Search Results (17)

Background/Objectives: The porcine respiratory disease complex (PRDC) is a multifaceted, polymicrobial syndrome resulting from a combination of environmental stressors, primary infections (e.g., PRRSV) and secondary infectious agents (viruses and bacteria). PRDC causes severe lung pathology, leading to reduced performance, increased mortality rates, and higher production costs in the global pig industry. Our goal was to conduct a comprehensive study correlating both the anti-PRRSV immune response and 21 secondary infectious agents with PRDC severity. Methods: To this end, PRRSV-negative weaners were vaccinated with a PRRSV-2 MLV and put into a farm with a history of PRDC. Subsequently, anti-PRRSV cellular and antibody responses were monitored pre-vaccination, at 28 days post vaccination (dpv) and during PRDC outbreak (49 dpv). NanoString was used to quantify 21 pathogens within the bronchoalveolar lavage (BAL) at the time of necropsy (51 dpv). PRRSV-2 was present in 53 out of 55 pigs, and the other five pathogens (PCMV, PPIV, B. bronchiseptica, G. parasuis, and M. hyorhinis) were detected in BAL samples. Results: Although the uncontrolled settings of field trials complicated data interpretation, multivariate correlation analyses highlighted valuable lessons: (i) high weaning weight predicted animal resilience to disease and high weight gains correlated with the control of the PRRSV-2 field strain; (ii) most pigs cleared MLV strain within 7 weeks, and the field PRRSV-2 strain was the most prevalent lung pathogen during PRDC; (iii) all pigs developed a systemic PRRSV IgG antibody response which correlated with IgG and IgA levels in BAL; (iv) the induction of anti-field strain-neutralizing antibodies by MLV PRRSV-2 vaccination was both late and limited; (v) cellular immune responses were variable but included strong systemic IFN-γ production against the PRRSV-2 field strain; (vi) the most detected lung pathogens correlated with PRRSV-2 viremia or lung loads; (vii) within the six detected pathogens, two viruses, PRRSV-2 and PCMV, significantly correlated with the severity of the clinical outcome. Conclusions: While a simple and conclusive answer to the multifaceted nature of PRDC remains elusive, the key lessons derived from this unique study provide a valuable framework for future research on porcine respiratory diseases. Full article

Lorentz invariance is such a basic principle in fundamental physics that it must be constantly tested and any proposal of its violation and breakdown of CPT symmetry that might characterize some approaches to quantum gravity should be treated with care. In this review, we examine, among other scenarios, such instances in supercritical (Liouville) string theory, particularly in some brane models for “quantum foam”. Using the phenomenological formalism introduced here, we analyze the observational hints of Lorentz violation in time-of-flight lags of cosmic photons and neutrinos which fit excellently stringy space–time foam scenarios. We further demonstrate how stringent constraints from other astrophysical data, including the recent first detections of multi-TeV events in $\gamma$-ray burst 221009A and PeV cosmic photons by the Large High Altitude Air Shower Observatory (LHAASO), are satisfied in this context. Such models thus provide a unified framework for all currently observed phenomenologies of space–time symmetry breaking at Planckian scales. Full article

Pregnant women are at an increased risk of severe influenza complications, necessitating vaccination as a preventive measure. Despite World Health Organization (WHO) recommendations for influenza vaccination during pregnancy, vaccination rates remain suboptimal in many regions. This study aims to identify key differentially expressed genes (DEGs) and biological pathways modulated by influenza vaccination in pregnant women pre- and post-vaccination, contributing to improved vaccine strategies. Microarray data from gene expression omnibus GEO dataset GSE166545 was analyzed to identify DEGs in blood samples from pregnant women at three time points: pre-vaccination (Day 0) and post-vaccination (Days 0 and 1) (Days 1 and 7). DEGs were filtered using an adjusted p-value < 0.05 and |log2 fold change| ≥ 1. Protein/protein interaction (PPI) networks, hub gene identification, and pathway enrichment analyses were conducted using STRING, Cytoscape, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome databases. Hub gene validation was performed using the Human Protein Atlas (HPA) and GTEx Portal. The GSE166545 dataset analysis revealed 60 up-regulated and 12,854 down-regulated genes (Day 1 vs. 7), 55 up-regulated and 12,933 down-regulated genes (Day 0 vs. 1), and two up-regulated with no down-regulated genes (Day 0 vs. 7). Key pathways included interferon alpha/beta (IFN-γ\ β) signaling and toll-like receptor signaling (TLR). Hub genes such as GBP1, CXCL10, RSAD2, and IFI44 demonstrated robust up-regulation, correlating with enhanced immune responses. The initial observation of JCHAIN’s notable up-regulation occurred on the seventh day following vaccination. Validation confirmed these genes’ roles in antiviral defense mechanisms and vaccine responses. The findings reveal distinct immune response dynamics in pregnant women following influenza vaccination, highlighting potential biomarkers for vaccine efficacy. This study underscores the importance of tailored vaccine strategies to improve maternal and neonatal outcomes. Full article

Background: Inflammation plays a critical role in myocardial infarction as a critical process in the development of heart failure, involving the development of cardiac fibrosis. Colchicine is a well-established anti-inflammatory drug, but its scientific application in controlling post-acute myocardial infarction (AMI) inflammatory processes has not been established. IL-10 is a key cytokine in modulating inflammatory responses, underscoring its potential as a crucial therapeutic target of colchicine. The objective was to explore the protective role of IL-10 modulated by colchicine in myocardial healing and repair following AMI, particularly cardiac fibrosis. Methods: The predicted protein of colchicine was assessed using WAY2DRUG PASS as probability active value. Proteins associated with colchicine, cardiac fibrosis, and acute myocardial infarction were analyzed with DisGeNET and Open Target databases. Analysis and visualization of protein–protein interactions were conducted using STRING and Cytoscape. A 3T3 cell line treated with CoCl₂ was used to mimic hypoxic. HIF-1α and IL-10 expression were measured by flow cytometry and analyzed using a one-way ANOVA test. This observational clinical trial examined acute myocardial infarction patients undergoing immediate and delayed primary percutaneous coronary interventions. Subjects were randomized into control groups receiving placebo and intervention groups treated with colchicine. Assessments occurred at 24 h and five days after the intervention. IL-10 expression in the clinical trial was measured by ELISA and analyzed using a T-test. Results: Colchicine demonstrates promising bioactivity in treating acute myocardial infarction, with notably activity values highlighting its probable role as a tubulin antagonist (0.744), beta-tubulin antagonist (0.673), and NOS2 inhibitor (0.529). Its primary action targets IL-10, with the protein–protein interactions analysis indicating interactions between IL-10 and key inflammatory mediators—IL-1β, IFN-γ, CCL2, TNF, and TGF-β1—during acute myocardial infarction and cardiac fibrosis. Hypoxic conditions in the CoCl₂-induced 3T3 cell model show significantly elevated HIF-1α compared to controls (p < 0.0001). Colchicine use significantly increased IL-10 expression in CoCl₂-treated cells (p < 0.0001) and in AMI patients within five days (p < 0.05). Conclusions: Colchicine may bolster the anti-inflammatory response post-myocardial infarction by activating IL-10 pathways in fibroblasts and in clinical settings, potentially reducing inflammation after AMI. Further investigation into broader aspects of this pathway, particularly in cardiac fibroblasts, is required. Full article

Adoptive T-cell therapies tailored for the treatment of solid tumors encounter intricate challenges, necessitating the meticulous selection of specific target antigens and the engineering of highly specific T-cell receptors (TCRs). This study delves into the cytotoxicity and functional characteristics of in vitro-cultured T-lymphocytes, equipped with a TCR designed to precisely target the cancer-testis antigen NY-ESO-1. Flow cytometry analysis unveiled a notable increase in the population of cells expressing activation markers upon encountering the NY-ESO-1-positive tumor cell line, SK-Mel-37. Employing the NanoString platform, immune transcriptome profiling revealed the upregulation of genes enriched in Gene Ontology Biological Processes associated with the IFN-γ signaling pathway, regulation of T-cell activation, and proliferation. Furthermore, the modified T cells exhibited robust cytotoxicity in an antigen-dependent manner, as confirmed by the LDH assay results. Multiplex immunoassays, including LEGENDplex™, additionally demonstrated the elevated production of cytotoxicity-associated cytokines driven by granzymes and soluble Fas ligand (sFasL). Our findings underscore the specific targeting potential of engineered TCR T cells against NY-ESO-1-positive tumors. Further comprehensive in vivo investigations are essential to thoroughly validate these results and effectively harness the intrinsic potential of genetically engineered T cells for combating cancer. Full article

The centrosome of mammalian cells is in constant movement and its motion plays a part in cell differentiation and cell division. The purpose of this study was to establish the involvement of the TUBG meshwork in centrosomal motility. In live cells, we used a monomeric red-fluorescence-protein-tagged centrin 2 gene and a green-fluorescence-protein-tagged TUBG1 gene for labeling the centrosome and the TUBG1 meshwork, respectively. We found that centrosome movements occurred in cellular sites rich in GTPase TUBG1 and single-guide RNA mediated a reduction in the expression of TUBG1, altering the motility pattern of centrosomes. We propose that the TUBG1 meshwork enables the centrosomes to move by providing them with an interacting platform that mediates positional changes. These findings uncover a novel regulatory mechanism that controls the behavior of centrosomes. Full article

We consider the Dirac quantization in the first-class formalism to investigate the hypersphere soliton model (HSM) defined on the $S^3$ hypersphere. To do this, we construct the first-class Hamiltonian possessing the Weyl ordering correction. In the HSM, we evaluate the baryon physical quantities such as the baryon masses, magnetic moments, axial coupling constant and charge radii, most predicted values of which are in good agreement with the corresponding experimental data. Moreover, shuffling the baryon and transition magnetic moments, we find the model independent sum rules. In the HSM we also evaluate the baryon intrinsic frequencies such as ${\omega }_N=0.87\times {10}^{23}{\mathrm{s}}^{-1}$ and ${\omega }_{\Delta }=1.74\times {10}^{23}{\mathrm{s}}^{-1}$ of the nucleon and delta baryon, respectively, to yield the identity ${\omega }_{\Delta }=2{\omega }_N$. Next, making use of the Nambu-Goto string action and its extended rotating bosonic string theory, we formulate the stringy photon model to obtain the energy of the string configuration, which consists of the rotational and vibrational energies of the open string. Exploiting this total string energy, we evaluate the photon intrinsic frequency ${\omega }_{\gamma }=9.00\times {10}^{23}{\mathrm{s}}^{-1}$, which is comparable to the corresponding baryon intrinsic frequencies. We also predict the photon size ${⟨r^2⟩}^{1/2}\left(\mathrm{photon}\right)=0.17\mathrm{fm}$, which is approximately 21% of the proton magnetic charge radius. Full article

OmpH is among the most important virulence factors of Pasteurella multocida, which mediates septicemia in yaks (Bos grunniens I) after infection with the bacteria. In the present study, yaks were infected with wild-type (WT) (P0910) and OmpH-deficient (ΔOmpH) P. multocida strains. The mutant strain was generated through the reverse genetic operation system of pathogens and proteomics technology. The live-cell bacterial count and clinical manifestations of P. multocida infection in Qinghai yak tissues (thymus, lung, spleen, lymph node, liver, kidney, and heart) were analyzed. The expression of differential proteins in the yak spleen under different treatments was analyzed using the marker-free method. We found that compared with the mutant strain, the titer of wild-type strains was significantly higher in tissues. Additionally, compared with other organs, the bacteria titer was significantly higher in the spleen. Compared with the WT p0910 strain, the mutant strain generated milder pathological changes in the tissues of yak. Proteomics analysis revealed that 57 of the 773 proteins expressed in P. multocida were significantly differentially expressed between the ΔOmpH and P0910 groups. Of the 57, 14 were over-expressed, whereas 43 were under-expressed. The differentially expressed proteins in the ΔompH group regulated the ABC transporter (ATP-powered translocation of many substrates across membranes) system, the two-component system, RNA degradation, RNA transcription, glycolysis/gluconeogenesis, biosynthesis of ubiquinone and other terpenoid-quinones, oxidative phosphorylation (citrate cycle) as well as fructose and mannose metabolism. The relationship among 54 significantly regulated proteins was analyzed using STRING. We found that WT P0910 and ΔOmpH of P. multocida infection activated the expression of ropE, HSPBP1, FERH, ATP10A, ABCA13, RRP7A, IL-10, IFN-γ, IL-17A, EGFR, and dnaJ. Overall, deletion of the OmpH gene weakened the virulence but maintained the immunogenicity of P. multocida in yak. The findings of this study provide a strong foundation for the pathogenesis of P. multocida and the management of related septicemia in yaks. Full article

Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), approximates the key histopathological, clinical, and immunological features of MS. Hippocampal dysfunction in MS and EAE causes varying degrees of cognitive and emotional impairments and synaptic abnormalities. However, the molecular alterations underlying hippocampal dysfunctions in MS and EAE are still under investigation. The purpose of this study was to identify differentially expressed genes (DEGs) in the hippocampus of mice with EAE in order to ascertain potential genes associated with hippocampal dysfunction. Gene expression in the hippocampus was analyzed by RNA-sequencing and validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gene expression analysis revealed 1202 DEGs; 1023 were upregulated and 179 were downregulated in the hippocampus of mice with EAE (p-value < 0.05 and fold change >1.5). Gene ontology (GO) analysis showed that the upregulated genes in the hippocampi of mice with EAE were associated with immune system processes, defense responses, immune responses, and regulation of immune responses, whereas the downregulated genes were related to learning or memory, behavior, and nervous system processes in the GO biological process. The expressions of hub genes from the search tool for the retrieval of interacting genes/proteins (STRING) analysis were validated by RT-qPCR. Additionally, gene set enrichment analysis showed that the upregulated genes in the hippocampus were associated with inflammatory responses: interferon-γ responses, allograft rejection, interferon-α responses, IL6_JAK_STAT3 signaling, inflammatory responses, complement, IL2_STAT5 signaling, TNF-α signaling via NF-κB, and apoptosis, whereas the downregulated genes were related to synaptic plasticity, dendritic development, and development of dendritic spine. This study characterized the transcriptome pattern in the hippocampi of mice with EAE and signaling pathways underpinning hippocampal dysfunction. However, further investigation is needed to determine the applicability of these findings from this rodent model to patients with MS. Collectively, these results indicate directions for further research to understand the mechanisms behind hippocampal dysfunction in EAE. Full article

We examine production and decay of heavy neutral SUSY Higgs bosons $pp\to H,A\to \tau \overline{\tau }$ within the hMSSM and compare against a perhaps more plausible natural supersymmetry scenario dubbed $m_h^{125}\left(\mathrm{nat}\right)$ which allows for a natural explanation for $m_{weak}\simeq m_{W,Z,h}\sim 100$ GeV while maintaining $m_h\simeq 125$ GeV. We evaluate signal against various Standard Model backgrounds from $\gamma ,Z\to \tau \overline{\tau }$, $t\overline{t}$ and vector boson pair production $VV$. We combine the transverse mass method for back-to-back (BtB) taus along with the ditau mass peak $m_{\tau \tau }$ method for acollinear taus as our signal channels. This technique ultimately gives a boost to the signal significance over the standard technique of using just the BtB signal channel. We evaluate both the 95% CL exclusion and $5\sigma$ discovery reach in the $m_A$ vs. $tan\beta$ plane for present LHC with 139 fb⁻¹, Run 3 with 300 fb⁻¹ and high luminosity LHC (HL-LHC) with 3000 fb⁻¹ of integrated luminosity. For $tan\beta =10$, the exclusion limits range up to $m_A\sim 1$, 1.1 and 1.4 TeV, respectively. These may be compared to the range of $m_A$ values gleaned from a statistical analysis of the string landscape wherein $m_A$ can range up to $\sim 8$ TeV. Full article

M. alba L. is a valuable nutraceutical plant rich in potential bioactive compounds with promising anti-gouty arthritis. Here, we have explored bioactives, signaling pathways, and key proteins underlying the anti-gout activity of M. alba L. leaves for the first-time utilizing network pharmacology. Bioactives in M. alba L. leaves were detected through GC-MS (Gas Chromatography-Mass Spectrum) analysis and filtered by Lipinski’s rule. Target proteins connected to the filtered compounds and gout were selected from public databases. The overlapping target proteins between bioactives-interacted target proteins and gout-targeted proteins were identified using a Venn diagram. Bioactives-Proteins interactive networking for gout was analyzed to identify potential ligand-target and visualized the rich factor on the R package via the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on STRING. Finally, a molecular docking test (MDT) between bioactives and target proteins was analyzed via AutoDock Vina. Gene Set Enrichment Analysis (GSEA) demonstrated that mechanisms of M. alba L. leaves against gout were connected to 17 signaling pathways on 26 compounds. AKT1 (AKT Serine/Threonine Kinase 1), γ-Tocopherol, and RAS signaling pathway were selected as a hub target, a key bioactive, and a hub signaling pathway, respectively. Furthermore, three main compounds (γ-Tocopherol, 4-Dehydroxy-N-(4,5-methylenedioxy-2-nitrobenzylidene) tyramine, and Lanosterol acetate) and three key target proteins—AKT1, PRKCA, and PLA2G2A associated with the RAS signaling pathway were noted for their highest affinity on MDT. The identified three key bioactives in M. alba L. leaves might contribute to recovering gouty condition by inactivating the RAS signaling pathway. Full article

Aim: To determine the relationship between gene expression profile (GEP) and overall survival (OS) by NanoString following treatment with Vigil. Patients and Methods: Recurrent ovarian cancer patients (n = 21) enrolled in prior clinical trials. Results: GEP stratified by TIS^HIGH vs. TIS^LOW demonstrated OS benefit (NR vs. 5.8 months HR 0.23; p = 0.0379), and in particular, MHC-II elevated baseline expression was correlated with OS advantage (p = 0.038). Moreover, 1-year OS was 75% in TIS^HIGH patients vs. 25% in TIS^LOW (p = 0.03795). OS was also correlated with positive γ-IFN ELISPOT response, 36.8 vs. 23.0 months (HR 0.19, p = 0.0098). Conclusion: Vigil demonstrates OS benefit in correlation with TIS^HIGH score, elevated MHC-II expression and positive γ-IFN ELISPOT in recurrent ovarian cancer patients. Full article

The wetted area of a sessile droplet on a practical substrate is limited by the three-phase contact line and characterized by contact angle, contact radius and drop height. Although, contact angles of droplets have been studied for more than two hundred years, there are still some unanswered questions. In the last two decades, it was experimentally proven that the advancing and receding contact angles, and the contact angle hysteresis of rough and chemically heterogeneous surfaces, are determined by interactions of the liquid and the solid at the three-phase contact line alone, and the interfacial area within the contact perimeter is irrelevant. However, confusion and misunderstanding still exist in this field regarding the relationship between contact angle and surface roughness and chemical heterogeneity. An extensive review was published on the debate for the dependence of apparent contact angles on drop contact area or the three-phase contact line in 2014. Following this old review, several new articles were published on the same subject. This article presents a review of the novel articles (mostly published after 2014 to present) on the dependency of contact angles on the three-phase contact line, after a short summary is given for this long-lasting debate. Recently, some improvements have been made; for example, a relationship of the apparent contact angle with the properties of the three-phase line was obtained by replacing the solid–vapor interfacial tension term, γ_SV, with a string tension term containing the edge energy, γ_SLV, and curvature of the triple contact line, k_m, terms. In addition, a novel Gibbsian thermodynamics composite system was developed for a liquid drop resting on a heterogeneous multiphase and also on a homogeneous rough solid substrate at equilibrium conditions, and this approach led to the same conclusions given above. Moreover, some publications on the line energy concept along the three-phase contact line, and on the “modified” Cassie equations were also examined in this review. Full article

γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter, playing a central role in the regulation of cortical excitability and the maintenance of the excitatory/inhibitory (E/I) balance. Several lines of evidence point to a remodeling of the cerebral GABAergic system in Alzheimer’s disease (AD), with past studies demonstrating alterations in GABA receptor and transporter expression, GABA synthesizing enzyme activity and focal GABA concentrations in post-mortem tissue. AD is a chronic neurodegenerative disorder with a poorly understood etiology and the temporal cortex is one of the earliest regions in the brain to be affected by AD neurodegeneration. Utilizing NanoString nCounter analysis, we demonstrate here the transcriptional downregulation of several GABA signaling components in the post-mortem human middle temporal gyrus (MTG) in AD, including the GABA_A receptor α₁, α₂, α₃, α₅, β₁, β₂, β₃, δ, γ₂, γ₃, and θ subunits and the GABA_B receptor 2 (GABA_BR2) subunit. In addition to this, we note the transcriptional upregulation of the betaine-GABA transporter (BGT1) and GABA transporter 2 (GAT2), and the downregulation of the 67 kDa isoform of glutamate decarboxylase (GAD₆₇), the primary GABA synthesizing enzyme. The functional consequences of these changes require further investigation, but such alterations may underlie disruptions to the E/I balance that are believed to contribute to cognitive decline in AD. Full article

Increasing incidences of multidrug-resistant (MDR) pathogens causing endophthalmitis threaten our ability to treat this condition, and the modulation of inflammatory responses by MDR bacteria is not known. In this study, using human microglia and retinal pigment epithelial (RPE) cells, we compare the inflammatory responses of sensitive (S-PA) and multidrug-resistant (MDR-PA) clinical isolates of Pseudomonas aeruginosa. Infected cells were subjected to qPCR analysis, enzyme-linked immunosorbent assay (ELISA), and immunostaining to assess the expression of inflammatory mediators. Both microglia and RPE cells, challenged with S-PA and MDR-PA, induced a time-dependent expression of inflammatory cytokines. Significant differences were observed in expression levels of Toll-like receptors (TLR) TLR4, TLR5, and TLR9 in microglia cells challenged with MDR-PA vs. S-PA. Similarly, mRNA levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, Interferon (IFN)-γ, and matrix metalloproteinase (MMP)-9 were also higher in MDR-PA-infected cells. At protein levels, upregulation was observed for IL-10 (p = 0.004), IL-8 (p = 0.0006), IL-1β (p = 0.02), and Granulocyte-macrophage colony-stimulating factor (GM-CSF) (p = 0.0006) in cells infected MDR-PA versus S-PA in both microglia and RPE cells; however, the response was delayed in RPE cells. Heatmap and STRING analysis highlighted the existence of a cross-talk between the inflammatory and cytokine-mediated signaling pathways. Our study highlights a differential inflammatory response evoked by MDR vs. sensitive pathogens in retinal cells during endophthalmitis. Full article