Reliability and Safety of Super-Thin ALT Flap: A Comprehensive Evaluation of Perfusion-Related Complications and Donor Morbidity.

BACKGROUND: With an increasing need for thin flap, the use of super-thin anterolateral thigh (ALT) flaps, raised above the supra-superficial fascia, has drawn great attention. Controversy remains regarding whether such thin flap elevation could affect postoperative outcomes, encompassing perfusion-related complications (PRC) and donor morbidities. This study aimed to evaluate the outcomes of super-thin ALT flap-based reconstruction compared with those of suprafascially elevated flaps. METHOD: Patients who underwent free ALT flap-based reconstruction between March 2017 and June 2023 were reviewed, and categorized into two groups based on flap elevation plane; super-thin, and suprafascial. Development of PRC and donor morbidities including paresthesia, were compared. Independent associations of the elevation plane with complication profiles were evaluated. Further analyses were conducted using propensity-score matching. RESULTS: In total, 208 cases were analyzed: 80 super-thin and 128 suprafascial ALT flaps. Nineteen cases (9.1%) experienced PRC, including four total and 14 partial necrosis. The incidence of overall and each type of PRC did not differ based on flap elevation plane even after adjusting for other variables. The super-thin group exhibited significantly lower donor complications compared to the others, upheld in multivariable analyses. Elevating the flaps with a super-thin fashion allowed for a higher rate of preservation of the lateral femoral cutaneous nerve, resulting in a significantly lower rate of postoperative paresthesia. Similar associations were observed in the propensity-score matching analysis. CONCLUSIONS: Super-thin ALT flap elevation might not appear to increase PRC risk, while reduces donor complications, compared to suprafascial elevation.

Thin Free Perforator Flap as a Viable Option for Forefoot Reconstruction: Comprehensive Evaluation of Outcomes.

BACKGROUND: Reconstruction of forefoot defects often necessitates free tissue transfer due to the limited availability of local tissue. Microsurgical reconstruction of the forefoot remains challenging as it requires durable yet thin, soft tissue coverage for functional restoration. This study aimed to evaluate the efficacy of free thin perforator flaps for forefoot reconstruction, with a focus on functional outcomes. METHODS: Patients who underwent microsurgical forefoot reconstruction between March 2020 and September 2023 were reviewed. Development of postoperative complications and functional outcomes were evaluated. RESULTS: In total 53 patients were analyzed, with a mean age of 62.7 years. The most common etiology of defects was oncologic surgery, followed by chronic wound, with a majority involving the plantar side. Super-thin anterolateral thigh flap and superficial circumflex iliac artery perforator flap were predominantly used. The median thickness of the flap was 4.0 mm. Digital vessels were the most frequently used as recipients. All but one flap survived, resulting in a success rate of 98.1 percent. Postoperative flap-site complications developed in 20 patients, the majority of which were resolved with conservative treatment. The median hospital stay was 8.0 days, and the mean time for initiating weight-bearing ambulation was 12.4 days. In postoperative foot function index questionnaire survey, the overall score remained 9.41, showing minimal impairment, and did not differ according to defect size and locations. Secondary debulking operation was necessitated in seven patients. CONCLUSION: Use of thin free perforator flaps might provide reliable outcomes with rapid recovery and excellent postoperative function in the forefoot reconstruction.

Comparison of Enlarged Perivascular Spaces in Early-Onset and Late-Onset Alzheimer Disease-related Cognitive Impairment: A Single Clinic-based Study in South Korea.

We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI). Patients with LOADCI exhibited a higher prevalence of hypertension, lacunes, white matter hyperintensities, and BG-ePVS than those with EOADCI. BG-ePVS showed a significant correlation with age at the onset and the number of lacunes, whereas CSO-ePVS did not exhibit any association. The higher prevalence of BG-ePVS in patients with LOADCI might be attributable to vascular risk factors (hypertension) and cerebral small vessel disease (CSVD). These findings support the hypothesis that BG-ePVS is associated with CSVD and vascular risk factors, whereas CSO-ePVS is associated with cerebral amyloid angiopathy.

Adaptation and validation of a Korean version of the speaking up about patient safety questionnaire (KSUPS-Q).

BACKGROUND: Speaking up by healthcare providers is an essential assertive communication strategy for ensuring patient safety and preventing incidents. However, more is needed to know about speaking up and instruments to assess it in the Korean context. Therefore, we assessed the psychometric properties of the Korean version of the Speaking Up about Patient Safety Questionnaire (KSUPS-Q) for measuring speaking up-related behavior and climate among nurses. METHODS: The translation and adaptation process followed the guidelines of the International Society for Pharmacoeconomics and Outcomes Research and the World Health Organization. Content validity was assessed by a six-member expert panel using the content validity index. In total, 314 nurses participated in an online survey to examine the psychometric properties. Internal consistencies were tested using Cronbach's alpha and McDonald's omega. Confirmatory factor analyses were conducted to examine the subscales' construct. The convergent validity of the speaking up-related climate scale was assessed by testing correlations with teamwork and safety climate domains of the Safety Attitudes Questionnaire. In addition, we investigated the convergent validity of the speaking up-related behavior scale by examining its correlation with the climate scale. RESULTS: The reliability of the 11-item behavior scale was satisfactory. Confirmatory factor analysis confirmed that a three-subscale model (perceived concerns, withholding voice, and speaking up) was appropriate (CFI = 0.98, TLI = 0.98, and SRMR = 0.05). Furthermore, the 11-item climate scale demonstrated satisfactory internal consistency. A three-subscale model (psychological safety, encouraging environment, and resignation) was confirmed (CFI = 0.98, TLI = 0.97, and SRMR = 0.05). The convergent validity of the climate scale was verified based on correlations with the teamwork (r = 0.68, p < 0.001) and safety climate (r = 0.68, p < 0.001) domains of the Safety Attitudes Questionnaire. In addition, speaking up-related behavior and climate showed a significant association, indicating that the behavior scale is conceptually valid. CONCLUSIONS: This study demonstrates that the KSUPS-Q is a valid and reliable instrument in Korea. This instrument can help nurse managers simultaneously monitor the behavior and climate of their organizations and evaluate the outcomes of interventions to enhance speaking up. Future research is needed to explore diverse factors contributing to speaking up, including clinical roles, team relationships, and supportive culture, to identify areas requiring further improvement.

Incidence and risk factors of COVID-19 in a tertiary hospital and the effectiveness of booster vaccination among health care workers: A retrospective cohort study, January 2020 to June 2022.

BACKGROUND: Health care workers (HCWs) face a higher risk of infection and may transmit pathogens to patients during a pandemic. This study aims to evaluate infection-control measures by analyzing the incidence and risk factors of COVID-19 and estimating vaccine effectiveness (VE) at a tertiary hospital in Seoul, Republic of Korea. METHODS: This study included 2,516 HCWs from January 1, 2020, to June 30, 2022. Data were analyzed to determine the incidence density and cumulative incidence; the results were compared by the age- and gender-specific standardized incidence ratios (SIR). VE was estimated with multivariate Cox proportional-hazard models as 1-adjusted hazard ratio × 100%. RESULTS: SIR indicated a lower COVID-19 risk in the hospital population than in the general Korean population (SIR, 0.81; 95% confidence interval [CI]: 0.76-0.87). Multivariate Cox analysis indicated that, compared to doctors, nonmedical service supporters and other HCWs (excluding doctors and nurses) were high-risk groups (adjusted hazard ratio [95% CI], 1.72 [1.04-2.83] and 1.76 [1.20-2.58], respectively). Compared to the outpatient unit, the emergency department was a high-risk department (1.70 [1.16-2.50]). The VE of the booster dose was 55.47%, compared to no or incomplete vaccination (95% CI: 22.63-74.37). CONCLUSIONS: Besides encouraging HCWs vaccination, effective infection-control measures should target high-risk groups and departments.

S6K1 deficiency in tumor stroma impairs lung metastasis of melanoma in mice.

Accumulating data suggest that ribosomal protein S6 kinase 1 (S6K1), an effector in the mammalian target of rapamycin (mTOR) pathway, plays pleiotropic roles in tumor progression. However, to date, while the tumorigenic function of S6K1 in tumor cells has been well elucidated, its role in the tumor stroma remains poorly understood. We recently showed that S6K1 mediates vascular endothelial growth factor A (VEGF-A) production in macrophages, thereby supporting tumor angiogenesis and growth. As macrophage-derived VEGF-A is crucial for both tumor cell intravasation and extravasation across the vascular endothelium, our previous findings suggest that stromal S6K1 signaling is required for tumor metastatic spread. Therefore, we aimed to determine the impact of host S6K1 depletion on tumor metastasis using a murine model of pulmonary metastasis (S6k1-/- mice implanted with B16F10 melanoma). The ablation of S6K1 in the host microenvironment significantly reduced the metastasized B16F10 melanoma cells on the lung surface in both spontaneous and intravenous lung metastasis mouse models without affecting the incidence of metastasis to distant lymph nodes. In addition, stromal S6K1 loss decreased the number of tumor cells circulating in the peripheral blood of mice bearing B16F10 xenografts without affecting the vascular leakage induced by VEGF-A in vivo. These observations demonstrate that S6K1 signaling in host cells other than endothelial cells is required to modulate the host microenvironment to facilitate the metastatic spread of tumors via blood circulation, thus revealing its novel role in the tumor stroma during tumor progression.

Association Between Oral Health Status and Survival Time in Terminally Ill Cancer Patients.

INTRODUCTION: Patients with terminal cancer often experience various oral problems. Whether oral health status is associated with the survival of terminally ill cancer patients receiving palliative care remains unclear. METHODS: We analyzed the data of 59 Korean patients with terminal cancer receiving palliative care, including their oral health status, using a modified Korean version of the Oral Health Assessment Tool (OHAT). Patients were categorized into "Good," "Moderate," or "Poor" groups based on OHAT scores. The Kaplan-Meier method was used to compare the median survival time, and the prognosis between groups was estimated using Cox proportional hazard models. RESULTS: The most common oral symptoms observed were xerostomia (69.5%) and mucositis (17.0%). Significantly shorter survival times were observed in patients with hyperbilirubinemia, elevated creatinine levels, and no use of dentures. The "Poor" group had a shorter survival than the "Good" oral group (P = .010). A multivariate Cox proportional hazards analysis revealed that the "Poor" group was significantly associated with poor survival compared to the "Good" group (hazard ratio, 2.05; P = .047). CONCLUSION: Terminally ill cancer patients with poor oral health may have a higher risk of shorter survival. Palliative care professionals should pay attention to oral health. Further research is needed to determine the effects of oral care on survival.

Activation of Lysosomal Function Ameliorates Amyloid-ß-Induced Tight Junction Disruption in the Retinal Pigment Epithelium.

Accumulation of pathogenic amyloid-ß disrupts the tight junction of retinal pigment epithelium (RPE), one of its senescence-like structural alterations. In the clearance of amyloid-ß, the autophagy-lysosome pathway plays the crucial role. In this context, mammalian target of rapamycin (mTOR) inhibits the process of autophagy and lysosomal degradation, acting as a potential therapeutic target for age-associated disorders. However, efficacy of targeting mTOR to treat age-related macular degeneration remains largely elusive. Here, we validated the therapeutic efficacy of the mTOR inhibitors, Torin and PP242, in clearing amyloid-ß by inducing the autophagy-lysosome pathway in a mouse model with pathogenic amyloid-ß with tight junction disruption of RPE, which is evident in dry age-related macular degeneration. High concentration of amyloid-ß oligomers induced autophagy-lysosome pathway impairment accompanied by the accumulation of p62 and decreased lysosomal activity in RPE cells. However, Torin and PP242 treatment restored the lysosomal activity via activation of LAMP2 and facilitated the clearance of amyloid-ß in vitro and in vivo. Furthermore, clearance of amyloid-ß by Torin and PP242 ameliorated the tight junction disruption of RPE in vivo. Overall, our findings suggest mTOR inhibition as a new therapeutic strategy for the restoration of tight junctions in age-related macular degeneration.

Factors influencing shared decision-making in long-term care facilities.

BACKGROUND: Shared decision-making, a communicative process to reach decisions based on informed preferences, evidence, and co-created goals, improves care satisfaction and patients' quality of life. However, shared decision-making has not been widely implemented in long-term care facilities, and few studies have examined how to promote the shared decision-making practice. This study aimed to identify the influencing factors of shared decision-making based on the Person-centered Practice Framework in long-term care facilities. METHODS: A total of 300 staff (nursing staff, social workers, and personal care workers) in 13 Korean long-term care facilities participated in this study. Data from 280 respondents were finally analyzed, excluding respondents with missing values. Data were collected using structured questionnaires that included items on shared decision-making, personal factors (e.g., knowledge about dementia, person-centered care education, person-centered attitude, communication behavior, and job tenure), and care environment factors (e.g., person-centered climate, staffing level, effective staff relationships, supportive supervisors, and power-sharing). Multilevel linear regression analyses were performed using Mplus Version 8.8. RESULTS: The mean shared decision-making score was 35.78 (range 8-45). Staff with experience of person-centered care education (ß = 0.198, p = 0.034), a higher person-centered attitude score (ß = 0.201, p = 0.007), and a higher communication behavior score (ß = 0.242, p < 0.001) were more likely to report a higher shared decision-making score. In addition, staff who viewed their care environment as more person-centered were more likely to report a higher shared decision-making score (ß = 0.416, p < 0.001). CONCLUSIONS: This study highlights that personal (e.g., person-centered care education, person-centered attitude, and communication behavior) and care environment (e.g., person-centered climate) factors could influence shared decision-making for long-term care residents. These findings could be foundational evidence for facilitating shared decision-making practice in long-term care settings.

Machine learning models of plasma proteomic data predict mood in chronic stroke and tie it to aberrant peripheral immune responses.

Post-stroke depression is common, long-lasting and associated with severe morbidity and death, but mechanisms are not well-understood. We used a broad proteomics panel and developed a machine learning algorithm to determine whether plasma protein data can predict mood in people with chronic stroke, and to identify proteins and pathways associated with mood. We used Olink to measure 1,196 plasma proteins in 85 participants aged 25 and older who were between 5 months and 9 years after ischemic stroke. Mood was assessed with the Stroke Impact Scale mood questionnaire (SIS3). Machine learning multivariable regression models were constructed to estimate SIS3 using proteomics data, age, and time since stroke. We also dichotomized participants into better mood (SIS3 > 63) or worse mood (SIS3 ≤ 63) and analyzed candidate proteins. Machine learning models verified that there is indeed a relationship between plasma proteomic data and mood in chronic stroke, with the most accurate prediction of mood occurring when we add age and time since stroke. At the individual protein level, no single protein or set of proteins predicts mood. But by using univariate analyses of the proteins most highly associated with mood we produced a model of chronic post-stroke depression. We utilized the fact that this list contained many proteins that are also implicated in major depression. Also, over 80% of immune proteins that correlate with mood were higher with worse mood, implicating a broadly overactive immune system in chronic post-stroke depression. Finally, we used a comprehensive literature review of major depression and acute post-stroke depression. We propose that in chronic post-stroke depression there is over-activation of the immune response that then triggers changes in serotonin activity and neuronal plasticity leading to depressed mood.

Non-Directional Property of Human-Body Communication Channel for Implantable Device Application.

In this paper, we present the properties of a communication channel used for implantable devices. The human-body communication (HBC) channel was proposed for data communication in implantable devices. The impulse response was measured using a channel-mimicking model, which mimics electrical losses caused by human body tissues. Furthermore, we compared two types of channel-mimicking models to evaluate their applicability depending on the measurement environment. The resultant impulse responses of the HBC channel showed that HBC does not cause severe changes in the channel properties even when the implantable device is rotated.

Fully stretchable textile-based triboelectric nanogenerators with crepe-paper-induced surface microstructures.

Currently, major energy sources such as fossil fuels and nuclear fuels face various issues such as resource depletion, environmental pollution, and climate change. Therefore, there is increasing interest in technology that converts mechanical, heat, vibration, and solar energy discarded in nature and daily life into electrical energy. As various wearable devices have been released in recent years, wearable energy-harvesting technologies capable of self-power generation have garnered attention as next-generation technologies. Among these, triboelectric nanogenerators (TENGs), which efficiently convert mechanical energy into electrical energy, are being actively studied. Textile-based TENG (T-TENGs) are one of the most promising energy harvesters for realizing wearable devices and self-powered smart clothing. This device exhibited excellent wearability, biocompatibility, flexibility, and breathability, making it ideal for powering wearable electronic devices. Most existing T-TENGs generate energy only in the intentional vertical contact mode and exhibit poor durability against twisting or bending deformation with metals. In this study, we propose a sandwich-structured T-TENG (STENG) with stretchability and flexibility for use in wearable energy harvesting. The STENG is manufactured with a structure that can maintain elasticity and generate a maximum voltage of 361.4 V and current of 58.2 µA based on the contact between the upper and lower triboelectric charges. In addition, it exhibited a fast response time and excellent durability over 5000 cycles of repetitive pushing motions. Consequently, the STENG could operate up to 135 light-emitting diodes (with output) without an external power source, and as an energy harvester, it could successfully harvest energy for various operations. These findings provide textile-based power sources with practical applications in e-textiles and self-powered electronics.

PLK1-mediated phosphorylation of ß-catenin enhances its stability and transcriptional activity for extracellular matrix remodeling in metastatic NSCLC.

Rationale: ß-catenin is a component for cell adhesion and a transcriptional coactivator in epithelial-mesenchymal transition (EMT). Previously we found that catalytically active PLK1 drives EMT in non-small cell lung cancer (NSCLC), upregulating extracellular matrix factors including TSG6, laminin γ2, and CD44. To understand the underlying mechanism and clinical significance of PLK1 and ß-catenin in NSCLC, their relationship and function in metastatic regulation were investigated. Methods: The clinical relevance between the survival rate of NSCLC patients and the expression of PLK1 and ß-catenin was analyzed by a KM plot. Immunoprecipitation, kinase assay, LC-MS/MS spectrometry, and site-directed mutagenesis were performed to reveal their interaction and phosphorylation. A lentiviral doxycycline-inducible system, Transwell-based 3D culture, tail-vein injection model, confocal microscopy, and chromatin immunoprecipitation assays were used to elucidate the function of phosphorylated ß-catenin in the EMT of NSCLC. Results: Clinical analysis revealed that the high expression of CTNNB1/PLK1 was inversely correlated with the survival rates of 1,292 NSCLC patients, especially in metastatic NSCLC. In TGF-ß-induced or active PLK1-driven EMT, ß-catenin, PLK1, TSG6, laminin γ2, and CD44 were concurrently upregulated. ß-catenin is a binding partner of PLK1 in TGF-ß-induced EMT and is phosphorylated at S311. Phosphomimetic ß-catenin promotes cell motility, invasiveness of NSCLC cells, and metastasis in a tail-vein injection mouse model. Its upregulated stability by phosphorylation enhances transcriptional activity through nuclear translocation for the expression of laminin γ2, CD44, and c-Jun, therefore enhancing PLK1 expression by AP-1. Conclusions: Our findings provide evidence for the critical role of the PLK1/ß-catenin/AP-1 axis in metastatic NSCLC, implying that ß-catenin and PLK1 may serve as a molecular target and prognostic indicator of the therapeutic response in metastatic NSCLC patients.

Comparison of Retinal Structural and Neurovascular Changes between Patients with and without Amyloid Pathology.

To evaluate whether an impaired anterior visual pathway (retinal structures with microvasculature) is associated with underlying beta-amyloid (Aß) pathologies in patients with Alzheimer's disease dementia (ADD) and mild cognitive impairment (MCI), we compared retinal structural and vascular factors in each subgroup with positive or negative amyloid biomarkers. Twenty-seven patients with dementia, thirty-five with MCI, and nine with cognitively unimpaired (CU) controls were consecutively recruited. All participants were divided into positive Aß (A+) or negative Aß (A-) pathology based on amyloid positron emission tomography or cerebrospinal fluid Aß. The retinal circumpapillary retinal nerve fiber layer thickness (cpRNFLT), macular ganglion cell/inner plexiform layer thickness (mGC/IPLT), and microcirculation of the macular superficial capillary plexus were measured using optical coherence tomography (OCT) and OCT angiography. One eye of each participant was included in the analysis. Retinal structural and vascular factors significantly decreased in the following order: dementia < MCI < CU controls. The A+ group had significantly lower microcirculation in the para- and peri-foveal temporal regions than did the A-. However, the structural and vascular parameters did not differ between the A+ and A- with dementia. The cpRNFLT was unexpectedly greater in the A+ than in the A- with MCI. mGC/IPLT was lower in the A+ CU than in the A- CU. Our findings suggest that retinal structural changes may occur in the preclinical and early stages of dementia but are not highly specific to AD pathophysiology. In contrast, decreased temporal macula microcirculation may be used as a biomarker for the underlying Aß pathology.

Plk2-mediated phosphorylation and translocalization of Nrf2 activates anti-inflammation through p53/Plk2/p21cip1 signaling in acute kidney injury.

The Plk2 is a cellular stress-responsive factor that is induced in response to oxidative stress. However, the roles of Plk2 in acute kidney injury (AKI) have not been clarified. We previously found that Plk2 is an interacting factor of Nrf2 in response to cellular stress, since Plk2 is upregulated in the Nrf2-dependent network. Here, we show that the levels of p53, Plk2, p21cip1, and chromatin-bound Nrf2 were all upregulated in kidney tissues of mice or NRK52E cells treated with either cisplatin or methotrexate. Upregulation of Plk2 by p53 led to an increase of Nrf2 in both soluble and chromatin fractions in cisplatin-treated NRK52E cells. Consistently, depletion of Plk2 suppressed the levels of Nrf2. Of note, Plk2 directly phosphorylated Nrf2 at Ser40, which facilitated its interaction with p21cip1 and translocation into the nuclei for the activation of anti-oxidative and anti-inflammatory factors in response to AKI. Together, these findings suggest that Plk2 may serve as an anti-oxidative and anti-inflammatory regulator through the phosphorylation and activation of Nrf2 to protect kidney cells from kidney toxicants and that Plk2 and Nrf2 therefore work cooperatively for the protection and survival of kidney cells from harmful stresses.

Relative Effectiveness of COVID-19 Vaccination in Healthcare Workers: 3-Dose Versus 2-Dose Vaccination.

The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to have high infectivity and is more likely to evade vaccine immunity. However, booster vaccination is expected to strengthen cross-reactive immunity, thereby increasing the vaccine effectiveness (VE). This study aimed to evaluate the relative VE of the 3-dose (booster) vaccination compared with the 2-dose primary series vaccination in healthcare workers during omicron variant-dominant periods. During the omicron-dominant period from February 1, 2022 to February 28, 2022, a 1:1 matched case-control study was conducted. Healthcare workers with positive SARS-CoV-2 test results were classified as positive cases, whereas those with negative results served as controls. Compared with the 2-dose primary series vaccination, booster vaccination with mRNA vaccine showed moderate VE (53.1%). However, in multivariate analysis including the time elapsed after vaccination, the significant VE disappeared, reflecting the impact of recent vaccination rather than the third dose itself.

Problematic smartphone use and functional somatic symptoms among adolescents: Mediating roles of depressive symptoms and peer relationships by gender.

This study explored the relationship between problematic smartphone use and depressive symptoms, peer relationships, and functional somatic symptoms with a representative sample of Korean male and female adolescents using serial multiple mediation models. The results identified the mediating effect of depressive symptoms and peer relationships for males in the association between problematic smartphone use and FSS. The serial mediating effect of the two mediators was also verified in the model for males. However, in the model for females, only depressive symptoms mediated the relationship between problematic smartphone use and FSS. The findings suggest that parents and professionals should assess adolescents with problematic smartphone use for the risk of FSS when depressive symptoms develop. Schools should also provide programs to build positive peer relationships to reduce FSS.

Application of Hexanoyl Glycol Chitosan as a Non-cell Adhesive Polymer in Three-Dimensional Cell Culture.

Cell culture technology has evolved into three-dimensional (3D) artificial tissue models for better reproduction of human native tissues. However, there are some unresolved limitations that arise due to the adhesive properties of cells. In this study, we developed a hexanoyl glycol chitosan (HGC) as a non-cell adhesive polymer for scaffold-based and -free 3D culture. The uniform cell distribution in a porous scaffold was well maintained during the long culutre period on the HGC-coated substrate by preventing ectopic adhesion and migration of cells on the substrate. In addition, when culturing many spheroids in one dish, supplementation of the culture medium with HGC prevented the aggregation of spheroids and maintained the shape and size of spheroids for a long culture duration. Collectively, the use of HGC in 3D culture systems is expected to contribute greatly to creating excellent regenerative therapeutics and screening models of bioproducts.

Mitotic protein kinase-driven crosstalk of machineries for mitosis and metastasis.

Accumulating evidence indicates that mitotic protein kinases are involved in metastatic migration as well as tumorigenesis. Protein kinases and cytoskeletal proteins play a role in the efficient release of metastatic cells from a tumor mass in the tumor microenvironment, in addition to playing roles in mitosis. Mitotic protein kinases, including Polo-like kinase 1 (PLK1) and Aurora kinases, have been shown to be involved in metastasis in addition to cell proliferation and tumorigenesis, depending on the phosphorylation status and cellular context. Although the genetic programs underlying mitosis and metastasis are different, the same protein kinases and cytoskeletal proteins can participate in both mitosis and cell migration/invasion, resulting in migratory tumors. Cytoskeletal remodeling supports several cellular events, including cell division, movement, and migration. Thus, understanding the contributions of cytoskeletal proteins to the processes of cell division and metastatic motility is crucial for developing efficient therapeutic tools to treat cancer metastases. Here, we identify mitotic kinases that function in cancer metastasis as well as tumorigenesis. Several mitotic kinases, namely, PLK1, Aurora kinases, Rho-associated protein kinase 1, and integrin-linked kinase, are considered in this review, as an understanding of the shared machineries between mitosis and metastasis could be helpful for developing new strategies to treat cancer.

Bovine colostrum derived-exosomes prevent dextran sulfate sodium-induced intestinal colitis via suppression of inflammation and oxidative stress.

Despite the rise in the global burden of inflammatory bowel disease, there is a lack of safe and effective therapies that can meet the needs of clinical patients. In this study, we investigated the beneficial effects of bovine milk, especially colostrum-derived exosomes (Col-exo) in a murine model of ulcerative colitis induced by dextran sodium sulfate (DSS). Col-exo activated the proliferation of colonic epithelial cells and macrophages, and created an environment to relieve inflammation by effectively removing reactive oxygen species and regulating the expression of immune cytokines. Besides, Col-exo could pass through the gastrointestinal tract intact and efficiently deliver bioactive cargoes to the stomach, small intestine, and colon. Our results showed that oral gavage of Col-exo can alleviate colitis symptoms including weight loss, gastrointestinal bleeding, and chronic diarrhea by modulating intestinal inflammatory immune responses. Overall, bovine colostrum-derived exosomes with excellent structural and functional stability may offer great potential as natural therapeutics for the recovery of colitis.