Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics.

Background: Aging is an important factor in the development of Alzheimer's disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD. Methods: The study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes. Results: A correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD. Conclusion: We explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation.

EL V.2 Model for Predicting Food Safety Risks at Taiwan Border Using the Voting-Based Ensemble Method.

Border management serves as a crucial control checkpoint for governments to regulate the quality and safety of imported food. In 2020, the first-generation ensemble learning prediction model (EL V.1) was introduced to Taiwan's border food management. This model primarily assesses the risk of imported food by combining five algorithms to determine whether quality sampling should be performed on imported food at the border. In this study, a second-generation ensemble learning prediction model (EL V.2) was developed based on seven algorithms to enhance the "detection rate of unqualified cases" and improve the robustness of the model. In this study, Elastic Net was used to select the characteristic risk factors. Two algorithms were used to construct the new model: The Bagging-Gradient Boosting Machine and Bagging-Elastic Net. In addition, Fß was used to flexibly control the sampling rate, improving the predictive performance and robustness of the model. The chi-square test was employed to compare the efficacy of "pre-launch (2019) random sampling inspection" and "post-launch (2020-2022) model prediction sampling inspection". For cases recommended for inspection by the ensemble learning model and subsequently inspected, the unqualified rates were 5.10%, 6.36%, and 4.39% in 2020, 2021, and 2022, respectively, which were significantly higher (p < 0.001) compared with the random sampling rate of 2.09% in 2019. The prediction indices established by the confusion matrix were used to further evaluate the prediction effects of EL V.1 and EL V.2, and the EL V.2 model exhibited superior predictive performance compared with EL V.1, and both models outperformed random sampling.

Artesunate alleviates intracerebral haemorrhage secondary injury by inducing ferroptosis in M1-polarized microglia and suppressing inflammation through AMPK/mTORC1/GPX4 pathway.

Intracerebral haemorrhage (ICH) is a catastrophic subtype of stroke with severe morbidity and mortality. However, little progress has been made in the subsequent secondary injury. Artesunate, a water-soluble semi-synthetic derivative of artemisinin, exhibits remarkable pharmacological effects on anti-neuroinflammation. However, the effects of artesunate on ICH remain unknown. In the present study, haemoglobin (Hb) treatment in BV2 cell and collagenase type IV intracerebroventricular injection in Sprague-Dawley rats were used to establish in vitro and in vivo ICH models, respectively. For in vivo, the neurological scores, haematoma volume, brain oedema, inflammatory factors and iron deposition were evaluated. Besides, lipopolysaccharide (LPS) was used in in vitro to polarize BV2 cell to M1 phenotype. Cell viability, cellular reactive oxygen species (ROS), Fe2+ concentration, and lipid peroxidation levels, ferroptosis-associated proteins and mRNA, morphological of mitochondria were measured in vitro. Additionally, the AMP-activated protein kinase (AMPK)/mammalian/mechanistic target of rapamycin (mTOR) pathway were measured by western blot and immunofluorescence staining. The present in vivo results indicated that artesunate significantly ameliorated neurological deficits, haematoma volume and brain oedema in ICH rats. Besides, artesunate suppressed the M1-microglia relative inflammatory factors and up-regulated iron deposition. For in vitro, artesunate significantly selectively decreased the viability of LPS-stimulated BV2 cell. Furthermore, ROS and lipid peroxidation levels were up-regulated. And the glutathione peroxidase 4 (GPX4) were silenced via the AMPK/mTORC1 axis. Our finding supports that artesunate ameliorates the ICH secondary injury both in vitro and in vivo by inducing ferroptosis in microglia and further inhibiting inflammation mainly through the AMPK/mTORC1/GPX4 pathway. This finding may provide a novel target for ICH treatment.

Clinical Characteristics and Follow-up of Cases of Streptococcus suis Meningitis in Patients of Liuzhou, China.

We analyzed the clinical characteristics and outcomes of patients with Streptococcus suis meningitis in Liuzhou, China, to improve diagnostic accuracy and lower the chances of misdiagnosis. The major clinical manifestations, auxiliary examination results, treatment strategies, treatment efficacy, and follow-up results of 17 consecutively admitted patients with S. suis meningitis were evaluated. The most common clinical manifestations were fever (15/17), sensorineural hearing loss (13/17), headache (11/17), and altered mental status (8/17). In addition, 64.71% of the patients had residual symptoms of sensorineural hearing loss at discharge, and moderate disabilities occurred in 68.75% of the patients in the form of sensorineural deafness (11/17) and hemiparesis (1/17). The cerebrospinal fluid (CSF) of nine patients was used for metagenomic analysis with next-generation sequencing. The metagenomic analysis of CSF of four patients was positive, whereas blood and CSF cultures were negative. The average modified Rankin Scale (mRS) and Activities of Daily Living (ADL) scores improved significantly at the 6-month follow-up compared with those at admission (P < 0.05). There was no correlation between altered mRS and ADL scores and the CSF findings (P > 0.05). Early administration of antibiotics can prevent sensorineural hearing loss. Early CSF metagenomic analysis may be superior to blood and CSF culture.

The Efficacy of Integrated Rehabilitation for Post-Stroke Anxiety: Study Protocol for a Prospective, Multicenter, Randomized Controlled Trial.

Background: Post-stroke anxiety (PSA) remains a challenging medical problem. Integrated rehabilitation involves a combination of traditional Chinese medicine (TCM) and Western conventional rehabilitation techniques. Theoretically, integrated rehabilitation is likely to have significant advantages in treating PSA. Nevertheless, the therapeutic effect of integrated rehabilitation needs to be verified based on large-scale trials with sound methodology. Thus, the aim of this trial is to assess the efficacy and safety of integrated rehabilitation on PSA. Methods: The study is a prospective, multicenter, randomized, controlled trial involving 188 PSA patients from four clinical centers in China. Eligible participants will be randomly divided into the integrated rehabilitation group or the standard care group. Participants in the integrated rehabilitation group will receive a combination of TCM and Western conventional rehabilitation methods, including acupuncture, repeated transcranial magnetic stimulation, traditional Chinese herbal medicine, and standard care. The primary outcome will be the Hamilton Anxiety Rating Scale (HAM-A). The secondary outcomes will include the Self-Rating Anxiety Scale (SAS), the Activities of Daily Living (ADL) scale, the Montreal Cognitive Assessment (MoCA) scale, the simplified Fugl-Meyer Assessment of motor function (FMA) scale, and the Pittsburgh Sleep Quality Index (PSQI). Outcome measurements will be performed at baseline, at the end of the 4-week treatment and the 8-week follow-up. Conclusion: Results of this trial will ascertain the efficacy and safety of integrated rehabilitation on PSA, thereby providing evidence regarding integrated rehabilitation strategies for treating PSA. It will also promote up-to-date evidence for patients, clinicians, and policy-makers. Trial Registration: ClinicalTrials.gov NCT05147077.

Light-induced expression of a novel marine laccase in Escherichia coli from Marinomonas profundimaris and its application in synthetic dye decolorization.

Laccases (EC 1.10.3.2) are green biocatalysts with a considerable potential in numerous environmental and industrial applications due to their abilities to oxidize a wide range of substrates, such as aromatic amines, while reducing molecular oxygen to water. In this study, a putative laccase, LacMp1, encoding a protein of 48.3 kDa and belonging to the Cu-oxidase_3 superfamily, was cloned and overexpressed in Escherichia coli with a light-induced expression system. High-level expression of recombinant protein LacMp1 was achieved under the light intensity of 6500 ± 200 lx from a white light-emitting diode (LED) belt. The purified LacMp1 showed high activity toward various laccase substrates, with the lowest Km value and highest kcat/Km value for syringaldazine at the optimal temperature and pH of 50 °C and 7.5. Dimethyl sulfoxide, ethanol, and metal ions such as Co2+, Ca2+, K+, Li+, Zn2+, Mn2+, Fe3+, and Ni2+ did not significantly inhibit the activity of LacMp1. Furthermore, LacMp1 showed tolerance to NaCl and kept 66.67 ± 2.24% of its initial activity at concentrations lower than 400 mM. Moreover, LacMp1 exhibited wide-spectrum decolorization ability towards indigoid, anthraquinonic, and azo dyes without the aid of redox mediators at pHs ranging from 5.0 to 9.0. It decolorized 99.83 ± 0.12% of indigo carmine, 99.54 ± 0.43% of Congo red, 88.41 ± 3.22% of Eriochrome black T, and 51.61 ± 1.82% of Reactive blue 4, respectively. These unusual properties demonstrated that LacMp1 had potential in specific industrial or environmental applications.

Effect of PCSK9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia (type III hyperlipidemia).

BACKGROUND AND AIMS: Familial dysbetalipoproteinemia (FDBL) is a rare inborn lipid disorder characterized by the formation of abnormal triglyceride- and cholesterol-rich lipoproteins (remnant particles). Patients with FDBL have a high risk for atherosclerotic disease. The effect of PCSK9 inhibition on lipoproteins and its subfractions has not been evaluated in FDBL. METHODS: Three patients (65±7 years, 23±3 kg/m2, 2 females) with FDBL (diagnosed by isoelectrofocusing) and atherosclerosis (coronary and/or cerebro-vascular and/or peripheral arterial disease) resistant or intolerant to statin and fibrate therapy received evolocumab (140mg every 14 days). In addition to a fasting lipid profile (preparative ultracentrifugation), apoB and cholesterol concentrations were determined in 15 lipoprotein-subfractions (density gradient ultracentrifugation; d 1.006-1.21g/ml) before and after 12 weeks of evolocumab treatment. Patients with LDL-hypercholesterolemia (n = 8, 56±8 years, 31±7 kg/m2) and mixed hyperlipidemia (n = 5, 68±12 years, 30±1 kg/m2) also receiving evolocumab for 12 weeks were used for comparison. RESULTS: All patients tolerated PCSK9 inhibition well. PCSK9 inhibitors reduced cholesterol (29-37%), non-HDL-cholesterol (36-50%) and apoB (40-52%) in all patient groups including FDBL. In FDBL, PCSK9 inhibition reduced VLDL-cholesterol and the concentration of apoB containing lipoproteins throughout the whole density spectrum (VLDL, IDL, remnants, LDL). Lipoprotein(a) was decreased in all patient groups to a similar extent. CONCLUSIONS: This indicates that the dominant fraction of apoB-containing lipoproteins is reduced with PCSK9 inhibition, i.e. LDL in hypercholesterolemia and mixed hyperlipidemia, and cholesterol-rich VLDL, remnants and LDL in FDBL. PCSK9 inhibition may be a treatment option in patients with FDBL resistant or intolerant to statin and/or fibrate therapy.

Identification of vasospasm biomarkers for cerebral hemorrhage via bio-informatics analysis.

BACKGROUND: The incidence of cerebral hemorrhage has rapidly increased over time, and vascular dysfunction has a significant influence on the pathogenesis and outcome of these patients. This is also the case for vasospasm in cerebral hemorrhage, but there is no method to assess this. We conducted this study to find molecular biomarkers of vasospasm in cerebral hemorrhage patients. METHODS: Raw data of GSE37924 was downloaded from the Gene Expression Omnibus (GEO) database, including 66 samples with cerebral vasospasm and 62 samples without cerebral vasospasm. Differentially expressed genes (DEGs) between samples with cerebral vasospasm and those without cerebral vasospasm were analyzed using the limma package in R software. To determine the functions of DEGs, we conducted functional enrichment analysis of DEGs through the clusterProfiler package in R. The protein-protein interaction (PPI) network of DEGs was constructed through STRING (https://string-db.org/) and generated via Cytoscape software. To understand the correlation between DEGs and immune-related genes, immune-related cerebral vasospasm genes were obtained via intersecting immune-related genes and cerebral vasospasm DEGs. We also compared the infiltration of 28 immune cells between cases with cerebral vasospasm and those without cerebral vasospasm. Finally, we constructed a model to perform the validation experiments. RESULTS: Of the DEGs, there were 24 upregulated and 21 downregulated genes in the vasospasm samples compared to the no-vasospasm samples. Functional enrichment analysis showed that these genes play key roles in several biological processes and signaling pathways such as the bone morphogenetic protein (BMP) signaling pathway, cellular response to BMP stimulus, natural killer cell chemotaxis, negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway, MHC protein complex binding, and receptor ligand activity, among others. CCL4, HLA-DQA1, IGF2, NTS, and so on were the significant immune-related genes. Furthermore, the immune cell infiltration results showed that there were differences between patients with vasospasm and those without vasospasm. Finally, we found that CCL4 had significantly higher expression in patients with vasospasm than those without vasospasm. CONCLUSIONS: CCL4 is an important regulator of vascular dysfunction in cerebral hemorrhage.

Diagnosis of Middle Cerebral Artery Stenosis Using Transcranial Doppler Images Based on Convolutional Neural Network.

BACKGROUND: The purpose of this study was to explore the diagnostic value of convolutional neural networks (CNNs) in middle cerebral artery (MCA) stenosis by analyzing transcranial Doppler (TCD) images. METHODS: Overall, 278 patients who underwent cerebral vascular TCD and cerebral angiography were enrolled and classified into stenosis and non-stenosis groups based on cerebral angiography findings. Manual measurements were performed on TCD images. The patients were divided into a training set and a test set, and the CNN architecture was used to classify TCD images. The diagnostic accuracies of manual measurements, CNNs, and TCD parameters for MCA stenosis were calculated and compared. RESULTS: Overall, 203 patients without stenosis and 75 patients with stenosis were evaluated. The sensitivity, specificity, and area under the curve (AUC) for manual measurements of MCA stenosis were 0.80, 0.83, and 0.81, respectively. After 24 iterations of the running model in the training set, the sensitivity, specificity, and AUC of the CNNs in the test set were 0.84, 0.86, and 0.80, respectively. The diagnostic value of CNNs differed minimally from that of manual measurements. Two parameters of TCD, peak systolic velocity and mean flow velocity, were higher in patients with stenosis than in those without stenosis; however, their diagnostic values were significantly lower than those of CNNs (P < 0.05). CONCLUSIONS: The diagnostic value of CNNs for MCA stenosis based on TCD images paralleled that of manual measurements. CNNs could be used as an auxiliary diagnostic tool to improve the diagnosis of MCA stenosis.

ANGPTL3 Inhibition With Evinacumab Results in Faster Clearance of IDL and LDL apoB in Patients With Homozygous Familial Hypercholesterolemia-Brief Report.

[Figure: see text].

Correction: In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model.

Correction for 'In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model' by Xiuying Li et al., Biomater. Sci., 2019, 7, 2861-2872, DOI: 10.1039/C9BM00242A.

Efficacy of Fe3O4@polydopamine nanoparticle-labeled human umbilical cord Wharton's jelly-derived mesenchymal stem cells in the treatment of streptozotocin-induced diabetes in rats.

Diabetes mellitus (DM) is characterized by the irreversible destruction of insulin-secreting pancreatic ß-islet cells and requires life-long exogenous insulin therapy. Umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been shown to improve islet function in animal models of diabetes. However, inadequate MSC homing to injured sites has limited their efficacy. Since efficient cell therapy heavily relies on appropriate homing to target tissues, increasing the specificity to the target organ and the extent of homing of the injected WJ-MSCs is paramount to successful clinical outcomes. Therefore, in this study, we synthesized Fe3O4@polydopamine nanoparticle (NP)-labeled MSCs and evaluated their therapeutic efficacy in a clinically relevant rat model of streptozotocin-induced diabetes using an external magnetic field. We found that NPs were successfully incorporated into WJ-MSCs and did not negatively affect stem cell properties. Magnetic targeting of WJ-MSCs contributed to long-term cell retention in pancreatic tissue and improved the islet function of diabetic rats, compared to injection of WJ-MSC alone. In addition, anti-inflammatory effects and the anti-apoptotic capacity of WJ-MSCs appeared to play a major role in the functional and structural recovery of the pancreas. Thus, therapy relying on the magnetic targeting of WJ-MSCs may serve as an effective approach for DM treatment.

Effectiveness and safety of atosiban versus conventional treatment in the management of preterm labor.

OBJECTIVE: To compare the efficacy of atosiban with conventional treatment of the threatened preterm labor. MATERIALS AND METHODS: All the data of pregnant women with threatened preterm labor from January 1 to December 31, 2017, who received atosiban were collected. Pregnant women with conventional treatment (including ß-agonists, indomethacin, magnesium sulphate and calcium channel blockers, alone or in combination) were used as control. RESULTS: The proportion of women not requiring an alternative tocolytic treatment within 48 h and remaining undelivered was significantly higher in atosiban treatment group (89.3%; n = 25/28) compared with conventional treatment (24.2%; n = 8/33) (P < 0.0001). For therapy efficacy, there was also no significant difference between atosiban groups and conventional treatment groups in the low gestational ages. However, for the high gestational ages, atosiban treatment group showed higher efficacy (84%; n = 21/25 vs. 37.5%; n = 3/8) (P < 0.05). Moreover, a significantly higher proportion of women in the atosiban treated group (89.3%; n = 25/28) was observed compared with the conventional treatment groups (51.5%; n = 17/33) who did not receive an alternative tocolytic within 48 h (P < 0.01). Maternal and fetal safety was significantly superior with atosiban treatment. CONCLUSIONS: Our results support that atosiban would represent an advance over current tocolytic therapy especially for the high gestational ages.

Anti-Inflammatory Effects of Magnetically Targeted Mesenchymal Stem Cells on Laser-Induced Skin Injuries in Rats.

INTRODUCTION: Mesenchymal stem cells (MSCs) are a promising resource for tissue regeneration and repair. However, their clinical application is hindered by technical limitations related to MSC enrichment at the target sites. METHODS: MSCs were labeled with magnetic Fe3O4 nanoparticles (NPs). We analyzed the effects of NP on cell proliferation, stem cell characteristics, and cytokine secretion. Furthermore, we induced NP-labeled MSC migration with an external magnetic field toward laser-induced skin wounds in rats and evaluated the associated anti-inflammatory effects. RESULTS: Fe3O4 NP application did not adversely affect MSC characteristics. Moreover, Fe3O4 NP-labeled MSCs presented increased anti-inflammatory cytokine and chemokine production compared with unlabeled MSCs. Furthermore, MSCs accumulated at the injury site and magnetic targeting promoted NP-labeled MSC migration toward burn injury sites in vivo. On day 7 following MSC injection, reduced inflammation and promoted angiogenesis were observed in the magnetically targeted MSC group. In addition, anti-inflammatory factors were upregulated, whereas pro-inflammatory factors were downregulated within the magnetically targeted MSC group compared with those in the PBS group. CONCLUSION: This study demonstrates that magnetically targeted MSCs contribute to cell migration to the site of skin injury, improve anti-inflammatory effects and enhance angiogenesis compared with MSC injection alone. Therefore, magnetically targeted MSC therapy may be an effective treatment approach for epithelial tissue injuries.

Magnetic targeting enhances the cutaneous wound healing effects of human mesenchymal stem cell-derived iron oxide exosomes.

Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo + NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and could significantly promote their proliferation, migration, and angiogenesis both in vitro and in vivo. Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration-related chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo + NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo + NPs with magnetic guidance significantly increased the number of Exo + NPs that accumulated at the injury site. Furthermore, these accumulated Exo + NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo; moreover, they reduced scar formation and increased CK19, PCNA, and collagen expression in vivo. Collectively, these findings confirm the development of therapeutically efficacious extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.

In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model.

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising therapeutic strategy for tissue regeneration and repair. However, efficient targeted delivery to specific tissues remains an open challenge. Here, we non-invasively monitored the migration of MSCs labeled with Fe3O4@polydopamine nanoparticles (Fe3O4@PDA NPs) toward laser burn injury sites in a living rat model and evaluated the effects of the labeled MSCs at the injury site. The Fe3O4@PDA NPs could be effectively incorporated into the MSCs without any negative effects on stem cell properties. Furthermore, they enhanced the migration ability of the MSCs by up-regulating the expression level of C-X-C chemokine receptor type 4 (CXCR4). They also increased the secretion of some cytokines and the expression of healing-related genes in comparison with unlabeled MSCs. Labeled MSCs were intravenously administered into injured rats, and live imaging was performed to monitor MSC migration. Fluorescent signals of the labeled MSCs appeared at burn injury lesions 1 day after injection and then gradually increased up to 7 days. After 7 days, the group injected with the labeled MSCs showed less inflammation compared with those injected with the unlabeled MSCs. Additionally, the labeled MSC group showed increased cytokines and reduced pro-inflammatory factors compared with the unlabeled MSC group. The Fe3O4@PDA NPs enhanced stromal cell-derived factor-1/CXCR4-mediated MSC migration in vivo. Thus, we demonstrated the safety, feasibility, and potential efficacy of using the Fe3O4@PDA NPs for optimizing MSC-based therapeutic strategies for burn wound healing.

Iron oxide nanoparticles promote the migration of mesenchymal stem cells to injury sites.

BACKGROUND: Developing new methods to deliver cells to the injured tissue is a critical factor in translating cell therapeutics research into clinical use; therefore, there is a need for improved cell homing capabilities. MATERIALS AND METHODS: In this study, we demonstrated the effects of labeling rat bone marrow-derived mesenchymal stem cells (MSCs) with fabricated polydopamine (PDA)-capped Fe3O4 (Fe3O4@PDA) superparticles employing preassembled Fe3O4 nanoparticles as the cores. RESULTS: We found that the Fe3O4@PDA composite superparticles exhibited no adverse effects on MSC characteristics. Moreover, iron oxide nanoparticles increased the number of MSCs in the S-phase, their proliferation index and migration ability, and their secretion of vascular endothelial growth factor relative to unlabeled MSCs. Interestingly, nanoparticles not only promoted the expression of C-X-C chemokine receptor 4 but also increased the expression of the migration-related proteins c-Met and C-C motif chemokine receptor 1, which has not been reported previously. Furthermore, the MSC-loaded nanoparticles exhibited improved homing and anti-inflammatory abilities in the absence of external magnetic fields in vivo. CONCLUSION: These results indicated that iron oxide nanoparticles rendered MSCs more favorable for use in injury treatment with no negative effects on MSC properties, suggesting their potential clinical efficacy.

Magnetic delivery of Fe3O4@polydopamine nanoparticle-loaded natural killer cells suggest a promising anticancer treatment.

Natural killer (NK)-cell-based immunotherapy has been reported to have promising prospects in the treatment of non-small cell lung cancer, one of the most common malignancies in the world. It has been proven that higher the NK cell infiltration into the tumor, the better is the curative effect. Therefore, it would be beneficial to develop a method that increases NK cell recruitment and infiltration into the tumor site. The purpose of this study was to establish an immune-cell delivery system for clear lung cancer cells based on magnetic nanoparticle (NP)-labeled NK cells that can be accumulated at the tumor site by placing a tiny external magnetic device inside animals. We developed superparamagnetic iron oxide NPs consisting of a magnetic Fe3O4 core and a shell of polydopamine (PDA) for magnetic targeting therapy. Fe3O4@PDA NPs possess favorable physiological stability and biocompatibility that facilitate their active uptake by NK cells. The biology of NK cells was not affected by the presence of NPs. In vitro and in vivo studies showed that Fe3O4@PDA NP-labeled NK cells significantly inhibited tumor growth and reduced the expression of Ki-67 and increased the apoptosis of A549 cancer cells. H&E staining showed Fe3O4@PDA NP-labeled NK cells, under a magnetic field, had higher intra-tumoral iron density and increased accumulation of CD56+ NK cells. Our results suggest that Fe3O4@PDA NPs are a promising magnetic nanomaterial that can manipulate immune cells, thereby inhibiting tumor growth.

A Walnut-Enriched Diet Affects Gut Microbiome in Healthy Caucasian Subjects: A Randomized, Controlled Trial.

Regular walnut consumption is associated with better health. We have previously shown that eight weeks of walnut consumption (43 g/day) significantly improves lipids in healthy subjects. In the same study, gut microbiome was evaluated. We included 194 healthy subjects (134 females, 63 ± 7 years, BMI 25.1 ± 4.0 kg/m²) in a randomized, controlled, prospective, cross-over study. Following a nut-free run-in period, subjects were randomized to two diet phases (eight weeks each); 96 subjects first followed a walnut-enriched diet (43 g/day) and then switched to a nut-free diet, while 98 subjects followed the diets in reverse order. While consuming the walnut-enriched diet, subjects were advised to either reduce fat or carbohydrates or both to account for the additional calories. Fecal samples were collected from 135 subjects at the end of the walnut-diet and the control-diet period for microbiome analyses. The 16S rRNA gene sequencing data was clustered with a 97% similarity into Operational Taxonomic Units (OTUs). UniFrac distances were used to determine diversity between groups. Differential abundance was evaluated using the Kruskal-Wallis rank sum test. All analyses were performed using Rhea. Generalized UniFrac distance shows that walnut consumption significantly affects microbiome composition and diversity. Multidimensional scaling (metric and non-metric) indicates dissimilarities of approximately 5% between walnut and control (p = 0.02). The abundance of Ruminococcaceae and Bifidobacteria increased significantly (p < 0.02) while Clostridium sp. cluster XIVa species (Blautia; Anaerostipes) decreased significantly (p < 0.05) during walnut consumption. The effect of walnut consumption on the microbiome only marginally depended on whether subjects replaced fat, carbohydrates or both while on walnuts. Daily intake of 43 g walnuts over eight weeks significantly affects the gut microbiome by enhancing probiotic- and butyric acid-producing species in healthy individuals. Further evaluation is required to establish whether these changes are preserved during longer walnut consumption and how these are linked to the observed changes in lipid metabolism.