Recurrent Spinal Canal Stenosis after Decompression and Fusion Surgery Due to Bone Overgrowth: Case Report.

Bone regrowth commonly occurs following lumbar decompression surgery. Although it is rare for neurological symptoms to occur due to bone regrowth, this study describes two patients who underwent both decompression and fusion surgeries but experienced spinal canal restenosisthat was severe enough to induce neurological symptoms. A 32-year-old man underwent posterior decompression and posterior lumbar interbody fusion for lumbar canal stenosis at the L4/L5 level 5 years prior. However, the sudden onset of lower back pain occurred 5 years later. Bone overgrowth on the left side was observed at the L4/L5 level. A second surgery was performed, and the patient's symptoms improved significantly. In the second case, a 56-year-old man underwent posterior decompression and posterior lumbar fusion at the L3/L4 and L4/L5 levels for an L4 burst fracture. One month later, he complained of lower back pain and underwent a second posterior decompression surgery. One year later, he presented to an outpatient clinic with lower back pain and neurological symptoms. Bone overgrowth was observed on both sides at the L4/L5 level. Thus, screw removal and laminectomy at the L3, L4, and L5 levels were performed as a third surgery. This study discusses the factors affecting bone regrowth and the methods that can be used to prevent it.

The Outcomes of Mini-Plate Fixation for Unstable Wagstaffe Tubercle Fracture, an Indirect Syndesmosis Injury in Rotational Ankle Fracture.

Background: Wagstaffe fracture constitutes an indirect injury to the AITFL and can precipitate syndesmotic instability. The prevailing fixation methods often involve the use of mini-screws or K-wires, with absorbable suture repair reserved for cases with small or comminuted fragments exhibiting instability. In this study, we devised a mini-plate fixation method capable of securing the fracture fragment irrespective of its size or condition. Methods: A retrospective chart review was conducted on patients who underwent surgery for ankle fractures between May 2022 and October 2023. The surgical technique involved direct fixation of the Wagstaffe fracture using mini-plate fixation. Radiologic evaluation was performed using postoperative CT images, and clinical outcomes were assessed using the OMAS and VAS. Results: Fourteen patients with an average age of 62.5 years were included. Most fractures were associated with the supination-external rotation type. The average preoperative OMAS significantly improved from 5.95 to 83.57 postoperatively. The average VAS score decreased from 7.95 preoperatively to 0.19 postoperatively. Conclusions: The mini-plate technique for Wagstaffe fractures exhibited dependable fixation strength, effective fracture reduction, a minimal complication rate, and judicious surgical procedure duration.

Coronal plane in opportunistic screening of osteoporosis using computed tomography: comparison with axial and sagittal planes.

OBJECTIVE: To compare the coronal plane with axial and sagittal planes in opportunistic screening of osteoporosis using computed tomography (CT). MATERIALS AND METHODS: A total of 100 patients aged ≥ 50 years who underwent both lumbar spine CT and dual-energy X-ray absorptiometry within 3 months were included. Osteoporosis was diagnosed based on dual-energy X-ray absorptiometry results. The CT number was measured at the center of the vertebral body in coronal, axial, and sagittal planes. To compare the coronal plane with axial and sagittal planes in diagnosing osteoporosis, the areas under the receiver operating characteristic curve (AUC) were compared and intraclass correlation coefficient (ICC) was calculated. The optimal cutoff values were calculated using Youden's index. RESULTS: The AUC of the coronal plane (0.80; 95% confidence interval [CI], 0.71-0.89) was not significantly different from that of the axial plane (0.78; 95% CI, 0.68-0.87; P = 0.39) and that of the sagittal plane (0.78; 95% CI, 0.69-0.87; P = 0.68). Excellent concordance rates were observed between coronal and axial planes with ICC of 0.95 (95% CI, 0.92-0.96) and between coronal and sagittal planes with ICC of 0.93 (95% CI, 0.85-0.96). The optimal cutoff values for the coronal, axial, and sagittal planes were 110, 112, and 112 HU, respectively. CONCLUSION: The coronal plane does not significantly differ from axial and sagittal planes in opportunistic screening of osteoporosis. Thus, the coronal plane as well as axial and sagittal planes can be used interchangeably in measuring bone mineral density using CT.

Biochemical and molecular docking-based strategies of Acalypha indica and Boerhavia diffusa extract by targeting bacterial strains and cancer proteins.

Antibiotic-resistant microbes have emerged around the world, presenting a risk to health. Plant-derived drugs have become a potential source for the production of antibiotic-resistant drugs and cancer therapies. In this study, we investigated the antibacterial, cytotoxic and antioxidant properties of Acalypha indica and Boerhavia diffusa, and conducted in silico molecular docking experiments against EGFR and VEGFR-2 proteins. The metabolic extract of A. indica inhibited Streptococcus iniae and Staphylococcus sciuri with inhibition zones of 21.66 ± 0.57 mm and 20.33 ± 0.57 mm, respectively. The B. diffusa leaf extract produced inhibition zones of 20.3333 ± 0.5773 mm and 20.33 ± 0.57 mm against Streptococcus iniae and Edwardsiella anguillarum, respectively. A. indica and B. diffusa extracts had toxicities of 162.01 µg/ml and 175.6 µg/ml, respectively. Moreover, B. diffusa (IC50 =154.42 µg/ml) leaf extract exhibited moderately higher antioxidant activity compared with the A. indica (IC50 = 218.97 µg/ml) leaf extract. Multiple interactions were observed at Leu694, Met769 and Leu820 sites for EGFR and at Asp1046 and Cys1045 sites for VEGFR during the molecular docking study. CID-235030, CID-70825 and CID-156619353 had binding energies of -7.6 kJ/mol, -7.5 kJ/mol and -7.6 kJ/mol, respectively, with EGFR protein. VEGFR-2 protein had docking energies of -7.5 kJ/mol, -7.6 kJ/mol and -7.3 kJ/mol, respectively, for CID-6420353, CID-156619353 and CID-70825 compounds. The MD simulation trajectories revealed the hit compound; CID-235030 and EGFR complex, CID-6420353 and VEGFR-2 exhibit stable profile in the root mean square deviation (RMSD), radius of gyration (Rg), solvent accessible surface area (SASA), hydrogen bond and root mean square fluctuation (RMSF) and the binding free energy by MM-PBSA method. This study indicates that methanol extracts of A. indica and B. diffusa may play a crucial role in developing antibiotic-resistant and cancer drugs.Communicated by Ramaswamy H. Sarma.

Trampoline Stiffness Estimation by Using Robotic System for Quantitative Evaluation of Jumping Exercises.

Trampolines are recognized as a valuable tool in exercise and rehabilitation due to their unique properties like elasticity, rebound force, low-impact exercise, and enhancement of posture, balance, and cardiopulmonary function. To quantitatively assess the effects of trampoline exercises, it is essential to estimate factors such as stiffness, elements influencing jump dynamics, and user safety. Previous studies assessing trampoline characteristics had limitations in performing repetitive experiments at various locations on the trampoline. Therefore, this research introduces a robotic system equipped with foot-shaped jigs to evaluate trampoline stiffness and quantitatively measure exercise effects. This system, through automated, repetitive movements at various locations on the trampoline, accurately measures the elastic coefficient and vertical forces. The robot maneuvers based on the coordinates of the trampoline, as determined by its torque and position sensors. The force sensor measures data related to the force exerted, along with the vertical force data at X, Y, and Z coordinates. The model's accuracy was evaluated using linear regression based on Hooke's Law, with Mean Absolute Error (MAE), Root Mean Square Error (RMSE), and Correlation Coefficient Squared (R-squared) metrics. In the analysis including only the distance between X and the foot-shaped jigs, the average MAE, RMSE, and R-squared values were 17.9702, 21.7226, and 0.9840, respectively. Notably, expanding the model to include distances in X, Y, and between the foot-shaped jigs resulted in a decrease in MAE to 15.7347, RMSE to 18.8226, and an increase in R-squared to 0.9854. The integrated model, including distances in X, Y, and between the foot-shaped jigs, showed improved predictive capability with lower MAE and RMSE and higher R-squared, indicating its effectiveness in more accurately predicting trampoline dynamics, vital in fitness and rehabilitation fields.

Minimally Invasive Open Reduction and Maintenance Technique for Anterior Sacrococcygeal Dislocation: A Case Report.

Anterior dislocation of the coccyx is rare, but it can occur due to trauma. Conservative treatment is usually performed. However, dislocation reduction may be required to control severe pain in the acute phase or to prevent chronic complications. If manual reduction fails, open reduction is required. The extent of the incision and the method used to maintain the reduction should be considered during open reduction. A 56-year-old male patient experienced a dislocation of the sacrococcygeal joint after falling backwards. Despite conservative treatment, the patient complained of persistent pain during sitting and when using the bathroom. A manual reduction was attempted but failed. We performed joystick reduction via minimal incision and maintained the reduction using a one-strand trans-osseous suture passing through the skin. The patient was advised to use a soft cushion when sitting or lying down for four weeks after surgery. The supine position was not restricted. The patient's symptoms significantly improved after surgery. At the 6-month follow-up, the sacrococcygeal joint showed good alignment and no surgical complications occurred. During the treatment of sacrococcygeal dislocation, the rapid alleviation of acute pain and minimizing potential complications are key points. If open reduction is needed, the minimally invasive reduction technique with a one-strand trans-osseous suture may offer patient satisfaction and a good surgical outcome.

Natural course of chronic subdural hematoma following surgical clipping of unruptured intracranial aneurysm by pterional approach.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a neurological complication following clipping surgery. However, the natural course and ideal approach for the treatment of clipping-related-CSDH (CR-CSDH) have not been clearly established. We aimed to investigate the course of CR-CSDH using chronological radiological findings. METHODS: We performed a retrospective analysis of 28 (3.8%) patients who developed CSDH among 736 patients who underwent surgical clipping using pterional approach for unruptured aneurysms at our institution between December 2010 and December 2018. Patients underwent follow-up CT scan 6-8 weeks after clipping surgery and decision to pursue surgical intervention rests upon the patient's symptom based on the Markwalder's grading scale (MGS) and numeric rating scale (NRS). RESULTS: Of the 28 patients, 3 patients (10.7%) underwent surgery, while 25 (89.2%) showed spontaneous resolution of CR-CSDH. Eighteen patients (64.2%) had mild headache with MGS of 0-1. The mean maximum hematoma volume was 41.9±30.9 ml (5.8-135 ml), and 26 patients (92.8%) had homogeneous hematoma. The mean time to hematoma resolution was 126.7±52.9 days (46-228 days). Comparing group of CR-CSDH volume ≥43 ml or a midline shift ≥5 mm, the difference in presence of linear low-density area (p=0.002) and age (p=0.026) between the conservative and operative groups were found to be statistically significant. CONCLUSIONS: Most CR-CSDH cases spontaneously resolved within 4 months. Therefore, we suggest that close observation should be performed if patient's symptoms are mild and special radiologic findings are present, despite its relatively large volume and midline shifting.

Indirect Decompression of Osteoporotic Vertebral Compression Fracture Using Intraoperative Motor Evoked Potential Monitoring-Guided Ligamentotaxis.

Osteoporotic vertebral compression fractures have become common in aging societies and can lead to a decreased quality of life with severe back pain and neurological deficits. Traditional direct decompression and stabilization surgeries can produce sufficient decompression and provide good results. However, after surgical treatment, some elderly patients with numerous chronic diseases often experience severe postoperative complications owing to the long surgery duration and massive bleeding. Therefore, to prevent perioperative morbidity, other surgical methods that simplify the surgical process and reduce the operation time are required. Herein, we describe a case of indirect decompression using ligamentotaxis and sequential anabolic agents. To examine their effectiveness during surgery, we monitored intraoperative motor-evoked potentials. The patient's neurological symptoms improved postoperatively. After the operation, the anabolic agent "romosozumab" was injected monthly to treat osteoporosis, prevent additional fractures, and accelerate posterolateral fusion. On serial follow-up, the anterior body height of the fractured vertebra improved significantly, demonstrating the importance of osteoporosis treatment using anabolic agents. Indirect decompression surgery may have early effects, whereas sequential anabolic agent use may consolidate the long-term effects of surgical treatment.

Different Expression and Clinical Implications of Cancer-Associated Fibroblast (CAF) Markers in Brain Metastases.

Aims: This study assessed the expression and clinical relevance of cancer-asssociated fibroblast (CAF)-related biomarkers in brain metastasis (BM). Moreover, molecular characterization of patient-derived primary CAFs and normal fibroblasts (NFs) was performed. Methods: Sixty-eight patients with BM from various primary cancer types were selected. Immunohistochemistry (IHC) and immunofluorescence (IF) staining were performed to evaluate the expression of various CAF-related biomarkers. CAFs and NFs were isolated from fresh tissues. Results: Various CAF-related biomarkers were expressed in CAFs in BMs of different primary cancers. However, only PDGFR-ß, α-SMA, and collagen type I were associated with BM size. PDGFR-ß and α-SMA were associated with BM recurrence after resection. PDGFR-ß was associated with recurrence-free survival (RFS). Interestingly, high expression of PDGFR-ß and α-SMA was found in the patients with previous chemotherapy or radiotherapy for primary cancer. In primary cell culture, PDGFR-ß and α-SMA were expressed at higher levels in patient-derived CAFs than in NFs or cancer cells. The origins of CAF in BM were presumed to be pericytes of blood vessels, circulating endothelial progenitor cells, or transformed astrocytes of the peritumoral glial stroma. Conclusion: Our results suggest that high expression of CAF-related biomarkers, particularly PDGFR-ß and α-SMA, is associated with poor prognosis and recurrence in patients with BM. With the elucidation of the role and origins of CAF in the tumor microenvironment, CAF can be a new imperative target for BM immunotherapy.

Pathways to post-traumatic growth in Korean female cancer patients: the mediation effects of coping strategies and resilience.

ABSTRACTBackground: Cancer is a life-threatening disease in Korean women. Female cancer patients in Korea have reported poor physical functioning and psychological distress after diagnosis. However, some patients experience post-traumatic growth (PTG), which includes positive feelings and changes.Objective: The main purpose of this study was to examine the relationships between PTG and its associated factors in Korean female cancer patients to understand how female cancer patients achieve PTG while experiencing cancer diagnosis and treatment. This study aimed to improve the quality of life of many Korean female patients with cancer.Methods: This study investigated the structural model of the paths from the disruption of core beliefs (CBD), coping strategies, and resilience to PTG in a sample of female cancer patients. In total, 164 middle-aged women diagnosed with cancer were included in the final sample.Results: First, it was determined that the proposed structural model was substantial and had high fit indices. Second, problem-solving was positively associated by the CBD routes. Third, it was also favorably expected that problem-solving would lead to resilience and resilience would lead to PTG. These findings are important for developing future interventions for Korean female cancer patients and can be considered as an important variable to improve their PTG.

The proposed structural model observed paths of how female cancer patients achieve post-traumatic growth while experiencing cancer diagnosis and treatment.Disruption of core beliefs as a factor positively associates problem-solving in Korean female cancer patients.Problem-solving and resilience as factors positively associate post-traumatic growth in Korean female cancer patients.

Breast Cancer to Meningioma: A Rare Case of Tumor-to-Tumor Metastasis.

Tumor-to-tumor metastasis (TTM) is defined as the hematogenous metastasis within a primary host tumor from a donor neoplasm. Since there is insufficient evidence regarding the pathophysiology, clinical course, and management of TTM, there are no precise guidelines for its management. A 73-year-old female patient diagnosed with breast cancer was found to have convexity meningioma. Since the size of tumor and peritumoral brain edema increased during follow-up period, the meningioma was treated with surgical resection. Postoperatively, histopathologic examination confirmed metastasis of invasive ductal carcinoma within a secretory meningioma. The final diagnosis was TTM of breast cancer in meningioma. Here, we report a rare case of intra-meningioma metastasis and a review of literature to provide a better understanding of this rare phenomenon.

Efficacy of 3D-printed simulation models of unruptured intracranial aneurysms in patient education and surgical simulation.

OBJECTIVE: The purpose of this study was to determine the efficacy of a 3D-printed aneurysm simulation model (3DPM) in educating patients and improving physicians' comprehension and performance. METHODS: This prospective study involved 40 patients who were diagnosed with unruptured intracranial aneurysms (UIAs) and scheduled for surgical clipping or endovascular coiling and randomly divided into two groups (the 3DPM group and the non-3DPM group). The 3DPM was used in preoperative consultation with patients and intraoperatively referenced by surgeons. The patients, 7 neurosurgical residents, and 10 surgeons completed questionnaires (5-point Likert scale) to determine the usefulness of the 3DPM. RESULTS: Patients in the 3DPM group had significantly higher scores in terms of their understanding of the disease (mean 4.85 vs. 3.95, p<0.001) and the treatment plan (mean 4.85 vs. 4.20, p=0.005) and reported higher satisfaction during consultation (5.0 vs. 4.60, p=0.036) than patients in the non-3DPM group. During patient consultation, 3DPMs were most useful in improving doctor-patient communication (mean 4.57, range 4-5). During clipping surgery, the models were most useful in assessing adjacent arteries (mean 4.9, range 4-5); during endovascular coiling, they were especially helpful in microcatheter shaping (mean 4.7, range 4-5). CONCLUSIONS: In general, 3DPMs are beneficial in educating patients and improving the physician's performance in terms of surgical clipping and endovascular coiling of UIAs.

Does the Surgical Approach Matter in Treating Odontoid Fractures? A Comparison of Mechanical Complication Rates Between Anterior Versus Posterior Surgical Approaches: A Meta-Analysis and Systematic Review.

Objective: Odontoid fractures are treated surgically through the anterior or posterior approach. Each surgical approach has its advantages and disadvantages, so the preferred approach remains debatable. There are few meta-analyses or systemic reviews on the mechanical complications of surgical treatment for odontoid fractures. This meta-analysis aimed to compare the operation-related morbidity, including mechanical complications, and mortality of patients with odontoid fractures, treated via the anterior or posterior approach. Methods: A systematic search was performed on PubMed/Medline, Embase, and the Cochrane Library for the studies up to October 2023 on the complication rate of the surgical treatment of odontoid fractures, related to the surgical approach. The risk ratios (RR) with the 95% confidence intervals (CIs) were pooled to assess the mechanical complication rates, other complications, revision surgery, and mortality, depending on the surgical approach. Results: A total of 1,519 studies were retrieved using the search strategy, and 782 patients from 15 articles were included in this meta-analysis. Mechanical complications were significantly more frequent in the anterior surgical group with low heterogeneity. The incidences of fracture nonunion and revision surgery were also higher in the anterior surgery group. However, there was no significant difference in systemic complications and mortality rates between the two groups. Conclusion: The posterior approach was more advantageous than the anterior approach in terms of mechanical complications, fusion rates, and incidence of revision surgery. However, further studies, should be performed to strengthen these results.

Rapid-Growing Intracranial Immature Teratoma Presenting Obstructive Hydrocephalus and Abducens Nerve Palsy: A Case Report and Literature Review.

Intracranial immature teratoma is an extremely rare disease with poor prognosis and requires complicated treatment. Owing to the deep midline location of the tumor, total surgical resection of the tumor is challenging. We present our experience with a fast-growing pineal gland immature teratoma in a 4-year-old boy, who presented with obstructive hydrocephalus and abducens nerve palsy, which was treated with total surgical resection of the tumor. In addition, we aimed to determine the appropriate treatment modality for intracranial immature teratomas by reviewing the literature and investigating the prognosis.

Subtrochanteric Insufficiency Fracture Occurring 5 Years after Surgery at the Steinmann Pin Insertion Site for Fracture Reduction.

Background and Objectives: Steinmann pins are commonly used in orthopedics, with a low rate of complications. However, thermal osteonecrosis may occur when a pin is inserted using a drill. There have been no reports on late-onset fractures at the Steinmann pin insertion site. Materials and Methods: A 32-year-old man who underwent surgery for a femoral shaft fracture 5 years ago complained of proximal thigh pain 1 month after the removal of the internal device. On physical examination, the patient showed a limping gait due to pain, and tenderness was observed on the lateral aspect of the proximal thigh. Magnetic resonance imaging was performed because the symptoms did not improve, despite conservative treatment. A new fracture line was observed in the lateral cortical bone of the proximal femur. It was found that a fracture occurred at the site where the Steinmann pin was inserted for a closed reduction at the time of the first operation. The patient was instructed to limit weight bearing and to use crutches while walking. Parathyroid hormone was additionally administered to promote bone formation. Results: Six months after diagnosis, a complete union was achieved at the subtrochanteric fracture site, and the patient's pain subsided. Conclusions: A fracture that occurs as a late onset at the provisional Steinmann pin insertion site is an extremely rare complication; however, orthopedic surgeons must consider this possibility and make more efforts to lower the occurrence of thermal damage. In addition, if the patient complains of pain in the region where the pin was inserted after surgery, surgeons should spare no effort to determine whether a new fracture has occurred.

Clinical outcomes of rescue stenting for failed endovascular thrombectomy: a multicenter prospective registry.

BACKGROUND: Mechanical thrombectomy (MT) is a primary endovascular modality for acute intracranial large vessel occlusion. However, further treatment, such as rescue stenting, is occasionally necessary for refractory cases. We aimed to investigate the efficacy and safety of rescue stenting in first-line MT failure and to identify the clinical factors affecting its clinical outcome. METHODS: A multicenter prospective registry was designed for this study. We enrolled consecutive patients who underwent rescue stenting for first-line MT failure. Endovascular details and outcomes, follow-up patency of the stented artery, and clinical outcomes were summarized and compared between the favorable and unfavorable outcome groups. RESULTS: A total of 78 patients were included. Intracranial atherosclerotic stenosis was the most common etiology for rescue stenting (97.4%). Seventy-seven patients (98.7%) were successfully recanalized by rescue stenting. A favorable outcome was observed in 66.7% of patients. Symptomatic intracranial hemorrhage and mortality were observed in 5.1% and 4.0% of patients, respectively. The stented artery was patent in 82.1% of patients on follow-up angiography. In a multivariable analysis, a patent stent on follow-up angiography was an independent factor for a favorable outcome (OR 87.6; 95% CI 4.77 to 1608.9; p=0.003). Postprocedural intravenous maintenance of glycoprotein IIb/IIIa inhibitor was significantly associated with the follow-up patency of the stented artery (OR 5.72; 95% CI 1.45 to 22.6; p=0.013). CONCLUSIONS: In this multicenter prospective registry, rescue stenting for first-line MT failure was effective and safe. For a favorable outcome, follow-up patency of the stented artery was important, which was significantly associated with postprocedural maintenance of glycoprotein IIb/IIIa inhibitors.

Transcriptomic analysis of effects of 1-methylcyclopropene (1-MCP) and ethylene treatment on kiwifruit (Actinidia chinensis) ripening.

Ethylene (ET) is a gaseous phytohormone with a crucial role in the ripening of many fruits, including kiwifruit (Actinidia spp.). Meanwhile, treatment with 1-methylcyclopropene (1-MCP), an artificial ET inhibitor delays the ripening of kiwifruit. The objective of this study was to determine the effect of ET and 1-MCP application during time-course storage of kiwifruit. In addition, we aimed to elucidate the molecular details underlying ET-mediated ripening process in kiwifruit. For this purpose, we conducted a time-course transcriptomic analysis to determine target genes of the ET-mediated maturation process in kiwifruit during storage. Thousands of genes were identified to be dynamically changed during storage and clustered into 20 groups based on the similarity of their expression patterns. Gene ontology analysis using the list of differentially expressed genes (DEGs) in 1-MCP-treated kiwifruit revealed that the identified DEGs were significantly enriched in the processes of photosynthesis metabolism and cell wall composition throughout the ripening process. Meanwhile, ET treatment rapidly triggered secondary metabolisms related to the ripening process, phenylpropanoid (e.g. lignin) metabolism, and the biosynthesis of amino acids (e.g. Phe, Cys) in kiwifruit. It was demonstrated that ET biosynthesis and signaling genes were oppositely affected by ET and 1-MCP treatment during ripening. Furthermore, we identified a ET transcription factor, AcEIL (Acc32482) which is oppositely responsive by ET and 1-MCP treatment during early ripening, potentially one of key signaling factor of ET- or 1-MCP-mediated physiological changes. Therefore, this transcriptomic study unveiled the molecular targets of ET and its antagonist, 1-MCP, in kiwifruit during ripening. Our results provide a useful foundation for understanding the molecular details underlying the ripening process in kiwifruit.

Policosanol attenuates Pi-induced calcification via AMPK-mediated INSIGs expression in rat VSMCs.

Policosanol is a hypocholesterolemic derived from sugar cane and corn that downregulates blood cholesterol levels. It can further lower blood pressure and reduce liver inflammation. Policosanol can also affect vascular calcification, however, its molecular mechanisms are not well understood. This study investigated the effect of policosanol on vascular calcification and its molecular mechanism. Policosanol decreased the expression of inorganic phosphate (Pi)-induced osteogenic genes such as distal-less homeobox 5 (Dlx5) and runt-related transcription factor 2 (Runx2). In addition, following policosanol treatment, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation increased in a time-dependent manner. The constitutively active form of AMPK (CA-AMPK) dramatically suppressed Pi-induced Dlx5 and Runx2 protein levels. Inactivation of AMPK using compound C (Com. C; AMPK inhibitor) recovered policosanol-suppressed Alizarin Red S staining levels. Insulin-induced genes (INSIGs) were induced by CA-AMPK, their overexpression suppressed Pi-induced Dlx5 and Runx2 expression. Taken together, the results demonstrate that policosanol inhibits Pi-induced vascular calcification by regulating AMPK-induced INSIG expression in vascular smooth muscle cells.

NSrp70 is a lymphocyte-essential splicing factor that controls thymocyte development.

Alternative pre-mRNA splicing is a critical step to generate multiple transcripts, thereby dramatically enlarging the proteomic diversity. Thus, a common feature of most alternative splicing factor knockout models is lethality. However, little is known about lineage-specific alternative splicing regulators in a physiological setting. Here, we report that NSrp70 is selectively expressed in developing thymocytes, highest at the double-positive (DP) stage. Global splicing and transcriptional profiling revealed that NSrp70 regulates the cell cycle and survival of thymocytes by controlling the alternative processing of various RNA splicing factors, including the oncogenic splicing factor SRSF1. A conditional-knockout of Nsrp1 (NSrp70-cKO) using CD4Cre developed severe defects in T cell maturation to single-positive thymocytes, due to insufficient T cell receptor (TCR) signaling and uncontrolled cell growth and death. Mice displayed severe peripheral lymphopenia and could not optimally control tumor growth. This study establishes a model to address the function of lymphoid-lineage-specific alternative splicing factor NSrp70 in a thymic T cell developmental pathway.

Cell-permeable transgelin-2 as a potent therapeutic for dendritic cell-based cancer immunotherapy.

BACKGROUND: Transgelin-2 is a 22 kDa actin-binding protein that has been proposed to act as an oncogenic factor, capable of contributing to tumorigenesis in a wide range of human malignancies. However, little is known whether this tiny protein also plays an important role in immunity, thereby keeping body from the cancer development and metastasis. Here, we investigated the functions of transgelin-2 in dendritic cell (DC) immunity. Further, we investigated whether the non-viral transduction of cell-permeable transgelin-2 peptide potentially enhance DC-based cancer immunotherapy. METHODS: To understand the functions of transgelin-2 in DCs, we utilized bone marrow-derived DCs (BMDCs) purified from transgelin-2 knockout (Tagln2-/-) mice. To observe the dynamic cellular mechanism of transgelin-2, we utilized confocal microscopy and flow cytometry. To monitor DC migration and cognate T-DC interaction in vivo, we used intravital two-photon microscopy. For the solid and metastasis tumor models, OVA+ B16F10 melanoma were inoculated into the C57BL/6 mice via intravenously (i.v.) and subcutaneously (s.c.), respectively. OTI TCR T cells were used for the adoptive transfer experiments. Cell-permeable, de-ubiquitinated recombinant transgelin-2 was purified from Escherichia coli and applied for DC-based adoptive immunotherapy. RESULTS: We found that transgelin-2 is remarkably expressed in BMDCs during maturation and lipopolysaccharide activation, suggesting that this protein plays a role in DC-based immunity. Although Tagln2-/- BMDCs exhibited no changes in maturation, they showed significant defects in their abilities to home to draining lymph nodes (LNs) and prime T cells to produce antigen-specific T cell clones, and these changes were associated with a failure to suppress tumor growth and metastasis of OVA+ B16F10 melanoma cells in mice. Tagln2-/- BMDCs had defects in filopodia-like membrane protrusion and podosome formation due to the attenuation of the signals that modulate actin remodeling in vitro and formed short, unstable contacts with cognate CD4+ T cells in vivo. Strikingly, non-viral transduction of cell-permeable, de-ubiquitinated recombinant transgelin-2 potentiated DC functions to suppress tumor growth and metastasis. CONCLUSION: This work demonstrates that transgelin-2 is an essential protein for both cancer and immunity. Therefore, transgelin-2 can act as a double-edged sword depending on how we apply this protein to cancer therapy. Engineering and clinical application of this protein may unveil a new era in DC-based cancer immunotherapy. Our findings indicate that cell-permeable transgelin-2 have a potential clinical value as a cancer immunotherapy based on DCs.