The Risk Factors of Postpartum Urinary Retention for Women by Vaginal Birth: A Systematic Review and Meta-Analysis.

INTRODUCTION AND HYPOTHESIS: Postpartum urinary retention is one of the most common complications in women during the immediate postpartum period. The objective was to systematically assess risk factors for postpartum urinary retention after vaginal delivery. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we retrieved relevant studies from PubMed, Embase, Cochrane Library, Web of Science Core Collection, China National Knowledge Internet, Wangfang Database, and Chinese Biomedical Database for observational studies investigating the risk factors for postpartum urinary retention from inception to 11 November 2022. The Newcastle-Ottawa Scale and Joanna Briggs Institute's tool were used to assess the risk of bias. We conducted a meta-analysis using RevMan 5.3. RESULTS: In total, 3,074 articles were screened and data from 27 studies were used in the meta-analysis. Sixteen risk factors were identified, namely, labor augmentation (OR = 1.72, 95% CI = 1.17-2.51), primiparity (OR = 2.36, 95% CI = 1.64-3.38), manual fundal pressure (OR = 2.84, 95% CI = 1.00-8.11), perineal hematoma (OR = 7.28, 95% CI = 1.62-32.72), vulvar edema (OR = 7.99, 95% CI = 5.50-11.63), the total duration of labor (MD = 90.10, 95% CI = 49.11-131.08), the duration of the first stage of labor (MD = 33.97, 95% CI = 10.28-57.65), the duration of the second stage of labor (MD = 14.92, 95% CI = 11.79-18.05), the duration of the second stage of labor > 60 min (OR = 3.18, 95% CI = 1.32-7.67), mediolateral episiotomy (OR = 3.65, 95% CI = 1.70-7.83), severe perineal tear (OR = 3.21, 95% CI = 1.84-5.61), epidural analgesia (OR = 3.23, 95% CI = 1.50-6.96), forceps delivery (OR = 4.95, 95% CI = 2.88-8.51), vacuum delivery (OR = 2.44, 95% CI = 1.30-4.58), neonatal birth weight > 4,000 g (OR = 3.61, 95% CI = 1.96-6.65), and neonatal birth weight > 3,500 g (OR = 1.89, 95% CI = 1.12-3.19). CONCLUSIONS: Our results demonstrated that labor augmentation, primiparity, manual fundal pressure, perineal hematoma, vulvar edema, the total duration of labor, the duration of the first stage of labor, the duration of the second stage of labor, the duration of the second stage of labor > 60 min, mediolateral episiotomy, severe perineal tear, epidural analgesia, forceps delivery, vacuum delivery, and neonatal birth weight > 4,000 g and > 3,500 g were risk factors for postpartum urinary retention in women with vaginal delivery. The specific ranges of the first and the second stages of labor causing postpartum urinary retention need to be clarified.

Aquatic and sediment ecotoxicity data of difenoconazole and its potential environmental risks in ponds bordering rice paddies.

Difenoconazole has a widespread agricultural use to control fungal diseases in crops, including rice. In edge-of-field surface waters the residues of this lipophilic fungicide may be toxic to both pelagic and benthic organisms. To allow an effect assessment we mined the regulatory and open literature for aquatic toxicity data. Since published sediment toxicity data were scarce we conducted 28 d sediment-spiked toxicity test with 8 species of benthic macroinvertebrates. Ecotoxicological threshold levels for effects were assessed by applying the species sensitivity distribution approach. Based on short-term L(E)C50's for aquatic organisms from water-only tests an acute Hazardous Concentration to 5% of the species (HC5) of 100 µg difenoconazole/L was obtained, while the HC5 based on chronic NOEC values was a factor of 104 lower (0.96 µg difenoconazole/L). For benthic macroinvertebrates the chronic HC5, based on 28d-L(E)C10 values, was 0.82 mg difenoconazole/kg dry weight sediment. To allow a risk assessment for water- and sediment-dwelling organisms, exposure concentrations were predicted for the water and sediment compartment of an edge-of-field pond bordering rice paddies treated with difenoconazole using the Chinese Top-Rice modelling approach, the Chinese Nanchang exposure scenario and the Equilibrium Partitioning theory. It appeared that in the vast majority of the 20 climate years simulated, potential risks to aquatic and sediment organisms cannot be excluded. Although the HC5 values based on laboratory toxicity data provide one line of evidence only, our evaluation suggests population- and community-level effects on these organisms due to chronic risks in particular.

Coal-mining subsidence changed distribution of the microbiomes and their functional genes in a farmland.

Land subsidence is a serious geological event, and can trigger severe environmental and ecological issues. In this study, the influences of coal-mining subsidence on distribution of farmland microbiomes and their functional genes were investigated by 16 S ribosomal RNA (rRNA) gene and metagenome sequencing. The results showed the existence of a core microbiome, which determined the community compositions across the subsidence farmland. Subsidence decreased the relative abundances of dominant Streptomyces, Nocardioides, and Rhizophagus, but increased the relative abundances of dominant Bradyrhizobium, Rhizobium, and Trichoderma. Subsidence also decreased the relative abundances of genes related to carbon metabolism, Quorum sensing, aminoacyl-transfer RNA (tRNA) biosynthesis, and oxidative phosphorylation, and increased the relative abundances of genes related to two-component system and bacterial chemotaxis. Furthermore, subsidence weakened the biosynthesis of organic carbons by decreasing the relative abundances of genes encoding glycosyl transferases, and strengthened decomposition of degradable organic carbons of the microbiomes and auxiliary activities by increasing the relative abundances of genes encoding glycoside hydrolases and polysaccharide lyases. The concentrations of total phosphorus, Mg2+ , and Ca2+ at the lower areas were significantly higher than those at the upper areas, indicating an associated loss of soil nutrients. Canonical correspondence analysis showed that soil moisture, pH, and the concentrations of NH4 + and Ca2+ were the main factors affecting the distribution of the microbiomes and their functional genes. Collectively, this study shows that coal-mining subsidence alters soil physicochemical properties and distribution of farmland microbiomes and their functional genes.

Neuroprotective effect of meglumine cyclic adenylate against ischemia/reperfusion injury via STAT3-Ser727 phosphorylation.

OBJECTIVES: Ischemia/reperfusion can induce neuronal apoptosis in the brain and lead to function deficits. The activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is neuroprotective against transient cerebral ischemia. The neuroprotective mechanisms of PKA mainly involve the regulation of gene transcription via the PKA/CREB pathway. The present study aims to investigate the neuroprotective effect of meglumine cyclic adenylate, an activator of PKA, under a rat model of global cerebral ischemia/reperfusion and to reveal the underlying mechanism involving signal transducer and activator of transcription 3 (STAT3)-Ser727 phosphorylation and mitochondrion modulation. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to 15 min global cerebral ischemia, and meglumine cyclic adenylate was treated through tail intravenous injection 30 min before ischemia. Cresyl violet staining was used to evaluate neuron injury at 5 d of reperfusion. Western blotting was used to detect p-Ser727-STAT3, total STAT3, cytochrome c (Cyt c) and active caspase-3 in the tissues of hippocampal CA1 region at 6 h of reperfusion. STAT3-S727A was overexpressed in HT22 cells to reveal the significance of STAT3-Ser727 phosphorylation in the neuroprotective effect of meglumine cyclic adenylate. RESULTS: Pretreatment with meglumine cyclic adenylate not only significantly ameliorated neuron loss in CA1 region after global cerebral ischemia but also enhanced STAT3-Ser727 phosphorylation, increased mitochondrial STAT3, and decreased cytosolic Cyt c and active caspase-3. Overexpression of STAT3-S727A in HT22 cells eliminated meglumine cyclic adenylate-induced increase of p-Ser727-STAT3, mitochondrial STAT3, cytosolic Cyt c and active caspase-3. CONCLUSION: Meglumine cyclic adenylate protects neurons against ischemia/reperfusion injury via promoting p-Ser727-STAT3-associated mitochondrion modulation and inhibiting apoptosis pathway.

Genome-Wide Identification, Characterization and Expression Analysis of the TaDUF724 Gene Family in Wheat (Triticum aestivum).

Unknown functional domain (DUF) proteins constitute a large number of functionally uncharacterized protein families in eukaryotes. DUF724s play crucial roles in plants. However, the insight understanding of wheat TaDUF724s is currently lacking. To explore the possible function of TaDUF724s in wheat growth and development and stress response, the family members were systematically identified and characterized. In total, 14 TaDUF724s were detected from a wheat reference genome; they are unevenly distributed across the 11 chromosomes, and, according to chromosome location, they were named TaDUF724-1 to TaDUF724-14. Evolution analysis revealed that TaDUF724s were under negative selection, and fragment replication was the main reason for family expansion. All TaDUF724s are unstable proteins; most TaDUF724s are acidic and hydrophilic. They were predicted to be located in the nucleus and chloroplast. The promoter regions of TaDUF724s were enriched with the cis-elements functionally associated with growth and development, as well as being hormone-responsive. Expression profiling showed that TaDUF724-9 was highly expressed in seedings, roots, leaves, stems, spikes and grains, and strongly expressed throughout the whole growth period. The 12 TaDUF724 were post-transcription regulated by 12 wheat MicroRNA (miRNA) through cleavage and translation. RT-qPCR showed that six TaDUF724s were regulated by biological and abiotic stresses. Conclusively, TaDUF724s were systematically analyzed using bioinformatics methods, which laid a theoretical foundation for clarifying the function of TaDUF724s in wheat.

Efficacy of concentrated growth factor (CGF) in the surgical treatment of oral diseases: a systematic review and meta-analysis.

BACKGROUND: Concentrated growth factor (CGF), a new autologous platelet concentrate, has been widely investigated to the adjunctive treatment of oral diseases. This study aims to evaluate the efficacy of CGF in the surgical treatment of oral diseases. METHODS: MEDLINE, Web of Science, Scopus, Cochrane, and EMBASE databases were searched up to July 2023. Only randomized clinical trials were included. The methodologic quality was evaluated by the Cochrane Risk of Bias Tool. RevMan 5.4 software was used for data analysis. RESULTS: In the treatment of periodontal intrabony defects, bone graft combined with CGF was significantly superior to bone graft (P < 0.01), with mean intrabony defect depth reduction of 1.41 mm and mean clinical attachment level gain of 0.55 mm. In the regenerative surgery of furcation defects, the effect of CGF group was significantly better than control group (P < 0.0001), with mean probing depth reduction of 0.99 mm, vertical bone gain of 0.25 mm, and horizontal bone gain of 0.34 mm. CGF combined with coronally advanced flap (CAF) was more effective than CAF alone (mean keratinized tissue width increase of 0.41 mm, mean gingival thickness increase of 0.26 mm, P < 0.00001), but less effective than connective tissue graft (CTG) combined with CAF (mean root coverage difference of -15.1%, mean gingival thickness difference of -0.5 mm, P < 0.0001). In the alveolar ridge preservation, additional use of CGF reduced horizontal bone resorption by 1.41 mm and buccal vertical bone resorption by 1.01 mm compared to control group (P < 0.0001). The VAS score of CGF group was significantly lower than that of the control group at the 1st and 7th day after oral surgery (P < 0.0001). CONCLUSIONS: CGF can exert a positive adjunctive effect for the regenerative surgery of periodontal intrabony defects, furcation defects, and alveolar ridge preservation procedure. CGF combined with CAF has a better therapeutic effect on gingival recession compared to CAF alone, although it is not as effective as CTG combined with CAF. CGF could promote postoperative healing and pain relief in oral surgery within a week. There is currently not enough evidence to support the clinical benefits of CGF in other oral surgeries.

Regulation of TRAF6 by MicroRNA-146a in Zebrafish Embryos after Exposure to Di(2-Ethylhexyl) Phthalate at Different Concentrations.

As an endocrine disruptor, di(2-ethylhexyl) phthalate (DEHP) is ubiquitous in multiple environmental media, causing long-term toxic effects on organisms. MicroRNAs are a class of noncoding RNAs with only 20-24 nucleotides in length, which regulate the expression of many protein-coding genes when organisms are exposed to environmental chemicals. MiR-146a, a differentially expressed miRNA after DEHP exposure, was screened by miRNA sequencing. As its target, TRAF6 was predicted and identified by double fluorescent protein assay and double fluorescent gene reporting assay. It shows the contrary expression pattern with miR-146a when mimics and inhibitors were transfected into ZF4 cells. MiR-146a and TRAF6 were downregulated and upregulated, respectively, in zebrafish embryos exposed to a low-dose concentration gradient of DEHP. These results deepen our understanding of the molecular mechanisms of DEHP toxicity and suggest that miR-146a can serve as a potential biomarker for DEHP exposure.

MFN2 silencing promotes neural differentiation of embryonic stem cells via the Akt signaling pathway.

Mitofusin 2 (MFN2) is a regulatory protein participating in mitochondria dynamics, cell proliferation, death, differentiation, and so on. This study aims at revealing the functional role of MFN2 in the pluripotency maintenance and primitive differetiation of embryonic stem cell (ESCs). A dox inducible silencing and routine overexpressing approach was used to downregulate and upregulate MFN2 expression, respectively. We have compared the morphology, cell proliferation, and expression level of pluripotent genes in various groups. We also used directed differentiation methods to test the differentiation capacity of various groups. The Akt signaling pathway was explored by the western blot assay. MFN2 upregulation in ESCs exhibited a typical cell morphology and similar cell proliferation, but decreased pluripotent gene markers. In addition, MFN2 overexpression inhibited ESCs differentiation into the mesendoderm, while MFN2 silencing ESCs exhibited a normal cell morphology, slower cell proliferation and elevated pluripotency markers. For differentiation, MFN2 silencing ESCs exhibited enhanced three germs' differentiation ability. Moreover, the protein levels of phosphorylated Akt308 and Akt473 decreased in MFN2 silenced ESCs, and recovered in the neural differentiation process. When treated with the Akt inhibitor, the neural differentiation capacity of the MFN2 silenced ESCs can reverse to a normal level. Taken together, the data indicated that the appropriate level of MFN2 expression is essential for pluripotency and differentiation capacity in ESCs. The increased neural differentiation ability by MFN2 silencing is strongly related to the Akt signaling pathway.

Overexpression of microRNA-204-5p alleviates renal ischemia-reperfusion injury in mice through blockage of Fas/FasL pathway.

The multiple roles of microRNA-204-5p (miR-204-5p) in numerous types of cancer have been reported, but its function in renal ischemia-reperfusion injury (RIRI) remains unclear. In this study, we aim to explore whether miR-204-5p was implicated in the RIRI in mice via regulating the Fas/Fas ligand (FasL) pathway. Firstly, the Gene Expression Omnibus (GEO) database was used to screen RIRI-related differentially expressed genes (DEGs). Then, RIRI mouse model was established, and the role of miR-204-5p and FasL in RIRI was explored by ectopic expression, depletion and reporter assay experiments. The blood urea nitrogen (BUN) and serum creatinine (Scr) levels in serum, as well as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in renal tissues of mice were also measured. Afterwards, the regulatory role of miR-204-5p on Fas/FasL pathway in RIRI was investigated. Renal tissues from RIRI mice showed lower miR-204-5p expression and higher Fas and FasL expression. FasL was identified as a direct target gene of miR-204-5p. In addition, the increased levels of BUN, Scr and MDA, as well as decreased levels of SOD and GSH-Px in RIRI mice were reversed by elevation of miR-204-5p and blockage of the Fas/FasL pathway. Taken together, this study demonstrated that increased miR-204-5p might suppress RIRI in mice through suppressing Fas/FasL pathway by targeting FasL.

Controlled cellular redox, repressive hemin utilization and adaptive stress responses are crucial to metronidazole tolerance of Porphyromonas gingivalis persisters.

BACKGROUND: Antimicrobial-tolerant microbial persisters critically account for various infections and inflammation. This study identified the characteristics of Porphyromonas gingivalis persisters, and explored their underlying survival mechanisms through proteomic profiling. METHODS: Porphyromonas gingivalis cultured with different concentrations of hemin was treated with 100 µg/ml of metronidazole (MTZ). The viability of P. gingivalis persisters was determined by colony-forming unit assay and LIVE/DEAD staining. The proteomic signature of P. gingivalis persister fractions was examined using LC-MS/MS and bioinformatic analysis. RESULTS: A small fraction of P. gingivalis persisters survived from lethal MTZ treatment without heritability. At late exponential phase, the frequency of these persisters significantly increased when incubated with 1 µg/ml of hemin compared to 10 µg/ml. Higher levels of P. gingivalis persisters formed at stationary phase than the late exponential phase. High-throughput proteomic analysis showed that the persisters markedly downregulated multiple proteins involved in electron transfer and heme/iron utilization essential for redox regulation and MTZ activation. Moreover, the persisters enabled to shut down major cellular activities (e.g. translation) and overexpress stress proteins. CONCLUSION: The presence and survival of metronidazole-tolerant P. gingivalis persisters may be dominated by regulation of cellular redox state and enhanced via repression of heme/iron utilization, dormancy and stress responses.

Antagonistic activities of volatiles produced by two Bacillus strains against Monilinia fructicola in peach fruit.

BACKGROUND: Brown rot caused by Monilinia fructicola is one of most serious diseases of postharvest peach fruit. The objective of this study was to select effective antagonistic bacteria against Monilinia fructicola and evaluate the effects of these strains against brown rot. RESULTS: Four bacterial strains producing inhibitory volatile gas against Monilinia fructicola were isolated from the peach rhizosphere soil. The volatiles produced by 12a (Bacillus vallismortis) and 14b (Bacillus altitudinis) showed considerable antagonistic activities. Monilinia fructicola showed 80.3% and 68.4% mycelial growth inhibition and cell damage in the presence of strains 12a and 14b, respectively. The inhibition rate of brown rot in peach fruit fumigated with the culture solution of 12a or 14b reached 77.1% and 50.0%, respectively. The volatile compounds produced by 12a and 14b were identified according to gas chromatographic-mass spectrometric analysis. Among them, 6-methyl-2-heptanone and 2-pentylfuran completely inhibited mycelial growth at 100 µL L-1 concentration. Cedrol showed strong inhibitory activity against mycelial growth at 100 µg L-1 and isodecyl methacrylate inhibited growth at high concentration. The inhibition rate of the 50 µL L-1 artificial mixture of these four volatiles was 59.3% in vitro. CONCLUSION: These results indicate that the two antagonistic bacteria and some volatiles produced by them have potential value in controlling brown rot in harvested peach fruit. © 2018 Society of Chemical Industry.

Generation and periodontal differentiation of human gingival fibroblasts-derived integration-free induced pluripotent stem cells.

Induced pluripotent stem cells (iPSCs) have been recognized as a promising cell source for periodontal tissue regeneration. However, the conventional virus-based reprogramming approach is associated with a high risk of genetic mutation and limits their therapeutic utility. Here, we successfully generated iPSCs from readily accessible human gingival fibroblasts (hGFs) through an integration-free and feeder-free approach via delivery of reprogramming factors of Oct4, Sox2, Klf4, L-myc, Lin28 and TP53 shRNA with episomal plasmid vectors. The iPSCs presented similar morphology and proliferation characteristics as embryonic stem cells (ESCs), and expressed pluripotent markers including Oct4, Tra181, Nanog and SSEA-4. Additionally, these cells maintained a normal karyotype and showed decreased CpG methylation ratio in the promoter regions of Oct4 and Nanog. In vivo teratoma formation assay revealed the development of tissues representative of three germ layers, confirming the acquisition of pluripotency. Furthermore, treatment of the iPSCs in vitro with enamel matrix derivative (EMD) or growth/differentiation factor-5 (GDF-5) significantly up-regulated the expression of periodontal tissue markers associated with bone, periodontal ligament and cementum respectively. Taken together, our data demonstrate that hGFs are a valuable cell source for generating integration-free iPSCs, which could be sequentially induced toward periodontal cells under the treatment of EMD and GDF-5.

Toward high permeability, selectivity and controllability of water desalination with FePc nanopores.

Nanoporous materials exhibit promising potential in water transportation applications, especially in ocean water desalination. It is highly desired to have great permeability, selectivity and controllability in the desalination performance of these nanopores. However, it is still a challenge to achieve all three features in one material or device. Here, we demonstrate efficient and controllable water desalination with a nanoporous 2D Fe phthalocyanine (FePc) membrane using molecular dynamics simulations. We find the FePc membrane not only conducts fast water flow, but it also suppresses ion permeation. The selectivity is attributed to a mechanism distinct from the traditional steric exclusion: cations are excluded due to electrostatic repulsion, whereas anions can be trapped in the nanopore and induce the reorganization of ions in the vicinity of the nanopore, which in turn creates a tendency for the trapped anions to move back into the saline reservoir. More interestingly, we find such mechanism is largely due to the sufficiently strong electrostatic interaction of the charged nanopore region with ions and is not restricted to the FePc nanopore. In addition, the number of protonated nitrogen atoms in FePc pores can be modulated by adjusting the pH value of the solution. The extent of the anion occupancy can thus be regulated, giving rise to control of the water flow. Taken together, great permeability, selectivity and controllability can be achieved with this nanosheet system. Moreover, our study suggests there is an alternative mechanism of water desalination which may be realized by intrinsically nanoporous materials such as FePc membranes.

Regulation on mechanical properties of collagen: enhanced bioactivities of metallofullerol.

Increased mechanical property of extracellular matrix (ECM) around tumor tissue is highly correlated to the progression of cancer, and now its efficient regulation is still a challenge. Here, we report that Gd@C82(OH)22-collagen composites greatly suppress the malignant progression of cancer cells in vitro, and the metallofullerol can efficiently reduce the mechanical property of collagen matrix. Further study indicates that Gd@C82(OH)22 can firmly bind to tropocollagen, facilitate the nuclei and microfibril formation. The interference to interactions among tropocollagens leads to decreased amount and disturbed structure of collagen fibers. C60(OH)24, the fullerol counterpart of Gd@C82(OH)22, is studied in parallel and their impacts on collagen are strikingly modest. The comparison data reveals that the enhanced bioactivity of Gd@C82(OH)22 is highly related with its surface-structure. This study is the first attempt to apply nanomedicines to manipulate the biophysical property of collagen matrix, providing a new sight to target ECM in cancer therapy. FROM THE CLINICAL EDITOR: Increased presence of "harder" collagen in the extracellular matrix (ECM) around the tumor tissue highly correlates with cancer progression. In this paper, a metallofullerol-based approach is reported as an efficient nanotechnology approach in reducing the mechanical properties of the synthesized collagen, paving the way to the development of novel anti-cancer therapies.

Simulation study on gold nanoparticle-cellular membrane complex in endocytosis process.

Gold nanoparticles (AuNPs) are of biomedical importance, such as delivery vectors. Therefore, we used all-atom molecular dynamic simulations to study the interaction of AuNPs with cell membrane (DMPC bilayer). We observed that the AuNPs adhered spontaneously on the surface of the cellular membrane from the bulk phase, largely as a result of the AuNP-DMPC headgroup attraction. We calculated the potential of mean force for transferring an AuNP through a DMPC bilayer. It was observed that a high energetic barrier to AuNP was inserted into the hydrophobic core of the bilayer. The inclusion of AuNP induced local bilayer deformation and slowed fluidity of the lipid molecules in the vicinity of it. As the size of the AuNP increased, the lipids in the vicinity of the AuNP had larger local deformation and slower fluidity. We found that a nanoparticle-membrane complex was formed by the AuNP and its neighbor lipids. These neighbor lipids moved laterally together with AuNP. On average, they moved significantly more slowly than the other lipids. The nanoparticle-membrane complex not only provided a clue for endocytosis mechanism regulating the translocation of AuNPs across the cellular membrane but also helped us to better understand the endocytosis process.

Alteration of podocyte protein expression and localization in the early stage of various hemodynamic conditions.

Given that podocalyxin (PCX) and nestin play important roles in podocyte morphogenesis and the maintenance of structural integrity, we examined whether the expression and localization of these two podocyte proteins were influenced in the early stage of various hemodynamic conditions. Mice kidney tissues were prepared by in vivo cryotechnique (IVCT). The distribution of glomeruli and podocyte proteins was visualized with DAB staining, confocal laser scanning microscopy and immunoelectron microscopy. The mRNA levels were examined by real-time quantitative PCR. The results showed the following: Under the normal condition, PCX stained intensely along glomerular epithelial cells, whereas nestin was clearly staining in the endothelial cells and appeared only weakly in the podocytes. Under the acute hypertensive and cardiac arrest conditions, PCX and nestin staining was not clear, with a disarranged distribution, but the colocalization of PCX and nestin was apparent under this condition. In addition, under the acute hypertensive and cardiac arrest conditions, the mRNA levels of PCX and nestin were significantly decreased. Collectively, the abnormal redistribution and decreased mRNA expressions of PCX and nestin are important molecular events at the early stage of podocyte injury during hemodynamic disorders. IVCT may have more advantages for morphological analysis when researching renal diseases.

Tumor cell-induced platelet aggregation accelerates hematogenous metastasis of malignant melanoma by triggering macrophage recruitment.

BACKGROUND: Tumor cell-induced platelet aggregation (TCIPA) is not only a recognized mechanism for paraneoplastic thrombocytosis but also a potential breakthrough alternative for a low response to immune checkpoint inhibitors (ICIs) in hematogenous metastasis of malignant melanoma (MM). However, there is no TCIPA-specific model for further investigation of the relationship among TCIPA, the tumor immune microenvironment (TIME), and metastasis. METHODS: We developed a TCIPA metastatic melanoma model with advanced hematogenous metastasis and enhanced TCIPA characteristics. We also investigated the pathway for TCIPA in the TIME. RESULTS: We found that TCIPA triggers the recruitment of tumor-associated macrophages (TAMs) to lung metastases by secreting B16 cell-educated platelet-derived chemokines such as CCL2, SDF-1, and IL-1ß. Larger quantities of TAMs in the TCIPA model were polarized to the M2 type by B16 cell reprocessing, and their surface programmed cell death 1 ligand 1 (PD-L1) expression was upregulated, ultimately assisting B16 cells in escaping host immunity and accelerating MM hematogenous metastasis. CONCLUSIONS: TCIPA accelerates MM lung metastasis via tumor-educated platelets (TEPs), triggering TAM recruitment, promoting TAM polarization (M2), and remodeling the suppressive TIME in lung metastases.

Activation and Denitrosylation of Procaspase-3 in KA-induced Excitotoxicity.

BACKGROUND: It has been reported that activation of glutamate kainate receptor subunit 2 (GluK2) subunit-containing glutamate receptors and the following Fas ligand(FasL) up-regulation, caspase-3 activation, result in delayed apoptosis-like neuronal death in hippocampus CA1 subfield after cerebral ischemia and reperfusion. Nitric oxide-mediated S-nitrosylation might inhibit the procaspase activation, whereas denitrosylation might contribute to cleavage and activation of procaspases. OBJECTIVES: The study aimed to elucidate the molecular mechanisms underlying procaspase-3 denitrosylation and activation following kainic acid (KA)-induced excitotoxicity in rat hippocampus. METHODS: S-nitrosylation of procaspase-3 was detected by biotin-switch method. Activation of procaspase-3 was shown as cleavage of procaspase-3 detected by immunoblotting. FasL expression was detected by immunoblotting. Cresyl violets and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining were used to detect apoptosis-like neuronal death in rat hippocampal CA1 and CA3 subfields. RESULTS: KA led to the activation of procaspase-3 in a dose- and time-dependent manner, and the activation was inhibited by KA receptor antagonist NS102. Procaspase-3 was denitrosylated at 3 h after kainic acid administration, and the denitrosylation was reversed by SNP and GSNO. FasL ASODNs inhibited the procaspase-3 denitrosylation and activation. Moreover, thioredoxin reductase (TrxR) inhibitor auranofin prevented the denitrosylation and activation of procaspase-3 in rat hippocampal CA1 and CA3 subfields. NS102, FasL AS-ODNs, and auranofin reversed the KAinduced apoptosis and cell death in hippocampal CA1 and CA3 subfields. CONCLUSIONS: KA led to denitrosylation and activation of procaspase-3 via FasL and TrxR. Inhibition of procaspase-3 denitrosylation by auranofin, SNP, and GSNO played protective effects against KA-induced apoptosis-like neuronal death in rat hippocampal CA1 and CA3 subfields. These investigations revealed that the procaspase-3 undergoes an initial denitrosylation process before becoming activated, providing valuable insights into the underlying mechanisms and possible treatment of excitotoxicity.

MFN2 knockdown promotes osteogenic differentiation of iPSC-MSCs through aerobic glycolysis mediated by the Wnt/ß-catenin signaling pathway.

BACKGROUND: Mitofusin-2 (MFN2) is a kind of GTPase that participates in the regulation of mitochondrial fusion, which is related to a variety of physiological and pathological processes, including energy metabolism, cell differentiation, and embryonic development. However, it remains unclear whether MFN2 is involved in the metabolism and osteogenic differentiation of mesenchymal stem cells (MSCs). METHODS: MFN2 knockdown (MFN2-KD) and MFN2-overexpressing (MFN2-OE) induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) were constructed by lentivirus. The commercial kits were utilized to detect the glycolysis and oxidative phosphorylation (OXPHOS) rate. Flow cytometry, Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), RNA-seq, immunofluorescence, and immunoprecipitation were employed for phenotype and molecular mechanism assessment. RESULTS: We demonstrated that MFN2 and Wnt/ß-catenin signaling pathway regulated glycolysis of iPSC-MSCs. The lack of MFN2 promoted the osteogenic differentiation of iPSC-MSCs, and aerobic glycolysis in the presence of sufficient oxygen, which increased glucose consumption and lactic acid production, as well as the glycolytic enzyme activity and gene expression. Inhibiting the Wnt/ß-catenin signaling pathway normalized the enhanced glycolytic rate and osteogenic differentiation of MFN2-KD iPSC-MSCs. MFN2-OE iPSC-MSCs displayed the opposite phenotype. CONCLUSIONS: Downregulating MFN2 promotes osteogenic differentiation of iPSC-MSCs through aerobic glycolysis mediated by the Wnt/ß-catenin signaling pathway. Our research reveals the new function of MFN2 in regulating the osteogenic differentiation and energy metabolism of MSCs, which will provide a new therapeutic target and theoretical basis for alveolar bone repair and periodontal regenerative treatment.