Background: Epidermal growth factor (EGF) is widely applied in dermatology for its regenerative effects; however, its clinical utility is limited by low stability and high production costs.To overcome these limitations, we developed a novel probiotic-derived epidermal growth factor (pEGF) by engineering Pediococcus pentosaceus CBT SL4 to express and secrete EGF. Objective: To investigate the anti-photoaging effects of topical pEGF in a ultraviolet B (UVB)-irradiated mice by assessing histological and molecular changes related to collagen synthesis, extracellular matrix (ECM) remodeling, oxidative stress, and inflammation. Methods: SKH1 hairless mice were exposed to UVB for twelve weeks to induce photoaging and treated with topical 10% pEGF cream from week 9 to 12. Skin samples were analyzed using dermoscopy, histology, immunohistochemistry, quantitative real-time polymerase chain reaction, western blotting, and proteomics to evaluate morphological and molecular alterations in ECM components and inflammatory markers. Results: Topical pEGF treatment improved skin texture and reduced wrinkles. Histological evaluation revealed that EGF significantly attenuated UVB-induced epidermal thickening and restored collagen density, with the strongest effects observed in the pEGF group. Molecular analysis showed downregulation of matrix metalloproteinases (MMPs; MMP-1, MMP-3), upregulation of collagen (type I collagen, type III collagen) and tissue inhibitors of metalloproteinases (TIMPs; TIMP-1, TIMP-2). Additionally, pEGF reduced pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β) and oxidative stress markers. Conclusion pEGF demonstrated potent anti-photoaging effects through ECM restoration, inflammation modulation, and barrier reinforcement. These findings support the therapeutic potential of pEGF as a stable, cost-effective alternative to conventional EGF in dermatological applications.

BACKGROUND AND OBJECTIVES: There is insufficient evidence regarding the optimal treatment for asymptomatic carotid stenosis. METHODS: Bayesian cross-design and network meta-analyses were performed to compare the safety and efficacy among carotid artery stenting (CAS), carotid endarterectomy (CEA), and medical treatment (MT). We identified 18 studies (4 randomized controlled trials [RCTs] and 14 nonrandomized, comparative studies [NRCSs]) comparing CAS with CEA, and 4 RCTs comparing CEA with MT from MEDLINE, Cochrane Library, and Embase databases. RESULTS: The risk for periprocedural stroke tended to increase in CAS, compared to CEA (odds ratio [OR], 1.86; 95% credible interval [CrI], 0.62–4.54). However, estimates for periprocedural myocardial infarction (MI) were quite heterogeneous in RCTs and NRCSs. Despite a trend of decreased risk with CAS in RCTs (OR, 0.70; 95% CrI, 0.27–1.24), the risk was similar in NRCSs (OR, 1.02; 95% CrI, 0.87–1.18). In indirect comparisons of MT and CAS, MT showed a tendency to have a higher risk for the composite of periprocedural death, stroke, MI, or nonperiprocedural ipsilateral stroke (OR, 1.30; 95% CrI, 0.74–2.73). Analyses of study characteristics showed that CEA-versus-MT studies took place about 10-year earlier than CEA-versus-CAS studies. CONCLUSIONS A similar risk for periprocedural MI between CEA and CAS in NRCSs suggested that concerns about periprocedural MI accompanied by CEA might not matter in real-world practice when preoperative evaluation and management are working. Maybe the benefits of CAS over MT have been overestimated considering advances in medical therapy within10-year gap between CEA-versus-MT and CEA-versus-CAS studies.

BACKGROUND AND OBJECTIVES: There is insufficient evidence regarding the optimal treatment for asymptomatic carotid stenosis.METHODS: Bayesian cross-design and network meta-analyses were performed to compare the safety and efficacy among carotid artery stenting (CAS), carotid endarterectomy (CEA), and medical treatment (MT). We identified 18 studies (4 randomized controlled trials [RCTs] and 14 nonrandomized, comparative studies [NRCSs]) comparing CAS with CEA, and 4 RCTs comparing CEA with MT from MEDLINE, Cochrane Library, and Embase databases.RESULTS: The risk for periprocedural stroke tended to increase in CAS, compared to CEA (odds ratio [OR], 1.86; 95% credible interval [CrI], 0.62–4.54). However, estimates for periprocedural myocardial infarction (MI) were quite heterogeneous in RCTs and NRCSs. Despite a trend of decreased risk with CAS in RCTs (OR, 0.70; 95% CrI, 0.27–1.24), the risk was similar in NRCSs (OR, 1.02; 95% CrI, 0.87–1.18). In indirect comparisons of MT and CAS, MT showed a tendency to have a higher risk for the composite of periprocedural death, stroke, MI, or nonperiprocedural ipsilateral stroke (OR, 1.30; 95% CrI, 0.74–2.73). Analyses of study characteristics showed that CEA-versus-MT studies took place about 10-year earlier than CEA-versus-CAS studies.CONCLUSIONS: A similar risk for periprocedural MI between CEA and CAS in NRCSs suggested that concerns about periprocedural MI accompanied by CEA might not matter in real-world practice when preoperative evaluation and management are working. Maybe the benefits of CAS over MT have been overestimated considering advances in medical therapy within10-year gap between CEA-versus-MT and CEA-versus-CAS studies.
Carotid Arteries ; Carotid Stenosis ; Endarterectomy, Carotid ; Myocardial Infarction ; Stents ; Stroke

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that delivers 1–2 mA of current to the scalp. Several clinical studies have been conducted to confirm the therapeutic effect of major depressive disorder (MDD) patients with tDCS. Some studies have shown tDCS's antidepressant effect, while the others showed conflicting results in antidepressant effects. Our aim of this review is to understand the biological bases of tDCS's antidepressant effect and review the results of studies on tDCS's antidepressant effect. For the review and search process of MDD treatment using tDCS, the US National Library of Medicine search engine PubMed was used. In this review, we discuss the biological mechanism of tDCS's antidepressant effect and the existing published literature including meta-analysis, systematic review, control trial, open studies, and case reports of antidepressant effects and cognitive function improvement in patients with MDD are reviewed. We also discuss the appropriate tDCS protocol for MDD patients, factors predictive of response to tDCS treatment, the disadvantages of tDCS in MDD treatment, and side effects.
Brain ; Cognition ; Depressive Disorder, Major* ; Humans ; Methods ; National Library of Medicine (U.S.) ; Scalp ; Search Engine ; Transcranial Direct Current Stimulation*

OBJECTIVE: Panic disorder (PD) is a common psychiatric disorder with a complex etiology, and several studies have suggested that it has a genetic component. Brain-derived neurotrophic factor (BDNF) is the most abundant of the neurotrophins in the brain and is recognized for its important role in the survival, differentiation and growth of neurons. Several lines of research have suggested possible associations between the BDNF gene and PD. In this study, we investigated the BDNF 196G/A (rs6265), 11757G/C (rs16917204), and 270C/T (rs56164415) single nucleotide polymorphisms (SNPs) in order to determine an association with PD. We also identified the genetic sequence associations with PD via haplotype analysis. METHODS: Participants in this study included 136 PD patients and 263 healthy controls. Male and female subjects were analyzed separately. The genotype and allele frequencies of the PD patients and controls were analyzed using chi2 statistics. Frequencies and haplotype reconstructions were calculated using the SNP analyzer 2.0. RESULTS: We found no significant statistical differences in the genotype distributions or allele frequencies of the three tested polymorphisms between the PD and control groups. In addition, no differences were found between PD patients and the controls in either male or female subgroups. However, we found that, the frequency of the G-C haplotype for 196G/A and 11757G/C was significantly higher in PD patients than in the controls. CONCLUSION: Our result suggest that patients with the G-C haplotype for 196G/A and 11757G/C may be more susceptible to the development of PD. Further studies are needed to replicate the associations that we observed.
Brain ; Brain-Derived Neurotrophic Factor* ; Female ; Gene Frequency ; Genotype ; Haplotypes* ; Humans ; Male ; Nerve Growth Factors ; Neurons ; Panic Disorder* ; Polymorphism, Single Nucleotide

OBJECTIVE: We aimed to investigate possible associations between three norepinephrine transporter gene (SLC6A2) single nucleotide polymorphisms (T182C, A3081T, and G1287A) and schizophrenia. Also, we investigated the relationships of those polymorphisms with clinical severity and characteristics of schizophrenia. METHODS: Participants were 220 schizophrenia patients in the acute phase and 167 healthy controls. The genotype, allele frequency, and haplotype of each group were analyzed for T182C, A3081T, and G1287A polymorphisms. Of the 220 schizophrenia patients, 163 patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Korean version of the Calgary depression scale for schizophrenia (K-CDSS) at baseline. RESULTS: We found no significant differences between the schizophrenia patient group and the control group in genotype distribution or allele frequency of the three tested polymorphisms. Likewise, we could not find any significant differences in genotype or allele frequency by analyzing according to gender. In the haplotype study, no significant association emerged between specific haplotype combinations and schizophrenia. We also found no association between clinical scales (PANSS and K-CDSS) and the studied polymorphisms. CONCLUSION: Our results suggest that the investigated polymorphisms of the NET gene are not associated with susceptibility to schizophrenia or its clinical features in a Korean population. However, this study remains significant because it is the first haplotype study to investigate associations between NET gene (SLC6A2) single nucleotide polymorphisms and schizophrenia in a Korean population. Future research with a larger sample size and more genetic markers is needed to replicate our results.
Gene Frequency ; Genetic Markers ; Genotype ; Haplotypes ; Humans ; Norepinephrine Plasma Membrane Transport Proteins* ; Norepinephrine* ; Polymorphism, Single Nucleotide ; Sample Size ; Schizophrenia* ; Weights and Measures

OBJECTIVE: Cytokines are believed to have a role in the pathophysiology of major depression. The alteration in levels of pro-inflammatory cytokines [interleukin 1beta (IL-1beta), IL-2, IL-6, IL-12, interferon gamma, and tumor necrosis factor alpha] in major depression supports the cytokine hypothesis of this illness. IL-23 and IL-17 are also pro-inflammatory cytokines, but few studies have focused on their role in major depression. This study investigated the potential role of the IL-23 and IL-17 axis in major depression. METHODS: Plasma IL-23 and IL-17 levels were measured in 26 major depressive disorder (MDD) patients before and after 6-week treatment with antidepressants; these levels were measured in 28 age- and sex-matched normal controls. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS). IL-23 and IL-17 plasma levels were estimated using quantitative enzyme-linked immunosorbent assay. RESULTS: Pre-treatment plasma levels of IL-23 and IL-17 in MDD patients were not significantly different from those of normal controls. In MDD patients, IL-23 and IL-17 levels after 6 weeks of antidepressant treatment were not different from the baseline levels. There was no significant correlation between changes in the cytokine levels and changes in the HDRS scores representing the severity of depression. CONCLUSION: The present study does not support a potential involvement of IL-23 and IL-17 axis in major depression. Replication and extension using a larger sample are required.
Antidepressive Agents ; Cytokines ; Depression ; Depressive Disorder, Major* ; Humans ; Interleukin-17* ; Interleukin-23* ; Th17 Cells

Neurotrophic factors are critical regulators of the formation and plasticity of neuronal networks. Brain-derived neurotrophic factor (BDNF) is abundant in the brain and periphery, and is found in both human serum and plasma. Animal studies have demonstrated that stress reduces BDNF expression or activity in the hippocampus and that this reduction can be prevented by treatment with antidepressant drugs. A similar change in BDNF activity occurs in the brain of patients with major depression disorder (MDD). Recently, clinical studies have indicated that serum or plasma BDNF levels are decreased in untreated MDD patients. Antidepressant treatment for at least four weeks can restore the decreased BDNF function up to the normal value. Therefore, MDD is associated with impaired neuronal plasticity. Suicidal behavior can be a consequence of severe impaired neuronal plasticity in the brain. Antidepressant treatment promotes increased BDNF activity as well as several forms of neuronal plasticity, including neurogenesis, synaptogenesis and neuronal maturation. BDNF could also play an important role in the modulation of neuronal networks. Such a neuronal plastic change can positively influence mood or recover depressed mood. These alterations of BDNF levels or neuronal plasticity in MDD patients before and after antidepressant treatment can be measured through the examination of serum or plasma BDNF concentrations. BDNF levels can therefore be useful markers for clinical response or improvement of depressive symptoms, but they are not diagnostic markers of major depression.
Animals ; Antidepressive Agents ; Brain ; Brain-Derived Neurotrophic Factor ; Depression ; Hippocampus ; Humans ; Nerve Growth Factors ; Neurogenesis ; Neuronal Plasticity ; Neurons ; Plasma ; Plastics ; Reference Values

OBJECTIVE: Serotonergic dysfunction is quite evident in panic disorder. We investigated whether the C(-1019)G polymorphism of 5-HT1A receptor gene may play a role in the pathogenesis of panic disorder in a Korean population. METHODS: The 5-HT1A receptor genotype for the single nucleotide polymorphism (SNP) C(-1019)G was analyzed in 94 patients and 111 healthy controls. The severity of the patients' symptoms was examined using the Spielberger State-Trait Anxiety Inventory (STAI), Panic Disorder Severity Scale (PDSS), Anxiety sensitivity index (ASI), Acute Panic Inventory (API) and Hamilton's Rating Scale for Anxiety (HAM-A). RESULTS: The distribution of the genotypes of the C/G polymorphism did not differ significantly from those predicted by Hardy-Weinberg equilibrium in patients as well as the controls. No association between the C(-1019)G polymorphism and panic disorder was detected in either the allele frequency or genotype distribution. There was no significant association with genotype distribution in the panic disorder with agoraphobia. However, there was a significant difference of symptom severity between C/C, C/G, and G/G genotype or between C and G allele in panic disorder patients without agoraphobia. PDSS scores were significantly higher in subjects with the G/G genotype or with G allele in patients without agoraphobia, not in total patients or patients with agoraphobia. CONCLUSION: Although there were no significant differences in the genotype and allele distributions, we found a significant association between panic symptom severity and the serotonin 1A receptor gene. This result suggests that the serotonin 1A receptor and serotonin may play a role in the pathogenesis of panic disorder.
Agoraphobia ; Alleles ; Anxiety ; Gene Frequency ; Genotype ; Humans ; Panic ; Panic Disorder ; Polymorphism, Single Nucleotide ; Receptor, Serotonin, 5-HT1A ; Serotonin

Brain-derived neurotrophic factor (BDNF) is an important member of the neurotrophic factors, which are critical regulators of the formation and plasticity of neuronal networks. BDNF is abundant in the brain and periphery and it is found in both human serum and plasma. Stressed animals and depressed patients show reduced BDNF expression in the hippocampus and this reduction can be prevented by antidepressant drug treatment. Recent several clinical studies have indicated the decreases of serum or plasma BDNF levels in untreated patients with major depression. These decreases of BDNF can recover after antidepressant treatment. Increasing BDNF after antidepressant treatment could result from improving depressive symptoms, not just from antidepressant treatment. BDNF can play a critical role in the action mechanism of antidepressant treatment. Taken together, major depression may be considered a dysfunction of critical neuronal networks, and the gradual network recovery may induce antidepressant effect. Serum or plasma BDNF levels could indirectly show the above processes of major depression.
Animals ; Brain ; Brain-Derived Neurotrophic Factor ; Depression ; Hippocampus ; Humans ; Nerve Growth Factors ; Neurons ; Plasma ; Plastics