Mid-term prognosis of endoscopic debridement combined with percutaneous cutaneo-fascial suture for the treatment of Morel-Lavallée lesion: a minimum 3-year follow-up study.

PURPOSE: Morel-Lavallée lesion (MLL) is a closed soft-tissue degloving injurie resulting from shear forces. With the advent of endoscopic technology and advancements in surgical techniques, innovative solutions are now available. However, there are few data on mid-term results after treatment of MLL, especially regarding arthroscopic method. The objective of this study is to evaluate the clinical outcomes of endoscopic debridement combined with percutaneous cutaneo-fascial suture in treating MLL. METHODS: A single-center retrospective study was conducted at a university teaching hospital investigating patients who underwent arthroscopic management of Morel-Lavallée lesion between 2014 and 2020.Patient demographics, postoperative recovery time, peri- and postoperative complications were investigated. Mid-term follow up clinical and radiological examinations were performed. RESULTS: The retrospective study included 38 patients aged between 11 and 90 years, with an average age of 50.9 ± 16.9 years. These patients waited an average of 36.6±23.5days to return to work after operation. The average time to follow-up was from 3 to 9 years, averaging 5.0 ± 1.8 years. At the end of follow-up, only one complication of superficial skin necrosis occurred, accounting for 2.6%. The imaging assessment at the final follow-up indicated improvement over the postoperative period for all 38patients. CONCLUSION: In mid-term experience, endoscopic debridement combined with percutaneous cutaneo-fascial suture for MLL management is a safe and effective option.

A Randomized Comparison Between Anterior Talofibular Ligament Repair Using Broström Operation with and without an Internal Brace.

The aim of the study was to compare the intermediate-term (>24 months) clinical outcomes between anterior talofibular ligament repair using Broström operation with and without an internal brace. Nineteen patients underwent surgery using an arthroscopic traditional Broström repair with an internal brace technique (IB) and Eighteen patients underwent surgery using an arthroscopic traditional Broström repair without an internal brace technique (TB) . All patients were evaluated clinically using the Foot and Ankle Outcome Score (FAOS) and Foot and Ankle Ability Measure (FAAM). According to FAAM, sports activity scores of TB and IB groups were 83.33 ± 5.66 and 90.63 ± 6.21 at the final follow-up (p = .02). There were no significant differences in preoperative and postoperative stress radiographs between the two groups. Total medical expense was more in the IB group (p < .001). It also has a significant superiority in the terms of FAAM scores at sports activity. However, there was no difference during daily life.

Enhanced Mechanical Properties, Corrosion Resistance, Cytocompatibility, Osteogenesis, and Antibacterial Performance of Biodegradable Mg-2Zn-0.5Ca-0.5Sr/Zr Alloys for Bone-Implant Application.

Magnesium (Mg) alloys are widely used in bone fixation and bone repair as biodegradable bone-implant materials. However, their clinical application is limited due to their fast corrosion rate and poor mechanical stability. Here, the development of Mg-2Zn-0.5Ca-0.5Sr (MZCS) and Mg-2Zn-0.5Ca-0.5Zr (MZCZ) alloys with improved mechanical properties, corrosion resistance, cytocompatibility, osteogenesis performance, and antibacterial capability is reported. The hot-extruded (HE) MZCZ sample exhibits the highest ultimate tensile strength of 255.8 ± 2.4 MPa and the highest yield strength of 208.4 ± 2.8 MPa and an elongation of 15.7 ± 0.5%. The HE MZCS sample shows the highest corrosion resistance, with the lowest corrosion current density of 0.2 ± 0.1 µA cm-2 and the lowest corrosion rate of 4 ± 2 µm per year obtained from electrochemical testing, and a degradation rate of 368 µm per year and hydrogen evolution rate of 0.83 ± 0.03 mL cm-2 per day obtained from immersion testing. The MZCZ sample shows the highest cell viability in relation to MC3T3-E1 cells among all alloy extracts, indicating good cytocompatibility except at 25% concentration. Furthermore, the MZCZ alloy shows good antibacterial capability against Staphylococcus aureus.

Comparison of Sentinel Lymph Node Biopsy by Blue Dye Conjunction With Indocyanine Green or Radioisotope in Early-Stage Breast Cancer: A Prospective Single-Center Observational Study.

Background: Although radioisotope (RI) combined with blue dye (BD) is the standard technique for sentinel lymph node (SLN) biopsy in breast cancer, the use of RI is limited at some institutions due to the specific equipment needed. Indocyanine green (ICG) fluorescence detection has been developed as a potential substitute for RI method. However, reports on the sensitivity of ICG and RI techniques in detecting SLN are inconsistent; hence, the present study was designed to compare the clinical efficacy between the combined method of ICG + BD (ICG-B) and RI + BD (RI-B). Methods: A prospective observational study was performed that identified 138 breast cancer patients who had undergone lymphatic mapping and SLN biopsy with ICG-B or RI-B. The SLN detection rate, positive SLN counts, and lymph node metastasis between the 2 groups were compared. Results: A total of 71 patients were recruited in the ICG-B group, while 67 were recruited in the RI-B group. The SLN detection rate was 100% in both the ICG-B and RI-B groups. Lymph node metastasis was found in 13 patients using ICG-B and in 12 patients using the RI-B technique (18.31% vs 17.91%, respectively; P = .61). No significant differences were observed in the positive SLN counts (3.12 ± 2.01 vs 3.33 ± 2.24, P = .37) between the 2 groups. Conclusions: Indocyanine green combined with BD has an equal efficacy compared with RI plus BD when performing an axillary SLN biopsy in breast cancer. The ICG plus BD procedure is a promising alternative to traditional standard mapping methods.

Targeting the ZNF-148/miR-335/SOD2 signaling cascade triggers oxidative stress-mediated pyroptosis and suppresses breast cancer progression.

BACKGROUND: The implication of zinc finger protein 148 (ZNF-148) in pathophysiology of most human cancers has been reported; however, the biological functions of ZNF-148 in breast cancer remain unclear. This study sought to elucidate the potential molecular mechanism of ZNF-148 on breast cancer pathology. METHODS: ZNF148 expression was tested in breast cancer tissues and cells. Then, cells were transfected with ZNF-148 overexpression or downregulation vector, and the cell proliferation, pyroptosis, apoptosis, and reactive oxygen species (ROS) production were analyzed by MTT, western blot, flow cytometry, and immunofluorescence staining, respectively. Tumor-bearing nude mouse was used to evaluate tumorigenesis of ZNF-148. Mechanisms underpinning ZNF-148 were examined using bioinformatics and luciferase assays. RESULTS: We found that ZNF-148 was upregulated in breast cancer tissues and cell lines. Knockdown of ZNF-148 suppressed malignant phenotypes, including cell proliferation, epithelial-mesenchymal transition, and tumorigenesis in vitro and in vivo, while ZNF-148 overexpression had the opposite effects. Further experiments showed that ZNF-148 deficiency promoted ROS production and triggered both apoptotic and pyroptotic cell death, which were restored by cotreating cells with ROS scavengers. A luciferase reporter assay revealed that miR-335 was the downstream target of ZNF-148 and that overexpressed ZNF-148 increased superoxide dismutase 2 (SOD2) expression by sponging miR-335. In parallel, both miR-335 downregulation and SOD2 overexpression abrogated the antitumor effects of ZNF-148 deficiency on proliferation and pyroptosis in breast cancer cells. CONCLUSIONS: Our findings indicated that ZNF-148 promotes breast cancer progression by triggering miR-335/SOD2/ROS-mediated pyroptotic cell death and aid the identification of potential therapeutic targets for breast cancer.

Construction of multifunctional coating with cationic amino acid-coupled peptides for osseointegration of implants.

Osseointegration is an important indicator of implant success. This process can be improved by coating modified bioactive molecules with multiple functions on the surface of implants. Herein, a simple multifunctional coating that could effectively improve osseointegration was prepared through layer-by-layer self-assembly of cationic amino acids and tannic acid (TA), a negatively charged molecule. Osteogenic growth peptide (OGP) and the arginine-glycine-aspartic acid (RGD) functional polypeptides were coupled with Lys6 (K6), the two polypeptides then self-assembled with TA layer by layer to form a composite film, (TA-OGP@RGD)n. The surface morphology and biomechanical properties of the coating were analyzed in gas and liquid phases, and the deposition process and kinetics of the two peptides onto TA were monitored using a quartz crystal microbalance. In addition, the feeding consistency and adsorption ratios of the two peptides were explored by using fluorescence visualization and quantification. The (TA-OGP@RGD)n composite membrane mediated the early migration and adhesion of cells and significantly promoted osteogenic differentiation and mineralization of the extracellular matrix in vitro. Additionally, the bifunctional peptide exhibited excellent osteogenesis and osseointegration owing to the synergistic effect of the OGP and RGD peptides in vivo. Simultaneously, the (TA-OGP@RGD)n membrane regulated the balance of reactive oxygen species in the cell growth environment, thereby influencing the complex biological process of osseointegration. Thus, the results of this study provide a novel perspective for constructing multifunctional coatings for implants and has considerable application potential in orthopedics and dentistry.

AMPK/mTOR/p70S6K axis prevents apoptosis of Porphyromonas gingivalis-infected gingival epithelial cells via BadSer136 phosphorylation.

Epithelial disruption is the initiation of most infectious disease. Regulation of epithelium apoptosis may play a key role in balance the survival competition between resident bacteria and host cells. The role of the mTOR/p70S6K pathway in preventing apoptosis of human gingival epithelial cells (hGECs) infected with Porphyromonas gingivalis (Pg) was investigated in order to further understand the survival strategy of the epithelial cells in during Pg infecting. hGECs was challenged with Pg for 4, 12, and 24 h. Additionally, hGECs was pretreated with LY294002 (PI3K signaling inhibitor) or Compound C (AMPK inhibitor) for 12 h and exposed them to Pg for 24 h. Subsequently, apoptosis was detected using flow cytometry, and expression and activity of Bcl-2, Bad, Bax, PI3K, AKT, AMPK, mTOR, and p70S6K proteins were analyzed using western blotting. Pg-infecting did not increase apoptosis of hGECs; but the expression ratio of Bad to Bcl-2 was increased after infecting. In contrast, BadSer136 phosphorylation was promoted, accompanied by a significant reduction of mTOR/p70S6K and PI3K/AKT signaling, along with the upregulation of AMPKThr172 signaling. Morrover, the PI3K inhibitor LY294002 promoted Pg-mediated reduction of mTOR/p70S6K expression, and the increase of AMPK signaling and BadSer136 phosphorylation rate, eventually decreasing apoptosis. While Compound C inhibited Pg-mediated activation of AMPK and downregulation of mTOR/p70S6K signaling, significantly reduced the BadSer136 phosphorylation rate, thereby increasing apoptosis. Thus, hGECs prevent apoptosis via an inherent cellular-homeostasis, pro-survival mechanism during Pg infection, the AMPK/mTOR/p70S6K pathway helps prevent apoptosis in hGECs infected with Pg by regulating BadSer136 phosphorylation.

Anatomical Study on the Reconstruction of the Anterior Talofibular Ligament.

The purpose of this study aimed to (1) identify the relationship between the fibula and the talus of the anterior talofibular ligament (ATFL); (2) collect detailed anatomical data and provide anatomical basis for ATFL anatomical reconstruction. We selected 27 ankle specimens of adult cadavers (9 left feet and 18 right feet in 11 males and 16 females; mean age 41.6 years) with the exception of ankle deformities, fractures, underdevelopment and degenerative diseases. In these 27 specimens,15 cases of ATFL were divided into two bundles and 12 cases of ATFL were single bundles. The average ATFL length was 20.31 ± 3.12mm. The center of the ATFL in 11 specimens was located in the calcaneofibular ligament (CFL) foot print area. The long axis of the fibula side stop point was 8.83±1.82 mm, and the short axis was 3.12±0.49 mm. The distance from the center of the ATFL fibula attachment area to the tip of the fibula was 14.22±2.87 mm, and the distance from the center of the CFL is 5.57±1.80mm. The distance from the center of the ATFL talar attachment area to the tibiotalar articular surface was (9.74±2.12) mm, and the distance from the anterior external cartilage surface of the talus was (4.87±1.82) mm. The angle between ATFL and the long axis of the fibula is 78°±12°. Our results suggest that in ATFL reconstruction, the anatomical attachment points around the ATFL or the angle between ATFL and the long axis of the fibula both can be used for bone canal positioning.

[Treatment for posterior root tear of lateral meniscus through bone tunnel suture under arthroscopy].

OBJECTIVE: To evaluate clinical effects of posterior root tear of lateral meniscus through bone tunnel suture under arthroscopy. METHODS: From January 2012 to December 2014, 23 patients with posterior root tear of lateral meniscus repaired through bone tunnel suture under arthroscopy, including 15 males and 8 females, aged from 19 to 48 years old with an average age of (25.0±4.7) years old; 10 knees on the left side and 13 knees on the right side. Complications were observed, Lysholm score before and after operation at 12 months were used to evaluate clinical results, and VAS score was applied to assess pain relief. MRI was used to check recovery outcomes of lateral meniscus injury. RESULTS: All patients were followed up from 13 to 24 months with an average of (17.0±4.3) months. No injury of vessels, nerve and incision infection occurred. Motion of knee joint of 19 patients reached normal, 4 patients manifested limited activity of knee joint at12 months after operation. Postoperative Lysholm score 88.52±6.48 at 12 months was higher than that of before operation 46.12±7.35; Postoperative VAS score 0.8±0.7 at 12 months was lower than that of before operation 4.3±1.6. CONCLUSIONS: Bone tunnel suture under arthroscopy for the treatment of posterior root tear of lateral meniscus could relieve pain, decrease postoperative complications and obtain good clinical efficacy.

Astrocyte-Conditioned Medium Protects Prefrontal Cortical Neurons from Glutamate-Induced Cell Death by Inhibiting TNF-α Expression.

OBJECTIVE: Both excitotoxicity and neurotrophin deficiency may contribute to the etiology of depression and neurodegeneration. Astrocytes not only regulate glutamate metabolism and clearance, they also produce neurotrophins in the brain. However, the direct interaction between neurons and astrocytes remains unknown. METHODS: This study evaluated the cellular mechanisms by which astrocyte-conditioned medium (ACM) protects prefrontal cortical neurons from glutamate-induced death by measuring cell viability and morphology as well as mRNA and protein expression of brain-derived neurotrophic factor (BDNF), BDNF receptors, glial cell line-derived neurotrophic factor (GDNF), and the proinflammatory cytokine, tumor necrosis factor (TNF)-α. Neurons and astrocytes were purified from the brains of neonatal 1-day-old Sprague-Dawley rats. ACM was harvested after exposing astrocytes to culture medium containing 100 µM glutamate for 48 h. RESULTS: Glutamate insult (100 µM for 6 h) significantly reduced neuronal cell viability and increased the mRNA expression of BDNF. Glutamate (24 h) decreased neuronal viability and the expression of BDNF, but increased mRNA expression of GFAP, p75 neurotrophin receptor (p75NTR), and TNF-α. ACM pretreatment (2 h) reversed glutamate-decreased cell viability and increased BDNF, but reduced the expression of GDNF, P75NTR, and TNF-α at the mRNA level. Western blotting generally confirmed the mRNA expression following 24 glutamate insults. Furthermore, the glutamate-induced decrease in the protein expression of BDNF and full-length TrkB receptor and increase in pro-BDNF, truncated TrkB isoform 1 receptor, p75NTR, GDNF, and TNF-α were significantly attenuated by ACM pretreatment. CONCLUSIONS: The study demonstrates that ACM exerts neuroprotective effects on cell viability, and this effect is most likely mediated through the modulation of neurotrophin and TNF-α expression.

A Polysaccharide Extract from Maitake Culinary-Medicinal Mushroom, Grifola frondosa (Agaricomycetes) Ameliorates Learning and Memory Function in Aluminum Chloride-Induced Amnesia in Mice.

Maitake (Grifola frondosa) is an edible mushroom exhibiting high nutritional value in terms of containing health-beneficial bioactive compounds. Previously, we reported that a protein-bound polysaccharide bioactive component of G. frondosa (PGM) could enhance the expression of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR), which is critical for learning and memory. However, the potential benefits of PGM on learning and memory function have never been investigated. In the current study, we aimed to explore the beneficial effect of PGM on learning and memory function in aluminum chloride (AlCl3)-induced amnesia in mice and to explore the underlying mechanisms. Mice were intraperitoneally administered with AlCl3 (60 mg/kg/d) and PGM (5, 10, or 20 mg/kg/d) for 6 weeks consecutively, and then the Morris water maze (MWM) test was conducted to assess the learning and memory function. Hematoxylin-eosin staining was performed to observe the morphology of neurons in the hippocampal dentate gyrus (DG). The expression of p-Tau (Ser396), Tau, p-GluA1 (S845), GluA1, and brain-derived neurotrophic factor (BDNF) proteins was evaluated with western blot. We found that PGM (5 and 10 mg/kg/d) significantly improved learning and memory function and attenuated histopathological abnormalities in the hippocampal DG region in the AlCl3-treated mice. Furthermore, PGM treatment significantly enhanced the level of AMPAR and BDNF in the hippocampus, while suppressing the tau protein hyperphosphorylation at the Ser396 site. These findings indicated that PGM could significantly attenuate the AlCl3-induced amnesia through the synergistic action of its active component on tau pathology, AMPAR and BDNF signaling pathway.

Involvement of Akt/CREB signaling pathways in the protective effect of EPA against interleukin-1ß-induced cytotoxicity and BDNF down-regulation in cultured rat hippocampal neurons.

BACKGROUND: Our published data have indicated that the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) provides beneficial effects by attenuating neuronal damage induced by interleukin-1ß (IL-1ß), and up-regulation of the expression of brain-derived neurotrophic factor (BDNF) represents a crucial part in the neuroprotective effect of EPA. However, the mechanisms of how EPA regulates BDNF expression remains incompletely understood. The present study investigated the role of Akt/CREB signaling in the effect of EPA on BDNF expression and its neuroprotective effect. RESULTS: The present results showed that IL-1ß reduced hippocampal neuronal viability and that EPA showed a concentration-dependent neuroprotective effect, but the neuroprotective effects of EPA were abolished by inhibition of Akt using KRX-0401, an inhibitor of Akt. Treatment of hippocampal neurons with EPA also ameliorated the decrease in Akt and CREB phosphorylation induced by IL-1ß and BDNF down-regulation mediated by IL-1ß. However, inhibition of Akt reversed the effect of EPA on levels of p-Akt, p-CREB, and BDNF. CONCLUSIONS: Our data indicate that EPA elicited neuroprotection toward IL-1ß-induced cell damage and BDNF decrease and that its effects potentially occurred via the Akt/CREB signaling pathway.

[Diagnostic value of MRI for posterior root tear of medial and lateral meniscus].

OBJECTIVE: To explore diagnostic value of MRI on posterior root tear of medial and lateral meniscus. METHODS: From January 2012 to January 2016, clinical data of 43 patients with meniscal posterior root tear confirmed by arthroscopy were retrospective analyzed, including 25 males and 18 females, aged from 27 to 69 years old with an average age of(42.5±8.3)years old;27 cases on the right side and 16 cases on the left side. MRI examinations of 43 patients with tear of posterior meniscus root confirmed by knee arthroscopies were retrospectively reviewed. MRI images were double-blinded, independently, retrospectively scored by two imaging physicians. Sensitivity, specificity and accuracy of MRI diagnosis of lateral and medial meniscus posterior root tear were calculated, and knee ligament injury and meniscal dislocation were calculated. RESULTS: Forty-three of 143 patients were diagnosed with meniscus posterior root tears by arthroscopy, including 19 patients with lateral tears and 24 patients with medial tears. The sensitivity, specificity and accuracy in diagnosis of posterior medial meniscus root tears for doctor A were 91.67%, 86.6% and 83.9% respectively, and for doctor B were 87.5%, 87.4% and 87.4%, 19 patients with medial meniscal protrusion and 2 patients with anterior cruciate ligament tear. The sensitivity, specificity and accuracy in diagnosis of posterior lateral meniscus root tears for doctor A were 73.7%, 79.9% and 79% respectively, and for doctor B were 78.9%, 82.3% and 82.5%, 4 patients with lateral meniscus herniation and 16 patients with cruciate ligament tear. Kappa statistics for posterior medial meniscus root tears and posterior lateral meniscus root tears were 0.84 and 0.72. CONCLUSIONS: MRI could effectively demonstrate imaging features of medial and lateral meniscal root tear and its accompanying signs. It could provide the basis for preoperative diagnosis of clinicians, and be worthy to be popularized.

MicroRNA-335 suppresses the proliferation, migration, and invasion of breast cancer cells by targeting EphA4.

MicroRNAs (miRNAs) are small noncoding RNAs that exert their functions by targeting specific mRNA sequences. Many studies have demonstrated that miRNAs are crucial for cancer progression, during which they can act as either oncogenes or tumor suppressors. Previous research has shown that miR-335 is downregulated in breast cancer, and it has been shown to be a breast cancer suppressor. In addition, emerging evidence indicates that erythropoietin-producing hepatocellular A4 (EphA4) is implicated in cancer cell proliferation, migration, and invasion. However, little is known about the relationship between miR-335 and EphA4 in breast cancer. In the present study, we used bioinformatic and biochemical analyses to demonstrate that EphA4 is a direct downstream target of miR-335 in human breast cancer MCF-7 and MDA-MB-23 cells and revealed that miR-335 negatively regulates the expression of EphA4 in these cells. Further investigation revealed that miR-335 overexpression inhibits MCF-7 and MDA-MB-231 cell proliferation and that this inhibition is attenuated by EphA4 coexpression. Similarly, miR-335 overexpression also inhibited growth and downregulated EphA4 expression in tumors in nude mice. Moreover, our results demonstrated that miR-335 overexpression suppresses migration and invasion in MCF-7 and MDA-MB-231 cells, an effect that was reversed by EphA4 overexpression. These findings confirmed that EphA4 is a direct target gene of miR-335 and that miR-335 suppresses breast cancer cell proliferation and motility in part by directly inhibiting EphA4 expression.

MicroRNA-374a Promotes Hepatocellular Carcinoma Cell Proliferation by Targeting Mitogen-Inducible Gene 6 (MIG-6).

Hepatocellular carcinoma (HCC) is a disease with poor prognosis rates and ineffective therapeutic options. Previous studies have reported the involvement of mitogen-inducible gene 6 (MIG-6) as a negative regulator in tumor formation. MicroRNAs (miRNAs) play crucial roles in the development of different types of cancer. However, the underlying mechanisms of miRNAs in HCC are poorly understood. This study was aimed to investigate the role of miR-374a in HCC and its role in the regulation of expression of MIG-6. The results showed that MIG-6 overexpression significantly inhibited cell viability of HepG2 cells after 4 days posttransfection. Moreover, MIG-6 was a direct target of miR-374a, and the expression of MIG-6 was remarkably downregulated by the overexpression of miR-374a in HepG2 cells. Furthermore, we found that overexpression of miR-374a promoted cell viability; however, the protective effect was abolished by MIG-6 overexpression. In addition, overexpression of miR-374a activated the EGFR and AKT/ERK signaling pathways by regulation of MIG-6. Our findings suggest that miR-374a could promote cell viability by targeting MIG-6 and activating the EGFR and AKT/ERK signaling pathways. These data provide a promising therapeutic strategy for HCC treatment.

Dietary eicosapentaenoic acid normalizes hippocampal omega-3 and 6 polyunsaturated fatty acid profile, attenuates glial activation and regulates BDNF function in a rodent model of neuroinflammation induced by central interleukin-1ß administration.

PURPOSE: Interleukin (IL)-1ß can activate glial cells to trigger neuroinflammation and neurodegeneration. Lower omega (n)-3 polyunsaturated fatty acids (PUFAs) and lower n-3/n-6 PUFA ratios occur in the brain of patients with Alzheimer's disease (AD). We have previously reported that an n-3 PUFA, eicosapentaenoic acid (EPA), can improve memory and attenuate neurodegeneration-like changes in animal models of AD. However, whether and how EPA modulates glial cell activity and functions remains unclear. The aim of this study was to test the hypothesis that EPA may attenuate neuroinflammation by inhibiting microglial activation and microglia-produced proinflammatory cytokines, and by enhancing the expression of astrocytes-produced neurotrophins and their receptors. METHODS: Male Long-Evans rats were fed either palm oil supplemented diet or EPA supplemented diet for 42 days. On day 36 of diet feeding, rats received an intracerebroventricular injection of IL-1ß or saline for 7 days. The glial activation, the expression of amyloid precursor protein (APP), calcium-dependent phospholipase (cPL) A2, brain-derived neurotrophic factor (BDNF) and its receptor, and PUFA profile in the hippocampus were analyzed. RESULTS: IL-1ß elevated biomarkers of microglial CD11b and astrocyte GFAP expression, increased the expression of APP, tumor-necrosis factor (TNF)-α, but reduced BDNF and its receptor (TrKB). IL-1ß also lowered n-3 EPA and docosapentaenoic acid concentrations but increased n-6 PUFAs and cPLA2 activity in the hippocampus. EPA supplement normalized the n-3 and n-6 PUFA profiles and cPLA2 levels, inhibited glial activation, reduced APP and TNF-α expression, as well as up-regulated BDNF and TrKB. CONCLUSION: Supplementation with EPA appear to have potential effects on improving glial over-activation, n3/n6 imbalance and BDNF down-regulation, which contribute to anti-inflammatory and may provide beneficial effects on inflammation-associated disease such as AD.

The complete genome sequence of Streptomyces autolyticus CGMCC 0516, the producer of geldanamycin, autolytimycin, reblastatin and elaiophylin.

Streptomyces autolyticus CGMCC 0516 produces the anti-tumor benzoquinone ansamycins geldanamycin, autolytimycin, and reblastatin and the 16-membered macrodiolide elaiophylin. Here, we report the complete genome sequence of S. autolyticus CGMCC 0516, which consists of a 10,029,028bp linear chromosome and seven circular plasmids. Fifty-seven putative biosynthetic gene clusters for secondary metabolites were found. The geldanamycin, autolytimycin, and reblastatin biosynthetic gene clusters were located on the left arm (2.06-2.15Mb) of the chromosome, and the elaiophylin gene cluster was located on the right arm (9.45-9.53Mb). Twenty-one putative gene clusters with high or moderate similarity to important antibiotic biosynthetic gene clusters were found, including the antitumor agents echoside, bafilomycin, hygrocin, and toxoflavin; the antibacterial/antifungal agents nigericin, skyllamycin, kanamycin, naphthomycin, eco-02301, and bottromycin A2; the immunosuppressants meridamycin and brasilicardin A; the anti-inflammatory agent cyclooctatin; and the acute iron poisoning medication desferrioxamine B. The genome sequence reported here will enable us to study the biosynthetic mechanism of these important antibiotics and will facilitate the discovery of novel secondary metabolites with potential applications to human health.

Femoral tunnel positioning using an anteromedial technique for ACL reconstruction: A radiographic study with a cadaveric model.

BACKGROUND: We studied the anatomic positioning of the femoral tunnel during simulated anterior cruciate ligament reconstruction using an anteromedial portal approach in cadaveric models. METHODS: In thirty cadaveric human knee specimens, simulation of an arthroscopic anterior cruciate ligament reconstruction was performed and the femoral tunnel was drilled using an anteromedial portal. A Kirschner wire was passed into the tunnel and radiographs were obtained. These radiographs were then evaluated in the coronal and sagittal planes. Angles between the axis of the femoral tunnel and the joint line in the coronal plane (alpha, α) or the femoral long axis in the sagittal plane (beta, ß) were calculated for each specimen. The external aperture of the femoral tunnel was defined as the point of exit of the Kirschner wire from the lateral femoral cortex. This was evaluated relative to a prescribed rectangle and coordinate axis, with the radiographic quadrant method of Bernard, to assess the accuracy of femoral tunnel placement. RESULTS: The mean α in the coronal plane was 48.53∘, the mean ß in the sagittal plane was 32.23∘. All of the femoral tunnel external apertures were located outside of the rectangleCONCLUSION: We evaluated the positioning of the femoral tunnel and the external aperture of the femoral tunnel with the anteromedial portal technique. This study provides a reference standard to assess accurately femoral tunnel positioning on postoperative radiographs.

The Role of Nutrients in Protecting Mitochondrial Function and Neurotransmitter Signaling: Implications for the Treatment of Depression, PTSD, and Suicidal Behaviors.

Numerous studies have linked severe stress to the development of major depressive disorder (MDD) and suicidal behaviors. Furthermore, recent preclinical studies from our laboratory and others have demonstrated that in rodents, chronic stress and the stress hormone cortisol cause oxidative damage to mitochondrial function and membrane lipids in the brain. Mitochondria play a key role in synaptic neurotransmitter signaling by providing adenosine triphosphate (ATP), mediating lipid and protein synthesis, buffering intracellular calcium, and regulating apoptotic and resilience pathways. Membrane lipids are similarly essential to central nervous system (CNS) function because cholesterol, polyunsaturated fatty acids, and sphingolipids form a lipid raft region, a special lipid region on the membrane that mediates neurotransmitter signaling through G-protein-coupled receptors and ion channels. Low serum cholesterol levels, low antioxidant capacity, and abnormal early morning cortisol levels are biomarkers consistently associated with both depression and suicidal behaviors. In this review, we summarize the manner in which nutrients can protect against oxidative damage to mitochondria and lipids in the neuronal circuits associated with cognitive and affective behaviors. These nutrients include ω3 fatty acids, antioxidants (vitamin C and zinc), members of the vitamin B family (Vitamin B12 and folic acid), and magnesium. Accumulating data have shown that these nutrients can enhance neurocognitive function, and may have therapeutic benefits for depression and suicidal behaviors. A growing body of studies suggests the intriguing possibility that regular consumption of these nutrients may help prevent the onset of mood disorders and suicidal behaviors in vulnerable individuals, or significantly augment the therapeutic effect of available antidepressants. These findings have important implications for the health of both military and civilian populations.