MiR-146b-5p enriched bioinspired exosomes derived from fucoidan-directed induction mesenchymal stem cells protect chondrocytes in osteoarthritis by targeting TRAF6.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.

SLC1A5 enhances malignant phenotypes through modulating ferroptosis status and immune microenvironment in glioma.

Glioma is the most common type of primary malignant tumor in the central nervous system with limited treatment satisfaction. Finding new therapeutic targets has remained a major challenge. Ferroptosis is a novel and distinct type of programmed cell death, playing a regulatory role in the progression of tumors. However, the role of ferroptosis or ferroptosis-related genes (FRGs) in glioma progression has not been extensively studied. In our study, a novel ferroptosis-related prognostic model, including 7 genes, was established, in which patients classified into the high-risk group had more immuno-suppressive status and worse prognosis. Among these 7 genes, we screened solute carrier family 1 member 5 (SLC1A5), an FRG, as a possible new target for glioma treatment. Our results showed that the expression of SLC1A5 was significantly upregulated in glioblastoma tissues compared with the low-grade gliomas. In addition, SLC1A5 knockdown could significantly inhibit glioma cell proliferation and invasion, and reduce the sensitivity of ferroptosis via the GPX4-dependent pathway. Furthermore, SLC1A5 was found to be related to immune response and SLC1A5 knockdown decreased the infiltration and M2 polarization of tumor-associated macrophages. Pharmacological inhibition of SLC1A5 by V9302 was confirmed to promote the efficacy of anti-PD-1 therapy. Overall, we developed a novel prognostic model for glioma based on the seven-FRGs signature, which could apply to glioma prognostic and immune status prediction. Besides, SLC1A5 in the model could regulate the proliferation, invasion, ferroptosis and immune state in glioma, and be applied as a prognostic biomarker and potential therapeutic target for glioma.

Bone-targeting delivery of platelet lysate exosomes ameliorates glucocorticoid-induced osteoporosis by enhancing bone-vessel coupling.

BACKGROUND: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. RESULTS: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. CONCLUSIONS: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP.

Astrocytic NDRG2-PPM1A interaction exacerbates blood-brain barrier disruption after subarachnoid hemorrhage.

Blood-brain barrier (BBB) injury critically exacerbates the poor prognosis of patients with subarachnoid hemorrhage (SAH). The massively increased matrix metalloproteinases 9 (MMP-9) plays a deleterious role in BBB. However, the main source and mechanism of MMP-9 production after SAH remain unclear. We reported that the increased MMP-9 was mainly derived from reactive astrocytes after SAH. Ndrg2 knockout in astrocytes inhibited MMP-9 expression after SAH and attenuated BBB damage. Astrocytic Ndrg2 knockout decreased the phosphorylation of Smad2/3 and the transcription of MMP-9. Notably, cytoplasmic NDRG2 bound to the protein phosphatase PPM1A and restricted the dephosphorylation of Smad2/3. Accordingly, TAT-QFNP12, a novel engineered peptide that could block the NDRG2-PPM1A binding and reduce Smad2/3 dephosphorylation, decreased astrocytic MMP-9 production and BBB disruption after SAH. In conclusion, this study identified NDRG2-PPM1A signaling in reactive astrocytes as a key switch for MMP-9 production and provided a novel therapeutic avenue for BBB protection after SAH.

Activating Parkin-dependent mitophagy alleviates oxidative stress, apoptosis, and promotes random-pattern skin flaps survival.

The random-pattern skin flap is a crucial technique in reconstructive surgery and flap necrosis caused by ischemia/reperfusion injury is a major postoperative complication. Herein, we investigated the mechanism of mitophagy induced by Melatonin (ML) and its effect on the survival of skin flaps. Our results demonstrated that ML could activate mitophagy, ameliorate oxidative stress and alleviate apoptosis in Tert-Butyl hydroperoxide solution (TBHP)-stimulated human umbilical vein endothelial cells in vitro. Inhibiting ML-induced mitophagy considerably abolished its protective effects. Moreover, knockdown of Parkin by siRNA inhibited ML-induced mitophagy, and subsequently exacerbated oxidative stress and apoptosis. Further study demonstrated that inhibition of AMPK reversed these protective effects of ML and downregulated the expression of TFEB. In the vivo study, ML effectively promoted flap survival by activating mitophagy and subsequently ameliorating oxidative stress and mitigating apoptosis. These results established that ML is a potent agent capable for increasing random-pattern skin flap survival by activating Parkin-dependent mitophagy through the AMPK-TFEB signaling pathway.

A high acromion-greater tuberosity impingement index increases the risk of retear after arthroscopic rotator cuff repair.

BACKGROUND: No evaluation has been done on the relationship of the acromion-greater tuberosity impingement index (ATI) with retear after arthroscopic rotator cuff repair (ARCR). Our purpose was to evaluate whether a higher ATI is associated with retear after ARCR. METHODS: 132 patients received ARCR and underwent MRI scan at a one year follow-up to assess tendon healing, and the findings were graded no retear (NR), partial-thickness retear (PR) or full-thickness retear (FR). The ATI, the critical shoulder angle (CSA), acromion index (AI) and lateral acromial angle (LAA) were measured with postoperative radiographs. Functional scores were obtained preoperatively and at a one year follow-up. RESULTS: Postoperative Constant scores and ASES scores were significantly different between groups with inferior outcomes in the FR group (p < 0.05 for all). The UCLA score was significantly better in the NR group compared with the PR and FR groups (p < 0.05), and in the PR group compared with the FR group (p < 0.05). For ATI and CSA, the values of the PR and FR groups were larger than the NR group (p < 0.05 for all), but there were no significant differences between the PR and FR groups (p > 0.05 for all). No significant differences were observed with regard to the AI and LAA (p > 0.05, respectively). The repair integrity was positively related to the ATI (0.304, p < 0.05) and CSA (0.252, p < 0.05), but not related to the AI or LAA (p > 0.05 for both). ATI was not related to any functional scores (p > 0.05 for all). CONCLUSION: This study revealed that the ATI was positively related to rotator cuff retear. Patients with retears had significantly greater ATIs after ARCR. Level of Evidence: III, case-control study.

Long-term outcome of stereotactic aspiration, endoscopic evacuation, and open craniotomy for the treatment of spontaneous basal ganglia hemorrhage: a propensity score study of 703 cases.

BACKGROUND: To compare the long-term therapeutic effects of stereotactic aspiration (SA), endoscopic evacuation (EE), and open craniotomy (OC) in the surgical treatment of spontaneous basal ganglia hemorrhage and explore the appropriate clinical indications for each technique. METHODS: Multiple-treatment inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis was performed to evaluate the therapeutic effects of these techniques. The primary and secondary outcomes were 6-month modified Rankin Scale (mRS) and mortality rates, respectively. RESULTS: A total of 703 patients were ultimately enrolled. For the entire cohort, the 6-month mortality rate was significantly higher (OR 2.396, 95% CI: 1.865-3.080), and the 6-month functional outcome was significantly worse (OR 1.359, 95% CI: 1.091-1.692) for SA than that of EE. The 6-month mortality rate for OC was significantly higher (OR 1.395, 95% CI: 1.059-1.837) than that of EE. Further subgroup analysis was stratified by initial hematoma volume and Glasgow Coma Scale (GCS) score. The mortality rate for SA was significantly higher for patients with hematoma volume of 20-40 mL (OR 6.226, 95% CI: 3.848-10.075), 40-80 mL (OR 2.121, 95% CI: 1.492-3.016), and ≥80 mL (OR 5.544, 95% CI: 3.315-9.269) than in the same subgroups of EE. The functional outcomes for SA were significantly worse than that of EE for hematoma volume subgroups of 40-80 mL (OR 1.424, 95% CI: 1.039-1.951) and ≥80 mL (OR 4.224, 95% CI: 1.655-10.776). The mortality rate for SA was significantly higher than that of EE for the GCS score subgroups of 6-8 (OR 2.082, 95% CI: 1.410-3.076) and 3-5 (OR 2.985, 95% CI: 1.904-4.678). The mortality rate for OC was significantly higher for the GCS score of 3-5 subgroup (OR 1.718, 95% CI: 1.115-2.648), and a tendency for a higher mortality rate of 6-8 subgroup (OR 1.442, 95% CI: 0.965-2.156) than that of EE. CONCLUSIONS: EE can decrease the 6-month mortality rate and improve the 6-month functional outcomes of spontaneous basal ganglia hemorrhage in patients with a hematoma volume ≥40 mL. EE can decrease the 6-month mortality rate of spontaneous basal ganglia hemorrhage in patients with a GCS score of 3-8.

Modified double-pulley suture-bridge techniques with or without medial knot tying show comparable clinical and radiological outcomes in arthroscopic rotator cuff repair.

PURPOSE: The optimal technique for arthroscopic rotator cuff repair is still controversial. The aim of this study was to compare modified arthroscopic double-pulley suture-bridge (DPSB) technique with medial knot tying to those without tying, considering clinical and radiological outcomes. METHODS: This study included 292 patients with large full-thickness rotator cuff tears treated with modified DPSB technique. The patients were divided into 158 cases with medial knot tying (knot-tying group) and 134 without tying (knotless group). At follow-up, clinical outcome was assessed by the Constant score, American Shoulder and Elbow Surgeons (ASES) score, and Shoulder Rating Scale of the University of California at Los Angeles (UCLA) score. The assessment of tendon healing was performed with magnetic resonance imaging (MRI) at a minimum of 12 months postoperatively. RESULTS: The Constant score, ASES score and UCLA score in the knot-tying and knotless groups all improved significantly from before surgery to 12 months postoperatively (P < 0.05, respectively). No significant differences were observed between groups for each phase evaluated (n.s.). Tendon healing was categorised according to Sugaya's classification. The retearing rate was 27/158 (17.0%) in the knot-tying group and 20/134 (14.9%) in the knotless group, with no statistically significant difference between groups (n.s.). Additionally, the retear was classified using the Cho's classification. When comparing the retear rates of different types independently, no statistically significant differences were found between groups (n.s.). CONCLUSIONS: The knotless modified DPSB technique showed comparable short-term functional outcomes to those of the knot tying method in large full-thickness rotator cuff tears. Additionally, no significant differences in repair integrity were observed between the two methods. Both techniques can be considered effective treatments for patients with large-sized full-thickness rotator cuff tears. LEVEL OF EVIDENCE: III.

Inhibiting TLR4 signaling by linarin for preventing inflammatory response in osteoarthritis.

Osteoarthritis (OA) is one of the most common degenerative diseases, ultimately leading to long-term joint pain and severe articular malformation. Controlling local chronic inflammation is a crucial strategy for delaying OA development. Linarin is a natural flavonoid glycoside that is widely available in Compositae, Chrysanthemum indicum and Dendrocalamus and processes protective effects in several animal models. The purpose of our work was to study the protective effect of Linarin for OA. Cellular experiments data showed that Linarin suppressed lipopolysaccharide (LPS)-caused the overproduction of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in chondrocyte. In addition, LPS-stimulated expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide nitrate (iNOS) was decreased by Linarin pre-treatment. Together, Linarin prevented the catabiosis of extracellular matrix caused by LPS. For mechanism, Linarin inhibited the formation of Toll-like receptor 4 (TLR4) / myeloid differentiation protein-2 (MD-2) dipolymer complex and subsequently intervened NF-κB activation. Our mouse DMM model further clarified the protection of Linarin in vivo. In summary, our results suggested that Linarin may be a potential effective agent for OA.

The use of 2-octyl cyanoacrylate as an adjuvant to wound closure in total knee arthroplasty.

PURPOSE: The efficacy of the use of 2-octyl cyanoacrylate (OCA) as an adjuvant to wound closure in preventing wound complications after total knee arthroplasty (TKA) is rarely reported. This study was aimed to determine whether the use of OCA as a supplement to conventional wound closure reduces the incidence of wound complications following TKA. PATIENTS AND METHODS: This retrospective study reviewed 1106 consecutive patients who underwent TKA for symptomatic end-stage osteoarthritis (OA) between 2012 and 2017. The first 562 patients who did not receive OCA were grouped into the Control group, and the subsequent 544 patients who received OCA as an adjuvant to wound closure were grouped into the OCA group. All patients were followed up for at least 2 years. The main outcome was the development of operative site complications, including aseptic and infectious complications. Aseptic wound complications were wound leakage, hematoma, wound dehiscence and delayed wound healing, and infectious complication was mainly referred to the superficial infection. RESULTS: No significant difference with regard to hematoma was observed between groups (3.0% vs. 3.7%, P = 0.617, φ = - 0.02). The incidences were significantly higher in the Control group versus the OCA group in regard to wound leakage (9.4% vs. 2.0%, P = 0.000, φ = 0.16), wound dehiscence (5.7% vs. 1.3%, P = 0.000, φ = 0.12), delayed wound healing (4.4% vs. 1.5%, P = 0.004, φ = 0.09) and superficial infection (2.0% vs. 0.4%, P = 0.022, φ = 0.07). No serious adverse events (AEs) occurred. CONCLUSIONS: The present study showed that the addition of OCA reduced the incidence of wound leakage, wound dehiscence, delayed wound healing and superficial infection after TKA compared to conventional wound closure. Based on the outcomes above, we decide to use OCA routinely for wound closure after TKA. LEVEL OF EVIDENCE: III, retrospective, cohort study.

Theaflavin protects chondrocytes against apoptosis and senescence via regulating Nrf2 and ameliorates murine osteoarthritis.

Oxidative stress-mediated excessive apoptosis and senescence of chondrocytes are the main pathological alterations in the osteoarthritis (OA) development. The protective effects of theaflavin (TF), a common group of polyphenols in black tea, against many degenerative diseases by attenuating oxidative stress are well reported. Nevertheless, its role in the OA treatment is still scantily understood. In the current research, by applying enzyme-linked immunosorbent assay (ELISA) kits and immunofluorescent staining, TF treatment was found to inhibit tert-Butyl hydroperoxide (TBHP)-induced imbalance of anabolism and catabolism in primary mouse chondrocytes. Then, according to western blot, live-dead staining, and SA-ß-gal staining, the dramatically increased level of apoptosis and senescence of chondrocytes in response to TBHP was also found to be reduced by TF administration. With regard to upstream signaling investigation, the in vitro molecular binding analysis indicated that the beneficial effects of TF might be related to the regulation of the Keap1/Nrf2/HO-1 axis. Furthermore, the Silencing of Nrf2 resulted in the abolishment of the anti-apoptosis and anti-senescence effects of TF. In addition, the oral administration of TF was demonstrated to ameliorate osteoarthritis development in a surgically induced mouse OA model. Taken together, these results suggest that TF might be a promising therapeutic option for the treatment of OA.

Comparison of Long-Term Outcomes of Endoscopic and Minimally Invasive Catheter Evacuation for the Treatment of Spontaneous Cerebellar Hemorrhage.

Recently, minimally invasive techniques, including endoscopic evacuation and minimally invasive catheter (MIC) evacuation, have been used for the treatment of patients with spontaneous cerebellar hemorrhage (SCH). However, credible evidence is still needed to validate the effects of these techniques. To explore the long-term outcomes of both surgical techniques in the treatment of SCH. Fifty-two patients with SCH who received endoscopic evacuation or MIC evacuation were retrospectively reviewed. Six-month mortality and the modified Rankin Scale (mRS) score were the primary and secondary outcomes, respectively. A multivariate logistic regression model was used to assess the effects of the different surgical techniques on patient outcomes. In the present study, the mortality rate for the entire cohort was 34.6%. Univariate analysis showed that the surgical technique and preoperative Glasgow Coma Scale (GCS) score affected 6-month mortality. However, no variables were found to be correlated with 6-month mRS scores. Further multivariate analysis demonstrated that 6-month mortality in the endoscopic evacuation group was significantly lower than that in the MIC evacuation group (OR = 4.346, 95% CI 1.056 to 17.886). The 6-month mortality rate in the preoperative GCS 9-14 group was significantly lower than that in the GCS 3-8 group (OR = 7.328, 95% CI 1.723 to 31.170). Compared with MIC evacuation, endoscopic evacuation significantly decreased 6-month mortality in SCH patients. These preliminary results warrant further large, prospective, randomized studies.

Pterostilbene Attenuates Cocultured BV-2 Microglial Inflammation-Mediated SH-SY5Y Neuronal Oxidative Injury via SIRT-1 Signalling.

Microglial inflammation plays an important part in the progression of multiple neurological diseases, including neurodegenerative diseases, stroke, depression, and traumatic encephalopathy. Here, we aimed to explore the role of pterostilbene (PTE) in the microglial inflammatory response and subsequent damage of cocultured neural cells and partially explain the underlying mechanisms. In the coculture system of lipopolysaccharide-activated BV-2 microglia and SH-SY5Y neuroblastoma, PTE (only given to BV-2) exhibited protection on SH-SY5Y cells, evidenced by improved SH-SY5Y morphology and viability and LDH release. It also attenuated SH-SY5Y apoptosis and oxidative stress, evidenced by TUNEL and DCFH-DA staining, as well as MDA, SOD, and GSH levels. Moreover, PTE upregulated SIRT-1 expression and suppressed acetylation of NF-κB p65 subunit in BV-2 microglia, thus decreasing the inflammatory factors, including TNF-α and IL-6. Furthermore, the effects above were reversed by SIRT-1 inhibitor EX527. These results suggest that PTE reduces the microglia-mediated inflammatory response and alleviates subsequent neuronal apoptosis and oxidative injury via increasing SIRT-1 expression and inhibiting the NF-κB signalling pathway.

Transdermal buprenorphine patch versus oral celecoxib for pain management after total knee arthroplasty: An open- label, randomized controlled trial.

BACKGROUND: This study was performed to evaluate the analgesic efficacy and safety of transdermal buprenorphine (TDB) patched for post-operative pain control after total knee arthroplasty (TKA). The hypothesis was that patients receiving the TDB patch would have less pain in comparison to those treated with the oral COX-2 inhibitor celecoxib without increasing side effects. PATIENTS AND METHODS: A total of 160 patients scheduled for primary TKA were randomly assigned to two groups: patients provided the TDB patch (10µg/h) (TDB group) and those provided oral celecoxib (CX group). The outcomes were pain scores measured using the visual analogue scale (VAS) during rest and activity, as well as morphine requirement, operated knee functional recovery and adverse events post-operatively. RESULTS: The total morphine given during the first 72h post-operatively was significantly lower in the TDB group than CX group. The VAS scores were significantly lower in the TDB group than CX group during rest at 2, 4, 6, 12, 24 and 48h post-operatively, and during activity at 12, 24 and 48h and 3 days post-operatively. The mean range of motion on post-operative days (PD) 1, 2 and 3 were significantly greater in the TDB group. In addition, the Lysholm score was significantly higher in the TDB group on PD 3. There were no remarkable adverse events in either group. DISCUSSION: Use of the TDB patch provides effective pain relief and reduces the requirement for rescue morphine without increasing side effects in comparison with oral celecoxib during the early post-operative stage following TKA. LEVEL OF EVIDENCE: II.

[Recombinant adiponectin inhibits the expression of inflammation-associated proteins from mouse astrocytes via AMPK-independent PKC pathway].

Objective To investigate whether recombinant adiponectin peptide (APN) plays an anti-inflammatory role in the oxy-glucose deprivation/reoxygenation (OGD/R) model of astrocytes via the protein kinase C (PKC) and AMP dependent protein kinase (AMPK) pathway. Methods The phosphorylation levels of PKC and AMPK in astrocytic cell line MA1800 was assessed by Western blotting under the condition of OGD/R with the time gradient (2, 4, 6, 8, 12, 24 hours) or the condition of cobalt chloride (CoCl2) treatment with the concentration gradient (20, 50, 100, 200, 400, 600, 800, 1000, 1200, 1600, 2000 µmol/L) to determine the optimal condition of OGD/R in the following study. The cells were grouped into a normal control group, OGD/R treatment group, APN only group, OGD/R combined with APN treatment group, and AMPK inhibition combined with OGD/R and APN treatment group. Western blotting was used to detect the levels of PKCα, phospho-PKC(pan), AMPKα, phospho-AMPKα, NLRP3 inflammasome in the cells, and tumor necrosis factor α (TNF-α) in the conditioned medium of cell culture. Results After OGD/R or 400 µmol/L CoCl2 treatment for 6 hours, the phosphorylation level of p-PKC reached a peak. Compared with the control group, the levels of PKCα, p-AMPKα, AMPK, NLRP3 and TNF-α in the supernatant increased significantly in the experimental groups. Compared with the ODG/R group, the phosphorylation level of PKC, the expression of TNF-α and NLRP3 significantly decreased in the APN treated groups, while the phosphorylation of AMPK remained unchanged. Conclusion APN treatment can inhibit the expression of inflammatory factors in astrocyte model of OGD/R via AMPK-independent PKC signaling pathway.

The acromion-greater tuberosity impingement index: A new radiographic measurement and its association with rotator cuff pathology.

PURPOSE: Several radiographic parameters describe humeral head coverage by the acromion. We describe a new radiographic measurement, the acromion-greater tuberosity impingement index (ATI), and its ability to predict rotator cuff pathology. METHODS: The ATI was measured with magnetic resonance imaging (MRI) and X-ray analysis in 83 patients with rotator cuff pathology and 76 patients with acute rotator cuff tears. The lateral acromial angle (LAA), acromion type, the acromion index (AI) and the critical shoulder angle (CSA) were measured to assess their correlations with the ATI. Receiver operating characteristic (ROC) curves were used to predict degenerative rotator cuff pathology. The change in the ATI after acromion surgery was evaluated in both groups. RESULTS: According to the ROC curves, the ATI is a good predictor of degenerative rotator cuff pathology on both X-ray (cut-off, 0.865) and MRI (cut-off, 0.965). Patients with degenerative rotator cuff pathology had a significantly higher average ATI compared to the trauma group (p = 0.001 for X-ray and MRI). The degenerative group had a significantly lower LAA (p = 0.001) and a higher ratio of type III acromion (p = 0.035) than the trauma group. The ATI on X-ray was negatively related to the LAA and positively related to the AI, the CSA and acromion type (each p < 0.05). The ATI on MRI was negatively related to the LAA and positively related to the AI and acromion type (each p <0.05). More patients in the degenerative group than the trauma group needed acromioplasty or acromion decompression (p < 0.05). The ATI on MRI was significantly lower after acromion surgery compared to before surgery in both groups (p < 0.05). CONCLUSION: The ATI is a good predictor of degenerative supraspinatus tendon tears or subacromial impingement syndrome. The ATI on MRI is more accurate and can precisely guide acromion surgery.

Arctigenin prevents the progression of osteoarthritis by targeting PI3K/Akt/NF-κB axis: In vitro and in vivo studies.

Osteoarthritis (OA), which is principally featured by progressive joint metabolic imbalance and subsequent degeneration of articular cartilage, is a common chronic joint disease. Arctigenin (ATG), a dietary phyto-oestrogen, has been described to have potent anti-inflammatory effects. Nevertheless, its protective effects on OA have not been clearly established. The target of our following study is to evaluate the protective effects of ATG on IL-1ß-induced human OA chondrocytes and mouse OA model. Our results revealed that the ATG pre-treatment effectively decreases the level of pro-inflammatory mediators, such as prostaglandin E2 (PGE2), nitrous oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-6 and tumour necrosis factor alpha (TNF-α) in IL-1ß-induced human chondrocytes. In addition, ATG protects against the degradation of extracellular matrix (ECM) under the stimulation of IL-1ß and the possible mechanism might be connected with the inactivation of phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor-kappa B (NF-κB) axis. Furthermore, a powerful binding capacity between ATG and PI3K was also uncovered in our molecular docking research. Meanwhile, ATG may act as a protector on the mouse OA model. Collectively, all these findings suggest that ATG could be utilized as a promising therapeutic agent for the treatment of OA.

Procyanidin B3 alleviates intervertebral disc degeneration via interaction with the TLR4/MD-2 complex.

As a chronic musculoskeletal degeneration disease, intervertebral disc degeneration (IVDD) has been identified as a crucial cause for low back pain. This condition has a prevalence of 80% among adults without effective preventative therapy. Procyanidin B3 (Pro-B3) is a procyanidin dimer, which is widely present in the human diet and has multiple functions, such as preventing inflammation. But the inhibiting effect of Pro-B3 in IVDD development is still no known. Thus, our study aimed to demonstrate the therapeutical effect of Pro-B3 in IVDD and explain the underlying mechanism. In vitro studies, human nucleus pulposus (NP) cells were isolated and exposed in lipopolysaccharide (LPS) to simulate IVDD development. Pro-B3 pre-treatment inhibited LPS-induced production of inflammation correlated factors such as tumour necrosis factor α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and Nitric oxide (NO). On the other hand, LPS-medicated extracellular matrix (ECM) breakdown was blocked in Pro-B3 treated NP cells. Additionally, Pro-B3 treatment blocked the activation of NF-κB/toll-like receptor 4 pathway in LPS-exposed NP cells. Mechanistically, Pro-B3 could occupy MD-2's hydrophobic pocket exhibiting high affinity for LPS to intervene LPS/TLR4/MD-2 complex formation. In vivo, Pro-B3 treatment prevented the loss of gelatin NP cells and structural damage of annulus fibrosus in rat IVDD model. In brief, Pro-B3 is considered to be a treatment agent for IVDD.

Comparison of endoscopic evacuation, stereotactic aspiration, and craniotomy for treatment of basal ganglia hemorrhage.

BACKGROUND: The main surgical techniques for spontaneous basal ganglia hemorrhage include stereotactic aspiration, endoscopic aspiration, and craniotomy. However, credible evidence is still needed to validate the effect of these techniques. OBJECTIVE: To explore the long-term outcomes of the three surgical techniques in the treatment of spontaneous basal ganglia hemorrhage. METHODS: Five hundred and sixteen patients with spontaneous basal ganglia hemorrhage who received stereotactic aspiration, endoscopic aspiration, or craniotomy were reviewed retrospectively. Six-month mortality and the modified Rankin Scale score were the primary and secondary outcomes, respectively. A multivariate logistic regression model was used to assess the effects of different surgical techniques on patient outcomes. RESULTS: For the entire cohort, the 6-month mortality in the endoscopic aspiration group was significantly lower than that in the stereotactic aspiration group (odds ratio (OR) 4.280, 95% CI 2.186 to 8.380); the 6-month mortality in the endoscopic aspiration group was lower than that in the craniotomy group, but the difference was not significant (OR=1.930, 95% CI 0.835 to 4.465). A further subgroup analysis was stratified by hematoma volume. The mortality in the endoscopic aspiration group was significantly lower than in the stereotactic aspiration group in the medium (≥40-<80 mL) (OR=2.438, 95% CI 1.101 to 5.402) and large hematoma subgroup (≥80 mL) (OR=66.532, 95% CI 6.345 to 697.675). Compared with the endoscopic aspiration group, a trend towards increased mortality was observed in the large hematoma subgroup of the craniotomy group (OR=8.721, 95% CI 0.933 to 81.551). CONCLUSION: Endoscopic aspiration can decrease the 6-month mortality of spontaneous basal ganglia hemorrhage, especially in patients with a hematoma volume ≥40 mL.

Pterostilbene Attenuates Astrocytic Inflammation and Neuronal Oxidative Injury After Ischemia-Reperfusion by Inhibiting NF-κB Phosphorylation.

Astrocyte-mediated inflammation and oxidative stress elicit cerebral ischemia-reperfusion (IR) injury after stroke. Nuclear factor (NF)-κB activates astrocytes and generates pro-inflammatory factors. The purpose of the present study is to elucidate the effect of pterostilbene (PTE, a natural stilbene) on astrocytic inflammation and neuronal oxidative injury following cerebral ischemia-reperfusion injury. A middle cerebral artery occlusion-reperfusion (MCAO/R) mouse model and HT22/U251 co-culture model subjected to oxygen-glucose deprivation and re-introduction (OGD/R) were employed, with or without PTE treatment. The data showed that PTE delivery immediately after reperfusion, at 1 h after occlusion, decreased infarct volume, brain edema, and neuronal apoptosis and improved long-term neurological function. PTE decreased oxidation (i.e., production of reactive oxygen species, malondialdehyde) and inflammatory mediators (tumor necrosis factor-α, interleukin-1ß, and interleukin-6) and increased anti-oxidative enzyme activities (i.e., of superoxide dismutase, glutathione peroxidase), by inhibiting phosphorylation and nuclear translocation of NF-κB. In conclusion, PTE attenuated astrocyte-mediated inflammation and oxidative injury following IR via NF-κB inhibition. Overall, PTE is a promising neuroprotective agent.