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A 16-year-old male adolescent with a history of retractile testes fell in the bath and hit his scrotum against the bathtub. The following day, he presented to the primary care clinic with severe right testicular pain and nausea 2 hours after the onset. Physical examination showed a tender right

Chemokines are a family of cytokines that mediate leukocyte trafficking and are involved in tumor cell migration, growth, and progression. Although there is emerging evidence that multiple chemokines are expressed in tumor tissues and that each chemokine induces receptor-mediated signaling, their collaboration to regulate tumor invasion and lymph node metastasis has not been fully elucidated. In this study, we examined the effect of CXCL12 on the CCR7-dependent signaling in MDA-MB-231 human breast cancer cells to determine the role of CXCL12 and CCR7 ligand chemokines in breast cancer metastasis to lymph nodes. CXCL12 enhanced the CCR7-dependent in vitro chemotaxis and cell invasion into collagen gels at suboptimal concentrations of CCL21. CXCL12 promoted CCR7 homodimer formation, ligand binding, CCR7 accumulation into membrane ruffles, and cell response at lower concentrations of CCL19. Immunohistochemistry of MDA-MB-231-derived xenograft tumors revealed that CXCL12 is primarily located in the pericellular matrix surrounding tumor cells, whereas the CCR7 ligand, CCL21, mainly associates with LYVE-1

Hepatic encephalopathy caused by a large portosystemic shunt (PSS) can be treated by endovascular embolization of the shunt. The PSS diameter can be >20 mm; it occasionally poses technical difficulties. Here, a 72-year-old woman with liver cirrhosis, hyperammonemia, and large spleno-renal shunt underwent shunt embolization using an Amplatzer vascular plug 2 (AVP2) and metallic coils. The preloading coil in plug method (p-CIP), which facilitated embolization inside the AVP2 without cannulation from outside, was employed to overcome technical difficulties. We propose the use of p-CIP with an AVP2 as a tool for treatment of hepatic encephalopathy with PSS.

Introduction In Western countries, the risk of a testicular germ cell tumor in men with male factor infertility is greater than in the general population. However, Japanese data on this risk are lacking. Additionally, the clinical course for the pathogenesis involved has not been clearly characterized. Case presentation A 35‐year‐old Japanese male underwent a right orchiectomy because of a mass in his right scrotum. He had a previous history of microdissection testicular sperm extraction undertaken 6 years ago. The final diagnosis of the right scrotal mass was a stage I seminoma. However, a relapse occurred in the left inguinal lymph node 2 years after surgery and the patient was consequently treated with systemic chemotherapy. Pathological analysis of a microdissection testicular sperm extraction sample yielded a germ cell neoplasia in situ in the right testis. Conclusion In Japan, men who seek an evaluation for infertility might be more likely to develop testicular germ cell tumor.

Chemotactic factors locally secreted from tissues regulate leukocyte migration via cell membrane receptors that induce intracellular signals. It has been suggested that neutrophils stimulated by bacterial peptides secrete a secondary stimulant that enhances the chemotactic cell migration of the surrounding cells. This paracrine mechanism contributes to chemokine-dependent neutrophil migration, however, it has not yet been extensively studied in lymphocytes. In this study, we provide evidence that lymphocytes stimulated by the chemokine, CXCL12, affect the CXCR4-independent chemotactic response of the surrounding cells. We found that CXCR4-expressing lymphocytes or the conditioned medium from CXCL12-stimulated cells promoted CXCR4-deficient cell chemotaxis. In contrast, the conditioned medium from CXCL12-stimulated cells suppressed CCR7 ligand-dependent directionality and the cell migration speed of CXCR4-deficient cells. These results suggest that paracrine factors from CXCL12-stimulated cells navigate surrounding cells to CXCL12 by controlling the responsiveness to CCR7 ligand chemokines and CXCL12., Graphical abstract Image 1, Highlights ● CXCL12-stimulated lymphocytes affect the CXCR4-independent chemotactic response of the surrounding cells. ● The conditioned medium from CXCL12-stimulated cells promoted CXCR4-deficient cell chemotaxis, whereas it suppresses CCR7 ligand-dependent directionality and the cell migration speed. ● The CXCL12/CXCR4 axis causes the production of a signal-relay molecule that contributes to chemokine-dependent lymphocyte migration.

We investigated the stress–strain relation and the applied strain dependence of the critical current I c ( ε a p p ) of high-strength Bi2Sr2Ca2Cu3O 10 + δ (Bi2223) R&D tapes reinforced by ∼ 100 μ m thick Ni-based alloy sheets with various pre-tensions F p r e applied during the lamination process. We confirmed that the thickening of Ni-alloy laminations is useful for enhancing Young’s modulus compared with commercial tapes ( ≃ 30 μ m thick laminations). I c ( ε a p p ) decreases gradually and reversibly with applied strains ε a p p and then degrades irreversibly with larger tensile and compressive strains. The reversible strain regime tends to shift toward the tensile side with larger F p r e , indicating that application of large F p r e is effective in improving the reversible tensile strain limit. The observed I c ( ε a p p ) can be reproduced well by model considering ε a p p -linear critical current density, cross-sectional strain distribution, and Weibull-type distribution of filament damage. We clarified that different irreversible I c ( ε a p p ) degradations with large tensile and compressive strains can be understood by differences in the dimensions and number of cracks and ruptures (tensile strains) and bucklings (compressive strains).

To directly detect the spatial distribution of a plasma current during the collisional merging of two field-reversed configurations (FRCs) in the FAT-CM (FRC Amplification via Translation–Collisional Merging) device, an internal current probe using Rogowski coils has been developed. An FRC is a type of magnetically confined plasma maintained by a diamagnetic plasma current flowing in the toroidal direction. Self-organized FRC formation and increased poloidal flux have been observed following the destructive perturbation during the collision in collisional merging FRC formation when two initial-plasmoids collide at a relative speed of 300–400 km/s to form one FRC. It is indicated that the toroidal plasma current is driven in those processes. In this research, an internal Rogowski probe was designed and developed to have a high-frequency response to capture a rapid change of the plasma current in a few microseconds during the collision/merging process. The FRC plasma in FAT-CM has relatively high temperature (∼100 to 200 eV) and high density (∼1020 to 1021 m−3). As a result, the probe was built to be as compact as possible to minimize disruption to the plasma. Because of its high melting point and low Z property, a machinable boron nitride ceramic was chosen to shield the Rogowski coils thermally and electrically from the plasma. All connections and seams were constructed such that the epoxy glue used for the probe assembly was not exposed to the plasma.

Collisional merging formation of field-reversed configuration (FRC) plasmas at supersonic velocities was performed using the FRC amplification via translation-collisional merging device. Supersonic collisional merging formation is a novel technique to form an FRC that is long-lived compared to a conventional initial formation FRC; however, this technique requires measuring the plasma parameters at multiple points simultaneously because of the dynamic translation/merging process. Herein, we have developed a new interferometer and have observed the dynamic behavior of FRCs in the formation, translation, and merging processes simultaneously. In this study, as one of the performance evaluations of the developed simultaneous density measurement, collision/merging of FRCs have been conducted in the confinement section with and without background neutral gas. Comparing translation into deuterium gas vs translation into a vacuum environment prior to the collisional merging, we found that the background neutral particles were trapped in the merged FRC; moreover, a difference in the decay rate of the stored internal energy was observed.

Objective: Bacillus Calmette-Guerin (BCG) intravesical therapy is currently established using a low dose because of the high incidence of side-effects. Moreover, shortening the dwell time of BCG is conducted in some facilities owing to the complications associated with a long dwell time after injection. The method of BCG administration varies in each facility and even with each doctor. We evaluated whether the dwell-time and dose differences in patients who underwent intravesical BCG therapy is related to completion rates, adverse effects, and nonrecurrence rates. Methods: From November 2006 to April 2016, a total of 173 patients who received intravesical BCG therapy after transurethral resection of bladder tumor or transurethral biopsy were evaluated retrospectively. We allocated them into 4 groups based on the dose (40 or 80 mg BCG) and the dwell time (1 or 2 hours). Completion rate, side effects, and nonrecurrence rates were evaluated. Results: No significant improvement in the completion rate or reduction in side-effects was observed in any of the regimens. Although nonrecurrence rates for the 1-hour dwell time tended to be lower than the 2-hour dwell time, the difference was not significant. Conclusion: Our study suggests that reducing the BCG dose or shortening the dwell time does not reduce adverse effects or affect the nonrecurrence rate.

Background: Patients with metastatic urothelial carcinoma (mUC) have an uncertain prognosis. The aim of the current study was to evaluate the prognostic potential of a skeletal muscle mass reduction index measured by computed tomography (CT) for mUC patients undergoing second-line gemcitabine and docetaxel (GD) chemotherapy. Methods: We retrospectively reviewed 44 patients with mUC who received second-line GD chemotherapy between 2006 and 2015 in our hospital. Skeletal muscle area (SMA) at the third lumbar vertebra was measured using CT images obtained from medical records, and a skeletal muscle index (SMI) was calculated for each patient as: SMI = SMA / height2. Changes in SMI across timepoints (SMI inclination) were calculated as: SMI inclination = [( SMI/SMI)/duration of the interval between imaging visits]. Patients were then divided into two groups: a “steep” group (SMI inclination < -0.01) and a “gentle” group (SMI inclination ≥ -0.01). Kaplan-Meier curves and multivariate Cox proportional hazards regression models were used to evaluate the relationship between SMI inclination and overall survival (OS). Results: There were no differences in patient characteristics between the two groups with respect to median age, gender, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), disease control rate or first-line treatment regimen. OS from the start of second-line GD therapy group was significantly shorter in the “steep” group relative to the “gentle” group. The multivariate analysis revealed that “steep” SMI inclination and presence of anemia were strong predictors of poor prognosis. Conclusion: Higher values of SMI inclination, indicating a faster rate of skeletal muscle mass reduction, may serve as a useful predictive marker for OS in mUC patients undergoing second-line GD chemotherapy.

Objective: In recent years, although reduced port surgeries (RPS) have been reported for many urological diseases, there have been no reports regarding simultaneous laparoscopic cystectomy and unilateral or bilateral nephroureterectomy with umbilical RPS. Therefore, the aim of this study was to evaluate outcomes and complications of simultaneous laparoscopic cystectomy and unilateral or bilateral nephroureterectomy with umbilical RPS. Methods: We performed a preliminary case series of 4 patients with synchronous upper urinary tract (UUT) tumor and invasive bladder cancer who underwent simultaneous laparoscopic cystectomy and unilateral or bilateral nephroureterectomy with umbilical RPS between 2014 and 2017 at our hospital. Demographic data, pathologic features, the surgical technique, and outcomes were retrospectively analyzed. Result: All 4 patients were men whose median age was 79 years (range 65-85 years) and median body mass index was 24.2 kg/m2 (range 21.5-27.3 kg/m2). The laparoscopic approach was technically successful in all 4 patients without the need for open conversion. The median total operative time was 434 minutes (range 372-481 minutes). The median estimated blood loss was 773 ml (range 153-923 ml), median interval to resuming oral intake was 2 days (range 1-7 days), and median hospital stay was 16 days (range 13-20 days). Conclusion: The reduced port approach is technically feasible in terms of many outcome measures, with significant cosmetic advantages. This method can be performed safely and recommended as a viable option for patients with concomitant UUT and bladder cancer.

A novel physical vapor deposition method involving electromagnetic acceleration using a set of coaxial electrodes has been developed. In this study, the coaxial ion acceleration method is applied for a diamond-like carbon (DLC) thin film formation. In the developed method, the central electrode made of the deposition material is sputtered by the noble gas plasma current and accelerated toward the deposition chamber. Because the sputtered ions are accelerated by the Lorentz self-force, the ion injection energy can be controlled separately from the plasma temperature. In addition, the gaseous hydrocarbon, which is commonly used for DLC formation, is not required since a noble gas is used as the discharge gas.

Peripheral nerve injury typically leads to chronic inflammation through recruitment of immune cells, which may induce neuropathic pain. We previously reported that M1-like macrophages at sites of peripheral nerve injury induced neuropathic pain; however, the involvement of other immune cells (e.g. M2-like macrophages) in the progression of neuropathic pain remains unclear. In addition, the immune responses that occur at sites of nerve injury have not been well characterized. In this study, we show that M2-like macrophages accumulate in injured nerves to participate in the clearance of dead or dying cells (i.e., efferocytosis). Because MerTK (a receptor of dead or dying cells) levels on the surface of macrophages are limited, it seems to induce the insufficient of efferocytosis, such that the levels of dead or dying cells cannot be controlled in injured nerves. Given that efferocytosis is pivotal for resolution of inflammation, our data suggest that insufficient efferocytosis is a contributing factor in the development of chronic inflammation in injured nerves.

Summary Cytokine and growth factor receptors localized on cell membranes play key roles in many biological events. Because the dynamic behaviors of receptors are deeply involved in cytokine- and growth-factor-dependent signaling pathways, reliable techniques for real-time imaging of receptors in live cells are strongly desired. Here, we describe a method of covalently labeling and imaging membrane receptors in live cells by using chemically reactive cytokines and growth factors coupled with 4-dimethylaminopyridine (DMAP), an organocatalyst that facilitates acyl transfer. Construction of the DMAP cytokines and growth factors relies on non-covalent coordination chemistry between an oligo-histidine tag and dimeric Ni(II)-nitrilotriacetate in an in situ manner. This supramolecular approach is relatively simple and flexible and can be applied to labeling not only transiently but also endogenously expressed receptors. Moreover, given the benefit of this traceless labeling of the receptors, our technique allows real-time imaging of the ligand-induced dynamics of endogenously expressed receptors in live cells.

Background Neuro–immune interaction underlies chronic neuroinflammation and aberrant sensory processing resulting in neuropathic pain. Despite the pathological significance of both neuroinflammation-driven peripheral sensitization and spinal sensitization, the functional relationship between these two distinct events has not been understood. Methods In this study, we determined whether inhibition of inflammatory macrophages by administration of α4β2 nicotinic acetylcholine receptor (nAChR) agonists improves neuropathic pain and affects microglial activation in the spinal dorsal horn (SDH) in mice following partial sciatic nerve ligation (PSL). Expression levels of neuroinflammatory molecules were evaluated by RT-qPCR and immunohistochemistry, and PSL-induced mechanical allodynia was defined by the von Frey test. Results Flow cytometry revealed that CD11b+ F4/80+ macrophages were accumulated in the injured sciatic nerve (SCN) after PSL. TC-2559, a full agonist for α4β2 nAChR, suppressed the upregulation of interleukin-1β (IL-1β) in the injured SCN after PSL and attenuated lipopolysaccharide-induced upregulation of IL-1β in cultured macrophages. Systemic (subcutaneous, s.c.) administration of TC-2559 during either the early (days 0–3) or middle/late (days 7–10) phase of PSL improved mechanical allodynia. Moreover, local (perineural, p.n.) administration of TC-2559 and sazetidine A, a partial agonist for α4β2 nAChR, during either the early or middle phase of PSL improved mechanical allodynia. However, p.n. administration of sazetidine A during the late (days 21–24) phase did not show the attenuating effect, whereas p.n. administration of TC-2559 during this phase relieved mechanical allodynia. Most importantly, p.n. administration of TC-2559 significantly suppressed morphological activation of Iba1+ microglia and decreased the upregulation of inflammatory microglia-dominant molecules, such as CD68, interferon regulatory factor 5, and IL-1β in the SDH after PSL. Conclusion These findings support the notion that pharmacological inhibition of inflammatory macrophages using an α4β2 nAChR agonist exhibit a wide therapeutic window on neuropathic pain after nerve injury, and it could be nominated as a novel pharmacotherapy to relieve intractable pain. Electronic supplementary material The online version of this article (10.1186/s12974-018-1133-5) contains supplementary material, which is available to authorized users.

Objective: UroVysion (Abbott Molecular, Inc., Illinois, USA) is based on multicolor fluorescence in situ hybridization (FISH). It has been used successfully in the USA following its Food and Drug Administration approval in 2001. However, the technology was not approved for use in Japan until 2017. Cystoscopy and urine cytology are the most frequently used examinations to detect bladder cancer in Japan, and there are only a few reports regarding the performance of UroVysion. Therefore, the aim of this study is to examine the diagnostic accuracy of UroVysion FISH in Japanese patients whose tumors are detected by cystoscopy before transurethral resection of bladder tumor (TURBT). Methods: From April 2018 to July 2018, a total of 40 patients who were diagnosed as having bladder tumors by cystoscopy, and therefore underwent TURBT were registered in this study. One day before TURBT, urine cytology and UroVysion FISH were used in order to compare the accuracy with which they could detect bladder carcinoma, as confirmed by pathological results of TURBT. Results: The pathological results of TURBT showed urothelial carcinoma in 33 cases. Urine cytology showed positive results for 0 cases (0%), suspicious results for 10 cases (30.3%), and negative results for 23 cases (69.7%). On the other hand, UroVysion FISH indicated 9 positive cases (27.3%) and 24 negative cases (72.7%). There were 19 cases of urothelial carcinoma (57.6%) that were not detected by either method. Conclusion: We conclude that UroVysion FISH alone is insufficient to detect bladder cancer and that cystoscopy is essential for the optimum detection or follow up of bladder cancer cases in our hospital.

Simple Summary In cases of cancer metastasis, some tumor cells circulate in blood (CTCs) and function as a seed for metastasis. These cells are important for detailed study of the molecular basis of metastasis. However, their few numbers and difficult isolation hinder its analysis. Apheresis, a process used to isolate a specific component of blood, can efficiently separate peripheral blood monocyte (PBMC), whose density is closely like that of CTCs. In the present study we used the dogs as a precious model of human’s cancers to check the safety and feasibility of apheresis and to separate PBMC and infused MCF7 cells using Spectra Optia apheresis machine (Terumo). The process was performed safely to capture PBMC and MCF7. The captured MCF7 cells were regrown up in vitro and characterized. In conclusion, Spectra Optia apheresis machine (Terumo) can be used safely to isolate CTCs from dogs blood with precautions to keep hemodynamic stability. Abstract In patients with solid tumors, circulating tumor cells (CTCs) spread in their blood and function as a seed for metastases. However, the study of CTCs has been limited by their rarity, low frequency, and heterogeneity. The efficient collection of CTCs will contribute to further research of metastatic cancers. Apheresis is a process in which the whole blood of an individual is passed through a machine that isolates a particular constituent and returns the remainder to the circulation. In the present study, we investigated the safety and feasibility of apheresis to separate peripheral blood monocytes (PBMCs), whose density is closely similar to that of CTCs, and to capture intravenously administered human breast cancer cells, MCF7s, from the dogs. No life-threatening events were observed in dogs during the apheresis process. The changes in the hemogram were transient and recovered gradually within a few days after apheresis. During apheresis, 50 mL of PBMCs could be collected from each dog. Notably, a thrombus was formed along the circuit wall during apheresis, which decreased the blood collection pressure. MCF7 cells were successfully captured by the apheresis machine. The captured cells were regrown in vitro and characterized compared with the original cells. In conclusion, apheresis could be safely performed in dogs to isolate CTCs with precautions to maintain hemodynamic stability.

Self-organized field-reversed configuration (FRC)-like formation was observed after the super-sonic/Alfvénic collisional merging of two FRCs in the FAT-CM device at Nihon University. In this experiment, two FRCs were generated initially in two separate field-reversed theta-pinch type formation regions. Those two formation regions are coaxially connected to opposite ends of a cylindrical confinement chamber. The formed FRCs are oppositely-translated and collide in the middle of the confinement chamber at super-sonic/Alfvénic velocity. During the collision, the merged plasmoid experiences destructive disturbance and loses its fast toroidal flow and characteristic FRC property of having a field-reversed magnetic configuration to become a magnetized plasma without ordered structure. After this dynamic collision, a magnetic configuration of FRC with fast toroidal rotation is self-organized within a few tens of microseconds. This observation indicates robustness of the extremely high-beta, simple magnetic configuration.

A 45-year-old Japanese man, who was undergoing HIV infection treatment, was aware that he had gross hematuria, and he was diagnosed as having a ureteral tumor by radiographic examination. Therefore, he was referred to our department for further examination and treatment. We considered that the ureteral tumor was a urothelial carcinoma (cT2N0M0) because of the left ureteral tumor and urine cytology results, and thus, laparoscopic ureteronephrectomy was performed. The pathological diagnosis was a solitary extramedullary plasmacytoma (EMP) of the ureter. Currently, he is alive and free of disease at 7 months postoperatively. EMP develops in the nasal cavity, paranasal cavity, gastrointestinal tract, lung, thyroid, eye socket, lymph node, and various organs, but the ureter is an extremely rare site of EMP. In addition, the patient had an HIV infection. To the best of our knowledge, this is the first case of EMP of the ureter in an HIV-positive patient.

Background: Magnetites (iron oxide nanoparticles in Fe3O4) coated with positively charged liposomes are called as magnetic cationic liposomes (MCLs). MCLs used in an 8-MHz radiofrequency (RF) capacitive heating device can increase the temperature of a specific site to up to 45℃. The aim of this study was to evaluate the safety of regional 8-MHz RF capacitive hyperthermia combined with MCL in patients with castration-resistant prostate cancer (CRPC).Materials and methods: Three CRPC patients resistant to standard cancer therapy were enrolled in this study. The patients were injected with 0.5 mL MCL containing Fe (30 mg/mL) into the prostate, followed by application of the heat using an 8-MHz RF capacitive heating device. The primary end point was to evaluate the presence, or absence, as well as the degree of adverse events. The secondary end point was to obtain preliminary efficacy data. Results: The temperature of the tumor was increased by more than 2℃ following MCL injection when compared with the 8-MHz RF treatment alone. No severe adverse events were noted in the prostate, rectum, or the bladder. After treatment, both levels of prostate-specific antigen (PSA) and interleukin-6 (IL-6) in the tissue were increased in three patients by varying degrees.Conclusion: The present study confirms the safety of regional 8-MHz RF capacitive hyperthermia combined with MCL.

Introduction Creation of an ileal conduit is associated with complications. A few cases have been reported on tumor development in an ileal conduit; diffuse large B‐cell lymphoma originating from an ileal conduit is extremely rare. Case presentation A 62‐year‐old Japanese man who had undergone radical cystectomy and ileal conduit diversion 6 years previously presented with a whitish bulge that had developed on the surface of the ileal conduit during follow‐up visit. Mass biopsy was performed and the histological diagnosis was diffuse large B‐cell lymphoma. Positron emission tomography showed no metastatic lesions. We attempted chemotherapy because the tumor cells tested positive for CD20; after six courses of a regimen involving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; diffuse large B‐cell lymphoma of the ileal conduit resolved gradually. The patient is alive and remains free from the diagnosed diffuse large B‐cell lymphoma. Conclusion We reported an extremely rare case of diffuse large B‐cell lymphoma originating from the ileal conduit created after radical cystectomy.

Introduction: Cabazitaxel (CBZ) is used worldwide for castration-resistant prostate cancer after docetaxel treatment. In July 2014 the drug was approved in Japan with the same induction dose used for Caucasian patients. In this study, we examined and compared the results of an initial low-dose CBZ treatment in patients admitted to our hospital. Patients and Methods: Between July 2014 and August 2018, sixteen mCRPC patients were enrolled and underwent a low-dose CBZ treatment at our hospital. We compared the results with those of a Japanese metastatic docetaxel- and castration-resistant prostate cancer Phase I study. Results: The median patient age was 77 years (range, 53-84 years). Of the 16 patients, eight (50%) had a lymph node metastasis and 11 (68.8%) had a distant metastasis, 10 of whom had only a bone metastasis. The median dose of CBZ was 30 mg (range, 20-32 mg) and the median number of CBZ cycles was 2.5 (range, 1-18). The PSA level of 9 (56.3%) patients decreased after CBZ treatment, including 4 (25%) who showed a decrease to

Excess scar formation can occur after skin injurふy and lead to abnormal scar formation, such as keloids and hypertrophic scars, which are characterised by substantial deposition of extracellular matrix in the dermis. Periostin, an extracellular matrix protein that plays a crucial role in skin development and maintaining homeostasis, is also involved in skin disorders such as systemic/limited scleroderma, wound closure, and abnormal scar formation. However, the mechanism of periostin involvement in abnormal scar formation is not yet fully understood. In this study, we investigated the mechanism by which periostin is involved in abnormal scar formation. Treatment of human dermal fibroblasts (HDFs) with IL-4 and IL-13, which are cytokines of Th2 type immune responses that are up-regulated in abnormal scars, dramatically elevated the levels of periostin mRNA and protein, and also promoted the secretion of periostin by HDFs. Transforming growth factor-β1 (TGF-β1) had the same effect on HDFs as IL-4 and IL-13. Stimulation of HDFs with periostin promoted RhoA/ROCK pathway-mediated TGF-β1 secretion from HDFs. Our results suggest that IL-4 and IL-13 induce periostin expression and secretion, and in turn, secreted periostin induces RhoA/ROCK pathway-mediated TGF-β1 secretion. Secreted TGF-β1 then induces further periostin production and secretion, thereby promoting abnormal scar formation.