Publications by authors named "Rakesh Mishra"

255 Publications

Reversible dysregulation of renal circadian rhythm in lupus nephritis.

Mol Med 2021 09 6;27(1):99. Epub 2021 Sep 6.

Institute for Molecular Medicine, Feinstein Institutes for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA.

Background: We have found disruption of expression of major transcriptional regulators of circadian rhythm in the kidneys of several mouse models of lupus nephritis. Here we define the consequence of this disturbance with respect to circadian gene expression and renal homeostatic function in a mouse model of lupus nephritis.

Methods: Molecular profiling of kidneys from 47 young and 41 nephritic female NZB/W F1 mice was performed at 4 hourly intervals over a 24 h period. Disruption of major circadian transcriptional regulators was confirmed by qPCR. Molecular data was normalized and analyzed for rhythmicity using RAIN analysis. Serum aldosterone and glucose and urine sodium and potassium were measured at 4 hourly intervals in pre-nephritic and nephritic mice and blood pressure was measured every 4 h. Analyses were repeated after induction of complete remission of nephritis using combination cyclophosphamide and costimulatory blockade.

Results: We show a profound alteration of renal circadian rhythms in mice with lupus nephritis affecting multiple renal pathways. Using Cosinor analysis we identified consequent alterations of renal homeostasis and metabolism as well as blood pressure dipper status. This circadian dysregulation was partially reversed by remission induction therapy.

Conclusions: Our studies indicate the role of inflammation in causing the circadian disruption and suggest that screening for loss of normal blood pressure dipping should be incorporated into LN management. The data also suggest a potential role for circadian agonists in the treatment of lupus nephritis.
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http://dx.doi.org/10.1186/s10020-021-00361-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419890PMC
September 2021

Homeotic Genes: Clustering, Modularity, and Diversity.

Front Cell Dev Biol 2021 11;9:718308. Epub 2021 Aug 11.

CSIR - Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India.

Hox genes code for transcription factors and are evolutionarily conserved. They regulate a plethora of downstream targets to define the anterior-posterior (AP) body axis of a developing bilaterian embryo. Early work suggested a possible role of clustering and ordering of to regulate their expression in a spatially restricted manner along the AP axis. However, the recent availability of many genome assemblies for different organisms uncovered several examples that defy this constraint. With recent advancements in genomics, the current review discusses the arrangement of in various organisms. Further, we revisit their discovery and regulation in . We also review their regulation in different arthropods and vertebrates, with a significant focus on expression in the crustacean . It is noteworthy that subtle changes in the levels of Hox gene expression can contribute to the development of novel features in an organism. We, therefore, delve into the distinct regulation of these genes during primary axis formation, segment identity, and extra-embryonic roles such as in the formation of hair follicles or misregulation leading to cancer. Toward the end of each section, we emphasize the possibilities of several experiments involving various organisms, owing to the advancements in the field of genomics and CRISPR-based genome engineering. Overall, we present a holistic view of the functioning of in the animal world.
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http://dx.doi.org/10.3389/fcell.2021.718308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386295PMC
August 2021

Biomass derived functional carbon materials for supercapacitor applications.

Chemosphere 2021 Aug 19;286(Pt 3):131961. Epub 2021 Aug 19.

Thermo-catalytic Process Area, Material Resource Efficiency Division, CSIR-Indian Institute of Petroleum, Haridwar Road, Mohkampur, Dehradun, 248005, Uttarakhand, India; Academy of Scientific and Innovative Research (AcSIR), Sector 19, Kamla Nehru Nagar, Ghaziabad, 201002, Uttar Pradesh, India. Electronic address:

Biochar produced from the thermochemical conversion of biomass, provides a green and sustainable platform for the preparation of various functional carbon materials (porous carbon, heteroatom doped biochar, carbon nanotubes, graphene, carbon quantum dots, etc.) towards advanced application. Their preparation involves the physical as well as chemical activation of biochar or directly from the biomass. The inherent versatile physicochemical properties of these versatile materials have been explored for the construction of the electrochemical energy storage devices like supercapacitors. In the present review, the various methodologies for the preparation of various biomass-derived carbon materials are summarized. Further utilization of these materials in supercapacitor electrodes and the properties associated with their charge storage ability, along with associated challenges and perspectives are also discussed.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131961DOI Listing
August 2021

Corrigendum to "Defining the methodological approach for wastewater-based epidemiological studies-Surveillance of SARS-CoV-2" [Environ. Technol. Innov. 23 (2021) 101696].

Environ Technol Innov 2021 Nov 11;24:101864. Epub 2021 Aug 11.

Bioengineering and Environmental Sciences Lab, Department of Energy and Environmental Engineering (DEEE), CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad 500007, India.

[This corrects the article DOI: 10.1016/j.eti.2021.101696.].
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http://dx.doi.org/10.1016/j.eti.2021.101864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356727PMC
November 2021

Antitumor drugs effect on the stability of double-stranded DNA: steered molecular dynamics analysis.

J Biomol Struct Dyn 2021 Aug 6:1-10. Epub 2021 Aug 6.

Computational Science Division, Saha Institute of Nuclear Physics, Kolkata, West Bengal, India.

Denaturation of the DNA double helix inside the cell is essential for cellular processes such as replication and transcription for the growth of the cells. However, the growth of unwanted cells, which are responsible for cancerous kind of disease, is one of the biggest challenges of modern therapeutics. DNA cross-linking agents may kill cancer cells by damaging their DNA and stopping them from dividing. In the present study, we have carried out steered molecular dynamics simulations to study the effects of rupture and unzipping forces on the stability of dsDNA in the absence and presence of covalently bonded drugs. We have found that the stability of dsDNA increases strongly in the presence of covalently bonded drugs. The microscopic study of disruption of hydrogen-bonds associated with base-pairs of the dsDNA and the study of the variation of stacking overlap parameters gives evidence of symmetry during the rupture and asymmetry in the unzip event. The significance of the mechanism of force-induced melting study of the dsDNA in the absence and presence of antitumor drugs might have a biological relevance as it provides a pathway to open the double helix in a specific position and may help for the pharmaceutical design of drugs.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1960193DOI Listing
August 2021

Synthetic Tunability and Biophysical Basis for Fabricating Highly Fluorescent and Stable DNA Copper Nanoclusters.

Langmuir 2021 08 27;37(31):9385-9395. Epub 2021 Jul 27.

School of Physical Sciences, Jawaharlal Nehru University, New Delhi 110067, India.

The real motivation in the present work is to tune the synthesis variables that can result in a highly fluorescent and stable DNA copper nanocluster (CuNC) and also to understand the intricate mechanism behind this process. Here, carefully optimized concentrations of various reactants enabled the creation of a DNA-encapsulated CuNC for AT-DNA, displaying a size of <1.0 nm as confirmed by transmission electron microscopy and dynamic light scattering. The extremely small size of the AT-DNACuNC supports the discrete electronic transitions, also characterized by an exceptionally strong negative circular dichroism (CD) band around 350 nm, whose intensity is well correlated with the observed strong fluorescence emission intensity. This remarkably strong CD can open new applications in the detection and quantification of a specific DNACuNC. Further, time-dependent fluorescence analysis suggested stronger photostabilization of these DNACuNCs. The simulation study, based on Cu ion distribution, explained how AT-DNA is a better candidate for NC formation than GC-DNA. In conclusion, the better-tuned synthesis procedure has resulted in a highly compact, well-defined three-dimensional conformation that promotes a more favorable microenvironment to sequester a DNA-based CuNC with high brightness and outstanding photostability.
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http://dx.doi.org/10.1021/acs.langmuir.1c00949DOI Listing
August 2021

Defining the methodological approach for wastewater-based epidemiological studies-Surveillance of SARS-CoV-2.

Environ Technol Innov 2021 Aug 17;23:101696. Epub 2021 Jun 17.

Bioengineering and Environmental Sciences Lab, Department of Energy and Environmental Engineering (DEEE), CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad 500007, India.

Since COVID-19 outbreak, wastewater-based epidemiology (WBE) studies as surveillance system is becoming an emerging interest due to its functional advantage as a tool for early warning signal and to catalyze effective disease management strategies based on the community diagnosis. An attempt was made in this study to define and establish a methodological approach for conducting WBE studies in the framework of identifying/selection of surveillance sites, standardizing sampling policy, designing sampling protocols to improve sensitivity, adopting safety protocol, and interpreting the data. Data from hourly sampling indicated a peak in the viral RNA during the morning hours (6-9 am) when the all the domestic activities are maximum. The daily sampling and processing revealed the dynamic nature of infection spread among the population. The two sampling methods viz. grab, and composite showed a good correlation. Overall, this study establishes a structured protocol for performing WBE studies that could provide useful insights on the spread of the pandemic at a given point of time. Moreover, this framework could be extrapolated to monitor several other clinically relevant diseases. Following these guidelines, it is possible to achieve measurable and reliable SARS-CoV-2 RNA concentrations in wastewater infrastructure and therefore, provides a methodological basis for the establishment of a national surveillance system.
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http://dx.doi.org/10.1016/j.eti.2021.101696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253532PMC
August 2021

Letter to the Editor Regarding: "Functional Motor Skills in Children that Underwent Fetal Myelomeningocele Repair: Does Anatomic Level Matter?"

World Neurosurg 2021 07;151:329-330

Department of Neurosurgery, All India Institute of Medical Sciences, Saket Nagar, Madhya Pradesh, India.

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http://dx.doi.org/10.1016/j.wneu.2021.03.053DOI Listing
July 2021

Endoscopic-Assisted Microsurgery for Vestibular Schwannomas: Operative Nuances.

Neurol India 2021 May-Jun;69(3):578-581

Former Dean and Professor of Neurosurgery, Sree Chitra Tirunal Insitute of Medical Sciences, Trivandrum, Kerala, India.

Vestibular schwannoma surgery is a challenging operative procedure. Intricate anatomy of vital neurovascular structures demands a meticulous planning and execution. The cerebellopontine angle is an unforgiving area of skull bases surgery which can have grave implications on patient outcome even after a successful tumor removal. As more and more tumors are being detected at early stage, functional preservation of seventh and eighth nerve complex is increasingly being demanded. The key to any minimally invasive approach is to minimize the collateral damage while ensuring complete tumor removal. Binocular microscopy is the workhorse for illumination and dissection via retrosigmoid approach. However, as instrumentation has improved, endoscopic dissections are increasingly being performed. The following video presents the step-by-step nuances for an endoscope-assisted microsurgery for small vestibular schwannomas with stress on endoscopic drilling of the meatal wall to deliver out intracanacular tumor while preserving the labrynthine structures.
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http://dx.doi.org/10.4103/0028-3886.319208DOI Listing
June 2021

Non-dysraphic extramedullary intradural spinal lipoma with neurocutaneous melanocytosis.

Br J Neurosurg 2021 Jun 21:1-5. Epub 2021 Jun 21.

Department of Neurosurgery, All India Institute of Medical Sciences, Bhopal, India.

Introduction: Intradural spinal lipomas are very rare and constitute less than 1% of all spinal tumors. Such tumors are usually associated with spinal dysraphism and occur mostly in the lumbosacral or cervical region. Intradural spinal lipomas tends to be intramedullary or subpial. Meningeal melanocytoma is further rarer cases that comprise less than 0.1% of cases. These usually occur in the fifth or fifth decade and chances of malignant transformation are high.

Case Report: Here, we report an extremely rare case (first to the best of our knowledge) of a 9 years female child who presented to us with rapid progressing paraparesis. She was operated and found to have an intradural purely extramedullary spinal lipoma without spinal dysraphism. Moreover, she had melanin pigment deposits all over her meninges which is further rare. On presentation, the patient was bedridden but after surgery, the patient improved and could walk without support.

Conclusions: To the best of our knowledge, this is the first case of spinal cord lipoma in dorsal location along with melanin pigments in the meninges. We discuss the pathogenesis, presentation and management of intradural extramedullary spinal lipomas.
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http://dx.doi.org/10.1080/02688697.2021.1937518DOI Listing
June 2021

Letter to the Editor Regarding "Females in Neurosurgery: from a Matter of Fortuitous Occasions Towards a Conscious Choice".

World Neurosurg 2021 06;150:242-243

Department of Neurosurgery, All India Institute of Medical Sciences, Saket Nagar, Bhopal, Madhya Pradesh, India.

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http://dx.doi.org/10.1016/j.wneu.2021.03.076DOI Listing
June 2021

Role of vertebrate GAGA associated factor (vGAF) in early development of zebrafish.

Cells Dev 2021 06 24;166:203682. Epub 2021 Apr 24.

Centre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcCSIR), India. Electronic address:

Homeotic genes and their genomic organization show remarkable conservation across bilaterians. Consequently, the regulatory mechanisms, which control hox gene expression, are also highly conserved. The crucial presence of conserved GA rich motifs between Hox genes has been previously observed but what factor binds to these is still unknown. Previously we have reported that the vertebrate homologue of Drosophila Trl-GAF preferentially binds to GA rich regions in Evx2-hoxd13 intergenic region of vertebrate HoxD cluster. In this study, we show that the vertebrate-GAF (v-GAF) binds at known cis-regulatory elements in the HoxD complex of zebrafish and mouse. We further used morpholino based knockdown and CRISPR-cas9 knockout technique to deplete the v-GAF in zebrafish. We checked expression of the HoxD genes and found gain of the HoxD4 gene in GAF knockout embryos. Further, we partially rescued the morphological phenotypes in GAF depleted embryos by providing GAF mRNA. Our results show that GAF binds at intergenic regions of the HoxD complex and is important for maintaining the spatial domains of HoxD4 expression during embryonic development.
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http://dx.doi.org/10.1016/j.cdev.2021.203682DOI Listing
June 2021

Development and optimization of a TaqMan assay for Nosema bombycis, causative agent of pébrine disease in Bombyx mori silkworm, based on the β-tubulin gene.

J Microbiol Methods 2021 07 13;186:106238. Epub 2021 May 13.

Genomic Division, Seri Biotech Research Laboratory, Carmelaram Post, Kodathi, Bangalore 560035, India.

"Pébrine" is a devastating disease of Bombyx mori silkworms that is highly contagious and can completely destroy an entire crop of silkworms and is thus a serious threat for the viability and profitability of sericulture. The disease is most commonly attributed to microsporidians of the genus Nosema, which are obligate intracellular parasites that are transmitted through spores. Nosema infections in silkworms are diagnosed primarily through light microscopy, which is labour intensive and less reliable, sensitive, and specific than PCR-based techniques. Here, we present the development and optimization of a new TaqMan based assay targeting the β-tubulin gene in the pébrine disease causing agent Nosema bombycis in silkworms. The assay displayed excellent quantification linearity over multiple orders of magnitude of target amounts and a limit of detection (LOD) of 6.9 × 10 copies of target per reaction. The method is highly specific to N. bombycis with no cross-reactivity to other Nosema species commonly infecting wild silkworms. This specificity was due to three nucleotides in the probe-binding region unique to N. bombycis. The assay demonstrated a high reliability with a Coefficient of variation (CV) <5% for both intra-assay and inter-assay variability. The assay was used to trace experimental N. bombycis infection of silkworm larvae, in the fat body, midgut and ovary tissues, through pupation and metamorphosis to the emerging female moth, and her larval off-spring, confirming the vertical transmission of N. bombycis in silkworms. The TaqMan assay revealed a gradual increase in infection levels in the post-infection samples. The assay is reliable and simple to implement and can be a suitable complement to microscopy for routine diagnostics and surveillance in silkworm egg production centres with appropriate infrastructure.
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http://dx.doi.org/10.1016/j.mimet.2021.106238DOI Listing
July 2021

Letter: Prepontine Shunting for Pseudotumor Cerebri in Previously Failed Shunt Patients: A 5-Year Analysis.

Neurosurgery 2021 07;89(2):E140-E141

Department of Neurosurgery All India Institute of Medical Sciences Bhopal, India.

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http://dx.doi.org/10.1093/neuros/nyab167DOI Listing
July 2021

Defogging Strategy for Protective Eye Goggles to Prevent Microorganism Transmission While Performing Neurosurgical Procedures.

J Neurosci Rural Pract 2021 Apr 9;12(2):447-449. Epub 2021 Feb 9.

Department of Neurosurgery, All India Institute of Medical Sciences, Saket Nagar, Bhopal, Madhya Pradesh, India.

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http://dx.doi.org/10.1055/s-0041-1723062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064850PMC
April 2021

Letter: Contemporary Analysis of Minimal Clinically Important Difference in the Neurosurgical Literature.

Neurosurgery 2021 06;89(1):E82-E83

Department of Neurosurgery All India Institute of Medical Sciences Bhopal, India.

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http://dx.doi.org/10.1093/neuros/nyab115DOI Listing
June 2021

Enigma of what is Known about Intracranial Aneurysm Occlusion with Endovascular Devices.

J Stroke Cerebrovasc Dis 2021 Jun 25;30(6):105737. Epub 2021 Mar 25.

Department of Neurosurgery, All India Institute of Medical Sciences, Saket Nagar, Bhopal 462020, Madhya Pradesh, India.

Aneurysmal subarachnoid Hemorrhage is a major cause of neurological morbidity and mortality. Over the years vascular neurosurgery has witnessed technological advances aimed to reduce the morbidity and mortality. Several endovascular devices have been used in clinical practice to achieve this goal in the management of ruptured and unruptured cerebral aneurysms. Recurrence due to recanalization is encountered in all of these endovascular devices as well as illustrated by Barrow Ruptured Aneurysm Trial. Histological and molecular characterization of the aneurysms treated with endovascular devices is an area of active animal and human research studies. Yet, the pathobiology illustrating the mechanisms of aneurysmal occlusion and healing lacks evidence. The enigma of aneurysmal healing following treatment with endovascular devices needs to be de-mystified to understand the biological interaction of endovascular device and aneurysm and thereby guide the future development of endovascular devices aimed at better aneurysm occlusion. We performed a comprehensive and detailed literature review to bring all the known facts of the pathobiology of intracranial aneurysm healing, the knowledge of which is of paramount importance to neurosurgeons, an interventional neuroradiologist, molecular biologist, geneticists, and experts in animal studies. This review serves as a benchmark of what is known and platform for future studies basic science research related to intracranial aneurysms.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105737DOI Listing
June 2021

SARS-CoV-2 genomics: An Indian perspective on sequencing viral variants.

J Biosci 2021 ;46

CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, Telangana 500 007, India.

Since its emergence as a pneumonia-like outbreak in the Chinese city of Wuhan in late 2019, the novel coronavirus disease COVID-19 has spread widely to become a global pandemic. The first case of COVID-19 in India was reported on 30 January 2020 and since then it has affected more than ten million people and resulted in around 150,000 deaths in the country. Over time, the viral genome has accumulated mutations as it passes through its human hosts, a common evolutionary mechanism found in all microorganisms. This has implications for disease surveillance and management, vaccines and therapeutics, and the emergence of reinfections. Sequencing the viral genome can help monitor these changes and provides an extraordinary opportunity to understand the genetic epidemiology and evolution of the virus as well as tracking its spread in a population. Here we review the past year in the context of the phylogenetic analysis of variants isolated over the course of the pandemic in India and highlight the importance of continued sequencing-based surveillance in the country.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895735PMC
March 2021

Surveillance of SARS-CoV-2 spread using wastewater-based epidemiology: Comprehensive study.

Sci Total Environ 2021 May 6;768:144704. Epub 2021 Jan 6.

CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India. Electronic address:

SARS-CoV-2 pandemic is having a devastating effect on human lives. Recent reports have shown that majority of the individuals recovered from COVID-19 have serious health complications, which is going to be a huge economic burden globally. Given the wide-spread transmission of SARS-CoV-2 it is almost impossible to test every individual in densely populated countries. Recent reports have shown that sewage-based surveillance can be used as holistic approach to understand the spread of the pandemic within a population or area. Here we have estimated the spread of SARS-CoV-2 in the city of Hyderabad, India, which is a home for nearly 10 million people. The sewage samples were collected from all the major sewage treatment plants (STPs) and were processed for detecting the viral genome using the standard Reverse Transcription Polymerase Chain Reaction (RT-PCR) method. Interestingly, inlet samples of STPs were positive for SARS-CoV-2, while the outlets were negative, which indicates that the standard sewage treatment methods are efficient in eliminating the SARS-CoV-2 viral particles. Based on the detected viral gene copies per litre and viral particle shedding per individual, the total number of individuals exposed to SARS-CoV-2 was estimated. Through this study we suggest that sewage-based surveillance is an effective approach to study the infection dynamics, which helps in efficient management of the SARS-CoV-2 spread.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787060PMC
May 2021

Letter to the Editor Regarding "Management of Traumatic Brain Injury at a Medium Complexity Hospital in a Remote Area of Amazonas, 2017-2019".

World Neurosurg 2021 03;147:256

Department of Neurosurgery, All India Institute of Medical Sciences, Saket Nagar, Bhopal, Madhya Pradesh (India). Electronic address:

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http://dx.doi.org/10.1016/j.wneu.2021.01.022DOI Listing
March 2021

Posture induced severe fixed cervical flexion deformity-a neurosurgical image.

Br J Neurosurg 2021 Feb 25:1-3. Epub 2021 Feb 25.

Department of Neurosurgery, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India.

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http://dx.doi.org/10.1080/02688697.2021.1886244DOI Listing
February 2021

Release of Mediator Enzyme β-Hexosaminidase and Modulated Gene Expression Accompany Hemocyte Degranulation in Response to Parasitism in the Silkworm Bombyx mori.

Biochem Genet 2021 Aug 22;59(4):997-1017. Epub 2021 Feb 22.

Seribiotech Research Laboratory, CSB-Kodathi Campus, Carmelaram. P.O, Bangalore, Karnataka, 560035, India.

In insects infections trigger hemocyte-mediated immune reactions including degranulation by exocytosis; however, involvement of mediator enzymes in degranulation process is unknown in insects. We report here that in silkworm Bombyx mori, infection by endoparasitoid Exorista bombycis and microsporidian Nosema bombycis activated granulation in granulocytes and promoted degranulation of accumulated structured granules. During degranulation the mediator lysosomal enzyme β-hexosaminidase showed increased activity and expression of β-hexosaminidase gene was enhanced. The events were confirmed in vitro after incubation of uninfected hemocytes with E. bombycis larval tissue protein. On infection, cytotoxicity marker enzyme lactate dehydrogenase (LDH) was released from the hemocytes illustrating cell toxicity. Strong positive correlation (R = 0.71) between LDH activity and β-hexosaminidase released after the infection showed parasitic-protein-induced hemocyte damage and accompanied release of the enzymes. Expression of β-hexosaminidase gene was enhanced in early stages after infection followed by down regulation. The expression showed positive correlation (R = 0.705) with hexosaminidase activity pattern. B. mori hexosaminidase showed 98% amino acid similarity with that of B. mandarina showing origin from same ancestral gene; however, 45-60% varied from other lepidopterans showing diversity. The observation signifies the less known association of hexosaminidase in degranulation of hemocytes induced by parasitic infection in B. mori and its divergence in different species.
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http://dx.doi.org/10.1007/s10528-021-10046-xDOI Listing
August 2021

Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes.

Sci Rep 2021 Feb 9;11(1):3385. Epub 2021 Feb 9.

Department of Biology, Centre of Excellence in Epigenetics, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pune, 411008, India.

Special AT-rich binding protein-1 (SATB1) integrates higher-order chromatin architecture with gene regulation, thereby regulating multiple signaling pathways. In mammalian cells SATB1 directly interacts with β-catenin and regulates the expression of Wnt targets by binding to their promoters. Whether SATB1 regulates Wnt/wg signaling by recruitment of β-catenin and/or its interactions with other components remains elusive. Since Wnt/Wg signaling is conserved from invertebrates to humans, we investigated SATB1 functions in regulation of Wnt/Wg signaling by using mammalian cell-lines and Drosophila. Here, we present evidence that in mammalian cells, SATB1 interacts with Dishevelled, an upstream component of the Wnt/Wg pathway. Conversely, ectopic expression of full-length human SATB1 but not that of its N- or C-terminal domains in the eye imaginal discs and salivary glands of third instar Drosophila larvae increased the expression of Wnt/Wg pathway antagonists and suppressed phenotypes associated with activated Wnt/Wg pathway. These data argue that ectopically-provided SATB1 presumably modulates Wnt/Wg signaling by acting as negative regulator in Drosophila. Interestingly, comparison of SATB1 with PDZ- and homeo-domain containing Drosophila protein Defective Proventriculus suggests that both proteins exhibit limited functional similarity in the regulation of Wnt/Wg signaling in Drosophila. Collectively, these findings indicate that regulation of Wnt/Wg pathway by SATB1 is context-dependent.
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http://dx.doi.org/10.1038/s41598-021-81324-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873079PMC
February 2021

Sivelestat-loaded nanostructured lipid carriers modulate oxidative and inflammatory stress in human dental pulp and mesenchymal stem cells subjected to oxygen-glucose deprivation.

Mater Sci Eng C Mater Biol Appl 2021 Jan 6;120:111700. Epub 2020 Nov 6.

Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College and Hospital, Sarfarazganj, Lucknow 226003, Uttar Pradesh, India; Department of Stem Cell Biology and Regenerative Medicine, Era University, Sarfarazganj, Lucknow 226003, Uttar Pradesh, India. Electronic address:

Stroke remains the leading cause of morbidity and mortality. Stem cell-based therapy offers promising hope for survivors and their families. Despite the clinical translation of stem cell-based therapies in stroke patients for almost two decades, results of these randomized controlled trials are not very optimistic. In these lines, an amalgamation of nanocarriers based drug delivery with stem cells holds great promise in enhancing stroke recovery. In the present study, we treated oxygen-glucose deprivation (OGD) exposed dental pulp stem cells (DPSCs) and mesenchymal stem cells (MSCs) with sivelestat-loaded nanostructured lipid carriers (NLCs). Various physicochemical limitations associated with sivelestat drug applications and its recent inefficacy in the clinical trials necessitates the development of novel delivery approaches for sivelestat. Therefore, to improve its efficacy on the survival of DPSCs and MSCs cell types under OGD insult, the current NLCs were formulated and characterized. Resulting NLCs exhibited a hydrodynamic diameter of 160-180 nm by DLS technique and possessed good PDI values of 0.2-0.3. Their shape, size and surface morphology were corroborated with microscopic techniques like TEM, SEM, and AFM. FTIR and UV-Vis techniques confirmed nanocarrier's loading capacity, encapsulation efficiency of sivelestat, and drug release profile. Oxidative stress in DPSCs and MSCs was assessed by DHE and DCFDA staining, and cell viability was assessed by Trypan blue exclusion test and MTT assay. Results indicated that sivelestat-loaded NLCs protected the loss of cell membrane integrity and restored cell morphology. Furthermore, NLCs successfully defended human DPSCs and MSCs against OGD-induced oxidative and inflammatory stress. In conclusion, modulation of oxidative and inflammatory stress by treatment with sivelestat-loaded NLCs in DPSCs and MSCs provides a novel strategy to rescue stem cells during ischemic stroke.
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http://dx.doi.org/10.1016/j.msec.2020.111700DOI Listing
January 2021

Deterioration of nuclear morphology and architecture: A hallmark of senescence and aging.

Ageing Res Rev 2021 05 2;67:101264. Epub 2021 Feb 2.

CSIR-Centre for Cellular and Molecular Biology, Hyderabad, 500007, Telangana, India. Electronic address:

The metazoan nucleus is a highly structured organelle containing several well-defined sub-organelles. It is the largest organelle inside a cell taking up from one tenth to half of entire cell volume. This makes it one of the easiest organelles to identify and study under the microscope. Abnormalities in the nuclear morphology and architecture are commonly observed in an aged and senescent cell. For example, the nuclei enlarge, loose their shape, appear lobulated, harbour nuclear membrane invaginations, carry enlarged/fragmented nucleolus, loose heterochromatin, etc. In this review we discuss about the age-related changes in nuclear features and elaborate upon the molecular reasons driving the change. Many of these changes can be easily imaged under a microscope and analysed in silico. Thus, computational image analysis of nuclear features appears to be a promising tool to evaluate physiological age of a cell and offers to be a legitimate biomarker. It can be used to examine progression of age-related diseases and evaluate therapies.
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http://dx.doi.org/10.1016/j.arr.2021.101264DOI Listing
May 2021

Biological effects of formation of protein corona onto nanoparticles.

Int J Biol Macromol 2021 Apr 27;175:1-18. Epub 2021 Jan 27.

Department of Nano-Therapeutics, Institute of Nano Science and Technology, Habitat Centre, Phase 10, Sector 64, Mohali, Punjab 160062, India. Electronic address:

Administration of nanomaterials based medicinal and drug carrier systems into systemic circulation brings about interaction of blood components e.g. albumin and globulin proteins with these nanosystems. These blood or serum proteins either get loosely attached over these nanocarriers and form soft protein corona or are tightly adsorbed over nanoparticles and hard protein corona formation occurs. Formation of protein corona has significant implications over a wide array of physicochemical and medicinal attributes. Almost all pharmacological, toxicological and carrier characteristics of nanoparticles get prominently touched by the protein corona formation. It is this interaction of nanoparticle protein corona that decides and influences fate of nanomaterials-based systems. In this article, authors reviewed several diverse aspects of protein corona formation and its implications on various possible outcomes in vivo and in vitro. A brief description regarding formation and types of protein corona has been included along with mechanisms and pharmacokinetic, pharmacological behavior and toxicological profiles of nanoparticles has been described. Finally, significance of protein corona in context of its in vivo and in vitro behavior, involvement of biomolecules at nanoparticle plasma interface and other interfaces and effects of protein corona on biocompatibility characteristics have also been touched upon.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.152DOI Listing
April 2021

The new generation double layered flow diverters for endovascular treatment of intracranial aneurysms: current status of ongoing clinical uses.

Expert Rev Med Devices 2021 Feb 27;18(2):139-144. Epub 2021 Jan 27.

Professor of Neurosurgery, Department of Neurosurgery, All India Institute of Medical Sciences, Bhopal, India.

Introduction: The treatment of intracranial aneurysms has significantly evolved over the last decade with the advancement in endovascular techniques and devices. Flow diverters are the latest in the armamentarium for vascular reconstruction, aneurysm exclusion, and preservation of branch vessels. The possibility of treating various types of intracranial aneurysms, including those previously considered untreatable, has represented a new paradigm in the neurovascular era.

Areas Covered: This paper describes in detail the current status in the use of new generation double-layered Flow Redirection Endoluminal Device (FRED; MicroVention Terumo, Tustin, California). For this report, we reviewed the published literature for properties of the currently available FRED devices regarding safety, efficacy, and potential risks and complications associated with their use.

Expert Opinion: FRED and FRED Jr are the new flow diverter devices for which the existing data suggest that they are safe and efficient in addressing the treatment issues with giant, wide-necked saccular and fusiform aneurysms and those with perforators and branch vessels at high risk of occlusion with surgical clipping. Evidence is mounting on their long-term durability which increases the confidence of both the endovascular surgeon in prescribing and the patient side in accepting these FDs as treatment option for intracranial aneurysms.
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http://dx.doi.org/10.1080/17434440.2021.1879636DOI Listing
February 2021
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