Association of audiovestibular findings with fluid-attenuated inversion recovery magnetic resonance imaging in patients with vestibular schwannoma.

BACKGROUND: Vestibular schwannoma (VS) is a benign tumor of the vestibular nerve. Flair-attenuated inversion recovery (FLAIR) of magnetic resonance imaging (MRI) images are sensitive in detecting high protein contents of fluids. OBJECTIVES: To investigate the association between signal intensity (SI) on FLAIR images and audiovestibular findings in patients with VS. METHODS: Medical records of twenty-five patients with VS were retrospectively analyzed. RESULTS: Larger tumors were associated with increased FLAIR SI of the cochlea, vestibule, and semicircular canal (SCC) on the affected side compared to those of the unaffected side. Pure-tone audiometry (PTA), and speech audiometry were associated with the SI of the affected cochlea. There was no significant correlation between the SI of the vestibule and vestibular evoked myogenic potential, SI of the SCC, and caloric test or video head impulse test results. CONCLUSION: Our study suggests that tumor size was significantly associated with high SI on FLAIR imaging, and audiological findings were associated with the SI of the affected cochlea. Further studies with larger cohorts are required to confirm the association between vestibular function and FLAIR imaging in VS.

Single-cell analysis reveals cellular and molecular factors counteracting HPV-positive oropharyngeal cancer immunotherapy outcomes.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV-positive) is associated with better clinical outcomes than HPV-negative OPSCC. However, the clinical benefits of immunotherapy in patients with HPV-positive OPSCC remain unclear. METHODS: To identify the cellular and molecular factors that limited the benefits associated with HPV in OPSCC immunotherapy, we performed single-cell RNA (n=20) and T-cell receptor sequencing (n=10) analyses of tonsil or base of tongue tumor biopsies prior to immunotherapy. Primary findings from our single-cell analysis were confirmed through immunofluorescence experiments, and secondary validation analysis were performed via publicly available transcriptomics data sets. RESULTS: We found significantly higher transcriptional diversity of malignant cells among non-responders to immunotherapy, regardless of HPV infection status. We also observed a significantly larger proportion of CD4+ follicular helper T cells (Tfh) in HPV-positive tumors, potentially due to enhanced Tfh differentiation. Most importantly, CD8+ resident memory T cells (Trm) with elevated KLRB1 (encoding CD161) expression showed an association with dampened antitumor activity in patients with HPV-positive OPSCC, which may explain their heterogeneous clinical outcomes. Notably, all HPV-positive patients, whose Trm presented elevated KLRB1 levels, showed low expression of CLEC2D (encoding the CD161 ligand) in B cells, which may reduce tertiary lymphoid structure activity. Immunofluorescence of HPV-positive tumors treated with immune checkpoint blockade showed an inverse correlation between the density of CD161+ Trm and changes in tumor size. CONCLUSIONS: We found that CD161+ Trm counteracts clinical benefits associated with HPV in OPSCC immunotherapy. This suggests that targeted inhibition of CD161 in Trm could enhance the efficacy of immunotherapy in HPV-positive oropharyngeal cancers. TRIAL REGISTRATION NUMBER: NCT03737968.

An exploratory study on spatiotemporal clustering of suicide in Korean adolescents.

BACKGROUND: Adolescent suicides are more likely to form clusters than those of other age groups. However, the definition of a cluster in the space-time dimension has not been established, neither are the factors contributing to it well known. Therefore, this study aimed to identify space-time clusters in adolescent suicides in Korea and to examine the differences between clustered and non-clustered cases using novel statistical methods. METHODS: From 2016 to 2020, the dates and locations, including specific addresses from which the latitude and longitude of all student suicides (aged 9-18 years) in Korea were obtained through student suicide reports. Sociodemographic characteristics of the adolescents who died by suicide were collected, and the individual characteristics of each student who died by suicide were reported by teachers using the Strengths and Difficulties Questionnaire (SDQ). Density-Based Spatial Clustering of Applications with Noise (DBSCAN) analysis was used to assess the clustering of suicides. RESULTS: We identified 23 clusters through the data analysis of 652 adolescent suicides using DBSCAN. By comparing the size of each cluster, we identified 63 (9.7%) spatiotemporally clustered suicides among adolescents, and the temporal range of these clusters was 7-59 days. The suicide cluster group had a lower economic status than the non-clustered group. There were no significant differences in other characteristics between the two groups. CONCLUSION: This study has defined the space-time cluster of suicides using a novel statistical method. Our findings suggest that when an adolescent suicide occurs, close monitoring and intervention for approximately 2 months are needed to prevent subsequent suicides. Future research using DBSCAN needs to involve a larger sample of adolescents from various countries to further corroborate these findings.

Tumor shape as a prognostic factor for the growth of intracanalicular vestibular schwannoma: a long-term observational study.

PURPOSE: To evaluate the predictive factors of tumor growth in patients with vestibular schwannoma (VS) managed with the wait-and-scan approach. METHODS: The data of 31 patients diagnosed with intracanalicular VS and followed for > 5 years were retrospectively analyzed. VS was diagnosed according to MRI findings and tumor growth was monitored. Tumor growth was defined as an increase of 2 mm or more in the maximal tumor diameter. The association between the initial tumor size and shape and tumor growth was assessed. RESULTS: Tumor growth was observed in 16 of 31 patients (51.6%) over a mean follow-up duration of 7.3 years. The initial tumor size was not statistically correlated with tumor growth. However, fusiform or cylindrical tumors exhibited higher growth rates than oval or round tumors. Additionally, a significant correlation was observed between cerebellopontine angle extension and tumor shape. CONCLUSION: In this study, 51.6% of the patients with intracanalicular VS who were managed with the wait-and-scan strategy over a follow-up period of > 5 years showed tumor growth. Tumor shape, especially fusiform or cylindrical shape, was found to be a significant predictor of tumor growth.

A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma.

PURPOSE: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. PATIENTS AND METHODS: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses. RESULTS: Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T. CONCLUSIONS: Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.

Phenology model development for Neodryinus typhlocybae: Evaluation of phenological synchrony with its host, Metcalfa pruinosa.

The invasive species Metcalfa pruinosa has inflicted significant economic losses in various European and Asian regions. To combat this pest, the parasitoid wasp Neodryinus typhlocybae has been effectively introduced in Europe. Despite its success, research on the field occurrence patterns of N. typhlocybae, particularly its phenology, remains scarce. This study aims to develop a degree-day model for predicting the adult emergence of N. typhlocybae from overwintering cocoons and to assess the phenological synchrony between N. typhlocybae adults and the nymphal stages of M. pruinosa in Korea. In this study, we estimated the thermal parameters of N. typhlocybae under field temperatures and six constant temperatures (13.92, 17.71, 18.53, 20.53, 22.78, and 24.03 °C) conditions. The lower developmental temperature was estimated using the values of the coefficient of variation for the cumulative degree days of emerged individual adults. The estimated lower developmental threshold temperature was 12.3 °C. With this developmental threshold, a degree-day model was developed, and this model well-predicted emergence in field conditions. By simulating this developed model with the actual occurrence of the nymphal stages of its host, M. pruinosa, adult wasp emergence was estimated to be 1.5 weeks later than the first instar nymph of the host but faster than other nymphal stages of M. pruinosa. Thus, the findings in this study would be helpful in determining the possibility of establishing N. typhlocybae and improving the management efficiency of M. pruinosa.

Suicide warning signs that are challenging to recognize: a psychological autopsy study of Korean adolescents.

BACKGROUND: In South Korea, the leading cause of youth death has been suicide for about 20 years. In this study, we conducted a multi-method psychological autopsy to identify the psychiatric diagnosis, developmental history, personality traits, family history, school life, warning signs of suicide, and risk factors related to suicide for the first time in Korea. METHODS: This was a postmortem, retrospective, and descriptive study of 36 adolescents who died by suicide between August 2015 and July 2021 in South Korea. We obtained qualitative and quantitative data from the Korean Psychological Autopsy of Adolescent, conducted by the Suicide and School Mental Health Institute, the official student mental health policy-focused research institute of the Korean Ministry of Education. RESULTS: The adolescents comprised equal percentage of girls and boys. Approximately half of the deaths (55.6%) occurred at home and most (72.2%) involved jumping from a height. Most of the adolescents (97.2%) had one major psychiatric disorder before death, with depressive disorder being the most prevalent (75%). They were at a high risk for internet addiction before death. The most common personality trait was avoidance (28.6%), followed by submissiveness (27.3%). Half of the parents reported that the adolescents were satisfied with their school life and the teachers observed that they had no behavioral problems. One year before death, seven (19.4%) adolescents injured themselves and five (13.9%) had attempted suicide. Most of the deceased (80.6%) had expressed suicide warning signs to their families within one year before death. Adolescents had a long experience of family-related adverse events. CONCLUSIONS: Most of the adolescents had mental health disorders and expressed suicidal intentions using verbal and nonverbal signs. However, it was challenging for families to recognize the risk signs because of adolescents' personality traits or a good school life. To prevent adolescent suicide, adolescents, parents, and teachers need to be educated to recognize signs of suicide warning signs and equipped to guide adolescents to appropriate care.

FGF2/HGF priming facilitates adipose-derived stem cell-mediated bone formation in osteoporotic defects.

Aims: The activity of adipose-derived stem cells (ADSCs) is susceptible to the physiological conditions of the donor. Therefore, employing ADSCs from donors of advanced age or with diseases for cell therapy necessitates a strategy to enhance therapeutic efficacy before transplantation. This study aims to investigate the impact of supplementing Fibroblast Growth Factor 2 (FGF2) and Hepatocyte Growth Factor (HGF) on ADSC-mediated osteogenesis under osteoporotic conditions and to explore the underlying mechanisms of action. Main methods: Adipose-derived stem cells (ADSCs) obtained from ovariectomized (OVX) rats were cultured ex vivo. These cells were cultured in an osteogenic medium supplemented with FGF2 and HGF and subsequently autologously transplanted into osteoporotic femur defects using Hydroxyapatite-Tricalcium Phosphate. The assessment of bone formation was conducted four weeks post-transplantation. Key findings: Osteoporosis detrimentally affects the viability and osteogenic differentiation potential of ADSCs, often accompanied by a deficiency in FGF2 and HGF signaling. However, priming with FGF2 and HGF facilitated the formation of immature osteoblasts from OVX ADSCs in vitro, promoting the expression of osteoblastogenic proteins, including Runx-2, osterix, and ALP, during the early phase of osteogenesis. Furthermore, FGF2/HGF priming augmented the levels of VEGF and SDF-1α in the microenvironment of OVX ADSCs under osteogenic induction. Importantly, transplantation of OVX ADSCs primed with FGF2/HGF for 6 days significantly enhanced bone formation compared to non-primed cells. The success of bone regeneration was confirmed by the expression of type-1 collagen and osteocalcin in the bone tissue of the deficient area. Significance: Our findings corroborate that priming with FGF2/HGF can improve the differentiation potential of ADSCs. This could be applied in autologous stem cell therapy for skeletal disease in the geriatric population.

Ultrastrong and ductile steel welds achieved by fine interlocking microstructures with film-like retained austenite.

The degradation of mechanical properties caused by grain coarsening or the formation of brittle phases during welding reduces the longevity of products. Here, we report advances in the weld quality of ultra-high strength steels by utilizing Nb and Cr instead of Ni. Sole addition of Cr, as an alternative to Ni, has limitations in developing fine weld microstructure, while it is revealed that the coupling effects of Nb and Cr additions make a finer interlocking weld microstructures with a higher fraction of retained austenite due to the decrease in austenite to acicular ferrite and bainite transformation temperature and carbon activity. As a result, an alloying design with Nb and Cr creates ultrastrong and ductile steel welds with enhanced tensile properties, impact toughness, and fatigue strength, at 45% lower material costs and lower environmental impact by removing Ni.

Preconditioning with Substance P Restores Therapeutic Efficacy of Aged ADSC by Elevating TNFR2 and Paracrine Potential.

Aging leads to a decline in stem cell activity by reducing the repopulation rate and paracrine potential, ultimately diminishing efficacy in vivo. TNF-α can exert inflammatory and cell death actions via Erk by binding to TNFR-1, and survival and tissue repair actions via Akt by binding to TNFR-2. Aged cells are reported to have insufficient expression of TNFR-2, indicating that aged adipose-derived stem cells (ADSCs-E) lack the ability for cell survival and immune control compared to young ADSCs (ADSCs-Y). This study aims to assess the preconditioning effect of SP on the response of ADSCs-E to inflammation. ADSCs-E were treated with SP and then exposed to a high dose of TNF-α for 24 h. Consequently, ADSC-E exhibited weaker viability and lower TNFR2 levels compared to ADSC-Y. In response to TNF-α, the difference in TNFR2 expression became more pronounced in ADSC-E and ADSC-Y. Moreover, ADSC-E showed a severe deficiency in proliferation and paracrine activity. However, preconditioning with SP significantly enhanced the viability of ADSCs-E and also restored TNFR2 expression and paracrine potential, similar to ADSC-Y under inflammatory conditions. Our findings support the idea that preconditioning with SP has the potential to restore the cellular function of senescent stem cells before transplantation.

Disruptive Effects of Two Curcuminoids (Demethoxycurcumin and Bisdemethoxycurcumin) on the Larval Development of Drosophila melanogaster.

Juvenile hormones (JHs) play a central role in insect development, reproduction, and various physiological functions. Curcuminoids generally exhibit a wide range of biological activities, such as antioxidant, anti-inflammatory, antibacterial, and insecticidal, and they exhibit insect growth inhibitory effects. However, research on insecticidal properties of curcuminoids has been limited. Moreover, to the best of our knowledge, studies on JHs of insects and curcuminoids are lacking. Therefore, this study aimed to identify the substances that act as JH disruptors (JHDs) from edible plants. Demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), two curcuminoids from the turmeric plant Curcuma longa L. inhibited the formation of a methoprene-tolerant (Met)-Taiman (Tai) heterodimer complex in Drosophila melanogaster, as shown through in vitro yeast two-hybrid assays. An artificial diet containing 1% (w/v) DMC or BDMC significantly reduced the number of D. melanogaster larvae in a concentration-dependent manner; larval development was disrupted, preventing the progression of larvae to pupal stages, resulting in an absence of adults. Building on the results obtained in this study on curcuminoids, researchers can use our study as a reference to develop eco-friendly pesticides.

Latent Classes based on Clinical Symptoms of Military Recruits with Mental Health Issues and Their Distinctive Clinical Responses to Treatment over 6 Months.

Objective: : This study aimed (1) to identify distinct subgroups of psychiatric patients referred for a mental health certificate for military service suitability and (2) to determine whether there is a difference in clinical features such as treatment responsiveness and prognosis among certain subgroups. Methods: : We conducted latent profile analysis (LPA) using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) clinical profiles of the participants. Linear mixed model analysis was performed to examine changes in the severity of clinical symptoms and functional level according to the treatment period of the latent classes derived from the LPA. Results: : The results indicated that the best-fitting model was a three-class model, comprising Class 1 (mild maladjustment), Class 2 (neurotic depression and anxiety), and Class 3 (highly vulnerable and hypervigilant). We demonstrated that the three subgroups displayed different characteristics in treatment responsiveness and clinical course based on their Clinical Global Impression-Severity and Global Assessment of Functioning scores over a treatment period of 6 months. While subjects in Classes 1 and 2 significantly improved over 6 months, those in Class 3 showed little or no improvement in our clinical parameters. Conclusion: : This study has yielded data with clinical implications for treatment planning and interventions for each subgroup classified that were based on MMPI-2 clinical profiles of military recruits who might be maladjusted to serve.

Clinical Utility of the Minnesota Multiphasic Personality Inventory-Adolescent Restructured Form in the Assessment of Internalizing and Externalizing Disorders in Adolescents: A Preliminary Approach.

Objectives: This study investigated whether the Minnesota Multiphasic Personality Inventory-Adolescent Restructured Form (MMPI-ARF) can differentiate between two groups of adolescents, one diagnosed with internalizing disorders and another with externalizing disorders, and examined the clinical utility of the MMPI-A-RF by examining which subscales can significantly discriminate between these two groups. Methods: A total of 105 adolescents aged 13-18 years completed the MMPI-A-RF (53 internalizing disorder and 52 externalizing disorder groups). Independent t-test, chi-square test (χ2), and discriminant analysis were used to examine whether MMPI-A-RF can distinguish between the two groups. Results: Sixteen MMPI-A-RF scales best predicted differences between the groups with internalizing and externalizing disorders. Fourteen scales (Higher-Order Scale [Emotional/Internalizing Dysfunction], Restructured Clinical [RC] Scale [RC demoralization, Somatic Complaints (RC1), and Low Positive Emotions (RC2)], Personality Psychopathology Five Scale [Introversion/Low Positive Emotionality- Revised, Negative Emotionality/Neuroticism-Revised], Somatic/Cognitive Scale [Malaise, Head Pain Complaints, and Gastrointestinal Complaints], Internalizing Scale [Stress/Worry, Self-Doubt], Externalizing Scale [Negative School Attitudes], Interpersonal Scale [Social Avoidance, Shyness]) were associated with the internalizing disorder group, whereas two scales (Externalizing Scale [Conduct Problems, Negative Peer Influence]) were associated with the externalizing disorder group. Conclusion: The MMPI-A-RF can be an efficient assessment tool for a quick diagnosis as it can classify individuals with internalizing and externalizing disorders in clinical settings that lack a variety of assessment tools for children and adolescents.

Spontaneous soliton mode-locking of a microcomb assisted by Raman scattering.

We successfully control the interaction dynamics between optical parametric oscillation (OPO) and stimulated Raman scattering, leading to the generation of distinct frequency comb states in a microresonator. Through Raman-scattered photons, a Raman comb with a sech2 envelope is demonstrated having a broad RF beat note linewidth of several hundred kHz. Moreover, under a specific coupling regime, we successfully generate self-locked Raman single-solitons which is confirmed by a narrow RF beat note of 25 Hz. Remarkably, this spontaneous Raman soliton is deterministically generated through adiabatic pump frequency detuning without the requirement of external locking mechanisms. Additionally, we identify a frequency comb with an unconventional envelope that can be fitted with a Lorentzian × sech2 function, generated via an anti-Stokes process with respect to the Raman comb.

Daidzein Inhibits Human Platelet Activation by Downregulating Thromboxane A2 Production and Granule Release, Regardless of COX-1 Activity.

Platelets play crucial roles in cardiovascular diseases (CVDs) by regulating hemostasis and blood coagulation at sites of blood vessel damage. Accumulating evidence indicates daidzein inhibits platelet activation, but the mechanism involved has not been elucidated. Thus, in this study, we investigated the mechanism responsible for the inhibition of collagen-induced platelet aggregation by daidzein. We found that in collagen-induced platelets, daidzein suppressed the production of thromboxane A2 (TXA2), a molecule involved in platelet activation and aggregation, by inhibiting the cytosolic phospholipase A2 (cPLA2) signaling pathway. However, daidzein did not affect cyclooxygenase-1 (COX-1). Furthermore, daidzein attenuated the PI3K/PDK1/Akt/GSK3αß and MAPK (p38, ERK) signaling pathways, increased the phosphorylation of inositol trisphosphate receptor1 (IP3R1) and vasodilator-stimulated phosphoprotein (VASP), and increased the level of cyclic adenosine monophosphate (cAMP). These results suggest that daidzein inhibits granule release (ATP, serotonin, P-selectin), integrin αIIbß3 activation, and clot retraction. Taken together, our study demonstrates that daidzein inhibits collagen-induced platelet aggregation and suggests that daidzein has therapeutic potential for the treatment of platelet aggregation-related diseases such as atherosclerosis and thrombosis.

No-Touch Radiofrequency Ablation for Early Hepatocellular Carcinoma: 2023 Korean Society of Image-Guided Tumor Ablation Guidelines.

Radiofrequency ablation (RFA) has been widely used to manage hepatocellular carcinomas (HCCs) equal to or smaller than 3 cm. No-touch RFA has gained attention and has recently been implemented in local ablation therapy for HCCs, despite its technical complexity, as it provides improved local tumor control compared to conventional tumor-puncturing RFA. This article presents the practice guidelines for performing no-touch RFA for HCCs, which have been endorsed by the Korean Society of Image-Guided Tumor Ablation (KSITA). The guidelines are primarily designed to assist interventional oncologists and address the limitations of conventional tumor-puncturing RFA with describing the fundamental principles, various energy delivery methods, and clinical outcomes of no-touch RFA. The clinical outcomes include technical feasibility, local tumor progression rates, survival outcomes, and potential complications.

Korean adolescent suicide and search volume for "self-injury" on internet search engines.

Introduction: Many adolescents with suicidal ideation receive support through the Internet. However, they also find ways to attempt suicide or strengthen their suicidal ideation through this medium. This study analyzed the association between the search volume of suicide-related terms and the number of suicides among Korean adolescents. We also analyzed the correlations between the search volumes of suicide-related terms. Methods: We selected seven words (suicide, self-injury, depression, academic score, school violence, outcasts, and family trouble) related to adolescent suicide. A dataset was constructed by combining data from the most commonly used search engine in Korea (Naver Datalab) and the daily number of adolescent suicides in school settings (n = 347) from January 1, 2016 to December 31, 2018, collected from the Ministry of Education. Poisson regression and Pearson correlation analyses were performed. Results: Significant associations were found between suicide attempts and search term volumes, which differed according to sex and time interval. Among the search terms, "self-injury" was most strongly associated with suicide, and this association was significant at all time intervals (daily, weekly, and monthly) in female adolescents and in the total population. Further, the association was strongest in the daily suicide data. More search term volumes were related to suicide in the daily and weekly data than in the monthly data. There were positive correlations between "suicide," "self-injury," and "depression" search volumes. Conclusion: Further studies with larger sample sizes, more search terms, and analysis of time intervals between suicide-related term search and suicide death are required. These studies can contribute to the establishment of an online suicide prevention system to detect suicide risk in adolescents and provide interventions.

Platelet-Derived Growth Factor-BB Priming Enhances Vasculogenic Capacity of Bone Marrow-Derived Endothelial Precursor Like Cells.

BACKGROUND: Human endothelial progenitor cells (EPCs) were first identified in the peripheral blood and later in the cord blood and bone marrow (BM) with different vascularization capacity and different surface marker profiles. However, their identity and functional roles in neovascularization have not been clearly demonstrated in vivo and in vitro. METHODS: Characterization of BM-EPC like cells were performed by fluorescence-activated cell sorting, immunofluorescence staining, enzyme-linked immunosorbent assay, Matrigel tube formation assay, and western blot analysis. RESULTS: BM-EPC like cells were identified by selective adhesion to fibronectin and collagen from BM mononuclear cells, which generate fast-growing colonies with spindle morphology, express surface markers of CD105, vWF, UEA-I lectin binding, secrete HGF, VEGF, TGF-beta1 but can be distinguished from circulating EPC and endothelial cells by no expression of surface markers such as CD31, CD309, CD45, and CD34. These BM-EPC like cells shared many cell surface markers of BM-mesenchymal stem cells (MSC) but also can be distinguished by their vasculogenic property and other unique surface markers. Furthermore, the vasculogenic capacity of BM-EPC like cells were enhanced by co-culture of BM-MSC or PDGF-BB priming. PDGF-BB stimulated cell migration, proliferation, and secretion of laminin ß-1, which was proposed as one of the mechanisms involved in the better vascularization of BM-EPC like cells. CONCLUSION: PDGF-BB priming may be applied to improve the potency and function of BM-EPC like cells as vasculogenic cell therapy for the ischemic vascular repair.

Lactobacillus fermentum HY7302 Improves Dry Eye Symptoms in a Mouse Model of Benzalkonium Chloride-Induced Eye Dysfunction and Human Conjunctiva Epithelial Cells.

(1) We investigated the effects of the Lactobacillus fermentum HY7302 (HY7302) in a mouse model of benzalkonium chloride (BAC)-induced dry eye, and the possibility of using HY7302 as a food supplement for preventing dry eye. (2) The ocular surface of Balb/c mice was exposed to 0.2% BAC for 14 days to induce dry eye (n = 8), and the control group was treated with the same amount of saline (n = 8). HY7302 (1 × 109 CFU/kg/day, 14 days, n = 8) was orally administered daily to the mice, and omega-3 (200 mg/kg/day) was used as a positive control. To understand the mechanisms by which HY7302 inhibits BAC-induced dry eye, we performed an in vitro study using a human conjunctival cell line (clone-1-5c-4). (3) The probiotic HY7302 improved the BAC-induced decreases in the corneal fluorescein score and tear break-up time. In addition, the lactic acid bacteria increased tear production and improved the detached epithelium. Moreover, HY7302 lowered the BAC-induced increases in reactive oxygen species production in a conjunctival cell line and regulated the expression of several apoptosis-related factors, including phosphorylated protein kinase B (AKT), B-cell lymphoma protein 2 (Bcl-2), and activated caspase 3. Also, HY7302 alleviated the expression of pro-inflammatory cytokines, such as interleukin-1ß (IL-1ß), IL-6, and IL-8, and also regulated the matrix metallopeptidase-9 production in the conjunctival cell line. (4) In this study, we showed that L. fermentum HY7302 helps prevent dry eye disease by regulating the expression of pro-inflammatory and apoptotic factors, and could be used as a new functional food composition to prevent dry eye disease.