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@#CpG oligonucleotide(CpG ODN)is a synthetic oligodeoxynucleotide containing non-methylated CpG,which has broad application prospects in disease prevention and clinical treatment. Among them,B class CpG ODN is widely used in vaccine research because of its strong immune stimulation and some motifs have entered the clinical research stage. At the same time,the problem of bacterial resistance in clinical treatment has become increasingly serious,and the development of bacterial vaccine with B class CpG ODN as adjuvant has become a research hotspot. This paper reviewed the current research status and related progress of the existing B class CpG ODN 1826,2006,2007 and 1668 motifs in bacterial vaccines,with a view to providing a reference for the subsequent development and application of bacterial vaccines.
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Purpose@#Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial. @*Materials and Methods@#The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)–based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis. @*Results@#Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable. @*Conclusion@#Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.
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In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
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Background@#and Purpose: Dementia subtypes, including Alzheimer’s dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18 F-Fluorodeoxyglucose Positron Emission Tomography ( 18 F-FDG PET) in differentiating these subtypes for precise treatment and management. @*Methods@#A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18 F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the goldstandard clinical diagnosis for dementia subtypes. @*Results@#From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88–0.98) and specificity was 0.84 (95% CI, 0.70–0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70–0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80–0.91) and the specificity was 0.88 (95% CI, 0.80–0.91). The studies mostly used case-control designs with visual and quantitative assessments. @*Conclusions@#18 F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.
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Background/Aims@#The gut microbiome has emerged as a key player that mechanistically links various risk factors to colorectal cancer (CRC) etiology. However, the role of the gut microbiome in CRC pathogenesis remains unclear. This study aimed to characterize the gut microbiota in healthy controls (HCs) and patients with colorectal adenoma (AD) and CRC in subgroups based on sex and age. @*Methods@#Study participants who visited the hospital for surveillance of CRC or gastrointestinal symptoms were prospectively enrolled, and the gut microbiome was analyzed based on fecal samples. @*Results@#In terms of HC-AD-CRC sequence, commensal bacteria, including lactate-producing (Streptococcus salivarius) and butyrate-producing (Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium hallii) bacteria, were more abundant in the HC group than in the AD and CRC groups. In the sex comparison, the female HC group had more lactate-producing bacteria (Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Lactobacillus ruminis) than the male HC group. In age comparison, younger subjects had more butyrate-producing bacteria (Agathobaculum butyriciproducens and Blautia faecis) than the older subjects in the HC group.Interestingly, lactate-producing bacteria (B. catenulatum) were more abundant in females than males among younger HC group subjects. However, these sex- and age-dependent differences were not observed in the AD and CRC groups. @*Conclusions@#The gut microbiome, specifically lactate- and butyrate-producing bacteria, which were found to be abundant in the HC group, may play a role in preventing the progression of CRC. In particular, lactate-producing bacteria, which were found to be less abundant in healthy male controls may contribute to the higher incidence of CRC in males.
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In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
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Morus alba L. is well-known for its medicinal and economic value, particularly in Asian countries. Among the isolated compounds from this plant, steppogenin is exhibited as a flavonoid with promising pharmacological properties. This study focused on isolating bioactive compounds, notably steppogenin, from the ethyl acetate extract of M. alba. Additionally, a high-performance liquid chromatography-diode array detector (HPLC-DAD) method for the simultaneous quantification of steppogenin and isolated compounds was developed and validated. The calibration curve showed excellent linearity, with a correlation coefficient (R 2 ) value greater than 0.9957. The limit of detection (LOD) ranged from 0.006 to 0.018 μg/mL, whereas the limit of quantification (LOQ) ranged from 0.020 to 0.061 μg/mL. In precision tests conducted intra-day and inter-day, the accuracy was between 97.32% and 106.39%, with relative standard deviations (RSD) less than 2.27% and 1.65%, respectively. The presence of steppogenin and other flavonoids was confirmed by the study, contributing to the understanding of the chemical composition of M. alba. This validated analytical method offers a reliable means of quantifying steppogenin and aiding future research into its therapeutic potential.
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Purpose@#This study was conducted to investigate the clinical characteristics of patients with advanced non–small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) mutations and to evaluate response to standard treatment and HER2-targeted agents. @*Materials and Methods@#Using tissue and/or blood next-generation sequencing, we identified 44 patients with NSCLC harboring HER2 mutations who were treated at Severance Hospital between December 2016 and February 2021. Clinical data, including patient characteristics, mutation status, incidence of metastasis for distant lesions, and response to chemotherapy, were retrospectively analyzed. @*Results@#The median age was 58 years, and 61% of the patients were female. Most patients (64%) were never-smokers. Adenocarcinoma was the most predominant subtype (98%). A total of 66% of the patients had extrathoracic metastatic lesions, and 32% had intracranial lesions at initial presentation. The median time to the development of brain metastasis was 15.6 months (range, 2.4 to 43.7). The most common type of HER2 mutation was 12 base pair in-frame insertion in exon 20, A775_G776insYVMA. Of the 44 patients, two had concomitant driver mutations, one with epidermal growth factor receptor (EGFR) mutation (V769M), and one with BRAF mutation (V600E). Patients treated with pemetrexed-based chemotherapy (75%) had an overall response rate (ORR) and progression-free survival (PFS) of 30% and 8.3 months (95% confidence interval [CI], 3.9 to 12.7), respectively. The ORR and PFS of HER2-targeted agent treated patients (14%) were 0.0% and 1.9 months (95% CI, 0.1 to 2.8), respectively. @*Conclusion@#Given its distinct characteristics and treatment responses, novel treatment strategies for HER2-mutant NSCLC should be developed promptly to improve survival outcomes of patients.
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Ovarian cancer is a primary global health concern, often diagnosed at advanced stages with limited treatment options and poor prognosis. Natural products have emerged as potential sources of safe and effective therapies. From the seeds of Myristica fragrans Houtt. (nutmeg), 24 compounds, including neolignans and diarylnonanoid derivatives, were isolated and structurally elucidated. The cytotoxic activities of these isolated metabolites against cisplatin-sensitive and resistant human ovarian cancer cell lines were evaluated. In particular, myrifragranone C (23) exhibited cytotoxicity against all test cancer cell lines A2780, TOV-112D, and SK-OV3 with IC50 values of 14.1, 16.9, and 33.4 μM, respectively. Furthermore, compound 23 induced the death of A2780 and SK-OV3 cancer cells via apoptosis. Western blotting revealed that compound 23 significantly increased the expression of cleaved caspase-3 and poly-ADP ribose polymerase and promoted apoptosis via the mitogenactivated protein kinase signaling pathway. Our findings may provide a preliminary understanding of the antiovarian cancer effect of the active compound myrifragranone C as a potential treatment using natural products.
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Objective@#Providing inpatient nursing care inevitably involves night shift work. However, night shift work nurses often face psychiatric health problems such as burnout. If night shift work is an essential work type for nurses, it is necessary to select personnel suitable for night shift work or establish improvement measures such as psychiatric intervention through psychiatric evaluation. The objective of this study was to identify factors that could be interventional among factors affecting burnout in shift-working nurses. @*Methods@#A total of 231 night shift female nurses participated in this study. A questionnaire survey was given to assess their general characteristics. To assess burnout, the Maslach Burnout Inventory–General Survey Korean version was adopted. In addition, several mental health scales were used to identify individual psychological characteristics. To identify variables associated with the presence of burnout, odds ratios were calculated using a logistic regression model taking three dimensions of burnout as a dependent variable after adjusting for psychological and occupational factors. @*Results@#High resilience was a significant preventive factor in the three dimensions of burnout. Regarding occupational factor, the longer the duration of employment, the higher depersonalization, but the professional efficacy was good. @*Conclusion@#Our results indicate that resilience and social support could be prevention factors for burnout. This study is meaningful in examining items that require active intervention and support for burnout targeting night shift nurses who are indispensable for patient care.
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Objectives@#Early pharmacologic intervention is considered necessary for improving the prognosis in patients with first-episode schizophrenia (FES). However, few nationwide population-based studies have focused on early medication adherence. We investigated the status of early adherence to antipsychotics and the effect of early adherence on later clinical outcomes in FES. @*Methods@#We used data from the South Korean Health Insurance Review Agency database (2009-2021). We selected 28,931 patients with FES who had a prescription record of at least one antipsychotic medication within 180 days after their diagnosis. We measured early medication adherence using the medication possession ratio (MPR) and compared demographic characteristics and results of psychiatric hospitalization between the adherence group (0.6≤MPR<1.1) and the non-adherence group (MPR<0.6). @*Results@#The average early medication adherence was 0.82 by MPR, and the non-adherence group accounted for 15.6% of all subjects. From 1 to 2 years after diagnosis, the adherence group showed a higher number of psychiatric hospitalizations per hospitalized patient but a shorter duration than the non-adherence group. Additionally, the proportion of patients who experienced psychiatric hospitalizations was smaller in the adherence group. @*Conclusion@#In patients with FES, early medication adherence is associated with lower rates of psychiatric hospitalization and shorter hospitalization durations.
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Salvia miltiorrhiza is a traditional medicinal plant used in Asian medicine for various therapeutic purposes. This plant contains numerous bioactive secondary metabolites, particularly abietane-type diterpenoids. In this study, 16 abietane-type diterpenoids were isolated from S. miltiorrhiza root extracts and structurally identified through advanced spectroscopic techniques. Among them, tanshinone IIA (6) and 15,16-dihydrotanshinone I (11) exhibited potent α-glucosidase inhibition, with IC 50 values of 48.38 ± 0.57 and 48.02 ± 0.47 µM, respectively. Enzyme kinetic studies revealed that these compounds served as non-competitive inhibitors of α-glucosidase. Our findings indicate that natural compounds from S. miltiorrhiza show promise as safe and effective α-glucosidase inhibitors, providing an alternative approach to diabetes treatment. This study contributes to the growing interest in utilizing natural sources for α-glucosidase inhibition and their potential application in healthcare and disease management.
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In this study, twenty known compounds were isolated from Houttuynia cordata Thunb., including four megastigmanes (1‒4), four phenolics (5, 6, 9, and 10), one tetrahydro-2-one derivative (12), four coumarins (7, 13, 14, and 16), six caffeic acid derivatives (8, 11, 15, 17, 18, and 19), and one triterpenoid (20). Their chemical structures were established using NMR spectra and comparison with literature. The anti-diabetic activity of the isolated compounds was assessed by investigating their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. The results revealed that ginnalin A (10) and 3-(4′-hydroxyphenyl)-2-propenoic acid (4′′-carboxyl)-phenyl ester (13) exhibited significant inhibitory effects on both PTP1B and α-glucosidase with IC 50 values of 7.9 ‒ 37.6 and 13.9 ‒ 31.9 μM, respectively. In the kinetic study, these two compounds showed noncompetitive-type PTP1B and α-glucosidase inhibition, with K i values of 35.6 and 7.3 μM for PTP1B and 13.9 and 31.0 μM for α-glucosidase, respectively. These findings highlight the potential of the isolated compounds as candidates for the development of novel therapeutic agents for diabetes.
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Diabetes, characterized by elevated blood glucose levels, has a significant impact on cardiovascular, neural, and vascular systems. α-Glucosidase inhibitors have emerged as potential therapeutic agents for type 2 diabetes, as they slow carbohydrate digestion and reduce postprandial blood sugar levels. In this study, we investigated the phytochemical and pharmacological properties of Celastrus orbiculatusThunb., renowned for its diverse phytochemical constituents and potential medicinal applications. Through the application of chromatographic and spectroscopic techniques, we successfully isolated and structurally elucidated 16 compounds from the stems of C. orbiculatus. The in vitro α-glucosidase inhibitory activity of these compounds was evaluated. Notably, celaphanol A (1) and (+) lariciresinol (7) exhibited strong α-glucosidase inhibition, with IC 50 values of 8.06 ± 0.30 and 48.02 ± 0.47 µM, respectively. Enzyme kinetics analysis revealed that the most active compound 1 acted as a non-competitive inhibitor against α-glucosidase, with a K i> value of 7.77 ± 0.16 µM. These findings underscore C. orbiculatus as a valuable source for discovering and developing new α-glucosidase inhibitors. Furthermore, compound 1 shows promise as a candidate for natural herbal therapy targeting α-glucosidase inhibition. This suggests the potential for further investigation into its effectiveness through in silico or in vivo studies using a diabetes model.
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Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.
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Purpose@#Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer. @*Materials and Methods@#The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell. @*Results@#We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA. @*Conclusion@#The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.
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Tendon disorders commonly cause wrist and hand disability and curtail the performance of work-related tasks. Sonography allows for cost-effective, noninvasive, and dynamic evaluation of soft tissue structures, thus representing a valuable tool for ruling out musculoskeletal disorders of the wrist and hand. Because of the complexity of the wrist joint, sonographic training and familiarity with normal and variant anatomy are needed to avoid misdiagnosis and improper treatment. The purpose of this article is to demonstrate the structures representing normal findings during sonographic evaluations of the wrist and hand. The main reviews the gross anatomy and procedures that are recommended to assess the soft tissue structures of the wrist and hand, with particular emphasis given to tendons, nerves, and ligaments. In conclusion, sonography is effective in assessing the tendons of the hand and wrist and related disorders and represents a valuable tool for diagnosis.
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Alzheimer’s disease (AD) is the most-common cause of neurodegenerative dementia, and it is characterized by abnormal amyloid and tau accumulation, which indicates neurodegeneration. AD has mostly been diagnosed clinically. However, ligand-specific positron emission tomography (PET) imaging, such as amyloid PET, and cerebrospinal fluid (CSF) biomarkers are needed to accurately diagnose AD, since they supplement the shortcomings of clinical diagnoses. Using biomarkers that represent the pathology of AD is essential (particularly when disease-modifying treatment is available) to identify the corresponding pathology of targeted therapy and for monitoring the treatment response. Although imaging and CSF biomarkers are useful, their widespread use is restricted by their high cost and the discomfort during the lumbar puncture, respectively. Recent advances in AD blood biomarkers shed light on their future use for clinical purposes. The amyloid β (Aβ)42/Aβ40 ratio and the concentrations of phosphorylated tau at threonine 181 and at threonine 217, and of neurofilament light in the blood were found to represent the pathology of Aβ, tau, and neurodegeneration in the brain when using automatic electrochemiluminescence technologies, single-molecule arrays, immunoprecipitation coupled with mass spectrometry, etc. These blood biomarkers are imminently expected to be incorporated into clinical practice to predict, diagnose, and determine the stage of AD. In this review we focus on advancements in the measurement technologies for blood biomarkers and the promising biomarkers that are approaching clinical application.We also discuss the current limitations, the needed further investigations, and the perspectives on their use.
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Background@#As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. @*Results@#In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. @*Conclusions@#This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.
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The gut microbiota interacts with the host gut environment, which is influenced by such factors as sex, age, and host diet. These factors induce changes in the microbial composition. The aim of this study was to identify differences in the gut microbiome of Fisher-344 (F344) rats fed a high-fat diet (HFD), depending on their age and sex. Fecal microbiomes from 6-, 31-, and 74-week-old, and 2-year-old both male and female rats (corresponding to 5-, 30-, 60-, and 80-year-old humans) were analyzed using 16S rRNA gene sequencing, phylogenetic investigation of communities by reconstruction of unobserved states, and enterotype (E) assessment. Moreover, the effect of an HFD on colonic epithelial cells was measured using real-time quantitative PCR. Alpha diversity decreased in the HFD group regardless of age and sex. Based on the enterotype clustering of the whole fecal microbiome, clusters from male rats were divided into E1 and E2 enterotypes, while clusters from female rats were divided into E1, E2, and E3 enterotypes. The female E3 group showed a significantly high abundance in the Ruminococcus genus and expression of Tlr2 mRNA, which may reflect compensation to the HFD. Moreover, the female E3 group showed a lower ratio of opportunistic pathogenic strains to commensal strains compared to the female E2 group. Administration of an HFD influenced the rat fecal microbiota in all assessed age groups, which could be further differentiated by sex. In particular, female rats showed a compensatory enterotype response to an HFD compared to male rats.