A modified nucleoside O6-methyl-2'-deoxyguanosine-5'-triphosphate exhibits anti-glioblastoma activity in a caspase-independent manner.

Resistance to temozolomide (TMZ), the frontline chemotherapeutic agent for glioblastoma (GBM), has emerged as a formidable obstacle, underscoring the imperative to identify alternative therapeutic strategies to improve patient outcomes. In this study, we comprehensively evaluated a novel agent, O6-methyl-2'-deoxyguanosine-5'-triphosphate (O6-methyl-dGTP) for its anti-GBM activity both in vitro and in vivo. Notably, O6-methyl-dGTP exhibited pronounced cytotoxicity against GBM cells, including those resistant to TMZ and overexpressing O6-methylguanine-DNA methyltransferase (MGMT). Mechanistic investigations revealed that O6-methyl-dGTP could be incorporated into genomic DNA, disrupting nucleotide pools balance, and inducing replication stress, resulting in S-phase arrest and DNA damage. The compound exerted its anti-tumor properties through the activation of AIF-mediated apoptosis and the parthanatos pathway. In vivo studies using U251 and Ln229 cell xenografts supported the robust tumor-inhibitory capacity of O6-methyl-dGTP. In an orthotopic transplantation model with U87MG cells, O6-methyl-dGTP showcased marginally superior tumor-suppressive activity compared to TMZ. In summary, our research, for the first time, underscores the potential of O6-methyl-dGTP as an effective candidate against GBM, laying a robust scientific groundwork for its potential clinical adoption in GBM treatment regimens.

Highly extensile approach for comminuted ulna coronoid process fractures with mini-plate fixation: a case series of 31 patients.

BACKGROUND: For the treatment of coronoid process fractures, medial, lateral, anterior, anteromedial, and posterior approaches have been increasingly reported; however, there is no general consensus on the method of fixation of coronal fractures. Here, we present a highly-extensile minimally invasive approach to treat coronoid process fractures using a mini-plate that can achieve anatomic reduction, stable fixation, and anterior capsular repair. Further, the study aimed to determine the complication rate of the anterior minimally invasive approach and to evaluate functional and clinical patient-reported outcomes during follow-up. METHODS: Thirty-one patients diagnosed with coronoid fractures accompanied with a "terrible triad" or posteromedial rotational instability between April 2012 and October 2018 were included in the analysis. Anatomical reduction and mini-plate fixation of coronoid fractures were performed using an anterior minimally invasive approach. Patient-reported outcomes were evaluated using the Mayo Elbow Performance Index (MEPI) score, range of motion (ROM), and the visual analog score (VAS). The time of fracture healing and complications were recorded. RESULTS: The mean follow-up time was 26.7 months (range, 14-60 months). The average time to radiological union was 3.6 ± 1.3 months. During the follow-up period, the average elbow extension was 6.8 ± 2.9° while the average flexion was 129.6 ± 4.6°. According to Morrey's criteria, 26 (81%) elbows achieved a normal desired ROM. At the last follow-up, the mean MEPI score was 98 ± 3.3 points. There were no instances of elbow instability, elbow joint stiffness, subluxation or dislocation, infection, blood vessel complications, or nerve palsy. Overall, 10 elbows (31%) experienced heterotopic ossification. CONCLUSION: An anterior minimally invasive approach allows satisfactory fixation of coronoid fractures while reducing incision complications due to over-dissection of soft tissue injuries. In addition, this incision does not compromise the soft tissue stability of the elbow joint and allows the patient a more rapid return to rehabilitation exercises.

Robot-assisted versus navigation-assisted screw placement in spinal vertebrae.

PURPOSE: Both robots and navigation are effective strategies for optimizing screw placement, as compared to freehand placement. However, few studies have compared the accuracy and efficiency of these two techniques. Thus, the purpose of this study is to compare the accuracy and efficiency of robotic and navigation-assisted screw placement in the spinal vertebrae. METHODS: The 24 spine models were divided into a robot- and navigation-assisted groups according to the left and right sides of the pedicle. The C-arm transmits image data simultaneously to the robot and navigates using only one scan. After screw placement, the accuracy of the two techniques were compared using "angular deviation" and "Gertzbein and Robbins scale" in different segments (C1-7, T1-4, T5-8, T9-12, and L1-S1). In addition, operation times were compared between robot- and navigation-assisted groups. RESULTS: Robots and navigation systems can simultaneously assist in screw placement. The robot-assisted group had significantly less angular deviation than the navigation-assisted group from C1 to S1 (p < 0.001). At the C1-7 and T1-4 segments, the robot-assisted group had a higher rate of acceptable screws than the robot-assisted group. However, at the T5-8, T9-12, and L1-S1 segments, no significant difference was found in the incidence of acceptable screws between the two groups. Moreover, robot-assisted screw placement required less operative time than navigation (p < 0.05). CONCLUSION: The robot is more accurate and efficient than navigation in aiding screw placement. In addition, robots and navigation can be combined without increasing the number of fluoroscopic views.

Transcriptomic analysis reveals process of autolysis of Kluyveromyces marxianus in vacuum negative pressure and the higher temperature.

Kluyveromyces marxianus is expected to be used in the production of yeast extracts due to its good fermentation ability and nutritional properties. Yeast autolysis is a key process to produce yeast extract and vacuum negative pressure stress can be used as an effective way to assist autolysis. However, the molecular mechanism of initiating Kluyveromyces marxianus autolysis induced by vacuum negative pressure and the higher temperature is still unclear. In this study, RNA-seq technology was performed mainly to analyze autolytic processes in Kluyveromyces marxianus strains. Considerable differentially expressed genes (DEGs) of downregulation were significantly enriched in 7 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to synthesis and transport of RNA and ribosome, which indicated that abnormal protein translations had already occurred in autolytic process. Interestingly, due to obvious change of related DEGs, endoplasmic reticulum-associated degradation (ERAD) and autophagy were activated and cell wall integrity pathway was hindered. Under the continuous influence of the external stress environment, the long-term changes of the above pathways triggered a vicious circle of gradual damage to yeast cells, which is the main cause of yeast autolysis. These results may provide important clues for the in-depth interpretation of the yeast autolytic mechanism.

Retraction Note: Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12944-020-01416-2.

Erratum: Association of Genes Variants in RANKL/RANK/OPG Signaling Pathway with the Development of Osteonecrosis of the Femoral Head in Chinese Population: Erratum.

[This corrects the article DOI: 10.7150/ijms.19124.].

Association of Genes Variants in RANKL/RANK/OPG Signaling Pathway with the Development of Osteonecrosis of the Femoral Head in Chinese Population.

The RANKL/RANK/OPG pathway plays an important role in regulating bone remodeling and bone turnover. However, the association of the genes variants with the risk of ONFH has rarely been reported. Here, we analyzed the correlation of the 10 SNPs polymorphisms of RANKL, RANK, OPG, TRAF6, and NFATC1 genes with the risk and development of ONFH in 200 ONFH patients and 177 health controls of Chinese population with using Mass ARRAY® platform. The results showed that the recessive model of NFATC1rs9518 was significantly associated with increased ONFH risk (OR:8.223, P=0.048); the proportion of stage Ⅳ patients in the rs9518TC genotype carriers was statistically higher than that of stage Ⅲ patients (P=0.03); in the T-C haplotype carriers of Naftac1, the proportion of bilateral hips lesions was also significantly enhanced than that of unilateral hip lesions(P=0.05). In addition, the proportion of idiopathic ONFH in the TT genotype carriers of OPGrs2073617 was significantly higher than that of steroid or alcohol-induced ONFH, respectively, while in the TC genotype carriers of the SNP, the proportion of idiopathic ONFH remarkably decreased compared with that of Alcohol-induced ONFH, P=0.021. Our results were first found that NFATC1rs9518 closely associated with the risk and the development of ONFH, while OPGrs2073617 statistically correlated with the etiological classification of ONFH.

[Prediction of Greenhouse Cucumber Disease Based on Chlorophyll Fluorescence Spectrum Index].

The occurrence of greenhouse vegetable diseases and its epidemic seriously affect the production and management of facility agriculture, which greatly reduce the economic benefits of facility agriculture. In order to achieve nondestructive and accurate prediction of greenhouse vegetable diseases, this paper taking cucumber downy mildew disease as the research object, constructed spectrum characteristic index by using chlorophyll fluorescence induced by laser and established the prediction model of greenhouse vegetable diseases. In this paper, the experiment used comparative analysis method. The healthy leaves of the crops were inoculated with the pathogen spores, the spectrum curves of four groups of test samples: healthy, 2 d inoculated, 6 d inoculated and the ones with obvious symptoms were collected; then qualitative analysis was given to the variation regulation of the fluorescence intensity with the leaf samples infected with the pathogen spores. The chlorophyll fluorescence spectrum index k1=F685/F512 and k2=F734/F512 were created by using the peak and valley values of different bands. According to the range of values, set k1=20 and k2=10 as the characteristic value to judge the sample with obvious symptoms or with no obvious symptoms, and the accuracy rate of the judgment was 96% and 94% respectively. Based on spectrum index created and the classification results of sample health status, we selected the spectrum index F685/F512, F685-F734, F715/F612 to determine the health status of the sample and selected spectrum index F685/F512, F734/F512, F685-F734, F715/F612 as the inputs of quantitative analysis model. Regarding classification accuracy of prediction set as the evaluation criteria, we compared three data modeling methods: discriminant analysis, BP neural network and support vector machine. The results showed that the forecasting ability can reach 91.38% when the support vector machine was used as the modeling method for predicting the downy mildew disease. Use the method with chlorophyll fluorescence induced by laser to construct spectrum index to study the prediction of plant diseases, which has a good classification and identification effect.

[Prediction Model on Net Photosynthetic Rate of Soybean Plant Groups Based on Kernel Function and Visible Light Spectrum].

The paper uses MSR-16 portable multispectral radiometer made in the USA and computes the numbers of the test units by pulling the formula on the radiometer effective observation area, which solves the problem on the uncertain numbers of computing the times on region visible light band spectral radiation ratio M_D. The paper uses CI-310 portable photosynthesis measurement system made by American CID Company and measures the net photosynthetic rate of a group of soybean plant. M_D and C_D are normalized by the normalization method [0,1]. Then, the normalization data M_D1 and C_D1 are gained . Based on the different test time, M_D1 is divided of M_D11 and M_D12. C_D1 is divided of C_D11 and C_D12. The paper uses polynomial kernel function, gauss kernel function, sigmoid kernel function and bio-selfadaption kernel function constructed by us with Support Vector Machine. Penalty parameter c and parameter g separately are optimized with optimization algorithms such as grid-search，genetic algorithm and particle swarm optimization. Based on the formula epsilon-SVR and the formula nu-SVR with Support Vector Machine, the paper constructs the prediction model on the net photosynthetic rate of a group of soybean plant by using of the cross combination with four kernel functions, three optimization methods and two formulas. The test results are as follows: in the condition of S=17 m2 which is the test plan area of soybean plant and the H=2 m which is the high on MSR-16 portable multispectral radiometer above the canopy of soybean plant, the prediction accuracy is up to 85% on the No.1 prediction set C_D12 and the prediction accuracy is up to 82% on the No.2 prediction set C_D12 based on the model epsilon-SVR-bio-selfadaption-grid-search. In the condition of other combinations with S and H, the prediction accuracy is up to 81% on the No.2 prediction set C_D12 based on the model epsilon-SVR-bio-selfadaption-grid-search. The model epsilon-SVR-bio-selfadaption-grid-search indicates the validity of bio-selfadaption kernel functions which is constructed by our previous research with support vector machine. The model epsilon-SVR-bio-selfadaption-grid-search indicates the rationality of the measure method on visible spectral data in the test area. The model epsilon-SVR-bio-selfadaption-grid-search indicates the feasibility of the prediction method on net photosynthetic rate of soybean plant groups by using of visible spectrum.

Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma.

BACKGROUND: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80% of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20% suggesting poor prognosis. METHODS: The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied. RESULTS: MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 µM with an IC50 of 20 µM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 µM RACC was decreased by 49 and 76% respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice. CONCLUSIONS: Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma.

Identification of the changes in the platelet proteomic profile of elderly individuals.

Background: Platelet hyperreactivity is a risk factor for thrombosis in elderly patients with cardiovascular diseases. However, the mechanism of platelet hyperactivation has not been elucidated. This study aims to investigate alterations in the proteomes of platelets and their correlation with platelet hyperreactivity among elderly individuals. Methods: This study included 10 young (28.1 ± 1.9 years), 10 middle-aged (60.4 ± 2.2 years), and 10 old (74.2 ± 3.0 years) subjects. Washed platelets were used in the present study. Platelet samples were analysed by using data-independent acquisition (DIA) quantitative mass spectrometry (MS). Results: The results showed that the platelet proteomic profile exhibited high similarity between the young and middle-aged groups. However, there were significant differences in protein expression profiles between the old group and the young group. By exploring the dynamic changes in the platelet proteome with ageing, clusters of proteins that changed significantly with ageing were selected for further investigation. These clusters were related to the initial triggering of complement, phagosome and haemostasis based on enrichment analysis. We found that platelet degranulation was the major characteristic of the differentially expressed proteins between the old and young populations. Moreover, complement activation, the calcium signalling pathway and the nuclear factor-κB (NF-κB) signalling pathway were enriched in differentially expressed proteins. Conclusions: The present study showed that there are obvious differences in the protein profiles of the elderly compared with young and middle-aged populations. The results provide novel evidence showing changes in platelet hyperactivity and susceptibility to thrombosis in the elderly population.

Untangling the environmental and tectonic drivers of the Noto earthquake swarm in Japan.

The underlying mechanism of the ongoing seismic swarm in the Noto Peninsula, Japan, which generates earthquakes at 10 times the average regional rate, remains elusive. We capture the evolution of the subsurface stress state by monitoring changes in seismic wave velocities over an 11-year period. A sustained long-term increase in seismic velocity that is seasonally modulated drops before the earthquake swarm. We use a three-dimensional hydromechanical model to quantify environmentally driven variations in excess pore pressure, revealing its crucial role in governing the seasonal modulation with a stress sensitivity of 6 × 10-9 per pascal. The decrease in seismic velocity aligns with vertical surface uplift, suggesting potential fluid migration from a high-pore pressure zone at depth. Stress changes induced by abnormally intense snow falls contribute to initiating the swarm through subsequent perturbations to crustal pore pressure.

Cell-free DNA methylation patterns in aging and their association with inflamm-aging.

Aim: Liquid biopsies analyzing cell-free DNA (cfDNA) methylation in plasma offer a noninvasive diagnostic for diseases, with the potential of aging biomarkers underexplored. Methods: Utilizing enzymatic methyl-seq (EM-seq), this study assessed cfDNA methylation patterns in aging with blood from 35 healthy individuals. Results: It found aging signatures, including higher cfDNA levels and variations in fragment sizes, plus approximately 2000 age-related differentially methylated CpG sites. A biological age predictive model based on 48 CpG sites showed a strong correlation with chronological age, verified by two datasets. Age-specific epigenetic shifts linked to inflammation were revealed through differentially methylated regions profiling and Olink proteomics. Conclusion: These findings suggest cfDNA methylation as a potential aging biomarker and might exacerbate immunoinflammatory reactivity in older individuals.

Our bodies undergo many changes as we age, some of which might affect our health. To better understand these changes, scientists study something called 'cell-free DNA' (cfDNA) in our blood. This cfDNA can give us clues about our health and the risk of diseases like cancer or heart conditions.In our research, we analyzed cfDNA from the blood of 35 people to identify patterns associated with aging. We discovered that approximately 2000 specific spots in our DNA change in a way that's linked to aging. These changes might help us figure out someone's biological age ­ essentially, how old their body seems based on various health factors, which can differ from their actual age.We also found that these DNA changes could indicate how aging might make the body's defense system ­ which fights off diseases ­ react more intensely. Understanding this could be crucial for managing health as we get older.Our study suggests that cfDNA could be a useful marker for aging, offering a new approach to understanding and possibly managing the health effects associated with growing older.

Combined degenerative and regenerative remodeling responses of the mandibular condyle to experimentally induced disordered occlusion.

INTRODUCTION: The purposes of this research were to investigate the long-term responses of mandibular condylar cartilage to experimentally induced disordered occlusion and to evaluate changes in the expression of the SDF-1/CXCR4 axis. METHODS: Experimentally induced disordered occlusions were created in 8-week-old female Sprague-Dawley rats by orthodontic methods. After 24 weeks, remodeling of the mandibular condylar cartilage was assessed by hematoxylin and eosin staining. Protein and mRNA expression of SDF-1, CXCR4, MMP9, IL6, OPG, and RANKL were investigated by means of immunohistochemical staining and real-time polymerase chain reaction. RESULTS: Obvious cartilage degenerative remodeling responses were observed; they appeared as uneven distributions of cellular disposition, loss of cartilage surface integrity, and cell-free areas. Regenerative responses presenting as thickening of the whole and the calcified cartilage layers in the experimental group were also observed. Compared with the age-matched controls, the protein and mRNA levels of SDF-1, CXCR4, MMP9, IL6, and OPG, but not RANKL, were increased in the experimental group (all, P <0.05). In addition, the mRNA level of RANKL/OPG showed a decreasing trend in the experimental group compared with the age-matched controls (P = 0.052). CONCLUSIONS: This study demonstrated that long-term experimentally induced disordered occlusion leads to a combined response in degeneration and regeneration of mandibular cartilage, accompanied by active interaction of the SDF-1/CXCR4 axis and local upregulation of MMP9, IL6, and OPG.

What makes low-frequency earthquakes low frequency.

Low-frequency earthquakes, atypical seismic events distinct from regular earthquakes, occur downdip of the seismogenic megathrust where an aseismic rheology dominates the subduction plate boundary. Well situated to provide clues on the slip regime of this unique faulting environment, their distinctive waveforms reflect either an unusual rupture process or unusually strong attenuation in their source zone. We take advantage of the unique geometry of seismicity in the Nankai Trough to isolate the spectral signature of low-frequency earthquakes after correcting for empirically derived attenuation. We observe that low-frequency earthquake spectra are consistent with the classical earthquake model, yet their rupture duration and stress drop are orders of magnitude different from ordinary earthquakes. We conclude their low-frequency nature primarily results from an atypical seismic rupture process rather than near-source attenuation.

Electrospun polymer nanocomposites for thermal management: a review.

Thermal management plays a vital role in technology (electronic and electrical equipment) and life (high-temperature injury). Therefore, thermal regulation has attracted worldwide attention. This review addresses the applications of electrospinning (e-spinning) in the thermal management of polymer matrix composites, mainly involving enhanced thermal conductivity (TC), thermal insulation, and passive daytime radiative cooling (PDRC). In particular, in the regulation of TC, e-spinning can uniformly distribute active fillers in the composites to achieve bidirectional control. The types of active filler and its connection forms in the composites are discussed emphatically. In addition, PDRC without energy consumption is also highlighted. Finally, the current challenges and future development are addressed.

Cross-linking electrospinning.

Although electrospinning (e-spinning) has witnessed rapid development in recent years, it has also been criticized by environmentalists due to the use of organic solvents. Therefore, aqueous e-spinning (green e-spinning) is considered a more attractive technique. However, considering the poor water resistance and mechanical properties of electrospun (e-spun) nanofibers, cross-linking is a perfect solution. In this review, we systematically discuss the cross-linking e-spinning system for the first time, including cross-linking strategies (in situ, liquid immersion, vapor, and spray cross-linking), cross-linking mechanism (physical and chemical cross-linking) of e-spun nanofibers, and the various applications (e.g., tissue engineering, drug delivery, water treatment, food packaging, and sensors) of cross-linked e-spun nanofibers. Among them, we highlight several cross-linking methods, including UV light cross-linking, electron beam cross-linking, glutaraldehyde (and other commonly used cross-linking agents) chemical cross-linking, thermal cross-linking, and enzymatic cross-linking. Finally, we confirm the significance of cross-linking e-spinning and reveal the problems in the construction of this system.

Surgical flip-dislocation of the bicolumnar approach without olecranon osteotomy versus olecranon osteotomy in type AO 13C3 distal humeral fracture: a matched-cohort study.

BACKGROUND: Our experience with the surgical flip-dislocation of the bicolumnar (SFDB) approach for type AO 13C3 humeral fractures indicates that this surgical approach can be performed safely and effectively in appropriately selected patients. We aimed to evaluate the clinical outcomes of the SFDB approach without olecranon osteotomy (OO) for type AO 13C3 distal humeral fractures. METHODS: We retrospectively reviewed 65 cases of type AO 13C3 distal humeral fractures treated between April 2008 and July 2018; 33 patients were treated with the SFDB approach, and the remaining were treated with OO. Propensity score matching was used to control for sex, age, and the American Society of Anesthesiology score. Elbow pain, range of motion, stability, and function were assessed using the Mayo Elbow Performance Index (MEPI) and the Disabilities of the Arm, Shoulder, and Hand questionnaire. Clinical complications, reoperation rates, and radiographic results were compared between the groups. RESULTS: Operative time and blood loss were significantly lower in the SFDB group than in the OO group (P = 0.001, P = 0.002, respectively). At the final follow-up, the mean postoperative MEPI did not significantly differ between the groups (P = 0.628). According to Morrey's criteria, a typical functional range of elbow motion was achieved in 12 and 15 patients in the SFDB and OO groups, respectively. CONCLUSIONS: The SFDB approach achieves superior exposure of the articular surface without injury to the extensor mechanism in type 13C3 articular surface fracture treatment. This approach also results in good early functional recovery and clinical outcomes, with a low risk of complications.

Colonic L-cell impairment in aged subjects with type 2 diabetes leads to diminished GLP-1 production.

AIMS: Glucagon-like peptide 1 (GLP-1) is produced by the L subtype of enteroendocrine cells (EECs). Patients with type 2 diabetes (T2D) exhibit reduced incretin effect, but the pathophysiology and functional change of the L-cells remain unclear. Deciphering the mechanisms of the biological changes in L-cells under T2D conditions may assist in the research of gut-based strategies for T2D therapy. METHODS: We investigated the fasting serum GLP-1 levels and the distribution of colonic L-cells in young and aged participants with and without T2D. Additionally, we established an aged male T2D Wistar rat model subjected to a long-term high-fat and high-fructose (HFHF) diet. Histological investigations and single-cell RNA sequencing (scRNA-seq) analyses were performed to explore the mechanisms underlying functional changes in the colonic EECs. RESULTS: We observed a decline in circulating GLP-1 levels and a reduced number of colonic L-cells in elderly patients with T2D. The mechanisms underlying impaired L-cell formation and disturbed GLP-1 production were revealed using aged T2D rats induced by a long-term HFHF diet. The scRNA-seq results showed that the transcription factors that regulate L-cell commitment, such as Foxa1, were downregulated, and the expression of genes that participate in encoding GLP-1, GLP-1 posttranslational processing, hormone secretion, and nutrient sensing was disturbed. CONCLUSIONS: Taken together, the reduced L-cell lineage commitment and disturbed L-cell functions might be the major cause of the reduced GLP-1 production in aged populations with T2D. Our study provides new insights for identifying novel targets in colonic L-cells for improving endogenous GLP-1 production.

Human umbilical cord blood-derived stromal cells, a new resource in the suppression of acute graft-versus-host disease in haploidentical stem cell transplantation in sublethally irradiated mice.

Human umbilical cord blood-derived stromal cells (hUCBDSCs), a novel population isolated from CD34(+) cells by our laboratory, exerted an immunosuppressive effect on xenogenic T cells. This study aimed to investigate whether hUCBDSCs play a critical role in the suppression of acute graft-versus-host disease (aGVHD). The hUCBDSCs were co-cultured with splenocytes (SPCs) of donor C57BL/6 mice. The aGVHD in the recipient (B6×BALB/c) F1 mice was induced by the infusion of bone marrow cells and SPCs from donor mice following sublethal irradiation. The shift in vivo for hUCBDSCs was detected. The proliferation and cell cycle of SPCs were tested by cell counting kit-8 and flow cytometry, respectively. The expression of CD49b natural killer (NK) cells and CD3 T cells was detected by flow cytometry in co-culture and post-transplantation. IL-4, and IFN-γ were detected by ELISA in the serum of co-culture and post-transplantation. The survival time, body weight, clinical score, and histopathological score were recorded for mice post-transplantation. The hUCBDSCs promoted the proliferation of SPCs and significantly increased the ratio of the S and G(2)/M phase (p < 0.05). The hUCBDSCs significantly increased the expression of CD49b NK cells and IL-4 protein and decreased the expression of CD3 T cells and IFN-γ protein both in vitro and in vivo. The survival time of mice with co-transplantation of hUCBDSCs was significantly prolonged, and decreased clinical and histopathological scores were also observed. The hUCBDSCs were continually detected in the target organs of GVHD. These results suggest that hUCBDSCs possess the capability of suppressing aGVHD, possibly via their influence on CD3 T cells, NK cells, and cytokines.