In Silico Investigation of AKT2 Gene and Protein Abnormalities Reveals Potential Association with Insulin Resistance and Type 2 Diabetes.

Type 2 diabetes (T2D) develops from insulin resistance (IR) and the dysfunction of pancreatic beta cells. The AKT2 protein is very important for the protein signaling pathway, and the non-synonymous SNP (nsSNPs) in AKT2 gene may be associated with T2D. nsSNPs can result in alterations in protein stability, enzymatic activity, or binding specificity. The objective of this study was to investigate the effect of nsSNPs on the AKT2 protein structure and function that may result in the induction of IR and T2D. The study identified 20 variants that were considered to be the most deleterious based on a range of analytical tools included (SIFT, PolyPhen2, Mut-pred, SNAP2, PANTHER, PhD-SNP, SNP&Go, MUpro, Cosurf, and I-Mut). Two mutations, p.A179T and p.L183Q, were selected for further investigation based on their location within the protein as determined by PyMol. The results indicated that mutations, p.A179T and p.L183Q alter the protein stability and functional characteristics, which could potentially affect its function. In order to conduct a more in-depth analysis of these effects, a molecular dynamics simulation was performed for wildtype AKT2 and the two mutants (p.A179T and p.L183Q). The simulation evaluated various parameters, including temperature, pressure, density, RMSD, RMSF, SASA, and Region, over a period of 100 ps. According to the simulation results, the wildtype AKT2 protein demonstrated higher stability in comparison to the mutant variants. The mutations p.A179T and p.L183Q were found to cause a reduction in both protein stability and functionality. These findings underscore the significance of the effects of nsSNPs (mutations p.A179T and p.L183Q) on the structure and function of AKT2 that may lead to IR and T2D. Nevertheless, they require further verifications in future protein functional, protein-protein interaction, and large-scale case-control studies. When verified, these results will help in the identification and stratification of individuals who are at risk of IR and T2D for the purpose of prevention and treatment.

Effect of prosthetic design and restorative material on the stress distribution of implant-supported 3-unit fixed partial dentures: 3D-FEA / Efeito do desenho protético e do material restaurador na distribuição de tensão de próteses parciais fixas de 3 elementos suportada por implante: FEA 3D

Objective: Evaluate the effect of Implant prosthetic designs and restorative material on the stress concentration of 3-unit implant-supported restoration with two restorative materials. Material and Methods: Six different screw-retained prostheses models were virtually designed and divided according to design: fixed bridge (FB), cantilever bridge (CB), and separate crowns (SC). Then, each model was also divided into two subgroups according to the material: Ultra-translucent multi-layered zirconia (Kuraray Noritake Dental Inc., Japan); or a combination of PEEK (Polyetheretherketone) framework (BioHPP, Bredent, GmbH & Co., KG, Germany) and zirconia (ZR) crowns (ultra-translucent multi-layered zirconia, Kuraray Noritake Dental Inc., Japan). A vertical load of 100 N was applied statically perpendicular to the central fossa of each crown. The von-Mises stress was computed using Solidworks software (SolidWorks Corp, Massachusetts, USA), based on the physical parameters of the materials. Results: FB showed the lowest von Mises stress values out of all 3 design models. Moreover, the combination of PEEK and zirconia showed strain values smaller than full zirconia. The highest von Mises stress value was recorded in CB with the zirconia subgroup at (1098 MPa) while the lowest von Mises stress value was recorded in FB with combined PEEK and zirconia subgroup at (190 MPa). Conclusion: For three-unit implant supported restorations, the use of PEEK framework and zirconia crowns was found to be more favorable biomechanically regarding the prosthetic components, implant and bone stresses. (AU)

Objetivo: Avaliar o efeito do desenho da prótese sobre implantes e do material restaurador na concentração de tensão de próteses fixas de 3 elementos implantossuportada, com dois materiais restauradores. Material e Métodos: Seis diferentes modelos de próteses aparafusadas foram virtualmente projetados e divididos de acordo com o desenho: ponte fixa (PF), ponte cantilever (PC) e coroas individuais (CI). Em seguida, cada modelo também foi dividido em dois subgrupos de acordo com o material: Zircônia multicamada ultra translúcida (Kuraray Noritake Dental Inc., Japão); ou associada a uma estrutura de PEEK (Polyetheretherketone) (BioHPP, Bredent, GmbH & Co., KG, Alemanha) e coroas de zircônia (CZ) (zircônia multicamada ultra translúcida, Kuraray Noritake Dental Inc., Japão). Uma carga vertical estática de 100 N foi aplicada perpendicular à fossa central de cada coroa. A tensão de von-Mises foi calculada usando o software Solidworks (SolidWorks Corp, Massachusetts, EUA), com base nos parâmetros físicos dos materiais. Resultados:PF apresentou os menores valores de tensão de von Mises de todos os 3 modelos propostos. Além disso, a combinação de PEEK e zircônia apresentou valores de deformação menores do que a zircônia pura. O maior valor de tensão de von Mises foi registrado em PC com o subgrupo de zircônia em (1098 MPa), enquanto o menor valor de tensão de von Mises foi registrado em PF com PEEK combinado e subgrupo de zircônia em (190 MPa). Conclusão: Para ponte fixa de 3 elementos implantossuportadas, o uso de estrutura PEEK e coroas de zircônia mostrou-se mais favorável biomecanicamente em relação aos componentes protéticos, implante e tensão sobre o osso. (AU)

Prosthetic design and restorative material effect on the biomechanical behavior of dental implants: strain gauge analysis / Efeito do desenho protético e do material restaurador no comportamento biomecânico de implantes dentários: análise de extensometria

Objective: The purpose of this in vitro study was to evaluate the effect of different implant prosthetic designs with two restorative materials on biomechanical behaviour using strain gauge analysis. Material and Methods:6 different screw-retained implant restorations were designed and fabricated using a CAD/CAM system. These implants were divided into three main groups according to each design: group FB (fixed bridge); CB (cantilever bridge); SC (separate crowns). Each group was divided into two subgroups according to their restorative material: subgroup I ­ ultra translucent multi-layered zirconia (Kuraray Noritake Dental Inc, Japan); subgroup II ­ a combination of PEEK framework (BioHPP, Bredent, GmbH & Co.KG, Germany) and zirconia crowns (ultra-translucent multi-layered zirconia, Kuraray Noritake Dental Inc, Japan). Each subgroup was subjected to a vertical load of 100 N and their biomechanical behaviour was evaluated using a strain gauge (Kyowa, Japan) with a resistance of 120 Ω, length of 1 mm and width of 2.4 mm. For the implants, two strain gauges were positioned buccally and lingually, parallel to the long axis of the implant. For the restoration, two strain gauges were positioned buccally and lingually in the middle of it. The results were analyzed using three-way analysis of variance (ANOVA), followed by serial two-way and one-way ANOVAs at each level of the study, followed by Tukey's post hoc test P-values were adjusted for multiple comparisons using BENFORRONI correction and the significance level was set at P ≤ 0.05 for all tests. Results: FB showed the lowest strain values out of all 3 design groups. Moreover, the combination of PEEK and zirconia showed strain values smaller than full zirconia. The highest mean strain value was recorded in CB at 299.50 while the lowest mean strain peak value was recorded in group FB (74.50). The highest strain peak was recorded in CB subgroup I (3901.0 ± 195.91) and the difference had statistical significance (P-value < 0.01). Conclusion: the fixed bridge designed with PEEK framework and zirconia crowns was found to be more favorable in restoring the posterior edentulous area regarding strain measurements on the level of prosthetic components, implant and bone level. (AU)

Objetivo: O objetivo deste estudo in vitro foi avaliar o comportamento biomecânico de diferentes desenhos protéticos com dois materiais restauradores em implantes dentários usando análise por extensometria. Material e Métodos: 6 diferentes restaurações parafusadas em implantes foram projetadas e fabricadas usando um sistema CAD/CAM. Esses implantes foram divididos em três grupos principais de acordo com cada desenho: grupo PF (ponte fixa); PC (ponte cantilever); CI (coroas individuais). Cada grupo foi dividido em dois subgrupos de acordo com o material restaurador: subgrupo I ­ zircônia multicamada ultra translúcida (Kuraray Noritake Dental Inc, Japão); subgrupo II ­ uma combinação de estrutura PEEK (BioHPP, Bredent, GmbH & Co.KG, Alemanha) e coroas de zircônia (zircônia multicamada ultra translúcida, Kuraray Noritake Dental Inc, Japão). Cada subgrupo foi submetido a uma carga vertical de 100 N e seu comportamento biomecânico foi avaliado usando um extensômetro (Kyowa, Japão) com resistência elétrica de 120 Ω, comprimento de 1 mm e largura de 2,4 mm. Para os implantes, dois extensômetros foram posicionados pela vestibular e lingual, paralelos ao longo eixo do implante. Para a restauração, dois extensômetros foram posicionados no centro da estrutura, pela vestibular e lingual. Os resultados foram analisados usando análise de variância de três fatores (ANOVA), seguida de ANOVA dois fatores e um fator em cada estágio do estudo, seguidas pelo teste de Tukey. Os valores P foram ajustados para comparações múltiplas usando a correção de BENFORRONI e o nível de significância foi estabelecido em P ≤ 0,05 para todos os testes. Resultados: PF apresentou os menores valores de deformação de todos os 3 grupos de desenho. Além disso, a combinação de PEEK e zircônia apresentou valores de deformação menores do que a zircônia total. O maior valor médio de deformação foi registrado no PC em 299,50, enquanto o menor valor médio de pico de deformação foi registrado no grupo PF (74,50). O maior pico de deformação foi registrado no subgrupo PC I (3901,0 ± 195,91) e a diferença teve significância estatística (P-valor < 0,01). Conclusão: a ponte fixa projetada com estrutura de PEEK e coroas de zircônia mostrou-se mais favorável na restauração da área edêntula posterior em relação às medidas de deformação dos componentes protéticos, implante e nível ósseo (AU)

Nogo-A regulates myogenesis via interacting with Filamin-C.

Among the three isoforms encoded by Rtn4, Nogo-A has been intensely investigated as a central nervous system inhibitor. Although Nogo-A expression is increased in muscles of patients with amyotrophic lateral sclerosis, its role in muscle homeostasis and regeneration is not well elucidated. In this study, we discovered a significant increase in Nogo-A expression in various muscle-related pathological conditions. Nogo-/- mice displayed dystrophic muscle structure, dysregulated muscle regeneration following injury, and altered gene expression involving lipid storage and muscle cell differentiation. We hypothesized that increased Nogo-A levels might regulate muscle regeneration. Differentiating myoblasts exhibited Nogo-A upregulation and silencing Nogo-A abrogated myoblast differentiation. Nogo-A interacted with filamin-C, suggesting a role for Nogo-A in cytoskeletal arrangement during myogenesis. In conclusion, Nogo-A maintains muscle homeostasis and integrity, and pathologically altered Nogo-A expression mediates muscle regeneration, suggesting Nogo-A as a novel target for the treatment of myopathies in clinical settings.

Minimally invasive prosthodontic correction of pseudo class III malocclusion by implementing a systematic digital workflow: A clinical report.

This clinical report describes the digital workflow for implementing different virtual and digital aids for the restoration of tooth wear and loss of occlusal vertical dimension (OVD). This conservative approach was implemented in an adult with pseudo class III malocclusion by using computer-aided design and computer-aided manufacturing (CAD-CAM) monolithic lithium disilicate ceramic restorations.

Computed Tomography and Magnetic Resonance Imaging of an Epidermoid Cyst in a Foot of a Horse.

An 18-year-old Quarter Horse mare was evaluated because of moderate left forelimb lameness of 4 weeks' duration. The clinical evaluation and diagnostic perineural analgesia localized the lameness to the distal portion of the left forelimb. There was swelling on the dorsal and lateral aspect of the coronary band. Radiography, ultrasound, magnetic resonance imaging, and computed tomography of the foot revealed circumscribed well-capsulated soft tissue mass causing a focal deformation of the dorsolateral border of the middle phalanx. The treatment aimed to remove the mass surgically and stabilized the interphalangeal joint, but the owner elected human euthanasia before treatment attempt. Histopathology diagnosis was an epidermoid cyst, which was characterized by multilayers of keratin surrounded by stratified squamous epithelium. Although rare, an epidermoid cyst should be considered as a differential diagnosis for space-occupying mass in horses' foot that develops chronic lameness after trauma. This report describes the multimodality appearance of the epidermoid cyst.

Sertoli Cell Tumor (SCT) in a Captive Black Bear (Ursus americanus).

A black bear of 29-year-old (Ursus americanus) died unexpectedly in captivity without any gross lesions or clinical signs. We identified a firm, lobulated, yellowish tan, and well-circumscribed mass embedded inside the testicular tissue at the time of necropsy. The tumor sections exhibited soft necrotic and hemorrhagic areas beneath its capsule. Histologically, the tumor comprised Sertoli cells arranged in tubules and solid sheets supported by prominent fibrous connective tissues. The Sertoli cells were positive for vimentin and ER-ß expression, whereas it showed negative staining for inhibin-α, cytokeratin 19, and S-100. To the best of our knowledge, this is the rare case report of testicular Sertoli cell tumor in black bear.

Establishment of stably expandable induced myogenic stem cells by four transcription factors.

Life-long regeneration of healthy muscle by cell transplantation is an ideal therapy for patients with degenerative muscle diseases. Yet, obtaining muscle stem cells from patients is very limited due to their exhaustion in disease condition. Thus, development of a method to obtain healthy myogenic stem cells is required. Here, we showed that the four transcription factors, Six1, Eya1, Esrrb, and Pax3, converts fibroblasts into induced myogenic stem cells (iMSCs). The iMSCs showed effective differentiation into multinucleated myotubes and also higher proliferation capacity than muscle derived stem cells both in vitro and in vivo. The iMSCs do not lose their proliferation capacity though the passaging number is increased. We further isolated CD106-negative and α7-integrin-positive iMSCs (sort-iMSCs) showing higher myogenic differentiation capacity than iMSCs. Moreover, genome-wide transcriptomic analysis of iMSCs and sort-iMSCs, followed by network analysis, revealed the genes and signaling pathways associated with enhanced proliferation and differentiation capacity of iMSCs and sort-iMSCs, respectively. The stably expandable iMSCs provide a new source for drug screening and muscle regenerative therapy for muscle wasting disease.

Papillomavirus Infection in Humans and Dromedary Camels in Eastern Sudan.

Cases of wart-like lesions in humans and dromedary camels occurred in eastern Sudan in 2015 were described. Involvement of papillomavirus (PV) in causing these cases was affirmed by PCR and immunoperoxidase test. Mostly, the lesions were observed on the skin of the chest and forearms in addition to lips and mandible. Sequence analysis revealed Camelus dromedarius PV types 1 and 2 genotypes as the causative genotypes. We also observed cases of wart-like lesions on hands and legs of two herders attending the infected camel herd. Partial genome sequencing revealed human PV type 2 in one of the two human samples providing no indications for interspecies transmission of camel PVs, yet provides, for the first time evidence of active circulation of this virus in eastern Sudan.

Preventive effect of anti-VacA egg yolk immunoglobulin (IgY) on Helicobacter pylori-infected mice.

BACKGROUND: Helicobacter pylori, a gram-negative bacterium, is the causative agent of gastric disorders and gastric cancer in the human stomach. Vacuolating cytotoxin A (VacA) is among the multi-effect protein toxins released by H. pylori that enables its persistence in the human stomach. METHODS: To evaluate the effect of anti-VacA egg yolk immunoglobulin (anti-VacA IgY) on H. pylori infection, a highly specific anti-VacA IgY was produced from egg yolks of hens immunized with a mixture of two purified recombinant VacAs. Female C57BL/6 mice were supplemented anti-VacA IgY daily with drinking water for 2 weeks before and 4 weeks after H. pylori ATCC 43504 inoculation. Anti-VacA IgY recognized both native and denatured structures of VacA by enzyme-linked immunosorbent assay and immunoblotting analyses, respectively. RESULTS: Oral administration of anti-VacA IgYs significantly (p < .05) reduced the serum levels of anti-H. pylori antibodies compared to those in the H. pylori-infected, untreated group. The reduction in the immune response was accompanied by a significant (p < .05) decrease in eosinophilic infiltration of the stomach in anti-VacA IgY treated group compared to other groups. Concomitantly, H. pylori-induced histological changes and H. pylori antigen-positivity in gastric tissues were decreased significantly (p < .05) in anti-VacA IgY treated group similar to the control group. CONCLUSIONS: Oral administration of anti-VacA IgY is correlated with a protective effect against H. pylori colonization and induced histological changes in gastric tissues. Our experimental study has proved that it is expected to be a new drug candidate of Hp infection by further study.

Preventive Effects of Vitamin C on Diethylnitrosamine-induced Hepatotoxicity in Smp30 Knockout Mice.

Vitamin C (L-ascorbic acid) is well known as a free radical scavenger that protects cells against damage from oxidative stress. Herein, we investigated the effects of vitamin C against diethylnitrosamine (DEN)-induced hepatotoxicity. Male wild-type (C57BL/6) and senescence marker protein-30 (Smp30) knockout (KO) mice were used and divided in the following four groups: WT group (n=15): Wild-type (WT) mice fed vitamin C-free diet with tap water; WV group (n=14): WT mice fed vitamin C-free diet with water supplemented with 1.5 g/kg vitamin C; KT group (n=12): Smp30 KO mice fed vitamin C-free diet with tap water; and KV group (n=13): Smp30 KO mice fed vitamin C-free diet with water supplemented with 1.5 g/kg vitamin C. A single intraperitoneal injection of DEN (5 mg/kg body weight) was injected in the second week during the experimental period. Mice were sacrificed after 17 weeks of treatment to investigate the effect of dietary vitamin C on DEN-induced hepatotoxicity. The results showed that vitamin C significantly increased the mean lifespan (p<0.05) in the WT, WV and KV groups compared with the KT group. The serum concentrations of γ-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase did not significantly differ among groups. The WT group exhibited significantly more acute cellular swelling accompanied by centrilobular necrosis, focal lymphocyte infiltration, and eosinophilic intracytoplasmic inclusion bodies as compared with the WV and KV groups, suggesting that vitamin C had a hepatoprotective effect. Dysplastic, large, and binucleated hepatocytes were also observed in the WT group, but these pathological signs were absent from the WV and KV groups. Our experimental evidence suggests that vitamin C supplementation in Smp30 KO mice was effective for the treatment of DEN-induced hepatotoxicity.

Inhibition of Formation of Azoxymethane-induced Colonic Aberrant Crypt Foci in Rats by Edible Green Algae Capsosiphon fulvescens and Brown Algae Hizikia fusiforme.

Capsosiphon fulvescens (green seaweed) and Hizikia fusiforme (brown seaweed) are marine algae consumed as food supplements, especially in Japan, China and Korea, and are considered traditional medicinal tonics for certain ailments. The aim of this study was to investigate the possible inhibitory effects of dietary C. fulvescens and H. fusiforme on azoxymethane (AOM)-induced colorectal cancer (CRC) in rats. F344 male rats (5 weeks, 150 g) were divided into six groups as follows. Group 1: Injected with normal saline solution and fed control diet (untreated control). Group 2: Injected with AOM and fed control diet (treated control). Group 3: Injected with AOM and fed 1% C. fulvescens diet. Group 4: Injected with AOM and fed 2% C. fulvescens diet. Group 5: Injected with AOM and fed 2% H. fusiforme diet. Group 6: Injected with AOM and fed 6% H. fusiforme diet. Test animals received subcutaneous injections of AOM (15 mg/1 ml/kg body weight) once a week for 2 weeks to induce aberrant crypt foci (ACF) in treated control and experimental groups. We evaluated the effects of dietary C. fulvescens and H. fusiforme at two different dose levels: 1 and 2% C. fulvescens, and 2 and 6% H. fusiforme, on colonic carcinogenesis by AOM in rats. Our results suggest that body weights were not significantly different amongst groups. We found that feeding C. fulvescens and H. fusiforme with a control diet significantly (p<0.05) inhibited the development of ACF in experimental groups. C. fulvescens and H. fusiforme in food also significantly (p<0.05) reduced the proliferating cell nuclear antigen labeling index in the colonic tissues of experimental groups. These results demonstrate the chemopreventive potential of C. fulvescens and H. fusiforme against CRC in an AOM-induced rats.

Effects of oral glucosamine hydrochloride and mucopolysaccharide protein in a rabbit model of osteoarthritis.

AIM: The aim was to study whether oral glucosamine hydrochloride (GlcN.HCl) or mucopolysaccharide protein (MucoP) has a structure-modifying effect on an anterior cruciate ligament transection (ACLT) rabbit model of osteoarthritis (OA). METHODS: OA was surgically induced in the right knees of rabbits by transection of the ACLT. The left knees served as a sham-operated control. The animals were divided into four groups (n = 6 each): negative control (phosphate buffered saline, orally), positive control (oral celecoxib 10 mg/kg body weight/day), GlcN.HCl (oral 100 mg/kg/day) and MucoP (oral 100 mg/kg/day). Experimental animals were sacrificed after 8 weeks of treatment and the distal femur was removed for macroscopic examination, histological assessment, and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay of the OA rabbits. RESULTS: On gross morphology, severe lesions were observed in articular cartilage in the negative control group. In the GlcN.HCl and MucoP treatment groups, fibrillations and cartilaginous lesions were significantly (P < 0.05) decreased compared to the negative control group. In particular, degenerative changes in cartilage and chondrocyte cellularity were significantly reduced (P < 0.05) in the positive control (celecoxib) group, GlcN.HCl treatment group and MucoP treatment group compared with the negative control group. TUNEL assay showed that apoptotic chondrocytes were significantly suppressed in the celecoxib group. Similar significant (P < 0.05) results were seen in the GlcN.HCl group and MucoP group but apoptosis of chondrocytes were high in the negative control group. CONCLUSION: These data suggest that the protective effects of GlcN.HCl and MucoP may play a useful role in the clinical treatment of OA.

Fatal fibrino-hemorrhagic bronchopneumonia associated with Morganella morganii in a bottlenose dolphin: a case report.

A 5 yr old, 184 kg, and 262 cm total length female bottlenose dolphin Tursiops truncatus was found dead in a display after bloody discharge from the blowhole was observed 3 h prior to death. Pathological examination revealed fibrinous bronchopneumonia with prominent areas of necrosis (sequestra) and numerous Gram-negative bacilli within alveoli and in blood vessels of the lungs and liver and between muscle fibers. The cause of death was attributed to septicemia. Often, cases of fibrinous bronchopneumonia are characterized by bacteremia in the latter stages of infection, resulting in the death of the animal. Septicemia likely accounts for the ecchymoses and petechiae noted on the spleen, pancreas, forestomach, lungs, visceral peritoneum, and small intestine. Additional lesions included hemothorax, stable red frothy fluid in the trachea, and lymphoid depletion in the spleen and lymph nodes. Pure growth of Morganella morganii was isolated from the lungs, blood, liver, and blowhole mucosa. Sequencing of 16s rRNA of the isolated bacteria showed more than 99.6% identity with M. morganii strain FDAARGOS_172. To our knowledge, this is the first report of fatal fibrinonecrotizing bronchopneumonia associated with M. morganii infection in a cetacean.

Melatonin ameliorates alcohol-induced bile acid synthesis by enhancing miR-497 expression.

Alcoholic liver disease is a major cause of chronic liver disease worldwide, and cannabinoid receptor type 1 (CB1R) is involved in a diverse metabolic diseases. B-cell translocation gene 2 (BTG2) and yin yang 1 (YY1) are a potent regulator of biological conditions. Melatonin plays a crucial role in regulating diverse physiological functions and metabolic homeostasis. MicroRNAs are key regulators of various biological processes. Herein, we demonstrate that melatonin improves bile acid synthesis in the liver of alcohol-fed mice by controlling miR-497 expression. The level of bile acid and the expression of Cb1r, Btg2, Yy1, and bile acid synthetic enzymes were significantly elevated in the livers of Lieber-DeCarli alcohol-fed mice. The overexpression of Btg2 enhanced Yy1 gene expression and bile acid production, whereas disrupting the CB1R-BTG2-YY1 cascade protected against the bile acid synthesis caused by alcohol challenge. We identified an alcohol-mediated YY1 binding site on the cholesterol 7α-hydroxylase (Cyp7a1) gene promoter using promoter deletion analysis and chromatin immunoprecipitation assays. Notably, melatonin attenuated the alcohol-stimulated induction of Btg2, Yy1 mRNA levels and bile acid production by promoting miR-497. Overexpression of a miR-497 mimic dramatically diminished the increase of Btg2 and Yy1 gene expression as well as bile acid production by alcohol, whereas this phenomenon was reversed by miR-497 inhibitor. These results demonstrate that the upregulation of miR-497 by melatonin represses alcohol-induced bile acid synthesis by attenuating the BTG2-YY1 signaling pathway. The melatonin-miR497 signaling network may provide novel therapeutic targets for the treatment of hepatic metabolic dysfunction caused by the alcohol-dependent pathway.