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1.
Neoplasia ; 23(6): 574-583, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34091121

RESUMO

Lung cancer is the leading cause of cancer related deaths worldwide. The present study investigated the effects of naproxen (NSAID) on lung adenocarcinoma in spontaneous lung cancer mouse model. Six-week-old transgenic KrasG12V mice (n = 20; male + female) were fed modified AIN-76A diets containing naproxen (0/400 ppm) for 30 wk and euthanized at 36 wk of age. Lungs were evaluated for tumor incidence, multiplicity, and histopathological stage (adenoma and adenocarcinoma). Lung tumors were noticeable as early as 12 wk of age exclusively in the KrasG12V mice. By 36 wk age, 100% of KrasG12V mice on control diet developed lung tumors, mostly adenocarcinomas. KrasG12V mice fed control diet developed 19.8 ± 0.96 (Mean ± SEM) lung tumors (2.5 ± 0.3 adenoma, 17.3 ± 0.7 adenocarcinoma). Administration of naproxen (400 ppm) inhibited lung tumor multiplicity by ∼52% (9.4 ± 0.85; P < 0001) and adenocarcinoma by ∼64% (6.1 ± 0.6; P < 0001), compared with control-diet-fed mice. However, no significant difference was observed in the number of adenomas in either diet, suggesting that naproxen was more effective in inhibiting tumor progression to adenocarcinoma. Biomarker analysis showed significantly reduced inflammation (COX-2, IL-10), reduced tumor cell proliferation (PCNA, cyclin D1), and increased apoptosis (p21, caspase-3) in the lung tumors exposed to naproxen. Decreased serum levels of PGE2 and CXCR4 were observed in naproxen diet fed KrasG12V mice. Gene expression analysis of tumors revealed a significant increase in cytokine modulated genes (H2-Aa, H2-Ab1, Clu), which known to further modulate the cytokine signaling pathways. Overall, the results suggest a chemopreventive role of naproxen in inhibiting spontaneous lung adenocarcinoma formation in KrasG12V mice.

2.
Cardiol Young ; : 1-3, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34092265

RESUMO

Pulmonary valve endocarditis after transcatheter pulmonary valve implantation has been an emerging concern due to the increasing prevalence of transcatheter placement of pulmonary valve in the treatment of residual right ventricular outflow tract stenosis or regurgitation. Pulmonary valve endocarditis is a dreadful complication of transcatheter pulmonary valve implantation that have been reported with Melody valve (Medtronic, Inc., Minneapolis, MN) and Edward Sapien valve (Edwards Life Sciences, Irvine, CA) till date. There are scanty available literatures for pulmonary valve endocarditis with Venus P valve (Venus Medtech, Hangzhou, China) implantation. Furthermore, cardiovascular comorbidity is common in COVID-19 infection with limited evidence of COVID-19 infection concomitant with infective endocarditis. This case happens to be the first reported case of infective endocarditis of pulmonary valve with concomitant COVID-19 infection and also delayed presentation of pulmonary valve endocarditis with Venus P valve implantation.

3.
World J Gastroenterol ; 27(18): 2090-2104, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34025066

RESUMO

Hepatitis E virus (HEV) is an important cause of repeated waterborne outbreaks of acute hepatitis. Recently, several extrahepatic manifestations (EHMs) have been described in patients with HEV infection. Of these, neurological disorders are the most common EHM associated with HEV. The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation. Patients can present with normal liver function tests, which can often be misleading for physicians. There is a paucity of data on HEV-related neurological manifestations; and these data are mostly described as case reports and case series. In this review, we analyzed data of 163 reported cases of HEV-related neurological disorders. The mechanisms of pathogenesis, clinico-demographic profile, and outcomes of the HEV-related neurological disorders are described in this article. Nerve root and plexus disorder were found to be the most commonly reported disease, followed by meningoencephalitis.


Assuntos
Neurite do Plexo Braquial , Vírus da Hepatite E , Hepatite E , Doenças do Sistema Nervoso , Sistema Nervoso Central , Hepatite E/complicações , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Humanos , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia
4.
Infect Dis Now ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33964485

RESUMO

Aspergillus is a ubiquitous ascomycete that can cause a variety of clinical presentations depending on immune status. Central nervous system aspergillosis is a fatal disease with non-specific clinical features. The aim of this systematic review was to evaluate the epidemiology, clinical features, diagnosis and therapeutic interventions in CNS aspergillosis patients. We also aimed to examine the possible predictors of mortality in neuroaspergillosis. Literature search was performed in Medline, PubMed, and Google scholar and all patients≥18 years with proven CNS aspergillosis were included. A total of 175 articles (235 patients) were included in the final analysis. Their mean age was 51 years and the majority were male (57.4%). Overall case-fatality was 45.1%. Aspergillus fumigatus was the most common species (70.8%) followed by A. flavus (18.6%). Corticosteroids (22.6%), malignancy (19.1%) and diabetes mellitus (14%) were the most common risk factors. Neuroimaging findings included cerebral abscess (70.2%), meningitis (14%), infarction (13.2%) and mycotic aneurysm (8.9%). Disseminated disease (29.2% vs 17.8%, p 0.03), CSF hypoglycorrhachia (48.1% vs 22.2%, P: 0.001) and heightened CSF galactomannan (3.62 vs 2.0ng/ml, p 0.05), were the factors associated with poor outcome in neuroaspergillosis. Persons infected with Aspergillus flavus (13.1% vs 3.1%, P: 0.01), and having been treated with Voriconazole (51.9% vs 29.2%, P: 0.004) were more likely to survive. Our review will provide insight into the different spectrums of CNS aspergillosis. Notwithstanding the promising role of Voriconazole, future work is required to ascertain the role of combination antifungal therapy.

5.
PLoS One ; 16(5): e0249841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33939697

RESUMO

We present further study of a subset of carbapenems, arising from a previously reported machine learning approach, with regard to their mouse pharmacokinetic profiling and subsequent study in a mouse model of sub-acute Mycobacterium tuberculosis infection. Pharmacokinetic metrics for such small molecules were compared to those for meropenem and biapenem, resulting in the selection of two carbapenems to be assessed for their ability to reduce M. tuberculosis bacterial loads in the lungs of infected mice. The original syntheses of these two carbapenems were optimized to provide multigram quantities of each compound. One of the two experimental carbapenems, JSF-2204, exhibited efficacy equivalent to that of meropenem, while both were inferior to rifampin. The lessons learned in this study point toward the need to further enhance the pharmacokinetic profiles of experimental carbapenems to positively impact in vivo efficacy performance.

6.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805762

RESUMO

Pertussis toxin (PTX) is a required co-adjuvant for experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin antigen. However, PTX's effects on EAE induced by the transfer of myelin-specific T helper cells is not known. Therefore, we investigated how PTX affects the Th17 transfer EAE model (Th17-EAE). We found that PTX significantly reduced Th17-EAE by inhibiting chemokine-receptor-dependent trafficking of Th17 cells. Strikingly, PTX also promoted the accumulation of B cells in the CNS, suggesting that PTX alters the disease toward a B-cell-dependent pathology. To determine the role of B cells, we compared the effects of PTX on Th17-EAE in wild-type (WT) and B-cell-deficient (µMT) mice. Without PTX treatment, disease severity was equivalent between WT and µMT mice. In contrast, with PTX treatment, the µMT mice had significantly less disease and a reduction in pathogenic Th17 cells in the CNS compared to the WT mice. In conclusion, this study shows that PTX inhibits the migration of pathogenic Th17 cells, while promoting the accumulation of pathogenic B cells in the CNS during Th17-EAE. These data provide useful methodological information for adoptive-transfer Th17-EAE and, furthermore, describe another important experimental system to study the pathogenic mechanisms of B cells in multiple sclerosis.


Assuntos
Linfócitos B/patologia , Encefalomielite Autoimune Experimental/patologia , Toxina Pertussis/administração & dosagem , Células Th17/patologia , Transferência Adotiva/métodos , Animais , Linfócitos B/imunologia , Movimento Celular/imunologia , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Glicoproteína Mielina-Oligodendrócito/administração & dosagem , Índice de Gravidade de Doença , Células Th17/imunologia , Células Th17/transplante
7.
PLoS One ; 16(4): e0249908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33861760

RESUMO

The single mitochondrial nucleoid (kinetoplast) of Trypanosoma brucei is found proximal to a basal body (mature (mBB)/probasal body (pBB) pair). Kinetoplast inheritance requires synthesis of, and scission of kinetoplast DNA (kDNA) generating two kinetoplasts that segregate with basal bodies into daughter cells. Molecular details of kinetoplast scission and the extent to which basal body separation influences the process are unavailable. To address this topic, we followed basal body movements in bloodstream trypanosomes following depletion of protein kinase TbCK1.2 which promotes kinetoplast division. In control cells we found that pBBs are positioned 0.4 um from mBBs in G1, and they mature after separating from mBBs by at least 0.8 um: mBB separation reaches ~2.2 um. These data indicate that current models of basal body biogenesis in which pBBs mature in close proximity to mBBs may need to be revisited. Knockdown of TbCK1.2 produced trypanosomes containing one kinetoplast and two nuclei (1K2N), increased the percentage of cells with uncleaved kDNA 400%, decreased mBB spacing by 15%, and inhibited cytokinesis 300%. We conclude that (a) separation of mBBs beyond a threshold of 1.8 um correlates with division of kDNA, and (b) TbCK1.2 regulates kDNA scission. We propose a Kinetoplast Division Factor hypothesis that integrates these data into a pathway for biogenesis of two daughter mitochondrial nucleoids.

8.
Signal Image Video Process ; : 1-8, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33897905

RESUMO

Diabetic retinopathy (DR) is a significant reason for the global increase in visual loss. Studies show that timely treatment can significantly bring down such incidents. Hence, it is essential to distinguish the stages and severity of DR to recommend needed medical attention. In this view, this paper presents DRISTI (Diabetic Retinopathy classIfication by analySing reTinal Images), where a hybrid deep learning model composed of VGG16 and capsule network is proposed, which yields statistically significant performance improvement over the state of the art. To validate our claim, we have reported detailed experimental and ablation studies. We have also created an augmented dataset to increase the APTOS dataset's size and check how robust the model is. The five-class training and validation accuracy for the expanded dataset is 99.21 % and 75.50 % . The two-class training and validation accuracy on augmented APTOS is 99.96 % and 97.05 % . Extending the two-class model for the mixed dataset, we get a training and validation accuracy of 99.92 % and 91.43 % , respectively. We have also performed cross-dataset and mixed dataset testing to demonstrate the efficiency of DRISTI.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33846916

RESUMO

Rice straw burning is causing huge economic losses and environmental hazards. Microbial mediated ex situ composting could be a viable solution which would not only reduce the straw burning but also will enrich nutrition to the soil. Strains of Trichoderma isolated from tree bark were tested to decompose rice straw efficiently, and the Trichoderma-mediated rice straw compost was used subsequently to improve rice growth. Two isolates of Trichoderma reesei (NRRIT-26 and NRRIT-27) decomposed the straw by producing higher decomposing enzymes, like total cellulase (≥ 1.87 IU mL-1), endoglucanase (≥ 0.75 IU mL-1), xylanase (≥ 163.49 nkat mL-1), and laccase (≥ 11.75 IU mL-1). Trichoderma decomposed rice straw compost had higher nutrient contents (1.97% N, 2.04% K, and 0.88% P) and optimum C/N ratio (28:2) as compared to control. The Trichoderma decomposed rice straw as a nutrient reduced the mean germination time (2.2 days as compared to 4 days in control) and enhanced the seedling vigor and total chlorophyll content in rice. Expression of defense enzymes, like catalase (≥ 200% both in shoot and root), peroxidase (≥ 180% in root and ≥ 300% in shoot), and superoxide dismutase (≥ 160% in root and ≥ 90% in shoot), were higher in treated plants as compared to control indicating higher stress tolerance ability to crops. We conclude that the Trichoderma-mediated rice straw management is a viable option and has the potential to reduce straw burning, and at the same time, the compost could enrich soil fertility and impart intrinsic stress tolerance to rice.

10.
Microorganisms ; 9(4)2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33801711

RESUMO

Of the various proteins encoded by plant viruses, one of the most interesting is the movement protein (MP). MPs are unique to plant viruses and show surprising structural and functional variability while maintaining their core function, which is to facilitate the intercellular transport of viruses or viral nucleoprotein complexes. MPs interact with components of the intercellular channels, the plasmodesmata (PD), modifying their size exclusion limits and thus allowing larger particles, including virions, to pass through. The interaction of MPs with the components of PD, the formation of transport complexes and the recruitment of host cellular components have all revealed different facets of their functions. Multitasking is an inherent property of most viral proteins, and MPs are no exception. Some MPs carry out multitasking, which includes gene silencing suppression, viral replication and modulation of host protein turnover machinery. This review brings together the current knowledge on MPs, focusing on their structural variability, various functions and interactions with host proteins.

11.
Cardiol Young ; : 1-3, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33888171

RESUMO

Congenital heart block is a rare and lethal condition in paediatric population associated with maternal connective tissue disorders and rarely with structural cardiac disease like atrioventricular canal defects with or without left isomerism and congenitally corrected transposition of great arteries. Pacing in neonate if indicated is generally accomplished by epicardial pacing systems. However, in cases of significant bradycardia and haemodynamic instability, temporary pacemaker implantation via transvenous approach remains as a suitable option. Despite the advances in percutaneous catheter interventions, use of transvenous pacing in newborn is extremely challenging due to inadvertent risk of vessel injury, thrombus formation and mortality, and most of the time technical inability to place the lead within the right ventricular cavity. We report a case of congenital complete atrioventricular block in a premature male with birth weight of 1.51 kg who was managed with temporary pacemaker implantation through umbilical vein.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33649164

RESUMO

OBJECTIVE: B cells have emerged as a therapeutic target for MS. Anti-CD20 antibodies, which deplete B cells, are effective therapies for MS. However, atacicept (TACI-Fc), which blocks BAFF and APRIL and reduces B cells, unexpectedly exacerbates MS. We tested the hypothesis that B cell maturation antigen (BCMA), a receptor for BAFF and APRIL, plays a role in the paradoxical effects of anti-CD20 antibody and TACI-Fc using experimental autoimmune encephalomyelitis (EAE). METHODS: EAE was induced in wild-type (BCMA+/+) and BCMA-deficient (BCMA-/-) mice with an immunization of rodent myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. Treatment with anti-CD20 antibody, TACI-Fc, and isotype controls was administered by intraperitoneal injections. CNS infiltration was evaluated by histology; immune cell phenotypes were evaluated by flow cytometry; MOG-specific antibodies were determined by ELISA. Mixed bone marrow chimeras and cell culture assays were used to identify the specific subsets of immune cells affected by BCMA deficiency. RESULTS: First, we found that BCMA-/- mice had more severe EAE compared with BCMA+/+ mice and the increased disease was associated with elevated anti-MOG B-cell responses. Second, we found that anti-CD20 therapy attenuated EAE in BCMA-/- mice but not in BCMA+/+ mice. Third, TACI-Fc attenuated EAE in BCMA+/+ mice but not in BCMA-/- mice. Mixed bone marrow chimeric and cell culture experiments demonstrated that BCMA deficiency elevates inflammatory B-cell responses but inhibits inflammatory responses in macrophages. CONCLUSIONS: BCMA has multifaceted roles during inflammation that affects therapeutic efficacies of anti-CD20 and TACI-Fc in EAE. Our results from BCMA-deficient mice provide insights into the failure of atacicept in MS.

13.
Syst Appl Microbiol ; 44(2): 126188, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33647766

RESUMO

Two axenic cultures of Planctomycetes were isolated from distinct geographical regions of the east coast of India. The two closely related strains (JC640 and CH01) showed <93.3% 16S rRNA gene sequence identity with members of the genus Roseimaritima followed by Rhodopirellula (<91%). Both strains displayed non-canonical cell morphology of Planctomycetes, such as rod shaped cells with division by lateral budding. Both strains showed crateriform structures on their surfaces and cells lack fimbriae. The genomes have a size of about 5.76 Mb and DNA G+C content of 63.6mol%. Phylogenetic analysis based on 16S rRNA gene sequence and 92 core genes based RAxML phylogenetic tree place both the strains in the family Pirellulaceae and indicated Roseimaritima sediminicola as their closest relative. The AAI and POCP values differentiate both strains from rest of the members of the family Pirellulaceae. The axenic cultures of both strains were able to grow up to 8-10 passages and subsequently the cells became non-viable with pleomorphic shapes. Supported by genomic, phylogenetic and morphological differences, we conclude that both strains belong to a novel genus. However, since the new isolates lost their viability on passaging, we propose the novel genus as "Candidatus Laterigemmans" gen. nov. and the novel species as "Candidatus Laterigemmans baculatus" sp. nov.

14.
Arch Virol ; 166(5): 1325-1336, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33660107

RESUMO

Rice tungro disease (RTD) is a devastating disease of rice caused by combined infection with rice tungro bacilliform virus (RTBV) and rice tungro spherical virus (RTSV), with one of the main symptoms being stunting. To dissect the molecular events responsible for RTD-induced stunting, the expression patterns of 23 cell-wall-related genes were examined in different rice lines with the same titers of RTSV but different titers of RTBV and in lines where only RTBV was present. Genes encoding cellulose synthases, expansins, glycosyl hydrolases, exostosins, and xyloglucan galactosyl transferase showed downregulation, whereas those encoding defensin or defensin-like proteins showed upregulation with increasing titers of RTBV. RTSV titers did not affect the expression levels of these genes. A similar relationship was seen for the reduction in the cellulose and pectin content and the accumulation of lignin. In silico analysis of promoters of the genes indicated a possible link to transcription factors reported earlier to respond to viral titers in rice. These results suggest a common network in which the genes related to the cell wall components are affected during infection with diverse viruses in rice.


Assuntos
Parede Celular/genética , Oryza/virologia , Doenças das Plantas/virologia , Tungrovirus/fisiologia , Carga Viral/fisiologia , Parede Celular/metabolismo , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Doenças das Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/virologia , Polissacarídeos/metabolismo , Waikavirus/fisiologia
15.
J Glob Health ; 11: 06001, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33692897

RESUMO

Background: Among all provinces of Pakistan, immunization coverage is poorest in Balochistan. There is no provincial immunization policy for Balochistan including a lack of human resource management policy. Maladministration and lack of accountability leading to health workforce demotivation and poor performance can be a crucial reason behind an inefficient and ineffective immunization program in Balochistan. The objective of this study was to better understand the accountability issues of EPI workforce at provincial and district level leading to poor program performance and to identify governance strategies for management of inefficiency, demotivation and absenteeism. Methods: An exploratory qualitative study was carried out to explore issues related to human resource (HR) accountability within immunization program of Balochistan for developing strategies to improve performance of the program. Five districts were selected using purposive sampling based on the comparative poor and good routine immunization coverages and Human Development Index (HDI). Interviews were conducted with EPI Staff and District Health Officers (DHOs) in each district including provincial EPI Staff. A semi-structured and open-ended questionnaire was used. Thematic analysis was used to analyze the qualitative data. Results: Major barriers to HR accountability included lack of a written HR policy, proper service structure including promotions and benefits and understanding of accurate job description coupled with inadequate HR development budget and activities. Most important demotivating factors were inadequate number of vaccinators, deficient budget with delayed wage and salary disbursements resulting in poor immunization coverage and a lack of appreciation/feedback from senior management for the frontline workers. Key challenge for vaccinators was poor community orientation and mobilization. Although, the participants proposed some solutions based on their perspective, none were elaborate or precise. Conclusions: Adaptation of National Immunization Policy tailored to the provincial context and proper implementation is much needed. Review of current allocations of vaccinators and need based relocation along with recruitment of new vaccinators with clear job description and terms of reference is desirable. Review of current incentive structure is required. Finally, trust building between community and the vaccination program and social mobilization about the benefits of vaccinations through community influential is vital.

16.
Antonie Van Leeuwenhoek ; 114(4): 341-353, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33582885

RESUMO

A Gram-stain-negative, aerobic, pear to oval shaped, rosette forming bacterium with crateriform structures well distributed on the cell surface designated as strain JC647T was isolated from a sponge specimen belonging to the genus Spongia. Strain JC647T reproduces through budding. Strain JC647T shared highest 16S rRNA gene sequence identity of 99.9% with "Crateriforma conspicua" Mal65T (not a valid species name). The genome size of strain JC647T is 6.9 Mb with a G + C content of 57.8 mol %. For the resolution of the phylogenetic congruence of the novel strain, the phylogeny was also constructed with the sequences of ninety-two housekeeping genes. Based on the phylogenetic analyses, low dDDH value (51.0%), low gANI (93.2%), low AAI (94.9%) results, chemotaxonomic characteristics and differential physiological properties, strain JC647T is recognized as a new species of the genus "Crateriforma", for which we propose the name Crateriforma spongiae sp. nov. The type species is JC647T (= KCTC 72176T = NBRC 114068T).

17.
Probiotics Antimicrob Proteins ; 13(2): 299-314, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33580864

RESUMO

Apical periodontitis (AP) is a biofilm-associated disease initiated by the invasion of dental pulp by microorganisms from the oral cavity. Eradication of intracanal microbial infection is an important goal of endodontic treatment, and this is typically accomplished by mechanical instrumentation and application of sodium hypochlorite and chlorhexidine. However, these agents are tissue-irritating at higher concentrations and cytotoxic. Certain probiotics have been found effective in controlling marginal periodontitis, as evidenced by reduction of pathogenic bacterial loads, gains in clinical attachment levels, and reduced bleeding on probing. In vitro studies have shown inhibitory activity of some probiotics against endodontic pathogens. Similarly, in vivo studies in rats have demonstrated a positive immuno-modulatory role of probiotics in AP, as manifested by decreased levels of proinflammatory markers and increased levels of anti-inflammatory markers. A role for probiotics in effecting a reduction of bone resorption has also been reported. This review provides an outline of current research into the probiotic management of AP, with a focus on understanding the mechanisms of their direct antagonistic activity against target pathogens and of their beneficial modulation of the immune system.

19.
Int J Hyperthermia ; 38(1): 263-272, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33612046

RESUMO

PURPOSE: While systemic tumor-stimulating effects can occur following ablation of normal liver linked to the IL-6/HGF/VEGF cytokinetic pathway, the potential for tumor cells themselves to produce these unwanted effects is currently unknown. Here, we study whether partially treated tumors induce increased tumor growth post-radiofrequency thermal ablation (RFA). METHODS: Tumor growth was measured in three immunocompetent, syngeneic tumor models following partial RFA of the target tumor (in subcutaneous CT26 and MC38 mouse colorectal adenocarcinoma, N = 14 each); and in a distant untreated tumor following partial RFA of target subcutaneous R3230 rat breast adenocarcinoma (N = 12). Tumor cell proliferation (ki-67) and microvascular density (CD34) was assessed. In R3230 tumors, in vivo mechanism of action was assessed following partial RFA by measuring IL-6, HGF, and VEGF expression (ELISA) and c-Met protein (Western blot). Finally, RFA was performed in R3230 tumors with adjuvant c-Met kinase inhibitor or VEGF receptor inhibitor (at 3 days post-RFA, N = 3/arm, total N = 12). RESULTS: RFA stimulated tumor growth in vivo in residual, incompletely treated surrounding CT26 and MC38 tumor at 3-6 days (p < 0.01). In R3230, RFA increased tumor growth in distant tumor 7 days post treatment compared to controls (p < 0.001). For all models, Ki-67 and CD34 were elevated (p < 0.01, all comparisons). IL-6, HGF, and VEGF were also upregulated post incomplete tumor RFA (p < 0.01). These markers were suppressed to baseline levels with adjuvant c-MET kinase or VEGF receptor inhibition. CONCLUSION: Incomplete RFA of a target tumor can sufficiently stimulate residual tumor cells to induce accelerated growth of distant tumors via the IL-6/c-Met/HGF pathway and VEGF production.

20.
Mol Biol Rep ; 48(2): 1045-1053, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33479827

RESUMO

Genome analysis of Halomonas shambharensis, a novel species, was performed to understand the osmoprotectant strategies used by the strain to overcome the salinity stress and to explore the prospective industrial uses. It will also help to better understand the ecological roles of Halomonas species in hypersaline habitats. Ultrastructure of the cell was determined by using transmission electron microscopy. Standard microbiological methods were used to find out growth parameters and heterotrophic mode of nutrition. For Genome analysis, complete bacterial genome sequencing was performed using the Oxford Nanopore MinION DNA Sequencer. Assembly, annotation and finishing of the obtained sequence were done by using a Prokaryotic Genome Annotation Pipeline (PGAP) (SPAdes v. 3.10.1). Predicted Coading sequences (CDSs) obtained through the PGAP were used for functional annotation using Clusters of Orthologous Groups and Kyoto Encyclopedia of Genes and Genomes (KEGG) platforms. The H. shambharensis was found to be a Gram-stain-negative, rod-shaped bacterium, motile with a peritrichous flagella. The H. shambharensis bacterium can grow in a wide range of temperature (from 25 to 65 °C), pH (pH 4 to pH 12.0) and salt concentration (5.0% NaCl to 30.0% NaCl). After annotation and assembly, the total genome size obtained was 1,533,947 bp, which revealed 146 subsystems, 3847 coding sequences, and 19RNAs with G+C content of 63.6%. Gene annotation identified the genes related to various metabolic pathways, including carbohydrate metabolism, fatty acid metabolism and stress tolerance. The genomic dataset of H. shambharensis will be useful for analysis of protein-coding gene families and how these coding genes are significant for the survival and metabolism among the different species of Halomonas. The complete genome sequence presented here will help to unravel the biotechnological potential of H. shambharensis for production of the high-value products such as betaine, or as a source of gene-mining for individual enzymes.


Assuntos
Genoma Bacteriano/genética , Halomonas/genética , Lagos/microbiologia , Filogenia , Composição de Bases/genética , Metabolismo dos Carboidratos/genética , Halomonas/classificação , Índia , Anotação de Sequência Molecular , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Salinidade , Sequenciamento Completo do Genoma
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