Clostridium butyricum upregulates GPR109A/AMPK/PGC-1α and ameliorates acute pancreatitis-associated intestinal barrier injury in mice.

Acute pancreatitis frequently causes intestinal barrier damage, which aggravates pancreatitis. Although Clostridium butyricum exerts anti-inflammatory and protective effects on the intestinal barrier during acute pancreatitis, the underlying mechanism is unclear. The G protein-coupled receptors 109 A (GPR109A) and adenosine monophosphate-activated protein kinase (AMPK)/ peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) signaling pathways can potentially influence the integrity of the intestinal barrier. Our study generated acute pancreatitis mouse models via intraperitoneal injection of cerulein and lipopolysaccharides. After intervention with Clostridium butyricum, the model mice showed reduced small intestinal and colonic intestinal barrier damage, dysbiosis amelioration, and increased GPR109A/AMPK/PGC-1α expression. In conclusion, Clostridium butyricum could improve pancreatic and intestinal inflammation and pancreatic injury, and relieve acute pancreatitis-induced intestinal barrier damage in the small intestine and colon, which may be associated with GPR109A/AMPK/PGC-1α.

Accuracy of machine learning in preoperative identification of genetic mutation status in lung cancer: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: We performed this systematic review and meta-analysis to investigate the performance of ML in detecting genetic mutation status in NSCLC patients. MATERIALS AND METHODS: We conducted a systematic search of PubMed, Cochrane, Embase, and Web of Science up until July 2023. We discussed the genetic mutation status of EGFR, ALK, KRAS, and BRAF, as well as the mutation status at different sites of EGFR. RESULTS: We included a total of 128 original studies, of which 114 constructed ML models based on radiomic features mainly extracted from CT, MRI, and PET-CT data. From a genetic mutation perspective, 121 studies focused on EGFR mutation status analysis. In the validation set, for the detection of EGFR mutation status, the aggregated c-index was 0.760 (95%CI: 0.706-0.814) for clinical feature-based models, 0.772 (95%CI: 0.753-0.791) for CT-based radiomics models, 0.816 (95%CI: 0.776-0.856) for MRI-based radiomics models, and 0.750 (95%CI: 0.712-0.789) for PET-CT-based radiomics models. When combined with clinical features, the aggregated c-index was 0.807 (95%CI: 0.781-0.832) for CT-based radiomics models, 0.806 (95%CI: 0.773-0.839) for MRI-based radiomics models, and 0.822 (95%CI: 0.789-0.854) for PET-CT-based radiomics models. In the validation set, the aggregated c-indexes for radiomics-based models to detect mutation status of ALK and KRAS, as well as the mutation status at different sites of EGFR were all greater than 0.7. CONCLUSION: The use of radiomics-based methods for early discrimination of EGFR mutation status in NSCLC demonstrates relatively high accuracy. However, the influence of clinical variables cannot be overlooked in this process. In addition, future studies should also pay attention to the accuracy of radiomics in identifying mutation status of other genes in EGFR.

NAT10-mediated upregulation of GAS5 facilitates immune cell infiltration in non-small cell lung cancer via the MYBBP1A-p53/IRF1/type I interferon signaling axis.

Interactions of tumor cells with immune cells in the tumor microenvironment play an important role during malignancy progression. We previously identified that GAS5 inhibited tumor development by suppressing proliferation of tumor cells in non-small cell lung cancer (NSCLC). Herein, we discovered a tumor-suppressing role for tumor cell-derived GAS5 in regulating tumor microenvironment. GAS5 positively coordinated with the infiltration of macrophages and T cells in NSCLC clinically, and overexpression of GAS5 promoted macrophages and T cells recruitment both in vitro and in vivo. Mechanistically, GAS5 stabilized p53 by directly binding to MYBBP1A and facilitating MYBBP1A-p53 interaction, and enhanced p53-mediated transcription of IRF1, which activated type I interferon signaling and increased the production of downstream CXCL10 and CCL5. We also found that activation of type I interferon signaling was associated with better immunotherapy efficacy in NSCLC. Furthermore, the stability of GAS5 was regulated by NAT10, the key enzyme responsible for N4-acetylcytidine (ac4C) modification, which bound to GAS5 and mediated its ac4C modification. Collectively, tumor cell-derived GAS5 could activate type I interferon signaling via the MYBBP1A-p53/IRF1 axis, promoting immune cell infiltration and potentially correlating with immunotherapy efficacy, which suppressed NSCLC progression. Our results suggested GAS5 as a promising predictive marker and potential therapeutic target for combination therapy in NSCLC. A schematic diagram demonstrating the regulatory effect of GAS5 on immune cell infiltration by activating type I interferon signaling via MYBBP1A-p53/IRF1 axis in non-small cell lung cancer. IFN, interferon.

Probing the occurrence, sources and cancer risk assessment of polycyclic aromatic hydrocarbons in PM2.5 in a humid metropolitan city in China.

Fifty-two consecutive PM2.5 samples from December 2021 to February 2022 (the whole winter) were collected in the center of Chongqing, a humid metropolitan city in China. These samples were analysed for the 16 USEPA priority polycyclic aromatic hydrocarbons (16 PAHs) to explore their composition and sources, and to assess their cancer risks to humans. The total concentrations of the 16 PAHs (ng m-3) ranged from 16.45 to 174.15, with an average of 59.35 ± 21.45. Positive matrix factorization (PMF) indicated that traffic emissions were the major source (42.4%), followed by coal combustion/industrial emission (31.3%) and petroleum leakage/evaporation (26.3%). The contribution from traffic emission to the 16 PAHs increased from 40.0% in the non-episode days to as high as 46.2% in the air quality episode during the sampling period. The population attributable fraction (PAF) indicates that when the unit relative risk (URR) is 4.49, the number of lung cancer cases per million individuals under PAH exposure is 27 for adults and 38 for seniors, respectively. It was 5 for adults and 7 for seniors, when the URR is 1.3. The average incremental lifetime cancer risk (ILCR) for children, adolescents, adults and seniors was 0.25 × 10-6, 0.23 × 10-6, 0.71 × 10-6, and 1.26 × 10-6, respectively. The results of these two models complemented each other well, and both implied acceptable PAH exposure levels. Individual genetic susceptibility and exposure time were identified as the most sensitive parameters. The selection and use of parameters in risk assessment should be further deepened in subsequent studies to enhance the reliability of the assessment results.

Therapeutic future of Fuchs endothelial corneal dystrophy: An ongoing way to explore.

Fuchs endothelial corneal dystrophy (FECD) is one of the most common corneal diseases that causes loss of visual acuity in the world. FECD is a genetically and pathogenetically heterogeneous disease that results in the failure of corneal endothelial cells to maintain fluid balance and functional homeostasis of the cornea. Corneal edema, central guttae formation, and bullae development are common corneal pathologies. Currently, the mainstay of FECD treatment is surgery. However, limited sources of corneal graft and postsurgical complications remain problematic. In recent years, with advances in medical science and technology, there have been a few promising trials of new treatment modalities for FECD. In addition to new surgical methods, novel modalities can be classified into pharmacological-associated treatment, cell therapy-associated treatment, and gene therapy-associated treatment. In this article, our primary focus is on the most recent clinical trials related to FECD, and we present a stepwise approach to enhance FECD management and ultimately improve patient outcomes. We thoroughly searched for FECD clinical trials and reviewed the study designs, methodologies, and outcomes of each trial conducted within the past decade. It is imperative for physicians to stay up-to-date with these cutting-edge treatment approaches.

The prognostic value of sialylation-related long non-coding RNAs in lung adenocarcinoma.

There has been increasing interest in the role of epigenetic modification in cancers recently. Among the various modifications, sialylation has emerged as a dominant subtype implicated in tumor progression, metastasis, immune evasion, and chemoresistance. The prognostic significance of sialylation-related molecules has been demonstrated in colorectal cancer. However, the potential roles and regulatory mechanisms of sialylation in lung adenocarcinoma (LUAD) have not been thoroughly investigated. Through Pearson correlation, univariate Cox hazards proportional regression, and random survival forest model analyses, we identified several prognostic long non-coding RNAs (lncRNAs) associated with aberrant sialylation and tumor progression, including LINC00857, LINC00968, LINC00663, and ITGA9-AS1. Based on the signatures of four lncRNAs, we classified patients into two clusters with different landscapes using a non-negative matrix factorization approach. Collectively, patients in Cluster 1 (C1) exhibited worse prognoses than those in Cluster 2 (C2), as well as heavier tumor mutation burden. Functional enrichment analysis showed the enrichment of several pro-tumor pathways in C1, differing from the upregulated Longevity and programmed cell death pathways in C2. Moreover, we profiled immune infiltration levels of important immune cell lineages in two subgroups using MCPcounter scores and single sample gene set enrichment analysis scores, revealing a relatively immunosuppressive microenvironment in C1. Risk analysis indicated that LINC00857 may serve as a pro-tumor regulator, while the other three lncRNAs may be protective contributors. Consistently, we observed upregulated LINC00857 in C1, whereas increased expressive levels of LINC00968, LINC00663, and ITGA9-AS1 were observed in C2. Finally, drug sensitivity analysis suggested that patients in the two groups may benefit from different therapeutic strategies, contributing to precise treatment in LUAD. By integrating multi-omics data, we identified four core sialylation-related lncRNAs and successfully established a prognostic model to distinguish patients with different characterizations. These findings may provide some insights into the underlying mechanism of sialylation, and offer a new stratification way as well as clinical guidance in LUAD.

A Photoelectrochemical Sensor for the Sensitive Detection of Cysteine Based on Cadmium Sulfide/Tungsten Disulfide Nanocomposites.

In this work, a CdS-nanoparticle-decorated WS2 nanosheet heterojunction was successfully prepared and first used to modify ITO electrodes for the construction of a novel photoelectrochemical sensor (CdS/WS2/ITO). The thin-film electrode was fabricated by combining electrophoretic deposition with successive ion layer adsorption and reaction techniques. The results indicated that the synthesized heterojunction nanomaterials displayed excellent photoelectrochemical performance which was much better than that of pristine CdS nanoparticles and 2D WS2 nanosheets. Owing to the formation of the surface heterojunction and the effective interfacial electric field, the enhanced separation of photogenerated electron-hole pairs led to a remarkable improvement in the photoelectrochemical activity of CdS/WS2/ITO. This heterojunction architecture can protect CdS against photocorrosion, resulting in a stable photocurrent. Based on the specific recognition between cysteine and CdS/WS2/ITO, through the specificity of Cd-S bonds, a visible-light-driven photoelectrochemical sensor was fabricated for cysteine detection. The novel photoelectrochemical biosensor exhibited outstanding analytical capabilities in detecting cysteine, with an extremely low detection limit of 5.29 nM and excellent selectivity. Hence, CdS-WS2 heterostructure nanocomposites are promising candidates as novel advanced photosensitive materials in the field of photoelectrochemical biosensing.

Surface Plasmon Resonance Enhanced Photoelectrochemical Sensing of Cysteine Based on Au Nanoparticle-Decorated ZnO@graphene Quantum Dots.

In this work, Au nanoparticle-decorated ZnO@graphene core-shell quantum dots (Au-ZnO@graphene QDs) were successfully prepared and firstly used to modify an ITO electrode for the construction of a novel photoelectrochemical biosensor (Au-ZnO@graphene QDs/ITO). Characterization of the prepared nanomaterials was conducted using transmission electron microscopy, steady-state fluorescence spectroscopy and the X-ray diffraction method. The results indicated that the synthesized ternary nanomaterials displayed excellent photoelectrochemical performance, which was much better than that of ZnO@graphene QDs and pristine ZnO quantum dots. The graphene and ZnO quantum dots formed an effective interfacial electric field, enhancing photogenerated electron-hole pairs separation and leading to a remarkable improvement in the photoelectrochemical performance of ZnO@graphene QDs. The strong surface plasmon resonance effect achieved by directly attaching Au nanoparticles to ZnO@graphene QDs led to a notable increase in the photocurrent response through electrochemical field effect amplification. Based on the specifical recognition between cysteine and Au-ZnO@graphene QDs/ITO through the specificity of Au-S bonds, a light-driven photoelectrochemical sensor was fabricated for cysteine detection. The novel photoelectrochemical biosensor exhibited outstanding analytical capabilities in detecting cysteine with an extremely low detection limit of 8.9 nM and excellent selectivity. Hence, the Au-ZnO@graphene QDs is a promising candidate as a novel advanced photosensitive material in the field of photoelectrochemical biosensing.

Oncogenic Roles of Laminin Subunit Gamma-2 in Intrahepatic Cholangiocarcinoma via Promoting EGFR Translation.

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal biliary epithelial cancer in the liver. Here, Laminin subunit gamma-2 (LAMC2) with important oncogenic roles in iCCA is discovered. In a total of 231 cholangiocarcinoma patients (82% of iCCA patients) across four independent cohorts, LAMC2 is significantly more abundant in iCCA tumor tissue compared to normal bile duct and non-tumor liver. Among 26.3% of iCCA patients, LAMC2 gene is amplified, contributing to its over-expression. Functionally, silencing LAMC2 significantly blocks tumor formation in orthotopic iCCA mouse models. Mechanistically, it promotes EGFR protein translation via interacting with nascent unglycosylated EGFR in the endoplasmic reticulum (ER), resulting in activated EGFR signaling. LAMC2-mediated EGFR translation also depends on its interaction with the ER chaperone BiP via their C-terminus. Together LAMC2 and BiP generate a binding "pocket" of nascent EGFR and facilitate EGFR translation. Consistently, LAMC2-high iCCA patients have poor prognosis in two iCCA cohorts. LAMC2-high iCCA cells are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) treatment both in vitro and in vivo. Together, these data demonstrate LAMC2 as an oncogenic player in iCCA by promoting EGFR translation and an indicator to identify iCCA patients who may benefit from available EGFR-targeted TKIs therapies.

Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. METHODS: Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. RESULTS: The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation. CONCLUSIONS: A novel method for harvesting MSCs with neural crest origin from 3D human brain organoids under serum-free culture conditions was reported. We demonstrate that the pMSCs support human UCB-HSPC expansion in vitro in a long-term culture and the maintenance of their transplantable ability. RNA and proteomic sequencing indicated that pMSCs provided an improved microenvironment for HSC maintenance via mechanisms involving cell-cell contact and secreted factors and suppression of Wnt signaling. This represents a novel method for large-scale production of MSCs of neural crest origin and provides a potential approach for development of human hematopoietic stromal cell therapy for treatment of dyshematopoiesis.

[Corrigendum] Bax inhibitor­1 suppresses early brain injury following experimental subarachnoid hemorrhage in rats.

Following the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 6 on p. 2898, the 'SAH' and 'SAH+NC' data panels contained an apparently overlapping section of data, such that these data appeared to have been derived from the same original source, even though they were intended to show the results from differently performed experiments. The authors have examined their original data, and realize that the 'SAH+NC' data panel had inadvertently been selected incorrectly for this figure. In addition, in response to a further query from the reader, the authors wished to point out that the standard deviations in their study were statistically analysed using GraphPad Prism software version 5.0a. The revised version of Fig. 6, now showing the correct data for the 'SAH+NC' experiment, is shown on the next page. The authors can confirm that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 42: 2891­2902, 2018; DOI: 10.3892/ijmm.2018.3858].

Gut microbiota dynamics and fecal SCFAs after colonoscopy: accelerating microbiome stabilization by Clostridium butyricum.

BACKGROUND: Colonoscopy is a classic diagnostic method with possible complications including abdominal pain and diarrhoea. In this study, gut microbiota dynamics and related metabolic products during and after colonoscopy were explored to accelerate gut microbiome balance through probiotics. METHODS: The gut microbiota and fecal short-chain fatty acids (SCFAs) were analyzed in four healthy subjects before and after colonoscopy, along with seven individuals supplemented with Clostridium butyricum. We employed 16S rRNA sequencing and GC-MS to investigate these changes. We also conducted bioinformatic analysis to explore the buk gene, encoding butyrate kinase, across C. butyricum strains from the human gut. RESULTS: The gut microbiota and fecal short-chain fatty acids (SCFAs) of four healthy subjects were recovered on the 7th day after colonoscopy. We found that Clostridium and other bacteria might have efficient butyric acid production through bioinformatic analysis of the buk and assessment of the transcriptional level of the buk. Supplementation of seven healthy subjects with Clostridium butyricum after colonoscopy resulted in a quicker recovery and stabilization of gut microbiota and fecal SCFAs on the third day. CONCLUSION: We suggest that supplementation of Clostridium butyricum after colonoscopy should be considered in future routine clinical practice.

Discovery of novel pyrrolo[2,3-d]pyrimidines as potent menin-mixed lineage leukemia interaction inhibitors.

To interfere the Menin-MLL interaction using small molecular inhibitors has been shown as new treatment of several special hematological malignancies. Herein, a series of Menin-MLL interaction inhibitors with pyrrolo[2,3-d]pyrimidine scaffold were designed, synthesized and evaluated. Among them, compound A6 exhibited potent binding affinity with an IC50 value of 0.38 µM, and strong anti-proliferative activity against MV4-11 cells with an IC50 value of 1.07 µM. Further study showed A6 reduced the transcriptional levels of HOXA9 and MEIS1 genes. Moreover, A6 induced cellular apoptosis, arrested the cell cycle in G0/G1 phase, and reversed the differentiation arrest in a concentration-dependent manner. This study suggested compound A6 was as a novel potent Menin-MLL interaction inhibitor, and it proved that introduction of 4-amino pyrrolo[2,3-d]pyrimidine to occupy the P10 hydrophobic pocket was new idea for design of novel Menin-MLL interaction inhibitors.

FMB: Dual-view fusion and registration of 2D DSA images and 3D MRA images for neurointerventional-based procedures.

OBJECTIVE: Alignment between preoperative images (high-resolution magnetic resonance imaging, magnetic resonance angiography) and intraoperative medical images (digital subtraction angiography) is currently required in neurointerventional surgery. Treating a lesion is usually guided by a 2D DSA silhouette image. DSA silhouette images increase procedure time and radiation exposure time due to the lack of anatomical information, but information from MRA images can be utilized to compensate for this in order to improve procedure efficiency. In this paper, we abstract this into the problem of relative pose and correspondence between a 3D point and its 2D projection. Multimodal images have a large amount of noise and anomalies that are difficult to resolve using conventional methods. According to our research, there are fewer multimodal fusion methods to perform the full procedure. APPROACH: Therefore, the paper introduces a registration pipeline for multimodal images with fused dual views is presented. Deep learning methods are introduced to accomplish feature extraction of multimodal images to automate the process. Besides, the paper proposes a registration method based on the Factor of Maximum Bounds (FMB). The key insights are to relax the constraints on the lower bound, enhance the constraints on the upper bounds, and mine more local consensus information in the point set using a second perspective to generate accurate pose estimation. MAIN RESULTS: Compared to existing 2D/3D point set registration methods, this method utilizes a different problem formulation, searches the rotation and translation space more efficiently, and improves registration speed. SIGNIFICANCE: Experiments with synthesized and real data show that the proposed method was achieved in accuracy, robustness, and time efficiency.

Protective effects of functional Nano-Selenium supplementation on spleen injury through regulation of p38 MAPK and NF-κB protein expression.

Selenium (Se) is a trace element necessary for humans to maintain normal physiological activities, and Se deficiency may lead to splenic injury, while Se supplementation can alleviate splenic injury. However, the mechanism is unclear. In this study, we constructed a Se deficiency animal model by feeding Sprague-Dawley (SD) rats with low Se feed. Meanwhile, we observed the repairing effect of Se supplementation on splenic injury with two doses of novel nano-selenium (Nano-Se) supplement by gavage. We measured the Se content in the spleens of the rats by atomic fluorescence spectroscopy (AFS) method and combined the results of hematoxylin-eosin (HE) and Masson staining to observe the splenic injury, comprehensively evaluating the construction of the animal model of low selenium-induced splenic injury. We measured the mRNA and protein expression levels of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa-B (NF-κB), and interleukin-6 (IL-6) in the spleen by Real-time quantitative polymerase chain reaction (qPCR), western blot (WB), and immunohistochemistry (IHC). We found that the Se deficiency group exhibited lower Se content, splenic fibrosis, and high expression of p38 MAPK, NF-κB, and IL-6 compared to the normal group. The Se supplement groups exhibited higher Se content, attenuated splenic injury, and down-regulated expression of p38 MAPK, NF-κB, and IL-6 relative to the Se deficiency group. This study suggests that Se deficiency leads to splenic injury in rats, and Se supplementation may attenuate splenic injury by inhibiting the expression of p38 MAPK, NF-κB and IL-6.

Experimental prognostic model integrating N6-methyladenosine-related programmed cell death genes in colorectal cancer.

Colorectal cancer (CRC) intricacies, involving dysregulated cellular processes and programmed cell death (PCD), are explored in the context of N6-methyladenosine (m6A) RNA modification. Utilizing the TCGA-COADREAD/CRC cohort, 854 m6A-related PCD genes are identified, forming the basis for a robust 10-gene risk model (CDRS) established through LASSO Cox regression. qPCR experiments using CRC cell lines and fresh tissues was performed for validation. The CDRS served as an independent risk factor for CRC and showed significant associations with clinical features, molecular subtypes, and overall survival in multiple datasets. Moreover, CDRS surpasses other predictors, unveiling distinct genomic profiles, pathway activations, and associations with the tumor microenvironment. Notably, CDRS exhibits predictive potential for drug sensitivity, presenting a novel paradigm for CRC risk stratification and personalized treatment avenues.

Mechanisms by which sheep milk consumption ameliorates insulin resistance in high-fat diet-fed mice.

Sheep milk is rich in fat, protein, vitamins and minerals and is also one of the most important sources of natural bioactives. Several biopeptides in sheep milk have been reported to possess antibacterial, antiviral and anti-inflammatory properties, and they may prevent type 2 diabetes (T2D), disease and cancer. However, the precise mechanism(s) underlying the protective role of sheep milk against T2D development remains unclear. Therefore, in the current study, we investigated the effect of sheep milk on insulin resistance and glucose intolerance in high-fat diet (HFD)-fed mice, by conducting intraperitoneal glucose tolerance tests, metabolic cage studies, genomic sequencing, polymerase chain reaction, and biochemical assays. Hyperinsulinemic-euglycemic clamp-based experiments revealed that mice consuming sheep milk exhibited lower hepatic glucose production than mice in the control group. These findings further elucidate the mechanism by which dietary supplementation with sheep milk alleviates HFD-induced systemic glucose intolerance.

The Antioxidant Mechanism of Peptides Extracted from Tuna Protein Revealed Using a Molecular Docking Simulation.

Tuna protein serves as a significant source of bioactive peptides, and its functional properties can be elucidated through predictive modeling, followed by experimental validation. In this study, the active polypeptides were obtained from tuna protein via enzymatic hydrolysis (TPP), and their peptide sequences were determined. Furthermore, the potential activity of these peptides was predicted, focusing on antioxidant peptides, and compared to the sequence library of known antioxidant peptides to identify common structural motifs. The accuracy of the prediction results was confirmed through in vitro antioxidant assays and molecular docking studies. We identified seven specific peptide segments derived from tuna protein that exhibit antioxidant potential, accounting for approximately 15% of all active peptides. Molecular docking and cell experiments were employed to provide compelling evidence for the presence of antioxidant peptides within tuna protein. This study not only lays a solid foundation for studying the structure of active peptides but also opens up a novel avenue for an expedited assessment of their properties.

Efficacy of mesenchymal stromal cells in the treatment of type 1 diabetes: a systematic review.

To investigate the efficacy of mesenchymal stromal cells in the treatment of type 1 diabetes. Articles about the effects of mesenchymal stromal cells for T1D were retrieved in PubMed, Web of Science, Embase, and the Cochrane Library databases up to July 2023. Additional relevant studies were manually searched through citations. HbA1c, FBG, PBG, insulin requirement and C-peptide were assessed. The risk of bias was evaluated with the ROB 2.0 and ROBINS-I tools. Six RCTs and eight nRCTs were included. Of the 14 studies included, two evaluated BM-MSCs, three evaluated UC-MSCs, five evaluated AHSCT, two evaluated CB-SCs, and two evaluated UC-SCs plus aBM-MNCs. At the end of follow-up, ten studies found that mesenchymal stromal cells improved glycemic outcomes in T1D, while the remaining four studies showed no significant improvement. Findings support the positive impacts observed from utilizing mesenchymal stromal cells in individuals with T1D. However, the overall methodological quality of the identified studies and findings is heterogeneous, limiting the interpretation of the therapeutic benefits of mesenchymal stromal cells in T1D. Methodically rigorous research is needed to further increase credibility.