Isolation and Culture of Primary Human Mammary Epithelial Cells.

The mammary gland is a fundamental structure of the breast and plays an essential role in reproduction. Human mammary epithelial cells (HMECs), which are the origin cells of breast cancer and other breast-related inflammatory diseases, have garnered considerable attention. However, isolating and culturing primary HMECs in vitro for research purposes has been challenging due to their highly differentiated, keratinized nature and their short lifespan. Therefore, developing a simple and efficient method to isolate and culture HMECs is of great scientific value for the study of breast biology and breast-related diseases. In this study, we successfully isolated primary HMECs from small amounts of mammary tissue by digestion with a mixture of enzymes combined with an initial culture in 5% fetal bovine serum-DMEM containing the Rho-associated kinase (ROCK) inhibitor Y-27632, followed by culture expansion in serum-free keratinocyte medium. This approach selectively promotes the growth of epithelial cells, resulting in an optimized cell yield. The simplicity and convenience of this method make it suitable for both laboratory and clinical research, which should provide valuable insights into these important areas of study.

Behavioral Studies of Zebrafish Reveal a New Perspective on the Reproductive Toxicity of Micro- and Nanoplastics.

The escalating prevalence of microplastics and nanoplastics in aquatic environments is a major challenge affecting the behavior and reproductive health of aquatic organisms while posing potential risks to human health and ecosystems. This review focuses on the neurobehavioral changes and reproductive toxicity of MNPs in zebrafish and their relationships. At the same time, the neurobehavioral changes caused by MNPs were studied, and the synergistic effects of the interaction of these pollutants with other environmental contaminants were explored. In addition, zebrafish, as a model organism, provide valuable insights into the subtle but important effects of MNPs on reproductive behavior, which is critical for understanding reproductive success, suggesting that behavioral changes can serve as an early biomarker of reproductive toxicity. In addition, based on classical endocrine disruptor models and behavioral research methods, the current status of the research on the reproductive toxicity of MNPs in zebrafish was reviewed, which further indicated that the behavioral parameters of zebrafish can be used as an effective and rapid tool to evaluate the reproductive toxicity of MNPs. However, behavioral methods for rapidly assessing the toxicity of MNPs are still an area of exploration. To address limitations and challenges in the current scope of research, this review outlines future research directions with the aim of improving our understanding of the environmental and health impacts of MNPs. This work aims to inform targeted environmental policies and advance public health strategies to address the growing challenge of MNPs pollution.

Generation of G51D and 3D mice reveals decreased α-synuclein tetramer-monomer ratios promote Parkinson's disease phenotypes.

Mutations in the α-Synuclein (αS) gene promote αS monomer aggregation that causes neurodegeneration in familial Parkinson's disease (fPD). However, most mouse models expressing single-mutant αS transgenes develop neuronal aggregates very slowly, and few have dopaminergic cell loss, both key characteristics of PD. To accelerate neurotoxic aggregation, we previously generated fPD αS E46K mutant mice with rationally designed triple mutations based on the α-helical repeat motif structure of αS (fPD E46K→3 K). The 3 K variant increased αS membrane association and decreased the physiological tetramer:monomer ratio, causing lipid- and vesicle-rich inclusions and robust tremor-predominant, L-DOPA responsive PD-like phenotypes. Here, we applied an analogous approach to the G51D fPD mutation and its rational amplification (G51D → 3D) to generate mutant mice. In contrast to 3 K mice, G51D and 3D mice accumulate monomers almost exclusively in the cytosol while also showing decreased αS tetramer:monomer ratios. Both 1D and 3D mutant mice gradually accumulate insoluble, higher-molecular weight αS oligomers. Round αS neuronal deposits at 12 mos immunolabel for ubiquitin and pSer129 αS, with limited proteinase K resistance. Both 1D and 3D mice undergo loss of striatal TH+ fibers and midbrain dopaminergic neurons by 12 mos and a bradykinesia responsive to L-DOPA. The 3D αS mice have decreased tetramer:monomer equilibria and recapitulate major features of PD. These fPD G51D and 3D mutant mice should be useful models to study neuronal αS-toxicity associated with bradykinetic motor phenotypes.

Secretome Analyses Identify FKBP4 as a GBA1-Associated Protein in CSF and iPS Cells from Parkinson's Disease Patients with GBA1 Mutations.

Mutations in the GBA1 gene increase the risk of developing Parkinson's disease (PD). However, most carriers of GBA1 mutations do not develop PD throughout their lives. The mechanisms of how GBA1 mutations contribute to PD pathogenesis remain unclear. Cerebrospinal fluid (CSF) is used for detecting pathological conditions of diseases, providing insights into the molecular mechanisms underlying neurodegenerative disorders. In this study, we utilized the proximity extension assay to examine the levels of metabolism-linked protein in the CSF from 17 PD patients carrying GBA1 mutations (GBA1-PD) and 17 idiopathic PD (iPD). The analysis of CSF secretome in GBA1-PD identified 11 significantly altered proteins, namely FKBP4, THOP1, GLRX, TXNDC5, GAL, SEMA3F, CRKL, APLP1, LRP11, CD164, and NPTXR. To investigate GBA1-associated CSF changes attributed to specific neuronal subtypes responsible for PD, we analyzed the cell culture supernatant from GBA1-PD-induced pluripotent stem cell (iPSC)-derived midbrain dopaminergic (mDA) neurons. The secretome analysis of GBA1-PD iPSC-derived mDA neurons revealed that five differently regulated proteins overlapped with those identified in the CSF analysis: FKBP4, THOP1, GLRX, GAL, and CRKL. Reduced intracellular level of the top hit, FKPB4, was confirmed via Western Blot. In conclusion, our findings identify significantly altered CSF GBA1-PD-associated proteins with FKPB4 being firmly attributed to mDA neurons.

Combined measurement of serum zinc with PSA ameliorates prostate cancer screening efficiency via support vector machine algorithms.

Background: Early screening of prostate cancer (PCa) is pivotal but challenging in the clinical scenario due to the phenomena of false positivity or false negativity of some serological evaluations, e.g. PSA testing. Decline of serum Zn2+ levels in PCa patients reportedly plays a crucial role in early screening of PCa. Accordingly, we combined 4 indices comprising the serum levels of total PSA (tPSA), free PSA (fPSA), Zn2+ and demographic information (especially age) in order to ameliorate the efficacies of PCa screening with support vector machine (SVM) algorithms. Methods: A total of 858 male patients with prostate disorders and 345 healthy male controls were enrolled. Patients' data included 4 variables and serum Zn2+ was quantified via a self-invented Zn2+ responsive AIE-based fluorescent probe as previously published. tPSA and fPSA were routinely determined by a chemiluminescent method. Mathematical simulations were conducted to establish a SVM model for the combined diagnostics with the four variables. Moreover, ROC and its characteristic AUC were also employed to evaluate the classification efficacy of the model. Sigmoid function was utilized to estimate corresponding probabilities of classifying the clinical subjects as per 5 grades, which were incorporated into our established prostate index (PI) stratification system. Results: In SVM model, the mean AUC of the ROC with the quartet of variables was approximately 84% for PCa diagnosis, whereas the mean AUC of the ROCs with tPSA, fPSA, [Zn2+] or age alone was 64%, 62%, 55% and 59%, respectively. We further established an integrated prostate index (PI) stratification system with 5 grades and a software package to support clinicians in predicting PCa, with the accuracy of our risk stratification system being 83.3%, 91.6% and 83.3% in predicting normal, benign and PCa cases in corresponding groups. Follow-up findings especially MRI results and PI-RADS scores supported the reliability of this stratification platform as well. Conclusion: Findings from our present study demonstrated that index combination via SVM algorithms may well facilitate clinicians in early differential screening of PCa. Meanwhile, our established PI stratification system based on SVM model and Sigmoid function provided substantial accuracy in preclinical risk prediction of developing prostate cancer.

Maternal deprivation causes CaMKII downregulation and modulates glutamate, norepinephrine and serotonin in limbic brain areas in a rat model of single prolonged stress.

BACKGROUND: Early life stress is a major risk factor for later development of psychiatric disorders, including post-traumatic stress disorder (PTSD). An intricate relationship exists between various neurotransmitters (such as glutamate, norepinephrine or serotonin), calcium/calmodulin-dependent protein kinase II (CaMKII), as an important regulator of glutamatergic synaptic function, and PTSD. Here, we developed a double-hit model to investigate the interaction of maternal deprivation (MD) as an early life stress model and single prolonged stress (SPS) as a PTSD model at the behavioral and molecular levels. METHODS: Male Wistar rats exposed to these stress paradigms were subjected to a comprehensive behavioral analysis. In hippocampal synaptosomes we investigated neurotransmitter release and glutamate concentration. The expression of CaMKII and the content of monoamines were determined in selected brain regions. Brain-derived neurotrophic factor (BDNF) mRNA was quantified by radioactive in situ hybridization. RESULTS: We report a distinct behavioral phenotype in the double-hit group. Double-hit and SPS groups had decreased hippocampal presynaptic glutamatergic function. In hippocampus, double-hit stress caused a decrease in autophosphorylation of CaMKII. In prefrontal cortex, both SPS and double-hit stress had a similar effect on CaMKII autophosphorylation. Double-hit stress, rather than SPS, affected the norepinephrine and serotonin levels in prefrontal cortex, and suppressed BDNF gene expression in prefrontal cortex and hippocampus. LIMITATIONS: The study was conducted in male rats only. The affected brain regions cannot be restricted to hippocampus, prefrontal cortex and amygdala. CONCLUSION: Double-hit stress caused more pronounced and distinct behavioral, molecular and functional changes, compared to MD or SPS alone.

A deep unrolled neural network for real-time MRI-guided brain intervention.

Accurate navigation and targeting are critical for neurological interventions including biopsy and deep brain stimulation. Real-time image guidance further improves surgical planning and MRI is ideally suited for both pre- and intra-operative imaging. However, balancing spatial and temporal resolution is a major challenge for real-time interventional MRI (i-MRI). Here, we proposed a deep unrolled neural network, dubbed as LSFP-Net, for real-time i-MRI reconstruction. By integrating LSFP-Net and a custom-designed, MR-compatible interventional device into a 3 T MRI scanner, a real-time MRI-guided brain intervention system is proposed. The performance of the system was evaluated using phantom and cadaver studies. 2D/3D real-time i-MRI was achieved with temporal resolutions of 80/732.8 ms, latencies of 0.4/3.66 s including data communication, processing and reconstruction time, and in-plane spatial resolution of 1 × 1 mm2. The results demonstrated that the proposed method enables real-time monitoring of the remote-controlled brain intervention, and showed the potential to be readily integrated into diagnostic scanners for image-guided neurosurgery.

Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents.

Prosaposin (PSAP) modulates glycosphingolipid metabolism and variants have been linked to Parkinson's disease (PD). Here, we find altered PSAP levels in the plasma, CSF and post-mortem brain of PD patients. Altered plasma and CSF PSAP levels correlate with PD-related motor impairments. Dopaminergic PSAP-deficient (cPSAPDAT) mice display hypolocomotion and depression/anxiety-like symptoms with mildly impaired dopaminergic neurotransmission, while serotonergic PSAP-deficient (cPSAPSERT) mice behave normally. Spatial lipidomics revealed an accumulation of highly unsaturated and shortened lipids and reduction of sphingolipids throughout the brains of cPSAPDAT mice. The overexpression of α-synuclein via AAV lead to more severe dopaminergic degeneration and higher p-Ser129 α-synuclein levels in cPSAPDAT mice compared to WT mice. Overexpression of PSAP via AAV and encapsulated cell biodelivery protected against 6-OHDA and α-synuclein toxicity in wild-type rodents. Thus, these findings suggest PSAP may maintain dopaminergic lipid homeostasis, which is dysregulated in PD, and counteract experimental parkinsonism.

Spatial multimodal analysis of transcriptomes and metabolomes in tissues.

We present a spatial omics approach that combines histology, mass spectrometry imaging and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular-weight metabolites across tissue regions. The workflow is compatible with commercially available Visium glass slides. We demonstrate the potential of our method using mouse and human brain samples in the context of dopamine and Parkinson's disease.

An orthogonal matching pursuit optimization method for solving minimum-monitor-unit problems: Applications to proton IMPT, ARC and FLASH.

BACKGROUND: The intensities (i.e., number of protons in monitor unit [MU]) of deliverable proton spots need to be either zero or meet a minimum-MU (MMU) threshold, which is a nonconvex problem. Since the dose rate is proportionally associated with the MMU threshold, higher-dose-rate proton radiation therapy (RT) (e.g., efficient intensity modulated proton therapy (IMPT) and ARC proton therapy, and high-dose-rate-induced FLASH effect needs to solve the MMU problem with larger MMU threshold, which however makes the nonconvex problem more difficult to solve. PURPOSE: This work will develop a more effective optimization method based on orthogonal matching pursuit (OMP) for solving the MMU problem with large MMU thresholds, compared to state-of-the-art methods, such as alternating direction method of multipliers (ADMM), proximal gradient descent method (PGD), or stochastic coordinate descent method (SCD). METHODS: The new method consists of two essential components. First, the iterative convex relaxation (ICR) method is used to determine the active sets for dose-volume planning constraints and decouple the MMU constraint from the rest. Second, a modified OMP optimization algorithm is used to handle the MMU constraint: the non-zero spots are greedily selected via OMP to form the solution set to be optimized, and then a convex constrained subproblem is formed and can be conveniently solved to optimize the spot weights restricted to this solution set via OMP. During this iterative process, the new non-zero spots localized via OMP will be adaptively added to or removed from the optimization objective. RESULTS: The new method via OMP is validated in comparison with ADMM, PGD and SCD for high-dose-rate IMPT, ARC, and FLASH problems of large MMU thresholds, and the results suggest that OMP substantially improved the plan quality from PGD, ADMM and SCD in terms of both target dose conformality (e.g., quantified by max target dose and conformity index) and normal tissue sparing (e.g., mean and max dose). For example, in the brain case, the max target dose for IMPT/ARC/FLASH was 368.0%/358.3%/283.4% respectively for PGD, 154.4%/179.8%/150.0% for ADMM, 134.5%/130.4%/123.0% for SCD, while it was <120% in all scenarios for OMP; compared to PGD/ADMM/SCD, OMP improved the conformity index from 0.42/0.52/0.33 to 0.65 for IMPT and 0.46/0.60/0.61 to 0.83 for ARC. CONCLUSIONS: A new OMP-based optimization algorithm is developed to solve the MMU problems with large MMU thresholds, and validated using examples of IMPT, ARC, and FLASH with substantially improved plan quality from ADMM, PGD, and SCD.

Identification and validation of a novel prognostic circadian rhythm-related gene signature for stomach adenocarcinoma.

Circadian rhythm genes were reported to be strongly associated with the development and prognosis of circadian rhythm disorders related to stomach adenocarcinoma (STAD), which is one of the most prevalent cancers. This study aimed to identify a circadian rhythm-related gene signature that could help predict STAD outcome. Using bioinformatics analysis approaches, 105 genes were examined in 350 patients with STAD. Overall, six hub-type circadian rhythm-associated genes (GNA11, PER1, SOX14, EZH2, MAGED1, and NR1D1) were identified using univariate and multivariate Cox regression analyses. These genes were then used to build a genetic predictive model, which was further validated using a publicly available dataset (GSE26899). Overall, genes associated with the circadian rhythm were found to be substantially correlated with the characteristics of the STAD patients (grade, sex, and M stage). In addition, the circadian rhythm-related gene signature was significantly associated with the MAPK and Notch signaling pathways, which are known risk factors for poorer STAD outcome. Taken together, these findings suggest that the herein proposed prognostic model based on six circadian rhythm-associated genes may have predictive value and potential application for clinical decision-making and for personalized treatment of STAD.

Aberrant somatic calcium channel function in cNurr1 and LRRK2-G2019S mice.

In Parkinson's disease (PD), axons of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) degenerate before their cell bodies. Calcium influx during pacemaker firing might contribute to neuronal loss, but it is not known if dysfunctions of voltage-gated calcium channels (VGCCs) occur in DA neurons somata and axon terminals. We investigated T-type and L-type VGCCs in SNc-DA neurons of two mouse models of PD: mice with a deletion of the Nurr1 gene in DA neurons from an adult age (cNurr1 mice), and mice bearing the G2019S mutation in the gene coding for LRRK2 (G2019S mice). Adult cNurr1 mice displayed motor and DA deficits, while middle-aged G2019S mice did not. The number and morphology of SNc-DA neurons, most of their intrinsic membrane properties and pacemaker firing were unaltered in cNurr1 and G2019S mice compared to their control and wild-type littermates. L-type VGCCs contributed to the pacemaker firing of SNc-DA neurons in G2019S mice, but not in control, wild-type, and cNurr1 mice. In cNurr1 mice, but not G2019S mice, the contribution of T-type VGCCs to the pacemaker firing of SNc-DA neurons was reduced, and somatic dopamine-D2 autoreceptors desensitized more. Altered contribution of L-type and T-type VGCCs to the pacemaker firing was not observed in the presence of a LRRK2 kinase inhibitor in G2019S mice, and in the presence of a flavonoid with antioxidant activity in G2019S and cNurr1 mice. The role of L-type and T-type VGCCs in controlling dopamine release from axon terminals in the striatum was unaltered in cNurr1 and G2019S mice. Our findings uncover opposite changes, linked to oxidative stress, in the function of two VGCCs in DA neurons somata, but not axon terminals, in two different experimental PD models.

On-Tissue Chemical Derivatization for Comprehensive Mapping of Brain Carboxyl and Aldehyde Metabolites by MALDI-MS Imaging.

The visualization of small metabolites by MALDI mass spectrometry imaging in brain tissue sections is challenging due to low detection sensitivity and high background interference. We present an on-tissue chemical derivatization MALDI mass spectrometry imaging approach for the comprehensive mapping of carboxyls and aldehydes in brain tissue sections. In this approach, the AMPP (1-(4-(aminomethyl)phenyl)pyridin-1-ium chloride) derivatization reagent is used for the covalent charge-tagging of molecules containing carboxylic acid (in the presence of peptide coupling reagents) and aldehydes. This includes free fatty acids and the associated metabolites, fatty aldehydes, dipeptides, neurotoxic reactive aldehydes, amino acids, neurotransmitters and associated metabolites, as well as tricarboxylic acid cycle metabolites. We performed sensitive ultrahigh mass resolution MALDI-MS detection and imaging of various carboxyl- and aldehyde-containing endogenous metabolites simultaneously in rodent brain tissue sections. We verified the AMPP-derivatized metabolites by tandem MS for structural elucidation. This approach allowed us to image numerous aldehydes and carboxyls, including certain metabolites which had been undetectable in brain tissue sections. We also demonstrated the application of on-tissue derivatization to carboxyls and aldehydes in coronal brain tissue sections of a nonhuman primate Parkinson's disease model. Our methodology provides a powerful tool for the sensitive, simultaneous spatial molecular imaging of numerous aldehydes and carboxylic acids during pathological states, including neurodegeneration, in brain tissue.

Impaired Aversive Memory Formation in GPR37L1KO Mice.

GPR37L1 is an orphan G-protein-coupled receptor, which is implicated in neurological disorders, but its normal physiological role is poorly understood. Its close homologue, GPR37, is implicated in Parkinson's disease and affective disorders. In this study, we set out to characterize adult and middle-aged global GPR37L1 knock-out (KO) mice regarding emotional behaviors. Our results showed that GPR37L1KO animals, except adult GPR37L1KO males, exhibited impaired retention of aversive memory formation as assessed by the shorter retention latency in a passive avoidance task. Interestingly, the viral-mediated deletion of GPR37L1 in conditional knockout mice in the hippocampus of middle-aged mice also showed impaired retention in passive avoidance tasks, similar to what was observed in global GPR37L1KO mice, suggesting that hippocampal GPR37L1 is involved in aversive learning processes. We also observed that middle-aged GPR37L1KO male and female mice exhibited a higher body weight than their wild-type counterparts. Adult and middle-aged GPR37L1KO female mice exhibited a reduced level of serum corticosterone and middle-aged GPR37L1KO females showed a reduced level of epinephrine in the dorsal hippocampus in the aftermath of passive avoidance task, with no such effects observed in GPR37L1KO male mice, suggesting that lack of GPR37L1 influences behavior and biochemical readouts in age- and sex-specific manners.

Decreased Prosaposin and Progranulin in the Cingulate Cortex Are Associated with Schizophrenia Pathophysiology.

Prosaposin (PSAP) and progranulin (PGRN) are two lysosomal proteins that interact and modulate the metabolism of lipids, particularly sphingolipids. Alterations in sphingolipid metabolism have been found in schizophrenia. Genetic associations of PSAP and PGRN with schizophrenia have been reported. To further clarify the role of PSAP and PGRN in schizophrenia, we examined PSAP and PGRN levels in postmortem cingulate cortex tissue from healthy controls along with patients who had suffered from schizophrenia, bipolar disorder, or major depressive disorder. We found that PSAP and PGRN levels are reduced specifically in schizophrenia patients. To understand the role of PSAP in the cingulate cortex, we used an AAV strategy to knock down PSAP in neurons located in this region. Neuronal PSAP knockdown led to the downregulation of neuronal PGRN levels and behavioral abnormalities. Cingulate-PSAP-deficient mice exhibited increased anxiety-like behavior and impaired prepulse inhibition, as well as intact locomotion, working memory, and a depression-like state. The behavioral changes were accompanied by increased early growth response protein 1 (EGR-1) and activity-dependent cytoskeleton-associated protein (ARC) levels in the sensorimotor cortex and hippocampus, regions implicated in circuitry dysfunction in schizophrenia. In conclusion, PSAP and PGRN downregulation in the cingulate cortex is associated with schizophrenia pathophysiology.

Prosaposin Reduces α-Synuclein in Cells and Saposin C Dislodges it from Glucosylceramide-enriched Lipid Membranes.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder affecting over 1% of the 65 + age population. Saposin C, a lysosomal protein required for the normal activity of glucocerebrosidase (GCase), may serve as a disease modifier in PD. Saposin C is cleaved from its precursor, Prosaposin (PSAP), which is secreted as an uncleaved protein and exerts neuroprotective effects. In this study, we aim to elucidate the neuroprotective roles of PSAP and saposin C in PD by evaluating their effects on α-synuclein accumulation in human neuroblastoma cells. Stable overexpression of PSAP reduced monomeric α-synuclein levels in SH-SY5Y cells, while PSAP knockdown by small interfering RNA led to the opposite effect, and those effects were independent of GCase activity. Autophagy flux was decreased by stable PSAP overexpression. Furthermore, a flow-through assay revealed that recombinant saposin C was able to detach α-synuclein from artificial glucosylceramide-enriched lipid membranes at the lysosomal pH. Taken together, our findings provide further evidence that PSAP and saposin C as key proteins involved in α-synuclein clearance by dislodging it from lipid membranes.

The protective effect of MiR-27a on the neonatal hypoxic-ischemic encephalopathy by targeting FOXO1 in rats.

Background: Neonatal hypoxic-ischemic encephalopathy (HIE), a kind of hypoxic-ischemic brain damage caused by perinatal asphyxia, is the most crucial cause of neonatal death and long-term neurological dysfunction in children. We aimed to investigate the protective effects of micro (mi)R-27a on HIE in neonatal rats. Methods: A rat model of neonatal HIE was constructed by modification of the Rice-Vannucci model. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to test the expressions of miR-27a, FOXO1 messenger RNA (mRNA), interleukin-1ß (IL-1ß) mRNA, and tumor necrosis factor-α (TNF-α) mRNA, and western blot was applied to test the expression of FOXO1. In order to overexpress miR-27a, an intracerebroventricular injection (i.c.v) of miR-27a mimic was administered. We adopted 2,3,5-triphenytetrazolium chloride (TTC) staining and brain water content measurement to test the effects of miR-27a on the infarcted volume and edema in brain after HIE. Flow cytometry (FCM) analysis was applied to test the effects of miR-27a on the infiltrated peripheral immune cells in the rat brains after HIE. Results: We successfully established a rat model of neonatal HIE. It was revealed that the expressions of miR-27a decreased gradually after HIE, however, the expressions of FOXO1 mRNA increased. After injection of the miR-27a mimic, the expression of miR-27a in the rat HIE model brains was significantly upregulated, however, the expression of FOXO1 was robustly downregulated. Both TTC staining and brain water content showed that the infarcted volume and brain edema was markedly increased after HIE. Interestingly, the overexpression of miR-27a reduced the infarcted volume and edema induced by HIE. Additionally, RT-qPCR and FCM analysis showed that HIE lead to increases of IL-1ß, TNF-α, and infiltrated immune cells. Overexpression of miR-27a could reduce the expressions of IL-1ß mRNA and TNF-α mRNA, and the cell numbers of infiltrated peripheral macrophages and neutrophils in the brain. Conclusions: MiR-27a plays protective roles by reducing infarct volume and brain edema, and inhibiting inflammatory factors and infiltrated peripheral immune cells by targeting FOXO1 in neonatal HIE rats.

Corrigendum to "Calorie Restriction Protects against Contrast-Induced Nephropathy via SIRT1/GPX4 Activation".

[This corrects the article DOI: 10.1155/2021/2999296.].

Clinical application value of serum neutrophil gelatinase-associated lipocalin in neonatal sepsis.

BACKGROUND: To explore the value of serum neutrophil gelatinase-associated lipocalin (sNGAL) in the diagnosis and follow up of neonatal late-onset sepsis. METHODS: A total of 69 infants were enrolled in this prospective study, including 49 infants of late-onset neonatal sepsis in the observation group, and 20 infants without infection serving as the control group. The sNGAL, C-reactive protein (CRP), and procalcitonin (PCT) concentrations were determined in both groups and compared at different time points. A receiver operating characteristic (ROC) curve was drawn to evaluate the values of the 3 parameters in the forecast of neonatal late-onset sepsis. RESULTS: The levels of sNGAL, CRP, and PCT were all increased obviously (P<0.05) in the observation group on the first and second day following onset, compared to the control group. The sNGAL level was associated with the time of treatment. Surprisingly, the sNGAL level started to drop in the observation group with effective treatment on the 7th day following onset. A correlation was found between the concentration of sNGAL and inflammatory markers, such as CRP and PCT, on the first day. The area under the ROC curve (AUC) for sNGAL, CRP, and PCT was: 0.964, 0.925, and 0.94, respectively. CONCLUSIONS: Increased sNGAL levels could reflect the inflammatory status in the acute stage of neonatal sepsis. When combined with other sepsis markers, such as CRP and PCT, the sNGAL is a useful marker in the rapid diagnosis and follow up of neonatal sepsis.