Wassamon Moyadee, Sittiruk Roytrakul, Janthima Jaresitthikunchai
et al.
Abstract Feline infectious peritonitis (FIP) is a lethal, viral-induced immune-mediated disease that remains a challenge for diagnosis and treatment in cats. Proteomic profiling, which analyzes the protein content of biological samples, offers the potential to identify novel biomarkers that could improve the diagnosis and management of FIP. This study aims to assess the serum proteome and identify proteins that differentiate healthy cats from cats diagnosed with effusive FIP using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). A total of 30 cats diagnosed with effusive FIP and 27 clinically normal cats were enrolled. Twenty-three proteins were significantly (p < 0.01, ≥ fivefold change in abundance) differentially expressed between cats with effusive FIP and controls. Among these, the P2X purinoceptor, DNA topoisomerase, Notch receptor 2, and cadherin-17 were identified as key proteins of interest in cats with effusive FIP. Our findings suggest that these differentially expressed proteins could serve as potential diagnostic biomarkers and therapeutic targets for FIP. However, further studies are needed to validate these findings and explore their potential applications.
Malaria is one of the infectious illnesses causing a public health burden worldwide. <i>Plasmodium vivax</i> (<i>P. vivax</i>) is the most prevalent malaria parasite in Asia and Asia Pacific. <i>P. vivax</i> is resistant to sulfadoxine–pyrimethamine (SP) and mefloquine. This resistance makes it extremely difficult to control and eradicate due to its ability to survive in the liver and reactivate if the person infected has a weakened immune system. Thus, this study aims to inhibit <i>P. vivax</i> via targeting Duffy-binding protein (DBP) with active compounds from Hops (<i>Humulus lupulus</i>). The inhibition of DBP is essential to reduce malaria invasion of human red blood cells. We performed a quality assessment and prediction of the active site of DBP to determine the effectiveness and prediction of ligands in inhibiting DBP. Furthermore, the mechanism and structural stability of active compounds against DBP were evaluated using a combination of molecular docking and molecular dynamics simulation and a density-functional theory (DFT) study. The results showed that rutin had the highest binding of 8.852 kcal/mol. However, after the molecular dynamics simulation was run for 50 ns, the ligand 6-prenylnaringenin via MM-PBSA calculation showed the most positive value of 106.760 kJ/mol. In addition, 6-prenylnaringenin is the most stable ligand via the analysis of root-mean-square deviation backbone (RMSDBb), root-mean-square deviation c-alpha (RMSDCa), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), radius of gyration (Rg), and the hydrogen bond formation. We conclude that 6-prenylnaringenin has a tight and stable bond with the targeted DBP protein. Finally, we propose the use of 6-prenylnaringenin as a potential antimalarial compound via in silico studies.
Hoa Nhu Le, Martiela Vaz de Freitas, Dinler Amaral Antunes
Cellular immunity relies on the ability of a T-cell receptor (TCR) to recognize a peptide (p) presented by a class I major histocompatibility complex (MHC) receptor on the surface of a cell. The TCR-peptide-MHC (TCRpMHC) interaction is a crucial step in activating T-cells, and the structural characteristics of these molecules play a significant role in determining the specificity and affinity of this interaction. Hence, obtaining 3D structures of TCRpMHC complexes offers valuable insights into various aspects of cellular immunity and can facilitate the development of T-cell-based immunotherapies. Here, we aimed to compare three popular web servers for modeling the structures of TCRpMHC complexes, namely ImmuneScape (IS), TCRpMHCmodels, and TCRmodel2, to examine their strengths and limitations. Each method employs a different modeling strategy, including docking, homology modeling, and deep learning. The accuracy of each method was evaluated by reproducing the 3D structures of a dataset of 87 TCRpMHC complexes with experimentally determined crystal structures available on the Protein Data Bank (PDB). All selected structures were limited to human MHC alleles, presenting a diverse set of peptide ligands. A detailed analysis of produced models was conducted using multiple metrics, including Root Mean Square Deviation (RMSD) and standardized assessments from CAPRI and DockQ. Special attention was given to the complementarity-determining region (CDR) loops of the TCRs and to the peptide ligands, which define most of the unique features and specificity of a given TCRpMHC interaction. Our study provides an optimistic view of the current state-of-the-art for TCRpMHC modeling but highlights some remaining challenges that must be addressed in order to support the future application of these tools for TCR engineering and computer-aided design of TCR-based immunotherapies.
Abstract Endothelial-mesenchymal transformation (EndoMT) is the process through which endothelial cells transform into mesenchymal cells, affecting their morphology, gene expression, and function. EndoMT is a potential risk factor for cardiovascular and cerebrovascular diseases, tumor metastasis, and fibrosis. Recent research has highlighted the role of exosomes, a mode of cellular communication, in the regulation of EndoMT. Exosomes from diseased tissues and microenvironments can promote EndoMT, increase endothelial permeability, and compromise the vascular barrier. Conversely, exosomes derived from stem cells or progenitor cells can inhibit the EndoMT process and preserve endothelial function. By modifying exosome membranes or contents, we can harness the advantages of exosomes as carriers, enhancing their targeting and ability to inhibit EndoMT. This review aims to systematically summarize the regulation of EndoMT by exosomes in different disease contexts and provide effective strategies for exosome-based EndoMT intervention.
Luis Alberto Perez-Quintero, Luis Alberto Perez-Quintero, Belma Melda Abidin
et al.
In the context of inflammation, T cell activation occurs by the concerted signals of the T cell receptor (TCR), co-stimulatory receptors ligation, and a pro-inflammatory cytokine microenvironment. Fine-tuning these signals is crucial to maintain T cell homeostasis and prevent self-reactivity while offering protection against infectious diseases and cancer. Recent developments in understanding the complex crosstalk between the molecular events controlling T cell activation and the balancing regulatory cues offer novel approaches for the development of T cell-based immunotherapies. Among the complex regulatory processes, the balance between protein tyrosine kinases (PTK) and the protein tyrosine phosphatases (PTPs) controls the transcriptional and metabolic programs that determine T cell function, fate decision, and activation. In those, PTPs are de facto regulators of signaling in T cells acting for the most part as negative regulators of the canonical TCR pathway, costimulatory molecules such as CD28, and cytokine signaling. In this review, we examine the function of two close PTP homologs, PTP1B (PTPN1) and T-cell PTP (TCPTP; PTPN2), which have been recently identified as promising candidates for novel T-cell immunotherapeutic approaches. Herein, we focus on recent studies that examine the known contributions of these PTPs to T-cell development, homeostasis, and T-cell-mediated immunity. Additionally, we describe the signaling networks that underscored the ability of TCPTP and PTP1B, either individually and notably in combination, to attenuate TCR and JAK/STAT signals affecting T cell responses. Thus, we anticipate that uncovering the role of these two PTPs in T-cell biology may lead to new treatment strategies in the field of cancer immunotherapy. This review concludes by exploring the impacts and risks that pharmacological inhibition of these PTP enzymes offers as a therapeutic approach in T-cell-based immunotherapies.
The emergence of breast cancer (BC) patients could be influenced by common polymorphisms in the ABCG2 gene which impact chemotherapeutic response. Reactive oxygen species (ROS) and altered redox conditions are two prevalent biochemical features that might be linked to cytological changes in breast cancer (BC) patients. This case-control study compares apoptosis, mitochondrial ROS levels, cytoplasmic ROS levels, and mitochondrial morphology with control for evaluating the relationship between mutations in the ABCG2 gene and the development of BC. It also evaluates oxidative stress in BC patients following diagnosis. The findings indicated that TT genotype was not linked to an elevated risk of BC (P more than 0.05) however, there has been a significant relationship between CT and CC and BC risk (P less than 0.05). A total of 11 new genetic mutations (SNPs) have been found; 6/11 (G71T), (T141C), (T148C), (G150C), (T169C), and (G172C) were non-synonymous mutations that altered the 3D protein's structure due to the amino acids in BC patients changing. Three of these mutations (G2559C), (G38A), and (G96428A) are synonymous mutations; two of these (163 GDel), and (167 ADel) are frameshift mutations that altered the 3D protein's structure. When put to comparison with normal tissue, the reaction to fluorescence dyes was more pronounced in BC tissue. According to our research, in addition to cytological changes, mutations and polymorphisms in the ABCG2 gene have been associated with the development of BC and its susceptibility to drugs. Additional validation of such results in a sizable population is required.
Denise Soares, Joana Lourenço, Ana Filipa Silva
et al.
PURPOSE Shot-put is a complex ballistic movement that involves segments’ translational and rotational motions. Its goal is to release the shot at maximum forward velocity (strength) at an angle of approximately 40º (rotation). Considering the adapted shot-put, those two components could be more limited in action. Therefore, the present study aimed to examine the correlations among the one-repe-tition maximum (1RM) test in the bench press (BP1RM) and trunk rotation (TR1RM) and the throwing distance of the adapted shot-put and body composition (Fat mass and Fat-free mass [FFM]), and the throwing distance of the adapted shot-put (TD) and 1RM results. METHODS Eighteen non-professional athletes were evaluated, and their anthropometric data were obtained (bio-impedance measurements). Afterward, the participants performed the BP1RM and TR1RM exercises. Finally, they performed the adapted shot-put in similar conditions as the official competitions, where three trials of ASP were performed, and the best of these trials were assessed. RESULTS The results showed a significant relationship between the throwing distance and 1RM results for both exercises (BP1RM (p=.040) and TR1RM (p=.002)) and with the amount of FFM (p=.045). Concerning FFM relationships, the results showed a positive relationship with both 1RM exercises (BP1RM (p=.034) and TR1RM (p=.003)). The Fat Mass results demonstrated an inverse correlation only with BP1RM (p=.035). CONCLUSIONS The results suggest that physical preparation, including BP1RM and TR1RM exercises, are fundamental to improving adapted shot-put performance. This showed preliminary indicators of which variables may influence the adapted shot-put that might help coaches and athletes to improve their performance. Nevertheless, those results should be carefully considered since the movement evaluated was very complex, especially when performed by participants unfamiliar with them, and because the same analysis included both sexes.
Abstract Background Exercise is postulated to be a promising non-pharmacological intervention for the improvement of neurodegenerative disease pathology. However, the mechanism of beneficial effects of exercise on the brain remains to be further explored. In this study, we investigated the effect of an exercise-induced metabolite, lactate, on the microglia phenotype and its association with learning and memory. Results Microglia were hyperactivated in the brains of AlCl3/D-gal-treated mice, which was associated with cognitive decline. Running exercise ameliorated the hyperactivation and increased the anti-inflammatory/reparative phenotype of microglia and improved cognition. Mice were injected intraperitoneally with sodium lactate (NaLA) had similar beneficial effects as that of exercise training. Exogenous NaLA addition to cultured BV2 cells promoted their transition from a pro-inflammatory to a reparative phenotype. Conclusion The elevated lactate acted as an “accelerator” of the endogenous “lactate timer” in microglia promoting this transition of microglia polarization balance through lactylation. These findings demonstrate that exercise-induced lactate accelerates the phenotypic transition of microglia, which plays a key role in reducing neuroinflammation and improving cognitive function.
Bojana B. Vidović, Danijel D. Milinčić, Mirjana D. Marčetić
et al.
Goji berries have long been used for their nutritional value and medicinal purposes in Asian countries. In the last two decades, goji berries have become popular around the world and are consumed as a functional food due to wide-range bioactive compounds with health-promoting properties. In addition, they are gaining increased research attention as a source of functional ingredients with potential industrial applications. This review focuses on the antioxidant properties of goji berries, scientific evidence on their health effects based on human interventional studies, safety concerns, goji berry processing technologies, and applications of goji berry-based ingredients in developing functional food products.
Depression, a complex epidemiological mental disorder, affects around 350 million people worldwide. Despite the availability of antidepressants based on monoamine hypothesis of depression, most patients suffer side effects from these drugs, including psychomotor impairment and dependence liability. Traditional Chinese medicine (TCM) is receiving more and more attention due to the advantages of high therapeutic performance and few side effects in depression treatment. However, complex multicomponents and multi-targets in TCM hinder our ability to identify the functional components and molecular mechanisms of its efficacy. In this study, we designed a novel strategy to capture the functional components and mechanisms of TCM based on a mathematical algorithm. To establish proof of principle, the TCM formula Danggui-Shaoyao-San (DSS), which possesses remarkable antidepressant effect but its functional components and mechanisms are unclear, is used as an example. According to the network motif detection algorithm, key core function motifs (CIM) of DSS in treating depression were captured, followed by a functional analysis and verification. The results demonstrated that 198 pathways were enriched by the target genes of the CIM, and 179 coincided with the enriched pathways of pathogenic genes, accounting for 90.40% of the gene enrichment pathway of the C-T network. Then the functional components group (FCG) comprising 40 components was traced from CIM based on the target coverage accumulation algorithm, after which the pathways enriched by the target genes of FCG were selected to elucidate the potential mechanisms of DSS in treating depression. Finally, the pivotal components in FCG of DSS and the related pathways were selected for experimental validation in vitro and in vivo. Our results indicated good accuracy of the proposed mathematical algorithm in sifting the FCG from the TCM formula, which provided a methodological reference for discovering functional components and interpreting molecular mechanisms of the TCM formula in treating complex diseases.
Shafat A. Mir, Javeed I.A. Bhat, Farooq Lone
et al.
Respirable dust sampler (Envirotech model APM-460DXNL) was used to estimate the spatial and seasonal variation of vehicular emissions (NO2, SO2, and SPM). Concentration of pollutants in ambient air have been extensively revealed. However, little information is provided on spatial and seasonal variation of vehicular emissions and their impacts on Crocus sativus. During the current study the concentration of vehicular emissions was SPM >SO2>NO2. Length, fresh & dry weight and biochemical parameters of Crocus sativus L. changed considerably along the pollution gradient. Shimadzu spectrophotometer model- UV1800ENG240V SOFT was used to estimate changes in biochemical parameters. The aforesaid findings manifest that vehicular emission is a vital factor impacting the progression of Crocus sativus. It is of utmost importance to mention here that on reducing vehicular emissions the progression of Crocus sativus can be increased substantially. Moreover, our results can also contribute in developing pollution models and hence reduce crop damage thereof.
Xianli Wei,1,* Junzi Ke,2,3,* Haonan Huang,2,3,* Shikun Zhou,2,3 Ao Guo,4 Kun Wang,2,3 Yujuan Zhan,2,3 Cong Mai,5 Weizhen Ao,3 Fuda Xie,6,7 Rongping Luo,8 Jianyong Xiao,2 Hang Wei,4 Bonan Chen2,3 1Department of Medical Instruments, Guangdong Food and Drug Vocational College, Guangzhou 510520, People’s Republic of China; 2Department of Biochemistry, Guangzhou University of Chinese Medicine, Guangzhou 510006, People’s Republic of China; 3Research Center of Integrative Medicine, School of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, People’s Republic of China; 4School of Medical Information Engineering, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5Department of Abdominal Surgery, Cancer Center of Guangzhou Medical University, Guangzhou 510095, People’s Republic of China; 6The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510006, People’s Republic of China; 7Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, People’s Republic of China; 8School of Foreign Language, Guangdong Pharmaceutical University, Guangzhou 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bonan Chen; Hang Wei Email 20171104455@stu.gzucm.edu.cn; crwei@gzucm.edu.cnIntroduction: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Up to now, many genes associated with HCC have not yet been identified. In this study, we screened the HCC-related genes through the integrated analysis of the TCGA database, of which the potential biomarkers were also further validated by clinical specimens. The discovery of potential biomarkers for HCC provides more opportunities for diagnostic indicators or gene-targeted therapies.Methods: Cancer-related genes in The Cancer Genome Atlas (TCGA) HCC database were screened by a random forest (RF) classifier based on the RF algorithm. Proteins encoded by the candidate genes and other associated proteins obtained via protein–protein interaction (PPI) analysis were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The newly identified genes were further validated in the HCC cell lines and clinical tissue specimens by Western blotting, immunofluorescence, and immunohistochemistry (IHC). Survival analysis verified the clinical value of genes.Results: Ten genes with the best feature importance in the RF classifier were screened as candidate genes. By comprehensive analysis of PPI, GO and KEGG, these genes were confirmed to be closely related to HCC tumors. Representative NOX4 and FLVCR1 were selected for further validation by biochemical analysis which showed upregulation in both cancer cell lines and clinical tumor tissues. High expression of NOX4 or FLVCR1 in cancer cells predicts low survival.Conclusion: Herein, we report that NOX4 and FLVCR1 are promising biomarkers for HCC that may be used as diagnostic indicators or therapeutic targets.Keywords: hepatocellular carcinoma, biomarkers, TCGA database, NOX4, FLVCR1
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Hae Seong Jeong, Dicky Tri Utama, Juntae Kim
et al.
Objective The aim of this study was to compare the quality characteristics of retorted Samgyetang (Korean ginseng chicken soup) made from white semi-broilers (WSB; Ross× Hyline white, 3 weeks old), commercial broilers (CB; Ross, 4 weeks old), Korean native chickens (KNC; Hanhyup-3-ho, 12 weeks old) and old laying hens (OLH; Hyline white, 72 weeks old) and to explore the possibility of using the carcasses of KNCs and OLHs as raw material for product diversification. Methods Raw and cooked meat quality, fatty acid composition and consumer acceptance were analyzed. Results Among the chicken breeds, OLH and KNC showed a higher shear force value than WSB and CB due to high insoluble collagen contents. However, the meat of KNC was more tender than that of OLH. The meat of OLH was characterized by the lowest moisture content and highest crude fat content. The meat of KNC was characterized by a higher proportion of saturated fatty acids, α-linolenic acid and arachidonic acid than that of OLH. The meat of OLH showed the highest content of unsaturated fatty acid, particularly linoleic acid, in its thigh meat. Electronic nose readings revealed that the meat aroma pattern was clearly different across breeds. OLH had the lowest overall acceptance score, while no differences were found in flavor, texture, juiciness and appearance among WSB, CB, and KNC. Conclusion KNC shows potential as raw material for Samgyetang, while additional preprocessing methods, such as tenderization and fat removal, are required for the utilization of OLH as raw material for retorted Samgyetang.
<p>Double electron–electron resonance (DEER) spectroscopy applied to orthogonally spin-labeled biomolecular complexes simplifies the assignment of intra- and intermolecular distances, thereby increasing the information content per sample. In fact, various spin labels can be addressed independently in DEER experiments due to spectroscopically nonoverlapping central transitions, distinct relaxation times, and/or transition moments; hence, they are referred to as spectroscopically orthogonal. Molecular complexes which are, for example, orthogonally spin-labeled with nitroxide (NO) and gadolinium (Gd) labels give access to three distinct DEER channels that are optimized to selectively probe NO–NO, NO–Gd, and Gd–Gd distances. Nevertheless, it has been previously recognized that crosstalk signals between individual DEER channels can occur, for example, when a Gd–Gd distance appears in a DEER channel optimized to detect NO–Gd distances. This is caused by residual spectral overlap between NO and Gd spins which, therefore, cannot be considered as perfectly orthogonal. Here, we present a systematic study on how to identify and suppress crosstalk signals that can appear in DEER experiments using mixtures of NO–NO, NO–Gd, and Gd–Gd molecular rulers characterized by distinct, nonoverlapping distance distributions. This study will help to correctly assign the distance peaks in homo- and heterocomplexes of biomolecules carrying not perfectly orthogonal spin labels.</p>
Alicia Mayeuf-Louchart, Steve Lancel, Yasmine Sebti
et al.
Summary: Browning induction or transplantation of brown adipose tissue (BAT) or brown/beige adipocytes derived from progenitor or induced pluripotent stem cells (iPSCs) can represent a powerful strategy to treat metabolic diseases. However, our poor understanding of the mechanisms that govern the differentiation and activation of brown adipocytes limits the development of such therapy. Various genetic factors controlling the differentiation of brown adipocytes have been identified, although most studies have been performed using in vitro cultured pre-adipocytes. We investigate here the differentiation of brown adipocytes from adipose progenitors in the mouse embryo. We demonstrate that the formation of multiple lipid droplets (LDs) is initiated within clusters of glycogen, which is degraded through glycophagy to provide the metabolic substrates essential for de novo lipogenesis and LD formation. Therefore, this study uncovers the role of glycogen in the generation of LDs. : Lipid droplet formation is a major feature of brown adipocyte differentiation. Mayeuf-Louchart et al. characterize the different steps of brown adipocyte differentiation in the mouse embryo and report the essential role of glycogen production and degradation by glycophagy for lipid droplet biogenesis. Keywords: brown adipose tissue, adipocyte differentiation, lipid droplet biogenesis, lipid, glycogen, autophagy, glycophagy, embryonic development, adipocyte metabolism, BAT
Fauziyyah Ramadhani, Mohammad Ghozali, Leni Lismayanti
Dengue hemorrhagic fever (DHF) is still the leading cause of hospitalization and death among children in Indonesia because of plasma leakage leading to shock syndromes. This study aimed to associate the hematocrit difference (first and second) from serial hematocrit (Hct) examination just after admission with DHF severity. A analytical cross-sectional study was involving medical records of pediatric patients with DHF admitted at the pediatric ward and the Pediatric Intensive Care Unit (PICU) of Dr. Hasan Sadikin General Hospital, Bandung in January–December 2015. The subjects excluded if other conditions also cause plasma leakage. The difference in first and second Hct (∆Hct) from serial Hct examination just after admission and DHF grade of severity (DHF I–IV) confirmed by a positive result in serologic tests (anti-dengue IgM/IgG), or detection of dengue virus antigen (NS1Ag test) obtained. Spearman association analysis test used for analysis. A total of 16 subjects with DHF I, 21 subjects with DHF II, 31 subjects with DHF III and two subjects with DHF IV included in this study. There was no significant correlation between positive ∆Hct value (hemoconcentration) and DHF severity (r=0.247, p=0.394, CI=95%). In conclusion, the difference in first and second Hct from serial Hct examination just after admission has no significant association with the disease severity.
DUA NILAI HEMATOKRIT SERIAL SESAAT SETELAH ADMISI SEBAGAI PREDIKTOR KEPARAHAN DEMAM BERDARAH DENGUE
Demam berdarah dengue (DBD) merupakan penyebab utama hospitalisasi dan kematian anak di Indonesia disebabkan oleh kebocoran plasma yang berujung pada syok. Tujuan penelitian ini mengetahui hubungan perbedaan hematokrit pertama dan kedua pada pemeriksaan hematokrit serial sesaat setelah admisi dengan keparahan DBD. Penelitian merupakan analytical cross-sectional study menggunakan data sekunder berupa rekam medis pasien anak yang dirawat di ruang perawatan anak dan Pediatric Intensive Care Unit (PICU) RSUP Dr. Hasan Sadikin Bandung pada Januari–Desember 2015. Subjek penelitian dieksklusi apabila pada rekam medis terdapat diagnosis lain yang menyebabkan kebocoran plasma. Variabel penelitian ini adalah perbedaan hematokrit pertama dan kedua (∆Hct) pada pemeriksaan hematokrit serial serta diagnosis DBD (DBD I–IV) yang dikonfirmasi oleh hasil positif pada pemeriksaan serologis (IgM/IgG antidengue) atau deteksi antigen virus (NS1Ag). Terdapat 16 subjek DBD I, 21 subjek DBD II, 31 subjek DBD III, dan 2 subjek DBD IV. Dengan menggunakan Uji Analisis Spearman, tidak terdapat korelasi yang signifikan antara nilai positif ∆Hct (hemokonsentrasi) dan tingkat keparahan DBD (r=0,247; p=0,394; CI=95%). Simpulan, perbedaan hematokrit pertama dan kedua pada pemeriksaan hematokrit serial tidak berhubungan dengan keparahan DBD.