Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

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

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.

Although the biological causes of depression have been well established, the current use of antidepressants are still mostly based on the monoamine hypothesis of depression. However, monoamine antidepressants delay treatment of depression, and there is the problem of depressed patients who are resistant. Ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, is firstly introduced as an anesthetic. The hypothesis on the mechanism of ketamine as an antidepressant has been proposed through direct NMDAR inhibition, inhibition of γ-aminobutyric acid-ergic interneuron NMDARs and the role of ketamine metabolite (2R,6R)-hydroxynorcetamine (HNK). The ketamine also reverses the lack of synaptic connectivity and neurotrophic factors in depressed states by downstream mechanism of action. Through preclinical trials, there is a growing body of evidence indicating that ketamine has the potential for treatment of depression. In recent clinical studies, ketamine exhibits rapid-acting antidepressants effects and improvement of depression and even suicidality. This review examines current researches on molecular and cellular mechanisms of ketamine as an antidepressant, and reviews the current status of clinical studies, problems, and clinical applicability of ketamine.
Antidepressive Agents ; Depression ; Glutamic Acid ; Humans ; Interneurons ; Ketamine* ; N-Methylaspartate ; Nerve Growth Factors

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: Brain-derived neurotrophic factor (BDNF) has possible neurobiologic impact on etiology of schizophrenia. We hypothesized that the specific allele or the genotype such as two single nucleotide polymorphisms (SNPs) , 196G/A (rs6265), 11757G/C(rs16917204) is associated with schizophrenia or its clinical features. METHODS: 241 normal controls and 157 schizophrenia patients are included. The differences in allele or genotype distribution for the patients and normal controls were analyzed. We also analyzed clinical variables among patients. RESULTS: We found no significant difference in genotype or allele distributions of two studied SNPs between the patient group and the control group. However, history of suicide attempt was relatively higher in patients with genotype with A allele, compared to patients with genotype G/G for 196G/A (p-value=0.045). CONCLUSION: Our results suggest that it is possible to use BDNF gene allele and genotype as a predictor for suicide attempt in schizophrenia patients. It can help manage the schizophrenia patients regarding suicidal behavior and furthermore, mortality.
Alleles ; Brain-Derived Neurotrophic Factor* ; Genotype ; Humans ; Mortality ; Polymorphism, Single Nucleotide ; Schizophrenia* ; Suicide

Treatment-resistant depression (TRD) is a major public health problem. It is estimated that about 30% of patients with major depressive disorder do not show substantial clinical improvement to somatic or psychosocial treatment. Most of studies for TRD have focused on the subjects already known as TRD. Patients with unipolar depressive episodes that do not respond satisfactorily to numerous sequential treatment regimens were included in the TRD studies. Such post hoc experimental design can be regarded only as consequences of having TRD, rather than as causal risk factors for it. Although informative, data derived from such studies often do not allow a distinction to be made between cause and effect. So, we should shift paradigm toward examining the risk for developing TRD in untreated depressed patients. To deal with this problem, untreated depressed patients should be enrolled in the study to identify biological markers for treatment resistance. The peripheral or central biological markers should be explored before starting treatment. Subsequent systematic administration of treatments with appropriate monitoring in the subjects can determine the risk for developing treatment resistance in untreated individuals. Such information could give a cue to improve the initial diagnosis and provide more effective treatment for TRD.
Biomarkers ; Cues ; Depression ; Depressive Disorder, Major ; Depressive Disorder, Treatment-Resistant* ; Diagnosis ; Humans ; Neuroimaging ; Public Health ; Research Design ; Risk Factors

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