Identification of key genes and long non­coding RNA expression profiles in osteoporosis with rheumatoid arthritis based on bioinformatics analysis.

BACKGROUND: Although rheumatoid arthritis (RA) is a chronic systemic tissue disease often accompanied by osteoporosis (OP), the molecular mechanisms underlying this association remain unclear. This study aimed to elucidate the pathogenesis of RA and OP by identifying differentially expressed mRNAs (DEmRNAs) and long non-coding RNAs (lncRNAs) using a bioinformatics approach. METHODS: Expression profiles of individuals diagnosed with OP and RA were retrieved from the Gene Expression Omnibus database. Differential expression analysis was conducted. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway enrichment analyses were performed to gain insights into the functional categories and molecular/biochemical pathways associated with DEmRNAs. We identified the intersection of common DEmRNAs and lncRNAs and constructed a protein-protein interaction (PPI) network. Correlation analysis between the common DEmRNAs and lncRNAs facilitated the construction of a coding-non-coding network. Lastly, serum peripheral blood mononuclear cells (PBMCs) from patients with RA and OP, as well as healthy controls, were obtained for TRAP staining and qRT-PCR to validate the findings obtained from the online dataset assessments. RESULTS: A total of 28 DEmRNAs and 2 DElncRNAs were identified in individuals with both RA and OP. Chromosomal distribution analysis of the consensus DEmRNAs revealed that chromosome 1 had the highest number of differential expression genes. GO and KEGG analyses indicated that these DEmRNAs were primarily associated with " platelets (PLTs) degranulation", "platelet alpha granules", "platelet activation", "tight junctions" and "leukocyte transendothelial migration", with many genes functionally related to PLTs. In the PPI network, MT-ATP6 and PTGS1 emerged as potential hub genes, with MT-ATP6 originating from mitochondrial DNA. Co-expression analysis identified two key lncRNA-mRNA pairs: RP11 - 815J21.2 with MT - ATP6 and RP11 - 815J21.2 with PTGS1. Experimental validation confirmed significant differential expression of RP11-815J21.2, MT-ATP6 and PTGS1 between the healthy controls and the RA + OP groups. Notably, knockdown of RP11-815J21.2 attenuated TNF + IL-6-induced osteoclastogenesis. CONCLUSIONS: This study successfully identified shared dysregulated genes and potential therapeutic targets in individuals with RA and OP, highlighting their molecular similarities. These findings provide new insights into the pathogenesis of RA and OP and suggest potential avenues for further research and targeted therapies.

Clinical effect of reduning combined with gamma globulin treatment on symptom improvement serum levels of IL-6, 25-(OH)D and LDH in children with severe mycoplasma pneumonia.

Objectives: To investigate the effects of Reduning combined with gamma globulin on symptom improvement and serum levels of interleukin-6 (IL-6), 25-hydroxyvitamin D[25-(OH)D] and lactate dehydrogenase (LDH) in children with severe mycoplasma pneumonia (MP). Methods: A total of 123 children with severe MP admitted to the Changzhou Cancer Hospital affiliated to Soochow University from May 2018 to April 2020 were selected as subjects and randomly divided into three groups: control Group-A, control Group-B and the observation group, with 41 cases in each group. Control Group-A was given with Reduning, control Group-B was treated with gamma globulin, while the observation group was treated with Reduning injection combined with gamma globulin. The clinical efficacy, symptom improvement, incidence of adverse reactions, serum levels of IL-6, 25-(OH)D, LDH, Toll-like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88) signaling pathway and T lymphocyte subsets before and after treatment were statistically compared between the three groups. Results: The total effective rate of treatment in the observation group was higher than that in control Group-A and control Group-B (p<0.05); The time for body temperature, lung rales, and cough to return to normal in the observation group was shorter than that in control Group-A and control Group-B (p<0.05). After treatment, the observation group had lower serum levels of IL-6, LDH, and higher levels of 25-(OH)D compared with control Group-A and control Group-B (p<0.05). Moreover, the observation group had lower serum expressions of TLR4 and MyD88 (p<0.05), higher serum levels of CD4+, CD4+/CD8+, and lower CD8+ compared with control Group-A and control Group-B (p<0.05). No significant difference can be seen in the comparison of the incidence of adverse reactions between the three groups (p>0.05). Conclusions: Reduning combined with gamma globulin in the treatment of severe MP is worthy of clinical promotion and application. With such a treatment regimen, the immune function of children with severe MP can be significantly enhanced, the inflammatory response can be suppressed, and symptom improvement can be promoted, further improving the treatment outcome.

Endometrial Epithelial Cell Apoptosis Is Inhibited by a ciR8073-miR181a-Neurotensis Pathway during Embryo Implantation.

Development of the receptive endometrium (RE) from the pre-receptive endometrium (PE) is essential for embryo implantation, but its molecular mechanisms have not been fully understood. In this study, lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed to explore the functions of potential competing endogenous RNAs (ceRNA) during the development of RE in dairy goats. We observed that circRNA8073 (ciR8073) decreased the levels of miR-181a by acting as a miRNA sponge. This effect indirectly increased the expression of neurotensin in endometrial epithelial cells (EECs). Neurotensin then inhibited EEC apoptosis by increasing the expression of BCL-2/BAX in favor of BCL-2 via the MAPK pathway and also induced increased expression of leukemia-inhibitory factor, cyclo-oxygenase 2, vascular endothelial growth factor A, and homeobox A10. We have thus identified a ciR8073-miR181a-neurotensin pathway in the endometrium of dairy goats. Through this pathway, ciR8073 functions as a ceRNA that sequesters miR-181a, thereby protecting neurotensin transcripts from miR-181a-mediated suppression in EECs.

Evolutionary progression of mitochondrial gene rearrangements and phylogenetic relationships in Strigidae (Strigiformes).

The bird mitogenome is generally considered to have a conservative genome size, consistent gene content, and similar gene order. As more mitogenomes are sequenced, mitochondrial (mt) gene rearrangements have been frequently identified among diverse birds. Within two genera (Bubo and Strix) of typical owls (Strigidae, Strigiformes), the rearrangement of the mt gene has been a subject of debate. In the current study, we first sequenced the whole mitogenomes of S. uralensis and B. scandiaca and resequenced the entire mitogenome of B. bubo. By combining our data with previously sequenced mitogenomes in Strigidae, we examined the mt gene rearrangements in the family and attempted to reconstruct the evolutionary progression of these rearrangements. The mitogenomes were then used to review the phylogenies of Strigidae. Most mitogenomes exhibited the ancestral gene order (A) in Strigidae. The ancestral gene order in the previously published mitogenome of B. bubo was found to be incorrect. We determined the mt gene order (the duplicate tRNAThr-CR, B) and discovered two additional mt gene orders (the duplicate tRNAGlu-L-CR and CR, C and D) in the Bubo and Strix genera. Gene order B was likely derived from A by a tandem duplication of the region spanning from tRNAThr to CR. The other two modified gene orders, C and D, were likely derived from B by further degenerations or deletions of one copy of specific duplicated genes. We also preliminarily reconstructed the evolutionary progression of mt gene rearrangements and discussed maintenance of the duplicated CR in the genera. Additionally, the phylogenetic trees based on the mitogenomes supported the division of Strigidae into three subfamilies: Ninoxinae + (Surniinae + Striginae). Within the Striginae clade, the four genera formed a phylogenetic relationship: Otus + (Asio + (Bubo + Strix)). This suggests that Otus firstly diverges in their evolutionary history, and Bubo and Strix show a close relationship. B. bubo, B. blakistoni and B. scandiaca form a clade should be considered members of the same genus. The well-supported topology obtained in our Bayesian inference (BI) and maximum likelihood (ML) analyses of Strigid mitogenomes suggests that these genomes are informative for constructing phylogenetic relationships.

Testin was regulated by circRNA3175-miR182 and inhibited endometrial epithelial cell apoptosis in pre-receptive endometrium of dairy goats.

Circular RNAs (circRNAs) in various tissues and cell types from mammalian sources have been studied. However, present knowledge on circRNAs in the development of pre-receptive endometrium (PE) in dairy goats is limited. In the pre-receptive endometrium of dairy goats, higher circRNA3175 (ciR3175) levels, lower miR-182 levels and higher Testin (TES) levels were detected. And ciR3175 could decreased the miR-182 levels by acting as a miRNA sponge, and miR-182 could down-regulated the expression level of TES via the predicted target site in endometrial epithelial cells (EECs) in vitro. Via this way, ciR3175 functioned as a competing endogenous RNAs (ceRNA) that sequestered miR-182, thereby protecting TES transcripts from miR-182-mediated suppression in EECs in vitro. Further, TES inhibited EECs apoptosis by decreasing the expression level of BCL-2/BAX via the MAPK pathway. Thus, a ciR3175-miR182-TES pathway in the endometrium was identified in EECs, and the modulation of which could emerge as a potential target in regulating the pre-receptive endometrium development in dairy goats.

miR-26a promoted endometrial epithelium cells (EECs) proliferation and induced stromal cells (ESCs) apoptosis via the PTEN-PI3K/AKT pathway in dairy goats.

Changes in endometrial cell morphology and function are absolutely necessary for successful embryo implantation. In this study, miR-26a was widely expressed in dairy goats, and was found to be regulated by ß-estradiol (E2) and progesterone (P4) in endometrial epithelium cells (EECs) as well as stromal cells (ESCs). Furthermore, miR-26a played a role in the regulation of cells proliferation and apoptosis by directly regulating PTEN and indirectly regulating the PI3K/AKT pathway in EECs but not in ESCs of dairy goats in vitro. In addition, miR-26a regulated the expression of osteopontin (OPN), vascular endothelial growth factor (VEGF), Cyclooxygenase-2 (COX-2), and prolactin (PRL) in endometrial cells. Therefore, we could get a conclusion that miR-26a had very complex and diverse functions in the endometrial cells during the development of endometrial receptivity in dairy goats. This study provided an efficient platform for studying the regulatory effect of miR-26a on endometrial cells during the development of endometrial receptivity in dairy goats.

[Research progress in cytokines and signaling pathways for promoting pulmonary angiogenesis and vascular development].

With the advances in pre- and post-natal medical care, the incidence of bronchopulmonary dysplasia (BPD) is on the rise, while its pathogenesis remains not clear. New BPD theory shows that the core pathogenesis of BPD is simple alveolar structure and pulmonary microvascular abnormalities that eventually lead to reduced pulmonary gas exchange, so the research on pulmonary microvascular development was gradually taken seriously. Pulmonary angiogenesis and vascular development require the participation of various cytokines and signaling pathways, the most important of which include VEGF/VEGFR pathway, Ang/Tie pathway, Ephrins/Eph pathway, and Notch/Jagged1 pathway. These cytokines and signaling pathways play important roles in pulmonary vascular development.

[Therapeutic effect of Ommaya reservoir implantation on hydrocephalus in premature infants following intraventricular hemorrhage and factors associted with the therapeutic effect].

OBJECTIVE: To observe the therapeutic effect of Ommaya reservoir implantation on hydrocephalus in premature infants following intraventricular hemorrhage (IVH) and to investigate factors influencing the therapeutic effect. METHODS: An ambispective cohort study was conducted on the clinical and follow-up data of 20 premature infants (gestational age <32 weeks, birth weight <1500 g) who received Ommaya reservoir implantation because of hydrocephalus following IVH. The therapeutic effect of Ommaya reservoir implantation was observed. These patients were divided into cure and treatment failure groups according to their treatment outcomes. The factors influencing therapeutic effects were investigated by univariate analysis. RESULTS: Hydrocephalus was relieved significantly at 30 days after Ommaya reservoir implantation. However, some patients showed significantly decreased therapeutic effects since 3 months after operation: during 3-6 months after operation, 7 cases underwent ventriculoperitoneal shunt, 4 cases discontinued treatment because of economic reasons, and 1 case underwent endoscopic third ventriculostomy due to scalp hematoma with skin necrosis. The ventricles of the remaining 8 cases returned to normal size at 12-18 months after operation. As for postoperative complications, secondary IVH was seen in 8 cases, intracranial infection in 2 cases, and scalp hematoma with skin necrosis in 1 case. The univariate analysis revealed significant differences in gestational age, birth weight and duration of hydrocephalus before Ommaya reservoir implantation between the cure and the treatment failure groups (P<0.05). CONCLUSIONS: Ommaya reservoir implantation has a remarkable short-term therapeutic effect on hydrocephalus in premature infants following IVH, but later the effect decreases in some patients. Low gestational age, low birth weight and long duration of hydrocephalus may be the main factors influencing therapeutic effects of Ommaya reservoir implantation.