disease development
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2022 ◽  
Vol 8 ◽  
Author(s):  
Chih-Ru Lin ◽  
Karim Bahmed ◽  
Beata Kosmider

Pulmonary emphysema is characterized by the destruction of alveolar septa and irreversible airflow limitation. Cigarette smoking is the primary cause of this disease development. It induces oxidative stress and disturbs lung physiology and tissue homeostasis. Alveolar type II (ATII) cells have stem cell potential and can repair the denuded epithelium after injury; however, their dysfunction is evident in emphysema. There is no effective treatment available for this disease. Challenges in this field involve the large complexity of lung pathophysiological processes and gaps in our knowledge on the mechanisms of emphysema progression. It implicates dysregulation of various signaling pathways, including aberrant inflammatory and oxidative responses, defective antioxidant defense system, surfactant dysfunction, altered proteostasis, disrupted circadian rhythms, mitochondrial damage, increased cell senescence, apoptosis, and abnormal proliferation and differentiation. Also, genetic predispositions are involved in this disease development. Here, we comprehensively review studies regarding dysregulated cell signaling, especially in ATII cells, and their contribution to alveolar wall destruction in emphysema. Relevant preclinical and clinical interventions are also described.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Elaine de Guise ◽  
Beatrice Soucy ◽  
Sven Joubert ◽  
José A. Correa ◽  
Jehane H. Dagher

Diseases ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
S. H. Nandana P. Gunawickrama ◽  
K. Imesha G. Hewavitharana ◽  
P. G. Chandra L. Nanayakkara ◽  
K. B. Suneetha Gunawickrama

CKDu needs to be characterized in fundamental areas to improve etiological understanding and disease management. In a cross-sectional study, blood cell profile and plasma inflammatory cytokines were followed by automated analysis and sandwich ELISA, respectively. Disease development stages and proteinuria were ascertained by eGFR and UACR. Comparison among control and stages (ANOVA/Dunnett’s MRT) revealed time-specific changes (p < 0.05), including decreased erythrocytes (G5) and hematocrit (G5), and increased MCHC (G3b, G4), MCV (G5), and MCH (G5). CKDu decreased (p < 0.05) lymphocytes (G3b, G4, G5), monocytes (G3b), MPV (G3b, G4, G5), and plateletcrit (G3b, G4), and increased basophils (G3a, G3b, G4), N/L (G4) and PLR (G4–G5). MCHC and aforesaid leukocyte variables were in correlation (rho > ±0.03, p < 0.05, Pearson’s test) with disease development. MCP-1 and IL-6 spiked (p > 0.05) at G3b. Multivariate analyses confirmed that MCP-1, lymphocytes, and BMI were related to renal dysfunction, pointing to inflammation, compromised immunity, and muscle wasting as CKDu effects. Nonproteinuric CKDu was prevalent (23.2–35.6% of total CKDu) with (p < 0.05) elevated basophils (G3a), N/L (G4), and depleted lymphocytes (G4). In both forms, G1–G2 were unaffected, and the earliest change was G3a basophils. Results suggest that MCP-1, lymphocyte count, N/L, and PLR may verify the stage and predict impending ESRD in advance proteinuric CKDu.


Author(s):  
Lei Tian ◽  
Hui Zhang ◽  
Li-Li Guo ◽  
Xiao Qin ◽  
Di Zhang ◽  
...  

Purpose: To analyze the changes in coordinates and distances among three typical geometric landmarks of the cornea, namely, the thinnest point (TP), maximum curvature (Kmax), and corneal apex (AP) during the development of keratoconus, and explore the potential relationship between these changes and the abnormalities of corneal biomechanics.Methods: Normal eyes (n = 127), clinical keratoconic eyes (CKC, n = 290), and the eyes of forme fruste keratoconus (FFKC, n = 85) were included; among them, the CKC group was classified into four grades based on the Topographic Keratoconus Classification (TKC) provided by Pentacam. A total of 38 Corvis ST output parameters and three distance parameters of three typical landmarks (DKmax-AP, DTP-AP, and DKmax-TP) based on Pentacam were included. The differences of parameters among the abovementioned six groups (Normal, FFKC, and CKC stage I to CKC stage IV) were analyzed. Spearman’s rank correlation test was performed to choose several dynamic corneal response (DCR) parameters that could best reflect the changes of corneal biomechanical characteristics during the progression of the disease, and the Pearson’s or Spearman’s correlation test was conducted to determine the association between the three distances and the selected DCR parameters in each grade. In addition, by flipping the X coordinate of the left eye on the vertical axis to reflect the direction of the right eye, the coordinates of TP and Kmax in different developmental grades were highlighted.Results: From CKC stage II, the three geometric landmark distances commenced to correlate with the corneal DCR parameters (CBI, SPA1, IR, DA Ratio 2, ARTh, MIR, Radius, Pachy, and DA Ratio 1), which could better represent the changes of biomechanical properties from normal cornea to keratoconus. From normal cornea to CKC stage IV, the coordinates of Kmax were gradually tended to the inferior temporal region from dispersion, while TP was always concentrated in the inferior temporal region. Although DKmax-AP, DKmax-TP, and DTP-AP all showed a gradual decreasing trend with the progress of the disease, the first two did not change significantly, and only DTP-AP significantly approached AP in the later stage of disease development. In addition, from the FFKC group, the corresponding values of DKmax-TP in each disease development group were smaller than DKmax-AP.Conclusions: In the later stage of keratoconus, the relationship between the three typical landmark distance parameters and DCR parameters is stronger, and even the weakening of corneal biomechanical properties may be accompanied by the merger of typical landmark positions.


2021 ◽  
Author(s):  
Amanda Karlstr&oumlm ◽  
Antonio G&oacutemez-Cortecero ◽  
Charlotte F Nellist ◽  
Matthew Ordidge ◽  
Jim M Dunwell ◽  
...  

Resistance to Neonectria ditissima, the fungus causing European canker in apple, was studied in a multiparental population of apple scions using several phenotyping methods. The studied population consists of individuals from multiple families connected through a common pedigree. The degree of disease of each individual in the population was assessed in three experiments: artificial inoculations of detached dormant shoots, potted trees in a glasshouse and in a replicated field experiment. The genetic basis of the differences in disease was studied using a pedigree-based analysis (PBA). Three quantitative trait loci (QTL), on linkage groups (LG) 6, 8 and 10 were identified in more than one of the phenotyping strategies. An additional four QTL, on LG 2, 5, 15 and 16 were only identified in the field experiment. The QTL on LG2 and 16 were further validated in a biparental population. QTL effect sizes were small to moderate with 4.3 to 19 % of variance explained by a single QTL. A subsequent analysis of QTL haplotypes revealed a dynamic response to this disease, in which the estimated effect of a haplotype varied over the field time-points. Two groups of QTL-haplotypes could be distinguished, one that displayed increased effect and one with a constant effect across time-points. These results suggest that there are different modes of control of N. ditissima in the early stages of infection compared to later time-points of disease development. It also shows that multiple QTL will need to be considered to improve resistance to European canker in apple breeding germplasm.


2021 ◽  
Vol 74 (2S) ◽  
pp. S20-S33
Author(s):  
Lizelle Vorster ◽  
Ruth C. Butler ◽  
Lauren Turner ◽  
Emma Patrick ◽  
Rebecca E. Campbell ◽  
...  

The effects of nitrogen on the interaction between apple trees and European canker caused by Neonectria ditissima are not well understood. Previous field and laboratory studies have shown that nitrogen affects N. ditissima disease development, germination and germ-tube growth in vitro but the type of nitrogen source has not been examined in vivo. Therefore, the aim of this study was to determine the effects of root-applied nitrogen from different sources on the development of European canker on inoculated potted trees. One-year-old ‘Royal Gala’ trees were planted in a low-nitrogen growth substrate and treated with a range of concentrations of calcium ammonium nitrate (CAN) or other nitrogen sources (Ca(NO3)2, KNO3, (NH4)2SO4, NH4NO3, urea, YaraMila™) at equivalent molar rates of nitrogen as the highest CAN treatment. Treatments were applied during the growing season (Nov to May). The control treatment received no applied nitrogen. Bud and leaf scar wounds were inoculated at leaf fall with N. ditissima conidia. Tree growth and health, disease progression and leaf nitrogen content were monitored. The rate of nitrogen application affected tree diameter and leaf nitrogen content while the nitrogen source mainly affected tree survival, powdery mildew incidence, leaf weights, leaf nitrogen and European canker symptom expression. Trees treated with (NH4)2SO4 had the lowest survival rates and highest leaf nitrogen content. Disease expression was highest with NH4NO3 and lowest with KNO3 applications. The control plants (which received no additional nitrogen), showed the least amount of both growth and disease expression. Applications of CAN, even at the lowest rate (20 g), increased disease susceptibility. Increasing rates of CAN applications did not significantly increase disease incidence. Nitrogen concentration is an important factor in the disease development of European canker of apple. Field evaluation is recommended to further validate these results.


Plant Disease ◽  
2021 ◽  
Author(s):  
Myriam Solís ◽  
Mike Wingfield ◽  
Almuth Hammerbacher ◽  
Sanushka Naidoo

Leaf blight caused by Teratosphaeria destructans is one of the most important diseases of Eucalyptus planted in the sub-tropics and tropics. In contrast, the better-known Teratosphaeria epicoccoides, while also a primary pathogen of Eucalyptus, causes less damage to trees in these areas. Although T. destructans is an aggressive pathogen, nothing is known about its infection biology. In this study, the conditions for infection and disease development caused by T. destructans and T. epicoccoides were evaluated and compared on a Eucalyptus grandis x Eucalyptus urophylla hybrid clone. The optimal temperature for the germination of T. destructans ranged from 25 to 30 oC and 15 to 20 oC for T. epicoccoides. The germination of these pathogens was favored under conditions of light and high levels of relative humidity. Penetration by T. destructans and T. epicoccoides occurred via stomata and the hyphae colonized the intercellular spaces of infected leaves. Symptoms were clearly visible three weeks after inoculation by both pathogens and reproductive structures started to develop in substomatal cavities at four weeks after inoculation. The results of this study will facilitate the establishment of rapid screening trials based on artificial inoculations aimed at reducing the impact of disease caused by T. destructans.


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