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Article ; Online: Regulation of Atg8 membrane deconjugation by cysteine proteases in the malaria parasite Plasmodium berghei.

Mishra, Akancha / Varshney, Aastha / Mishra, Satish

Cellular and molecular life sciences : CMLS

2023 Volume 80, Issue 11, Page(s) 344

Abstract: During macroautophagy, the Atg8 protein is conjugated to phosphatidylethanolamine (PE) in autophagic membranes. In Apicomplexan parasites, two cysteine proteases, Atg4 and ovarian tumor unit (Otu), have been identified to delipidate Atg8 to release this ... ...

Abstract	During macroautophagy, the Atg8 protein is conjugated to phosphatidylethanolamine (PE) in autophagic membranes. In Apicomplexan parasites, two cysteine proteases, Atg4 and ovarian tumor unit (Otu), have been identified to delipidate Atg8 to release this protein from membranes. Here, we investigated the role of cysteine proteases in Atg8 conjugation and deconjugation and found that the Plasmodium parasite consists of both activities. We successfully disrupted the genes individually; however, simultaneously, they were refractory to deletion and essential for parasite survival. Mutants lacking Atg4 and Otu showed normal blood and mosquito stage development. All mice infected with Otu KO sporozoites became patent; however, Atg4 KO sporozoites either failed to establish blood infection or showed delayed patency. Through in vitro and in vivo analysis, we found that Atg4 KO sporozoites invade and normally develop into early liver stages. However, nuclear and organelle differentiation was severely hampered during late stages and failed to mature into hepatic merozoites. We found a higher level of Atg8 in Atg4 KO parasites, and the deconjugation of Atg8 was hampered. We confirmed Otu localization on the apicoplast; however, parasites lacking Otu showed no visible developmental defects. Our data suggest that Atg4 is the primary deconjugating enzyme and that Otu cannot replace its function completely because it cleaves the peptide bond at the N-terminal side of glycine, thereby irreversibly inactivating Atg8 during its recycling. These findings highlight a role for the Atg8 deconjugation pathway in organelle biogenesis and maintenance of the homeostatic cellular balance.
MeSH term(s)	Animals ; Mice ; Cysteine Proteases/genetics ; Cysteine Proteases/metabolism ; Parasites/metabolism ; Plasmodium berghei ; Autophagy-Related Protein 8 Family/genetics ; Autophagy-Related Protein 8 Family/metabolism ; Autophagy ; Malaria ; Protozoan Proteins/metabolism
Chemical Substances	Cysteine Proteases (EC 3.4.-) ; Autophagy-Related Protein 8 Family ; Protozoan Proteins
Language	English
Publishing date	2023-11-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-023-05004-2
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Article ; Online: Response: Comment and Update on "Using Artificial Intelligence to Manage Thrombosis Research, Diagnosis, and Clinical Management".

Mishra, Aastha / Ashraf, Mohammad Zahid

Seminars in thrombosis and hemostasis

2021 Volume 47, Issue 1, Page(s) 115–116

MeSH term(s)	Artificial Intelligence ; Humans ; Thrombosis/diagnosis ; Thrombosis/therapy
Language	English
Publishing date	2021-02-01
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0040-1721755
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Article ; Online: Unraveling Epigenetic Interplay between Inflammation, Thrombosis, and Immune-Related Disorders through a Network Meta-analysis.

Chanchal, Shankar / Sharma, Swati / Mohd, Syed / Sultan, Armiya / Mishra, Aastha / Ashraf, Mohammad Zahid

TH open : companion journal to thrombosis and haemostasis

2024 Volume 8, Issue 1, Page(s) e81–e92

Abstract: Inflammation and thrombosis are two distinct yet interdependent physiological processes. The inflammation results in the activation of the coagulation system that directs the immune system and its activation, resulting in the initiation of the ... ...

Abstract	Inflammation and thrombosis are two distinct yet interdependent physiological processes. The inflammation results in the activation of the coagulation system that directs the immune system and its activation, resulting in the initiation of the pathophysiology of thrombosis, a process termed immune-thrombosis. Still, the shared underlying molecular mechanism related to the immune system and coagulation has not yet been explored extensively. Inspired to answer this, we carried out a comprehensive gene expression meta-analysis using publicly available datasets of four diseases, including venous thrombosis, systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. A total of 609 differentially expressed genes (DEGs) shared by all four datasets were identified based on the combined effect size approach. The pathway enrichment analysis of the DEGs showed enrichment of various epigenetic pathways such as histone-modifying enzymes, posttranslational protein modification, chromatin organization, chromatin-modifying enzymes, HATs acetylate proteins. Network-based protein-protein interaction analysis showed epigenetic enzyme coding genes dominating among the top hub genes. The miRNA-interacting partner of the top 10 hub genes was determined. The predomination of epitranscriptomics regulation opens a layout for the meta-analysis of miRNA datasets of the same four diseases. We identified 30 DEmiRs shared by these diseases. There were 9 common DEmiRs selected from the list of miRNA-interacting partners of top 10 hub genes and shared significant DEmiRs from microRNAs dataset acquisition. These common DEmiRs were found to regulate genes involved in epigenetic modulation and indicate a promising epigenetic aspect that needs to be explored for future molecular studies in the context of immunothrombosis and inflammatory disease.
Language	English
Publishing date	2024-02-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2901738-5
ISSN	2512-9465 ; 2567-3459
ISSN (online)	2512-9465
ISSN	2567-3459
DOI	10.1055/a-2222-9126
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Article ; Online: Three-way Philadelphia Translocation [t(46, XX, t(9;22;16) (q34;q11.2;q24)] in Chronic Myeloid Leukemia: A Report of Two Cases with Review of the Literature.

Bhardwaj, Mohit / Mishra, Sourav K / Gupta, Aastha / Mehta, Prashant / Sharma, Shivani / Mohanty, Sambit K

Journal of cancer research and therapeutics

2024

Abstract: Abstract: Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm that is genetically characterized by the presence of the Philadelphia (Ph) chromosome. Variant Ph translocation has been observed in 5% to 10% of the CML cases. In the ... ...

Abstract	Abstract: Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm that is genetically characterized by the presence of the Philadelphia (Ph) chromosome. Variant Ph translocation has been observed in 5% to 10% of the CML cases. In the previous studies, many different types of variant Ph translocations have been observed involving chromosomes 1p36, 3p21, 5q13, 6p21, 9q22, 11q13, 12p13, 17p13, and 10p15. According to the published literature, only two cases with the complex translocations involving long arm of chromosome 16 at band q24 have been reported. We report two female patients with complex translocation (three-way) involving chromosomes 9, 22, and 16 at breakpoint q24 and both patients responded well to Imatinib. The present study included 469 patients of clinically diagnosed CML patients who were referred for cytogenetic analysis to our laboratory. Cytogenetic analysis was performed by GTG banding, and the karyotype was designated according to the International System for Human Cytogenetic Nomenclature. Fluorescence in situ hybridization (FISH) analysis was performed for complex and variant BCR-ABL cases. Of total 469 cases, 248 patients showed classical Ph chromosome [t(9;22)(q34;q11.2)], 198 cases were normal, and 23 patients had variant and complex Ph chromosome translocation. Two patients showed three-way translocation involving long arm of chromosomes 9, 22, and 16 at band 9q34, 22q11.2, and 16q24. In this report, patients with variant Ph translocation did not have a significantly different outcome as compared to the classical translocation. Both cases responded well to Imatinib.
Language	English
Publishing date	2024-01-22
Publishing country	India
Document type	Journal Article
ZDB-ID	2187633-2
ISSN	1998-4138 ; 0973-1482
ISSN (online)	1998-4138
ISSN	0973-1482
DOI	10.4103/jcrt.jcrt_274_21
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Article: Response: Comment and Update on “Using Artificial Intelligence to Manage Thrombosis Research, Diagnosis, and Clinical Management”

Mishra, Aastha / Ashraf, Mohammad Zahid

Seminars in Thrombosis and Hemostasis

(Editorial Compilation IX)

2021 Volume 47, Issue 01, Page(s) 115–116

Series title	Editorial Compilation IX
Language	English
Publishing date	2021-02-01
Publisher	Thieme Medical Publishers, Inc.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0040-1721755
Database	Thieme publisher's database

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Article ; Online: COVID-19 Induced Coagulopathy (CIC): Thrombotic Manifestations of Viral Infection.

Sharma, Swati / Mishra, Aastha / Ashraf, Zahid

TH open : companion journal to thrombosis and haemostasis

2022 Volume 6, Issue 1, Page(s) e70–e79

Abstract: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may result in an overactive coagulative system, thereby resulting in serious cardiovascular consequences in critically affected patients. ...

Abstract	Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may result in an overactive coagulative system, thereby resulting in serious cardiovascular consequences in critically affected patients. The respiratory tract is a primary target for COVID-19 infection, which is manifested as acute lung injury in the most severe form of the viral infection, leading to respiratory failure. A proportion of infected patients may progress to serious systemic disease including dysfunction of multiple organs, acute respiratory distress syndrome (ARDS), and coagulation abnormalities, all of which are associated with increased mortality, additionally depending on age and compromised immunity. Coagulation abnormalities associated with COVID-19 mimic other systemic coagulopathies otherwise involved in other severe infections, such as disseminated intravascular coagulation (DIC) and may be termed COVID-19 induced coagulopathy (CIC). There is substantial evidence that patients with severe COVID-19 exhibiting CIC can develop venous and arterial thromboembolic complications. In the initial stages of CIC, significant elevation of D-dimer and fibrin/fibrinogen degradation products is observed. Alteration in prothrombin time, activated partial thromboplastin time, and platelet counts are less common in the early phase of the disease. In patients admitted to intensive care units (ICUs), coagulation test screening involving the measurement of D-dimer and fibrinogen levels, has been recommended. Prior established protocols for thromboembolic prophylaxis are also followed for CIC, including the use of heparin and other standard supportive care measures. In the present review, we summarize the characteristics of CIC and its implications for thrombosis, clinical findings of coagulation parameters in SARS-CoV-2 infected patients with incidences of thromboembolic events and plausible therapeutic measures.
Language	English
Publishing date	2022-03-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2901738-5
ISSN	2512-9465 ; 2567-3459
ISSN (online)	2512-9465
ISSN	2567-3459
DOI	10.1055/s-0042-1744185
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Article ; Online: Biopesticidal potential of cyclotides: an insight

Shambhawi / Srivastava, Shreya / Mishra, Aastha / Mishra, Reema / Mohanty, Aparajita

Phytochem Rev. 2022 Dec., v. 21, no. 6 p.2027-2047

2022

Abstract: Cyclotides are cyclic, plant-derived cysteine rich peptides (CRP) with experimentally proven pesticidal activity thus, qualifying them as potential biopesticides. They are preferred over synthetic pesticides for their ecofriendly attributes and are safer ...

Abstract	Cyclotides are cyclic, plant-derived cysteine rich peptides (CRP) with experimentally proven pesticidal activity thus, qualifying them as potential biopesticides. They are preferred over synthetic pesticides for their ecofriendly attributes and are safer for humans and livestock. Their natural role in plants is defense against pests and pathogens. They consist of 26 to 37 amino acids alongwith six cysteine residues that are highly conserved and form three disulfide linkages (Cysᴵ-Cysᴵⱽ, Cysᴵᴵ-Cysⱽ, Cysᴵᴵᴵ-Cysⱽᴵ) producing a knotted ring topology, or the cyclic cystine knot (CCK). This conserved CCK motif protects the cyclotides from heat, chemical and proteolytic degradation making them extremely stable peptides and consequently the ability to resist pest attack on the plant. Their mode of action is by binding, interacting with host cell membrane and eventually disrupting them, thus resulting in pest mortality. Recently the commercialization of bioinsecticidal spray, Sero-X (mix of cyclotides from Clitoria ternatea) to control pests affecting cotton crops, emphasizes the biopesticidal potential of cyclotides. To date more than 750 cyclotides have been discovered, but only 26 cyclotides have been investigated for pesticidal activity against pests affecting crops, animals and humans. Considering the potential of cyclotides, the present review describes pesticidal activity of 26 cyclotides relevant to agricultural crops and animal husbandry. Further, the mechanism of action and implication of multiple bioactivities (hemolytic and cytotoxic) of pesticidal cyclotides for developing commercial biopesticides have been discussed. Future prospects include the importance of screening more numbers of cyclotides against a wider range of pests for formulating biopesticidal sprays.
Keywords	Clitoria ternatea ; animal husbandry ; biopesticides ; cell membranes ; commercialization ; cotton ; cysteine ; cystine ; cytotoxicity ; heat ; livestock ; mechanism of action ; mortality ; peptides ; pesticidal properties ; pests ; proteolysis ; topology
Language	English
Dates of publication	2022-12
Size	p. 2027-2047.
Publishing place	Springer Netherlands
Document type	Article ; Online
Note	Review
ZDB-ID	2065661-0
ISSN	1572-980X ; 1568-7767
ISSN (online)	1572-980X
ISSN	1568-7767
DOI	10.1007/s11101-022-09825-0
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Association of transient mitochondrial functional impairment with acute heat exposure in children from Muzaffarpur region of Bihar, India.

Singh, Kanika / Kumari, Swati / Ali, Manzoor / Das, Manoja K / Mishra, Aastha / Singh, Arun K

International journal of biometeorology

2023 Volume 67, Issue 12, Page(s) 1975–1989

Abstract: Over the past several years, the Muzaffarpur district of Bihar (India) has witnessed recurrent outbreaks of acute encephalitis illness of unknown etiology, called acute encephalitis syndrome (AES) among young children, especially during the peak-summer ... ...

Abstract	Over the past several years, the Muzaffarpur district of Bihar (India) has witnessed recurrent outbreaks of acute encephalitis illness of unknown etiology, called acute encephalitis syndrome (AES) among young children, especially during the peak-summer season. Pesticide exposure, viral encephalitis, and litchi toxin intake have all been postulated as potential sources of the ailment. However, no conclusive etiology for AES has been identified in the affected children. During recent rounds of the outbreak, metabolic abnormalities have been documented in these children, and a direct correlation was observed between higher environmental temperature during the peak-summer month and AES caseload. The clinical and metabolic profiles of these children suggested the possible involvement of mitochondrial dysfunction during heat stress as one of the several contributory factors leading to multisystem metabolic derangement. The present study observed that mitochondrial function parameters such as cell death, mitochondrial membrane potential, oxidative stress, and mitochondrial pathway-related gene expression in peripheral blood mononuclear cells (PBMCs) isolated from children were affected in peak-summer when compared to post-summer months. Similar observations of mitochondrial function parameters along with impaired bioenergetic parameters were demonstrated in the heat-exposed model of PBMCs isolated from healthy adult individuals. In conclusion, the results suggested that there is an association of transient mitochondrial dysfunction when exposed to sustained heat during the summer months. One may consider mitochondrial dysfunction as one of the important factors leading to an outbreak of AES among the children from affected regions though this needs to be substantiated with further studies.
MeSH term(s)	Adult ; Humans ; Child ; Child, Preschool ; Leukocytes, Mononuclear ; India/epidemiology ; Disease Outbreaks ; Energy Metabolism ; Acute Febrile Encephalopathy/epidemiology ; Acute Febrile Encephalopathy/etiology ; Mitochondria
Language	English
Publishing date	2023-10-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	280324-0
ISSN	1432-1254 ; 0020-7128
ISSN (online)	1432-1254
ISSN	0020-7128
DOI	10.1007/s00484-023-02555-8
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Article: Therapeutic Role of Sirtuins Targeting Unfolded Protein Response, Coagulation, and Inflammation in Hypoxia-Induced Thrombosis.

Sadia, Khan / Ashraf, Mohammad Zahid / Mishra, Aastha

Frontiers in physiology

2021 Volume 12, Page(s) 733453

Abstract: Thrombosis remains one of the leading causes of morbidity and mortality across the world. Many pathological milieus in the body resulting from multiple risk factors escort thrombosis. Hypoxic condition is one such risk factor that disturbs the integrity ... ...

Abstract	Thrombosis remains one of the leading causes of morbidity and mortality across the world. Many pathological milieus in the body resulting from multiple risk factors escort thrombosis. Hypoxic condition is one such risk factor that disturbs the integrity of endothelial cells to cause an imbalance between anticoagulant and procoagulant proteins. Hypoxia generates reactive oxygen species (ROS) and triggers inflammatory pathways to augment the coagulation cascade. Hypoxia in cells also activates unfolded protein response (UPR) signaling pathways in the endoplasmic reticulum (ER), which tries to restore ER homeostasis and function. But the sustained UPR linked with inflammation, generation of ROS and apoptosis stimulates the severity of thrombosis in the body. Sirtuins, a group of seven proteins, play a vast role in bringing down inflammation, oxidative and ER stress and apoptosis. As a result, sirtuins might provide a therapeutic approach towards the treatment or prevention of hypoxia-induced thrombosis. Sirtuins modulate hypoxia-inducible factors (HIFs) and counteract ER stress-induced apoptosis by attenuating protein kinase RNA-like endoplasmic reticulum kinase (PERK)/Eukaryotic translation initiation factor 2α (eIF2α) pathway activation. It prevents ER-stress mediated inflammation by targeting X-Box Binding Protein 1 (XBP1) and inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ) signaling through deacetylation. Sirtuins also obstruct nucleotide-binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3) inflammasome activation to reduce the expression of several pro-inflammatory molecules. It protects cells against oxidative stress by targeting nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), forkhead box O3 (FOXO3), superoxide dismutase (SOD), catalase (CAT), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), glucose-6-phosphate dehydrogenase (G6PD), phosphoglucomutase-2 (PGAM2), and NF-κB, to name few. This review, thus, discusses the potential role of sirtuins as a new treatment for hypoxia-induced thrombosis that involves an intersection of UPR and inflammatory pathways in its pathological manifestation.
Language	English
Publishing date	2021-11-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2021.733453
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Article ; Online: Using Artificial Intelligence to Manage Thrombosis Research, Diagnosis, and Clinical Management.

Mishra, Aastha / Ashraf, Mohammad Zahid

Seminars in thrombosis and hemostasis

2019 Volume 46, Issue 4, Page(s) 410–418

Abstract: Thrombosis development in either arterial or venous system remains a major cause of death and disability worldwide. This poorly controlled in vivo clotting could result in many severe complications including myocardial infarction, venous thromboembolism, ...

Abstract	Thrombosis development in either arterial or venous system remains a major cause of death and disability worldwide. This poorly controlled in vivo clotting could result in many severe complications including myocardial infarction, venous thromboembolism, stroke, and cerebral venous thrombosis, to name a few. These conditions are collectively known as thromboembolic disorders (TEDs). Appropriate understanding of TEDs is challenging, as they are multifactorial and involve several and often different risk factors. Hence, it requires a collective effort and data from numerous research studies to fully comprehend molecular mechanisms for prediction, prevention, treatment, and overall management of these conditions. To accomplish this arduous feat, a comprehensive approach is required that can compile thousands of available experimental data and transform these into more applicable and purposeful findings. Thus, large datasets could be utilized to generate models that could be predictive of how an individual would respond when subjected to any kind of additional risk factors or surgery, hospitalization, etc., or in the presence of some susceptible genetic variations. Artificial intelligence-based methods harness the capabilities of computer software to imitate human behaviors such as language translation, visual perception, and, most importantly, decision making. These emerging tools, if appropriately explored, might assist in processing of large data and tackle the complexities of identifying novel or interesting pathways that could otherwise be hidden due to their enormity. This narrative review attempts to compile the applications of various subfields of artificial intelligence and machine learning in the context of thrombosis research to date. It further reflects on the potential of artificial intelligence in transforming enormous research data into translational application in the form of predictive computational models.
MeSH term(s)	Artificial Intelligence/standards ; Humans ; Risk Factors ; Thrombosis/diagnosis ; Thrombosis/therapy
Language	English
Publishing date	2019-09-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0039-1697949
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