, appear to be linked to inflammation. Inflammation is activated mechanistically, and nuclear factor–κB (NF-κB) is a significant mediator. NF-κB, one of the most studied transcription factors, was first identified in the nucleus of B lymphocytes almost three decades ago. This protein has a key function in regulating the human immune system, and its dysregulation has been linked to many chronic diseases including asthma, cancer, diabetes, rheumatoid arthritis, inflammation, and neurological disorders. Physiologically, many cytokines have been discovered that activate NF-κB. Pathologically, environmental carcinogens such as cigarette smoke, radiation, bacteria, and viruses can also activate this transcription factor. NF-κB activation controls expression of more than 500 genes, and most are deleterious to the human body when dysregulated. More than 70,000 articles have been published regarding NF-κB. This review emphasizes the upside and downside of NF-κB in normal and disease conditions and the ways in which we can control this critical transcription factor in patients. © 2020 by Begell House, Inc. www.begellhouse.com.
Is curcumin bioavailability a problem in humans: lessons from clinical trials
(Taylor and Francis Ltd, 2019) Ajaikumar B. Kunnumakkara; Choudhary Harsha; Kishore Banik; Rajesh Vikkurthi; Bethsebie L. Sailo; Devivasha Bordoloi; Subash C. Gupta; Bharat B. Aggarwal
Introduction: Since ancient times, turmeric has been used in several folklore remedies against various ailments. The principal component of turmeric is curcumin and its efficacy has been advocated in various in vitro, in vivo and clinical studies for different chronic diseases. However, some studies suggest that curcumin bioavailability is a major problem. Areas covered: This article discusses over 200 clinical studies with curcumin that have demonstrated the pronounced protective role of this compound against cardiovascular diseases, inflammatory diseases, metabolic diseases, neurological diseases, skin diseases, liver diseases, various types of cancer, etc. The review also describes the combination of curcumin with many natural and synthetic compounds as well as various formulations of curcumin that have shown efficacy in multiple clinical studies. Expert opinion: The therapeutic potential of curcumin, as demonstrated by clinical trials has overpowered the myth that poor bioavailability of curcumin poses a problem. Low curcumin bioavailability in certain studies has been addressed by using higher concentrations of curcumin within nontoxic limits. Moreover, curcumin, in combination with other compounds or as formulations, has shown enhanced bioavailability. Hence, bioavailability is not a problem in the curcumin-mediated treatment of chronic diseases. Therefore, this golden nutraceutical presents a safe, low-cost and effective treatment modality for different chronic diseases. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
Neem (Azadirachta indica): An indian traditional panacea with modern molecular basis
(Elsevier GmbH, 2017) Subash Chandra Gupta; Sahdeo Prasad; Amit K. Tyagi; Ajaikumar B. Kunnumakkara; Bharat B. Aggarwal
Background For centuries, agents derived from natural sources (mother nature), especially plants have been the primary source of medicine. Neem, also referred to as Azadirachta indica is one such plant that has been so named because it provides freedom from all diseases, and used for thousands of years in Indian and African continents. Different parts of the plant including flowers, leaves, seeds and bark have been used to treat both acute and chronic human diseases; and used as insecticide; antimicrobial, larvicidal, antimalarial, antibacterial, antiviral, and spermicidal. Purpose What is there in neem and how it manifests its wide variety of effects is the focus of this review. How neem and its constituents modulate various cellular pathways is discussed. The animal and human studies carried out with neem and its constituents is also discussed. Conclusion Over 1000 research articles published on neem has uncovered over 300 structurally diverse constituents, one third of which are limonoids including nimbolide, azadarachtin, and gedunin. These agents manifest their effects by modulating multiple cell signaling pathways. © 2017
Regulation of cell signaling pathways by dietary agents for cancer prevention and treatment
(Academic Press, 2017) Manoj K. Pandey; Subash C. Gupta; Ali Nabavizadeh; Bharat B. Aggarwal
Although it is widely accepted that better food habits do play important role in cancer prevention and treatment, how dietary agents mediate their effects remains poorly understood. More than thousand different polyphenols have been identified from dietary plants. In this review, we discuss the underlying mechanism by which dietary agents can modulate a variety of cell-signaling pathways linked to cancer, including transcription factors, nuclear factor κB (NF-κB), signal transducer and activator of transcription 3 (STAT3), activator protein-1 (AP-1), β-catenin/Wnt, peroxisome proliferator activator receptor- gamma (PPAR-γ), Sonic Hedgehog, and nuclear factor erythroid 2 (Nrf2); growth factors receptors (EGFR, VEGFR, IGF1-R); protein Kinases (Ras/Raf, mTOR, PI3K, Bcr-abl and AMPK); and pro-inflammatory mediators (TNF-α interleukins, COX-2, 5-LOX). In addition, modulation of proteasome and epigenetic changes by the dietary agents also play a major role in their ability to control cancer. Both in vitro and animal based studies support the role of dietary agents in cancer. The efficacy of dietary agents by clinical trials has also been reported. Importantly, natural agents are already in clinical trials against different kinds of cancer. Overall both in vitro and in vivo studies performed with dietary agents strongly support their role in cancer prevention. Thus, the famous quote “Let food be thy medicine and medicine be thy food” made by Hippocrates 25 centuries ago still holds good. © 2017 Elsevier Ltd
Serendipity in Cancer Drug Discovery: Rational or Coincidence?
(Elsevier Ltd, 2016) Sahdeo Prasad; Subash C. Gupta; Bharat B. Aggarwal
Novel drug development leading to final approval by the US FDA can cost as much as two billion dollars. Why the cost of novel drug discovery is so expensive is unclear, but high failure rates at the preclinical and clinical stages are major reasons. Although therapies targeting a given cell signaling pathway or a protein have become prominent in drug discovery, such treatments have done little in preventing or treating any disease alone because most chronic diseases have been found to be multigenic. A review of the discovery of numerous drugs currently being used for various diseases including cancer, diabetes, cardiovascular, pulmonary, and autoimmune diseases indicates that serendipity has played a major role in the discovery. In this review we provide evidence that rational drug discovery and targeted therapies have minimal roles in drug discovery, and that serendipity and coincidence have played and continue to play major roles. The primary focus in this review is on cancer-related drug discovery. © 2016 Elsevier Ltd.
The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis
(Elsevier GmbH, 2023) Rajeev K. Singla; Ronita De; Thomas Efferth; Bruno Mezzetti; Md. Sahab Uddin; Sanusi; Fidele Ntie-Kang; Dongdong Wang; Fabien Schultz; Kiran R. Kharat; Hari Prasad Devkota; Maurizio Battino; Daniel Sur; Ronan Lordan; Sourav S Patnaik; Christos Tsagkaris; Chandragiri Siva Sai; Surya Kant Tripathi; Mihnea-Alexandru Găman; Mosa E.O. Ahmed; Elena González-Burgos; Smith B. Babiaka; Shravan Kumar Paswan; Joy Ifunanya Odimegwu; Faizan Akram; Jesus Simal-Gandara; Mágali S. Urquiza; Aleksei Tikhonov; Himel Mondal; Shailja Singla; Sara Di Lonardo; Eoghan J Mulholland; Merisa Cenanovic; Abdulkadir Yusif Maigoro; Francesca Giampieri; Soojin Lee; Nikolay T. Tzvetkov; Anna Maria Louka; Pritt Verma; Hitesh Chopra; Scarlett Perez Olea; Johra Khan; José M. Alvarez Suarez; Xiaonan Zheng; Michał Tomczyk; Manoj Kumar Sabnani; Christhian Delfino Villanueva Medina; Garba M. Khalid; Hemanth Kumar Boyina; Milen I. Georgiev; Claudiu T. Supuran; Eduardo Sobarzo-Sánchez; Tai-Ping Fan; Valeria Pittala; Antoni Sureda; Nady Braidy; Gian Luigi Russo; Rosa Anna Vacca; Maciej Banach; Gérard Lizard; Amira Zarrouk; Sonia Hammami; Ilkay Erdogan Orhan; Bharat B. Aggarwal; George Perry; Mark JS Miller; Michael Heinrich; Anupam Bishayee; Anake Kijjoa; Nicolas Arkells; David Bredt; Michael Wink; Bernd l. Fiebich; Gangarapu Kiran; Andy Wai Kan Yeung; Girish Kumar Gupta; Antonello Santini; Massimo Lucarini; Alessandra Durazzo; Amr El-Demerdash; Albena T. Dinkova-Kostova; Alejandro Cifuentes; Eliana B. Souto; Muhammad Asim Masoom Zubair; Pravin Badhe; Javier Echeverría; Jarosław Olav Horbańczuk; Olaf K. Horbanczuk; Helen Sheridan; Sadeeq Muhammad Sheshe; Anna Maria Witkowska; Ibrahim M. Abu-Reidah; Muhammad Riaz; Hammad Ullah; Akolade R. Oladipupo; Víctor Lopez; Neeraj Kumar Sethiya; Bhupal Govinda Shrestha; Palaniyandi Ravanan; Subash Chandra Gupta; Qushmua E. Alzahrani; Preethidan Dama Sreedhar; Jianbo Xiao; Mohammad Amin Moosavi; Parasuraman Aiya Subramani; Amit Kumar Singh; Ananda Kumar Chettupalli; Jayanta Kumar Patra; Gopal Singh; Tomasz M. Karpiński; Fuad Al-Rimawi; Rambod Abiri; Atallah F. Ahmed; Davide Barreca; Sharad Vats; Said Amrani; Carmela Fimognari; Andrei Mocan; Lucian Hritcu; Prabhakar Semwal; Md. Shiblur Rahaman; Mila Emerald; Akinleye Stephen Akinrinde; Abhilasha Singh; Ashima Joshi; Tanuj Joshi; Shafaat Yar Khan; Gareeballah Osman Adam Balla; Aiping Lu; Sandeep Ramchandra Pai; Imen Ghzaiel; Niyazi Acar; Nour Eddine Es-Safi; Gokhan Zengin; Azazahemad A. Kureshi; Arvind Kumar Sharma; Bikash Baral; Neeraj Rani; Philippe Jeandet; Monica Gulati; Bhupinder Kapoor; Yugal Kishore Mohanta; Zahra Emam-Djomeh; Raphael Onuku; Jennifer R. Depew; Omar M. Atrooz; Bey Hing Goh; Jose Carlos Andrade; Bikramjit Konwar; V.J. Shine; João Miguel Lousa Dias Ferreira; Jamil Ahmad; Vivek K. Chaturvedi; Krystyna Skalicka-Woźniak; Rohit Sharma; Rupesh K. Gautam; Sebastian Granica; Salvatore Parisi; Rishabh Kumar; Atanas G. Atanasov; Bairong Shen
Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled “International Natural Product Sciences Taskforce” (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week “2021 INPST Twitter Networking Event” (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events. © 2022 The Author(s)
The p60 tumor necrosis factor (TNF) receptor-associated kinase (TRAK) binds residues 344-397 within the cytoplasmic domain involved in TNF signaling
(American Society for Biochemistry and Molecular Biology Inc., 1995) Bryant G. Darnay; Sanjaya Singh; Madan M. Chaturvedi; Bharat B. Aggarwal
The p60 form of the tumor necrosis factor (TNF) receptor lacks motifs characteristic of tyrosine or serine/threonine protein kinases. Our recent observations have indicated that a p60 TNF receptor-associated kinase (p60- TRAK) from U-937 cells physically interacts with and causes the phosphorylation of the cytoplasmic domain of the TNF receptor. To define which region of the cytoplasmic domain is necessary for physical interaction with p60-TRAK, we constructed a series of deletions (grouped into three sets Δ1-ΔS, Δ6-Δ12, and Δ13-Δ16) of the p60 cytoplasmic domain, expressed them as glutathione S-transferase (GST) fusion proteins, and used them in affinity precipitations, followed by in vitro kinase assays. Our detailed analysis indicated that a serine-, threonine-, and proline-rich region (residues 243-274, Δ2) and the N-terminal half of the cytoplasmic domain (residues 243-323, Δ3) neither associated with p60-TRAK nor underwent phosphorylation. We found that out of 222 residues (205-426) in the cytoplasmic domain, only 54 (344-397, Δ12) were sufficient for binding p60- TRAK and for phosphorylation of the cytoplasmic domain. A region of approximately 30 residues (397426) at the C-terminal end was found to interfere with optimal binding of the p60-TRAK activity. Thus, our results indicate that the minimal region of the cytoplasmic domain necessary for interacting with p60-TRAK and for phosphorylation resides within the domain previously reported to be needed for signaling the cytotoxic effect of TNF.
Upside and downside of tumor necrosis factor blockers for treatment of immune/inflammatordiseases
(Begell House Inc., 2019) Ajaikumar B. Kunnumakkara; Krishan Kumar Thakur; Varsha Rana; Bidisha Bora; Kishore Banik; Elina Khatoon; Bethsebie L. Sailo; Bano Shabnam; Sosmitha Girisa; Subhash C. Gupta; Bharat B. Aggarwal
Tumor necrosis factor (TNF)-α, the most potent proinflammatory cytokine discovered to date, was first isolated in 1984 from human macrophage cells. Initially, it was thought to be a protein that was cytotoxic to tumor cells. But later, it was regarded as an agent that promotes inflammation and other chronic diseases found in humans. Currently, we know that the TNF superfamily (TNFS) has 19 members that perform a wide variety of functions via > 40 TNF receptors. Of TNFS members, TNF-α has been studied extensively and was found to be implicated in numerous autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, juvenile idiopathic arthritis, and diabetes. Thus, agents that can inhibit TNF-α have great potential for prevention and treatment of chronic diseases. To date, the U.S. Food and Drug Administration has approved many TNF-α blockers, such as etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab. These agents can block TNF-α actions and be used to treat different diseases. However, the uses of TNF-α blockers are not without serious adverse effects. Therefore, natural TNF-α blockers are best for developing safe, efficacious, and affordable agents for prevention and treatment of chronic diseases. The current review details the TNFS, functions of TNF-α in normal and disease conditions, roles of TNF-α blockers, and advantages and disadvantages. © 2019 by Begell House.
γ-Tocotrienol suppresses growth and sensitises human colorectal tumours to capecitabine in a nude mouse xenograft model by down-regulating multiple molecules
(Nature Publishing Group, 2016) Sahdeo Prasad; Subash C. Gupta; Amit K. Tyagi; Bharat B. Aggarwal
Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide and even develops resistance to chemotherapeutic agents over time. As a result survival for patients with CRC remains poor.Method:We investigated both in vitro and in vivo effects of γ-tocotrienol (γ-T3) alone and in combination with capecitabine. Apoptosis and cytotoxicity assays were performed by MTT and FACS analysis, whereas expression of proteins was investigated using western blotting and immunohistochemistry. Results: The γ-T3 inhibited the proliferation of CRC cells with wild-type or mutated KRAS. It also induced apoptosis, inhibited colony formation, and suppressed key regulators of cell survival, cell proliferation, invasion, angiogenesis, and metastasis. Furthermore, γ-T3 enhanced the anticancer effects of capecitabine in CRC cells. In a nude mouse xenograft model of human CRC, oral administration of γ-T3 inhibited tumour growth and enhanced the antitumour efficacy of capecitabine. Western blot and immunohistochemical analysis results indicated that expression of Ki-67, cyclin D1, MMP-9, CXCR4, NF-κB/p65, and VEGF was lower in tumour tissue from the combination treatment group. Combination treatment also downregulated NF-κB and NF-κB-regulated gene products. Conclusions: Our findings suggest that γ-T3 inhibited the growth of human CRC and sensitised CRC to capecitabine by regulating proteins linked to tumourigenesis. © 2016 Cancer Research UK.