Sophoridine exerts anti-arthritic effects on fibroblast-like synoviocytes and collagen-induced arthritis in rats.

The discovery of alternative medicines with fewer adverse effects is urgently needed for rheumatoid arthritis (RA). Sophoridine (SR), the naturally occurring quinolizidine alkaloid isolated from the leguminous sophora species, has been demonstrated to possess a wide range of pharmacological activities. However, the effect of SR on RA remains unknown. In this study, the collagen-induced arthritis (CIA) rat model and tumor necrosis factor alpha (TNFα)-induced fibroblast-like synoviocytes (FLSs) were utilized to investigate the inhibitory effect of SR on RA. The anti-arthritic effect of SR was evaluated using the CIA rat model in vivo and TNFα-stimulated FLSs in vitro. Mechanistically, potential therapeutic targets and pathways of SR in RA were analyzed through drug target databases and disease databases, and validation was carried out through immunofluorescence, immunohistochemistry, and Western blot. The in vivo results revealed that SR treatment effectively ameliorated synovial inflammation and bone erosion in rats with CIA. The in vitro studies showed that SR could significantly suppress the proliferation and migration in TNFα-induced arthritic FLSs. Mechanistically, SR treatment efficiently inhibited the activation of MAPKs (JNK and p38) and NF-κB pathways in TNFα-induced arthritic FLSs. These findings were further substantiated by Immunohistochemistry results in the CIA rat. SR exerts an anti-arthritic effect in CIA rats through inhibition of the pathogenic characteristic of arthritic FLSs via suppressing NF-κB and MAPKs (JNK and p38) signaling pathways. SR may have a great potential for development as a novel therapeutic agent for RA treatment.

Percutaneous Endoscopic Unilateral-Approach Bilateral Decompression for Lumbar Spinal Stenosis.

Lumbar spinal stenosis (LSS) involves the narrowing of the spinal canal due to degenerative changes in the vertebral joints, intervertebral discs, and ligaments. LSS encompasses central canal stenosis (CCS), lateral recess stenosis (LRS), and intervertebral foramen stenosis (IFS). The utilization of lumbar endoscopic unilateral laminotomy for bilateral decompression (LE-ULBD) has gained popularity in the treatment of CCS and LRS. This popularity is attributed to the rapid development of endoscopic instruments and the progress of endoscopic philosophy. In this technical report, a detailed introduction to the steps and key points of LE-ULBD is provided. Simultaneously, a retrospective review of 132 consecutive patients who underwent LE-ULBD for central canal and/or lateral recess stenosis was conducted. The outcomes after more than two years of follow-up were assessed using the visual analogue score (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores, and the modified MacNab criteria to evaluate surgical efficacy. All 132 patients underwent LE-ULBD successfully. Among them, 119 patients were rated as "excellent," while 13 patients were rated as "good" based on the modified MacNab criteria during the last follow-up. Incidental dural tears occurred in four cases, but there were no post-operative epidural hematomas or infections. The experience demonstrates that LE-ULBD is a less invasive, effective, and safe approach. It can be considered as an alternative option for treating patients with lumbar central canal stenosis and/or lateral recess stenosis.

Inhibitory effects of norcantharidin on titanium particle-induced osteolysis, osteoclast activation and bone resorption via MAPK pathways.

Wear particles generated from the surface of implanted prostheses can lead to peri-implant osteolysis and subsequent aseptic loosening. In the inflammatory environment, extensive formation and activation of osteoclasts are considered the underlying cause of peri-implant osteolysis. Current medications targeting osteoclasts for the treatment of particle-induced bone resorption are not ideal due to significant side effects. Therefore, there is an urgent need to develop more effective drugs with fewer side effects. Norcantharidin (NCTD), a derivative of cantharidin extracted from blister beetles, is currently primarily used for the treatment of solid tumors in clinical settings. However, the potential role of NCTD in treating aseptic loosening of the prosthesis has not been reported. In this study, the in vitro results demonstrated that NCTD could effectively inhibit the formation of osteoclasts and bone resorption induced by the RANKL. Consistently, NCTD strongly inhibited RANKL-induced mRNA and protein levels of c-Fos and NFATc1, concomitant with reduced expression of osteoclast specific genes including TRAP, CTR and CTSK. The in vivo data showed that NCTD exerted significant protective actions against titanium particle-induced inflammation and subsequent osteolysis. The molecular mechanism investigation revealed that NCTD could suppress the activations of RANKL-induced MAPK (p38, ERK). Overall, these findings support the potential use of NCTD for the treatment of aseptic loosening following total joint arthroplasty.

In vitro inhibitory effect of zingerone on TNFα-stimulated fibroblast-like synoviocytes.

Targeting Fibroblast-like synoviocytes (FLSs) is an attractive complementary approach for RA therapy. This study aimed to investigate the inhibitory effects of zingerone on TNFα-induced arthritic FLSs. MTS, EdU, wound healing, DHE staining and real-time PCR were used to determine the effects of zingerone on the destructive behaviors of arthritic FLSs induced by TNFα. Western blot analysis was used to analyze cell signaling pathways. Zingerone treatment significantly inhibited TNFα-induced proliferation, migration, ROS formation and pro-inflammatory cytokines expression of FLSs. Molecular mechanism studies revealed that zingerone could suppress TNFα-induced activations of MAPKs (ERK, JNK and p38) in arthritic FLSs. Zingerone attenuated pathological features of FLSs via MAPKs pathways, indicating its potential as a complementary or alternative drug for RA therapy.

Erratum: [Corrigendum] Upregulation of LINC00659 expression predicts a poor prognosis and promotes migration and invasion of gastric cancer cells.

[This corrects the article DOI: 10.3892/ol.2021.12818.].

Ultrasonic Osteotome Assisted Posterior Endoscopic Cervical Foraminotomy in the Treatment of Cervical Spondylotic Radiculopathy Due to Osseous Foraminal Stenosis.

OBJECTIVE: To investigate the efficacy and safety of the posterior endoscopic cervical foraminotomy (PECF) using ultrasonic osteotome for the treatment of cervical osseous foraminal stenosis，focusing on introduction of the advantages of ultrasonic osteotome in partial pediculectomy and ventral osteophyte resection in PECF. METHODS: Nineteen patients with cervical osseous foraminal stenosis who underwent PECF using ultrasonic osteotome in our institution between April 2018 and April 2021 were enrolled in this study. All the patients were followed up more than 12 months. The patients' medical data, as well as pre- and postoperative radiologic findings were thoroughly investigated. The visual analogue score (VAS), Japanese Orthopaedic Association (JOA) score, cervical dysfunction index (Neck disability index, NDI), and modified MacNab criteria were used to assess the surgical efficacy. RESULTS: All the patients were successfully treated with PECF using ultrasonic osteotome. The pre- and postoperative VAS, NDI, and JOA scores were significantly improved (p<0.05). According to the modified MacNab criteria, 17 patients were assessed as "excellent", two patients were assessed as "good" at the last follow-up. There was no dura tear, nerve root damage, incision infection, neck deformity, or other complications. CONCLUSION: Adequate nerve root decompression can be accomplished successfully with the help of ultrasonic osteotome in PECF, which has the advantage of reducing the probability of damage to the nerve root and dura mater, in addition to the original merits of endoscopic surgery.

Nanoengineered sonosensitive platelets for synergistically augmented sonodynamic tumor therapy by glutamine deprivation and cascading thrombosis.

Ultrasound (US)-activated sonodynamic therapy (SDT) stands for a distinct antitumor modality because of its attractive characteristics including intriguing noninvasiveness, desirable safety, and high tissue penetration depth, which, unfortunately, suffers from compromised therapeutic efficacy due to cancer cell-inherent adaptive mechanisms, such as glutathione (GSH) neutralization response to reactive oxygen species (ROS), and glutamine addictive properties of tumors. In this work, we developed a biological sonosensitive platelet (PLT) pharmacytes for favoring US/GSH-responsive combinational therapeutic of glutamine deprivation and augmented SDT. The amino acid transporter SLC6A14 blockade agent α-methyl-DL-tryptophan (α-MT)-loaded and MnO2-coated porphyrinic metal-organic framework (MOF) nanoparticles were encapsulated in the PLTs through the physical adsorption of electrostatic attraction and the intrinsic endocytosis of PLTs. When the sonosensitive PLT pharmacytes reached tumor sites through their natural tendencies to TME, US stimulated the PLTs-loaded porphyrinic MOF to generate ROS, resulting in morphological changes of the PLTs and the release of nanoparticles. Subsequently, intracellular high concentration of GSH and extracellular spatio-temporal controlled US irradiation programmatically triggered the release of α-MT, which enabled the synergistically amplified SDT by inducing amino acid starvation, inhibiting mTOR, and mediating ferroptosis. In addition, US stimulation achieved the targeted activation of PLTs at tumor vascular site, which evolved from circulating PLTs to dendritic PLTs, effectively blocking the blood supply of tumors through thrombus formation, and revealing the encouraging potential to facilitate tumor therapeutics.

EID3 Promotes Glioma Cell Proliferation and Survival by Inactivating AMPKα1.

OBJECTIVE: EID3 (EP300-interacting inhibitor of differentiation) was identified as a novel member of EID family and plays a pivotal role in colorectal cancer development. However, its role in glioma remained elusive. In current study, we identified EID3 as a novel oncogenic molecule in human glioma and is critical for glioma cell survival, proliferation and invasion. METHODS: A total of five patients with glioma were recruited in present study and fresh glioma samples were removed from patients. Four weeks old male non-obese diabetic severe combined immune deficiency (NOD/SCID) mice were used as transplant recipient models. The subcutaneous tumor size was calculated and recorded every week with vernier caliper. EID3 and AMP-activated protein kinase α1 (AMPKα1) expression levels were confirmed by real-time polymerase chain reaction and Western blot assays. Colony formation assays were performed to evaluate cell proliferation. Methyl thiazolyl tetrazolium (MTT) assays were performed for cell viability assessment. Trypan blue staining approach was applied for cell death assessment. Cell Apoptosis DNA ELISA Detection Kit was used for apoptosis assessment. RESULTS: EID3 was preferentially expressed in glioma tissues/cells, while undetectable in astrocytes, neuronal cells, or normal brain tissues. EID3 knocking down significantly hindered glioma cell proliferation and invasion, as well as induced reduction of cell viability, apoptosis and cell death. EID3 knocking down also greatly inhibited tumor growth in SCID mice. Knocking down of AMPKα1 could effectively rescue glioma cells from apoptosis and cell death caused by EID3 absence, indicating that AMPKα1 acted as a key downstream regulator of EID3 and mediated suppression effects caused by EID3 knocking down inhibition. These findings were confirmed in glioma cells generated patient-derived xenograft models. AMPKα1 protein levels were affected by MG132 treatment in glioma, which suggested EID3 might down regulate AMPKα1 through protein degradation. CONCLUSION: Collectively, our study demonstrated that EID3 promoted glioma cell proliferation and survival by inhibiting AMPKα1 expression. Targeting EID3 might represent a promising strategy for treating glioma.

Imperatorin Inhibits Proliferation, Migration, and Inflammation via Blocking the NF-κB and MAPK Pathways in Rheumatoid Fibroblast-like Synoviocytes.

Rheumatoid arthritis (RA) is a chronic joint inflammatory disease associated with the aberrant activation of fibroblast-like synoviocytes (FLSs). Searching for natural compounds that may suppress the activation of FLSs has become a complementary approach for RA treatment. Here, we investigated the effects and mechanisms of imperatorin (IPT) on proliferation, migration, and inflammation in primary cultured arthritic FLSs. We found that IPT significantly suppressed TNFα-induced proliferation and migration of arthritic FLSs, but showed little effect on survival and apoptosis. In addition, IPT treatment significantly reduced the TNFα-induced expression of pro-inflammatory cytokines (IL-1ß, TNFα, IL-6, and IL-8) in arthritic FLSs. Further mechanism studies suggested that IPT inhibited the activations of p38 and extracellular signal-regulated kinase (ERK). Also, IPT blocked the nuclear factor of κB (NF-κB) activation by suppressing the phosphorylation and degradation of IκBα, thereby preventing the translocation of p65. Collectively, our results demonstrated that IPT could inhibit the over-activated phenotypes of arthritic FLSs via the mitogen-activated protein kinase (MAPK) (p38 and ERK) and NF-κB pathways leading to the down-regulation of pro-inflammatory cytokines, which might be beneficial to the anti-proliferative and anti-migratory activities of FLS cells. These findings suggest that IPT has the potential to be developed as a novel agent for RA treatment.

Percutaneous full-endoscopic uniportal decompression for the treatment of symptomatic idiopathic lumbar spinal epidural lipomatosis: Technical note.

Background: Lumbar spinal epidural lipomatosis (SEL) is a rare condition characterized by an excessive accumulation of adipose tissue within the spinal canal, compressing the dura sac and/or nerve roots. When conservative treatments fail and clinical symptoms progress quickly and seriously, surgical decompression should be considered. With the rapid development of endoscopic armamentaria and techniques, the pathological scope that can be treated by percutaneous endoscopic spine surgery is ever expanding. Objective: In this paper, the authors describe a patient with lumbar spinal epidural lipomatosis who was treated with a percutaneous full-endoscopic uniportal decompression surgery successfully. This article aims to validate the feasibility of percutaneous full-endoscopic uniportal decompression for the treatment of symptomatic idiopathic spinal epidural lipomatosis via interlaminar approach. Methods: We describe a case of a 69-year-old man with a 10-year history of low back pain, intermittent claudication, and bilateral leg neuropathic pain. He was diagnosed with lumbar epidural lipomatosis, which did not respond to conservative therapy. After a comprehensive evaluation, he underwent percutaneous endoscopic spine surgery to remove hyperplastic adipose tissue and decompress nerve roots and dura sac. Results: The patient was treated with a percutaneous full-endoscopic uniportal decompression surgery successfully. After the procedure, his leg pain decreased and his walking capacity improved. There were no surgery-related complications, such as cerebrospinal fluid leakage, incision infection, etc. Conclusions: The case with SEL was successfully treated with a percutaneous full-endoscopic uniportal surgery, which has the advantages of excellent presentation of anatomical structures, expanded field of vision, less surgical-related trauma, and bleeding. The key point of the procedure is to release and cut off the bands which divide the epidural space into small rooms filled with excess adipose tissue.

Peimine suppresses collagen-induced arthritis, activated fibroblast-like synoviocytes and TNFα-induced MAPK pathways.

BACKGROUND AND PURPOSE: Peimine (PM), a main isosterol alkaloid component isolated from the bulbs of traditional Chinese herb Fritillaria cirrhosa D. Don, has been demonstrated to exhibit multiple pharmacological properties, including anti-inflammation, anti-cancer and pain suppression. However, its effect on rheumatoid arthritis (RA) remains unknown. In the present study, we investigated the effect of PM on collagen-induced arthritis (CIA) rats in vivo and its inhibition on destructive behaviors of arthritic fibroblast-like synoviocytes (FLSs) in vitro. METHODS: Arthritis was induced in rats by chicken type II collagen. Arthritis score, radiological evaluation, and histopathological assessment were used to evaluate the therapeutic effects of PM on CIA rats. EdU assay, wound healing assay and real-time PCR were used to examine the inhibitory effect of PM on proliferation, migration, and over-expression of pro-inflammatory cytokines in TNFα-induced arthritic FLSs. TRAP staining and scanning electron microscopy were used to analyze the effect of PM on osteoclastogensis and bone resorption. Western blot was used to reveal PM's molecular mechanism of action on RA. RESULTS: PM significantly suppressed synovitis and bone destruction in CIA rats. In vitro experiments showed that PM treatment significantly inhibited TNFα-induced destructive behaviors of arthritic FLSs, including over-proliferation, migration and over-expression of pro-inflammatory cytokines. Additionally, RANKL-induced osteoclast formation and bone-resorpting function were also inhibited by PM. Further molecular mechanism studies revealed that PM treatment significantly suppressed TNFα-induced activations of MAPKs (ERK, JNK and p38) in arthritic FLSs. CONCLUSION: Our findings provide strong evidence that PM has the potential to be developed as a therapeutic agent for patients with RA.

Active Vibration Control of Piezoelectric Sandwich Plates.

This paper deals with the active vibration control of piezoelectric sandwich plate. The structure consists of a substrate plate layer sandwiched between two layers of piezoelectric sensor and actuator. Based on laminate theory and constitutive equation of piezoelectric material, the vibration active control dynamic equation of the sandwich structure is established by using hypothetical mode method and Hamilton principle. The Rayleigh-Ritz method is used to solve it. The form of hypothetical solution is used for approximate solution, which is simple and accurate. The method of this paper is verified by several examples. The parametric studies of the sandwich plate structures are carried out. The results show that applying different boundary conditions and piezoelectric patch positions to the structures have a great influence on the natural frequency. When the driving voltage increases, the deflection of the plate structures increase approximately linearly. The active vibration control studies are investigated as well. The results show that within a certain range, the larger the value of the speed feedback coefficient, the better the active control effect. The positions of the piezoelectric patches affect the effectiveness and cost of active control. When the piezoelectric plate is located at the fixed end, the effect and cost of active control are better than that at the midpoint and free end of the plate.

Piperlongumine Inhibits Titanium Particles-Induced Osteolysis, Osteoclast Formation, and RANKL-Induced Signaling Pathways.

Wear particle-induced aseptic loosening is the most common complication of total joint arthroplasty (TJA). Excessive osteoclast formation and bone resorptive activation have been considered to be responsible for extensive bone destruction and prosthesis failure. Therefore, identification of anti-osteoclastogenesis agents is a potential therapy strategy for the treatment of aseptic loosening and other osteoclast-related osteolysis diseases. In the present study, we reported, for the first time, that piperlongumine (PL), a key alkaloid compound from Piper longum fruits, could significantly suppress the formation and activation of osteoclasts. Furthermore, PL effectively decreased the mRNA expressions of osteoclastic marker genes such as tartrate-resistant acid phosphatase (TRAP), calcitonin receptor (CTR), and cathepsin K (CTSK). In addition, PL suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced activations of MAPKs (ERK, JNK and p38) and NF-κB, which down-regulated the protein expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). Using a titanium (Ti) particle-induced calvarial osteolysis model, we demonstrated that PL could ameliorate Ti particle-induced bone loss in vivo. These data provide strong evidence that PL has the potential to treat osteoclast-related diseases including periprosthetic osteolysis (PPO) and aseptic loosening.

Tomatidine Suppresses the Destructive Behaviors of Fibroblast-Like Synoviocytes and Ameliorates Type II Collagen-Induced Arthritis in Rats.

Fibroblast-like synoviocytes (FLSs) are the prominent non-immune cells in synovium and play a pivotal role in rheumatoid arthritis (RA) pathogenesis. Searching for natural compounds that may suppress the pathological phenotypes of FLSs is important for the development of RA treatment. Tomatidine (Td), a steroidal alkaloid derived from the solanaceae family, has been reported to have anti-inflammatory, anti-tumor and immunomodulatory effects. However, its effect on RA remains unknown. Here, we examined the inhibitory effect of Td on TNFα-induced arthritic FLSs, and subsequently investigated its therapeutic effect on collagen-induced arthritis (CIA) rats. Our results revealed that Td significantly inhibited TNFα-induced proliferation and migration of arthritic FLSs. In addition, we found that Td treatment could efficaciously ameliorate synovial inflammation and joint destruction of rats with CIA. Both in vitro and in vivo studies showed that Td significantly suppressed the production of pro-inflammatory cytokines including IL-1ß, IL-6 and TNFα, and downregulated the expression of MMP-9 and RANKL. Further molecular mechanism studies revealed that the inhibitory effect of Td on RA might attribute to the decreased activations of MAPKs (ERK and JNK) and NF-κB. These findings provide evidence that Td has the potential to be developed into a complementary or alternative agent for RA therapy.

A novel vertebral trench technique (VTT) involving transforaminal endoscopic lumbar foraminotomy (TELF) for very highly up-migrated lumbar disc herniation above L5.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) has become popular for the treatment of symptomatic lumbar disc herniation (LDH). The very highly up-migrated lumbar disc herniation (VHUM-LDH) is difficult to remove under PELD. The purpose of this research is to investigate the feasibility, clinical efficacy and operative nuances of a novel VTT involving TELF for this type of herniation. METHODS: Eleven patients with very highly up-migrated LDH who underwent VTT involving TELF discectomy from May 2016 to May 2019 were included in this study. The operative time, length of hospital stay, and postoperative complications were recorded. Pre-and postoperative radiologic findings were investigated. All the patients were followed more than 1 year. The visual analogue score (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores and modified MacNab criteria were used to assess surgical efficacy. RESULTS: All the 11 patients underwent successful surgery. We compared the VAS, ODI, and JOA scores before and after surgery. The differences were statistically significant (P < 0.05). According to the modified MacNab criteria, 10 patients were assessed as "excellent", 1 patient was assessed as "good" at the last follow up. CONCLUSION: The novel VTT involving TELF discectomy is a supplement to the traditional PELD. This technique enables the endoscope with working cannula to get closer the sequestrated nucleus pulposus without irritating the exiting nerve root, and facilitates the nucleus pulposus be removed successfully under direct visualization. The VTT involving TELF discectomy can be a safe, effective and feasible surgical procedure for the treatment of LDH with very highly up-migrated.

Percutaneous Full-Endoscopic C2 Ganglionectomy for the Treatment of Intractable Occipital Neuralgia: Technical Note.

BACKGROUND: The C-2 dorsal root ganglionectomy procedure can provide effective treatment for intractable occipital neuralgia (ON). However, the traditional microsurgery of C2 ganglionectomy needs a wide incision and significant paraspinous muscle dissection for adequate visualization. The indications of endoscopic spine surgery are ever expanding, with the development of endoscopic armamentaria and technological innovations. OBJECTIVE: To validate the feasibility of the approach and describe several operative nuances based on the authors' experience. In this paper, the authors describe a patient with intractable ON who was successfully treated with a percutaneous full-endoscopic C2 ganglionectomy. METHODS: We describe the case of an 83-yr-old female with a 2-yr history of left ON who did not respond to a series of treatments, including physical therapy, drug therapy, injection therapy, and radiofrequency therapy. After careful examination, we performed a percutaneous, full-endoscopic left C2 ganglionectomy. RESULTS: The patient was successfully treated with a percutaneous full-endoscopic ganglionectomy. Afterwards, her intractable and constant pain was relieved. There was no cerebrospinal fluid leakage, incision infection, neck deformity, or other complications. CONCLUSION: C2 ganglionectomy can be accomplished successfully using a full-endoscopic uniportal surgical technique under continuous irrigation, which has the advantages of excellent illumination and visualization, reduced surgery-related trauma, and reduced bleeding.

Upregulation of LINC00659 expression predicts a poor prognosis and promotes migration and invasion of gastric cancer cells.

Long non-coding RNAs (lncRNAs) serve an important role in the progression of cancer. LINC00659 was recently identified as a novel oncogenic lncRNA involved in colon cancer cell proliferation via modulating the cell cycle. However, the function of LINC00659 in other types of cancer, especially in gastric cancer (GC), remains unknown. In the present study, bioinformatics analysis combined with cell experiments were performed to explore the function of LINC00659 in GC. It was revealed that LINC00659 expression was significantly upregulated in GC tissues and cell lines. Increased levels of LINC00659 were associated with advanced tumor stage and unfavorable prognosis of patients with GC. Additionally, upregulated LINC00659 expression promoted the migration and invasion of GC cells. Further analysis using a bioinformatics method revealed that matrix metalloproteinase 15 and IQ motif-containing GTPase activating protein 3 were potential downstream targets of LINC00659 involved in tumor metastasis, although the precise underlying mechanism requires further exploration.

HOXB-AS1 accelerates the tumorigenesis of glioblastoma via modulation of HOBX2 and HOBX3 at transcriptional and posttranscriptional levels.

Glioblastoma (GBM) is the most universal and invasive brain tumor among adults. Increasing studies have reported that long noncoding RNAs play vital roles in regulating downstream molecules at the transcriptional or posttranscriptional level in tumor progression. The purpose of the current research was to inquire the modulation mechanism by which homeobox B cluster antisense RNA 1 (HOXB-AS1) functioned in GBM. Our study first discovered the lifted expression of HOXB-AS1 and its nearby genes HOXB2 and HOXB3 in GBM and the positive relationship between HOXB-AS1 and HOXB2 or HOXB3. Loss-of-function assays and in vivo study detected that silencing of HOXB-AS1, HOXB2, or HOXB3 restrained the proliferation and induced the apoptosis in GBM. In addition, mechanism experiments demonstrated that HOXB-AS1 recruited interleukin enhancer-binding factor 3 (ILF3) to regulate HOXB2 and HOXB3 expression at the transcriptional level, and HOXB-AS1 sponged miR-186-5p to modulate HOXB2 and HOXB3 expression at posttranscriptional level. Finally, the regulatory mechanism of HOXB-AS1 in GBM was certified through rescue experiments. Our results indicated that HOXB-AS1 boost the HOXB2 or HOXB3 expression at the transcriptional and posttranscriptional levels. We detected the HOXB-AS1-ILF3-HOXB2/HOXB3 axis and HOXB-AS1-miR-186-5p-HOXB2/HOXB3 axis driving the GBM progression, which might generate more effective diagnostic biomarkers and therapeutic targets for patients with GBM.

Long noncoding RNA HNF1A-AS1 regulates proliferation and apoptosis of glioma through activation of the JNK signaling pathway via miR-363-3p/MAP2K4.

Long noncoding RNAs (lncRNAs) have been proven to exert important functions in the various biological processes of human cancers. It has been reported that lncRNA HNF1 homeobox A antisense RNA 1 (HNF1A-AS1) was abnormally expressed and played a role in the initiation and development of various human cancers. In this study, we confirmed that the expression level of HNF1A-AS1 was increased in glioma tissues and cells. Knockdown of HNF1A-AS1 inhibited cell proliferation and promoted cell apoptosis in glioma. Then, we disclosed the downregulation of miR-363-3p in glioma tissues and cell lines. The interaction between HNF1A-AS1 and miR-363-3p was identified in glioma cells. Furthermore, an inverse correlation between HNF1A-AS1 and miR-363-3p was observed in glioma tissues. Afterwards, we recognized that MAP2K4 was a direct target of miR-363-3p. The expression of MAP2K4 was negatively correlated with miR-363-3p while positively related to HNF1A-AS1 in glioma tissues. We also found the regulatory effect of HNF1A-AS1 on the MAP2K4-dependent JNK signaling pathway. All findings indicated that HNF1A-AS1 induces the upregulation of MAP2K4 to activate the JNK signaling pathway to promote glioma cell growth by acting as a miR-363-3p sponge.

Sonodynamic therapy-derived multimodal synergistic cancer therapy.

Sonodynamic therapy (SDT) represents a promising modality that provides the possibility of non-invasively eliminating solid tumors in a site-directed manner. In light of the complexity and heterogeneity of tumors, more and more studies are attempting to combine SDT with other therapeutic methods so as to achieve better tumor treatment effect, which sheds new light on the potential of SDT-based synergistic therapeutics. Herein, the representative studies of SDT-instructed multimodal synergistic cancer therapy are comprehensively presented, such as sono-chemotherapy, sono-radiotherapy, sono-immunotherapy, and sono-chemodynamic therapy, etc., and their incorporate mechanisms are discussed in detail. The current challenges and future prospects to promote the advanced development of SDT-based nanomedicines in this burgeoning research field are highlighted. It is believed that such an emerging synergistic therapeutic modality based on SDT will play a more significant role in the field of tumor precision treatment medicine.