Development Of Strategies Research Articles

Rediscovering the human thymus through cutting-edge technologies.

Recent technological advances have transformed our understanding of the human thymus. Innovations such as high-resolution imaging, single-cell omics, and organoid cultures, including thymic epithelial cell (TEC) differentiation and culture, and improvements in biomaterials, have further elucidated the thymus architecture, cellular dynamics, and molecular mechanisms underlying T cell development, and have unraveled previously unrecognized levels of stromal cell heterogeneity. These advancements offer unprecedented insights into thymic biology and hold promise for the development of novel therapeutic strategies for immune-related disorders.

Tumor cell-intrinsic Piezo2 drives radioresistance by impairing CD8+ T cell stemness maintenance.

Changes in mechanosensitive ion channels following radiation have seldom been linked to therapeutic sensitivity or specific factors involved in antitumor immunity. Here, in this study, we found that the mechanical force sensor, Piezo2, was significantly upregulated in tumor cells after radiation, and Piezo2 knockout in tumor cells enhanced tumor growth suppression by radiotherapy. Specifically, loss of Piezo2 in tumor cells induced their IL-15 expression via unleashing JAK2/STAT1/IRF-1 axis after radiation. This increase in IL-15 activates IL-15Rα on tumor-infiltrating CD8+ T cells, thereby leading to their augmented effector and stem cell-like properties, along with reduced terminal exhausted feature. Importantly, Piezo2 expression was negatively correlated with CD8 infiltration, as well as with radiosensitivity of patients with rectum adenocarcinoma receiving radiotherapy treatment. Together, our findings reveal that tumor cell-intrinsic Piezo2 induces radioresistance by dampening the IRF-1/IL-15 axis, thus leading to impaired CD8+ T cell-dependent antitumor responses, providing insights into the further development of combination strategies to treat radioresistant cancers.

“Efficient novel fungal-enriched biochar formulation for hexavalent chromium bioremediation”

Chromium (Cr), a key element in industrial processes such as leather tanning, poses severe environmental hazards, particularly its hexavalent form, Cr(VI), which is highly toxic and prevalent in tannery effluents/sludge. The persistence and toxicity of Cr(VI) necessitate the development of effective remediation strategies to mitigate its environmental impact. This study investigated the potential of Trichoderma yunnanense (NBRICRF_97) and its combination with 0.5% sugarcane bagasse biochar (SBC) for the reduction of Cr(VI). The results demonstrated that T. yunnanense alone achieved a 91.04% reduction of 50 mg L−1 Cr(VI) within 72 h. Combined with 0.5% SBC, the reduction efficiency increased to 99.65% within 48 h. However, the efficiency decreased at higher concentrations (200 mg L−1). The combination also improved fungal growth and increased extracellular ChrR enzyme activity (13.07 U mg−1 protein compared to the control). Total glutathione activity was boosted by 161.07% at 100 mg L−1 Cr(VI). Antioxidant enzymes (SOD, POD, CAT) and proline mitigated oxidative stress and FTIR analysis revealed changes in fungal cell wall functional groups (-OH and -NH) upon Cr(VI) exposure. SEM-EDX confirmed chromium deposition on fungal surfaces. These results underscore the Cr(VI) detoxification capabilities of T. yunnanense and the synergistic benefits of SBC, suggesting a promising bioremediation strategy for Cr(VI)-contaminated environments. The integration of T. yunnanense with SBC offers a sustainable and cost-effective approach for the bioremediation of Cr(VI)-contaminated sites, with potential for implementation in large-scale environmental cleanup efforts.

Adaptive designs in clinical trials: a systematic review-part I.

Adaptive designs (ADs) are intended to make clinical trials more flexible, offering efficiency and potentially cost-saving benefits. Despite a large number of statistical methods in the literature on different adaptations to trials, the characteristics, advantages and limitations of such designs remain unfamiliar to large parts of the clinical and research community. This systematic review provides an overview of the use of ADs in published clinical trials (Part I). A follow-up (Part II) will compare the application of AD in trials in adult and pediatric studies, to provide real-world examples and recommendations for the child health community. Published studies from 2010 to April 2020 were searched in the following databases: MEDLINE (Ovid), Embase (Ovid), and International Pharmaceutical Abstracts (Ovid). Clinical trial protocols, reports, and a secondary analyses using AD were included. We excluded trial registrations and interventions other than drugs or vaccines to align with regulatory guidance. Data from the published literature on study characteristics, types of adaptations, statistical analysis, stopping boundaries, logistical challenges, operational considerations and ethical considerations were extracted and summarized herein. Out of 23,886 retrieved studies, 317 publications of adaptive trials, 267 (84.2%) trial reports, and 50 (15.8%) study protocols), were included. The most frequent disease was oncology (168/317, 53%). Most trials included only adult participants (265, 83.9%),16 trials (5.4%) were limited to only children and 28 (8.9%) were for both children and adults, 8 trials did not report the ages of the included populations. Some studies reported using more than one adaptation (there were 390 reported adaptations in 317 clinical trial reports). Most trials were early in drug development (phase I, II (276/317, 87%). Dose-finding designs were used in the highest proportion of the included trials (121/317, 38.2 %). Adaptive randomization (53/317, 16.7%), with drop-the-losers (or pick-the-winner) designs specifically reported in 29 trials (9.1%) and seamless phase 2-3 design was reported in 27 trials (8.5%). Continual reassessment methods (60/317, 18.9%) and group sequential design (47/317, 14.8%) were also reported. Approximately two-thirds of trials used frequentist statistical methods (203/309, 64%), while Bayesian methods were reported in 24% (75/309) of included trials. This review provides a comprehensive report of methodological features in adaptive clinical trials reported between 2010 and 2020. Adaptation details were not uniformly reported, creating limitations in interpretation and generalizability. Nevertheless, implementation of existing reporting guidelines on ADs and the development of novel educational strategies that address the scientific, operational challenges and ethical considerations can help in the clinical trial community to decide on when and how to implement ADs in clinical trials. STUDY PROTOCOL REGISTRATION: https://doi.org/10.1186/s13063-018-2934-7 .

Development Strategy for the Climate Village Program in Palopo City, South Sulawesi, Indonesia

Development Strategy for the Climate Village Program in Palopo City, South Sulawesi, Indonesia

Nanoengineered Neutrophil as 19F-MRI Tracer for Alert Diagnosis and Severity A of Acute Lung Injury.

Acute lung injury (ALI) is a severe complication in clinical settings. Alert diagnosis and severity assessment of ALI is pivotal to ensure curative treatment and increase survival rates. However, the development of a precise ALI diagnostic strategy remains a pending task. Here, leveraging neutrophil's inflammation-homing and physiological barrier-navigating capability, a facile strategy is proposed for achieving targeted 19F-MRI detection of ALI based on the nanoengineered neutrophil internalized with perfluorocarbon nanoemulsion (Neu@PFC). The remodeling process poses a negligible impact on the neutrophil's inherent activation and transmigration functions. The migratory behavior of Neu@PFC toward pneumonia is confirmed in vivo using an LPS-induced ALI murine model. Direct intratracheal (i.t.) administration contributes to a vast deposition of Neu@PFC within the lung, allowing for real-time 19F-MRI visualization and the potential to predict progressive pneumonia. Furthermore, intravenous (i.v.) administration of Neu@PFC enables quantitative assessment of the extent of ALI due to the chemokine-guided neutrophil migration. This study not only provides a pathway to diagnose ALI, but also sheds light on the neutrophil recruitment and activation cues in different tissues and inflammatory conditions, which is a prerequisite for developing potential therapeutic approaches.

Genomic characteristics of antimicrobial resistance and virulence factors of carbapenem-resistant Stutzerimonas nitrititolerans isolated from the clinical specimen

BackgroundStutzerimonas nitrititolerans (S. nitrititolerans) is a rare human pathogenic bacterium and has been inadequately explored at the genomic level. Here, we report the first case of carbapenem-resistant S. nitrititolerans isolated from the peritoneal dialysis fluid of a patient with chronic renal failure. This study analyzed the genomic features, antimicrobial resistance, and virulence factors of the isolated strain through whole genome sequencing (WGS).MethodsThe bacterial isolate from the peritoneal dialysis fluid was named PDI170223, and preliminary identification was conducted through Matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS). WGS of the strain PDI170223 was performed using the Illumina platform, and a phylogenetic tree was constructed based on the 16S rRNA gene sequences. Antimicrobial susceptibility test (AST) was conducted using the TDR-200B2 automatic bacteria identification/drug sensitivity tester.ResultsS. nitrititolerans may emerge as a human pathogen due to its numerous virulence genes, including those encoding toxins, and those involved in flagellum and biofilm formation. The AST results revealed that the strain is multidrug- and carbapenem-resistant. The antimicrobial resistance genes of S. nitrititolerans are complex and diverse, including efflux pump genes and β⁃lactam resistance genes.ConclusionThe analysis of virulence factors and antimicrobial resistance of S. nitrititolerans provides clinical insight into the pathogenicity and potential risks of this bacterium. It is crucial to explore the mechanisms through which S. nitrititolerans causes diseases and maintains its antimicrobial resistance, thereby contributing to development of effective treatment and prevention strategies.

Innate lymphoid cells and infectious diseases.

Innate lymphoid cells (ILCs) are the main resident lymphocytes that mostly reside in tissues owing to the lack of adaptive antigen receptors. These cells are involved in early anti-infective immunity, antitumour immunity, regulation of tissue inflammation, and maintenance of homeostasis in the internal environment of tissues and have been referred to as the "first armies stationed in the human body". ILCs are widely distributed in the lungs, colon, lymph nodes, oral mucosa and even embryonic tissues. Due to the advantage of their distribution location, they are often among the first cells to come into contact with pathogens.Relevant studies have demonstrated that ILCs play an early role in the defence against a variety of pathogenic microorganisms, including bacteria, viruses, fungi and helminths, before they intervene in the adaptive immune system. ILCs can initiate a rapid, nonspecific response against pathogens prior to the initiation of an adaptive immune response and can generate a protective immune response against specific pathogens, secreting different effectors to play a role.There is growing evidence that ILCs play an important role in host control of infectious diseases. In this paper, we summarize and discuss the current known infectious diseases in which ILCs are involved and ILC contribution to the defence against infectious diseases. Further insights into the mechanisms of ILCs action in different infectious diseases will be useful in facilitating the development of therapeutic strategies for early control of infections.

Lepidium meyenii (Maca) polysaccharides mitigate liver toxicity of aflatoxin B1 through activation of NRF-2/GPX and AhR/STAT3 signaling pathways

Aflatoxin B1 (AFB1) can induce serious liver toxicity in human. While completely avoiding AFB1 exposure is difficult, dietary intake of natural products may be leveraged to mitigate its adverse health effects. The roots of Lepidium meyenii (Maca) is rich in beneficial polysaccharides. Here we first evaluated dietary safety of MPs and then investigated MPs mitigating effects on the liver toxicity of AFB1. A 28-day sub-acute administration of Maca polysaccharides (MPs) demonstrated to be safe in mice at dose 0.2–1.2 g/kg.bw/day that significantly elevated mice stamina. Also, no toxicity was observed in human PC12 cells treated with MPs 25–100 μg/mL which successfully alleviated cobalt-caused cell apoptosis by ∼20%. In terms of anti-AFB1 hepatoxicity function, MPs 0.4–1.6 g/kg.bw/day significantly alleviated liver tissue damage, lipid accumulation, ROS damage, NF-κB p65, secretion of cytokines such as IL-6 and TNF-α in AFB1-treated mice. Flow cytometry found that MPs treatment recovered the elevation of F4/80 in the primary macrophages of AFB1-treated mice. At molecular level, MPs treatment activated liver NRF-2/GPX/SOD anti-oxidant system. In human macrophage model, MPs restored the inflammatory AhR/STAT3 pathway and mRNA expressions of Tnf-a, Inos, Arg-1 disrupted by AFB1. Our findings not only add to the current understanding on the toxicity mechanism of AFB1, but also provide references to the development of dietary intervention strategy using MPs.

Exploring the effects of pemetrexed on drug resistance mechanisms in human lung adenocarcinoma and its association with PGRMC1

According to the 2022 cancer statistics of the World Health Organization, lung cancer ranks among the top ten causes of death, with lung adenocarcinoma being the most prevalent type. Despite significant advancements in lung cancer therapeutics, many clinical limitations remain, primarily due to the development of drug resistance. The present study investigated the effects of pemetrexed on the drug resistance mechanisms in human lung adenocarcinoma and its association with progesterone receptor membrane component 1 (PGRMC1) expression. Given that KRAS-mutant lung adenocarcinoma cell lines (e.g., A549) exhibit a high folate synthesis activity, pemetrexed, which is structurally similar to folate, was selected as the therapeutic drug. The present study used a lung adenocarcinoma cell line (A549) and established a drug-resistant lung adenocarcinoma cell line (A549/PEM). The findings demonstrated that PGRMC1 expression was elevated in the A549/PEM cells. It has been hypothesized that PGRMC1 regulates iron absorption through heme binding, resulting in a preference for iron-related cell death pathways (ferroptosis). Our findings indicate that drug-resistant lung adenocarcinoma cells with high PGRMC1 levels exhibit elevated antioxidant activity on the cell membrane and increased reliance on iron-dependent cell death pathways. This suggests a correlation between PGRMC1 and pemetrexed-induced iron-dependent cell death. Our study contributes to the development of more effective therapeutic strategies to improve the prognosis of patients with lung adenocarcinoma, particularly those facing drug resistance challenges.

CIEC: Cross-tissue Immune Cell Type Enrichment and Expression Map Visualization for Cancer.

Single-cell transcriptome sequencing technology has been applied to decode the cell types and functional states of immune cells, revealing their tissue-specific gene expression patterns and functions in cancer immunity. Comprehensive assessments of immune cells within and across tissues will provide us with a deeper understanding of the tumor immune system in general. Here, we present Cross-tissue Immune cell type or state Enrichment analysis of gene lists for Cancer (CIEC), the first web-based application that integrates database and enrichment analysis to estimate the cross-tissue immune cell type or state. CIEC version 1.0 consists of 480 samples covering primary tumor, adjacent normal tissue, lymph node, metastasis tissue, and peripheral blood from 323 cancer patients. By applying integrative analysis, we constructed an immune cell-type/state map for each context and adopted our previously developed Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology Based Annotation System (KOBAS) algorithm to estimate the enrichment for context-specific immune cell type/state. In addition, CIEC also provides an easy-to-use online interface for users to comprehensively analyze the immune cell characteristics mapped across multiple tissues, including expression map, correlation, similar genes detection, signature score, and expression comparison. We believe that CIEC will be a valuable resource for exploring the intrinsic characteristics of immune cells in cancer patients and for potentially guiding novel cancer-immune biomarker development and immunotherapy strategies. CIEC is freely accessible at http://ciec.gene.ac/.

Effects of cognitive training under hypoxia on cognitive proficiency and neuroplasticity in remitted patients with mood disorders and healthy individuals: ALTIBRAIN study protocol for a randomized controlled trial.

Cognitive impairment is prevalent across neuropsychiatric disorders but there is a lack of treatment strategies with robust, enduring effects. Emerging evidence indicates that altitude-like hypoxia cognition training may induce long-lasting neuroplasticity and improve cognition. We will investigate whether repeated cognition training under normobaric hypoxia can improve cognitive functions in healthy individuals and patients with affective disorders and theneurobiological underpinnings of such effects. In sub-study 1, 120 healthy participants are randomized to one of four treatment arms in a double-blind manner, allowing for examination of separate and combined effects of three-week repeated moderate hypoxia and cognitive training, respectively. In sub-study 2, 60 remitted patients with major depressive disorder or bipolar disorder are randomized to hypoxia with cognition training or treatment as usual. Assessments of cognition, psychosocial functioning, and quality of life are performed at baseline, end-of-treatment, and at 1-month follow-up. Functional magnetic resonance imaging (fMRI) scans are conducted at baseline and 1-month follow-up, and [11C]UCB-J positron emission tomography (PET) scans are performed at end-of-treatment to quantify the synaptic vesicle glycoprotein 2A (SV2A). The primary outcome is a cognitive composite score of attention, verbal memory, and executive functions. Statistical power of ≥ 80% is reached to detect a clinically relevant between-group difference with minimumn = 26 per treatment arm. Behavioral data are analyzed with an intention-to-treat approach using mixed models. fMRI data is analyzed with the FMRIB Software Library, while PET data is quantified using the simplified reference tissue model (SRTM) with centrum semiovale as reference region. The results will provide novel insights into whether repeated hypoxia cognition training increases cognition and brain plasticity, which can aid future treatment development strategies. ClinicalTrials.gov, NCT06121206 . Registered on 31 October 2023.

A-317 Development of a patient-focused volumetric absorptive microsampling strategy to assess urinary amino acid excretion

Abstract Background Biochemical determinations of urinary amino acid excretion patterns can diagnose specific inborn errors of metabolism (IEM). Clinical management of these genetic metabolic patients may require frequent urine amino acid tests. A simplified process for transporting home collected urine specimens would benefit the IEM community. Volumetric absorptive microsampling (VAMS) is an emergent alternative sampling technique for the collection of dried biological specimens. We describe the development and preliminary validation results of a VAMS strategy for the analysis of creatinine and amino acids (N=22) from microsampled dried urine. Methods Urine creatinine and amino acids were respectively measured in a clinical laboratory setting using established assays on a CobasPro (Roche) and a MassTrak ultra-performance liquid chromatography (UPLC) amino acid analysis (AAA) solution (Waters). Two 30 µL VAMS tips from a Mitra device (Neoteryx) were used to sample each random urine specimen. An ultrasonication-based solvent extraction procedure was optimized to extract the amino acids and creatinine from the VAMS tips. Solvent extracts were subsequently dried by centrifugal evaporation. Extract from one tip was re-dissolved in water and tested for creatinine using an enzymatic method. The other extract was re-dissolved in 0.02 N sodium hydroxide and tested according to the MassTrak AAA procedure, which deploys pre-column AccQTag derivatization with reversed-phase UPLC on a C18 column (2.1 × 150 mm; 1.7 µm) and UV detection at 260 nm. Accuracy, within-batch precision and short-term stability of the optimized VAMS protocol were determined. Results Extraction solvent with a 60:40 (v/v) water:methanol mixture provided the highest average amino acid recovery. This extraction solvent produced higher average amino acid recoveries at pH 11 (89±13%), than pH 3 (82±10%) or pH 7 (72±11%). Creatinine measured from the VAMS tips (N=44) had a consistent negative bias of 20% relative to neat urine (R=0.9905, slope=0.802, intercept=0.02). The creatinine corrected urine amino acid results from the Mitra device were corrected for this observed concentration bias. The accuracy of the amino acid results derived from the VAMS tip vs neat urine was 104 ± 14%. The average within-batch precision (CV%) of the amino acids was 9.8% (range=6.7% (cystine) to 17.6% (arginine)) and 6.2% for creatinine. The average 1 week storage stability at ambient temperature was 91% (range=73% (ornithine) to 107% (glycine)) for the amino acids and 107% for creatinine. The devised VAMS strategy was applied to the analysis of microsampled dried urine from a patient with cystinuria (OMIM no. 220100). Marked elevations in arginine, cystine, lysine and ornithine were respectively observed and are consistent with the biochemical diagnosis of the patient. Conclusions Creatinine corrected amino acid results from the devised VAMS strategy exhibit good precision and accuracy when compared to tradition analyses of neat urine. The potential use of microsampled dried urine for the diagnosis and monitoring of selected IEM has been demonstrated. The analytical and clinical performance of this VAMS protocol must be further validated, including the use of microsampled dried urine from home specimen collections.

Strategies to control humidity sensitivity of azobenzene isomerisation kinetics in polymer thin films

Azobenzenes are versatile photoswitches that garner interest in applications ranging from photobiology to energy storage. Despite their great potential, transforming azobenzene-based discoveries and proof-of-concept demonstrations from the lab to the market is highly challenging. Herein we give an overview of a journey that started from a discovery of hydroxyazobenzene’s humidity sensitive isomerisation kinetics, developed into commercialization efforts of azobenzene-containing thin film sensors for optical monitoring of the relative humidity of air, and arrives to the present work aiming for better design of such sensors by understanding the different factors affecting the humidity sensitivity. Our concept is based on thermal isomerisation kinetics of tautomerizable azobenzenes in polymer matrices which, using pre-defined calibration curves, can be converted to relative humidity at known temperature. We present a small library of tautomerizable azobenzenes exhibiting humidity sensitive isomerisation kinetics in hygroscopic polymer films. We also investigate how water absorption properties of the polymer used, and the isomerisation kinetics are linked and how the azobenzene content in the thin film affects both properties. Based on our findings we propose simple strategies for further development of azobenzene-based optical humidity sensors.

Density as an indicator of sustainable urban development: insights from Helsinki?

ABSTRACT Densification has become a dominant strategy for sustainable urban development in recent decades, viewed as a main antidote to urban sprawl and essential for achieving a range of urban qualities from economic to ecological. Despite its prominence as an indicator and driver of sustainable development, measuring density in a meaningful way poses significant challenges. Arbitrary metrics often overlook the complexity of density and its associations, leading to potential unintended outcomes in density-driven planning. Using the Helsinki region as a case study, this article demonstrates the sensitivity of density measurements to minor changes in reference areas and calculation units, highlighting how different types of density can loosely relate to each other. Our findings underscore the importance of precise methodological choices in avoiding misguided planning decisions and policy advice that could compromise sustainability goals, revealing the complex dynamics of infill and edge growth often obscured in regional density measures.

Magnesium-Induced Rapid Nucleation of Tetrahydrofuran Hydrates.

Hydrates are ice-like crystalline structures of hydrogen-bonded water molecules that trap a guest molecule. Hydrates have several applications, including carbon sequestration, gas separation, desalination, etc. A classical major challenge associated with artificial hydrate formation is the very long induction time to nucleate hydrates. This has spurred the development of multiple chemical, mechanical, and electrical strategies to promote nucleation. Presently, we discover that magnesium can significantly promote the nucleation of tetrahydrofuran (THF) hydrates. While magnesium has been recently shown (by our group) to promote the formation of carbon dioxide hydrates (gas-liquid system), this study discovers that the benefits of magnesium extend to liquid-liquid hydrate systems as well. Experiments show that magnesium reduces the induction time for THF hydrate nucleation with deionized (DI) water and saltwater by six and eight times, respectively. Magnesium-induced nucleation rate enhancements for hydrate formation with DI water and saltwater were 12 and 99 times, respectively. Importantly, we demonstrate near-instantaneous nucleation when magnesium is introduced after the hydrate-forming system reaches suitable thermodynamic conditions. We conduct statistically significant measurements of nucleation and XPS analysis to identify the underlying mechanisms responsible for nucleation. We discuss multiple phenomena at play, including chemical and mechanistic promotion pathways. The formation of hydrogen bubbles and the presence of magnesium ions in solution are seen as important to magnesium-based nucleation promotion. Importantly, very low amounts of Mg are consumed in this process unlike in traditional chemical promotion techniques. Overall, our discovery can enable on-demand nucleation of liquid-liquid hydrate systems, which is critical to the development of several applications.

Synergistic effects of peripheral GABA and GABA-transaminase inhibitory drugs on food intake control and weight loss in high-fat diet-induced obese mice

BackgroundDeveloping anti-obesity interventions targeting appetite or food intake, the primary driver of obesity, remains challenging. Here, we demonstrated that dietary γ-aminobutyric acid (GABA) with GABA-degradation inhibitory drugs could be an anti-obesity intervention possessing strong food intake-suppressive and weight-loss effects.MethodsHigh-fat (HF)-diet-induced obese mice were divided into six groups receiving either the HF diet or the 2% GABA-HF diet with daily administration of PBS or the GABA-degradation inhibitory drugs, vigabatrin and ethanolamine-O-sulfate (EOS). In 24-h fast-induced refeeding, lean mice with a basal diet were used, and food intake was measured from 0.5 to 24 h after refeeding.ResultsCoadministration of the 2% GABA-HF diet with vigabatrin or EOS significantly decreased food intake (−53%, −35%) and body weight (−22%, −16%) within 11 days in obese mice, along with a marked increase in plasma GABA levels. Mice receiving dietary GABA alone or the drugs alone exhibited no such effects. Hypothalamic GABA levels increased in drug-treated mice, regardless of diet. At 0.5 h after refeeding, food intake was similar in all groups. However, at 0.5 h, plasma GABA levels were markedly increased only in mice receiving coadministration of dietary GABA and the drugs, and their food intake was completely inhibited for over 6 h, while mice in other groups gradually increased their food intake.ConclusionCombining dietary GABA with GABA-degradation inhibitory drugs effectively suppresses food intake and promotes weight loss in obese mice, primarily through increased plasma GABA availability. These findings may advance the development of food intake-controlling strategies for obesity management.

Cardiovascular Disease May Be Triggered by Gut Microbiota, Microbial Metabolites, Gut Wall Reactions, and Inflammation

Cardiovascular disease (CVD) may be inherited, as recently shown with the identification of single nucleotide polymorphisms (SNPs or “snips”) on a 250 kb DNA fragment that encodes 92 proteins associated with CVD. CVD is also triggered by microbial dysbiosis, microbial metabolites, metabolic disorders, and inflammatory intestinal epithelial cells (IECs). The epithelial cellular adhesion molecule (Ep-CAM) and trefoil factor 3 (TFF3) peptide keeps the gut wall intact and healthy. Variations in Ep-CAM levels are directly linked to changes in the gut microbiome. Leptin, plasminogen activator inhibitor 1 (PAI1), and alpha-1 acid glycoprotein 1 (AGP1) are associated with obesity and may be used as biomarkers. Although contactin 1 (CNTN1) is also associated with obesity and adiposity, it regulates the bacterial metabolism of tryptophan (Trp) and thus appetite. A decrease in CNTN1 may serve as an early warning of CVD. Short-chain fatty acids (SCFAs) produced by gut microbiota inhibit pro-inflammatory cytokines and damage vascular integrity. Trimethylamine N-oxide (TMAO), produced by gut microbiota, activates inflammatory Nod-like receptors (NLRs) such as Nod-like receptor protein 3 (NLRP3), which increase platelet formation. Mutations in the elastin gene (ELN) cause supra valvular aortic stenosis (SVAS), defined as the thickening of the arterial wall. Many of the genes expressed by human cells are regulated by gut microbiota. The identification of new molecular markers is crucial for the prevention of CVD and the development of new therapeutic strategies. This review summarizes the causes of CVD and identifies possible CVD markers.

Curcumin activates the Wnt/β-catenin signaling pathway to alleviate hippocampal neurogenesis abnormalities caused by intermittent hypoxia: A study based on network pharmacology and experimental verification

The purpose of this work was to investigate how curcumin (Cur) might enhance cognitive function and to gain a better understanding of the molecular mechanisms behind Cur’s impacts on neurogenesis deficits brought on by intermittent hypoxia (IH). Using network pharmacology, we explored possible targets for Cur’s obstructive sleep apnea (OSA) therapy. We established an IH model using C57BL/6 mice and c17.2 cells, and we assessed the influence of Cur on treatment outcomes as well as the effect of IH on cognitive function. Hippocampal damage and neurogenesis, as well as expression of core targets, were then examined. Network pharmacology analysis revealed that Cur has the potential for multi-target, multi-pathway therapy, with CTNNB1 and MYC as core target genes. The Morris water maze test showed that Cur (100 mg/kg, intragastrically) significantly improved cognitive dysfunction induced by IH. The hematoxylin and eosin (H&E) and Nissl staining indicated that Cur could alleviate damage to the hippocampus caused by IH. Immunohistochemistry, immunofluorescence, and western blotting results showed that Cur might promote neurogenesis and upregulate the expression of β-catenin and c-myc. In vitro, Cur (0.5 μM) has a protective effect on IH-induced neural stem cells (NSCs) injury and apoptosis and can restore the Wnt/β-catenin. Cur significantly increased the neurogenesis via the Wnt/β-catenin pathway, providing the scientific groundwork for the development of new treatment strategies for neurological damage linked to OSA.

Barriers and facilitators to dissemination of non-communicable diseases research: a mixed studies systematic review

BackgroundThere is a large number of research studies about the prevention of non-communicable diseases (NCD), with findings taking several years to be translated into practice. One reason for this lack of translation is a limited understanding of how to best disseminate NCD research findings to user-groups in a way that is salient and useful. An understanding of barriers and facilitators to dissemination is key to informing the development of strategies to increase dissemination. Therefore, this review aims to identify and synthesise the barriers and facilitators to dissemination of NCD research findings.MethodsA mixed studies systematic review was performed following JBI (formerly known as Joanna Briggs Institute) methodology. The search included articles from January 2000 until May 2021. We conducted a comprehensive search of bibliographic and grey literature of five databases to identify eligible studies. Studies were included if they involved end-users of public health research that were decision-makers in their setting and examined barriers/facilitators to disseminating research findings. Two pairs of reviewers mapped data from included studies against the Framework of Knowledge Translation (FKT) and used a convergent approach to synthesise the data.ResultsThe database search yielded 27,192 reports. Following screening and full text review, 15 studies (ten qualitative, one quantitative and four mixed methods) were included. Studies were conducted in 12 mostly high-income countries, with a total of 871 participants. We identified 12 barriers and 14 facilitators mapped to five elements of the FKT. Barriers related to: (i) the user-group (n = 3) such as not perceiving health as important and (ii) the dissemination strategies (n = 3) such as lack of understanding of content of guidelines. Several facilitators related to dissemination strategies (n = 5) such as using different channels of communication. Facilitators also related to the user-group (n = 4) such as the user-groups’ interest in health and research.ConclusionResearchers and government organisations should consider these factors when identifying ways to disseminate research findings to decision-maker audiences. Future research should aim to build the evidence base on different strategies to overcome these barriers.Systematic review registrationThe protocol of this review was deposited in Open Science Framework (https://doi.org/10.17605/OSF.IO/5QSGD).