Pinocembrin alleviates pyroptosis and apoptosis through ROS elimination in random skin flaps via activation of SIRT3.

Random skin flap grafting is the most common skin grafting technique in reconstructive surgery. Despite progress in techniques, the incidence of distal flap necrosis still exceeds 3%, which limits its use in clinical practice. Current methods for treating distal flap necrosis are still lacking. Pinocembrin (Pino) can inhibit reactive oxygen species (ROS) and cell death in a variety of diseases, such as cardiovascular diseases, but the role of Pino in random flaps has not been explored. Therefore, we explore how Pino can enhance flap survival and its specific upstream mechanisms via macroscopic examination, Doppler, immunohistochemistry, and western blot. The results suggested that Pino can enhance the viability of random flaps by inhibiting ROS, pyroptosis and apoptosis. The above effects were reversed by co-administration of Pino with adeno-associated virus-silencing information regulator 2 homolog 3 (SIRT3) shRNA, proving the beneficial effect of Pino on the flaps relied on SIRT3. In addition, we also found that Pino up-regulates SIRT3 expression by activating the AMP-activated protein kinase (AMPK) pathway. This study proved that Pino can improve random flap viability by eliminating ROS, and ROS-induced cell death through the activation of SIRT3, which are triggered by the AMPK/PGC-1α signaling pathway.

Identification and comparison of novel circular RNAs with associated co-expression and competing endogenous RNA networks in postmenopausal osteoporosis.

BACKGROUND: Circular RNAs (circRNAs) are emerging as crucial regulators in various human diseases. So far, the expression profile and regulatory mechanism of circRNAs in postmenopausal osteoporosis (PMOP) are less studied and should be deciphered urgently. Herein, we aimed to reveal key circRNAs affecting PMOP and clarify their compounding regulatory actions. METHODS: To reveal key circRNAs affecting PMOP and clarify their compounding regulatory actions, whole transcriptome sequencing and bioinformatics analysis were performed to identify differentially expressed circRNAs (DECs). The expression pattern and regulatory networks of DECs in peripheral blood mononuclear cells (PBMCs) were unearthed. RESULTS: A total of 373 DECs comprising 123 intronic, 100 antisense, 70 exonic, 55 intergenic, and 25 sense-overlapping circRNAs were identified. Among these, 73 circRNAs were upregulated and 300 were downregulated. These DECs exerted pivotal functions in the pathogenesis of PMOP as demonstrated by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The circRNA-miRNA-mRNA co-expression network comprising 28 DECs, 145 miRNAs, and 175 differentially expressed mRNAs predicted the possible mechanism of the pathogenesis and progression of PMOP. CONCLUSION: The results of the present study provided a further comprehension of circRNA-associated competing endogenous RNA regulatory mechanism in PMOP. The steadily expressed and disease-specific DECs may serve as promising diagnostic and prognostic biomarkers for PMOP.

Can fusion to S1 maintain favorable surgical outcomes following one-level pedicle subtraction osteotomy in patients with thoracolumbar kyphosis secondary to ankylosing spondylitis?

PURPOSE: To compare the surgical outcomes between ankylosing spondylitis (AS)-related thoracolumbar kyphosis patients with the lowest instrumented vertebra (LIV) at S1 or above following one-level pedicle subtraction osteotomy (PSO). METHODS: One hundred and two AS patients undergoing one-level PSO with a minimum of 2-year follow-up were included. Twenty-two patients were in group S1 (LIV at S1), and eighty were in group non-S1 (LIV above S1). Radiographic parameters including lumbar lordosis (LL), sacral slope (SS), pelvic incidence (PI), and sagittal vertical axis (SVA) were measured. Oswestry Disability Index (ODI) and visual analog scale (VAS) were applied for clinical assessment. RESULTS: In both S1 and non-S1 groups, the radiographic parameters and clinical outcomes were significantly improved after surgery (P < 0.05). Patients undergoing distal fusion to S1 had significantly larger preoperative PI-LL mismatch, SVA, and smaller preoperative LL and SS compared to those in group non-S1 (P < 0.05). No significant difference was found between the two groups regarding preoperative and final follow-up ODI and VAS (P > 0.05), as well as the improvement in ODI and VAS (P > 0.05). The incidence of overall complications and each type of complication including the implant failure was similar between group S1 and non-S1 (P > 0.05). CONCLUSION: Selecting S1 as the LIV without pelvic fixation following one-level PSO in thoracolumbar kyphosis caused by AS could achieve satisfactory surgical outcomes and might not increase the complications. Patients with relatively severe sagittal imbalance, loss of LL, PI-LL mismatch, and small SS might be the potential candidates for distal fusion to S1 following one-level PSO.

Does the preoperative lumbar sagittal profile affect the selection of osteotomy level in pedicle subtraction osteotomy for thoracolumbar kyphosis secondary to ankylosing spondylitis?

OBJECTIVE: To investigate the different preoperative lumbar sagittal profiles of ankylosing spondylitis (AS) patients and the selection of osteotomy level for one-level pedicle subtraction osteotomy (PSO) for the correction of thoracolumbar kyphosis. PATIENTS AND METHODS: Seventy-one consecutive AS patients with an average age of 35.3 years and a mean follow-up time of 35.9 months who underwent one-level PSO for thoracolumbar kyphosis were divided into 2 groups based on their preoperative lumbar sagittal profiles as follows: group A, lordotic lumbar sagittal profiles; and group B, kyphotic lumbar sagittal profiles. The following radiological parameters were measured and compared: chin-brow vertical angle (CBVA), global kyphosis (GK), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS). Clinical evaluation included Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS). Perioperative and mid-term complications were reviewed. RESULTS: There were 28 patients in group A and 43 in group B. The preoperative LL was -21.0° in group A and 2.3° in group B (P < 0.05). The preoperative SVA was 122.5 mm in group A and 184.3 mm in group B (P < 0.05). All the patients in group A (100%) underwent PSO at L1/L2, while 90% of group B patients underwent PSO at L2/L3, with no significant difference of postoperative GK, LL and SVA between the 2 groups (P > 0.05). No obvious loss of correction was observed in either group at the final follow-up. The correction of LL and SVA showed a strong but not statistically significant increasing trend as the PSO level descended from L1 to L3 (P > 0.05). The postoperative ODI was significantly lower in patients underwent PSO at L1 or L2 (P < 0.05). CONCLUSIONS: Patients in group B had significantly worse preoperative sagittal alignments compared to group A. The distribution of osteotomy levels varied between the 2 groups due to the different lumbar profiles; however, satisfactory correction was achieved in both groups. The preoperative lumbar profiles need to be considered in selecting the optimal osteotomy level. Patients with kyphotic lumbar profiles are suitable candidates for PSO at L2/L3, while L1/L2 PSO is appropriate for patients with lordotic lumbar profiles.

The organic anion transporting polypeptide 1a5 is a pivotal transporter for the uptake of microcystin-LR by gonadotropin-releasing hormone neurons.

Microcystins (MCs) are widely distributed hepatotoxic polypeptides produced by cyanobacteria. Microcystin-LR (MC-LR) has the broadest distribution and strongest toxicity among more than 80 isoforms of hepatotoxic MCs. MC-LR suppresses the expression of gonadotropin-releasing hormone (GnRH) that is critically required for the release of testosterone, resulting in the induction of male reproductive toxicity. However, the specific mechanisms of the uptake of MC-LR by GnRH-secreting neurons still remain unclear. In this study, GT1-7 cells were exposed to MC-LR in order to determine whether the GnRH-secreting neurons were the target of MC-LR that could induce male reproductive toxicity. Our data demonstrated that at least four organic anion transporting polypeptides (Oatp1a4, Oatp1a5, Oatp5a1, Oatp2b1) were expressed in GnRH neurons at the mRNA level, but only Oatp1a5 was expressed at the protein level. Furthermore, we demonstrated that MC-LR could not be transported into Oatp1a5-deficient GT1-7 cells which were protected from cell viability loss induced by MC-LR. These data suggest that Oatp1a5 may play an important role in the toxic effect of MC-LR on GnRH neurons.