bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection
Authors: Chaudhuri Somshukla , Rasooli Iraj , Oskouei Ramin Hatefi , Pishgahi Mahdi , Jahangir Abolfazl , Andisi Vahid Farshchi , Schryvers Anthony B.
Published: August 2022

Acinetobacter baumannii is a human bacterial pathogen of increasing concern in clinical settings due to the emergence of antibiotic resistant strains and the lack of effective therapeutics. Researchers have been exploring new treatment options such as novel drug candidates and vaccines to prevent severe infections and mortality. Bacterial surface antigens that are essential to A. baumannii for acquiring micronutrients (e.g. iron, zinc) from nutrient restricted environments are being considered as targets for vaccines or immunotherapy due to their crucial role for growth and pathogenesis in the human host. BauA, the outer membrane receptor for the siderophore acinetobactin was targeted for vaccine development in this study. Due to challenges in the commercial production of membrane proteins for vaccines, a novel hybrid antigen method developed by our group was used. Exposed loops of BauA were selected and displayed on a foreign scaffold to generate novel hybrid antigens designed to elicit an immune response against the native BauA protein. The potential epitopes were incorporated into a scaffold derived from the C-lobe of Neisseria meningitidis transferrin binding protein B (TbpB), named the loopless C-lobe (LCL). Hybrid proteins displaying three selected loops (5, 7 and 8) individually or in combination were designed and produced and evaluated in an A. baumannii murine sepsis model as vaccine antigens. Immunization with the recombinant BauA protein protected 100% of the mice while immunization with hybrid antigens displaying individual loops achieved between 50 and 100% protection. The LCL scaffold did not induce a protective immune response, enabling us to attribute the observed protection elicited by the hybrid antigens to the displayed loops. Notably, the mice immunized with the hybrid antigen displaying loop 7 were completely protected from infection. Taken together, these results suggest that our hybrid antigen approach is a viable method for generating novel vaccine antigens that target membrane surface proteins necessary for bacterial growth and pathogenesis and the loop 7 hybrid antigen can be a foundation for approaches to combat A. baumannii infections.
Clinical and immunological features associated to the development of a sustained immune humoral response in COVID-19 patients: Results from a cohort study
Authors: Torres-Ruiz Jiram , Lomelín-Gascón Julieta , Vargas-Castro Ana Sofía , Lira-Luna Jaquelin , Pérez-Fragoso Alfredo , Tapia-Conyer Roberto , Nuñez-Aguirre Miroslava , Alcalá-Carmona Beatriz , Absalón-Aguilar Abdiel , Maravillas-Montero José Luis , Mejía-Domínguez Nancy Raquel , Núñez-Álvarez Carlos , Rull-Gabayet Marina , Llorente Luis , Romero-Ramírez Sandra , Sosa-Hernández Victor Andrés , Cervantes-Díaz Rodrigo , Juárez-Vega Guillermo , Meza-Sánchez David Eduardo , Martínez-Juárez Luis Alberto , Morales-Juárez Linda , López-López Lizeth Naomi , Negrete-Trujillo José Adrián , Falcón-Lezama Jorge Abelardo , Valdez-Vázquez Rafael Ricardo , Gallardo-Rincón Héctor , Gómez-Martín Diana
Published: August 2022

Background

Until now, most of the research addressing long-term humoral responses in coronavirus disease 2019 (COVID-19) had only evaluated the serum titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgGs, without the assessment of the baseline antiviral clinical and immune profile, which is the aim of this study and may be the key factor leading to a broad and sustained antibody response.

Methods

We included 103 patients with COVID-19. When the patients sought medical attention (baseline), a blood sample was drawn to perform immunophenotype of lymphocytes by flow cytometry. The patients were assessed 15 days after baseline and then every month until the third month, followed by a last visit 6 months after recruitment. We evaluated the anti-SARS-COV-2 IgG at all time points, and the serum levels of cytokines, chemokines, anti-cellular (AC) antibodies and neutrophil extracellular traps were also assessed during the follow-up. The primary outcome of the study was the presence of a sustained immune humoral response, defined as an anti-SARS-CoV-2 IgG titer >4.99 arbitrary units/mL in at least two consecutive measures. We used generalized lineal models to assess the features associated with this outcome and to assess the effect of the changes in the cytokines and chemokines throughout time on the development of a sustained humoral immune response.

Results

At baseline the features associated to a sustained immune humoral response were the diagnosis of critical disease, absolute number of lymphocytes, serum IP-10, IL-4, IL-2, regulatory T cells, CD8+ T cells, and positive AC antibodies. Critical illness and the positivity of AC antibodies were associated with a sustained humoral immune response after 3 months, whilst critical illness and serum IL-13 were the explanatory variables after 6 months.

Conclusion

A sustained immune humoral response is strongly related to critical COVID-19, which is characterized by the presence of AC antibodies, quantitative abnormalities in the T cell compartment, and the serum cytokines and chemokines during acute infection and throughout time.
Immune responses in diabetic nephropathy: Pathogenic mechanisms and therapeutic target
Authors: Chen Jiahao , Liu Qinhui , He Jinhan , Li Yanping
Published: August 2022

Diabetic nephropathy (DN) is a chronic, inflammatory disease affecting millions of diabetic patients worldwide. DN is associated with proteinuria and progressive slowing of glomerular filtration, which often leads to end-stage kidney diseases. Due to the complexity of this metabolic disorder and lack of clarity about its pathogenesis, it is often more difficult to diagnose and treat than other kidney diseases. Recent studies have highlighted that the immune system can inadvertently contribute to DN pathogenesis. Cells involved in innate and adaptive immune responses can target the kidney due to increased expression of immune-related localization factors. Immune cells then activate a pro-inflammatory response involving the release of autocrine and paracrine factors, which further amplify inflammation and damage the kidney. Consequently, strategies to treat DN by targeting the immune responses are currently under study. In light of the steady rise in DN incidence, this timely review summarizes the latest findings about the role of the immune system in the pathogenesis of DN and discusses promising preclinical and clinical therapies.
The mechanistic immunosuppressive role of the tumour vasculature and potential nanoparticle-mediated therapeutic strategies
Authors: Ileiwat Zakaria Elias , Tabish Tanveer A. , Zinovkin Dmitry A. , Yuzugulen Jale , Arghiani Nahid , Pranjol Md Zahidul I.
Published: August 2022

The tumour vasculature is well-established to display irregular structure and hierarchy that is conducive to promoting tumour growth and metastasis while maintaining immunosuppression. As tumours grow, their metabolic rate increases while their distance from blood vessels furthers, generating a hypoxic and acidic tumour microenvironment. Consequently, cancer cells upregulate the expression of pro-angiogenic factors which propagate aberrant blood vessel formation. This generates atypical vascular features that reduce chemotherapy, radiotherapy, and immunotherapy efficacy. Therefore, the development of therapies aiming to restore the vasculature to a functional state remains a necessary research target. Many anti-angiogenic therapies aim to target this such as bevacizumab or sunitinib but have shown variable efficacy in solid tumours due to intrinsic or acquired resistance. Therefore, novel therapeutic strategies such as combination therapies and nanotechnology-mediated therapies may provide alternatives to overcoming the barriers generated by the tumour vasculature. This review summarises the mechanisms that induce abnormal tumour angiogenesis and how the vasculature’s features elicit immunosuppression. Furthermore, the review explores examples of treatment regiments that target the tumour vasculature.
Case report: Cytokine hemoadsorption in a case of hemophagocytic lymphohistiocytosis secondary to extranodal NK/T-cell lymphoma
Authors: Ruiz-Rodríguez Juan Carlos , Chiscano-Camón Luis , Ruiz-Sanmartin Adolf , Palmada Clara , Bajaña Ivan , Iacoboni Gloria , Bonilla Camilo , García-Roche Alejandra , Paola Plata-Menchaca Erika , Maldonado Carolina , Pérez-Carrasco Marcos , Martinez-Gallo Mónica , Franco-Jarava Clara , Hernández-González Manuel , Ferrer Ricard
Published: August 2022

We discuss a single case of Hemophagocytic lymphohistiocytosis (HLH) due to NK-type non-Hodgkin lymphoma and Epstein-Barr virus reactivation with multiorgan dysfunction and distributive shock in which we performed cytokine hemoadsorption with Cytosorb ®. A full microbiological panel was carried out, including screening for imported disease, standard serologies and cultures for bacterial and fungal infection. A liver biopsy and bone marrow aspirate were performed, confirming the diagnosis. The patients fulfilled the HLH-2004 diagnostic criteria, and according to the 2018 Consensus Statements by the HLH Steering Committee of the Histiocyte Society, dexamethasone and etoposide were started. There was an associated hypercytokinemia and, due to refractory distributive shock, rescue therapy with cytokine hemoadsorption was performed during 24 h (within day 2 and 3 from ICU admission). After starting this procedure, rapid hemodynamic control was achieved with a significant reduction in vasopressor support requirements. This case report highlights that cytokine hemoadsorption can be an effective since rapid decrease in IL-10 levels and a significant hemodynamic improvement was achieved.
Hotspots of single-strand DNA “breakome” are enriched at transcriptional start sites of genes
Authors: Cao Huifen , Zhang Yufei , Cai Ye , Tang Lu , Gao Fan , Xu Dongyang , Kapranov Philipp
Published: August 2022

Single-strand breaks (SSBs) represent one of the most common types of DNA damage, yet not much is known about the genome landscapes of this type of DNA lesions in mammalian cells. Here, we found that SSBs are more likely to occur in certain positions of the human genome—SSB hotspots—in different cells of the same cell type and in different cell types. We hypothesize that the hotspots are likely to represent biologically relevant breaks. Furthermore, we found that the hotspots had a prominent tendency to be enriched in the immediate vicinity of transcriptional start sites (TSSs). We show that these hotspots are not likely to represent technical artifacts or be caused by common mechanisms previously found to cause DNA cleavage at promoters, such as apoptotic DNA fragmentation or topoisomerase type II (TOP2) activity. Therefore, such TSS-associated hotspots could potentially be generated using a novel mechanism that could involve preferential cleavage at cytosines, and their existence is consistent with recent studies suggesting a complex relationship between DNA damage and regulation of gene expression.
Analysis of metabolic disturbances attributable to sepsis-induced myocardial dysfunction using metabolomics and transcriptomics techniques
Authors: Jia Xiaonan , Peng Yahui , Ma Xiaohui , Liu Xiaowei , Yu Kaijiang , Wang Changsong
Published: August 2022

Background: Sepsis-induced myocardial dysfunction (SIMD) is the most common and severe sepsis-related organ dysfunction. We aimed to investigate the metabolic changes occurring in the hearts of patients suffering from SIMD.

Methods: An animal SIMD model was constructed by injecting lipopolysaccharide (LPS) into mice intraperitoneally. Metabolites and transcripts present in the cardiac tissues of mice in the experimental and control groups were extracted, and the samples were studied following the untargeted metabolomics–transcriptomics high-throughput sequencing method. SIMD-related metabolites were screened following univariate and multi-dimensional analyses methods. Additionally, differential analysis of gene expression was performed using the DESeq package. Finally, metabolites and their associated transcripts were mapped to the relevant metabolic pathways after extracting transcripts corresponding to relevant enzymes. The process was conducted based on the metabolite information present in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.

Results: One hundred and eighteen significant differentially expressed metabolites (DEMs) (58 under the cationic mode and 60 under the anionic mode) were identified by studying the SIMD and control groups. Additionally, 3,081 significantly differentially expressed genes (DEGs) (1,364 were down-regulated and 1717 were up-regulated DEGs) were identified in the transcriptomes. The comparison was made between the two groups. The metabolomics–transcriptomics combination analysis of metabolites and their associated transcripts helped identify five metabolites (d-mannose, d-glucosamine 6-phosphate, maltose, alpha-linolenic acid, and adenosine 5′-diphosphate). Moreover, irregular and unusual events were observed during the processes of mannose metabolism, amino sugar metabolism, starch metabolism, unsaturated fatty acid biosynthesis, platelet activation, and purine metabolism. The AMP-activated protein kinase (AMPK) signaling pathways were also accompanied by aberrant events.

Conclusion: Severe metabolic disturbances occur in the cardiac tissues of model mice with SIMD. This can potentially help in developing the SIMD treatment methods.
Use of hand hydraulic dynamometers as an overall evaluation of the upper-limb weakness in patients with thoracic outlet syndrome
Authors: Fouasson-Chailloux Alban , Daley Pauline , Menu Pierre , Gadbled Guillaume , Bouju Yves , Gautier Giovanni , Pomares Germain , Dauty Marc
Published: August 2022

Patients with neurogenic thoracic outlet syndrome report pain and upper-limb weakness. They complain about weakness occurring on the entire upper-limb, especially at the hand and the shoulder levels. Hydraulic dynamometers can reliably assess the strength of the hand, and isokinetic shoulder testing can provide accurate and reliable evaluations of the rotators strength. Yet, isokinetic proximal assessment needs expensive tools, whereas hydraulic hand dynamometers are cheap and easy to use. We aimed to assess the correlation between the isokinetic shoulder strength and the hand grip and the key pinch strength. The grip strength was evaluated with a hydraulic hand dynamometer and the key pinch with a pinch gauge. Isokinetic rotators strength tests were performed using a Humac Norm® dynamometer at 60 and 180°/s. One-hundred and thirty patients had been included, 72% of women, mean age of 39.8 ± 9.5. Symptomatic hands presented a strength deficit of 12.2% on the grip (p < 0.0001) and 10% on the key pinch (p = 0.01). Isokinetic strength was lower on the symptomatic shoulders at 60 and 180°/s concerning medial rotators [−10.3 and −8.8%, respectively (p = 0.02)] and lateral rotators [−10.8 and −10%, respectively (p = 0.04 and p = 0.03)]. There was a moderate correlation between the grip strength of the symptomatic upper-limbs and the isokinetic rotators strength (p < 0.001). The key pinch strength was moderately correlated to the isokinetic medial and lateral rotators strength at 60°/s (p < 0.001). Hand dynamometers could prove useful during medical consultations or in outpatient management to assess upper-limb overall weakness, but isokinetic measurement remains the gold standard for a precise evaluation.
The effects of ruminant milk treatments on hippocampal, striatal, and prefrontal cortex gene expression in pigs as a model for the human infant
Authors: Jena Ankita , Montoya Carlos A. , Young Wayne , Mullaney Jane A. , Roy Debashree , Dilger Ryan N. , Giezenaar Caroline , McNabb Warren C. , Roy Nicole C.
Published: August 2022

While infant formula is usually bovine milk-based, interest in other ruminant milk-based formulas is growing. However, whether different ruminant milk treatments with varying nutrient compositions influence the infant’s brain development remains unknown. The aim was to determine the effects of consuming bovine, caprine, or ovine milk on brain gene expression in the early postnatal period using a pig model of the human infant. Starting at postnatal day 7 or 8, pigs were exclusively fed bovine, ovine, or caprine milk for 15 days. The mRNA abundance of 77 genes in the prefrontal cortex, hippocampus, and striatum regions was measured at postnatal day 21 or 22 using NanoString. The expression level of two hippocampal and nine striatal genes was most affected by milk treatments, particularly ovine milk. These modulatory genes are involved in glutamate, gamma-aminobutyric acid, serotonin, adrenaline and neurotrophin signaling and the synaptic vesicle cycle. The expression level of genes involved in gamma-aminobutyric acid signaling was associated with pigs’ lactose intake. In contrast, milk treatments did not affect the mRNA abundance of the genes in the prefrontal cortex. This study provides the first evidence of the association of different ruminant milk treatments with brain gene expression related to cognitive function in the first 3 months of postnatal life.
S100A10 and its binding partners in depression and antidepressant actions
Authors: Chen Michelle X. , Oh Yong-Seok , Kim Yong
Published: August 2022

S100A10 (p11) is an emerging player in the neurobiology of depression and antidepressant actions. p11 was initially thought to be a modulator of serotonin receptor (5-HTR) trafficking and serotonergic transmission, though newly identified binding partners of p11 and neurobiological studies of these proteins have shed light on multifunctional roles for p11 in the regulation of glutamatergic transmission, calcium signaling and nuclear events related to chromatin remodeling, histone modification, and gene transcription. This review article focuses on direct binding partners of p11 in the brain including 5-HTRs, mGluR5, annexin A2, Ahnak, Smarca3, and Supt6h, as well as their roles in neuronal function, particularly in the context of depressive-like behavior as well as behavioral effects of antidepressant drug treatments in mice. In addition, we discuss neurobiological insights from recently uncovered p11 pathways in multiple types of neurons and non-neuronal cells and cast major remaining questions for future studies.
Cellular and circuit diversity determines the impact of endogenous opioids in the descending pain modulatory pathway
Authors: McPherson Kylie B. , Ingram Susan L.
Published: August 2022

The descending pain modulatory pathway exerts important bidirectional control of nociceptive inputs to dampen and/or facilitate the perception of pain. The ventrolateral periaqueductal gray (vlPAG) integrates inputs from many regions associated with the processing of nociceptive, cognitive, and affective components of pain perception, and is a key brain area for opioid action. Opioid receptors are expressed on a subset of vlPAG neurons, as well as on both GABAergic and glutamatergic presynaptic terminals that impinge on vlPAG neurons. Microinjection of opioids into the vlPAG produces analgesia and microinjection of the opioid receptor antagonist naloxone blocks stimulation-mediated analgesia, highlighting the role of endogenous opioid release within this region in the modulation of nociception. Endogenous opioid effects within the vlPAG are complex and likely dependent on specific neuronal circuits activated by acute and chronic pain stimuli. This review is focused on the cellular heterogeneity within vlPAG circuits and highlights gaps in our understanding of endogenous opioid regulation of the descending pain modulatory circuits.
An anti-inflammatory and low fermentable oligo, di, and monosaccharides and polyols diet improved patient reported outcomes in fibromyalgia: A randomized controlled trial
Authors: Silva Ana Rita , Bernardo Alexandra , de Mesquita Maria Fernanda , Vaz-Patto José , Moreira Pedro , Silva Maria Leonor , Padrão Patrícia
Published: August 2022

Background

Fibromyalgia (FM) has been associated with dysbiosis and low-grade inflammation. Studies have reported that diet influences clinical features in FM.

Objective

To evaluate the effect of an anti-inflammatory and low fermentable oligo, di, and monosaccharides and polyols (FODMAP) diet on clinical outcomes of patients with FM.

Methods

This two arms Randomized Controlled Trial (NCT04007705) included 46 female patients with FM. The intervention group (n = 22) adopted an anti-inflammatory diet for 3 months, excluding gluten, dairy, added sugar, and ultra-processed foods, along with a low FODMAPs diet in the first month. The control group (n = 24) followed general healthy eating recommendations. Both diets were applied by a certified dietitian. Before and after the intervention, participants were assessed regarding pain, fatigue, gastrointestinal symptoms, quality of sleep, and quality of life, through the Revised Fibromyalgia Impact Questionnaire (FIQR), Visual Analogue Pain Scale (VAS), Visual Analog Scale from gastrointestinal symptoms (VAS GI), Brief Pain Inventory (BPI), Pittsburg Sleep Quality Index (PSQI), Fatigue Severity Survey (FSS), and The Short Form Health Survey (SF-36). A blood sample was collected and high-sensitive C-Reactive Protein and Erythrocyte Sedimentation Rate were quantified. Paired Samples t-test/Wilcoxon and independent samples t-test/Mann−Whitney were used to compare variables between groups.

Results

After intervention, there was an improvement in intervention group scores of FIQR (p = 0.001), VAS (p = 0.002), BPI (p = 0.011), FSS (p = 0.042), VAS_GI (p = 0.002), PSQI (p = 0.048), and SF36 (p = 0.045) compared to control group. Inflammatory biomarkers (hs-CRP, ESR) did not change in both groups. The intervention was beneficial in the intervention group, regardless of age, disease duration, body mass index variation, and body fat change between baseline and post-intervention.

Conclusion

An anti-inflammatory and low-FODMAP diet improved clinical features in patients with FM and may be useful as a complement to pharmacological therapy.

Clinical Trial Registration

[https://clinicaltrials.gov/ct2/show/NCT04007705], identifier [NCT04007705].
Use of the term whole grain on the label of processed and ultra-processed foods based on cereals and pseudocereals in Brazil
Authors: Bez Batti Érika Arcaro , Nascimento Amanda Bagolin do , Geraldo Ana Paula Gines , Fernandes Ana Carolina , Bernardo Greyce Luci , Proença Rossana Pacheco da Costa , Uggioni Paula Lazzarin
Published: August 2022

There has been an increasing consumption of processed and ultra-processed foods, accompanied by growing concerns about the relationship between diet quality and health. Whole-grain foods, composed of cereals and pseudocereals, are recommended as part of a healthy diet, and food labeling is an important tool for consumers to identify the presence of whole grains in packaged foods. This study aimed to analyze the use of the term whole grain on the label of processed and ultra-processed foods based on cereals and pseudocereals (amaranth, quinoa, and buckwheat) in Brazil. Data were collected by a census of all food labels in a Brazilian supermarket. Foods were classified into eight groups according to Brazilian legislation and according to the presence or absence of the term whole grain. The prevalence of foods displaying the term whole grain or related expressions on the front label was assessed, and differences between groups were analyzed using Pearson's chi-squared test. Comparisons were also made in relation to the position of whole-grain ingredients in the ingredients list, given that Brazilian food labeling regulations require that ingredients be listed in descending order of weight on packaged foods. The level of significance was defined as p < 0.05. The sample included 1,004 processed and ultra-processed foods based on cereals and pseudocereals, 156 (15.6%) of which displayed the term whole grain and/or similar expressions on the front label. Of these, 98 (9.8%) contained the term whole grain, 25 (2.5%) displayed analogous expressions, and 33 (3.3%) contained the term whole grain concomitantly with analogous terms, identified in foods of the groups Bakery goods, bread, cereals, and related products and Sugars, sugary foods, and snacks. Half of the food products displaying the term whole grain or related expressions on the front label did not have a whole-grain ingredient listed in the first position of the ingredients list. The frequency of whole grains was even lower when analyzing the second and third ingredients. These findings reveal the existence of inaccurate information regarding the term whole grain or analogous expressions on the front label of cereal- and pseudocereal-based packaged foods. It is expected that these results will contribute to stimulating the food industry and regulatory bodies to improve the use of the term whole grain and related expressions on packaged food labels, given that, up to the moment of data collection, there were no regulatory requirements for these statements. Furthermore, the findings might contribute to improving the clarity of information available on food labels, thereby preventing consumer deception at the time of purchase.
Association between serum zinc level and lipid profiles in children with spinal muscular atrophy
Authors: Long Qi , Feng Yijie , Chen Fei , Wang Wenqiao , Ma Ming , Mao Shanshan
Published: August 2022

Background and aims

Children with spinal muscular atrophy (SMA) have a high rate of dyslipidaemia, which is a risk factor of vital importance for cardiovascular diseases in adulthood. Studies have demonstrated that the serum zinc level is associated with lipid profiles in the general population as well as in individuals diagnosed with obesity or diabetes. The purpose of this study was to evaluate the relationship between serum zinc level and lipid profiles in children with SMA.

Methods

This cross-sectional study was launched in a tertiary children's medical center in China and involved pediatric patients with SMA under the management of a multidisciplinary team of outpatient services from July 2019 to July 2021. Anthropometric information, general clinical data, serum zinc level, lipid profiles, and body composition data were collected. Multivariate analysis was used for a thorough inquiry on the association between the serum zinc level and lipid profiles.

Results

Among the 112 patients with SMA [median (IQR) age 5.54 years (2.75–8.29), 58.04% female], who fulfilled the inclusion criteria of the study, dyslipidaemia was detected in 60 patients (53.57%). Based on multivariable linear regression, serum zinc level was positively associated with high-density lipoprotein cholesterol (HDL-C; β = 1.63, 95% CI = 0.44–3.22) and apolipoprotein A1 (APO A1; β = 2.94, 95% CI = 0.03–5.85) levels, independently of age, sex, type, activity, percentage of body fat, and body mass index. As the serum zinc level increased by 10 μmol/L, the risk of low APO A1 levels decreased by 35% (OR = 0.65, 95% CI = 0.44–0.97) according to multivariable logistic regression analyses.

Conclusion

Serum zinc concentration was positively correlated with HDL-C and APO A1 levels among children with SMA. We suggest measures to correct the lower level of serum zinc to improve HDL-C and APO A1 levels.
Novel electrochemical and electrochemiluminescence dual-modality sensing platform for sensitive determination of antimicrobial peptides based on probe encapsulated liposome and nanochannel array electrode
Authors: Luo Xuan , Zhang Tongtong , Tang Hongliang , Liu Jiyang
Published: August 2022

With the increasing application of antimicrobial peptides (AMPs) to replace antibiotics in medicine, food and agriculture, it is highly desired to develop a fast, reliable, and convenient strategy for sensitive detection of AMPs. Herein, a novel electrochemical (EC) and electrochemiluminescence (ECL) dual-modality sensing platform was developed based on probe encapsulated liposomes and nanochannel array modified electrodes, which enables sensitive determination of nisin in food samples. The bifunctional probe with both EC and ECL signals, tris(2,2-bipyridyl) dichlororuthenium (II) (Ru(bpy)32+), was chosen to be easily encapsulated in liposomes (Ru(bpy)32+@liposome). Based on the unique sterilization mechanism that AMPs can disrupt cell membranes, Ru(bpy)32+@liposome can be destroyed by nisin and release a large number of Ru(bpy)32+ probes. Vertically-ordered mesoporous silica-nanochannel film (VMSF) modified ITO electrodes (VMSF/ITO) prepared by electrochemically assisted self-assembly (EASA) method were applied as the sensing electrode. Due to the efficient enrichment of Ru(bpy)32+ by the negatively charged nanochannel arrays, VMSF/ITO enables detection of the EC/ECL signals of the released Ru(bpy)32+ probes with ultrahigh sensitivity. In consequence, sensitive dual-modality detection of nisin was achieved by the combination of Ru(bpy)32+@liposome and VMSF/ITO. The developed sensing system can realize sensitive determination of nisin in ECL mode in the concentration range of 10 ng/ml to 50 μg/ml with a limit of detection (LOD) of 9.3 ng/ml, or in EC mode from 800 ng/ml to 100 μg/ml with a LOD of 70 ng/ml. Combined with the excellent anti-fouling and anti-interference performance of VMSF, rapid and sensitive detection of nisin in milk or egg white was also achieved by the sensor.
The Nutri-Score algorithm: Evaluation of its validation process
Authors: van der Bend Daphne L. M. , van Eijsden Manon , van Roost Michelle H. I. , de Graaf Kees , Roodenburg Annet J. C.
Published: August 2022

The Nutri-Score front-of-pack label, which classifies the nutritional quality of products in one of 5 classes (A to E), is one of the main candidates for standardized front-of-pack labeling in the EU. The algorithm underpinning the Nutri-Score label is derived from the Food Standard Agency (FSA) nutrient profile model, originally a binary model developed to regulate the marketing of foods to children in the UK. This review describes the development and validation process of the Nutri-Score algorithm. While the Nutri-Score label is one of the most studied front-of-pack labels in the EU, its validity and applicability in the European context is still undetermined. For several European countries, content validity (i.e., ability to rank foods according to healthfulness) has been evaluated. Studies showed Nutri-Score's ability to classify foods across the board of the total food supply, but did not show the actual healthfulness of products within different classes. Convergent validity (i.e., ability to categorize products in a similar way as other systems such as dietary guidelines) was assessed with the French dietary guidelines; further adaptations of the Nutri-Score algorithm seem needed to ensure alignment with food-based dietary guidelines across the EU. Predictive validity (i.e., ability to predict disease risk when applied to population dietary data) could be re-assessed after adaptations are made to the algorithm. Currently, seven countries have implemented or aim to implement Nutri-Score. These countries appointed an international scientific committee to evaluate Nutri-Score, its underlying algorithm and its applicability in a European context. With this review, we hope to contribute to the scientific and political discussions with respect to nutrition labeling in the EU.
131I-Caerin 1.1 and 131I-Caerin 1.9 for the treatment of non-small-cell lung cancer
Authors: Liu Na , He Tiantian , Xiao Zewei , Du Juan , Zhu Keke , Liu Xiongying , Chen Tongsheng , Liu Wenjuan , Ni Guoying , Liu Xiaosong , Wang Tianfang , Quan Jiangtao , Zhang Jinhe , Zhang Peipei , Yuan Jianwei
Published: August 2022

Objective

To investigate the effect of the 131I-labeled high-affinity peptides Caerin 1.1 and Caerin 1.9 for the treatment of A549 human NSCLC cells.

Methods

① 3-[4,5-Dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and plate clone formation assays were performed to confirm the in vitro anti-tumor activity of Caerin 1.1 and Caerin 1.9. ② Chloramine-T was used to label Caerin 1.1 and Caerin 1.9 with 131I, and the Cell Counting Kit 8 assay was performed to analyze the inhibitory effect of unlabeled Caerin 1.1, unlabeled Caerin 1.9, 131I-labeled Caerin 1.1, and 131I-labeled Caerin 1.9 on the proliferation of NSCLC cells. An A549 NSCLC nude mouse model was established to investigate the in vivo anti-tumor activity of unlabeled Caerin 1.1, unlabeled Caerin 1.9, 131I-labeled Caerin 1.1, and 131I-labeled Caerin 1.9.

Results

① Caerin 1.1 and Caerin 1.9 inhibited the proliferation of NSCLC cells in vitro in a concentration-dependent manner. The half-maximal inhibitory concentration was 16.26 µg/ml and 17.46 µg/ml, respectively, with no significant intergroup difference (P>0.05). ② 131I-labeled Caerin 1.1 and 131I-labeled Caerin 1.9 were equally effective and were superior to their unlabeled versions in their ability to inhibit the proliferation and growth of NSCLC cells (P>0.05).

Conclusions

131I-labeled Caerin 1.1 and 131I-labeled Caerin 1.9 inhibit the proliferation and growth of NSCLC cells and may become potential treatments for NSCLC.
The immune-related role of beta-2-microglobulin in melanoma
Authors: Wang Chuqiao , Wang Zeqi , Yao Tengteng , Zhou Jibo , Wang Zhaoyang
Published: August 2022

Despite the remarkable success of immunotherapy in the treatment of melanoma, resistance to these agents still affects patient prognosis and response to therapies. Beta-2-microglobulin (β2M), an important subunit of major histocompatibility complex (MHC) class I, has important biological functions and roles in tumor immunity. In recent years, increasing studies have shown that B2M gene deficiency can inhibit MHC class I antigen presentation and lead to cancer immune evasion by affecting β2M expression. Based on this, B2M gene defect and T cell-based immunotherapy can interact to affect the efficacy of melanoma treatment. Taking into account the many recent advances in B2M-related melanoma immunity, here we discuss the immune function of the B2M gene in tumors, its common genetic alteration in melanoma, and its impact on and related improvements in melanoma immunotherapy. Our comprehensive review of β2M biology and its role in tumor immunotherapy contributes to understanding the potential of B2M gene as a promising melanoma therapeutic target.
Anoikis resistance in diffuse glioma: The potential therapeutic targets in the future
Authors: Zhu Zhengyang , Fang Chaoyou , Xu Houshi , Yuan Ling , Du Yichao , Ni Yunjia , Xu Yuanzhi , Shao Anwen , Zhang Anke , Lou Meiqing
Published: August 2022

Glioma is the most common malignant intracranial tumor and exhibits diffuse metastasis and a high recurrence rate. The invasive property of glioma results from cell detachment. Anoikis is a special form of apoptosis that is activated upon cell detachment. Resistance to anoikis has proven to be a protumor factor. Therefore, it is suggested that anoikis resistance commonly occurs in glioma and promotes diffuse invasion. Several factors, such as integrin, E-cadherin, EGFR, IGFR, Trk, TGF-β, the Hippo pathway, NF-κB, eEF-2 kinase, MOB2, hypoxia, acidosis, ROS, Hsp and protective autophagy, have been shown to induce anoikis resistance in glioma. In our present review, we aim to summarize the underlying mechanism of resistance and the therapeutic potential of these molecules.
Diagnosis by metagenomic next-generation sequencing of a Talaromyces marneffei bloodstream infection in an HIV-negative child: A case report
Authors: Yang Aimei , Hu Yan , Chen Peiling , Zheng Guilang , Hu Xuejiao , Zhang Jingwen , Wang Jing , Wang Chun , Huang Zijian , Zhang Yuxin , Guo Yuxiong
Published: August 2022

Background

Talaromyces marneffei (TM) bloodstream infections are life- threatening in immunocompromised individuals. The lack of specific clinical features for these infections and poor sensitivity associated with routine examination procedures make diagnosis challenging. Untimely diagnosis and delayed antifungal treatment threatens the life of such patients.

Case description

We report a case of a TM bloodstream infection, confirmed by the results of blood culture, of a child who was HIV negative and possessed a CD40LG gene mutation. A diagnosis of TM was established by blood metagenomic next-generation sequencing (mNGS) of the patient's blood, which was confirmed by microbiological culture of blood. On admission, this previously healthy male patient was 8-months of age, who presented with recurrent fever and a cough of 6-days in duration. His condition did not improve after antibacterial treatment for 5-days, with significant and recurrent fever and worsening spirit. He was referred to the Department of Pediatrics in our tertiary medical institution with a white blood cell count of 21.5*10∧9/L, C-reactive protein of 47.98 mg/L, and procalcitonin of 0.28 ng/mL. A bloodstream infection was not excluded and blood was collected for microbial culture. The patient received a 1-day treatment of cefoperazone sulbactam and 6-days of imipenem cilastatin. Symptoms did not improve and fever persisted. Blood was submitted for mNGS analysis and within 14-h, 14,352 TM reads were detected with a relative abundance of 98.09%. Antibiotic treatment was immediately changed to intravenous amphotericin B combined with oral itraconazole. The condition of the child gradually improved. Blood culture showed TM on the 7th day after hospitalization, confirming bloodstream infection. After the 13th day of hospital admission, the patient's body temperature dropped close to 38°C and was discharged on the 30th day of hospitalization. Oral itraconazole was prescribed with follow up at the outpatient clinic.

Conclusions

HIV-negative patients with CD40LG mutations may be potential hosts for TM. TM infections are rare in children and their detection by conventional microbial culture methods are inadequate for an early diagnosis. mNGS is a rapid detection method that permits early diagnosis of uncommon infectious agents, such as TM, allowing for improved patient outcomes.
Central role of the sentinel acute pancreatitis event (SAPE) model in understanding recurrent acute pancreatitis (RAP): Implications for precision medicine
Authors: Whitcomb David C.
Published: August 2022

Traditional approaches to understanding the origins of chronic pancreatitis (CP) and find treatments led to abysmal failure. Thus, no drugs now exists to meet this need. Outdated concepts of the etiopathogenesis of CP have been replaced with new insights and disease models that provide the framework for early detection of the pathogenic pancreatitis process. Application of these principals require a new paradigm in disease definition and management, i.e. personalized / precision medicine. The key is acute pancreatitis (AP) starting with the first (sentinel) acute pancreatitis (AP) event (SAPE). This event sensitizes the pancreas to recurrent acute pancreatitis (RAP) as ongoing stressors drive various inflammatory responses to cause CP. The problem is the complex etiologies of AP and the additional genetic and environmental factors that promote progression to RAP and CP. This paper provides a background on the key conceptual changes that facilitate new approaches and the rationale for using mechanism-specific therapies to prevent RAP and CP.
Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ameliorates Chronic Stress-Induced Depression-Like Behavior and Inflammation in Mice
Authors: Xu Guanglei , Zou Tao , Deng Lijiao , Yang Guang , Guo Tingting , Wang Yi , Niu Chunxiao , Cheng Qianqian , Yang Xiqin , Dong Jie , Zhang Jiyan
Published: August 2022

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder. But the treatment of depression remains challenging. Anti-inflammatory treatments frequently produce antidepressant effects. EPO-derived helix-B peptide ARA290 has been reported to retain the anti-inflammatory and tissue-protective functions of EPO without erythropoiesis-stimulating effects. The effects of ARA290 on MDD remain elusive. This study established chronic unpredictable mild stress and chronic social defeat stress mouse models. Daily administration of ARA290 during chronic stress induction in two mouse models ameliorated depression-like behavior, similar to fluoxetine. With marginal effects on peripheral blood hemoglobin and red cells, ARA290 and fluoxetine reversed chronic stress-induced increased frequencies and/or numbers of CD11b+Ly6Ghi neutrophils and CD11b+Ly6Chi monocytes in the bone marrow and meninges. Furthermore, both drugs reversed chronic stress-induced microglia activation. Thus, ARA290 ameliorated chronic stress-induced depression-like behavior in mice through, at least partially, its anti-inflammatory effects.
Role of ferroptosis and ferroptosis-related non-coding RNAs in the occurrence and development of gastric cancer
Authors: Lu Ling , Chen Bei , Xu Yumeng , Zhang Xinyi , Jin Longtao , Qian Hui , Wang Yi , Liang Zhao Feng
Published: August 2022

Gastric cancer (GC) is a malignant cancer of the digestive tract and is a life-threatening disease worldwide. Ferroptosis is a newly discovered form of regulated cell death, which involves the accumulation of iron-dependent lipid peroxides. It has been found that ferroptosis plays an important regulatory role in the occurrence, development, drug resistance, and prognosis of GC. Non-coding RNAs (ncRNAs) play a critical role in the occurrence and progression of a variety of diseases including GC. In recent years, the role of ferroptosis and ferroptosis-related ncRNAs (miRNA, lncRNA, and circRNA) in the occurrence, development, drug resistance, and prognosis of GC has attracted more and more attention. Herein, we briefly summarize the roles and functions of ferroptosis and ferroptosis-related ncRNAs in GC tumorigenesis, development, and prognosis. We also prospected the future research direction and challenges of ferroptosis and ferroptosis-related ncRNAs in GC.
A synthetic BBB-permeable tripeptide GCF confers neuroprotection by increasing glycine in the ischemic brain
Authors: Chen Juan , Zhuang Yang , Zhang Ya , Liao Huabao , Liu Rui , Cheng Jing , Zhang Zhifeng , Sun Jiangdong , Gao Jingchen , Wang Xiyuran , Chen Shujun , Zhang Liang , Che Fengyuan , Wan Qi
Published: August 2022

Background: We and others have previously demonstrated that glycine is neuroprotective in cerebral ischemia-reperfusion injury. But glycine has low permeability to the blood–brain barrier (BBB). To deliver glycine into the ischemic brain to confer neuroprotection, we designed a novel glycine-containing and BBB-permeable tripeptide, the H-glycine-cysteine-phenylalanine-OH (GCF).

Methods: For the synthesis of GCF, phenylalanine was included to increase the BBB permeability of the tripeptide. Cysteine was conjugated with glycine to enable the release of glycine from GCF. With the use of immunofluorescence labeling and HPLC assays, we measured the distribution and level of GCF. We used TTC labeling, LDH release, and MTT assays to evaluate the neuroprotective effect of GCF.

Results: Following intravenous injection in a rat model of cerebral ischemia-reperfusion injury, GCF was intensively distributed in the ischemic neurons. Intravenous injection of GCF, but not the non-cleavable acetyl-GCF, resulted in the elevation of glycine in the ischemic brain. GCF but not acetyl-GC conferred neuroprotection in ischemic stroke animals.

Conclusion: GCF protects against cerebral ischemia-reperfusion injury in the rat. In contrast to peptide drugs that exert therapeutic effect by interfering with signaling interaction, GCF acts as a BBB shuttle and prodrug to deliver glycine to confer neuroprotection, representing a novel therapeutic strategy for acute ischemic stroke.
Determining quantum topological semion code decoder performance and error correction effectiveness with reinforcement learning
Authors: Wang Hao-Wen , Cao Qian , Xue Yun-Jia , Ding Li , Liu Han-Yang , Dong Yu-Min , Ma Hong-Yang
Published: August 2022

Quantum error correction technology is a vital method to eliminate noise during the operation of quantum computers. To solve the problem caused by noise, in this paper, reinforcement learning is used to encode defects of Semion codes, and the experience replay technique is used to realize the design of decoder. Semion codes are quantum topological error correction codes with the same symmetry group Z2 as Kitaev toric codes, we used the topological characteristics of error correction codes to map qubits to multi-dimensional space, and error correction accuracy of the decoder is calculated to be 77.5%. Calculate the threshold of topological quantum Semion code, depending on the code distance, resulting in different thresholds, pthreshold = 0.081574 when the code distance is d = 3, 5, 7 and threshold pthreshold = 0.09542 when the code distance is d = 5, 7, 9. And we design the Q-network to optimize the cost of quantum circuit gates and compare the size of the cost reduction under different thresholds. Reinforcement learning is an important method for designing Semion code decoders and optimizing numerical values, providing more general error models and error correction codes for future machine engineering decoders.
The effect of cold acclimation, deacclimation and reacclimation on metabolite profiles and freezing tolerance in winter wheat
Authors: Vaitkevičiūtė Gabija , Aleliūnas Andrius , Gibon Yves , Armonienė Rita
Published: August 2022

Global climate change will cause longer and warmer autumns, thus negatively affecting the quality of cold acclimation (CA) and reducing the freezing tolerance (FT) of winter wheat. Insufficient FT and fluctuating temperatures during winter can accelerate the deacclimation (DEA) process, whereas reacclimation (REA) is possible only while the vernalization requirement is unfulfilled. Six winter wheat genotypes with different winter hardiness profiles were used to evaluate the impact of constant low-temperature (2°C) and prolonged higher low-temperature (28 days at 10°C followed by 2°C until day 49) on shoot biomass and metabolite accumulation patterns in leaf and crown tissues throughout 49 days of CA, 7 days of DEA, and 14 days of REA. The FT of winter wheat was determined as LT30 values by conducting freezing tests after CA, DEA, and REA. Shoot biomass accumulation, projected as the green leaf area (GLA), was investigated by non-destructive RGB imaging-based phenotyping. Dynamics of carbohydrates, hexose phosphates, organic acids, proteins, and amino acids were assessed in leaf and crown tissues. Results revealed that exposure to higher low-temperature induced higher accumulation of shoot biomass and had a negative impact on FT of winter wheat. Prolonged higher low-temperature negatively affected the accumulation of soluble carbohydrates, protein content and amino acids, and had a positive effect on starch accumulation in leaf and crown tissues after CA, in comparison with the constant low-temperature treatment. DEA resulted in significantly reduced FT. Lower concentrations of glucose-6-phosphate, sucrose and proline, as well as higher concentrations of starch in leaves and crowns were found after DEA. The majority of the genotypes regained FT after REA; higher concentrations of glucose and malate in leaves, and sucrose in crown tissue were observed, whereas starch accumulation was decreased in both tissues. Negative correlations were determined between FT and starch concentration in leaves and crowns, while proline and proteins, accumulated in crowns, showed positive correlations with FT. This study broadens the knowledge regarding the effect of different low-temperature regimes on the dynamics of metabolite accumulation in winter wheat throughout CA, DEA, and REA, and its relationship to biomass accumulation and FT.