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Article: Quercetin Impairs HuR-Driven Progression and Migration of Triple Negative Breast Cancer (TNBC) Cells

Umar, Sheikh Mohammad / Patra, Sushmita / Kashyap, Akanksha / Dev J R, Arundhathi / Kumar, Lalit / Prasad, Chandra Prakash

Nutrition and cancer. 2022 Apr. 21, v. 74, no. 4

2022

Abstract: In the present study, we have explored the prognostic value of HuR gene as well as protein in breast cancers. Furthermore, we have also investigated the HuR therapeutic relevance in TNBCs, which is an aggressive breast cancer subtype. Using an online ... ...

Abstract	In the present study, we have explored the prognostic value of HuR gene as well as protein in breast cancers. Furthermore, we have also investigated the HuR therapeutic relevance in TNBCs, which is an aggressive breast cancer subtype. Using an online meta-analysis tool, we found that HuR protein overexpression positively correlates with reduced overall survival of TNBC patients (p = 0.028). Furthermore, we demonstrated that the TNBC breast cancer cell lines i.e., MDA-MB-231 and MDA-MB-468 are good model systems to study HuR protein, as they both exhibit a significant amount of cytoplasmic HuR (active form). Quercetin treatment significantly inhibited the cytoplasmic HuR in both TNBC cell lines. By using specific HuR siRNA, we established that quercetin-mediated inhibition of adhesion and migration of TNBC cells is dependent on HuR. Upon analyzing adhesion proteins i.e., β-catenin and CD44, we found that quercetin mediated effect on TNBC adhesion and migration was through the HuR-β-catenin axis and CD44, independently. Overall, the present results demonstrate that elevated HuR levels are associated with TNBC progression and relapse, and the ability of quercetin to inhibit cytoplasmic HuR protein provides a rationale for using it as an anticancer agent for the treatment of aggressive TNBCs. Supplemental data for this article is available online at at 10.1080/01635581.2021.1952628.
Keywords	adhesion ; antineoplastic agents ; breast neoplasms ; breasts ; genes ; meta-analysis ; neoplasm cells ; quercetin ; relapse ; therapeutics
Language	English
Dates of publication	2022-0421
Size	p. 1497-1510.
Publishing place	Taylor & Francis
Document type	Article
ZDB-ID	424433-3
ISSN	1532-7914 ; 0163-5581
ISSN (online)	1532-7914
ISSN	0163-5581
DOI	10.1080/01635581.2021.1952628
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 1496: Show issues

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Article ; Online: Advancement in precision diagnosis and therapeutic for triple-negative breast cancer: Harnessing diagnostic potential of CRISPR-cas & engineered CAR T-cells mediated therapeutics.

Nayak, Vinayak / Patra, Sushmita / Singh, Kshitij Rb / Ganguly, Bristy / Kumar, Das Nishant / Panda, Deepak / Maurya, Ganesh Kumar / Singh, Jay / Majhi, Sanatan / Sharma, Rohit / Pandey, Shyam S / Singh, Ravindra Pratap / Kerry, Rout George

Environmental research

2023 Volume 235, Page(s) 116573

Abstract: Cancer is characterized by uncontrolled cell growth, disrupted regulatory pathways, and the accumulation of genetic mutations. These mutations across different types of cancer lead to disruptions in signaling pathways and alterations in protein ... ...

Abstract	Cancer is characterized by uncontrolled cell growth, disrupted regulatory pathways, and the accumulation of genetic mutations. These mutations across different types of cancer lead to disruptions in signaling pathways and alterations in protein expression related to cellular growth and proliferation. This review highlights the AKT signaling cascade and the retinoblastoma protein (pRb) regulating cascade as promising for novel nanotheranostic interventions. Through synergizing state-of-the-art gene editing tools like the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system with nanomaterials and targeting AKT, there is potential to enhance cancer diagnostics significantly. Furthermore, the integration of modified CAR-T cells into multifunctional nanodelivery systems offers a promising approach for targeted cancer inhibition, including the eradication of cancer stem cells (CSCs). Within the context of highly aggressive and metastatic Triple-negative Breast Cancer (TNBC), this review specifically focuses on devising innovative nanotheranostics. For both pre-clinical and post-clinical TNBC detection, the utilization of the CRISPR-Cas system, guided by RNA (gRNA) and coupled with a fluorescent reporter specifically designed to detect TNBC's mutated sequence, could be promising. Additionally, a cutting-edge approach involving the engineering of TNBC-specific iCAR and syn-Notch CAR T-cells, combined with the co-delivery of a hybrid polymeric nano-liposome encapsulating a conditionally replicative adenoviral vector (CRAdV) against CSCs, could present an intriguing intervention strategy. This review thus paves the way for exciting advancements in the field of nanotheranostics for the treatment of TNBC and beyond.
MeSH term(s)	Humans ; CRISPR-Cas Systems ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/therapy ; Triple Negative Breast Neoplasms/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Gene Editing ; T-Lymphocytes/metabolism
Chemical Substances	Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2023-07-15
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2023.116573
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Article ; Online: Regulation of neuroinflammation in Alzheimer's disease via nanoparticle-loaded phytocompounds with anti-inflammatory and autophagy-inducing properties.

Nayak, Vinayak / Patra, Sushmita / Rout, Shrushti / Jena, Atala Bihari / Sharma, Rohit / Pattanaik, Kali Prasad / Singh, Jay / Pandey, Shyam S / Singh, Ravindra Pratap / Majhi, Sanatan / Singh, Kshitij Rb / Kerry, Rout George

Phytomedicine : international journal of phytotherapy and phytopharmacology

2023 Volume 122, Page(s) 155150

Abstract: Background: Alzheimer's disease (AD) is characterized by neuroinflammation linked to amyloid β (Aβ) aggregation and phosphorylated tau (τ) protein in neurofibrillary tangles (NFTs). Key elements in Aβ production and NFT assembly, like γ-secretase and ... ...

Abstract	Background: Alzheimer's disease (AD) is characterized by neuroinflammation linked to amyloid β (Aβ) aggregation and phosphorylated tau (τ) protein in neurofibrillary tangles (NFTs). Key elements in Aβ production and NFT assembly, like γ-secretase and p38 mitogen-activated protein kinase (p38MAPK), contribute to neuroinflammation. In addition, impaired proteosomal and autophagic pathways increase Aβ and τ aggregation, leading to neuronal damage. Conventional neuroinflammation drugs have limitations due to unidirectional therapeutic approaches and challenges in crossing the Blood-Brain Barrier (BBB). Clinical trials for non-steroidal anti-inflammatory drugs (NSAIDs) and other therapeutics remain uncertain. Novel strategies addressing the complex pathogenesis and BBB translocation are needed to effectively tackle AD-related neuroinflammation. Purpose: The current scenario demands for a much-sophisticated theranostic measures which could be achieved via customized engineering and designing of novel nanotherapeutics. As, these therapeutics functions as a double edge sword, having the efficiency of unambiguous targeting, multiple drug delivery and ability to cross BBB proficiently. Methods: Inclusion criteria involve selecting recent, English-language studies from the past decade (2013-2023) that explore the regulation of neuroinflammation in neuroinflammation, Alzheimer's disease, amyloid β, tau protein, nanoparticles, autophagy, and phytocompounds. Various study types, including clinical trials, experiments, and reviews, were considered. Exclusion criteria comprised non-relevant publication types, studies unrelated to Alzheimer's disease or phytocompounds, those with methodological flaws, duplicates, and studies with inaccessible data. Results: In this study, polymeric nanoparticles loaded with specific phytocompounds and coated with an antibody targeting the transferrin receptor (anti-TfR) present on BBB. Thereafter, the engineered nanoparticles with the ability to efficiently traverse the BBB and interact with target molecules within the brain, could induce autophagy, a cellular process crucial for neuronal health, and exhibit potent anti-inflammatory effects. Henceforth, the proposed combination of desired phytocompounds, polymeric nanoparticles, and anti-TfR coating presents a promising approach for targeted drug delivery to the brain, with potential implications in neuroinflammatory conditions such as Alzheimer's disease.
MeSH term(s)	Humans ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Neuroinflammatory Diseases ; Autophagy ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Nanoparticles
Chemical Substances	Amyloid beta-Peptides ; Anti-Inflammatory Agents, Non-Steroidal
Language	English
Publishing date	2023-10-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2023.155150
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Article ; Online: AFB1 induced free radicals cause encephalopathy in goat kids via intrinsic pathway of apoptosis: pathological and immunohistochemical confirmation of non-hepatic neuroaflatoxicosis.

Sahoo, Monalisa / Thakor, Jigarji Chaturji / Kumar, Pradeep / Singh, Rajendra / Kumar, Pawan / Singh, Karampal / Puvvala, Bhavani / Kumar, Ajay / Gopinathan, Aswathy / Palai, Santwana / Patra, Sushmita / Tripathy, Jagannath Prasad / Acharya, Ramakant / Sahoo, Nihar Ranjan / Behera, Pratima

Veterinary research communications

2023 Volume 48, Issue 1, Page(s) 317–327

Abstract: Aflatoxins, particularly AFB1, are the most common feed contaminants worldwide, causing significant economic losses to the livestock sector. The current paper describes an outbreak of aflatoxicosis in a herd of 160 male young goat kids (3-4 months), of ... ...

Abstract	Aflatoxins, particularly AFB1, are the most common feed contaminants worldwide, causing significant economic losses to the livestock sector. The current paper describes an outbreak of aflatoxicosis in a herd of 160 male young goat kids (3-4 months), of which 68 young kids succumbed over a period of 25 days after showing neurological signs of abnormal gait, progressive paralysis and head pressing. The haematobiochemical investigation showed reduced haemoglobin, leucocyte count, PCV level, increased levels of AST, ALT, glucose, BUN, creatinine and reduced level of total protein. Grossly, kids had pale mucous membranes, pale and swollen liver; right apical lobe consolidation, and petechiation of the synovial membrane of the hock joints. The microscopic changes were characterized by multifocal hemorrhages, status spongiosus/ vacuolation, vasculitis, focal to diffuse gliosis, satellitosis, and ischemic apoptotic neurons in different parts of the brain and spinal cord. These changes corresponded well with strong immunoreactivity for AFB1 in neurons, glia cells (oligodendrocytes, astrocytes, and ependymal cells) in various anatomical sites of the brain. The higher values of LPO and reduced levels of antioxidant enzymes (Catalase, SOD, GSH) with strong immunoreactivity of 8-OHdG in the brain indicating high level of oxidative stress. Further, the higher immunosignaling of caspase-3 and caspase-9 in the brain points towards the association with intrinsic pathway of apoptosis. The toxicological analysis of feed samples detected high amounts of AFB1 (0.38ppm). These findings suggest that AFB1 in younger goat kids has more of neurotoxic effect mediated through caspase dependent intrinsic pathway.
MeSH term(s)	Male ; Animals ; Goats/metabolism ; Aflatoxin B1/toxicity ; Aflatoxin B1/metabolism ; Apoptosis ; Oxidative Stress ; Liver/metabolism ; Free Radicals/metabolism ; Free Radicals/pharmacology ; Brain Diseases/metabolism ; Brain Diseases/veterinary ; Goat Diseases/chemically induced
Chemical Substances	Aflatoxin B1 (9N2N2Y55MH) ; Free Radicals
Language	English
Publishing date	2023-09-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	406735-6
ISSN	1573-7446 ; 0165-7380
ISSN (online)	1573-7446
ISSN	0165-7380
DOI	10.1007/s11259-023-10216-9
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Zs.A 3453: Show issues

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Article ; Online: Quercetin Impairs HuR-Driven Progression and Migration of Triple Negative Breast Cancer (TNBC) Cells.

Umar, Sheikh Mohammad / Patra, Sushmita / Kashyap, Akanksha / Dev J R, Arundhathi / Kumar, Lalit / Prasad, Chandra Prakash

Nutrition and cancer

2021 Volume 74, Issue 4, Page(s) 1497–1510

Abstract	In the present study, we have explored the prognostic value of HuR gene as well as protein in breast cancers. Furthermore, we have also investigated the HuR therapeutic relevance in TNBCs, which is an aggressive breast cancer subtype. Using an online meta-analysis tool, we found that HuR protein overexpression positively correlates with reduced overall survival of TNBC patients (
MeSH term(s)	Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; ELAV-Like Protein 1/genetics ; Humans ; Quercetin/pharmacology ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/metabolism ; beta Catenin/genetics ; beta Catenin/metabolism
Chemical Substances	ELAV-Like Protein 1 ; beta Catenin ; Quercetin (9IKM0I5T1E)
Language	English
Publishing date	2021-07-19
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
ZDB-ID	424433-3
ISSN	1532-7914 ; 0163-5581
ISSN (online)	1532-7914
ISSN	0163-5581
DOI	10.1080/01635581.2021.1952628
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Article: Emerging Molecular Prospective of SARS-CoV-2: Feasible Nanotechnology Based Detection and Inhibition.

Patra, Sushmita / Kerry, Rout George / Maurya, Ganesh Kumar / Panigrahi, Bijayananda / Kumari, Swati / Rout, Jyoti Ranjan

Frontiers in microbiology

2020 Volume 11, Page(s) 2098

Abstract: The rapid dissemination of SARS-CoV-2 demonstrates how vulnerable it can make communities and is why it has attained the status of global pandemic. According to the estimation from Worldometer, the SARS-CoV-2 affected cases and deaths are exponentially ... ...

Abstract	The rapid dissemination of SARS-CoV-2 demonstrates how vulnerable it can make communities and is why it has attained the status of global pandemic. According to the estimation from Worldometer, the SARS-CoV-2 affected cases and deaths are exponentially increasing worldwide, marking the mortality rate as ∼3.8% with no probability of its cessation till now. Despite massive attempts and races among scientific communities in search of proper therapeutic options, the termination of this breakneck outbreak of COVID-19 has still not been made possible. Therefore, this review highlights the diverse molecular events induced by a viral infection, such as autophagy, unfolded protein response (UPR), and inflammasome, illustrating the intracellular cascades regulating viral replication inside the host cell. The SARS-CoV-2-mediated endoplasmic reticulum stress and apoptosis are also emphasized in the review. Additionally, host's immune response associated with SARS-CoV-2 infection, as well as the genetic and epigenetic changes, have been demonstrated, which altogether impart a better understanding of its epidemiology. Considering the drawbacks of available diagnostics and medications, herein we have presented the most sensitive nano-based biosensors for the rapid detection of viral components. Moreover, conceptualizing the viral-induced molecular changes inside its target cells, nano-based antiviral systems have also been proposed in this review.
Keywords	covid19
Language	English
Publishing date	2020-10-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2020.02098
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Article ; Online: Emerging Molecular Prospective of SARS-CoV-2

Patra, Sushmita / Kerry, Rout George / Maurya, Ganesh Kumar / Panigrahi, Bijayananda / Kumari, Swati / Rout, Jyoti Ranjan

Frontiers in Microbiology

Feasible Nanotechnology Based Detection and Inhibition

2020 Volume 11

Keywords	Microbiology (medical) ; Microbiology ; covid19
Publisher	Frontiers Media SA
Publishing country	ch
Document type	Article ; Online
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2020.02098
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular prospect of type-2 diabetes: Nanotechnology based diagnostics and therapeutic intervention.

Kerry, Rout George / Mahapatra, Gyana Prakash / Maurya, Ganesh Kumar / Patra, Sushmita / Mahari, Subhasis / Das, Gitishree / Patra, Jayanta Kumar / Sahoo, Sabuj

Reviews in endocrine & metabolic disorders

2020 Volume 22, Issue 2, Page(s) 421–451

Abstract: About ninety percent of all diabetic conditions account for T2D caused due to abnormal insulin secretion/ action or increased hepatic glucose production. Factors that contribute towards the aetiology of T2D could be well explained through biochemical, ... ...

Abstract	About ninety percent of all diabetic conditions account for T2D caused due to abnormal insulin secretion/ action or increased hepatic glucose production. Factors that contribute towards the aetiology of T2D could be well explained through biochemical, molecular, and cellular aspects. In this review, we attempt to explain the recent evolving molecular and cellular advancement associated with T2D pathophysiology. Current progress fabricated in T2D research concerning intracellular signaling cascade, inflammasome, autophagy, genetic and epigenetics changes is discretely explained in simple terms. Present available anti-diabetic therapeutic strategies commercialized and their limitations which are needed to be acknowledged are addressed in the current review. In particular, the pre-eminence of nanotechnology-based approaches to nullify the inadequacy of conventional anti-diabetic therapeutics and heterogeneous nanoparticulated systems exploited in diabetic researches are also discretely mentioned and are also listed in a tabular format in the review. Additionally, as a future prospect of nanotechnology, the review presents several strategic hypotheses to ameliorate the austerity of T2D by an engineered smart targeted nano-delivery system. In detail, an effort has been made to hypothesize novel nanotechnological based therapeutic strategies, which exploits previously described inflammasome, autophagic target points. Utilizing graphical description it is explained how a smart targeted nano-delivery system could promote β-cell growth and development by inducing the Wnt signaling pathway (inhibiting Gsk3β), inhibiting inflammasome (inhibiting NLRP3), and activating autophagic target points (protecting Atg3/Atg7 complex from oxidative stress) thereby might ameliorate the severity of T2D. Additionally, several targeting molecules associated with autophagic and epigenetic factors are also highlighted, which can be exploited in future diabetic research.
MeSH term(s)	Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/therapy ; Humans ; Inflammasomes/metabolism ; Insulin-Secreting Cells ; Nanotechnology ; Oxidative Stress
Chemical Substances	Inflammasomes
Language	English
Publishing date	2020-10-14
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2185718-0
ISSN	1573-2606 ; 1389-9155
ISSN (online)	1573-2606
ISSN	1389-9155
DOI	10.1007/s11154-020-09606-0
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Zs.A 6069: Show issues

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Article ; Online: An overview of remote monitoring methods in biodiversity conservation.

Kerry, Rout George / Montalbo, Francis Jesmar Perez / Das, Rajeswari / Patra, Sushmita / Mahapatra, Gyana Prakash / Maurya, Ganesh Kumar / Nayak, Vinayak / Jena, Atala Bihari / Ukhurebor, Kingsley Eghonghon / Jena, Ram Chandra / Gouda, Sushanto / Majhi, Sanatan / Rout, Jyoti Ranjan

Environmental science and pollution research international

2022 Volume 29, Issue 53, Page(s) 80179–80221

Abstract: Conservation of biodiversity is critical for the coexistence of humans and the sustenance of other living organisms within the ecosystem. Identification and prioritization of specific regions to be conserved are impossible without proper information ... ...

Abstract	Conservation of biodiversity is critical for the coexistence of humans and the sustenance of other living organisms within the ecosystem. Identification and prioritization of specific regions to be conserved are impossible without proper information about the sites. Advanced monitoring agencies like the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) had accredited that the sum total of species that are now threatened with extinction is higher than ever before in the past and are progressing toward extinct at an alarming rate. Besides this, the conceptualized global responses to these crises are still inadequate and entail drastic changes. Therefore, more sophisticated monitoring and conservation techniques are required which can simultaneously cover a larger surface area within a stipulated time frame and gather a large pool of data. Hence, this study is an overview of remote monitoring methods in biodiversity conservation via a survey of evidence-based reviews and related studies, wherein the description of the application of some technology for biodiversity conservation and monitoring is highlighted. Finally, the paper also describes various transformative smart technologies like artificial intelligence (AI) and/or machine learning algorithms for enhanced working efficiency of currently available techniques that will aid remote monitoring methods in biodiversity conservation.
MeSH term(s)	Artificial Intelligence ; Biodiversity ; Conservation of Natural Resources/methods ; Ecosystem
Language	English
Publishing date	2022-10-05
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-022-23242-y
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Article ; Online: Advancement in precision diagnosis and therapeutic for triple-negative breast cancer: Harnessing diagnostic potential of CRISPR-cas & engineered CAR T-cells mediated therapeutics

Nayak, Vinayak / Patra, Sushmita / Singh, Kshitij RB / Ganguly, Bristy / Kumar, Das Nishant / Panda, Deepak / Maurya, Ganesh Kumar / Singh, Jay / Majhi, Sanatan / Sharma, Rohit / Pandey, Shyam S. / Singh, Ravindra Pratap / Kerry, Rout George

Environmental Research. 2023 Oct., v. 235 p.116573-

2023

Abstract	Cancer is characterized by uncontrolled cell growth, disrupted regulatory pathways, and the accumulation of genetic mutations. These mutations across different types of cancer lead to disruptions in signaling pathways and alterations in protein expression related to cellular growth and proliferation. This review highlights the AKT signaling cascade and the retinoblastoma protein (pRb) regulating cascade as promising for novel nanotheranostic interventions. Through synergizing state-of-the-art gene editing tools like the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system with nanomaterials and targeting AKT, there is potential to enhance cancer diagnostics significantly. Furthermore, the integration of modified CAR-T cells into multifunctional nanodelivery systems offers a promising approach for targeted cancer inhibition, including the eradication of cancer stem cells (CSCs). Within the context of highly aggressive and metastatic Triple-negative Breast Cancer (TNBC), this review specifically focuses on devising innovative nanotheranostics. For both pre-clinical and post-clinical TNBC detection, the utilization of the CRISPR-Cas system, guided by RNA (gRNA) and coupled with a fluorescent reporter specifically designed to detect TNBC's mutated sequence, could be promising. Additionally, a cutting-edge approach involving the engineering of TNBC-specific iCAR and syn-Notch CAR T-cells, combined with the co-delivery of a hybrid polymeric nano-liposome encapsulating a conditionally replicative adenoviral vector (CRAdV) against CSCs, could present an intriguing intervention strategy. This review thus paves the way for exciting advancements in the field of nanotheranostics for the treatment of TNBC and beyond.
Keywords	Adenoviridae ; CRISPR-Cas systems ; RNA ; T-lymphocytes ; breast neoplasms ; cell growth ; composite polymers ; diagnostic techniques ; fluorescence ; genes ; metastasis ; nanomaterials ; protein synthesis ; research ; therapeutics ; Cancer ; Cancer stem cells ; Nanotechnology ; CRISPR-Cas system ; CAR T-cells ; Viral gene delivery
Language	English
Dates of publication	2023-10
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2023.116573
Database	NAL-Catalogue (AGRICOLA)

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