Publications by authors named "Preeti Sharma"

138 Publications

Identification of steroidal saponins from Tribulus terrestris and their in silico docking studies.

J Cell Biochem 2021 Aug 1. Epub 2021 Aug 1.

Department of Biotechnology, Veer Narmad South Gujarat University, Surat, Gujarat, India.

Tribulus terrestris is known to possess many pharmacological properties, most notably its anticancer activities, owing to its rich steroidal saponin contents. Even though many reports are available elucidating the anticancer potential of the herb, we, for the very first time have attempted to isolate and identified the active compound present in seed crude saponin extract and confers its in silico docking ability with various cellular targets proteins. High performance thin layer chromatography confirms the presence of active saponins in leaf and seed saponin extracts which were further fractionated by silica gel column chromatography. Fractions collected were assessed for cytotoxicity on human breast cancer cells. High resolution liquid chromatography and mass spectroscopy was employ to identify the active components present in fraction with highest cytotoxicity. Intriguingly, Nautigenin type of steriodal saponin was identified to present in the active fraction of seed extract (SF11) and the identified compound was further analyzed for its in silico docking interaction using PyRx AutodockVina. Docking studies revealed the high binding affinity of Nuatigenin at significant sites with apoptotic proteins Bcl-2, Bax, caspase-3, caspase-8, p53 and apoptosis inducing factor along with cell surface receptors estrogen receptor, projesterone receptor, epidermal growth factor receptor, and human epidermal growth factor receptor-2. Thus, the conclusions were drawn that saponin fraction of Tribulus terrestis possesses active compounds having anticancer property and specifically, Nuatigenin saponin can be considered as an important therapeutic drug for the breast cancer treatment.
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http://dx.doi.org/10.1002/jcb.30113DOI Listing
August 2021

Year in Review 2020: Multisystemic impact of cystic fibrosis.

Pediatr Pulmonol 2021 Jul 29. Epub 2021 Jul 29.

Department of Pediatrics, Division of Pulmonary Medicine, Tulane University School of Medicine, Children's Hospital of New Orleans, New Orleans, Louisiana, USA.

Clinical care in cystic fibrosis (CF) has continued to advance over the last several years, particularly with the widespread eligibility and use of highly effective modulator therapy. Improved outcomes and longevity of persons with CF (PwCF) have increased recognition of the multisystem impact of the disease on the daily lives of PwCF. This review will cover a broad array of topics, from diagnosis to multisystem effects related to mental health, endocrine, palliative care, reproductive health, otolaryngology, and cardiac issues. Additionally, worldwide care delivery will be reviewed, demonstrating variation in outcomes based on resources and populations served. This review is part of the CF Year in Review 2020 series, focusing on the multi-system effects of CF. This review focuses on articles from Pediatric Pulmonology but also includes articles published in 2020 from other journals that are of particular interest to clinicians.
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http://dx.doi.org/10.1002/ppul.25584DOI Listing
July 2021

Year in review 2020: Nutrition and gastrointestinal disease in cystic fibrosis.

Pediatr Pulmonol 2021 Jul 26. Epub 2021 Jul 26.

Division of Pulmonary Medicine, Department of Pediatrics, Tulane University School of Medicine, Children's Hospital of New Orleans, New Orleans, Louisiana, USA.

The multisystemic manifestations of cystic fibrosis (CF) involve all parts of the gastrointestinal (GI) system, including the pancreas, intestine, and liver. As providers who care for people with CF, knowledge of the manifestations, treatment, and research related to nutrition and GI disease are important. This review is the last installment of the CF year in review 2020 series, focusing on nutritional, GI, and hepatobiliary articles from Pediatric Pulmonology and other journals of particular interest to clinicians.
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http://dx.doi.org/10.1002/ppul.25587DOI Listing
July 2021

Study of the Expression and Function of Calcium-Sensing Receptor in Human Skeletal Muscle.

Int J Mol Sci 2021 Jul 6;22(14). Epub 2021 Jul 6.

Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50139 Florence, Italy.

Skeletal muscle has an outstanding capacity for regeneration in response to injuries, but there are disorders in which this process is seriously impaired, such as sarcopenia. Pharmacological treatments to restore muscle trophism are not available, therefore, the identification of suitable therapeutic targets that could be useful for the treatment of skeletal reduced myogenesis is highly desirable. In this in vitro study, we explored the expression and function of the calcium-sensing receptor (CaSR) in human skeletal muscle tissues and their derived satellite cells. The results obtained from analyses with various techniques of gene and protein CaSR expression and of its secondary messengers in response to calcium (Ca) and CaSR drugs have demonstrated that this receptor is not present in human skeletal muscle tissues, neither in the established satellite cells, nor during in vitro myogenic differentiation. Taken together, our data suggest that, although CaSR is a very important drug target in physiology and pathology, this receptor probably does not have any physiological role in skeletal muscle in normal conditions.
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http://dx.doi.org/10.3390/ijms22147282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304165PMC
July 2021

Synthesis, Antimicrobial Evaluation of Substituted Indole and Nitrobenzenamine based Cr(III), Mn(III) and Fe(III) Metal Complexes.

Drug Res (Stuttg) 2021 Jul 22. Epub 2021 Jul 22.

Department of Chemistry, FoE, Teerthanker Mahaveer University, Moradabad Uttar Pradesh, India.

Schiff base ligand (E)-5-methyl-3-(1-(4-nitrophenylimino)ethyl)-1H-indol-2-amine was synthesized by the condensation of 1-(2-amino-5-methyl-1H-indol-3-yl)ethanone and 4-nitrobenzenamine in methanol at 70 C. The prepared Schiff base ligand doped with Cr(III), Mn(III) and Fe(III) ion, respectively and it is denoted as [M(CHNO)X]X. The complexes have been characterized with the help of elemental analysis, conductance measurements, magnetic measurements and their structural configuration have been determined by various spectroscopic (electronic, IR, H NMR, C NMR, GCMS) techniques. Electronic and magnetic moments of the complexes indicate that the geometry of the metal center was five coordinate square pyramidal. These metal complexes were also tested for their antimicrobial activities to assess their inhibiting potential against (positive bacteria) and , (negative bacteria) and fungi . [Cr(CHNO)OAc](OAc) shows best antimicrobial activity against all the pathogens.
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http://dx.doi.org/10.1055/a-1527-1307DOI Listing
July 2021

Analysis of erythrocytes in oral submucous fibrosis - A morphometric study.

Indian J Dent Res 2021 Jan-Feb;32(1):27-30

Department of Oral Pathology & Microbiology, LLRM Medical College, Meerut, Uttar Pradesh, India.

Background: Oral submucous fibrosis (OSMF) is a chronic progressive scarring oral disease caused due to areca quid chewing. The constituents of areca nut can enter into the circulation by swallowing the liquid mixture of areca quid which evokes oxidative stress on RBC membrane integrity.

Aims: To study the morphometric characteristics of erythrocytes under light microscopy and to assess the role of areca quid constituents on the morphology of circulating erythrocytes.

Materials And Methods: Peripheral blood smears prepared from blood samples of 50 patients selected according to Lai's classification. Group I: Normal individuals (10 cases); Group II: Mouth opening > 35 mm (10 cases); Group III: Mouth opening 30-35 mm (10 cases); Group IV: Mouth opening 20-30 mm (10 cases) and Group V: Mouth opening < 20 mm (10 cases). The slides were stained with Leishman's stain and assessed by light microscopy. A total of 100 randomly selected RBCs from 5 different fields in each smear were selected and the RBC circumference was measured and tabulated.

Statistical Analysis And Results: Data was analyzed using GraphPad Prism 5.03 software. Tukey's multiple comparison test showed statistically significant difference (p < 0.05) between groups I and IV; I and V; II and IV; II and V; III and IV; III and V.

Conclusion: These results suggest the possibility of cytotoxic effect of areca quid constituents on circulating erythrocytes in advanced cases of OSMF, which might result in microcytic anaemia.
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http://dx.doi.org/10.4103/ijdr.IJDR_718_18DOI Listing
July 2021

Biological modification in air-cathode microbial fuel cell: Effect on oxygen diffusion, current generation and wastewater degradation.

Chemosphere 2021 Jun 23;284:131243. Epub 2021 Jun 23.

Department of Biotechnology, Veer Narmad South Gujarat University, Surat, 395007, India.

Oxygen diffusion in the anodic chamber is the major limitation of air-cathode microbial fuel cell (MFC) design. To address this drawback, the application of microbial (Escherichia coli EC) patch on cathode was tested. Pseudomonas aeruginosa BR was used as exoelectrogen during the study. The MFC reactor with a patch had a better electron transfer rate, degraded 94.64% of synthetic wastewater (BR) and its current generation was increased by 95.66%. The maximum power density recorded for BR was 259.34 ± 7.28 mW/m. Application of patch in real wastewater (BR + Sludge) condition registered 63.18% of wastewater degradation, increment in current generation (59.71%) and decreased the charge transfer and ohmic resistances by 97.95% and 97.01% respectively. Apart from hindering oxygen diffusion and better current generation, this simple design also worked as a two-step degradation system. Thus, such MFC reactor is a potential candidate for wastewater management and green energy generation.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131243DOI Listing
June 2021

Comparative evaluation of the efficacy of diode laser as an adjunct to modified Widman flap surgery for the treatment of chronic periodontitis: A randomized split-mouth clinical trial.

J Indian Soc Periodontol 2021 May-Jun;25(3):213-219. Epub 2021 May 3.

Department of Periodontology and Implantology, ITS-Center for Dental Studies and Research, Ghaziabad, Uttar Pradesh, India.

Background: Periodontitis is a chronic inflammatory disease that is mainly initiated by plaque biofilm which may require treatment using periodontal flap surgery. Recently, diode lasers have become popular in the field of periodontology owing to advantages such as antibacterial effect, promoting angiogenesis, and providing hemostasis. However, scientific data on application of diode laser in periodontal flap surgery and its benefits are limited. Hence, the aim of the study was to investigate the adjunctive effect of removal of remnant pocket epithelium by 980 nm diode laser and biostimulation in modified Widman flap (MWF) surgery for the treatment of chronic periodontitis.

Materials And Methods: A total of 20 patients with generalized chronic periodontitis with pocket probing depth (PPD) ≥5mm post Phase I therapy were selected for this split-mouth study. MWF surgery was performed in Group 1, and in Group 2, MWF surgery with adjunctive diode laser de-epithelization and biostimulation was done. Clinical parameters including PPD, clinical attachment level, plaque index, and gingival index were recorded at baseline and 3 months following treatment, and postprocedural pain (Visual Analog Scale [VAS] score) was assessed 1-week posttreatment. In addition, colony-forming units/milliliter (CFU/ml) of anaerobic bacteria at baseline and 3 months were microbiologically examined.

Results: MWF surgery along with diode laser led to a significant improvement in Group 2 compared to Group 1 in clinical parameters such as PPD, relative clinical attachment level, VAS score as well as microbial parameter CFU/ml after 3 months.

Conclusion: Diode laser as an adjunct to MWF in chronic periodontitis can provide enhanced clinical attachment gain with little postoperative discomfort.
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http://dx.doi.org/10.4103/jisp.jisp_252_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177179PMC
May 2021

CRISPR-based genome editing of zebrafish.

Prog Mol Biol Transl Sci 2021 12;180:69-84. Epub 2021 Mar 12.

Department of Zoology, Biomedical Technology & Human Genetics, University School of Sciences, Gujarat University, Ahmedabad, Gujarat, India.

CRISPR/Cas9, once discovered as an adaptive immune system in bacteria, has emerged as a disruptive technology in the field of genetic engineering. Technological advancements in the recent past has enhanced the applicability of CRISPR/Cas9 tool for gene editing, gene therapies, developmental studies and mutational analysis in various model organisms. Zebrafish, one of the excellent animal models, is preferred for conducting CRISPR/Cas9 studies to assess the functional implication of specific genes of interest. CRISPR/Cas9 mediated gene editing techniques, such as, knock-out and knock-in approaches, provide evidences to identify the role of different genes through loss-of-function studies. Also, CRISPR/Cas9 has been proved to be an efficient tool for designing disease models for gene expression studies based on phenotypic screening. The present chapter provides an overview of CRISPR/Cas9 mechanism, different strategies for DNA modifications and gene function analysis, highlighting the translational applications for future prospects, such as screening of drug toxicity and efficacy.
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http://dx.doi.org/10.1016/bs.pmbts.2021.01.005DOI Listing
March 2021

Does Intraoperative Computed Tomography Improve the Outcome in Zygomatico-Orbital Complex Fracture Reduction?

J Maxillofac Oral Surg 2021 Jun 16;20(2):189-200. Epub 2020 Jul 16.

Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012 India.

Purpose: Zygomatico-orbital (ZMO) fractures pose considerable difficulty in intraoperative assessment during open reduction and internal fixation (ORIF), and this can be attributed to its three-dimensional complex anatomy and articulations. Recent advancements in the form of intraoperative imaging and navigation have led to an adequate assessment and correct reduction of these fractures minimizing chances of any revision surgery. The purpose of this study was to evaluate the advantage of intraoperative computerized tomography (CT) scan in the management of ZMO/isolated orbital complex fracture and further to develop a protocol for managing such fractures.

Methods: Twenty-three cases of ZMO/isolated orbital fractures were managed with ORIF, followed by an intraoperative CT scan. The evaluation was focused on the articulations of the zygoma and orbital wall reconstruction. The score of 0 and 1 was given for inadequate and adequate reduction, respectively. Necessary corrections were performed in case of improper reduction followed by a repeat CT scan if required. The reduction score was statistically correlated with number of incisions.

Results: In 8 (35%) out of 23 patients, clinical judgment was inaccurate when radiologically assessed with an intraoperative CT scan. In 6 out of 8 cases, a repeat CT scan was done after revision of reduction. The reduction score improved with additional incision and revision in the second CT scan.

Conclusion: Intraoperative CT has an important role in assessing the accuracy of reduction and confirming implant position in ZMO/isolated orbital fractures. This can avoid the need for secondary corrective surgery and postoperative imaging. Intraoperative CT is an important tool to improve surgical outcomes in the management of ZMO orbital fractures.
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http://dx.doi.org/10.1007/s12663-020-01420-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042092PMC
June 2021

Dermatoses in the Elderly: Clinico-Demographic Profile of Patients Attending a Tertiary Care Centre.

Indian J Dermatol 2021 Jan-Feb;66(1):74-80

Department of Dermatology, All India Institute of Medical Sciences, Patna, Bihar, India.

Background: Elderly population is vulnerable to develop a multitude of dermatological diseases, owing to comorbidities and polypharmacies.

Objective: To know the prevalence of dermatological conditions in elderly patients attending outpatient department, determine the pattern and relative frequency of skin diseases, and find the relation with associated comorbidities.

Materials And Methods: We performed a cross-sectional study on 250 patients, aged ≥60 years. Clinical diagnosis was done, followed by appropriate investigations when required. Descriptive data was analyzed on the parameters of range, mean ± S.D., frequencies, etc., Continuous variables were analyzed using unpaired -test/Mann-Whitney U test and categorical data by Fisher's exact test/Chi-square test. Statistical software Medcalc version 10.2.0.0 for Windows vista was used. value =0.05 was considered statistically significant.

Results: 250 patients were evaluated, 164 males (65.5%) and 86 females (34.4%). Mean age was 67.87 ± 7.29 years. Commonest disease category was infection (30%), followed by dermatitis (29.6%), papulo-squamous (18.4%), and immunobullous (6.4%). Difference in acute and chronic disease was significant ( = 0.0001). 30% had infections; fungal (50.66%), bacterial (32%), and viral (17.33%). 74 patients had dermatitis (29.6% of study population). Commonest systemic disease was hypertension (23.2%), followed by diabetes mellitus (19.6%). Association of diabetes mellitus was significant ( = 0.0014), more in infective dermatoses ( = 0.0007). All had signs of aging; idiopathic guttate hypomelanosis (51.2%), xerosis (45.2%), seborrheic keratosis (42.6%), cherry angioma (33.2%), senile acne (6.6%). Photoaging was noted as wrinkling (98.8%), freckles (35.6%), purpura (10.8%), telangiectasia (5.6%). People involved in outdoor activity had higher Glogau scale (3.01 ± 0.69) compared to those indoors (2.44 ± 0.74), statistically significant difference ( = 0.001).

Conclusion: Our study is the first of its kind, in Eastern India, where we evaluated and explored the disease pattern and extent of geriatric dermatoses among patients attending dermatology OPD of a tertiary care hospital.
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http://dx.doi.org/10.4103/ijd.IJD_245_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061490PMC
April 2021

Hooked on mushrooms: Preparation and mechanics of a bioinspired soft probabilistic fastener.

Biointerphases 2021 01 19;16(1):011002. Epub 2021 Jan 19.

Physical Chemistry and Soft Matter, Wageningen University & Research, Wageningen 6708 WE, Netherlands.

Probabilistic fasteners are known to provide strong attachment onto their respective surfaces. Examples are Velcro® and the "3M dual lock" system. However, these systems typically only function using specific counter surfaces and are often destructive to other surfaces such as fabrics. Moreover, the design parameters to optimize their functionality are not obvious. Here, we present a surface patterned with soft micrometric features inspired by the mushroom shape showing a nondestructive mechanical interlocking and thus attachment to fabrics. We provide a scalable experimental approach to prepare these surfaces and quantify the attachment strength with rheometric and video-based analysis. In these "probabilistic fasteners," we find that higher feature densities result in higher attachment force; however, the individual feature strength is higher on a low feature density surface. We interpret our results via a load-sharing principle common in fiber bundle models. Our work provides new handles for tuning the mechanical attachment properties of soft patterned surfaces that can be used in various applications including soft robotics.
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http://dx.doi.org/10.1116/6.0000634DOI Listing
January 2021

Anticancer and antimicrobial potential of enterocin 12a from Enterococcus faecium.

BMC Microbiol 2021 02 4;21(1):39. Epub 2021 Feb 4.

Department of Microbiology, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.

Background: Increase in the number of infections caused by Gram-negative bacteria in neutropenic cancer patients has prompted the search for novel therapeutic agents having dual anticancer and antimicrobial properties. Bacteriocins are cationic proteins of prokaryotic origin that have emerged as one of the most promising alternative antimicrobial agents with applications as food preservatives and therapeutic agents. Apart from their antimicrobial activities, bacteriocins are also being explored for their anticancer potential.

Results: In this study, a broad-spectrum, cell membrane-permeabilizing enterocin with a molecular weight of 65 kDa was purified and characterized from the culture supernatant of vaginal Enterococcus faecium 12a. Enterocin 12a inhibited multidrug-resistant strains of various Gram-negative pathogens such as Salmonella enterica, Shigella flexneri, Vibrio cholerae, Escherichia coli and Gram-positive, Listeria monocytogenes, but had no activities against different strains of gut lactobacilli. The mass spectrometric analysis showed that the enterocin 12a shared partial homology with 4Fe-4S domain-containing redox protein of E. faecalis R712. Further, enterocin 12a selectively inhibited the proliferation of various human cancer cell lines in a dose-dependent manner but not that of normal human peripheral blood mononuclear cells. Enterocin 12a-treated cancer cells showed apoptosis-like morphological changes.

Conclusion: Enterocin 12a is a novel bacteriocin that has anticancer properties against human cell lines and negligible activity towards non-malignant cells. Therefore, it should be further evaluated for its anticancer potential in animal models.
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http://dx.doi.org/10.1186/s12866-021-02086-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860584PMC
February 2021

Comparative evaluation of efficacy of subepithelial connective tissue graft versus platelet-rich fibrin membrane in surgical reconstruction of interdental papillae using Han and Takie technique: A randomized controlled clinical trial.

J Indian Soc Periodontol 2020 Nov-Dec;24(6):547-553. Epub 2020 Nov 14.

Department of Periodontology and Implantology, I.T.S-CDSR, Ghaziabad, Uttar Pradesh, India.

Background: Platelet-rich fibrin (PRF) has emerged as one of the promising regenerative materials in the field of periodontics. Hence, this study evaluated the efficacy of subepithelial connective tissue graft (SCTG) and PRF in surgical reconstruction of interdental papillae using Han and Takei technique.

Materials And Methods: A total of 20 sites with Class I and Class II interdental papilla defects were assigned to two groups (Group 1 - Han and Takie technique + SCTG and Group 2 - Han and Takie technique + PRF). Parameters such as papillary height (PH), distance from the contact point to the tip of papillae (CPTP), papilla presence index (PPI), pocket probing depth (PPD), relative clinical attachment level (RCAL), plaque index (PI), gingival index (GI), and distance from contact point to alveolar crest (CP-BC) were measured at baseline and after 3 months. The significance of difference within and between the groups was evaluated with paired and unpaired -tests.

Results: The mean PI, GI, PPD, RCAL, PPI, and CPTP distance decreased significantly, whereas the mean PH increased significantly in Group 1 as well as in Group 2. After 3 months, mean reduction in CPTP distance and mean gain in PH were statistically significant in Group 1 as compared to Group 2. However, there was no significant difference in mean CPBC distance between baseline and 3 months in Group 1 as well as in Group 2.

Conclusion: Both the techniques were effective in the treatment of papillary recession defects; however, more significant clinical papillary enhancement was achieved after the surgical reconstruction with SCTG.
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http://dx.doi.org/10.4103/jisp.jisp_125_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781246PMC
November 2020

To Evaluate the Role and Relevance of Cytokines IL-17, IL-18, IL-23 and TNF-α and Their Correlation with Disease Severity in Chronic Urticaria.

Indian Dermatol Online J 2020 Jul-Aug;11(4):594-597. Epub 2020 Jan 24.

Department of Dermatology, DR RMLH PGIMER, New Delhi, India.

Introduction: The basic event in the pathogenesis of urticaria is inappropriate activation and degranulation of dermal mast cells. Cytokines are soluble polypeptide mediators that play a key role in immunological, inflammatory and reparative host responses including chronic urticaria.

Objective: The aim of this study was to evaluate the role and relevance of cytokines interleukin-17 (IL-17), interleukin-18(IL-18), interleukin-23(IL-23) and tumor necrosis factor-alpha (TNF-α) and their correlation with disease severity in patients with chronic urticaria.

Materials And Methods: A prospective cross-sectional study was conducted to measure the serum concentration of IL-17, IL-18, IL-23 and TNF-α in 50 chronic urticaria patients and in 30 healthy controls. Disease activity was assessed by using urticaria activity score (UAS).

Results: Serum concentration of IL-17, IL-18, IL-23 and TNF-α were significantly higher during the acute episode in chronic urticaria patients as compared with the healthy control subjects (mean: 1.84 ± 0.81 vs 0.03 ± 0.02 pg/ml; < 0.001, 501.41 ± 208.98 vs 218.39 ± 39.83 pg/ml; < 0.001; 25.57 ± 10.79 vs 0.15 ± 0.14 pg/ml, < 0.001; and 455.54 ± 253.54 vs 8.498 ± 3.644 pg/ml, < 0.001, respectively). There was a significant positive correlation between serum levels of IL-17, IL-18, IL-23 and TNF-α and severity of disease.

Conclusion: The serum levels of IL-17, IL-18, IL-23 and TNF-α were raised in patients of chronic urticaria and positively correlated with the severity of urticaria.
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http://dx.doi.org/10.4103/idoj.IDOJ_396_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413447PMC
January 2020

Management Strategies for Cancer Patients in the Time of COVID-19 Pandemic.

J Maxillofac Oral Surg 2020 Sep 10;19(3):473-474. Epub 2020 Jul 10.

Department of Dentistry, Government Medical College and Hospital (GMCH), Sector 32 B, Chandigarh, 160030 India.

Coronavirus disease 2019 commonly designated as COVID-19 has been declared by World health Organisation (WHO) as a pandemic on 11 March 2020. 'Lock down' is found to be the only effective method to control this outbreak and due to the contagious nature of this disease most of the hospitals have stopped elective interventions. Cancer is a second leading cause of death globally and the bystander victims in this scenario are the patients with suspected and proven cancer. Head and neck cancer has a survival rate of 40% to 50% after definitive therapy and the delay in treatment for even 1-2 months may lead to inoperability and poorer outcomes. On contacting the colleagues in different countries, it was found that different strategies have been adapted to prioritize cancer patients. Hence, such type of measures appropriately amended can be implemented as soon as possible to avoid harm to cancer patients.
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http://dx.doi.org/10.1007/s12663-020-01402-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348570PMC
September 2020

Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2.

Science 2020 09 4;369(6508):1261-1265. Epub 2020 Aug 4.

Department of Biochemistry and Cancer Center at Illinois, University of Illinois, Urbana, IL 61801, USA.

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds angiotensin-converting enzyme 2 (ACE2) on host cells to initiate entry, and soluble ACE2 is a therapeutic candidate that neutralizes infection by acting as a decoy. By using deep mutagenesis, mutations in ACE2 that increase S binding are found across the interaction surface, in the asparagine 90-glycosylation motif and at buried sites. The mutational landscape provides a blueprint for understanding the specificity of the interaction between ACE2 and S and for engineering high-affinity decoy receptors. Combining mutations gives ACE2 variants with affinities that rival those of monoclonal antibodies. A stable dimeric variant shows potent SARS-CoV-2 and -1 neutralization in vitro. The engineered receptor is catalytically active, and its close similarity with the native receptor may limit the potential for viral escape.
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http://dx.doi.org/10.1126/science.abc0870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574912PMC
September 2020

Development and validation of temporomandibular joint ankylosis quality of life questionnaire.

J Craniomaxillofac Surg 2020 Aug 27;48(8):779-785. Epub 2020 Jun 27.

Unit of Oral and Maxillofacial Surgery, Oral Health Sciences Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

The patient-reported outcome measures are endorsed for better evaluation of disease impact and treatment outcomes. Temporomandibular joint (TMJ) ankylosis has been observed to adversely impact the quality of life (QoL) of the patients, affecting both the physical and psychosocial aspects of their lives. The study was conducted to develop and validate a TMJ ankylosis specific QoL questionnaire (TMJAQoL). It had two phases. Phase 1 was associated with the development of the questionnaire while phase 2 examined its psychometric properties and validated the instrument. In phase 1, a 65 item pool was generated and was eventually reduced to a 37 item pool after sequential evaluation by two expert groups. The 37 item draft was subjected to item reduction by the impact method, resulting in a 12 item draft divided into 4 domains, which formed the TMJAQoL questionnaire. In phase 2, the TMJAQoL was completed by 51 TMJ ankylosis patients and was found to have optimum validity, reliability and internal consistency. 44 of these patients completed the TMJAQoL again after the surgery. A significant change in mean cumulative TMJAQoL scores (pre-op = 14.10, post op = 4.05, p = .001) was found after the surgery. This change was significantly correlated to the improvement in the maximal incisal opening and the right and left lateral movements (r > .30). Amongst the TMJAQoL domains, significant improvement was seen in functional limitation (p = .026), psychological well being (p = .017) and social wellbeing domains (p = .038). Overall, improved QoL was observed after the TMJ surgery. The TMJAQoL demonstrated optimum psychometric properties and promises to be an effective QoL instrument for the TMJ ankylosis patients.
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http://dx.doi.org/10.1016/j.jcms.2020.06.005DOI Listing
August 2020

Importance of investigating high-risk human papillomavirus in lymph node metastasis of esophageal adenocarcinoma.

World J Gastroenterol 2020 Jun;26(21):2729-2739

Gastro-Intestinal Viral Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, Sydney, New South Wales 2170, Australia.

High-risk human papillomavirus has been suggested as a risk factor for esophageal adenocarcinoma. Tumor human papillomavirus status has been reported to confer a favorable prognosis in esophageal adenocarcinoma. The size of the primary tumor and degree of lymphatic spread determines the prognosis of esophageal carcinomas. Lymph node status has been found to be a predictor of recurrent disease as well as 5-year survival in esophageal malignancies. In human papillomavirus driven cancers, . cervical, anogenital, head and neck cancers, associated lymph nodes with a high viral load suggest metastatic lymph node involvement. Thus, human papillomavirus could potentially be useful as a marker of micro-metastases. To date, there have been no reported studies regarding human papillomavirus involvement in lymph nodes of metastatic esophageal adenocarcinoma. This review highlights the importance of investigating human papillomavirus in lymph node metastasis of esophageal adenocarcinoma based on data derived from other human papillomavirus driven cancers.
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http://dx.doi.org/10.3748/wjg.v26.i21.2729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284187PMC
June 2020

Structure-guided engineering of the affinity and specificity of CARs against Tn-glycopeptides.

Proc Natl Acad Sci U S A 2020 06 15;117(26):15148-15159. Epub 2020 Jun 15.

Department of Biochemistry, Cancer Center, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

The potency of adoptive T cell therapies targeting the cell surface antigen CD19 has been demonstrated in hematopoietic cancers. It has been difficult to identify appropriate targets in nonhematopoietic tumors, but one class of antigens that have shown promise is aberrant O-glycoprotein epitopes. It has long been known that dysregulated synthesis of O-linked (threonine or serine) sugars occurs in many cancers, and that this can lead to the expression of cell surface proteins containing O-glycans comprised of a single -acetylgalactosamine (GalNAc, known as Tn antigen) rather than the normally extended carbohydrate. Previously, we used the scFv fragment of antibody 237 as a chimeric antigen receptor (CAR) to mediate recognition of mouse tumor cells that bear its cognate Tn-glycopeptide epitope in podoplanin, also called OTS8. Guided by the structure of the 237 Fab:Tn-OTS8-glycopeptide complex, here we conducted a deep mutational scan showing that residues flanking the Tn-glycan contributed significant binding energy to the interaction. Design of 237-scFv libraries in the yeast display system allowed us to isolate scFv variants with higher affinity for Tn-OTS8. Selection with a noncognate human antigen, Tn-MUC1, yielded scFv variants that were broadly reactive with multiple Tn-glycoproteins. When configured as CARs, engineered T cells expressing these scFv variants showed improved activity against mouse and human cancer cell lines defective in O-linked glycosylation. This strategy provides CARs with Tn-peptide specificities, all based on a single scFv scaffold, that allows the same CAR to be tested for toxicity in mice and efficacy against mouse and human tumors.
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http://dx.doi.org/10.1073/pnas.1920662117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334454PMC
June 2020

Atypical Cutaneous Presentation of Chronic Tophaceous Gout: A Case Report.

Indian Dermatol Online J 2020 Mar-Apr;11(2):235-238. Epub 2020 Mar 9.

Department of Radiodiagnosis, AIIMS Patna, Bihar, India.

Gout is a metabolic disease that occurs either because of increased uric acid production or decreased uric acid secretion. It most commonly affects middle-aged to elderly men and postmenopausal women. Chronic tophaceous gout frequently occurs after 10 years or more of recurrent polyarticular gout. Gouty tophi are deposition of monosodium urate (MSU) crystals in and around joints as well as soft tissues. We present a case of chronic tophaceous gout in a 21-year-old male, which occurred after 4 years of onset of gouty arthritis. The patient presented with tophaceous gout in four forms, that is, periarticular subcutaneous tophi, disseminated intradermal tophi, ulcerative form, and miliarial tophi along with multiple sinuses discharging chalky white material. The case was diagnosed as chronic tophaceous gout on the basis of raised serum uric acid, imprint smear showing needle-shaped crystals and negatively birefringent crystals on polarized microscopy. The case is interesting for varied morphological forms of tophaceous gout in a patient at an early age and shorter interval between onset of gouty arthritis and tophaceous gout.
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http://dx.doi.org/10.4103/idoj.IDOJ_205_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247644PMC
March 2020

Novel enterocin E20c purified from Enterococcus hirae 20c synergised with ß-lactams and ciprofloxacin against Salmonella enterica.

Microb Cell Fact 2020 May 4;19(1):98. Epub 2020 May 4.

Department of Microbiology, Guru Nanak Dev University, Amritsar, Punjab, India.

Background: An increasing rate of antibiotic resistance among Gram-negative bacterial pathogens has created an urgent need to discover novel therapeutic agents to combat infectious diseases. Use of bacteriocins as therapeutic agents has immense potential due to their high potency and mode of action different from that of conventional antibiotics.

Results: In this study, a novel bacteriocin E20c of molecular weight 6.5 kDa was purified and characterized from the probiotic strain of Enterococcus hirae. E20c had bactericidal activities against several multidrug resistant (MDR) Gram-negative bacterial pathogens. Flow cytometry and scanning electron microscopy studies showed that it killed the Salmonella enterica cells by forming ion-permeable channels in the cell membrane leading to enhanced cell membrane permeability. Further, checkerboard titrations showed that E20c had synergistic interaction with antibiotics such as ampicillin, penicillin, ceftriaxone, and ciprofloxacin against a ciprofloxacin- and penicillin-resistant strain of S. enterica.

Conclusion: Thus, this study shows the broad spectrum antimicrobial activity of novel enterocin E20c against various MDR pathogens. Further, it highlights the importance of bacteriocins in lowering the minimum inhibitory concentrations of conventional antibiotics when used in combination.
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http://dx.doi.org/10.1186/s12934-020-01352-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197179PMC
May 2020

Bioelectrochemical behaviour of a sequentially added biocatalytic coculture in a microbial fuel cell.

J Basic Microbiol 2020 Jul 20;60(7):562-573. Epub 2020 Apr 20.

Department of Biotechnology, Veer Narmad South Gujarat University, Surat, India.

Bacterial isolates Pseudomonas aeruginosa BR, Alcaligenes faecalis SW and Escherichia coli EC from a microbial fuel cell (MFC) were cocultured with each other. The isolates were added in a specific sequence one after the other (two cultures in one reactor). The study helped us conceptualise the synergistic and antagonistic behaviour of bacterial isolates and also emphasised the sequence in which a culture can be introduced in an anode chamber. The coculture conditions were evaluated on the basis of redox activity, electron transfer rate, columbic efficiency, and internal resistances. A good syntropy in terms of power production was found between P. aeruginosa BR and E. coli EC that recorded a power generation of 207.593 ± 1.705 µW/m . The addition of any culture in any sequence affected the performance of P. aeruginosa BR. This culture when added as a secondary culture in the reactor enhanced the performance of that reactor. The sequence of addition of a culture in a reactor affected the performance in the combinations of (a) P. aeruginosa BR and A. faecalis SW and (b) A. faecalis SW and E. coli EC.
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http://dx.doi.org/10.1002/jobm.202000042DOI Listing
July 2020

Characterization of Skeletal Muscle Endocrine Control in an In Vitro Model of Myogenesis.

Calcif Tissue Int 2020 07 27;107(1):18-30. Epub 2020 Feb 27.

Department of Experimental and Clinical Biomedical Sciences, University of Florence, Largo Palagi 1, 50139, Florence, Italy.

Skeletal muscle has remarkable regenerative abilities regulated by a highly orchestrated process involving the activation of cellular and molecular responses, which are dependent on satellite cells. These cells maintain the stem cell population and provide numerous myogenic cells that proliferate, differentiate, fuse and lead to new myofiber formation for a functional contractile tissue. We have isolated and characterized satellite cells obtained from human biopsies and established an in vitro model of myogenesis, evaluating muscle regeneration, monitoring the dynamic increases of the specific myogenic regulatory factors and the final formation of multinucleated myofibers. As the skeletal muscle is an endocrine tissue able of producing many substances that can act on distant organs, and it can be physiologically modulated by a variety of hormones, we embarked in a project of characterization of muscle cell endocrinology machinery. The expression of a large array of hormone receptors was quantified during the process of myogenesis. The results obtained showed a significant and generalized increase of all the tested hormone receptors along the process of differentiation of human cultured cells from myoblasts to myocytes. Interestingly, also the production of the myokine irisin increased in a parallel manner. These findings point to the human cultured myoblasts as an ideal model to characterize the skeletal muscle endocrine machinery and its hormonal regulation.
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http://dx.doi.org/10.1007/s00223-020-00678-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271047PMC
July 2020

Association of Biomarkers for Human Papillomavirus With Survival Among Adults With Barrett High-grade Dysplasia and Esophageal Adenocarcinoma.

JAMA Netw Open 2020 02 5;3(2):e1921189. Epub 2020 Feb 5.

Ingham Institute for Applied Medical Research, Liverpool, Sydney, New South Wales, Australia.

Importance: The presence of high-risk human papillomavirus (HPV) has been associated with a favorable outcome in Barrett high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Nevertheless, the prognostic significance of other HPV-related biomarkers (ie, retinoblastoma protein [pRb], cyclin D1 [CD1], minichromosome maintenance protein [MCM2] and Ki-67) is unknown.

Objective: To examine the association between HPV-related biomarkers and survival in adult patients with Barrett HGD and EAC.

Design, Setting, And Participants: This retrospective case-control study examined the hypothesis that the HPV-related cell cycle markers (pRb, CD1, and Ki-67) and the viral surrogate marker (MCM2) may be associated with a favorable prognosis in Barrett HGD and EAC. Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction and immunohistochemistry for the HPV-related biomarkers. Recruitment of patients occurred in secondary and tertiary referral centers, with 151 patients assessed for eligibility. The study period was from December 1, 2002, to November 28, 2017, and the dates of analysis were from September 9, 2011, to November 28, 2017.

Main Outcomes And Measures: Disease-free survival and overall survival.

Results: Of 151 patients assessed for eligibility, 9 were excluded. Among the 142 patients with Barrett HGD or EAC (126 [88.7%] men; mean [SD] age, 66.0 [12.1] years; 142 [100%] white), 37 were HPV positive and 105 were HPV negative. No association with disease-free survival was noted for pRb, CD1, Ki-67, and MCM2. In regard to overall survival, only low expression of CD1 had a favorable prognosis (hazard ratio [HR], 0.53; 95% CI, 0.30-0.95; adjusted P = .03). All the biomarkers stratified by HPV status showed significant associations with survival. Patients with HPV-positive, low-expression pRb esophageal tumors were associated with a significantly improved disease-free survival compared with the HPV-negative, high-expression Rb tumors (HR, 0.33; 95% CI, 0.12-0.93; adjusted P = .04). Similarly, HPV-positive, low-expression CD1 was associated with a significantly favorable disease-free survival (HR, 0.26; 95% CI, 0.09-0.76; adjusted P = .01), as was HPV-positive, high-expression MCM2 (HR, 0.27; 95% CI, 0.09-0.78; adjusted P = .02). In regard to overall survival, HPV was significantly associated only with low CD1 (HR, 0.38; 95% CI, 0.15-0.94; adjusted P = .04).

Conclusions And Relevance: This study's findings suggest that low expression of CD1 appears to be an independent prognostic marker in Barrett HGD and EAC. Human papillomavirus positivity in combination with pRb, CD1, MCM2, and Ki-67 was associated with a survival benefit in esophageal tumors. These findings suggest the possibility of personalization of therapy for Barrett HGD and EAC based on viral status.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.21189DOI Listing
February 2020

Probiotic properties of a phytase producing Pediococcus acidilactici strain SMVDUDB2 isolated from traditional fermented cheese product, Kalarei.

Sci Rep 2020 02 5;10(1):1926. Epub 2020 Feb 5.

School of Biotechnology, Shri Mata Vaishno Devi University, Katra, Jammu & Kashmir, 182320, India.

The nutritional challenge faced by the monogastric animals due to the chelation effects of phytic acid, fuel the research on bioprospecting of probiotics for phytase production. Pediococcus acidilactici SMVDUDB2 isolated from Kalarei, exhibited extracellular phytase activity of 5.583 U/mL after statistical optimization of fermentation conditions viz. peptone (1.27%); temperature (37 °C); pH (6.26) and maltose (1.43%). The phytase enzyme possessed optimum pH and temperature of 5.5 and 37 °C, respectively and was thermostable at 60 °C. The enzyme was purified 6.42 fold with a specific activity of 245.12 U/mg with hydrophobic interaction chromatography. The purified enzyme had K and V values of 0.385 mM and 4.965 μmol/min respectively, with sodium phytate as substrate. The strain depicted more than 80% survival rate at low pH (pH 2.0, 3.0), high bile salt concentration (0.3 and 0.5%), after gastrointestinal transit, highest hydrophobicity affinity with ethyl acetate (33.33 ± 0%), autoaggregation (77.68 ± 0.68%) as well as coaggregation (73.57 ± 0.47%) with Staphylococcus aureus (MTCC 3160). The strain exhibited antimicrobial activity against Bacillus subtilis (MTCC 121), Mycobacterium smegmatis (MTCC 994), Staphylococcus aureus (MTCC 3160), Proteus vulgaris (MTCC 426), Escherichia coli (MTCC 1652) and Lactobacillus rhamnosus (MTCC 1408). The amount of exopolysaccharide produced by the strain was 2 g/L. This strain having the capability of phytate degradation and possessing probiotic traits could find application in food and feed sectors.
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http://dx.doi.org/10.1038/s41598-020-58676-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002416PMC
February 2020

Design of a novel rapid immunoassay for simultaneous detection of hepatitis C virus core antigen and antibodies.

Arch Virol 2020 Mar 21;165(3):627-641. Epub 2020 Jan 21.

Department of Biotechnology, Veer Narmad South Gujarat University, Surat, Gujarat, 395007, India.

HCV is a potential cause of viral hepatitis, which leads to blood-borne chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Anti-HCV antibody detection assays detect HCV infection after approximately 70 days. HCV core antigen can be detected much earlier than anti-HCV antibodies. However, it disappears soon after the appearance of anti-HCV antibodies. Thus, there is a need for a rapid assay for simultaneous detection of HCV core antigen and anti-HCV antibodies for early diagnosis of HCV infection. A rapid diagnostic assay (HCV Ag-Ab Combo) for simultaneous detection of HCV core antigen and anti-HCV antibodies for early diagnosis of HCV infection was developed. HCV Ag-Ab Combo was evaluated in order to determine its potential for detection of HCV infection earlier than anti-HCV antibody detection assays. We compared the sensitivity of the newly developed assay with anti-HCV antibody detection assays (ELISA [HCV Ab ELISA] and rapid test [HCV Ab Rapid]) and HCV core antigen/anti-HCV antibody detection ELISA (HCV Ag-Ab ELISA). This study included 11 samples that were found positive in HCV RNA detection and HCV Ag-Ab ELISA but negative in HCV antibody detection assays (HCV Ab ELISA and rapid), 10 samples that were found positive in HCV Ag-Ab ELISA and HCV Ab ELISA but negative in HCV Ab Rapid, 69 samples that were found positive in HCV Ag-Ab ELISA, HCV Ab ELISA, and HCV Ab Rapid, and 509 samples that were found negative in HCV Ag-Ab ELISA, HCV Ab ELISA, and HCV Ab Rapid. Three seroconversion panels, PHV 913, PHV 911 (M) and PHV904-00-1.0, and a HCV RNA genotype qualification panel (2400-0182) acquired from Seracare Life Sciences (USA) were also tested. HCV Ag-Ab Combo showed a combined sensitivity and specificity of 100% when tested with 90 samples that were positive for HCV by HCV Ag-Ab ELISA and 509 HCV-negative samples. Its positive predictive value (PPV) and negative predictive value (NPV) were found to be 100%. It detected HCV infection approximately 7 to 12 days earlier than the HCV Ab detection assays, and its performance was not affected when testing different genotypes of HCV. HCV Ag-Ab Combo did not detect HCV infection as early as HCV RNA or HCV Ag-Ab ELISA. HCV Ag-Ab Combo provided a significant improvement for the early detection of HCV infection during the preseroconversion phase when compared with anti-HCV antibody detection assays. It could be a useful screening assay, and an alternative to HCV RNA detection or HCV Ag-Ab ELISA when nucleic acid technologies cannot be implemented.
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http://dx.doi.org/10.1007/s00705-019-04518-0DOI Listing
March 2020

Epithelial-mesenchymal transition in serous and mucinous epithelial tumors of the ovary.

J Cancer Res Ther 2019 Oct-Dec;15(6):1309-1315

Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.

Context: The concept of epithelial-mesenchymal transition (EMT) in cancer origin, progression, and metastasis is of recent origin and not fully understood. So far, many cell culture studies have been done to investigate the role of EMT in epithelial ovarian cancer, but only a few human studies have been conducted.

Aims: The aim of the study is to study the expression of E-cadherin and vimentin in serous and mucinous tumors of the ovary and to compare their expression in benign and malignant serous and mucinous ovarian tumors.

Methods: This study was a prospective study done on 60 patients with a histological diagnosis of serous and mucinous ovarian malignancy. The study was conducted in the Department of Pathology and Department of Obstetrics and Gynaecology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi. The expression of epithelial marker E-cadherin and mesenchymal marker vimentin was studied in each of the tumors.

Statistical Analysis: Unpaired t-test/Mann-Whitney test, Chi-Square test/Fisher's exact test, and Kolmogorov-Smirnov test were used.

Results: Of the total 60 cases included in the study, 30 benign and 30 malignant cases of serous and mucinous tumors were taken. Of the 30 benign cases, 22 cases (73.3%) were that of serous cystadenomas, whereas 8 (26.67%) cases were of mucinous cystadenomas. Among the malignant cases, 21 cases (70%) were serous surface epithelial ovarian carcinoma, whereas 9 (30%) were mucinous surface epithelial ovarian carcinoma. Subsequently, the malignant cases were graded according to their glandular differentiation. Immunohistochemistry was performed in each of the 60 cases.

Conclusion: In the malignant cases with increasing grade of the tumor, a reduced expression of E-cadherin and an increased expression of vimentin were seen in the epithelial cells.
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http://dx.doi.org/10.4103/jcrt.JCRT_35_18DOI Listing
May 2020
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