Search

Osteoarthritis (OA) is the most common degenerative joint disease and results from progressive loss and destruction of articular cartilage and the underlying bone. The disease affects millions of people worldwide with an associated risk of mobility disability. However, the molecular basis underlying OA initiation and progression is not well understood and, currently, there is no effective intervention available to decelerate disease progression or restore degraded cartilage. We have found that lncRNA long intergenic nonprotein coding RNA 341 (LINC00341) is aberrantly downregulated in OA patient tissues and cultured OA chondrocytes. This is likely responsible for the increased apoptosis of chondrocytes and pathological destruction of cartilage. Further investigation has revealed that LINC00341 interacts with miR-141 to suppress its functional binding to the 3'-untranslated region of YY1-associated factor 2 (YAF2) messenger RNA. Aberrant downregulation of LINC00341 thus may ultimately lead to inhibition of the YAF2 protein, which has been implicated to be an antiapoptotic factor. Our study has revealed a new noncoding RNA-mediated regulatory network that highly likely protects chondrocytes by preventing apoptosis under normal conditions. The results will help further explore the molecular details pertaining to the progression of OA and stimulate efforts to develop effective therapies.

Systemic lupus erythematosus (SLE) is a severe autoimmune disorder, the pathogenesis of which remains largely unknown. The present study aimed to investigate the role and mechanism of circular RNAs in the etiopathogenesis of SLE. CD4+ T cells in patients with SLE expressed higher levels of hsa_circ_0010957 compared with healthy individuals and was a good differentiator of the active from inactive SLE disease. It was also determined that hsa_circ_0010957 mediated microRNA (miR)‑125b/STAT3 signaling and subsequent secretion of inflammatory cytokines interleukin (IL)‑18, IL‑6 and IL‑17, which are important factors in the process of SLE. Hsa_circ_0010957 abrogated the proinflammatory effect of IL‑6 via the blockade of STAT3 signaling. In conclusion, increased hsa_circ_0010957 may be involved in SLE pathogenesis via miR‑125b/STAT3 signaling. Hsa_circ_0010957 promises to be a potential biomarker and therapeutic target for SLE.

OBJECTIVE The aim of the study was to explore the mechanism of excessive apoptosis of nucleus pulposus cells induced by short hairpin RNA (shRNA) Piezo type mechanosensitive ion channel component 1 (Piezo1) under abnormal mechanical stretch stress. METHODS In vitro mechanical stretch stress model of nucleus pulposus cells in vitro was established, in which the expression of Piezo1 was interfered by transfection of shRNA-Piezo1 interfering vector. Both messenger RNA and protein level of Piezo1 were measured by reverse-transcription polymerase chain reaction and Western blot analysis, respectively. Cytoplasmic Ca2+ was detected by Fluo3-AM kit, and changes of mitochondrial membrane potential in cells were detected using Cell Meter Assay kit. Finally, the apoptosis was evaluated with annexin V-fluorescein isothiocyanate kit. RESULTS The highest transfection efficiency of lentivirus titer was 1 × 10 TU/mL and the nucleus pulposus cells were transfected with plural multiplicity of infection = 50. Homo-3201 sequence exhibited the most effective silencing effect and was used in subsequent experiments as the default sequence of shRNA-Piezo1. The calcium content in the cytoplasm of the tension stress group increased significantly compared with that in the blank control group ( q = 3.773; P

The effect of Lactobacillus pentosus strain S-PT84 (S-PT84) on postprandial hypertriacylglycerolemia was investigated in rats. S-PT84 dose-dependently inhibited the hydrolysis of triacylglycerols by pancreatic lipase in vitro. Intragastric administration of S-PT84 significantly reduced the lymphatic recovery of (3)H-trioleoylglycerol up to 8 h. The oral administration of a fat emulsion, with or without S-PT84, resulted in the concentration of plasma triacylglycerol 2 h and 3 h after administration being significantly lower in the S-PT84 group than in the group without S-PT84 (control group). These results suggest that S-PT84 alleviated postprandial hypertriacylglycerolemia by delaying triacylglycerol absorption in the intestine through the inhibition of pancreatic lipase.

The avulsion fracture of the femoral attachment from the posterior cruciate ligament (PCL) is quite rare, particularly in adults. The patient we presented here was admitted to receive treatment in June 2017, whose knee injury resulted in avulsion fractures at three sites, the femoral attachment of the PCL, the tibial insertion of the anterior cruciate ligament (ACL), and the femoral attachment of the medial collateral ligament (MCL). We repaired PCL femoral attachment by arthroscopy and fixed MCL femoral insertion with cannulated screws.

A polymerase chain reaction (PCR) method was used to detect the interleukin-2 receptor alpha-chain (IL-2R alpha) chain which lacks the conventional transmembrane (TM) domain in mRNA from human T-cell leukaemia virus type-I (HTLV-I)-infected cell lines or peripheral blood mononuclear cells (PBMC) isolated from adult T-cell leukaemia (ATL) patients. Primer pairs encompassing the TM domain were selected to generate a 357-base pair (bp) fragment. A 146-bp PCR product was observed consistently in addition to the target 357-bp PCR product in mRNA from HTLV-I-infected cell lines, such as MT-1, MT-2, MT-4 and in PBMC isolated from ATL patients. However, this 146-bp PCR product was undetectable in HTLV-I-negative cell lines. The product was also detected in PBMC from normal individuals if activated in vitro with phytohaemagglutinin but not without stimulation. DNA sequence analyses revealed that exons from 5 to 7, which define a 211-bp region containing the conventional TM domain, were deleted in the 146-bp PCR product. The C-terminal amino acid sequence starting from Gly174 of the 211-bp-deleted molecule was distinct from that of conventional IL-2R alpha as a result of an altered reading frame. We identified a 45000 MW peptide generated from IL-2R alpha mRNA through this exon skip in cell lysate of MT-1 and MT-2 by Western blot analyses using an antibody raised against the peptides specific to an altered IL-2R alpha. Our results indicate that an altered IL-2R alpha chain is expressed in HTLV-I-infected T lymphocytic cell lines and in ATL patients.

To detect transcripts encoding the interleukin-6 receptor (IL-6R) molecule lacking the transmembrane (TM) domain, in various cell lines and peripheral blood mononuclear cells (PBMC), we used the polymerase chain reaction (PCR) with primer pairs that flank the TM domain and which were selected to generate a 398-bp fragment. We detected 398-bp and 304-bp DNA molecules in the PCR products of the U1, J22HL60, MT-2, MT-4, U937 and HL60 cell lines and of PBMC isolated from several individuals. The sequencing analysis of both DNA molecules showed that a 94-bp region consisting of the TM domain of IL-6R was deleted in the 304-bp molecule. Moreover, we detected a soluble (s) IL-6R protein of 45 kDa in culture supernatants of the MT-2, MT-4 and U937 cell lines by radioimmunoprecipitation using specific antibodies against sIL-6R. Our results indicate that active deletion of the TM domain by alternative splicing of mRNA represents one mechanism for release of sIL-6R into the culture supernatants of cells, or into serum or urine.