Publications by authors named "Anjali Yadav"

20 Publications

  • Page 1 of 1

Wilms tumor with Mulibrey Nanism: A case report and review of literature.

Cancer Rep (Hoboken) 2021 Jul 26:e1512. Epub 2021 Jul 26.

Pediatric Hematology Oncology and Bone Marrow Transplant Unit, Cancer Institute, Medanta The Medicity Hospital, Gurgaon, Haryana, India.

Background: Mulibrey-Nanism (Muscle-liver-brain-eye Nanism = dwarfism; MUL) is a rare genetic syndrome. The underlying TRIM37 mutation predisposes these children to develop tumors frequently. In the largest published series of MUL, 8% patients were reported to develop Wilms tumor (WT). The published literature lacks data regarding the best treatment protocol and outcome of this cohort of children with WT and MUL. We report here a 2-year-old boy with WT and MUL and present a review of literature on WT in MUL.

Case: Our patient had associated cardiac problems of atrial septal defect, atrial flutter and an episode of sudden cardiac arrest. We managed him successfully with chemotherapy, surgery and multi-speciality care. He is alive and in remission at follow-up of 6 months.

Conclusion: A total of 14 cases (including present case) of WT have been reported in MUL and treatment details were available for six cases. They were managed primarily with surgery, chemotherapy with/without radiotherapy, and all achieved remission. The outcome data is available only for two cases, one has been followed up till 15 years post treatment for WT and other is our patient.
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http://dx.doi.org/10.1002/cnr2.1512DOI Listing
July 2021

Dengue virus transmission from donor to recipient during haploidentical stem cell transplantation.

IDCases 2021 7;25:e01220. Epub 2021 Jul 7.

Pediatric Hematology Oncology and Bone Marrow Transplant Unit, Cancer Institute, Medanta The Medicity Hospital, Gurgaon, Haryana, 122001, India.

Dengue fever is endemic in tropical and subtropical countries. Dengue virus transmission through hematopoietic stem cells is very rare and just two such cases have been reported previously. We report here only third case of dengue virus transmission in a 2-year-old child with thalassemia major who underwent hematopoietic stem cell transplant (HSCT) from a haploidentical related donor. One week after HSCT, the recipient developed fever, pancytopenia and signs of capillary leak. On day 10, his dengue NS1 antigen test was positive which confirmed diagnosis of dengue fever. Donor also had fever few days prior to stem cell donation which was later diagnosed to be due to dengue fever. Child had a severe clinical course of dengue leading to primary graft failure. However, he had autologous recovery of his own bone marrow and is alive and well on day+200 post HSCT. Our report highlights the transmission of dengue virus from donor to recipient through hematopoietic stem cell graft although rare but possible. We suggest that in tropical and subtropical countries where dengue is endemic, hematopoietic stem cell donors should be screened for it.
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http://dx.doi.org/10.1016/j.idcr.2021.e01220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282947PMC
July 2021

Investigation of Neuropathology after Nerve Release in Chronic Constriction Injury of Rat Sciatic Nerve.

Int J Mol Sci 2021 Apr 29;22(9). Epub 2021 Apr 29.

Division of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

Peripheral compressive neuropathy causes significant neuropathic pain, muscle weakness and prolong neuroinflammation. Surgical decompression remains the gold standard of treatment but the outcome is suboptimal with a high recurrence rate. From mechanical compression to chemical propagation of the local inflammatory signals, little is known about the distinct neuropathologic patterns and the genetic signatures after nerve decompression. In this study, controllable mechanical constriction forces over rat sciatic nerve induces irreversible sensorimotor dysfunction with sustained local neuroinflammation, even 4 weeks after nerve release. Significant gene upregulations are found in the dorsal root ganglia, regarding inflammatory, proapoptotic and neuropathic pain signals. Genetic profiling of neuroinflammation at the local injured nerve reveals persistent upregulation of multiple genes involving oxysterol metabolism, neuronal apoptosis, and proliferation after nerve release. Further validation of the independent roles of each signal pathway will contribute to molecular therapies for compressive neuropathy in the future.
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http://dx.doi.org/10.3390/ijms22094746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125611PMC
April 2021

Genetic variability in multidrug-resistant Mycobacterium tuberculosis isolates from patients with pulmonary tuberculosis in North India.

BMC Microbiol 2021 04 21;21(1):123. Epub 2021 Apr 21.

Department of Microbiology and Molecular Biology, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, Uttar Pradesh, 282004, India.

Background: Information on the genetic variability of drug resistant isolates of Mycobacterium tuberculosis is of paramount importance to understand transmission dynamics of disease and to improve TB control strategies. Despite of largest number of multidrug-resistant (MDR) tuberculosis cases (1, 30,000; 27% of the global burden), strains responsible for the expansion or development of drug-resistant Mycobacterium tuberculosis infections have been poorly characterized in India. Present study was aimed to investigate the genetic diversity in MDR isolates of Mycobacterium tuberculosis in North India.

Results: Spacer oligonucleotide typing (spoligotyping) was performed on 293 clinical MDR isolates of Mycobacterium tuberculosis recovered from cases of pulmonary tuberculosis from North India. Spoligotyping identified 74 distinct spoligotype patterns. Comparison with an international spoligotype database (spoldb4 database) showed that 240 (81.91%) and 32 (10.92%) strains displayed known and shared type patterns, while 21 (7.16%) strains displayed unique spoligotype patterns. Among the phylogeographic lineages, lineage 3 (East African-Indian) was found most predominant lineage (n = 159, 66.25%), followed by lineage 2 (East Asian; n = 34, 14.16%), lineage 1 (Indo-Oceanic; n = 30, 12.50%) and lineage 4 (Euro American; n = 17, 7.08%). Overall, CAS1_DEL (60.41%; SITs 2585, 26, 2694, 309, 381, 428, 1401, 141, 25, 1327) was found most pre-dominant spoligotype pattern followed by Beijing (14.16%; SITs255, 260, 1941, 269) and EAI3_IND (5.00%; SITs 298, 338, 11). The demographic and clinical characteristics were not found significantly associated with genotypic lineages of MDR-M.tuberculosis isolates recovered from pulmonary TB patients of North India.

Conclusions: Present study reveals high genetic diversity among the Mycobacterium tuberculosis isolates and highlights that SIT141/CAS1_Del followed by SIT26/ Beijing lineage is the most common spoligotype responsible for the development and transmission of MDR-TB in North India. The high presence of shared type and unique spoligotype patterns of MDR strains indicates epidemiological significance of locally evolved strains in ongoing transmission of MDR-TB within this community which needs to be further monitored using robust molecular tools with high discriminatory power.
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http://dx.doi.org/10.1186/s12866-021-02174-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059304PMC
April 2021

Reduction in MicroRNA-4488 Expression Induces NFκB Translocation in Venous Endothelial Cells Under Arterial Flow.

Cardiovasc Drugs Ther 2021 02;35(1):61-71

Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Purpose: Little is known about the molecular interactions among inflammatory responses that damage venous endothelial cells (vECs) during venous-to-arterial flow transition in vein graft diseases. Because arterial flow triggers excessive autophagy and inflammation in vECs, this study aimed to investigate the mediator of inflammation and methods to prevent vEC damage.

Methods: Arterial laminar shear stress (ALSS; 12 dynes/cm) was applied to vECs via in vitro and ex vivo perfusion systems. Inflammation in vECs was measured using inflammatory protein markers, NFκB translocation, cyclooxygenase-2 (COX-2) and COX-2 and NFκB promoter assays. The involvement of microRNA-4488 (miR-4488) was measured and confirmed by altering the specific miR using a miR-4488 mimic or inhibitor. The potential anti-inflammatory drugs and/or nitric oxide (NO) donor L-arginine (L-Arg) to prevent damage to vECs under ALSS was investigated.

Results: ALSS triggered reactive oxygen species production, excessive autophagy, COX-2 protein expression, and NFκB translocation during vEC inflammation. Reduction in miR-4488 expression was detected in inflamed vECs treated with LPS, lipopolysaccharide (LPS) TNFα, and ALSS. Transfection of miR-4488 mimic (50 nM) prior to ALSS application inhibited the accumulation of inflammatory proteins as well as the translocation of NFκB. Combined treatment of vECs with COX-2-specific inhibitor (SC-236) and L-Arg alleviated the ALSS-induced inflammatory responses. Protective effects of the combined treatment on vECs against ALSS-induced damage were abolished by the application of miR-4488 inhibitor.

Conclusion: We showed that ALSS triggered the COX-2/NFκB pathway to induce vEC inflammation with a reduction in miR-4488. Combination of SC-236 and L-Arg prevented ALSS-induced vEC damage, thus, shows high potential for preventing vein graft diseases.
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http://dx.doi.org/10.1007/s10557-020-06944-8DOI Listing
February 2021

Targeting AGTR1/NF-κB/CXCR4 axis by miR-155 attenuates oncogenesis in glioblastoma.

Neoplasia 2020 10 5;22(10):497-510. Epub 2020 Sep 5.

Molecular Oncology Laboratory, Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India; Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India. Electronic address:

Glioblastoma (GBM) represents the most aggressive malignancy of the central nervous system. Increased expression of Angiotensin II Receptor Type 1 (AGTR1) has been associated with proliferative and infiltrative properties of glioma cells. However, the underlying mechanism of AGTR1 upregulation in GBM is still unexplored. To understand the post-transcriptional regulation of AGTR1 in GBM, we screened 3'untranslated region (3'UTR) of AGTR1 for putative miRNA binding by using prediction algorithms. Interestingly, miR-155 showed conserved binding on the 3'UTR of AGTR1, subsequently confirmed by luciferase reporter assay. Furthermore, miR-155 overexpressing GBM cells show decrease in AGTR1 expression accompanied with reduced cell proliferation, invasion, foci formation and anchorage-independent growth. Strikingly, immunodeficient mice implanted with stable miR-155 overexpressing SNB19 cells show negligible tumor growth. Notably, miR-155 attenuates NF-κB signaling downstream of AGTR1 leading to reduced CXCR4 as well as AGTR1 levels. Mechanistically, miR-155 mitigates AGTR1-mediated angiogenesis, epithelial-to-mesenchymal transition, stemness, and MAPK signaling. Similar effects were observed by using pharmacological inhibitor of IκB Kinase (IKK) complex in multiple cell-based assays. Taken together, we established that miRNA-155 post-transcriptionally regulates AGTR1 expression, abrogates AGTR1/NF-κB/CXCR4 signaling axis and elicits pleiotropic anticancer effects in GBM. This study opens new avenues for using IKK inhibitors and miRNA-155 replacement therapies for the treatment of AGTR1-positive malignancies.
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http://dx.doi.org/10.1016/j.neo.2020.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481885PMC
October 2020

Nevus Comedonicus Suppurativa: A Report of a Novel Entity.

J Clin Aesthet Dermatol 2020 Jun 1;13(6):36-39. Epub 2020 Jun 1.

Drs. Sharma, Sahu, Dayal, and Yadav are with the Department of Dermatology at the Pandit B.D. Sharma Postgraduate Institute of Medical Sciences in Rohtak, Haryana, India.

Nevus comedonicus and hidradenitis suppurativa (HS) are disorders of the pilosebaceous unit sharing a similar pathogenesis of follicular occlusion. To our knowledge, less than 10 cases of HS-like lesions complicating nevus comedonicus have been reported. We describe a six-year-old female child with congenital linear nevus comedonicus in the left axilla and groin, complicated by recurrent HS-like lesions in the two years prior to presenting to our clinic. After a meticulous review of the literature, we propose a novel term, , for this clinical entity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442311PMC
June 2020

Denaturant Induced Equilibrium Unfolding and Conformational Transitional Studies of Germinated Fenugreek β-Amylase Revealed Molten Globule like State at Low pH.

Protein Pept Lett 2020 ;27(10):1046-1057

School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.

Background: β-Amylase (EC 3.2.1.2) is a maltogenic enzyme, which releases β-maltose from the non-reducing end of the substrates. The enzyme plays important roles for the production of vaccine, maltiol and maltose rich syrups. Apart from these applications the enzyme protects cells from abiotic as well as oxidative damage. The enzyme is βwell characterized in βplants and microbes and crystal structures of β-amylases βhave been βobtained from sweet potato, soybean and Bacillus cereus.

Objective: Find out correlation between structural and functional stability induced by change in pH, temperature and chaotropes.

Methods: Activity, intrinsic fluorescence, extrinsic fluorescence, near- and far- ultraviolet circular dichroism spectroscopic measurements were performed.

Results: Peaks about 208 nm and 222 nm obtained by near-ultraviolet circular dichroism correspond to α-helix whereas peak at 215 nm shows presence of β-sheet. At pH 2.0, absence of tertiary structures, exposed of hydrophobic regions and presence of substantial secondary structures, revealed the existence of molten globule like state. Temperature induced denaturation studies showed that the enzyme was stable up to 75 ºC and the process was found to be irreversible in nature. Chaotropes dependent equilibrium unfolding studies revealed that at low concentration of chaotropes, ellipticity and intrinsic fluorescence βintensity were βdecreased βwhereas βenzymatic activity remained unchanged, which revealed fenugreek β-amylase is multi-domains enzyme and catalytic βdomain βis more βstable compare to non-catalytic domain. Moreover, the transition was sigmoidal and non-coincidental.

Conclusion: Results indicate the probable existence of intermediate states that might perform significant role in physiological process and biotechnological applications.
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http://dx.doi.org/10.2174/0929866527666200403082721DOI Listing
January 2021

Androgen deprivation upregulates SPINK1 expression and potentiates cellular plasticity in prostate cancer.

Nat Commun 2020 01 20;11(1):384. Epub 2020 Jan 20.

Molecular Oncology Laboratory, Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, UP, 208016, India.

Emergence of an aggressive androgen receptor (AR)-independent neuroendocrine prostate cancer (NEPC) after androgen-deprivation therapy (ADT) is well-known. Nevertheless, the majority of advanced-stage prostate cancer patients, including those with SPINK1-positive subtype, are treated with AR-antagonists. Here, we show AR and its corepressor, REST, function as transcriptional-repressors of SPINK1, and AR-antagonists alleviate this repression leading to SPINK1 upregulation. Increased SOX2 expression during NE-transdifferentiation transactivates SPINK1, a critical-player for maintenance of NE-phenotype. SPINK1 elicits epithelial-mesenchymal-transition, stemness and cellular-plasticity. Conversely, pharmacological Casein Kinase-1 inhibition stabilizes REST, which in cooperation with AR causes SPINK1 transcriptional-repression and impedes SPINK1-mediated oncogenesis. Elevated levels of SPINK1 and NEPC markers are observed in the tumors of AR-antagonists treated mice, and in a subset of NEPC patients, implicating a plausible role of SPINK1 in treatment-related NEPC. Collectively, our findings provide an explanation for the paradoxical clinical-outcomes after ADT, possibly due to SPINK1 upregulation, and offers a strategy for adjuvant therapies.
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http://dx.doi.org/10.1038/s41467-019-14184-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971084PMC
January 2020

Lens culinaris β-galactosidase (Lsbgal): Insights into its purification, biochemical characterization and trisaccharides synthesis.

Bioorg Chem 2020 01 23;95:103543. Epub 2019 Dec 23.

School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi 221005, India. Electronic address:

Present work describes the purification of an acidic β-galactosidase from Lens culinaris (Lsbgal) to homogeneity via 857 fold with specific activity of 87 U/mg. The molecular mass of purified Lsbgal was estimated ~ 76 kDa by Size Exclusion Chromatography on Superdex-200 (ÄKTA purifier) and on SDS-PAGE, showed hetero-dimeric subunits i.e. 45 kDa and 30 kDa. The purified Lsbgal showed glycoproteinous nature when applied to Con-A Sepharose chromatography. Biochemical studies revealed that optimum condition for purified Lsbgal against o, nitophenyl β-d-galactopyranoside (ONPG) as a substrate was pH 3.0, 58 °C with an activation energy (E) 8.1 kcal/mole and Q 1.8. Lsbgal hydrolyses ONPG with K value 1.21 mM and V 90.90 µmoles/min/mg. Purified Lsbgal when incubated with high lactose concentration showed transgalactosylation activity which lead to the formation of trisaccharides as a major product of total GOS. Therefore, the purified Lsbgal could be used as potential alternative in food industry and would be further explicated for trisaccharides synthesis.
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http://dx.doi.org/10.1016/j.bioorg.2019.103543DOI Listing
January 2020

Comparative Evaluation of Mineral Trioxide Aggregate, Biodentine, and Calcium Phosphate Cement in Single Visit Apexification Procedure for Nonvital Immature Permanent Teeth: A Randomized Controlled Trial.

Int J Clin Pediatr Dent 2020 ;13(Suppl 1):S1-S13

Department of Paediatric and Preventive Dentistry, King George's Medical University, Lucknow, Uttar Pradesh, India.

Aim And Objective: This study assesses the efficacy of mineral trioxide aggregate (MTA), biodentine, and calcium phosphate cement (CPC) as single visit apexification agents for nonvital immature permanent teeth, both clinically and radiographically.

Materials And Methods: The study was conducted as a double-blinded randomized, controlled clinical trial after approval of the Institutional Ethical Committee of King George's Medical University, Lucknow, Uttar Pradesh, India, the approval letter (Ref. no. 81st ECM II B-Thesis/P24). A total of 60 patients in the age group of 6-15 years, fulfilling all the inclusion and exclusion criteria were enrolled for the study. Patients were randomly divided into three groups having 20 in each group.

Results: On the basis of present study, it can hence, be inferred that clinical success for MTA, biodentine and calcium phosphate cement in apexification was 100%. The radiographic outcomes of calcium phosphate cement showed better results as compared to MTA and biodentine at 9 months of follow-up periods.

Conclusion: These finding suggest that calcium phosphate cement can be used as a substitute for MTA and biodentine because of its comparable clinical and superior radiographic success.

How To Cite This Article: Yadav A, Chak RK, Khanna R. Comparative Evaluation of MTA, Biodentine and Calcium Phosphate Cement in Single Visit Apexification Procedure for Nonvital Immature Permanent Teeth: A Randomized Controlled Trial. Int J Clin Pediatr Dent 2020;13(S-1):S1-S13.
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http://dx.doi.org/10.5005/jp-journals-10005-1830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359875PMC
January 2020

Immobilization of fenugreek β-amylase onto functionalized graphene quantum dots (GQDs) using Box-Behnken design: Its biochemical, thermodynamic and kinetic studies.

Int J Biol Macromol 2020 Feb 13;144:170-182. Epub 2019 Dec 13.

School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi 221005, India. Electronic address:

β-Amylase was immobilized onto GQDs using 3-aminopropyltriethoxysilane and glutaraldehyde. Optimization was carried out by Box-Behnken design and binding was confirmed by SEM, AFM, FTIR and fluorescence microscopy. Predicted optimum immobilization efficiency (88.64%) was very close to actual (87.98%), which confirmed the success of the immobilization process. The immobilized enzyme showed maximum activity at pH 5.0 and 57 °C, whereas K and V were found to be 6.40 mg/mL and 714.28 μmol/min/mg, respectively. The enzyme retained 75% activity after 12 uses at 30 °C. Increased values of ΔG° ΔH°, half-life and activation energy of the enzyme inactivation (ΔE) revealed that thermo-stability increases after immobilization and the process followed first-order kinetics (r > 0.96). The activation energy of catalysis (ΔE) and ΔE for immobilized enzyme were 22.58 and 158.99 ± 1.10 kJ/mol, respectively which revealed that denaturation of the enzyme requires a higher amount of energy rather than catalysis. Thermodynamic and fluorescence spectroscopic studies revealed that the process is non-spontaneous (ΔG > 0) and endothermic (ΔH > 0) and occurred through protein unfolding rather than aggregation (ΔS > 0). Thus increase in thermo-stability of immobilized fenugreek β-amylase and non-toxic nature of GQDs could be exploited for maltose production in beverage, food and pharmaceutical industries.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.12.033DOI Listing
February 2020

Nanoparticles decorated carbon nanotubes as novel matrix: A comparative study of influences of immobilization on the catalytic properties of Lensculinarisβ-galactosidase (Lcβ-gal).

Int J Biol Macromol 2020 Feb 12;144:770-780. Epub 2019 Nov 12.

School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi 221005, India. Electronic address:

In the present study, Multiwalled carbon nanotubes (MWCNT) decorated with two different nanoparticles namely tungsten disulfide (WS) and tin oxide (SnO), nanocomposites (NCs) were synthesized via hydrothermal method. Spectroscopic studies showed that both synthesized NCs possess nearly same functional groups but MWCNT-SnO NCs are rich in O-functional group. Microscopic studies revealed that both NCs have different morphological microstructure. Lens culinaris β-galactosidase (Lcβ-gal) was immobilized using glutaraldehyde cross-linker resulted in immobilization efficiency of 91.5% and 88% with MWCNT-WS and MWCNT-SnO NCs, respectively. Remarkable increase in rate of hydrolysis of whey lactose has been observed with both NCs i.e. Lcβ-gal immobilized MWCNT-WS hydrolyzes the 97% whey lactose in 1.5 h while MWCNT-SnO showed maximum 92% of whey hydrolysis in 2 h at optimum conditions. Both nanobiocatalyst could serve as a promising candidates for dairy industries and would offer a potential platform for enzyme based biosensor fabrication.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.09.194DOI Listing
February 2020

Immobilization of fenugreek β-amylase onto functionalized tungsten disulfide nanoparticles using response surface methodology: Its characterization and interaction with maltose and sucrose.

Colloids Surf B Biointerfaces 2020 Jan 22;185:110600. Epub 2019 Oct 22.

School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi 221005, India. Electronic address:

In this communication, fenugreek β-amylase was immobilized onto functionalized tungsten disulfide nanoparticles through cross-linker glutaraldehyde and successful immobilization was confirmed by SEM, AFM and FTIR spectroscopy. To make the process economical and efficient, optimization of independent variables was carried out using Box-Behnken design of response surface methodology. Approximately similar predicted (85.6%) and experimental (84.2%) immobilization efficiency revealed that the model is suitable for design of space. Optimum temperature was calculated to be 60 °C. After immobilization, an increased K (2.12 times) and a decreased V (0.58 times), indicated inaccessibility of active site residues to the substrate. The immobilized enzyme retained 77% relative activity after 10 uses whereas 40% residual activity was obtained after 120 days. An increased half-life with concomitantly decreased kinetic rate constant revealed that the immobilized enzyme is more stable at a higher temperature and the process followed first-order kinetics (R > 0.93). The limit of detection for maltose and sucrose fluorescence biosensor was found to be 0.052 and 0.096 mM, respectively. Thermodynamic parameters such as changes in Gibbs free energy (ΔG < 0), enthalpy (ΔH > 0) and entropy (ΔS >0) revealed that the process is spontaneous and endothermic, driven by hydrophobic interactions. Thermo-stability data at higher temperature for the immobilized enzyme makes it a suitable candidate for industrial applications in the production of maltose in food and pharmaceutical industries. Furthermore, fluorescence biosensor could be used to detect and quantify maltose and sucrose to maintain the quality of industrial products.
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http://dx.doi.org/10.1016/j.colsurfb.2019.110600DOI Listing
January 2020

Nitrogen Doped Carbon Quantum Dots Modified by Lens culinaris β-Galactosidase as a Fluorescent Probe for Detection of Lactose.

J Fluoresc 2019 Sep 16;29(5):1213-1219. Epub 2019 Sep 16.

School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.

Nitrogen doped carbon quantum dots (NCQDs) were synthesized via hydrothermal route. The NCQDs are thermally and optically stable with high flouresence yield. For the synthesis of NCQDs, citric acid and urea was taken as carbon and nitrogen sources, respectively. The Transmission Electron Microscopy (TEM) of these quantum dots revealed nearly spherical shape and average size of 1.5 nm, which was calculated using Image J software. The quantum dots were also well-characterized using spectroscopic techniques such as FTIR, UV-Visible absorption and fluorescence. These synthesized and characterized dots were utilized for selective detection of lactose in Milli Q water. The bioprobe provide a wide linear range varying from (10.00-77.41) μM with limit of detection 11.36 μM and sensitivity equal to (0.0065 ± 0.0002) μM. Graphical Abstract.
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http://dx.doi.org/10.1007/s10895-019-02430-zDOI Listing
September 2019

Carbon nanotubes molybdenum disulfide 3D nanocomposite as novel nanoscaffolds to immobilize Lens culinaris β-galactosidase (Lsbgal): Robust stability, reusability, and effective bioconversion of lactose in whey.

Food Chem 2019 Nov 12;297:125005. Epub 2019 Jun 12.

School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi 221005, India. Electronic address:

Multiwalled carbon nanotubes molybdenum disulfide 3D nanocomposite (MWCNT-MoS NC) was successfully synthesized via eco-friendly hydrothermal method. The microstructural characterization of synthesized nanocomposite was carried out using different spectroscopic and microscopic techniques. Nanocomposite was activated using glutaraldehyde chemistry and used as a platform to immobilize Lens culinaris β-galactosidase (Lsbgal) which resulted in 93% of immobilization efficiency. Attachment of Lsbgal onto nanocomposite was confirmed by AFM, FE-SEM, FTIR, and CLSM. The nanobiocatalyst showed broadening in operational pH and temperature working range. Remarkable increase in thermal stability was observed as compared to soluble enzyme. Nanobiocatalyst showed outstanding increase in storage stability, retained 92% of residual activity over a period of 8 months. This offers good reusability as it retained ∼50% residual activity up to 21 reuses and exhibited higher rate of lactose hydrolysis in whey. MWCNT-MoS NC conjugated to biomolecules can serve as a potential platform for fabrication of lactose biosensor.
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http://dx.doi.org/10.1016/j.foodchem.2019.125005DOI Listing
November 2019

Epigenetic Silencing of miRNA-338-5p and miRNA-421 Drives SPINK1-Positive Prostate Cancer.

Clin Cancer Res 2019 May 26;25(9):2755-2768. Epub 2018 Dec 26.

Molecular Oncology Lab, Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, India.

Purpose: Serine peptidase inhibitor, Kazal type-1 (SPINK1) overexpression defines the second most recurrent and aggressive prostate cancer subtype. However, the underlying molecular mechanism and pathobiology of SPINK1 in prostate cancer remains largely unknown.

Experimental Design: miRNA prediction tools were employed to examine the 3'UTR for miRNA binding. Luciferase reporter assays were performed to confirm the 3'UTR binding of shortlisted miR-338-5p/miR-421. Furthermore, miR-338-5p/-421-overexpressing cancer cells (SPINK1-positive) were evaluated for oncogenic properties using cell-based functional assays and a mouse xenograft model. Global gene expression profiling was performed to unravel the biological pathways altered by miR-338-5p/-421. IHC and RNA hybridization were carried out on prostate cancer patients' tissue microarray for SPINK1 and expression, respectively. Chromatin immunoprecipitation assay was performed to examine EZH2 occupancy on the miR-338-5p/-421-regulatory regions. Bisulfite sequencing and methylated DNA immunoprecipitation were performed on prostate cancer cell lines and patients' specimens.

Results: We established a critical role of miRNA-338-5p/-421 in posttranscriptional regulation of . Ectopic expression of miRNA-338-5p/-421 in SPINK1-positive cells abrogates oncogenic properties including cell-cycle progression, stemness, and drug resistance, and shows reduced tumor burden and distant metastases in a mouse model. Importantly, we show that patients with SPINK1-positive prostate cancer exhibit increased EZH2 expression, suggesting its role in epigenetic silencing of miRNA-338-5p/-421. Furthermore, presence of CpG dinucleotide DNA methylation marks on the regulatory regions of miR-338-5p/-421 in SPINK1-positive prostate cancer cells and patients' specimens confirms epigenetic silencing.

Conclusions: Our findings revealed that miRNA-338-5p/-421 are epigenetically silenced in SPINK1-positive prostate cancer, although restoring the expression of these miRNAs using epigenetic drugs or synthetic mimics could abrogate SPINK1-mediated oncogenesis..
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http://dx.doi.org/10.1158/1078-0432.CCR-18-3230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517268PMC
May 2019

Current status of subspecies infection in animals & humans in India: What needs to be done?

Indian J Med Res 2016 Nov;144(5):661-671

Department of Microbiology and Molecular Biology, National JALMA Institute for Leprosy & Other Mycobacterial Diseases, Agra, India.

Mycobacterium avium subspecies paratuberculosis (MAP) has emerged as a major health problem for domestic livestock and human beings. Reduced per animal productivity of domestic livestock seriously impacts the economics of dairy farming globally. High to very high bioload of MAP in domestic livestock and also in the human population has been reported from north India. Presence of live MAP bacilli in commercial supplies of raw and pasteurized milk and milk products indicates its public health significance. MAP is not inactivated during pasteurization, therefore, entering into human food chain daily. Recovery of MAP from patients with inflammatory bowel disease or Crohn's disease and animal healthcare workers suffering with chronic gastrointestinal problems indicate a close association of MAP with a number of chronic and other diseases affecting human health. Higher bioload of MAP in the animals increases the risk of exposure to the human population with MAP. This review summarizes the current status of MAP infection in animals as well as in human beings and also highlights the prospects of effective management and control of disease in animals to reduce the risk of exposure to human population.
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http://dx.doi.org/10.4103/ijmr.IJMR_1401_14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393076PMC
November 2016

Targeting NF-kappa B Signaling by Artesunate Restores Sensitivity of Castrate-Resistant Prostate Cancer Cells to Antiandrogens.

Neoplasia 2017 04 19;19(4):333-345. Epub 2017 Mar 19.

Molecular Oncology Lab, Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur-208016, U.P., India. Electronic address:

Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells. Mechanistically, AS and Bic combination inhibits nuclear factor (NF)-κB signaling and decreases AR and/or AR-variant 7 expression via ubiquitin-mediated proteasomal degradation. The combination induces oxidative stress and apoptosis via survivin downregulation and caspase-3 activation, resulting in poly-ADP-ribose polymerase (PARP) cleavage. Moreover, preclinical castrate-resistant PC3 xenograft studies in NOD/SCID mice (n =28, seven per group) show remarkable tumor regression and significant reduction in lungs and bone metastases upon administering AS (50 mg/kg per day in two divided doses) and Bic (50 mg/kg per day) via oral gavage. Taken together, we for the first time provide a compelling preclinical rationale that AS could disrupt AR antagonist-mediated resistance observed in mCRPC. The current study also indicates that the therapeutic combination of Food and Drug Administration-approved AS or NF-κB inhibitors and AR antagonists may enhance the clinical efficacy in the treatment of mCRPC patients.
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http://dx.doi.org/10.1016/j.neo.2017.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358938PMC
April 2017

Carcinogenic and cocarcinogenic potential of cypermethrin on mouse skin.

Cancer Lett 2002 Aug;182(1):33-41

Environmental Carcinogenesis Division, Industrial Toxicology Research Centre, P.O. Box No. 80, M.G. Marg, Lucknow 226 001, India.

Cypermethrin (CYM), a synthetic pyrethroid insecticide, is used widely because of its high bio-efficacy and low mammalian toxicity. In the present set of investigations, CYM has been evaluated for it's carcinogenic and co-carcinogenic (tumour initiating and tumour promoting) potential in mouse skin model of carcinogenesis. The results revealed that CYM possess complete carcinogenic as well as tumour initiating and promoting potential in both the sexes of Swiss albino mice. At the end point, i.e. 32 weeks in a single dose (10 mg/kg body weight (wt.), once only), initiated mice, 9 out of 12 surviving males, and 10 out of 14 surviving females developed benign tumours, while a higher incidence of tumourigenesis was recorded in multiple dose-initiated (10 mg/kg body wt., total nine applications) group, where 7 out of 9 surviving male and 10 out of 13 surviving female mice developed tumours at the site of topical exposure. The application of CYM as a tumour promoter on 7,12-dimethylbenz(a)anthracene initiated animals induced tumour incidence in about 4 out of surviving 10 male and 5 out of surviving 13 female Swiss albino mice. CYM when tested for complete carcinogenic activity induced tumour formation in both male and female animals at all the three tested dose levels.
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http://dx.doi.org/10.1016/s0304-3835(02)00077-0DOI Listing
August 2002
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