Pritam Kumar Panda

All Publications

• Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes. Nature medicine Sahoo, S. S., Pastor, V. B., Goodings, C., Voss, R. K., Kozyra, E. J., Szvetnik, A., Noellke, P., Dworzak, M., Starý, J., Locatelli, F., Masetti, R., Schmugge, M., De Moerloose, B., Catala, A., Kállay, K., Turkiewicz, D., Hasle, H., Buechner, J., Jahnukainen, K., Ussowicz, M., Polychronopoulou, S., Smith, O. P., Fabri, O., Barzilai, S., de Haas, V., Baumann, I., Schwarz-Furlan, S., Niewisch, M. R., Sauer, M. G., Burkhardt, B., Lang, P., Bader, P., Beier, R., Müller, I., Albert, M. H., Meisel, R., Schulz, A., Cario, G., Panda, P. K., Wehrle, J., Hirabayashi, S., Derecka, M., Durruthy-Durruthy, R., Göhring, G., Yoshimi-Noellke, A., Ku, M., Lebrecht, D., Erlacher, M., Flotho, C., Strahm, B., Niemeyer, C. M., Wlodarski, M. W. 2021; 27 (10): 1806-1817

  Abstract

  Germline SAMD9 and SAMD9L mutations (SAMD9/9Lmut) predispose to myelodysplastic syndromes (MDS) with propensity for somatic rescue. In this study, we investigated a clinically annotated pediatric MDS cohort (n = 669) to define the prevalence, genetic landscape, phenotype, therapy outcome and clonal architecture of SAMD9/9L syndromes. In consecutively diagnosed MDS, germline SAMD9/9Lmut accounted for 8% and were mutually exclusive with GATA2 mutations present in 7% of the cohort. Among SAMD9/9Lmut cases, refractory cytopenia was the most prevalent MDS subtype (90%); acquired monosomy 7 was present in 38%; constitutional abnormalities were noted in 57%; and immune dysfunction was present in 28%. The clinical outcome was independent of germline mutations. In total, 67 patients had 58 distinct germline SAMD9/9Lmut clustering to protein middle regions. Despite inconclusive in silico prediction, 94% of SAMD9/9Lmut suppressed HEK293 cell growth, and mutations expressed in CD34+ cells induced overt cell death. Furthermore, we found that 61% of SAMD9/9Lmut patients underwent somatic genetic rescue (SGR) resulting in clonal hematopoiesis, of which 95% was maladaptive (monosomy 7 ± cancer mutations), and 51% had adaptive nature (revertant UPD7q, somatic SAMD9/9Lmut). Finally, bone marrow single-cell DNA sequencing revealed multiple competing SGR events in individual patients. Our findings demonstrate that SGR is common in SAMD9/9Lmut MDS and exemplify the exceptional plasticity of hematopoiesis in children.

  View details for DOI 10.1038/s41591-021-01511-6

  View details for PubMedID 34621053

  View details for PubMedCentralID PMC9330547

• Degradation of Alzheimer's Amyloid-β by a Catalytically Inactive Insulin-Degrading Enzyme. Journal of molecular biology Sahoo, B. R., Panda, P. K., Liang, W., Tang, W. J., Ahuja, R., Ramamoorthy, A. 2021; 433 (13): 166993

  Abstract

  It is known that insulin-degrading-enzyme (IDE) plays a crucial role in the clearance of Alzheimer's amyloid-β (Aβ). The cysteine-free IDE mutant (cf-E111Q-IDE) is catalytically inactive against insulin, but its effect on Aβ degradation is unknown that would help in the allosteric modulation of the enzyme activity. Herein, the degradation of Aβ(1-40) by cf-E111Q-IDE via a non-chaperone mechanism is demonstrated by NMR and LC-MS, and the aggregation of fragmented peptides is characterized using fluorescence and electron microscopy. cf-E111Q-IDE presented a reduced effect on the aggregation kinetics of Aβ(1-40) when compared with the wild-type IDE. Whereas LC-MS and diffusion ordered NMR spectroscopy revealed the generation of Aβ fragments by both wild-type and cf-E111Q-IDE. The aggregation propensities and the difference in the morphological phenotype of the full-length Aβ(1-40) and its fragments are explained using multi-microseconds molecular dynamics simulations. Notably, our results reveal that zinc binding to Aβ(1-40) inactivates cf-E111Q-IDE's catalytic function, whereas zinc removal restores its function as evidenced from high-speed AFM, electron microscopy, chromatography, and NMR results. These findings emphasize the catalytic role of cf-E111Q-IDE on Aβ degradation and urge the development of zinc chelators as an alternative therapeutic strategy that switches on/off IDE's function.

  View details for DOI 10.1016/j.jmb.2021.166993

  View details for PubMedID 33865867

  View details for PubMedCentralID PMC8169600

• Structure-based drug designing and immunoinformatics approach for SARS-CoV-2. Science advances Panda, P. K., Arul, M. N., Patel, P., Verma, S. K., Luo, W., Rubahn, H. G., Mishra, Y. K., Suar, M., Ahuja, R. 2020; 6 (28): eabb8097

  Abstract

  The prevalence of respiratory illness caused by the novel SARS-CoV-2 virus associated with multiple organ failures is spreading rapidly because of its contagious human-to-human transmission and inadequate globalhealth care systems. Pharmaceutical repurposing, an effective drug development technique using existing drugs, could shorten development time and reduce costs compared to those of de novo drug discovery. We carried out virtual screening of antiviral compounds targeting the spike glycoprotein (S), main protease (Mpro), and the SARS-CoV-2 receptor binding domain (RBD)-angiotensin-converting enzyme 2 (ACE2) complex of SARS-CoV-2. PC786, an antiviral polymerase inhibitor, showed enhanced binding affinity to all the targets. Furthermore, the postfusion conformation of the trimeric S protein RBD with ACE2 revealed conformational changes associated with PC786 drug binding. Exploiting immunoinformatics to identify T cell and B cell epitopes could guide future experimental studies with a higher probability of discovering appropriate vaccine candidates with fewer experiments and higher reliability.

  View details for DOI 10.1126/sciadv.abb8097

  View details for PubMedID 32691011

  View details for PubMedCentralID PMC7319274

• Investigation of the Factors That Dictate the Preferred Orientation of Lexitropsins in the Minor Groove of DNA. Journal of medicinal chemistry Alniss, H. Y., Witzel, I. I., Semreen, M. H., Panda, P. K., Mishra, Y. K., Ahuja, R., Parkinson, J. A. 2019; 62 (22): 10423-10440

  Abstract

  Lexitropsins are small molecules that bind to the minor groove of DNA as antiparallel dimers in a specific orientation. These molecules have shown therapeutic potential in the treatment of several diseases; however, the development of these molecules to target particular genes requires revealing the factors that dictate their preferred orientation in the minor grooves, which to date have not been investigated. In this study, a distinct structure (thzC) was carefully designed as an analog of a well-characterized lexitropsin (thzA) to reveal the factors that dictate the preferred binding orientation. Comparative evaluations of the biophysical and molecular modeling results of both compounds showed that the position of the dimethylaminopropyl group and the orientation of the amide links of the ligand with respect to the 5'-3'-ends; dictate the preferred orientation of lexitropsins in the minor grooves. These findings could be useful in the design of novel lexitropsins to selectively target specific genes.

  View details for DOI 10.1021/acs.jmedchem.9b01534

  View details for PubMedID 31658809

• Azacitidine is effective for targeting leukemia-initiating cells in juvenile myelomonocytic leukemia. Leukemia Krombholz, C. F., Gallego-Villar, L., Sahoo, S. S., Panda, P. K., Wlodarski, M. W., Aumann, K., Hartmann, M., Lipka, D. B., Daskalakis, M., Plass, C., Niemeyer, C. M., Erlacher, M., Flotho, C. 2019; 33 (7): 1805-1810

  View details for DOI 10.1038/s41375-018-0343-2

  View details for PubMedID 30679798

• Monosomy 7 As the Initial Hit Followed By Sequential Acquisition of <i>SETBP1</i> and <i>ASXL1</i> Driver Mutations in Childhood Myelodysplastic Syndromes Loyola, V., Panda, P., Sahoo, S., Szvetnik, E., Kozyra, E. J., Voss, R. K., Lebrecht, D., Wehrle, J., Erlacher, M., Stary, J., Flotho, C., Goehring, G., Schlegelberger, B., Strahm, B., Niemeyer, C., Wlodarski, M. W. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-118910

  View details for Web of Science ID 000454837600159

• SAMD9 and SAMD9L Germline Disorders in Patients Enrolled in Studies of the European Working Group of MDS in Childhood (EWOG-MDS): Prevalence, Outcome, Phenotype and Functional Characterisation Sahoo, S., Loyola, V., Panda, P., Szvetnik, E., Kozyra, E. J., Voss, R. K., Lebrecht, D., Barzilai, S., Buchner, J., Catala, A., De Moerloose, B., Dworzak, M., Fabri, O., Hasle, H., Jahnukainen, K., Kallay, K., Locatelli, F., Masetti, R., Polychronopoulou, S., Schmugge, M., Stary, J., Smith, O. P., Turkiewicz, D., Ussowicz, M., van den Heuvel-Eibrink, M. M., Noellke, P., Goehring, G., Erlacher, M., Flotho, C., Strahm, B., Niemeyer, C., Wlodarski, M. W. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-118389

  View details for Web of Science ID 000454837602021

• A novel professional-use synergistic peel technology to reduce visible hyperpigmentation on face: Clinical evidence and mechanistic understanding by computational biology and optical biopsy. Experimental dermatology Bhardwaj, V., Handler, M. Z., Mao, J., Azadegan, C., Panda, P. K., Breunig, H. G., Wenskus, I., Diaz, I., König, K. 2024; 33 (4): e15069

  Abstract

  Topicals and chemical peels are the standard of care for management of facial hyperpigmentation. However, traditional therapies have come under recent scrutiny, such as topical hydroquinone (HQ) has some regulatory restrictions, and high concentration trichloroacetic acid (TCA) peel pose a risk in patients with skin of colour. The objective of our research was to identify, investigate and elucidate the mechanism of action of a novel TCA- and HQ-free professional-use chemical peel to manage common types of facial hyperpigmentation. Using computational modelling and in vitro assays on tyrosinase, we identified proprietary multi-acid synergistic technology (MAST). After a single application on human skin explants, MAST peel was found to be more effective than a commercial HQ peel in inhibiting melanin (histochemical imaging and gene expression). All participants completed the case study (N = 9) without any adverse events. After administration of the MAST peel by a dermatologist, the scoring and VISIA photography reported improvements in hyperpigmentation, texture and erythema, which could be linked to underlying pathophysiological changes in skin after peeling, visualized by non-invasive optical biopsy of face. Using reflectance confocal microscopy (VivaScope®) and multiphoton tomography (MPTflex™), we observed reduction in melanin, increase in metabolic activity of keratinocytes, and no signs of inflammatory cells after peeling. Subsequent swabbing of the cheek skin found no microbiota dysbiosis resulting from the chemical peel. The strong efficacy with minimum downtime and no adverse events could be linked to the synergistic action of the ingredients in the novel HQ- and TCA-free professional peel technology.

  View details for DOI 10.1111/exd.15069

  View details for PubMedID 38568090

• Network analysis of chromophore binding site in LOV domain. Computers in biology and medicine Panda, R., Panda, P. K., Krishnamoorthy, J., Kar, R. K. 2023; 161: 106996

  Abstract

  Photoreceptor proteins are versatile toolbox for developing biosensors for optogenetic applications. These molecular tools get activated upon illumination of blue light, which in turn offers a non-invasive method for gaining high spatiotemporal resolution and precise control of cellular signal transduction. The Light-Oxygen-Voltage (LOV) domain family of proteins is a well-recognized system for constructing optogenetic devices. Translation of these proteins into efficient cellular sensors is possible by tuning their photochemistry lifetime. However, the bottleneck is the need for more understanding of the relationship between the protein environment and photocycle kinetics. Significantly, the effect of the local environment also modulates the electronic structure of chromophore, which perturbs the electrostatic and hydrophobic interaction within the binding site. This work highlights the critical factors hidden in the protein networks, linking with their experimental photocycle kinetics. It presents an opportunity to quantitatively examine the alternation in chromophore's equilibrium geometry and identify details which have substantial implications in designing synthetic LOV constructs with desirable photocycle efficiency.

  View details for DOI 10.1016/j.compbiomed.2023.106996

  View details for PubMedID 37201443

• Nanocarrier vaccine therapeutics for global infectious and chronic diseases MATERIALS TODAY Simnani, F., Singh, D., Patel, P., Choudhury, A., Sinha, A., Nandi, A., Samal, S., Verma, S. K., Panda, P. 2023; 66: 371-408

  View details for DOI 10.1016/j.mattod.2023.04.008

  View details for Web of Science ID 001028923400001

• Putative targeting by BX795 causes decrease in protein kinase C protein levels and inhibition of HSV1 infection. Antiviral research Suryawanshi, R. K., Patil, C. D., Wu, D., Panda, P. K., Singh, S. K., Volety, I., Ahuja, R., Mishra, Y. K., Shukla, D. 2022; 208: 105454

  Abstract

  Herpes simplex virus type-1 (HSV1) exploits cellular machinery for its own replicative advantage. Current treatment modalities against HSV1 cause toxicity and drug resistance issues. In the search for alternative forms of treatment, we have uncovered a small molecule, BX795, as a candidate drug with strong antiviral potential owing to its multitargeted mode of action. In this study, we show that in addition to a previously known mechanism of action, BX795 can directly interact with the proviral host factor protein kinase C (PKC) in silico. When administered to HSV1 or mock infected human corneal epithelial (HCE) cells, BX795 significantly reduces the protein level and perinuclear localization of proviral PKC-α and PKC-ζ isoforms. This activity closely mimics that of a known PKC inhibitor, Bisindolylmaleimide I (BIM I), which also inhibits viral replication. Taken together our studies demonstrate a previously unknown mechanism by which BX795 exerts its antiviral potential.

  View details for DOI 10.1016/j.antiviral.2022.105454

  View details for PubMedID 36334637

• Phage delivered CRISPR-Cas system to combat multidrug-resistant pathogens in gut microbiome. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Nath, A., Bhattacharjee, R., Nandi, A., Sinha, A., Kar, S., Manoharan, N., Mitra, S., Mojumdar, A., Panda, P. K., Patro, S., Dutt, A., Ahuja, R., Verma, S. K., Suar, M. 2022; 151: 113122

  Abstract

  The Host-microbiome interactions that exist inside the gut microbiota operate in a synergistic and abnormal manner. Additionally, the normal homeostasis and functioning of gut microbiota are frequently disrupted by the intervention of Multi-Drug Resistant (MDR) pathogens. CRISPR-Cas (CRISPR-associated protein with clustered regularly interspersed short palindromic repeats) recognized as a prokaryotic immune system has emerged as an effective genome-editing tool to edit and delete specific microbial genes for the expulsion of bacteria through bactericidal action. In this review, we demonstrate many functioning CRISPR-Cas systems against the anti-microbial resistance of multiple pathogens, which infiltrate the gastrointestinal tract. Moreover, we discuss the advancement in the development of a phage-delivered CRISPR-Cas system for killing a gut MDR pathogen. We also discuss a combinatorial approach to use bacteriophage as a delivery system for the CRISPR-Cas gene for targeting a pathogenic community in the gut microbiome to resensitize the drug sensitivity. Finally, we discuss engineered phage as a plausible potential option for the CRISPR-Cas system for pathogenic killing and improvement of the efficacy of the system.

  View details for DOI 10.1016/j.biopha.2022.113122

  View details for PubMedID 35594718

• Antibodies Against Phosphorylcholine Among 60-Year-Olds: Clinical Role and Simulated Interactions. Frontiers in cardiovascular medicine Samal, S. K., Panda, P. K., Vikström, M., Leander, K., de Faire, U., Ahuja, R., Frostegård, J. 2022; 9: 809007

  Abstract

  Antibodies against phosphorylcholine (anti-PC) are implicated as protection markers in atherosclerosis, cardiovascular disease (CVD), and other chronic inflammatory conditions. Mostly, these studies have been focused on IgM. In this study, we determined IgG, IgG1, and IgG2 anti-PC among 60-year-olds.Based on a 7-year follow-up of 60-year-olds (2,039 men and 2,193 women) from Stockholm County, we performed a nested case-control study of 209 incident CVD cases with 620 age- and sex-matched controls. Anti-PC was determined using ELISA. We predicted the binding affinity of PC with our fully human, in-house-produced IgG1 anti-PC clones (i.e., A01, D05, and E01) using the molecular docking and molecular dynamics simulation approach, to retrieve information regarding binding properties to PC.After adjustment for confounders, IgG and IgG2 anti-PC showed some significant associations, but IgG1 anti-PC was much stronger as a protection marker. IgG1 anti-PC was associated with an increased risk of CVD below 33rd, 25th, and 10th percentile and of stroke below 33rd and 25th, and of myocardial infarction (MI) below 10th percentile. Among men, a strong association with stroke was determined below the 33rd percentile [HR 9.20, CI (2.22-38.12); p = 0.0022]. D05 clone has higher binding affinity followed by E01 and A01 using molecular docking and further have been confirmed during the course of 100 ns simulation. The stability of the D05 clone with PC was substantially higher.IgG1 anti-PC was a stronger protection marker than IgG anti-PC and IgG2 anti-PC and also separately for men. The molecular modeling approach helps in identifying the intrinsic properties of anti-PC clones and atomistic interactions with PC.

  View details for DOI 10.3389/fcvm.2022.809007

  View details for PubMedID 35479288

  View details for PubMedCentralID PMC9035555

• Nanocarrier cancer therapeutics with functional stimuli-responsive mechanisms. Journal of nanobiotechnology Kaushik, N., Borkar, S. B., Nandanwar, S. K., Panda, P. K., Choi, E. H., Kaushik, N. K. 2022; 20 (1): 152

  Abstract

  Presently, nanocarriers (NCs) have gained huge attention for their structural ability, good biocompatibility, and biodegradability. The development of effective NCs with stimuli-responsive properties has acquired a huge interest among scientists. When developing drug delivery NCs, the fundamental goal is to tackle the delivery-related problems associated with standard chemotherapy and to carry medicines to the intended sites of action while avoiding undesirable side effects. These nanocarriers were able of delivering drugs to tumors through regulating their pH, temperature, enzyme responsiveness. With the use of nanocarriers, chemotherapeutic drugs could be supplied to tumors more accurately that can equally encapsulate and deliver them. Material carriers for chemotherapeutic medicines are discussed in this review keeping in viewpoint of the structural properties and targeting methods that make these carriers more therapeutically effective, in addition to metabolic pathways triggered by drug-loaded NCs. Largely, the development of NCs countering to endogenous and exogenous stimuli in tumor regions and understanding of mechanisms would encourage the progress for tumor therapy and precision diagnosis in future.

  View details for DOI 10.1186/s12951-022-01364-2

  View details for PubMedID 35331246

  View details for PubMedCentralID PMC8944113

• Dynamical modeling of miR-34a, miR-449a, and miR-16 reveals numerous DDR signaling pathways regulating senescence, autophagy, and apoptosis in HeLa cells. Scientific reports Gupta, S., Panda, P. K., Hashimoto, R. F., Samal, S. K., Mishra, S., Verma, S. K., Mishra, Y. K., Ahuja, R. 2022; 12 (1): 4911

  Abstract

  Transfection of tumor suppressor miRNAs such as miR-34a, miR-449a, and miR-16 with DNA damage can regulate apoptosis and senescence in cancer cells. miR-16 has been shown to influence autophagy in cervical cancer. However, the function of miR-34a and miR-449a in autophagy remains unknown. The functional and persistent G1/S checkpoint signaling pathways in HeLa cells via these three miRNAs, either synergistically or separately, remain a mystery. As a result, we present a synthetic Boolean network of the functional G1/S checkpoint regulation, illustrating the regulatory effects of these three miRNAs. To our knowledge, this is the first synthetic Boolean network that demonstrates the advanced role of these miRNAs in cervical cancer signaling pathways reliant on or independent of p53, such as MAPK or AMPK. We compared our estimated probability to the experimental data and found reasonable agreement. Our findings indicate that miR-34a or miR-16 may control senescence, autophagy, apoptosis, and the functional G1/S checkpoint. Additionally, miR-449a can regulate just senescence and apoptosis on an individual basis. MiR-449a can coordinate autophagy in HeLa cells in a synergistic manner with miR-16 and/or miR-34a.

  View details for DOI 10.1038/s41598-022-08900-y

  View details for PubMedID 35318393

  View details for PubMedCentralID PMC8941124

• The Hha-TomB toxin-antitoxin module in Salmonella enterica serovar Typhimurium limits its intracellular survival profile and regulates host immune response. Cell biology and toxicology Paul, P., Patel, P., Verma, S. K., Mishra, P., Sahu, B. R., Panda, P. K., Kushwaha, G. S., Senapati, S., Misra, N., Suar, M. 2022; 38 (1): 111-127

  Abstract

  The key to bacterial virulence relies on an exquisite balance of signals between microbe and hosts. Bacterial toxin-antitoxin (TA) system is known to play a vital role in response to stress adaptation, drug resistance, biofilm formation, intracellular survival, persistence as well as pathogenesis. In the present study, we investigated the role of Hha-TomB TA system in regulating virulence of Salmonella enterica serovar Typhimurium (S. Typhimurium) in a host model system, where we showed that deletion of hha and tomB genes displayed impaired cell adhesion, invasion, and uptake. The isogenic hha and tomB mutant strain was also found to be deficient in intracellular replication in vitro, with a highly repressed Salmonella Pathogenicity Island-2 (SPI-2) genes and downregulation of Salmonella Pathogenicity Island-1 (SPI-1) genes. In addition, the Δhha and ΔtomB did not show acute colitis in C57BL/6 mice and displayed less dissemination to systemic organs followed by their cecal pathology. The TA mutants also showed reduction in serum cytokine and nitric oxide levels both in vitro and in vivo. However, the inflammation phenotype was restored on complementing strain of TA gene to its mutant strain. In silico studies depicted firm interaction of Hha-TomB complex and the regulatory proteins, namely, SsrA, SsrB, PhoP, and PhoQ. Overall, we demonstrate that this study of Hha-TomB TA system is one of the prime regulating networks essential for S. Typhimurium pathogenesis. 1. Role of Hha-TomB toxin-antitoxin (TA) system in Salmonella pathogenesis was examined. 2. The TA mutants resulted in impaired invasion and intracellular replication in vitro. 3. The TA mutants displayed alteration in SPI-1 and SPI-2 regulatory genes inside host cells. 4. Mutation in TA genes also limited systemic colonization and inflammatory response in vivo.

  View details for DOI 10.1007/s10565-021-09587-z

  View details for PubMedID 33651227

  View details for PubMedCentralID 7269643

• Plasmodium falciparum HSP40 protein eCiJp traffics to the erythrocyte cytoskeleton and interacts with the human HSP70 chaperone HSPA1. FEBS letters Sahu, W., Bai, T., Panda, P. K., Mazumder, A., Das, A., Ojha, D. K., Verma, S. K., Elangovan, S., Reddy, K. S. 2022; 596 (1): 95-111

  Abstract

  Renovation of host erythrocytes is vital for pathogenesis by Plasmodium falciparum. These changes are mediated by parasite proteins that translocate beyond the parasitophorous vacuolar membrane in an unfolded state, suggesting protein folding by chaperones is imperative for the functionality of exported proteins. We report a type IV P. falciparum heat-shock protein 40, PF11_0034, that localizes to the cytoplasmic side of J-dots and interacts with the erythrocyte cytoskeleton, and therefore named eCiJp (erythrocyte cytoskeleton-interacting J protein). Recombinant eCiJp binds to the human heat-shock protein 70 HsHSPA1 and promotes its ATPase activity. In addition, eCiJp could suppress protein aggregation. Our data suggest that eCiJp recruits HsHSPA1 to the host erythrocyte cytoskeleton, where it may become involved in remodeling of the erythrocyte cytoskeleton and/or folding of exported parasite proteins.

  View details for DOI 10.1002/1873-3468.14255

  View details for PubMedID 34890056

• Molecular nanoinformatics approach assessing the biocompatibility of biogenic silver nanoparticles with channelized intrinsic steatosis and apoptosis GREEN CHEMISTRY Panda, P., Kumari, P., Patel, P., Samal, S., Mishra, S., Tambuwala, M. M., Dutt, A., Hilscherova, K., Mishra, Y., Varma, R. S., Suar, M., Ahuja, R., Verma, S. K. 2022; 24 (3): 1190-1210

  View details for DOI 10.1039/d1gc04103g

  View details for Web of Science ID 000741040300001

• Publisher Correction: Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes. Nature medicine Sahoo, S. S., Pastor, V. B., Goodings, C., Voss, R. K., Kozyra, E. J., Szvetnik, A., Noellke, P., Dworzak, M., Starý, J., Locatelli, F., Masetti, R., Schmugge, M., De Moerloose, B., Catala, A., Kállay, K., Turkiewicz, D., Hasle, H., Buechner, J., Jahnukainen, K., Ussowicz, M., Polychronopoulou, S., Smith, O. P., Fabri, O., Barzilai, S., de Haas, V., Baumann, I., Schwarz-Furlan, S., Niewisch, M. R., Sauer, M. G., Burkhardt, B., Lang, P., Bader, P., Beier, R., Müller, I., Albert, M. H., Meisel, R., Schulz, A., Cario, G., Panda, P. K., Wehrle, J., Hirabayashi, S., Derecka, M., Durruthy-Durruthy, R., Göhring, G., Yoshimi-Noellke, A., Ku, M., Lebrecht, D., Erlacher, M., Flotho, C., Strahm, B., Niemeyer, C. M., Wlodarski, M. W. 2021; 27 (12): 2248

  View details for DOI 10.1038/s41591-021-01632-y

  View details for PubMedID 34799732

• Autoimmunity roots of the thrombotic events after COVID-19 vaccination. Autoimmunity reviews Elrashdy, F., Tambuwala, M. M., Hassan, S. S., Adadi, P., Seyran, M., Abd El-Aziz, T. M., Rezaei, N., Lal, A., Aljabali, A. A., Kandimalla, R., Bazan, N. G., Azad, G. K., Sherchan, S. P., Choudhury, P. P., Serrano-Aroca, Á., Takayama, K., Chauhan, G., Pizzol, D., Barh, D., Panda, P. K., Mishra, Y. K., Palù, G., Lundstrom, K., Redwan, E. M., Uversky, V. N. 2021; 20 (11): 102941

  Abstract

  Although vaccination represents the most promising way to stop or contain the coronavirus disease 2019 (COVID-19) pandemic and safety and effectiveness of available vaccines were proven, a small number of individuals who received anti-SARS-CoV-2 vaccines developed a prothrombotic syndrome. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can be triggered by the adenoviral vector-based vaccine, whereas lipid nanoparticle-mRNA-based vaccines can induce rare cases of deep vein thrombosis (DVT). Although the main pathogenic mechanisms behind this rare phenomenon have not yet been identified, both host and vaccine factors might be involved, with pathology at least in part being related to the vaccine-triggered autoimmune reaction. In this review, we are considering some aspects related to pathogenesis, major risk factors, as well as peculiarities of diagnosis and treatment of this rare condition.

  View details for DOI 10.1016/j.autrev.2021.102941

  View details for PubMedID 34508917

  View details for PubMedCentralID PMC8426137

• Bio-acceptable 0D and 1D ZnO nanostructures for cancer diagnostics and treatment MATERIALS TODAY Ortiz-Casas, B., Galdamez-Martinez, A., Gutierrez-Flores, J., Baca Ibanez, A., Panda, P., Santana, G., Astudillo de la Vega, H., Suar, M., Gutierrez Rodelo, C., Kaushik, A., Mishra, Y., Dutt, A. 2021; 50: 533-569

  View details for DOI 10.1016/j.mattod.2021.07.025This

  View details for Web of Science ID 000731398000005

• The mechanism behind flaring/triggering of autoimmunity disorders associated with COVID-19. Autoimmunity reviews Redwan, E. M., Alghamdi, M. F., El-Aziz, T. M., Adadi, P., Aljabali, A. A., Attrish, D., Azad, G. K., Baetas-da-Cruz, W., Barh, D., Bazan, N. G., Brufsky, A. M., Chauhan, G., Hassan, S. K., Kandimalla, R., Lal, A., Lundstrom, K., Mishra, Y. K., Choudhury, P. P., Palù, G., Panda, P. K., Pizzol, D., Rezaei, N., Serrano-Aroca, Á., Sherchan, S. P., Seyran, M., Takayama, K., Tambuwala, M. M., Uhal, B. D., Uversky, V. N. 2021; 20 (10): 102909

  View details for DOI 10.1016/j.autrev.2021.102909

  View details for PubMedID 34274539

  View details for PubMedCentralID PMC8282442

• Effects of Atorvastatin on T-Cell Activation and Apoptosis in Systemic Lupus Erythematosus and Novel Simulated Interactions With C-Reactive Protein and Interleukin 6. ACR open rheumatology Sun, J., Kumar Panda, P., Kumar Samal, S., Ahuja, R., Ajeganova, S., Hafström, I., Liu, A., Frostegård, J. 2021; 3 (9): 642-653

  Abstract

  We study activation of T helper 17 (Th17) and regulatory T (Treg) cells and induction of apoptosis in cells from patients with systemic lupus erythematosus (SLE) compared with controls and effects of atorvastatin and its simulated interactions with other compounds.Mononuclear cells from 10 patients with SLE and 10 controls were cultured in conditions that induce Th17 and/or Treg cell polarization and/or apoptosis and were studied by FACScan. Gene expression was determined by quantitative real-time reverse transcription-polymerase chain reaction. Cytokines in plasma were determined by enzyme-linked immunosorbent assay. The Search Tool for Interactions of Chemicals (STITCH) was used to retrieve information regarding the binding properties of atorvastatin.Among patients with SLE, the proportion of Th17 (CD4+ IL17+ ) cells was higher compared with controls after activation, with Th17 or Treg polarizing cytokines, phorbol myristate acetate, and ionomycin. In contrast, Treg cells (CD4+ CD25+ CD127dim/- ) frequencies were lower. CD95 stimulation induced relatively more apoptosis in Treg cells and less in Th17 cells, as compared with controls. Addition of atorvastatin normalized Th17/Treg cell balance and apoptosis induction. Accordingly, the ratio of RORC/FoxP3 decreased in patients with SLE. Interleukin 17 and interleukin 6 (IL-6) levels were increased in patients with SLE. Atorvastatin interacted strongly with C-reactive protein (CRP) and also significantly with IL-6.There is a higher proportion of Th17 cells and a lower proportion of Treg cells in patients with SLE after activation. Th17 cells were more resistant than Treg cells to CD95-induced apoptosis in SLE. Atorvastatin normalized these effects. Our findings reveal a novel mechanism behind the imbalance of Th17/Treg cells with implications for treatment in SLE. We determine for the first time simulated interaction between atorvastatin, CRP, and IL-6, implying a novel role of atorvastatin.

  View details for DOI 10.1002/acr2.11305

  View details for PubMedID 34302321

  View details for PubMedCentralID PMC8449041

• A unique view of SARS-CoV-2 through the lens of ORF8 protein. Computers in biology and medicine Hassan, S. S., Aljabali, A. A., Panda, P. K., Ghosh, S., Attrish, D., Choudhury, P. P., Seyran, M., Pizzol, D., Adadi, P., Abd El-Aziz, T. M., Soares, A., Kandimalla, R., Lundstrom, K., Lal, A., Azad, G. K., Uversky, V. N., Sherchan, S. P., Baetas-da-Cruz, W., Uhal, B. D., Rezaei, N., Chauhan, G., Barh, D., Redwan, E. M., Dayhoff, G. W., Bazan, N. G., Serrano-Aroca, Á., El-Demerdash, A., Mishra, Y. K., Palu, G., Takayama, K., Brufsky, A. M., Tambuwala, M. M. 2021; 133: 104380

  Abstract

  Immune evasion is one of the unique characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributed to its ORF8 protein. This protein modulates the adaptive host immunity through down-regulation of MHC-1 (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the host's interferon-mediated antiviral response. To understand the host's immune perspective in reference to the ORF8 protein, a comprehensive study of the ORF8 protein and mutations possessed by it have been performed. Chemical and structural properties of ORF8 proteins from different hosts, such as human, bat, and pangolin, suggest that the ORF8 of SARS-CoV-2 is much closer to ORF8 of Bat RaTG13-CoV than to that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 in SARS-CoV-2 can be grouped into four classes based on their predicted effects (Hussain et al., 2021) [1]. Based on the geo-locations and timescale of sample collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were found upon sequence similarity analyses and consideration of the amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of the rapidly evolving SARS-CoV-2 through the ORF8.

  View details for DOI 10.1016/j.compbiomed.2021.104380

  View details for PubMedID 33872970

  View details for PubMedCentralID PMC8049180

• Green synthesized MgO nanoparticles infer biocompatibility by reducing in vivo molecular nanotoxicity in embryonic zebrafish through arginine interaction elicited apoptosis. The Science of the total environment Verma, S. K., Nisha, K., Panda, P. K., Patel, P., Kumari, P., Mallick, M. A., Sarkar, B., Das, B. 2020; 713: 136521

  Abstract

  Increasing demand for magnesium oxide (MgO) nanoparticles (NP) due to their extensive use in different physical and biological applications has raised concern on their biocompatibility and toxicity to human health and ecological safety. This has instigated quest for detailed information on their toxicity mechanism, along with ecofriendly synthesis as a potential solution. This study explores the toxicity of MgO NP at the molecular level using embryonic zebrafish (Danio rerio) and depicts the green synthesis of MgO (G-MgO) NP using the extract from a medicinal plant Calotropis gigantea. Synthesized G-MgO NP were characterized using microscopy, spectroscopy, and dynamic light scattering. Stable 55 ± 10 nm sized MgO NP were generated with a zeta potential of 45 ± 15 mV and hydrodynamic size 110 ± 20 nm. UV-Vis spectrum showed a standard peak at 357 nm. Comparative cellular toxicity analysis showed higher biocompatibility of G-MgO NP compared to MgO NP with reference to the morphological changes, notochord development, and heartbeat rate in embryonic zebrafish LC50 of G-MgO NP was 520 μg/mL compared to 410 μg/mL of MgO NP. Molecular toxicity investigation revealed that the toxic effects of MgO NP was mainly due to the influential dysregulation in oxidative stress leading to apoptosis because of the accumulation and internalization of nanoparticles and their interaction with cellular proteins like Sod1 and p53, thereby affecting structural integrity and functionality. The study delineated the nanotoxicity of MgO NP and suggests the adoption and use of new green methodology for future production.

  View details for DOI 10.1016/j.scitotenv.2020.136521

  View details for PubMedID 31951838

• Landscape of ROD9 Island: Functional annotations and biological network of hypothetical proteins in Salmonella enterica. Computational biology and chemistry Soni, N., Swain, S. K., Kant, R., Singh, A., Ravichandran, R., Verma, S. K., Panda, P. K., Suar, M. 2019; 83: 107110

  Abstract

  Salmonella, an Enterobacteria is a therapeutically important pathogen for the host. The advancement of genome sequencing of S. enterica serovar Enteritidis have identified a distinct ROD9 pathogenic island, imparting virulence. The occurrence of 17 ROD9 hypothetical proteins, necessitates subsequent bioinformatics approach for structural and functional aspects of protein-protein relations or networks in different pathogenic phenotypes express. A collective analysis using predictive bioinformatics tools that includes NCBI-BLASTp and BLAST2GO annotated the motif patterns and functional significance. The VFDB identified 10 virulence proteins at both genomic and metagenomic level. Phylogenetic analysis revealed a divergent and convergent relationship between 17 ROD9 and 41 SP-1 proteins. Here, combining a comprehensive approach from sequence based, motif recognitions, domain identification, virulence ability to structural modelling provides a precise function to ROD9 proteins biological network, for which no experimental information is available.

  View details for DOI 10.1016/j.compbiolchem.2019.107110

  View details for PubMedID 31445418

• Molecular insight to influential role of Hha-TomB toxin-antitoxin system for antibacterial activity of biogenic silver nanoparticles. Artificial cells, nanomedicine, and biotechnology Paul, P., Verma, S., Kumar Panda, P., Jaiswal, S., Sahu, B. R., Suar, M. 2018; 46 (sup3): S572-S584

  Abstract

  Emergence of silver nanoparticles (AgNPs) as a potent antibacterial agent for clinical application has raised attention towards its mode of action and needs detailed understanding of the mechanism. The current study investigates the influential role of Hha-TomB toxin-antitoxin system in determination of AgNPs antibacterial activity. AgNPs were synthesized by biogenic process using bacterial supernatant and were characterized for their physiochemical properties. Microbiological and computational assays like molecular docking, growth curve analysis, live/dead assay, oxidative stress and apoptosis assay were performed with wild type (WT) and mutants (Δhha, ΔtomB) strains treated with AgNPs for elucidation of mechanism. Stable AgNPs having size 30-40 nm and zeta potential -32 ± 09 mV were synthesized. AgNPs have shown significant antibacterial activity against S. typhimurium. Influential role of Hha-TomB TA proteins was observed in antibacterial effect by their altered expression level change in ROS level and programmed cell death. Molecular investigation elucidated the effect of AgNPs as consequence of their interaction with cellular proteins with different amino acids via hydrophobic interaction leading to alteration of cellular metabolic processes like ROS induction and apoptosis causing ultimate death. The study provided a detail illustration of Hha-TomB TA system influence on antibacterial mechanism of AgNPs for wide spectrum clinical application.

  View details for DOI 10.1080/21691401.2018.1503598

  View details for PubMedID 30444141

• Structural discordance in HIV-1 Vpu from brain isolate alarms amyloid fibril forming behavior- a computational perspective. Journal of theoretical biology Sneha, P., Panda, P. K., Gharemirshamlu, F. R., Bamdad, K., Balaji, S. 2018; 451: 35-45

  Abstract

  HIV-1 being the most widespread type worldwide, its accounts for almost 95% of all infections including HIV associated dementia (HAD) that triggers neurological dysfunction and neurodegeneration in patients. The common features associated with HAD and other neurodegenerative diseases are accumulation of amyloid plaques, neuronal loss and deterioration of cognitive abilities, amongst which amyloid fibrillation is considered to be a hallmark. The success of effective therapeutics lies in the understanding of mechanisms leading to neurotoxicity. Few viral proteins like gp-120 are known to be involved in aggregation and enhancement of viral infectivity while comprehending the neurotoxic role of some other proteins is still underway. In the current study, amyloidogenic potential of HIV-1 Vpu protein from brain isolate is investigated through computational approaches. The aggregation propensity of brain derived HIV-1 Vpu was assessed by several amyloid prediction servers that projected the region 4-35 to be amyloidogenic. The protein structure was modeled and subjected to 70 ns molecular dynamics (MD) simulation to investigate the transformation of α-helical conformation of the predicted aggregate region into β-sheet, proposing the protein's ability to initiate fibril formation that is central to amyloidogenic proteins. The structural features of brain derived HIV-1 Vpu were consistent with the in silico amyloid prediction results that depicts the conformational change in the region 8-28 of which residues Ala8, Ile9, Val10, Ala19, Ile20 and Val21 constitutes β-sheet formation. The α-helix/β-sheet discordance of the predicted region was reflected in the simulation study highlighting the possible structural transition associated with HIV-1 Vpu protein of brain isolate.

  View details for DOI 10.1016/j.jtbi.2018.04.033

  View details for PubMedID 29705491

• Molecular aspects of core-shell intrinsic defect induced enhanced antibacterial activity of ZnO nanocrystals. Nanomedicine (London, England) Verma, S. K., Jha, E., Panda, P. K., Das, J. K., Thirumurugan, A., Suar, M., Parashar, S. 2018; 13 (1): 43-68

  Abstract

  To investigate molecular aspects of the antibacterial effect of size-dependent core-shell intrinsic defects of nanocrystalline ZnO synthesized through high energy ball milling technique.Mechanically synthesized and characterized 7, 10 and 15 h milled ZnO nanoparticles were evaluated for antibacterial activity with molecular investigation by computational molecular docking.Synthesized ZnO nanoparticles displayed shrinkage of core and increase of shell with reduction in size of bulk ZnO particles from 250 to 80, 40 and 20 nm and increase in zeta potential up to -19 mV in 7, 10 and 15 h nano ZnO. Antibacterial activity was found increased with decrease in size due to increased reactive oxygen species and membrane damage in bacteria.Synthesized nano ZnO exhibit size-dependent antibacterial action as consequences of interactions with cell membrane proteins via hydrogen bond interaction with amino acid residues followed by internalization, membrane depolarization and induction of reactive oxygen species generation.

  View details for DOI 10.2217/nnm-2017-0237

  View details for PubMedID 29173091

• Genetics of PCOS: A systematic bioinformatics approach to unveil the proteins responsible for PCOS. Genomics data Panda, P. K., Rane, R., Ravichandran, R., Singh, S., Panchal, H. 2016; 8: 52-60

  Abstract

  Polycystic ovary syndrome (PCOS) is a hormonal imbalance in women, which causes problems during menstrual cycle and in pregnancy that sometimes results in fatality. Though the genetics of PCOS is not fully understood, early diagnosis and treatment can prevent long-term effects. In this study, we have studied the proteins involved in PCOS and the structural aspects of the proteins that are taken into consideration using computational tools. The proteins involved are modeled using Modeller 9v14 and Ab-initio programs. All the 43 proteins responsible for PCOS were subjected to phylogenetic analysis to identify the relatedness of the proteins. Further, microarray data analysis of PCOS datasets was analyzed that was downloaded from GEO datasets to find the significant protein-coding genes responsible for PCOS, which is an addition to the reported protein-coding genes. Various statistical analyses were done using R programming to get an insight into the structural aspects of PCOS that can be used as drug targets to treat PCOS and other related reproductive diseases.

  View details for DOI 10.1016/j.gdata.2016.03.008

  View details for PubMedID 27114910

  View details for PubMedCentralID PMC4832036

• Mutation-based structural modification and dynamics study of amyloid beta peptide (1-42): An in-silico-based analysis to cognize the mechanism of aggregation. Genomics data Panda, P. K., Patil, A. S., Patel, P., Panchal, H. 2016; 7: 189-94

  Abstract

  Alzheimer's disease is the prevalent cause of premature senility, a progressive mental disorder due to degeneration in brain and deposition of amyloid β peptide (1-42, a misfolded protein) in the form of aggregation that prevails for a prolonged time and obstructs every aspect of life. One of the primary hallmarks of the neuropathological disease is the accretion of amyloid β peptide in the brain that leads to Alzheimer's disease, but the mechanism is still a mystery. Several investigations have shown that mutations at specific positions have a significant impact in stability of the peptide as predicted from aggregation profiles. Here in our study, we have analyzed the mutations by substituting residues at position A22G, E22G, E22K, E22Q, D23N, L34V and molecular dynamics have been performed to check the deviation in stability and conformation of the peptide. The results validated that the mutations at specific positions lead to instability and the proline substitution at E22P and L34P stalled the aggregation of the peptide.

  View details for DOI 10.1016/j.gdata.2016.01.003

  View details for PubMedID 26981406

  View details for PubMedCentralID PMC4778649