Predicting lncRNA-disease associations based on combining selective similarity matrix fusion and bidirectional linear neighborhood label propagation.

Recent studies have revealed that long noncoding RNAs (lncRNAs) are closely linked to several human diseases, providing new opportunities for their use in detection and therapy. Many graph propagation and similarity fusion approaches can be used for predicting potential lncRNA-disease associations. However, existing similarity fusion approaches suffer from noise and self-similarity loss in the fusion process. To address these problems, a new prediction approach, termed SSMF-BLNP, based on organically combining selective similarity matrix fusion (SSMF) and bidirectional linear neighborhood label propagation (BLNP), is proposed in this paper to predict lncRNA-disease associations. In SSMF, self-similarity networks of lncRNAs and diseases are obtained by selective preprocessing and nonlinear iterative fusion. The fusion process assigns weights to each initial similarity network and introduces a unit matrix that can reduce noise and compensate for the loss of self-similarity. In BLNP, the initial lncRNA-disease associations are employed in both lncRNA and disease directions as label information for linear neighborhood label propagation. The propagation was then performed on the self-similarity network obtained from SSMF to derive the scoring matrix for predicting the relationships between lncRNAs and diseases. Experimental results showed that SSMF-BLNP performed better than seven other state of-the-art approaches. Furthermore, a case study demonstrated up to 100% and 80% accuracy in 10 lncRNAs associated with hepatocellular carcinoma and 10 lncRNAs associated with renal cell carcinoma, respectively. The source code and datasets used in this paper are available at: https://github.com/RuiBingo/SSMF-BLNP.

Karyotype and LTR-RTs analysis provide insights into oak genomic evolution.

BACKGROUND: Whole-genome duplication and long terminal repeat retrotransposons (LTR-RTs) amplification in organisms are essential factors that affect speciation, local adaptation, and diversification of organisms. Understanding the karyotype projection and LTR-RTs amplification could contribute to untangling evolutionary history. This study compared the karyotype and LTR-RTs evolution in the genomes of eight oaks, a dominant lineage in Northern Hemisphere forests. RESULTS: Karyotype projections showed that chromosomal evolution was relatively conservative in oaks, especially on chromosomes 1 and 7. Modern oak chromosomes formed through multiple fusions, fissions, and rearrangements after an ancestral triplication event. Species-specific chromosomal rearrangements revealed fragments preserved through natural selection and adaptive evolution. A total of 441,449 full-length LTR-RTs were identified from eight oak genomes, and the number of LTR-RTs for oaks from section Cyclobalanopsis was larger than in other sections. Recent amplification of the species-specific LTR-RTs lineages resulted in significant variation in the abundance and composition of LTR-RTs among oaks. The LTR-RTs insertion suppresses gene expression, and the suppressed intensity in gene regions was larger than in promoter regions. Some centromere and rearrangement regions indicated high-density peaks of LTR/Copia and LTR/Gypsy. Different centromeric regional repeat units (32, 78, 79 bp) were detected on different Q. glauca chromosomes. CONCLUSION: Chromosome fusions and arm exchanges contribute to the formation of oak karyotypes. The composition and abundance of LTR-RTs are affected by its recent amplification. LTR-RTs random retrotransposition suppresses gene expression and is enriched in centromere and chromosomal rearrangement regions. This study provides novel insights into the evolutionary history of oak karyotypes and the organization, amplification, and function of LTR-RTs.

4 mC site recognition algorithm based on pruned pre-trained DNABert-Pruning model and fused artificial feature encoding.

DNA 4 mC plays a crucial role in the genetic expression process of organisms. However, existing deep learning algorithms have shortcomings in the ability to represent DNA sequence features. In this paper, we propose a 4 mC site identification algorithm, DNABert-4mC, based on a fusion of the pruned pre-training DNABert-Pruning model and artificial feature encoding to identify 4 mC sites. The algorithm prunes and compresses the DNABert model, resulting in the pruned pre-training model DNABert-Pruning. This model reduces the number of parameters and removes redundancy from output features, yielding more precise feature representations while upholding accuracy.Simultaneously, the algorithm constructs an artificial feature encoding module to assist the DNABert-Pruning model in feature representation, effectively supplementing the information that is missing from the pre-trained features. The algorithm also introduces the AFF-4mC fusion strategy, which combines artificial feature encoding with the DNABert-Pruning model, to improve the feature representation capability of DNA sequences in multi-semantic spaces and better extract 4 mC sites and the distribution of nucleotide importance within the sequence. In experiments on six independent test sets, the DNABert-4mC algorithm achieved an average AUC value of 93.81%, outperforming seven other advanced algorithms with improvements of 2.05%, 5.02%, 11.32%, 5.90%, 12.02%, 2.42% and 2.34%, respectively.

Orientational transitions of discotic columnar liquid crystals in cylindrical pores.

Confined in a cylindrical pore with homeotropic anchoring condition, the hexagonal columnar phase of discotic liquid crystals can form a "log-pile" configuration, in which the columns are perpendicular to the long axis of the pore. However, the {100} planes of the hexagonal lattice can orient either parallel (termed (100)‖ orientation) or perpendicular ((100)⊥) to pore axis. Here we experimentally show that the (100)‖ orientation is found in narrower cylindrical pores, and the (100)‖-(100)⊥ transition can be controlled by engineering the structure of the molecules. The (100)‖ orientation is destroyed in asymmetric discotics hepta(heptenyloxy)triphenylene (SATO7); replacing the oxygen linkage in hexa(hexyloxy)triphenylene (HATO6) by sulphur (HATS6) improves the (100)‖ orientation in small pores; adding a perfluorooctyl end to each alkyl chain of HATO6 (HATO6F8) moves the (100)‖-(100)⊥ transition to larger pores. We have provided a semi-quantitative explanation of the experimental observations, and discussed them in the context of previous findings on related materials in a wider pore size range from 60 nm to 100 µm. This allows us to produce a comprehensive picture of confined columnar liquid crystals whose applications critically depend on our ability to align them.

LUNCRW: Prediction of potential lncRNA-disease associations based on unbalanced neighborhood constraint random walk.

Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are associated with various complex human diseases. They can serve as disease biomarkers and hold considerable promise for the prevention and treatment of various diseases. The traditional random walk algorithms generally exclude the effect of non-neighboring nodes on random walking. In order to overcome the issue, the neighborhood constraint (NC) approach is proposed in this study for regulating the direction of the random walk by computing the effects of both neighboring nodes and non-neighboring nodes. Then the association matrix is updated by matrix multiplication for minimizing the effect of the false negative data. The heterogeneous lncRNA-disease network is finally analyzed using an unbalanced random walk method for predicting the potential lncRNA-disease associations. The LUNCRW model is therefore developed for predicting potential lncRNA-disease associations. The area under the curve (AUC) values of the LUNCRW model in leave-one-out cross-validation and five-fold cross-validation were 0.951 and 0.9486 ± 0.0011, respectively. Data from published case studies on three diseases, including squamous cell carcinoma, hepatocellular carcinoma, and renal cell carcinoma, confirmed the predictive potential of the LUNCRW model. Altogether, the findings indicated that the performance of the LUNCRW method is superior to that of existing methods in predicting potential lncRNA-disease associations.

A GP130-Targeting Small Molecule, LMT-28, Reduces LPS-Induced Bone Resorption around Implants in Diabetic Models by Inhibiting IL-6/GP130/JAK2/STAT3 Signaling.

In this study, we examined the effect of the GP130-targeting molecule, LMT-28, on lipopolysaccharide- (LPS-) induced bone resorption around implants in diabetic models using in vitro and rat animal experiments. First, LMT-28 was added to osteoblasts stimulated by LPS and advanced glycation end products (AGEs), and nuclear factor-κB receptor-activating factor ligand (RANKL) and associated pathways were evaluated. Then, LMT-28 was administered by gavage at 0.23 mg/kg once every 5 days for 2 weeks to type 2 diabetic rats with peri-implantitis induced by LPS injection and silk ligature. The expression of IL-6 and RANKL was evaluated by immunohistochemistry, and the bone resorption around implants was evaluated by microcomputed tomography. The results showed that LMT-28 downregulated the expression of RANKL through the JAK2/STAT3 signaling pathway in osteoblasts stimulated by LPS and AGEs, reduced bone resorption around implants with peri-implantitis, decreased the expression of IL-6 and RANKL, and decreased osteoclast activity in type 2 diabetic rats. This study confirmed the ability of LMT-28 to reduce LPS-induced bone resorption around implants in diabetic rats.

Association of dietary total antioxidant capacity with all-cause and cardiovascular mortality in patients with chronic kidney disease: based on two retrospective cohort studies of NHANES.

BACKGROUND: The relationship between dietary total antioxidant capacity (DTAC) and death risk among CKD populations remains unclear. METHODS: Based on vitamin C equivalent antioxidant capacity (VCEAC) and the component dietary antioxidant index (CDAI) indices, we analyzed two cohorts to investigate the association of DTAC with all-cause and CVD mortality in CKD patients using data from National Health and Nutrition Examination Survey (2007-2018). VCEAC (n = 6330) and CDAI (n = 6300) cohorts with mortality follow-up data available through 2018 were included. Cox models with restricted cubic splines was used to model the nonlinear association between VCEAC/CDAI and outcomes in CKD patients. RESULTS: Our results showed L-shaped associations of DTAC with all-cause mortality among individuals with CKD stages 1-2 in both cohorts. Compared to the lowest quartile, higher dietary total antioxidant intake was associated with lower all-cause mortality risks among CKD stages 1-2 after adjustment for covariates, with HRs (95%CI) of 1.00, 0.91 (0.71,1.17), 0.69 (0.53,0.90), and 0.70 (0.54,0.91) in VCEAC, and similar respective estimate trends in CDAI. After sensitivity and subgroup analyses, there were no benefits for patients with stage 3-5 CKD or albuminuria. Mediation analysis revealed that the proportions mediated in both cohorts were less consistent. CONCLUSIONS: Moderate dietary total antioxidants intake has potential benefits for early-stage CKD patients. However, further evidence is needed to confirm whether patients with worsening CKD can benefit in the long term.

Model construction of factors influencing intensive care unit nurses' medical device-related pressure injury knowledge, attitude, and practice.

The ability of knowledge, attitude, and practice of intensive care unit (ICU) nurses to perform medical device-related pressure injuries (MDRPIs) can affect the incidence of MDRPI in ICU patients. Therefore, in order to improve ICU nurses' understanding and nursing ability of MDRPIs, we investigated the non-linear relationship (synergistic and superimposed relationships) between the factors influencing ICU nurses' ability of knowledge, attitude, and practice. A Clinical Nurses' Knowledge, Attitude, and Practice Questionnaire for the Prevention of MDRPI in Critically Ill Patients was administered to 322 ICU nurses from tertiary hospitals in China from January 1, 2022 to June 31, 2022. After the questionnaire was distributed, the data were collected and sorted out, and the corresponding statistical analysis and modelling software was used to analyse the data. IBM SPSS 25.0 software was used to conduct Single factor analysis and Logistic regression analysis on the data, so as to screen the statistically significant influencing factors. IBM SPSS Modeler18.0 software was used to construct a decision tree model of the factors influencing MDRPI knowledge, attitude, and practice of ICU nurses, and ROC curves were plotted to analyse the accuracy of the model. The results showed that the overall passing rate of ICU nurses' knowledge, attitude, and practice score was 72%. The statistically significant predictor variables ranked in importance were education background (0.35), training (0.31), years of working (0.24), and professional title (0.10). AUC = 0.718, model prediction performance is good. There is a synergistic and superimposed relationship between high education background, attended training, high years of working and high professional title. Nurses with the above factors have strong MDRPI knowledge, attitude, and practice ability. Therefore, nursing managers can develop a reasonable and effective scheduling system and MDRPI training program based on the study results. The ultimate goal is to improve the ability of ICU nurses to know and act on MDRPI and to reduce the incidence of MDRPI in ICU patients.

[Research progress of Codonopsis Radix and prediction of its Q-markers].

Codonopsis Radix is a traditional tonic medicine commonly used in China, which has the effects of strengthening the spleen and tonifying the lung, as well as nourishing blood and engendering liquid. The chemical constituents of Codonopsis species are mainly polyacetylenes, alkaloids, phenylpropanoids, lignans, terpenoids and saponins, flavonoids, steroids, organic acids, saccharides, and so on. Modern pharmacological studies showed that Codonopsis Radix also has a variety of pharmacological effects such as enhancing body immunity, protecting gastrointestinal mucosa and resisting ulcers, promoting hematopoietic function, regulating blood sugar, and delaying aging. In this paper, the chemical constituents of Codonopsis species and the pharmacological effects of Codonopsis Radix were summarized, and on this basis, the quality markers of Codonopsis Radix were analyzed. It was predicted that lobetyolin, tangshenoside I, codonopyrrolidium A, and the oligosaccharides were the possible Q-markers of Codonopsis Radix. This paper will provide scientific references for the quality evaluation and profound research and the development of Codonopsis Radix.

An emerging potential of metabolomics in multiple sclerosis: a comprehensive overview.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the nervous system that primarily affects young adults. Although the exact etiology of the disease remains obscure, it is clear that alterations in the metabolome contribute to this process. As such, defining a reliable and disease-specific metabolome has tremendous potential as a diagnostic and therapeutic strategy for MS. Here, we provide an overview of studies aimed at identifying the role of metabolomics in MS. These offer new insights into disease pathophysiology and the contributions of metabolic pathways to this process, identify unique markers indicative of treatment responses, and demonstrate the therapeutic effects of drug-like metabolites in cellular and animal models of MS. By and large, the commonly perturbed pathways in MS and its preclinical model include lipid metabolism involving alpha-linoleic acid pathway, nucleotide metabolism, amino acid metabolism, tricarboxylic acid cycle, D-ornithine and D-arginine pathways with collective role in signaling and energy supply. The metabolomics studies suggest that metabolic profiling of MS patient samples may uncover biomarkers that will advance our understanding of disease pathogenesis and progression, reduce delays and mistakes in diagnosis, monitor the course of disease, and detect better drug targets, all of which will improve early therapeutic interventions and improve evaluation of response to these treatments.

Giant subcutaneous bronchogenic cyst in the intergluteal cleft region of an adult: a case report and literature review.

BACKGROUND: Bronchogenic cysts (BCs) are generally detected in the mediastinum, along the tracheobronchial tree, or in the lung parenchyma. Subcutaneous BCs are rare, but, when found, are usually small (< 3 cm) and detected in children. CASE PRESENTATION: In an unusual adult case, we treated a 52-year-old woman who presented with a mass in the left intergluteal cleft region. Ultrasonography showed a well-circumscribed hypoechoic lesion with posterior enhancement and internal echogenic foci within the mass. Color Doppler images showed no signals. Computed tomography showed the mass as a homogeneous, 6.8- × 6.3- × 5.1-cm soft tissue-attenuation lesion lodged in subcutaneous fatty tissue. Magnetic resonance imaging revealed a cystic lesion of similar dimensions with heterogeneous hyperintensity on both T1- and T2-weighted images. No contrast enhancement, solid components, or restricted diffusion foci were apparent. The cyst was completely excised, and histopathological evaluation indicated it was a BC. The patient's recovery was uneventful. CONCLUSIONS: BCs should be considered in the differential diagnosis of all subcutaneous cystic masses, regardless of their location and size and the patient's age.

Increased number and function of endothelial progenitor cells in breast cancer patients and the linear correlation with VEGF level.

The number of circulating endothelial progenitor cells (EPCs) was found to increase in patients with breast cancer, but the alteration in EPC function remains to be elusive. We conducted this study to evaluate the number and function of peripheral EPCs of breast cancer patients and its possible underlying mechanism. Besides, the vascular endothelial growth factor (VEGF), VCAM-1, IL-6, and IL-34 levels were measured in blood samples and also in vitro in a medium of EPCs. We found that the number of circulating EPCs in breast cancer patients was significantly higher than that in normal control and remarkably augmented in a stage-dependent manner. Meanwhile, a similar enhancement was observed in the migratory, proliferative, and adhesive activity of circulating EPCs originating from breast cancer patients. More importantly, the VEGF level in blood samples was dramatically elevated in comparison to the control, which was correlated positively with the number and activity of circulating EPCs from breast cancer patients. Moreover, in vitro medium of EPCs from breast cancer patients highly expressed VEGF compared with that from the control, which also had a positive correlation with the number and activity of circulating EPCs from breast cancer patients. This is the first time to demonstrate that the number and function of circulating EPCs are promoted in breast cancer patients, which are positively related to an enhanced VEGF production. These may provide a novel target for improving the outcome of breast cancer.

Tao-Hong-Si-Wu decoction improves depressive symptoms in model rats via amelioration of BDNF-CREB-arginase I axis disorders.

CONTEXT: The traditional Chinese medicine formula Tao-Hong-Si-Wu decoction (TSD), used for treating ischaemic stroke, has the potential to treat depressive disorder (DD). OBJECTIVE: To explore the effective targets of TSD on DD animal models. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were modelled by inducing chronic unpredictable mild stress (CUMS) during 35 days and treated with three dosages of TSD (2.5, 5 and 10 g/kg) or fluoxetine (10 mg/kg) by oral gavage for 14 days. Bodyweight measurements and behavioural tests were performed to observe the effect of TSD on the CUMS animals. A gas chromatography coupled with mass spectrometry (GC-MS)-based metabolomic analysis was conducted to reveal the metabolic characteristics related to the curative effect of TSD. Levels of the proteins associated with the feature metabolites were analysed. RESULTS: Reduced immobile duration and crossed squares in the behavioural tests were raised by 48.6% and 32.9%, on average, respectively, by TSD treatment (ED50=3.2 g/kg). Antidepressant effects of TSD were associated with 13 decreased metabolites and the restorations of ornithine and urea in the serum. TSD (5 g/kg) raised serum serotonin by 54.1 mg/dL but suppressed arginase I (Arg I) by 47.8 mg/dL in the CUMS rats. Proteins on the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) axis that modulate the inhibition of Arg I were suppressed in the CUMS rats but reversed by the TSD intervention. DISCUSSION AND CONCLUSIONS: TSD improves depression-like symptoms in CUMS rats. Further study will focus on the antidepressant-like effects of effective compounds contained in TSD.

Behavioral sensitization induced by methamphetamine causes differential alterations in gene expression and histone acetylation of the prefrontal cortex in rats.

BACKGROUND: Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats. METHODS: We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays. RESULTS: In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 genes were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure. CONCLUSIONS: The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.

Prevalence and patterns of tongue deformation in obstructive sleep apnea: A whole-night simultaneous ultrasonographic and polysomnographic study.

Tongue deformation during whole-night natural sleep in adult patients with obstructive sleep apnea has not been well evaluated. Through simultaneous ultrasonography and polysomnography during whole-night sleep, we examined the prevalence and patterns of tongue depth changes and their relationship with the severity of obstructive sleep apnea. Sixty consecutive eligible adults presenting with symptoms suggesting obstructive sleep apnea were enrolled. We observed that 88.4% (38/43) of patients with obstructive sleep apnea exhibited a significant increase in the maximum ultrasonographic tongue depth when hypopnea or apnea occurred during sleep. A mixed-model analysis of variance demonstrated that compared with patients with primary snoring or mild obstructive sleep apnea, those with moderate to severe obstructive sleep apnea have significantly greater maximum ultrasonographic tongue depth during respiratory events (p = .0047). We identified three different ultrasonographic patterns of tongue deformation, namely en bloc, tongue body and tongue base. Approximately 82% (27/33) of patients with moderate to severe obstructive sleep apnea demonstrated an en bloc tongue deformation. By contrast, 70% (19/27) of primary snorers or patients with mild obstructive sleep apnea showed a tongue body obstruction. Recognizing the prevalence and patterns of tongue deformation during sleep may provide insights into pathogenesis and treatment decisions in patients with obstructive sleep apnea. Future studies are warranted to verify the treatment results of various tongue procedures by using this approach.

Risk stratification and outcomes of intracranial hemorrhage in patients with immune thrombocytopenia under 60 years of age.

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.

Liquid Organic Frameworks: The Single-Network "Plumber's Nightmare" Bicontinuous Cubic Liquid Crystal.

Novel bolapolyphiles, built of a p-terphenyl or bistolane core with polar glycerol end-groups and two laterally attached n-alkyl or semiperfluoroalkyl chains, form the first "single plumber's nightmare network", the simplest soft-matter cubic phase (Pm3̅m). Its cage-like grid comprises bundles of aromatic rods lying along the cubic unit cell edges, connected by six-way hydrogen-bonded junctions. Side-chains fill the remaining volume of this unique noninterpenetrating liquid-crystalline organic framework.

Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020.

To determine distribution of severe acute respiratory syndrome coronavirus 2 in hospital wards in Wuhan, China, we tested air and surface samples. Contamination was greater in intensive care units than general wards. Virus was widely distributed on floors, computer mice, trash cans, and sickbed handrails and was detected in air ≈4 m from patients.

Long non-coding RNA Snhg3 protects against hypoxia/ischemia-induced neonatal brain injury.

Hypoxic-ischemic brain damage (HIBD) is a major cause of morbidity and mortality in the preterm and term infant. However, the precise mechanism of HIBD remains largely elusive. As a newly discovered long non-coding RNA, small nucleolar RNA host gene 3 (Snhg3) has shown its important roles in cell apoptosis, proliferation, and disease development. In this study, we determined the role of Snhg3 in the pathogenesis of HIBD. Snhg3 expression was significantly down-regulated in the neonatal brain and primary hippocampal cells response to hypoxic/ischemic stress. Snhg3 overexpression protected against hypoxic/ischemic-induced brain injury in vivo and hippocampal cell injury in vitro. Snhg3 acted as the sponge of miR-196 in the hippocampal cells by regulating the expression of miR-196 target genes, XIAP and CAAP1. Moreover, Snhg3 overexpression decreased brain infarct size and ameliorated hypoxic-ischemic neonatal brain damage. This study suggests that Snhg3 is a potential target for the treatment of HIBD.

Lung and general health effects of Toll-like receptor-4 (TLR4)-interacting SPA4 peptide.

BACKGROUND: A surfactant protein-A-derived peptide, which we call SPA4 peptide (amino acids: GDFRYSDGTPVNYTNWYRGE), alleviates lung infection and inflammation. This study investigated the effects of intratracheally administered SPA4 peptide on systemic, lung, and health parameters in an outbred mouse strain, and in an intratracheal lipopolysaccharide (LPS) challenge model. METHODS: The outbred CD-1 mice were intratracheally administered with incremental doses of SPA4 peptide (0.625-10 µg/g body weight) once every 24 h, for 3 days. Mice left untreated and those treated with vehicle were included as controls. Mice were euthanized after 24 h of last administration of SPA4 peptide. In order to assess the biological activity of SPA4 peptide, C57BL6 mice were intratracheally challenged with 5 µg LPS/g body weight and treated with 50 µg SPA4 peptide via intratracheal route 1 h post LPS-challenge. Mice were euthanized after 4 h of LPS challenge. Signs of sickness and body weights were regularly monitored. At the time of necropsy, blood and major organs were harvested. Blood gas and electrolytes, serum biochemical profiles and SPA4 peptide-specific immunoglobulin G (IgG) antibody levels, and common lung injury markers (levels of total protein, albumin, and lactate, lactate dehydrogenase activity, and lung wet/dry weight ratios) were determined. Lung, liver, spleen, kidney, heart, and intestine were examined histologically. Differences in measured parameters were analyzed among study groups by analysis of variance test. RESULTS: The results demonstrated no signs of sickness or changes in body weight over 3 days of treatment with various doses of SPA4 peptide. It did not induce any major toxicity or IgG antibody response to SPA4 peptide. The SPA4 peptide treatment also did not affect blood gas, electrolytes, or serum biochemistry. There was no evidence of injury to the tissues and organs. However, the SPA4 peptide suppressed the LPS-induced lung inflammation. CONCLUSIONS: These findings provide an initial toxicity profile of SPA4 peptide. Intratracheal administration of escalating doses of SPA4 peptide does not induce any significant toxicity at tissue and organ levels. However, treatment with a dose of 50 µg SPA4 peptide, comparable to 2.5 µg/g body weight, alleviates LPS-induced lung inflammation.