Citrus sudachi Peel Extract Suppresses Cell Proliferation and Promotes the Differentiation of Keratinocytes through Inhibition of the EGFR–ERK Signaling Pathway

Citrus sudachi is a well-known fruit in Tokushima Prefecture, Japan, and its peels are rich in phytochemicals, including phenolic compounds. Although it is expected that the extract of the C. sudachi peel elicits various beneficial physiological activities, the effect on the skin has not been investigated. In this study, we report that the aqueous extract from the peel of C. sudachi suppresses cell proliferation of the immortalized human keratinocyte cell line, HaCaT, and primary normal human epidermal keratinocytes. The extract of C. sudachi peel suppressed epidermal growth factor (EGF)-induced EGF receptor activation and tumor necrosis factor (TNF)-α-induced extracellular regulated kinase (ERK) 1/2 activation, which suggests that the extract exerts its inhibitory effect through inhibition of both the EGF receptor (EGFR) and its downstream molecules. Additionally, the extract of C. sudachi peel potentiated calcium-induced keratinocyte differentiation. These results suggest that the extract of C. sudachi peel may have beneficial effects against skin diseases that are characterized by hyperproliferation of epidermal keratinocytes, such as those seen in psoriasis and in cutaneous squamous cell carcinoma

Exploring the genetics of lithium response in bipolar disorders

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium’s possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response — defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10−12, R2 = 1.9%) and continuous (P = 6.4 × 10−9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22–5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10−4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment

Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study

\ua9 The Author(s) 2024.Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD

Type 2 diabetes – an autoinflammatory disease driven by metabolic stress

Type 2 diabetes has traditionally been viewed as a metabolic disorder characterised by chronic high glucose levels, insulin resistance, and declining insulin secretion from the pancreas. Modern lifestyle, with abundant nutrient supply and reduced physical activity, has resulted in dramatic increases in the rates of obesity-associated disease conditions, including diabetes. The associated excess of nutrients induces a state of systemic low-grade chronic inflammation that results from production and secretion of inflammatory mediators from the expanded pool of activated adipocytes. Here, we review the mechanisms by which obesity induces adipose tissue dysregulation, detailing the roles of adipose tissue secreted factors and their action upon other cells and tissues central to glucose homeostasis and type 2 diabetes. Furthermore, given the emerging importance of adipokines, cytokines and chemokines in disease progression, we suggest that type 2 diabetes should now be viewed as an autoinflammatory disease, albeit one that is driven by metabolic dysregulation

Concentration of anesthetic for long-term exposure and the effects of inter-suture distance in the goldfish Carassius auratus = Concentração de anestésico para exposição em longo prazo e efeitos da distância entre suturas em kinguyo Carassius auratus

This study aimed to determine the minimum concentration of 2-phenoxyethanol for long-term exposure and evaluate the effect of inter-suture distance on wound healing in the goldfish Carassius auratus. Twenty adult goldfish (standard length = 12.4 ± 1.1 cm; weight = 58.7 ± 17.2 g) were anesthetized in 2-phenoxiethanol at 1.2‰ and placed in an anesthesia delivery system at the following concentrations of 2-phenoxiethanol: 0.0 (control); 0.1; 0.2; 0.3 and 0.4‰, and the duration of sedation was measured. Fifteen dayslater, fishes were anesthetized using the same procedure, and a 36 mm incision was performed in the ventro-lateral region. The incision was sutured using a simple-interrupted pattern with 3, 6 or 9 mm as inter-suture distances. Results demonstrated that 2-phenoxiethanol at 0.4‰maintain the sedation for surgical procedures up to 60 minutes, and 9 mm as inter-suture distance optimized the wound healing in goldfish.Objetivou-se com o presente trabalho obter a concentração mínima de 2-phenoxyethanol para a exposição em longo prazo e avaliar o efeito da distância entre suturas (DES) no tempo de cicatrização de incisãoem kinguio Carassius auratus. Vinte kinguyos adultos (comprimento-padrão = 12,39 ± 1,1 cm; peso = 58,71 ± 17,24 g) foram anestesiados em 2-phenoxiethanol a 1,2‰ e então colocados em um sistema de recirculação de anestesia contendo 2-phenoxiethanol nasseguintes concentrações: 0,0 (controle); 0,1; 0,2; 0,3 e 0,4‰, e foi observada a duração da sedação. Quinze dias depois, os peixes foram novamente anestesiados, utilizando-se o mesmo procedimento, e então foi realizada uma incisão de 36 mm na região ventro-lateral.A incisão foi suturada utilizando-se o padrão interrompido-simples, em nylon, com distância entre suturas de 3, 6 e 9 mm. Os resultados demonstram que 0,4‰ 2- phenoxiethanol permite a manutenção do estado de sedação para procedimentos cirúrgicos acima de 60 min., e 9 mm como distância entre suturas otimiza a cicatrização em kinguyo

<b>Concentration of anesthetic for long-term exposure and the effects of inter-suture distance in the goldfish <em>Carassius auratus</em></b> - DOI: 10.4025/actascibiolsci.v31i2.802 <b>Concentration of anesthetic for long-term exposure and the effects of inter-suture distance in the goldfish <em>Carassius auratus</em></b> - DOI: 10.4025/actascibiolsci.v31i2.802

This study aimed to determine the minimum concentration of 2-phenoxyethanol for long-term exposure and evaluate the effect of inter-suture distance on wound healing in the goldfish <em>Carassius auratus</em>. Twenty adult goldfish (standard length = 12.4 ± 1.1 cm; weight = 58.7 ± 17.2 g) were anesthetized in 2-phenoxiethanol at 1.2‰ and placed in an anesthesia delivery system at the following concentrations of 2-phenoxiethanol: 0.0 (control); 0.1; 0.2; 0.3 and 0.4‰, and the duration of sedation was measured. Fifteen days later, fishes were anesthetized using the same procedure, and a 36 mm incision was performed in the ventro-lateral region. The incision was sutured using a simple-interrupted pattern with 3, 6 or 9 mm as inter-suture distances. Results demonstrated that 2-phenoxiethanol at 0.4‰ maintain the sedation for surgical procedures up to 60 minutes, and 9 mm as inter-suture distance optimized the wound healing in goldfish.<br>This study aimed to determine the minimum concentration of 2-phenoxyethanol for long-term exposure and evaluate the effect of inter-suture distance on wound healing in the goldfish <em>Carassius auratus</em>. Twenty adult goldfish (standard length = 12.4 ± 1.1 cm; weight = 58.7 ± 17.2 g) were anesthetized in 2-phenoxiethanol at 1.2‰ and placed in an anesthesia delivery system at the following concentrations of 2-phenoxiethanol: 0.0 (control); 0.1; 0.2; 0.3 and 0.4‰, and the duration of sedation was measured. Fifteen days later, fishes were anesthetized using the same procedure, and a 36 mm incision was performed in the ventro-lateral region. The incision was sutured using a simple-interrupted pattern with 3, 6 or 9 mm as inter-suture distances. Results demonstrated that 2-phenoxiethanol at 0.4‰ maintain the sedation for surgical procedures up to 60 minutes, and 9 mm as inter-suture distance optimized the wound healing in goldfish

Unraveling mating behavior for Axiidea (Crustacea: Decapoda): Burrow-dwelling callianassid shrimp in intertidal sandflat

Mating behaviors and mating systems in decapod crustaceans have attracted significant attentions. Dendrobranchiata and several infraorders of Pleocyemata (Caridea, Achelata, Astacidea, Anomura, and Brachyura) are the focal taxa. Virtually nothing is known about the members of Thalassinidea (recently separated into Axiidea including Callianassidae and Gebiidea including Upogebiidae) due to observational difficulties for their deep burrow-dwelling habit. Giving a little sediment and minute artificial tubes for one male and two females of the callianassid, Nihonotrypaea harmandi, in small transparent containers under illumination, observations and video-recordings of mating behaviors were made for the one pair three times, for the first time for Axiidea. The combined time schedule for each behavioral component was obtained. In inactive states, the shrimps stayed in their own burrows. The pre-mating visit was initiated by the male 3?4 d before the copulation, in which mutual signaling between sexes with movement of antennules, maxillipeds, chelipeds, and pleopods occurred. The final access was made by the hard-shelled female. The copulation lasted 91?105 s, with male onto female, during which a single spermatophore was transferred to sternite 8 surface with no sperm-storage structure. After the copulation, intimate exchanges occurred for 3?14 min. The female then isolated herself to an enclosed space for 60?74 min, during which oviposition started 44 min after the copulation, with embryo attachment to pleopods 1?2 completed in 12 min. The embryos were carried for 13?19 d before hatching. These findings would become basic to the understanding of thalassinidean shrimp population dynamics conducive to their key roles as benthic community organizers and ecosystem engineers in marine soft sediments