SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD.

Posttranslational modifications regulate the properties and abundance of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that mediate fast excitatory synaptic transmission and synaptic plasticity in the central nervous system. During long-term depression (LTD), protein tyrosine phosphatases (PTPs) dephosphorylate tyrosine residues in the C-terminal tail of AMPA receptor GluA2 subunit, which is essential for GluA2 endocytosis and group I metabotropic glutamate receptor (mGluR)-dependent LTD. However, as a selective downstream effector of mGluRs, the mGluR-dependent PTP responsible for GluA2 tyrosine dephosphorylation remains elusive at Schaffer collateral (SC)-CA1 synapses. In the present study, we find that mGluR5 stimulation activates Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) by increasing phospho-Y542 levels in SHP2. Under steady-state conditions, SHP2 plays a protective role in stabilizing phospho-Y869 of GluA2 by directly interacting with GluA2 phosphorylated at Y869, without affecting GluA2 phospho-Y876 levels. Upon mGluR5 stimulation, SHP2 dephosphorylates GluA2 at Y869 and Y876, resulting in GluA2 endocytosis and mGluR-LTD. Our results establish SHP2 as a downstream effector of mGluR5 and indicate a dual action of SHP2 in regulating GluA2 tyrosine phosphorylation and function. Given the implications of mGluR5 and SHP2 in synaptic pathophysiology, we propose SHP2 as a promising therapeutic target for neurodevelopmental and autism spectrum disorders.

Systematic Proteome Profiling of Maternal Plasma for Development of Preeclampsia Biomarkers.

Preeclampsia (PE) is a hypertensive disorder of pregnancy with various clinical symptoms. However, traditional markers for the disease including high blood pressure and proteinuria are poor indicators of the related adverse outcomes. Here, we performed systematic proteome profiling of plasma samples obtained from pregnant women with PE to identify clinically effective diagnostic biomarkers. Proteome profiling was performed using TMT-based liquid chromatography-mass spectrometry (LC-MS/MS) followed by subsequent verification by multiple reaction monitoring (MRM) analysis on normal and PE maternal plasma samples. Functional annotations of differentially expressed proteins (DEPs) in PE were predicted using bioinformatic tools. The diagnostic accuracies of the biomarkers for PE were estimated according to the area under the receiver-operating characteristics curve (AUC). A total of 1307 proteins were identified, and 870 proteins of them were quantified from plasma samples. Significant differences were evident in 138 DEPs, including 71 upregulated DEPs and 67 downregulated DEPs in the PE group, compared with those in the control group. Upregulated proteins were significantly associated with biological processes including platelet degranulation, proteolysis, lipoprotein metabolism, and cholesterol efflux. Biological processes including blood coagulation and acute-phase response were enriched for down-regulated proteins. Of these, 40 proteins were subsequently validated in an independent cohort of 26 PE patients and 29 healthy controls. APOM, LCN2, and QSOX1 showed high diagnostic accuracies for PE detection (AUC >0.9 and p < 0.001, for all) as validated by MRM and ELISA. Our data demonstrate that three plasma biomarkers, identified by systematic proteomic profiling, present a possibility for the assessment of PE, independent of the clinical characteristics of pregnant women.

The Association of Vitamin B-12 Plasma Concentration with Stroke Incidence According to Sex.

BACKGROUND: Previous studies reported that vitamin B-12 deficiency is associated with an increased risk of stroke. However, studies examining the association between excessive vitamin B-12 and stroke risk are limited. Our study aimed to investigate the relationship between excessive vitamin B-12 concentrations and risk of stroke and explore whether this association varies according to sex. METHODS: Utilizing the Korean Genome Epidemiology Study (KoGES) prospective cohort data, our primary exposure variables were vitamin B-12 plasma concentration and sex. The occurrence of stroke served as the main outcome of interest. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis. An interaction analysis was conducted to assess the interaction effect of vitamin B-12 and sex on stroke incidence. RESULTS: Cox proportional logistic regression analysis, adjusting for confounders, showed that excessive vitamin B-12 did not significantly alter stroke risk (HR: 1.22, 95% CI: 0.82, 1.71) and revealed no significant sex-based differences in stroke risk (HR: 0.90, 95% CI: 0.75, 1.04). However, interaction analysis indicated that excessive vitamin B-12 was linked to a significant increase in stroke risk in males (HR: 1.81, 95% CI: 1.10, 2.99) but not in females (HR: 1.04, 95% CI: 0.66, 1.60), with statistically significant interaction effect (P < 0.01). CONCLUSIONS: Our study demonstrated that although excessive vitamin B-12 alone does not significantly increase stroke risk, it increases risk in males when considering the interaction with sex.

Vitamin D deficiency as a risk factor for sudden cardiac arrest: A multicenter case-control study.

BACKGROUND AND AIMS: Vitamin D is known to influence the risk of cardiovascular disease, which is a recognized risk factor for sudden cardiac arrest (SCA). However, the relationship between vitamin D and SCA is not well understood. Therefore, this study aims to investigate the association between vitamin D and SCA in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls. METHODS AND RESULTS: Using the Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES II) registry, a 1:1 propensity score-matched case-control study was conducted between 2017 and 2020. Serum 25-hydroxyvitamin D (vitamin D) levels in patients with OHCA (454 cases) and healthy controls (454 cases) were compared after matching for age, sex, cardiovascular risk factors, and lifestyle behaviors. The mean vitamin D levels were 14.5 ± 7.6 and 21.3 ± 8.3 ng/mL among SCA cases and controls, respectively. Logistic regression analysis was used adjusting for cardiovascular risk factors, lifestyle behaviors, corrected serum calcium levels, and estimated glomerular filtration rate (eGRF). The adjusted odds ratio (aOR) for vitamin D was 0.89 (95% confidence interval [CI] 0.87-0.91). The dose-response relationship demonstrated that vitamin D deficiency was associated with SCA incidence (severe deficiency, aOR 10.87, 95% CI 4.82-24.54; moderate deficiency, aOR 2.24, 95% CI 1.20-4.20). CONCLUSION: Vitamin D deficiency was independently and strongly associated with an increased risk of SCA, irrespective of cardiovascular and lifestyle factors, corrected calcium levels, and eGFR.

Impact of snoring on the risk of stroke in patients with diabetes mellitus.

BACKGROUND: The impact of snoring and diabetes on stroke risk is unclear. This study examined the association between snoring and stroke risk and how it varies with diabetes mellitus (DM) status. METHODS: This research was conducted as a prospective cohort study. A total of 4,352 subjects were included in the analysis, with a mean follow-up time of 13.7 years. The study used snoring history obtained through interviews as the primary exposure variable and DM as the secondary exposure variable. The main outcome measured was the occurrence of stroke. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Additionally, a joint test was conducted to evaluate the combined effect of snoring and diabetes on the occurrence of stroke. RESULTS: In our study of 4,352 subjects, 1,135 (26.1%) had a history of snoring, 233 (5.4%) had diabetes mellitus, and over the 18-year observation period, there were 168 cases of new-onset stroke. Snoring was not associated with an increased risk of stroke (HR: 0.95, 95% CI [0.68-1.33]), but DM significantly elevated the risk of stroke (3.02 [1.96-4.65]). In the interaction analysis of snoring and DM status on stroke risk, snoring was a significant risk factor for stroke only in the population with DM (2.89 [1.07-7.60]). Compared to non-snoring and non-DM, the multivariate HRs for stroke were 1.09 (0.76-1.57) for snoring and non-DM, 1.64 (0.83-2.82) for non-snoring and DM, and 2.95 (1.42-5.45) for snoring and DM. CONCLUSION: Diabetes mellitus was associated with an increased risk of stroke, while a history of snoring was not. In a sub analysis, snoring appeared to be associated with an increased risk of stroke among subjects with diabetes mellitus.

Risk Factors of Postpartum Depression Among Korean Women: An Analysis Based on the Korean Pregnancy Outcome Study (KPOS).

BACKGROUND: Postpartum depression (PPD) can negatively affect infant well-being and child development. Although the frequency and risk factors of PPD symptoms might vary depending on the country and culture, there is limited research on these risk factors among Korean women. This study aimed to elucidate the potential risk factors of PPD throughout pregnancy to help improve PPD screening and prevention in Korean women. METHODS: The pregnant women at 12 gestational weeks (GW) were enrolled from two obstetric specialized hospitals from March 2013 to November 2017. A questionnaire survey was administered at 12 GW, 24 GW, 36 GW, and 4 weeks postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale, and PPD was defined as a score of ≥ 10. RESULTS: PPD was prevalent in 16.3% (410/2,512) of the participants. Depressive feeling at 12 GW and postpartum factors of stress, relationship with children, depressive feeling, fear, sadness, and neonatal intensive care unit admission of baby were significantly associated with a higher risk of PPD. Meanwhile, high postpartum quality of life and marital satisfaction at postpartum period were significantly associated with a lower risk of PPD. We developed a model for predicting PPD using factors as mentioned above and it had an area under the curve of 0.871. CONCLUSION: Depressive feeling at 12 GW and postpartum stress, fear, sadness, relationship with children, low quality of life, and low marital satisfaction increased the risk of PPD. A risk model that comprises significant factors can effectively predict PPD and can be helpful for its prevention and appropriate treatment.

Impact of Thermo-Responsive N-Acetylcysteine Hydrogel on Dermal Wound Healing and Oral Ulcer Regeneration.

This study investigates the efficacy of a thermo-responsive N-acetylcysteine (NAC) hydrogel on wound healing and oral ulcer recovery. Formulated by combining NAC with methylcellulose, the hydrogel's properties were assessed for temperature-induced gelation and cell viability using human fibroblast cells. In vivo experiments on Sprague Dawley rats compared the hydrogel's effects against saline, NAC solution, and a commercial NAC product. Results show that a 5% NAC and 1% methylcellulose solution exhibited optimal outcomes. While modest improvements in wound healing were observed, significant enhancements were noted in oral ulcer recovery, with histological analyses indicating fully regenerated mucosal tissue. The study concludes that modifying viscosity enhances NAC retention, facilitating tissue regeneration. These findings support previous research on the beneficial effects of antioxidant application on damaged tissues, suggesting the potential of NAC hydrogels in improving wound care and oral ulcer treatment.

Antiseptic, Hemostatic, and Wound Activity of Poly(vinylpyrrolidone)-Iodine Gel with Trimethyl Chitosan.

Wound management practices have made significant advancements, yet the search for improved antiseptics persists. In our pursuit of solutions that not only prevent infections but also address broader aspects of wound care, we investigated the impact of integrating trimethyl chitosan (TMC) into a widely used poly(vinylpyrrolidone)-iodine gel (PVP-I gel). Our study assessed the antimicrobial efficacy of the PVP gel with TMC against Escherichia coli, Staphylococcus aureus, multidrug-resistant S. aureus MRSA, and Candida albicans. Additionally, we compared hemostatic effects using a liver puncture bleeding model and evaluated wound healing through histological sections from full-thickness dermal wounds in rats. The results indicate that incorporating TMC into the commercially available PVP-I gel did not compromise its antimicrobial activity. The incorporation of TMC into the PVP-I gel markedly improves its hemostatic activity. The regular application of the PVP-I gel with TMC resulted in an increased blood vessel count in the wound bed and facilitated the development of thicker fibrous tissue with a regenerated epidermal layer. These findings suggest that TMC contributes not only to antimicrobial activity but also to the intricate processes of tissue regeneration. In conclusion, incorporating TMC proves beneficial, making it a valuable additive to commercially available antiseptic agents.

Characteristics and Outcomes of Traumatic Cardiac Arrests in the Pan-Asian Resuscitation Outcomes Study.

OBJECTIVE: Little is known about survival outcomes after traumatic cardiac arrest in Asia, or the association of Utstein factors with survival after traumatic cardiac arrests. This study aimed to describe the epidemiology and outcomes of traumatic cardiac arrests in Asia, and analyze Utstein factors associated with survival. METHODS: Traumatic cardiac arrest patients from 13 countries in the Pan-Asian Resuscitation Outcomes Study registry from 2009 to 2018 were analyzed. Multilevel logistic regression was performed to identify factors associated with the primary outcomes of survival to hospital discharge and favorable neurological outcome (Cerebral Performance Category (CPC) 1-2), and the secondary outcome of return of spontaneous circulation (ROSC). RESULTS: There were 207,455 out-of-hospital cardiac arrest cases, of which 13,631 (6.6%) were trauma patients aged 18 years and above with resuscitation attempted and who had survival outcomes reported. The median age was 57 years (interquartile range 39-73), 23.0% received bystander cardiopulmonary resuscitation (CPR), 1750 (12.8%) had ROSC, 461 (3.4%) survived to discharge, and 131 (1.0%) had CPC 1-2. Factors associated with higher rates of survival to discharge and favorable neurological outcome were arrests witnessed by emergency medical services or private ambulances (survival to discharge adjusted odds ratio (aOR) = 2.95, 95% confidence interval (CI) = 1.99-4.38; CPC 1-2 aOR = 2.57, 95% CI = 1.25-5.27), bystander CPR (survival to discharge aOR = 2.16; 95% CI 1.71-2.72; CPC 1-2 aOR = 4.98, 95% CI = 3.27-7.57), and initial shockable rhythm (survival to discharge aOR = 12.00; 95% CI = 6.80-21.17; CPC 1-2 aOR = 33.28, 95% CI = 11.39-97.23) or initial pulseless electrical activity (survival to discharge aOR = 3.98; 95% CI = 2.99-5.30; CPC 1-2 aOR = 5.67, 95% CI = 3.05-10.53) relative to asystole. CONCLUSIONS: In traumatic cardiac arrest, early aggressive resuscitation may not be futile and bystander CPR may improve outcomes.

Electrochemical lipolysis of subcutaneous adipose tissue in a porcine animal model.

OBJECTIVES: There is a considerable demand for noninvasive low-cost fat reduction methods with fewer side effects and shorter recovery times. This study aims to develop a fat-reduction method through electrochemical lipolysis of subcutaneous adipocytes using needle-based electrodes, body tissue fluids, and electrical current application. METHODS: Electrochemical lipolysis was performed by inserting a 4-pin needle electrode connected to a DC power supply into the pig's abdomen. Applied electrical current (0.5 and 1 mA) and treatment time (5 or 10 minutes) were varied systematically. Ultrasound imaging was performed before and after treatment to determine changes in fat thickness. Tissue samples were collected at 0, 2, and 4 weeks posttreatment for histological evaluation to determine the mechanism of action and the procedure's efficacy. RESULTS: Electrochemical subcutaneous adipose tissue lipolysis in a porcine model was achieved through hydrolysis of physiologic fluid within the vicinity of the inserted electrode where an electric current is applied, leading to localized disruption of fat cell membranes and necrosis. Electric current configuration 1.0 mA showed more pronounced lipolysis effects applied for 10 minutes, significantly decreasing adipocyte content per treatment area. The electrochemical treatment method also stimulates collagen synthesis, which helps reduce fat. CONCLUSIONS: Electrochemical lipolysis is a potential new noninvasive localized technique to reduce fat. The treatment method induces fat cell necrosis via in situ reduction-oxidation reaction by the electrochemical activation of physiologic fluid in the surrounding tissue. Electrochemical lipolysis is a simple, low-cost, fat-reducing treatment method without harmful side effects.

Association between post-cardiac arrest treatments and clinical outcomes according to scene time interval in out-of-hospital cardiac arrest: Retrospective cross-sectional study.

BACKGROUND: Previous studies have reported that Post-Cardiac arrest (PCA) treatments including targeted temperature management (TTM), coronary reperfusion therapy (CRT), and extracorporeal membrane oxygenation (ECMO) are time-sensitive; however, there are no reports of the clinical outcomes of PCA treatment according to the scene time interval (STI). Our study aimed to investigated the clinical outcomes of PCA treatment according to the STI. METHODS: We used a Korean nationwide OHCA cohort database from January 2017 to December 2020. The inclusion criteria were all adult OHCA patients with a presumed cardiac etiology, bystander-witnessed arrest, and prehospital return of spontaneous circulation (ROSC). The outcomes were survival to discharge and good neurological recovery. The main exposure of interest was PCA treatment. We compared the outcomes using multivariable logistic regression, and interaction terms were included in the final model to assess whether the STI modified the effect of PCA treatment on clinical outcomes of OHCA. RESULTS: TTM and CRT were associated with high survival to discharge and good neurological recovery. In the interaction analysis, ECMO had an interaction effect with the STI on a good CPC among patients with OHCA [short STI (0 to 11 min) (1.16 (0.77-1.75)), middle STI (12 to 15 min) (0.66 (0.41-1.06)), and long STI (16 to 30 min) (0.59 (0.40-0.88)) (p for interaction <0.05)]. CONCLUSION: In adult bystander-witnessed patients with OHCA with prehospital ROSC, an STI of >16 min was a risk factor for poor neurological outcome in those patients who underwent ECMO.

Chromosomal Abnormality, fetal/neonatal Death and Socioeconomic Status: A Prospective Cohort Study.

OBJECTIVES: To assess the risk gradient of chromosomal abnormalities and fetal or neonatal death across a socioeconomic spectrum of pregnant women. METHODS: We used the data from the Korean Prenatal Diagnosis Study (KPDS), which included singleton pregnancies who were candidates for fetal aneuploidy screening enrolled from the Seoul Capital Area from December 2016 to April 2018. We analyzed chromosomal abnormalities which were diagnosed pre- or postnatally, and fetal or neonatal death. The highest level of education among the women and the average monthly household income were used as proxies for socioeconomic status. RESULTS: Among the 6,715 women, the majority of were 30-39 years old and university graduates, with a reported household income higher than the national median. Chromosomal abnormalities occurred in 45 women (6.7 per 1,000). Fetal or neonatal death occurred in 70 (11.3 per 1,000), excluding pregnancies affected by chromosomal abnormality diagnosis. The adjusted odds ratio for chromosomal abnormalities was higher when household income was < 4,484 USD per month. For fetal or neonatal death, the risk estimates for lower education and lower household income were generally positive but remained imprecise. CONCLUSION: We observed some evidence of an inverse association between the risk of fetal chromosomal abnormality and level of household income in a prospective cohort of pregnant women. Interventions to reduce socioeconomic disparities in perinatal health should focus on those with a low household income.

The reverse shock index multiplied by Glasgow coma scale (rSIG) is predictive of mortality in trauma patients according to age.

OBJECTIVE: The role of reverse shock index multiplied Glasgow coma scale (rSIG) in patients post-trauma with traumatic brain injury (TBI) has not yet been defined well. Our study aimed to investigate the predictive performance of rSIG according to age group. METHOD: This is a prospective multi-national and multi-center cohort study using Pan-Asian Trauma Outcome Study registry in Asian-Pacific, conducted on patients post-trauma who visited participating hospitals. The main exposure was low rSIG measured at emergency department. The main outcome was in-hospital mortality. We performed multilevel logistic regression analysis to estimate the association low rSIG and study outcomes. Interaction analysis between rSIG and age group were also conducted. RESULTS: Low rSIG was significantly associated with an increase in in-hospital mortality in patients post-trauma with and without TBI (aOR (95% CI): 1.49 (1.04-2.13) and 1.71 (1.16-2.53), respectively). The ORs for in-hospital mortality differed according to the age group in patients post-trauma with TBI (1.72 (1.44-1.94) for the young group and 1.13 (1.07-1.52) for the old group; p < 0.05). CONCLUSION: Low rSIG is associated with an increase in in-hospital mortality in adult patients post-trauma. However, in patients with TBI, the prediction of mortality is significantly better in younger patient group.

The Effect of Vanishing Twin on First- and Second-Trimester Maternal Serum Markers and Nuchal Translucency: A Multicenter Prospective Cohort Study.

BACKGROUND: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). METHODS: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. RESULTS: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment, AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. CONCLUSION: VT can be considered as an adjustment factor for risk assessment in the second-trimester serum screening test.

The Neuroprotective Effects of Dendropanax morbifera Water Extract on Scopolamine-Induced Memory Impairment in Mice.

This study investigated the neuroprotective effects of Dendropanax morbifera leaves and stems (DMLS) water extract on scopolamine (SCO)-induced memory impairment in mice. First, we conducted experiments to determine the protective effect of DMLS on neuronal cells. Treatment with DMLS showed a significant protective effect against neurotoxicity induced by Aß(25-35) or H2O2. After confirming the neuroprotective effects of DMLS, we conducted animal studies. We administered DMLS orally at concentrations of 125, 250, and 375 mg/kg for 3 weeks. In the Y-maze test, SCO decreased spontaneous alternation, but treatment with DMLS or donepezil increased spontaneous alternation. In the Morris water-maze test, the SCO-treated group showed increased platform reach time and decreased swim time on the target platform. The passive avoidance task found that DMLS ingestion increased the recognition index in short-term memory. Furthermore, memory impairment induced by SCO reduced the ability to recognize novel objects. In the Novel Object Recognition test, recognition improved with DMLS or donepezil treatment. In the mouse brain, except for the cerebellum, acetylcholinesterase activity increased in the SCO group and decreased in the DMLS and donepezil groups. We measured catalase and malondialdehyde, which are indicators of antioxidant effectiveness, and found that oxidative stress increased with SCO but was mitigated by DMLS or donepezil treatment. Thus, our findings suggest that ingestion of DMLS restored memory impairment by protecting neuronal cells from Aß(25-35) or H2O2-induced neurotoxicity, and by reducing oxidative stress.

Impact of pre-pregnancy body mass index and gestational weight gain on the risk of maternal and infant pregnancy complications in Korean women.

BACKGROUND/OBJECTIVE: Healthy weight maintenance before and during pregnancy has a significant effect on pregnancy outcomes; however, there are no specific guidelines for gestational weight gain in pregnant Korean women. Therefore, we investigated the impact of pre-pregnancy body mass index (BMI) and gestational weight gain on the risk of maternal and infant pregnancy complications in pregnant Korean women. METHODS: Study participants comprised 3454 singleton pregnant women from the Korean Pregnancy Outcome Study who had baseline examination and pregnancy outcome data. Maternal pre-pregnancy BMI and gestational weight gain were categorized according to the Asia-pacific regional guidelines and the Institute of Medicine recommendations, respectively. The primary outcome was any adverse outcomes, defined as the presence of one or more of the following: hypertensive disorders of pregnancy, gestational diabetes mellitus, peripartum depressive symptom, cesarean delivery, delivery complications, preterm birth, small or large weight infant, neonatal intensive care unit admission, or a congenital anomaly. Multiple logistic regression models were applied to examine the independent and combined impact of pre-pregnancy BMI and gestational weight gain on the risk of maternal and infant outcomes. RESULTS: Obesity before pregnancy significantly increased the risk of perinatal adverse outcomes by more than 2.5 times [odds ratio (OR): 2.512, 95% confidence interval (CI): 1.817-3.473]. Compared to that in women with appropriate gestational weight gain, women with excessive weight gain had a 36.4% incremental increase in the risk of any adverse outcomes [OR: 1.364, 95% CI: 1.115-1.670]. Moreover, women who were overweight or obese before pregnancy and had excessive gestational weight gain had a three-fold increase in the risk of adverse outcomes [OR: 3.460, 95% CI: 2.210-5.417]. CONCLUSION: This study highlights the need for appropriate weight recommendations before and during pregnancy to prevent perinatal complications in Korean women of childbearing age.

Irradiation with 590-nm yellow light-emitting diode light attenuates oxidative stress and modulates UVB-induced change of dermal fibroblasts.

Recently, light-emitting diode (LED)-based devices have emerged as effective and safe tools for the treatment of photoaged skin. However, few studies have been conducted to elucidate the underlying mechanism behind the effect on photoageing of LED light. In this study, we induced photoageing of human dermal fibroblasts (HDFs) with Ultraviolet B (UVB) irradiation and evaluated the ability of 590-nm LED radiation to induce recovery from oxidative stress, restore collagen formation and regulate inflammatory changes. Photoageing was induced in cultured human dermal fibroblasts (HDFs) using UVB irradiation of 50 mJ/cm2 . Then, the photoaged HDFs were irradiated with LED using a custom-built 590-nm LED device which emits light with an intensity of 38 mW/cm2 (irradiated for 900 s with 34.2 J/cm2 of total energy). LED irradiation significantly attenuated UVB-induced reactive oxygen species generation and UVB-induced phosphorylation of JNK, c-Fos and c-Jun. In addition, the procollagen levels were recovered significantly, and MMP-9 levels were significantly suppressed after LED irradiation. The UVB-induced phosphorylation levels of NF-κB and pro-inflammatory enzyme COX-2 also significantly decreased. Our results suggest that 590-nm yellow light irradiation may be an effective and safe anti-oxidative and anti-inflammatory treatment modality for photoaged skin.

Cystatin C and mortality risk in the general population: systematic review and dose response meta-analysis.

INTRODUCTION: Cystatin C has been identified as an independent predictor of all-cause and cardiovascular mortality in the general population. This meta-analysis to evaluate the association between serum cystatin C level and all-cause and cardiovascular mortality. We additionally conducted a dose-response analysis to examine a linear association between cystatin C and cardiovascular mortality. METHODS: PudMed and Embase databases were searched until January, 2021. All prospective cohort studies that reported a multivariate-adjusted risk estimated of all-cause and cardiovascular mortality for the highest compared with lowest cystatin C level were included. RESULTS: 13 prospective cohort studies, a total of 57,214 participants were included in this analysis. Meta-analysis indicated that the highest compared with lowest cystatin C level was associated with an increase of all-cause mortality (hazard ratio [HR]: 2.01; 95% confidence intervals [CI]: 1.60-2.53; I2=89%) and cardiovascular mortality (2.62 [1.96-3.51]; I2=52%). We found a significant log-linear dose-response association between cystatin C and cardiovascular mortality (p < 0.01). Every 0.1 mg/L increase in cystatin C level was associated with a 7.3% increased cardiovascular mortality. CONCLUSIONS: Elevated serum cystatin C is associated with an increased risk of all-cause and cardiovascular mortality in the general populations. Particularly, cystatin C level and cardiovascular mortality showed linear correlation.

Maternal disease factors associated with neonatal jaundice: a case-control study.

BACKGROUND: Neonatal jaundice is common, and despite the considerable medical costs associated with it, there are still few studies on the maternal factors associated with it. Identification of maternal factors associated with neonatal jaundice is very important in terms of prevention, screening and management of neonatal jaundice. The current study aimed to identify maternal disease factors associated with neonatal jaundice. METHODS: We compared the maternal disease diagnostic codes during pregnancy (study A) and 1 year before conception (study B) in mothers whose insurance claims data included newborns treated for neonatal jaundice before birth registration via the National Health Insurance Service-National Sample Cohort (control group). To decrease the effect of confounding variables, the neonatal jaundice and control groups were matched at a ratio of 1:10 via propensity score matching using covariates including age and income. RESULTS: The matched samples for studies A and B included 4,026 and 3,278 (jaundice group: 366 and 298) delivery cases, respectively. In both studies, the jaundice group had a higher proportion of patients who underwent cesarean section than the control group. In study A, other diseases of the digestive system had the highest odds ratio (OR) (K92; adjusted OR: 14.12, 95% confidence interval [CI]: 2.70-82.26). Meanwhile, gastritis and duodenitis had the lowest OR (K29; adjusted OR: 0.39, 95% CI: 0.22-0.69). In study B, salpingitis and oophoritis had the highest OR (N70; adjusted OR: 3.33, 95% CI: 1.59-6.94). Heartburn had the lowest OR (R12; adjusted OR: 0.29, 95% CI:0.12-0.71). CONCLUSIONS: This study identified maternal disease factors correlated with neonatal jaundice during pregnancy and 1 year before conception. Maternal risk factors for neonatal jaundice included syphilis and leiomyoma during pregnancy, and salpingo-oophoritis before pregnancy. The protective factors included infection, inflammatory diseases, and dyspepsia.

Improved healing and macrophage polarization in oral ulcers treated with photobiomodulation (PBM).

OBJECTIVES: The effect of photobiomodulation (PBM) treatment on wound healing and macrophage polarization was investigated in vivo. Animal models of oral ulcers were simulated through chemically induced oral ulcers in rats. MATERIALS AND METHODS: PBM treatment using an infrared pulsed laser was used to treat oral ulcers in the animal models. Twelve Sprague-Dawley rats were randomly divided into four groups depending on set absorbed energy: Group 1 (control), Group 2 (30 J), Group 3 (60 J), and Group 4 (100 J). Laser treatment was performed every other day for 8 days after ulcer confirmation. Parameters used were as follows: wavelength 808 nm, power output 50 mW, spot size 10 mm, frequency 10 Hz, and pulse duration 1 millisecond. Ulcers were measured to determine the effect of the treatments over time. Histology, immunostaining, and real-time polymerase chain reaction analyses were performed to evaluate the effect of PBM treatment on macrophage-related (IL-6/IL-10) and wound-healing-related (TNF-α/TGF-ß/MMP-2) cytokine expression. RESULTS: Histological examinations indicate that the PBM treatment stimulated a higher level of wound recovery after 8 days of treatment at 60 J absorbed energy compared to other treatment groups. Analyses of relative gene expression of proinflammatory, anti-inflammatory, and tissue remodeling cytokines indicate that the macrophages in the tissue samples were predominantly characterized as M2 subtypes (alternatively activated), which possibly accounts for the accelerated tissue repair in the animal model of oral ulcer. CONCLUSION: This preliminary study stands as a proof of concept regarding the potential use of infrared laser PBM treatment for oral ulcers which have not been previously investigated upon. PBM treatment affects macrophage polarization and enhances wound healing. Further experimentation will be conducted to expand the understanding of how PBM treatment affects the healing mechanism of ulcers.