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Abstract Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.

Purpose The aim of this study was to investigate the clinical efficacy of near-infrared reflectance (NIR) imaging and optical coherence tomography (OCT) in identifying ocular manifestations of neurofibromatosis type 1 (NF1) in Korean children. Methods This retrospective chart review study included five Korean children with NF1 aged under 18 years who had undergone ophthalmic procedures, including slit-lamp examinations, NIR imaging, and OCT scanning. Results Multiple patchy bright lesions were observed on NIR imaging in all eyes (10 eyes in five patients). Further NIR imaging and OCT scans showed that these lesions, confined to the choroid, were choroidal nodules. Lisch nodules, contrastingly, were found in only four of 10 eyes by slit-lamp examinations on the same day as the NIR imaging. One of those four eyes had only one Lisch nodule, which did not meet the NF1 diagnostic criteria. Conclusion NIR imaging enabled the detection of choroidal nodules in Korean children with NF1. Moreover, for Korean children with NF1, choroidal nodules were earlier-detected ocular manifestations relative to Lisch nodules. NIR imaging, along with OCT, is a useful protocol for localizing NF1 nodules in children.

Semiconductors processed at low temperature for complementary metal–oxide semiconductors (CMOS) devices are receiving considerable attention in the field of integrated electronic applications. In this work, we demonstrated a CMOS inverter constructed by n-type ZnON and p-type Te TFTs where all the processes have been done at low temperature. The electrical measurements of proposed TFTs exhibit high mobility (> 100 and > 3 cm2/Vs in case of ZnON and Te TFTs, respectively) and a stable on/off current ratio. The resulted CMOS inverter exhibits a high voltage swing and a high voltage gain of 15.89. Since all the synthesis and fabrication processes are performed at low temperatures with easy processing techniques, the results may open new opportunities in the field of integrated electronics field.

Here, we report the case of a patient with multiple parallel-line endotheliitis with myopic shift, which has not been previously reported. A 36-year-old man visited our clinic with blurred vision in his left eye. A slit lamp examination revealed an interesting pattern of multiple parallel lines of keratic precipitates, along with subtle corneal edema. The spherical equivalents measured in the right and left eyes were −9.25 and −11.875 diopter, respectively, with the left eye showing more myopic progression. On specular microscopy, endothelial cell loss was found in the left eye. After administration of a weak topical steroid, keratic precipitates and corneal edema resolved completely within 2 days. The myopic shift in his left eye recovered to −10.0 diopters. Multiple parallel-line endotheliitis can be easily treated with a weak topical steroid in a short period. A temporary myopic shift may occur, which in this case resolved upon disease recovery. However, corneal endothelial cell loss is inevitable; therefore, careful monitoring is needed.

Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn’s disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end.

Integration of communication and radar functions with a single waveform has been actively investigated in various wireless communication applications, including unmanned aerial vehicles (UAVs). This means that communication frames consisting of a pilot part and subsequent data part can be utilized to transmit information and detect the surrounding objects simultaneously. Because a predetermined waveform is required for the radar function, the pilot part in the communication frame can be utilized for radar purposes. Specifically, the pilot is used for both channel estimation, which is required for data decoding, and a radar waveform. Assuming that the length of the pilot and data parts is given and the transmit energy for each frame is limited, the optimal transmit power for the pilot and data parts can be analytically obtained by considering both radar and communication performance metrics. The optimality of the proposed analytical solution was verified through numerical simulations.

Objective: Dicer is an enzyme that processes microRNAs (miRNAs) precursors into mature miRNAs, which have been implicated in various aspects of cancer progressions, such as clinical aggressiveness, prognosis, and survival outcomes. We previously showed that high expression of Dicer is associated with gemcitabine (GEM) resistance in pancreatic ductal adenocarcinoma (PDAC); thus, in this study, we aimed to focus on how Dicer is involved in GEM resistance in PDAC, including cancer prognosis, cell proliferation, and metabolic regulation. Methods: We generated stable shRNA knockdown of Dicer in GEM-resistant PANC-1 (PANC-1 GR) cells and explored cell viability by MTT and clonogenicity assays. Metabolomic profiling was employed to investigate metabolic changes between parental cells, PANC-1, and PANC-1 GR cells, and further implied to compare their sensitivity to the glutaminase inhibitor, CB839, and GEM treatments. To identify putative phosphorylation site involves with Dicer and its effects on GEM resistance in PDAC cells, we further generated phosphomimetic or phosphomutant Dicer at S1016 site and examined the changes in drug sensitivity, metabolic alteration, and miRNA regulation. Results: We observed that high Dicer levels in pancreatic ductal adenocarcinoma cells were positively correlated with advanced pancreatic cancer and acquired resistance to GEM. Metabolomic analysis indicated that PANC-1 GR cells rapidly utilised glutamine as their major fuel and increased levels of glutaminase (GLS): glutamine synthetase (GLUL) ratio which is related to high Dicer expression. In addition, we found that phosphomimetic Dicer S1016E but not phosphomutant Dicer S1016A facilitated miRNA maturation, causing an imbalance in GLS and GLUL and resulting in an increased response to GLS inhibitors. Conclusion: Our results suggest that phosphorylation of Dicer on site S1016 affects miRNA biogenesis and glutamine metabolism in GEM-resistant pancreatic cancer.

Abstract Pancreatic cancer is one of the most lethal diseases which lack an early diagnostic marker. We investigated whether serum ferritin (SF) reflects risk for pancreatic cancer and potential genes that may contribute ferritin and pancreatic cancer risks. We performed a meta-analysis of relevant studies on SF and pancreatic cancer risk by searching articles in PUBMED and EMBASE published up to 1 March 2020. We also collected serum samples from Taipei Medical University Joint Biobank and compared SF levels in 34 healthy controls and 34 pancreatic cancer patients. An Oncomine database was applied as a platform to explore a series of genes that exhibited strong associations between ferritin and pancreatic cancer. Herein, we show that high levels of SF can indicate risk of pancreatic cancer, suggesting SF as the new tumor marker that may be used to help pancreatic cancer diagnosis. We also found that expressions of iron homeostasis genes (MYC, FXN) and ferroptosis genes (ALOX15, CBS, FDFT1, LPCAT3, RPL8, TP53, TTC35) are significantly altered with pancreatic tumor grades, which may contribute to differential expression of ferritin related to pancreatic cancer prognosis.

Oxaliplatin, a third-generation platinum derivative, has become one of the main chemotherapeutic treatments for esophagus, gastric and colorectal cancer; however, it is still unclear the potential effectiveness for pancreatic ductal adenocarcinoma (PDAC) with gemcitabine resistance. Here, we observed that PDAC tumors have low level of organic cation transporter 2 (OCT2, also known as SLC22A2) compared with non-tumor tissues and identified that OCT2 expression is positively correlated with oxaliplatin sensitivity in PDAC cells. Treatment of OCT2 inhibitors or knockdown of OCT2 expression significantly decreased the sensitivity to oxaliplatin in PANC-1 cells. In addition, bisulfite sequencing polymerase chain reaction analysis revealed that higher methylation frequency represses OCT2 expression in gemcitabine-resistant PANC-1 (PANC-1/GR) cells. Moreover, we found that treatment of DNA methyltransferase (DNMT) inhibitors, decitabine or 5-azacytidine recover OCT2 expression and oxaliplatin sensitivity in PANC-1/GR cells, and DNMT1 level has inverse correlation with OCT2 expression in PDAC cells and tumors. Our findings jointly suggest that OCT2 expression is a potential and predictive marker for evaluating oxaliplatin sensitivity and developing alternative treatments for PDAC patients with gemcitabine resistance.

Purpose: We report a case of corneal verticillata in a patient who had been taking raloxifene for a prolonged period. To our knowledge, this is the first case report of an ocular side effect of raloxifene. Observations: A 69-year-old female patient presented to our clinic for her routine eye check-up. On slit-lamp examination, whorl-like subepithelial deposits were observed in the bilateral corneas. She was diagnosed with corneal verticillata (vortex keratopathy) caused by raloxifene. A follow-up evaluation was conducted after discontinuation of the drug; however, the corneal opacity did not improve. Conclusions and importance: Patients with corneal verticillata should be asked regarding any intake of raloxifene for osteoporosis, as it may cause corneal verticillata.

Objective: Breast cancer is the second leading cause of cancer deaths in women worldwide and represents a highly aggressive nature with limited therapeutic options; thus, investigating novel therapeutic agents for breast cancer is much needed. In this study, we investigated the anticancer effects of a novel camptothecin derivative, CPT211, against human breast cancer. Methods: We used hormone receptor-positive MCF-7, triple-negative (TNBC) MDA-MB-231, and HER2-positive BT-474 human breast cancer cells to examine cytotoxicity of CPT211. We measured cell viability with dose dependence of CPT211 treatments by an MTT assay and investigated the potential underlying mechanism through flow cytometric and Western blot methods. Furthermore, we evaluated the efficacy of the treatment combination of CPT211 and doxorubicin in a mouse model bearing MDA-MB-231 xenografts. Results: CPT211 treatment led to dose-dependent decreases in cell viability of both MCF-7 and MDA-MB-231 cells, but not BT-474 cells. Analysis of the underlying molecular mechanism revealed that CPT211 activated p53-mediated apoptosis, by triggering intrinsic and extrinsic apoptotic pathways in MCF-7 cells. Additionally, CPT211 induced apoptosis and cell cycle arrest of MDA-MB-231 cells by activating Fas/FADD/caspase-8 signaling, suggesting that CPT211-mediated MDA-MB-231 cell apoptosis may occur through an extrinsic apoptosis pathway. CPT211 treatment with doxorubicin in mice bearing MDA-MB-231 xenografts was shown to enhance caspase-8 and caspase-7 activation, resulting in significant inhibition of tumor growth. Conclusions: These results indicate that Fas/FADD/caspase-8 activation plays an important role in CPT211-mediated tumor growth suppression in TNBC, and the novel camptothecin derivative, CPT211, can be exploited for specific targeted therapies and potentially improve approaches to combination treatments for human breast cancer.

Background: The oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types; however, the underlying mechanism of HPS/FGL1 in the KRAS mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear. Methods: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a KRAS-wild-type PDAC cell line (BxPC-3), and KRAS-mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. HEK293T cells were transiently transfected with corresponding KRAS-expressing plasmids to examine the level of HPS expression with KRAS activation. We knocked-down HPS/FGL1 using lentiviral vectors in SUIT-2 cells and measured the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenicity assays. Furthermore, a lipidomic analysis was performed to profile changes in lipid metabolism after HPS/FGL1 knockdown. Results: We found that the HPS/FGL1 level was significantly upregulated in KRAS-mutated PDAC cells and was involved in KRAS/phosphorylated (p)-signal transduction and activator of transcription 3 (STAT3) signaling, and the knockdown of HPS/FGL1 in SUIT-2 cells decreased cell proliferation through increasing G2/M cell cycle arrest and cyclin B1 expression. In addition, the knockdown of HPS/FGL1 in SUIT-2 cells significantly increased omega-3 polyunsaturated fatty acids (PUFAs) and EPA production but not docosahexaenoic acid (DHA). Moreover, EPA treatment in SUIT-2 cells reduced the expression of de novo lipogenic protein, acetyl coenzyme A carboxylase (ACC)-1, and decreased p-STAT3 and HPS/FGL1 expressions, resulting in the suppression of cell viability. Conclusions: Results of this study indicate that HPS is highly expressed by KRAS-mutated PDAC cells, and HPS/FGL1 plays a crucial role in altering lipid metabolism and increasing cell growth in pancreatic cancer. EPA supplements could potentially inhibit or reduce ACC-1-involved lipogenesis and HPS/FGL1-mediated cell survival in KRAS-mutated pancreatic cancer cells.

This study aimed to determine the association between consumption of ultra-processed foods and obesity among Korean adults. We used the data of 7364 participants (men 3219, women 4145) aged 19–64 years from the Korea National Health and Nutrition Examination Survey (KNHANES), 2016–2018. Food items were classified using the NOVA food classification system, depending on the extent and purpose of food processing: (1) unprocessed or minimally processed foods, (2) processed culinary ingredients, (3) processed foods, and (4) ultra-processed foods. Consumption of ultra-processed foods accounted for 26.8% of the total energy intake. After adjusting for potential confounders including sociodemographic and lifestyle characteristics, subjects with the highest consumption of ultra-processed foods (fourth quartile of % energy intake from ultra-processed foods) had 0.61 kg/m2 higher body mass index (BMI; 95% confidence interval [CI] 0.23–0.99, p-trend 0.0047), 1.34 cm higher waist circumference (WC; 95% CI 0.35–2.34, p-trend 0.0146), 51% higher odds of being obese (BMI > 25 kg/m2; odds ratio [OR] 1.51, 95% CI 1.14–1.99, p-trend 0.0037), and 64% higher odds of abdominal obesity (men: WC ≥ 90 cm, women: WC ≥ 85 cm; OR 1.64, 95% CI 1.24–2.16, p-trend 0.0004) than those with the lowest consumption (first quartile) among women. However, no association was found in men. These findings provide evidence that high consumption of ultra-processed foods is positively associated with obesity in Korean women. Further studies with a large-scale cohort or intervention trial are needed to identify the mechanism of associations between consumption of ultra-processed foods and health-related outcomes including obesity in Korea.

Cancer cells can secrete exosomes under various stressful conditions, whose functions are involved in the delivery of various biologically active materials into host cells and/or modulation of host immune responses. Therefore, an improved understanding of the immunological interventions that stress-induced tumor exosomes have may provide novel therapeutic approaches and more effective vaccine designs. Here, we confirmed the phenotypical and functional alterations of dendritic cells (DCs), which act as a bridge between the innate and adaptive arms of immunity, following non-irradiated (N-exo) and gamma-irradiated melanoma cancer cell-derived exosome (G-exo) stimulation, and evaluated the N-exo- and G-exo-stimulated DCs as therapeutic cancer vaccine candidates. We demonstrated that G-exo-stimulated DCs result in DC maturation by the upregulation of surface molecule expression, pro-inflammatory cytokine release, and antigen-presenting ability, and the downregulation of endocytic capacity. In addition, these cells promoted T cell proliferation and the generation of T helper type 1 (Th1) and interferon (IFN)-γ-producing CD8+ T cells. However, N-exo-stimulated DCs induced semi-mature phenotypes and functions, eventually inhibiting T cell proliferation, decreasing IFN-γ, and increasing IL-10-producing CD4+ T cells. In addition, although N-exo and G-exo stimulations showed similar levels of antigen-specific IFN-γ production, which served as tumor antigen sources in melanoma-specific T cells, G-exo-stimulated DC vaccination conferred a stronger tumor growth inhibition than N-exo-stimulated DC vaccination; further, this was accompanied by a high frequency of tumor-specific, multifunctional effector T cells. These results suggest that gamma irradiation could provide important clues for designing and developing effective exosome vaccines that can induce strong immunogenicity, especially tumor-specific multifunctional T cell responses.

The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 disease (COVID)-19 is having profound effects on the global economy and food trade. Limited data are available on how this pandemic is affecting our dietary and lifestyle-related behaviors at the global level. Google Trends was used to obtain worldwide relative search volumes (RSVs) covering a timeframe from before the COVID-19 pandemic 1 June 2019 to 27 April 2020. Spearman’s rank-order correlation coefficients were used to measure relationships between daily confirmed cases and aforementioned RSVs between 31 December 2019 and 15 April 2020. RSV curves showed increased interest in multiple keywords related to dietary and lifestyle behaviors during the COVID-19 lockdown period in March and April 2020. Spearman’s correlation analysis showed that the strongest variables in each keyword category were (1) food security (food shortage: r = 0.749, food bank: r = 0.660, and free food: r = 0.555; all p < 0.001), (2) dietary behaviors (delivery: r = 0.780, restaurant: r = −0.731, take-away: r = 0.731, and food-delivery: r = 0.693; all p < 0.001), (3) outdoor-related behaviors (resort: r = −0.922, hotel: r = −0.913, cinema: r = −0.844, park: r = −0.827, fitness: r = −0.817, gym: r = −0.811; plant: r = 0.749, sunbathing: r = 0.668, and online: r = 0.670; all p < 0.001), and (4) immune-related nutrients/herbs/foods (vitamin C: r = 0.802, vitamin A: r = 0.780, zinc: r = 0.781, immune: r = 0.739, vitamin E: r = 0.707, garlic: r = 0.667, omega-3 fatty acid: r = −0.633, vitamin D: r = 0.549, and turmeric: r = 0.545; all p < 0.001). Restricted movement has affected peoples’ dietary and lifestyle behaviors as people tend to search for immune-boosting nutrients/herbs and have replaced outdoor activities with sedentary indoor behaviors.

Purpose : We aimed to prove the relative limitation of 99mTc-DMSA scintigraphy (DMSA) compared to computed tomography (CT) in diagnosing acute pyelonephritis (APN) in children. Methods : Since September 2006, after a 64-channel CT was imported, 10 DMSA false-negative patients have been identified: these patients underwent a CT scan for acute abdomen or acute febrile symptoms and were diagnosed as having APN; however, their DMSA scans were clear. We focused on these 10 DMSA false-negative patients and analyzed their clinical findings and CT results. We used Philips Brilliance Power 64-channel CT scanner for the CT scan and Siemens Orbitor Nuclear Camera 60 Hz for the DMSA scan. Results:The 10 DMSA false-negative patients were mostly males (80%) and infants (80%). They had fever for a mean of 1.1-day duration before admission and showed increase in acute reactants: leukocyte, erythrocyte sedimentation rate, and C-reactive protein. The CT findings of renal lesions were focal in 6 (60%) cases and diffuse in 4 (40%) cases, and most of the lesions were unilateral in 80% of patients. CT proved that 22 renal lesions were neglected by DMSA. Differential renal function test by DMSA was also of no use in the evaluation of renal lesions. Conclusion:In this study, DMSA scan showed limitation in finding renal cortical lesions of CT-proven APN patients. DMSA false-negative results seem to occur at early-phase disease of infantile age, but more prospective studies are needed to determine the reasons and their prevalence.

Background: Myositis is an inflammatory myopathy that can be caused by a variety of drugs, diseases, and toxins. The U.S. military uses chemoprophylaxis with intramuscular penicillin G to prevent group A streptococcal infection. We present a case of penicillin G-induced myositis, a rare cause of drug-induced myositis with limited discussion in the medical literature. Case Report: A 25-year-old man with no pertinent medical history presented to the Emergency Department with right hip and leg pain after receiving a single dose of intramuscular penicillin G as part of standard prophylaxis for group A streptococcal infection during basic military training. He reported pain and leg weakness that was exacerbated by physical exertion and weight bearing but had no systemic symptoms, such as fevers or chills. Initial radiographs of the hip were normal; however, subsequent magnetic resonance imaging of the hip revealed intramuscular edema and features consistent with myositis of the right proximal thigh and hip musculature. He was admitted for isolated right gluteal myositis, attributed to his preceding local penicillin injection. He recovered with symptomatic care over the following 2 weeks, with return to baseline function. Conclusions: This case highlights a rare complication of intramuscular penicillin G as a cause of acute isolated myositis. It serves to inform physicians of this rare complication and to recommend the consideration of intramuscular penicillin G as a causative etiology in individuals presenting with myositis and recent penicillin G exposure. [ABSTRACT FROM AUTHOR]