Genome to phenome Association for Pork Belly Parameters Elucidates Three Regulation Distinctions: Adipogenesis, muscle formation, and their transcription factors.

Genome to phenome analysis is necessary in livestock areas because of its various and complex phenotypes. Pork belly is a favorable part of meat worldwide, including East Asia. A previous study has suggested that the three key transcription factors (ZNF444, NFYA and PPARG) affecting pork belly traits include total volume, the volume of total fat and muscle, and component muscles of the corresponding slice. However, other transcription factor genes affecting each slice other than pork belly component traits still needed to be identified. Thus, we aimed to analyze pork belly components at the genome to phenome level for identifying key transcription factor genes and their co-associated networks. The range of node numbers against each component trait via the association weight matrix was from 598 to 3020. Premised on the result, an in silico functional approach was performed. Each co-association network enriched three key transcription factors in adipogenesis and skeletal muscle proliferation, mesoderm development, metabolism, and gene transcription. The three key transcription factors and their related genes may be useful in comprehending their effect of pork belly construction.

Trends in Electroconvulsive Therapy Utilization in South Korea: Health Insurance Review Data From 2008 to 2018.

OBJECTIVE: The study aimed to analyze and clinically correlate 10-year trends in the demographic characteristics of patients receiving electroconvulsive therapy (ECT) to provide an overview of ECT utilization in South Korea. METHODS: Using health insurance claims data from 2008 to 2018 retrieved from Health Insurance Review and Assessment Service database in South Korea, we identified individuals undergoing ECT based on procedural codes. Descriptive analysis evaluated baseline clinical characteristics, and trend analysis used a linear regression model. RESULTS: The prevalence of ECT increased by 240.49% (0.405/105 inhabitants in 2008 to 0.974/105 inhabitants in 2018). The increasing trend was more pronounced in younger and older patients. The proportion of women consistently exceeded that of men. A rise in the proportion of patients with affective disorders, and a decrease in the proportion of psychotic disorders was observed. More antidepressants and atypical antipsychotics were prescribed to patients undergoing ECT. The proportion of ECT sessions conducted in large hospital inpatient settings also decreased during the observation period. Despite increasing global trends, ECT prevalence in South Korea remains significantly lower than worldwide rates. CONCLUSION: This study demonstrated an increasing trend of ECT across a wide range of population demographics and in more accessible settings. The comparatively low prevalence of ECT in Korea compared to other countries might be attributed to insufficient mental health literacy and the stigma associated with ECT. Given the elevated suicide rates in Korea, more extensive adoption of ECT appears imperative.

Effects of body mass index on mortality in elderly patients with hip fractures.

Hip fractures remain a substantial health concern, particularly among elderly individuals with osteoporosis, leading to high global mortality rates. This study aimed to analyze the association between body mass index (BMI) and postoperative mortality in patients who underwent surgery for hip fractures. A total of 680 patients treated at a single institution between January 2018 and December 2022 were included. Factors such as age, BMI, sex, Charlson Comorbidity Index (CCI), preoperative hemoglobin levels, American Society of Anesthesiologists score, anesthesia method, duration of surgery, and time from injury to surgery were assessed. Underweight status, male sex, higher CCI, and general anesthesia were significantly associated with 1-year and in-hospital mortality. Notably, underweight individuals exhibited a higher risk of mortality than normal-weight individuals, and female patients had lower mortality rates. This study underscores the importance of considering BMI, along with other demographic and clinical factors, in predicting postoperative mortality among patients with hip fractures, aiding the development of tailored management strategies to improve outcomes and reduce complications in this vulnerable patient population.

CHI3L1 on fibrinolytic system imbalance in chronic rhinosinusitis with nasal polyp.

Background: Chronic rhinosinusitis (CRS) is an inflammatory disease affecting more than 10% of the global adult population. It is classified into Th1, Th2, and Th17 endotypes and eosinophilic and non-eosinophilic types. Th2-based inflammation and eosinophilic CRS (ECRS) are associated with tissue remodeling and fibrinolytic system impairment. Objective: To elucidate the role of eosinophils in inducing fibrin deposition in CRS nasal polyp tissues and explore potential regulatory mechanisms. Methods: We analyzed the expression of genes related to the serpin family and fibrinolytic system using Gene Expression Omnibus and Next-generation sequencing data. Differentially expression genes (DEGs) analysis was used to compare control and nasal polyp tissues, followed by KEGG and Gene ontology (GO) analysis. We measured the expression and correlation of plasminogen activator-1 (PAI-1), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and urokinase plasminogen activator surface receptor (u-PAR) in CRS tissues, and evaluated the effect of eosinophils on the fibrinolytic system using a cytokine array and co-culture. Results: Nasal polyp tissues showed upregulated PAI-1, u-PA, and u-PAR expression and downregulated t-PA expression. Fibrinolytic system-related genes positively correlated with Th2 cytokines, except for t-PA. Eosinophil-derived Chitinase-3-like protein 1 (CHI3L1) increased PAI-1 expression and decreased t-PA levels in fibroblasts and epithelial cells. The inhibition of CHI3L1 suppresses these alterations. Conclusion: CHI3L1 contributes to fibrin deposition by impairing the fibrinolytic system during nasal polyp formation. The regulation of CHI3L1 expression may inhibit fibrin deposition and edema in ECRS, presenting a potential treatment for this condition.

Overexpression of Hypermethylated Homeobox A11 (HOXA11) Inhibits Tumor Cell Growth and Induces Apoptosis in Cervical Cancer.

This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene expression analysis using cDNA microarray in cervical cancer cell lines revealed significantly reduced expression of the HOXA11 gene. Subsequent investigation of HOXA11 promoter methylation in samples from normal individuals and invasive cervical cancer patients showed over 53.2% higher methylation in cancer scrapes compared to normal scrapes. Furthermore, overexpression of HOXA11, which is downregulated in cervical cancer, strongly suppressed cell growth in cervical cancer cell lines, HeLa and HT3. Additionally, we performed transferase dUTP nick end labeling assay and confirmed that the inhibition of cervical cancer cell proliferation occurred via apoptosis. Mechanistically, overexpression of HOXA11 led to mitochondrial apoptosis characterized by PARP cleavage due to increased c-Myc and enhanced cytochrome C secretion into the cytoplasm. These findings suggest that HOXA11 could potentially serve as a methylation marker for diagnosing cervical cancer and as a novel therapeutic target for its treatment.

Psychological resilience and suicidality in the general population: A cross-sectional study based on data from the National Mental Health Survey of Korea 2021.

BACKGROUND: The relationship between suicidality and resilience is underexplored among the general population. This study aimed to explore the relationship between lifetime, one-year, and one-month prevalence of suicidality (ideation, plan, attempt) and resilience in the general population. METHODS: Data on suicidality, resilience, prevalence of major mental disorders, and other key psychological factors were collected from the National Mental Health Survey of Korea 2021. Interviewees comprised 5511 South Koreans aged 18-79 years. The contribution of resilience to suicidality was evaluated using Rao-Scot logistic regression, adjusting for possible confounders such as mental disorder prevalence and demographic and psychological characteristics. RESULTS: Significantly lower resilience levels were noted among participants who reported lifetime, one-year, and one-month suicidal ideation, plan, or attempts. High resilience levels predicted no suicidal ideation, plans, and attempts in the lifetime, and no suicidal ideation and plans in the one-year and one-month time frames. LIMITATIONS: First, this study's cross-sectional design has limitations for ascertaining a causal relationship between resilience and suicidality. Second, because the number of participants who had attempted suicide in the past year and reported suicidal thoughts/attempts in the past month was small, there were limitations in the analysis of suicidality in these time frames. Third, it was difficult to rule out the mediating effects of personality and temperament on the relationship between resilience and suicidality. CONCLUSIONS: High resilience levels predicted lower lifetime and current suicidal ideation and suicidal planning in the general population. This study shows that psychological resilience is an important factor in evaluating an individual's current suicidality.

Swimming exercise alleviates pathological bone features in curdlan-injected SKG mice by inducing irisin expression.

This study assessed the therapeutic potential of swimming exercise in the curdlan-injected SKG mouse model and investigated the modulatory effects of irisin on inflammation. Curdlan-injected SKG were randomly assigned to either a home-cage group or a swimming group for 6 weeks. Changes in clinical arthritis scores and ankle thickness were measured weekly. Post-swimming program, mice were anesthetized for collection of vastus lateralis muscle and blood, which was followed by histological analysis, micro-CT imaging of the ankle joints, and the measurement of pro-inflammatory cytokines and irisin levels. Additionally, curdlan-injected SKG mice were intravenously injected with recombinant irisin protein and observed. Finally, serum levels of irisin in healthy control and ankylosing spondylitis (AS) patient groups were measured by ELISA. The swimming group of curdlan-injected SKG mice exhibited significant improvements in arthritis and enthesitis compared to the home-cage group. In particular, micro-CT and histological analyses revealed a notable reduction in pathological bone features in the swimming group compared to the home-cage group. Muscle endurance was also enhanced in the swimming group compared to the home-cage group, as determined by the wire-hanging test. Intriguingly, irisin levels not only were statistically increased in the swimming group but, also, TNF-α, IL-1ß, and IL-6 levels were decreased. Additionally, injection of irisin protein slightly attenuated both arthritis and enthesitis in curdlan-injected SKG mice. Meanwhile, irisin serum levels were declined in AS patients. Overall, we found that swimming exercise attenuated pathological bone features in an AS animal model, potentially mediated by increased irisin serum levels with associated anti-inflammatory effects.

CE9A215 (inotodiol), a lanostane-type oxysterol, mitigates LPS-induced sepsis through multifaceted mechanisms.

Dysregulated host response against infection triggers sepsis that leads to multiple organ dysfunction due to uncontrolled inflammatory responses. Despite marked progress in understanding of sepsis, numerous clinical trials for treatment of sepsis have proven daunting and a new therapeutic approach is highly needed. CE9A215 (inotodiol), a fungal secondary metabolite, has been researched for its pharmacological activities and has shown potent anti-allergic effects. In this study, we evaluated the anti-inflammatory activities of CE9A215 upon lipopolysaccharide (LPS) stimulation in vivo and in vitro for the first time. CE9A215 decreased the production of interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and IL-1ß in a concentration-dependent manner in LPS-stimulated RAW264.7 cells. Intriguingly, in human mast cell line LUVA, CE9A215 significantly lowered IL-4 and IL-10, and this effect could be beneficial for the clearance of bacterial infection. In addition, administration of CE9A215 improved the survival rate of LPS-stimulated mice and inhibited the pro-inflammatory cytokines, IL-6, TNF-α, and IL-1ß in blood. Moreover, CE9A215 enhanced the expression levels of plasma phospholipid transfer protein (PLTP), apolipoprotein E (ApoE), and ATP-binding cassette transporter (ABCA1) in LPS-stimulated RAW246.7 cells. Liver PLTP level increased significantly in the CE9A215-administered group compared with the control group, which implies that CE9A215 promotes LPS clearance and neutralization by reverse transport of LPS by increasing the expressions of PLTP, ApoE, and ABCA1. Our results highlight CE9A215's potential as a novel therapeutic option for the treatment of sepsis.

Global hyperperfusion after successful endovascular thrombectomy is linked to worse outcome in acute ischemic stroke.

Patients with stroke may develop hyperperfusion after a successful endovascular thrombectomy (EVT). However, the relationship between post-EVT hyperperfusion and clinical outcomes remains unclear and requires further clarification. We reviewed consecutive patients with anterior circulation occlusion who were successfully recanalized with EVT. Based on post-EVT arterial spin-labeling images, hyperperfusion was categorized as follows: global hyperperfusion (GHP), increased cerebral blood flow (CBF) in ≥ 50% of the culprit vessel territory; focal hyperperfusion (FHP), increased CBF in < 50% of the culprit vessel territory; no hyperperfusion (NHP), no discernible CBF increase. Factors associated with hyperperfusion were assessed, and clinical outcomes were compared among patients under different hyperperfusion categories. Among 131 patients, 25 and 40 patients developed GHP and FHP, respectively. Compared to other groups, the GHP group had worse National Institutes of Health Stroke Scale score (GHP vs. NHP/FHP, 18.1 ± 7.4 vs. 12.3 ± 6.0; p < 0.001), a larger post-EVT infarct volume (98.9 [42.3-132.7] vs. 13.5 [5.0-34.1] mL; p < 0.001), and a worse 90-day outcome (modified Rankin Scale, 3 [1-4] vs. 2 [0-3]; p = 0.030). GHP was independently associated with infarct volume (B = 0.532, standard error = 0.163, p = 0.001), and infarct volume was a major mediator of the association of GHP with unfavorable outcomes (total effect: ß = 0.176, p = 0.034; direct effect: ß = 0.045, p = 0.64; indirect effect: ß = 0.132, p = 0.017). Patients presenting with post-EVT GHP had poorer neurological prognosis, which is likely mediated by a large infarct volume.

Age-Related Variations in Patterns of Patent Foramen Ovale-Stroke versus Other Cryptogenic Stroke.

INTRODUCTION: Patent foramen ovale (PFO)-stroke, a form of cryptogenic stroke, has certain identifying clinical and imaging features. However, data describing this stroke type remain inconsistent. This study examined the potential variations in PFO-stroke features, depending on age. METHODS: From a hospital registry, cryptogenic stroke patients were retrospectively selected, and PFO-strokes were identified by the presence of >10 microembolic signals on transcranial Doppler saline agitation test. Cryptogenic strokes were grouped according to age (<70 as young, ≥70 as elderly). Clinical and imaging variables of PFO-strokes and non-PFO-strokes were compared, with and without age considered. RESULTS: Of the 462 cryptogenic patients, 30.5% (141/462) were PFO-strokes, while majority (321/462) had no PFO. When cryptogenic strokes were analyzed by age, the significant difference was noted in the lesion number, pattern, and side. A single (72.8 vs. 57.9%, p = 0.020) and a small single lesion (51.1 vs. 35.5%, p = 0.039) were frequently seen in the younger PFO-strokes than the non-PFO counterpart, while mixed territory lesions identified the elderly PFO-strokes (30.6 vs. 8.9%, p = 0.001). A multivariate logistic regression analysis of PFO-strokes further showed that age was independently associated with lesion side (OR 1.12 [1.05-1.20], p < 0.001) and lesion number (OR 1.06 [1.02-1.10], p = 0.005). CONCLUSIONS: Incorporating age-specific imaging criteria in the identification of PFO-strokes may be of additional value. Further, PFO may remain contributory to the stroke risk in the elderly, in association with vascular risk factors.

Solution-processable low-voltage carbon nanotube field-effect transistors with high-krelaxor ferroelectric polymer gate insulator.

Achieving energy-efficient and high-performance field-effect transistors (FETs) is one of the most important goals for future electronic devices. This paper reports semiconducting single-walled carbon nanotube FETs (s-SWNT-FETs) with an optimized high-krelaxor ferroelectric insulator P(VDF-TrFE-CFE) thickness for low-voltage operation. The s-SWNT-FETs with an optimized thickness (∼800 nm) of the high-kinsulator exhibited the highest average mobility of 14.4 cm2V-1s-1at the drain voltage (ID) of 1 V, with a high current on/off ratio (Ion/off>105). The optimized device performance resulted from the suppressed gate leakage current (IG) and a sufficiently large capacitance (>50 nF cm-2) of the insulating layer. Despite the extremely high capacitance (>100 nF cm-2) of the insulating layer, an insufficient thickness (<450 nm) induces a highIG, leading to reducedIDand mobility of s-SWNT-FETs. Conversely, an overly thick insulator (>1200 nm) cannot introduce sufficient capacitance, resulting in limited device performance. The large capacitance and sufficient breakdown voltage of the insulating layer with an appropriate thickness significantly improved p-type performance. However, a reduced n-type performance was observed owing to the increased electron trap density caused by fluorine proportional to the insulator thickness. Hence, precise control of the insulator thickness is crucial for achieving low-voltage operation with enhanced s-SWNT-FET performance.

Quantification of Choroidal Vascular Hyperpermeability on Ultra-Widefield Indocyanine Green Angiography in Macular Neovascularization.

To obtain a quantitative parameter for the measurement of choroidal vascular hyperpermeability (CVH) on ultra-widefield indocyanine green angiography (UWICGA) using an objective analysis method in macular choroidal neovascularization (CNV). A total of 113 UWICGA images from 113 subjects were obtained, including with 25 neovascular age-related macular degeneration (nAMD), 37 with polypoidal choroidal vasculopathy (PCV) (19 with thin-choroid and 18 with thick-choroid), 33 with pachychoroid neovasculopathy (PNV), and 18 age-matched controls. CVH was quantified on a gray image by the subtraction of 2 synchronized UWICGA images of early and late phases. The measured CVH parameter was compared with human graders and among CNV subtypes and correlated with choroidal vascular density (CVD) and subfoveal choroidal thickness (SFCT). The mean CVH values were 28.58 ± 4.97, 33.36 ± 8.40, 33.61 ± 11.50, 42.19 ± 13.25, and 43.59 ± 7.86 in controls and patients with nAMD, thin-choroid PCV, thick-choroid PCV, and PNV, respectively (p < 0.001). CVH was higher in thick-choroid PCV and PNV compared to the other groups (all p ≤ 0.006). The measured CVH value positively correlated with those reported by human graders (p < 0.001), CVD, and SFCT (p = 0.001 and p < 0.001, respectively). CVH can be measured objectively using quantitative UWICGA analysis. The CVH parameter differs among macular CNV subtypes and correlates with CVD and SFCT.

The Potential Role of Aripiprazole Augmentation for Major Depressive Disorder with Anxious Distress in Naturalistic Treatment Setting.

Objective: : This study tried to observe clinical benefit of aripiprazole augmentation (ARPA) treatment for major depressive disorder with anxious distress (MDDA) in routine practice. Methods: : Retrospective chart review (n = 41) was conducted for clinical benefit of ARPA in patients with MDDA in routine practice. The primary endpoint was the mean change of Hamilton Anxiety Rating scale (HAMA) total scores from baseline to the endpoint. Additional secondary endpoints were also retrieved. Results: : The changes of primary endpoint HAMA (t = 5.731, -4.6, p = 0.001), and secondary endpoints including Hamilton Depression Rating scale (HAMD, t = 4.284, -3.4, p ＜ 0.001), Clinical Global Impression-Clinical Benefit (CGI-CB, -0.9, t = 1.821, p = 0.026), and Clinical Global Impression Score-Severity (CGI-S, t = 3.556, -0.4, p ＜ 0.001) scores were also significantly improved during the study. No significant adverse events were observed. Conclusion: : This study has shown additional benefit of ARPA treatment for MDDA patients in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.

Embitterment in Vietnam War Veterans Predicted by Symptoms of Posttraumatic Stress Disorder.

OBJECTIVE: Research on the association between posttraumatic embitterment disorder (PTED) and other psychopathologies in veterans and adults aged ≥65 years is lacking. This study aimed to assess embitterment among elderly war veterans and its association with major psychopathological factors. METHODS: Participants included Vietnam War veterans who visited a psychiatric clinic. Based on the Posttraumatic Embitterment Disorder Self-Rating Scale (PTEDS) score, the participants were divided into the embitterment (PTED(+), mean score of PTEDS items [mPTEDS] ≥1.6) and non-embitterment (PTED(-), mPTEDS <1.6) groups. Demographic characteristics, combat exposure severity, depression, anxiety, sleep, and alcohol use disorder symptom scores of the participants were collected and compared between the PTED(+) and PTED(-) groups. A correlation analysis between symptom measure scores and the mPTEDS was conducted. The influence of psychopathology on embitterment was investigated using stepwise multiple linear regression analysis. RESULTS: In total, 60 participants (28 in PTED(+) and 32 in PTED(-)) were included. Among those in PTED(+), 21 (35.0%) showed mild embitterment symptoms (1.6≤ mPTEDS <2.5) and 7 (11.7%) reported moderate or severe embitterment symptoms (mPTEDS ≥2.5). The mean scores of posttraumatic stress disorder (PTSD), depression, and anxiety were significantly higher in the PTED(+) than in the PTED(-) group. The mPTEDS were significantly correlated with PTSD, depression, anxiety, and sleep disorder scores. The PTSD symptoms significantly explained the higher mPTEDS score in a regression model. CONCLUSION: Embitterment symptoms were associated with PTSD, depression, anxiety, and insomnia symptoms in elderly veterans, similar to the results of prior studies involving only the general population.

Diabetic Ketoacidosis Associated With Second Generation Antipsychotics: A Case Study and Review of Literature.

OBJECTIVE: Second-generation antipsychotics (SGAs) have revolutionized the treatment of psychiatric disorders, but are associated with significant metabolic risks, including diabetes and hyperglycemic crises. This review explores the complex interplay between antipsychotics, diabetes, and hyperglycemic crises, highlighting the mechanisms underlying SGA-induced diabetes. METHODS: We present the case of a patient with schizophrenia who was taking antipsychotic medication and was admitted to the emergency room due to the sudden onset of diabetic ketoacidosis (DKA) without any history of diabetes. We extensively searched databases, including Elsevier, PubMed, IEEE, SpringerLink, and Google Scholar, for papers on the effects of antipsychotic drugs on DKA from 2002 to 2021. We focused on DKA, hyperglycemia, and atypical antipsychotics, and retrieved 117 papers. After full-text review, 32 papers were included in this comprehensive review. RESULTS: DKA was significantly more frequent in patients taking SGAs. Antipsychotics can induce insulin resistance either directly or through the onset of obesity. Antipsychotics can reduce insulin secretion from pancreatic ß-cells, which is associated with absolute insulin deficiency. CONCLUSION: As the use of antipsychotics continues to increase, understanding their risks and mechanisms is crucial for clinicians to enable informed treatment decisions and prevent potentially life-threatening complications.

BTN1A1 is a novel immune checkpoint mutually exclusive to PD-L1.

BACKGROUND: While Programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockade is a potent antitumor treatment strategy, it is effective in only limited subsets of patients with cancer, emphasizing the need for the identification of additional immune checkpoints. Butyrophilin 1A1 (BTN1A1) has been reported to exhibit potential immunoregulatory activity, but its ability to function as an immune checkpoint remains to be systematically assessed, and the mechanisms underlying such activity have yet to be characterized. METHODS: BTN1A1 expression was evaluated in primary tumor tissue samples, and its ability to suppress T-cell activation and T cell-dependent tumor clearance was examined. The relationship between BTN1A1 and PD-L1 expression was further characterized, followed by the development of a BTN1A1-specific antibody that was administered to tumor-bearing mice to test the amenability of this target to immune checkpoint inhibition. RESULTS: BTN1A1 was confirmed to suppress T-cell activation in vitro and in vivo. Robust BTN1A1 expression was detected in a range of solid tumor tissue samples, and BTN1A1 expression was mutually exclusive with that of PD-L1 as a consequence of its inhibition of Janus-activated kinase/signal transducer and activator of transcription signaling-induced PD-L1 upregulation. Antibody-mediated BTN1A1 blockade suppressed tumor growth and enhanced immune cell infiltration in syngeneic tumor-bearing mice. CONCLUSION: Together, these results confirm that the potential of BTN1A1 is a bona fide immune checkpoint and a viable immunotherapeutic target for the treatment of individuals with anti-PD-1/PD-L1 refractory or resistant disease, opening new avenues to improving survival outcomes for patients with a range of cancers.

The complement factor H-related protein-5 (CFHR5) exacerbates pathological bone formation in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by excessive new bone formation. We previously reported that the complement factor H-related protein-5 (CFHR5), a member of the human factor H protein family, is significantly elevated in patients with AS compared to other rheumatic diseases. However, the pathophysiological mechanism underlying new bone formation by CFHR5 is not fully understood. In this study, we revealed that CFHR5 and proinflammatory cytokines (TNF, IL-6, IL-17A, and IL-23) were elevated in the AS group compared to the HC group. Correlation analysis revealed that CFHR5 levels were not significantly associated with proinflammatory cytokines, while CFHR5 levels in AS were only positively correlated with the high CRP group. Notably, treatment with soluble CFHR5 has no effect on clinical arthritis scores and thickness at hind paw in curdlan-injected SKG, but significantly increased the ectopic bone formation at the calcaneus and tibia bones of the ankle as revealed by micro-CT image and quantification. Basal CFHR5 expression was upregulated in AS-osteoprogenitors compared to control cells. Also, treatment with CFHR5 remarkedly induced bone mineralization status of AS-osteoprogenitors during osteogenic differentiation accompanied by MMP13 expression. We provide the first evidence demonstrating that CFHR5 can exacerbate the pathological bone formation of AS. Therapeutic modulation of CFHR5 could be promising for future treatment of AS. KEY MESSAGES: Serum level of CFHR5 is elevated and positively correlated with high CRP group of AS patients. Recombinant CFHR5 protein contributes to pathological bone formation in in vivo model of AS. CFHR5 is highly expressed in AS-osteoprogenitors compared to disease control. Recombinant CFHR5 protein increased bone mineralization accompanied by MMP13 in vitro model of AS.

TRPC4 deletion elicits behavioral defects in sociability by dysregulating expression of microRNA-138-2.

To investigate whether the defects in transient receptor potential canonical 4 (TRPC4), which is strongly expressed in the hippocampus, are implicated in ASD, we examined the social behaviors of mice in which Trpc4 was deleted (Trpc4-/-). Trpc4-/- mice displayed the core symptoms of ASD, namely, social disability and repetitive behaviors. In microarray analysis of the hippocampus, microRNA (miR)-138-2, the precursor of miR-138, was upregulated in Trpc4-/- mice. We also found that binding of Matrin3 (MATR3), a selective miR-138-2 binding nuclear protein, to miR-138-2 was prominently enhanced, resulting in the downregulation of miR-138 in Trpc4-/- mice. Some parameters of the social defects and repetitive behaviors in the Trpc4-/- mice were rescued by increased miR-138 levels following miR-138-2 infusion in the hippocampus. Together, these results suggest that Trpc4 regulates some signaling components that oppose the development of social behavioral deficits through miR-138 and provide a potential therapeutic strategy for ASD.

Molecular mechanism of the anti-inflammatory and skin protective effects of Syzygium formosum in human skin keratinocytes.

Irradiation injury, especially caused by UVB, of the skin is one of the critical reasons for skin inflammation and damage. The present study aimed to explore the protective effect of Syzygium formosum leafy extract (SFLE) and its mechanism of action against UVB-induced damages of human keratinocytes. In this study, SFLE was prepared from 100 kg dried leaves using industrial-scale processes. We found that SFLE markedly reduced markers of the skin inflammation in UVB-induced pro-inflammatory cytokines. Only 2 µg/mL of SFLE exhibited significantly stronger anti-inflammatory effects than the fivefold concentration of positive control. Intriguingly, an anti-inflammatory enzyme, heme oxygenase-1 expression was significantly induced by SFLE treatment. MMP-3 and -9 were, but not MMP-1, significantly reduced. SFLE inhibited the expression of the MAPK pathway, resulting in a decrease on UVB-induced reactive oxygen species. In conclusion, SFLE can potentially be used to treat skin inflammatory diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01380-4.