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1.
J Med Internet Res ; 26: e56664, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963937

ABSTRACT

BACKGROUND: Liver transplantation has become increasingly common as a last-resort treatment for end-stage liver diseases and liver cancer, with continually improving success rates and long-term survival rates. Nevertheless, liver transplant recipients face lifelong challenges in self-management, including immunosuppressant therapy, lifestyle adjustments, and navigating complex health care systems. eHealth technologies hold the potential to aid and optimize self-management outcomes, but their adoption has been slow in this population due to the complexity of post-liver transplant management. OBJECTIVE: This study aims to examine the use of eHealth technologies in supporting self-management for liver transplant recipients and identify their benefits and challenges to suggest areas for further research. METHODS: Following the Arksey and O'Malley methodology for scoping reviews, we conducted a systematic search of 5 electronic databases: PubMed, CINAHL, Embase, PsycINFO, and Web of Science. We included studies that (1) examined or implemented eHealth-based self-management, (2) included liver transplant recipients aged ≥18 years, and (3) were published in a peer-reviewed journal. We excluded studies that (1) were case reports, conference abstracts, editorials, or letters; (2) did not focus on the posttransplantation phase; (3) did not focus on self-management; and (4) did not incorporate the concept of eHealth or used technology solely for data collection. The quality of the selected eHealth interventions was evaluated using (1) the Template for Intervention Description and Replication guidelines and checklist and (2) the 5 core self-management skills identified by Lorig and Holman. RESULTS: Of 1461 articles, 15 (1.03%) studies were included in the final analysis. Our findings indicate that eHealth-based self-management strategies for adult liver transplant recipients primarily address lifestyle management, medication adherence, and remote monitoring, highlighting a notable gap in alcohol relapse interventions. The studies used diverse technologies, including mobile apps, videoconferencing, and telehealth platforms, but showed limited integration of decision-making or resource use skills essential for comprehensive self-management. The reviewed studies highlighted the potential of eHealth in enhancing individualized health care, but only a few included collaborative features such as 2-way communication or tailored goal setting. While adherence and feasibility were generally high in many interventions, their effectiveness varied due to diverse methodologies and outcome measures. CONCLUSIONS: This scoping review maps the current literature on eHealth-based self-management support for liver transplant recipients, assessing its potential and challenges. Future studies should focus on developing predictive models and personalized eHealth interventions rooted in patient-generated data, incorporating digital human-to-human interactions to effectively address the complex needs of liver transplant recipients. This review emphasizes the need for future eHealth self-management research to address the digital divide, especially with the aging liver transplant recipient population, and ensure more inclusive studies across diverse ethnicities and regions.


Subject(s)
Liver Transplantation , Self-Management , Telemedicine , Humans , Liver Transplantation/methods , Self-Management/methods , Transplant Recipients/statistics & numerical data
2.
Front Psychol ; 15: 1356172, 2024.
Article in English | MEDLINE | ID: mdl-38966727

ABSTRACT

The present research explores the role of positive emotion norms and positive illusions in explaining the higher subjective well-being observed among Europeans compared to East Asians in Canada. Specifically, we investigate the underlying psychological mechanisms contributing to the prevalence of positive self-views among individuals with European backgrounds, characterized by individualism, versus those with East Asian backgrounds, associated with collectivism. Our study compares Europeans and East Asians in Canada to determine whether cultural norms regarding positive emotions account for the elevated positive self-views and subjective well-being in Europeans. With a sample of 225 participants (112 Europeans and 113 East Asians), our findings reveal significant indirect effects of culture on subjective well-being through positive emotion norms and positive illusions. This study highlights that Europeans, compared to East Asians, believe it is more appropriate to experience and express positive emotions, and this norm influences their positive self-views, subsequently impacting subjective well-being. These findings offer valuable insights into how cultural factors shape subjective well-being across different groups.

3.
Cancer Sci ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38888067

ABSTRACT

The rhizome of Zingiber officinale (Z. officinale), commonly known as ginger, has been characterized as a potential drug candidate due to its antitumor effects. However, the chemotherapeutic effect of ginger on human oral cancer remains poorly understood. In this study, we examined the effects of an ethanol extract of Z. officinale rhizomes (ZOE) on oral cancer and identified the components responsible for its pharmacological activity. ZOE exerts its inhibitory activity in oral cancer by inducing both autophagy and apoptosis simultaneously. Mechanistically, ZOE-induced autophagy and apoptosis in oral cancer are attributed to the reactive oxygen species (ROS)-mediated endoplasmic reticulum stress response. Additionally, we identified two active components of ZOE, 1-dehydro-6-gingerdione and 8-shogaol, which were sufficient to stimulate autophagy initiation and apoptosis induction by enhancing CHOP expression. These results suggest that ZOE and its two active components induce ROS generation, upregulate CHOP, initiate autophagy and apoptosis, and hold promising therapeutics against human oral cancer.

4.
J Biotechnol ; 390: 62-70, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38761885

ABSTRACT

Human serum albumin (HSA), a polypeptide featuring 17 disulfide bonds, acts as a crucial transport protein in human blood plasma. Its extended circulation half-life, mediated by FcRn (neonatal Fc receptor)-facilitated recycling, positions HSA as an excellent carrier for long-acting drug delivery. However, the conventional method of obtaining HSA from human blood faces limitations due to availability and potential contamination risks, such as blood-borne diseases. This study introduced SHuffle, an oxidative Escherichia coli (E. coli) expression system, for the production of recombinant HSA (rHSA) that spontaneously self-folds into its native conformation. This system ensures precise disulfide bond formation and correct folding of cysteine-rich rHSA, eliminating the need for chaperone co-expression or domain fusion of a folding enhancer. The purified rHSA underwent thorough physicochemical characterization, including mass spectrometry, circular dichroism spectroscopy, intrinsic fluorescence spectroscopy, esterase-like activity assay, and size exclusion chromatography, to assess critical quality attributes. Importantly, rHSA maintained native binding affinity to FcRn and the albumin-binding domain. Collectively, our analyses demonstrated a high comparability between rHSA and plasma-derived HSA. The expression of rHSA in E. coli with an oxidizing cytosol provides a secure and cost-effective approach, enhancing the potential of rHSA for diverse medical applications.


Subject(s)
Escherichia coli , Oxidation-Reduction , Protein Folding , Recombinant Proteins , Serum Albumin, Human , Escherichia coli/genetics , Escherichia coli/metabolism , Humans , Serum Albumin, Human/metabolism , Serum Albumin, Human/chemistry , Recombinant Proteins/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Cytoplasm/metabolism , Receptors, Fc/metabolism , Receptors, Fc/chemistry , Histocompatibility Antigens Class I/metabolism
5.
Carbohydr Polym ; 338: 122204, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38763712

ABSTRACT

This study presents the development and characterization of a novel double-network self-healing hydrogel based on N-carboxyethyl chitosan (CEC) and oxidized dextran (OD) with the incorporation of crosslinked collagen (CEC-OD/COL-GP) to enhance its biological and physicochemical properties. The hydrogel formed via dynamic imine bond formation exhibited efficient self-healing within 30 min, and a compressive modulus recovery of 92 % within 2 h. In addition to its self-healing ability, CEC-OD/COL-GP possesses unique physicochemical characteristics including transparency, injectability, and adhesiveness to various substrates and tissues. Cell encapsulation studies confirmed the biocompatibility and suitability of the hydrogel as a cell-culture scaffold, with the presence of a collagen network that enhances cell adhesion, spreading, long-term cell viability, and proliferation. Leveraging their unique properties, we engineered assemblies of self-healing hydrogel modules for controlled spatiotemporal drug delivery and constructed co-culture models that simulate angiogenesis in tumor microenvironments. Overall, the CEC-OD/COL-GP hydrogel is a versatile and promising material for biomedical applications, offering a bottom-up approach for constructing complex structures with self-healing capabilities, controlled drug release, and support for diverse cell types in 3D environments. This hydrogel platform has considerable potential for advancements in tissue engineering and therapeutic interventions.


Subject(s)
Cell Adhesion , Chitosan , Dextrans , Hydrogels , Hydrogels/chemistry , Hydrogels/pharmacology , Chitosan/chemistry , Dextrans/chemistry , Humans , Cell Adhesion/drug effects , Cell Survival/drug effects , Collagen/chemistry , Animals , Drug Liberation , Cell Proliferation/drug effects , Cell Encapsulation/methods , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Mice , Biomimetics/methods , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Tissue Scaffolds/chemistry
6.
Sci Total Environ ; 932: 173090, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38729360

ABSTRACT

The understanding of the essential environmental factors affecting the spatiotemporal variation in methylmercury (MeHg) in river water is limited to date, despite its importance for predicting the effect of ongoing climate change on MeHg accumulation in freshwater ecosystems. This study aimed to explore the variation in MeHg concentration and related environmental factors in the downstream zone of the Yeongsan River under highly dynamic hydrologic conditions by using water quality and hydrologic data collected from 1997 to 2022, and Hg and MeHg data collected from 2017 to 2022. The mean concentration of unfiltered MeHg was 35.7 ± 13.7 pg L-1 (n = 24) in summer and 26.7 ± 7.43 pg L-1 (n = 24) in fall. Dissolved oxygen (DO), conductivity, nitrate, and dissolved organic carbon (DOC) were determined to be the most influential variables in terms of MeHg variation based on the partial least squares regression model, and their effects on the MeHg concentration were negative, except for DOC. Heatmaps representing the similarity distances between temporal trends of hydrologic and water quality variables were constructed to determine fundamental factors related to the time-based variations in DO, conductivity, nitrate, and DOC using a dynamic time warping algorithm. The heatmap cluster analysis showed that the temporal trends of these variables were closely related to rainfall variation rather than irradiance or water temperature. Overall, biogeochemical factors directly related to in situ methylation rate of Hg(II)-rather than transport of Hg(II) and MeHg from external sources-mainly control the spatiotemporal variation of MeHg in the downstream zone of the Yeongsan River.

7.
Brain Neurorehabil ; 17(1): e4, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38585030

ABSTRACT

In this study, we conducted a survey targeting 191 physical therapists (PTs) and 159 occupational therapists (OTs) in South Korea to explore attitudes toward virtual rehabilitation. Utilizing the Korean version of the ADOPT VR by Glegg et al., OT exhibited significantly more experience with virtual reality (VR) and active video games (AVG) than PT. Therapists with VR/AVG experience scored significantly higher in most categories, and the scores in each category were significantly correlated with the Behavioral Intention category, reflecting the willingness to use VR/AVG. The biggest barriers identified were insufficient funds and setup assistance for the equipment. Differences in responses between the groups with and without VR/AVG experience were most prominent in terms of lack of interest and funding. Therapists' attitudes, perceptions, and intentions toward VR/AVG are crucial factors in the establishment and implementation of VR/AVG; thus, the results of this study provide valuable evidence for future policies related to VR/AVG in rehabilitation medicine.

8.
Mult Scler Relat Disord ; 85: 105551, 2024 May.
Article in English | MEDLINE | ID: mdl-38564996

ABSTRACT

BACKGROUND: Sphingolipids are signaling molecules and structural components of the axolemma and myelin sheath. Plasma sphingolipid levels may reflect disease status of neuromyelitis optica spectrum disorder (NMOSD). We aimed to examine plasma sphingolipids as disease severity biomarkers for NMOSD and compare their characteristics with those of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). METHODS: We measured plasma sphingolipids, sNfL, and sGFAP levels in NMOSD cases with anti-aquaporin-4-antibody. An unbiased approach, partial least square discriminant analysis (PLS-DA), was utilized to determine whether sphingolipid profiles differ according to the disease state of NMOSD (presence, moderate-to-severe disability [Expanded Disease Severity Scale, (EDSS) > 3.0], and relapses). RESULTS: We investigated 81 patients and 10 controls. PLS-DA models utilizing sphingolipids successfully differentiated patients with EDSS > 3.0, but failed to identify the presence of disease and relapses. Ceramide-C14-a significant contributor to differentiating EDSS > 3.0-positively correlated with EDSS, while its levels were independent of age and the presence of relapses. This characteristic was unique from those of sNfL and sGFAP, which were affected by age and relapses as well as EDSS. CONCLUSION: Plasma sphingolipids may be useful NMOSD biomarkers for disability with distinct characteristics compared to sNfL and sGFAP.


Subject(s)
Biomarkers , Neurofilament Proteins , Neuromyelitis Optica , Sphingolipids , Humans , Neuromyelitis Optica/blood , Neuromyelitis Optica/diagnosis , Biomarkers/blood , Female , Sphingolipids/blood , Adult , Male , Middle Aged , Neurofilament Proteins/blood , Glial Fibrillary Acidic Protein/blood , Severity of Illness Index , Aquaporin 4/blood , Aquaporin 4/immunology
9.
Sleep ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38629490

ABSTRACT

Binaural beat (BB) has been investigated as a potential modality to enhance sleep quality. In this study, we introduce a new form of BB, referred to as dynamic BB (DBB), which incorporates dynamically changing carrier frequency differences between the left and right ears. Specifically, the carrier frequency of the right ear varied between 100 and 103 Hz over a period, while the left ear remained fixed at 100 Hz, yielding a frequency difference range of 0 to 3 Hz. The objective of this study was to examine the effect of DBB on sleep quality. Ten healthy participants were included in a cross-over design, where they experienced both DBB and a SHAM (absence of sound) condition across two consecutive nights, with polysomnography evaluation. DBB was administrated during pre-sleep initiation, sleep onset, and transition from rapid-eye-movement (REM) to non-REM stage. DBB significantly reduced sleep latency compared to the SHAM condition. Electrocardiogram analysis revealed that exposure to DBB led to diminished heart rate variability during the pre-sleep initiation and sleep onset periods, accompanied by a decrease in low frequency power of heart rate during the sleep onset period. DBB might be effective in improving the sleep quality, suggesting its possible application in insomnia treatments.

10.
Nat Commun ; 15(1): 387, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38195614

ABSTRACT

Switchable tribological properties of ferroelectrics offer an alternative route to visualize and control ferroelectric domains. Here, we observe the switchable friction and wear behavior of ferroelectrics using a nanoscale scanning probe-down domains have lower friction coefficients and show slower wear rates than up domains and can be used as smart masks. This asymmetry is enabled by flexoelectrically coupled polarization in the up and down domains under a sufficiently high contact force. Moreover, we determine that this polarization-sensitive tribological asymmetry is widely applicable across various ferroelectrics with different chemical compositions and crystalline symmetry. Finally, using this switchable tribology and multi-pass patterning with a domain-based dynamic smart mask, we demonstrate three-dimensional nanostructuring exploiting the asymmetric wear rates of up and down domains, which can, furthermore, be scaled up to technologically relevant (mm-cm) size. These findings demonstrate that ferroelectrics are electrically tunable tribological materials at the nanoscale for versatile applications.

11.
Exp Aging Res ; 50(1): 117-132, 2024.
Article in English | MEDLINE | ID: mdl-36709762

ABSTRACT

BACKGROUND: In prior research, about half of undergraduate students claimed to have "borrowed" a story, by telling someone else's autobiographical memory as if it was their own. Given that borrowing stories often involves intentional fabrication, and given that there are age-related declines in lying, we hypothesized that reports of intentionally borrowing stories should decline with age. METHODS: We recruited participants who ranged in age from 18 to 86 and asked them to complete an online retrospective survey about borrowing stories. RESULTS: Consistent with our hypothesis, older age was associated with lower reports of borrowing stories. Furthermore, among people who did report borrowing a story, older age was associated with less frequent story borrowing and less recent story borrowing. CONCLUSION: These findings highlight the importance of using age-diverse samples when examining social memory phenomena. Findings based upon undergraduate students do not always replicate in other age groups.


Subject(s)
Aging , Memory, Episodic , Humans , Sex Factors , Retrospective Studies , Surveys and Questionnaires
12.
Int J Biol Macromol ; 254(Pt 3): 127965, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37944724

ABSTRACT

Biomolecules and their functional subdomains are essential building blocks in the creation of multifunctional nanocomplexes. Methyl-binding domain protein 2 (MBD2) and p66α stand out as small α-helical motifs with an ability to self-assemble into a heterodimeric coiled-coil, making them promising building units. Yet, their practical use is hindered by rapid dissociation upon dilution. In this study, novel fusion tags, MBD2 and p66α variants, were developed to covalently link during co-expression in E. coli SHuffle. Through strategic placement of cysteine at each α-helix's terminus, intracellular crosslinking occurred with high specificity and yield, facilitated by preserved α-helical interactions. This instant disulfide bonding in the oxidative cytoplasm of E. coli SHuffle efficiently overcame the need for inefficient in vitro oxidation and protein extraction prone to creating non-specific adducts and suboptimal bioprocesses. In contrast to their wild-type counterparts, the GFP-mCherry protein complex cross-linked by the fusion tags maintained the heterodimeric state even under extensive dilution. The fusion tags, when combined with the E. coli SHuffle system, allowed for the streamlined co-expression of a stable protein complex through self-induced intracellular cysteine coupling. The approach demonstrated herein holds great promise for producing multifunctional and robust heteroprotein complexes.


Subject(s)
Disulfides , Escherichia coli , Escherichia coli/genetics , Disulfides/chemistry , Cysteine/metabolism , Proteins/metabolism , Cytoplasm/metabolism
13.
Oncol Rep ; 51(2)2024 02.
Article in English | MEDLINE | ID: mdl-38099422

ABSTRACT

Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare form of head and neck cancer that is notorious for its poor prognosis and low overall survival rate. This highlights the need for new therapeutic options for this malignancy. The objective of the present study was to examine the ability of caffeic acid phenethyl ester (CAPE), which is an active compound found in propolis, to combat HSCC tumor growth. CAPE exerted its tumor­suppressive activity in HSCC cell lines through the induction of apoptosis. Mechanistically, the CAPE­mediated apoptotic process was attributed to the perturbation of the mitochondrial membrane potential and the activation of caspase­9. CAPE also modulated survivin and X­linked inhibitor of apoptosis, which are potent members of the inhibitors of apoptosis protein family, either through transcriptional or post­translational regulation, leading to HSCC cell line death. Therefore, the findings of the present study suggested that CAPE is an effective treatment alternative for HSCC via the stimulation of mitochondria­dependent apoptosis.


Subject(s)
Head and Neck Neoplasms , Phenylethyl Alcohol , Humans , Squamous Cell Carcinoma of Head and Neck/drug therapy , Cell Line, Tumor , Phenylethyl Alcohol/pharmacology , Phenylethyl Alcohol/therapeutic use , Apoptosis , Caffeic Acids/pharmacology , Caffeic Acids/therapeutic use , Head and Neck Neoplasms/drug therapy
14.
Clin Exp Emerg Med ; 10(4): 418-425, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38012817

ABSTRACT

OBJECTIVE: This study examined the characteristics of patients who attempted suicide in the emergency department before and during the COVID-19 pandemic. METHODS: We compared data from patients in the emergency department following suicide attempts between January 2018 and December 2021. The patients were categorized into two groups: "pre-COVID-19" and "during COVID-19" pandemic. RESULTS: The findings revealed an increasing trend of suicide attempts during the study period. Suicide attempts were reported at 1,107 before the COVID-19 pandemic and 1,356 during the COVID-19 pandemic. Patients who attempted suicide during the COVID-19 pandemic were younger (38.0±18.5 years vs. 40.7±18.4 years, P<0.01), had a smaller proportion of men (36% vs. 44%, P<0.01), and had fewer medical comorbidities (20.2% vs. 23.6%, P<0.05). The group during the COVID-19 pandemic reported better hygiene conditions (50.5% vs. 40.8%, P<0.01) and lower alcohol consumption (27.7% vs. 37.6%, P<0.01). Patients who attempted suicide during the COVID-19 pandemic had higher rates of use of psychiatric medications and previous suicide attempts. The most common reasons for the suicide attempt were unstable psychiatric disorders (38.8%), poor interpersonal relationships (20.5%), and economic difficulties (14.0%). Drug poisoning (44.1%) was the most common method of suicide attempts. Subgroup analysis with patients who attributed their suicide attempts to COVID-19 revealed a higher level of education (30.8%) and employment status (69.2%), with economic difficulties (61.6%) being the primary cause of suicide attempts. CONCLUSION: These findings suggest that the prolonged duration of the COVID-19 pandemic and its effects on social and economic factors have influenced suicide attempts.

15.
J Korean Med Sci ; 38(42): e347, 2023 Oct 30.
Article in English | MEDLINE | ID: mdl-37904658

ABSTRACT

BACKGROUND: In this study, we aimed to compare the effectiveness and adverse reactions of nirmatrelvir/ritonavir and molnupiravir in high-risk outpatients with coronavirus disease 2019 (COVID-19). METHODS: This multicenter prospective observational study evaluated the rate of hospitalization, death, and adverse events within 28 days of oral antiviral agent prescription (molnupiravir, n = 240; nirmatrelvir/ritonavir, n = 240) to 480 nonhospitalized adult patients with COVID-19 from August 2, 2022 to March 31, 2023. RESULTS: Patients receiving molnupiravir had a higher prevalence of comorbidities (85.8% vs. 70.4%; P < 0.001) and a higher Charlson comorbidity index (2.8 ± 1.4 vs. 2.5 ± 1.5; P = 0.009) than those receiving nirmatrelvir/ritonavir. Three patients required hospitalization (nirmatrelvir/ritonavir group, n = 1 [0.4%]; molnupiravir group, n = 2 [0.8%]; P = 1.000). Nirmatrelvir/ritonavir was associated with a higher risk of adverse events than molnupiravir (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.27-3.03), especially for patients aged 65 years and older (OR, 3.04; 95% CI, 1.71-5.39). The severity of adverse events in both groups was mild to moderate and improved after discontinuation of medication. In the molnupiravir group, age ≥ 65 years (OR, 0.43 95% CI, 0.22-0.86) and appropriate vaccination (OR, 0.37; 95% CI, 0.15-0.91) reduced the occurrence of adverse events. CONCLUSION: The rates of hospitalization and death were low and not significantly different between high-risk patients who received either nirmatrelvir/ritonavir or molnupiravir. Although adverse events were more frequent with nirmatrelvir/ritonavir than with molnupiravir, none were severe. Nirmatrelvir/ritonavir can be safely used to treat COVID-19, while molnupiravir could be considered as an alternative treatment option for high-risk groups.


Subject(s)
COVID-19 , Outpatients , Adult , Humans , Ritonavir/adverse effects , COVID-19 Drug Treatment , Antiviral Agents/adverse effects
16.
Cell Oncol (Dordr) ; 2023 Oct 03.
Article in English | MEDLINE | ID: mdl-37787967

ABSTRACT

PURPOSE: Neuropilin-2 (NRP2) is a multifunctional single-pass transmembrane receptor that binds to two disparate ligands, namely, vascular endothelial growth factors (VEGFs) and semaphorins (SEMAs). It is reportedly involved in neuronal and vascular development. In this study, we uncovered the exact functional role of NRP2 and its molecular mechanism during aggressive behaviors and lymph node (LN) metastasis in human head and neck cancer (HNC) and identified algal methanol extract as a potential novel NRP2 inhibitor. METHODS: In silico analyses and immunohistochemistry were used to investigate the relationship between NRP2 expression and the prognosis of HNC patients. The functional role of NRP2 on the proliferation, migration, invasion, and cancer stem cell (CSC) properties of HNC cells was examined by MTS, soft agar, clonogenic, transwell migration and invasion assays, and sphere formation assays. Signaling explorer antibody array, western blot, and qPCR were performed toward the investigation of a molecular mechanism that is related to NRP2. RESULTS: NRP2 was highly expressed in HNC and positively correlated with LN metastasis and advanced tumor stage and size in patients. Using loss- or gain-of-function approaches, we found that NRP2 promoted the proliferative, migratory, and invasive capacities of human HNC cells. Furthermore, NRP2 regulated Sox2 expression to exhibit aggressiveness and CSC properties of human HNC cells. We demonstrated that p90 ribosomal S6 kinase 1 (RSK1) elevates the aggressiveness and CSC properties of human HNC cells, possibly by mediating NRP2 and Sox2. Zeb1 was necessary for executing the NRP2/RSK1/Sox2 signaling pathway during the induction of epithelial-to-mesenchymal transition (EMT) and aggressive behaviors of human HNC cells. Moreover, the methanol extract of Codium fragile (MECF) repressed NRP2 expression, inhibiting the RSK1/Sox2/Zeb1 axis, which contributed to the reduction of aggressive behaviors of human HNC cells. CONCLUSIONS: These findings suggest that NRP2 is a critical determinant in provoking EMT and aggressive behaviors in human HNC through the RSK1/Sox2/Zeb1 axis, and MECF may have the potential to be a novel NRP2 inhibitor for treating metastasis in HNC patients.

17.
Cell Biochem Funct ; 41(8): 1319-1329, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37792550

ABSTRACT

Genipin, a natural compound derived from the fruit of Gardenia jasminoides Ellis, was reported to have activity against various cancer types. In this study, we determined the underlying mechanism for genipin-induced cell death in human oral squamous cell carcinoma (OSCC). The growth-inhibitory effects of genipin in human OSCC cells was examined by the Cell Counting Kit-8 and soft agar assays. The effects of genipin on apoptosis were assessed by nuclear morphological changes by 4',6-diamidino-2-phenylindole staining, measurement of the sub-G1 population, and Annexin V-fluorescein isothiocyanate/propidium iodide double staining. The underlying mechanism of genipin activity was analyzed by western blot analysis, subcellular fractionation of the nucleus and cytoplasm, immunocytochemistry, and quantitative real-time polymerase chain reaction. Genipin inhibited the growth of OSCC cells and induced apoptosis, which was mediated by a caspase-dependent pathway. Genipin reduced the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and its nuclear localization. Furthermore, inhibition of p-STAT3Tyr705 levels following genipin treatment was required for the reduction of survivin and myeloid cell leukemia-1 (Mcl-1) expression, leading to apoptotic cell death. The genipin-mediated reduction in survivin and Mcl-1 expression was caused by transcriptional and/or posttranslational regulatory mechanisms. The results provide insight into the regulatory mechanism by which genipin induces apoptotic cell death through the abrogation of nuclear STAT3 phosphorylation and suggest that genipin may represent a potential therapeutic option for the treatment of human OSCC.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/pathology , Survivin/metabolism , Survivin/pharmacology , Survivin/therapeutic use , Squamous Cell Carcinoma of Head and Neck , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Myeloid Cell Leukemia Sequence 1 Protein/therapeutic use , STAT3 Transcription Factor/metabolism , Mouth Neoplasms/pathology , Apoptosis , Cell Line, Tumor , Cell Proliferation
18.
J Neuroinflammation ; 20(1): 225, 2023 Oct 04.
Article in English | MEDLINE | ID: mdl-37794409

ABSTRACT

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) stands out among CNS inflammatory demyelinating diseases (CIDDs) due to its unique disease characteristics, including severe clinical attacks with extensive lesions and its association with systemic autoimmune diseases. We aimed to investigate whether characteristics of B cell receptors (BCRs) differ between NMOSD and other CIDDs using high-throughput sequencing. METHODS: From a prospective cohort, we recruited patients with CIDDs and categorized them based on the presence and type of autoantibodies: NMOSD with anti-aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with anti-myelin oligodendrocyte glycoprotein antibodies, double-seronegative demyelinating disease (DSN), and healthy controls (HCs). The BCR features, including isotype class, clonality, somatic hypermutation (SHM), and the third complementarity-determining region (CDR3) length, were analyzed and compared among the different disease groups. RESULTS: Blood samples from 33 patients with CIDDs (13 NMOSD, 12 MOGAD, and 8 DSN) and 34 HCs were investigated for BCR sequencing. Patients with NMOSD tended to have more activated BCR features compare to the other disease groups. They showed a lower proportion of unswitched isotypes (IgM and IgD) and a higher proportion of switched isotypes (IgG), increased clonality of BCRs, higher rates of SHM, and shorter lengths of CDR3. Notably, advanced age was identified as a clinical factor associated with these activated BCR features, including increased levels of clonality and SHM rates in the NMOSD group. Conversely, no such clinical factors were found to be associated with activated BCR features in the other CIDD groups. CONCLUSIONS: NMOSD patients, among those with CIDDs, displayed the most pronounced B cell activation, characterized by higher levels of isotype class switching, clonality, SHM rates, and shorter CDR3 lengths. These findings suggest that B cell-mediated humoral immune responses and characteristics in NMOSD patients are distinct from those observed in the other CIDDs, including MOGAD. Age was identified as a clinical factor associated with BCR activation specifically in NMOSD, implying the significance of persistent B cell activation attributed to anti-aquaporin-4 antibodies, even in the absence of clinical relapses throughout an individual's lifetime.


Subject(s)
Neuromyelitis Optica , Humans , Aquaporin 4 , Prospective Studies , Myelin-Oligodendrocyte Glycoprotein , Autoantibodies , Receptors, Antigen, B-Cell
19.
PLoS One ; 18(9): e0291914, 2023.
Article in English | MEDLINE | ID: mdl-37733749

ABSTRACT

Out-toeing gait may cause alterations in lower limb biomechanics that could lead to an increased risk of overuse injuries. Surgery and physical therapy are conventional methods for mitigating such gait, but they are costly and time-consuming. Wearable devices like braces and orthoses are used as affordable alternatives, but they apply non-negligible stress on the skin. Haptic feedback-delivering shoes were also recently developed, but they require actuators and power sources. The purpose of our study is to develop compression tights with inward directing taping lines that apply compression to lower limb muscles and segments to facilitate inward rotation of the foot, overcoming the drawbacks of previous methods. These compression tights were manufactured to fit the average height, leg length, hip girth, and waist girth of South Korean females in their twenties. The efficacy of these compression tights was evaluated by comparing walking kinematics and user satisfaction of 12 female dancers with an out-toeing gait under three conditions: wearing tights with taping lines, tights without taping lines, and basic bicycle shorts. The foot rotation angles and joint kinematics were recorded using a pressure-pad treadmill and motion capture system, respectively. Multiple pairwise comparisons revealed that the compression tights with inward-directing lines significantly reduced foot rotation angles (up to an average of 20.1%) compared with the bicycle shorts (p = 0.002 and 0.001 for dominant and non-dominant foot, respectively) or the compression tights without taping lines (p = 0.005 and p = 0.001 for dominant and non-dominant foot, respectively). Statistical parametric mapping revealed significant main effects of the tight type on joint kinematics. Also, t-tests revealed that the participants reported significantly higher ratings of perceived functionality and usability on the compression tights with inward-directing taping lines. In conclusion, we developed a comfortable and practical apparel-type wearable and demonstrated its short-term efficacy in mitigating out-toeing gait.


Subject(s)
Metatarsal Valgus , Female , Humans , Feasibility Studies , Foot , Gait , Lower Extremity
20.
Article in English | MEDLINE | ID: mdl-37652665

ABSTRACT

The diagnosis of maturity-onset diabetes of the young (MODY), a monogenic form of diabetes mellitus caused by a mutation in a single gene, is often uncertain until genetic testing is performed. We report a 13-yr-old Korean boy who was initially diagnosed with type 2 diabetes (T2DM). MODY was suspected because of his nonobese body habitus and family history of multiple affected members. Targeted panel sequencing of all MODY-related genes was performed using the NextSeq 550Dx platform (Illumina). Sanger sequencing was performed using blood samples from the parents, siblings, and other relatives. A frameshift variant in the 3' region of the last exon of PDX1 was detected in the patient and his family members with diabetes. PP1_Moderate criterion was applied and this variant was confirmed to be the genetic cause of diabetes in the family and classified as likely pathogenic. The study highlights the importance of genetic testing for nonobese, early-onset diabetic patients with multiple affected family members. Increased awareness and aggressive genetic testing for MODY are needed.


Subject(s)
Diabetes Mellitus, Type 2 , Male , Humans , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/diagnosis , High-Throughput Nucleotide Sequencing , Genetic Testing , Mutation , Republic of Korea
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