Department Of Microbiology

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Organophosphate-pesticides induced survival mechanisms and APE1-mediated Nrf2 regulation in non-small-cell lung cancer cells
(John Wiley and Sons Inc, 2020-10-20T00:00:00) Thakur, Shweta; Sarkar, Bibekananda; Dhiman, Monisha; Mantha, Anil K.
Epidemiological and molecular studies have indicated that environmental exposure to organophosphate pesticides (OPPs) is associated with increased cancer risk; however, the underlying molecular mechanisms still need to be explained. Increasing cancer incidence is linked�to OPPs-induced oxidative stress (OS). Our study evaluates monocrotophos (MCP) and chlorpyrifos (CP)-induced OS responses and apurinic/apyrimidinic endonuclease 1 (APE1) role in human non-small-cell lung cancer (NSCLC) cells. Our prior study has implicated OPPs-induced base excision repair (BER)-pathway dysregulation and APE1-mediated regulation of transcription factor (TF) c-jun in A549 cells. We further investigated the effects of MCP and CP on apoptosis, proliferation, and APE1's redox-regulation of nuclear factor-like 2 (Nrf2). Data demonstrates that MCP and CP at subtoxic concentrations induced reactive oxygen species generation and oxidative DNA base damage 8-oxo-dG lesions in NCI-H1299 cells. CP moderately upregulated�the apoptosis-inducing factor (AIF) in A549 cells, however, it did not trigger other pro-apoptotic factors viz. caspase-9 and caspase-3, suggesting early caspase-independent apoptosis. However, dose-dependent AIF-downregulation was observed for MCP treatment. Furthermore, CP and MCP treatments upregulated proliferating cell nuclear antigen levels. Immunofluorescent confocal imaging showed the colocalization of APE1 with Nrf2 in 10 �M CP- and MCP-treated NCI-H1299 cells. Immunoprecipitation confirmed that APE1 and Nrf2 physically interacted, indicating the role of APE1-mediated Nrf2 activation following OPPs treatment. This study suggests that low concentration MCP and CP exposure generates OS along with DNA damage, and modulates apoptosis, and APE1-mediated Nrf2 activation, which might be considered as the possible mechanism promoting lung cancer cell survival, suggesting that APE1 may have the potential to become a therapeutic target for the treatment of NSCLC. � 2020 Wiley Periodicals LLC
Organophosphate-pesticides induced survival mechanisms and APE1-mediated Nrf2 regulation in non-small-cell lung cancer cells
(John Wiley and Sons Inc, 2020-10-20T00:00:00) Thakur, Shweta; Sarkar, Bibekananda; Dhiman, Monisha; Mantha, Anil K.
Epidemiological and molecular studies have indicated that environmental exposure to organophosphate pesticides (OPPs) is associated with increased cancer risk; however, the underlying molecular mechanisms still need to be explained. Increasing cancer incidence is linked�to OPPs-induced oxidative stress (OS). Our study evaluates monocrotophos (MCP) and chlorpyrifos (CP)-induced OS responses and apurinic/apyrimidinic endonuclease 1 (APE1) role in human non-small-cell lung cancer (NSCLC) cells. Our prior study has implicated OPPs-induced base excision repair (BER)-pathway dysregulation and APE1-mediated regulation of transcription factor (TF) c-jun in A549 cells. We further investigated the effects of MCP and CP on apoptosis, proliferation, and APE1's redox-regulation of nuclear factor-like 2 (Nrf2). Data demonstrates that MCP and CP at subtoxic concentrations induced reactive oxygen species generation and oxidative DNA base damage 8-oxo-dG lesions in NCI-H1299 cells. CP moderately upregulated�the apoptosis-inducing factor (AIF) in A549 cells, however, it did not trigger other pro-apoptotic factors viz. caspase-9 and caspase-3, suggesting early caspase-independent apoptosis. However, dose-dependent AIF-downregulation was observed for MCP treatment. Furthermore, CP and MCP treatments upregulated proliferating cell nuclear antigen levels. Immunofluorescent confocal imaging showed the colocalization of APE1 with Nrf2 in 10 �M CP- and MCP-treated NCI-H1299 cells. Immunoprecipitation confirmed that APE1 and Nrf2 physically interacted, indicating the role of APE1-mediated Nrf2 activation following OPPs treatment. This study suggests that low concentration MCP and CP exposure generates OS along with DNA damage, and modulates apoptosis, and APE1-mediated Nrf2 activation, which might be considered as the possible mechanism promoting lung cancer cell survival, suggesting that APE1 may have the potential to become a therapeutic target for the treatment of NSCLC. � 2020 Wiley Periodicals LLC
A short review on cross-link between pyruvate kinase (PKM2) and Glioblastoma Multiforme
(Springer, 2021-03-02T00:00:00) Verma, Harkomal; Cholia, Ravi P.; Kaur, Sharanjot; Dhiman, Monisha; Mantha, Anil K.
Pyruvate kinase (PK) catalyzes the last irreversible reaction of glycolysis pathway, generating pyruvate and ATP, from Phosphoenol Pyruvate (PEP) and ADP precursors. In mammals, four different tissue-specific isoforms (M1, M2, L and R) of PK exist, which are translated from two genes (PKL and PKR). PKM2 is the highly expressed isoform of PK in cancers, which regulates the aerobic glycolysis via reprogramming cancer cell�s metabolic pathways�to provide an anabolic�advantage to the tumor cells. In addition to the established role of PKM2 in aerobic glycolysis of multiple cancer types, various recent findings have highlighted the non-metabolic functions of PKM2 in brain tumor development. Nuclear PKM2 acts as a co-activator and directly regulates gene transcription. PKM2 dependent transactivation of various oncogenic genes is instrumental in the progression and aggressiveness of Glioblastoma Multiforme (GBM). Also, PKM2 acts as a protein kinase in histone modification which regulates gene expression and tumorigenesis. Ongoing research has explored novel regulatory mechanisms of PKM2 and its association in GBM progression. This review enlists and summarizes the metabolic and non-metabolic roles of PKM2 at the cellular level, and its regulatory function highlights the importance of the nuclear functions of PKM2 in GBM progression, and an emerging role of PKM2 as novel cancer therapeutics. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
A short review on cross-link between pyruvate kinase (PKM2) and Glioblastoma Multiforme
(Springer, 2021-03-02T00:00:00) Verma, Harkomal; Cholia, Ravi P.; Kaur, Sharanjot; Dhiman, Monisha; Mantha, Anil K.
Pyruvate kinase (PK) catalyzes the last irreversible reaction of glycolysis pathway, generating pyruvate and ATP, from Phosphoenol Pyruvate (PEP) and ADP precursors. In mammals, four different tissue-specific isoforms (M1, M2, L and R) of PK exist, which are translated from two genes (PKL and PKR). PKM2 is the highly expressed isoform of PK in cancers, which regulates the aerobic glycolysis via reprogramming cancer cell�s metabolic pathways�to provide an anabolic�advantage to the tumor cells. In addition to the established role of PKM2 in aerobic glycolysis of multiple cancer types, various recent findings have highlighted the non-metabolic functions of PKM2 in brain tumor development. Nuclear PKM2 acts as a co-activator and directly regulates gene transcription. PKM2 dependent transactivation of various oncogenic genes is instrumental in the progression and aggressiveness of Glioblastoma Multiforme (GBM). Also, PKM2 acts as a protein kinase in histone modification which regulates gene expression and tumorigenesis. Ongoing research has explored novel regulatory mechanisms of PKM2 and its association in GBM progression. This review enlists and summarizes the metabolic and non-metabolic roles of PKM2 at the cellular level, and its regulatory function highlights the importance of the nuclear functions of PKM2 in GBM progression, and an emerging role of PKM2 as novel cancer therapeutics. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
Tah1, A Key Component of R2TP Complex that Regulates Assembly of snoRNP, is Involved in De Novo Generation and Maintenance of Yeast Prion [URE3]
(Academic Press, 2021-03-31T00:00:00) Puri, Anuradhika; Singh, Priyanka; Kumar, Navinder; Kumar, Rajesh; Sharma, Deepak
The cellular chaperone machinery plays key role in the de novo formation and propagation of yeast prions (infectious protein). Though the role of Hsp70s in the prion maintenance is well studied, how Hsp90 chaperone machinery affects yeast prions remains unclear. In the current study, we examined the role of Hsp90 and its co-chaperones on yeast prions [PSI+] and [URE3]. We show that the overproduction of Hsp90 co-chaperone Tah1, cures [URE3] which is a prion form of native protein Ure2 in yeast. The Hsp90 co-chaperone Tah1 is involved in the assembly of small nucleolar ribonucleoproteins (snoRNP) and chromatin remodelling complexes. We found that Tah1 deletion improves the frequency of de novo appearance of [URE3]. The Tah1 was found to interact with Hsp70. The lack of Tah1 not only represses antagonizing effect of Ssa1 Hsp70 on [URE3] but also improves the prion strength suggesting role of Tah1 in both fibril growth and replication. We show that the N-terminal tetratricopeptide repeat domain of Tah1 is indispensable for [URE3] curing. Tah1 interacts with Ure2, improves its solubility in [URE3] strains, and affects the kinetics of Ure2 fibrillation in vitro. Its inhibitory role on Ure2 fibrillation is proposed to influence [URE3] propagation. The present study shows a novel role of Tah1 in yeast prion propagation, and that Hsp90 not only promotes its role in ribosomal RNA processing but also in the prion maintenance. Prions are self-perpetuating infectious proteins. What initiates the misfolding of a protein into its prion form is still not clear. The understanding of cellular factors that facilitate or antagonize prions is crucial to gain insight into the mechanism of prion formation and propagation. In the current study, we reveal that Tah1 is a novel modulator of yeast prion [URE3]. The Hsp90 co-chaperone Tah1, is required for the formation of small nucleolar ribonucleoprotein complex. We show that the absence of Tah1 improves the induction of [URE3] prion. The overexpressed Tah1 cures [URE3], and this function is promoted by Hsp90 chaperones. The current study thus provides a novel cellular factor and the underlying mechanism, involved in the prion formation and propagation � 2021 Elsevier Ltd
Tah1, A Key Component of R2TP Complex that Regulates Assembly of snoRNP, is Involved in De Novo Generation and Maintenance of Yeast Prion [URE3]
(Academic Press, 2021-03-31T00:00:00) Puri, Anuradhika; Singh, Priyanka; Kumar, Navinder; Kumar, Rajesh; Sharma, Deepak
The cellular chaperone machinery plays key role in the de novo formation and propagation of yeast prions (infectious protein). Though the role of Hsp70s in the prion maintenance is well studied, how Hsp90 chaperone machinery affects yeast prions remains unclear. In the current study, we examined the role of Hsp90 and its co-chaperones on yeast prions [PSI+] and [URE3]. We show that the overproduction of Hsp90 co-chaperone Tah1, cures [URE3] which is a prion form of native protein Ure2 in yeast. The Hsp90 co-chaperone Tah1 is involved in the assembly of small nucleolar ribonucleoproteins (snoRNP) and chromatin remodelling complexes. We found that Tah1 deletion improves the frequency of de novo appearance of [URE3]. The Tah1 was found to interact with Hsp70. The lack of Tah1 not only represses antagonizing effect of Ssa1 Hsp70 on [URE3] but also improves the prion strength suggesting role of Tah1 in both fibril growth and replication. We show that the N-terminal tetratricopeptide repeat domain of Tah1 is indispensable for [URE3] curing. Tah1 interacts with Ure2, improves its solubility in [URE3] strains, and affects the kinetics of Ure2 fibrillation in vitro. Its inhibitory role on Ure2 fibrillation is proposed to influence [URE3] propagation. The present study shows a novel role of Tah1 in yeast prion propagation, and that Hsp90 not only promotes its role in ribosomal RNA processing but also in the prion maintenance. Prions are self-perpetuating infectious proteins. What initiates the misfolding of a protein into its prion form is still not clear. The understanding of cellular factors that facilitate or antagonize prions is crucial to gain insight into the mechanism of prion formation and propagation. In the current study, we reveal that Tah1 is a novel modulator of yeast prion [URE3]. The Hsp90 co-chaperone Tah1, is required for the formation of small nucleolar ribonucleoprotein complex. We show that the absence of Tah1 improves the induction of [URE3] prion. The overexpressed Tah1 cures [URE3], and this function is promoted by Hsp90 chaperones. The current study thus provides a novel cellular factor and the underlying mechanism, involved in the prion formation and propagation � 2021 Elsevier Ltd
Global, regional, and national sex differences in the global burden of tuberculosis by HIV status, 1990�2019: results from the Global Burden of Disease Study 2019
(Elsevier Ltd, 2021-09-23T00:00:00) Ledesma, Jorge R.; Ma, Jianing; Vongpradith, Avina; Maddison, Emilie R.; Novotney, Amanda; Biehl, Molly H.; Legrand, Kate E.; Ross, Jennifer M.; Jahagirdar, Deepa; Bryazka, Dana; Feldman, Rachel; Abolhassani, Hassan; Abosetugn, Akine Eshete; Abu-Gharbieh, Eman; Adebayo, Oladimeji M.; Adnani, Qorinah Estiningtyas Sakilah; Afzal, Saira; Ahinkorah, Bright Opoku; Ahmad, Sajjad Ahmad; Ahmadi, Sepideh; Rashid, Tarik Ahmed; Salih, Yusra Ahmed; Aklilu, Addis; Akunna, Chisom Joyqueenet; Al Hamad, Hanadi; Alahdab, Fares; Alemayehu, Yosef; Alene, Kefyalew Addis; Ali, Beriwan Abdulqadir; Ali, Liaqat; Alipour, Vahid; Alizade, Hesam; Al-Raddadi, Rajaa M.; Alvis-Guzman, Nelson; Amini, Saeed; Amit, Arianna Maever L.; Anderson, Jason A.; Androudi, Sofa; Antonio, Carl Abelardo T.; Antony, Catherine M.; Anwer, Razique; Arabloo, Jalal; Arja, Asrat; Asemahagn, Mulusew A.; Atre, Sachin R.; Azhar, Gulrez Shah; Darshan, B.B.; Babar, Zaheer-Ud-Din; Baig, Atif Amin; Banach, Maciej; Barqawi, Hiba Jawdat; Barra, Fabio; Barrow, Amadou; Basu, Sanjay; Belgaumi, Uzma Iqbal; Bhagavathula, Akshaya Srikanth; Bhardwaj, Nikha; Bhardwaj, Pankaj; Bhattacharjee, Natalia V.; Bhattacharyya, Krittika; Bijani, Ali; Bikbov, Boris; Boloor, Archith; Briko, Nikolay Ivanovich; Buonsenso, Danilo; Nagaraja, Sharath Burugina; Butt, Zahid A.; Carter, Austin; Carvalho, Felix; Charan, Jaykaran; Chatterjee, Souranshu; Chattu, Soosanna Kumary; Chattu, Vijay Kumar; Christopher, Devasahayam J.; Chu, Dinh-Toi; Claassens, Mareli M.; Dadras, Omid; Dagnew, Amare Belachew; Dai, Xiaochen; Dandona, Lalit; Dandona, Rakhi; Daneshpajouhnejad, Parnaz; Darwesh, Aso Mohammad; Dhamnetiya, Deepak; Dianatinasab, Mostafa; Diaz, Daniel; Doan, Linh Phuong; Eftekharzadeh, Sahar; Elhadi, Muhammed; Emami, Amir; Enany, Shymaa; Faraon, Emerito Jose A.; Farzadfar, Farshad; Fernandes, Eduarda; Desideri, Lorenzo Ferro; Filip, Irina; Fischer, Florian; Foroutan, Masoud; Frank, Tahvi D.; Garcia-Basteiro, Alberto L.; Garcia-Calavaro, Christian; Garg, Tushar; Geberemariyam, Biniyam Sahiledengle; Ghadiri, Keyghobad; Ghashghaee, Ahmad; Golechha, Mahaveer; Goodridge, Amador; Gupta, Bhawna; Gupta, Sapna; Gupta, Veer Bala; Gupta, Vivek Kumar; Haider, Mohammad Rifat; Hamidi, Samer; Hanif, Asif; Haque, Shaful; Harapan, Harapan; Hargono, Arief; Hasaballah, Ahmed I.; Hashi, Abdiwahab; Hassan, Shoaib; Hassankhani, Hadi; Hayat, Khezar; Hezam, Kamal; Holla, Ramesh; Hosseinzadeh, Mehdi; Hostiuc, Mihaela; Househ, Mowafa; Hussain, Rabia; Ibitoye, Segun Emmanuel; Ilic, Irena M.; Ilic, Milena D.; Irvani, Seyed Sina Naghibi; Ismail, Nahlah Elkudssiah; Itumalla, Ramaiah; Jaafari, Jalil; Jacobsen, Kathryn H.; Jain, Vardhmaan; Javanmardi, Fatemeh; Jayapal, Sathish Kumar; Jayaram, Shubha; Jha, Ravi Prakash; Jonas, Jost B.; Joseph, Nitin; Joukar, Farahnaz; Kabir, Zubair; Kamath, Ashwin; Kanchan, Tanuj; Kandel, Himal; Katoto, Patrick D.M.C.; Kayode, Gbenga A.; Kendrick, Parkes J.; Kerbo, Amene Abebe; Khajuria, Himanshu; Khalilov, Rovshan; Khatab, Khaled; Khoja, Abdullah T.; Khubchandani, Jagdish; Kim, Min Seo; Kim, Yun Jin; Kisa, Adnan; Kisa, Sezer; Kosen, Soewarta; Koul, Parvaiz A.; Laxminarayana, Sindhura Lakshmi Koulmane; Koyanagi, Ai; Krishan, Kewal; Bicer, Burcu Kucuk; Kumar, Avinash; Kumar, G. Anil; Kumar, Narinder; Kumar, Nithin; Kwarteng, Alexander; Lak, Hassan Mehmood; Lal, Dharmesh Kumar; Landires, Iv�n; Lasrado, Savita; Lee, Shaun Wen Huey; Lee, Wei-Chen; Lin, Christine; Liu, Xuefeng; Lopukhov, Platon D.; Lozano, Rafael; Machado, Daiane Borges; Kunjathur, Shilpashree Madhava; Madi, Deepak; Mahajan, Preetam Bhalchandra; Majeed, Azeem; Malik, Ahmad Azam; Martins-Melo, Francisco Rogerl�ndio; Mehta, Saurabh; Memish, Ziad A.; Mendoza, Walter; Menezes, Ritesh G.; Merie, Hayimro Edemealem; Mersha, Amanual Getnet; Mesregah, Mohamed Kamal; Mestrovic, Tomislav; Mheidly, Nour Mheidly; Misra, Sanjeev; Mithra, Prasanna; Moghadaszadeh, Masoud; Mohammadi, Mokhtar; Mohammadian-Hafshejani, Abdollah; Mohammed, Shafu; Molokhia, Mariam; Moni, Mohammad Ali; Al Montasir, Ahmed; Moore, Catrin E.; Nagarajan, Ahamarshan Jayaraman; Nair, Sanjeev; Nair, Suma; Naqvi, Atta Abbas; Swamy, Sreenivas Narasimha; Nayak, Biswa Prakash; Nazari, Javad; Kandel, Sandhya Neupane; Nguyen, Trang Huyen; Nixon, Molly R.; Nnaji, Chukwudi A.; Ntsekhe, Mpiko; Nu�ez-Samudio, Virginia; Oancea, Bogdan; Odukoya, Oluwakemi Ololade; Olagunju, Andrew T.; Oren, Eyal; Mahesh, P.A.; Parthasarathi, Ramakrishnan; Kan, Fatemeh Pashazadeh; Pattanshetty, Sanjay M.; Paudel, Rajan; Paul, Pintu; Pawar, Shrikant; Pepito, Veincent Christian Filipino; Perico, Norberto; Pirestani, Majid; Polibin, Roman V.; Postma, Maarten J.; Pourshams, Akram; Prashant, Akila; Pribadi, Dimas Ria Angga; Radfar, Amir; Rafei, Alireza; Rahim, Fakher; Rahimi-Movaghar, Vafa; Rahman, Mahfuzar; Rahman, Mosiur; Rahmani, Amir Masoud; Ranasinghe, Priyanga; Rao, Chythra R.; Rawaf, David Laith; Rawaf, Salman; Reitsma, Marissa B.; Remuzzi, Giuseppe; Renzaho, Andre M. N.; Reta, Melese Abate; Rezaei, Nima; Rezahosseini, Omid; Rezai, Mohammad Sadegh; Rezapour, Aziz; Roshandel, Gholamreza; Roshchin, Denis O.; Sabour, Siamak; Saif-Ur-rahman, K.M.; Salam, Nasir; Kafl, Hossein Samadi; Samaei, Mehrnoosh; Samy, Abdallah M.; Saroshe, Satish; Sartorius, Benn; Sathian, Brijesh; Sawyer, Susan M.; Senthilkumaran, Subramanian; Seylani, Allen; Shafaat, Omid; Shaikh, Masood Ali; Sharaf, Kiomars; Shetty, Ranjitha S.; Shigematsu, Mika; Shin, Jae Il; Silva, Jo�o Pedro; Singh, Jitendra Kumar; Sinha, Smriti; Skryabin, Valentin Yurievich; Skryabina, Anna Aleksandrovna; Spurlock, Emma Elizabeth; Sreeramareddy, Chandrashekhar T.; Steiropoulos, Paschalis; Sufyan, Mu'awiyyah Babale; Tabuchi, Takahiro; Tadesse, Eyayou Girma; Tamir, Zemenu; Tarkang, Elvis Enowbeyang; Tekalegn, Yohannes; Tesfay, Fisaha Haile; Tessema, Belay; Thapar, Rekha; Tleyjeh, Imad I.; Tobe-Gai, Ruoyan; Tran, Bach Xuan; Tsegaye, Berhan; Tsegaye, Gebiyaw Wudie; Ullah, Anayat; Umeokonkwo, Chukwuma David; Tahbaz, Sahel Valadan; Vo, Bay; Vu, Giang Thu; Waheed, Yasir; Walters, Magdalene K.; Whisnant, Joanna L.; Woldekidan, Mesfn Agachew; Wubishet, Befkadu Legesse; Jabbari, Seyed Hossein Yahyazadeh; Yazie, Taklo Simeneh Yazie; Yeshaw, Yigizie; Yi, Siyan; Yigit, Vahit; Yonemoto, Naohiro; Yu, Chuanhua; Yunusa, Ismaeel; Zastrozhin, Mikhail Sergeevich; Zastrozhina, Anasthasia; Zhang, Zhi-Jiang; Zumla, Alimuddin; Mokdad, Ali H.; Salomon, Joshua A.; Reiner, Robert C.; Lim, Stephen S.; Naghavi, Mohsen; Vos, Theo; Hay, Simon I.; Murray, Christopher J. L.; Kyu, Hmwe Hmwe
Background: Tuberculosis is a major contributor to the global burden of disease, causing more than a million deaths annually. Given an emphasis on equity in access to diagnosis and treatment of tuberculosis in global health targets, evaluations of differences in tuberculosis burden by sex are crucial. We aimed to assess the levels and trends of the global burden of tuberculosis, with an emphasis on investigating differences in sex by HIV status for 204 countries and territories from 1990 to 2019. Methods: We used a Bayesian hierarchical Cause of Death Ensemble model (CODEm) platform to analyse 21 505 site-years of vital registration data, 705 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, and 680 site-years of mortality surveillance data to estimate mortality due to tuberculosis among HIV-negative individuals. We used a population attributable fraction approach to estimate mortality related to HIV and tuberculosis coinfection. A compartmental meta-regression tool (DisMod-MR 2.1) was then used to synthesise all available data sources, including prevalence surveys, annual case notifications, population-based tuberculin surveys, and tuberculosis cause-specific mortality, to produce estimates of incidence, prevalence, and mortality that were internally consistent. We further estimated the fraction of tuberculosis mortality that is attributable to independent effects of risk factors, including smoking, alcohol use, and diabetes, for HIV-negative individuals. For individuals with HIV and tuberculosis coinfection, we assessed mortality attributable to HIV risk factors including unsafe sex, intimate partner violence (only estimated among females), and injection drug use. We present 95% uncertainty intervals for all estimates. Findings: Globally, in 2019, among HIV-negative individuals, there were 1�18 million (95% uncertainty interval 1�08�1�29) deaths due to tuberculosis and 8�50 million (7�45�9�73) incident cases of tuberculosis. Among HIV-positive individuals, there were 217 000 (153 000�279 000) deaths due to tuberculosis and 1�15 million (1�01�1�32) incident cases in 2019. More deaths and incident cases occurred in males than in females among HIV-negative individuals globally in 2019, with 342 000 (234 000�425 000) more deaths and 1�01 million (0�82�1�23) more incident cases in males than in females. Among HIV-positive individuals, 6250 (1820�11 400) more deaths and 81 100 (63 300�100 000) more incident cases occurred among females than among males in 2019. Age-standardised mortality rates among HIV-negative males were more than two times greater in 105 countries and age-standardised incidence rates were more than 1�5 times greater in 74 countries than among HIV-negative females in 2019. The fraction of global tuberculosis deaths among HIV-negative individuals attributable to alcohol use, smoking, and diabetes was 4�27 (3�69�5�02), 6�17 (5�48�7�02), and 1�17 (1�07�1�28) times higher, respectively, among males than among females in 2019. Among individuals with HIV and tuberculosis coinfection, the fraction of mortality attributable to injection drug use was 2�23 (2�03�2�44) times greater among males than females, whereas the fraction due to unsafe sex was 1�06 (1�05�1�08) times greater among females than males. Interpretation: As countries refine national tuberculosis programmes and strategies to end the tuberculosis epidemic, the excess burden experienced by males is important. Interventions are needed to actively communicate, especially to men, the importance of early diagnosis and treatment. These interventions should occur in parallel with efforts to minimise excess HIV burden among women in the highest HIV burden countries that are contributing to excess HIV and tuberculosis coinfection burden for females. Placing a focus on tuberculosis burden among HIV-negative males and HIV and tuberculosis coinfection among females might help to diminish the overall burden of tuberculosis. This strategy will be crucial in reaching both equity and burden targets outlined by global health milestones. Funding: Bill & Melinda Gates Foundation. � 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Global, regional, and national sex differences in the global burden of tuberculosis by HIV status, 1990�2019: results from the Global Burden of Disease Study 2019
(Elsevier Ltd, 2021-09-23T00:00:00) Ledesma, Jorge R.; Ma, Jianing; Vongpradith, Avina; Maddison, Emilie R.; Novotney, Amanda; Biehl, Molly H.; Legrand, Kate E.; Ross, Jennifer M.; Jahagirdar, Deepa; Bryazka, Dana; Feldman, Rachel; Abolhassani, Hassan; Abosetugn, Akine Eshete; Abu-Gharbieh, Eman; Adebayo, Oladimeji M.; Adnani, Qorinah Estiningtyas Sakilah; Afzal, Saira; Ahinkorah, Bright Opoku; Ahmad, Sajjad Ahmad; Ahmadi, Sepideh; Rashid, Tarik Ahmed; Salih, Yusra Ahmed; Aklilu, Addis; Akunna, Chisom Joyqueenet; Al Hamad, Hanadi; Alahdab, Fares; Alemayehu, Yosef; Alene, Kefyalew Addis; Ali, Beriwan Abdulqadir; Ali, Liaqat; Alipour, Vahid; Alizade, Hesam; Al-Raddadi, Rajaa M.; Alvis-Guzman, Nelson; Amini, Saeed; Amit, Arianna Maever L.; Anderson, Jason A.; Androudi, Sofa; Antonio, Carl Abelardo T.; Antony, Catherine M.; Anwer, Razique; Arabloo, Jalal; Arja, Asrat; Asemahagn, Mulusew A.; Atre, Sachin R.; Azhar, Gulrez Shah; Darshan, B.B.; Babar, Zaheer-Ud-Din; Baig, Atif Amin; Banach, Maciej; Barqawi, Hiba Jawdat; Barra, Fabio; Barrow, Amadou; Basu, Sanjay; Belgaumi, Uzma Iqbal; Bhagavathula, Akshaya Srikanth; Bhardwaj, Nikha; Bhardwaj, Pankaj; Bhattacharjee, Natalia V.; Bhattacharyya, Krittika; Bijani, Ali; Bikbov, Boris; Boloor, Archith; Briko, Nikolay Ivanovich; Buonsenso, Danilo; Nagaraja, Sharath Burugina; Butt, Zahid A.; Carter, Austin; Carvalho, Felix; Charan, Jaykaran; Chatterjee, Souranshu; Chattu, Soosanna Kumary; Chattu, Vijay Kumar; Christopher, Devasahayam J.; Chu, Dinh-Toi; Claassens, Mareli M.; Dadras, Omid; Dagnew, Amare Belachew; Dai, Xiaochen; Dandona, Lalit; Dandona, Rakhi; Daneshpajouhnejad, Parnaz; Darwesh, Aso Mohammad; Dhamnetiya, Deepak; Dianatinasab, Mostafa; Diaz, Daniel; Doan, Linh Phuong; Eftekharzadeh, Sahar; Elhadi, Muhammed; Emami, Amir; Enany, Shymaa; Faraon, Emerito Jose A.; Farzadfar, Farshad; Fernandes, Eduarda; Desideri, Lorenzo Ferro; Filip, Irina; Fischer, Florian; Foroutan, Masoud; Frank, Tahvi D.; Garcia-Basteiro, Alberto L.; Garcia-Calavaro, Christian; Garg, Tushar; Geberemariyam, Biniyam Sahiledengle; Ghadiri, Keyghobad; Ghashghaee, Ahmad; Golechha, Mahaveer; Goodridge, Amador; Gupta, Bhawna; Gupta, Sapna; Gupta, Veer Bala; Gupta, Vivek Kumar; Haider, Mohammad Rifat; Hamidi, Samer; Hanif, Asif; Haque, Shaful; Harapan, Harapan; Hargono, Arief; Hasaballah, Ahmed I.; Hashi, Abdiwahab; Hassan, Shoaib; Hassankhani, Hadi; Hayat, Khezar; Hezam, Kamal; Holla, Ramesh; Hosseinzadeh, Mehdi; Hostiuc, Mihaela; Househ, Mowafa; Hussain, Rabia; Ibitoye, Segun Emmanuel; Ilic, Irena M.; Ilic, Milena D.; Irvani, Seyed Sina Naghibi; Ismail, Nahlah Elkudssiah; Itumalla, Ramaiah; Jaafari, Jalil; Jacobsen, Kathryn H.; Jain, Vardhmaan; Javanmardi, Fatemeh; Jayapal, Sathish Kumar; Jayaram, Shubha; Jha, Ravi Prakash; Jonas, Jost B.; Joseph, Nitin; Joukar, Farahnaz; Kabir, Zubair; Kamath, Ashwin; Kanchan, Tanuj; Kandel, Himal; Katoto, Patrick D.M.C.; Kayode, Gbenga A.; Kendrick, Parkes J.; Kerbo, Amene Abebe; Khajuria, Himanshu; Khalilov, Rovshan; Khatab, Khaled; Khoja, Abdullah T.; Khubchandani, Jagdish; Kim, Min Seo; Kim, Yun Jin; Kisa, Adnan; Kisa, Sezer; Kosen, Soewarta; Koul, Parvaiz A.; Laxminarayana, Sindhura Lakshmi Koulmane; Koyanagi, Ai; Krishan, Kewal; Bicer, Burcu Kucuk; Kumar, Avinash; Kumar, G. Anil; Kumar, Narinder; Kumar, Nithin; Kwarteng, Alexander; Lak, Hassan Mehmood; Lal, Dharmesh Kumar; Landires, Iv�n; Lasrado, Savita; Lee, Shaun Wen Huey; Lee, Wei-Chen; Lin, Christine; Liu, Xuefeng; Lopukhov, Platon D.; Lozano, Rafael; Machado, Daiane Borges; Kunjathur, Shilpashree Madhava; Madi, Deepak; Mahajan, Preetam Bhalchandra; Majeed, Azeem; Malik, Ahmad Azam; Martins-Melo, Francisco Rogerl�ndio; Mehta, Saurabh; Memish, Ziad A.; Mendoza, Walter; Menezes, Ritesh G.; Merie, Hayimro Edemealem; Mersha, Amanual Getnet; Mesregah, Mohamed Kamal; Mestrovic, Tomislav; Mheidly, Nour Mheidly; Misra, Sanjeev; Mithra, Prasanna; Moghadaszadeh, Masoud; Mohammadi, Mokhtar; Mohammadian-Hafshejani, Abdollah; Mohammed, Shafu; Molokhia, Mariam; Moni, Mohammad Ali; Al Montasir, Ahmed; Moore, Catrin E.; Nagarajan, Ahamarshan Jayaraman; Nair, Sanjeev; Nair, Suma; Naqvi, Atta Abbas; Swamy, Sreenivas Narasimha; Nayak, Biswa Prakash; Nazari, Javad; Kandel, Sandhya Neupane; Nguyen, Trang Huyen; Nixon, Molly R.; Nnaji, Chukwudi A.; Ntsekhe, Mpiko; Nu�ez-Samudio, Virginia; Oancea, Bogdan; Odukoya, Oluwakemi Ololade; Olagunju, Andrew T.; Oren, Eyal; Mahesh, P.A.; Parthasarathi, Ramakrishnan; Kan, Fatemeh Pashazadeh; Pattanshetty, Sanjay M.; Paudel, Rajan; Paul, Pintu; Pawar, Shrikant; Pepito, Veincent Christian Filipino; Perico, Norberto; Pirestani, Majid; Polibin, Roman V.; Postma, Maarten J.; Pourshams, Akram; Prashant, Akila; Pribadi, Dimas Ria Angga; Radfar, Amir; Rafei, Alireza; Rahim, Fakher; Rahimi-Movaghar, Vafa; Rahman, Mahfuzar; Rahman, Mosiur; Rahmani, Amir Masoud; Ranasinghe, Priyanga; Rao, Chythra R.; Rawaf, David Laith; Rawaf, Salman; Reitsma, Marissa B.; Remuzzi, Giuseppe; Renzaho, Andre M. N.; Reta, Melese Abate; Rezaei, Nima; Rezahosseini, Omid; Rezai, Mohammad Sadegh; Rezapour, Aziz; Roshandel, Gholamreza; Roshchin, Denis O.; Sabour, Siamak; Saif-Ur-rahman, K.M.; Salam, Nasir; Kafl, Hossein Samadi; Samaei, Mehrnoosh; Samy, Abdallah M.; Saroshe, Satish; Sartorius, Benn; Sathian, Brijesh; Sawyer, Susan M.; Senthilkumaran, Subramanian; Seylani, Allen; Shafaat, Omid; Shaikh, Masood Ali; Sharaf, Kiomars; Shetty, Ranjitha S.; Shigematsu, Mika; Shin, Jae Il; Silva, Jo�o Pedro; Singh, Jitendra Kumar; Sinha, Smriti; Skryabin, Valentin Yurievich; Skryabina, Anna Aleksandrovna; Spurlock, Emma Elizabeth; Sreeramareddy, Chandrashekhar T.; Steiropoulos, Paschalis; Sufyan, Mu'awiyyah Babale; Tabuchi, Takahiro; Tadesse, Eyayou Girma; Tamir, Zemenu; Tarkang, Elvis Enowbeyang; Tekalegn, Yohannes; Tesfay, Fisaha Haile; Tessema, Belay; Thapar, Rekha; Tleyjeh, Imad I.; Tobe-Gai, Ruoyan; Tran, Bach Xuan; Tsegaye, Berhan; Tsegaye, Gebiyaw Wudie; Ullah, Anayat; Umeokonkwo, Chukwuma David; Tahbaz, Sahel Valadan; Vo, Bay; Vu, Giang Thu; Waheed, Yasir; Walters, Magdalene K.; Whisnant, Joanna L.; Woldekidan, Mesfn Agachew; Wubishet, Befkadu Legesse; Jabbari, Seyed Hossein Yahyazadeh; Yazie, Taklo Simeneh Yazie; Yeshaw, Yigizie; Yi, Siyan; Yigit, Vahit; Yonemoto, Naohiro; Yu, Chuanhua; Yunusa, Ismaeel; Zastrozhin, Mikhail Sergeevich; Zastrozhina, Anasthasia; Zhang, Zhi-Jiang; Zumla, Alimuddin; Mokdad, Ali H.; Salomon, Joshua A.; Reiner, Robert C.; Lim, Stephen S.; Naghavi, Mohsen; Vos, Theo; Hay, Simon I.; Murray, Christopher J. L.; Kyu, Hmwe Hmwe
Background: Tuberculosis is a major contributor to the global burden of disease, causing more than a million deaths annually. Given an emphasis on equity in access to diagnosis and treatment of tuberculosis in global health targets, evaluations of differences in tuberculosis burden by sex are crucial. We aimed to assess the levels and trends of the global burden of tuberculosis, with an emphasis on investigating differences in sex by HIV status for 204 countries and territories from 1990 to 2019. Methods: We used a Bayesian hierarchical Cause of Death Ensemble model (CODEm) platform to analyse 21 505 site-years of vital registration data, 705 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, and 680 site-years of mortality surveillance data to estimate mortality due to tuberculosis among HIV-negative individuals. We used a population attributable fraction approach to estimate mortality related to HIV and tuberculosis coinfection. A compartmental meta-regression tool (DisMod-MR 2.1) was then used to synthesise all available data sources, including prevalence surveys, annual case notifications, population-based tuberculin surveys, and tuberculosis cause-specific mortality, to produce estimates of incidence, prevalence, and mortality that were internally consistent. We further estimated the fraction of tuberculosis mortality that is attributable to independent effects of risk factors, including smoking, alcohol use, and diabetes, for HIV-negative individuals. For individuals with HIV and tuberculosis coinfection, we assessed mortality attributable to HIV risk factors including unsafe sex, intimate partner violence (only estimated among females), and injection drug use. We present 95% uncertainty intervals for all estimates. Findings: Globally, in 2019, among HIV-negative individuals, there were 1�18 million (95% uncertainty interval 1�08�1�29) deaths due to tuberculosis and 8�50 million (7�45�9�73) incident cases of tuberculosis. Among HIV-positive individuals, there were 217 000 (153 000�279 000) deaths due to tuberculosis and 1�15 million (1�01�1�32) incident cases in 2019. More deaths and incident cases occurred in males than in females among HIV-negative individuals globally in 2019, with 342 000 (234 000�425 000) more deaths and 1�01 million (0�82�1�23) more incident cases in males than in females. Among HIV-positive individuals, 6250 (1820�11 400) more deaths and 81 100 (63 300�100 000) more incident cases occurred among females than among males in 2019. Age-standardised mortality rates among HIV-negative males were more than two times greater in 105 countries and age-standardised incidence rates were more than 1�5 times greater in 74 countries than among HIV-negative females in 2019. The fraction of global tuberculosis deaths among HIV-negative individuals attributable to alcohol use, smoking, and diabetes was 4�27 (3�69�5�02), 6�17 (5�48�7�02), and 1�17 (1�07�1�28) times higher, respectively, among males than among females in 2019. Among individuals with HIV and tuberculosis coinfection, the fraction of mortality attributable to injection drug use was 2�23 (2�03�2�44) times greater among males than females, whereas the fraction due to unsafe sex was 1�06 (1�05�1�08) times greater among females than males. Interpretation: As countries refine national tuberculosis programmes and strategies to end the tuberculosis epidemic, the excess burden experienced by males is important. Interventions are needed to actively communicate, especially to men, the importance of early diagnosis and treatment. These interventions should occur in parallel with efforts to minimise excess HIV burden among women in the highest HIV burden countries that are contributing to excess HIV and tuberculosis coinfection burden for females. Placing a focus on tuberculosis burden among HIV-negative males and HIV and tuberculosis coinfection among females might help to diminish the overall burden of tuberculosis. This strategy will be crucial in reaching both equity and burden targets outlined by global health milestones. Funding: Bill & Melinda Gates Foundation. � 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Brain Exosomes: Friend or Foe in Alzheimer�s Disease?
(Springer, 2021-09-30T00:00:00) Kaur, Sharanjot; Verma, Harkomal; Dhiman, Monisha; Tell, Gianluca; Gigli, Gian Luigi; Janes, Francesco; Mantha, Anil K.
Alzheimer�s disease (AD) is the most common neurodegenerative disease. It is known to be a multifactorial disease and several causes are associated with its occurrence as well as progression. However, the accumulation of amyloid beta (A?) is widely considered its major pathogenic hallmark. Additionally, neurofibrillary tangles (NFT), mitochondrial dysfunction, oxidative stress, and aging (cellular senescence) are considered as additional hits affecting the disease pathology. Several studies are now suggesting important role of inflammation in AD, which shifts our thought towards the brain�s resident immune cells, microglia, and astrocytes; how they interact with neurons; and how these interactions are affected by intra and extracellular stressful factors. These interactions can be modulated by different mechanisms and pathways, in which exosomes could play an important role. Exosomes are multivesicular bodies secreted by nearly all types of cells. The exosomes secreted by glial cells or neurons affect the interactions and thus the physiology of these cells by transmitting miRNAs, proteins, and lipids. Exosomes can serve as a friend or foe to the neuron function, depending upon the carried signals. Exosomes, from the healthy microenvironment, may assist neuron function and health, whereas, from the stressed microenvironment, they carry oxidative and inflammatory signals to the neurons and thus prove detrimental to the neuronal function. Furthermore, exosomes can cross the blood�brain barrier (BBB), and from the blood plasma they can enter the brain cells and activate microglia and astrocytes. Exosomes can transport A? or Tau, cytokines, miRNAs between the cells, and alter the physiology of recipient cells. They can also assist in A? clearance and regulation of synaptic activity. The exosomes derived from different cells play different roles, and this field is still in its infancy stage. This review advocates exosomes� role as a friend or foe in neurodegenerative diseases, especially in the case of Alzheimer�s disease. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Brain Exosomes: Friend or Foe in Alzheimer�s Disease?
(Springer, 2021-09-30T00:00:00) Kaur, Sharanjot; Verma, Harkomal; Dhiman, Monisha; Tell, Gianluca; Gigli, Gian Luigi; Janes, Francesco; Mantha, Anil K.
Alzheimer�s disease (AD) is the most common neurodegenerative disease. It is known to be a multifactorial disease and several causes are associated with its occurrence as well as progression. However, the accumulation of amyloid beta (A?) is widely considered its major pathogenic hallmark. Additionally, neurofibrillary tangles (NFT), mitochondrial dysfunction, oxidative stress, and aging (cellular senescence) are considered as additional hits affecting the disease pathology. Several studies are now suggesting important role of inflammation in AD, which shifts our thought towards the brain�s resident immune cells, microglia, and astrocytes; how they interact with neurons; and how these interactions are affected by intra and extracellular stressful factors. These interactions can be modulated by different mechanisms and pathways, in which exosomes could play an important role. Exosomes are multivesicular bodies secreted by nearly all types of cells. The exosomes secreted by glial cells or neurons affect the interactions and thus the physiology of these cells by transmitting miRNAs, proteins, and lipids. Exosomes can serve as a friend or foe to the neuron function, depending upon the carried signals. Exosomes, from the healthy microenvironment, may assist neuron function and health, whereas, from the stressed microenvironment, they carry oxidative and inflammatory signals to the neurons and thus prove detrimental to the neuronal function. Furthermore, exosomes can cross the blood�brain barrier (BBB), and from the blood plasma they can enter the brain cells and activate microglia and astrocytes. Exosomes can transport A? or Tau, cytokines, miRNAs between the cells, and alter the physiology of recipient cells. They can also assist in A? clearance and regulation of synaptic activity. The exosomes derived from different cells play different roles, and this field is still in its infancy stage. This review advocates exosomes� role as a friend or foe in neurodegenerative diseases, especially in the case of Alzheimer�s disease. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
New pentacyclic triterpene from Potentilla atrosanguinea Lodd. as anticancer agent for breast cancer targeting estrogen receptor-?
(Taylor and Francis Ltd., 2021-10-04T00:00:00) Kumar, Amit; Gupta, Kunj Bihari; Dhiman, Monisha; Arora, Saroj; Jaitak, Vikas
One new (compound 3) along with two previously known ursane type triterpenoids (compounds 1 and 2) were purified by chromatographic techniques from ethyl acetate extract of aerial parts of Potentilla atrosanguniea and characterized by HRMS, 1 D and 2 D-NMR. Compounds 1 (ursolic acid), 2 (euscaphic acid) and 3 (3?,20?-dihydroxy 2-oxo-urs-12-en-28-oic acid) were tested for their antiproliferative activity along with standard bazedoxifene. Compounds 1 and 3 were found to be of higher activity (3.71 and 6.05 ?g/mL) as compared to compound 2 and bazedoxifene (IC50: 24.53 and 17.87 ?g/mL). Anti-estrogenic activity of three compounds on breast cancer (BC) were studied in vitro by accessing their antiproliferative activity and binding with estrogen receptor alpha (ER-?). All three compounds have effective binding affinity towards ER-? and decreased cell growth by downregulating the expression of mRNA and its translational protein as tested by semi-qRT-PCR and western blotting. In terms of effectiveness compounds 1 and 3 were found more active due to their antiproliferative, and antiestrogenic activity as compared to standard bazedoxifene. � 2021 Informa UK Limited, trading as Taylor & Francis Group.
New pentacyclic triterpene from Potentilla atrosanguinea Lodd. as anticancer agent for breast cancer targeting estrogen receptor-?
(Taylor and Francis Ltd., 2021-10-04T00:00:00) Kumar, Amit; Gupta, Kunj Bihari; Dhiman, Monisha; Arora, Saroj; Jaitak, Vikas
One new (compound 3) along with two previously known ursane type triterpenoids (compounds 1 and 2) were purified by chromatographic techniques from ethyl acetate extract of aerial parts of Potentilla atrosanguniea and characterized by HRMS, 1 D and 2 D-NMR. Compounds 1 (ursolic acid), 2 (euscaphic acid) and 3 (3?,20?-dihydroxy 2-oxo-urs-12-en-28-oic acid) were tested for their antiproliferative activity along with standard bazedoxifene. Compounds 1 and 3 were found to be of higher activity (3.71 and 6.05 ?g/mL) as compared to compound 2 and bazedoxifene (IC50: 24.53 and 17.87 ?g/mL). Anti-estrogenic activity of three compounds on breast cancer (BC) were studied in vitro by accessing their antiproliferative activity and binding with estrogen receptor alpha (ER-?). All three compounds have effective binding affinity towards ER-? and decreased cell growth by downregulating the expression of mRNA and its translational protein as tested by semi-qRT-PCR and western blotting. In terms of effectiveness compounds 1 and 3 were found more active due to their antiproliferative, and antiestrogenic activity as compared to standard bazedoxifene. � 2021 Informa UK Limited, trading as Taylor & Francis Group.
Structure, regulation, and host interaction of outer membrane protein U (OmpU) of Vibrio species
(Academic Press, 2021-10-27T00:00:00) Ganie, Hilal A.; Choudhary, Aaina; Baranwal, Somesh
OmpU is a multimeric, cation selective outer membrane protein of Vibrio and related species that non-covalently interact with peptidoglycan layer. Interaction of OmpU with human host cells triggers signaling pathways to promote cytokine secretion, reactive oxygen species production, and caspase independent death in immune and epithelial cells. Non-choleric OmpU imparts resistance to antimicrobial peptides and induces actin cytoskeletal reorganization in the host cells. Further, OmpU isolated from Vibrio species elicits an immune response in several aquaculture hosts. Importantly, in-vivo studies using recombinant OmpU or OmpU derived mimotopes reveal a short-lasting immunity, and protection against Vibrio in the aquaculture sector. In conclusion, OmpU is a key adhesion protein and an important virulence factor for successful colonization of Vibrio species into hosts. This review article provides a broad overview of structural, regulatory, and functional mechanisms of OmpU in normal and disease states. � 2021
Structure, regulation, and host interaction of outer membrane protein U (OmpU) of Vibrio species
(Academic Press, 2021-10-27T00:00:00) Ganie, Hilal A.; Choudhary, Aaina; Baranwal, Somesh
OmpU is a multimeric, cation selective outer membrane protein of Vibrio and related species that non-covalently interact with peptidoglycan layer. Interaction of OmpU with human host cells triggers signaling pathways to promote cytokine secretion, reactive oxygen species production, and caspase independent death in immune and epithelial cells. Non-choleric OmpU imparts resistance to antimicrobial peptides and induces actin cytoskeletal reorganization in the host cells. Further, OmpU isolated from Vibrio species elicits an immune response in several aquaculture hosts. Importantly, in-vivo studies using recombinant OmpU or OmpU derived mimotopes reveal a short-lasting immunity, and protection against Vibrio in the aquaculture sector. In conclusion, OmpU is a key adhesion protein and an important virulence factor for successful colonization of Vibrio species into hosts. This review article provides a broad overview of structural, regulatory, and functional mechanisms of OmpU in normal and disease states. � 2021
Methods to Assess Oxidative DNA Base Damage Repair of Apurinic/Apyrimidinic (AP) Sites Using Radioactive and Nonradioactive Oligonucleotide-Based Assays
(NLM (Medline), 2022-01-19T00:00:00) Gupta, Kunj Bihari; Kaur, Sharanjot; Dhiman, Monisha; Mantha, Anil Kumar
Reactive oxygen species (ROS) overproduction results in oxidative stress leading to genomic instability via the generation of small base lesions in the genome, and this unrepaired DNA base damage leads to various cellular consequences. The oxidative stress-mediated DNA base damage is involved in various human disorders like cancer, cardiovascular, ocular, and neurodegenerative diseases. Base excision repair (BER) pathway, one of the DNA repair pathways, is majorly involved in the repair of oxidative DNA base lesions, which utilizes a different set of enzymes, including endonuclease viz Apurinic/apyrimidinic endonuclease 1 (APE1). APE1 is a well-known multifunctional enzyme with DNA repair, REDOX regulatory, and protein-protein interaction/cross-talk functions associated with the cell survival mechanisms. APE1 acts as an important player in both normal and cancerous cell survival; thus, evaluating its endonuclease activity in the biological samples provide useful readout of the DNA repair capacity/ability, which can be used to tune for the development of therapeutic candidates via either stimulating or blocking its DNA repair function in normal vs. cancer cells, respectively. This chapter enlists two methods used for the determination of APE1's endonuclease activity by oligonucleotide-based radioactive P32-labeled and nonradioactive fluorescence dyes using the cell extracts and recombinant APE1 protein. � 2022. Springer Science+Business Media, LLC, part of Springer Nature.
Methods to Assess Oxidative DNA Base Damage Repair of Apurinic/Apyrimidinic (AP) Sites Using Radioactive and Nonradioactive Oligonucleotide-Based Assays
(NLM (Medline), 2022-01-19T00:00:00) Gupta, Kunj Bihari; Kaur, Sharanjot; Dhiman, Monisha; Mantha, Anil Kumar
Reactive oxygen species (ROS) overproduction results in oxidative stress leading to genomic instability via the generation of small base lesions in the genome, and this unrepaired DNA base damage leads to various cellular consequences. The oxidative stress-mediated DNA base damage is involved in various human disorders like cancer, cardiovascular, ocular, and neurodegenerative diseases. Base excision repair (BER) pathway, one of the DNA repair pathways, is majorly involved in the repair of oxidative DNA base lesions, which utilizes a different set of enzymes, including endonuclease viz Apurinic/apyrimidinic endonuclease 1 (APE1). APE1 is a well-known multifunctional enzyme with DNA repair, REDOX regulatory, and protein-protein interaction/cross-talk functions associated with the cell survival mechanisms. APE1 acts as an important player in both normal and cancerous cell survival; thus, evaluating its endonuclease activity in the biological samples provide useful readout of the DNA repair capacity/ability, which can be used to tune for the development of therapeutic candidates via either stimulating or blocking its DNA repair function in normal vs. cancer cells, respectively. This chapter enlists two methods used for the determination of APE1's endonuclease activity by oligonucleotide-based radioactive P32-labeled and nonradioactive fluorescence dyes using the cell extracts and recombinant APE1 protein. � 2022. Springer Science+Business Media, LLC, part of Springer Nature.
Leishmania donovani secretory protein nucleoside diphosphate kinase b localizes in its nucleus and prevents ATP mediated cytolysis of macrophages
(Academic Press, 2022-02-25T00:00:00) Kushawaha, Pramod K.; Pati Tripathi, Chandra Dev; Dube, Anuradha
Leishmania donovani pathogenicity is closely linked to its ability to live and replicate in the hostile environment of macrophages. All protozoan parasites, including Leishmania, are unable to synthesize purines de novo, and nucleoside diphosphate kinases (NDKs) are enzymes required to preserve the intracellular nucleoside phosphate equilibrium. For some pathogens, secretion of ATP-utilizing enzymes into the extracellular environment aids in pathogen survival via P2Z receptor mediated, ATP-induced death of infected macrophages. Here, Leishmanaia donovani nucleoside diphosphate kinase (LdNDKb) was cloned, expressed and purified by Ni2+-NTA affinity chromatography to elucidate its biological significance. The presence of secreted form of LdNDKb in the medium was confirmed by Western blot analysis. Interestingly, cellular localization by confocal microscopy showed that this protein was localized in the nucleus, inner leaflet of membrane and on the flagella of this parasite which indicates its multiple role in the life cycle of Leishmania donovani. Its possibility to bind with DNA was confirmed by gel retardation assay and electrophoretic mobility shift assay (EMSA) which show the binding with linear and supercoiled is not sequence specific. Further, treatment of J774 macrophages with recombinant LdNdKb and periodate oxidized ATP - a P2X7 receptor antagonist, inhibited ATP-induced cytolysis in vitro, as determined by lactate dehydrogenise release from J774 macrophages. Thus, LdNDKb prevents ATP-mediated host-cell plasma membrane permeabilization by hydrolyzing extracellular ATP, thereby, preserving the integrity of the host cells for the benefit of the parasite. This study indicates that LdNDKb could be explored for its potentiality as a drug/vaccine target against visceral leishmaniasis. � 2022
Leishmania donovani secretory protein nucleoside diphosphate kinase b localizes in its nucleus and prevents ATP mediated cytolysis of macrophages
(Academic Press, 2022-02-25T00:00:00) Kushawaha, Pramod K.; Pati Tripathi, Chandra Dev; Dube, Anuradha
Leishmania donovani pathogenicity is closely linked to its ability to live and replicate in the hostile environment of macrophages. All protozoan parasites, including Leishmania, are unable to synthesize purines de novo, and nucleoside diphosphate kinases (NDKs) are enzymes required to preserve the intracellular nucleoside phosphate equilibrium. For some pathogens, secretion of ATP-utilizing enzymes into the extracellular environment aids in pathogen survival via P2Z receptor mediated, ATP-induced death of infected macrophages. Here, Leishmanaia donovani nucleoside diphosphate kinase (LdNDKb) was cloned, expressed and purified by Ni2+-NTA affinity chromatography to elucidate its biological significance. The presence of secreted form of LdNDKb in the medium was confirmed by Western blot analysis. Interestingly, cellular localization by confocal microscopy showed that this protein was localized in the nucleus, inner leaflet of membrane and on the flagella of this parasite which indicates its multiple role in the life cycle of Leishmania donovani. Its possibility to bind with DNA was confirmed by gel retardation assay and electrophoretic mobility shift assay (EMSA) which show the binding with linear and supercoiled is not sequence specific. Further, treatment of J774 macrophages with recombinant LdNdKb and periodate oxidized ATP - a P2X7 receptor antagonist, inhibited ATP-induced cytolysis in vitro, as determined by lactate dehydrogenise release from J774 macrophages. Thus, LdNDKb prevents ATP-mediated host-cell plasma membrane permeabilization by hydrolyzing extracellular ATP, thereby, preserving the integrity of the host cells for the benefit of the parasite. This study indicates that LdNDKb could be explored for its potentiality as a drug/vaccine target against visceral leishmaniasis. � 2022
Prevalence of Amoebiasis and Associated Complications in India: A Systematic Review
(Springer Science and Business Media Deutschland GmbH, 2022-04-11T00:00:00) Gupta, Palak; Singh, Kiran Kumari; Balodhi, Ashutosh; Jain, Khushi; Deeba, Farah; Salam, Nasir
Purpose: Intestinal protozoan parasites are responsible for diarrheal diseases causing significant morbidity and mortality. Entamoeba histolytica is the principle protozoan parasite associated with diarrheal infections. The infection is often associated with inaccessibility to clean drinking water and poor sanitary conditions in low- and middle-income countries including India. A comprehensive systematic review was performed to evaluate a reliable nationwide estimate for prevalence and geographic distribution of amoebiasis in India and the complications associated with it. Methods: We used the PRISMA guidelines to perform a systematic review and meta-analysis of articles published between the year 2001�2020. Two English language databases PubMed and Web of Science were searched to achieve relevant studies. Results: Initial searches resulted in 467 studies out of which 64 eligible articles involving data from 289,659 human subjects from 12 states and 4 union territories were included in the final analysis. Prevalence of amoebiasis ranged from 3-23% in asymptomatic population, 0.64�11% in symptomatic patients and 1�17.5% in HIV-infected patients. Highest prevalence was seen in Tamil Nadu, Andaman Nicobar Island and North East India. Extra intestinal invasion of Entamoeba histolytica leading to complications such as amoebic liver abscess, amoebic colitis, colonic perforation and ameboma were also reported. Such complications have the potential to increase healthcare burden and may prove to be fatal. Conclusion: Amoebiasis remains a significant public health issue in India responsible for diarrheal diseases causing significant morbidity and mortality. Entamoeba histolytica is the principle protozoan parasite associated with amoebiasis. Public health efforts should be directed towards its control and better diagnostic methods should be employed for distinguishing between pathogenic and non-pathogenic species of Entamoeba. � 2022, The Author(s) under exclusive licence to Witold Stefa?ski Institute of Parasitology, Polish Academy of Sciences.
Prevalence of Amoebiasis and Associated Complications in India: A Systematic Review
(Springer Science and Business Media Deutschland GmbH, 2022-04-11T00:00:00) Gupta, Palak; Singh, Kiran Kumari; Balodhi, Ashutosh; Jain, Khushi; Deeba, Farah; Salam, Nasir
Purpose: Intestinal protozoan parasites are responsible for diarrheal diseases causing significant morbidity and mortality. Entamoeba histolytica is the principle protozoan parasite associated with diarrheal infections. The infection is often associated with inaccessibility to clean drinking water and poor sanitary conditions in low- and middle-income countries including India. A comprehensive systematic review was performed to evaluate a reliable nationwide estimate for prevalence and geographic distribution of amoebiasis in India and the complications associated with it. Methods: We used the PRISMA guidelines to perform a systematic review and meta-analysis of articles published between the year 2001�2020. Two English language databases PubMed and Web of Science were searched to achieve relevant studies. Results: Initial searches resulted in 467 studies out of which 64 eligible articles involving data from 289,659 human subjects from 12 states and 4 union territories were included in the final analysis. Prevalence of amoebiasis ranged from 3-23% in asymptomatic population, 0.64�11% in symptomatic patients and 1�17.5% in HIV-infected patients. Highest prevalence was seen in Tamil Nadu, Andaman Nicobar Island and North East India. Extra intestinal invasion of Entamoeba histolytica leading to complications such as amoebic liver abscess, amoebic colitis, colonic perforation and ameboma were also reported. Such complications have the potential to increase healthcare burden and may prove to be fatal. Conclusion: Amoebiasis remains a significant public health issue in India responsible for diarrheal diseases causing significant morbidity and mortality. Entamoeba histolytica is the principle protozoan parasite associated with amoebiasis. Public health efforts should be directed towards its control and better diagnostic methods should be employed for distinguishing between pathogenic and non-pathogenic species of Entamoeba. � 2022, The Author(s) under exclusive licence to Witold Stefa?ski Institute of Parasitology, Polish Academy of Sciences.