Case Report: Endoscopic trans-cerebellar medullary fissure approach for the management of brainstem hemorrhage.

Objective: Brainstem hematoma (BSH) is a high-risk condition that can lead to deadly and disabling consequences if not properly managed. However, recent advances in endoscopic techniques, employed for removing supratentorial intracerebral hemorrhage have shown significant improvements in operative morbidity and mortality rates compared to other approaches. In this study, we demonstrate the utility and feasibility of the endoscopic trans-cerebellar medullary fissure approach for the management of brain stem hemorrhage in carefully selected patients. Patients and methods: A 55-year-old man presented to the emergency department in a comatose state with respiratory distress. A CT scan revealed the presence of a brainstem hemorrhage. Given the location of the hemorrhage and the need to quickly manage the associated developmental obstructive hydrocephalus and respiratory distress, an endoscopic trans-cerebellar medullary fissure approach was chosen as the most appropriate method of treatment. Results: Total resection was achieved, and the patient gradually improved postoperatively with no new neurological deficits. He is currently under routine follow-up and is conscious but has partial hemiplegia. Conclusion: This approach provided direct visualization of the lesion and was minimally invasive. The endoscopic trans-cerebellar medullary fissure approach may be considered an alternative to open approaches for brainstem hemorrhage in carefully selected patients.

Positioning and design by computed tomography imaging in neuroendoscopic surgery of patients with chronic subdural hematoma.

BACKGROUND: Neuroendoscopy is a very useful technique to Chronic Subdural Hematoma (CSH). But how to achieve the goal of treatment more minimally invasive? AIM: To develop a simple, fast and accurate preoperative planning method in our way for endoscopic surgery of patients with CSH. METHODS: From June 2018 to May 2020, forty-two patients with CSH, admitted to our hospital, were performed endoscopic minimally invasive surgery; computed tomography (CT) imaging was employed to locate the intracerebral hematoma and select the appropriate endoscopic approach before the endoscopic surgery. The clinical data and treatment efficacy were analyzed. RESULTS: According to the learning of CT scanning images, the surgeon can accurately design the best minimally invasive neuroendoscopic surgical approach and realize the precise positioning and design of the drilling site of the skull and the size of the bone window, so as to provide the most effective operation space with the smallest bone window. In this group, the average operation time was only about 1 h, and the clearance rate of hematoma was about 95%. CONCLUSION: Patients with CSH can achieve good therapeutic effect by using our way to positioning and design to assist the operation of CSH according to CT scan and image, and our way is very useful and necessary.

Efficacy evaluation of neuroendoscopy vs burr hole drainage in the treatment of chronic subdural hematoma: An observational study.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common disease in neurosurgery. The traditional treatment methods include burr hole drainage, bone flap craniectomy and other surgical methods, and there are certain complications such as recurrence, pneumocephalus, infection and so on. With the promotion of neuroendoscopic technology, its treatment effect and advantages need to be further evaluated. AIM: To study the clinical effect of endoscopic small-bone approach in CSDH. METHODS: A total of 122 patients with CSDH admitted to our hospital from August 2018 to August 2021 were randomly divided into two groups using the digital table method: the neuroendoscopy group (n = 61 cases) and the burr hole drainage group (n = 61 cases). The clinical treatment effect of the two groups of patients with CSDH was compared. RESULTS: At the early postoperative stage (1 d and 3 d), the proportion of 1/2 re-expansion of brain tissue in the hematoma cavity and the proportion of complete re-expansion was higher in the neuroendoscopy group than in the burr hole drainage group, and the difference between the two groups was statistically significant (P < 0.05). The recurrence rate of hematoma in the neuroendoscopy group was lower than that in the burr hole drainage group, and the difference between the two groups was statistically significant (P < 0.05). No intracranial hematoma, low cranial pressure, tension pneumocephalus or other complications occurred in the neuroendoscopy group. CONCLUSION: The neuroendoscopic approach for the treatment of CSDH can clear the hematoma under direct vision and separate the mucosal lace-up. The surgical effect is apparent with few complications and definite curative effect, which is worthy of clinical promotion and application.

Knockdown of long non-coding RNA LEF1-AS1 attenuates apoptosis and inflammatory injury of microglia cells following spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development. METHODS: Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique. RESULTS: We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation. CONCLUSION: In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.

Simple Analogues of Quaternary Benzo[c]phenanthridine Alkaloids: Discovery of a Novel Antifungal 2-Phenylphthalazin-2-ium Scaffold with Excellent Potency against Phytopathogenic Fungi.

Inspired by sanguinarine and chelerythrine, a novel antifungal 2-phenylphthalazin-2-ium scaffold as a simple analogue was designed. Most of the 30 compounds showed excellent inhibition activity against almost all eight phytopathogenic fungi, far superior to sanguinarine and chelerythrine. A third of the compounds were more active than azoxystrobin in most cases. Compounds 26 and 27 showed the highest total activity against all the fungi with EC50 means of ca. 4.6 µg/mL. Fusarium solani showed the highest susceptibility with an EC50 mean of 3.62 µg/mL to 19 compounds. A concentration of 25.0 µg/mL 27 can fully control the Colletotrichum gloeosporioides infection in apples over 9 days. Electron microscopic observations showed that 27 was able to damage the structures of the hypha and cell membrane. The structure-activity relationship showed that the presence of electron-withdrawing groups on the C-ring increases the activity against most of the fungi. Thus, 2-phenylphthalazin-2-ium compounds represent promising leads for the development of novel fungicides.

Resveratrol alleviates the interleukin-1ß-induced chondrocytes injury through the NF-κB signaling pathway.

BACKGROUND: Osteoarthritis (OA) is a regular age-related disease that affects millions of people. Resveratrol (RSV) is a flavonoid with a stilbene structure with different pharmacological effects. The purpose of the experiment was to evaluate the protective role of RSV against the human OA chondrocyte injury induced by interleukin-1ß (IL-1ß). METHODS: Chondrocytes were isolated from OA patients and identified by type II collagen, safranin O staining, and toluidine blue staining. Differentially expressed genes in chondrocytes treated RSV were identified by RNA sequencing. Kyoto encyclopedia of genes and genomes (KEGG) pathway as well as gene ontology (GO) were further conducted through Metascape online tool. A cell counting kit-8 (CCK-8) assay was applied to discover the viability of chondrocytes (6, 12, 24, and 48 µM). Many genes associated with inflammation and matrix degradation are evaluated by real-time PCR (RT-PCR) as well as western blot (WB). The mechanism of RSV for protecting IL-1ß induced chondrocytes injury was further measured through immunofluorescence and WB assays. RESULTS: A total of 845 differentially expressed genes (upregulated = 499, downregulated = 346) were found. These differentially expressed genes mainly enriched into negative regulation of catabolic process, autophagy, and cellular catabolic process, intrinsic apoptotic, apoptotic, and regulation of apoptotic signaling pathway, cellular response to abiotic stimulus, external stimuli, stress, and radiation. These differentially expressed genes were obviously enriched in NF-kB signaling pathway. RSV at the concentration of 48 µM markedly weakened the viability of the cells after 24 h of treatment (87% vs 100%, P < 0.05). No obvious difference was observed between the 6, 12, and 24 µM groups (106% vs 100%, 104% vs 100%, 103% vs 100%, P > 0.05). RSV (24 µM) also markedly depressed the levels of PGE2 and NO induced by IL-1ß by 25% and 29% respectively (P < 0.05). Our experiment pointed out that RSV could dramatically inhibit the inflammatory response induced by IL-1ß, including the MMP-13, MMP-3, and MMP-1 in human OA chondrocytes by 50%, 35%, and 33% respectively. On the other hand, RSV inhibited cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, and inducible nitric oxide synthase (iNOs) expression (P < 0.05), while increased collagen-II and aggrecan levels (P < 0.05). From a mechanistic perspective, RSV inhibited the degradation of IκB-α as well as the activation of nuclear factor-kappa B (NF-κB) induced by IL-1ß. CONCLUSION: In summary, RSV regulates the signaling pathway of NF-κB, thus inhibiting inflammation and matrix degradation in chondrocytes. More studies should be focused on the treatment efficacy of RSV for OA in vivo.

Enhanced osteogenic activity and antibacterial ability of manganese-titanium dioxide microporous coating on titanium surfaces.

Titanium (Ti) and its alloys are widely used in clinical practice as preferred materials for bone tissue repair and replacement because of their good mechanical properties; however, as Ti lacks biological activity, clinical application has been limited. Herein, we prepared a manganese-titanium dioxide (Mn-TiO2) microporous biotic coating on Ti surfaces by micro-arc oxidation (MAO). The coating showed good surface topography and was uniformly doped with Mn, and the Mn ions were slowly released. In vitro, the Mn-TiO2 microporous biotic coating promoted the adhesion, proliferation, differentiation, and mineralization of MC3T3-E1 osteoblasts. Moreover, in vivo experiments showed that the coating promoted early osseointegration. We also conducted a preliminary investigation to explore the molecular mechanism underlying the regulation of the function of osteoblasts by the coating. Furthermore, we found that the coating could inhibit the growth of Escherichia coli in vitro, demonstrating reliable antibacterial ability. To conclude, Mn-TiO2 microporous biotic coating can improve the biological activity of Ti implants, which can potentially improve their clinical applications.

microRNA-7 inhibition protects human osteoblasts from dexamethasone via activation of epidermal growth factor receptor signaling.

Sustained dexamethasone (Dex) treatment could induce secondary osteoporosis, osteonecrosis, or even bone fractures. Dex can induce potent cytotoxicity in cultured human osteoblasts. The aim of this study was to test the potential role of microRNA-7 (miR-7), which targets the epidermal growth factor receptor (EGFR), in Dex-treated human osteoblasts. In OB-6, hFOB1.19, and primary human osteoblasts, miR-7 depletion by a lentiviral antagomiR-7 construct (LV-antagomiR-7) increased EGFR expression and downstream Akt activation, protecting cells from Dex-induced viability reduction, cell death, and apoptosis. In contrast, forced overexpression of miR-7 by a lentiviral miR-7 construct (LV-miR-7) inhibited EGFR expression and Akt activation, potentiating Dex-induced cytotoxicity in OB-6, hFOB1.19, and primary human osteoblasts. EGFR is the primary target of miR-7 in human osteoblasts. Luciferase activity of the EGFR 3-untranslated region was enhanced by LV-antagomiR-7, but decreased by LV-miR-7 in OB-6 cells. Further, LV-antagomiR-7-induced osteoblast cytoprotection against Dex was abolished by the EGFR inhibitors AG1478 and PD153035. Moreover, neither LV-antagomiR-7 nor LV-miR-7 was functional in EGFR-KO OB-6 cells. We also show that miR-7 is upregulated in the necrotic femoral head tissues of Dex-administered patients, correlating with EGFR downregulation. Together, we conclude that miR-7 inhibition protects human osteoblasts from Dex via activation of EGFR signaling.

Clinical and Imaging Characteristics of Malignant Tumor Concurrent with Stroke.

Objectives: The present study aimed to retrospectively compare the clinical and imaging characteristics and laboratory data of patients with malignant tumor concurrent with acute ischemic stroke (IS) and patients with cerebral infarction only, and to analyze the potential related risk factors. Method: A total of 126 patients with acute cerebral infarction concurrent with malignant tumor were collected and assigned to the malignant tumor group. In addition, 120 patients hospitalized for routine acute IS during the same period were randomly selected as the control group. Demographic data and common risk factors of cerebrovascular disease, laboratory data, and imaging characteristics in these two groups were compared. Results: In the malignant tumor group, the age of onset was relatively low, and the National Institutes of Health Stroke Scale score, 90 d recurrence rate, and fatality rate were higher than for those in the control group (p < 0.05). However, most patients had no traditional risk factors of stroke. Biochemical results revealed that the peripheral hemoglobin of patients with malignant tumor and cerebral infarction was lower than for those in the control group (p < 0.05). Furthermore, the levels of D-dimer, fibrinogen, tumor markers CA125, CA199, and carcinoembryonic antigen were significantly elevated, and the difference was statistically significant (p < 0.05). Magnetic resonance imaging results revealed that multiple intracranial infarcts were more common in patients in the malignant tumor group, and the difference was statistically significant compared with patients with cerebral infarction only (p < 0.05). Conclusion: Patients with cancer and IS had fewer traditional stroke risk factors but more anemia as well as higher D-dimer level, tumor marker rate, short-term mortality, and stroke recurrence rate. Furthermore, lower age of onset and other characteristics, including multiple intracranial infarcts, can be regarded as important characteristics of such patients.

Clinical and imaging features of vertebrobasilar dolichoectasia combined with posterior circulation infarction: A retrospective case series study.

This study aims to analyze the clinical and imaging features of vertebrobasilar dolichoectasia (VBD) combined with posterior circulation infarction, and to explore risk factors for the occurrence of posterior circulation infarction in VBD patients.VBD patients were divided into 2 groups, according to the results of the imaging examination: posterior circulation infarction group and nonposterior circulation infarction group. The demographics, vascular risk factors, imaging, and other clinical data of the VBD patients were collected and retrospectively compared, and the risk factors for the occurrence of posterior circulation infarction in VBD patients were analyzed. The relationship between imaging features of the VBD blood supply artery and the infarct site was also analyzed.A total of 56 VBD patients were included into the analysis. Among these patients, 26 patients had posterior circulation infarction. Infarction occurred in the blood supply area of the posterior cerebral artery in 14 patients. The difference in the height of the basilar artery bifurcation between patients with vertebrobasilar artery blood supply area infarction and patients with posterior cerebral artery supply area infarction was statistically significant. Hypertension and posterior circulation intracranial atherosclerosis were the risk factors for posterior circulation infarction in VBD patients.Elevated basilar artery bifurcation is a risk factor for infarction in the posterior cerebral artery supply area in VBD patients. Posterior circulation infarction in VBD may be the comprehensive result of multiple factors, such as congenital defects of the basilar artery wall, hypertension, and atherosclerotic lesions.

Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling.

BACKGROUND/AIMS: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process. MATERIALS: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay. RESULTS: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg2+/ Mn2+-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts. CONCLUSION: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling.

Altered Wnt and NF-κB Signaling in Facet Joint Osteoarthritis: Insights from RNA Deep Sequencing.

Facet joint osteoarthritis is common lumbar osteoarthritis characterized by facet joint cartilage degeneration. However, the molecular basis of facet joint osteoarthritis remains largely undetermined. In the current study, we collected facet joint tissue samples from 10 control patients and 48 patients with facet joint osteoarthritis (20 patients with moderate degeneration and 28 with severe degeneration). The control patients underwent internal fixation of the lumbar spine due to vertebral fracture. RNA deep sequencing was performed, and Bioinformatic tools were applied. Among top 30 enriched signaling pathways, we focused on two inflammation-related signaling pathways, Wnt and NF-κB signaling pathways. Subsequently, using the quantitative RT-PCR analysis, we confirmed that in Wnt signaling pathway, the mRNA levels of Dickkopf WNT Signaling Pathway Inhibitor 2 (DKK2), Sex-determining Region Y-box 17 (SOX17), MYC, Cyclin D1, Calcium/Calmodulin Dependent Protein Kinase II Alpha (CAMK2A), and Wnt Family Member 11 and 5 were increased in facet joint osteoarthritis, while the mRNA levels of WNT Inhibitory Factor 1, Casein Kinase 1 Alpha 1, Transcription Factor 7/Lymphoid Enhancer Binding Factor 1 (TCF7/LEF1), and VANGL Planar Cell Polarity Protein 2 were decreased. In NF-κB signaling pathway, the mRNA levels of C-C Motif Chemokine Ligand 4 (CCL4) and C-C Motif Chemokine Ligand 4 Like 2 (CCL4L2) were increased, while the mRNA levels of BCL2 Related Protein A1 were decreased. These results suggest that Wnt and NF-κB signaling may be altered in the process of facet joint cartilage degeneration. The present study will expand our understanding of the molecular bases underlying facet joint osteoarthritis.

Knockdown of LSD1 ameliorates the severity of rheumatoid arthritis and decreases the function of CD4 T cells in mouse models.

Rheumatoid arthritis (RA) is an immune-mediated disease that causes chronic inflammation of the joints and involves CD4+ T cell activation. In RA, CD4+ T cells are the main drivers of disease initiation and the perpetuation of the damaging inflammatory process. In the present study, we investigated the role of Lysine-specific histone demethylase 1 (LSD1) in RA. The frequency of LSD1-positive CD4+ T cells in the synovial fluid (SF) of active RA patients was higher than that of inactive RA patients. In CD4+ T cells isolated from SF of active RA patients, LSD1 downregulation significantly increased cell proliferation, as shown by MTT assay. LSD1 knockdown also significantly increased the production of IFN-γ and IL-17, and increased that of IL-10, as determined by ELISA and qRT-PCR aasay. In CD4+ T cells isolated from SF of inactive RA patients, LSD1 was overexpressed by LSD1 plasmid transfection. As expected, LSD1 overexpression resulted in an opposite effect on cell proliferation and the production of cytokines, including IFN-γ, IL-17 and IL-10. LSD1 was downregulated in RA mouse by lenti-vector infection. As expected, LSD1 knockdown in vivo significantly alleviated the disease severity and increased the levels of anti-collagen II antibodies. LSD1 downregulation in the early stage was more effective to ameliorate disease severity. Our data suggested the potential therapeutic role of LSD1 in RA patients.

microRNA-25 targets PKCζ and protects osteoblastic cells from dexamethasone via activating AMPK signaling.

AMP-activated protein kinase (AMPK) activation could protect osteoblasts from dexamethasone (Dex). This study aims to provoke AMPK activation via microRNA downregulation of its negative regulator protein kinase C ζ (PKCζ). Results show that microRNA-25-5p (miR-25-5p) targets PKCζ's 3' untranslated regions (UTRs). Forced-expression of miR-25 downregulated PKCζ and activated AMPK in human osteoblastic cells (OB-6 and hFOB1.19 lines), which thereafter protected cells from Dex. Reversely, expression of antagomiR-25, the miR-25 inhibitor, upregulated PKCζ and inhibited AMPK activation, exacerbating Dex damages. Notably, PKCζ shRNA knockdown similarly activated AMPK and protected osteoblastic cells from Dex. AMPK activation was required for miR-25-induced osteoblastic cell protection. AMPKα shRNA or dominant negative mutation almost completely blocked miR-25-induced cytoprotection against Dex. Further studies showed that miR-25 expression increased NADPH activity and suppressed Dex-induced oxidative stress in osteoblastic cells. Such effects by miR-25 were abolished with AMPKα knockdown or mutation. Significantly, miR-25-5p level was increased in patients' necrotic femoral head tissues, which was correlated with PKCζ downregulation and AMPK hyper-activation. These results suggest that miR-25-5p targets PKCζ and protects osteoblastic cells from Dex possibly via activating AMPK signaling.

miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone.

Activation of AMP-activated protein kinase (AMPK) could potently protect osteoblasts/osteoblastic cells from dexamethasone (Dex). We aim to induce AMPK activation via microRNA ("miRNA") downregulation of its phosphatase Ppm1e. We discovered that microRNA-135b ("miR-135b") targets the 3' untranslated regions (UTRs) of Ppm1e. In human osteoblasticOB-6 cells and hFOB1.19 cells, forced-expression of miR-135b downregulated Ppm1e and activated AMPK signaling. miR-135b also protected osteoblastic cells from Dex. shRNA-induced knockdown of Ppm1e similarly activated AMPK and inhibited Dex-induced damages. Intriguingly, in the Ppm1e-silenced osteoblastic cells, miR-135b expression failed to offer further cytoprotection against Dex. Notably, AMPK knockdown (via shRNA) or dominant negative mutation abolished miR-135b-induced AMPK activation and cytoprotection against Dex. Molecularly, miR-135b, via activating AMPK, increased nicotinamide adenine dinucleotide phosphate (NADPH) activity and inhibited Dex-induced oxidative stress. At last, we found that miR-135b level was increased in human necrotic femoral head tissues, which was correlated with Ppm1e downregulation and AMPK activation. There results suggest that miR-135b expression downregulates Ppm1e to activate AMPK signaling, which protects osteoblastic cells from Dex.

OSU53 Rescues Human OB-6 Osteoblastic Cells from Dexamethasone through Activating AMPK Signaling.

Excessive dexamethasone (Dex) application causes osteoblast cell death, which could lead to osteoporosis or osteonecrosis. AMP-activated protein kinase (AMPK) activation is shown to protect osteoblasts/osteoblastic cells from Dex. In this report, we tested the potential effect of OSU53, a novel AMPK activator, in Dex-treated osteoblastic cells. We show that OSU53 activated AMPK signaling in human OB-6 osteoblastic cells. Further, Dex-induced osteoblastic OB-6 cell death and apoptosis were largely attenuated with pre-treatment with OSU53. OSU53 was more efficient than other known AMPK activators (A-769662 and Compound 13) in protecting OB-6 cells against Dex. AMPK activation is required for OSU53-induced actions in OB-6 cells. AMPKα shRNA knockdown or dominant-negative mutation (dn-AMPKα T172A) almost completely blocked OSU53-induced AMPK activation and OB-6 cell protection against Dex. Further studies showed that OSU53 increased NADPH (nicotinamide adenine dinucleotide phosphate) activity and alleviated Dex-induced oxidative stress in OB-6 cells. Such effects by OSU53 were again almost abolished with AMPKα shRNA or dn-AMPKα in OB-6 cells. Together, these results demonstrate that OSU53 protects osteoblastic cells from Dex possibly via activating AMPK-dependent signaling.

Epigallocatechin-3-gallate protects against tumor necrosis factor alpha induced inhibition of osteogenesis of mesenchymal stem cells.

Anabolic bone accruement through osteogenic differentiation is important for the maintenance of physiological bone mass and often disrupted in various inflammatory diseases. Epigallocatechin-3-gallate, as an antioxidant and anti-inflammatory agent, has been suggested for potential therapeutic use in this context, possibly by the inhibition of bone resorption as well as the enhancement of bone formation through directly activating osteoblast differentiation. However, the reported effects of epigallocatechin-3-gallate modulating osteoblast differentiation are mixed, and the underlying molecular mechanism is still elusive. Moreover, there is limited information regarding the effects of epigallocatechin-3-gallate on osteogenic potential of mesenchymal stem cell in inflammation. Here, we examined the in vitro osteogenic differentiation of human mesenchymal stem cells. We found that the cell viability and osteoblast differentiation of human bone marrow-derived mesenchymal stem cells are significantly inhibited by inflammatory cytokine TNFα treatment. Epigallocatechin-3-gallate is able to enhance the cell viability and osteoblast differentiation of mesenchymal stem cells and is capable of reversing the TNFα-induced inhibition. Notably, only low doses of epigallocatechin-3-gallate have such benefits, which potentially act through the inhibition of NF-κB signaling that is stimulated by TNFα. These data altogether clarify the controversy on epigallocatechin-3-gallate promoting osteoblast differentiation and further provide molecular basis for the putative clinical use of epigallocatechin-3-gallate in stem cell-based bone regeneration for inflammatory bone loss diseases, such as rheumatoid arthritis and prosthetic osteolysis.

Comparison of procalcitonin and C-reactive protein for the diagnosis of periprosthetic joint infection before revision total hip arthroplasty.

OBJECTIVE: To compare the clinical informative value of procalcitonin (PCT) and C-reactive protein (CRP) serum concentrations in the diagnosis of periprosthetic joint infection (PJI) before revision total hip arthroplasty (THA). DESIGN AND METHODS: We conducted a prospective observational study of 71 consecutive patients (74 hips) undergoing revision THA. Procalcitonin and CRP serum concentrations and white blood cell (WBC) count were measured pre-operatively. Diagnostic accuracy was analyzed by the receiver-operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: The PJI incidence was 35.2% in patients with revision THA. Procalcitonin and CRP serum concentrations and WBC count were statistically higher in the PJI cohort compared with the no PJI cohort (p<0.05). The AUCs for PCT, CRP, and WBC count were 0.851 (95% confidence interval [CI] 0.773-0.929), 0.830 (95% CI 0.751-0.910), and 0.633 (95% CI 0.518-0.747), respectively. Serum PCT and CRP showed a significantly higher diagnostic ability than WBC count (p<0.05). No significant difference was found between serum PCT and CRP (p=0.367). CONCLUSION: Procalcitonin does not offer an advantage over CRP in diagnosing PJI. However, PCT and CRP proved to be more reliable than WBC count.