Background
Powdery mildew was found in most of the sunflower fields in Egypt, causing severe yellowing of the blade, petiole, stem and calyx, as well as a considerable defoliation during the summer ...season of 2018. Out of the fungal mycelium from infected leaves, collected from sunflower fields in the four Egyptian Governorates (Kafr El-Sheikh, Gharbia, Giza and El-Beheira), five isolates of powdery mildew pathogen were obtained and identified using morphological and molecular identification methods.
Results
In 2019 and 2020 seasons, five biocontrol agents (
Bacillus subtilis
,
B. pumilus
,
Trichoderma harzianum
,
T. virid
e and
T. koningii
) were used to control powdery mildew disease on sunflower plants under field conditions compared with the fungicide (Vectra 10% SC). Treatments were significantly effective for controlling the powdery mildew disease relative to the control. The best treatment for reducing disease parameters (final disease severity (FDS%), area under disease progress curve (AUDPC) and efficacy) than the control was
T. koningii.
Foliar application of all the tested treatments improved plant height, head and stem diameters and seed yield in relation to untreated plants (control). The components (FDS%, AUDPC and efficacy) were extracted and described approximately 95.251% of the pooled data of seasons 2019 and 2020. In such pooled data, the principal components (PC1, PC2 and PC3) of all disease parameters, plant development parameters and yield components were recorded 76.305, 86.635 and 96.265% of the total variance, respectively.
Conclusion
A biological control agent, such as
T. koningii
, can be suggested for disease control based on the experimental findings.
The diagnosis and prognosis of chronic wounds are demanding and require objective assessment. Because of their potential medicinal applications, the syntheses of biopolymeric chitosan (CHN) structure ...and PVA-based mixed electrospun nanofibers with biomimetic features were thoroughly investigated. This study created different formulas, including a guest molecule and capping agent, using supporting PVA as a vehicle. CHN was used as a biomodifier, and beta-cyclodextrin (ß-CD) as a smoother and more efficiently entraps streptomycin (STP) compared with the silver sheet wound dressing. The relevant analyses showed that the size distribution increased with the incorporation of PVA, CHN, and ß-CD to 120.3, 161.9, and 192.02 nm. The webs boosted particle size and released content stability to 96.4% without compromising the nanofiber structure. Examining the synergistic effects of the PVA/CHN/STP/ß-CD nanoformulation against pathogenic strains of S. aureus, P. aeruginosa, and Aspergillus niger, clean zones were 47 ± 3.4, 45 ± 3.0, and 49 ± 3.7 mm were produced. PVA/CHN/STP/ß-CD formula exhibited a 98.9 ± 0.6% cell viability and wound closure of 100% at 72 h. The results reveal that the PVA/CHN/STP/ß-CD formula is promising for medical applications, especially in wound healing, compared with the silver sheet.
Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults. ZIKV uses glycosylation of its envelope ...(E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines. Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells. We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature. Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV. Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.
Objective: The present study aimed to investigate the possible role of IL-6 and 1α,25-dihydroxyvitamin D3 (1,25D)
signaling in epithelial-mesenchymal transition (EMT) and stemness in triple-negative ...breast cancer (TNBC) cell line.
Methods: TNBC cell line, HCC 1806, was treated with IL-6 and 1,25D for three and six days. Also, the role of vitamin
D receptor (VDR) was studied by transfection of TNBC cell line with VDR gene and transfection efficiency was assessed
using Human VDR enzyme-linked immunosorbent assay (ELISA). Changes in E-cadherin gene expression were
analyzed by quantitative real-time PCR (qRT-PCR). Also, changes in CD44+ cells were analyzed by flow cytometry.
Finally, morphological changes were investigated by light microscopy after 6 days. Results: Treatment of HCC1806
cells with IL-6 has no significant effect either on E-cadherin gene expression or CD44+ cells, (p > 0.05). However,
E-cadherin gene expression was significantly up-regulated after treatment with 1,25D for 6 days, (p < 0.05). Also, CD44+
cells were significantly reduced after treatment with 1,25D either for 3 or 6 days, (p < 0.05). Transfection of TNBC
cell line with VDR gene significantly up-regulated VDR protein expression, (p < 0.05). In addition, overexpression of
VDR in TNBC cells and treatment with 1,25D significantly up-regulated E-cadherin gene expression, (p < 0.05) and
reduced CD44+ cells, (p < 0.05). Moreover, transfection with VDR and treatment with a combination of 1,25D and
IL-6 significantly down-regulated E-cadherin gene expression and increased CD44+ cells compared with transfected
cells with VDR treated with 1,25D alone, (p < 0.05). No significant morphological changes were observed in treated
cells, 6 days post-treatment. Conclusion: The presence of IL-6 in the breast tumor microenvironment may impair the
activity of vitamin D3 signaling, limiting its anti-tumor effects in TNBC.
Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, it's unclear whether homologous recombination (HR) status-dependent glycosylation can be ...therapeutically explored. Here, we show that the inhibition of branched N-glycans sensitizes HR-proficient, but not HR-deficient, epithelial ovarian cancers (EOCs) to immune checkpoint blockade (ICB). In contrast to fucosylation whose inhibition sensitizes EOCs to anti-PD-L1 immunotherapy regardless of HR-status, we observe an enrichment of branched N-glycans on HR-proficient compared to HR-deficient EOCs. Mechanistically, BRCA1/2 transcriptionally promotes the expression of MGAT5, the enzyme responsible for catalyzing branched N-glycans. The branched N-glycans on HR-proficient tumors augment their resistance to anti-PD-L1 by enhancing its binding with PD-1 on CD8
T cells. In orthotopic, syngeneic EOC models in female mice, inhibiting branched N-glycans using 2-Deoxy-D-glucose sensitizes HR-proficient, but not HR-deficient EOCs, to anti-PD-L1. These findings indicate branched N-glycans as promising therapeutic targets whose inhibition sensitizes HR-proficient EOCs to ICB by overcoming immune evasion.
Persistence of HIV in people living with HIV (PWH) on suppressive antiretroviral therapy (ART) has been linked to physiological mechanisms of CD4+ T cells. Here, in the same 37 male PWH on ART we ...measure longitudinal kinetics of HIV DNA and cell turnover rates in five CD4 cell subsets: naïve (T
), stem-cell- (T
), central- (T
), transitional- (T
), and effector-memory (T
). HIV decreases in T
and T
but not in less-differentiated subsets. Cell turnover is ~10 times faster than HIV clearance in memory subsets, implying that cellular proliferation consistently creates HIV DNA. The optimal mathematical model for these integrated data sets posits HIV DNA also passages between CD4 cell subsets via cellular differentiation. Estimates are heterogeneous, but in an average participant's year ~10 (in T
and T
) and ~10
(in T
, T
, T
) proviruses are generated by proliferation while ~10
proviruses passage via cell differentiation (per million CD4). In simulations, therapies blocking proliferation and/or enhancing differentiation could reduce HIV DNA by 1-2 logs over 3 years. In summary, HIV exploits cellular proliferation and differentiation to persist during ART but clears faster in more proliferative/differentiated CD4 cell subsets and the same physiological mechanisms sustaining HIV might be temporarily modified to reduce it.
The gastrointestinal mucosa is critical for maintaining the integrity and functions of the gut. Disruption of this barrier is a hallmark and a risk factor for many intestinal and chronic inflammatory ...diseases. Inflammatory bowel disease (IBD) and HIV infection are characterized by microbial translocation and systemic inflammation. Despite the clinical overlaps between HIV and IBD, significant differences exist such as the severity of gut damage and mechanisms of immune cell homeostasis. Studies have supported the role of metabolic activation of immune cells in promoting chronic inflammation in HIV and IBD. This inflammatory response persists in HIV+ persons even after long-term virologic suppression by antiretroviral therapy (ART). Here, we review gut dysfunction and microbiota changes during HIV infection and IBD, and discuss how this may induce metabolic reprogramming of monocytes, macrophages and T cells to impact disease outcomes. Drawing from parallels with IBD, we highlight how factors such as lipopolysaccharides, residual viral replication, and extracellular vesicles activate biochemical pathways that regulate immunometabolic processes essential for HIV persistence and non-AIDS metabolic comorbidities. This review highlights new mechanisms and support for the use of immunometabolic-based therapeutics towards HIV remission/cure, and treatment of metabolic diseases.
Sialic acid-binding Immunoglobulin-like lectin-9 (Siglec-9) is a glyco-immune negative checkpoint expressed on several immune cells. Siglec-9 exerts its inhibitory effects by binding to sialoglycan ...ligands expressed on cancer cells, enabling them to evade immunosurveillance. We developed a panel of human anti-Siglec-9 hybridoma clones by immunizing mice with Siglec-9-encoding DNA and Siglec-9 protein. The lead antibodies, with high specificity and functionality against Siglec-9, were identified through screening of clones. The
in vitro
cytotoxicity assays showed that our lead antibody enhances anti-tumor immune activity. Further,
in vivo
testing utilizing ovarian cancer humanized mouse model showed a drastic reduction in tumor volume. Together, we developed novel antibodies that augment anti-tumor immunity through interference with Siglec-9-mediated immunosuppression.
High-parameter single-cell phenotyping has enabled in-depth classification and interrogation of immune cells, but to date has not allowed for glycan characterization. Here, we develop CyTOF-Lec as an ...approach to simultaneously characterize many protein and glycan features of human immune cells at the single-cell level. We implemented CyTOF-Lec to compare glycan features between different immune subsets from blood and multiple tissue compartments, and to characterize HIV-infected cell cultures. Using bioinformatics approaches to distinguish preferential infection of cellular subsets from viral-induced remodeling, we demonstrate that HIV upregulates the levels of cell-surface fucose and sialic acid in a cell-intrinsic manner, and that memory CD4+ T cells co-expressing high levels of fucose and sialic acid are highly susceptible to HIV infection. Sialic acid levels were found to distinguish memory CD4+ T cell subsets expressing different amounts of viral entry receptors, pro-survival factors, homing receptors, and activation markers, and to play a direct role in memory CD4+ T cells' susceptibility to HIV infection. The ability of sialic acid to distinguish memory CD4+ T cells with different susceptibilities to HIV infection was experimentally validated through sorting experiments. Together, these results suggest that HIV remodels not only cellular proteins but also glycans, and that glycan expression can differentiate memory CD4+ T cells with vastly different susceptibility to HIV infection.
Novel association between intrinsic viral resistance genes and HLA class I provide additional mechanistic determinants in HIV‐1 disease outcomes.
The genetic background of HIV‐1‐infected subjects, ...particularly the HLA class I haplotype, appears to be critical in determining disease progression rates, thought to be a result of the role of HIV‐1‐specific CD8+ T cell responses. The HLA‐B*57 allele is strongly associated with viremic suppression and slower disease progression. However, there is considerable heterogeneity in HIV‐1 disease progression rates among HLA‐B*57‐positive subjects, suggesting that additional factors may help to contain viral replication. In this report, we investigated the association between host restriction factors, other established immunological parameters, and HLA type in HIV‐1‐seronegative individuals. Our results demonstrate that healthy, uninfected HLA‐B*57‐positive individuals exhibit significantly higher gene‐expression levels of host restriction factors, such as APOBEC3A, APOBEC3B, BST‐2/tetherin, and ISG15. Interestingly, HLA‐B*57 individuals have significantly lower CD4+ T cell frequencies but harbor slightly more activated CD4+ T cells compared with their HLA‐B*35 counterparts. We detected significant correlations between CD4+ T cell activation and expression of several APOBEC3 family members, BST‐2/tetherin, SAMHD1, and TRIM5α in HLA‐B*57‐positive individuals. To our knowledge, this is the first report showing distinct associations between host restriction factors and HLA class I genotype. Our results provide insights into natural protection mechanisms and immunity against HIV‐1 that fall outside of classical HLA‐mediated effects.
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