Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury.

Spinal cord injury (SCI) is a serious, disabling injury to the central nervous system that can lead to motor, sensory, and autonomic dysfunction below the injury plane. SCI can be divided into primary injury and secondary injury according to its pathophysiological process. Primary injury is irreversible in most cases, while secondary injury is a dynamic regulatory process. Secondary injury involves a series of pathological events, such as ischemia, oxidative stress, inflammatory events, apoptotic pathways, and motor dysfunction. Among them, oxidative stress is an important pathological event of secondary injury. Oxidative stress causes a series of destructive events such as lipid peroxidation, DNA damage, inflammation, and cell death, which further worsens the microenvironment of the injured site and leads to neurological dysfunction. The nuclear factor erythrocyte 2-associated factor 2 (Nrf2) is considered to be a key pathway of antioxidative stress and is closely related to the pathological process of SCI. Activation of this pathway can effectively inhibit the oxidative stress process and promote the recovery of nerve function after SCI. Therefore, the Nrf2 pathway may be a potential therapeutic target for SCI. This review deeply analyzed the generation of oxidative stress in SCI, the role and mechanism of Nrf2 as the main regulator of antioxidant stress in SCI, and the influence of cross-talk between Nrf2 and related pathways that may be involved in the pathological regulation of SCI on oxidative stress, and summarized the drugs and other treatment methods based on Nrf2 pathway regulation. The objective of this paper is to provide evidence for the role of Nrf2 activation in SCI and to highlight the important role of Nrf2 in alleviating SCI by elucidating the mechanism, so as to provide a theoretical basis for targeting Nrf2 pathway as a therapy for SCI.

Deciphering layer formation in Red Heart Qu: A comprehensive study of metabolite profile and microbial community influenced by raw materials and environmental factors.

Environmental-origin microbiota significantly influences Red Heart Qu (RH_Qu) stratification, but their microbial migration and metabolic mechanisms remain unclear. Using high-throughput sequencing and metabolomics, we divided the stratification of RH_Qu into three temperature-based stages. Phase I features rising temperatures, causing microbial proliferation and a two-layer division. Phase II, characterized by peak temperatures, sees the establishment of thermotolerant species like Bacillus, Thermoactinomyces, Rhodococcus, and Thermoascus, forming four distinct layers and markedly altering metabolite profiles. The Huo Quan (HQ), developing from the Pi Zhang (PZ), is driven by the tyrosine-melanin pathway and increased MRPs (Maillard reaction products). The Hong Xin evolves from the Rang, associated with the phenylalanine-coumarin pathway and QCs (Quinone Compounds) production. Phase III involves the stabilization of the microbial and metabolic profile as temperatures decline. These findings enhance our understanding of RH_Qu stratification and offer guidance for quality control in its fermentation process.

Four New Polyprenylated Acylphloroglucinols from Hypericum perforatum L.

Hyperforatums A-D (1-4), four new polyprenylated acylphloroglucinols, together with 13 known compounds were isolated and identified from the aerial parts of Hypericum perforatum L. (St. John's wort). Their structures were confirmed with a comprehensive analysis comprising spectroscopic methods, including 1D and 2D NMR, HRESIMS, and electronic circular dichroism (ECD) calculations. Hyperforatum A featured an unusual chromene-1,4-dione bicyclic system, and hyperforatums B and C were two rare monocyclic PPAPs with five-membered furanone cores. Compound 1 exhibited a moderate inhibition effect on NO production in BV-2 microglial cells stimulated by LPS.

SPI1 exacerbates iron accumulation and promotes osteoclast formation through inhibiting the expression of Hepcidin.

BACKGROUND: Osteoporosis (OP) can be caused by an overactive osteoclastic function. Anti-osteoporosis considerable therapeutic effects in tissue repair and regeneration because bone resorption is a unique osteoclast function. In this study, we mainly explored the underlying mechanisms of osteoclasts' effects on osteoporosis. METHODS: RAW264.7 cells were used and induced toward osteoclast and iron accumulation by M-CSF and RANKL administration. We investigated Hepcidin and divalent metal transporter 1 (DMT1) on iron accumulation and osteoclast formation in an ovariectomy (OVX)-induced osteoporosis. Osteoporosis was induced in mice by OVX, and treated with Hepcidin (10, 20, 40, 80 mg/kg, respectively) and overexpression of DMT1 by tail vein injection. Hepcidin, SPI1, and DMT1 were detected by immunohistochemical staining, western blot and RT-PCR. The bioinformatics assays, luciferase assays, and Chromatin Immunoprecipitation (ChIP) verified that Hepcidin was a direct SPI1 transcriptional target. Iron accumulation was detected by laser scanning confocal microscopy, Perl's iron staining and iron content assay. The formation of osteoclasts was assessed using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: We found that RAW264.7 cells differentiated into osteoclasts when exposed to M-CSF and RANKL, which increased the protein levels of osteoclastogenesis-related genes, including c-Fos, MMP9, and Acp5. We also observed higher concentration of iron accumulation when M-CSF and RANKL were administered. However, Hepcidin inhibited the osteoclast differentiation cells and decreased intracellular iron concentration primary osteoclasts derived from RAW264.7. Spi-1 proto-oncogene (SPI1) transcriptionally repressed the expression of Hepcidin, increased DMT1, facilitated the differentiation and iron accumulation of mouse osteoclasts. Overexpression of SPI1 significantly declined luciferase activity of HAMP promoter and increased the enrichment of HAMP promoter. Furthermore, our results showed that Hepcidin inhibited osteoclast differentiation and iron accumulation in mouse osteoclasts and OVX mice. CONCLUSION: Therefore, the study revealed that SPI1 could inhibit Hepcidin expression contribute to iron accumulation and osteoclast formation via DMT1 signaling activation in mouse with OVX.

Iron accumulation induced by hepcidin1 knockout accelerates the progression of aging osteoporosis.

OBJECTIVE: Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis. METHODS: Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl's staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively. RESULTS: In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin. CONCLUSION: Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis.

Reduction of the trans-cortical vessel was associated with bone loss, another underlying mechanism of osteoporosis.

RATIONALE: Numerous studies have established a robust association between bone morrow microvascular diseases and osteoporosis. This study sought to investigate the relationship between alterations in trans-cortical vessel (TCVs) and the onset of osteoporosis in various mouse models. METHODS: Aged mice, ovariectomized mice, and db/db mice, were utilized as osteoporosis models. TCVs in the tibia were detected using tissue clearing and light sheet fluorescence microscopy imaging. Femurs bone mass were analyzed using micro-CT scanning. Correlations between the number of TCVs and bone mass were analyzed using Pearson correlation analysis. RESULTS: All osteoporosis mouse models showed a significant reduction in the number of TCVs compared to the control group. Correlation analysis revealed a positive association between the number of TCVs and bone mass. TCVs were also expressed high levels of CD31 and EMCN proteins as type H vessels. CONCLUSIONS: This study underscores a consistent correlation between the number of TCVs and bone mass. Moreover, TCVs may serve as a potential biomarker for bone mass evaluation.

Hyperelatolides A-D, Antineuroinflammatory Constituents with Unusual Carbon Skeletons from Hypericum elatoides.

Four new δ- and γ-lactone derivatives, hyperelatolides A-D (1-4, respectively), were discovered from the aerial portions of Hypericum elatoides R. Keller. Their structures were elucidated by analysis of NMR spectra, HRESIMS, quantum chemical calculations of NMR and ECD spectra, and X-ray crystallographic data. Hyperelatolides A (1) and B (2) represent the first examples of δ-lactone derivatives characterized by a (Z)-(5,5-dimethyl-2-(2-oxopropyl)cyclohexylidene)methyl moiety and a benzoyloxy group attached to the ß- and γ-positions of the δ-lactone core, respectively, while hyperelatolides C (3) and D (4) are unprecedented γ-lactone derivatives featuring substituents similar to those of 1 and 2. All compounds were tested for their inhibitory effects on NO production in LPS-activated BV-2 cells. Lactones 1 and 2 exhibited considerable antineuroinflammatory activity, with IC50 values of 5.74 ± 0.27 and 7.35 ± 0.26 µM, respectively. Moreover, the mechanistic study revealed that lactone 1 significantly suppressed nuclear factor kappa B signaling and downregulated the expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-induced cells, which may contribute to its antineuroinflammatory activity.

LncRNA HEIH expression in cancer prognosis: A review and meta-analysis.

BACKGROUND: As a newly discovered lncRNA, lncRNA High expression in hepatocellular carcinoma (HEIH) has been reported to correlate with poor clinical outcomes in several different cancers, In addition, studies have shown that HEIH is overexpressed in a variety of cancers and plays an oncogenic role. The present meta-analysis aims to elucidate the relationship between HEIH expression and prognosis and clinicopathological features among cancer patients. METHODS: PubMed, Web of Science, Cochrane Library, and EMBASE database were comprehensively and systematically searched. pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence interval (CI) were employed to assess the relationship between HEIH expression and clinical outcomes and clinicopathological features in cancer patients. CONCLUSION: The present study finally enrolled 11 studies which included 1227 cancer patients. The combined results indicated that HEIH overexpression was significantly associated with shorter overall survival (OS) (pooled HR = 2.03, 95% CI 1.74-2.38, P < .00001).Meanwhile, regarding clinicopathology of cancer patients, upregulated HEIH expression was closely related to larger tumor size (OR = 2.65, 95% CI: 1.52-4.65, P = .0006), advanced tumor T stage (OR = 2.41, 95 % CI: 1.54-3.77, P = .0001), advanced TNM stage (OR = 4.76, 95% CI: 2.73-8.29, P < .00001), distant metastasis (OR = 2.94, 95% CI: 1.75-4.96, P < .0001) and lymph node metastasis (OR = 2.07, 95% CI: 1.05-4.07, P = .04), respectively. CONCLUSIONS: High expression of HEIH in some cancers predicts shorter overall survival and higher clinical stage as well as larger tumor size. HEIH has great potential to become a prognostic marker for cancer patients.

Unilateral biportal endoscopy versus microscopic decompression in the treatment of lumbar spinal stenosis: A meta-analysis.

BACKGROUND: The aim of this study was to evaluate whether there is a superior clinical effect of unilateral biportal endoscopy compared with microscopic decompression in the treatment of lumbar spinal stenosis. METHODS: We searched CNKI, WANFANG, CQVIP, CBM, PubMed, and Web of Science up to January 2022, and selected studies that met our inclusion criteria. RESULTS: The results of this meta-analysis indicated that unilateral biportal endoscopy was demonstrated to be more beneficial for patients compared with microscopic decompression for the following outcomes: Operation time [standardized mean difference (SMD) = -0.943, 95% confidence interval (CI) (-1.856, -0.031), P = .043], hospital stays [SMD = -2.652, 95% CI (-4.390, -0.914), P = .003], EuroQol 5-Dimension questionnaire [SMD = 0.354, 95% CI (0.070, 0.638), P = .014], back pain visual analogue score [SMD = -0.506, 95% CI (-0.861, -0.151), P = .005], leg pain visual analogue score [SMD = -0.241, 95% CI (-0.371, -.0112), P = .000], the C-reactive protein level [SMD = -1.492,95% CI (-2.432, -0.552), P = .002]. Other outcomes demonstrated no significant differences between the 2 groups. CONCLUSION: For patients with lumbar spinal stenosis, unilateral biportal endoscopy was found to be more superior than microscopic decompression in terms of operation time, hospital stays, EuroQol 5-Dimension questionnaire, back visual analogue score, leg visual analogue score and the C-reactive protein level. There was no significant difference between the 2 groups in other outcome indicators.

Structural Versus Nonstructural Bone Grafting Via the Posterior Approach in the Treatment of Thoracic and Lumbar Tuberculosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Bone grafting is necessary in spinal tuberculosis surgery. Structural bone grafting is considered the gold standard treatment for spinal tuberculosis bone defects; however, nonstructural bone grafting via the posterior approach has recently gained attention. In this meta-analysis, we evaluated the clinical efficacy of structural versus nonstructural bone grafting via the posterior approach in the treatment of thoracic and lumbar tuberculosis. METHODS: Studies comparing the clinical efficacy of structural and nonstructural bone grafting via the posterior approach in spinal tuberculosis surgery were identified from 8 databases from inception to August 2022. Study selection, data extraction, and evaluation of the risk of bias were performed, and meta-analysis was conducted. RESULTS: Ten studies including 528 patients with spinal tuberculosis were enrolled. Meta-analysis revealed no between-group differences in fusion rate (P = 0.29), complications (P = 0.21), postoperative Cobb angle (P = 0.7), visual analog scale score (P = 0.66), erythrocyte sedimentation rate (P = 0.74), or C-reactive protein level (P = 0.14) at the final follow-up. Nonstructural bone grafting was associated with less intraoperative blood loss (P < 0.00001), shorter operation time (P < 0.0001), shorter fusion time (P < 0.01), and shorter hospital stay (P < 0.00001), while structural bone grafting was associated with lower Cobb angle loss (P = 0.002). CONCLUSIONS: Both techniques can achieve a satisfactory bony fusion rate for spinal tuberculosis. Nonstructural bone grafting has the advantages of less operative trauma, shorter fusion time, and shorter hospital stay, making it an attractive option for short-segment spinal tuberculosis. Nevertheless, structural bone grafting is superior for maintaining corrected kyphotic deformities.

N-acetyl-L-cysteine attenuates oxidative stress-induced bone marrow endothelial cells apoptosis by inhibiting BAX/caspase 3 pathway.

Bone marrow endothelial cells (BMECs) play a crucial role in the maintenance of bone homeostasis. The decline in BMECs is associated with abnormal bone development and loss. At present, the mechanism of age-related oxidative stress enhancement in BMEC dysfunction remains unclear. Our experiment explored injury caused by oxidative stress enhancement in BMECs both in vivo and in vitro. The BMECs, indicators of oxidative stress, bone mass, and apoptosis-related proteins were analyzed in different age groups. We also evaluated the ability of N-Acetyl-L-cysteine (NAC) attenuate oxidative stress injury in BMECs. NAC treatment attenuated reactive oxygen species (ROS) overgeneration and apoptosis in BMECs in vitro and alleviated the loss of BMECs and bone mass in vivo. In conclusion, this study could improve our understanding of the mechanism of oxidative stress-induced BMECs injury and whether NAC has therapeutic potential in senile osteoporosis.

Complications of Unilateral Biportal Endoscopic Spinal Surgery for Lumbar Spinal Stenosis: A Meta-Analysis and Systematic Review.

BACKGROUND: In recent years, unilateral biportal endoscopic spinal surgery has been used for the treatment of lumbar spinal stenosis with good results. Some investigators counted the total incidence of complications in unilateral biportal endoscopic surgery for lumbar spinal stenosis, but none have analyzed the incidence of specific complications. The present study further counted the incidence of specific complications and gave the possible causes of the complications. METHODS: English databases including PubMed were searched to collect relevant literature on unilateral biportal endoscopic spinal surgery for lumbar spinal stenosis. The inquiry period is from January 1, 2015, to July 1, 2022. The literature was screened, information extracted, and risk of bias evaluated by the researchers, followed by Meta analysis using R4.2.1 and RStudio statistical software. RESULTS: In total, we included 14 studies involving 707 patients. The included studies were retrospective case series, The results of the single-arm rate meta-analysis showed that the total complication rate of unilateral biportal endoscopic surgery treatment of lumbar spinal stenosis was 8.1% (95% confidence interval [CI] [0.060; 0.103]); of which, the highest incidence of dural tear was 4.5% (95% CI [0.030; 0.064]), the incidence of symptomatic postoperative spinal epidural hematoma was approximately 1.1% (95% CI [0.001; 0.027]), the incidence of incomplete decompression was 2.0% (95% CI [0.007; 0.038]), the incidence of transient palsy was 2.6% (95% CI [0.005; 0.057]). CONCLUSIONS: The incidence of total complications of unilateral biportal endoscopic surgery for lumbar spinal stenosis was 8.1%, dural tear remained a major complication with an incidence of 4.5%, incomplete decompression was 2.0%, transient palsy was 2.6%, and, unexpectedly, symptomatic postoperative spinal epidural hematoma was only 1.1%.

The role of PI3K/Akt signalling pathway in spinal cord injury.

Spinal cord injury (SCI) is a severely disabling central nervous system injury with complex pathological mechanisms that leads to sensory and motor dysfunction. The current treatment for SCI is aimed at symptomatic symptom relief rather than the pathological causes. Several studies have reported that signaling pathways play a key role in SCI pathological processes and neuronal recovery mechanisms. The PI3K/Akt signaling pathway is an important pathway closely related to the pathological process of SCI, and activation of this pathway can delay the inflammatory response, prevent glial scar formation, and promote neurological function recovery. Activation of this pathway can promote the recovery of neurological function after SCI by reducing cell apoptosis. Based on the role of the PI3K/Akt pathway in SCI, it may be a potential therapeutic target. This review highlights the role of activating or inhibiting the PI3K/Akt signaling pathway in SCI-induced inflammatory response, apoptosis, autophagy, and glial scar formation. We also summarize the latest evidence on treating SCI by targeting the PI3K/Akt pathway, discuss the shortcomings and deficiencies of PI3K/Akt research in the field of SCI, and identify potential challenges in developing these clinical therapeutic SCI strategies, and provide appropriate solutions.

ATF1/miR-214-5p/ITGA7 axis promotes osteoclastogenesis to alter OVX-induced bone absorption.

BACKGROUND: The dynamic balance of osteoblast and osteoclast is critical for bone homeostasis and overactive osteoclastic function may lead to osteoporosis. Activating transcription factor 1 (ATF1) is involved in osteoclastogenesis. However, the detailed mechanisms remain to be explored. METHODS: RAW264.7 cells were used and induced toward osteoclast by RANKL administration. We performed flow cytometry, CCK-8 assay and tartrate-resistant acid phosphatase (TRAP) staining to examine cell apoptosis, proliferation and differentiation of RAW264.7 cells, respectively. Mice were subjected to ovariectomy to induce osteoporosis. Micro CT, HE staining and TRAP staining were performed to evaluate bone loss in the OVX mouse model. Bioinformatics methods, luciferase assays and Chromatin Immunoprecipitation (ChIP) were used to predict and validate the interaction among ATF1, miR-214-5p, and ITGA7. RESULTS: ATF1 and miR-214-5p were up-regulated while ITGA7 was inhibited in RANKL-induced osteoclasts. MiR-214-5p was transcriptionally activated by ATF1. ATF1 knockdown suppressed osteoclast formation by miR-214-5p inhibition. ITGA7 was the direct target of miR-214-5p. Knockdown of miR-214-5p abolished osteoclastogenesis, which was reversed by ITGA7 knockdown. In OVX model, miR-214-5p knockdown suppressed osteoclast differentiation and prevented bone loss. CONCLUSION: ATF1/miR-214-5p/ITGA7 axis regulated osteoclast formation both in vivo and in vitro, thereby affecting OVX-induced bone resorption in mice. Knockdown of ATF1 might be a promising strategy to manage osteoporosis.

Long non-coding RNA-small nucleolar RNA host gene 7 regulates inflammatory responses following spinal cord injury by regulating the microRNA-449a/TNF-α-induced protein 3-interacting protein 2 axis.

The current study aimed to explore the anti-inflammatory effects of long non-coding RNA-small nucleolar RNA host gene 7 (lncRNA-SNHG7) and its mechanism in spinal cord injury (SCI) models. SCI models were established both in vivo and in vitro. Reverse transcription-quantitative PCR was performed to determine the expression levels of lncRNA-SNHG7 in SCI models. Bioinformatics analysis and dual-luciferase reporter assays were carried out to confirm the interaction between lncRNA-SNHG7 with microRNA (miR)-499a and TNF-α-induced protein 3-interacting protein 2 (TNIP2). In addition, cell viability, apoptosis, and the secretion of inflammatory cytokines were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometric analysis, and enzyme linked immunosorbent assay (ELISA), respectively. The results showed that lncRNA-SNHG7 was markedly downregulated in the SCI model group. LncRNA-SNHG7 directly bound to miR-499a, which in turn directly targeted TNIP2. In addition, TNIP2 was significantly decreased in SCI rats and lipopolysaccharide (LPS)-treated PC-12 cells. The in vitro results in PC-12 cells revealed that lncRNA-SNHG7 overexpression attenuated neuronal cell death and SCI-mediated inflammatory responses by regulating miR-449a expression. Furthermore, miR-499a knockdown inhibited LPS-induced PC-12 cell injury by targeting TNIP2. In conclusion, lncRNA-SNHG7 modulates the apoptosis and inflammation of PC-12 cells by regulating the miR-449a/TNIP2/NF-κB signaling pathway.

Early Clinical Efficacy of Endo-TLIF in the Treatment of Lumbar Disc Herniation.

OBJECTIVE: We aimed to compare the early clinical efficacy of endoscopy-assisted transforaminal lumbar interbody fusion (Endo-TLIF) and traditional Open-TLIF in the treatment of lumbar disc herniation and lumbar instability. METHODS: Forty-six patients with lumbar disc herniation and lumbar instability admitted to the hospital were retrospectively studied from October 11, 2018 to October 11, 2020. Patients (including 17 males and 29 females) were randomly divided into Endo-TLIF and Open-TLIF groups according to the different surgical treatment. Parameters such as intraoperative blood loss, operation time, and intraoperative fluoroscopy time during the surgery as well as preoperative and postoperative lumbar lordosis angle and lumbar clearance height and related complications were recorded in detail. RESULTS: Endo-TLIF significantly reduced intraoperative blood loss and bleeding volume compared with traditional Open-TLIF. The incision length in the Endo-TLIF group was shorter than in the Open-TLIF group and the intraoperative fluoroscopy time was also shorter than in the Open-TLIF group. The bed rest time and hospital discharge time were shortened in Endo-TLIF surgery compared with traditional Open-TLIF surgery. The creatine kinase (CK) values of the Endo-TLIF group were lower than that of the Open-TLIF group on the 1st and 3rd day after operation. Although computed tomography images of the lumbar lordosis angle did not show a significant difference between the Endo-TLIF group (43.97 ± 8.91°) and Open-TLIF group (49.08 ± 9.42°), the visual analogue scale score and Oswestry dysfunction index of lower back pain in the Endo-TLIF group were significantly lower than in the Open-TLIF group at 1 month and half a year after surgery. Complications in the Endo-TLIF group, such as lower limb neurological dysfunction and diseases of the respiratory or urinary system, effectively improved compared with the Open-TLIF group. CONCLUSION: Endo-TLIF appears to be a safer and more effective option for the treatment of lumbar disc herniation and lumbar instability, with a shorter recovery time, less trauma, less bleeding, no need for postoperative drainage, and less iatrogenic injury.

LncRNA LOXL1-AS1 expression in cancer prognosis: A meta-analysis.

BACKGROUND: Several studies showed that LncRNA LOXL1 antisense RNA 1 (LOXL1-AS1) is overexpressed in a variety of cancers and plays a role as an oncogene in cancer. The present meta-analysis aims to elucidate the relationship between LOXL1-AS1 expression and prognosis and clinicopathological features among cancer patients. METHODS: PubMed, Web of Science, Cochrane Library, and EMBASE database were comprehensively and systematically searched. Pooled odds ratios (ORs) and hazard ratios with a 95% confidence interval (CI) were employed to assess the relationship between LOXL1-AS1 expression and clinical outcomes and clinicopathological features in cancer patients. RESULTS: The present study finally enrolled 8 studies which included 657 cancer patients. The combined results indicated that the overexpression of LOXL1-AS1 was significantly associated with shorter overall survival (pooled hazard ratio = 1.99, 95% CI 1.49-2.65, P < .00001). Meanwhile, regarding clinicopathology of cancer patients, the upregulation of LOXL1-AS1 expression was closely related to lymph node metastasis (yes vs no OR = 4.01, 95% CI: 2.02-7.96, P < .0001) and distant metastasis (yes vs no OR = 3.04, 95% CI: 1.82-5.06, P < .0001), respectively. CONCLUSION: High expression of LOXL1-AS1 in some cancers predicts shorter overall survival, distant metastasis, and lymph node metastasis. LOXL1-AS1 shows great promise as a prognostic biomarker in cancer patients.

Kaempferol attenuates the effects of XIST/miR-130a/STAT3 on inflammation and extracellular matrix degradation in osteoarthritis.

Aim: To investigate whether kaempferol exhibited protective effects on osteoarthritis chondrocytes by modulating the XIST/miR-130a/STAT3 axis. Methods: qRT-PCR and western blot assays were used for gene and protein determination. Dual luciferase reporter and RNA immunoprecipitation assays were employed to study the interaction between miRNA and lncRNA or genes. Results: Kaempferol decreased proinflammatory cytokine production and extracellular matrix degradation in C28/I2 cells. Additionally, kaempferol ameliorated XIST expression and enhanced miR-130a expression. XIST interacted with miR-130a, and STAT3 was identified as a target of miR-130a. Knockdown of XIST expression suppressed proinflammatory cytokine production and extracellular matrix degradation in C28/I2 cells. Overexpression of STAT3 rescued the effects of XIST knockdown. Conclusion: Kaempferol inhibited inflammation and extracellular matrix degradation by modulating the XIST/miR-130a/STAT3 axis in chondrocytes.

Single Posterior Approach versus Combined Anterior and Posterior Approach in the Treatment of Spinal Tuberculosis: A Meta-Analysis.

BACKGROUND: Spinal tuberculosis is the most common form of tuberculosis affecting bone and often needs surgical treatment. Single anterior, single posterior, and combined anterior and posterior approaches are the 3 most commonly used approaches in surgical treatment. Clinically, the choice of optimal surgical approach remains controversial. The purpose of this meta-analysis was to evaluate clinical efficacy of single posterior approach versus combined anterior and posterior approach. METHODS: Studies comparing surgical treatment of spinal tuberculosis by single posterior approach versus combined anterior and posterior approach were identified in a literature search conducted from study inception to July 2020. Selection of studies, extraction of data, and evaluation of bias risk of studies were performed independently by 2 authors, and meta-analysis was conducted using RevMan 5.3 software. RESULTS: The meta-analysis included 15 studies and 793 spinal tuberculosis cases. Single posterior approach was used in 397 patients, and combined anterior and posterior approach was used in 396 patients. There were no statistical differences in visual analog scale score (P = 0.51), correction of Cobb angle (P = 0.14), neurological improvement (P = 0.71), erythrocyte sedimentation rate (P = 0.32), C-reactive protein after operation (P = 0.81), and loss of correction at final follow-up (P = 0.44) between approaches. Single posterior approach was associated with less intraoperative hemorrhage (P < 0.00001), shorter operative time (P < 0.00001), shorter length of hospital stay (P < 0.00001), and fewer complications (P < 0.00001). Combined anterior and posterior approach was associated with shorter fusion time (P = 0.04). CONCLUSIONS: Both approaches can achieve satisfactory clinical outcomes. Posterior-only approach can safely and effectively achieve lesion débridement, decompression, and stability reconstruction and maintenance with advantages of less invasive surgery, less bleeding, shorter surgery time and hospital stay, and fewer complications and seems to be superior to combined posterior-anterior approach.

Ferric Ion Induction of Triggering Receptor Expressed in Myeloid Cells-2 Expression and PI3K/Akt Signaling Pathway in Preosteoclast Cells to Promote Osteoclast Differentiation.

OBJECTIVE: Iron plays a significant role in multiple biological processes. The purpose of this study was to measure whether iron mediated osteoclast differentiation through regulation of triggering receptor expressed in myeloid cells-2 (Trem-2) expression and the PI3K/Akt signaling pathway. METHODS: The effects of six different concentrations of ferric ammonium citrate (FAC) (100, 80, 40, 20, 10 and 0 µmol/L) on RAW 264.7 cells proliferation were assessed by Cell Counting Kit-8 (CCK-8) gassay. Tartrate resistant acid phosphatase (TRAP) assay was performed to detect the effects of FAC on osteoclast formation. The expression of osteoclast differentiation-related (TRAP, NFATc-1, and c-Fos) and Trem-2 mRNA and proteins was analyzed by reverse transcription-polymerase chain reaction and western blot, respectively. Si-Trem-2 was constructed and transfected to RAW264.7 to measure the effects of Trem-2 on FAC-mediated osteoclast formation. TRAP assay and osteoclast differentiation-related gene analyses were further performed to identify the role of Trem-2 in osteoclastogenesis. The Search Tool for the Retrieval of Interacting Genes (STRING) was used to explore the target genes of Trem-2. Trem-2-related gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used for further in-depth analysis. PI3K/Akt pathway-related proteins were detected by immunofluorescence and western blot. RESULTS: In groups with FAC concentration of 10 (102.5 ± 3.1), 20 (100.5 ± 1.5), and 40 µmol/L (98.7 ± 3.1), compared with the control group (100.1 ± 2.2), cell viability was not significantly different from the control (P > 0.05). When the concentration of FAC exceeded 80 µmol/L, cell viability was significantly decreased (87.5 ± 2.8 vs 100.1 ± 2.2, P < 0.05). FAC promotes Trem-2 expression and osteoclast differentiation in a dose-response manner (P < 0.05). The number of osteoclast-like cells was found to be reduced following transfection with the siRNA of Trem-2 (42 ± 3 vs 30 ± 5, P < 0.05). We observed that most of Trem-2 target genes are primarily involved in response to organic substance, regulation of reactive oxygen species metabolic process, and regulation of protein phosphorylation. The STRING database revealed that Trem-2 directly target two gene nodes (Pik3ca and Pik3r1), which are key transcriptional cofactors of the PI3K/Akt signaling pathway. KEGG pathways include the "PI3K-Akt signaling pathway," the "thyroid hormone signaling pathway", "prostate cancer," the "longevity regulating pathway," and "insulin resistance." Expression of p-PI3K and p-Akt protein, measured by immunofluorescence and western blotting, was markedly increased in the FAC groups. Trem-2 siRNA caused partial reduction of these two proteins (p-PI3K and p-Akt) compared to the FAC alone group. CONCLUSION: The FAC promoted osteoclast differentiation through the Trem-2-mediated PI3K/Akt signaling pathway. However, its regulation osteoclastogenesis should be verified through further in vivo studies.