scholarly journals Role of β-defensins in immune response in tuberculosis patients

2020 ◽  
Vol 7 (2) ◽  
pp. 102-106
Author(s):  
O. Pohorielova ◽  
O. Shevchenko

ROLE OF Β-DEFENSINS IN IMMUNE RESPONSE IN TUBERCULOSIS PATIENTS Shevchenko O., Pohorielova O. Expanding of tuberculosis drug-resistance makes host-directed treatment an important part of tuberculosis treatment. Host-directed treatment is aimed at stimulating the production of antimicrobial peptides by the patient's immune cells. The use of β-defensins is very interesting in this field because of their pronounced bactericidal and bacteriostatic effects, as well as the ability to stimulate the chemotaxis of immune cells. The article presents a review on the immunological properties of the defensin family and the possibility of their use in practice. To complete the review 114 articles from “PubMed” resource were analyzed to perform the study. 34 of them were chosen to review immunomodulatory and antimicrobial action of β-defensins. The own research results on Human-beta-defensine-1 use as tuberculosis severity marker are also added to the research. To obtain our own research results, 100 TB patients and 20 healthy persons were included in the study. Human-beta-defensin-1 level in serum was investigated in all the patients at the treatment onset and in healthy persons. Mann-Whitney U test (for comparison of 2 independent groups) and Spearman's rank correlation coefficient were used for statistical data processing. It was found that Human-beta-defensin-1 level was significantly higher in TB patients than in healthy persons. A correlation of medium strength (r=+0.53, p<0.05) between Human-beta-defensin-1 and tuberculosis lesion volume was revealed. The data obtained allows to use human β-defensin-1 as a diagnostic marker of tuberculosis. Key words: tuberculosis, β-defensins, immunity, prognostic marker   Резюме. РОЛЬ Β-ДЕФЕНЗИНІВ В ІМУННІЙ ВІДПОВІДІ У ХВОРИХ НА ТУБЕРКУЛЬОЗ Шевченко О.С., Погорєлова О.О. Розширення лікарської стійкості туберкульозу робить лікування, спрямоване на активацію власних резервів організму-хазяїна, важливою частиною терапії. Таке лікування спрямоване на стимулювання продукції антимікробних пептидів імунними клітинами пацієнта. Використання β-дефензинів в даній області є перспективним через їх виражену бактерицидну і бактеріостатичну дію, а також здатність стимулювати хемотаксис імунних клітин. У статті представлений огляд імунологічних властивостей сімейства дефензинів і можливостей їх використання на практиці. Для створення огляду було проаналізовано 114 статей з ресурсу «PubMed». З них 34 були обрані для вивчення імуномодулюючої і антимікробної дії β-дефензинів. Результати власного дослідження можливостей використання β-дефензину-1 також були включені в роботу. Для отримання власних результатів у дослідження було включено 100 хворих на туберкульоз і 20 здорових людей. Рівень β-дефензіну-1 в сироватці крові був досліджений у всіх пацієнтів на початку лікування і у здорових людей. U-критерій Манна-Уїтні (для порівняння 2 незалежних груп) і коефіцієнт кореляції застосовувалися для статистичної обробки даних. Було виявлено, що рівень β-дефензину-1 був значно вищим у хворих на туберкульоз, ніж у здорових людей. Виявлено кореляцію середньої сили (r = + 0,53, р <0,05) між рівнем β-дефензину-1 і об’ємом туберкульозного ураження. Отримані дані дозволяють використовувати β-дефензин-1 в якості діагностичного маркеру перебігу туберкульозу. Ключові слова: туберкульоз, β-дефензини, імунітет, прогностичний маркер   Резюме. РОЛЬ Β-ДЕФЕНЗИНОВ В ИММУННОМ ОТВЕТЕ У БОЛЬНЫХ ТУБЕРКУЛЕЗОМ Шевченко О.С., Погорелова О.А. Расширение лекарственной устойчивости туберкулеза делает лечение, направленное на активацию резервов организма-хозяина, важной частью терапии. Такое лечение направлено на стимулирование производства антимикробных пептидов иммунными клетками пациента. Использование β-дефензинов в данной области является перспективным из-за их выраженного бактерицидного и бактериостатического действия, а также способности стимулировать хемотаксис иммунных клеток. В статье представлен обзор иммунологических свойств семейства дефензинов и возможности их использования на практике. Для создания обзора было проанализировано 114 статей из ресурса «PubMed». 34 из них были выбраны для изучения иммуномодулирующего и антимикробного действия β-дефензинов. Собственные результаты исследования возможностей использования β-дефензина-1 в качестве маркера тяжести туберкулеза также были включены в работу. Для получения собственных результатов в исследование были включены 100 больных туберкулезом и 20 здоровых людей. Уровень β-дефензина-1 в сыворотке был исследован у всех пациентов в начале лечения и у здоровых людей. U-критерий Манна-Уитни (для сравнения 2 независимых групп) и коэффициент корреляции Спирмена были использованы для статистической обработки данных. Было обнаружено, что уровень β-дефензина-1 был значительно выше у больных туберкулезом, чем у здоровых людей. Выявлена ​​корреляция средней силы (r = + 0,53, р <0,05) между уровнем β-дефензина-1 и туберкулезного поражения. Полученные данные позволяют использовать β-дефензин-1 в качестве диагностического маркера течения туберкулеза. Ключевые слова: туберкулез, β-дефензины, иммунитет, прогностический маркер

2021 ◽  
Author(s):  
Amir Valizadeh ◽  
Elham Barati ◽  
Mohammad Ali Sahraian ◽  
Mohammad Reza Fattahi ◽  
Mana Moassefi

Abstract Introduction: As the role of neurodegeneration in the pathophysiology of multiple sclerosis (MS) has become more prominent, the formation and evolution of chronic or persistent T1-hypointense lesions (Black Holes) have been used as markers of axonal loss and neuronal destruction to measure disease activity. However, findings regarding this subject are controversial. In this study we aim to clarify the level of importance of T1 hypointense lesions for estimating the prognosis of patients.Methods: We will search MEDLINE (through PubMed), Embase and Web of Science for relevant studies. We will extract the Spearman's rank correlation coefficient (SRCC) between the T1 hypointense lesion volume and Extended Disability Status Scale (EDSS) in participants. All included studies will be evaluated for the risk of bias. We will also perform a meta-analysis on the data. The risk of publication bias will be evaluated using Funnel plots. Finally, we will assess the confidence in cumulative evidence using an adapted version of GRADE.


Author(s):  
A. I. Zheltikov ◽  
T. V. Konovalova ◽  
O. I. Sebezhko ◽  
V. V. Ilyin ◽  
P. N. Palchikov ◽  
...  

The characteristic of bulls-producers of red breeds of OAO Barnaulskoe breeding enterprise on the quality of sperm and its resistance to cryopreservation are presented. The breeding enterprise has examined samples of water, soil, feed for the content of heavy metals. In the studied samples, no excess of the LOC was found. The research results were processed on a PC using population statistics methods. Angler bulls produced the largest amount of ejaculates unsuitable for cryopreservation. It is 20.6%. According to this indicator, they surpassed the producers of red Danish and red steppe breeds by 4.1-7.8%. The animals of the latter breed showed the smallest amount (1.7%) of ejaculates rejected after defrost. In Angler bulls, this indicator was 5.95%, in red Danish bulls it was 2.95%, which is 3.52 and 1.75 times higher than in red steppe breeders (P <0.01-0.001). Significant differences were established between individual bulls of the red steppe breed in the number of ejaculates rejected before cryopreservation (2.84-22.29%) and after defrost (0-7.09%). The differences between breeds in the frequency of rejected ejaculates before freezing and after cryopreservation indicate a certain role of heredity in the resistance of animals for these indicators. Spearman’s rank correlation coefficient between these traits was 0.312. It indicates the possibility of preliminary assessment and selection of bulls according to the first indicator. But the final assessment of the bull-producers can be made by the frequency of rejected ejaculates after thawing. We propose to consider the issue of additional accounting in breeding programs for the resistance of the seed of bulls-producers to cryopreservation.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2051-2051
Author(s):  
Shinichiro Takahashi ◽  
Hideo Harigae ◽  
Mitsue Inomata ◽  
Keiko Kumura Ishii ◽  
Jonathan D. Licht ◽  
...  

Abstract Nuclear factor kappa B (NFkB) regulates transcription of many genes involved in the immune response, including cytokines (e.g. IL-6) and growth factors. NFkB suppresses apoptosis as well, through various mechanisms including activation of cellular inhibitor of apoptosis-1 (cIAP-1). NFkB can be activated by the activation of Ras/phosphatidylinositol 3′-kinase (PI3K)/protein kinase B pathway in acute myeloblastic leukemia (AML). It was reported that in large proportion of primary AML cells, NFkB is constitutively activated, and the target genes are upregulated. Flt3 is a member of receptor tyrosine kinases. Flt3 receptor phosphorylation/activation results in the activation of downstream kinase pathways, like Ras, PI3K, leading to abnormal cell growth and aberrant gene regulation. Increased levels of Flt3 transcript are observed in a large number of AML specimens, and the over-expression of Flt3 contributes to the phosphorylation of Flt3 and activation of this pathway. In this study, we addressed the role of Flt3 over-expression in the activation of NFkB, which is a target molecule of various kinase pathways. We first tested the effect of Flt3 expression to NFkB responsive reporter by transient transfection and revealed the significant induction of the reporter. Next, we generated Flt3 transgenic BaF3 (BaF3-Flt3) cells that stably over-expressing Flt3 to confirm this effect. The introduction of NFkB-responsive reporter, as well as serum response element (SRE)-luciferase fused reporter into these cells resulted in the activation of the reporters. These results suggest that Flt3 over-expression mediated signal transduction activates NFkB pathways and affects growth factor pathways as well. Real time quantitative PCR demonstrated that in BaF3-Flt3 cells, mRNA expression of IL-6 and cIAP-1, both known target genes of NFkB, were increased. AG1296 or PDTC, potent inhibitors of Flt3 and NFkB respectively, completely abrogated the induction of these genes, suggesting the importance of Flt3-NFkB pathway to these effects. Moreover, we measured the expression level of Flt3 and NFkB target genes in 24 primary AML samples. As a result, there was a tendency of moderate to weak positive correlation between Flt3 and NFkB target genes. (Flt3 vs IL-6 [Spearman’s rank correlation coefficient: r= 0.35], Flt3 vs cIAP-1 [r=0.16]). These facts may also indicate the positive influence of Flt3 over-expression to NFkB target genes. Overall, these suggest a role of Flt3 over-expression in the activation of NFkB pathway in AML.


2021 ◽  
Author(s):  
Amir Valizadeh ◽  
Elham Barati ◽  
Mohammad Ali Sahraian ◽  
Mohammad Reza Fattahi ◽  
Mana Moassefi

Abstract Introduction: As the role of neurodegeneration in the pathophysiology of multiple sclerosis (MS) has become more prominent, the formation and evolution of chronic or persistent T1-hypointense lesions (Black Holes) have been used as markers of axonal loss and neuronal destruction to measure disease activity. However, findings regarding this subject are controversial. In this study we aim to clarify the level of importance of T1 hypointense lesions for estimating the prognosis of patients.Methods: We will search MEDLINE (through PubMed), Embase and Web of Science for relevant studies. We will extract the Spearman's rank correlation coefficient (SRCC) between the T1 hypointense lesion volume and Extended Disability Status Scale (EDSS) in participants. All included studies will be evaluated for the risk of bias. We will also perform a meta-analysis on the data. The risk of publication bias will be evaluated using Funnel plots. Finally, we will assess the confidence in cumulative evidence using an adapted version of GRADE.


2021 ◽  
Vol 11 ◽  
Author(s):  
Longhai Li ◽  
Kai Jiang ◽  
Dongpeng Li ◽  
Dongxiao Li ◽  
Zitong Fan ◽  
...  

ObjectiveThe present study was designed to investigate the role of the chemokine CXCL7 in angiogenesis and explore its prognostic value in colorectal cancer (CRC).MethodsA total of 160 CRC patients who had undergone surgery were included in this study, and staged according to the guidelines of the AJCC, 7th Edition. Expression of CXCL7 and VEGF was detected by immunohistochemical (IHC) staining and divided into high and low expression subgroups. The correlation between CXCL7 and VEGF expression was evaluated by Spearman’s rank-correlation coefficient. Prognosis based on CXCL7 and VEGF was evaluated using the Cox proportional hazards regression model and a nomogram of 5-year overall survival (OS) time.ResultsCXCL7 was highly expressed in tumor tissues (65.63% vs 25.00% in paracancerous tissue, P &lt; 0.001), as was VEGF. CXCL7 and VEGF expression correlated well with N and TNM stage cancers (all P &lt; 0.001). Importantly, CXCL7 was positively correlated with VEGF expression in CRC tissues. CXCL7 was an independent predictor of poor OS of CRC patients (HR = 2.216, 95% CI: 1.069-4.593, P = 0.032), and co-expression of CXCL7 and VEGF of predicted poor OS of 56.96 months.ConclusionExpression of CXCL7 correlated with VEGF and was associated with poor clinical outcomes in CRC patients.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hui Jiang ◽  
Peian Lou ◽  
Xiaoluo Chen ◽  
Chenguang Wu ◽  
Shihe Shao

Abstract Background Type 2 diabetes mellitus (T2DM) is mainly affected by genetic and environmental factors; however, the correlation of long noncoding RNAs (lncRNAs) with T2DM remains largely unknown. Methods Microarray analysis was performed to identify the differentially expressed lncRNAs and messenger RNAs (mRNAs) in patients with T2DM and healthy controls, and the expression of two candidate lncRNAs (lnc-HIST1H2AG-6 and lnc-AIM1-3) were further validated using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman’s rank correlation coefficient was used to measure the degree of association between the two candidate lncRNAs and differentially expressed mRNAs. Furthermore, the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and GO (Gene Ontology) enrichment analysis were used to reveal the biological functions of the two candidate lncRNAs. Additionally, multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed. Results The microarray analysis revealed that there were 55 lncRNAs and 36 mRNAs differentially expressed in patients with T2DM compared with healthy controls. Notably, lnc-HIST1H2AG-6 was significantly upregulated and lnc-AIM1-3 was significantly downregulated in patients with T2DM, which was validated in a large-scale qRT-PCR examination (90 controls and 100 patients with T2DM). Spearman’s rank correlation coefficient revealed that both lncRNAs were correlated with 36 differentially expressed mRNAs. Furthermore, functional enrichment (KEGG and GO) analysis demonstrated that the two lncRNA-related mRNAs might be involved in multiple biological functions, including cell programmed death, negative regulation of insulin receptor signal, and starch and sucrose metabolism. Multivariate logistic regression analysis revealed that lnc-HIST1H2AG-6 and lnc-AIM1-3 were significantly correlated with T2DM (OR = 5.791 and 0.071, respectively, both P = 0.000). Furthermore, the ROC curve showed that the expression of lnc-HIST1H2AG-6 and lnc-AIM1-3 might be used to differentiate patients with T2DM from healthy controls (area under the ROC curve = 0.664 and 0.769, respectively). Conclusion The profiles of lncRNA and mRNA were significantly changed in patients with T2DM. The expression levels of lnc-HIST1H2AG-6 and lnc-AIM1-3 genes were significantly correlated with some features of T2DM, which may be used to distinguish patients with T2DM from healthy controls and may serve as potential novel biomarkers for diagnosis in the future.


Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 70
Author(s):  
Malgorzata Kloc ◽  
Ahmed Uosef ◽  
Martha Villagran ◽  
Robert Zdanowski ◽  
Jacek Z. Kubiak ◽  
...  

The small GTPase RhoA, and its down-stream effector ROCK kinase, and the interacting Rac1 and mTORC2 pathways, are the principal regulators of the actin cytoskeleton and actin-related functions in all eukaryotic cells, including the immune cells. As such, they also regulate the phenotypes and functions of macrophages in the immune response and beyond. Here, we review the results of our and other’s studies on the role of the actin and RhoA pathway in shaping the macrophage functions in general and macrophage immune response during the development of chronic (long term) rejection of allografts in the rodent cardiac transplantation model. We focus on the importance of timing of the macrophage functions in chronic rejection and how the circadian rhythm may affect the anti-chronic rejection therapies.


Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 769
Author(s):  
Yuko Hara ◽  
Kenichi Goda ◽  
Shinichi Hirooka ◽  
Takehiro Mitsuishi ◽  
Masahiro Ikegami ◽  
...  

We previously reported that superficial non-ampullary duodenal tumors (SNADETs) commonly had a whitish mucosal surface, named milk-white mucosa (MWM). The aim of this study was to evaluate the association of MWM with epithelial intracellular lipid droplets (immunohistochemically stained by adipose differentiation-related protein (ADRP)) and histological tumor grades. We reviewed endoscopic images and the histopathology of SNADETs resected en bloc endoscopically. We analyzed the correlation between the positive rates of endoscopic MWM in preoperative endoscopy and resected specimens, and ADRP-positive rates in the resected specimens. Associations between the MWM-positive rates and tumor grades, high-grade intraepithelial neoplasia (HGIN)/intramucosal carcinoma (IC), and low-grade intraepithelial neoplasia (LGIN) were analyzed. All the 92 SNADETs analyzed were <20 mm and histologically classified into 39 HGIN/IC and 53 LGIN. Spearman’s rank correlation coefficient showed a significant correlation between MWM-positive and ADRP-positive rates (p < 0.001). MWM-positive rates were significantly lower in the HGIN/IC than in the LGIN in preoperative endoscopy (p < 0.001) and resected specimens (p = 0.02). Our results suggest that endoscopic MWM is closely associated with epithelial intracellular lipid droplets and that the MWM-positive rate may be a predictor of histological grade in small SNADETs.


2012 ◽  
Vol 16 (02) ◽  
pp. 209-216 ◽  
Author(s):  
Luana Berwig ◽  
Ana da Silva ◽  
Eliane Corrêa ◽  
Eliane Serpa ◽  
Rodrigo Ritzel

Summary Introduction: Hyperplasia of the pharyngeal tonsil is one of the main causes of mouth breathing, and accurate diagnosis of this alteration is important for proper therapeutic planning. Therefore, studies have been conducted in order to provide information regarding the procedures that can be used for the diagnosis of pharyngeal obstruction. Objective: To verify the correlation between nasopharyngoscopy and cephalometric examinations in the diagnosis of pharyngeal tonsil hyperplasia. Method: This was a cross-sectional, clinical, experimental, and quantitative study. Fifty-five children took part in this study, 30 girls and 25 boys, aged between 7 and 11 years. The children underwent nasofibropharyngoscopic and cephalometric evaluation to determine the grade of nasopharyngeal obstruction. The Spearman's rank correlation coefficient at the 5% significance level was used to verify the correlation between these exams. Results: In the nasopharyngoscopy evaluation, most children showed grade 2 and 3 hyperplasia of the pharyngeal tonsil, which was followed by grade 1. In the cephalometry assessment, most children showed grade 1 hyperplasia of the pharyngeal tonsil, which was followed by grade 2. A statistically significant regular positive correlation was observed between the exams. Conclusion: It was concluded that the evaluation of the pharyngeal tonsil hyperplasia could be carried out by fiber optic nasopharyngoscopy and cephalometry, as these examinations were regularly correlated. However, it was found that cephalometry tended to underestimate the size of the pharyngeal tonsil relative to nasopharyngoscopy.


2018 ◽  
Vol 23 (3) ◽  
Author(s):  
Urszula Kaczmarek ◽  
Wojciech Kowalczyk ◽  
Dariusz Gozdowski ◽  
Dorota Olczak-Kowalczyk

Introduction. The use of age- and risk-adjusted caries prevention requires up-to-date knowledge on the cariostatic effects of fluoride, as well as the methods and safety of fluoride prophylaxis. Aim. The aim of the study was to assess dentists’ knowledge of the safety and mechanism of anticaries effects of fluoride. Material and methods. An anonymous questionnaire was conducted among 212 dentists participating in dental training. The questions included in the questionnaire related to knowledge about water fluoridation, fluoride cariostatic mechanisms and the safety of fluoride prophylaxis. The chi-square test and the Spearman’s rank correlation coefficient were used for statistical analysis. A significance level of 0.05 was used. Results. Incorrect knowledge about water fluoridation was demonstrated by 26.9% of respondents in the country and 16.0% of respondents in Europe. Most respondents (80.7%) reported higher efficacy of exogenous vs endogenous anticaries approaches, and more than half of respondents (59.0%) considered the processes of remineralisation and demineralisation as the most important anticaries activity. Almost all respondents (95.7%) agreed that the use of fluoride for caries prevention is controversial, mainly due to its dose-dependent therapeutic or toxic effects (85.4%). According to about 20% of respondents, cariostatic fluoride doses have adverse effects on the general health, mainly in the form of bone fragility (10.4%). Conclusions. Lack of correct knowledge about the dominant cariostatic effects of fluoride may result in the choice of an inappropriate preventive method or avoiding local application of fluoride preparations for fear of adverse systemic effects, which may in turn lead to increased caries prevalence in a given population.


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