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  1. Article ; Online: Molecular tools are crucial for malaria elimination.

    Gupta, Himanshu / Sharma, Sonal / Gilyazova, Irina / Satyamoorthy, Kapaettu

    Molecular biology reports

    2024  Volume 51, Issue 1, Page(s) 555

    Abstract: The eradication of Plasmodium parasites, responsible for malaria, is a daunting global public health task. It requires a comprehensive approach that addresses symptomatic, asymptomatic, and submicroscopic cases. Overcoming this challenge relies on ... ...

    Abstract The eradication of Plasmodium parasites, responsible for malaria, is a daunting global public health task. It requires a comprehensive approach that addresses symptomatic, asymptomatic, and submicroscopic cases. Overcoming this challenge relies on harnessing the power of molecular diagnostic tools, as traditional methods like microscopy and rapid diagnostic tests fall short in detecting low parasitaemia, contributing to the persistence of malaria transmission. By precisely identifying patients of all types and effectively characterizing malaria parasites, molecular tools may emerge as indispensable allies in the pursuit of malaria elimination. Furthermore, molecular tools can also provide valuable insights into parasite diversity, drug resistance patterns, and transmission dynamics, aiding in the implementation of targeted interventions and surveillance strategies. In this review, we explore the significance of molecular tools in the pursuit of malaria elimination, shedding light on their key contributions and potential impact on public health.
    MeSH term(s) Animals ; Humans ; Malaria/epidemiology ; Malaria/prevention & control ; Plasmodium ; Parasites ; Public Health ; Microscopy/methods
    Language English
    Publishing date 2024-04-20
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-024-09496-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: DNA damage-induced senescence is associated with metabolomic reprogramming in breast cancer cells.

    George, Neena / Joshi, Manjunath B / Satyamoorthy, Kapaettu

    Biochimie

    2023  Volume 216, Page(s) 71–82

    Abstract: Senescence due to exogenous and endogenous stresses triggers metabolic reprogramming and is associated with many pathologies, including cancer. In solid tumors, senescence promotes tumorigenesis, facilitates relapse, and changes the outcomes of anti- ... ...

    Abstract Senescence due to exogenous and endogenous stresses triggers metabolic reprogramming and is associated with many pathologies, including cancer. In solid tumors, senescence promotes tumorigenesis, facilitates relapse, and changes the outcomes of anti-cancer therapies. Hence, cellular and molecular mechanisms regulating senescent pathways make attractive therapeutic targets. Cancer cells undergo metabolic reprogramming to sustain the growth-arrested state of senescence. In the present study, we aimed to understand the metabolic reprogramming in MCF-7 breast tumor cells in response to two independent inducers of DNA damage-mediated senescence, including ionizing radiation and doxorubicin. Increased DNA double-strand breaks, as demonstrated by γH2AX staining, showed a senescence phenotype, with expression of senescence-associated β-galactosidase accompanied by the upregulation of p21 and p16 in both groups. Further, untargeted analysis of the senescence-related extracellular metabolome profile of MCF-7 cells showed significantly reduced concentrations of carnitine and pantothenic acid and increased levels of S-adenosylhomocysteine in doxorubicin-treated cells, indicating the accumulation of ROS mediated DNA damage and impaired mitochondrial membrane potential. Similarly, a significant decline in the creatine level was observed in radiation-exposed cells, suggesting an increase in oxidative stress-mediated DNA damage. Our study, therefore, provides key effectors of the metabolic changes in doxorubicin and radiation-induced early senescence in MCF-7 breast cancer cells.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Doxorubicin/pharmacology ; DNA Damage ; MCF-7 Cells ; Cellular Senescence/genetics
    Chemical Substances Doxorubicin (80168379AG)
    Language English
    Publishing date 2023-09-25
    Publishing country France
    Document type Journal Article
    ZDB-ID 120345-9
    ISSN 1638-6183 ; 0300-9084
    ISSN (online) 1638-6183
    ISSN 0300-9084
    DOI 10.1016/j.biochi.2023.09.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Integrated multiomics analysis of chromosome 19 miRNA cluster in bladder cancer.

    Ware, Akshay Pramod / Satyamoorthy, Kapaettu / Paul, Bobby

    Functional & integrative genomics

    2023  Volume 23, Issue 3, Page(s) 266

    Abstract: With 46 microRNAs (miRNAs) embedded tandemly over a distance of ~100 kb, chromosome 19 microRNA cluster (C19MC) is the largest miRNA cluster in the human genome. The C19MC is transcribed from a long noncoding genomic region and is usually expressed ... ...

    Abstract With 46 microRNAs (miRNAs) embedded tandemly over a distance of ~100 kb, chromosome 19 microRNA cluster (C19MC) is the largest miRNA cluster in the human genome. The C19MC is transcribed from a long noncoding genomic region and is usually expressed simultaneously at a higher level. Hence, we performed an integrative multiomics data analysis to examine C19MC regulation, expression patterns, and their impact on bladder cancer (BCa). We found that 43 members of C19MC were highly expressed in BCa. However, its co-localization with recurrent copy number variation (CNV) gain was not statistically significant to implicate its upregulation. It has been reported that C19MC expression is regulated by a well-established CpG island situated 17.6 kb upstream of the transcription start site, but we found that CpG probes at this island were hypomethylated, which was not statistically significant in the BCa cohort. In addition, the promoter region of C19MC is strongly regulated by a group of seven transcription factors (NR2F6, SREBF1, TBP, GATA3, GABPB1, ETV4, and ZNF444) and five chromatin modifiers (SMC3, KDMA1, EZH2, RAD21, and CHD7). Interestingly, these 12 genes were found to be overexpressed in BCa patients. Further, C19MC targeted 42 tumor suppressor (TS) genes that were downregulated, of which 15 were significantly correlated with patient survival. Our findings suggest that transcription factors and chromatin modifiers at the promoter region may regulate C19MC overexpression. The upregulated C19MC members, transcription regulators, and TS genes can be further exploited as potential diagnostic and prognostic indicators as well as for therapeutic management of BCa.
    MeSH term(s) Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; DNA Copy Number Variations ; Chromosomes, Human, Pair 19/metabolism ; Multiomics ; Urinary Bladder Neoplasms/genetics ; Transcription Factors/genetics ; Chromatin ; Gene Expression Regulation, Neoplastic ; Repressor Proteins/genetics
    Chemical Substances MicroRNAs ; Transcription Factors ; Chromatin ; NR2F6 protein, human ; Repressor Proteins
    Language English
    Publishing date 2023-08-05
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2014670-X
    ISSN 1438-7948 ; 1438-793X
    ISSN (online) 1438-7948
    ISSN 1438-793X
    DOI 10.1007/s10142-023-01191-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The regulation of plasma gelsolin by DNA methylation in ovarian cancer chemo-resistance.

    Manzoor, Hafiza Bushra / Asare-Werehene, Meshach / Pereira, Satyajit Dey / Satyamoorthy, Kapaettu / Tsang, Benjamin K

    Journal of ovarian research

    2024  Volume 17, Issue 1, Page(s) 15

    Abstract: Background: Ovarian cancer (OVCA) is the most lethal gynecologic cancer and chemoresistance remains a major hurdle to successful therapy and survival of OVCA patients. Plasma gelsolin (pGSN) is highly expressed in chemoresistant OVCA compared with their ...

    Abstract Background: Ovarian cancer (OVCA) is the most lethal gynecologic cancer and chemoresistance remains a major hurdle to successful therapy and survival of OVCA patients. Plasma gelsolin (pGSN) is highly expressed in chemoresistant OVCA compared with their chemosensitive counterparts, although the mechanism underlying the differential expression is not known. Also, its overexpression significantly correlates with shortened survival of OVCA patients. In this study, we investigated the methylation role of Ten eleven translocation isoform-1 (TET1) in the regulation of differential pGSN expression and chemosensitivity in OVCA cells.
    Methods: Chemosensitive and resistant OVCA cell lines of different histological subtypes were used in this study to measure pGSN and TET1 mRNA abundance (qPCR) as well as protein contents (Western blotting). To investigate the role of DNA methylation specifically in pGSN regulation and pGSN-induced chemoresistance, DNMTs and TETs were pharmacologically inhibited in sensitive and resistant OVCA cells using specific inhibitors. DNA methylation was quantified using EpiTYPER MassARRAY system. Gain-and-loss-of-function assays were used to investigate the relationship between TET1 and pGSN in OVCA chemoresponsiveness.
    Results: We observed differential protein and mRNA expressions of pGSN and TET1 between sensitive and resistant OVCA cells and cisplatin reduced their expression in sensitive but not in resistant cells. We observed hypomethylation at pGSN promoter upstream region in resistant cells compared to sensitive cells. Pharmacological inhibition of DNMTs increased pGSN protein levels in sensitive OVCA cells and decreased their responsiveness to cisplatin, however we did not observe any difference in methylation level at pGSN promoter region. TETs inhibition resulted in hypermethylation at multiple CpG sites and decreased pGSN protein level in resistant OVCA cells which was also associated with enhanced response to cisplatin, findings that suggested the methylation role of TETs in the regulation of pGSN expression in OVCA cells. Further, we found that TET1 is inversely related to pGSN but positively related to chemoresponsiveness of OVCA cells.
    Conclusion: Our findings broaden our knowledge about the epigenetic regulation of pGSN in OVCA chemoresistance and reveal a novel potential target to re-sensitize resistant OVCA cells. This may provide a future therapeutic strategy to improve the overall OVCA patient survival.
    MeSH term(s) Humans ; Female ; Cisplatin/pharmacology ; Cisplatin/therapeutic use ; Gelsolin/genetics ; Gelsolin/metabolism ; DNA Methylation ; Epigenesis, Genetic ; Drug Resistance, Neoplasm/genetics ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; RNA, Messenger/metabolism ; Mixed Function Oxygenases/genetics ; Mixed Function Oxygenases/metabolism ; Mixed Function Oxygenases/therapeutic use ; Proto-Oncogene Proteins/metabolism
    Chemical Substances Cisplatin (Q20Q21Q62J) ; Gelsolin ; RNA, Messenger ; TET1 protein, human (EC 1.-) ; Mixed Function Oxygenases (EC 1.-) ; Proto-Oncogene Proteins
    Language English
    Publishing date 2024-01-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2455679-8
    ISSN 1757-2215 ; 1757-2215
    ISSN (online) 1757-2215
    ISSN 1757-2215
    DOI 10.1186/s13048-023-01332-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Molecular Mechanisms of Asparagus racemosus Willd. and Withania somnifera (L.) Dunal as Chemotherapeutic Adjuvants for Breast Cancer Treatment.

    Prasad, Keshava / Saggam, Akash / Guruprasad, Kanive Parashiva / Tillu, Girish / Patwardhan, Bhushan / Satyamoorthy, Kapaettu

    Journal of ethnopharmacology

    2024  , Page(s) 118261

    Abstract: Ethnopharmacological relevance: Despite various treatment modalities, the progression and metastasis of breast cancer (BC) are grave concerns due to the alarming disease-free survival rate (DFS) and overall survival rate (OS) of affected patients. Over ... ...

    Abstract Ethnopharmacological relevance: Despite various treatment modalities, the progression and metastasis of breast cancer (BC) are grave concerns due to the alarming disease-free survival rate (DFS) and overall survival rate (OS) of affected patients. Over the years, many antibiotics, synthetic compounds, medicinal plant isolates and polyherbal combinations have been used as adjuvants in therapy for the management of primary and secondary tumors. Paclitaxel (PTX)-based chemotherapy for breast cancer causes multiple adverse side effects in patients. Withania somnifera (L.) Dunal (WS) and Asparagus racemosus Willd. (AR) as Ayurveda-inspired plant-based adjuvants were investigated for their anticancer effects on MDA-MB-231 and 4T1 cells in mouse model systems.
    Aim of the study: This study focused on evaluating the adjuvant properties of WS and AR plant extracts with PTX and their effectiveness over PTX alone in terms of tumor inhibition.
    Materials and methods: The effects of WS and AR on DNA double-strand breaks (DSBs), senescence induction and mitochondrial functions were evaluated in BC cells in vitro. The potential for cancer stem cell (CSC) inhibition was evaluated via mammosphere formation assays and CD44/CD24 immunostaining. In vivo tumor growth studies were conducted in athymic BALB/c mice for MDA-MB-231 cells and in BALB/c mice for 4T1 cells.
    Results: Induction of senescence was evident due to DSBs induced by the WS and AR extracts. Mammosphere formation and CD44/CD24 CSC markers were reduced after treatment with WS, AR or the combination of both in MCF-7 cells. WS or AR inhibited epithelial-to-mesenchymal transition (EMT). In vivo studies demonstrated that tumor growth inhibition was more pronounced in the treated group than in the PTX alone group and the untreated control group.
    Conclusion: Our study showed that the use of WS or AR plant hydroalcoholic extracts in combination with paclitaxel (PTX) has better effects on sensitivity and efficacy than PTX alone, as demonstrated in in vitro BC cells and mouse models with BC cell grafts. Hence, scheduling adjuvant therapy with WS or AR alone or combined with PTX can be advantageous for the management of triple-negative BC (TNBC). Further studies are warranted in human clinical conditions to ascertain the efficacy of these treatments.
    Language English
    Publishing date 2024-04-27
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2024.118261
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  6. Article ; Online: Synergistic therapeutics: Co-targeting histone deacetylases and ribonucleotide reductase for enhanced cancer treatment.

    Shetty, Manasa Gangadhar / Pai, Padmini / Padavu, Mythili / Satyamoorthy, Kapaettu / Kampa Sundara, Babitha

    European journal of medicinal chemistry

    2024  Volume 269, Page(s) 116324

    Abstract: The development of cancer is influenced by several variables, including altered protein expression, and signaling pathways. Cancers are inherently heterogeneous and exhibit genetic and epigenetic aberrations; therefore, developing therapies that act on ... ...

    Abstract The development of cancer is influenced by several variables, including altered protein expression, and signaling pathways. Cancers are inherently heterogeneous and exhibit genetic and epigenetic aberrations; therefore, developing therapies that act on numerous biological targets is encouraged. To achieve this, two approaches are employed: combination therapy and dual/multiple targeting chemotherapeutics. Two enzymes, histone deacetylases (HDACs) and ribonucleotide reductase (RR), are crucial for several biological functions, including replication and repair of DNA, division of cells, transcription of genes, etc. However, it has been noted that different cancers exhibit abnormal functions of these enzymes. Potent inhibitors for each of these proteins have been extensively researched. Many medications based on these inhibitors have been successfully food and drug administration (FDA) approved, and the majority are undergoing various stages of clinical testing. This review discusses various studies of HDAC and RR inhibitors in combination therapy and dual-targeting chemotherapeutics.
    MeSH term(s) Humans ; Ribonucleotide Reductases/therapeutic use ; Histone Deacetylases/metabolism ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Neoplasms/genetics
    Chemical Substances Ribonucleotide Reductases (EC 1.17.4.-) ; Histone Deacetylases (EC 3.5.1.98) ; Histone Deacetylase Inhibitors
    Language English
    Publishing date 2024-03-16
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 188597-2
    ISSN 1768-3254 ; 0009-4374 ; 0223-5234
    ISSN (online) 1768-3254
    ISSN 0009-4374 ; 0223-5234
    DOI 10.1016/j.ejmech.2024.116324
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Mitochondria in biology and medicine - 2023.

    Disha, B / Mathew, Rohan Peter / Dalal, Ashwin B / Mahato, Ajay K / Satyamoorthy, Kapaettu / Singh, Keshav K / Thangaraj, Kumarasamy / Govindaraj, Periyasamy

    Mitochondrion

    2024  Volume 76, Page(s) 101853

    Abstract: Mitochondria are an indispensable part of the cell that plays a crucial role in regulating various signaling pathways, energy metabolism, cell differentiation, proliferation, and cell death. Since mitochondria have their own genetic material, they differ ...

    Abstract Mitochondria are an indispensable part of the cell that plays a crucial role in regulating various signaling pathways, energy metabolism, cell differentiation, proliferation, and cell death. Since mitochondria have their own genetic material, they differ from their nuclear counterparts, and dysregulation is responsible for a broad spectrum of diseases. Mitochondrial dysfunction is associated with several disorders, including neuro-muscular disorders, cancer, and premature aging, among others. The intricacy of the field is due to the cross-talk between nuclear and mitochondrial genes, which has also improved our knowledge of mitochondrial functions and their pathogenesis. Therefore, interdisciplinary research and communication are crucial for mitochondrial biology and medicine due to the challenges they pose for diagnosis and treatment. The ninth annual conference of the Society for Mitochondria Research and Medicine (SMRM)- India, titled "Mitochondria in Biology and Medicine" was organized at the Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, India, on June 21-23, 2023. The latest advancements in the field of mitochondrial biology and medicine were discussed at the conference. In this article, we summarize the entire event for the benefit of researchers working in the field of mitochondrial biology and medicine.
    Language English
    Publishing date 2024-02-28
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2056923-3
    ISSN 1872-8278 ; 1567-7249
    ISSN (online) 1872-8278
    ISSN 1567-7249
    DOI 10.1016/j.mito.2024.101853
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  8. Article: Therapeutics through glycobiology: an approach for targeted elimination of malaria.

    Divya, Mallya / Prabhu, Sowmya R / Satyamoorthy, Kapaettu / Saadi, Abdul Vahab

    Biologia

    2023  , Page(s) 1–5

    Abstract: The emergence of drug resistance ... ...

    Abstract The emergence of drug resistance in
    Language English
    Publishing date 2023-01-10
    Publishing country Slovakia
    Document type Editorial
    ZDB-ID 419136-5
    ISSN 1336-9563 ; 0006-3088 ; 1335-6372 ; 1335-6380
    ISSN (online) 1336-9563
    ISSN 0006-3088 ; 1335-6372 ; 1335-6380
    DOI 10.1007/s11756-023-01312-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: CmirC: an integrated database of clustered miRNAs co-localized with copy number variations in cancer.

    Ware, Akshay Pramod / Satyamoorthy, Kapaettu / Paul, Bobby

    Functional & integrative genomics

    2022  Volume 22, Issue 6, Page(s) 1229–1241

    Abstract: Genomic rearrangements and copy number variations (CNVs) are the major regulators of clustered microRNAs (miRNAs) expression. Several clustered miRNAs are harbored in and around chromosome fragile sites (CFSs) and cancer-associated genomic hotspots. ... ...

    Abstract Genomic rearrangements and copy number variations (CNVs) are the major regulators of clustered microRNAs (miRNAs) expression. Several clustered miRNAs are harbored in and around chromosome fragile sites (CFSs) and cancer-associated genomic hotspots. Aberrant expression of such clusters can lead to oncogenic or tumor suppressor activities. Here, we developed CmirC (Clustered miRNAs co-localized with CNVs), a comprehensive database of clustered miRNAs co-localized with CNV regions. The database consists of 481 clustered miRNAs co-localized with CNVs and their expression patterns in 35 cancer types of the TCGA. The portal also provides information on CFSs, miRNA cluster candidates, genomic coordinates, target gene networks, and gene functionality. The web portal is integrated with advanced tools such as JBrowse, NCBI-BLAST, GeneSCF, visNetwork, and NetworkD3 to help the researchers in data analysis, visualization, and browsing. This portal provides a promising avenue for integrated data analytics and offers additional evidence for the complex regulation of clustered miRNAs in cancer. The web portal is freely accessible at http://slsdb.manipal.edu/cmirclust to explore clinically significant miRNAs.
    MeSH term(s) Humans ; DNA Copy Number Variations ; MicroRNAs/genetics ; Genomics ; Gene Regulatory Networks ; Neoplasms/genetics
    Chemical Substances MicroRNAs
    Language English
    Publishing date 2022-10-26
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2014670-X
    ISSN 1438-7948 ; 1438-793X
    ISSN (online) 1438-7948
    ISSN 1438-793X
    DOI 10.1007/s10142-022-00909-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Pharmacogenomics deliberations of 2-deoxy-d-glucose in the treatment of COVID-19 disease: an in silico approach.

    Prabhu, Navya B / Vinay, Chigateri M / Satyamoorthy, Kapaettu / Rai, Padmalatha S

    3 Biotech

    2022  Volume 12, Issue 11, Page(s) 287

    Abstract: The outbreak of COVID-19 caused by the coronavirus (SARS-CoV-2) prompted number of computational and laboratory efforts to discover molecules against the virus entry or replication. Simultaneously, due to the availability of clinical information, drug- ... ...

    Abstract The outbreak of COVID-19 caused by the coronavirus (SARS-CoV-2) prompted number of computational and laboratory efforts to discover molecules against the virus entry or replication. Simultaneously, due to the availability of clinical information, drug-repurposing efforts led to the discovery of 2-deoxy-d-glucose (2-DG) for treating COVID-19 infection. 2-DG critically accumulates in the infected cells to prevent energy production and viral replication. As there is no clarity on the impact of genetic variations on the efficacy and adverse effects of 2-DG in treating COVID-19 using in silico approaches, we attempted to extract the genes associated with the 2-DG pathway using the Comparative Toxicogenomics Database. The interaction between selected genes was assessed using ClueGO, to identify the susceptible gene loci for SARS-CoV infections. Further, SNPs that were residing in the distinct genomic regions were retrieved from the Ensembl genome browser and characterized. A total of 80 SNPs were retrieved using diverse bioinformatics resources after assessing their (a) detrimental influence on the protein stability using Swiss-model, (b) miRNA regulation employing miRNASNP3, PolymiRTS, MirSNP databases, (c) binding of transcription factors by SNP2TFBS, SNPInspector, and (d) enhancers regulation using EnhancerDB and HaploReg reported A2M rs201769751, PARP1 rs193238922 destabilizes protein, six polymorphisms of XIAP effecting microRNA binding sites,
    Supplementary information: The online version contains supplementary material available at 10.1007/s13205-022-03363-4.
    Language English
    Publishing date 2022-09-21
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2600522-0
    ISSN 2190-5738 ; 2190-572X
    ISSN (online) 2190-5738
    ISSN 2190-572X
    DOI 10.1007/s13205-022-03363-4
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