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Background: This study aimed to determine the relationship between resistive indices (RIs) and changes in prostate size after medical treatment in patients with benign prostatic hyperplasia (BPH). Methods: A total of 86 patients with BPH were included in the study, excluding 42 patients with a total prostate volume (TPV) of

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

Purpose: There is no consensus on the optimal duration of preoperative antibiotic treatment prior to ureteroscopic lithotripsy in patients presenting with urolithiasis-induced obstructive acute pyelonephritis (APN). We aimed to identify surgeon-modifiable, preoperative risk factors associated with postoperative systemic inflammatory response syndrome (SIRS) in these patients. Materials and Methods: This multicenter retrospective study evaluated 115 patients who presented with urolithiasis-induced obstructive APN between January 2008 and December 2019. All patients were administered intravenous third-generation cephalosporin until culture sensitivity confirmation or until ureteroscopic lithotripsy. Data were collected for age, sex, diabetes mellitus, performance status, stone features, hydronephrosis grade, preoperative renal collecting system drainage, laboratory data, operative time, and duration of preoperative antibiotic treatment. Sensitivity analysis using Youden's index and logistic regression analysis were used to assess risk factors of postoperative SIRS. Results: Postoperative SIRS was identified in 32 (27.8%) patients. The incidence of postoperative SIRS was higher in patients who received preoperative antibiotic treatment for fewer than 14 days (38.8% vs. 12.5%; p=0.001). Backward variable selection logistic regression analysis revealed maximal stone diameter ≥15 mm, duration of preoperative antibiotic treatment

Background Lymph node fine-needle aspiration (LN FNA) cytology indicates necrosis in various diseases. Dominant necrotic features make the diagnosis of underlying conditions very difficult. Methods We retrospectively reviewed 460 patients who underwent cervical LN aspiration cytology that revealed necrotic findings at Keimyung University Dongsan Hospital in Daegu, Korea, from 2003–2017. Each specimen was evaluated and analyzed in association with the clinical findings, biopsy findings, and/or other ancillary tests, including acid-fast bacilli staining and molecular testing for Mycobacterium tuberculosis. Results When necrotic features were noted upon cervical LN FNA cytology, the most common pathologic LN FNA category was necrosis alone (31.5%). The second most common category was granulomatous inflammation (31.3%), followed by Kikuchi disease (20.0%) and malignant neoplasm (8.7%). In cases where the cervical LN FNA revealed necrosis alone, the most common final diagnosis was tuberculosis. In young patients, Kikuchi disease should be considered as one cervical LN FNA category, while metastatic carcinoma should be suspected in older patients. Conclusions Even when necrosis alone is observed in LN FNA cytology, it is important to determine the cause through further evaluation.

Purpose: To analyze the efficacy and safety of standard-dose antimuscarinic treatment on male patients with overactive bladder (OAB) symptoms showing poor efficacy after low-dose antimuscarinics. Materials and Methods: We retrospectively reviewed the data of 566 male patients aged ≥40 with OAB symptoms between January 2017 and June 2018. They were treated with low-dose antimuscarinics for at least 4 weeks and showed poor efficacy; therefore, they were switched to standard dose antimuscarinic treatment (5 mg of solifenacin) for ≥12 weeks. The international prostate symptom score (IPSS) and overactive bladder symptom score (OABSS) at baseline (V0), 4 weeks (V1), and 12 weeks (V2) were analyzed. Post void residual urine volume (PVR) was also recorded. Results: The median age, body mass index, and prostate-specific antigen levels were 69.0 years, 24.2 kg/m2, and 1.24 ng/dL, respectively. The mean value of the total IPSS and OABSS significantly decreased between V0 and V2 (from 16.73 to 13.69 and 7.33 to 5.34, respectively, all p

Purpose: To compare the efficacies of mirabegron 50 mg addition after alpha-adrenoreceptor blocker in terms of reducing storage symptoms in patients with BPH. Materials and Methods: Fifty-eight patients that had been taking alpha-adrenoreceptor blocker for more than 8 weeks, but had an OABSS of greater than 3 points, were initially enrolled. One group added any alpha-adrenoreceptor blocker with mirabegron 50 mg (n=39; the mirabegron group) and the other group received alpha-adrenoreceptor blocker only (n=19; the control group) for 8 weeks. Results: In the control group, mean total IPSS decreased from 15.7 to 13.1 (p=0.298) and in mirabegron group, mean total IPSS decreased from 19.4 to 16.5 (p=0.024). Mean storage symptom scores reduced in the control and mirabegron groups from 8.5 to 7.9 (p=0.584) and from 9.1 to 7.6 (p=0.015), respectively, and mean QoL scores from 3.7 to 3.1 (p=0.052) and 3.6 to 3.2 (p=0.027), respectively. Mean overall OABSS in the control and mirabegron groups reduced from 8.4 to 7.2 (p=0.173) and from 8.8 to 7.3, respectively (p=0.005); mean OABSS Q3 from 3.6 to 2.9 (p=0.073) and from 3.5 to 2.7 (p=0.002), respectively; and mean OABSS Q4 from 2.4 to 2.0 (p=0.306) and from 2.7 to 2.0 (p=0.016), respectively. The change of mean Qmax and PVR was insignificant in 2 groups. Conclusions: IPSS total scores, storage symptom scores, QoL, overall OABSS, OABSS Q3 and Q4 were more improved significantly by alpha-adrenoreceptor blocker with mirabegron 50 mg in BPH patients with persistent overactive symptoms. Mirabegron 50 mg addition is considered to patients with persistent storage symptoms after alpha-adrenoreceptor blocker.

Schisandra chinensis (Turcz.) Baill. has been traditionally used as a medicine for bronchial tube ailments in Northeast Asia. Recently, the demand for S. chinensis has increased for use as food and medicine because of the lignans found in its fruits. However, the species germplasm collection has rarely been studied to evaluate their phenotypic traits in Korea. In this study, 96 accessions of S. chinensis were collected in South Korea for two years to evaluate their phenotypes, and principal component analysis (PCA) and cluster analysis were conducted. Significant variations among the measured phenotypic traits were observed. The total bunch weight produced from a single tree ranged from 109 to 5844 g; the contents in schizandrin, gomisin A, and gomisin N—three types of lignan—were 2.2–14.5, 0.9–9.8, and 2.1–12.2 mg/g, respectively. Gomisin N positively correlated with flowering traits (flowering start, period, and peduncle length) and leaf characteristics (leaf width and length). PCA and cluster analyses revealed four clusters among the 96 S. chinensis accessions. These results provide valuable information for systematic characterization of species germplasm collections and tools for further research.

Abstract Background It has been suggested that the anterolateral ligament (ALL) is an important anterolateral stabilizer of the knee joint which functions to prevent anterolateral subluxation and anterior subluxation at certain flexion angles in the knee. Purpose To analyze and systematically interpret the biomechanical function of the ALL. Methods An online search was conducted for human cadaveric biomechanical studies that tested function of the ALL in resisting anterolateral subluxation and anterior subluxation of the knee. Two reviewers independently searched Medline, Embase, and the Cochrane Database of Systematic Reviews for studies up to 25 September 2018. Biomechanical studies not reporting the magnitude of anterior tibial translation or tibial internal rotation in relation to the function of the ALL were excluded. Results Twelve biomechanical studies using human cadavers evaluating parameters including anterior tibial translation and/or internal tibial rotation in anterior cruciate ligament (ACL)-sectioned and ALL-sectioned knees were included in the review. Five studies reported a minor increase or no significant increase in anterior tibial translation and internal tibial rotation with further sectioning of the ALL in ACL-deficient knees. Five studies reported a significant increase in knee laxity in tibial internal rotation or pivot shift with addition of sectioning the ALL in ACL-deficient knees. Two studies reported a significant increase in both anterior tibial translation and internal tibial rotation during application of the anterior-drawer and pivot-shift tests after ALL sectioning. Conclusion There was inconsistency in the biomechanical characteristics of the ALL of the knee in resisting anterolateral and anterior subluxation of the tibia.

We screened acid soil-tolerant wild soybean (Glycine soja Sieb. and Zucc.) accessions and evaluated their agronomic and tolerant performance under acid sulfate soil (ASS) conditions. Only three accessions, J-13, J-19 and J-55, among 381 G. soja accessions obtained from G. soja Germplasm Collection of Japan, were identified as having strong tolerance by the acid soil toxicity score (ATS) at soil pH 3.3. These three tolerant G. soja accessions showed significantly lower aluminum (Al), iron (Fe) and manganese (Mn) contents in the aboveground part than the intolerant ones in 0.25 lime requirement (LR) conditions (pH 3.8). Aboveground dry matter weights (DW) and seed yields of three tolerant G. soja accessions, except seed yield of a tolerant accession J-55, were also significantly higher than intolerant ones under the 0.25 LR condition. This clearly indicates that lower contents of toxic mineral in the ASS-tolerant G. soja led to higher macro-nutrient uptake, DW, and seed yields. We conclude that the three tolerant G. soja accessions identified in the present study possess high levels of tolerance to the soil acidity and Al-excess soil conditions, and could be valuable genetic resources for soybean improvement programs.

Restoration of neutral mechanical alignment of the lower limb is an important factor in the treatment of unicompartmental arthrosis. Traditionally, medial opening wedge high tibial osteotomy has been widely performed to correct varus malalignment with unicompartmental arthrosis. However, an ideal indication for the high tibial osteotomy is the knee with metaphyseal tibial varus malalignment. The basic principle of corrective osteotomy is performing an osteotomy at the center of the deformity to prevent abnormal joint line obliquity. If pathologic distal femoral varus deformity is the cause of genu varum, the osteotomy should be performed in the distal femur. Reports of medial opening wedge distal femoral osteotomy (DFO) to correct varus malalignment are rare. We present a case of this very rare and challenging condition in a 47-year-old male, which was successfully treated by medial opening wedge DFO. [ABSTRACT FROM AUTHOR]

Spirulina maxima is a microalgae which contains flavonoids and other polyphenols. Although Spirulina maxima 70% ethanol extract (SM70EE) has diverse beneficial effects, its effects on neurotoxicity have not been fully understood. In this study, we investigated the neuroprotective effects of SM70EE against trimethyltin (TMT)-induced neurotoxicity in HT-22 cells. SM70EE inhibited the cleavage of poly-ADP ribose polymerase (PARP). Besides, ROS production was decreased by down-regulating oxidative stress-associated enzymes. SM70EE increased the factors of brain-derived neurotrophic factor (BDNF)/cyclic AMP-responsive element-binding protein (CREB) signalling pathways. Additionally, acetylcholinesterase (AChE) was suppressed by SM70EE. Furthermore, we investigated whether SM70EE prevents cognitive deficits against scopolamine-induced neurotoxicity in mice by applying behavioral tests. SM70EE increased step-through latency time and decreased the escape latency time. Therefore, our data suggest that SM70EE may prevent TMT neurotoxicity through promoting activation of BDNF/CREB neuroprotective signaling pathways in neuronal cells. In vivo study, SM70EE would prevent cognitive deficits against scopolamine-induced neurotoxicity in mice. [ABSTRACT FROM AUTHOR]

Ferulic acid (FA) is phenolic compound found in fruits. Many studies have reported that FA has diverse therapeutic effects against metabolic diseases. However, the mechanism by which FA modulates adipogenesis via the expression of heme oxygenase-1 (HO-1) implicated in suppression of adipocyte differentiation is not fully understood.We investigated whether HO-1 can be activated by FA and suppress adipogenic factors in 3T3-L1. Our results showed that FA suppresses triglyceride-synthesizing enzymes, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). We observed that the expression of CCAAT/enhancer binding protein γ (C/EBPγ) and peroxisome proliferator-activated receptor (PPAR ) were suppressed by FA. In addition, HO-1 inhibitor stimulated lipid accumulation, while FA attenuated lipid accumulation in 3T3-L1 treated with HO-1 inhibitor. We also observed that the expression of HO-1 had the same tendency as C/EBP homologous protein 10 (CHOP10) during the mitotic clonal expansion (MCE) of adipogenesis. We next employed siRNA against HO-1 to clarify whether HO-1 regulates CHOP10. The results indicated that CHOP10 is downstream of HO-1. Furthermore, FA-mediated HO-1/CHOP10 axis activation prevented the initiation of MCE. Therefore, we demonstrated that FA is a positive regulator of HO-1 in 3T3-L1, and may be an effective bioactive compound to reduce adipocyte tissue mass. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare the clinical outcomes of arthroscopic anatomical double bundle (DB) anterior cruciate ligament (ACL) reconstruction with either selective anteromedial (AM) or posterolateral (PL) bundle reconstruction while preserving a relatively healthy ACL bundle. Materials and Methods: The authors evaluated 98 patients with a mean follow-up of 30.8±4.0 months who had undergone DB or selective bundle ACL reconstructions. Of these, 34 cases underwent DB ACL reconstruction (group A), 34 underwent selective AM bundle reconstruction (group B), and 30 underwent selective PL bundle reconstructions (group C). These groups were compared with respect to Lysholm and International Knee Documentation Committee (IKDC) score, side-to-side differences of anterior laxity measured by KT-2000 arthrometer at 30 lbs, and stress radiography and Lachman and pivot shift test results. Pre- and postoperative data were objectively evaluated using a statistical approach. Results: The preoperative anterior instability measured by manual stress radiography at 90° of knee flexion in group A was significantly greater than that in groups B and C (all p<0.001). At last follow-up, mean side-to-side instrumented laxities measured by the KT-2000 and manual stress radiography were significantly improved from preoperative data in all groups (all p<0.001). There were no significant differences between the three groups in anterior instability measured by KT-2000 arthrometer, pivot shift, or functional scores. Conclusion: Selective bundle reconstruction in partial ACL tears offers comparable clinical results to DB reconstruction in complete ACL tears. [ABSTRACT FROM AUTHOR]

The demand for an accurate and accessible image segmentation to generate 3D models from CT scan data has been increasing as such models are required in many areas of orthopedics. In this paper, to find the optimal image segmentation to create a 3D model of the knee CT data, we compared and validated segmentation algorithms based on both objective comparisons and finite element (FE) analysis. For comparison purposes, we used 1 model reconstructed in accordance with the instructions of a clinical professional and 3 models reconstructed using image processing algorithms (Sobel operator, Laplacian of Gaussian operator, and Canny edge detection). Comparison was performed by inspecting intermodel morphological deviations with the iterative closest point (ICP) algorithm, and FE analysis was performed to examine the effects of the segmentation algorithm on the results of the knee joint movement analysis. [ABSTRACT FROM AUTHOR]

Sphingosine analogues display immunosuppressive activities and thus have therapeutic potential in the treatment of autoimmune diseases. In this study, we investigated the effects of the sphingosine analogue AAL-R (FTY720 derivative) on dendritic cell (DC) response upon TLR stimulation. Unlike its known immunosuppressive activity, AAL-R increased TLR7-mediated DC responses by elevating the levels of MHC class I and costimulatory molecules and type IFFN expression and by enhancing the capacity of DCs to induce CD8+ T cell proliferation. Importantly, the stimulatory activity of AAL-R was dependent on type I IFN signaling, as type I IFN receptor-deficient DCs failed to respond to AAL-R. Also, AAL-R activated p38 MAPK to increase type I IFN synthesis and TLR7-mediated DC maturation. These findings enhance our understanding of sphingosine regulation of the host immune system, in particular upon pathogenic infections. [ABSTRACT FROM AUTHOR]

To evaluate significance of nipple enhancement of Paget’s disease in contrast enhanced (CE) breast MRI. Ten patients of biopsy proven Paget’s disease were included in this study. Preoperative mammogram and ultrasonogram (US) were obtained in all 10 patients, and 8 patients underwent CE breast MRI prior to surgery. Mammographic and US findings were reviewed retrospectively. On MRI, morphology (flattening or asymmetry or thickening) and enhancement of pathologically involved nipple were analyzed comparing with the opposite side, and also reviewed the abnormal enhancing lesion in the breast parenchyma. Morphologic changes of the nipple were detected in 2 out of 10 patients by mammogram and 6 out of 10 patients by US. On MRI, morphologic change was also revealed in 7 patients and abnormal enhancement of involved nipple was observed in all 8 patients. Associated parenchymal enhancing lesions were proved to be DCIS (7 out of 10) and invasive ductal carcinoma (2 out of 10). Remaining one patient had no underlying breast parenchymal malignancy. CE breast MRI allows for the correct detection of nipple involvement of Paget’s disease even when clinical information or mammographic/US findings are not provided. [ABSTRACT FROM AUTHOR]

Sphingosine 1-phosphate (S1P)-metabolizing enzymes regulate the level of sphingolipids and have important biological functions. However, the effects of S1P-metabolizing enzymes on host defense against invading viruses remain unknown. In this study, we investigated the role of S1P-metabolizing enzymes in modulating cellular responses to influenza virus infection. Overexpression of S1P lyase (SPL), which induces the degradation of S1P, interfered with the amplification of infectious influenza virus. Accordingly, SPL-overexpressing cells were much more resistant than control cells to the cytopathic effects caused by influenza virus infection. SPL-mediated inhibition of virus-induced cell death was supported by impairment of the upregulation of the proapoptotic protein Bax, a critical factor for influenza virus cytopathogenicity. Importantly, influenza virus infection of SPL-overexpressing cells induced rapid activation of extracellular signal-regulated kinase (ERK) and STAT1 but not of p38 mitogen-activated protein kinase (MAPK), Akt, or c-Jun N-terminal kinase (JNK). Blockade of STAT1 expression or inhibition of Janus kinase (JAK) activity elevated the level of influenza virus replication in the cells, indicating that SPL protects cells from influenza virus via the activation of JAK/STAT signaling. In contrast to that of SPL, the overexpression of S1P-producing sphingosine kinase 1 heightened the cells' susceptibility to influenza virus infection, an effect that was reversed by the inhibition of its kinase activity, representing opposed enzymatic activity. These findings indicate that the modulation of S1P-metabolizing enzymes is crucial for controlling the host defense against infection with influenza virus. Thus, S1P-metabolizing enzymes are novel potential targets for the treatment of diseases caused by influenza virus infection. [ABSTRACT FROM AUTHOR]

The article investigates the behavior of cinnamate-layered double hydroxide (LDH) hybrid in soils as well as the assessment of its potentials as a green pesticide. Study shows safe intercalation of cinnamate molecules into the interlayer space of LDH inorganic layers through the electrostatic interaction. It demonstrates that the hybridization of natural antibiotic substances with double hydroxides may serve as an alternative for pesticides' green formulation.

AbstractPurpose:This multiinstitutional report assesses the oncologic efficacy of hand-assisted laparoscopic radical nephrectomy (HLRN) compared with open radical nephrectomy (ORN) in patients with localized clear cell renal-cell carcinoma (RCC).Patients and Methods:We analyzed the data from 2561 patients who underwent radical nephrectomy at 26 institutions in Korea between June 1998 and December 2007 for localized RCC. One hundred ninety-seven patients with clear cell RCC in the HLRN group were compared with 917 patients with clear cell RCC in the ORN group. To evaluate the technical adequacy and oncologic outcome, we compared the operative time, estimated blood loss, and 5-year overall and disease-free survival rates.Results:The median follow-up was 36 months for the HLRN group and 27 months for the ORN group. The operative time was significantly longer in the HLRN group than in the ORN group (206.8 ± 68.7 minutes vs. 179.1 ± 61.5 minutes, p< 0.001), and blood loss was significantly lower in the HLRN group than in the ORN group (311.6 ± 238.7 mL vs. 372.4 ± 367.3 mL, p= 0.003). There was no significant difference in pathologic T stage and Fuhrman's nuclear grade in the two groups. No statistically significant difference was found in the 5-year overall (91.2% vs. 90.3%, p= 0.286) and disease-specific (95.2% vs. 92.1%, p= 0.222) survival rates between the HLRN and ORN groups.Conclusions:Despite the longer operative time, HLRN was an effective and less-invasive treatment option for localized clear cell RCC. HLRN could achieve cancer control similar to that obtained with ORN. [ABSTRACT FROM AUTHOR]

Abstract The lymphatic system plays a key role in tissue fluid homeostasis, immune cell trafficking, and fat absorption. We previously reported a bacterial artificial chromosome (BAC)-based lymphatic reporter mouse, where EGFP is expressed under the regulation of the Prox1 promoter. This reporter line has been widely used to conveniently visualize lymphatic vessels and other Prox1-expressing tissues such as Schlemm’s canal. However, mice have a number of experimental limitations due to small body size. By comparison, laboratory rats are larger in size and more closely model the metabolic, physiological, and surgical aspects of humans. Here, we report development of a novel lymphatic reporter rat using the mouse Prox1-EGFP BAC. Despite the species mismatch, the mouse Prox1-EGFP BAC enabled a reliable expression of EGFP in Prox1-expressing cells of the transgenic rats and allowed a convenient visualization of all lymphatic vessels, including those in the central nervous system, and Schlemm’s canal. To demonstrate the utility of this new reporter rat, we studied the contractile properties and valvular functions of mesenteric lymphatics, developed a surgical model for vascularized lymph node transplantation, and confirmed Prox1 expression in venous valves. Together, Prox1-EGFP rat model will contribute to the advancement of lymphatic research as a valuable experimental resource.

Purpose: We report the unusual case of a 63-year-old man with gout and coexisting pseudogout (calcium pyrophosphate dihydrate crystal deposition disease) affecting the same joint. In this report, we describe the clinical features of the patient in addition to the characteristics of the crystals extracted from his affected joint, examined using compensated polarized microscopy. Methods: Synovial fluid and specimens of the lateral meniscus of the patient's knee joint taken during arthroscopy were analyzed using compensated polarized microscopy to evaluate the presence and type of crystals. Results: Compensated polarized microscopy revealed both monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals extracted from the knee joint. Conclusions: Our findings suggest that the coexistence of gout and pseudogout should be considered in the diagnosis of crystal-induced arthritis. Careful crystal evaluation using compensated polarized microscopy may reveal similar cases with MSU and CPPD crystals in the same joint. [ABSTRACT FROM AUTHOR]

Viruses have long been recognized as significant pathogens, contributing to multiple global pandemics throughout human history. Recent examples include the 2009 influenza pandemic and the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. Despite ongoing experimental and clinical efforts, the development of effective antiviral treatments and vaccines remains challenging due to the high mutation rates of many human pathogenic viruses including influenza virus and SARS-CoV-2. As an alternative approach, antiviral strategies targeting host factors shared by multiple viruses could provide a more universally applicable solution. Emerging evidence suggests that viruses exploit the host cytoskeletal network to facilitate efficient viral replication and propagation. Therefore, a comprehensive understanding of the interactions between viral components and the cytoskeletal machinery may offer valuable insights for the development of broad-spectrum antiviral therapeutics. This review compiles and discusses current knowledge on the interactions between viruses and cytoskeletal elements, including kinesin, dynein, myosin, and vimentin, and explores their potential as therapeutic targets. The potential for these cytoskeletal components to serve as targets for new antiviral interventions is discussed in the context of diverse human viruses, including influenza virus, SARS-CoV-2, herpes simplex virus, human papillomavirus, and human immunodeficiency virus.

Several lymphatic reporter mouse lines have recently been developed to significantly improve imaging of lymphatic vessels. Nonetheless, the usage of direct visualization of lymphatic vessels has not been fully explored and documented. Here, we characterized a new Prox1-tdTomato transgenic lymphatic reporter mouse line, and demonstrated how this animal tool enables the researchers to efficiently assess developmental, surgical and pathological lymphangiogenesis by direct visualization of lymphatic vessels. Moreover, we have derived embryonic stem cells from this reporter line, and successfully differentiated them into lymphatic vessels in vivo. In conclusion, these experimental tools and techniques will help advance lymphatic research.

Chronic viral infections are often established by the exploitation of immune-regulatory mechanisms that result in nonfunctional T cell responses. Viruses that establish persistent infections remain a serious threat to human health. Sphingosine kinase 2 (SphK2) generates sphingosine 1-phosphate, which is a molecule known to regulate multiple cellular processes. However, little is known about SphK2's role during the host immune responses to viral infection. Here, we demonstrate that SphK2 functions during lymphocytic choriomeningitis virus Cl 13 (LCMV Cl 13) infection to limit T cell immune pathology, which subsequently aids in the establishment of virus-induced immunosuppression and the resultant viral persistence. The infection of Sphk2-deficient (Sphk2-/-) mice with LCMV Cl 13 led to the development of nephropathy and mortality via T cell-mediated immunopathology. Following LCMV infection, Sphk2-/- CD4+ T cells displayed increased activity and proliferation, and these cells promoted overactive LCMV Cl 13-specific CD8+ T cell responses. Notably, oral instillation of an SphK2-selective inhibitor promoted protective T cell responses and accelerated the termination of LCMV Cl 13 persistence in mice. Thus, SphK2 is indicated as an immunotherapeutic target for the control of persistent viral infections. [ABSTRACT FROM AUTHOR]

Osteoporosis is a common skeletal disease, primarily associated with aging, that results from decreased bone density and bone volume. This reduction significantly increases the risk of fractures in osteoporosis patients compared to individuals with normal bone density. Additionally, the bone regeneration process in these patients is slow, making complete healing difficult. Along with the decline in bone volume and density, osteoporosis is characterized by an increase in marrow adipose tissue (MAT), which is fat within the bone. In this altered bone microenvironment, osteoblasts are influenced by various factors secreted by adipocytes. Notably, saturated fatty acids promote osteoclast activity, inhibit osteoblast differentiation, and induce apoptosis, further reducing osteoblast formation. In contrast, monounsaturated fatty acids inhibit osteoclast formation and mitigate the apoptosis caused by saturated fatty acids. Leveraging these properties, we aimed to investigate the effects of overexpressing stearoyl-CoA desaturase 1 (SCD1), an enzyme that converts saturated fatty acids into monounsaturated fatty acids, on osteogenic differentiation and bone regeneration in both in vivo and in vitro models. Through this novel approach, we seek to develop a stem cell-based therapeutic strategy that harnesses SCD1 to improve bone regeneration in the adipocyte-rich osteoporotic environment.

Microfluidic devices are becoming a standard method of lab analysis of many different types of samples. This letter presents a uniquely shaped micropost structure set in an arrayed fashion for sensing and cell capture purposes. After simulating the design to confirm its improved functionality, a model cell line was used to determine the capture yield and capture rate of the device. Specific capture was achieved by coating the array of microposts with antibodies that target the epithelial cell adhesion molecule, a common biomarker for many types of metastatic cancer. [ABSTRACT FROM PUBLISHER]

ABSTRACTCircular RNA (circRNA) is a non-coding RNA with a covalently closed loop structure and usually more stable than messenger RNA (mRNA). However, coding sequences (CDSs) following an internal ribosome entry site (IRES) in circRNAs can be translated, and this property has been recently utilized to produce proteins as novel therapeutic tools. However, it is difficult to produce large proteins from circRNAs because of the low circularization efficiency of lengthy RNAs. In this study, we report that we successfully synthesized circRNAs with the splint DNA ligation method using RNA ligase 1 and the splint DNAs, which contain complementary sequences to both ends of precursor linear RNAs. This method results in more efficient circularization than the conventional enzymatic method that does not use the splint DNAs, easily generating circRNAs that express relatively large proteins, including IgG heavy and light chains. Longer splint DNA (42 nucleotide) is more effective in circularization. Also, the use of splint DNAs with an adenine analog, 2,6-diaminopurine (DAP), increase the circularization efficiency presumably by strengthening the interaction between the splint DNAs and the precursor RNAs. The splint DNA ligation method requires 5 times more splint DNA than the precursor RNA to efficiently produce circRNAs, but our modified splint DNA ligation method can produce circRNAs using the amount of splint DNA which is equal to that of the precursor RNA. Our modified splint DNA ligation method will help develop novel therapeutic tools using circRNAs, to treat various diseases and to develop human and veterinary vaccines.

This study presents a new structure for transient liquid phase (TLP) bonding using Cu foam and Cu–Sn paste. Cu foam and Cu–Sn paste with large reaction surface areas were used to reduce the long bonding time, which is a disadvantage of the conventional TLP bonding process. After applying the Cu–Sn paste at an optimized ratio to the top and bottom of the Cu foam, pressure was applied to fill the pores inside the Cu foam with the paste, and a bonding process was performed at 260 °C under a pressure of 3 kgf. Bonded joints composed of only the Cu skeleton and Cu–Sn intermetallic compounds (IMCs) were confirmed within a bonding time of 5 min. In addition, the proportion of the Cu3Sn phase in the joint increased with the bonding time. After a bonding time of 40 min, the joint was mostly composed of a Cu skeleton and Cu3Sn, with a measured shear strength of approximately 39.2 MPa. After the joint analysis of the as-bonded samples, a high-temperature storage test (HTST) was conducted to evaluate their high-temperature long-term reliability. As a result of HTST, because most of the joint was converted to Cu3Sn after the bonding process, the shear strength did not decrease despite heat treatment at a high temperature of 240 °C, and a similar microstructure of the joint was maintained.

Abstract DNA methylation is an epigenetic modification that regulates gene expression and plays an essential role in hematopoiesis. UHRF1 and DNMT1 are both crucial for regulating genome-wide maintenance of DNA methylation. Specifically, it is well known that hypermethylation is crucial characteristic of acute myeloid leukemia (AML). However, the mechanism underlying how DNA methylation regulates the differentiation of AML cells, including THP-1 is not fully elucidated. In this study, we report that UHRF1 or DNMT1 depletion enhances the phorbol-12-myristate-13-acetate (PMA)-induced differentiation of THP-1 cells. Transcriptome analysis and genome-wide methylation array results showed that depleting UHRF1 or DNMT1 induced changes that made THP-1 cells highly sensitive to PMA. Furthermore, knockdown of UHRF1 or DNMT1 impeded solid tumor formation in xenograft mouse model. These findings suggest that UHRF1 and DNMT1 play a pivotal role in regulating differentiation and proliferation of THP-1 cells and targeting these proteins may improve the efficiency of differentiation therapy in AML patients.

The mouse model of West Nile virus (WNV), which is a leading cause of mosquito-borne encephalitis worldwide, has provided fundamental insights into the host and viral factors that regulate viral pathogenesis and infection outcome. In particular, CD8+ T cells are critical for controlling WNV replication and promoting protection against infection. Here, we present the characterization of a T cell receptor (TCR)- transgenic mouse with specificity for the immunodominant epitope in the WNV NS4B protein (here referred to as transgenic WNV-I mice). Using an adoptive-transfer model, we found that WNV-I CD8+ T cells behave similarly to endogenous CD8+ T cell responses, with an expansion phase in the periphery beginning around day 7 postinfection (p.i.) followed by a contraction phase through day 15 p.i. Through the use of in vivo intravascular immune cell staining, we determined the kinetics, expansion, and differentiation into effector and memory subsets of WNV-I CD8+ T cells within the spleen and brain. We found that red-pulp WNV-I CD8+ T cells were more effector-like than whitepulp WNV-I CD8+ T cells, which displayed increased differentiation into memory precursor cells. Within the central nervous system (CNS), we found that WNV-I CD8+ T cells were polyfunctional (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]), displayed tissue-resident characteristics (CD69+ and CD103+), persisted in the brain through day 15 p.i., and reduced the viral burden within the brain. The use of these TCR-transgenic WNV-I mice provides a new resource to dissect the immunological mechanisms of CD8+ T cell-mediated protection during WNV infection. [ABSTRACT FROM AUTHOR]

Abstract Background It is unclear whether different anterior cruciate ligament (ACL) graft trajectories in the distal femur would have different effects on stress generated within the distal femur around the femoral tunnel during knee motion. Thus, the purpose of this study was to determine differences in stress patterns around the femoral tunnel created by trans-portal (TP) vs. modified trans-tibial (TT) technique in anatomical ACL reconstruction at different knee flexion angles. Methods Twelve male subjects’ right knees were scanned with a high-resolution computed tomography (CT) scanner (slice thickness: 1 mm) at four different knee flexion angles (0°, 45°, 90°, and 135°). Three-dimensional (3D) models of these four different flexion angles were created and manipulated with several modelling programs. For the TP group, the virtual femoral tunnelling procedure was performed in a 135° flexion model from the low far anteromedial (AM) portal. For the modified TT group, the same knee models were drilled through the modified TT technique at 90° of flexion separately. Virtual grafts under tension of 40 N were put into corresponding bone tunnel and fixed at the outer aperture of femoral tunnels to simulate the suspensory fixation, followed by fixation of the grafts at the middle of tibial tunnels in the 0° knee flexion models. Finally, the models were exported to a finite element analysis package and analysed using ABAQUS/Explicit code (ABAQUS, USA) to monitor the stress occurring at the node where stress distribution occurred most significantly in the femoral bone around the bone tunnel. Results In general, both groups showed a high stress distribution in bony structures around inner and outer orifices of the femoral tunnel. Mean maximal stresses occurring at the lateral femoral condyle around the inner orifice of the femoral tunnel in the TP group were found to be significantly greater than those in the modified TT group at all flexion angles except 90° of flexion. Mean maximal stresses monitored around the outer orifice of the femoral tunnel in the TP group were also significantly greater than those in the modified TT group at all flexion angles. Conclusions Different tunnelling technologies could yield different stress patterns in the lateral femoral condyle around the femoral tunnel. During knee motion, higher stresses were noticed in the TP group than in the modified TT group, especially around inner and outer orifices of the tunnel. Position of the tunnel after reconstruction with the TP technique can have a greater effect on the stress increase in the femur compared to that with the modified TT technique.

This study aimed to assess the safety and effectiveness of the highly cross-linked hyaluronic acid—LBSA0103—in patients with knee osteoarthritis (OA) as per the prescribing information (PI) in South Korea. A total of 3,140 subjects aged ≥19 years were enrolled in this post-marketing surveillance (PMS) study from 2013 to 2019. The subjects received one or two injections of LBSA0103. The median duration of follow-up was 308 days. Adverse events (AEs), adverse drug reactions (ADRs), and serious AEs (SAEs) were monitored. Effectiveness was evaluated based on an index of effectiveness in accordance with the guidelines established by the Ministry of Food and Drug Safety and using a 100-mm visual analog scale (VAS) for weight-bearing pain. Overall, 250 subjects (7.96%) experienced 292 AEs and of these, unexpected AEs occurred in 114 subjects (3.63% [95% CI: 3.00–4.35]). Injection site pain was the most frequent AE reported by 81 subjects (2.58% [95% confidence intervals (CI): 2.05–3.20]). One hundred subjects experienced 108 ADRs (3.18% [95% CI: 2.60, 3.86]) and 15 unexpected ADRs were experienced by 13 subjects (0.41% [95% CI: 0.22–0.71]). Seventeen subjects experienced 22 SAEs (0.54% [95% CI: 0.32–0.87]) during the entire PMS period, and all were considered “unlikely” related to the study drug. Most AEs were mild in terms of severity and resolved during the study period. LBSA0103 was also effective in relieving symptomatic pain in knee OA patients. The condition in more than 80% of the subjects was considered to be improved when assessed by the investigators. LBSA0103 resulted in a significant reduction in the mean VAS score at 12 weeks after the first and second injections (24.79 (± 20.55) mm and 17.63 (±12.31) mm, respectively; p

Several antiviral drugs are clinically approved to treat influenza that is a highly prevalent acute respiratory disease. However, emerging drug-resistant virus strains undermine treatment efficacy, highlighting the exigency for novel antiviral drugs to counter these drug-resistant strains. Plants and their derivates have been historically utilized as medicinal remedies, and extensive studies have evidenced the antiviral potential of phytochemicals. Notably, apigenin is a predominant flavonoid with minimal toxicity and substantial therapeutic effects in various disease models. Despite its many anti-inflammatory, anti-oxidant, anti-cancer, anti-bacterial, and other beneficial bioactivities, existing reviews have yet to focus on apigenin’s antiviral effects. Therefore, this review elucidates apigenin’s therapeutic and antiviral properties in vitro and in vivo, discussing its mode of action and future prospects. Apigenin’s remarkable inhibition by modulating multiple mechanisms against viruses has promising potential for novel plant-derived antiviral drugs and further clinical study developments.

Abstract Mechanical forces are pervasive in the inflammatory site where dendritic cells (DCs) are activated to migrate into draining lymph nodes. For example, fluid shear stress modulates the movement patterns of DCs, including directness and forward migration indices (FMIs), without chemokine effects. However, little is known about the effects of biomechanical forces on the activation of DCs. Accordingly, here we fabricated a microfluidics system to assess how biomechanical forces affect the migration and activity of DCs during inflammation. Based on the structure of edema, we proposed and experimentally analyzed a novel concept for a microchip model that mimicked such vascular architecture. The intensity of shear stress generated in our engineered chip was found as 0.2–0.6 dyne/cm2 by computational simulation; this value corresponded to inflammation in tissues. In this platform, the directness and FMIs of DCs were significantly increased, whereas the migration velocity of DCs was not altered by shear stress, indicating that mechanical stimuli influenced DC migration. Moreover, DCs with shear stress showed increased expression of the DC activation markers MHC class I and CD86 compared with DCs under static conditions. Taken together, these data suggest that the biomechanical forces are important to regulate the migration and activity of DCs.

Abstract Background There has been no gold standard of the initial treatment strategy for acute patellar dislocation (APD) with osteochondral fracture (OCF). Hence the study aim is firstly, to review and compare clinical outcomes of patients who underwent conservative treatment for APD with or without OCF. Secondly, to characterize the location and size of fracture fragment. Methods Sixty-nine consecutive patients who were retrospectively evaluated after first-time APD over a 2- year period were divided into two groups (group 1 (n = 24): APD with OCF and group 2 (n = 45): APD only). Magnetic resonance imaging (MRI) was used to assess patients with APD and OCF from the medial patella. All patients were treated with a supervised course of immobilization followed by progressive range of motion and strength exercise protocol. History of a recurrent dislocation, radiologic and functional scores were analyzed. Results Redislocation rate was 31.2% in group 1 and 26.6% in group 2, showing no significant difference between the two groups (p = 0.690). Intergroup differences in terms of final Kujala and IKDC scores were not significant (p = 0.117 and p = 0.283, respectively). Fracture sites of the patella in group 1 were classified as follows: patellar medial margin (12), inferomedial facet (7), and inferomedial facet involving central ridge (5). In the subgroup of patient with OCF of the inferomedial facet of the patella, the fragments were found in the lateral gutter and did not cause pain or mechanical symptoms. Thus, loose body removal was not performed. However, all five patients with large OCF involving the central ridge of the patella failed non-operative treatment with recurrent dislocations, ultimately requiring fragment refixation and medial retinacular imbrication. Conclusions First, APD patients with OCFs of medial margin or inferomedial facet showed similar redislocation rates and functional knee scores with those without OCFs after conservative treatment. Second, initial conservative treatment failed in some APD patients with large OCF, especially when OCFs were fractured from inferomedial facet involving central ridge. Surgery should be considered with this type.

Embryonic stem cells: extra protection for DNA Embryonic stem cells (ESCs), which give rise to the many specialized cells of the body, have highly effective molecular processes of DNA maintenance and repair which protect their genetic information from damage. Keun Pil Kim and colleagues at Chung-Ang University, Seoul, South Korea, review the strategies found in ESCs to maintain the integrity of their DNA as they develop and multiply. A key feature is the process of homologous recombination (HR) in which one copy of a section of DNA acts as the template allowing a damaged version of the DNA to be repaired. HR also facilitates swapping of sections of DNA when sperm and egg cells form, promoting genetic diversity. HR appears to be especially significant in maintaining ESC DNA as ESCs possess higher levels of key proteins involved in its maintenance and regulation.

We sequenced the complete mitochondrial genome of the copepod Labidocera rotunda (family Pontellidae) collected from Ihotaewoo Beach in Jeju, Korea. The mitochondrial genome was 16,564 bp in length and contained 13 protein-coding genes (PCGs), 22 transfer RNAs, and two ribosomal RNAs. The concatenated phylogenetic tree of L. rotunda was reconstructed using the maximum-likelihood method based on the eight PCGs obtained from eight species of copepods including L. rotunda. The results of the phylogeny analysis showed that L. rotunda was closely related to the family Temoridae among the three families. The complete mitochondrial genome of L. rotunda analyzed for the first time in this study provides insight into the phylogenetic and evolutionary relationship of Labidocera.

Background: Continuous exposure to high temperatures can lead to heat stress. This stress response alters the expression of multiple genes and can contribute to the onset of various diseases. In particular, heat stress induces oxidative stress by increasing the production of reactive oxygen species. The liver is an essential organ that plays a variety of roles, such as detoxification and protein synthesis. Therefore, it is important to protect the liver from oxidative stress caused by heat stress. Korean ginseng has a variety of beneficial biological properties, and our previous studies showed that it provides an effective defense against heat stress. Methods: We investigated the ability of Korean Red Ginseng and Korean black ginseng extracts (JP5 and BG1) to protect against heat stress using a rat model. We then confirmed the active ingredients and mechanism of action using a cell-based model. Results: Heat stress significantly increased gene and protein expression of oxidative stress–related factors such as catalase and SOD2, but treatment with JP5 (Korean Red Ginseng extract) and BG1 (Korean black ginseng extract) abolished this response in both liver tissue and HepG2 cells. In addition, JP5 and BG1 inhibited the expression of inflammatory proteins such as p-NF-κB and tumor necrosis factor alpha-α. In particular, JP5 and BG1 decreased the expression of components of the NLRP3 inflammasome, a key inflammatory signaling factor. Thus, JP5 and BG1 inhibited both oxidative stress and inflammation. Conclusions: JP5 and BG1 protect against oxidative stress and inflammation induced by heat stress and help maintain liver function by preventing liver damage. Keywords: Heat stress, Inflammation, Korean ginseng extracts, Oxidative stress, Sprague–Dawley rats

Background: Panax ginseng Meyer is known as a conventional herbal medicine, and ginsenoside Rg1, a steroid glycoside, is one of its components. Although Rg1 has been proved to have an antiobesity effect, the mechanism of this effect and whether it involves adipose browning have not been elucidated. Methods: 3T3-L1 and subcutaneous white adipocytes from mice were used to access the thermogenic effect of Rg1. Adipose mitochondria and uncoupling protein 1 (UCP1) expression were analyzed by immunofluorescence. Protein level and mRNA of UCP1 were also evaluated by Western blotting and real-time polymerase chain reaction, respectively. Results: Rg1 dramatically enhanced expression of brown adipocyte–specific markers, such as UCP1 and fatty acid oxidation genes, including carnitine palmitoyltransferase 1. In addition, it modulated lipid metabolism, activated 5′ adenosine monophosphate (AMP)-activated protein kinase, and promoted lipid droplet dispersion. Conclusions: Rg1 increases UCP1 expression and mitochondrial biogenesis in 3T3-L1 and subcutaneous white adipose cells isolated from C57BL/6 mice. We suggest that Rg1 exerts its antiobesity effects by promoting adipocyte browning through activation of the AMP-activated protein kinase pathway. Keywords: Adipocytes, Browning, Ginsenoside Rg1, Thermogenesis, Uncoupling protein 1

Bacteria utilize endoribonuclease-mediated RNA processing and decay to rapidly adapt to environmental changes. Here, we report that the modulation of hns mRNA stability by the endoribonuclease RNase G plays a key role in Salmonella Typhimurium pathogenicity. We found that RNase G determines the half-life of hns mRNA by cleaving its 5' untranslated region and that altering its cleavage sites by genome editing stabilizes hns mRNA, thus decreasing S. Typhimurium virulence in mice. Under anaerobic conditions, the FNR-mediated transcriptional repression of rnc encoding RNase III, which degrades rng mRNA, and simultaneous induction of rng transcription resulted in rapid hns mRNA degradation, leading to the derepression of genes involved in the Salmonella pathogenicity island 1 (SPI-1) type III secretion system (T3SS). Together, our findings show that RNase III and RNase G levels-mediated control of hns mRNA abundance acts as a regulatory pathway upstream of a complex feed-forward loop for SPI-1 expression.

Tumor metastasis is the end state of a multistep process that includes dissemination of tumor cells to distant organs and requires tumor cells to adapt to different tissue microenvironments. During metastasis, tumor cells undergo a morphological change known as transdifferentiation or the epithelial-to-mesenchymal transition (EMT). In normal embryonic development, the EMT occurs in the context of morphogenesis in a variety of tissues. Over the course of this process, epithelial cells lose their cell–cell adhesion and polarity properties. In this study, we investigated whether magnolol could suppress the EMT in human colorectal cancer cells. To this end, we examined the epithelial markers E-cadherin, ZO-1, and claudin and the mesenchymal markers N-cadherin, TWIST1, Slug, and Snail. Magnolol effectively inhibited EMT in human colon cancer cell lines by upregulating epithelial markers and downregulating mesenchymal markers. The EMT is induced by the TGF-β signaling pathway. To determine whether magnolol disrupts TGF-β signaling, we examined several mediators of this pathway, and found that magnolol decreased the levels of phosphorylated (i.e., active) ERK, GSK3β, and Smad. We conclude that magnolol blocks migration in HCT116 cells by suppressing TGF-β signaling.

The immune-suppressive effects of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on T cells have been observed via multiple in vitro and in vivo models. However, the precise mechanism that causes these effects is still undefined. In this study, we investigated whether n-3 PUFAs regulated T cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) interactions. The expansion of anti-viral CD8+ T cells that endogenously synthesize n-3 PUFAs (FAT-1) dramatically decreased upon lymphocytic choriomeningitis virus (LCMV) infection in vivo. This decrease was not caused by the considerable reduction of TCR expression or the impaired chemotactic activity of T cells. Interestingly, a highly inclined and laminated optical sheet (HILO) microscopic analysis revealed that the TCR motility was notably reduced on the surface of the FAT-1 CD8+ T cells compared to the wild type (WT) CD8+ T cells. Importantly, the adhesion strength of the FAT-1 CD8+ T cells to the peptide-MHC was significantly lower than that of the WT CD8+T cells. Consistent with this result, treatment with docosahexaenoic acid (DHA), one type of n-3 PUFA, significantly decreased CD8+ T cell adhesion to the pMHC. Collectively, our results reveal a novel mechanism through which n-3 PUFAs decrease TCR-pMHC interactions by modulating TCR mobility on CD8+ T cell surfaces.

Type 2 diabetes mellitus and related metabolic disorders, such as dyslipidemia, present increasing challenges to health worldwide, as a result of urbanization, the increasing prevalence of obesity, poor lifestyle, and other stress-related factors. Ishige okamurae extract (IOE) is known to be effective at lowering blood glucose and ameliorating metabolic disease. However, detailed mechanisms for these effects have yet to be elucidated. Here, we show that IOE ameliorates substrate (IRS)/ phosphatidylinositol 3-kinase (PI3K)/Akt pathway and increasing glucose transporter 4 (GLUT4) expression in skeletal muscle and white adipose tissue (WAT). We also demonstrate that IOE increases the expression of fibroblast growth factor (FGF)21, a regulator of glucose and energy metabolism in muscle and WAT. In addition, IOE administration increased peroxisome proliferator-activated receptor γ coactivator 1α expression, which regulates expression of the key thermogenic molecule uncoupling protein 1 in WAT. Thus, the effects of IOE to ameliorate hyperglycemia and adiposity may be mediated through FGF21 activating insulin signaling and increasing the expression of GLUT4 and pro-thermogenic factors.

Influenza continues to pose a threat to humans by causing significant morbidity and mortality. Thus, it is imperative to investigate mechanisms by which influenza virus manipulates the function of host factors and cellular signal pathways. In this study, we demonstrate that influenza virus increases the expression and activation of sphingosine kinase (SK) 1, which in turn regulates diverse cellular signaling pathways. Inhibition of SK suppressed virus-induced NF-κB activation and markedly reduced the synthesis of viral RNAs and proteins. Further, SK blockade interfered with activation of Ran-binding protein 3 (RanBP3), a cofactor of chromosome region maintenance 1 (CRM1), to inhibit CRM1-mediated nuclear export of the influenza viral ribonucleoprotein complex. In support of this observation, SK inhibition altered the phosphorylation of ERK, p90RSK, and AKT, which is the upstream signal of RanBP3/CRM1 activation. Collectively, these results indicate that SK is a key pro-viral factor regulating multiple cellular signal pathways triggered by influenza virus infection.