Publications by authors named "Gaurav Chauhan"

56 Publications

Dorsal root ganglion stimulation lead fractures: potential mechanisms and ways to avoid.

BMJ Case Rep 2021 May 20;14(5). Epub 2021 May 20.

Pain Management, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Dorsal root ganglion stimulation (DRGS) therapy is a rapidly emerging tool being used by pain physicians in the treatment of chronic pain. Complex regional pain syndrome (CRPS), a debilitating disease whose mechanism is still has yet to be fully elucidated, is a common pathology targeted by DRGS therapy, often better results than traditional spinal cord stimulation. DRGS therapy, however, is not bereft of complications. Lead migration and fracture are two examples in particular that are among the most common of these complications. The authors report an unusual case of lost efficacy due to lead fractures in patients with CRPS treated with DRGS. The case report narrates identification, management and probable mechanism of DRGS lead fracture. The structural instability of DRGS leads can yield distressing symptoms at any point during the therapy, and physicians should be cognisant of the complications of DRGS therapy.
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http://dx.doi.org/10.1136/bcr-2020-241353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141429PMC
May 2021

Unleashing the potential of cell membrane-based nanoparticles for COVID-19 treatment and vaccination.

Expert Opin Drug Deliv 2021 Jun 6:1-20. Epub 2021 Jun 6.

Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal.

: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a particular coronavirus strain responsible for the coronavirus disease 2019 (COVID-19), accounting for more than 3.1 million deaths worldwide. Several health-related strategies have been successfully developed to contain the rapidly-spreading virus across the globe, toward reduction of both disease burden and infection rates. Particularly, attention has been focused on either the development of novel drugs and vaccines, or by adapting already-existing drugs for COVID-19 treatment, mobilizing huge efforts to block disease progression and to overcome the shortage of effective measures available at this point.: This perspective covers the breakthrough of multifunctional biomimetic cell membrane-based nanoparticles as next-generation nanosystems for cutting-edge COVID-19 therapeutics and vaccination, specifically cell membrane-derived nanovesicles and cell membrane-coated nanoparticles, both tailorable cell membrane-based nanosystems enriched with the surface repertoire of native cell membranes, toward maximized biointerfacing, immune evasion, cell targeting and cell-mimicking properties.: Nano-based approaches have received widespread interest regarding enhanced antigen delivery, prolonged blood circulation half-life and controlled release of drugs. Cell membrane-based nanoparticles comprise interesting antiviral multifunctional nanoplatforms for blocking SARS-CoV-2 binding to host cells, reducing inflammation through cytokine neutralization and improving drug delivery toward COVID-19 treatment.
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http://dx.doi.org/10.1080/17425247.2021.1922387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182831PMC
June 2021

A unique view of SARS-CoV-2 through the lens of ORF8 protein.

Comput Biol Med 2021 06 15;133:104380. Epub 2021 Apr 15.

Center for IPS Cell Research and Application, Kyoto University, Kyoto, 606-8397, Japan.

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.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049180PMC
June 2021

Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 in the Microbial-Resistant Era.

ACS Nano 2021 05 7;15(5):8069-8086. Epub 2021 Apr 7.

University of Pittsburgh School of Medicine, Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania 15232, United States.

Therapeutic options for the highly pathogenic human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the current pandemic coronavirus disease (COVID-19) are urgently needed. COVID-19 is associated with viral pneumonia and acute respiratory distress syndrome causing significant morbidity and mortality. The proposed treatments for COVID-19 have shown little or no effect in the clinic so far. Additionally, bacterial and fungal pathogens contribute to the SARS-CoV-2-mediated pneumonia disease complex. The antibiotic resistance in pneumonia treatment is increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, and their derivatives constitute a promising alternative due to their wide-spectrum antimicrobial activity, biocompatibility, biodegradability, and capacity to induce tissue regeneration. Furthermore, the antimicrobial mode of action is mainly physical (, membrane distortion), characterized by a low risk of antimicrobial resistance. In this Review, we evaluated the literature on the antiviral activity and broad-spectrum antimicrobial properties of CBNs. CBNs had antiviral activity against 13 enveloped positive-sense single-stranded RNA viruses, including SARS-CoV-2. CBNs with low or no toxicity to humans are promising therapeutics against the COVID-19 pneumonia complex with other viruses, bacteria, and fungi, including those that are multidrug-resistant.
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http://dx.doi.org/10.1021/acsnano.1c00629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043205PMC
May 2021

Getting More Out of Follow-up Three-Dimensional Time-of-Flight Magnetic Resonance Angiography in Endovascularly Treated Intracranial Aneurysms.

Asian J Neurosurg 2020 Oct-Dec;15(4):889-898. Epub 2020 Dec 21.

Department of Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

Background: We retrospectively re-evaluated follow-up three-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) in patients with aneurysms treated with coiling at our Institute.

Aims: To document the type and frequency of postcoiling residue patterns as seen on follow-up MRA and to document their evolution with time where a further follow-up MRA was available. To assess the implications of the location of the aneurysm on residue and recurrence.

Subjects And Methods: 3D TOF MRA for 104 aneurysms were evaluated for residue size and residue pattern. Mainly, three residue patterns were identified. The aneurysms were allocated to different groups depending on the location. Multiple MRA studies were available in subgroup 1* and subgroup 2* where the residue growth or reduction and pattern change was noted and residue growth rates were calculated.

Results: Collectively 54 (51.92%) aneurysms showed occlusion (pattern 1 and 1A), 31 (29.81%) showed neck residue (pattern 2A, 2B and 2C) and 19 (18.27%) showed recurrence (pattern 3A, 3B and 3C, residue size >3 mm) at the last follow-up MRA. Type 2A/3A patterns were more common. In terms of residue and recurrence, the distally located aneurysms (Group 3) appeared to do well. For those showing growing residue/recurrence, the average growth rate was calculated at 0.094 mm/month and 0.15 mm/month, respectively, for subgroup 1* and subgroup 2*, although the difference was not statistically significant. With longer follow-up the persisting and growing residues from both the subgroups, not warranting early re-treatment, showed a low growth rate at approximately 0.05 mm/month.

Conclusions: TOF MRA helps in identifying different residue patterns in coiled aneurysms. Serial follow-up MRA appears useful in showing the pattern and size changes in the residual aneurysm. Although more work is required in this regard, calculation of aneurysm/residue growth rate may be useful in prognostication and in scheduling further follow-up or retreatment. The risk factor related to the location of the aneurysm warrants further study.
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http://dx.doi.org/10.4103/ajns.AJNS_374_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869283PMC
December 2020

Impact of Thyroid Dysfunction on Insulin Resistance: A Study from a Tertiary Care Center in India.

J Assoc Physicians India 2021 Feb;69(2):49-53

Resident, Medicine, SMS Medical College and Hospital, Jaipur, Rajasthan.

Introduction: The thyroid hormones perpetuate a fine equilibrium of glucose metabolism. Abnormalities of thyroid function can disrupt this balance leading to glucose metabolism abnormalities and insulin resistance.

Objectives: We studied the correlation between insulin resistance and thyroid status in hyperthyroid, euthyroid, and hypothyroid individuals.

Methods: In this observational comparative analysis conducted at a tertiary care center, the 3 study groups comprised of 35 patients each with newly detected hyperthyroidism, hypothyroidism and euthyroid individuals. Assays were conducted for serum insulin, thyroid profile, blood sugar and routine biochemistry in the fasting state. The homeostasis model assessment for insulin resistance (HOMA-IR) was used to evaluate insulin resistance.

Results: The mean HOMA-IR was highest in patients with hypothyroidism (3.22 ± 2.69) followed by the hyperthyroid group (2.25 ± 1.59). It was lowest in the euthyroid group (0.79 ± 0.58) with the intergroup difference being statistically significant (P<0.001). Hypothyroid patients showed a significant a positive correlation between TSH and HOMA-IR (r=0.945, P=<0.001) whereas hyperthyroid patients showed positive correlation between FT3 and insulin resistance (r=0.706, P<0.001).

Conclusion: Thyroid dysfunction is associated with an increase in insulin resistance and glucose abnormalities validating the resultant higher risk of related cardiovascular and metabolic abnormalities observed in these patients.
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February 2021

Gadolinium-based contrast agent-induced neurotoxicity: seeing is believing!

BMJ Case Rep 2021 Jan 26;14(1). Epub 2021 Jan 26.

Anesthesiology, Pain Management and Perioperative Medicine, Henry Ford Health System, Detroit, Michigan, USA.

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http://dx.doi.org/10.1136/bcr-2020-241372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843330PMC
January 2021

A Universal Craniometric Index for Establishing the Diagnosis of Basilar Invagination.

Neurospine 2021 Mar 25;18(1):206-216. Epub 2021 Jan 25.

Department of Neurosurgery, Sanjay Gandi Post Graduate Institute of Medical Science, Lucknow, India.

Objective: The conventional criteria for defining the basilar invagination (BI) focus on the relationship of odontoid tip to basion and opisthion, landmarks that are intrinsically variable especially in presence of occipitalised atlas. A universal single reference line is proposed that helps in unequivocally establishing the diagnosis of BI, may be relevant in establishing both Goel types A and B BI, as well as in differentiating a 'very high' from 'regular' BI.

Methods: Study design - case-control study. In 268 patients (group I with BI [n = 89] including Goel type A BI [n = 66], Goel type B BI [n = 23], and group II controls [n = 179]), the perpendicular distance between odontoid tip and line subtended between posterior tip of hard palate-internal occipital protuberance (P-IOP line) was measured. Logistic regression analysis determined factors influencing the proposed parameter (p < 0.05).

Results: In patients with a 'very high' BI (n = 5), the odontoid tip intersected/or was above the P-IOP line. In patients with a 'regular' BI (n = 84), the odontoid tip was 6.56 ± 3.9mm below the P-IOP line; while in controls, this distance was 12.53 ± 4.28 mm (p < 0.01). In Goel type A BI, the distance was 7.01 ± 3.78 mm and in type B BI, it was 5.07 ± 4.19 mm (p = 0.004). Receiver-operating characteristic curve analysis identified 9.0 mm (8.92-9.15 mm) as the cut-point for diagnosing BI using the odontoid tip-P-IOP line distance as reference.

Conclusion: The odontoid tip either intersecting the P-IOP line (very high BI) or being < 9 mm below the P-IOP line (Goel types A and B BI) is recommended as highly applicable criteria to establish the diagnosis of BI. This parameter may be useful in establishing the diagnosis in all varieties of BI.
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http://dx.doi.org/10.14245/ns.2040608.304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021813PMC
March 2021

Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features.

Molecules 2020 Dec 13;25(24). Epub 2020 Dec 13.

Division of Hematology/Oncology, Department of Medicine, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.
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http://dx.doi.org/10.3390/molecules25245906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763092PMC
December 2020

The structural basis of accelerated host cell entry by SARS-CoV-2†.

FEBS J 2020 Dec 2. Epub 2020 Dec 2.

Department of Physiology, Michigan State University, East Lansing, MI, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic coronavirus disease 2019 (COVID-19) that exhibits an overwhelming contagious capacity over other human coronaviruses (HCoVs). This structural snapshot describes the structural bases underlying the pandemic capacity of SARS-CoV-2 and explains its fast motion over respiratory epithelia that allow its rapid cellular entry. Based on notable viral spike (S) protein features, we propose that the flat sialic acid-binding domain at the N-terminal domain (NTD) of the S1 subunit leads to more effective first contact and interaction with the sialic acid layer over the epithelium, and this, in turn, allows faster viral 'surfing' of the epithelium and receptor scanning by SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE-2) protein on the epithelial surface is the primary entry receptor for SARS-CoV-2, and protein-protein interaction assays demonstrate high-affinity binding of the spike protein (S protein) to ACE-2. To date, no high-frequency mutations were detected at the C-terminal domain of the S1 subunit in the S protein, where the receptor-binding domain (RBD) is located. Tight binding to ACE-2 by a conserved viral RBD suggests the ACE2-RBD interaction is likely optimal. Moreover, the viral S subunit contains a cleavage site for furin and other proteases, which accelerates cell entry by SARS-CoV-2. The model proposed here describes a structural basis for the accelerated host cell entry by SARS-CoV-2 relative to other HCoVs and also discusses emerging hypotheses that are likely to contribute to the development of antiviral strategies to combat the pandemic capacity of SARS-CoV-2.
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http://dx.doi.org/10.1111/febs.15651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753708PMC
December 2020

Crowding-induced interactions of ring polymers.

Soft Matter 2021 Jan 6;17(1):16-23. Epub 2020 Nov 6.

Department of Chemical and Biomolecular Engineering, University of Tennessee, Knoxville, Tennessee 37996, USA.

Macromolecular crowding and the presence of surfaces can significantly impact the spatial organization of biopolymers. While the importance of crowding-induced depletion interactions in biology has been recognized, much remains to be understood about the effect of crowding on biopolymers such as DNA plasmids. A fundamental problem highlighted by recent experiments is to characterize the impact of crowding on polymer-polymer and polymer-surface interactions. Motivated by the need for quantitative insight, we studied flexible ring polymers in crowded environments using Langevin dynamics simulations. The simulations demonstrated that crowding can lead to compaction of isolated ring polymers and enhanced interactions between two otherwise repulsive polymers. Using umbrella sampling, we determined the potential of mean force (PMF) between two ring polymers as a function of their separation distance at different volume fractions of crowding particles, φ. An effective attraction emerged at φ≈ 0.4, which is similar to the degree of crowding in cells. Analogous simulations showed that crowding can lead to strong adsorption of a ring polymer to a wall, with an effective attraction to the wall emerging at a smaller volume fraction of crowders (φ≈ 0.2). Our results reveal the magnitude of depletion interactions in a biologically-inspired model and highlight how crowding can be used to tune interactions in both cellular and cell-free systems.
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http://dx.doi.org/10.1039/d0sm01847cDOI Listing
January 2021

A perspective on potential target proteins of COVID-19: Comparison with SARS-CoV for designing new small molecules.

Bioorg Chem 2020 11 29;104:104326. Epub 2020 Sep 29.

Department of Pharmaceutical Technology (Process Chemistry), National Institute of Pharmaceutical Education and Research, SAS Nagar, Sector 67, Mohali, Punjab 160062, India. Electronic address:

SARS-CoV-2 (COVID-19) epidemic has created an unprecedented medical and economic crisis all over the world. SARS-CoV-2 is found to have more contagious character as compared to MERS-CoV and is spreading in a very fast manner all around the globe. It has affected over 31 million people all over the world till date. This virus shares around 80% of genome similarity with SARS-CoV. In this perspective, we have explored three major targets namely; SARS-CoV-2 spike (S) protein, RNA dependent RNA polymerase, and 3CL or M Protease for the inhibition of SARS-CoV-2. These targets have attracted attention of the medicinal chemists working on computer-aided drug design in developing new small molecules that might inhibit these targets for combating COVID-19 disease. Moreover, we have compared the similarity of these target proteins with earlier reported coronavirus (SARS-CoV). We have observed that both the coronaviruses share around 80% similarity in their amino acid sequence. The key amino acid interactions which can play a crucial role in designing new small molecule inhibitors against COVID-19 have been reported in this perspective. Authors believe that this study will help the medicinal chemists to understand the key amino acids essential for interactions at the active site of target proteins in SARS-CoV-2, based on their similarity with earlier reported viruses. In this review, we have also described the lead molecules under various clinical trials for their efficacy against COVID-19.
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http://dx.doi.org/10.1016/j.bioorg.2020.104326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524440PMC
November 2020

Is highly expressed ACE 2 in pregnant women "a curse" in times of COVID-19 pandemic?

Life Sci 2021 Jan 28;264:118676. Epub 2020 Oct 28.

Department of Pharmacology, Central University of Punjab, Bathinda, Punj, ab-151001, India. Electronic address:

Angiotensin-converting enzyme 2 (ACE 2) is a membrane-bound enzyme that cleaves angiotensin II (Ang II) into angiotensin (1-7). It also serves as an important binding site for SARS-CoV-2, thereby, facilitating viral entry into target host cells. ACE 2 is abundantly present in the intestine, kidney, heart, lungs, and fetal tissues. Fetal ACE 2 is involved in myocardium growth, lungs and brain development. ACE 2 is highly expressed in pregnant women to compensate preeclampsia by modulating angiotensin (1-7) which binds to the Mas receptor, having vasodilator action and maintain fluid homeostasis. There are reports available on Zika, H1N1 and SARS-CoV where these viruses have shown to produce fetal defects but very little is known about SARS-CoV-2 involvement in pregnancy, but it might have the potential to interact with fetal ACE 2 and enhance COVID-19 transmission to the fetus, leading to fetal morbidity and mortality. This review sheds light on a path of SARS-CoV-2 transmission risk in pregnancy and its possible link with fetal ACE 2.
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http://dx.doi.org/10.1016/j.lfs.2020.118676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598563PMC
January 2021

Oncogenic transformation of human benign prostate hyperplasia with chronic cadmium exposure.

J Trace Elem Med Biol 2020 Dec 7;62:126633. Epub 2020 Aug 7.

Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat 390002, India. Electronic address:

Experimentally, it has been proved that cadmium served as an effective carcinogen and able to induce tumors in rodents in a dose-specific manner. However, systemic evaluation of cadmium exposure for the transformation of prostatic hyperplasia into prostate cancer (PCa) is still unclear. In the present study, an attempt has been made to establish cadmium-induced human prostate carcinogenesis using an in vitro model of BPH cells. Wide range of cadmium concentrations, i.e., 1 nM, 10 nM, 100 nM and 1μM, were chronically exposed to the human BPH cells for transformation into PCa and monitored using cell and molecular biology approaches. After eight weeks of exposure, the cells showed subtle morphological changes and shifts of cell cycle in the G2M phase. Significant increase in expression of prostatic genes AR, PSA, ER-β, and 5αR with increased nuclear localization of AR and pluripotency markers Cmyc, Klf4 indicated the carcinogenic effect of Cd. Further, the BPH cells exposed to Cd showed a substantial increase in the secretion of MMP-2 and MMP-9, influencing migratory potential of the cells along with decreased expression of the p63 protein which further strengthen the progression towards carcinogenesis and aggressive tumor studies. Data from the present study state that Cd exhibited marked invasiveness in BPH cells. These observations established a connecting link of BPH towards PCa pathogenesis. Further, the study will also help in investigating the intricate pathways involved in cancer progression.
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http://dx.doi.org/10.1016/j.jtemb.2020.126633DOI Listing
December 2020

Nanotechnology for COVID-19: Therapeutics and Vaccine Research.

ACS Nano 2020 07 29;14(7):7760-7782. Epub 2020 Jun 29.

School of Engineering and Sciences, Tecnologico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, 64849 Monterrey, Nuevo León, Mexico.

The current global health threat by the novel coronavirus disease 2019 (COVID-19) requires an urgent deployment of advanced therapeutic options available. The role of nanotechnology is highly relevant to counter this "virus" nano enemy. Nano intervention is discussed in terms of designing effective nanocarriers to counter the conventional limitations of antiviral and biological therapeutics. This strategy directs the safe and effective delivery of available therapeutic options using engineered nanocarriers, blocking the initial interactions of viral spike glycoprotein with host cell surface receptors, and disruption of virion construction. Controlling and eliminating the spread and reoccurrence of this pandemic demands a safe and effective vaccine strategy. Nanocarriers have potential to design risk-free and effective immunization strategies for severe acute respiratory syndrome coronavirus 2 vaccine candidates such as protein constructs and nucleic acids. We discuss recent as well as ongoing nanotechnology-based therapeutic and prophylactic strategies to fight against this pandemic, outlining the key areas for nanoscientists to step in.
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http://dx.doi.org/10.1021/acsnano.0c04006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325519PMC
July 2020

Stromal-AR influences the growth of epithelial cells in the development of benign prostate hyperplasia.

Mol Cell Biochem 2020 Aug 5;471(1-2):129-142. Epub 2020 Jun 5.

Department of Biochemistry, The M. S. University of Baroda, Vadodara, Gujarat, 390002, India.

Activation of epithelial-AR signaling is identified as the major cause of hyperproliferation of the cells during benign and malignant prostate conditions. However, the contribution of stromal-AR is also precarious due to its secretory actions that contribute to the progression of benign and malignant tumors. The present study was aimed to understand the influence of stromal-AR mediated actions on epithelial cells during BPH condition. The secretome (conditioned media-CM) was collected from AR agonist (testosterone-propionate-TP) and antagonist (Nilutamide-Nil) treated BPH patient-derived stromal cells and exposed to BPH epithelial cells. Epithelial cells exhibited increased cell proliferation with the treatment of CM derived from TP-treated stromal cells (TP-CM) but did not support the clonogenic growth of BPH epithelial cells. However, CM derived from Nil-treated stromal cells (Nil-CM) depicted delayed and aggressive BPH epithelial cell proliferation with increased clonogenicity of BPH epithelial cells. Further, decreased AR levels with increased cMyc transcripts and pAkt levels also validated the clonogenic transformation under the paracrine influence of inhibition of stromal-AR. Moreover, the CM of stromal-AR activation imparted positive regulation of basal/progenitor pool through LGR4, β-Catenin, and ΔNP63α expression. Hence, the present study highlighted the restricted disease progression and retains the basal/progenitor state of BPH epithelial cells through the activation of stromal-AR. On the contrary, AR-independent aggressive BPH epithelial cell growth due to paracrine action of loss stromal-AR directs us to reform AR pertaining treatment regimes for better clinical outcomes.
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http://dx.doi.org/10.1007/s11010-020-03773-zDOI Listing
August 2020

Differential functions of ERK1 and ERK2 in lung metastasis processes in triple-negative breast cancer.

Sci Rep 2020 05 22;10(1):8537. Epub 2020 May 22.

Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer characterized by metastasis, drug resistance and high rates of recurrence. With a lack or targeted therapies, TNBC is challenging to treat and carries a poor prognosis. Patients with TNBC tumors expressing high levels of ERK2 have a poorer prognosis than those with low ERK2-expressing tumors. The MAPK pathway is often found to be highly activated in TNBC, however the precise functions of the ERK isoforms (ERK1 and ERK2) in cancer progression have not been well defined. We hypothesized that ERK2, but not ERK1, promotes the cancer stem cell (CSC) phenotype and metastasis in TNBC. Stable knockdown clones of the ERK1 and ERK2 isoforms were generated in SUM149 and BT549 TNBC cells using shRNA lentiviral vectors. ERK2 knockdown significantly inhibited anchorage-independent colony formation and mammosphere formation, indicating compromised self-renewal capacity. This effect correlated with a reduction in migration and invasion. SCID-beige mice injected via the tail vein with ERK clones were employed to determine metastatic potential. SUM149 shERK2 cells had a significantly lower lung metastatic burden than control mice or mice injected with SUM149 shERK1 cells. The Affymetrix HGU133plus2 microarray platform was employed to identify gene expression changes in ERK isoform knockdown clones. Comparison of gene expression levels between SUM149 cells with ERK2 or ERK1 knockdown revealed differential and in some cases opposite effects on mRNA expression levels. Those changes associated with ERK2 knockdown predominantly altered regulation of CSCs and metastasis. Our findings indicate that ERK2 promotes metastasis and the CSC phenotype in TNBC.
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http://dx.doi.org/10.1038/s41598-020-65250-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244517PMC
May 2020

Augmented healing of full thickness chronic excision wound by rosmarinic acid loaded chitosan encapsulated graphene nanopockets.

Drug Dev Ind Pharm 2020 Jun 13;46(6):878-888. Epub 2020 May 13.

Institute of Nuclear Medicine and Allied Sciences, New Delhi, India.

Nanoparticles have emerged as an important carrier system to treat wounds as they permit the topical administration of an antimicrobial drug in a sustained and effective manner. On the other hand, if active excipients are added during the formulation, such as chitosan or graphene oxide, the developed Nano formulation could significantly improve its potential for chronic wound healing. Given that, we have conceived the fabrication and evaluation of rosmarinic acid loaded chitosan encapsulated graphene nanoparticles (RA-CH-G-NPOs) formulation to enhance wound healing capacity. The prepared nanoparticles were characterized by particle size, Zeta potential, FT-IR, SEM, TEM and AFM. It was observed the average diameter of RA-CH-G-NPOS is around 417.5 ± 18.3 nm and showed sustained release behavior. Optimized RA-CH-G-NPOs were incorporated into Carbopol gel and evaluated for drug content, pH, release, texture analysis, and viscosity. The antibacterial activity of optimized formulation was examined as a minimum inhibitory concentration against . The fabricated RA-CH-G-NPOs were than evaluated for antimicrobial activity by microdilution assay The combination of RA, Chitosan and Graphene oxide (GO) showed higher antibacterial activity of 0.0038 ± 0.2 mg/mL. Further, these nanoparticles were evaluated in- vivo for wound healing efficacy in rats. Histopathological evaluations demonstrated that RA-CH-G-NPOs showed significantly enhanced wound contraction, enhanced cell adhesion, epithelial migration, and high hydroxyproline content leading to faster and more efficient collagen synthesis as compared to plain carbopol, plain RA and controls. Hence the topical administration of fabricated RA-CH-G-NPOs appears to be an interesting and suitable strategy for the treatment of chronic wounds.
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http://dx.doi.org/10.1080/03639045.2020.1762200DOI Listing
June 2020

Posterior Cerebral Artery Aneurysms: Parent Vessel Occlusion Being a Viable Option in the Era of Flowdivertors.

Neurol India 2020 Mar-Apr;68(2):316-324

Department of Neuroradiology, SGPGIMS, Lucknow, Uttar Pradesh, India.

Background And Purpose: The purpose of this study is to evaluate posterior cerebral artery (PCA) aneurysms along with the efficacy, safety, procedural, and clinical outcome of the endovascular management of these aneurysms. We studied different techniques of endovascular treatment such as selective aneurysmal coiling, parent artery occlusion, and stent-assisted coiling in PCA aneurysms.

Methods: From 2010 to 2017, 11 patients (8 females, 3 males) harboring a PCA aneurysm were treated via an endovascular approach. Seven of eleven aneurysms were saccular in nature; four were fusiform shaped. All aneurysms were treated using detachable coils either by selective obliteration of the aneurysm sac or by parent artery occlusion. In one patient, stent-assisted coiling of PCA aneurysm was done, and in one patient, flowdivertor along with few coils used to treat the aneurysm.

Results: Five of the eleven aneurysms were successfully treated with preservation of the parent artery, and the other six were treated with aneurysm coiling along with parent vessel occlusion. Of the six where parent vessel occlusion was done, one developed transient hemiparesis which recovered on follow-up and none developed significant disabling vision abnormality. No mortality was noted.

Conclusion: Aneurysms of the PCA are rare compared with other locations in the intracranial circulation. These aneurysms can effectively be treated by permanent occlusion of the parent artery even in this era of flowdivertors - however, in these cases, thorough knowledge of PCA segmental anatomy is crucial in order to select the site of occlusion and to avoid major neurological deficits.
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http://dx.doi.org/10.4103/0028-3886.280635DOI Listing
March 2021

Combining Citizen Science and Genomics to Investigate Tick, Pathogen, and Commensal Microbiome at Single-Tick Resolution.

Front Genet 2019 21;10:1322. Epub 2020 Jan 21.

Bioinformatics and Integrative Biology Program, University of Massachusetts Medical School, Worcester, MA, United States.

The prevalence of tickborne diseases worldwide is increasing virtually unchecked due to the lack of effective control strategies. The transmission dynamics of tickborne pathogens are influenced by the tick microbiome, tick co-infection with other pathogens, and environmental features. Understanding this complex system could lead to new strategies for pathogen control, but will require large-scale, high-resolution data. Here, we introduce Project Acari, a citizen science-based project to assay, at single-tick resolution, species, pathogen infection status, microbiome profile, and environmental conditions of tens of thousands of ticks collected from numerous sites across the United States. In the first phase of the project, we collected more than 2,400 ticks wild-caught by citizen scientists and developed high-throughput methods to process and sequence them individually. Applying these methods to 192 ticks collected in a region with a high incidence of Lyme disease, we found that 62% were colonized by , the Lyme disease pathogen. In contrast to previous reports, we did not find an association between the microbiome diversity of a tick and its probability of carrying . However, we did find undescribed associations between carriage and the presence of specific microbial taxa within individual ticks. Our findings underscore the power of coupling citizen science with high-throughput processing to reveal pathogen dynamics. Our approach can be extended for massively parallel screening of individual ticks, offering a powerful tool to elucidate the ecology of tickborne disease and to guide pathogen-control initiatives.
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http://dx.doi.org/10.3389/fgene.2019.01322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985576PMC
January 2020

Recurrent Ischemic Strokes due to Chronic Otomastoiditis: A Rare Clinical Entity.

Saudi J Med Med Sci 2019 Sep-Dec;7(3):234-236. Epub 2019 Aug 28.

Department of Neuro-anaesthesia, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

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http://dx.doi.org/10.4103/sjmms.sjmms_152_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734743PMC
August 2019

IGF-II-Conjugated Nanocarrier for Brain-Targeted Delivery of p11 Gene for Depression.

AAPS PharmSciTech 2019 Jan 7;20(2):50. Epub 2019 Jan 7.

Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, India.

Gene therapy involving p11 cDNA has been thought to be a futuristic approach for the effective management of depression as the existing treatment regimen presents many issues regarding late onset of action, patient withdrawal and their side effects. For the effective transfection of p11 gene intracellularly, two cationic lipids based on phospholipid DOPE conjugated to basic amino acids histidine and arginine were synthesised, used for liposome formulation and evaluated for their ability as gene delivery vectors. They were further converted using IGF-II mAb into immunoliposomes for CNS targeting and mAb conjugation to liposomes were characterised by SDS-PAGE. They were further analysed by in vitro characterisation studies that include erythrocyte aggregation study, electrolyte-induced study, heparin compatibility study and serum stability studies. SHSY5Y cells were used for conducting cytotoxicity of synthesised lipids and live imaging of cell uptake for 25 min. Finally, the brain distribution studies and western blot were carried out in animals to evaluate them for their BBB permeation ability and effects on p11 protein which is believed to be a culprit. These formulated liposomes from synthesised lipids offer a promising approach for the treatment of depression.
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http://dx.doi.org/10.1208/s12249-018-1206-xDOI Listing
January 2019

A Randomized Controlled Trial of Fluoroscopically-Guided Sacroiliac Joint Injections: A Comparison of the Posteroanterior and Classical Oblique Techniques.

Neurospine 2019 Jun 7;16(2):317-324. Epub 2018 Oct 7.

Anesthesiology, Pain management, and Perioperative Medicine, Henry Ford Health System, Detroit, MI, USA.

Objective: The sacroiliac joint can be a primary source of pain or part of multifactorial syndromes. As there is no single historical, physical examination-based, or radiological feature that definitively establishes a diagnosis of sacroiliac joint pain, diagnostic blocks are regarded as the gold standard. The primary aim of this randomized trial was to compare the posteroanterior approach with the classic oblique approach for sacroiliac joint injection based on an assessment of procedure times and patient-reported pain outcomes in subjects scheduled for fluoroscopically-guided sacroiliac joint injections.

Methods: Thirty patients were randomized into 2 groups of 15 patients each. The endpoints measured included the total length of procedure time, fluoroscopic time, needling time (length of time the needle was maneuvered), and pre- and postprocedure visual analogue scale pain scores.

Results: The posteroanterior approach was significantly shorter in terms of procedure time (p=0.03) and needling time (p=0.01) than the oblique approach. Adjusting for body mass index, the mean procedure and needling times were significantly shorter in the posteroanterior group than in the oblique group.

Conclusion: This study of the posteroanterior approach for fluoroscopic-guided sacroiliac joint injection observed shorter times for fluoroscopy, needling, and the overall procedure than were recorded for the widely prevalent oblique approach. This may translate to lower radiation exposure, lower procedural costs, and enhanced ergonomics of fluoroscopicallyguided sacroiliac joint injections.
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http://dx.doi.org/10.14245/ns.1836122.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603830PMC
June 2019

Retrospective Review of Magnetic Resonance Imaging of the Lumbosacral Spine: Are We Overinvestigating?

Neurospine 2018 Dec 7;15(4):383-387. Epub 2018 Oct 7.

Department of Anesthesiology, Henry Ford Hospital, Detroit, MI, USA.

Objective: Lower back pain (LBP) is a worldwide health problem, and magnetic resonance imaging (MRI) is a common modality used to aid in its diagnosis. Although specific guidelines for assessing the necessity of MRI usage exist, the use of MRI as the initial imaging method for LBP seems to be more common than necessary in general practice.

Methods: We conducted a retrospective chart review of 313 patients who had undergone MRI of the lumbosacral spine during 2014-2015. We recorded and compared various factors, including age, sex, body mass index, current smoking status, race, symptoms, MRI findings, and progression to surgery within the next year. All rates were compared according to whether the MRI results showed radiographically significant findings (MRI-positive) or not (MRI-negative) using the chi-square or Fisher exact tests (if the expected cell count was <5). All analyses were performed using SAS version 9.4.

Results: There were no statistically significant differences in the rates of each symptom between the MRI-positive and MRI-negative groups, which accounted for 58.5% (183 of 313) and 41.5% (130 of 313) of the MRIs, respectively. The difference in the rate of surgery in the next year (18% among MRI-positive patients and 8.5% among MRI-negative patients) was found to be statistically significant (p<0.05).

Conclusion: Based on our findings, 41.5% of patients underwent lumbar MRI unnecessarily and 81% of patients with positive MRIs did not have surgery within the next year. Further physician training is needed to avoid unnecessary investigations and expenditures.
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http://dx.doi.org/10.14245/ns.1836110.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347347PMC
December 2018

Macromolecular Crowding Induces Spatial Correlations That Control Gene Expression Bursting Patterns.

ACS Synth Biol 2018 05 25;7(5):1251-1258. Epub 2018 Apr 25.

Center for Nanophase Materials Sciences , Oak Ridge National Laboratory , Oak Ridge , Tennessee 37831 , United States.

Recent superresolution microscopy studies in E. coli demonstrate that the cytoplasm has highly variable local concentrations where macromolecular crowding plays a central role in establishing membrane-less compartmentalization. This spatial inhomogeneity significantly influences molecular transport and association processes central to gene expression. Yet, little is known about how macromolecular crowding influences gene expression bursting-the episodic process where mRNA and proteins are produced in bursts. Here, we simultaneously measured mRNA and protein reporters in cell-free systems, showing that macromolecular crowding decoupled the well-known relationship between fluctuations in the protein population (noise) and mRNA population statistics. Crowded environments led to a 10-fold increase in protein noise even though there were only modest changes in the mRNA population and fluctuations. Instead, cell-like macromolecular crowding created an inhomogeneous spatial distribution of mRNA ("spatial noise") that led to large variability in the protein production burst size. As a result, the mRNA spatial noise created large temporal fluctuations in the protein population. These results highlight the interplay between macromolecular crowding, spatial inhomogeneities, and the resulting dynamics of gene expression, and provide insights into using these organizational principles in both cell-based and cell-free synthetic biology.
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http://dx.doi.org/10.1021/acssynbio.8b00139DOI Listing
May 2018

Non-invasive systemic drug delivery through mucosal routes.

Artif Cells Nanomed Biotechnol 2018 24;46(sup2):539-551. Epub 2018 Apr 24.

a Department of Pharmaceutics , ISF College of Pharmacy , Moga , India.

Science of drug delivery has achieved tremendous milestones in the last few decades. Emergence of novel drug delivery techniques and the most popular nanotechnology directed the drug delivery to another level. Without any doubt, present technology holds the proficiency to approach even the intercellular targets. Between all these success auras, there lies wads of giant challenges. One such challenge is delivering the molecule directly to the blood stream. Parenteral route is considered as the most effective route for delivering active pharmaceutical substances, but is associated with major disadvantages of painful drug delivery. Modern drug delivery suggests several approaches to outstrip this painful phenomenon. In the present article, we represent a new systematic vision to understand the ability and desirability of mucosal sites to achieve painless drug delivery. Human mucosa presents supreme proximity to the blood circulation that one can even observe with naked eye. Advances in drug delivery provide numerous approaches to exploit the mucosa for systemic reach. However, the revolutionary success is still unapproachable, with an understandable reason of associated complexities and challenges. This manuscript summarizes the significance of each mucosal site, on the basis of anatomical-physiological grounds. Particular attention is given to rationalize the selection of disease and a suitable drug delivery approach for its treatment.
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http://dx.doi.org/10.1080/21691401.2018.1463230DOI Listing
June 2019

Indole-3-carbinol improves neurobehavioral symptoms in a cerebral ischemic stroke model.

Naunyn Schmiedebergs Arch Pharmacol 2018 06 30;391(6):613-625. Epub 2018 Mar 30.

Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India.

Stroke is one of the most common causes of death worldwide and also responsible for permanent disability. Ischemic stroke has been found to affect 80% of stroke patients. Recombinant tissue plasminogen activator (rtPA) is the widely used drug for the ischemic stroke with narrow therapeutic window. Indole-3-carbinol (I3C) is a natural compound obtained from brassica species having antithrombotic activity. Middle cerebral artery occlusion (MCAO) model was used followed by reperfusion after 2 h of ischemia for the evaluation of the I3C against ischemic stroke. After reperfusion, I3C (12.5, 25, and 50 mg/kg) was given by oral route once daily and continued up to the 14th day. Behavioral studies including postural reflex, forelimb placing, and cylinder tests showed I3C attenuated the MCAO-induced increase in average score and asymmetry score efficiently. Mean cerebral blood flow (CBF) was improved by treatment with I3C (12.5 mg/kg) by 60% of baseline at 6 h. I3C inhibited ADP-induced platelet aggregation and reduced ischemic volume significantly. It also inhibited in vitro the ADP-induced platelet aggregation in healthy human volunteers. I3C improves behavioral scores and mean CBF after focal cerebral ischemia in rats. Furthermore, I3C showed prophylactic anti-thrombotic activity against carrageenan induced tail thrombosis. Therefore, preclinical evidence points to I3C as a potential candidate for use in cerebral ischemic stroke.
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http://dx.doi.org/10.1007/s00210-018-1488-2DOI Listing
June 2018

Osmotic demyelination syndrome in the setting of hypernatremia.

Neurol India 2018 Mar-Apr;66(2):559-560

Department of Anaesthesiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

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http://dx.doi.org/10.4103/0028-3886.227332DOI Listing
September 2019

Efaverinz and nano-gold-loaded mannosylated niosomes: a host cell-targeted topical HIV-1 prophylaxis via thermogel system.

Artif Cells Nanomed Biotechnol 2018 12;46(sup1):79-90. Epub 2017 Dec 12.

a Indo-Soviet Friendship College of Pharmacy , DBT Lab , Moga , India.

Sexual dissemination of Human Immunodeficiency Virus-1 (HIV-1) is the prime mode of its spread. Topical microbicidal approach has gained much attention, but no real success is observed till date, either due to toxicity or resistance of active moieties and the lack of efficient drug delivery approaches. In this research protocol, a unique combination approach of a standard drug moiety, that is, Efaverinz (EFV) and a nanometal, that is, gold nanoparticles (GNPs) was tried. Both these candidates were delivered through a mannosylated niosomal system, to exploit protein (lectins present on HIV host cells) - carbohydrate (oligosaccharides such as mannan present on HIV gp-120 receptor) interaction. GNPs (10.4 nm average size) were entrapped inside the aqueous core, whereas lipophilic EFV was loaded in the bilayer membrane. Results demonstrated a significant increase in antiviral activity when EFV was fired with GNPs. Delivery of this combination via mannosylated niosomes proved to be a perfect approach with exceedingly well potential compared to non liganded niosomal system. A thermosensitive gel vehicle was prepared and the loaded niosomes were dispersed in it to have a nanogel system. The optimized formulation was evaluated for its prophylactic activity and the results showed completely inhibited viral dissemination at folds dilution levels.
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http://dx.doi.org/10.1080/21691401.2017.1414054DOI Listing
May 2019