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Purpose: Local corticosteroid injections are routinely used as first-line treatment for trigger finger. However, accurate delivery of steroids into the tendon sheath is important for the effectiveness of the treatment and the prevention of complications. This study aimed to introduce our steroid injection technique for trigger finger, which uses tendon excursion of the flexor tendon, and evaluate the clinical outcomes in patients who were treated with this technique.Methods: A total of 171 patients with trigger finger who were treated with steroid injections were retrospectively reviewed. The efficacy of injection and complications were investigated. The evaluation of the efficacy was classified into “good,” “fair,” and “poor.” The results were analyzed according to the type of finger and the Quinnell grading system.Results: The total efficacy was 83.6% (good/fair, 143 digits; poor, 28 digits). The treatment success rate for Quinnell grade IV was 43.8% (7 of 16), which was significantly lower than those of Quinnell grades II and III, which were 88.9% (88 of 99) and 87.5% (49 of 56), respectively (II vs. IV, p=0.004; III vs. IV, p=0.010). In four fingers (excluding the thumb), the success rate was significantly higher than that of the thumb (88.2% vs. 75.4%, p=0.048).Conclusion: The steroid injection technique using tendon excursion showed excellent results and low complication rates. In particular, the second to fourth fingers and low-grade fingers showed more effective results.

An improved understanding of the computed tomographic (CT) features for malignant versus benign oral tumors would be helpful for guiding prognosis and treatment planning decisions in dogs. This retrospective, multi-center, observational study compared the CT features of malignant and benign tumors in 28 dogs with 31 oral masses. Malignant tumors were present in 20 dogs, including malignant melanoma (n = 14), squamous cell carcinoma (SCC, n = 4), adenocarcinoma (n = 1), and fibrosarcoma (n = 1). Eight dogs had benign tumors, including giant cell granuloma (n = 2), peripheral odontogenic fibroma (n = 2), acanthomatous ameloblastoma (n = 2), plasmacytoma (n = 1), and oncocytoma (n = 1). Common CT features of malignant tumors included heterogeneous enhancement, tumor invasion into the adjacent bone, tooth loss, and ipsilateral mandibular lymphadenopathy. Malignant tumors were significantly larger than benign tumors. Bone lysis was found in benign tumors (n = 4) such as acanthomatous ameloblastoma, giant cell granuloma, and plasmacytoma. The bone lysis was a well-defined geographic area regardless of malignancy and tumor type. In periosteal reactions, amorphous patterns were seen in both malignant (n = 2) and benign tumors (n = 2); the latter subgroup also showed solid patterns. Bone expansion (n = 2) was identified in malignant melanoma and acanthomatous ameloblastoma. Findings supported a diagnosis of possible malignancy for dogs with oral tumors having the following CT characteristics: large size, heterogeneous contrast enhancement pattern, bone lysis, tooth loss, and ipsilateral lymphadenopathy. However, there was a considerable overlap of CT findings among the different types of oral tumors and between benign and malignant tumors. Histological evaluation therefore remains necessary for definitive diagnosis.

Dysregulation of inflammation induced by noninfectious stress conditions, such as nutrient deprivation, causes tissue damage and intestinal permeability, resulting in the development of inflammatory bowel diseases. We studied the effect of autophagy on cytokine secretion related to intestinal permeability under nutrient deprivation. Autophagy removes NLRP3 inflammasomes via ubiquitin-mediated degradation under starvation. When autophagy was inhibited, starvation-induced NLRP3 inflammasomes and their product, IL-1β, were significantly enhanced. A prolonged nutrient deprivation resulted in an increased epithelial mesenchymal transition (EMT), leading to intestinal permeability. Under nutrient deprivation, IL-17E/25, which is secreted by IL-1β, demolished the intestinal epithelial barrier. Our results suggest that an upregulation of autophagy maintains the intestinal barrier by suppressing the activation of NLRP3 inflammasomes and the release of their products, including proinflammatory cytokines IL-1β and IL-17E/25, under nutrient deprivation. [BMB Reports 2021; 54(5): 260-265].

In clinical studies, the effect of heart rate (HR) alone as feedback for maintaining homeostasis cannot be observed. Therefore, in this study, the effect of HR on pulse wave velocity (PWV) was investigated using a simulator without feedback. This was achieved via a one-tube model that simplifies the human arterial system and an arterial tree model similar to the human body, using a cardiovascular simulator. The one-tube model measured the pressure waveform at two measuring points 1.2 m apart, while the arterial tree model measured the pressure waveform in the carotid and femoral arteries. In the one-tube experiment, the effects of HR, mean pressure (MP), and stroke volume (SV) on PWV were independently investigated. PWV was found to increase as HR increased, but was not affected when MP and SV were changed. Further, in the arterial tree model experiment, it was observed that the PWV increased with an increase in HR. The results of this study showed that even in a simulator containing a human arterial model made of silicone material with no human feedback action, changes in HR alone affect the PWV.

The immunoproteasome (iP), an inducible proteasome variant harboring three immunosubunits, low molecular mass polypeptide-2 (LMP2), multicatalytic endopeptidase complex subunit-1, and low molecular mass polypeptide-7 (LMP7), is involved in multiple facets of inflammatory responses. We recently reported that YU102, a dual inhibitor of the iP subunit LMP2 and the constitutive proteasome catalytic subunit β1, ameliorates cognitive impairments in mouse models of Alzheimer's disease (AD) independently of amyloid deposits. To investigate whether inhibition of LMP2 is sufficient to improve the cognitive functions of AD mice, here we prepared 37 YU102 analogues and identified a potent LMP2 inhibitor DB-310 (28) (IC50: 80.6 nM) with improved selectivity and permeability in cells overexpressing ABCB1 transporters. We show that DB-310 induces suppression of IL-1α production in microglia cells and improves cognitive functions in the Tg2576 transgenic mouse model of AD. This study supports that inhibition of LMP2 is a promising therapeutic strategy for treatment of AD.

Here, we study an efficient reduction treatment for improving the electron transport properties in n-type organic field-effect transistors (OFETs) based on solution-processed polymer semiconductors. If complementary-type printed electronic circuits are to be enabled, equivalently high-performance p-type and n-type organic semiconductors have to develop. Most organic semiconductors have p-type performance superior to the n-type performance. Therefore, high-performance n-type organic semiconductors and their doping process are essential. Reduced-state viologen is known to be a powerful molecular dopant via donating electrons to the conjugated polymer semiconductors. However, the reduced-state viologen readily converts to its initial ionic species under ambient conditions, which leads to insufficient n-doping performance, especially for low electron affinity organic semiconductors. N-doped polymer semiconductors using pristine viologen molecular dopants show inadequate n-channel OFET behavior. For enhancing the electron transfer doping process, solution-based reduction treatment is used to improve remarkably the performance of n-channel OFETs based on initially p-type dominant donor-acceptor-type ambipolar polymer semiconductors. This solution-processed organic active channel layer can be produced at low cost and can be applied to flexible electronic and optoelectronic devices by using various graphic art printing techniques.

RNase E is a component of the RNA degradosome complex and plays a key role in RNA degradation and maturation in Escherichia coli. RNase E–mediated target RNA degradation typically involves the RNA chaperone Hfq and requires small guide RNAs (sRNAs) acting as a seed by binding to short (7–12-bp) complementary regions in target RNA sequences. Here, using recombinantly expressed and purified proteins, site-directed mutagenesis, and RNA cleavage and protein cross-linking assays, we investigated Hfq-independent RNA decay by RNase E. Exploring its RNA substrate preferences in the absence of Hfq, we observed that RNase E preferentially cleaves AU-rich sites of single-stranded regions of RNA substrates that are annealed to an sRNA that contains a monophosphate at its 5′-end. We further found that the quaternary structure of RNase E is also important for complete, Hfq-independent cleavage at sites both proximal and distal to the sRNA-binding site within target RNAs containing monophosphorylated 5′-ends. Of note, genetic RNase E variants with unstable quaternary structure exhibited decreased catalytic activity. In summary, our results show that RNase E can degrade its target RNAs in the absence of the RNA chaperone Hfq. We conclude that RNase E–mediated, Hfq-independent RNA decay in E. coli requires a cognate sRNA sequence for annealing to the target RNA, a 5′-monophosphate at the RNA 5′-end, and a stable RNase E quaternary structure.

In this study, we developed a drug-loading liposome linked with two types of DNA aptamers targeting the surface marker transmembrane glycoprotein mucin 1 antigen (MUC1) on breast cancer cells and cell surface glycoprotein CD44 antigen (CD44) on their cancer stem cells (CSCs). Dual-aptamer-conjugated liposomes, called dual-aptamosomes, were prepared to encapsulate doxorubicin (Dox) and tested for Dox delivery to the 3D-cultured breast cancer cells as well as CSCs. Dox was readily delivered into the cancer cells via ligand-mediated cellular uptake of dual-aptamosomes. Dual-aptamosomes harboring Dox (dual-Apt-Dox) showed a significantly higher cytotoxicity to both CSCs and cancer cells than to liposomes lacking the aptamers. Furthermore, we demonstrated inhibitory activity of dual-Apt-Dox against metastasis of breast cancer stems cells in athymic nude mice. Thus, the dual-aptamer-conjugated liposomal system can be a useful drug delivery carrier for treatment of breast cancer, given its efficiency in targeting both breast cancer cells and their CSCs.

The Alu element, the most abundant transposable element, is transcribed to Alu RNA. We hypothesized that the PIWI protein regulates the expression of Alu RNA in retinal pigment epithelial (RPE) cells, where accumulated Alu RNA leads to macular degeneration. Alu transcription was induced in RPE cells treated with H2O2. At an early stage of oxidative stress, PIWIL4 was translocated into the nucleus; however, subsequently it was sequestered into cytoplasmic stress granules, resulting in the accumulation of Alu RNA. An elevated amount of Alu RNA was positively correlated with the disruption of the epithelial features of RPE via induction of mesenchymal transition. Therefore, we suggest that oxidative stress causes Alu RNA accumulation via PIWIL4 sequestration into the cytoplasmic stress granules. [BMB Reports 2019; 52(3): 196-201].

Dysregulation of mitochondrial homeostasis and accumulation of damaged mitochondria cause degenerative diseases such as age-related macular degeneration (AMD). We studied the effects of the intermediate cytofilament KRT8 (keratin 8) on mitochondrial homeostasis in relation to the morphology and function of mitochondria in retinal pigment epithelial cells under oxidative stress. When the mitochondria were damaged owing to oxidative stress, the damaged mitochondria were readily disposed of via mitophagy following mitochondrial fission. During this process, KRT8 was found to physically interact with the mitochondria through PLEC (plectin) and facilitate the mitochondrial fission-mediated mitophagy. However, the association between PLEC-anchoring mitochondria and KRT8 was dwindled by KRT8 phosphorylation under oxidative stress. The efficient KRT8-facilitated mitophagy flux suppressed the accumulation of damaged mitochondria and consequently diminished necrotic cell death under oxidative stress. Thus, by facilitating mitophagy, KRT8 protects RPE cells against necrotic cell death due to oxidative stress. Abbreviations: 3-MA: 3-methyladenine; AMD: age-related macular degeneration; DDIT3: DNA damage inducible transcript 3; DNM1L: dynamin 1 like; ER: endoplasmic reticulum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCN1: GCN1 activator of EIF2AK4; IF: intermediate filament; KRT8: keratin 8; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3; MFF: mitochondrial fission factor; MMP: mitochondrial membrane potential; OCR: oxygen consumption rate; PLEC: plectin; ROS: reactive oxygen species; RPE: retinal pigment epithelium; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20

Background In late January, a worldwide crisis known as COVID-19 was declared a Public Health Emergency of International Concern by the WHO. Within only a few weeks, the outbreak took on pandemic proportions, affecting over 100 countries. It was a significant issue to prevent and control COVID-19 on both national and global scales due to the dramatic increase in confirmed cases worldwide. Government guidelines provide a fundamental resource for communities, as they guide citizens on how to protect themselves against COVID-19, however, they also provide critical guidance for policy makers and healthcare professionals on how to take action to decrease the spread of COVID-19. We aimed to identify the differences and similarities between six different countries’ (US, China, South Korea, UK, Brazil and Haiti) government-provided community and healthcare system guidelines, and to explore the relationship between guideline issue dates and the prevalence/incidence of COVID-19 cases. Methods To make these comparisons, this exploratory qualitative study used document analysis of government guidelines issued to the general public and to healthcare professionals. Documents were purposively sampled (N = 55) and analyzed using content analysis. Results The major differences in the evaluation and testing criteria in the guidelines across the six countries centered around the priority of testing for COVID-19 in the general population, which was strongly dependent on each country’s healthcare capacity. However, the most similar guidelines pertained to the clinical signs and symptoms of COVID-19, and methods to prevent its contraction. Conclusion In the initial stages of the outbreak, certain strategies were universally employed to control the deadly virus’s spread, including quarantining the sick, contact tracing, and social distancing. However, each country dealt with differing healthcare capacities, risks, threats, political and socioeconomic challenges, and distinct healthcare systems and infrastructure. Acknowledging these differences highlights the importance of examining the various countries’ response to the COVID-19 pandemic with a nuanced view, as each of these factors shaped the government guidelines distributed to each country’s communities and healthcare systems.

Epidermal growth factor receptor (EGFR) mutations are not only genetic markers for diagnosis but also biomarkers of clinical-response against tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). Among the EGFR mutations, the in-frame deletion mutation in EGFR exon 19 kinase domain (EGFR exon 19-del) is the most frequent mutation, accounting for about 45% of EGFR mutations in NSCLCs. Development of sensitive method for detecting the EGFR mutation is highly required to make a better screening for drug-response in the treatment of NSCLC patients. Here, we developed a fluorometric tandem gene amplification assay for sensitive detection of low-abundance EGFR exon 19-del mutant genomic DNA. The method consists of pre-amplification with PCR, thermal cycling of ligation by Taq ligase, and subsequent rolling circle amplification (RCA). PCR-amplified DNA from genomic DNA samples was used as splint DNA to conjugate both ends of linear padlock DNA, generating circular padlock DNA template for RCA. Long stretches of ssDNA harboring multiple copies of G-quadruplex structure was generated in RCA and detected by thioflavin T (ThT) fluorescence, which is specifically intercalated into the G-quadruplex, emitting strong fluorescence. Sensitivity of tandem gene amplification assay for detection of the EGFR exon 19-del from gDNA was as low as 3.6 pg, and mutant gDNA present in the pooled normal plasma was readily detected as low as 1% fraction. Hence, fluorometric detection of low-abundance EGFR exon 19 deletion mutation using tandem gene amplification may be applicable to clinical diagnosis of NSCLC patients with appropriate TKI treatment.

OBJECTIVE To investigate the effects of respiratory phase, body position, beam center location, and gastric distention on radiographic assessment of liver size in dogs. ANIMALS 12 Beagles. PROCEDURES Liver length and the ratio of liver length to T11 length were determined on lateral radiographic views obtained with various techniques. Images were acquired at maximal expiration or maximal inspiration, with dogs in right or left recumbency, with the beam centered on the caudal border of the scapula or the 13th rib, and after food was withheld or with gastric distention. Effects on organs adjacent to the liver were assessed with CT. Changes of the thoracic cavity during the respiratory cycle were investigated with fluoroscopy. RESULTS Liver length was significantly greater on radiographs obtained at maximal expiration than at maximal inspiration, but there was no increase in the ratio of liver length to T11 length. Body position, beam center location, and gastric distention did not significantly affect liver size. For CT, location of the spleen and stomach and location or size of the liver did not change markedly between right and left recumbency. Fluoroscopy revealed that thoracic width was less at maximal expiration than maximal inspiration. CONCLUSIONS AND CLINICAL RELEVANCE Liver length was greater at maximal expiration than at maximal inspiration because of a smaller thoracic width. Body position, beam center location, and gastric distention did not affect liver length. The ratio of liver length to T11 length was not significantly affected by any of the factors investigated.

Oxidative stress is a key mediator of neuronal death in acute brain injuries, such as epilepsy, trauma, and stroke. Although it is accompanied by diverse cellular changes, increases in levels of intracellular zinc ion (Zn2+) and calcium ion (Ca2+) may play a critical causative role in oxidative neuronal death. However, the mechanistic link between Zn2+ and Ca2+ dyshomeostasis in neurons during oxidative stress is not well-understood. Here, we show that the exposure of cortical neurons to H2O2 led to a zinc-triggered calcium influx, which resulted in neuronal death. The cyclin-dependent kinase inhibitor, NU6027, inhibited H2O2-induced Ca2+ increases and subsequent cell death in cortical neurons, without affecting the early increase in Zn2+. Therefore, we attempted to identify the zinc-regulated Ca2+ pathway that was inhibited by NU6027. The expression profile in cortical neurons identified transient receptor potential cation channel 5 (TRPC5) as a candidate that is known to involve in the generation of epileptiform burst firing and epileptic neuronal death (Phelan KD et al. 2012a; Phelan KD et al. 2013b). NU6027 inhibited basal and zinc-augmented TRPC5 currents in TRPC5-overexpressing HEK293 cells. Consistently, cortical neurons from TRPC5 knockout mice were highly resistant to H2O2-induced death. Moreover, NU6027 is neuroprotective in kainate-treated epileptic rats. Our results demonstrate that TRPC5 is a novel therapeutic target against oxidative neuronal injury in prolonged seizures and that NU6027 is a potent inhibitor of TRPC5.

Pigmented villonodular synovitis (PVNS)/tenosynovial giant cell tumor (TGCT) is a benign, proliferative lesion of the synovium, the bursa, and the tendon sheath. Little is known about the anatomical distribution pattern of diffuse extra-articular PVNS/TGCT around the knee joint. In this retrospective study, anatomical distribution of PVNS/TGCT using magnetic resonance imaging (MRI) and arthroscopy was analyzed. This study was designed as a retrospective, observational cross-sectional study based on MRI and arthroscopy. Twenty-four PVNS/TGCT patients (24 knees) who underwent arthroscopic or posterior open surgery between 2009 and 2016 were enrolled. Of these, eight intra-articular and 16 diffuse extra-articular PVNS/TGCT of the knee were classified. The anatomical locations of the PVNS/TGCT masses were determined with a newly devised mapping scheme. Analysis was performed on the prevalence of each compartment and agreement rates between each compartment. The point prevalence of intra-articular posterior compartment was higher in diffuse extra-articular PVNS/TGCT group compared with intra-articular PVNS/TGCT group. The point prevalence of diffuse PVNS/TGCT was most prevalent in the extra-articular posterolateral compartment (12 out of 16 diffuse extra-articular PVNS/TGCT patients, 75%) and second most common in the below to joint capsule compartment (11 out of 16, 68.8%). The agreement rate was the highest between intra-articular posterolateral and extra-articular posterolateral compartments (75%). Extra-articular invasion of diffuse PVNS/TGCT occurred in specific patterns in the knee joint. Extra-articular lesions were always accompanied by lesions in intra-articular compartments. In particular, lesions in the intra-articular posterior compartments were observed in all of the diffuse extra-articular PVNS/TGCT patients. The point prevalence of diffuse extra-articular PVNS/TGCT for each compartment was the highest [12 out of 16 (75%)] in extra-articular posterolateral compartment. In contrast, invasion to the extra-articular posteromedial side was less frequent [5 out of 16 (31.3%)] than to the extra-articular posterolateral side. Knowing where the lesions frequently occur may provide important information for deciding the timing, method, and extent of surgery. Level IV.

The aim of the present study was to compare the clinical outcomes of mobile-bearing unicompartmental knee arthroplasty (MB-UKA) and open-wedge high tibial osteotomy (OWHTO) for advanced isolated medial osteoarthritis (OA). Patients with advanced medial compartment OA (Ahlback grade ≥ II) who underwent either MB-UKA with Oxford Knee or OWHTO were included. The minimum follow-up was two years. Clinical outcomes were evaluated using the Hospital for Special Surgery (HSS) score, knee score (KS), and function score (FS) of the Knee Society Knee Scoring System. Pre-operative and post-operative values were compared within groups. Pre-operative and post-operative values and the degree of change were compared between the two groups. Radiologic progression of OA in either the lateral or patellofemoral compartment was evaluated. Forty knees (20 received MB-UKA, 20 received OWHTO) were enrolled. The mean age was higher in the MB-UKA group (67.9 ± 9.0 years) than in the OWHTO group (58.4 ± 5.5 years). The HSS score, KS, and FS were significantly increased post-operatively in both groups. The preoperative HSS score, KS, and FS were significantly lower in the MB-UKA than in the OWHTO group; however, only the post-operative HSS score was significantly higher in the MB-UKA group. The changes in HSS score and KS were also greater in the MB-UKA group. There was no significant difference in OA progression. Although there was an age difference between the two groups, MB-UKA demonstrated superior short-term clinical outcomes to OWHTO for advanced isolated medial OA. In particular, MB-UKA was more effective in terms of pain relief.

Resistance to anoikis and growth in anchorage-independent conditions are hallmarks of highly metastatic cancer cells. Anoikis is a type of apoptosis induced by inadequate cell/extracellular matrix (ECM) attachment and an attractive anti-cancer therapeutic strategy in cancer chemotherapeutic field. Therefore, the development of anoikis-inducing agents is useful and promising to overcome cancer. When FPDHP, a novel anoikis-inducing agent, was treated within 3 h, FPDHP induced massive cell detachment in various human cancer cells, irrespective of apoptosis. Moreover, FPDHP decreased the expression of integrins, FAK, focal adhesion signaling effectors (talin1 and talin2), tight junction proteins (ZO-1, ZO-2, and ZO-3), transcriptional mediators of epithelial-mesenchymal transition (EMT) (Snail1 and Snail2), and anoikis-related protein, such as Mcl-1 (L). Interestingly, Caki/ZO-2 and Caki/α6 are significantly suppressed the FPDHP-mediated cell detachment, and the constitutive active form of Akt and overexpression of Mcl-1 (L) partially inhibited the cellular detachment induced by FPDHP. On the other hand, when FPDHP was treated for more than 12 h, FPDHP induced caspase-dependent apoptosis and release of AIF and cytochrome c from mitochondria. Furthermore, FPDHP down regulated Mcl-1 (L) at post-transcriptional level, and overexpression of Mcl-1 (L) partially attenuated the apoptosis induced by FPDHP. Additionally, PD150606, a calpain inhibitor, attenuated FPDHP-mediated cell detachment and apoptosis. Taken together, these results suggest that FPDHP possesses anoikis-inducing activity or potential making cancer cells susceptible to anoikis, and may be developed as a novel active compound for cancer treatment.

OBJECTIVE: This study was performed to evaluate ocular structures using contrast‐enhanced ultrasonography (CEUS) in dogs to assess the feasibility of CEUS for investigating the blood perfusion of canine eyes. ANIMAL STUDIED: Eight purpose‐bred beagles were used. PROCEDURES: Blood perfusion and vascularity of the right eye were evaluated using color Doppler, power Doppler, and CEUS with Sonazoid®. Vascular changes were quantitatively evaluated by measuring peak intensity, time to initial upslope, and time to peak from the ciliary body, iris, choroid, retina, and the retrobulbar region by CEUS. RESULTS: On CEUS images, all parts of the examined ocular structures were markedly enhanced and clearly identified from the adjacent region. After injection, the contrast agent initially flowed to the choroid and retina at 14.2 seconds, then to the ciliary body and iris at 20 seconds. The blood signal reached its peak intensity in the ciliary body at 27.2 seconds (47.4 ± 10.63), in the iris at 31.6 seconds (74.00 ± 41.85), and in the retrobulbar region at 23.4 seconds (149 ± 24.59). The optic nerve was clearly distinguished from the retrobulbar region over 5 minutes after the initiation of CEUS. Significantly, more vascular signals were detected in the ciliary body and iris by CEUS than by color and power Doppler. CONCLUSION: Blood perfusion of the intraocular structures and the retrobulbar region can be quantitatively and qualitatively analyzed by CEUS. CEUS may be a useful, noninvasive, and sensitive tool for the evaluation of blood perfusion in ocular diseases.

Lytic induction of latent Epstein-Barr virus (EBV) has been considered as a therapeutic approach for efficient treatment of EBV-associated malignancies. Here, we established a robust assay system quantitatively measuring EBV lytic induction and identified three Euphorbia extracts as strong inducers from a screen of Korean medicinal plant extracts library. Expression of lytic genes were efficiently induced by each Euphorbia extract in SNU-719 (EBV-positive gastric carcinoma cells). Euphorbia pekinensis, out of three extracts, exhibited the most potent lytic-inducing activity. Importantly, treatment with E. pekinensis extract led to an obvious cytotoxic effect on SNU-719 cells, but little on MKN-74 cells (EBV-negative gastric carcinoma cells), indicating the selective oncolytic effect on EBV-positive gastric carcinoma. We further revealed that lytic-inducing activity of E. pekinensis was mediated by PKC/MEK signal. Moreover, we defined two structural analogs of PMA with strong lytic-inducing activity, suggesting their therapeutic applicability for the treatment of EBV-associated gastric carcinoma.

The study purpose was to investigate the jacket-fit satisfaction level of men in their 20s and 30s, using body-scanning data and a questionnaire. Thirty-five men were scanned using a 3D body scanner. The participants were divided into three groups (Small, Medium, and Large) based on their chest-circumference measurement. Their levels of satisfaction with the fit of their tailored jacket were compared by group. Chest, waist, and hip circumferences increased substantially as group size increased. The M-group was mostly satisfied with all body-site views. The S-group was especially dissatisfied with height, back width, waist circumference, and upper-arm circumference. The L-group was especially dissatisfied with waist circumference and hip circumference. The majority of the participants preferred the jacket closely fitted to their body. More than half of the participants thought finding a jacket of suitable size was difficult. When purchasing ready-to-wear jackets, the S-group and the M-group considered shoulder width important, while the L-group considered chest circumference the most important area. When evaluating the fit of ready-to-wear jackets, the L-group evaluated chest circumference, back width, and waist circumference as poor fits. The M-group evaluated sleeve length and shoulder width as poor fits, and the S-group agreed with respect to sleeve length. Body-satisfaction levels and matching jacket-satisfaction levels differed by body-size group, as did areas that need improvement. The conclusion is that size-group analysis using 3D body scanning can be utilized effectively for jacket-fit analysis. The findings of the current study can be applied to improving jacket fit among young male consumers.

Summary Cellular senescence is a stress or damage response that causes a permanent proliferative arrest and secretion of numerous factors with potent biological activities. This senescence-associated secretory phenotype (SASP) has been characterized largely for secreted proteins that participate in embryogenesis, wound healing, inflammation, and many age-related pathologies. By contrast, lipid components of the SASP are understudied. We show that senescent cells activate the biosynthesis of several oxylipins that promote segments of the SASP and reinforce the proliferative arrest. Notably, senescent cells synthesize and accumulate an unstudied intracellular prostaglandin, 1a,1b-dihomo-15-deoxy-delta-12,14-prostaglandin J2. Released 15-deoxy-delta-12,14-prostaglandin J2 is a biomarker of senolysis in culture and in vivo. This and other prostaglandin D2-related lipids promote the senescence arrest and SASP by activating RAS signaling. These data identify an important aspect of cellular senescence and a method to detect senolysis.

We demonstrate a microfiltration chip that separates blood plasma by using water-head-driven pulsatile pressures rather than any external equipment and use it for on-chip amplification of nucleic acids. The chip generates pulsatile pressures to significantly reduce filter clogging without hemolysis, and consists of an oscillator, a plasma-extraction pump, and filter units. The oscillator autonomously converts constant water-head pressure to pulsatile pressure, and the pump uses the pulsatile pressure to extract plasma through the filter. Because the pulsatile pressure can periodically clear blood cells from the filter surface, filter clogging can be effectively reduced. In this way, we achieve plasma extraction with 100% purity and 90% plasma recovery at 15% hematocrit. During a 10 min period, the volume of plasma extracted was 43 μL out of a 243 μL extraction volume at 15% hematocrit. We also studied the influence of the pore size and diameter of the filter, blood loading volume, oscillation period, and hematocrit level on the filtration performance. To demonstrate the utility of our chip for point-of-care testing (POCT) applications, we successfully implemented on-chip amplification of a nucleic acid (miDNA21) in plasma filtered from blood. We expect our chip to be useful not only for POCT applications but also for other bench-top analysis tools using blood plasma.

Psiguadial B (8), and its fluoro- (8a), chloro- (8b), and bromo- (8c) derivatives were synthesized using a sodium acetate-catalyzed single step coupling of three components: β-caryophyllene (5), diformylphloroglucinol (11), and benzaldehyde (12). These compounds efficiently and dose-dependently decreased H2O2-induced cell death, a quantitative marker of cell death, in primary cultures of mouse cortical neurons. Psiguadial B also decreased neuronal death and accumulation of ROS induced by FeCl2 in cortical cultures. The in vitro effects of these compounds in lipopolysaccharide (LPS)-induced expression of nitric oxide (NO), and TNF-α and IL-6 by suppressing the NF-κB pathway in immune cells demonstrated their antioxidative and anti-inflammatory activity. The present findings warrant further research on the development of psiguadial B-based neuroprotective agents for the treatment of neurodegenerative diseases, acute brain injuries and immunological disorders.

Gemcitabine, an anti-cancer chemotherapy drug, has additionally shown the antiviral activity against a broad range of viruses and we also have previously reported its synergistic antiviral activity with ribavirin against enteroviruses. As a cytidine analog, gemcitabine has been reported to have an inhibitory activity on the pyrimidine biosynthesis. In addition, a few inhibitors of the pyrimidine biosynthesis have shown to induce the innate immunity in a yet-to-be-determined manner and inhibit the virus infection. Thus, we also investigated whether the anti-enteroviral activity of gemcitabine is mediated by innate immunity, induction of which is related with the inhibition of the pyrimidine synthesis. In this study, we found that the addition of exogenous cytidine, uridine and uridine mono-phosphate (UMP) effectively reversed the antiviral activity of gemcitabine in enterovirus-infected as well as enteroviral replicon-harboring cells, demonstrating gemcitabine's targeting of the salvage pathway. Moreover, the expression of several interferon (IFN)-stimulated genes (ISGs) was significantly induced by the treatment of gemcitabine, which was also suppressed by the co-treatment with cytidine. These results suggest that the antiviral activity of gemcitabine involves ISGs induced by the inhibition of the pyrimidine biosynthesis.

Thioridazine is known to have anti-tumor effects by inhibiting PI3K/Akt signaling, which is an important signaling pathway in cell survival. However, thioridazine alone does not induce apoptosis in head and neck squamous cell carcinoma (AMC-HN4), human breast carcinoma (MDA-MB231), and human glioma (U87MG) cells. Therefore, we investigated whether combined treatment with thioridazine and curcumin induces apoptosis. Combined treatment with thioridazine and curcumin markedly induced apoptosis in cancer cells without inducing apoptosis in human normal mesangial cells and human normal umbilical vein cells (EA.hy926). We found that combined treatment with thioridazine and curcumin had synergistic effects in AMC-HN4 cells. Among apoptosis-related proteins, thioridazine plus curcumin induced down-regulation of c-FLIP and Mcl-1 expression at the post-translational levels in a proteasome-dependent manner. Augmentation of proteasome activity was related to the up-regulation of proteasome subunit alpha 5 (PSMA5) expression in curcumin plus thioridazine-treated cells. Combined treatment with curcumin and thioridazine produced intracellular ROS in a NOX4-dependent manner, and ROS-mediated activation of Nrf2/ARE signaling played a critical role in the up-regulation of PSMA5 expression. Furthermore, ectopic expression of c-FLIP and Mcl-1 inhibited apoptosis in thioridazine and curcumin-treated cells. Therefore, we demonstrated that thioridazine plus curcumin induces proteasome activity by up-regulating PSMA5 expression via NOX4-mediated ROS production and that down-regulation of c-FLIP and Mcl-1 expression post-translationally is involved in apoptosis., Graphical abstract fx1

Objective: The purpose of this study was to identify the effects of taping therapy and inner arch support on pes planus lower extremity alignment and gait. Method: The study was conducted on 13 women in their 20s who had pes planus and no gait problems. Independent variables were the condition of wearing basic socks (S1) and the condition of wearing socks with taping therapy and inner arch support (S2). The dependent variables were resting calcaneal stance position (RCSP), plantar pressure distribution during gait, and underlying and medial longitudinal arch angle measured using radiography. Statistical analysis was performed using the Wilcoxon test with SPSS 23.0 for comparison of S1 and S2. Results: In the RCSP measurement, the angle range of S2 changed to normal. Meary`s angle appeared to be less than the angle of S1, indicating alleviation of the degree of pes planus. The calcaneal pitch angle increased at S2 from that at S1. The plantar pressure distribution was divided into four areas (toe, forefoot, midfoot, and hindfoot). At S2, the maximum pressure increased in the toe and midfoot. The maximum force increased significantly in the toe and midfoot but decreased significantly in the forefoot and hindfoot. In addition, the contact area increased overall especially at the midfoot and hindfoot. Contact time decreased in the toe and forefoot, but increased in the midfoot and hindfoot. Conclusion: Taping therapy and inner arch support showed structural improvement of the pes planus. In addition, the force and pressure applied to the foot during walking are distributed evenly in the area of the sole, thus positively affecting walking.

Rapid contrast injection is recommended for triple-phase helical computed tomography (CT) of the liver. However, a large-gauge catheter is needed for faster contrast injection and this is not practical for small breed dogs or cats. The purpose of this crossover group study was to evaluate applicability of a lower injection rate with a small-gauge (G) catheter for triple-phase hepatic CT in small dogs. Triple-phase CT images were acquired for six beagle dogs using three protocols: an injection rate of 1.5 ml/s with a 24 G catheter, 3.0 ml/s with a 22 G catheter, and 4.5 ml/s with a 20 G catheter. Enhancement of the aorta, portal vein, and hepatic parenchyma was measured in each phase (arterial, portal, and delayed) and image quality was scored subjectively by two observers. Injection duration, time to scan delay, and time to peak enhancement were also recorded. Contrast injection duration decreased with a higher injection rate (n = 6, P ≤ 0.01), but time to peak enhancement and time to scan delay were not significantly affected by injection rates and catheter sizes. Contrast injection rate did not significantly affect aortic, portal, and hepatic enhancement. In addition, separation between each phase and quality of images was subjectively scored as good regardless of injection rate. Findings from the current study supported using an injection rate of 1.5 ml/s with a catheter size of 24 G for triple-phase hepatic CT in small dogs (weight < 12 kg).

This study examined user needs for compression pant development for women with pes planus in their 50s and 60s. A total of 355 women aged 50 to 69 participated in the survey and interview. Questions were asked if they had pes planus, the using condition of foot orthotic, inconveniences during gait, ...

Quantum dots (QDs) are powerful materials in various bioapplications based on their excellent optical and electronic properties. For the application of various fields of QDs, surface modification of QDs is necessary. However, surface modification in QDs may result in a reduction in quantum yield (QY). This reduction of QY causes many weaknesses in the biological application of QDs. In this study, CdSeZnS/ZnS alloy QDs were used to prepare antibody-conjugated QDs for a sandwich immunoassay. The alloy QDs displayed a QY of 84.5% that was maintained at 83.0% (98.2% of QY was maintained) after surface modification with the anti-rabbit IgG as a model study. Surface-modified QDs successfully detected their corresponding target through antibody-antigen binding. The limit of detection was 1.1 × 10 2 ng mL-1 for rabbit IgG.

SummaryCellular senescence is a stress or damage response that results in a permanent proliferative arrest and secretion of numerous factors with potent biological activities. This senescence-associated secretory phenotype (SASP) has been characterized largely for secreted proteins that participate in embryogenesis, wound healing, inflammation and many age-related pathologies. By contrast, lipid components of the SASP have been understudied. We show that senescent cells activate the biosynthesis of several eicosanoids that promote segments of the SASP and reinforce the proliferative arrest. Notably, senescent cells synthesize an unstudied intracellular prostaglandin, 1a,1b-dihomo-15-deoxy-delta-12,14-prostaglandin J2, which, together with other prostaglandin D2 derivatives, promote the senescence arrest and SASP by activating RAS signaling. Further, 15-deoxy-delta-12,14-prostaglandin J2 is a biomarker of senolysis in culture and in vivo. These data identify an important new aspect of cellular senescence and a novel method to detect senolysis.

The decline in early life mortality since the 1950s has resulted in dramatic demographic shift towards aged population. Aging manifests as a decline in health, multiple organ dysfunction and increased vulnerability to diseases, which degrades quality of life. A verity of genetic and pharmacological interventions, mostly from non-vertebrate models, have been identified that can enhance lifespan. Whether these interventions extend healthspan, the disease free and functional period of life, has only sometimes been tested and is often a matter of debate. Human aging indices have been developed to assess elements of functional decline with aging (e.g. sarcopenia, cognitive function). However, corresponding comprehensive indices in mice are seldom applied to aging studies. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically-relevant healthspan measurements. Metabolism and aging are tightly connected and specific perturbations of nutrient-sensing pathways can enhance longevity in laboratory animals. Here we show that alpha-ketoglutarate (delivered in the form of a Calcium salt, CaAKG), a key metabolite in tricarboxylic (TCA) cycle that is reported to extend lifespan in worms, can significantly extend lifespan and healthspan in mice. AKG is involved in various fundamental processes including collagen synthesis and epigenetic changes. Due to its broad roles in multiple biological processes, AKG has been a subject of interest for researchers in various fields. AKG also influences several age-related processes, including stem cell proliferation and osteoporosis. To determine its role in mammalian aging, we administered CaAKG in 18 months old mice and determined its effect on the onset of frailty and survival, discovering that the metabolite promotes longer, healthier life associated with a decrease in levels of inflammatory factors. Interestingly the reduction in frailty was more dramatic than the increase in lifespan, leading us to propose that CaAKG compresses morbidity.

Trans-activator (Tat)-mediated human immunodeficiency virus type 1 (HIV-1) transcription is essential for the replication of HIV-1 and is considered a potent therapeutic target for HIV-1 inhibition. In this study, the Library of Pharmacologically Active Compounds (LOPAC1280) was screened using our dual-reporter screening system for repositioning as Tat-inhibitory compounds. Consequently, two compounds were found to be potent, with low cytotoxicity. Of these two compounds, Roscovitine (CYC202) is already known to be a Tat inhibitor, while gemcitabine has been newly identified as an inhibitor of Tat-mediated transcription linked to viral production and replication. In an additional screening using the ribonucleoside analogues of gemcitabine, two analogues (2'-C-methylcytidine and 3-deazauridine) showed a specific Tat-inhibitory effect linked to their anti-HIV-1 activity. Interestingly, these compounds did not affect Tat protein directly, while the mechanism underlying their inhibition of Tat-mediated transcription was linked to pyrimidine biosynthesis, rather than to alteration of the dNTP pool, influenced by the inhibition of ribonucleotide reductase. Taken together, the proposed functional screening system is a useful tool for the identification of inhibitors of Tat-mediated HIV-1 transcription from among a large number of compounds, and the inhibitory effect of HIV-1 transcription by gemcitabine and its analogues may suggest a strategy for developing a new class of therapeutic anti-HIV drugs.

WP1130, a partially selective deubiquitinases (DUB) inhibitor, inhibits the deubiquitinating activities of USP5, USP9X, USP14, USP37, and UCHL1. In this study, we investigate whether WP1130 exerts sensitizing effect on TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human renal carcinoma cells. Combinations of WP1130 and TRAIL significantly induced apoptosis in renal carcinoma, lung carcinoma and hepatocellular carcinoma cells, but not in normal cells (human mesangial cells (MC) and normal mouse kidney cells (TCMK-1)). The downregulation of c-FLIP protein expression was involved in combined treatment-induced apoptosis. WP1130-induced c-FLIP downregulation was regulated by microRNA (miR)-708 upregulation via inhibition of USP9X. Interestingly, knockdown of USP9X markedly induced c-FLIP downregulation, upregulation of miR-708 expression and sensitivity to TRAIL. Furthermore, ectopic expression of USP9X prevented c-FLIP downregulation and apoptosis upon combined treatment. In sum, WP1130 sensitized TRAIL-induced apoptosis through miR-708-mediated downregulation of c-FLIP by inhibition of USP9X.

According to recent trends, smart clothing products that can receive electromyography (EMG) signals during the wearer’s muscle activity are being developed and commercialized. On the other hand, there is a lack of knowledge on the way to specify the electrode locations on the clothing pattern. Accurately located EMG electrodes in the clothing support the reliability and usefulness of the products. Moreover, a systematic process to construct anatomically validated smart clothing digitally should be performed to facilitate the application of a mass-customized manufacturing system. The current study explored the EMG measurement locations of nine muscles and analyzed them in association with various anthropometric points and even postures based on the 3D body scan data. The results suggest that several line segments of the patterns can be substituted by size-dependent equations for the electrodes in place. As a final step, a customized pattern of a smart EMG suit was developed virtually. The current study proposes a methodology to develop body-size dependent equations and patterns of a smart EMG suit with well-located electrodes using 3D scan data. These results suggest ways to produce smart EMG suits in response to impending automation and mass customization of the clothing manufacturing system.

Contribution of autophagy and regulation of related proteins to the degeneration of retinal pigment epithelium (RPE) in age-related macular degeneration (AMD) remain unknown. We report that upregulation of KRT8 (keratin 8) as well as its phosphorylation are accompanied with autophagy and attenuated with the inhibition of autophagy in RPE cells under oxidative stress. KRT8 appears to have a dual role in RPE pathophysiology. While increased expression of KRT8 following autophagy provides a cytoprotective role in RPE, phosphorylation of KRT8 induces pathologic epithelial-mesenchymal transition (EMT) of RPE cells under oxidative stress, which is mediated by MAPK1/ERK2 (mitogen-activated protein kinase 1) and MAPK3/ERK1. Inhibition of autophagy further promotes EMT, which can be reversed by inhibition of MAPK. Thus, regulated enhancement of autophagy with concurrent increased expression of KRT8 and the inhibition of KRT8 phosphorylation serve to inhibit oxidative stress-induced EMT of RPE cells as well as to prevent cell death, suggesting that pharmacological manipulation of KRT8 upregulation through autophagy with combined inhibition of the MAPK1/3 pathway may be attractive therapeutic strategies for the treatment of AMD.

Purpose To prospectively evaluate whether cardiac gating can improve the reproducibility of intravoxel incoherent motion (IVIM) parameters in the head and neck, we performed IVIM diffusion-weighted imaging (DWI) using 4 b values (4b), 4 b values with cardiac gating (4b gating) and 17 b values (17b). Methods We performed IVIM DWI twice per person on nine healthy volunteers using 4b, 4b gating and 17b and five patients with head and neck masses using 4b gating and 17b. The ADC, perfusion fraction (f), diffusion coefficient (D) and perfusion-related diffusion coefficient (D*) were calculated in the brain, masticator muscle, parotid gland, submandibular gland, tonsil and masses. Intraclass coefficient (ICC), Bland-Altman analysis (BAA) and coefficient of variation (CV) were used to assess short-term test-retest reproducibility. Kruskal-Wallis test and Mann-Whitney test were used to investigate whether 4b, 4b gating or 17b had significant influences on the parameters. Results For normal tissues and masses, ICC was excellent for all maps except the D* map. All parameters showed the lowest CV in the 4b gating. BAA also revealed the narrowest 95% limits of agreement using 4b gating for all parameters. In the subgroup analysis, almost all parameters in brain, muscle, parotid gland and submandibular gland showed the best reproducibility using 4b gating. In the muscle, parotid gland and submandibular gland, the values of ADC, f and D were not significantly different between among the three methods. Conclusion 4b gating was more reproducible with respect to measurements of IVIM parameters in comparison with 4b or 17b.

Previous studies have demonstrated the anticancer effects of the newly developed cyclin-dependent kinase inhibitor BAI in various cancer cells. However, the molecular mechanisms of the cellular effects induced by BAI have not been fully elucidated. The objective of this study was to investigate the mechanisms underlying the regulation of B cell lymphoma-2 (Bcl-2) family proteins in BAI-induced apoptosis of cancer cells. BAI induced poly(ADP-ribose) polymerase cleavage and DEVDase activation dose- and time-dependently. However, BAI-induced apoptosis was not involved in reactive oxygen species generation or mitogen-activated protein kinases pathways. On the other hand, BAI reduced the mitochondrial membrane potential (∆ψm) dose- and time-dependently, and induced the release of apoptosis-inducing factor (AIF) and cytochrome c from mitochondria in A549 and Caki cells. Furthermore, BAI-induced apoptosis was strongly associated with downregulation of B-cell lymphoma-extra large (Bcl-xL), but not Bcl-2, and BAI modulated the interactions among p53 and Bcl-2 family proteins in human cancer cells. Taken together, these results revealed that the regulations of Bcl-2 family proteins are correlated with BAI-induced apoptosis, suggesting that BAI is a potential multi-target agent of cancer.

This study examined the wearing conditions of compression wear for weight training. Compression wear has recently received significant attention from the public and athletes as high-level functional sportswear. The survey was conducted on 373 men in their 20s for general information on purchase behavior, preferred brand, function, and preferred design. The majority of participants (n=181) were aware of the function of compression wear. The most selected reason for wearing compression wear was for its convenience during sports activities. Respondents had the greatest preference for designs with a round neckline, regular leggings type, upper arm-length sleeve, and thigh-length bottom. Respondents also wanted a stronger compression in the core muscle part (abdomen, back, and waist).

// Seung-Hee Jo 1,2 , Dong Eun Kim 3 , Andrea Clocchiatti 1,2 and G. Paolo Dotto 1,3 1 Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA, USA 2 Department of Dermatology, Harvard Medical School, Boston, MA, USA 3 Department of Biochemistry, University of Lausanne, Epalinges, CH, Switzerland Correspondence to: G. Paolo Dotto, email: // Keywords : PDCD4, Notch/CSL signaling, transcription repression, squamous cancer, CAFs Received : May 12, 2016 Accepted : July 22, 2016 Published : August 11, 2016 Abstract The Notch/CSL pathway plays an important role in skin homeostasis and carcinogenesis. CSL, the key effector of canonical Notch signaling endowed with an intrinsic transcription repressive function, suppresses stromal fibroblast senescence and Cancer Associated Fibroblast (CAF) activation through direct down-modulation of key effector genes. Interacting proteins that participate with CSL in this context are as yet to be identified. We report here that Programmed Cell Death 4 (PDCD4), a nuclear/cytoplasmic shuttling protein with multiple functions, associates with CSL and plays a similar role in suppressing dermal fibroblast senescence and CAF activation. Like CSL, PDCD4 is down-regulated in stromal fibroblasts of premalignant skin actinic keratosis (AKs) lesions and squamous cell carcinoma (SCC). While devoid of intrinsic DNA binding capability, PDCD4 is present at CSL binding sites of CAF marker genes as well as canonical Notch/CSL targets and suppresses expression of these genes in a fibroblast-specific manner. Thus, we propose that PDCD4 is part of the CSL repressive complex involved in negative control of stromal fibroblasts conversion into CAFs.

Tau is a cytosolic protein that functions in the assembly and stabilization of axonal microtubule networks. Its oligomerization may be the rate-limiting step of insoluble aggregate formation, which is a neuropathological hallmark of Alzheimer's disease (AD) and a number of other tauopathies. Recent evidence indicates that soluble tau oligomers are the toxic species for tau-mediated pathology during AD progression. Herein, we describe novel RNA aptamers that target human tau and were identified through an in vitro selection process. These aptamers significantly inhibited the oligomerization propensity of tau both in vitro and in cultured cell models of tauopathy without affecting the half-life of tau. Tauopathy model cells treated with the aptamers were less sensitized to proteotoxic stress induced by tau overexpression. Moreover, the tau aptamers significantly alleviated synthetic tau oligomer-mediated neurotoxicity and dendritic spine loss in primary hippocampal neurons. Thus, our study demonstrates that delaying tau assembly with RNA aptamers is an effective strategy for protecting cells under various neurodegenerative stresses originating from pathogenic tau oligomerization.

Department of Rehabilitation Medicine of Korean Medicine, Colle ge of Korean Medicine, Dong-Eui University, Department of Rehabilitation Medicine of Korean Medicine, College of Korean M edicine, Sang-Ji University*, Department of Pediatrics, College of Korean Medicine, Dong-Eui University