Advantages of New Endoscopic Unilateral Laminectomy for Bilateral Decompression (ULBD) over Conventional Microscopic ULBD.

BACKGROUD: Biportal endoscopic unilateral laminectomy for bilateral decompression (ULBD) is an emerging minimally invasive procedure for spinal stenosis. However, reports of the results associated with this surgical method are still lacking. METHODS: We conducted a retrospective study of 60 patients who underwent bilateral decompression for lumbar central canal stenosis. The patients were divided into 2 groups according to the surgical method (endoscopic ULBD vs. microscopic ULBD). We compared the outcomes between the 2 groups in terms of postoperative segmental spinal instability, dura expansion, operation time, estimated blood loss, serum creatine kinase (CK), serum C-reactive protein (CRP), visual analog scale (VAS) score, Oswestry Disability Index (ODI), modified MacNab score, and the incidence of complications. RESULTS: The mean VAS, ODI, and modified MacNab score improved significantly from the preoperative period to the last follow-up in both groups and were better in the endoscopic ULBD group until the first day after treatment. The degree of horizontal displacement was lower in the endoscopic ULBD group than in the microscopic ULBD group at postoperative 12 months. Dura expansion, operation time, and estimated blood loss did not differ significantly between the 2 groups. Serum CK and CRP on the first day after treatment were lower in the endoscopic ULBD group than in the microscopic ULBD group. CONCLUSIONS: This study shows that both endoscopic ULBD and microscopic ULBD can provide favorable outcomes for lumbar central canal stenosis. However, compared to microscopic ULBD, endoscopic ULBD has advantages in terms of postoperative segmental spinal instability, pain control, and serum CK and CRP.

Comparison of the postoperative analgesic effect for infiltration between the popliteal artery and the capsule of the posterior knee and that of periarticular multimodal drug injection in total knee arthroplasty: retrospective study in the immediate postoperative period.

BACKGROUND: The aim of this study is to compare the postoperative analgesic effect of infiltration between the popliteal artery and the capsule of the knee (IPACK) and the effect of periarticular multimodal drug injection (PMDI) in addition to adductor canal block (ACB) after total knee arthroplasty. METHODS: Among patients who received total knee arthroplasty from June 2017 to December 2017, 50 who underwent ACB with additional IPACK and 50 who received ACB with additional PMDI were selected for this study. We compared the postoperative pain numerical rating scale (NRS), the number of times patient-controlled analgesia was administered and the amount administered, the total amount of opioids given, and complications associated with the procedure between the two groups. RESULTS: NRS measured at rest and 45° knee flexion at days 1 and 2 after surgery was significantly lower in the IPACK group than in the PMDI group. The resting NRS measured at day 3 after surgery was also significantly lower in the IPACK group than in the PMDI group, and the NRS at 45° knee flexion measured from day 3 to day 5 showed a significant reduction in the IPACK group. No complications relating to the procedure occurred. CONCLUSIONS: IPACK may be a better option than PMDI for controlling acute phase pain in patients undergoing total knee arthroplasty.

GI inflammation Increases Sodium-Glucose Cotransporter Sglt1.

A correlation between gastrointestinal (GI) inflammation and gut hormones has reported that inflammatory stimuli including bacterial endotoxins, lipopolysaccharides (LPS), TNFα, IL-1ß, and IL-6 induces high levels of incretin hormone leading to glucose dysregulation. Although incretin hormones are immediately secreted in response to environmental stimuli, such as nutrients, cytokines, and LPS, but studies of glucose-induced incretin secretion in an inflamed state are limited. We hypothesized that GI inflammatory conditions induce over-stimulated incretin secretion via an increase of glucose-sensing receptors. To confirm our hypothesis, we observed the alteration of glucose-induced incretin secretion and glucose-sensing receptors in a GI inflammatory mouse model, and we treated a conditioned media (Mϕ 30%) containing inflammatory cytokines in intestinal epithelium cells and enteroendocrine L-like NCI-H716 cells. In GI-inflamed mice, we observed that over-stimulated incretin secretion and insulin release in response to glucose and sodium glucose cotransporter (Sglt1) was increased. Incubation with Mϕ 30% increases Sglt1 and induces glucose-induced GLP-1 secretion with increasing intracellular calcium influx. Phloridzin, an sglt1 inhibitor, inhibits glucose-induced GLP-1 secretion, ERK activation, and calcium influx. These findings suggest that the abnormalities of incretin secretion leading to metabolic disturbances in GI inflammatory disease by an increase of Sglt1.

Apoptosis and G2/M cell cycle arrest induced by a timosaponin A3 from Anemarrhena asphodeloides Bunge on AsPC-1 pancreatic cancer cells.

BACKGROUND: Timosaponin A3 (TA3), one of the active components of spirostanol saponin isolated from A. asphodeloides, is widely used as an anticancer agent in a variety of cancer cell lines. However, the research on the anticancer efficacy is very limited in human pancreatic cancer models. PURPOSE: In this study, we investigated the molecular targets in the active components of A. asphodeloides, which showed anti-cancer effects in human pancreatic cancer cells, and confirmed the pathways involved. STUDY DESIGN: The apoptotic effects of five solvent extracts of A. asphodeloides in human pancreatic cancer cells (AsPC-1) was studied, and the phytochemical leading to their effects identified. Next, we determined whether the phytochemical inhibit STAT3 and ERK1/2, and investigated the pathways involved. METHODS: Five solvent extracts of A. asphodeloides (100  µg/ml, 24  h) was investigated for their cytotoxicity against AsPC-1 cells. The active ingredient of the extract exhibiting the highest toxicity were analyzed by liquid chromatography-mass spectrometry. Next, we studied the mechanism of action of the phytochemical in pancreatic cancer. Cell cycle and annexin V/FITC assays were performed to assess cell growth and apoptosis capacity. The effects on apoptosis and proliferation-related pathways, STAT3, and MAPKs were confirmed at the protein level using immunoblotting. The factors regulated in the pathways were investigated using reverse transcription polymerase chain reaction. RESULTS: The results showed that the ethyl acetate extract of A. asphodeloides (EAA) induced apoptotic and anti-proliferative activities through the STAT3 and MAPKs pathways. We found that TA3, an active component of EAA, inhibits constitutive STAT3 and ERK1/2 proteins. EAA and TA3 decreased the viability of AsPC-1 cells, leading to cell cycle arrest at the sub-G1 and G2/M phases. Moreover, TA3 inhibited the expression of various genes encoding anti-apoptotic (Bcl-2, Bcl-xl), proliferative (Cyclin D1), metastatic (MMP-9), and angiogenic (VEGF-1) proteins. CONCLUSION: The results indicated that TA3, an active phytochemical from A. asphodeloides, could induce apoptosis and suppress cell proliferation by inhibiting the STAT3 and ERK1/2 pathways. Thus, TA3 is a candidate cancer chemotherapeutic agent instead to treat human pancreatic cancer.

Cucurbitacin B Induces Hypoglycemic Effect in Diabetic Mice by Regulation of AMP-Activated Protein Kinase Alpha and Glucagon-Like Peptide-1 via Bitter Taste Receptor Signaling.

Taste receptors exist in several organs from tongue to colon and have diverse functions dependent on specific cell type. In enteroendocrine L-cells, stimulation of taste receptor signaling induces incretin hormones. Among incretin hormones, glucagon-like peptide-1 (GLP-1) induces insulinotropic action by activating GLP-1 receptor of pancreatic ß-cells. However, GLP-1 mimetic medicines have reported clinical side effects, such as autoimmune hepatitis, acute kidney injury, pancreatitis, and pancreatic cancer. Here, we hypothesized that if natural components in ethnomedicines can activate agonistic action of taste receptor; they may stimulate GLP-1 and therefore, could be developed as safe and applicable medicines to type 2 diabetes mellitus (T2DM) with minimal side effects. Cucurbitacin B (CuB) is composed of triterpenoid structure and its structural character, that represents bitterness, can stimulate AMP-activated protein kinase (AMPK) pathway. CuB ameliorated hyperglycemia by activating intestinal AMPK levels and by inducing plasma GLP-1 and insulin release in diabetic mice. This hypoglycemic action was decreased in dorsomorphin-injected mice and α-gustducin null mice. Moreover, systemic inhibition study in differentiated NCI-H716 cell line showed that CuB-mediated GLP-1 secretion was involved in activation of AMPK through α-gustducin and Gßγ-signaling of taste receptors. In summary, we conclude that, CuB represents novel hypoglycemic agents by activation of AMPK and stimulation of GLP-1 in differentiated enteroendocrine L-cells. These results suggest that taste receptor signaling-based therapeutic agents within tremendously diverse ethnomedicines, could be applied to developing therapeutics for T2DM patients.

Efficacy of Taurolidine Irrigation in Primary Total Knee Arthroplasty.

PURPOSE: Taurolidine is an antimicrobial agent that was originally used in the local treatment of peritonitis. The aim of this study was to evaluate the efficacy of taurolidine irrigation in primary total knee arthroplasty (TKA). MATERIALS AND METHODS: All patients who underwent TKA at our institute from January 2015 to March 2017 were eligible. There were 300 patients in the taurolidine irrigation group and 300 patients in the control group. The patients in the taurolidine irrigation group were irrigated after implantation with a mix of 250 mL of taurolidine and 750 mL of normal saline. The patients in the control group were not irrigated after implantation. We compared postoperative C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and infection rate between groups. RESULTS: The taurolidine irrigation group had a significantly lower CRP (5.39 mg/dL vs. 7.55 mg/dL; p＜0.001) and ESR (53.21 mm/hr vs. 58.74 mm/hr; p=0.003) on postoperative day 3 after TKA, as compared with the control group. However, there was no difference between the two groups on postoperative days 6, 13, and 20. Periprosthetic joint infection occurred in one patient in the taurolidine irrigation group. CONCLUSIONS: We believe that it is not necessary to use taurolidine for patients who undergo primary TKA.

The therapeutic effects of Yongdamsagan-tang on autoimmune hepatitis models.

Autoimmune hepatitis (AIH) is an immunity disorder that is the result of antibodies in the liver tissue of the patient that are attacked by activated immune cells due to an unknown cause. In this study, we aimed to investigate the anti-inflammatory effect of Yongdamsagan-tang (YST) extracts and confirm effects on autoimmune hepatitis models as the therapeutic agent using the YST extracted by various solvents. YST, a mixture of 11 herbal extracts, is known in traditional Korean medicine as a widely used treatment for inflammatory diseases. We proposed the AIH-condition in vitro model by the addition of recombinant IL-17A and then observed several markers linked to AIH symptoms, including an increase of IL-6 expression, lipid accumulation, and fibrosis. In AIH-condition hepatic cell model, YST reduced IL-6 expression and lipid accumulation caused by treatment of IL-17 combination in hepatocyte cells. Also, YST blocked several activated fibrosis factors including transforming growth factor-ß (TGF- ß1), collagen type 1 (Col-α1(I)), and α-smooth muscle actin (α-SMA) in liver stellate cells. Furthermore, pretreatment with YST protected hepatic damage and reduces histological injury by suppressing apoptosis mediator and inflammatory cytokines expression in concanavalin A (Con A)-induced autoimmune hepatitis mice model. The findings here improve our understanding of YST extracted by 80% ethanol, suggesting that YST can be used as a therapeutic treatment for AIH.

Ginkgolide A ameliorates non-alcoholic fatty liver diseases on high fat diet mice.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide and has continuously increased. NAFLD refers to a spectrum of diseases ranging from fatty liver to steatohepatitis, cirrhosis, and even to hepatocyte carcinoma. Excessive fatty acid enters the cell and the mitochondria undergo stress and unremoved ROS can trigger a form of cell apoptosis known as 'lipoapoptosis'. NASH arises from damaged liver hepatocytes due to lipotoxicity. NASH not only involves lipid accumulation and apoptosis but also inflammation. Ginkgo biloba has been tested clinical trials as a traditional medicine for asthma, bronchitis and cardiovascular disease. The effects of Ginkgolide A (GA), derived from the ginkgo biloba leaf, are still unknown in NAFLD. To determine the protective effects of GA in NAFLD, we examined the fatty liver disease condition in the non-esterified fatty acid (NEFA)-induced HepG2 cell line and in a high fat diet mouse model. The findings of this study suggest that GA is non-toxic at high concentrations in hepatocytes. Moreover, GA was found to inhibit cellular lipogenesis and lipid accumulation by causing mitochondrial oxidative stress. GA showed hepatoprotective efficacy by inducing cellular lipoapoptosis and by inhibiting cellular inflammation. The results demonstrated that GA may be feasible as a therapeutic agent for NAFLD patients.

Complications and Short-Term Outcomes of Medial Opening Wedge High Tibial Osteotomy Using a Locking Plate for Medial Osteoarthritis of the Knee.

PURPOSE: The purpose of this study was to investigate complications and radiologic and clinical outcomes of medial opening wedge high tibial osteotomy (MOWHTO) using a locking plate. MATERIALS AND METHODS: This study reviewed 167 patients who were treated with MOWHTO using a locking plate from May 2012 to June 2014. Patients without complications were classified into group 1 and those with complications into group 2. Medical records, operative notes, and radiographs were retrospectively reviewed to identify complications. Clinically, Oxford Knee score and Knee Injury and Osteoarthritis Outcome score (KOOS) were evaluated. RESULTS: Overall, complications were observed in 49 patients (29.3%). Minor complications included lateral cortex fracture (15.6%), neuropathy (3.6%), correction loss (2.4%), hematoma (2.4%), delayed union (2.4%), delayed wound healing (2.4%), postoperative stiffness (1.2%), hardware irritation (1.2%), tendinitis (1.2%), and hardware failure without associated symptoms (0.6%). Major complications included hardware failure with associated symptoms (0.6%), deep infection (0.6%), and nonunion (0.6%). At the first-year follow-up, there were no significant differences in radiologic measurements between groups 1 and 2. There were no significant differences in knee scores except for the KOOS pain score. CONCLUSIONS: Our data showed that almost all complications of the treatment were minor and the patients recovered without any problems. Most complications did not have a significant impact on radiologic and clinical outcomes.

Metabolic Profiling of Liver Tissue in Diabetic Mice Treated with Artemisia Capillaris and Alisma Rhizome Using LC-MS and CE-MS.

Artemisia Capillaris (AC) and Alisma Rhizome (AR) are natural products for the treatment of liver disorders in oriental medicine clinics. Here, we report metabolomic changes in the evaluation of the treatment effects of AC and AR on fatty livers in diabetic mice, along with a proposition of the underlying metabolic pathway. Hydrophobic and hydrophilic metabolites extracted from mouse livers were analyzed using HPLC-QTOF and CE-QTOF, respectively, to generate metabolic profiles. Statistical analysis of the metabolites by PLS-DA and OPLA-DA fairly discriminated between the diabetic, and the AC- and AR-treated mice groups. Various PEs mostly contributed to the discrimination of the diabetic mice from the normal mice, and besides, DG (18:1/16:0), TG (16:1/16:1/20:1), PE (21:0/20:5), and PA (18:0/21:0) were also associated with discrimination by s-plot. Nevertheless, the effects of AC and AR treatment were indistinct with respect to lipid metabolites. Of the 97 polar metabolites extracted from the CE-MS data, 40 compounds related to amino acid, central carbon, lipid, purine, and pyrimidine metabolism, with [Formula: see text] values less than 0.05, were shown to contribute to liver dysregulation. Following treatment with AC and AR, the metabolites belonging to purine metabolism preferentially recovered to the metabolic state of the normal mice. The AMP/ATP ratio of cellular energy homeostasis in AR-treated mice was more apparently increased ([Formula: see text]) than that of AC-treated mice. On the other hand, amino acids, which showed the main alterations in diabetic mice, did not return to the normal levels upon treatment with AR or AC. In terms of metabolomics, AR was a more effective natural product in the treatment of liver dysfunction than AC. These results may provide putative biomarkers for the prognosis of fatty liver disorder following treatment with AC and AR extracts.

Anti-lipoapoptotic effects of Alisma orientalis extract on non-esterified fatty acid-induced HepG2 cells.

BACKGROUND: Liver steatosis was caused by lipid accumulation in the liver. Alisma orientale (AO) is recognized as a promising candidate with therapeutic efficacy for the treatment of nonalcoholic fatty liver disease (NAFLD). HepG2 hepatocyte cell line is commonly used for liver disease cell model. METHOD: The HepG2 cells were cultured with the NEFAs mixture (oleic and palmitic acids, 2:1 ratio) for 24 h to induce hepatic steatosis. Then different doses of Alisma orientale extract (AOE) was treated to HepG2 for 24 h. Incubated cells were used for further experiments. RESULTS: The AOE showed inhibitory effects on lipid accumulation in the Oil Red O staining and Nile red staining tests with no cytotoxicity at a concentration of 300 µg/mL. Fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1) mRNA and protein expression level were down-regulated after AOE treatment. Bcl-2 associated X protein (Bax) and c-Jun N-terminal kinase (JNK) mRNA expression level were decreased as well as p-JNK (activated form of JNK), Bax, cleaved caspase-9, caspase-3 protein expression level. Anti-apopototic B-cell lymphoma 2 (Bcl-2) protein level increased after AOE treatment. In addition, inflammatory protein expression including p-p65, p65, COX-2 and iNOS were inhibited by AOE treatment. CONCLUSION: The results suggest that AOE has anti-steatosis effects that involve lipogenesis, anti-lipoapoptosis, and anti-inflammation in the NEFA-induced NAFLD pathological cell model.

Anti-Inflammatory Effects of Ginsenoside Rg3 via NF-κB Pathway in A549 Cells and Human Asthmatic Lung Tissue.

Objective. There is limited information of the anti-inflammatory effects of Rg3 on inflamed lung cells and tissues. Therefore, we confirmed the anti-inflammatory mechanism of ginsenoside Rg3 in inflamed human airway epithelial cells (A549) and tissues whether Rg3 regulates nuclear factor kappa B (NF-κB) activity. Methods. To induce the inflammation, IL-1ß (10 ng/ml) was treated to A549 cells for 4 h. The effects of Rg3 on NF-κB activity and COX-2 expression were evaluated by western blotting analysis in both IL-1ß-induced inflamed A549 cell and human asthmatic airway epithelial tissues. Using multiplex cytokines assay, the secretion levels of NF-κB-mediated cytokines/chemokines were measured. Result. Rg3 showed the significant inhibition of NF-κB activity thereby reduced COX-2 expression was determined in both IL-1ß-induced inflamed A549 cell and human asthmatic airway epithelial tissues. In addition, among NF-κB-mediated cytokines, the secretion levels of IL-4, TNF-α, and eotaxin were significantly decreased by Rg3 in asthma tissues. Even though there was no significant difference, IL-6, IL-9, and IL-13 secretion showed a lower tendency compared to saline-treated human asthmatic airway epithelial tissues. Conclusion. The results from this study demonstrate the potential of Rg3 as an anti-inflammatory agent through regulating NF-κB activity and reducing the secretion of NF-κB-mediated cytokines/chemokines.

The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice.

Ginsenosides can be classified on the basis of the skeleton of their aglycones. Here, we hypothesized that the sugar moieties attached to the dammarane backbone enable binding of the ginsenosides to the sweet taste receptor, eliciting glucagon-like peptide-1 (GLP-1) secretion in the enteroendocrine L cells. Using the human enteroendocrine NCI-H716 cells, we demonstrated that 15 ginsenosides stimulate GLP-1 secretion according to the position of their sugar moieties. Through a pharmacological approach and RNA interference technique to inhibit the cellular signal cascade and using the Gαgust(-/-) mice, we elucidated that GLP-1 secreting effect of Rg3 mediated by the sweet taste receptor mediated the signaling pathway. Rg3, a ginsenoside metabolite that transformed the structure through a steaming process, showed the strongest GLP-1 secreting effects in NCI-H716 cells and also showed an anti-hyperglycemic effect on a type 2 diabetic mouse model through increased plasma GLP-1 and plasma insulin levels during an oral glucose tolerance test. Our study reveals a novel mechanism where the sugar moieties of ginsenosides Rg3 stimulates GLP-1 secretion in enteroendocrine L cells through a sweet taste receptor-mediated signal transduction pathway and thus has an anti-hyperglycemic effect on the type 2 diabetic mouse model.