Effects of miR-29c on proliferation and adipogenic differentiation of porcine bone marrow mesenchymal stromal cells.

microRNAs (miRNAs), a subclass of noncoding short RNAs, direct cells fate decisions that are important for cell proliferation and cell lineage decisions. Adipogenic differentiation contributes greatly to the development of white adipose tissue, involving of highly organized regulation by miRNAs. In the present study, we screened and identified 78 differently expressed miRNAs of porcine BMSCs during adipogenic differentiation. Of which, the role of miR-29c in regulating the proliferation and adipogenic differentiation was proved and detailed. Specifically, over-expression miR-29c inhibits the proliferation and adipogenic differentiation of BMSCs, which were reversed upon miR-29c inhibitor. Interference of IGF1 inhibits the proliferation and adipogenic differentiation of BMSCs. Mechanistically, miR-29c regulates the proliferation and adipogenic differentiation of BMSCs by targeting IGF1 and further regulating the MAPK pathway and the PI3K-AKT-mTOR pathway, respectively. In conclusion, we highlight the important role of miR-29c in regulating proliferation and adipogenic differentiation of BMSCs.

Transcriptome analysis of pigeon pituitary gland: expression changes of genes encoding protein and peptide hormones at different breeding stages.

Unlike other poultry, parent pigeons produce "pigeon milk" in their crops to nurture their squabs, which is mainly controlled by prolactin (PRL). Exception for PRL, the pituitary gland may also release various other peptide and protein hormones. However, whether these hormones change during pigeon crop lactation and their potential physiological functions remain unclear. Here, to identify potential peptide or protein hormone genes that regulate crop lactation, we conducted transcriptome analysis of pigeon pituitary glands at 3 different breeding stages (the ceased stage-nonincubation and non-nurturing stage, the 11th d of the incubation, and the 1st d of the nurturing stage) using RNA sequencing (RNA-Seq). Our analysis identified a total of 15,191 mRNAs and screened out 297 differentially expressed genes (DEG), including PRL, VIP, etc. The expression abundance of PRL mRNA on the 1st d of the nurturing stage was respectively 4.93 and 3.62 folds higher when compared to the ceased stage and the 11th d of the incubation stage. Additionally, the expression abundance of VIP is higher in the 1st d of the nurturing stage than in the ceased stage. Protein-protein interaction (PPI) network and Molecular Complex Detection (MCODE) analysis identified several vital DEGs (e.g., GHRHR, VIP, etc.), being closely linked with hormone and enriched in neuropeptide signaling pathway and response to the hormone. Expression pattern analysis revealed that these DEGs exhibited 4 distinct expression patterns (profile 10, 16, 18, 19). Genes in profile 10 and 19 presented a trend with the highest expression level on 1st d of the nurturing stage, and functional enrichment analysis indicated that these genes are involved in neuropeptide hormone activity, receptor-ligand activity, and the extracellular matrix, etc. Taken together, being consistent with PRL, some genes encoding peptide and protein hormones (e.g., VIP) presented differentially expressed in different breeding stages. It suggests that these hormones may be involved in regulation of the crop lactation process or corresponding behavior in domestic pigeons. The results of this study help to gain new insights into the role of pituitary gland in regulating pigeon lactation.

Reorganization of the structural connectome during vision recovery in pituitary adenoma patients post-transsphenoidal surgery.

Pituitary adenomas (PAs) can exert pressure on the optic apparatus, leading to visual impairment. A subset of patients may observe a swift improvement in their vision following surgery. Nevertheless, the alterations in the structural connectome during the early postoperative period remain largely unexplored. The research employed probabilistic tractography, graph theoretical analysis, and statistical methods on preoperative and postoperative structural magnetic resonance imaging and diffusion tensor images from 13 PA patients. Postoperative analysis revealed an increase in global and local efficiency, signifying improved network capacity for parallel information transfer and fault tolerance, respectively. Enhanced clustering coefficient and reduced shortest path length were also observed, suggesting a more regular network organization and shortened communication steps within the brain network. Furthermore, alterations in node graphical properties were detected, implying a restructuring of the network's control points, possibly contributing to more efficient visual processing. These findings propose that rapid vision recovery post-surgery may be associated with significant reorganization of the brain's structural connectome, enhancing the efficiency and adaptability of the network, thereby facilitating improved visual processing.

Clipping versus coiling in the treatment of oculomotor nerve palsy induced by unruptured posterior communicating artery aneurysms: A meta-analysis of cohort studies.

BACKGROUND: Although the superiority of clipping compared to coiling on the oculomotor nerve palsy (ONP) recovery for ruptured posterior communicating artery aneurysms (PcomAAs) has been widely accepted, which treatment modality is better in the treatment of ONP induced by unruptured PcomAAs still remains unclear. METHODS: A meta-analysis of studies that compared clipping with coiling was performed after a literature search. Perioperative data and clinical outcome were extracted. Analysis on the effect of the two treatment modalities was then performed. RESULTS: Nine eligible studies with a total of 136 patients met the inclusion criteria. There was a significant difference in the total efficiency (any degree of improvement) on ONP favoring clipping [RR= 1.21, 95%CI (1.01, 1.44), p = 0.04], the effect was most notable for complete recovery of ONP after having suffered preoperative partial palsy [RR= 0.72, 95%CI (0.55, 0.95), p = 0.02]. There was neither a significant difference regarding the complete recovery of ONP [RR= 1.11, 95%CI (0.77, 1.61), p = 0.58] nor the frequency of complications [RR= 0.07, 95%CI (0.00, 1.10), p = 0.06]. Also when subdividing there was no significant difference in complete recovery of ONP in patients who had initially suffered a complete ONP [RR= 0.79, 95%CI (0.38, 1.64), p = 0.53] and partial ONP [RR= 1.16, 95%CI (0.65, 2.08), p = 0.61] between clipping and coiling. CONCLUSIONS: A superiority of clipping over coiling for the improvement of ONP secondary to unruptured PcomAAs was found. Patients with partial ONP were more likely to attain a complete resolution of ONP, as compared to complete ONP.

11C-Methionine Integrated PET/MRI-Based Texture Analysis Features May Have a Potential Ability to Distinguish Oligodendroglioma (IDH-Mutant and 1p/19q-Codeleted) From Varied Gliomas.

RATIONALE AND OBJECTIVES: Different histology and gene status of gliomas results in different natural history, treatment, and prognosis in different subgroups. Low-grade gliomas (LGGs) with isocitrate dehydrogenase (IDH) mutant and 1p/19q-codeleted are kind of gliomas with the most favorable outcome, reflecting operational strategy. Less invasive method for prediction of pathological type-even gene status-is desired. MATERIALS AND METHODS: This study investigates the potential ability of methionine-positron emission tomography (MET-PET) to determine LGGs with IDH-mutant and 1p/19q-codeleted through a retrospective review of information of 70 glioma patients. Patients underwent preoperative MET-PET, followed by operation and histopathological analysis including Immunohistochemistry and polymerase chain reaction analysis for IDH-mutant and fluorescence capillary electrophoresis analysis for 1p/19q codeletion. Texture analysis was performed for further data mining. The t-test and receiver operating characteristic curve analysis were conducted for statistical analysis. RESULTS: In the whole cohort analysis, SUVmax, SUVmean and texture features (SD and median) of oligodendroglioma, IDH-mutant and 1p/19q-codeleted patients were lower than these values of other patients. In WHO grade II subgroup analysis, no statistical difference of conventional features was observed between groups. Texture analysis displayed higher diffEntropy, diffVariance, and entropy in oligodendroglioma, IDH-mutant and 1p/19q-codeleted patients. Receiver operating characteristic analysis suggested AUCs of some conventional features and texture features ranged from 0.722 to 0.892 that are effective for diagnosis, determining LGGs with IDH-mutant and 1p/19q-codeleted in this cohort and WHO II grade glioma subgroup analysis respectively. CONCLUSION: 11C-Methionine integrated PET/MRI based texture analysis and conventional features may be a promising noninvasive predictor for differentiating the varied gliomas.

Omega-3 polyunsaturated fatty acid attenuates the inflammatory response by modulating microglia polarization through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway following experimental traumatic brain injury.

BACKGROUND: Microglial polarization and the subsequent neuroinflammatory response are contributing factors for traumatic brain injury (TBI)-induced secondary injury. High mobile group box 1 (HMGB1) mediates the activation of the NF-κB pathway, and it is considered to be pivotal in the late neuroinflammatory response. Activation of the HMGB1/NF-κB pathway is closely related to HMGB1 acetylation, which is regulated by the sirtuin (SIRT) family of proteins. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are known to have antioxidative and anti-inflammatory effects. We previously demonstrated that ω-3 PUFA inhibited TBI-induced microglial activation and the subsequent neuroinflammatory response by regulating the HMGB1/NF-κB signaling pathway. However, no studies have elucidated if ω-3 PUFA affects the HMGB1/NF-κB pathway in a HMGB1 deacetylation of dependent SIRT1 manner, thus regulating microglial polarization and the subsequent neuroinflammatory response. METHODS: The Feeney DM TBI model was adopted to induce brain injury in rats. Modified neurological severity scores, rotarod test, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Assessment of microglia polarization and pro-inflammatory markers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and HMGB1, were used to evaluate the neuroinflammatory responses and the anti-inflammatory effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1/NF-κB signaling pathway activation to evaluate the effects of ω-3 PUFA supplementation. The impact of SIRT1 deacetylase activity on HMGB1 acetylation and the interaction between HMGB1 and SIRT1 were assessed to evaluate anti-inflammation effects of ω-3 PUFAs, and also, whether these effects were dependent on a SIRT1-HMGB1/NF-κB axis to gain further insight into the mechanisms underlying the development of the neuroinflammatory response after TBI. RESULTS: The results of our study showed that ω-3 PUFA supplementation promoted a shift from the M1 microglial phenotype to the M2 microglial phenotype and inhibited microglial activation, thus reducing TBI-induced inflammatory factors. In addition, ω-3 PUFA-mediated downregulation of HMGB1 acetylation and its extracellular secretion was found to be likely due to increased SIRT1 activity. We also found that treatment with ω-3 PUFA inhibited HMGB1 acetylation and induced direct interactions between SIRT1 and HMGB1 by elevating SIRT1 activity following TBI. These events lead to inhibition of HMGB1 nucleocytoplasmic translocation/extracellular secretion and alleviated HMGB1-mediated activation of the NF-κB pathway following TBI-induced microglial activation, thus inhibiting the subsequent inflammatory response. CONCLUSIONS: The results of this study suggest that ω-3 PUFA supplementation attenuates the inflammatory response by modulating microglial polarization through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway, leading to neuroprotective effects following experimental traumatic brain injury.

ATP Induces Disruption of Tight Junction Proteins via IL-1 Beta-Dependent MMP-9 Activation of Human Blood-Brain Barrier In Vitro.

Disruption of blood-brain barrier (BBB) follows brain trauma or central nervous system (CNS) stress. However, the mechanisms leading to this process or the underlying neural plasticity are not clearly known. We hypothesized that ATP/P2X7R signaling regulates the integrity of BBB. Activation of P2X7 receptor (P2X7R) by ATP induces the release of interleukin-1ß (IL-1ß), which in turn enhances the activity of matrix metalloproteinase-9 (MMP-9). Degradation of tight junction proteins (TJPs) such as ZO-1 and occludin occurs, which finally contributes to disruption of BBB. A contact coculture system using human astrocytes and hCMEC/D3, an immortalized human brain endothelial cell line, was used to mimic BBB in vitro. Permeability was used to evaluate changes in the integrity of TJPs. ELISA, Western blot, and immunofluorescent staining procedures were used. Our data demonstrated that exposure to the photoreactive ATP analog, 3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate (BzATP), induced a significant decrease in ZO-1 and occludin expression. Meanwhile, the decrease of ZO-1 and occludin was significantly attenuated by P2X7R inhibitors, as well as IL-1R and MMP antagonists. Further, the induction of IL-1ß and MMP-9 was closely linked to ATP/P2X7R-associated BBB leakage. In conclusion, our study explored the mechanism of ATP/P2X7R signaling in the disruption of BBB following brain trauma/stress injury, especially focusing on the relationship with IL-1ß and MMP-9.

Cell segmentation, tracking, and mitosis detection using temporal context.

The Large Scale Digital Cell Analysis System (LSDCAS) developed at the University of Iowa provides capabilities for extended-time live cell image acquisition. This paper presents a new approach to quantitative analysis of live cell image data. By using time as an extra dimension, level set methods are employed to determine cell trajectories from 2D + time data sets. When identifying the cell trajectories, cell cluster separation and mitotic cell detection steps are performed. Each of the trajectories corresponds to the motion pattern of an individual cell in the data set. At each time frame, number of cells, cell locations, cell borders, cell areas, and cell states are determined and recorded. The proposed method can help solving cell analysis problems of general importance including cell pedigree analysis and cell tracking. The developed method was tested on cancer cell image sequences and its performance compared with manually-defined ground truth. The similarity Kappa Index is 0.84 for segmentation area and the signed border positioning segmentation error is 1.6 +/- 2.1 microm.