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Dong Soo Suh,1,2,&ast; Yong Jung Song,1,2,&ast; Hyun-Jin Roh,3 Sang Hun Lee,3 Dae Hoon Jeong,4 Tae Hwa Lee,5 Kyung Un Choi,6 Ki Hyung Kim1,2 1Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan, South Korea; 2Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea; 3Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea; 4Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea; 5Department of Obstetrics and Gynecology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, South Korea; 6Department of Pathology, Pusan National University School of Medicine, Busan, South Korea&ast;These authors contributed equally to this workCorrespondence: Ki Hyung KimDepartment of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan, South KoreaTel +82-51-240-7287Fax +82-51-248-2384Email ghkim@pusan.ac.krPurpose: Preoperative diagnosis of uterine leiomyosarcoma (LMS) is challenging because the disease can mimic benign leiomyoma (LM). The objective of the present study was to investigate the role of preoperative clinical characteristics and hematologic parameters to differentiate uterine LMS and LM.Methods: Preoperative clinical and laboratory variables were reviewed retrospectively in patients with LMS or LM, and the significances of intergroup differences were assessed. Receiver operating characteristic (ROC) curves were used to determine optimal cut-off values for each variable. Logistic regression analysis was applied to identify variables predicting the presence of LMS.Results: The preoperative clinical and laboratory variables of 336 patients with uterine tumor were analyzed. Seventy-nine patients had LMS and 257 had LM. A significant difference was observed between LMS and LM in terms of the median value of age at diagnosis, menopausal status, white blood cell (WBC) count, absolute neutrophil count (ANC), C-reactive protein (CRP), lactate dehydrogenase (LDH), and neutrophil-to-lymphocyte ratio (NLR) (all P < 0.001). Multivariate analyses showed that menopausal status (odds ratio [OR] = 3.40, P= 0.002), WBC count (OR = 2.09, P = 0.012), ANC (OR = 3.17, P < 0.001), CRP (OR = 21.74, P < 0.001), LDH (OR = 10.77, P < 0.001), and NLR (OR = 2.58, P = 0.001) predicted the presence of LMS.Conclusion: Our results suggest that in older or postmenopausal patients, high WBC count, ANC, CRP, LDH, and NLR could be useful biomarkers for the differentiation of LMS and LM, which indicate that serum markers might be useful, cost-effective, and broadly available diagnostic markers for uterine LMS.Keywords: C-reactive protein, lactate dehydrogenase, leiomyoma, leiomyosarcoma, neutrophil-to-lymphocyte ratio

Background. Timely treatment is important for patients with acute ischemic stroke (AIS). However, the coronavirus disease 2019 (COVID-19) outbreak may have caused delays in patient management. Therefore, we analyzed the prognosis and the time spent at the prehospital and hospital stages in managing patients diagnosed with AIS during the COVID-19 outbreak. Methods. This retrospective study evaluated patients diagnosed with AIS in the emergency department (ED) at five medical centers in Daegu city between February 18 and April 17 each year from 2018 to 2020. Data on the patients’ clinical features and time spent on management were collected and compared according to COVID-19 and pre-COVID-19 summaries. Results. From a total of 533 patients diagnosed with AIS, 399 patients visited the ED before COVID-19 and 134 during the COVID-19 outbreak. During the COVID-19 outbreak, compared with pre-COVID-19, AIS patients had poor National Institute of Health Stroke Scale scores at the initial hospital visit (6 vs. 4, p = 0.013 ) and discharge (3 vs. 2, p = 0.001 ). During the COVID-19 outbreak, the proportion of direct visits to hospitals through public emergency medical services (EMS) increased, and the onset of symptoms-to-ED door time via the public EMS was delayed (87 min vs. 68 min, p = 0.006 ). Conclusions. The prognosis of AIS patients during the COVID-19 outbreak was worse than that of pre-COVID-19 patients with delays at the prehospital stage, despite the need for timely care.

Purpose:G9a histone methyltransferase exerts oncogenic effects in several tumor types and its inhibition promotes anticancer effects. However, the impact on checkpoint inhibitor blockade response and the utility of G9a or its target genes as a biomarker is poorly studied. We aimed to examine whether G9a inhibition can augment the efficacy of checkpoint inhibitor blockade and whether LC3B, a G9a target gene, can predict treatment response.Experimental Design:Clinical potential of LC3B as a biomarker of checkpoint inhibitor blockade was assessed using patient samples including tumor biopsies and circulating tumor cells from liquid biopsies. Efficacy of G9a inhibition to enhance checkpoint inhibitor blockade was examined using a mouse model.Results:Patients with melanoma who responded to checkpoint inhibitor blockade were associated with not only a higher level of tumor LC3B but also a higher proportion of cells expressing LC3B. A higher expression of MAP1LC3B or LC3B protein was associated with longer survival and lower incidence of acquired resistance to checkpoint inhibitor blockade, suggesting LC3B as a potential predictive biomarker. We demonstrate that G9a histone methyltransferase inhibition is able to not only robustly induce LC3B level to augment the efficacy of checkpoint inhibitor blockade, but also induces melanoma cell death.Conclusions:Checkpoint inhibitor blockade response is limited to a subset of the patient population. These results have implications for the development of LC3B as a predictive biomarker of checkpoint inhibitor blockade to guide patient selection, as well as G9a inhibition as a strategy to extend the proportion of patients responding to immunotherapy.

The LIF-JAK2-STAT3 pathway is the central signal transducer that maintains undifferentiated mouse embryonic stem cells (mESCs), which is achieved by the recruitment of activated STAT3 to the master pluripotency genes and activation of the gene transcriptions. It remains unclear, however, how the epigenetic status required for the master gene transcriptions is built into LIF-treated mESC cultures. In this study, Jak2, but not Stat3, in the LIF canonical pathway, establishes an open epigenetic status in the pluripotency gene promoter regions. Upon LIF activation, cytosolic JAK2 was translocalized into the nucleus of mESCs, and reduced DNA methylation (5mC levels) along with increasing DNA hydroxymethylation (5hmC) in the pluripotent gene (Nanog/Pou5f1) promoter regions. In addition, the repressive histone codes H3K9m3/H3K27m3 were reduced by JAK2. Activated JAK2 directly interacted with the core epigenetic enzymes TET1 and JMJD2, modulating its activity and promotes the DNA and histone demethylation, respectively. The JAK2 effects were attained by tyrosine phosphorylation on the epigenetic enzymes. The effects of JAK2 phosphorylation on the enzymes were diverse, but all were merged to the epigenetic signatures associated with open DNA/chromatin structures. Taken together, these results reveal a previously unrecognized epigenetic regulatory role of JAK2 as an important mediator of mESC maintenance.

Although mechanical thrombectomy is a powerful predictor of stroke outcome, it induces vessel wall injury in the acute phase. This study aimed to analyze the degree and the condition of recovery of wall injury after the acute phase via angiography and histopathological analysis of autopsied canine models. Digital subtraction angiography (DSA) and embolization with autologous thrombus were performed in six canines. The model of arterial occlusion was effective in all target vessels. Mechanical thrombectomy was performed in completely occluded vessels using stent retriever. Follow-up angiographic and histopathologic evaluations were performed 1 month later. Complete recanalization using stent retriever was achieved in four cases. Slight residual vessel narrowing after recanalization and moderate narrowing was observed in one case each. Histopathological analysis showed that inflammation, hemorrhage, and device-induced medial injury were not observed in any of the cases. Severe intimal proliferation (grade 4), marked diffuse thrombosis (grade 4), and weak vascular endothelial cell loss (grade 1) were observed in one case and weak endovascular proliferation was observed in one case. Although successful complete recanalization was achieved with a single mechanical thrombectomy attempt and no change was observed in the follow-up DSA, special attention should be paid to postoperative follow-up, as device-induced intimal proliferation, diffuse thrombosis, and endothelial cell loss may remain after 1 month.

Purpose The aim of this study was to compare survival outcomes of total abdominal radical hysterectomy (TARH) versus laparoscopy-assisted radical vaginal hysterectomy (LARVH) in stage IA2-IB2 cervical cancer. Methods 812 patients who underwent RH between 2008 and 2017 were evaluated in 3 institutions. Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier method and compared by log-rank test. The clinical noninferiority of the LARVH to TARH was assessed with a margin of −7.2%. Noninferiority was demonstrated if the low limit of 95% confidence interval (CI) exceeded its predefined margin. Results 258 patients were treated with TARH and 252 patients with LARVH. TARH and LARVH group had similar 5-year PFS (84.4% vs 86.6%, p = 0.467) and OS rates (85.8% vs 88.0%, p = 0.919). Noninferiority of LARVH to TARH were confirmed with 5-year PFS and OS difference rates of 2.2% (95% CI -2.9–7.3, p = 0.001) and 2.2% (95% CI -2.7–7.1, p = 0.001), respectively. In subgroup of patients with tumors size >2 cm, 5-year PFS (77.6% vs 79.0%, p = 0.682) and OS rates (79.2% vs 81.5%, p = 0.784) did not differ statistically between the two groups. Noninferiority of LARVH to TARH were also confirmed with 5-year PFS and OS difference rates of 1.4% (95% CI -7.0–9.8, p = 0.046) and 2.3% (95% CI -5.8–10.4, p = 0.027), respectively. Conclusion LARVH showed significant noninferiority for PFS and OS versus TARH in early cervical cancer, suggesting the potential oncologic safety of LARVH.

Current guidelines suggest the maintenance of systolic blood pressure (SBP) at90 mmHg and mean arterial pressure (MAP) at65 mmHg in postcardiac arrest patients. There remains a lack of clarity regarding optimal values and timing of blood pressure parameters associated with the improvement of neurologic outcome. We investigated the association of time-weighted average (TWA) blood pressure parameters with favorable neurological outcome (FO) in postcardiac arrest patients. This was a registry-based observational study with consecutive adult out-of-hospital cardiac arrest (OHCA) survivors who were treated using targeted temperature management (TTM). During 72 hours of TTM period, we abstracted hemodynamic parameters such as SBP, diastolic blood pressure, pulse rate (PR), and MAP. Shock index (SI; PR/SBP) and modified shock index (MSI; PR/MAP) were calculated from each measured hemodynamics. Logistic regression was performed to assess the associations between TWA blood pressure parameters and FO, defined as cerebral performance category 1 or 2 at hospital discharge. Among the 173 patients (median age: 58 years; 64% male), 51 (29.3%) had FO in this study. MAP, SI, and MSI at 6 hours after return of spontaneous circulation (ROSC) showed considerable differences in patients with FO (MAP: 89.1 ± 14.7 vs. 83.6 ± 15.8 mmHg

Background/aim Cancer stem cell characteristics and drug resistance of colorectal cancer are associated with failure of cancer treatment. In this study, we investigated the effects of PrPC on cancer stem cell characteristics, migration, invasion, and drug resistance of 5FU-resistant CRC cells. Materials and methods PrPC negative and PrPC positive cells were isolated from 5FU-resistant CRC cells using magnetic activated cell sorting. Sphere formation, cancer stem cell marker expression, migration, invasion, and drug resistance were analyzed. Results PrPC positive cells showed increased sphere formation capacity and increased expression of cancer stem cell markers compared to PrPC negative cells. In addition, PrPC positive cells showed increased migration, invasion and drug resistance compared to PrPC negative cells. Furthermore, knockdown of PrPC abolished these effects. Conclusion PrPC expression is important in CRC cell behavior, such as sphere formation, migration, invasion, and drug resistance. PrPC is an important therapeutic target for the treatment of CRC.

Conservatives are more sensitive to threatening/anxious situations in perceptual and cognitive levels, experiencing emotional responses and stress, while liberals are more responsive to but tolerant of ambiguous and uncertain information. Interestingly, conservatives have greater psychological well-being and are more satisfied with their lives than liberals despite their psychological vulnerability to stress caused by threat and anxiety sensitivities. We investigated whether conservatives have greater resilience and self-regulation capacity, which are suggested to be psychological buffers that enhance psychological well-being, than liberals and moderates. We also explored associations between intrinsic functional brain organization and these psychological resources to expand our neurobiological understanding of self-regulatory processes in neuropolitics. We found that conservatives, compared to liberals and moderates, had greater psychological resilience and self-regulation capacity that were attributable to greater impulse control and causal reasoning. Stronger intrinsic connectivities between the orbitofrontal cortex (OFC) and precuneus and between the insula and frontal pole/OFC in conservatives were correlated with greater resilience and self-regulation capacity. These results suggest the neural underpinnings that may allow conservatives to manage the psychological stress and achieve greater life satisfaction. This study provides neuroscientific evidence for the different responses of liberals and conservatives to politically relevant social issues.

The adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) is known to facilitate caspase-1 activation, which is essential for innate host immunity via the formation of the inflammasome complex, a multiprotein structure responsible for processing IL1β and IL18 into their active moieties. Here, we demonstrated that ASC-deficient CD8+ T cells failed to induce severe graft-versus-host disease (GVHD) and had impaired capacity for graft rejection and graft-versus-leukemia (GVL) activity. These effects were inflammasome independent because GVHD lethality was not altered in recipients of caspase-1/11–deficient T cells. We also demonstrated that ASC deficiency resulted in a decrease in cytolytic function, with a reduction in granzyme B secretion and CD107a expression by CD8+ T cells. Altogether, our findings highlight that ASC represents an attractive therapeutic target for improving outcomes of clinical transplantation.

Background/Aims Maintaining a mean arterial pressure (MAP) ≥ 65 mmHg during septic shock should be based on individual circumstances, but specific target is poorly understood. We investigated associations between time-weighted average (TWA) hemodynamic parameters during the initial resuscitative period and 28-day mortality. Methods Prospectively collected data were obtained from a septic shock patient registry, according to the Sepsis-3 definition, between 2016 and 2018. The TWA systolic blood pressure, diastolic blood pressure, MAP, shock index, and pulse pressure (PP) during the first 6 hours after shock recognition were compared. Multivariable regression analysis was performed to assess associations between these parameters and 28-day mortality. Results Of 340 patients with septic shock, 92 died. Only the median TWA PP differed between the survivors and non-survivors (39.2 mmHg vs. 43.0 mmHg, p = 0.020), whereas the other indexes did not. When PP was divided into quartiles (< 34, 34 to 40, 40 to 48, and > 48 mmHg), the mortality rate was higher in the highest quartile (41.2%). Multivariable logistic analysis revealed that PP (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.012 to 1.622; p = 0.039) and PP of > 48 mmHg (OR, 2.25; 95% CI, 1.272 to 3.981; p = 0.005) were independently associated with 28-day mortality. Conclusions PP was significantly associated with 28-day mortality in patients with septic shock and MAP maintained at > 65 mmHg during the first 6 hours. Further studies are warranted to optimize strategies for maintaining PP and MAP at > 65 mmHg during the early resuscitative period.

Background: This study investigated the inhibition of tumor growth in castrate-resistant prostate cancer (CRPC)-bearing mice by tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)-overexpressing adipose-derived stem cells (ADSCs) (hTERT-ADSC.sTRAIL), which was enhanced by combined treatment with CPT-11. Materials and methods: An hTERT-ADSC.sTRAIL cell line was established by transfection with a lentiviral vector (CLV-Ubic) encoding the human sTRAIL gene. Quantitative polymerase chain reaction and Western blots were performed to confirm gene overexpression. An invasion study for the selective migration ability toward PC3 cells was performed. In the in vivo study, the tumor volume in mice treated with ADSC. sTRAIL and CPT-11 was measured. Results: Carboxylesterase was generated from hTERT-ADSCs. The gene expression of sTRAIL from hTERT-ADSC.sTRAIL was shown. The directional migration of ADSC.sTRAIL cells toward PC3 cells was significantly stimulated by PC3 cells in vitro (P

Background Isolated middle cerebral artery dissection is uncommon and occurs in patients reporting headaches as the only symptom. This makes intracranial artery dissection challenging to diagnose and treat. Case description: We describe two cases of positional headache caused by isolated middle cerebral artery dissection, confirmed using high-resolution magnetic resonance imaging. The two patients presented with sudden-onset headache, occurring when lying in the lateral decubitus position. When lying down in the decubitus position ipsilateral to the intracranial artery dissection, the headache aggravated and middle cerebral artery flow velocity increased on transcranial Doppler ultrasonography compared to when in the supine position. Both patients were treated with antiplatelet agents, and the headache completely resolved within 1–2 weeks. Conclusion We recommend additional imaging studies evaluating intracranial artery dissection as a cause of positional headache.

Despite the therapeutic effect of mesenchymal stem cells (MSCs) in ischemic diseases, pathophysiological conditions, including hypoxia, limited nutrient availability, and oxidative stress restrict their potential. To address this issue, we investigated the effect of melatonin on the bioactivities of MSCs. Treatment of MSCs with melatonin increased the expression of peroxisome proliferatoractivated receptor gamma coactivator-1 alpha (PGC-1α). Melatonin treatment enhanced mitochondrial oxidative phosphorylation in MSCs in a PGC-1α-dependent manner. Melatonin-mediated PGC-1α expression enhanced the proliferative potential of MSCs through regulation of cell cycle-associated protein activity. In addition, melatonin promoted the angiogenic ability of MSCs, including migration and invasion abilities and secretion of angiogenic cytokines by increasing PGC-1α expression. In a murine hindlimb ischemia model, the survival of transplanted melatonin-treated MSCs was significantly increased in the ischemic tissues, resulting in improvement of functional recovery, such as blood perfusion, limb salvage, neovascularization, and protection against necrosis and fibrosis. These findings indicate that the therapeutic effect of melatonin-treated MSCs in ischemic diseases is mediated via regulation of PGC-1α level. This study suggests that melatonin-induced PGC-1α might serve as a novel target for MSC-based therapy of ischemic diseases, and melatonin-treated MSCs could be used as an effective cell-based therapeutic option for patients with ischemic diseases.

Diabetes-mediated hyperglycemia is a major risk factor for renal fibrosis, resulting in the development of chronic kidney diseases. To address this issue, the effect of melatonin, which has an antioxidative potential, on renal fibrosis in human renal proximal tubule epithelial cells under high glucose conditions was investigated. Under high glucose conditions, the generation of reactive oxygen species was drastically increased in human renal proximal tubule epithelial cells, which lead to the inhibition of cell proliferation, enlargement of cell size, reduction of cell survival, and suppression of antioxidant enzyme activities. High glucose also increased the expression of transforming growth factor-β, leading to an increase in Smad2 phosphorylation. These fibrotic phenotype changes increased the expression of fibrosis-mediated extracellular matrix proteins, such as fibronectin, collagen I, and α-smooth muscle actin. In addition, the level of cellular prion protein (PrPC), which is associated with several biological processes, was decreased by exposure to high glucose conditions. Melatonin recovered the expression levels of PrPC under high glucose conditions via phosphorylation of Akt, resulting in the prevention of high glucose-induced fibrosis. In particular, overexpression of PrPC blocked the high glucose-mediated fibrotic phenotype change. These findings indicate that melatonin could be a powerful agent for treating hyperglycemia-induced renal fibrosis.

Microbial cellulases have become the mainstream biocatalysts due to their complex nature and widespread industrial applications. Here, homogeneous endoglucanase GluCB31 from Bacillus subtilis subsp. inaquosorum CBS31 was studied. GluCB31 was purified to 17.68-fold with an 8.33% yield and a specific activity of 1066.37 U/mg. Biochemical properties of GluCB31 were performed and the results are as follows; molecular mass of 35 kDa with an optimum pH at 7.5 and temperature at 50°C. GluCB31 was immobilized in calcium alginate gel and it exhibited the highest activity at 10°C higher temperature than soluble enzyme, as the entrapment in alginate gel made GluCB31 more stable. Kinetic studies showed the Vmax of 1293.33 ± 2.51 U/mg and Km of 0.0183 mg/mL. Enzymatic activity was activated by Tween-20 (106.7%), Tween-80 (111.6%), Triton X-100 (142.3%), SDS (135.5%), Mg++ (185.7%), Cu++ (167.6%), Zn++ (153.7%), Mn++ (106.3%), Ba++ (181.9%), Ni++ (107.2%) while inhibited by Fe++ (15.8%), β-mercaptoethanol (46.8%), EDTA (54.5%). Enthalpy, free energy, and entropy of activation were calculated to be 38.526 kJmol-1, 44.187 kJmol-1, and -17.518 Jmol-1K-1 respectively. Also, ΔGE-S and ΔGE-T were found to be -10.75 kJmol-1 and -45.92 kJmol-1 respectively. A low ΔS, ΔGE-S, and ΔGE-T values were signified enzyme-catalyzed reaction occurs at a fast rate and the existence of the enzyme in its stable state. Cellobiose was the major end product of hydrolysis. These attributes of GluCB31 demonstrated the diversity of catalytic activities and serve in various biotechnological processes, thus deserve to be developed as a bio-industrial agent.

Renal fibrosis is one of the main causes of chronic kidney disease. Many studies have focused on fibroblasts and myofibroblasts involved in renal fibrogenesis. Recently, several studies have reported that renal proximal tubule epithelial cells are possible initiators of renal fibrosis. However, the mechanism through which cells induce renal fibrosis is poorly understood. In this study, we found that CK2α induces fibrosis in renal proximal tubule epithelial cells (TH1) by regulating the expression of profilin-1 (Pfn1). CKD mouse model and TH1 cells treated with P-cresol also showed an increased level of Pfn1. The knockdown of CK2α suppressed fibrosis in TH1 cells via the downregulation of Pfn1. In particular, CK2α knockdown inhibited the expression of stress fibers and fibrosis-related proteins in P-cresol-treated TH1 cells. Furthermore, the knockdown of CK2α inhibited mitochondrial dysfunction and restored cellular senescence and cell cycle in P-cresol-treated TH1 cells. These results indicate that CK2α induces renal fibrosis through Pfn1, which makes CK2α a key target molecule in the treatment of fibrosis related to chronic kidney disease.

Rationale: Epigenetic mechanisms are fundamental processes that can modulate gene expression, allowing cellular adaptation to environmental conditions. Hypoxia is an important factor known to initiate the metastatic cascade in cancer, activating cell motility and invasion by silencing cell adhesion genes. G9a is a histone methyltransferase previously shown to accumulate in hypoxic conditions. While its oncogenic activity has been previously reported, not much is known about the role G9a plays in the hypoxia-mediated metastatic cascade. Methods: The role of G9a in cell motility in hypoxic condition was determined by inhibiting G9a either by short-hairpin mediated knock down or pharmacologically using a small molecule inhibitor. Through gene expression profiling, we identified CDH10 to be an important G9a target that regulates breast cancer cell motility. Lung metastasis assay in mice was used to determine the physiological significance of G9a. Results: We demonstrate that, while hypoxia enhances breast cancer migratory capacity, blocking G9a severely reduces cellular motility under both normoxic and hypoxic conditions and prevents the hypoxia-mediated induction of cellular movement. Moreover, inhibition of G9a histone methyltransferase activity in mice using a specific small molecule inhibitor significantly reduced growth and colonisation of breast cancer cells in the lung. We identify the type-II cadherin CDH10 as being a novel hypoxia-dependent gene, directly repressed by G9a through histone methylation. CDH10 overexpression significantly reduces cellular movements in breast cancer cell lines and prevents the hypoxia-mediated increase in cell motility. In addition, we show that CDH10 expression is prognostic in breast cancer and that it is inversely correlated to EHMT2 (G9a) transcript levels in many tumor-types, including breast cancer. Conclusion: We propose that G9a promotes cellular motility during hypoxic stress through the silencing of the cell adhesion molecule CDH10 and we describe CDH10 as a novel prognostic biomarker for breast cancer.

Background: Intracranial artery dissection (IAD) is gaining recognition as an important cause of stroke, but limited information is available about the morphology of the dissection. This study aimed to investigate the relationship between acute cerebral infarctions and the shape of hematoma in patients with IADs using high-resolution magnetic resonance imaging (HRMRI). Methods: We enrolled consecutive patients who presented with vascular headaches, transient ischemic attacks, or ischemic strokes with acute IAD confirmed by HRMRI using key pathognomonic radiological findings of IAD, including intimal flap, intramural hematoma (IMH), and double lumen. All patients were enrolled and HRMRI was performed, both within 7 days of symptom onset. All patients with acute ischemic infarction within 7 days were enrolled. Patients were divided into 2 groups: those with a proximal dominant intramural hematoma (PIMH) and those with a distal dominant intramural hematoma (DIMH). A PIMH was defined as when the volume of the hematoma in the proximal region was greater than that in the distal region, and a DIMH was defined as when the distal region was greater than that in the proximal region. Clinical and radiological characteristics between the 2 groups were compared using univariable and multivariable logistic regression. Results: The mean age of the 42 participants was 52.6 ± 12.7 years, and 24 (57.1%) were male. Twenty-seven (64.3%) had a PIMH and 15 (35.7%) had a DIMH. Thirty-six (85.7%) showed a double lumen and 27 (64.3%) showed a dissecting flap. Acute infarction was observed in 31 (73.8%) patients. Patients with PIMHs showed a higher prevalence of cerebral infarction than those with DIMHs (96.3 vs. 33.3%; p < 0.001). Univariable (odds ratio [OR] 52.00; 95% confidence interval [CI] 5.386–502.082; p = 0.001) and multivariable (OR 65.43; 95% CI 5.20–822.92; p = 0.001) analyses showed that only dissection type was independently associated with the risk of cerebral infarction. Conclusion: In patients with cerebral artery dissections, the shape of IMHs was independently associated with cerebral infarction. PIMHs may be more closely associated with cerebral infarctions than DIMHs.

DNI is the immature granulocyte fraction provided by a blood cell analyzer, which is determined by subtracting the fraction of mature polymorphonuclear leukocytes from the sum of myeloperoxidase-reactive cells. We aimed to evaluate the role of Delta-neutrophil index (DNI) in cardiac prognosis prediction in children with Kawasaki disease (KD). Medical records of 193 patients were retrospectively reviewed. The values of DNI, white blood cells, erythrocyte sedimentation rate, the percent of polymorphonuclear leucocytes, C-reactive protein, aspartate transaminase, alanine aminotransferase, total bilirubin data of children with KD were analyzed. Also, sex and age of children were compared. The value of DNI was higher in children with cardiac complications [median 0.8 (0–0.26) vs 5.3 (3.55–8.95); P

Natural products (NPs) are useful sources of bioactive compounds and play important roles in the development and discovery of new drugs for diverse human diseases. Most natural products originate from terrestrial species, but diverse marine organisms are another source of new agents for cancer therapy. Natural products derived from marine organisms show diverse pharmacological activities via bioactive secondary metabolites. They regulate biological activities, such as cell proliferation, cell viability, induction of ROS production, ER stress, and apoptosis via modulation of cellular mechanisms in many cancers. Many natural products isolated from marine species require further study to elucidate the efficacy of their biological activity and anticancer effects. In this review, we summarize the biological properties and anticancer effects of diverse natural products extracted from marine organisms and their roles in tumor therapy.

Background/aim Administration of cisplatin in cancer patients is limited by the kidney-related adverse effects; however, a protective strategy is absent. We hypothesized that fucoidan protects the proximal tubule epithelial (TH-1) cells against the effects of cisplatin. Materials and methods To assess the effect of fucoidan, its effect on reactive oxygen species (ROS) formation, endoplasmic reticulum (ER) stress response, DNA damage response (DDR), apoptosis, and cell-cycle arrest in TH-1 cells was investigated. Results Cisplatin increased the accumulation of ROS, leading to excessive ER stress. In presence of cisplatin, treatment of TH-1 cells with fucoidan significantly reduced the ER stress by maintaining the complex of GRP78 with PERK and IRE1α. In particular, fucoidan enhanced the antioxidative capacity through up-regulation of PrPC Furthermore, fucoidan suppressed cisplatin-induced apoptosis and cell-cycle arrest, whereas silencing of PRNP blocked these effects of fucoidan. Conclusion Fucoidan may be a potential adjuvant therapy for cancer patients treated with cisplatin as it preserves renal functionality.

Background/aim Hypoxia promotes tumor proliferation and metastasis in colorectal cancer (CRC). Since the tumor microenvironment is generally characterized by hypoxia, its understanding is important for cancer therapy. We hypothesized that hypoxia promotes the mitochondrial function, mobility, and proliferation of CRC by up-regulating peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Materials and methods To assess the effects of PGC-1α under hypoxia, we investigated the mitochondrial function, cell motility, and sphere formation as well as proliferation and apoptosis of CRC. Results Under hypoxia, we confirmed the increased expression of PGC-1α and reduced production of reactive oxygen species (ROS) by activating anti-oxidant enzymes. Also, up-regulation of PGC-1α enhanced the motility, sphere formation, and proliferation of CRC. Under the presence of the anti-cancer drug 5-fluorouracil (5FU), up-regulation of PGC-1α under hypoxia promoted resistance of CRC against 5FU-induced apoptosis. Conclusion Targeting PGC-1α could to be a powerful strategy for CRC therapy.

Background In patients with unilateral posterior inferior cerebellar artery (PICA) territory infarction, the absence of relevant vessel stenosis may make it difficult to determine the etiology of the infarction. The incidence of cardioembolic (CE) infarction and the factors associated with infarction in such patients remains largely unknown. We hypothesized that the PICA angle would affect the flow direction of embolic sources. Thus, we analyzed the association between high-risk CE sources and the PICA angle. Methods Patients with an isolated unilateral PICA territory infarction without relevant vessel stenosis who were admitted between 2014 and 2017 were included from the Korea University Stroke Registry, which includes data from 3 university hospitals. We classified patients according to the presence of CE sources. For each case, we measured the angle between the vertebral artery (VA) and the proximal PICA. Results In all, 71 patients met the final study entry criteria. Multivariable analysis showed that the PICA angle was independently associated with the risk of a CE source. The optimal cut-off value using Youden's index was 89°. We classified the PICA shape based on the optimal cut-off value. A CE source was identified in 83.3% of cases in which the PICA angle exceeded 89°. Conclusions The angle between the PICA and VA was an independent predictor of unilateral PICA stroke with high-risk CE sources without relevant artery stenosis, suggesting that an angle greater than 89° could be a new image marker for determining the stroke subtype.

Background: Since the first report of a diaphragmatic hernia from Ambroise Paré’s necropsy in 1610, the Bochdalek hernia (BH) of the congenital diaphragmatic hernia (CDH) has been the most common types with high morbidity and mortality in the neonatal period. Due to the nature of the disease, CDH associated with pregnancy is too infrequent to warrant reporting in the literature. Mortality of obstruction or strangulation is mostly due to failure to diagnose symptoms early. Data sources and study selection: A systematic literature search of maternal BH during pregnancy was conducted using the electronic databases (PubMed and EMBASE) from January 1941 to December 2020. Because of the rarity of the disease, this review included all primary studies, including case reports or case series that reported at least one case of maternal BH in pregnant. Searches, paper selection, and data extraction were conducted in duplicate. The analysis was performed narratively regardless of the control groups’ presence due to their rarity. Results: The search retrieved 3450 papers, 94 of which were deemed eligible and led to a total of 43 cases. Results of treatment showed 16 cases in delayed delivery after hernia surgery, 10 cases in simultaneous delivery with hernia surgery, 3 cases in non-surgical treatment, and 14 cases in hernia surgery after delivery. Of 16 cases with delayed delivery after hernia surgery, 13 (81%) cases had emergency surgery and three (19%) cases had surgery after expectant management. Meanwhile, 10 cases underwent simultaneous delivery with hernia surgery, 6 cases (60%) had emergent surgery, and 4 cases (40%) had delayed hernia surgery after expectant management. 3 cases underwent non-surgical treatment. In this review, the maternal death rate and fetal/neonatal loss rate from maternal BH was 5% (2/43) and 16% (7/43), respectively. The preterm birth rate has been reported in 35% (15/43) of maternal BH, resulting from maternal deaths in 13% (2/15) of cases and 6 fetal loss in 40% (6/15) of cases; 44% (19/43) of cases demonstrated signs of bowel obstruction, ischemia, or perforation of strangulated viscera in the operative field, resulting from maternal deaths in 11% (2/19) of cases and fetal-neonatal loss in 21% (4/19) of cases. Conclusion: Early diagnosis and surgical intervention are imperative, as a gangrenous or non-viable bowel resection significantly increases mortality. Therefore, multidisciplinary care should be required in maternal BH during pregnancies that undergo surgically repair, and individualized care allow for optimal results for the mother and fetus.

Prostate-specific antigen (PSA) is the best-known biomarker for early diagnosis of prostate cancer. For prostate cancer in particular, the threshold level of PSA &lt, 4.0 ng/mL in clinical samples is an important indicator. Quick and easy visual detection of the PSA level greatly helps in early detection and treatment of prostate cancer and reducing mortality. In this study, we developed optimized silica-coated silver-assembled silica nanoparticles (SiO2@Ag@SiO2 NPs) that were applied to a visual lateral flow immunoassay (LFIA) platform for PSA detection. During synthesis, the ratio of silica NPs to silver nitrate changed, and as the synthesized NPs exhibited distinct UV spectra and colors, most optimized SiO2@Ag@SiO2 NPs showed the potential for early prostate cancer diagnosis. The PSA detection limit of our LFIA platform was 1.1 ng/mL. By applying each SiO2@Ag@SiO2 NP to the visual LFIA platform, optimized SiO2@Ag@SiO2 NPs were selected in the test strip, and clinical samples from prostate cancer patients were successfully detected as the boundaries of non-specific binding were clearly seen and the level of PSA was &lt, 4 ng/mL, thus providing an avenue for quick prostate cancer diagnosis and early treatment.

Biofiltration (BF) facilitates the removal of organic and inorganic compounds through microbial reactions. Water is one of the most important elements in biotrickling filters that provides moisture and nutrients to microbial biofilms. The maintenance of proper trickle watering is very critical in biotrickling filtration because the flow rate of the trickling water significantly influences contaminant removal, and its optimal control is associated with various physicochemical and biological mechanisms. The lack of water leads to the drying of the media, creating several issues, including the restricted absorption of hydrophilic contaminants and the inhibition of microbial activities, which ultimately deteriorates the overall contaminant removal efficiency (RE). Conversely, an excess of water limits the mass transfer of oxygen or hydrophobic gases. In-depth analysis is required to elucidate the role of trickle water in the overall performance of biotrickling filters. The processes involved in the treatment of various polluted gases under specific water conditions have been summarized in this study. Recent microscopic studies on biofilms were reviewed to explain the process by which water stress influences the biological mechanisms involved in the treatment of hydrophobic contaminated gases. In order to maintain an effective mass transfer, hydrodynamic and biofilm conditions, a coherent understanding of water stress and the development of extracellular polymeric substances (EPS) in biofilms is necessary. Future studies on the realistic local distribution of hydrodynamic patterns (trickle flow, water film thickness, and wet efficiency), integrated with biofilm distributions, should be conducted with respect to EPS development.

Chemotherapy is used as a standard-of-care against cancers that display high levels of inherent genome instability. Chemotherapy induces DNA damage and intensifies pressure on the DNA repair pathways that can lead to deregulation. There is an urgent clinical need to be able to track the emergence of DNA repair driven chemotherapy resistance and tailor patient staging appropriately. There have been numerous studies into chemoresistance but to date no study has elucidated in detail the roles of the key DNA repair components in resistance associated with the frontline clinical combination of anthracyclines and taxanes together. In this study, we hypothesized that the emergence of chemotherapy resistance in triple negative breast cancer was driven by changes in functional signaling in the DNA repair pathways. We identified that consistent pressure on the non-homologous end joining pathway in the presence of genome instability causes failure of the key kinase DNA-PK, loss of p53 and compensation by p73. In-turn a switch to reliance on the homologous recombination pathway and RAD51 recombinase occurred to repair residual double strand DNA breaks. Further we demonstrate that RAD51 is an actionable target for resensitization to chemotherapy in resistant cells with a matched gene expression profile of resistance highlighted by homologous recombination in clinical samples.

Simple Summary Cellular prion protein (PrPC) are overexpressed in cancers and related to cancer proliferation, invasion, metastasis, and drug resistance. The aim of our study was to investigate the role of PrPC-expressing exosomes regulating the colorectal cancer cells (CRC) behavior and tumor progression. We confirmed the increased sphere formation, expression of cancer initiating genes, motility, and tumor growth by hypoxic exosomes. Also, PrPC-expressing exosomes induced the microenvironment of metastasis via increase of endothelial permeability and angiogenic cytokine secretion. The treatment of anti-PrPC and 5-fluorouracil decreased the tumor progression. Targeting PrPC is an effective therapeutic strategy in cancer therapy. Abstract Colorectal cancer (CRC) is one of the leading causes of cancer-related death due to its aggressive metastasis in later stages. Although there is a growing interest in the tumorigenic role of cellular prion protein (PrPC) in the process of metastasis, the precise mechanism behind the cellular communication involving prion proteins remains poorly understood. This study found that hypoxic tumor microenvironment increased the PrPC-expressing exosomes from CRC, and these exosomes regulate the CRC cell behavior and tumor progression depending on the expression of PrPC. Hypoxic exosomes from CRC cells promoted sphere formation, the expression of tumor-inducing genes, migration, invasion, and tumor growth. Furthermore, these exosomes increased endothelial permeability, migration, invasion, and angiogenic cytokine secretion. These effects were associated with PrPC expression. Application of anti-PrPC antibody with 5-fluorouracil significantly suppressed the CRC progression in a murine xenograft model. Taken together, these findings indicate that PrP-expressing exosomes secreted by hypoxic CRC cells are a key factor in the tumorigenic CRC-to-CRC and CRC-to-endothelial cell communication. Significance: These findings suggest that inhibiting PrPC in hypoxic exosomes during chemotherapy may be an effective therapeutic strategy in colorectal cancer.

Loss-of-function mutations of DNAJC6, encoding HSP40 auxilin, have recently been identified in patients with early-onset Parkinson’s disease (PD). To study the roles of DNAJC6 in PD pathogenesis, we used human embryonic stem cells with CRISPR-Cas9–mediated gene editing. Here, we show that DNAJC6 mutations cause key PD pathologic features, i.e., midbrain-type dopamine (mDA) neuron degeneration, pathologic α-synuclein aggregation, increase of intrinsic neuronal firing frequency, and mitochondrial and lysosomal dysfunctions in human midbrain-like organoids (hMLOs). In addition, neurodevelopmental defects were also manifested in hMLOs carrying the mutations. Transcriptomic analyses followed by experimental validation revealed that defects in DNAJC6-mediated endocytosis impair the WNT-LMX1A signal during the mDA neuron development. Furthermore, reduced LMX1A expression during development caused the generation of vulnerable mDA neurons with the pathologic manifestations. These results suggest that the human model of DNAJC6-PD recapitulates disease phenotypes and reveals mechanisms underlying disease pathology, providing a platform for assessing therapeutic interventions.

Bone is constantly balanced between the formation of new bone by osteoblasts and the absorption of old bone by osteoclasts. To promote bone growth and improve bone health, it is necessary to promote the proliferation and differentiation of osteoblasts. Although bovine milk is known to exert a beneficial effect on bone formation, the study on the effect of bovine milk extracellular vesicles (EVs) on osteogenesis in osteoblasts is limited. In this study, we demonstrated that bovine milk EVs promoted the proliferation of human osteogenic Saos-2 cells by increasing the expression of cell cycle-related proteins. In addition, bovine milk EVs also induced the differentiation of Saos-2 cells by increasing the expression of RUNX2 and Osterix which are key transcription factors for osteoblast differentiation. Oral administration of milk EVs did not cause toxicity in Sprague-Dawley rats. Furthermore, milk EVs promoted longitudinal bone growth and increased the bone mineral density of the tibia. Our findings suggest that milk EVs could be a safe and powerful applicant for enhancing osteogenesis. PRACTICAL APPLICATIONS: Until now, calcium and vitamin D have been prescribed to promote bone formation or to prevent bone diseases such as osteoporosis. Recently, several studies to find bioactive molecules that regulate cellular functions of osteoblasts or osteoclasts are actively underway. Milk basic proteins and lactoferrin present in milk are known to promote bone formation, but they exist in small quantities and the isolation of these proteins is complicated making mass production difficult. Recently, it has been found that milk contains large quantities of EVs, and that they promote bone formation. Studies on the effect of Milk EVs on osteoblasts during osteogenesis will help in the development of biomaterials for osteogenesis.

Anticancer drugs, such as fluorouracil (5-FU), oxaliplatin, and doxorubicin (Dox) are commonly used to treat colorectal cancer (CRC), however, owing to their low response rate and adverse effects, the development of efficient drug delivery systems (DDSs) is required. The cellular prion protein PrPC, which is a cell surface glycoprotein, has been demonstrated to be overexpressed in CRC, however, there has been no research on the development of PrPC-targeting DDSs for targeted drug delivery to CRC. In this study, PrPC aptamer (Apt)-conjugated gold nanoparticles (AuNPs) were synthesized for targeted delivery of Dox to CRC. Thiol-terminated PrPC-Apt was conjugated to AuNPs, followed by hybridization of its complementary DNA for drug loading. Finally, Dox was loaded onto the AuNPs to synthesize PrPC-Apt-functionalized doxorubicin-oligomer-AuNPs (PrPC-Apt DOA). The PrPC-Apt DOA were spherical nanoparticles with an average diameter of 20 nm. Treatment of CRC cells with PrPC-Apt DOA induced reactive oxygen species generation by decreasing catalase and superoxide dismutase activities. In addition, treatment with PrPC-Apt DOA inhibited mitochondrial functions by decreasing the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, complex 4 activity, and oxygen consumption rates. Compared to free Dox, PrPC-Apt DOA decreased proliferation and increased apoptosis of CRC cells to a greater degree. In this study, we demonstrated that PrPC-Apt DOA targeting could effectively deliver Dox to CRC cells. PrPC-Apt DOA can be used as a treatment for CRC, and have the potential to replace existing anticancer drugs, such as 5-FU, oxaliplatin, and Dox.

Astrocytes and microglia are brain‐resident glia that can establish harmful inflammatory environments in disease contexts and thereby contribute to the progression of neuronal loss in neurodegenerative disorders. Correcting the diseased properties of glia is therefore an appealing strategy for treating brain diseases. Previous studies have shown that serum/ glucocorticoid related kinase 1 (SGK1) is upregulated in the brains of patients with various neurodegenerative disorders, suggesting its involvement in the pathogenesis of those diseases. In this study, we show that inhibiting glial SGK1 corrects the pro‐inflammatory properties of glia by suppressing the intracellular NFκB‐, NLRP3‐inflammasome‐, and CGAS‐STING‐mediated inflammatory pathways. Furthermore, SGK1 inhibition potentiated glial activity to scavenge glutamate toxicity and prevented glial cell senescence and mitochondrial damage, which have recently been reported as critical pathologic features of and therapeutic targets in Parkinson disease (PD) and Alzheimer disease (AD). Along with those anti‐inflammatory/neurotrophic functions, silencing and pharmacological inhibition of SGK1 protected midbrain dopamine neurons from degeneration and cured pathologic synuclein alpha (SNCA) aggregation and PD‐associated behavioral deficits in multiple in vitro and in vivo PD models. Collectively, these findings suggest that SGK1 inhibition could be a useful strategy for treating PD and other neurodegenerative disorders that share the common pathology of glia‐mediated neuroinflammation., Pathogenic involvement of SGK1 has been implicated in various neurodegenerative disorders. In this study, we show that inhibition of SGK1 in glia treats Parkinson disease (PD) via suppressing glial inflammation and potentiating glial neurotrophic functions.

Temporal lobe epilepsy (TLE) is characterized by recurrent spontaneous seizures and behavioral comorbidities. Reduced hippocampal theta oscillations and hyperexcitability that contribute to cognitive deficits and spontaneous seizures are present beyond the sclerotic hippocampus in TLE. However, the mechanisms underlying compromised network oscillations and hyperexcitability observed in circuits remote from the sclerotic hippocampus are largely unknown. Cholecystokinin (CCK)-expressing basket cells (CCKBCs) critically participate in hippocampal theta rhythmogenesis, and regulate neuronal excitability. Thus, we examined whether CCKBCs were vulnerable in nonsclerotic regions of the ventral hippocampus remote from dorsal sclerotic hippocampus using the intrahippocampal kainate (IHK) mouse model of TLE, targeting unilateral dorsal hippocampus. We found a decrease in the number of CCK+ interneurons in ipsilateral ventral CA1 regions from epileptic mice compared to those from sham controls. We also found that the number of boutons from CCK+ interneurons was reduced in the stratum pyramidale, but not in other CA1 layers, of ipsilateral hippocampus in epileptic mice, suggesting that CCKBCs are vulnerable. Electrical recordings showed that synaptic connectivity and strength from surviving CCKBCs to CA1 pyramidal cells (PCs) were similar between epileptic mice and sham controls. In agreement with reduced CCKBC number in TLE, electrical recordings revealed a significant reduction in amplitude and frequency of IPSCs in CA1 PCs evoked by carbachol (commonly used to excite CCK+ interneurons) in ventral CA1 regions from epileptic mice versus sham controls. These findings suggest that loss of CCKBCs beyond the hippocampal lesion may contribute to hyperexcitability and compromised network oscillations in TLE.

In this review, we focus on sensing techniques and biological applications of various luminescent nanoparticles including quantum dot (QD), up-conversion nanoparticles (UCNPs) following the previous chapter. Fluorescent phenomena can be regulated or shifted by interaction between biological targets and luminescence probes depending on their distance, which is so-called Fӧrster resonance energy transfer (FRET). QD-based FRET technique, which has been widely applied as a bioanalytical tool, is described. We discuss time-resolved fluorescence (TRF) imaging and flow cytometry technique, using photoluminescent nanoparticles with unique properties for effectively improving selectivity and sensitivity. Based on these techniques, bioanalytical and biomedical application, bioimaging with QD, UCNPs, and Euripium-activated luminescent nanoprobes are covered. Combination of optical property of these luminescent nanoparticles with special functions such as drug delivery, photothermal therapy (PTT), and photodynamic therapy (PDT) is also described.

It is almost impossible to fabricate size-controlled nanomaterials without full understanding about nanoscience, because nanomaterials sometimes suddenly grow up and precipitated, meanwhile other nanomaterials are disappeared during fabrication process. With this reason, it is necessary to understand the principle theories about nanoscience for fabrication of "well-defined" nanoparticles. This chapter explains basic theories about nanomaterials. And based on the theory, methods for controlling the size of nanoparticles and preventing the aggregation after fabrication are described.

This review presents the main characteristics of metal nanoparticles (NPs), especially consisting of noble metal such as Au and Ag, and brief information on their synthesis methods. The physical and chemical properties of the metal NPs are described, with a particular focus on the optically variable properties (surface plasmon resonance based properties) and surface-enhanced Raman scattering of plasmonic materials. In addition, this chapter covers ways to achieve advances by utilizing their properties in the biological studies and medical fields (such as imaging, diagnostics, and therapeutics). These descriptions will help researchers new to nanomaterials for biomedical diagnosis to understand easily the related knowledge and also will help researchers involved in the biomedical field to learn about the latest research trends.

Nanobiotechnology is known as the application of nanoscaled techniques in biology which bridges natural science to living organism for improving the quality of life of humans. Nanotechnology was first issued in 1959 and has been rapidly developed, supplying numerous benefits to basic scientific academy and to clinical application including human healthcare, specifically in cancer therapy. This chapter discusses recent advances and potentials of nanotechnology in pharmaceutics, therapeutics, biosensing, bioimaging, and gene delivery that demonstrate the multifunctionality of nanotechnology.

Nano is a fine metric unit which means "one billionth." Nanotechnology is attracting attention as a technological basis to lead the fourth industry. By utilizing synergistic properties obtained from controlling the structure or arrangement of materials at the nanoscale, nanotechnology has evolved rapidly over the past half century and is active in a variety of fields such as materials, pharmaceuticals, and biology. This chapter briefly describes the concept and features of nanotechnology, as well as the preparation, analysis, characterization, and application of nanomaterials. Also, the prospects for nanotechnology along with the nanotoxicity are described.

Micro and nanofabrication technologies are integral to the development of miniaturized systems. Lithography plays a key role in micro and nanofabrication techniques. Since high functional miniaturized systems are required in various fields, such as the development of a semiconductor, chemical and biological analysis, and biomedical researches, lithography techniques have been developed and applied for their appropriate purpose. Lithography can be classified into conventional and unconventional lithography, or top-down and bottom-up, or with mask and mask-less approaches. In this chapter, various lithography techniques are categorized and classified into conventional and unconventional lithography. In the first part, photolithography, electron beam, and focused-ion beam lithography are introduced as conventional lithography techniques. The second part introduces nanoimprint lithography, deformation lithography, and colloidal lithography as unconventional lithography techniques. In the last part, the pros and cons of each lithography are discussed for an appropriate design of fabrication processes.

The use of carbon-based nanomaterials (CNs) with outstanding properties has been rising in many scientific and industrial application fields. These CNs represent a tunable alternative for applications with biomolecules, which allow interactions in either covalent or noncovalent way. Diverse carbon-derived nanomaterial family exhibits unique features and has been widely exploited in various biomedical applications, including biosensing, diagnosis, cancer therapy, drug delivery, and tissue engineering. In this chapter, we aim to present an overview of CNs with a particular interest in intrinsic structural, electronic, and chemical properties. In particular, the detailed properties and features of CNs and its derivatives, including carbon nanotube (CNT), graphene, graphene oxide (GO), and reduced GO (rGO) are summarized. The interesting biomedical applications are also reviewed in order to offer an overview of the possible fields for scientific and industrial applications of CNs.

Following the previous chapter, recent synthetic methods of metal-based nanoparticles and their applications based on plasmonic resonance properties are described in this chapter. This differs from the previous chapter, which described the general uses of metal-based nanoparticles, in that various recent advanced applications of metal-based nanoparticles are described in this chapter.

Not only is fabrication important for research in materials science, but also materials characterization and analysis. Special microscopes capable of ultra-high magnification are more essential for observing and analyzing nanoparticles than for macro-size particles. Recently, electron microscopy (EM) and scanning probe microscopy (SPM) are commonly used for observing and analyzing nanoparticles. In this chapter, the basic principles of various techniques in optical and electron microscopy are described and classified. In particular, techniques such as transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are explained.

Purpose This study aimed to confirm the association between developmentally regulated GTP-binding protein 2 (DRG2) expression and docetaxel-induced apoptosis and to determine whether prostate cancer responses to docetaxel treatment differ with DRG2 expression. Materials and Methods PC3, DU145, and LNCaP prostate cancer cell lines were used. The MTT assay was used to determine cell viability. Western blotting analysis was performed using anti-DRG2 antibodies. Cells were transfected with 50 nmol DRG2 siRNA using an siRNA transfection reagent for DRG2 knockdown. The cell cycle was analyzed by using flow cytometry, and apoptosis was detected by using the Annexin V cell death assay. Results DRG2 expression differed in each prostate cancer cell line. Docetaxel reduced DRG2 expression in a dose-dependent manner. Upon DRG2 knockdown in prostate cancer cells, an increase in the sub-G1 phase was observed without a change in the G1 or G2/M phases. When 4 nM docetaxel was administered to DRG2 knockdown prostate cancer cell lines, an increase in the sub-G1 phase was observed without increasing the G2/M phase, which was similar to that in DU145 cells before DRG2 knockdown. In PC3 and DU145 cell lines, DRG2 knockdown increased docetaxel-induced Annexin V (+) apoptosis by 8.7 and 2.7 times, respectively. Conclusions In prostate cancer cells, DRG2 regulates G2/M arrest after docetaxel treatment. In prostate cancer cells with DRG2 knockdown, apoptosis increases without G2/M arrest in response to docetaxel treatment. These results show that inhibition of DRG2 expression can be useful to enhance docetaxel-induced apoptosis despite low-dose administration in castration-resistant prostate cancer., Graphical Abstract

There is substantial experimental evidence to indicate that Leishmania infections that are transmitted naturally by the bites of infected sand flies differ in fundamental ways from those initiated by needle inocula. We have used flow cytometry and intravital microscopy (IVM) to reveal the heterogeneity of sand fly transmission sites with respect to the subsets of phagocytes in the skin that harbor L. major within the first hours and days after infection. By flow cytometry analysis, dermis resident macrophages (TRMs) were on average the predominant infected cell type at 1 hr and 24 hr. By confocal IVM, the co-localization of L. major and neutrophils varied depending on the proximity of deposited parasites to the presumed site of vascular damage, defined by the highly localized swarming of neutrophils. Some of the dermal TRMs could be visualized acquiring their infections via transfer from or efferocytosis of parasitized neutrophils, providing direct evidence for the “Trojan Horse” model. The role of neutrophil engulfment by dermal TRMs and the involvement of the Tyro3/Axl/Mertk family of receptor tyrosine kinases in these interactions and in sustaining the anti-inflammatory program of dermal TRMs was supported by the effects observed in neutrophil depleted and in Axl-/-Mertk-/- mice. The Axl-/-Mertk-/- mice also displayed reduced parasite burdens but more severe pathology following L. major infection transmitted by sand fly bite., Author Summary Sand flies transmit Leishmania major which causes cutaneous leishmaniasis in humans and in non-human hosts. Our analyses of sand fly transmission sites of L. major in the mouse skin revealed that dermis resident macrophages (TRM) were the predominant phagocytes to take up the parasite within the first 24 hr post-bite. The early involvement of neutrophils varied depending on the proximity of deposited parasites to the site of tissue damage around which the neutrophils coalesced. By intra-vital microscopy, some of the dermal TRMs could be visualized acquiring their infections by direct transfer from or phagocytosis of parasitized neutrophils. The involvement of the Tyro3/Axl/Mertk family of receptor tyrosine kinases in these cellular interactions and in sustaining the anti-inflammatory functions of dermal TRMs was supported by the reduced parasite burdens but more severe pathology observed in Axl-/-Mertk-/- mice. The heterogeneity of sand fly transmission sites with respect to the dose of parasites and the early cellular interactions described here likely contribute to the wide range of infection outcomes that are associated with natural transmission of L. major observed in mouse models and possibly humans.

Background Abdominal examination (AE), one of the primary diagnostic tools used in traditional Korean medicine (TKM), has a limitation of being subjective due to depending on individual practitioner's experience. Therefore, we devised a novel patient-report pressure algometer (PA) and performed a clinical trial to investigate its validity. Methods In total, 44 participants with functional dyspepsia and 44 healthy participants completed the study. The participants were allocated into one of two groups according to the existence of abdominal stiffness at 5 acupoints or abdominal tenderness at 12 acupoints diagnosed by TKM doctors. The pressure depth and pressure pain threshold (PPT) were evaluated using the PA at the same acupoints. We assessed the validity (sensitivity and specificity) of PA and calculated the area under the curve (AUC) and optimal cutoff value of the test variables (pressure depth and PPT) to criterion standards (abdominal stiffness and tenderness). Results Pressure depth and PPT assessed by PA showed high sensitivity and specificity in diagnosing abdominal stiffness and tenderness. The validity at CV-14 of diagnosing abdominal tenderness with PPT by PA had a sensitivity of 73.1%, specificity of 77.8%, and an AUC of 0.807 with a P value of Conclusion This study may provide evidence of standardization and quantification of AE through PA.

Infectious diseases of immigrant populations have recently become important issues for the health of both Korean nationals and foreigners living in Korea. This case report of general paresis is intended to raise awareness about re-emerging neurosyphilis in Korea as a possible etiology of psychotic disorders. A 68-year-old male Chinese resident came to Korea in 2019 with disorientation, auditory hallucination, persecutory delusion, and aggressive behavior, and was admitted to a psychiatric ward for further evaluation and treatment via the emergency department. He was confirmed to have neurosyphilis by serum test, analysis of cerebrospinal fluid, and brain magnetic resonance imaging. After treatment with antibiotics, including intravenous penicillin, in combination with atypical antipsychotics for 6 weeks, his disorientation, auditory hallucination, delusion, and aggressive behavior had attenuated. Neurosyphilis should still be included as a possible etiology of psychotic disorders in Korea. At the initial evaluation, syphilis screening serum tests are recommended for psychotic patients, especially those with pleomorphic symptoms and cognitive dysfunction., Graphical Abstract

Background: For acute adnexal torsion of pregnant women, appropriate treatment based on an accurate diagnosis is especially important for fertility preservation and timely treatment. The 2017 American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 723 announced its practice-changing guidelines to ensure that diagnostic magnetic resonance imaging (MRI) conducted during the first trimester and gadolinium exposure at any time during pregnancy are safe for fetal stability. Unfortunately, few studies have been performed to evaluate the usefulness of the diagnostic accuracy of MRI for acute adnexal torsion during pregnancy. Objective: We sought to determine the efficacy of diagnostic MRI modality using multiparameter for maternal adnexal torsion during pregnancy. Methods: From 1 January 2007 to 31 January 2019, 131 pregnant with MRI tests were reviewed. In this retrospective cohort study, 94 women were excluded due to conditions other than an adnexal mass, and 37 were identified through MRI analyses conducted before surgery for suspected adnexal torsion. The primary outcome was the diagnostic accuracy of sonography and MRI, and the secondary outcome was the usefulness of Apparent diffusion coefficient (ADC) values for predicting the severity of hemorrhagic infarction between the medulla and cortex of the torsed ovarian parenchyma. Results: Our study demonstrates that in the diagnosis of adnexal torsion during pregnancy, the sensitivity, specificity, positive predictive value, and negative predictive value are 62.5%, 83.3%, 90.9%, and 45.5% for sonography and 100%, 77.8%, 90.5%, and 100% for MRI. MRI results in surgical-proven adnexal torsion patients revealed unilocular ovarian cysts (36.8% (7/19)), multilocular ovarian cysts (31.6% (6/19)), and near normal-appearing ovaries (31.6% (6/19)). Pathology in adnexal torsion revealed a corpus luteal ovarian cyst (63.2% (12/19)) and underlying adnexal pathology (46.8% (7/19)). Maternal adnexal torsion during pregnancy was more likely to occur in corpus luteal ovarian cysts than in underlying adnexal masses (odds ratio, 2.14, 95% confidence interval (CI), 0.428&ndash, 10.738). MRI features for adnexal torsion were as follows: tubal wall thickness, 100% (19/19), ovarian stromal (medullary) edema, 100% (19/19), symmetrical or asymmetrical ovarian cystic wall, 100%(19/19), prominent follicles in the ovarian parenchyma periphery, 57.9% (11/19), periadenxal fat stranding, 84.2% (16/19), uterine deviation to the twisted side, 21.1% (4/19), and peritoneal fluid, 42.1% (8/19). The signal intensity of the ADC values of the ovarian medulla and cortex were compared between the cystectomy and detorsion (CD) and salpingo-oophorectomy (SO) groups. The ADC values of the CD and SO groups were 1.81 &plusmn, 0.09 &times, 10&minus, 3 mm2/s and 1.91 &plusmn, 0.18 &times, 3 mm2/s, respectively (P = 0.209), in the ovarian medulla and 1.37 &plusmn, 0.32 &times, 3 mm2/s and 0.96 &plusmn, 0.36 &times, 3 mm2/s, respectively (P = 0.022), in the ovarian cortex. The optimal cut-off value of ADC values for predictable total necrosis in the torsed ovarian cortex was &le, 1.31 &times, 3 mm2/s (area under the curve (AUC) = 0.81, 95% CI 0.611&ndash, 1.0, P = 0.028). Conclusion: Our data showed that maternal adnexal torsion during pregnancy occurred in most corpus luteal cystic ovary cases and some normal-appearing ovary during the 1st and 2nd trimesters of gestation. Therefore, this study is the first study to elaborate on the existence or usefulness of the diagnostic MRI for acute maternal adnexal torsion during pregnancy and to provide a predictive diagnosis of the severity of hemorrhagic infarction for deciding surgical radicality.

Adult cervical deformity management is complex and is a growing field with many recent advancements. The cervical spine functions to maintain the position of the head and plays a pivotal role in influencing subjacent global spinal alignment and pelvic tilt as compensatory changes occur to maintain horizontal gaze. There are various types of cervical deformity and a variety of surgical options available. The major advancements in the management of cervical deformity have only been around for a few years and continue to evolve. Therefore, the goal of this article is to provide a comprehensive review of cervical alignment parameters, deformity classification, clinical evaluation, and surgical treatment of adult cervical deformity. The information presented here may be used as a guide for proper preoperative evaluation and surgical treatment in the adult cervical deformity patient.

Up to 80% of endometrial and breast cancers express oestrogen receptor alpha (ERα). Unlike breast cancer, anti-oestrogen therapy has had limited success in endometrial cancer, raising the possibility that oestrogen has different effects in both cancers. We investigated the role of oestrogen in endometrial and breast cancers using data from The Cancer Genome Atlas (TCGA) in conjunction with cell line studies. Using phosphorylation of ERα (ERα-pSer118) as a marker of transcriptional activation of ERα in TCGA datasets, we found that genes associated with ERα-pSer118 were predominantly unique between tumour types and have distinct regulators. We present data on the alternative and novel roles played by SMAD3, CREB-pSer133 and particularly XBP1 in oestrogen signalling in endometrial and breast cancer.