Publications by authors named "Payal Gupta"

40 Publications

Self Nano-Emulsifying Curcumin (SNEC30) attenuates arsenic-induced cell death in mice.

Toxicol Rep 2021 17;8:1428-1436. Epub 2021 Jul 17.

Cancer Research Laboratory, Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700 019, India.

Several precedents have confirmed numerous infirmities caused by arsenic poisoning, including immune suppression and cancer. Exposure to arsenic leads to alterations of the cellular machinery and eventually cell death, depending on the dose and duration of exposure. Oxidative stress induced by arsenic is the major mechanism by which it inflicts cellular toxicity, challenging the survival-support - autophagy and culminating in apoptosis in the thymus and spleen of mice. Curcumin, a potent dietary anti-oxidant with known anti-apoptotic and anti-inflammatory properties, was assessed for therapeutic benefits. However, the major caveat of this polyphenol is its low water solubility and limited bioavailability. Therefore, Self Nano-Emulsifying Curcumin (SNEC30) was used to treat mice exposed to arsenic. When administered, SNEC30 effectively ameliorated the adverse effects of arsenic in mice, by restoring structural alterations and reducing ROS-mediated cell death, thereby endorsing the importance of nutraceuticals in counteracting heavy metal-induced cellular toxicity.
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http://dx.doi.org/10.1016/j.toxrep.2021.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322040PMC
July 2021

Delivery of novel coumarin-dihydropyrimidinone conjugates through mixed polymeric nanoparticles to potentiate therapeutic efficacy against triple-negative breast cancer.

Biomater Sci 2021 Aug 14;9(16):5665-5690. Epub 2021 Jul 14.

Center for Research in Nanoscience and Nanotechnology, Technology Campus, University of Calcutta, JD-2, Sector-III, Salt Lake, Kolkata-700106, West Bengal, India.

To date, most of the accessible therapeutic options are virtually non-responsive towards triple-negative breast cancer (TNBC) due to its highly aggressive and metastatic nature. Interestingly, chemotherapy reacts soundly in many TNBC cases compared to other types of breast cancer. However, the side effects of many chemotherapeutic agents are still under cross-examination, and thus prohibit their extensive uses. In this present study, we have developed a series of coumarin-dihydropyrimidinone conjugates (CDHPs) and subsequently their poly(lactic-co-glycolic acid) (PLGA)-PEG mixed copolymer nanoparticles as excellent chemotherapeutic nanomedicine to control TNBC. Among all the synthesized CDHPs, CDHP-4 (prepared by the combination of EDCO with 3,4-difluorobenzaldehyde) showed excellent therapeutic effect on a wide variety of cancer cell lines, including TNBC. Besides, it can control the metastasis and stemness property of TNBC. Furthermore, the nano-encapsulation of CDHP-4 in a mixed polymer nanoparticle system ([email protected]) and simultaneous delivery showed much improved therapeutic efficacy at a much lower dose, and almost negligible side effects in normal healthy cells or organs. The effectiveness of the present therapeutic agent was observed both in intravenous and oral mode of administration in in vivo experiments. Moreover, on elucidating the molecular mechanism, we found that [email protected] could exhibit apoptotic, anti-migratory, as well as anti-stemness activity against TNBC cell lines through the downregulation of miR-138. We validated our findings in MDA-MB-231 xenograft chick embryos, as well as in 4T1-induced mammary tumor-bearing BALB/c mice models, and studied the bio-distribution of [email protected] on the basis of the photoluminescence property of nanoparticles. Our recent study, hence for the first time, unravels the synthesis of [email protected] and the molecular mechanism behind the anti-migration, anti-stemness and anti-tumor efficacy of the nanoparticles against the TNBC cells through the miR-138/p65/TUSC2 axis.
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http://dx.doi.org/10.1039/d1bm00424gDOI Listing
August 2021

Pomegranate Polyphenols Attenuate Inflammation and Hepatic Damage in Tumor-Bearing Mice: Crucial Role of NF-κB and the Nrf2/GSH Axis.

J Nutr Biochem 2021 Jul 2;97:108812. Epub 2021 Jul 2.

Department of Physiology, University of Calcutta; Kolkata, India; Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Kolkata, India. Electronic address:

It has been widely reported that cancer, along with its treatment regimens, cause severe toxicity in the host. A suitable agent having chemopreventive properties as well as capabilities of ameliorating tumor- and drug-induced toxicities is of imminent need. Pomegranate has been projected as an excellent anti-tumor, anti-inflammatory and anti-oxidant agent. In this study, for the first time, we delineated the exact signaling cascade by which dietary supplementation of pomegranate fruit extract (PFE) protects tumor-bearing mice from tumor-induced hepatotoxicity. Increased activities of serum Alanine transaminase, Aspartate transaminase, Lactate dehydrogenase and Alkaline phosphatase, as well as histological studies confirmed the establishment of a state of hepatic dysfunction in tumor-bearers. Further investigations revealed that increased hepatic reactive oxygen species content and glutathione depletion-initiated apoptosis in these hepatocytes as we observed an alteration in the apoptotic proteins. PFE supplementation in tumor-bearing mice, on the other hand, differentially modulated redox-sensitive transcription factors Nrf2 and NF-κB, ultimately decreasing tumor-induced hepatic oxidative damage and cell death. siRNA-mediated inhibition of Nrf2 and NF-κB completely abolished the hepato-protective activities of PFE while pre-treatment of tumor-conditioned hepatocytes with N-acetyl cysteine augmented the cyto-protective properties of PFE. The present study clearly identified Nrf2/NF-κB/glutathione axis as the key factor behind the hepatoprotective potential of PFE. These findings would add to the existing knowledge about cancer chemoprevention by dietary polyphenols and might lead to the application of pomegranate polyphenols as supplement to escalate the effectiveness of cancer therapy by protecting normal cells from cancer related toxicities.
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http://dx.doi.org/10.1016/j.jnutbio.2021.108812DOI Listing
July 2021

Geraniol eradicates Candida glabrata biofilm by targeting multiple cellular pathways.

Appl Microbiol Biotechnol 2021 Jul 1;105(13):5589-5605. Epub 2021 Jul 1.

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India.

Global burden of fungal infections and associated health risk has accelerated at an incredible pace and needs to be attended at the earliest with an unbeatable therapeutic intervention. Candida glabrata is clinically the most relevant and least drug susceptible Candida species. In the pursuit of mining alternative novel drug candidates, the antifungal activity of a monoterpene phytoactive molecule geraniol (GR) against C. glabrata biofilm was evaluated. Biofilm inhibitory and eradication ability of GR evaluated against C. glabrata along with its clinical isolates. Impact of GR on various cellular pathways was evaluated to delineate its antifungal mode of action. GR has inhibited both planktonic and sessile growth of all the studied C. glabrata strains and eradicated the mature biofilm. GR reduced the carbohydrate and eDNA content, as well as hydrolytic enzyme activity in extracellular matrix of C. glabrata. The chemical profiling, microscopic, and spectroscopic studies revealed that GR targets chitin and β-glucan in cell wall. Further, results highlighted the reduction of cell membrane ergosterol content, and blocking of ABC drug efflux pump by GR which was also confirmed by RT-PCR where expression of CDR1 and ERG4 was downregulated in GR exposed C. glabrata cells. The fluorescence microscopy and flow cytometry results emphasized the alteration in mitochondrial activity, increased Ca uptake, thus changing the membrane permeability ensuing increased cytochrome C release from mitochondria to cytoplasm. Indeed, GR also has arrested cell cycle in G1/S phase and interfered with DNA replication. These observations suggest GR targets multiple cellular pathways and mediated killing of C. glabrata cells via apoptosis. In conclusion, the present study strengthens the candidacy of GR as novel antifungal therapeutic. Key points • GR inhibits growth and eradicates biofilm of C. glabrata and its clinical isolates. • GR inactivates the hydrolytic enzymes in extracellular matrix. • GR mediates C. glabrata apoptosis by interfering with multiple signaling pathways.
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http://dx.doi.org/10.1007/s00253-021-11397-6DOI Listing
July 2021

Ex-foliar application of glycine betaine and its impact on protein, carbohydrates and induction of ROS scavenging system during drought stress in flax (Linum usitatissimum).

J Biotechnol 2021 Aug 7;337:80-89. Epub 2021 Jun 7.

ICAR- National Institute for Plant Biotechnology, PUSA, New Delhi, 110012, India. Electronic address:

Crop plants have an innate capacity to acclimatize and survive myriad stresses in field conditions. This acclimatization to stress enhances crop stand in field and productivity of plant. Inter alia field crops withstand drought stress (hydropenia) by inducing synthesis or accumulation of osmolytes such as (i) proline and other amino acids, (ii) glycine betaine (GB), (iii) soluble carbohydrates, and (iv) reactive oxygen species (ROS) scavenging system as intrinsic drought antagonizing molecules. Precise in vivo induction of osmolytes and their effect on ROS scavenging system in flax/linseed has not been elucidated. The investigation was carried out to identify a tolerant and susceptible cultivar of flax from a core collection of 53 core accessions and evaluate the role of compatible osmolytes in Linum usitatissimum under hydropenia. We screened eight morphometrically diverse flax genotypes in field under irrigated and un-irrigated condition and classified them as tolerant and susceptible genotypes. Further, we examined the effect of ex-foliar glycine betaine application - a signature molecule involved in drought tolerance, on selected tolerant and susceptible varieties. Our results showed stimulatory impact of glycine betaine on accumulation of ROS scavenging antioxidants, total soluble protein and on its own accumulation. While the ex-foliar application had no inhibitory effect on the growth of plants; accumulation of free proline, amino acids and carbohydrates are inhibited par se in flax. Our findings reveal, flax is a non-accumulator of glycine betaine and exogenous application of glycine betaine enhances its own levels during drought stress.
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http://dx.doi.org/10.1016/j.jbiotec.2021.06.012DOI Listing
August 2021

Impact of Bacillus licheniformis SV1 Derived Glycolipid on Candida glabrata Biofilm.

Curr Microbiol 2021 May 27;78(5):1813-1822. Epub 2021 Mar 27.

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, 247667, Uttarakhand, India.

In the present investigation, we have evaluated the antibiofilm potential of Bacillus licheniformis SV1 derived glycolipid against C. glabrata biofilm. Impact of isolated glycolipid on the viability of C. glabrata and on inhibiting as well as eradicating ability of its biofilm were studied. Further, morphological alterations, reactive oxygen species generation (ROS) production and transcriptional expression of selected genes (RT-PCR) of C. glabrata in response with isolated glycolipid were studied. The isolated glycolipid (1.0 mg ml) inhibited and eradicated C. glabrata biofilm approximately 80% and 60%, respectively. FE-SEM images revealed glycolipid exposure results in architectural alteration and eradication of C. glabrata biofilm and ROS generation. Transcriptional studies of selected genes showed that the expression of AUS1, FKS1 and KRE1 were down-regulated, while that of ergosterol biosynthesis pathway and multidrug transporter increased, in the presence of glycolipid.
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http://dx.doi.org/10.1007/s00284-021-02461-5DOI Listing
May 2021

Dissecting the therapeutic potency of antimicrobial peptides against microbial biofilms.

Curr Protein Pept Sci 2021 Mar 22. Epub 2021 Mar 22.

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand. India.

Microbial resistance to conventional therapeutics has become a significant threat to human society. Biofilms serve as the major virulence factor for the microorganisms by resisting the antibiotics and host innate immune system. Antimicrobial peptides (AMPs) have emerged as a potential alternative to conventional therapeutics due to their exceptional anti-biofilm and broad-spectrum antimicrobial property. Researchers have applied bioinformatics, genetic engineering, tissue culture, and drug delivery approaches to enhance the production and therapeutic efficacy of antimicrobial peptides. This review comprehensively describes the various aspects of AMPs with particular focus on their anti-biofilm potential. Other detailed information highlighted in this review includes different classes of AMPs, their mode of action, and anti-biofilm activity both alone and in synergy with other AMPs or conventional antibiotics. Further, challenges and opportunities of AMPs based drug delivery systems such as nano-formulations, polymeric micelles, and vesicles are also summarized.
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http://dx.doi.org/10.2174/1389203722666210322145810DOI Listing
March 2021

Dissecting the anti-biofilm potency of kappa-carrageenan capped silver nanoparticles against Candida species.

Int J Biol Macromol 2021 Mar 10;172:30-40. Epub 2021 Jan 10.

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India; Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India. Electronic address:

Global antimicrobial crisis and advent of drug resistant fungal strains has substantially distressed disease management for clinicians. Biodegradable silver nanoparticles (AgNps) emerge as an excellent alternative remedial option. In the current study, the anti-biofilm activity of microwave irradiated kappa-carrageenan (CRG) capped AgNps against Candida albicans, and Candida glabrata was investigated in terms of their effect on reactive oxygen species (ROS) generation, cellular morphology, biochemical composition, and the activity of enzymes of extracellular matrix. Minimum inhibitory concentration and fungicidal concentration value of CRG-AgNps against both Candida spp. ranged between 400 and 500 μg/mL. The 80% of Candida biofilm was inhibited and eradicated by CRG-AgNps at a concentration of ~300 μg/mL. Microscopic studies indicate that CRG-AgNps caused morphological damage through membrane disruption and pore formation. Further, CRG-AgNps generated ROS in a concentration-dependent manner and modulated the composition of Candida biofilm ECM by increasing the carbohydrate and eDNA content. CRG-AgNps also significantly inactivated the hydrolytic enzymes, thus hindering the biofilm forming ability. In conclusion, all these results suggest that the CRG-AgNps are potential antifungal agents against Candida biofilms, and they inhibit/eradicate the fungal biofilms through multiple signalling mechanisms.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.035DOI Listing
March 2021

Hyaluronic acid engrafted metformin loaded graphene oxide nanoparticle as CD44 targeted anti-cancer therapy for triple negative breast cancer.

Biochim Biophys Acta Gen Subj 2021 03 5;1865(3):129841. Epub 2021 Jan 5.

Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, JD-2, Sector III, Salt lake, Kolkata 700098, India. Electronic address:

Background: Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited treatment modalities. It is associated with high propensity of cancer recurrence.

Methods: UV Spectroscopy, FTIR, DLS, Zeta potential, TEM and SEM were employed to characterize nanoparticles. MTT assay, Wound healing assay, SEM, Immunocytochemistry analysis, Western blot, RT-PCR, mammosphere formation assay were employed to study apoptosis, cell migration and stemness. Tumor regression was studied in chick embryo xenograft and BALB/c mice model.

Results: Hylaluronic acid engrafted metformin loaded graphene oxide (HA-GO-Met) nanoparticles exhibited an anti-cancer efficacy at much lower dosage as compared to metformin alone. HA-GO-Met nanoparticles induced apoptosis and inhibited cell migration of TNBC cells by targeting miR-10b/PTEN axis via NFkB-p65. Upregulation of PTEN affected pAKT(473) expression that induced apoptosis. Cell migration was inhibited by reduction of pFAK/integrinβ1 expressions. Treatment inhibited epithelial mesenchymal transition (EMT) and reduced stemness as evident from the increase in E-cadherin expression, inhibition of mammosphere formation and low expression levels of stemness markers including nanog, oct4 and sox2 as compared to control. Moreover, tumor regression was studied in chick embryo xenograft and BALB/c mice model. HA-GO-Met nanoparticle treatment reduced tumor load and nullified toxicity in peripheral organs imparted by tumor.

Conclusions: HA-GO-Met nanoparticles exhibited an enormous anti-cancer efficacy in TNBC in vitro and in vivo.

General Significance: HA-GO-Met nanoparticles induced apoptosis and attenuated cell migration in TNBC. It nullified overall toxicity imparted by tumor load. It inhibited EMT and reduced stemness and thereby addressed the issue of cancer recurrence.
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http://dx.doi.org/10.1016/j.bbagen.2020.129841DOI Listing
March 2021

Cinnamaldehyde incorporated gellan/PVA electrospun nanofibers for eradicating Candida biofilm.

Mater Sci Eng C Mater Biol Appl 2021 Feb 27;119:111450. Epub 2020 Aug 27.

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India. Electronic address:

Immunocompromised patients encounter fungal infections more frequently than healthy individuals. Conventional drugs associated health risk and resistance, portrayed fungal infections as a global health problem. This issue needs to be answered immediately by designing a novel anti-fungal therapeutic agent. Phytoactive molecules based therapeutics are most suitable candidate due to their low cytotoxicity and minimal side effects to the host. In this study, cinnamaldehyde (CA), an FDA approved phytoactive molecule present in cinnamon essential oil was incorporated into gellan (GA)/poly vinyl alcohol (PVA) based electrospun nanofibers to resolve the issues like low water solubility, high volatility and irritant effect associated with CA and also to enhance its therapeutic applications. The drug encapsulation, morphology and physical properties of the synthesized CA nanofibers were evaluated by FESEM, AFM, TGA, FTIR and static water contact angle analysis. The average diameters of CA encapsulated GA/PVA nanofibers and GA/PVA nanofibers were recorded to be 278.5 ± 57.8 nm and 204.03 ± 39.14 nm, respectively. These nanofibers were evaluated for their anti-biofilm activity against Candida using XTT (2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-2H-tetrazolium salt) reduction assay. Data demonstrated that CA encapsulated GA/PVA nanofibers can effectively eradicate 89.29% and 50.45% of Candida glabrata and Candida albicans biofilm respectively. CA encapsulated nanofibers exhibited brilliant antimicrobial property against Staphylococcus aureus and Pseudomonas aeruginosa. The cytotoxicity assay demonstrated that nanofibers loaded with CA have anticancer properties as it reduces cell viability of breast cancer cells (MCF-7) by 27.7%. These CA loaded GA/PVA (CA-GA/PVA) nanofibers could be used as novel wound dressing material and coatings on biomedical implants to eradicate biofilm.
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http://dx.doi.org/10.1016/j.msec.2020.111450DOI Listing
February 2021

Functional characterization of Candida glabrata ORF, CAGL0M02233g for its role in stress tolerance and virulence.

Microb Pathog 2020 Dec 2;149:104469. Epub 2020 Sep 2.

Department of Biotechnology, Graphic Era (Deemed to be University), 566/6, Bell Road, Clement Town, Dehradun, PIN-248002, India. Electronic address:

Present investigation is aimed to analyze the role of an uncharacterized ORF of Candida glabrata (CBS138), CAGL0M02233g (an ortholog of RAD53, a key DNA checkpoint effector in Saccharomyces cerevisiae) in tolerance of various stresses and in biofilm formation. The CAGL0M02233g was cloned in p416TEF shuttle vector for constitutive expression under TEF1 promoter in BG14 strain (ura3 auxotrophic C. glabrata), and upregulated expression of the cloned ORF was confirmed by immunoblotting. The constitutive expression of CAGL0M02233g rendered cells resistant to the DNA damage stressor (MMS), replication stressor (HU) and hypoxia mimetic (CoCl) in plate spot and growth curve assays. Hypoxia (a low oxygen condition) is an imperative host factor that influences Candida pathogenesis. Biofilm formation by the BG14 cells transformed with p416TEF-CAGL0M02233g (REX cell) was reduced to approximately 50% under hypoxia. It is notable that biofilm formation by the REX cells was significantly lower than that of BG14 cells transformed with p416TEF vector (VC cell) under hypoxia. The biofilm of the REX cells has shown higher susceptibility to fluconazole than that of VC cells under hypoxia and REX cells at normoxia. This is the first report on the function of CAGL0M02233g in tolerance of various stressors and in modulation of the biofilm under hypoxia.
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http://dx.doi.org/10.1016/j.micpath.2020.104469DOI Listing
December 2020

Delivery of dual miRNA through CD44-targeted mesoporous silica nanoparticles for enhanced and effective triple-negative breast cancer therapy.

Biomater Sci 2020 May 22;8(10):2939-2954. Epub 2020 Apr 22.

Center for Research in Nanoscience and Nanotechnology, Technology Campus, University of Calcutta, JD-2, Sector-III, Salt Lake City, Kolkata 700106, India.

The development of new therapeutic strategies to target triple-negative breast cancer (TNBC) is in much demand to overcome the roadblocks associated with the existing treatment procedures. In this regard, therapies targeting the CD44 receptor have drawn attention for more than a decade. MicroRNAs (miRNAs) modulate post-transcriptional gene regulation and thus, the correction of specific miRNA alterations using miRNA mimics or antagomiRs is an emerging strategy to normalize the genetic regulation in the tumor microenvironment. It has been acknowledged that miR-34a is downregulated and miR-10b is upregulated in TNBC, which promotes tumorigenesis and metastatic dissemination. However, there are a few barriers related to miRNA delivery. Herein, we have introduced tailored mesoporous silica nanoparticles (MSNs) for the co-delivery of miR-34a-mimic and antisense-miR-10b. MSN was functionalized with a cationic basic side chain and then loaded with the dual combination to overexpress miR-34a and downregulate miR-10b simultaneously. Finally, the loaded MSNs were coated with an hyaluronic acid-appended PEG-PLGA polymer for specific targeting. The cellular uptake, release profile, and subsequent effect in TNBC cells were evaluated. In vitro and in vivo studies demonstrated high specificity in TNBC tumor targeting, leading to efficient tumor growth inhibition as well as the retardation of metastasis, which affirmed the clinical application potential of the system.
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http://dx.doi.org/10.1039/d0bm00015aDOI Listing
May 2020

Delivery of thymoquinone through hyaluronic acid-decorated mixed Pluronic® nanoparticles to attenuate angiogenesis and metastasis of triple-negative breast cancer.

J Control Release 2020 06 31;322:357-374. Epub 2020 Mar 31.

Center for Research in Nanoscience and Nanotechnology, University of Calcutta, Technology Campus, JD-2, Sector-III, Salt Lake, Kolkata 700106, West Bengal, India. Electronic address:

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic subtype of breast cancer showing non-responsiveness to most available therapeutic options. Therefore, smart therapeutic approaches to selectively transport and target TNBCs are required. Herein, we developed thymoquinone (TQ)-loaded, hyaluronic acid (HA)-conjugated Pluronic® P123 and F127 copolymer nanoparticles (HA-TQ-Nps) as a selective drug-carrying vehicle to deliver anticancer phytochemical TQ to TNBC cells. The mean size of nanoparticles was around 19.3 ± 3.2 nm. and they were stable at room temperature up to 4 months. HA-TQ-Nps were immensely cytotoxic towards TNBC cells but did not show the toxic effect on normal cells. Detailed investigations also demonstrated its pro-apoptotic, anti-metastatic and anti-angiogenic activity. In-depth mechanistic studies highlighted that HA-TQ-Nps retarded cell migration of TNBC cells through up-regulation of microRNA-361 which in turn down-regulated Rac1 and RhoA mediated cell migration and also perturbed the cancer cell migration under the influence of the autocrine effect of VEGF-A. Moreover, HA-TQ-Np-treatment also perturbed tumor-induced vascularization by reducing the secretion of VEGF-A. The anti-metastatic and anti-angiogenic activity of HA-TQ-Nps was found to be evident in both MDA-MB-231 xenograft chick embryos and 4T1-mammary solid tumor model in syngeneic mice. Thus, an innovative targeted nano-therapeutic approach is being established to reduce the tumor burden and inhibit metastasis and angiogenesis simultaneously for better management of TNBC.
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http://dx.doi.org/10.1016/j.jconrel.2020.03.033DOI Listing
June 2020

Inflammation-induced behavioral changes is driven by alterations in Nrf2-dependent apoptosis and autophagy in mouse hippocampus: Role of fluoxetine.

Cell Signal 2020 04 24;68:109521. Epub 2019 Dec 24.

Department of Physiology, University of Calcutta; UCSTA, 92, Acharya Prafulla Chandra Road, Kolkata 700009, India; Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, JD-2, Salt Lake, Sector III, Kolkata 700098, India. Electronic address:

Inflammation has been associated with the progression of many neurological diseases. Peripheral inflammation has also been vaguely linked to depression-like symptoms in animal models, but the underlying pathways that orchestrate inflammation-induced behavioral or molecular changes in the brain are still elusive. We have recently shown that intraperitoneal injections of lipopolysaccharide (LPS) to Swiss albino mice triggers systemic inflammation, leading to an activated immune response along with changes in monoamine levels in the brain. Herein we pinpoint the fundamental pathways linking peripheral inflammation and depression-like behavior in a mouse model, thereby identifying suitable targets of intervention to combat the situation. We show that LPS-induced peripheral inflammation provoked a depression-like behavior in mice and a distinct pro-inflammatory bias in the hippocampus, as evident from increased microglial activation and elevated levels of pro-inflammatory cytokines IL-6 and TNF-α, and activation of NFκB-p65 pathway. Significant alterations in Nrf2-dependent cellular redox status, coupled with altered autophagy and increased apoptosis were noticed in the hippocampus of LPS-exposed mice. We and others have previously shown that, fluoxetine (an anti-depressant) has effective anti-inflammatory and antioxidant properties by virtue of its abilities to regulate NFκB and Nrf2 signaling. We observed that treatment with fluoxetine or the Nrf2 activator tBHQ (tert-butyl hydroquinone), could reverse depression-like-symptoms and mitigate alterations in autophagy and cell death pathways in the hippocampus by activating Nrf2-dependent gene expressions. Taken together, the data suggests that systemic inflammation potentiates Nrf2-dependent changes in cell death and autophagy pathway in the hippocampus, eventually leading to major pathologic sequelae associated with depression. Therefore, targeting Nrf2 could be a novel approach in combatting depression and ameliorating its associated pathogenesis.
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http://dx.doi.org/10.1016/j.cellsig.2019.109521DOI Listing
April 2020

ADMET profiling of geographically diverse phytochemical using chemoinformatic tools.

Future Med Chem 2020 01 3;12(1):69-87. Epub 2019 Dec 3.

Bioinformatics Division, ICMR-National Institute of Cancer Prevention & Research, I-7, Sector 39, Noida 201301, India.

Phytocompounds are important due to their uniqueness, however, only few reach the development phase due to their poor pharmacokinetics. Therefore, preassessing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties is essential in drug discovery. Biologically diverse databases (Phytochemica, SerpentinaDB, SANCDB and NuBBE) covering the region of India, Brazil and South Africa were considered to predict the ADMET using chemoinformatic tools (Qikprop, pkCSM and DataWarrior). Screening through each of pharmacokinetic criteria resulted in identification of 24 compounds that adhere to all the ADMET properties. Furthermore, assessment revealed that five have potent anticancer biological activity against cancer cell lines. We have established an open-access database (ADMET-BIS) to enable identification of promising molecules that follow ADMET properties and can be considered for drug development.
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http://dx.doi.org/10.4155/fmc-2019-0206DOI Listing
January 2020

Effectiveness of Phytoactive Molecules on Transcriptional Expression, Biofilm Matrix, and Cell Wall Components of and Its Clinical Isolates.

ACS Omega 2018 Sep 28;3(9):12201-12214. Epub 2018 Sep 28.

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.

Toxicity challenges by antifungal arsenals and emergence of multidrug resistance scenario has posed a serious threat to global community. To cope up with this alarming situation, phytoactive molecules are richest, safest, and most effective source of broad spectrum antimicrobial compounds. In the present investigation, six phytoactive molecules [cinnamaldehyde (CIN), epigallocatechin, vanillin, eugenol (EUG), furanone, and epigallocatechin gallate] were studied against and its clinical isolates. Among these, CIN and EUG which are active components of cinnamon and clove essential oils, respectively, exhibited maximum inhibition against planktonic growth of at a concentration of 64 and 128 μg mL, respectively. These two molecules effectively inhibited and eradicated approximately 80% biofilm of and its clinical isolates from biomaterials. CIN and EUG increased reactive oxygen species generation, cell lysis, and ergosterol content in plasma membrane and reduced virulence attributes (phospholipase and proteinase) as well as catalase activity of cells. Reduction of mitochondrial membrane potential with increased release of cytochrome from mitochondria to cytosol indicated initiation of early apoptosis in CIN- and EUG-treated cells. Transcriptional analysis showed that multidrug transporter () and ergosterol biosynthesis genes were downregulated in the presence of CIN, while getting upregulated in EUG-treated cells. Interestingly, genes such as 1,3-β-glucan synthase (), GPI-anchored protein (), and sterol importer () were downregulated upon treatment of CIN/EUG. These results provided molecular-level insights about the antifungal mechanism of CIN and EUG against including its resistant clinical isolate. The current data established that CIN and EUG can be potentially formulated in new antifungal strategies.
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http://dx.doi.org/10.1021/acsomega.8b01856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645245PMC
September 2018

Transferrin-decorated thymoquinone-loaded PEG-PLGA nanoparticles exhibit anticarcinogenic effect in non-small cell lung carcinoma via the modulation of miR-34a and miR-16.

Biomater Sci 2019 Oct 14;7(10):4325-4344. Epub 2019 Aug 14.

Center for Research in Nanoscience and Nanotechnology, Technology Campus, University of Calcutta, JD-2, Sector III, Salt Lake City, Kolkata-700106, West Bengal, India.

Non-small cell lung carcinoma (NSCLC) is a highly lethal type of cancer with limited therapeutic avenues available to date. In the present study, we formulated PEGylated PLGA thymoquinone nanoparticles (TQ-Np) for improved TQ delivery to NSCLC cells. Transferrin (TF), a biodegradable, non-immunogenic and non-toxic protein, is well known to bind to TFR (transferrin receptor) over-expressed in non-small cell lung carcinoma A549 cells. Thus, the further decoration of the PEGylated PLGA thymoquinone nanoparticles with transferrin (TF-TQ-Np) enhanced the internalization of the nanoparticles within the A549 cells and the activity of TQ. We established TF-TQ-Np as a potent anti-tumorigenic agent through the involvement of p53 and the ROS feedback loop in regulating the microRNA (miRNA) circuitry to control apoptosis and migration of NSCLC cells. TF-TQ-Np-mediated p53 up-regulation favored the potential simultaneous activation of miR-34a and miR-16 targeting Bcl2 to induce apoptosis in the A549 cells. Additionally, TF-TQ-Np also restricted the migration through actin de-polymerization via activation of the p53/miR-34a axis. Further studies in chick CAM xenograft models confirmed the anti-cancer activity of TF-TQ-Np by controlling the p53/miR-34a/miR-16 axis. Furthermore, in vivo experiments conducted in a xenograft model in immunosuppressed Balb/c mice also proved the efficacy of the nanoparticles as an antitumor agent against NSCLC. Thus, our findings cumulatively suggest that the transferrin-adorned TQ-Np successfully coupled two distinct miRNA pathways to potentiate the apoptotic death cascade in the very lethal NSCLC cells and also restricts the migration of these cells without imparting any significant toxicity, which occurs in the widely used chemotherapeutic combinations. Thereby, our findings rekindle new hopes for the development of improved targeted therapeutic options with specified molecular objectives for combating the deadly NSCLC.
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http://dx.doi.org/10.1039/c9bm00912dDOI Listing
October 2019

50 Years Ago in TheJournal ofPediatrics: Funduscopic Photography and Fluorescein Angioretinography in Evaluation of Children with Neurologic Handicaps.

J Pediatr 2019 Jun;209:124

Department of Pediatrics, University College of Medical Sciences, Delhi, India.

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http://dx.doi.org/10.1016/j.jpeds.2018.12.032DOI Listing
June 2019

Miosis in a case of congenital fibrosis of extraocular muscles: a rare presentation of a rare disease.

BMJ Case Rep 2019 Mar 20;12(3). Epub 2019 Mar 20.

Ophthalmology, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1136/bcr-2019-229680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453339PMC
March 2019

50 Years Ago in The Journal of Pediatrics: Normal Inner Canthal and Outer Orbital Dimensions.

J Pediatr 2019 Mar;206:48

Department of Pediatrics University College of Medical Sciences Delhi, India.

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http://dx.doi.org/10.1016/j.jpeds.2018.09.055DOI Listing
March 2019

Dietary pomegranate supplement alleviates murine pancreatitis by modulating Nrf2-p21 interaction and controlling apoptosis to survival switch.

J Nutr Biochem 2019 04 21;66:17-28. Epub 2018 Dec 21.

Department of Physiology, University of Calcutta, UCSTA, 92, A.P.C. Road, Kolkata, 700009, West Bengal, India. Electronic address:

Dietary supplementation of polyphenol-rich pomegranate extract (POMx) has been shown to have anti-oxidant and anti-inflammatory activities. Here, we evaluate the efficacy of POMx in mitigating pancreatitis in mice and provide a mechanistic outline of the process. Age-matched male Swiss albino mice were injected with Lipopolysaccharide (LPS) and given POMx supplement alone or in combination with LPS. After 4 weeks of treatment histological scoring for pancreatic edema and vacuolization was performed. Serum insulin levels were estimated and the glucose tolerance test (IPGTT) data revealed that POMx reduced inflammation induced hyperglycemia in mice. Analysis of TLR4, IκB expression, and NF-κB nuclear translocation, and concentrations of IL-6 and TNFα showed that POMx is able to modulate the molecular instigators of inflammatory responses. Annexin V assay indicated that POMx protects against inflammation-mediated apoptosis in the pancreas. Expression profile of SAPK/JNK pathway, p53, Bax, Bcl-2 and Caspase-3 validate an apoptotic to survival shift in POMx treatment group. Co-immunoprecipitation studies show that POMx stabilizes p21 and Nrf2 interaction and increases its nuclear translocation. The study also proves that the nuclear fraction of Nrf2 is able to bind to the Bcl-2 promoter and activate an anti-apoptotic program. The findings of our study underline an anti-inflammatory, anti-oxidative and anti-apoptotic role of POMx and provide a mechanistic idea of how POMx confers protection during pancreatitis.
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http://dx.doi.org/10.1016/j.jnutbio.2018.12.009DOI Listing
April 2019

Fluoxetine triggers selective apoptosis in inflammation-induced proliferating (Ki-67 ) thymocytes.

Immunol Cell Biol 2019 05 14;97(5):470-484. Epub 2019 Feb 14.

Department of Physiology, University of Calcutta, UCSTA, 92, Acharya Prafulla Chandra Road, 700009, Kolkata, India.

Inappropriate functioning of the immune system is observed during sustained systemic inflammation, which might lead to immune deficiencies, autoimmune disorders and cancer. Primary lymphoid organs may progress to a deregulated proliferative state in response to inflammatory signals in order to intensify host defense mechanisms and exacerbate an inflammatory niche. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been projected as an anti-inflammatory agent. This study had been designed to evaluate the potential novel role of fluoxetine in reversing inflammation-induced immune dysfunction. Lipopolysaccharide (LPS) administration in Swiss albino mice potentiated a systemic inflammatory response, along with increased proliferation of thymocytes and peripheral blood mononuclear cells, as evident from increased Ki-67 expression. The proliferative changes in the immune system were mainly associated with increased phosphorylation of PI3k, AKT and IκB along with elevated NFκB-p65 nuclear translocation. The Ki-67 thymocytes obtained from LPS administered mice demonstrated significantly low p53 nuclear activity, which was established to be mediated by NFκB through reduced nuclear translocation of p53 during LPS-induced proliferative conditions, thereby blocking p53-dependent apoptosis. Fluoxetine supplementation not only reversed the proinflammatory condition, but also induced selective apoptosis in the proliferation-dictated Ki-67 thymocytes possibly by modulating the hypothalamus-pituitary-adrenal axis and inducing glucocorticoid receptor activation and apoptosis in these proliferation-biased immune cells, authenticating a novel antiproliferative role of an established drug.
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http://dx.doi.org/10.1111/imcb.12227DOI Listing
May 2019

Microwave assisted κ-carrageenan capped silver nanocomposites for eradication of bacterial biofilms.

Carbohydr Polym 2019 Feb 14;206:854-862. Epub 2018 Nov 14.

Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, 247667, Uttarakhand, India; Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, 247667, Uttarakhand, India. Electronic address:

Maturation of bacterial biofilms and their resistance to recurrent antimicrobial agents results in convoluted infectious diseases. In the current study, kappa-Carrageenan (κ-Carrageenan/CRG), was used to formulate CRG-silver nanocomposites through a facile microwave green synthesis approach. CRG-Ag nanoparticles of size 50 ± 10 nm were obtained by using CRG as a reducing and stabilizing agent. CRG-Ag nanoparticles were highly effective against both S. aureus and P. aeruginosa mediated biofilms and acted as a broad spectrum antibacterial agent even after six months. CRG-Ag nanoparticles encapsulated in KCl cross-linked hydrogel also exhibited excellent thermal stability, and antimicrobial potency. All these results depict that CRG-Ag nanocomposites appear as a promising approach to eradicate bacterial biofilms in food packaging and biomedical applications.
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http://dx.doi.org/10.1016/j.carbpol.2018.11.033DOI Listing
February 2019

Chemistry and Biology of Farnesol and its Derivatives: Quorum Sensing Molecules with Immense Therapeutic Potential.

Curr Top Med Chem 2018 ;18(22):1937-1954

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee-247667, Uttarakhand, India.

Background: Farnesol is an acyclic sesquiterpene alcohol, endogenously synthesized via the ergosterol pathway. It is a quorum sensing molecule (QSM) that was first discovered in C. albicans, and is involved in the inhibition of hyphae formation.

Methods: This review focuses on the comprehensive details of occurrence, chemical/biological synthesis of farnesol and its derivatives, and the factors involved in the regulation of their production. Further, the review also presents their cellular functions and diversified biomedical applications.

Results: Large-scale production of farnesol can be achieved using chemical synthesis and metabolic engineering approach. Farnesol is involved in the regulation of various physiological processes including filamentation, biofilm development, drug efflux, and apoptosis, etc. Farnesol and its derivatives/ analogues have also been reported to exhibit anti-biofilm, anti-cancer, anti-tumor and fungicidal properties. The antimicrobial potential of farnesol has been enhanced by synergizing it with known antifungal drugs, and also through nano-formulation(s).

Conclusion: Apart from its quorum sensing activity, farnesol can be used as an effective anti-microbial, anti-inflammatory, ant-allergic, anti-cancerous, and anti-obesity agent.
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http://dx.doi.org/10.2174/1568026619666181210124159DOI Listing
January 2019

Long-term Effect of Scleral Encircling on Axial Elongation.

Am J Ophthalmol 2018 09 14;193:252. Epub 2018 Jul 14.

Bhopal, India.

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http://dx.doi.org/10.1016/j.ajo.2018.05.034DOI Listing
September 2018

Peripheral primitive neuroendocrine tumor of the chest wall-A case report with pathological correlation.

Radiol Case Rep 2018 Apr 5;13(2):392-396. Epub 2018 Feb 5.

Tufts Medical Center, 800 Washington St, Boston, MA 02111, USA.

Primitive neuroectodermal tumor is a high-grade malignant tumor originating from the neural crest and neuroectoderm, which can be subdivided into central and peripheral categories. Peripheral primitive neuroectodermal tumor is thought to be identical to Ewing's sarcoma, and falls under a broader category of Ewing's sarcoma family of tumors. Very rarely, it may present without osseous involvement, known as extraosseous Ewing's sarcoma. Here we present a case of a 38-year-old woman, who presented with several-month history of a slow-growing chest wall mass, initially thought to be a breast mass. The mass was diagnosed as extraosseous Ewing's sarcoma upon tissue biopsy. The patient was started on a dose-intensified neoadjuvant therapy, based on protocol from pediatric population given rarity of this tumor in the adult population. While the patient was initially planned for surgical resection, the tumor showed excellent response to chemotherapy on follow-up imaging, and radiation therapy was elected in lieu of resection.
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http://dx.doi.org/10.1016/j.radcr.2018.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000041PMC
April 2018

Insight into structural requirements of antiamoebic flavonoids: 3D-QSAR and G-QSAR studies.

Chem Biol Drug Des 2018 10 26;92(4):1743-1749. Epub 2018 Jun 26.

Bioinformatics Division, ICMR-National Institute of Cancer Prevention and Research, Noida, India.

Plant-based flavonoids have been found to exhibit strong inhibitory capability against Entamoeba histolytica. So, various QSAR models have been developed to identify the critical features that are responsible for the potency of these molecules. 3D-QSAR analysis using k-nearest neighbour molecular field analysis via stepwise forward-backward variable selection method showed best results for both internal and external predictive ability of the model (i.e., q  = 0.64 and pred_r  = 0.56). Also, a group-based QSAR (G-QSAR) model was developed based on partial least squares regression combined with stepwise forward-backward variable selection method. It gave best parametric results (r  = 0.74, q  = 0.56 and pred_r  = 0.54) which implied that the model is highly predictive. 3D-QSAR established that presence/absence of bulk near rings B and C is important in deciding the inhibitory potential of these molecules. Additionally, G-QSAR provided site-specific clue wherein modifications related to molecular weight, electronegativity and separation of an oxygen atom in rings A and C can result in enhanced biological activity. To the best of the author's knowledge, this is the first QSAR study of antiamoebic flavonoids, and therefore, we expect the results to be useful in the design of more potent antiamoebic inhibitors.
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http://dx.doi.org/10.1111/cbdd.13343DOI Listing
October 2018

Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Inhibits Candida Biofilms: A Metabolomic Approach.

Int J Med Mushrooms 2017 ;19(8):685-696

Department of Biochemical Sciences (DBCS) Defense Institute of Physiology and Allied Sciences( DIPAS) Lucknow Road, Timarpur Delhi-110054.

This article presents a comparative gas chromatography (GC)-mass spectrometry (MS)-based metabolomic analysis of mycelia and fruiting bodies of the medicinal mushroom Ganoderma lucidum. Three aqueous extracts-mycelia, fruiting bodies, and a mixture of them-and their sequential fractions (methanolic and ethyl acetate), prepared using an accelerated solvent extractor, were characterized by GC-MS to determine volatile organic compounds and by high-performance thin-layer chromatography to quantify ascorbic acid, a potent antioxidant. In addition, these extracts and fractions were assessed against Candida albicans and C. glabrata biofilms via the XTT reduction assay, and their antioxidant potential was evaluated. Application of chemometrics (hierarchical cluster analysis and principal component analysis) to GC data revealed variability in volatile organic compound profiles among G. lucidum extracts and fractions. The mycelial aqueous extract demonstrated higher anti-Candida activity and ascorbic acid content among all the extracts and fractions. Thus, this study illustrates the preventive effect of G. lucidum against C. albicans and C. glabrata biofilms along with its nutritional value.
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http://dx.doi.org/10.1615/IntJMedMushrooms.2017021225DOI Listing
July 2018

Molecular details of secretory phospholipase A from flax (Linum usitatissimum L.) provide insight into its structure and function.

Sci Rep 2017 09 11;7(1):11080. Epub 2017 Sep 11.

ICAR-National Research Centre on Plant Biotechnology, Pusa Campus, New Delhi, 110012, India.

Secretory phospholipase A (sPLA) are low molecular weight proteins (12-18 kDa) involved in a suite of plant cellular processes imparting growth and development. With myriad roles in physiological and biochemical processes in plants, detailed analysis of sPLA in flax/linseed is meagre. The present work, first in flax, embodies cloning, expression, purification and molecular characterisation of two distinct sPLAs (I and II) from flax. PLA activity of the cloned sPLAs were biochemically assayed authenticating them as bona fide phospholipase A. Physiochemical properties of both the sPLAs revealed they are thermostable proteins requiring di-valent cations for optimum activity.While, structural analysis of both the proteins revealed deviations in the amino acid sequence at C- & N-terminal regions; hydropathic study revealed LusPLAI as a hydrophobic protein and LusPLAII as a hydrophilic protein. Structural analysis of flax sPLAs revealed that secondary structure of both the proteins are dominated by α-helix followed by random coils. Modular superimposition of LusPLA isoforms with rice sPLA confirmed monomeric structural preservation among plant phospholipase A and provided insight into structure of folded flax sPLAs.
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http://dx.doi.org/10.1038/s41598-017-10969-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593939PMC
September 2017

Origin and evolution of group XI secretory phospholipase A from flax (Linum usitatissimum) based on phylogenetic analysis of conserved domains.

3 Biotech 2017 Jul 1;7(3):216. Epub 2017 Jul 1.

ICAR-National Research Centre on Plant Biotechnology, Pusa Campus, New Delhi, 110012, India.

Phospholipase A (PLA) belongs to class of lipolytic enzymes (EC 3.1.1.4). Lysophosphatidic acid (LPA) and free fatty acids (FFAs) are the products of PLA catalyzed hydrolysis of phosphoglycerides at sn-2 position. LPA and FFA that act as second mediators involved in the development and maturation of plants and animals. Mining of flax genome identified two phospholipase A encoding genes, viz., LusPLA I and LusPLA II (Linum usitatissimum secretory phospholipase A). Molecular simulation of LusPLAs with already characterized plant sPLAs revealed the presence of conserved motifs and signature domains necessary to classify them as secretory phospholipase A. Phylogenetic analysis of flax sPLA with representative sPLAs from other organisms revealed that they evolved rapidly via gene duplication/deletion events and shares a common ancestor. Our study is the first report of detailed phylogenetic analysis for secretory phospholipase A in flax. Comparative genomic analysis of two LusPLAs with earlier reported plant sPLAs, based on their gene architectures, sequence similarities, and domain structures are presented elucidating the uniqueness of flax sPLA.
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http://dx.doi.org/10.1007/s13205-017-0790-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494027PMC
July 2017
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