Different Profiles of Cytokines, Chemokines and Coagulation Mediators Associated with Severity in Brazilian Patients Infected with Dengue Virus

Solórzano, Victor Edgar Fiestas; Faria, Nieli Rodrigues da Costa; Santos, Caroline Ferreira dos; Corrêa, Gladys; Cipitelli, Márcio da Costa; Dornelas-Ribeiro, Marcos; Souza, Luíz José de; Damasco, Paulo Vieira; Cunha, Rivaldo Venâncio da; Santos, Flávia Barreto dos; Pinto, Luciana Wernersbach; Azeredo, Elzinandes Leal de

doi:10.3390/v13091789

Cited by 10 publications

(4 citation statements)

References 62 publications

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“…2 , differences in the retinal pigmented epithelium compared to macrophage responses in particular differing host responses in uninfected bystander MDM in the DENV-challenged population, or differences due to the primary nature of MDM compared to the immortalized ARPE19 cell line. Increased IL-6 has been associated with severe dengue in many studies ( 74 – 76 ), and results here suggest modulating Vav does not compromise control of DENV replication but may not benefit control of IL-6 production. In addition to inflammation and antiviral responses, Vav has a role in maintaining vascular integrity and the impact of Vav on DENV-induced changes to the endothelium remains to be defined ( 12 ).…”

Section: Discussionmentioning

confidence: 51%

Vav proteins do not influence dengue virus replication but are associated with induction of phospho-ERK, IL-6, and viperin mRNA following DENV infection in vitro

Cowell,

Jaber,

Kris

et al. 2024

Microbiol Spectr

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Vav proteins are guanine exchange factors that activate Rac1/RhoA signaling to regulate many biological processes including inflammatory responses. Here, the expression and functional significance of Vav’s were investigated during dengue virus (DENV) infection. In primary monocyte-derived macrophages, Vav1, −2, and −3 mRNA levels demonstrate variable responses to DENV infection and correlate with DENV-induced host inflammatory (IL-6 and TNF-α), antiviral (viperin), or cell adhesion [intercellular cell adhesion molecule (ICAM-1)] mRNA induction. Strong positive correlations were seen in particular for Vav2 with TNF-α and Vav3 with IL-6 mRNA. In the retinal pigmented epithelial cell line, ARPE-19, Vav2 was the main Vav expressed and was not affected by DENV infection. Heterologous Vav1 expression in ARPE-19 cells induced an increase in basal IL-6 mRNA but did not enhance DENV-induced mRNA responses. DENV RNA and DENV-induced viperin and IL-6 mRNA responses were also unaffected by Vav2 siRNA knockdown. Treatment of DENV-infected ARPE-19 cells with EHop-016 to block Vav signaling did not affect DENV RNA levels but increased DENV-mediated induction of IL-6 mRNA. More detailed assessment of DENV-induced responses to azathioprine, a clinically used immunosuppressant that can also block Vav signaling and act as a nucleoside analog, similarly demonstrated no change in DENV RNA levels but resulted in inhibition of DENV-induced phospho-ERK and increased DENV-induced-IL-6 and viperin mRNA in ARPE-19 cells. Thus, levels of Vav are associated with DENV-induced inflammatory responses, and blocking Vav signaling pathways does not compromise control of viral replication but may influence DENV-induced host responses. IMPORTANCE Dengue disease is characterized by an inflammatory-mediated immunopathology, with elevated levels of circulating factors including TNF-α and IL-6. If the damaging inflammatory pathways could be blocked without loss of antiviral responses or exacerbating viral replication, then this would be of potential therapeutic benefit. The study here has investigated the Vav guanine exchange factors as a potential alternative signaling pathway that may drive dengue virus (DENV)-induced inflammatory responses, with a focus on Vav1 and 2. While Vav proteins were positively associated with mRNA for inflammatory cytokines, blocking Vav signaling didn’t affect DENV replication but prevented DENV-induction of p-ERK and enhanced IL-6 (inflammatory) and viperin (antiviral) mRNA. These initial data suggest that Vav proteins could be a target that does not compromise control of viral replication and should be investigated further for broader impact on host inflammatory responses, in settings such as antibody-dependent enhancement of infection and in different cell types.

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Section: Discussionmentioning

confidence: 51%

Vav proteins do not influence dengue virus replication but are associated with induction of phospho-ERK, IL-6, and viperin mRNA following DENV infection in vitro

Cowell,

Jaber,

Kris

et al. 2024

Microbiol Spectr

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“…Interestingly, in this study, feeding diet CP80 increased the relative abundance of Oceanicaulis , Aliihoeflea , and Ochrobactrum in the gut of golden pompano, but its function in aquatic animals is less reported and unclear. When pathogens invade fish, nonspecific immunity first acts as a defense to maintain body health [ 79 , 80 ]. In the study, the expression of il -8 and tnf-α expression of AP80 and PP80 groups was higher than that of the FM30 group, but the opposite was true for the expression of il -10.…”

Section: Discussionmentioning

confidence: 99%

Terrestrial Compound Protein Replacing Dietary Fishmeal Improved Digestive Enzyme Activity, Immune Response, Intestinal Microflora Composition, and Protein Metabolism of Golden Pompano (Trachinotus ovatus)

Ma,

Su,

Chen

et al. 2023

Aquaculture Nutrition

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Terrestrial compound protein (Cpro) can be potentially used to replace fishmeal (FM) in the marine carnivorous teleost, golden pompano (Trachinotus ovatus). Four isonitrogenous (45%) and isolipidic (12%) diets named FM30, AP80, PP80, and CP80 were formulated. FM30 (control) contained 30% FM and 25% basic protein, while AP80, PP80, and CP80 only contained 6% FM, where 80% FM and 25% basic protein of control diet were completely replaced by animal protein, plant protein, and Cpro, respectively. After golden pompano juveniles (initial weight: 10.32 ± 0.09 g) were, respectively, fed the four diets in floating sea cages for 10 weeks, the growth performance, intestinal digestive enzyme activity, and immune responses, protein metabolism indices of the CP80 group were similar to or better than those of the FM30 group ( P > 0.05 ), and significantly better than those of the AP80 and PP80 groups. Specifically, the weight gain (WG), feed conversion ratio (FCR), activity of alanine transaminase (ALT), growth hormone (GH), and insulin-like growth factor-1 (IGF-1) contents of serum, mRNA level of interleukin-10 (il-10), zonula occludens-2 (zo-2), claudin-3, claudin-12, and eukaryotic translation initiation factor 4G (eif4g) were significantly higher, and the activity of α-amylase (AMS), lipase (LPS) in the foregut and midgut, interleukin-8 (il-8) expression in the intestine was significantly lower than that in the CP80 group, compared with those in AP80 and PP80 groups ( P < 0.05 ). Moreover, the intestinal microflora composition of golden pompano fed with the CP80 diet was improved. Specifically, at the phylum level, the relative abundance of harmful bacterial strains cyanobacteria and TM7 of CP80 group was similar to those of FM30 group ( P > 0.05 ), but was significantly lower than those of AP80 and PP80 groups ( P < 0.05 ). At the genus level, the beneficial bacterial strains Agrobacterium and Blantia of CP80 group were also similar to those of FM30 group ( P < 0.05 ), which were significantly higher than those of AP80 and PP80 groups, but the beneficial bacterial strains Bifidobacterium and Devosia of CP80 group were significantly higher than that in the other groups ( P < 0.05 ). Besides, in diet CP80, the contents of amino acids and anti-nutritional factor, as well as the in vitro digestion rate were comparable to those of FM30, and the anti-nutritional factor content was between AP80 and PP80; total essential amino acids (EAAs) and methionine contents were higher than those in AP80, the glycine content was higher than that in PP80. Taken together, these results indicated that the CP80 diet had better amino acid composition and relatively low content of anti-nutritional factors, as well as high-digestion rate, and thus leads to the fish fed CP80 displaying improved effects in digestive enzyme activity, immune response, protein metabolism, and intestinal microbiota composition, which may be the important reasons to explain why that 80% of FM can be replaced by Cpro in the diet of golden pompano.

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“…Một nghiên cứu khác của tác giả Solórzano và cộng sự tại Brazil (2021) chỉ ra giá trị của chỉ số APRI ở nhóm bệnh nhân được chẩn đoán SXHD có dấu hiệu cảnh báo và SXHD nặng cao hơn có ý nghĩa thống kê so với nhóm bệnh nhân SXHD. Ngoài ra, chỉ số APRI cũng cao hơn ở những bệnh nhân có triệu chứng đau bụng, xuất huyết niêm mạc (p < 0,01) 5 .…”

Section: Các Nghiên Cứu Liên Quan Ngoài Nướcunclassified

Giá Trị Tiên Lượng Của Chỉ Số Apri Trong Bệnh Sốt Xuất Huyết Dengue

Phan,

Trần

2023

vjid

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Trong những thập kỷ gần đây, sốt xuất huyết Dengue (SXHD) được ghi nhận là một trong những bệnh truyền nhiễm có tỷ lệ mắc và tỷ lệ tử vong cao nhất trên thế giới. Bệnh hiện đang lưu hành ở hơn 129 quốc gia, chủ yếu ở các vùng nhiệt đới và cận nhiệt đới, Châu Á chiếm khoảng 70% gánh nặng bệnh tật toàn cầu. Tại Việt Nam, bệnh cũng đã và đang trở thành vấn đề y tế nghiêm trọng. Trong năm 2022, cả nước có hơn 300 nghìn trường hợp mắc bệnh với 115 trường hợp tử vong. Việc tìm hiểu các yếu tố tiên lượng có ý nghĩa giúp phát hiện sớm các trường hợp nặng, giảm tỷ lệ tử vong do bệnh gây ra. Trong bệnh sốt xuất huyết Dengue, tổn thương gan và giảm tiểu cầu là những biểu hiện lâm sàng rất thường gặp. Việc kết hợp hai chỉ số tăng transaminase và giảm tiểu cầu thông qua chỉ số APRI có ý nghĩa tiên lượng mức độ nặng của bệnh trong nhiều nghiên cứu. Một nghiên cứu năm 2019 chỉ ra rằng chỉ số APRI cao giúp phân biệt bệnh nhân SXHD và SXHD nặng với độ nhạy là 60,53% và độ đặc hiệu là 79,89%. Năm 2021, một nghiên cứu được tiến hành trên 4.069 bệnh nhân sốt xuất huyết chỉ ra giá trị APRI ≥ 19,18 có ý nghĩa tiên lượng tử vong là 100%. Một nghiên cứu khác năm 2023 kết luận với giá trị điểm cắt là 2,5, độ nhạy và độ đặc hiệu của giá trị APRI để tiên đoán mức độ nặng của bệnh lần lượt là 80,0% và 76,8%. Bên cạnh đó, nghiên cứu khác cho thấy rằng chỉ số APRI giúp phân biệt nhiễm Dengue nguyên phát và thứ phát với độ nhạy và độ đặc hiệu là 75% và 76% với điểm cắt chỉ số APRI là 1,06. Như vậy, qua các nghiên cứu, APRI được coi là một công cụ hữu ích giúp phân biệt nhiễm Dengue nguyên phát và thứ phát cũng như tiên lượng mức độ nặng của bệnh, có ý nghĩa trong việc phát hiện sớm, giúp điều trị kịp thời và giảm tỷ lệ tử vong do sốt xuất huyết Dengue gây ra.

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Different Profiles of Cytokines, Chemokines and Coagulation Mediators Associated with Severity in Brazilian Patients Infected with Dengue Virus

Cited by 10 publications

References 62 publications

Vav proteins do not influence dengue virus replication but are associated with induction of phospho-ERK, IL-6, and viperin mRNA following DENV infection in vitro

Vav proteins do not influence dengue virus replication but are associated with induction of phospho-ERK, IL-6, and viperin mRNA following DENV infection in vitro

Terrestrial Compound Protein Replacing Dietary Fishmeal Improved Digestive Enzyme Activity, Immune Response, Intestinal Microflora Composition, and Protein Metabolism of Golden Pompano (Trachinotus ovatus)

Giá Trị Tiên Lượng Của Chỉ Số Apri Trong Bệnh Sốt Xuất Huyết Dengue

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