Publications by authors named "Ruchi Srivastava"

73 Publications

Comparative evaluation of improvement in periodontal and glycemic health status of type 2 diabetes mellitus patients after scaling and root planing with or without adjunctive use of diode laser.

Lasers Med Sci 2021 Feb 1. Epub 2021 Feb 1.

Department of Periodontology, Saraswati Dental College, 233, Tiwari Ganj, Faizabad Road, Chinhat, Lucknow, UP, 226028, India.

Background: Periodontal treatment in diabetic patients reduces systemic inflammatory burden and hence should be closely coordinated with the patient's overall clinical diabetic management.

Objective: To evaluate the effectiveness of diode laser (DL) (Biolase Epic, 940 nm, Irvine, CA, USA) as an adjunct to scaling root and planing (SRP) on periodontal health and glycated hemoglobin (HbA1c) level of type 2 diabetes mellitus (T2DM) patients suffering from generalized chronic periodontitis (CP), currently, stage II or above/grade B or C periodontitis.

Materials And Methodology: After initial screening of 55 T2DM patients, a total of 44 T2DM-CP patients (between the age group of 30 and 65 years) were selected and randomly assigned into two groups. The groups were divided into control group (n=22), treated with scaling and root planing alone (SRP alone), and experimental group (n=22), treated with scaling and root planing along with laser therapy (SRP + DL). Laser irradiation was accomplished at perio pocket setting of 0.8 W (average) in a pulse interval of 1.0 ms and pulse length of 1.0 ms delivering 24 J of energy using a 300-μm fiber optic delivery system.

Results: Thirty-seven out of 44 enrolled T2DM-CP patients completed the study. Both treatment modalities, i.e., SRP alone and SRP+DL resulted in mean significant (p < 0.001) improvement in periodontal health parameters (plaque index (PI), gingival index (GI), probing pocket depth (PPD) and clinical attachment loss (CAL)) and glycemic level (RBS, FBS, and HbA1c) in T2DM-CP patients after 6 months, and was higher in SRP+DL group in comparison to SRP alone. Among the periodontal health parameters, the mean PPD reduction and CAL gain were 51.78% and 48.26% in control as compared to 61.56% and 62.54% in experimental group respectively, whereas the mean significant reduction in HbA1c was 13.8% in SRP alone and 22.52% in SRP+DL group after 6 months (p < 0.05).

Conclusion: Periodontal treatment involving SRP+DL contributes to improved periodontal health parameters and HbA1c level in T2DM-CP patients.
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http://dx.doi.org/10.1007/s10103-021-03261-wDOI Listing
February 2021

DFT Study on the Electronic Properties, Spectroscopic Profile, and Biological Activity of 2-Amino-5-trifluoromethyl-1,3,4-thiadiazole with Anticancer Properties.

ACS Omega 2020 Nov 13;5(46):30073-30087. Epub 2020 Nov 13.

Department of Physics, University of Lucknow, Lucknow 226007, India.

Extensive investigation on the molecular and electronic structure of 2-amino-5-trifluoromethyl-1,3,4-thiadiazole in the ground state and in the first excited state has been performed. The energy barrier corresponding to the conversion between imino and amino tautomers has been calculated, which indicates the existence of amino tautomer in solid state for the title compound. The FT-Raman and FT-IR spectra were recorded and compared with theoretical vibrational wavenumbers, and a good coherence has been observed. The MESP map, dipole moment, polarizability, and hyperpolarizability have been calculated to comprehend the properties of the title molecule. High polarizability value estimation of the title compound may enhance its bioactivity. Natural bonding orbital analysis has been done on monomer and dimer to investigate the charge delocalization and strength of hydrogen bonding, respectively. Strong hydrogen bonding interaction energies of 17.09/17.49 kcal mol have been calculated at the B3LYP/M06-2X functional. The UV-vis spectrum was recorded and related to the theoretical spectrum. The title compound was biologically examined for anticancer activity by studying the cytotoxic performance against two human cancer cell lines (A549 and HeLa) along with the molecular docking simulation. Both molecular docking and cytotoxic performance against cancer cell lines show positive outcomes, and the title compound appears to be a promising anticancer agent.
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http://dx.doi.org/10.1021/acsomega.0c04474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689922PMC
November 2020

Leptomeningeal relapse in primary cutaneous DLBCL: Implications for a prophylactic CNS therapy.

Cancer Rep (Hoboken) 2021 Feb 7;4(1):e1295. Epub 2020 Oct 7.

Department of Medical Oncology, Hematology, All India Institute of Medical Sciences, Rishikesh, India.

Background: Isolated leptomeningeal relapse in a case of cutaneous lymphoma is an uncommon event more so in a case of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL). This phenomenon is of great significance as the subsequent prognosis becomes poor and the prophylactic central nervous system (CNS) therapy if administered, can reduce the chances of relapse, however, the survival benefit remains uncertain. The role of prophylactic CNS therapy is not well defined in the case of PCDLBCL.

Case: We report a case of PCDLBCL leg type with a low CNS International Prognostic Index (CNS-IPI) risk, who developed isolated leptomeningeal relapse in the form of bilateral facial nerve palsy. He was managed by 2nd line chemotherapy and CNS directed therapy and achieved complete remission.

Conclusion: PCDLBCL leg type is an aggressive malignancy. Molecular/genomic mechanism likely responsible for CNS dissemination should be identified by prospective multi-centric studies that can better define the subsets of patients eligible for prophylactic therapy in the absence of a high CNS-IPI risk.
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http://dx.doi.org/10.1002/cnr2.1295DOI Listing
February 2021

Genome-Wide Asymptomatic B-Cell, CD4 and CD8 T-Cell Epitopes, that are Highly Conserved Between Human and Animal Coronaviruses, Identified from SARS-CoV-2 as Immune Targets for Pre-Emptive Pan-Coronavirus Vaccines.

bioRxiv 2020 Sep 28. Epub 2020 Sep 28.

Over the last two decades, there have been three deadly human outbreaks of Coronaviruses (CoVs) caused by emerging zoonotic CoVs: SARS-CoV, MERS-CoV, and the latest highly transmissible and deadly SARS-CoV-2, which has caused the current COVID-19 global pandemic. All three deadly CoVs originated from bats, the natural hosts, and transmitted to humans various intermediate animal reservoirs. Because there is currently no universal pan-Coronavirus vaccine available, two worst-case scenarios remain highly possible: (1) SARS-CoV-2 mutates and transforms into a seasonal "flu-like" global pandemic; and/or (2) Other global COVID-like pandemics will emerge in the coming years, caused by yet another spillover of an unknown zoonotic bat-derived SARS-like Coronavirus (SL-CoV) into an unvaccinated human population. Determining the antigen and epitope landscapes that are conserved among human and animal Coronaviruses as well as the repertoire, phenotype and function of B cells and CD4 and CD8 T cells that correlate with resistance seen in asymptomatic COVID-19 patients should inform in the development of pan-Coronavirus vaccines . In the present study, using several immuno-informatics and sequence alignment approaches, we identified several human B-cell, CD4 and CD8 T cell epitopes that are highly conserved in: ( ) greater than 81,000 SARS-CoV-2 human strains identified to date in 190 countries on six continents; ( ) six circulating CoVs that caused previous human outbreaks of the "Common Cold"; ( ) five SL-CoVs isolated from bats; ( ) five SL-CoV isolated from pangolins; ( ) three SL-CoVs isolated from Civet Cats; and ( ) four MERS strains isolated from camels. Furthermore, we identified cross-reactive asymptomatic epitopes that: ( ) recalled B cell, CD4 and CD8 T cell responses from both asymptomatic COVID-19 patients and healthy individuals who were never exposed to SARS-CoV-2; and ( ) induced strong B cell and T cell responses in "humanized" Human Leukocyte Antigen (HLA)-DR/HLA-A*02:01 double transgenic mice. The findings herein pave the way to develop a pre-emptive multi-epitope pan-Coronavirus vaccine to protect against past, current, and potential future outbreaks.
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http://dx.doi.org/10.1101/2020.09.27.316018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536874PMC
September 2020

Pan-genome analysis of Exiguobacterium reveals species delineation and genomic similarity with Exiguobacterium profundum PHM 11.

Environ Microbiol Rep 2020 12 11;12(6):639-650. Epub 2020 Oct 11.

ICAR-National Bureau of Agriculturally Important Microorganisms (NBAIM), Maunath Bhanjan, UP, 275103, India.

The stint of the bacterial species is convoluting, but the new algorithms to calculate genome-to-genome distance (GGD) and DNA-DNA hybridization (DDH) for comparative genome analysis have rejuvenated the exploration of species and sub-species characterization. The present study reports the first whole genome sequence of Exiguobacterium profundum PHM11. PHM11 genome consist of ~ 2.92 Mb comprising 48 contigs, 47.93% G + C content. Functional annotations revealed a total of 3033 protein coding genes and 33 non-protein coding genes. Out of these, only 2316 could be characterized and others reported as hypothetical proteins. The comparative analysis of predicted proteome of PHM11 with five other Exiguobacterium sp. identified 3806 clusters, out of which the PHM11 shared a total of 2723 clusters having 1664 common clusters, 131 singletons and 928 distributed between five species. The pan-genome analysis of 70 different genomic sequences of Exigubacterium strains devoid of a species taxon was done on the basis of GGD and the DDH which identified eight genomes analogous to the PHM11 at species level and may be characterized as E. profundum. The ANI value and phylogenetic tree analysis also support the same. The results regarding pan-genome analysis provide a convincing insight for delineation of these eight strains to species.
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http://dx.doi.org/10.1111/1758-2229.12890DOI Listing
December 2020

Unique molecular signatures of antiviral memory CD8 T cells associated with asymptomatic recurrent ocular herpes.

Sci Rep 2020 08 14;10(1):13843. Epub 2020 Aug 14.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Hewitt Hall, Room 2032; 843 Health Sciences Rd, Irvine, CA, 92697, USA.

The nature of antiviral CD8 T cells associated with protective and pathogenic herpes simplex virus type 1 (HSV-1) infections remains unclear. We compared the transcriptome, phenotype, and function of memory CD8 T cells, sharing the same HSV-1 epitope-specificities, from infected HLA-A*0201 positive symptomatic (SYMP) vs. asymptomatic (ASYMP) individuals and HLA-A*0201 transgenic rabbits. Compared to higher frequencies of multifunctional effector memory CD8 T cells in ASYMP individuals, the SYMP individuals presented dysfunctional CD8 T cells, expressing major exhaustion pathways. Compared to protected ASYMP HLA transgenic rabbits, the trigeminal ganglia of non-protected SYMP HLA transgenic rabbits had higher frequencies of dysfunctional tissue-resident CD8 T cells. Moreover, blockade of T cell exhaustion pathways restored the function of CD8 T cells, reduced virus reactivation, and diminished recurrent disease in HLA transgenic rabbits. These findings reveal unique molecular signatures of protective CD8 T cells and pave the way for T-cell-based immunotherapy to combat recurrent ocular herpes.
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http://dx.doi.org/10.1038/s41598-020-70673-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427992PMC
August 2020

Efficacy of Platelet-rich Fibrin in Interdental Papilla Reconstruction as Compared to Connective Tissue Using Microsurgical Approach.

Contemp Clin Dent 2019 Oct-Dec;10(4):643-651

Department of Periodontology, Saraswati Dental College, Lucknow, Uttar Pradesh, India.

Aim: This study aims to evaluate autologous platelet-rich fibrin (PRF) and autogenous connective tissue graft (CTG) in interdental papilla (IDP) reconstruction with buccal and palatal split-thickness flap (STF) using microsurgical technique.

Materials And Methods: Forty Class I or Class II open gingival or cervical embrasure in maxillary anterior region in 14 patients were surgical treated for the reconstruction of IDP. For experimental Group I (STF with PRF, = 20), surgical site was flushed with PRF fluid. PRF was then placed under the buccal flap and in the IDP region and squeezed. For experimental Group II (STF with CTG, = 20) after the preparation of recipient site, CTG procured from palate was trimmed to the desired size and shape and placed at the site. Clinical parameters and patient satisfaction response recorded were plaque index, gingival index, probing pocket depth, clinical attachment level, height of IPD, and papilla index score (PIS).

Results: STF surgery in combination with PRF or CTG, are an effective procedure to increase IDP-height with mean values of 3.10 mm (87.3%) and 3.45 mm (95.8%) for Group I (STF + PRF) and Group II (STF + CTG), respectively. In terms of complete fill (CF) achieved at 3 months, in the present study, the result showed that 90% CF was obtained in Group I (STF + PRF) and 95% in Group II (STF + CTG). The patient response and acceptance for surgical treatment modality in terms of patient postsurgical discomfort score and patient esthetic score was higher for Group II (STF + CTG) than Group I (STF + PRF).

Conclusion: Based on single-centered 3 months' follow-up, it may be concluded that STF surgery in combination with PRF or CTG is an effective procedure to increase IDP-height; however, a long-term multicentric randomized clinical trial may be necessary to evaluate the clinical outcome for autologous PRF in comparison to CTG with STF.
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http://dx.doi.org/10.4103/ccd.ccd_936_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390422PMC
August 2020

Upregulation of Multiple CD8 T Cell Exhaustion Pathways Is Associated with Recurrent Ocular Herpes Simplex Virus Type 1 Infection.

J Immunol 2020 07 15;205(2):454-468. Epub 2020 Jun 15.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California, Irvine, Irvine, CA 92697;

A large proportion of the world's population harbors latent HSV type 1 (HSV-1). Cross-talk between antiviral CD8 T cells and HSV-1 appear to control latency/reactivation cycles. We found that compared with healthy asymptomatic individuals, in symptomatic (SYMP) patients, the CD8 T cells with the same HLA-A*0201-restricted HSV-1 epitope specificities expressed multiple genes and proteins associated to major T cell exhaustion pathways and were dysfunctional. Blockade of immune checkpoints with anti-LAG-3 and anti-PD-1 antagonist mAbs synergistically restored the frequency and function of antiviral CD8 T cells, both 1) ex vivo, in SYMP individuals and SYMP HLA-A*0201 transgenic mice; and 2) in vivo in HSV-1-infected SYMP HLA-A*0201 transgenic mice. This was associated with a significant reduction in virus reactivation and recurrent ocular herpetic disease. These findings confirm antiviral CD8 T cell exhaustion during SYMP herpes infection and pave the way to targeting immune checkpoints to combat recurrent ocular herpes.
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http://dx.doi.org/10.4049/jimmunol.2000131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343593PMC
July 2020

Prevalence of Periodontal Disease in Type 2 Diabetes Mellitus Patients: A Cross-sectional Study.

Contemp Clin Dent 2019 Apr-Jun;10(2):349-357

Department of Periodontology, Saraswati Dental College and Hospital, Lucknow, Uttar Pradesh, India.

Aim: The aim of this study was to determine the prevalence of periodontal disease in type 2 diabetes mellitus (T2DM) patients of North India.

Materials And Methods: A total of 500 patients fulfilling the selection criteria were initially given a health questionnaire to gather information regarding their demographic characteristics, attitude for oral hygiene, and disease status. Based on eligibility 427 patients were finally recruited for statistical analysis. A partial-mouth periodontal examination (PMPE) protocol which assessed one maxillary quadrant and one mandibular quadrant was used to examine three fixed sites per tooth (mesiobuccal, midbuccal, and distobuccal). Gingival Index, Oral Hygiene Index-Simplified, Debris Index-Simplified, Calculus Index-Simplified (CI-S), probing pocket depth, and clinical attachment level were examined.

Results: More than 90% (95.1%) of the total diabetic participants had some degree of periodontal destruction. Of the total population, 27.1% of participants had good oral hygiene, 68.8% had fair oral hygiene, and 3.9% had poor oral hygiene status. The prevalence of severe periodontitis in participants with good, fair, and poor oral hygiene status was reported as 0.8%, 17%, and 29.4%, respectively. The prevalence of severe periodontitis in participants with good, fair, and poor oral hygiene status with poor glycemic control (glycated hemoglobin ≥8%) was 2.5%, 28.1%, and 30.7%, respectively.

Conclusion: This single-centered cross-sectional study represents that more than 95% of type 2 diabetic patients have some periodontal destruction. These results may act as baseline data to promote the collaborative integrated management of diabetes for reducing its burden on society.
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http://dx.doi.org/10.4103/ccd.ccd_652_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145232PMC
April 2020

High Frequency of Gamma Interferon-Producing PLZFRORγt Invariant Natural Killer 1 Cells Infiltrating Herpes Simplex Virus 1-Infected Corneas Is Associated with Asymptomatic Ocular Herpesvirus Infection.

J Virol 2020 04 16;94(9). Epub 2020 Apr 16.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA

Invariant natural killer (iNKT) cells are among the first innate immune cells to elicit early protective immunity that controls invading viral pathogens. The role of the iNKT cell subsets iNKT1, iNKT2, and iNKT17 in herpesvirus immunity remains to be fully elucidated. In this study, we examined the protective role of cornea-resident iNKT cell subsets using the mouse model of ocular herpesvirus infection and disease. Wild-type (WT) C57BL/6 (B6) mice and CD1d knockout (KO) mice were infected ocularly with herpes simplex virus 1 (HSV-1) (strain McKrae). Cornea, spleen, and liver were harvested at 0, 2, 5, 8, and 14 days postinfection (p.i.), and the frequency and function of the three major iNKT cell subsets were analyzed and correlated with symptomatic and asymptomatic corneal herpesvirus infections. The profiles of 16 major pro- and anti-inflammatory cytokines were analyzed in corneal lysates using Western blot and Luminex assays. Early during ocular herpesvirus infection (i.e., day 2), the gamma interferon (IFN-γ)-producing PLZFRORγt (promyelocytic leukemia zinc finger, retinoic acid-related orphan receptor gT) iNKT1 cell subset was the predominant iNKT cell subset in infected asymptomatic corneas. Moreover, compared to the asymptomatic corneas of HSV-1-infected WT mice, the symptomatic corneas CD1d KO mice, with iNKT cell deficiency, had increased levels of the inflammatory cytokine interleukin-6 (IL-6) and decreased levels of IL-12, IFN-γ, and the JAK1, STAT1, NF-κB, and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways. Our findings suggest that IFN-γ-producing PLZFRORγt iNKT1 cells play a role in the protective innate immune response against symptomatic ocular herpes. We investigated the protective role of iNKT cell subsets in asymptomatic ocular herpesvirus infection. We found that early during ocular herpesvirus infection (i.e., on day 2 postinfection), IFN-γ-producing PLZFRORγt iNKT1 cells were the predominant iNKT cell subset in infected corneas of asymptomatic B6 mice (with little to no corneal herpetic disease), compared to corneas of symptomatic mice (with severe corneal herpetic disease). Moreover, compared to asymptomatic corneas of wild-type (WT) B6 mice, the symptomatic corneas of CD1d KO mice, which lack iNKT cells, showed (i) decreases in the levels of IFN-γ and IL-12, (ii) an increase in the level of the inflammatory cytokine IL-6; and (iii) downregulation of the JAK1, STAT1, NF-κB, and ERK1/2 pathways. The findings suggest that early during ocular herpesvirus infection, cornea-resident IFN-γ-producing PLZFRORγt iNKT1 cells provide protection from symptomatic ocular herpes.
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http://dx.doi.org/10.1128/JVI.00140-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163123PMC
April 2020

Metagenome dataset of wheat rhizosphere from Ghazipur region of Eastern Uttar Pradesh.

Data Brief 2020 Feb 3;28:105094. Epub 2020 Jan 3.

ICAR-National Bureau of Agriculturally Important Microorganism (NBAIM), Kushmaur, Mau, 275103, U.P, India.

Wheat is the major crop in India and like other crops also subjected to influence by microbial communities of the rhizospheric region which are extremely diverse and undoubtedly play a central role in the nutrient cycle, plant productivity and growth promotion. In order to know how changes in the rhizospheric microbial community can make an impact on overall crop function, wheat rhizospheric soil samples from Ghazipur (25.913824 N 83.529715 E) regions of Eastern Uttar Pradesh (Eastern Indogangatic Plain), were collected and analyzed. Full length 16S rRNA gene amplification sequencing was performed to reveal the bacterial community in wheat rhizosphere. A total of 51,909 read were analyzed, out of that only 44,125 reads were classified and 7784 were unclassified using oxford nanopore sequencing and EPI2ME data analysis platform. MinION oxford nanopore sequencing uncovered that dominant phyla were (68%), (13%), (3%), (3%) and (3%). The data is available at the NCBI - Sequence Read Archive (SRA) with accession number: SRX5275271.
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http://dx.doi.org/10.1016/j.dib.2019.105094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956763PMC
February 2020

Human Epitopes Identified from Herpes Simplex Virus Tegument Protein VP11/12 (UL46) Recall Multifunctional Effector Memory CD4 T Cells in Asymptomatic Individuals and Protect from Ocular Herpes Infection and Disease in "Humanized" HLA-DR Transgenic Mice.

J Virol 2020 03 17;94(7). Epub 2020 Mar 17.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA

While the role of CD8 T cells in the control of herpes simplex virus 1 (HSV-1) infection and disease is gaining wider acceptance, a direct involvement of effector CD4 T cells in this protection and the phenotype and function of HSV-specific human CD4 T cell epitopes remain to be fully elucidated. In the present study, we report that several epitopes from the HSV-1 virion tegument protein (VP11/12) encoded by UL46 are targeted by CD4 T cells from HSV-seropositive asymptomatic individuals (who, despite being infected, never develop any recurrent herpetic disease). Among these, we identified two immunodominant effector memory CD4 T cell epitopes, amino acids (aa) 129 to 143 of VP11/12 (VP11/12) and VP11/12, using , , and approaches based on the following: (i) a combination of the TEPITOPE algorithm and PepScan library scanning of the entire 718 aa of HSV-1 VP11/12 sequence; (ii) an peptide-protein docking analysis and binding assay that identify epitopes with high affinity to soluble HLA-DRB1 molecules; and (iii) an ELISpot assay and intracellular detection of gamma interferon (IFN-γ), CD107 degranulation, and CD4 T cell carboxyfluorescein succinimidyl ester (CFSE) proliferation assays. We demonstrated that native VP11/12 and VP11/12 epitopes presented by HSV-1-infected HLA-DR-positive target cells were recognized mainly by effector memory CD4 T cells while being less targeted by FOXP3 CD4 CD25 regulatory T cells. Furthermore, immunization of HLA-DR transgenic mice with a mixture of the two immunodominant human VP11/12 CD4 T cell epitopes, but not with cryptic epitopes, induced HSV-specific polyfunctional IFN-γ-producing CD107 CD4 T cells associated with protective immunity against ocular herpes infection and disease. We report that naturally protected HSV-1-seropositive asymptomatic individuals develop a higher frequency of antiviral effector memory CD4 T cells specific to two immunodominant epitopes derived from the HSV-1 tegument protein VP11/12. Immunization of HLA-DR transgenic mice with a mixture of these two immunodominant CD4 T cell epitopes induced a robust antiviral CD4 T cell response in the cornea that was associated with protective immunity against ocular herpes. The emerging concept of developing an asymptomatic herpes vaccine that would boost effector memory CD4 and CD8 T cell responses is discussed.
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http://dx.doi.org/10.1128/JVI.01991-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081904PMC
March 2020

Metabolic syndrome and periodontal disease: An overview for physicians.

J Family Med Prim Care 2019 Nov 15;8(11):3492-3495. Epub 2019 Nov 15.

Faculty of Dental Sciences, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

The metabolic syndrome (MetS) (also known as insulin resistance syndrome, syndrome X) is a cluster of factors associated with increased risk of developing coronary heart disease or type 2 diabetes mellitus. Several studies in the past have reviewed an association between MetS and periodontitis. Periodontal disease is considered an infectious and chronic inflammatory disease, and it has been considered to be a potential risk in cardiovascular and respiratory diseases and diabetes, and has implications in adverse pregnancy outcomes, osteoporosis, and so on. These systemic disorders have been documented as capable of affecting the periodontium or treatment of periodontal disease. Oral inflammatory lesions have different basic mechanisms concerning the possible association with systemic diseases. They concern local spread, metastatic spread, or immunologic cross-reactivity. In many studies, sometimes contrasting, periodontal pathogens have been evaluated in atheromatous plaques isolated from patients with chronic periodontitis. Oral inflammatory lesions have been shown unequivocally to contribute to elevated systemic inflammatory responses. In some studies, intensive periodontal therapy showed a significant reduction in c-reactive protein levels, interleukin-6, and low-density lipoprotein cholesterol after 2 months. The aim of this article is to reflect the association between MetS and periodontitis and to suggest an understanding to promote interprofessional practice; with proper oral care and plaque control, we can reduce the severity of MetS.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_866_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881921PMC
November 2019

NLRP3, NLRP12, and IFI16 Inflammasomes Induction and Caspase-1 Activation Triggered by Virulent HSV-1 Strains Are Associated With Severe Corneal Inflammatory Herpetic Disease.

Front Immunol 2019 16;10:1631. Epub 2019 Jul 16.

Laboratory of Cellular and Molecular Immunology, School of Medicine, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA, United States.

The crosstalk between the host's inflammasome system and the invading virulent/less-virulent viruses determines the outcome of the ensuing inflammatory response. An appropriate activation of inflammasomes triggers antiviral inflammatory responses that clear the virus and heal the inflamed tissue. However, an aberrant activation of inflammasomes can result in a harmful and overwhelming inflammation that could damage the infected tissue. The underlying host's immune mechanisms and the viral virulent factors that impact severe clinical inflammatory disease remain to be fully elucidated. In this study, we used herpes simplex virus type 1 (HSV-1), the causative agent of corneal inflammatory herpetic disease, as a model pathogen to determine: (i) Whether and how the virulence of a virus affects the type and the activation level of the inflammasomes; and (ii) How triggering specific inflammasomes translates into protective or damaging inflammatory response. We showed that, in contrast to the less-virulent HSV-1 strains (RE, F, KOS, and KOS63), corneal infection of B6 mice with the virulent HSV-1 strains (McKrae, 17 or KOS79): (i) Induced simultaneous expression of the NLRP3, NLRP12, and IFI16 inflammasomes; (ii) Increased production of the biologically active Caspase-1 and pro-inflammatory cytokines IL-1β and IL-18; (iii) Heightened recruitment into the inflamed cornea of CD45Ly6CLy6GF4/80CD11bCD11c inflammatory monocytes and CD45CD11bF4/80Ly6GLy6C neutrophils; and (iv) This intensified inflammatory response was associated with a severe corneal herpetic disease, irrespective of the level of virus replication in the cornea. Similarly, infection of human corneal epithelial cells and human monocytic THP-1 cells with the virulent HSV-1 strains triggered a synchronized early expression of NLRP3, NLRP12 and IFI16, 2 h post-infection, associated with formation of single and dense specks of the adapter molecule ASC in HSV cells, but not in the neighboring bystander HSV cells. This was associated with increased cleavages of Caspase-1, IL-1β, and IL-18. These findings suggest a previously unappreciated role of viral virulence in a synchronized early induction of the NLRP3, NLRP12, and IFI16 inflammasomes that lead to a damaging inflammatory response. A potential role of common virus virulent factors that stimulate this harmful inflammatory corneal disease is currently under investigation.
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http://dx.doi.org/10.3389/fimmu.2019.01631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644090PMC
October 2020

Blockade of PD-1 and LAG-3 Immune Checkpoints Combined with Vaccination Restores the Function of Antiviral Tissue-Resident CD8 T Cells and Reduces Ocular Herpes Simplex Infection and Disease in HLA Transgenic Rabbits.

J Virol 2019 09 28;93(18). Epub 2019 Aug 28.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California-Irvine, Irvine, California, USA

Chronic viruses such as herpes simplex virus 1 (HSV-1) evade the hosts' immune system by inducing the exhaustion of antiviral T cells. In the present study, we found that exhausted HSV-specific CD8 T cells, with elevated expression of programmed death ligand-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) receptors were frequent in symptomatic patients, with a history of numerous episodes of recurrent corneal herpetic disease, compared to asymptomatic patients who never had corneal herpetic disease. Subsequently, using a rabbit model of recurrent ocular herpes, we found that the combined blockade of PD-1 and LAG-3 pathways with antagonist antibodies significantly restored the function of tissue-resident antiviral CD8 T cells in both the cornea and the trigeminal ganglia (TG). An increased number of functional tissue-resident HSV-specific CD8 T cells in latently infected rabbits was associated with protection against recurrent herpes infection and disease. Compared to the PD-1 or LAG-3 blockade alone, the combined blockade of PD-1 and LAG-3 appeared to have a synergistic effect in generating frequent polyfunctional Ki-67, IFN-γ, CD107, and CD8 T cells. Moreover, using the human leukocyte antigen (HLA) transgenic rabbit model, we found that dual blockade of PD-1 and LAG-3 reinforced the effect of a multiepitope vaccine in boosting the frequency of HSV-1-specific CD8 T cells and reducing disease severity. Thus, both the PD-1 and the LAG-3 exhaustion pathways play a fundamental role in ocular herpes T cell immunopathology and provide important immune checkpoint targets to combat ocular herpes. HSV-specific tissue-resident memory CD8 T cells play a critical role in preventing virus reactivation from latently infected TG and subsequent virus shedding in tears that trigger the recurrent corneal herpetic disease. In this report, we determined how the dual blockade of PD-1 and LAG-3 immune checkpoints, combined with vaccination, improved the function of CD8 T cells associated with a significant reduction in recurrent ocular herpes in HLA transgenic (Tg) rabbit model. The combined blockade of PD-1 and LAG-3 appeared to have a synergistic effect in generating frequent polyfunctional CD8 T cells that infiltrated both the cornea and the TG. The preclinical findings using the established HLA Tg rabbit model of recurrent herpes highlight that blocking immune checkpoints combined with a T cell-based vaccine would provide an important strategy to combat recurrent ocular herpes in the clinic.
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http://dx.doi.org/10.1128/JVI.00827-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714801PMC
September 2019

Draft genome sequence of a cold-adapted phosphorous-solubilizing P2 isolated from Sela Lake, India.

3 Biotech 2019 Jul 8;9(7):256. Epub 2019 Jun 8.

1ICAR-National Bureau of Agriculturally Important Microorganisms (NBAIM), Mau, Uttar Pradesh 275103 India.

The draft genome sequence of a cold-adapted phosphorus-solubilizing strain P2 isolated from the Sela Lake contains 6,436,246 bp with G + C content of 59.8%. The genome sequence includes 5743 protein coding genes, 68 non-protein coding genes, 1007 putative proteins, 5 rRNA genes, 64 tRNAs and two prophage regions in 40 contigs. Besides these, genes involved in phosphate solubilization, siderophore production, iron uptake, heat shock and cold shock tolerance, multidrug resistance and glycine-betaine production were also identified.
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http://dx.doi.org/10.1007/s13205-019-1784-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556163PMC
July 2019

Draft Genome Sequence of Halotolerant Bacterium Chromohalobacter salexigens ANJ207, Isolated from Salt Crystal Deposits in Pipelines.

Microbiol Resour Announc 2019 Apr 11;8(15). Epub 2019 Apr 11.

Indian Council of Agricultural Research (ICAR)-National Bureau of Agriculturally Important Microorganisms (NBAIM), Mau, Uttar Pradesh, India.

ANJ207 was isolated from a salt crystal and is known to tolerate up to 30% NaCl concentration. Here, we report the draft assembly of ANJ207. The genome was determined to have 3.66 Mb represented in 13 scaffolds, with a total of 3,406 genes predicted.
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http://dx.doi.org/10.1128/MRA.00049-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460019PMC
April 2019

Therapeutic Mucosal Vaccination of Herpes Simplex Virus 2-Infected Guinea Pigs with Ribonucleotide Reductase 2 (RR2) Protein Boosts Antiviral Neutralizing Antibodies and Local Tissue-Resident CD4 and CD8 T Cells Associated with Protection against Recurrent Genital Herpes.

J Virol 2019 05 17;93(9). Epub 2019 Apr 17.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA

Reactivation of herpes simplex virus 2 (HSV-2) from latency causes viral shedding that develops into recurrent genital lesions. The immune mechanisms of protection against recurrent genital herpes remain to be fully elucidated. In this preclinical study, we investigated the protective therapeutic efficacy, in the guinea pig model of recurrent genital herpes, of subunit vaccine candidates that were based on eight recombinantly expressed HSV-2 envelope and tegument proteins. These viral protein antigens (Ags) were rationally selected for their ability to recall strong CD4 and CD8 T-cell responses from naturally "protected" asymptomatic individuals, who, despite being infected, never develop any recurrent herpetic disease. Out of the eight HSV-2 proteins, the envelope glycoprotein D (gD), the tegument protein VP22 (encoded by the gene), and ribonucleotide reductase subunit 2 protein (RR2; encoded by the gene) produced significant protection against recurrent genital herpes. The RR2 protein, delivered either intramuscularly or intravaginally with CpG and alum adjuvants, (i) boosted the highest neutralizing antibodies, which appear to cross-react with both gB and gD, and (ii) enhanced the numbers of functional gamma interferon (IFN-γ)-producing CRTAM CFSE CD4 and CRTAM CFSE CD8 T cells, which express low levels of PD-1 and TIM-3 exhaustion markers and were localized to healed sites of the vaginal mucocutaneous (VM) tissues. The strong B- and T-cell immunogenicity of the RR2 protein was associated with a significant decrease in virus shedding and a reduction in both the severity and frequency of recurrent genital herpes lesions. depletion of either CD4 or CD8 T cells significantly abrogated the protection. Taken together, these preclinical results provide new insights into the immune mechanisms of protection against recurrent genital herpes and promote the tegument RR2 protein as a viable candidate Ag to be incorporated in future genital herpes therapeutic mucosal vaccines. Recurrent genital herpes is one of the most common sexually transmitted diseases, with a global prevalence of HSV-2 infection predicted to be over 536 million worldwide. Despite the availability of many intervention strategies, such as sexual behavior education, barrier methods, and the costly antiviral drug treatments, eliminating or at least reducing recurrent genital herpes remains a challenge. Currently, no FDA-approved therapeutic vaccines are available. In this preclinical study, we investigated the immunogenicity and protective efficacy, in the guinea pig model of recurrent genital herpes, of subunit vaccine candidates that were based on eight recombinantly expressed herpes envelope and tegument proteins. We discovered that similar to the 5-29 vaccine, based on a replication-defective HSV-2 mutant virus, which has been recently tested in clinical trials, the RR2 protein-based subunit vaccine elicited a significant reduction in virus shedding and a decrease in both the severity and frequency of recurrent genital herpes sores. This protection correlated with an increase in numbers of functional tissue-resident IFN-γ CRTAM CFSE CD4 and IFN-γ CRTAM CFSE CD8 T cells that infiltrate healed sites of the vaginal tissues. Our study sheds new light on the role of T cells in protection against recurrent genital herpes and promotes the RR2-based subunit therapeutic vaccine to be tested in the clinic.
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http://dx.doi.org/10.1128/JVI.02309-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475797PMC
May 2019

Blockade of LAG-3 Immune Checkpoint Combined With Therapeutic Vaccination Restore the Function of Tissue-Resident Anti-viral CD8 T Cells and Protect Against Recurrent Ocular Herpes Simplex Infection and Disease.

Front Immunol 2018 17;9:2922. Epub 2018 Dec 17.

Laboratory of Cellular and Molecular Immunology, School of Medicine, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA, United States.

Recurrent viral diseases often occur after the viruses evade the hosts' immune system, by inducing exhaustion of antiviral T cells. In the present study, we found that functionally exhausted herpes simplex virus type 1 (HSV-1) -specific CD8 T cells, with elevated expression of lymphocyte activation gene-3 (LAG-3), an immune checkpoint receptor that promotes T cell exhaustion, were frequent in symptomatic (SYMP) patients with a history of numerous episodes of recurrent corneal herpetic disease. Similarly, following UV-B induced virus reactivation from latency the symptomatic wild-type (WT) B6 mice that developed increase virus shedding and severe recurrent corneal herpetic disease had more exhausted HSV-specific LAG-3CD8 T cells in both trigeminal ganglia (TG) and cornea. Moreover, a therapeutic blockade of LAG-3 immune checkpoint with antagonist antibodies combined with a therapeutic immunization with gB peptide immunodominant epitope of latently infected B6 mice significantly restored the quality and quantity of functional HSV-1 gB specific CD8 T cells in both TG and cornea and protected against UV-B induced recurrent corneal herpes infection and disease. In contrast to dysfunctional HSV-specific CD8 T cells from WT B6 mice, more functional HSV-specific CD8 T cells were detected in LAG-3 deficient mice and were associated with less UV-B induced recurrent corneal herpetic disease. Thus, the LAG-3 pathway plays a fundamental role in ocular herpes T cell immunopathology and provides an important immune checkpoint target that can synergizes with T cell-based therapeutic vaccines against symptomatic recurrent ocular herpes.
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http://dx.doi.org/10.3389/fimmu.2018.02922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304367PMC
October 2019

First Draft Genome Sequence of the Pathogenic Fungus Fusarium udum F02845, Associated with Pigeonpea (Cajanus cajan L. Millspaugh) Wilt.

Microbiol Resour Announc 2018 Oct 4;7(13). Epub 2018 Oct 4.

ICAR-National Bureau of Agriculturally Important Microorganisms (NBAIM), Mau, Uttar Pradesh, India.

Fusarium udum F02845 is a destructive fungal pathogen which causes pigeonpea (Cajanus cajan L. Millspaugh) wilt. Here we report the first draft assembly of Fusarium udum F02845, isolated from an infected pigeonpea stem. The genome was determined to be 56.38 Mb in size, with a G+C content of 42.44%, and predicted to have 712 scaffolds with a total number of 11,829 genes.
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http://dx.doi.org/10.1128/MRA.01001-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256552PMC
October 2018

Unique Type I Interferon, Expansion/Survival Cytokines, and JAK/STAT Gene Signatures of Multifunctional Herpes Simplex Virus-Specific Effector Memory CD8 T Cells Are Associated with Asymptomatic Herpes in Humans.

J Virol 2019 02 5;93(4). Epub 2019 Feb 5.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA

A large proportion of the world population harbors herpes simplex virus 1 (HSV-1), a major cause of infectious corneal blindness. HSV-specific CD8 T cells protect from herpesvirus infection and disease. However, the genomic, phenotypic, and functional characteristics of CD8 T cells associated with the protection seen in asymptomatic (ASYMP) individuals, who, despite being infected, never experienced any recurrent herpetic disease, remains to be fully elucidated. In this investigation, we compared the phenotype, function, and level of expression of a comprehensive panel of 579 immune genes of memory CD8 T cells, sharing the same HSV-1 epitope specificities, and freshly isolated peripheral blood from well-characterized cohorts of protected ASYMP and nonprotected symptomatic (SYMP) individuals, with a history of numerous episodes of recurrent herpetic disease, using the high-throughput digital NanoString nCounter system and flow cytometry. Interestingly, our results demonstrated that memory CD8 T cells from ASYMP individuals expressed a unique set of genes involved in expansion and survival, type I interferon (IFN-I), and JAK/STAT pathways. Frequent multifunctional HSV-specific effector memory CD62L CD44 CD8 T cells were detected in ASYMP individuals compared to more of monofunctional central memory CD62L CD44 CD8 T cells in SYMP individuals. Shedding light on the genotype, phenotype, and function of antiviral CD8 T cells from "naturally protected" ASYMP individuals will help design future T-cell-based ocular herpes immunotherapeutic vaccines. A staggering number of the world population harbors herpes simplex virus 1 (HSV-1) potentially leading to blinding recurrent herpetic disease. While the majority are asymptomatic (ASYMP) individuals who never experienced any recurrent herpetic disease, symptomatic (SYMP) individuals have a history of numerous episodes of recurrent ocular herpetic disease. This study elucidates the phenotype, the effector function, and the gene signatures of memory CD8 T-cell populations associated with protection seen in ASYMP individuals. Frequent multifunctional HSV-specific effector memory CD8 T cells were detected in ASYMP individuals. In contrast, nonprotected SYMP individuals had more central memory CD8 T cells. The memory CD8 T cells from ASYMP individuals expressed unique gene signatures characterized by higher levels of type I interferon (IFN), expansion and expansion/survival cytokines, and JAK/STAT pathways. Future studies on the genotype, phenotype, and function of antiviral CD8 T cells from "naturally protected" ASYMP individuals will help in the potential design of T-cell-based ocular herpes vaccines.
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http://dx.doi.org/10.1128/JVI.01882-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364001PMC
February 2019

Phenotypic and Functional Signatures of Herpes Simplex Virus-Specific Effector Memory CD73CD45RACCR7CD8 T and CD73CD45RACCR7CD8 T Cells Are Associated with Asymptomatic Ocular Herpes.

J Immunol 2018 10 10;201(8):2315-2330. Epub 2018 Sep 10.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697;

HSV type 1 (HSV-1)-specific CD8 T cells protect from herpes infection and disease. However, the nature of protective CD8 T cells in HSV-1 seropositive healthy asymptomatic (ASYMP) individuals (with no history of clinical herpes disease) remains to be determined. In this study, we compared the phenotype and function of HSV-specific CD8 T cells from HLA-A*02:01-positive ASYMP and symptomatic (SYMP) individuals (with a documented history of numerous episodes of recurrent ocular herpetic disease). We report that although SYMP and ASYMP individuals have similar frequencies of HSV-specific CD8 T cells, the "naturally" protected ASYMP individuals have a significantly higher proportion of multifunctional HSV-specific effector memory CD8 T cells (CD73CD45RACCR7CD8 effector memory RA (T) and CD73CD45RACCR7CD8 effector memory (T) as compared with SYMP individuals. Similar to humans, HSV-1-infected ASYMP B6 mice had frequent multifunctional HSV-specific CD73CD8 T cells in the cornea, as compared with SYMP mice. Moreover, in contrast to wild type B6, CD73 deficient mice infected ocularly with HSV-1 developed more recurrent corneal herpetic infection and disease. This was associated with less functional CD8 T cells in the cornea and trigeminal ganglia, the sites of acute and latent infection. The phenotypic and functional characteristics of HSV-specific circulating and in situ CD73CD8 T cells, demonstrated in both ASYMP humans and mice, suggest a positive role for effector memory CD8 T cells expressing the CD73 costimulatory molecule in the protection against ocular herpes infection and disease. These findings are important for the development of safe and effective T cell-based herpes immunotherapy.
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http://dx.doi.org/10.4049/jimmunol.1800725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195422PMC
October 2018

Human Asymptomatic Epitope Peptide/CXCL10-Based Prime/Pull Vaccine Induces Herpes Simplex Virus-Specific Gamma Interferon-Positive CD107 CD8 T Cells That Infiltrate the Corneas and Trigeminal Ganglia of Humanized HLA Transgenic Rabbits and Protect against Ocular Herpes Challenge.

J Virol 2018 08 31;92(16). Epub 2018 Jul 31.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California, Irvine, Irvine, California, USA

Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that infects the cornea, causing potentially blinding herpetic disease. A clinical herpes vaccine is still lacking. In the present study, a novel prime/pull vaccine was tested in a human leukocyte antigen (HLA) transgenic rabbit model of ocular herpes (HLA Tg rabbits). Three peptide epitopes were selected, from the HSV-1 membrane glycoprotein C (UL44), the DNA replication binding helicase (UL9), and the tegument protein (UL25), all preferentially recognized by CD8 T cells from "naturally protected" HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who never had recurrent corneal herpetic disease). HLA Tg rabbits were immunized with a mixture of these three ASYMP CD8 T cell peptide epitopes (UL44, UL9, and UL25), which were delivered subcutaneously with CpG adjuvant (prime). Fifteen days later, half of the rabbits received a topical ocular treatment with a recombinant neurotropic adeno-associated virus type 8 (AAV8) vector expressing the T cell-attracting CXCL10 chemokine (pull). The frequency and function of HSV-specific CD8 T cells induced by the prime/pull vaccine were assessed in the peripheral blood, cornea, and trigeminal ganglion (TG). Compared to the cells generated in response to peptide immunization alone, the peptide/CXCL10 prime/pull vaccine generated frequent polyfunctional gamma interferon-positive (IFN-γ) CD107 CD8 T cells that infiltrated both the cornea and TG. CD8 T cell mobilization into the cornea and TG of prime/pull-vaccinated rabbits was associated with a significant reduction in corneal herpesvirus infection and disease following an ocular HSV-1 (strain McKrae) challenge. These findings draw attention to the novel prime/pull vaccine strategy for mobilizing antiviral CD8 T cells into tissues to protect against herpesvirus infection and disease. There is an urgent need for a vaccine against widespread herpes simplex virus infections. The present study demonstrates that immunization of HLA transgenic rabbits with a peptide/CXCL10 prime/pull vaccine triggered mobilization of HSV-specific CD8 T cells locally into the cornea and TG, the sites of acute and latent herpesvirus infections, respectively. Mobilization of antiviral CD8 T cells into the cornea and TG of rabbits that received the prime/pull vaccine was associated with protection against ocular herpesvirus infection and disease following an ocular HSV-1 challenge. These results highlight the importance of the prime/pull vaccine strategy to bolster the number and function of protective CD8 T cells within infected tissues.
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http://dx.doi.org/10.1128/JVI.00535-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069188PMC
August 2018

Halotolerant PHM11 Tolerate Salinity by Accumulating L-Proline and Fine-Tuning Gene Expression Profiles of Related Metabolic Pathways.

Front Microbiol 2018 12;9:423. Epub 2018 Mar 12.

Laboratory of Genomics, ICAR-National Bureau of Agriculturally Important Microorganisms, Maunath Bhanjan, India.

Salinity stress is one of the serious factors, limiting production of major agricultural crops; especially, in sodic soils. A number of approaches are being applied to mitigate the salt-induced adverse effects in agricultural crops through implying different halotolerant microbes. In this aspect, a halotolerant, PHM11 was evaluated under eight different salinity regimes; 100, 250, 500, 1000, 1500, 2000, 2500, and 3000 mM to know its inherent salt tolerance limits and salt-induced consequences affecting its natural metabolism. Based on the stoichiometric growth kinetics; 100 and 1500 mM concentrations were selected as optimal and minimal performance limits for PHM11. To know, how salt stress affects the expression profiles of regulatory genes of its key metabolic pathways, and total production of important metabolites; biomass, carotenoids, beta-carotene production, IAA and proline contents, and expression profiles of key genes affecting the protein folding, structural adaptations, transportation across the cell membrane, stress tolerance, carotenoids, IAA and mannitol production in PHM11 were studied under 100 and 1500 mM salinity. PHM11 showed maximum and minimum growth, biomass and metabolite production at 100 and 1500 mM salinity respectively. Salt-induced fine-tuning of expression profiles of key genes of stress pathways was determined in halotolerant bacterium PHM11.
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http://dx.doi.org/10.3389/fmicb.2018.00423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890156PMC
March 2018

CXCL17 Chemokine-Dependent Mobilization of CXCR8CD8 Effector Memory and Tissue-Resident Memory T Cells in the Vaginal Mucosa Is Associated with Protection against Genital Herpes.

J Immunol 2018 04 16;200(8):2915-2926. Epub 2018 Mar 16.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine School of Medicine, Irvine, CA 92697;

Circulating conventional memory CD8 T cells (i.e., the CD8 effector memory T [T] cell and CD8 central memory T [T] cell subsets) and the noncirculating CD8 tissue-resident memory T (T) cell subset play a critical role in mucosal immunity. Mucosal chemokines, including the recently discovered CXCL17, are also important in mucosal immunity because they are homeostatically expressed in mucosal tissues. However, whether the CXCL17 chemokine contributes to the mobilization of memory CD8 T cell subsets to access infected mucosal tissues remains to be elucidated. In this study, we report that after intravaginal HSV type 1 infection of B6 mice, we detected high expression levels of CXCL17 and increased numbers of CD44CD62LCD8 T and CD103CD8 T cells expressing CXCR8, the cognate receptor of CXCL17, in the vaginal mucosa (VM) of mice with reduced genital herpes infection and disease. In contrast to wild-type B6 mice, the CXCL17 mice developed 1) fewer CXCR8CD8 T and T cells associated with more virus replication in the VM and more latency established in dorsal root ganglia, and 2) reduced numbers and frequencies of functional CD8 T cells in the VM. These findings suggest that the CXCL17/CXCR8 chemokine pathway plays a crucial role in mucosal vaginal immunity by promoting the mobilization of functional protective CD8 T and CD8 T cells, within this site of acute and recurrent herpes infection.
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http://dx.doi.org/10.4049/jimmunol.1701474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893430PMC
April 2018

Evaluation of peri-implant tissues around nanopore surface implants with or without platelet rich fibrin: a clinico-radiographic study.

Biomed Mater 2018 01 9;13(2):025002. Epub 2018 Jan 9.

Department of Periodontology, Saraswati Dental College, Lucknow, India.

Objective: To comparatively evaluate peri-implant tissue changes around the nano-pore implant surface with or without platelet rich fibrin (PRF).

Material And Methods: For the present study, a total of 17 patients was initially enrolled (6 females, 11 males), and 38 sites (19 control and 19 experimental sites) were randomly assigned to either group 1 (control), i.e. extraction site received immediate implants without any PRF, and group 2 (experimental), i.e. extraction sites received immediate implants with PRF. Clinical and radiographic parameters were recorded for 9 months after the implant-loading phase.

Results: Clinically, there was a significant (p < 0.001) increase in the peri-implant probing depth from the prosthetic phase up to 9 months in both the groups, and the increase was greater in the control group. However, the mean difference in the changes between the two groups was non-significant. The modified gingiva index for group 2 was significantly lower than that for group 1 in the prosthetic phase. Radiographically, in the control group and experimental group, there was a significant increase (<0.01) in bone loss (BL) in the mesial and distal aspect of the implant from the surgical to prosthetic phase, surgical up to 9 months and from the prosthetic phase up to 9 months. There was greater BL in the control group than in the experimental group in both the mesial and distal aspect of the implant; however the difference in BL was non-significant (<0.01). There was greater BL in the distal aspect than in the mesial aspect in both groups; however, the difference in BL was non-significant.

Conclusion: PRF treatment may provide a way to prevent BL during the surgical-to-prosthetic phase. These results were based on a short-term, low sample randomized clinical study, therefore a long-term study with more sites and homogenous sampling is recommended.
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http://dx.doi.org/10.1088/1748-605X/aa8fa3DOI Listing
January 2018

Patient-centered Microsurgical Management of Gingival Recession using Coronally Advanced Flap with Either Platelet-rich Fibrin or Connective Tissue Graft: A Comparative Analysis.

Contemp Clin Dent 2017 Apr-Jun;8(2):293-304

Department of Periodontology, Saraswati Dental College, Lucknow, Uttar Pradesh, India.

Purpose: To evaluate autologous platelet-rich fibrin (PRF) and autogenous connective tissue graft (CTG) in gingival recession defects in conjunction with coronally advanced flap (CAF) using a microsurgical technique.

Materials And Methods: Forty-five Class I and II recession defects were randomly equally ( = 15) divided into three groups: Group I sites treated with CAF with PRF, Group II sites treated with CAF with CTG, and Group III sites treated with CAF alone using microsurgical approach. Parameters recorded were vertical gingival recession (VGR) and horizontal gingival recession (HGR), % complete root coverage (CRC), patient comfort score (PCS), patient esthetic score (PES), and hypersensitivity score (HS) at 10 days, 3 months, and 6 months.

Results: CAF surgery alone and in combination with PRF or CTG are effective procedures to cover denuded roots with mean VGR values of 1.26 ± 0.70 mm (74.4%), 1.26 ± 0.59 mm (58%), and 1.06 ± 0.79 mm (53.3%) for Groups I, II, and III, respectively. In terms of CRC achieved at 6 months, results showed that 100% CRC was obtained in 60% sites of Group I, 20% sites of Group II, and 27% sites of Group III. Patient response and acceptance for surgical treatment modality in terms of PCS and PES were highest for Group I (PRF and CAF) followed by Group III and Group II, and there was decrease in HS for Group I (PRF and CAF) while no significant changes in HS were observed for Group II and Group III. At the end of 6 months follow-up, there was a significant increase in gingival thickness measurements using transgingival probing in Group II, whereas nonsignificant changes were observed in Group I and Group III.

Conclusions: A long-term multicenter randomized controlled clinical study may be necessary to evaluate the clinical outcome for autologous PRF in comparison to CTG and CAF alone.
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http://dx.doi.org/10.4103/ccd.ccd_70_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551337PMC
August 2017

Correlation of ABO Blood Group Phenotype and Rhesus Factor with Periodontal Disease: An Observational Study.

Contemp Clin Dent 2017 Apr-Jun;8(2):253-258

Department of Conservative Dentistry and Endodontics, Saraswati Dental College, Lucknow, Uttar Pradesh, India.

Background: The knowledge of the ABO blood group phenotype of the patients and their correlation with the periodontal disease maybe important in the development of early treatment strategies, and it would be helpful to target non-responding areas to periodontal therapy of the susceptible individuals.

Aims: The present study was conducted to determine whether there was any correlation between periodontal diseases and ABO blood groups and Rh factor.

Material And Method: This study was carried out on 537 subjects attending Faculty of Dental Sciences OPD in BHU. Subjects were divided into three groups: group I (healthy subjects), group II (subjects with gingivitis), and group III (subjects with periodontitis) based on periodontal examination (Gingival index, Bleeding Index, Probing pocket depth and clinical attachment level). ABO Blood grouping were done and correlated with the periodontal status of study subjects. Statistical Analysis: Data was analyzed using the statistical software namely Statistical Package for the Social Sciences (SPSS, Version 16, IBM Analytics) and Systat 8.0.

Results: In this study, there was a greater prevalence of gingivitis in blood group O and periodontitis in blood group B. The blood group AB showed the least prevalence of periodontal diseases. Similarly gingivitis and peridontitis were significantly higher among Rhesus positive groups when compared with Rhesus negative groups.

Conclusion: Considering the results of this study, it can be concluded that ABO blood groups and Rh factor could be a risk factor for the development of periodontal disease.
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http://dx.doi.org/10.4103/ccd.ccd_307_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551331PMC
August 2017

Bolstering the Number and Function of HSV-1-Specific CD8 Effector Memory T Cells and Tissue-Resident Memory T Cells in Latently Infected Trigeminal Ganglia Reduces Recurrent Ocular Herpes Infection and Disease.

J Immunol 2017 07 24;199(1):186-203. Epub 2017 May 24.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697;

HSV type 1 (HSV-1) is a prevalent human pathogen that infects >3.72 billion individuals worldwide and can cause potentially blinding recurrent corneal herpetic disease. HSV-1 establishes latency within sensory neurons of trigeminal ganglia (TG), and TG-resident CD8 T cells play a critical role in preventing its reactivation. The repertoire, phenotype, and function of protective CD8 T cells are unknown. Bolstering the apparent feeble numbers of CD8 T cells in TG remains a challenge for immunotherapeutic strategies. In this study, a comprehensive panel of 467 HLA-A*0201-restricted CD8 T cell epitopes was predicted from the entire HSV-1 genome. CD8 T cell responses to these genome-wide epitopes were compared in HSV-1-seropositive symptomatic individuals (with a history of numerous episodes of recurrent herpetic disease) and asymptomatic (ASYMP) individuals (who are infected but never experienced any recurrent herpetic disease). Frequent polyfunctional HSV-specific IFN-γCD107CD44CD62LCD8 effector memory T cells were detected in ASYMP individuals and were primarily directed against three "ASYMP" epitopes. In contrast, symptomatic individuals have more monofunctional CD44CD62LCD8 central memory T cells. Furthermore, therapeutic immunization with an innovative prime/pull vaccine, based on priming with multiple ASYMP epitopes (prime) and neurotropic TG delivery of the T cell-attracting chemokine CXCL10 (pull), boosted the number and function of CD44CD62LCD8 effector memory T cells and CD103CD8 tissue-resident T cells in TG of latently infected HLA-A*0201-transgenic mice and reduced recurrent ocular herpes following UV-B-induced reactivation. These findings have profound implications in the development of T cell-based immunotherapeutic strategies to treat blinding recurrent herpes infection and disease.
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http://dx.doi.org/10.4049/jimmunol.1700145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515716PMC
July 2017

CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8 T and CD8 T Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease.

J Virol 2017 07 26;91(14). Epub 2017 Jun 26.

Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA

Herpes simplex virus 1 (HSV-1) establishes latency within the sensory neurons of the trigeminal ganglia (TG). HSV-specific memory CD8 T cells play a critical role in preventing HSV-1 reactivation from TG and subsequent virus shedding in tears that trigger recurrent corneal herpetic disease. The CXC chemokine ligand 10 (CXCL10)/CXC chemokine receptor 3 (CXCR3) chemokine pathway promotes T cell immunity to many viral pathogens, but its importance in CD8 T cell immunity to recurrent herpes has been poorly elucidated. In this study, we determined how the CXCL10/CXCR3 pathway affects TG- and cornea-resident CD8 T cell responses to recurrent ocular herpesvirus infection and disease using a well-established murine model in which HSV-1 reactivation was induced from latently infected TG by UV-B light. Following UV-B-induced HSV-1 reactivation, a significant increase in both the number and function of HSV-specific CXCR3 CD8 T cells was detected in TG and corneas of protected C57BL/6 (B6) mice, but not in TG and corneas of nonprotected CXCL10 or CXCR3 deficient mice. This increase was associated with a significant reduction in both virus shedding and recurrent corneal herpetic disease. Furthermore, delivery of exogenous CXCL10 chemokine in TG of CXCL10 mice, using the neurotropic adeno-associated virus type 8 (AAV8) vector, boosted the number and function of effector memory CD8 T cells (T) and tissue-resident memory CD8 T cells (T), but not of central memory CD8 T cells (T), locally within TG, and improved protection against recurrent herpesvirus infection and disease in CXCL10 deficient mice. These findings demonstrate that the CXCL10/CXCR3 chemokine pathway is critical in shaping CD8 T cell immunity, locally within latently infected tissues, which protects against recurrent herpesvirus infection and disease. We determined how the CXCL10/CXCR3 pathway affects CD8 T cell responses to recurrent ocular herpesvirus infection and disease. Using a well-established murine model, in which HSV-1 reactivation in latently infected trigeminal ganglia was induced by UV-B light, we demonstrated that lack of either CXCL10 chemokine or its CXCR3 receptor compromised the mobilization of functional CD8 T and CD8 T cells within latently infected trigeminal ganglia following virus reactivation. This lack of T cell mobilization was associated with an increase in recurrent ocular herpesvirus infection and disease. Inversely, augmenting the amount of CXCL10 in trigeminal ganglia of latently infected CXCL10-deficient mice significantly restored the number of local antiviral CD8 T and CD8 T cells associated with protection against recurrent ocular herpes. Based on these findings, a novel "prime/pull" therapeutic ocular herpes vaccine strategy is proposed and discussed.
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http://dx.doi.org/10.1128/JVI.00278-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487556PMC
July 2017