Uvaol ameliorates lipid deposition in hyperlipidemic hepatocytes by suppressing protein-tyrosine phosphatase 1B/ER stress signaling.

Uvaol (UV), a pentacyclic triterpene found in olives and virgin olive oil, is known for its anti-inflammatory and antioxidant effects in various disease models. While olive oil is reported to reduce obesity and insulin resistance, the specific impact of UV on liver lipid metabolism and its molecular mechanisms are not fully understood. In this study, hepatic lipid accumulation was measured using oil red O staining, and protein expression levels in liver cells were assessed via Western blot analysis. Apoptosis was evaluated through cell viability and caspase 3 activity assays. UV treatment reduced lipid accumulation, fatty acid uptake, apoptosis, and ER stress in palmitate-treated liver cells. Additionally, UV enhanced fatty acid oxidation. Mechanistically, increased SIRT6 expression and autophagy were observed in UV-treated cells. SIRT6-targeted siRNA or 3-methyladenine blocked the effects of UV in hyperlipidemic cells. In conclusion, UV improves SIRT6/autophagy signaling, reducing lipid deposition and apoptosis in liver cells under high lipid conditions. This in vitro study provides strong evidence for potential therapeutic strategies for hepatic steatosis.

DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells.

BACKGROUND: Age-related macular degeneration (AMD) is an irreversible eye disease that can cause blurred vision. Regular exercise has been suggested as a therapeutic strategy for treating AMD, but how exercise improves AMD is not yet understood. This study investigated the protective effects of developmental endothelial locus-1 (DEL-1), a myokine upregulated during exercise, on endoplasmic reticulum (ER) stress-induced injury in retinal pigment epithelial cells. METHODS: We evaluated the levels of AMPK phosphorylation, autophagy markers, and ER stress markers in DEL-1-treated human retinal pigment epithelial cells (hRPE) using Western blotting. We also performed cell viability, caspase 3 activity assays, and autophagosome staining. RESULTS: Our findings showed that treatment with recombinant DEL-1 dose-dependently reduced the impairment of cell viability and caspase 3 activity in tunicamycin-treated hRPE cells. DEL-1 treatment also alleviated tunicamycin-induced ER stress markers and VEGF expression. Moreover, AMPK phosphorylation and autophagy markers were increased in hRPE cells in the presence of DEL-1. However, the effects of DEL-1 on ER stress, VEGF expression, and apoptosis in tunicamycin-treated hRPE cells were reduced by AMPK siRNA or 3-methyladenine (3-MA), an autophagy inhibitor. CONCLUSIONS: Our study suggests that DEL-1, a myokine, may have potential as a treatment strategy for AMD by attenuating ER stress-induced injury in retinal pigment epithelial cells.

A novel surgical approach using the "lateral corridor" for minimally invasive oblique lumbar interbody fusion at L5-S1: a clinical series and technical note.

PURPOSE: The minimally invasive oblique lumbar interbody fusion (MI-OLIF) L5-S1 was introduced to overcome the limitations of conventional fusion techniques, however, MI-OLIF is not possible using the standard method due to vascular structures in some cases. We aimed to introduce the "lateral corridor" and report the details of the surgical technique with a clinical case series. METHODS: We utilized the lateral access route of the left common iliac vein and named it the "lateral corridor", to distinguish the technique from the standard technique (central corridor). The type and frequency of branch vessels that required additional manipulations were reviewed, and the frequency of intraoperative vascular injury was investigated. RESULTS: Among the 107 patients who underwent MI-OLIF L5-S1, 26 patients (24.3%) who received the "lateral corridor" technique were included. Branch vessel ligation was required in 42.3% of the patients. The types of branch vessels that required ligation were seven cases (26.9%) of the iliolumbar vein (ILV) and six cases (23.1%) of ascending lumbar vein (ALV). The ILV and ALV were ligated in two cases. None of the patients developed intraoperative vascular injuries. CONCLUSION: We introduced the "lateral corridor" as an alternative approach for MI-OLIF L5-S1, implemented it in 24.3% of the patient cohort, and reported favorable outcomes devoid of vascular complications. The "lateral corridor" necessitated ligation of the ILV or ALV in 42.3% of cases. The "lateral corridor" approach appears to be a promising surgical technique, offering feasibility even in instances where the vascular anatomy precludes the employment of the conventional approach.

Adipokine gremlin-1 promotes hepatic steatosis via upregulation of ER stress by suppressing autophagy-mediated signaling.

Gremlin-1 (GR1) is a novel adipokine that is highly expressed in human adipocytes and has been shown to inhibit the BMP2/4-TGFb signaling pathway. It has an effect on insulin sensitivity. Elevated levels of Gremlin have been shown to lead to insulin resistance in skeletal muscle, adipocytes, and hepatocytes. In this study, we investigated the effect of GR1 on hepatic lipid metabolism under hyperlipidemic conditions and explored the molecular mechanisms associated with GR1 by in vitro and in vivo studies. We found that palmitate increased GR1 expression in visceral adipocytes. Recombinant GR1 increased lipid accumulation, lipogenesis, and ER stress markers in cultured primary hepatocytes. Treatment with GR1 increased EGFR expression and mTOR phosphorylation and reduced autophagy markers. EGFR or rapamycin siRNA reduced the effects of GR1 on lipogenic lipid deposition and ER stress in cultured hepatocytes. Administration of GR1 via the tail vein induced lipogenic proteins and ER stress while suppressing autophagy in the livers of experimental mice. Suppression of GR1 by in vivo transfection reduced the effects of a high-fat diet on hepatic lipid metabolism, ER stress, and autophagy in mice. These results suggest that the adipokine GR1 promotes hepatic ER stress due to the impairment of autophagy, ultimately causing hepatic steatosis in the obese state. The current study demonstrated that targeting GR1 may be a potential therapeutic approach for treating metabolic diseases, including metabolic-associated fatty liver disease (MAFLD).

CTRP4 attenuates apoptosis and epithelial-mesenchymal transition markers in podocytes through an AMPK/autophagy-dependent pathway.

Hyperglycemia, characterized by high blood glucose levels resulting from pancreatic beta cell dysfunction or impaired insulin signaling, is a contributing factor in the development of diabetic nephropathy. This study aimed to investigate the effects of C1q/TNF-related protein 4 (CTRP4), known for its anti-obesity and anti-inflammatory properties in various disease models, on podocyte apoptosis and endoplasmic reticulum (ER) stress in the presence of elevated glucose levels. The expression levels of various proteins in podocytes and adipocytes were evaluated by Western blotting. Autophagosomes in podocytes were stained by MDC. Chromatin condensation in podocytes was examined by Hoechst staining. The research revealed increased expression of CTRP4 in 3T3-L1 adipocytes and CIHP-1 podocytes exposed to high glucose (HG) conditions. Treatment with CTRP4 effectively mitigated HG-induced apoptosis and ER stress and normalized epithelial-to-mesenchymal transition (EMT) markers in CIHP-1 cells. Furthermore, elevated levels of AMPK phosphorylation and autophagy were observed in CIHP-1 cells treated with CTRP4. Silencing of AMPK or the use of 3-methyl adenine (3 MA) reduced the impacts of CTRP4 on apoptosis, EMT markers and ER stress in CIHP-1 cells. In conclusion, these findings suggest that CTRP4 alleviates ER stress in podocytes under hyperglycemic conditions, leading to the suppression of apoptosis and the restoration of EMT through AMPK/autophagy-mediated signaling. These insights provide valuable information for the development of therapeutic strategies for diabetic nephropathy.

Myokine musclin alleviates lipid accumulation in 3T3-L1 adipocytes through PKA/p38-mediated upregulation of lipolysis and suppression of lipogenesis.

Musclin (MUS), an exercise-responsive myokine, has been documented to attenuate inflammation and enhance physical endurance. However, the effects of MUS on differentiation and related molecular mechanisms in adipocytes have not yet been studied. In this study, we found that treatment with MUS attenuated lipid accumulation in fully differentiated 3T3-L1 cells. Furthermore, MUS treatment enhanced lipolysis assessed by glycerol release, and caused apoptosis, whereas it reduced the expression of lipogenic proteins, such as PPARγ and processed SREBP1. Treatment with MUS augmented phosphorylated PKA expression, whereas suppressed p38 phosphorylation in 3T3-L1 adipocytes. H89, a selective PKA inhibitor reduced the effects of MUS on lipogenic lipid accumulation as well as lipolysis except for apoptosis. These results suggest that MUS promotes lipolysis and suppresses lipogenesis through a PKA/p38-dependent pathway, thereby ameliorating lipid deposition in cultured adipocytes. The current study offers the potential of MUS as a therapeutic approach for treating obesity with few side effects.

Oroxylin-A alleviates hepatic lipid accumulation and apoptosis under hyperlipidemic conditions via AMPK/FGF21 signaling.

Oroxylin-A (OA) is an O-methylated flavone that has been demonstrated to have anti-inflammatory properties in various disease models. However, the roles of OA in hepatic lipid metabolism and the specific molecular mechanisms by which it exerts these effects are not yet fully understood. In the current study, we aimed to investigate the effects of OA on hepatic lipid deposition and apoptosis, which play a pivotal role in the development of nonalcoholic fatty liver disease (NAFLD) in obesity in vitro models. We found that treatment with OA attenuated lipid accumulation, the expression of lipogenesis-associated proteins and apoptosis in palmitate-treated primary mouse hepatocytes. OA treatment suppressed phosphorylated NFκB and IκB expression in as well as TNFα and MCP-1 release from hepatocytes treated with palmitate. Treatment of hepatocytes with OA augmented AMPK phosphorylation and FGF21 expression. siRNA of AMPK or FGF21 abolished the effects of OA on inflammation as well as lipid accumulation and apoptosis in hepatocytes under palmitate treatment conditions. In conclusion, OA improves inflammation through the AMPK/FGF21 pathway, thereby attenuating lipid accumulation and apoptosis in hepatocytes. This study may help identify new targets for developing treatments for NAFLD.

Musclin attenuates lipid deposition in hepatocytes through SIRT7/autophagy-mediated suppression of ER stress.

Musclin, an exercise-responsive myokine, has the ability to attenuate inflammation, oxidative stress, and apoptosis in cardiomyocytes under pathogenic conditions. While the potential benefits of musclin in the cardiovascular system have been well documented, its effects on hepatic endoplasmic reticulum (ER) stress and lipid metabolism are not fully understood. The present study showed that musclin treatment reduced lipid accumulation and lipogenic protein expression in primary hepatocytes exposed to palmitate. Palmitate treatment led to an increase in markers of ER stress, which was reversed by musclin treatment. Musclin treatment increased SIRT7 expression and markers of autophagy in a dose-dependent manner. Small interfering (si) RNA of SIRT7 or 3-methyladenine (3 MA) reduced the effects of musclin on lipogenic lipid deposition in hepatocytes under hyperlipidemic conditions. These findings suggest that musclin can suppress palmitate-induced ER stress by upregulating SIRT7 and autophagy signaling, thereby alleviating lipid accumulation in primary hepatocytes. The current study provides a potential therapeutic strategy for the treatment of liver diseases characterized by lipid accumulation and ER stress, such as nonalcoholic fatty liver disease (NAFLD).

Long-Term Clinical and Radiological Outcomes of Minimally Invasive Transforaminal Lumbar Interbody Fusion: 10-Year Follow-up Results.

BACKGROUND: Many studies have reported that minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) provides satisfactory treatment comparable to other fusion methods. However, in the case of MI-TLIF, there are concerns about the long-term outcome compared to conventional bilateral PLIF due to the small amount of disc removal and the lack of autogenous bone graft. Long-term follow-up studies are still lacking as most of the previous reports have follow-up periods of up to 5 years. METHODS: Thirty patients who underwent MI-TLIF were followed up for > 10 years (mean, 11.1 years). Interbody fusion rates were determined using a modified Bridwell grading system. Adjacent segment disease (ASD) was defined as radiological adjacent segment degeneration (R-ASDeg) as seen on plain X-rays; reoperated adjacent segment disease referred to the subsequent need for revision surgery. Clinical outcomes after surgery were assessed based on back and leg pain as well as the Oswestry disability index (ODI). RESULTS: The overall radiological fusion rate, at the 1-, 5-, and 10-year follow-up was 77.1%, 91.4%, and 94.3%, respectively. The incidence of R-ASDeg 1, 5, and 10 years after surgery was 6.7%, 16.7%, and 43.3% at the proximal adjacent segment and 4.8%, 14.3%, and 28.6% at the distal adjacent segment, respectively. R-ASDeg at either the proximal or distal segment was determined in 50.0% of the patients 10 years postoperatively. All clinical parameters improved significantly during follow-up, although the ODI and the visual analog scale (VAS) for leg pain at the 10-year follow-up were significantly worse in the R-ASDeg group than in the other patients (P = 0.009, P = 0.040). CONCLUSION: MI-TLIF improved both clinical and radiological outcomes, and the improvements were maintained for up to 10 years after surgery. However, R-ASDeg developed in up to 50% of the patients within 10 years, and both leg pain on the VAS and the ODI were worse in patients with R-ASDeg.

Objective predictors of delayed neurological sequelae in patients with altered mental status after carbon monoxide poisoning.

BACKGROUND AND PURPOSE: Following carbon monoxide (CO) poisoning, altered mental status is an important predictor of poor neurological prognosis, including delayed neurological sequelae (DNS). However, it is difficult to interview CO-poisoned patients accurately about exposure intervals and loss of consciousness (LOC). Thus, we investigated whether DNS can be predicted using objective factors such as laboratory results and brain imaging in patients suffering CO poisoning with altered mental status. METHODS: This was a prospective observational study involving all CO-poisoned patients who visited the university hospital emergency department (ED) in Bucheon, South Korea, between January 2019 and April 2020. All were registered in the CO registry. We excluded patients who were under 18 years of age, had no change in mental status, were lost to follow-up, had neurological deficits persisting at discharge from the ED, and/or were transferred from another hospital 24 hours after exposure. RESULTS: A total of 21 (25.3%) of 82 patients had DNS with a median onset of 21 (12 to 30) days. Creatinine kinase (CK) (odds ratio 1.0002, 95% confidence interval 2.734-105.231) and brain imaging (odds ratio 3.206, 95% confidence interval 1.008-10.199) were independent prognostic factors of DNS. CONCLUSION: A high level of serum CK and abnormal brain-imaging results were significant predictors of the occurrence of DNS in CO-poisoned patients with altered mental status. Critically, these are objective rather than subjective factors such as CO exposure interval.

Physician Confidence in Artificial Intelligence: An Online Mobile Survey.

BACKGROUND: It is expected that artificial intelligence (AI) will be used extensively in the medical field in the future. OBJECTIVE: The purpose of this study is to investigate the awareness of AI among Korean doctors and to assess physicians' attitudes toward the medical application of AI. METHODS: We conducted an online survey composed of 11 closed-ended questions using Google Forms. The survey consisted of questions regarding the recognition of and attitudes toward AI, the development direction of AI in medicine, and the possible risks of using AI in the medical field. RESULTS: A total of 669 participants completed the survey. Only 40 (5.9%) answered that they had good familiarity with AI. However, most participants considered AI useful in the medical field (558/669, 83.4% agreement). The advantage of using AI was seen as the ability to analyze vast amounts of high-quality, clinically relevant data in real time. Respondents agreed that the area of medicine in which AI would be most useful is disease diagnosis (558/669, 83.4% agreement). One possible problem cited by the participants was that AI would not be able to assist in unexpected situations owing to inadequate information (196/669, 29.3%). Less than half of the participants(294/669, 43.9%) agreed that AI is diagnostically superior to human doctors. Only 237 (35.4%) answered that they agreed that AI could replace them in their jobs. CONCLUSIONS: This study suggests that Korean doctors and medical students have favorable attitudes toward AI in the medical field. The majority of physicians surveyed believed that AI will not replace their roles in the future.

Evaluation of nefazodone-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes.

The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), which express the major cardiac ion channels and recapitulate spontaneous mechanical and electrical activities, may provide a possible solution for the lack of in vitro human-based cardiotoxicity testing models. Cardiotoxicity induced by the antidepressant nefazodone was previously revealed to cause an acquired QT prolongation by hERG channel blockade. To elucidate the cellular mechanisms underlying the cardiotoxicity of nefazodone beyond hERG, its effects on cardiac action potentials (APs) and ion channels were investigated using hiPSC-CMs with whole-cell patch clamp techniques. In a proof of principle study, we examined the effects of cardioactive channel blockers on the electrophysiological profile of hiPSC-CMs in advance of the evaluation of nefazodone. Nefazodone dose-dependently prolonged the AP duration at 90% (APD90) and 50% (APD50) repolarization, reduced the maximum upstroke velocity (dV/dtmax) and induced early after depolarizations. Voltage-clamp studies of hiPSC-CMs revealed that nefazodone inhibited various voltage-gated ion channel currents including IKr, IKs, INa, and ICa. Among them, IKr and INa showed relatively higher sensitivity to nefazodone, consistent with the changes in the AP parameters. In summary, hiPSC-CMs enabled an integrated approach to evaluate the complex interactions of nefazodone with cardiac ion channels. These results suggest that hiPSC-CMs can be an effective model for detecting drug-induced arrhythmogenicity beyond the current standard assay of heterologously expressed hERG K(+) channels.

Highly improved reliability of amber light emitting diode with Ca -α-SiAlON phosphor in glass formed by gas pressure sintering for automotive applications.

Phosphor in glass (PiG) with 40 wt% of Ca-α-SiAlON phosphor and 60 wt% of Pb-free silicate glass was synthesized and mounted on a high-power blue LED to make an amber LED for automotive applications. Gas pressure sintering was applied after the conventional sintering process was used to achieve fully dense PiG plates. Changes in photoluminescence spectra and color coordination were inspected by varying the thickness of the plates that were mounted after optical polishing and machining. A trade-off between luminous flux and color purity was observed. The commercial feasibility of amber PiG packaged LED, which can satisfy international regulations for automotive components, was successfully demonstrated by examining the practical reliability under 85% humidity at an 85°C condition.

Hybrid selective noncatalytic reduction (SNCR)/selective catalytic reduction (SCR) for NOx removal using low-temperature SCR with Mn-V2O5/TiO2 catalyst.

UNLABELLED: A hybrid selective noncatalytic reduction/selective catalytic reduction (SNCR/SCR) system that uses two types of technology, low-temperature SCR process and SNCR process, was designed to develop nitrogen oxide (NOx) reduction technology. SCR was conducted with space velocity (SV)=2400 hr(-1) and hybrid SNCR/SCR with SV=6000 hr(-1), since the study focused on reducing the amount of catalyst and both achieved 98% NOx reduction efficiency. Characteristics of NOx reduction by NH3 were studied for low-temperature SCR system at 150 °C using Mn-V2O5/TiO2 catalyst. Mn-added V2O5/TiO2 catalyst was produced, and selective catalyst reduction of NOx by NH3 was experimented. NOx reduction rate according to added Mn content in Mn-V2O5/TiO2 catalyst was studied with varying conditions of reaction temperature, normalized stoichiometric ratio (NSR), SV, and O2 concentration. In the catalyst experiment according to V2O5 concentration, 1 wt.% V2O5 catalyst showed the highest NOx reduction rate: 98% reduction at temperature window of 200~250 °C. As a promoter of the V2O5 catalyst, 5 wt.% Mn was added, and the catalyst showed 47~90% higher efficiency even with low temperatures, 100~200 °C. Mn-V2O5/TiO2 catalyst, prepared by adding 5 wt.% Mn in V2O5/TiO2 catalyst, showed increments of catalyst activation at 150 °C as well as NOx reduction. Mn-V2O5/TiO2 catalyst showed 8% higher rate for NOx reduction compared with V2O5/TiO2 catalyst in 150 °C SCR. Thus, (5 wt.%)Mn-(1 wt.%)V2O5/TiO2 catalyst was applied in SCR of hybrid SNCR/SCR system of low temperature at 150 °C. Low-temperature SCR hybrid SNCR/SCR (150 °C) system and hybrid SNCR/SCR (350 °C) showed 91~95% total reduction rate with conditions of SV=2400~6000 hr(-1) SCR and 850~1050 °C SNCR, NSR=1.5~2.0, and 5% O2. Hybrid SNCR/SCR (150 °C) system proved to be more effective than the hybrid SNCR/SCR (350 °C) system at low temperature. IMPLICATIONS: NOx control is very important, since they are the part of greenhouse gases as well as the cause of acid rain and ozone hole. A technology, so-called hybrid SNCR/SCR process, was tested using Mn-V2O5/TiO2 monolithic catalyst for NOx reduction, and the method is promising. The results of this study would provide some ideas to parties such as policy makers, environmental engineers, and so on.

Examination of the cutoff value of postchemotherapy increase in tumor volume as a predictor of subsequent oncologic events in stage IIB osteosarcoma.

BACKGROUND: Tumor enlargement after chemotherapy is a predictor of a poor histological response, poor survival, and local recurrence. However, the cutoff point of tumor enlargement for predicting subsequent oncologic events has not been determined. METHODS: We retrospectively reviewed 567 patients who were treated at our institute for stage IIB osteosarcoma. We used receiver operating characteristic (ROC) curve analysis of tumor volume increase for the prediction of subsequent metastasis or local recurrence, and calculated diagnostic indices for different cutoff values. RESULTS: A tumor volume increase of >15% predicted subsequent metastasis or local recurrence with a sensitivity of 64.7%, a specificity of 81.5%, a positive predictive value of 71.6%, and a negative predictive value of 76.1%. Increases in tumor volumes based on this cutoff value were able to predict subsequent oncologic events in all clinical subgroups, except in cases of rare pathologic subtypes. However, for tumors in the proximal humerus, a cutoff value of 25% had optimal predictive value. CONCLUSIONS: This study shows that a cutoff value of 15% for tumor volume increase is useful for predicting subsequent metastasis or local recurrence. Our results suggest that tumor enlargement after chemotherapy serves as an easily assessable clinical parameter for risk-adapted therapy.

Overlapping allograft for primary or salvage bone tumor reconstruction.

BACKGROUND: Compared with end-to-end allograft coaptation, overlapping allograft offer a superior union rate by increasing the contact area. However, reports on overlapping allograft are scarce. Therefore, we attempted to confirm the usefulness of this technique either after primary tumor resection or in salvaging a failed reconstruction. METHODS: We analyzed the outcome of 35 overlapping allografts reconstructions. Indications were primary reconstruction of a skeletal defect (n = 19) and salvage of a failed reconstruction (n = 16). Graft survival, union rate, and time to union were evaluated as a function of clinical variables such as age, use of chemotherapy, type of junction, method of fixation, length of overlapped bone, and method of overlapping. RESULTS: All 35 overlapping allografts showed union at a mean of 5.6 months (range, 3-14 months). One allograft was removed with local recurrence at 19 months post-operatively. Average length of overlapped bone was 3.5 cm (range, 1.4-6.5 cm). Patient age <15-years (P = 0.001) and circumferential overlapping (P = 0.011) shortened the time to union. CONCLUSIONS: In terms of graft failure rate, union rate, and time to union, overlapping allograft is an excellent technique, which overcomes the limitations of end-to-end fixation.

Regenerative medicine approaches for the treatment of spinal cord injuries: Progress and challenges.

Spinal cord injury (SCI) is a profound medical condition that significantly hampers motor function, imposing substantial limitations on daily activities and exerting a considerable financial burden on patients and their families. The constrained regenerative capacity of endogenous spinal cord tissue, exacerbated by the inflammatory response following the initial trauma, poses a formidable obstacle to effective therapy. Recent advancements in the field, stem cells, biomaterials, and molecular therapy, show promising outcomes. This review provides a comprehensive analysis of tissue engineering and regenerative medicine approaches for SCI treatment, including cell transplantation, tissue-engineered construct implantation, and other potential therapeutic strategies. Additionally, it sheds light on preclinical animal studies and recent clinical trials incorporating these modalities, providing a glimpse into the evolving landscape of SCI management. STATEMENT OF SIGNIFICANCE: The investigation into spinal cord injury (SCI) treatments focuses on reducing long-term impacts by targeting scar inhibition and enhancing regeneration through stem cells, with or without growth factors. Induced pluripotent stem cells (iPSCs) show promise for autologous use, with clinical trials confirming their safety. Challenges include low cell viability and difficulty in targeted differentiation. Biomaterial scaffolds hold potential for improving cell viability and integration, and extracellular vesicles (EVs) are emerging as a novel therapy. While EV research is in its early stages, stem cell trials demonstrate safety and potential recovery. Advancing tissue engineering approaches with biomaterial scaffolds is crucial for human trials.

Musclin Mitigates the Attachment of HUVECs to THP-1 Monocytes in Hyperlipidemic Conditions through PPARα/HO-1-Mediated Attenuation of Inflammation.

Musclin, a myokine, undergoes modulation during exercise and has demonstrated anti-inflammatory effects in cardiomyocytes and glomeruli. However, its role in atherosclerotic responses remains unclear. This study aimed to explore the impact of musclin on inflammatory responses and the interaction between endothelial cells and monocytes under hyperlipidemic conditions. The attachment levels of THP-1 monocytes on cultured HUVECs were examined. Inflammation and the expression of cell adhesion molecules were also evaluated. To explore the molecular mechanisms of musclin, PPARα or heme oxygenase 1 (HO-1) siRNA transfection was performed in HUVECs. The results revealed that treatment with recombinant musclin effectively suppressed the attachment of palmitate-induced HUVECs to THP-1 cells and reduced the expression of cell adhesion proteins (ICAM-1, VCAM-1, and E-selectin) in HUVECs. Furthermore, musclin treatment ameliorated the expression of inflammation markers (phosphorylated NFκB and IκB) in both HUVECs and THP-1 monocytes, as well as the release of TNFα and MCP-1 from HUVECs and THP-1 monocytes. Notably, musclin treatment augmented the expression levels of PPARα and HO-1. However, when PPARα or HO-1 siRNA was employed, the beneficial effects of musclin on inflammation, cell attachment, and adhesion molecule expression were abolished. These findings indicate that musclin exerts anti-inflammatory effects via the PPARα/HO-1 pathway, thereby mitigating the interaction between endothelial cells and monocytes. This study provides evidence supporting the important role of musclin in ameliorating obesity-related arteriosclerosis and highlights its potential as a therapeutic agent for treating arteriosclerosis.

Effectiveness of vancomycin powder for preventing postoperative spinal infection.

OBJECTIVE: This study aimed to assess the effectiveness of Vancomycin Power (VP) and the occurrence of resistant organisms after four-year of routine VP use. METHODS: The study included 1063 patients who underwent posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) between January 2010 and February 2020. Intrawound VP was applied to all instrumented fusions starting in January 2016. The patients were divided into two groups: those who did not apply VP (non-VP) (n = 605) between 2010 and 2015, and those who did apply VP (VP) (n = 458) between 2016 and 2020. The baseline characteristics, clinical symptoms, infection rate, and causative organisms were compared between the two groups. RESULTS: The rate of PSI was not significantly different between the non-VP group (1.32 %, n = 8) and the VP group (1.09 %, n = 5). Although adjusted by diabetes mellitus, VP still did not show statistical significance (OR = 0.757 (0.245-2.345), p = 0.630). There were no critical complications that were supposed to relation with vancomycin powder. In the 13 cases of PSI, seven pathogens were isolated, with a gram-negative organism identified in the non-VP group. However, the type of organism was not significantly different between the two groups. CONCLUSIONS: The use of intrawound VP may not affect the PSI and occurrence of resistant organism and may not cause critical complications. Therefore, clinicians may decide whether to use VP for preventing PSI not worrying about its safety.

Pilot study on the feasibility of shape memory alloy implantation for Vancouver type B1 periprosthetic femoral fractures in a canine model: a step toward advancing treatment modalities.

BACKGROUND: Cerclage wiring is commonly used for treating fractures; however, it has several limitations, including mechanical weakness, decreased blood circulation, and technical complexity. In this study, we developed an implant using a shape memory alloy (SMA) and tested its efficacy in treating Vancouver type B1 (VB1) periprosthetic femoral fractures (PFFs) in a canine model. METHODS: The mid-diaphyseal fracture models underwent reduction via the SMA plate (SMA group) or the cerclage cable plate (cable group) method in randomly selected pelvic limbs. An intraoperative evaluation was conducted to assess the surgical time and difficulty related to implant fitting. Clinical assessments, radiography, microcomputed tomography (micro-CT), histological analysis, positron emission tomography (PET)/CT, and galvanic corrosion analysis were conducted for 52 weeks to evaluate bone healing and blood perfusion. RESULTS: The results for bone healing and blood perfusion were not significantly different between the groups (p > 0.05). In addition, no evidence of galvanic corrosion was present in any of the implants. However, the median surgical time was 75 min (range, 53-82 min) for the SMA group and 126 min (range, 120-171 min) for the cable group, which was a statistically significant difference (p = 0.0286). CONCLUSIONS: This study assessed the ability of a newly developed shape memory alloy (SMA) to treat VB1 periprosthetic femoral fractures (PFFs) in canines for over a 52-week period and revealed outcomes comparable to those of traditional methods in terms of bone healing and mechanical stability. Despite the lower surgical complexity and potential time-saving benefits of this treatment, further research is needed to confirm its efficacy.