Role of cytosolic and endoplasmic reticulum Ca2+ in pancreatic beta-cells: pros and cons.

Pancreatic beta cells utilize Ca2+ to secrete insulin in response to glucose. The glucose-dependent increase in cytosolic Ca2+ concentration ([Ca2+]C) activates a series of insulin secretory machinery in pancreatic beta cells. Therefore, the amount of insulin secreted in response to glucose is determined in a [Ca2+]C-dependent manner, at least within a moderate range. However, the demand for insulin secretion may surpass the capability of beta cells. Abnormal elevation of [Ca2+]C levels beyond the beta-cell endurance capacity can damage them by inducing endoplasmic reticulum (ER) stress and cell death programs such as apoptosis. Therefore, while Ca2+ is essential for the insulin secretory functions of beta cells, it could affect their survival at pathologically higher levels. Because an increase in beta-cell [Ca2+]C is inevitable under certain hazardous conditions, understanding the regulatory mechanism for [Ca2+]C is important. Therefore, this review discusses beta-cell function, survival, ER stress, and apoptosis associated with intracellular and ER Ca2+ homeostasis.

EGFR, HER2, and MET gene amplification and protein expression profiles in biliary tract cancer and their prognostic significance.

BACKGROUND: There are limited conventional chemotherapy options for biliary tract cancers (BTCs), a heterogenous group of lethal, rare malignancies. The receptor tyrosine kinase (RTK) is closely associated with the progression of human malignancies through the regulation of cell cycle. Overexpression or amplification of RTKs has been investigated as a potential biomarker and therapeutic target in BTC; herein, we investigate the value of such interventions. MATERIALS AND METHODS: Overexpression of RTK proteins was examined by immunohistochemistry in 193 BTC samples, of which 137 were gallbladder carcinoma, 29 were perihilar cholangiocarcinoma, and 27 were intrahepatic cholangiocarcinoma. Silver in situ hybridization of MET and HER2 was performed to assess gene amplification. RESULTS: In the entire cancer group, gallbladder, perihilar, and intrahepatic, MET amplification rates were 15.7%, 19.0%, 3.4%, and 14.8%, respectively, and of HER2 amplification rates were 22.4%, 27.2%, 17.2%, and 3.7%, respectively. MET and HER2 protein expressions were significantly correlated with their gene amplification status. RTKs were significantly associated with adverse clinicopathologic features such as advanced pT category and lymph node metastasis. Overall survival was significantly shorter in MET-amplified (P = .024) and EGFR-overexpressed cases (P = .045). Recurrence-free survival was significantly correlated with HER2-amplified (P = .038) and EGFR-overexpressed cases (P = .046) in all patient groups. Overall and recurrence-free survival were significantly shorter in patients who were double positive for HER2 and EGFR. CONCLUSION: Our data suggested that MET, HER2, and EGFR might be potential therapeutic targets and that their co-expression is a strong prognostic factor for BTCs.

Engineering Stem Cell Fate Controlling Biomaterials to Develop Muscle Connective Tissue Layered Myofibers.

Skeletal muscle connective tissue (MCT) surrounds myofiber bundles to provide structural support, produce force transduction from tendons, and regulate satellite cell differentiation during muscle regeneration. Engineered muscle tissue composed of myofibers layered within MCT has not yet been developed. Herein, a bioengineering strategy to create MCT-layered myofibers through the development of stem cell fate-controlling biomaterials that achieve both myogenesis and fibroblast differentiation in a locally controlled manner at the single construct is introduced. The reciprocal role of transforming growth factor-beta 1 (TGF-ß1) and its inhibitor as well as 3D matrix stiffness to achieve co-differentiation of MCT fibroblasts and myofibers from a human-induced pluripotent stem cell (hiPSC)-derived paraxial mesoderm is studied. To avoid myogenic inhibition, TGF-ß1 is conjugated on the gelatin-based hydrogel to control the fibroblasts' populations locally; the TGF-ß1 degrades after 2 weeks, resulting in increased MCT-specific extracellular matrix (ECM) production. The locations of myofibers and fibroblasts are precisely controlled by using photolithography and co-axial wet spinning techniques, which results in the formation of MCT-layered functional myofibers in 3D constructs. This advanced engineering strategy is envisioned as a possible method for obtaining biomimetic human muscle grafts for various biomedical applications.

Injectable Self-Oxygenating Cardio-Protective and Tissue Adhesive Silk-Based Hydrogel for Alleviating Ischemia After Mi Injury.

Myocardial infarction (MI) is a significant cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and noncontractile fibrotic scar tissue formation. Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by ≈30% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by ≈10% and 20%, respectively, with a ≈25% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy.

Massilia litorea sp. nov., Marinobacter salinisoli sp. nov. and Rhodobacter xanthinilyticus sp. nov., isolated from coastal environments.

Three bacterial strains, namely LPB0304T, LPB0319T and LPB0142T, were isolated from coastal environments. The 16S rRNA gene sequences of the three isolates were found to show the highest sequence similarities to Massilia litorea (98.44 %), Marinobacter salinisoli (97.55 %) and Rhodobacter lacus (97.60 %), respectively. The low (<98.7 %) sequence similarities and tree topologies implied the novelty of the three isolates, representing novel genomic species of the genus Massilia, Marinobacter and Rhodobacter. Numerous biochemical and physiological features also supported the distinctiveness of the isolates from previously known species. Based on the phenotypic and phylogenetic data presented in this study, three novel species are suggested with the following names: Massilia litorea sp. nov. (LPB0304T=KACC 21523T=ATCC TSD-216T), Marinobacter salinisoli sp. nov. (LPB0319T=KACC 21522T=ATCC TSD-218T) and Rhodobacter xanthinilyticus sp. nov. (LPB0142T=KACC 18892T=JCM 31567T).

Postoperative pain of minimally invasive root canal treatment:a randomized clinical trial.

This randomized clinical trial compared postoperative pain between a minimally invasive (MP) and conventional root canal treatment protocol (CP). A total of 170 mature permanent teeth (either with vital or necrotic pulp), were randomly assigned into two groups. In the CP group, ProTaper Gold (Dentsply Sirona, Ballaigues, Switzerland) and a continuous wave of condensation technique were used, whereas, in the MP group, TruNatomy (Dentsply Sirona), ultrasonic-assisted irrigation (UI), calcium hydroxide, and a sealer-based obturation technique were used. Patients recorded preoperative and postoperative pain using a 0-10 numerical rating scale (NRS) at 4 h, 1, 2, 3, 4, 5, 6, and 7 days after instrumentation and 1 day after canal obturation, respectively. There were no significant differences in pain intensity at any time points assessed between the two groups (p > 0.05). The occurrence of moderate/intense pain after instrumentation was significantly associated with preoperative periapical index (PAI) (p = 0.017) and NRS scores (p < 0.001). Preoperative pulp status (p = 0.009) and NRS score (p = 0.006) were identified as significant factors in the occurrence of moderate/intense pain after obturation. Instrumentation unequivocally reduced pain severity for both groups. The post-endodontic pain associated with the use of MP, combined with UI, Ca(OH)2, and calcium-silicate cement, did not differ from that of CP. Preoperative pain score, PAI, and preoperative pulp status were determined to be prognostic factors for postoperative pain.

Genomic and evolutionary characteristics of metastatic gastric cancer by routes.

BACKGROUND: In gastric cancer (GC) patients, metastatic progression through the lymphatic, hematogenous, peritoneal, and ovarian routes, is the ultimate cause of death. However, the genomic and evolutionary characteristics of metastatic GC have not been widely evaluated. METHODS: Whole-exome sequencing data were analyzed for 99 primary and paired metastatic gastric cancers from 15 patients who underwent gastrectomy and metastasectomy. RESULTS: Hematogenous metastatic tumors were associated with increased chromosomal instability and de novo gain/amplification in cancer driver genes, whereas peritoneal/ovarian metastasis was linked to sustained chromosomal stability and de novo somatic mutations in driver genes. The genomic distance of the hematogenous and peritoneal metastatic tumors was found to be closer to the primary tumors than lymph node (LN) metastasis, while ovarian metastasis was closer to LN and peritoneal metastasis than the primary tumor. Two migration patterns for metastatic GCs were identified; branched and diaspora. Both molecular subtypes of the metastatic tumors, rather than the primary tumor, and their migration patterns were related to patient survival. CONCLUSIONS: Genomic characteristics of metastatic gastric cancer is distinctive by routes and associated with patients' prognosis along with genomic evolution pattenrs, indicating that both primary and metastatic gastric cancers require genomic evaluation.

Chronic inflammation in high-fat diet-fed mice: Unveiling the early pathogenic connection between liver and adipose tissue.

Obesity-induced chronic inflammation has been linked to several autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. The underlying mechanisms are not yet fully understood, but it is believed that chronic inflammation in adipose tissue can lead to the production of pro-inflammatory cytokines and chemokines, which can trigger immune responses and contribute to the development of autoimmune diseases. However, the underlying mechanisms that lead to the infiltration of immune cells into adipose tissue are not fully understood. In this study, we observed a time-dependent response to a high-fat diet in the liver and epididymal white adipose tissue using gene set enrichment analysis. Our findings revealed a correlation between early abnormal innate immune responses in the liver and late inflammatory response in the adipose tissue, that eventually leads to systemic inflammation. Specifically, our data suggest that the dysregulated NADH homeostasis in the mitochondrial matrix, interacting with the mitochondrial translation process, could serve as a sign marking the transition from liver inflammation to adipose tissue inflammation. Taken together, our study provides valuable insights into the molecular mechanisms underlying the development of chronic inflammation and associated autoimmune diseases in obesity.

Wnt/ß-catenin pathway is a key signaling pathway to trastuzumab resistance in gastric cancer cells.

BACKGROUND: Trastuzumab is the only approved target agent for the first-line treatment of human epidermal growth factor receptor-2 (HER-2) positive gastric cancer; however, trastuzumab resistance is a major problem in clinical practice. To comprehend the mechanism of trastuzumab resistance, we focused on the Wnt/ß-catenin signaling pathway and its influence on the phenotypes and behavior of trastuzumab-resistant gastric cancer cells. METHODS: Trastuzumab-resistant NCI-N87R cells were established in vitro from the human gastric cancer cell line NCI-N87 by dose-escalating repeated trastuzumab treatment. We investigated the phenotypes of NCI-N87R cells, including Wnt signaling pathway activity. Gastric cancer organoid cells were incubated with complete medium and Wnt3a-depletion medium, and their resistance to trastuzumab was compared. RESULTS: NCI-N87R exhibited stemness and epithelial-mesenchymal transition (EMT)-like phenotypes, along with decreased levels of the epithelial marker E-cadherin and increased levels of the mesenchymal markers Vimentin and Snail along with an increased Wnt signaling pathway activity. When gastric cancer cells were incubated in Wnt3a-conditioned medium. Wnt signaling pathway activity and resistance to trastuzumab increased. Gastric cancer patient-derived organoids incubated in Wnt3a-depletion medium were more susceptible to dose-dependent inhibition of cell viability by trastuzumab than those incubated in complete medium. CONCLUSIONS: Trastuzumab-resistant gastric cancer cells exhibited EMT-like phenotype, and trastuzumab resistance was promoted by the Wnt/ß-catenin signaling pathway. The Wnt/ß-catenin pathway is a key signaling pathway for trastuzumab resistance in gastric cancer cells.

Phonozen-mediated photodynamic therapy comparing two wavelengths in a mouse model of peritoneal carcinomatosis.

BACKGROUND: This study assessed the therapeutic efficacy of intraperitoneal photodynamic therapy (PDT) using photosensitizer activation at two different wavelengths, 405 and 664 nm, in a mouse model of peritoneal carcinomatosis. METHODS: The dark and light cytotoxicity of chlorin e6-polyvinylpyrrolidone (Phonozen) were measured in vitro under 402 ± 14 and 670 ± 18 nm LED activation in bioluminescent human gastric cancer cells, MKN45-luc. Cell viability was measured at 6 h after irradiation using the PrestoBlue assay. Corresponding in vivo studies were performed in athymic nude mice by intraperitoneal injection of 1 × 106 MKN45-luc cells. PDT was performed 10 d after tumor induction and comprised intraperitoneal injection of Phonozen followed by light irradiation at 3 h, delivered by a diffusing-tip optical fiber placed in the peritoneal cavity and coupled to a 405 or 664 nm diode laser to deliver a total energy of 50 J (20 mice per cohort). Whole-body bioluminescence imaging was used to track the tumor burden after PDT out to 130 days, and 5 mice in each cohort were sacrificed at 4 h post treatment to measure the acute tumor necrosis. RESULTS: Photosensitizer dose-dependent photocytotoxicity was higher in vitro at 405 than 664 nm. In vivo, PDT reduced the tumor growth rate at both wavelengths, with no statistically significant difference. There was substantial necrosis, and median survival was significantly prolonged at both wavelengths compared with controls (46 and 46 vs. 34 days). CONCLUSIONS: Phonozen-mediated PDT results in significant cytotoxicity in vitro as well as tumor necrosis and prolonged survival in vivo following intraperitoneal light irradiation. Blue light was more photocytotoxic than red in vitro and had marginally higher efficacy in vivo.

Formulation of chitosan microsphere-based oral vaccine against the scuticociliate parasite Miamiensis avidus: Evaluation of its protective immune potency in olive flounder (Paralichthys olivaceus).

Miamiensis avidus is a parasitic pathogen that causes scuticociliatosis, a severe and often lethal marine infection that affects marine fishes worldwide, including olive flounder (Paralichthys olivaceus) in Korea. This parasite infects all size groups of flounder year-round, causing recurring mortalities and huge economic losses to the Korean flounder industry each year. However, few efforts have been made to implement effective remedial measures to control this parasite. Therefore, our study sought to develop a chitosan microsphere (MS)-encapsulated inactivated vaccine (IMa + chitosan) for oral delivery (adsorbed in feed) to flounder fingerlings and assess its protective efficacy at different modalities via three in vivo experimental trials. Immunisation trial-1 was conducted to determine the effective concentration of chitosan. Our findings indicated that an IMa + chitosan 0.05 % vaccine formulation was safe and effective in providing moderate protection [46.67%-53.3 % relative percent survival (RPS)] against M. avidus intraperitoneal (IP) injection challenge at two weeks post-vaccination (wpv) compared to the IMa + chitosan 0.01 % and IMa + chitosan 0.005 % vaccines (0%-13.3 % RPS) irrespective of the antigen doses. In trial-2, the IMa + chitosan 0.05 % vaccine elicited similar protective immunity (30.8%-57.1 % RPS) in olive flounder against M. avidus at varying antigen doses (high: 2.38 × 106 cells/fish; low: 1.5 × 105 cells/fish), immunisation periods (2 and 5 wpv), and challenge modes (IP injection and immersion). Furthermore, experimental trial-3 validated the use of chitosan MS as an IMa antigen carrier to improve survivability (41.7 % RPS) in the host by significantly (p < 0.05) upregulating specific anti-M. avidus antibody titres in the fish sera and mucus of the group immunised with IMa-containing chitosan MS. In contrast, non-specific immunomodulatory effects (16.7 % RPS and enhanced mucosal antibody titres) were observed in the group treated with chitosan MS without IMa. Therefore, our findings suggested that oral administration of chitosan MS (0.05 %)-encapsulated IMa vaccine is a promising immunisation strategy against M. avidus that can protect the IMa antigen from digestive degradation, facilitates its targeted delivery to the host immune organs, and helps in orchestrating protective immune induction in olive flounder, thus controlling parasite infection.

Deep learning reconstruction in pediatric brain MRI: comparison of image quality with conventional T2-weighted MRI.

INTRODUCTION: Deep learning-based MRI reconstruction has recently been introduced to improve image quality. This study aimed to evaluate the performance of deep learning reconstruction in pediatric brain MRI. METHODS: A total of 107 consecutive children who underwent 3.0 T brain MRI were included in this study. T2-weighted brain MRI was reconstructed using the three different reconstruction modes: deep learning reconstruction, conventional reconstruction with an intensity filter, and original T2 image without a filter. Two pediatric radiologists independently evaluated the following image quality parameters of three reconstructed images on a 5-point scale: overall image quality, image noisiness, sharpness of gray-white matter differentiation, truncation artifact, motion artifact, cerebrospinal fluid and vascular pulsation artifacts, and lesion conspicuity. The subjective image quality parameters were compared among the three reconstruction modes. Quantitative analysis of the signal uniformity using the coefficient of variation was performed for each reconstruction. RESULTS: The overall image quality, noisiness, and gray-white matter sharpness were significantly better with deep learning reconstruction than with conventional or original reconstruction (all P < 0.001). Deep learning reconstruction had significantly fewer truncation artifacts than the other two reconstructions (all P < 0.001). Motion and pulsation artifacts showed no significant differences among the three reconstruction modes. For 36 lesions in 107 patients, lesion conspicuity was better with deep learning reconstruction than original reconstruction. Deep learning reconstruction showed lower signal variation compared to conventional and original reconstructions. CONCLUSION: Deep learning reconstruction can reduce noise and truncation artifacts and improve lesion conspicuity and overall image quality in pediatric T2-weighted brain MRI.

Ultra-low-dose computed tomography with deep learning reconstruction for craniosynostosis at radiation doses comparable to skull radiographs: a pilot study.

BACKGROUND: Craniofacial computed tomography (CT) is the diagnostic investigation of choice for craniosynostosis, but high radiation dose remains a concern. OBJECTIVE: To evaluate the image quality and diagnostic performance of an ultra-low-dose craniofacial CT protocol with deep learning reconstruction for diagnosis of craniosynostosis. MATERIALS AND METHODS: All children who underwent initial craniofacial CT for suspected craniosynostosis between September 2021 and September 2022 were included in the study. The ultra-low-dose craniofacial CT protocol using 70 kVp, model-based iterative reconstruction and deep learning reconstruction techniques was compared with a routine-dose craniofacial CT protocol. Quantitative analysis of the signal-to-noise ratio and noise was performed. The 3-dimensional (D) volume-rendered images were independently evaluated by two radiologists with regard to surface coarseness, step-off artifacts and overall image quality on a 5-point scale. Sutural patency was assessed for each of six sutures. Radiation dose was compared between the two protocols. RESULTS: Among 29 patients (15 routine-dose CT and 14 ultra-low-dose CT), 23 patients had craniosynostosis. The 3-D volume-rendered images of ultra-low-dose CT without deep learning showed decreased image quality compared to routine-dose CT. The 3-D volume-rendered images of ultra-low-dose CT with deep learning reconstruction showed higher noise level, higher surface coarseness but decreased step-off artifacts, comparable signal-to-noise ratio and overall similar image quality compared to the routine-dose CT images. Diagnostic performance for detecting craniosynostosis at the suture level showed no significant difference between ultra-low-dose CT without deep learning reconstruction, ultra-low-dose CT with deep learning reconstruction and routine-dose CT. The estimated effective radiation dose for the ultra-low-dose CT was 0.05 mSv (range, 0.03-0.06 mSv), a 95% reduction in dose over the routine-dose CT at 1.15 mSv (range, 0.54-1.74 mSv). This radiation dose is comparable to 4-view skull radiography (0.05-0.1 mSv) and lower than previously reported effective dose for craniosynostosis protocols (0.08-3.36 mSv). CONCLUSION: In this pilot study, an ultra-low-dose CT protocol using radiation doses at a level similar to skull radiographs showed preserved diagnostic performance for craniosynostosis, but decreased image quality compared to the routine-dose CT protocol. However, by combining the ultra-low-dose CT protocol with deep learning reconstruction, image quality was improved to a level comparable to the routine-dose CT protocol, without sacrificing diagnostic performance for craniosynostosis.

In vitro response of dental pulp stem cells to dural substitute grafts: Analysis of cytocompatibility and bioactivity.

AIM: The objective of this study was to assess and compare the cytocompatibility of decellularized porcine small intestine submucosal dural graft from Biodesign (BD) and polyester urethane-based Neuro-Patch (NP) dural substitute with the mineral trioxide aggregate (MTA) and the cyanoacrylate-based Histoacryl surgical adhesive. Furthermore, the study evaluated the inflammatory response and osteogenic differentiation of human dental pulp stem cells (hDPSCs) when cultured in direct contact with the dural substitutes in comparison with MTA. METHODOLOGY: The viability of hDPSCs in direct contact with the tested materials was investigated in vitro by a CCK-8 assay. Additionally, the effects of dural substitutes and MTA on the expression of the inflammatory mediator interleukin-6 (IL-6) was investigated via enzyme-linked immunosorbent assay (ELISA), whilst effects on the differentiation were evaluated using alizarin red staining, alkaline phosphatase staining, ELISA and energy-dispersive X-ray elemental mapping. RESULTS: The dural substitutes were cytocompatible and promoted cellular adhesion. The Histoacryl and MTA demonstrated cytotoxicity in fresh preparations but showed a more favourable cellular reaction when set. Investigations of biological activity indicated that dural substitute membranes did not induce an inflammatory response or osteogenic differentiation of hDPSCs. In contrast, MTA induced the expression of IL-6 and alkaline phosphatase activity contributing to enhanced differentiation and mineralization. CONCLUSIONS: The dural substitute membranes showed cytocompatibility, did not provoke an inflammatory response and maintained the stemness of hDPSCs better than MTA. Additionally, the set Histoacryl surgical adhesive demonstrated good biocompatibility. Taken together, these results highlight the potential use of dural substitutes in regenerative endodontic procedures as coronal barriers alternative to MTA to reduce the incidence of intracanal calcifications.

Effect of icariin surface treatment on the resorption of denuded roots after replantation in rat.

AIM: Limiting the incidence of resorption associated with delayed replantation of avulsed teeth is critical for long-term tooth survival. In this study, we assessed whether icariin, a natural product with anti-osteoclastic properties, could reduce root resorption in a rat model of tooth replantation. METHODOLOGY: Cytocompatibility of icariin (10, 20, 40 and 80 µM) was evaluated by CCK-8 proliferation assay in vitro, and an osteoclastogenesis assay was performed to evaluate the effect of icariin on the differentiation of rat bone marrow macrophages and human peripheral blood monocytes into tartrate-resistant acid phosphatase-stained (TRAP+ ) multinucleated giant cells (MNGCs). Differentiation of human periodontal ligament stem cells (hPDLSCs) treated with icariin (10 µM) was also evaluated at 5, 10 and 21 days of osteogenic induction. The first maxillary molars of five-week-old male Sprague-Dawley rats were extracted, denuded of PDL, then treated either with neutralized collagen solution (Carrier control) or icariin in collagen (3 µg/µL) before replantation into their sockets. The animals were euthanized 2 weeks post-surgery for micro-computed tomography (micro-CT) imaging and histological analyses. RESULTS: Icariin was cytocompatible and significantly reduced the differentiation of TRAP+ MNGCs in a dose-dependent manner compared to the control. Moreover, icariin enhanced alkaline phosphatase activity, expression of osteogenic marker genes and proteins, and calcium deposition in hPDLSCs. Micro-CT imaging of the replanted samples demonstrated a significantly higher volume of remaining roots in the icariin-treated group than in the control group. Histological analysis revealed a marked number of resorptive lacunae with TRAP activity in the control group, whereas icariin-treated samples showed signs of functional healing and reduced osteoclastic activity. CONCLUSIONS: Icariin was biocompatible and demonstrated potent anti-osteoclastic and pro-osteogenic properties that reduced resorption and promoted functional healing of denuded roots in a rat maxillary first molar model of replantation. These findings indicate that root surface treatment with icariin may be a clinically relevant and practical method for improving the retention and survival of teeth with compromised PDL after delayed replantation following traumatic avulsion.

ASAP1 Expression in Invasive Breast Cancer and Its Prognostic Role.

Breast cancer is a major global health burden with high morbidity and mortality rates. Previous studies have reported that increased expression of ASAP1 is associated with poor prognosis in various types of cancer. This study was conducted on 452 breast cancer patients who underwent surgery at Hanyang University Hospital, Seoul, South Korea. Data on clinicopathological characteristics including molecular pathologic markers were collected. Immunohistochemical staining of ASAP1 expression level were used to classify patients into high and low groups. In total, 452 cases low ASAP1 expression group was associated with significantly worse recurrence-free survival (p = 0.029). In ER-positive cases (n = 280), the low ASAP1 expression group was associated with significantly worse overall survival (p = 0.039) and recurrence-free survival (p = 0.029). In multivariate cox analysis, low ASAP1 expression was an independent significant predictor of poor recurrence-free survival in the overall patient group (hazard ratio = 2.566, p = 0.002) and ER-positive cases (hazard ratio = 4.046, p = 0.002). In the analysis of the TCGA dataset, the low-expression group of ASAP1 protein demonstrated a significantly poorer progression-free survival (p = 0.005). This study reports that low ASAP1 expression was associated with worse recurrence-free survival in invasive breast cancer.

Cardiac Manifestations after Ingestion of a Commercial Desiccant: A Case Report.

Background and Objectives: The rise in suicidal attempts has led to an increase in unusual intoxication cases. The ingestion of anhydrous calcium chloride (CaCl2) causes direct injury to the gastrointestinal wall via a thermal burn. Therefore, previous reports on CaCl2 ingestion primarily considered the gastrointestinal injury. Severe CaCl2 intoxication can induce a hypercalcemic crisis, presenting with arrhythmia, acute pancreatitis, and acute kidney injury. This case report details a patient with hematemesis and hypercalcemia following the ingestion of a commercial desiccant. We aimed to report the progression of the case, with a focus on the electrocardiographic manifestations. Case Presentation: A 39-year-old female presented at a regional emergency center with blood in her vomit after the ingestion of a commercial desiccant. Bloody emesis was the initial symptom, and various electrolyte imbalances developed during admission. Electrocardiogram (ECG) changes occurred early after hospitalization and disappeared before the electrolyte levels normalized. The patient was maintained in an NPO (Nil Per Os) state throughout her hospital stay. The bloody emesis and abdominal pain resolved quite early, despite her minimal mention of symptoms, possibly due to her suspected negative psychiatric symptoms. Conclusions: In this case, we observed dynamic and prolonged multiple electrolyte imbalances along with the early-phase ECG changes, all of which responded well to supportive care. This report adds to the understanding of the diverse manifestations and management of CaCl2 intoxication.

PLAG co-treatment increases the anticancer effect of Adriamycin and cyclophosphamide in a triple-negative breast cancer xenograft mouse model.

Chemotherapy induces tumor cell death and inhibits tumor progression, but the accompanying immune responses in the surrounding dying tissue cause significant inflammation. These responses, such as excessive neutrophil infiltration into tumor tissue, are the main causes of resistance to anticancer treatment. The development of drugs that reduce neutrophil infiltration into tumors is necessary to increase the anticancer effect of chemotherapy. Here, we show that the antitumor effect of the chemotherapy AC regimen (Adriamycin and cyclophosphamide) was increased by 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) cotreatment in the MDA-MB-231 triple-negative breast cancer xenograft mouse model. Tumor growth was inhibited up to 56% in mice treated with AC and inhibited up to 94% in mice cotreated with AC and PLAG. Side effects of chemotherapy, such as a reduction in body weight, were alleviated in mice cotreated with AC and PLAG. Excessive neutrophil infiltration caused by the AC regimen was successfully cleared in mice cotreated with AC and PLAG. We conclude that PLAG inhibits excessive neutrophil infiltration that aids tumor growth. Reduced neutrophils and increased lymphocytes in PLAG-treated mice can maximize the antitumor effect of the AC regimen and inhibit tumor growth.

Wirelessly Powered 3D Printed Hierarchical Biohybrid Robots with Multiscale Mechanical Properties.

The integration of flexible and stretchable electronics into biohybrid soft robotics can spur the development of new approaches to fabricate biohybrid soft machines, thus enabling a wide variety of innovative applications. Inspired by flexible and stretchable wireless-based bioelectronic devices, we have developed untethered biohybrid soft robots that can execute swimming motions, which are remotely controllable by the wireless transmission of electrical power into a cell simulator. To this end, wirelessly-powered, stretchable, and lightweight cell stimulators were designed to be integrated into muscle bodies without impeding the robots' underwater swimming abilities. The cell stimulators function by generating controlled monophasic pulses of up to ∼9 V in biological environments. By differentiating induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) directly on the cell stimulators using an accordion-inspired, three-dimensional (3D) printing construct, we have replicated the native myofiber architecture with comparable robustness and enhanced contractibility. Wirelessly modulated electrical frequencies enabled us to control the speed and direction of the biohybrid soft robots. A maximum locomotion speed of ∼580 µm/s was achieved in robots possessing a large body size by adjusting the pacing frequency. This innovative approach will provide a platform for building untethered and biohybrid systems for various biomedical applications.

Association of Albumin-Bilirubin Grade and Myosteatosis with its Prognostic Significance for Patients with Colorectal Cancer.

BACKGROUND: The albumin-bilirubin (ALBI) grade is a useful prognostic and predictive marker for patients with liver disease. Its clinical significance has been limited to patients with colorectal cancer (CRC). Furthermore, the association between the ALBI grade and skeletal muscle-related indices is unclear. METHODS: This study enrolled 1015 patients who underwent computed tomography (CT) scans within 31 days before surgery. The prognostic value of the ALBI grade in predicting overall survival (OS) was assessed using the Cox proportional hazards model. The correlation between the ALBI grade and the skeletal muscle index or radiodensity (myosteatosis) was evaluated. The predictive accuracy of ALBI alone and in combination with myosteatosis was compared using Harrell's concordance index (C-index). RESULTS: The significant prognostic factors for OS identified in the multivariable analysis were the ALBI group (low vs high: hazard ratio [HR], 1.566; 95 % confidence interval [CI], 1.174-2.089; p = 0.002) and myosteatosis (low vs. high: HR, 0.648; 95 % CI, 0.486-0.865; p = 0.003). The rate of low-grade myosteatosis increased as the ALBI grade increased. The C-index of combined ALBI and myosteatosis (0.650; 95 % CI, 0.618-0.683) was superior to that of ALBI alone (0.603; 95 % CI, 0.575-0.631; bootstrap incremental area under the curve [iAUC] mean difference, 0.047; 95 % CI, 0.012-0.070) and myosteatosis alone (0.608; 95 % CI, 0.577-0.640; bootstrap iAUC mean difference, 0.042; 95 % CI, 0.023-0.064). CONCLUSION: The ALBI grade is significantly associated with myosteatosis. The ALBI grade is a significant prognostic factor, and the combination of ALBI and myosteatosis show an additive value in discriminating survival of patients with CRC.