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1.
Front Pediatr ; 12: 1165492, 2024.
Article in English | MEDLINE | ID: mdl-38415210

ABSTRACT

Background: Pathogenic variants in the IGHMBP2 gene are associated with two distinct autosomal recessive neuromuscular disorders: spinal muscular atrophy with respiratory distress type 1 (SMARD1; OMIM #604320) and Charcot-Marie-Tooth type 2S (CMT2S; OMIM #616155). SMARD1 is a severe and fatal condition characterized by infantile-onset respiratory distress, diaphragmatic palsy, and distal muscular weakness, while CMT2S follows a milder clinical course, with slowly progressive distal muscle weakness and sensory loss, without manifestations of respiratory disorder. Methods: Whole-exome sequencing of the IGHMBP2 gene was performed for eight Vietnamese patients with IGHMBP2-related neuromuscular disorders including five patients with SMARD1 and the others with CMT2S. Results: We identified one novel IGHMBP2 variant c.1574T > C (p.Leu525Pro) in a SMARD1 patient. Besides that, two patients shared the same pathogenic variants (c.1235 + 3A > G/c.1334A > C) but presented completely different clinical courses: one with SMARD1 who deceased at 8 months of age, the other with CMT2S was alive at 3 years old without any respiratory distress. Conclusion: This study is the first to report IGHMBP-2-related neuromuscular disorders in Vietnam. A novel IGHMBP2 variant c.1574T > C (p.Leu525Pro) expressing SMARD1 phenotype was detected. The presence of three patients with the same genotype but distinct clinical outcomes suggested the interaction of variants and other factors including relating modified genes in the mechanism of various phenotypes.

2.
Ann Ig ; 36(3): 335-352, 2024.
Article in English | MEDLINE | ID: mdl-38085560

ABSTRACT

Background: Vaccination plays a central role in protecting children against severe diseases and preventing child mortality. Objectives: This study aimed to determine the rate and factors associated with complete and timely vaccination in 2-year-old children, as well as maternal knowledge on expanded vaccination in Go Cong Tay district, Tien Giang province, Vietnam. Methods: A cross-sectional descriptive study was conducted on 558 2-year-old children and their mothers residing in Go Cong Tay district, Tien Giang province, Vietnam. The study employed a systematic random sampling method from June to September 2021. Results: The rate of complete vaccination in children was 74.7%. Factors associated with the rate of complete vaccination were occupation (OR=0.3; 95%CI: 0.1-0.7; p=0.006), economic status (OR=3.8; 95%CI: 1.7-8.6; p=0.001), and maternal general knowledge on expanded vaccination (OR=1.7; 95%CI: 1.1-2.6; p=0.01). The rate of timely vaccination was 47.8%. Factors associated with the rate of timely vaccination were maternal age group (OR=3.1; 95%CI: 1.6-6.0; p=0.001; OR=3.0; 95%CI: 1.3-6.6; p=0.006) and economic status (OR=0.4; 95%CI: 0.2-0.9; p=0.04). The rate of both complete and timely vaccination was 22.6%. Factors associated with the rate of complete and timely vaccination were maternal age group (OR=3.1; 95%CI: 1.3-7.2; p=0.009; OR=3.3; 95%CI: 1.2-9.1; p=0.02) and maternal general knowledge on expanded vaccination (OR=1.5; 95%CI: 1.0-2.4; p=0.03). The rate of maternal general knowledge on expanded vaccination was 57.5%. Conclusion: The rates of complete and timely vaccination are still low, and various factors influence expanded vaccination. The-refore, it is crucial to continue health education campaigns to improve knowledge on expanded vaccination, remind mothers of vaccination schedules, strengthen confidence in vaccination programs and vaccine safety, attract customers to vaccination services, provide adequate healthcare for children, and ensure vaccination activities during disease outbreaks.

3.
Cells ; 12(21)2023 10 25.
Article in English | MEDLINE | ID: mdl-37947600

ABSTRACT

Maintenance of skeletal muscle quantity and quality is essential to ensure various vital functions of the body. Muscle homeostasis is regulated by multiple cytoskeletal proteins and myogenic transcriptional programs responding to endogenous and exogenous signals influencing cell structure and function. Since actin is an essential component in cytoskeleton dynamics, actin-binding proteins (ABPs) have been recognized as crucial players in skeletal muscle health and diseases. Hence, dysregulation of ABPs leads to muscle atrophy characterized by loss of mass, strength, quality, and capacity for regeneration. This comprehensive review summarizes the recent studies that have unveiled the role of ABPs in actin cytoskeletal dynamics, with a particular focus on skeletal myogenesis and diseases. This provides insight into the molecular mechanisms that regulate skeletal myogenesis via ABPs as well as research avenues to identify potential therapeutic targets. Moreover, this review explores the implications of non-coding RNAs (ncRNAs) targeting ABPs in skeletal myogenesis and disorders based on recent achievements in ncRNA research. The studies presented here will enhance our understanding of the functional significance of ABPs and mechanotransduction-derived myogenic regulatory mechanisms. Furthermore, revealing how ncRNAs regulate ABPs will allow diverse therapeutic approaches for skeletal muscle disorders to be developed.


Subject(s)
Actins , Microfilament Proteins , Microfilament Proteins/metabolism , Actins/metabolism , Mechanotransduction, Cellular , Muscle, Skeletal/metabolism , RNA, Untranslated/metabolism , Muscle Development/genetics
4.
Microbiol Resour Announc ; 12(12): e0070623, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-37933965

ABSTRACT

Here, we present the whole-genome sequence of Streptomyces strain VNUA116 was obtained by combining sequencing data from both PacBio RS II and DNBseq platforms. The complete circular genome is 8,306,919 bp with a GC content of 72.49%.

5.
Sci Rep ; 13(1): 14789, 2023 09 08.
Article in English | MEDLINE | ID: mdl-37684332

ABSTRACT

Influenza virus is a main cause of acute respiratory tract infections (ARTIs) in children. This is the first double-blind, randomized, and controlled clinical trial examining the efficacy of nasal-spraying probiotic LiveSpo Navax, which contains 5 billion of Bacillus subtilis and B. clausii spores in 5 mL, in supporting treatment of influenza viral infection in pediatric patients. We found that the nasal-spraying Bacillus spores significantly shortened the recovery period and overall treatment by 2 days and increased treatment effectiveness by 58% in resolving all ARTIs' symptoms. At day 2, the concentrations of influenza virus and co-infected bacteria were reduced by 417 and 1152 folds. Additionally, the levels of pro-inflammatory cytokines IL-8, TNF-α, and IL-6 in nasopharyngeal samples were reduced by 1.1, 3.7, and 53.9 folds, respectively. Compared to the standard control group, treatment regimen with LiveSpo Navax demonstrated significantly greater effectiveness, resulting in 26-fold reduction in viral load, 65-fold reduction in bacterial concentration, and 1.1-9.5-fold decrease in cytokine levels. Overall, nasal-spraying Bacillus spores can support the symptomatic treatment of influenza virus-induced ARTIs quickly, efficiently and could be used as a cost-effective supportive treatment for respiratory viral infection in general.Clinical trial registration no: NCT05378022 on 17/05/2022.


Subject(s)
Bacillus , Communicable Diseases , Influenza, Human , Orthomyxoviridae Infections , Orthomyxoviridae , Probiotics , Respiratory Tract Infections , Humans , Child , Animals , Influenza, Human/therapy , Viral Load , Spores, Bacterial , Respiratory Tract Infections/therapy , Cytokines , Nasal Sprays , Neoptera , Probiotics/therapeutic use
6.
Int J Mol Sci ; 24(18)2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37762638

ABSTRACT

The dynamic rearrangement of the actin cytoskeleton plays an essential role in myogenesis, which is regulated by diverse mechanisms, such as mechanotransduction, modulation of the Hippo signaling pathway, control of cell proliferation, and the influence of morphological changes. Despite the recognized importance of actin-binding protein Flightless-1 (FLII) during actin remodeling, the role played by FLII in the differentiation of myogenic progenitor cells has not been explored. Here, we investigated the roles of FLII in the proliferation and differentiation of myoblasts. FLII was found to be enriched in C2C12 myoblasts, and its expression was stable during the early stages of differentiation but down-regulated in fully differentiated myotubes. Knockdown of FLII in C2C12 myoblasts resulted in filamentous actin (F-actin) accumulation and inhibited Yes-associated protein 1 (YAP1) phosphorylation, which triggers its nuclear translocation from the cytoplasm. Consequently, the expressions of YAP1 target genes, including PCNA, CCNB1, and CCND1, were induced, and the cell cycle and proliferation of myoblasts were promoted. Moreover, FLII knockdown significantly inhibited the expression of myogenic regulatory factors, i.e., MyoD and MyoG, thereby impairing myoblast differentiation, fusion, and myotube formation. Thus, our findings demonstrate that FLII is crucial for the differentiation of myoblasts via modulation of the F-actin/YAP1 axis and suggest that FLII is a putative novel therapeutic target for muscle wasting.


Subject(s)
Actins , Mechanotransduction, Cellular , Genes, cdc , Stem Cells , Adaptor Proteins, Signal Transducing/genetics , Cell Differentiation/genetics
7.
Foods ; 12(13)2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37444243

ABSTRACT

Food choices that shape human diets and health are influenced by various socio-economic factors. Vietnam struggles to meet many nutrition targets where links between food choice and diet have not been widely explored. This study assesses the food choice motives, based on a 28-item food choice questionnaire (FCQ), and the diet quality of 603 adults in three sites (urban, peri-urban, and rural) in northern Vietnam. We assess diet quality using the Diet Quality Index-Vietnam (DQI-V) which consists of variety, adequacy, moderation, and balance components. Using factor analysis, we grouped FCQ items into five factors: health focus, sensory appeal, mood ethics, convenience, and familiarity. The structural equation modeling indicates that food choice motives significantly impact the DQI-V and its components but in different directions. The results show that sensory appeal has a positive association with the overall DQI-V score, while having a negative impact on the variety component. Findings present a potential trade-off issue for interventions and policies related to food products. Nutrition knowledge is positively associated with all elements of diet quality across all three study sites. Vietnamese agrobiodiversity could be better utilized to increase dietary diversity. Differentiated policies are necessary to address the poor dietary diversity and adequacy in northern Vietnam.

8.
Cells ; 12(8)2023 04 08.
Article in English | MEDLINE | ID: mdl-37190023

ABSTRACT

Actin dynamics are known to orchestrate various myogenic processes in progenitor cells. Twinfilin-1 (TWF1) is an actin-depolymerizing factor that plays a crucial role in the differentiation of myogenic progenitor cells. However, little is known about the mechanisms underlying the epigenetic regulation of TWF1 expression and impaired myogenic differentiation in the background of muscle wasting. This study investigated how miR-665-3p affects TWF1 expression, actin filaments' modulation, proliferation, and myogenic differentiation in progenitor cells. Palmitic acid, the most prevalent saturated fatty acid (SFA) in food, suppressed TWF1 expression and inhibited the myogenic differentiation of C2C12 cells while increasing the level of miR-665-3p expression. Interestingly, miR-665-3p inhibited TWF1 expression by targeting TWF1 3'UTR directly. In addition, miR-665-3p accumulated filamentous actin (F-actin) and enhanced the nuclear translocation of Yes-associated protein 1 (YAP1), consequently promoting cell cycle progression and proliferation. Furthermore, miR-665-3p suppressed the expressions of myogenic factors, i.e., MyoD, MyoG, and MyHC, and consequently impaired myoblast differentiation. In conclusion, this study suggests that SFA-inducible miR-665-3p suppresses TWF1 expression epigenetically and inhibits myogenic differentiation by facilitating myoblast proliferation via the F-actin/YAP1 axis.


Subject(s)
MicroRNAs , Actins/metabolism , Cell Differentiation/genetics , Cell Line , Cell Proliferation , Epigenesis, Genetic , MicroRNAs/metabolism , Myoblasts/metabolism , Stem Cells/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Animals , Mice
9.
Int J Mol Sci ; 24(7)2023 Mar 28.
Article in English | MEDLINE | ID: mdl-37047312

ABSTRACT

Actin cytoskeleton dynamics have been found to regulate myogenesis in various progenitor cells, and twinfilin-1 (TWF1), an actin-depolymerizing factor, plays a vital role in actin dynamics and myoblast differentiation. Nevertheless, the molecular mechanisms underlying the epigenetic regulation and biological significance of TWF1 in obesity and muscle wasting have not been explored. Here, we investigated the roles of miR-302a in TWF1 expression, actin filament modulation, proliferation, and myogenic differentiation in C2C12 progenitor cells. Palmitic acid, the most prevalent saturated fatty acid (SFA) in the diet, decreased the expression of TWF1 and impeded myogenic differentiation while increasing the miR-302a levels in C2C12 myoblasts. Interestingly, miR-302a inhibited TWF1 expression directly by targeting its 3'UTR. Furthermore, ectopic expression of miR-302a promoted cell cycle progression and proliferation by increasing the filamentous actin (F-actin) accumulation, which facilitated the nuclear translocation of Yes-associated protein 1 (YAP1). Consequently, by suppressing the expressions of myogenic factors, i.e., MyoD, MyoG, and MyHC, miR-302a impaired myoblast differentiation. Hence, this study demonstrated that SFA-inducible miR-302a suppresses TWF1 expression epigenetically and impairs myogenic differentiation by facilitating myoblast proliferation via F-actin-mediated YAP1 activation.


Subject(s)
Actins , MicroRNAs , Actin Cytoskeleton/metabolism , Actins/genetics , Actins/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Cell Differentiation/genetics , Cell Proliferation/genetics , Epigenesis, Genetic , MicroRNAs/metabolism , Muscle Development/genetics , Myoblasts/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
10.
Korean J Physiol Pharmacol ; 27(3): 277-287, 2023 May 01.
Article in English | MEDLINE | ID: mdl-37078301

ABSTRACT

Actin dynamics play an essential role in myogenesis through multiple mechanisms, such as mechanotransduction, cell proliferation, and myogenic differentiation. Twinfilin-1 (TWF1), an actin-depolymerizing protein, is known to be required for the myogenic differentiation of progenitor cells. However, the mechanisms by which they epigenetically regulate TWF1 by microRNAs under muscle wasting conditions related to obesity are almost unknown. Here, we investigated the role of miR-103-3p in TWF1 expression, actin filament modulation, proliferation, and myogenic differentiation of progenitor cells. Palmitic acid, the most abundant saturated fatty acid (SFA) in the diet, reduced TWF1 expression and impeded myogenic differentiation of C2C12 myoblasts, while elevating miR-103-3p levels in myoblasts. Interestingly, miR-103-3p inhibited TWF1 expression by directly targeting its 3'UTR. Furthermore, ectopic expression of miR-103-3p reduced the expression of myogenic factors, i.e., MyoD and MyoG, and subsequently impaired myoblast differentiation. We demonstrated that miR-103-3p induction increased filamentous actin (F-actin) and facilitated the nuclear translocation of Yes-associated protein 1 (YAP1), thereby stimulating cell cycle progression and cell proliferation. Hence, this study suggests that epigenetic suppression of TWF1 by SFA-inducible miR-103-3p impairs myogenesis by enhancing the cell proliferation triggered by F-actin/YAP1.

11.
Cells ; 13(1)2023 12 20.
Article in English | MEDLINE | ID: mdl-38201213

ABSTRACT

Skeletal myogenesis is an intricate process involving the differentiation of progenitor cells into myofibers, which is regulated by actin cytoskeletal dynamics and myogenic transcription factors. Although recent studies have demonstrated the pivotal roles of actin-binding proteins (ABPs) as mechanosensors and signal transducers, the biological significance of WAVE2 (Wiskott-Aldrich syndrome protein family member 2), an ABP essential for actin polymerization, in myogenic differentiation of progenitor cells has not been investigated. Our study provides important insights into the regulatory roles played by WAVE2 in the myocardin-related transcription factor A (MRTFA)-serum response factor (SRF) signaling axis and differentiation of myoblasts. We demonstrate that WAVE2 expression is induced during myogenic differentiation and plays a pivotal role in actin cytoskeletal remodeling in C2C12 myoblasts. Knockdown of WAVE2 in C2C12 cells reduced filamentous actin levels, increased globular actin accumulation, and impaired the nuclear translocation of MRTFA. Furthermore, WAVE2 depletion in myoblasts inhibited the expression and transcriptional activity of SRF and suppressed cell proliferation in myoblasts. Consequently, WAVE2 knockdown suppressed myogenic regulatory factors (i.e., MyoD, MyoG, and SMYD1) expressions, thereby hindering the differentiation of myoblasts. Thus, this study suggests that WAVE2 is essential for myogenic differentiation of progenitor cells by modulating the mechanosensitive MRTFA-SRF axis.


Subject(s)
Actins , Serum Response Factor , Trans-Activators , Nuclear Proteins , Stem Cells , Animals , Mice
12.
Cells ; 11(13)2022 06 26.
Article in English | MEDLINE | ID: mdl-35805114

ABSTRACT

Actin cytoskeleton dynamics are essential regulatory processes in muscle development, growth, and regeneration due to their modulation of mechanotransduction, cell proliferation, differentiation, and morphological changes. Although the KN motif and ankyrin repeat domain-containing protein 1 (Kank1) plays a significant role in cell adhesion dynamics, actin polymerization, and cell proliferation in various cells, the functional significance of Kank1 during the myogenic differentiation of progenitor cells has not been explored. Here, we report that Kank1 acts as a critical regulator of the proliferation and differentiation of muscle progenitor cells. Kank1 was found to be expressed at a relatively high level in C2C12 myoblasts, and its expression was modulated during the differentiation. Depletion of Kank1 by siRNA (siKank1) increased the accumulation of filamentous actin (F-actin). Furthermore, it facilitated the nuclear localization of Yes-associated protein 1 (YAP1) by diminishing YAP1 phosphorylation in the cytoplasm, which activated the transcriptions of YAP1 target genes and promoted proliferation and cell cycle progression in myoblasts. Notably, depletion of Kank1 suppressed the protein expression of myogenic regulatory factors (i.e., MyoD and MyoG) and dramatically inhibited myoblast differentiation and myotube formation. Our results show that Kank1 is an essential regulator of actin dynamics, YAP1 activation, and cell proliferation and that its depletion impairs the myogenic differentiation of progenitor cells by promoting myoblast proliferation triggered by the F-actin-induced nuclear translocation of YAP1.


Subject(s)
Actins , Mechanotransduction, Cellular , Actins/metabolism , Cell Proliferation , Muscle Development/genetics , Myoblasts/metabolism
13.
Sci Rep ; 12(1): 12402, 2022 07 20.
Article in English | MEDLINE | ID: mdl-35858943

ABSTRACT

Respiratory syncytial virus (RSV) is a leading cause of Acute Respiratory Tract Infections (ARTIs) in young children. However, there is currently no vaccine or treatment available for children. Here, we demonstrated that nasal-spraying probiotics containing 5 billion of Bacillus spores (LiveSpo Navax) is an effective symptomatic treatment in a 6-day randomized controlled clinical study for RSV-infected children (n = 40-46/group). Navax treatment resulted in 1-day faster recovery-time and 10-50% better efficacy in relieving ARTI symptoms. At day 3, RSV load and level of pro-inflammatory cytokines in nasopharyngeal samples was reduced by 630 folds and 2.7-12.7 folds respectively. This showed 53-fold and 1.8-3.6-fold more effective than those in the control-standard of care-group. In summary, nasal-spraying Bacillus spores can rapidly and effectively relieve symptoms of RSV-induced ARTIs while exhibit strong impacts in reducing viral load and inflammation. Our nasal-spraying probiotics may provide a basis for simple-to-use, low-cost, and effective treatment against viral infection in general.


Subject(s)
Bacillus , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Child , Child, Preschool , Humans , Nasal Sprays , Respiratory Tract Infections/therapy , Spores, Bacterial
14.
Clin Case Rep ; 10(5): e05868, 2022 May.
Article in English | MEDLINE | ID: mdl-35600009

ABSTRACT

Performing peripherally inserted central catheters for children with bilateral bidirectional Glenn shunt, Fontan circulation, and persistent left superior vena cava differs from those with normal central venous anatomy. This study presents two PICC procedures for a toddler with this condition to demonstrate an accurate PICC approach for such children.

15.
Am J Case Rep ; 23: e935577, 2022 May 10.
Article in English | MEDLINE | ID: mdl-35535009

ABSTRACT

BACKGROUND COVID-19 is a pandemic caused by a coronavirus that has only recently been discovered. The disorder is characterized by persistent respiratory system malfunction, which can range from modest difficulty breathing to potentially lethal complications such as acute respiratory distress syndrome. Additional organs are affected as a result of its presence. An adverse impact of COVID-19 infection is myocarditis, which is a condition that affects the heart muscle. CASE REPORT We describe the case of a 38-year-old woman who was hospitalized at University Medical Center Ho Chi Minh City following a 15-day fever, a 3-day bout of dyspnea, and a positive nasal PCR SAR-CoV-2 test. The Lake Louise criteria were used to determine that the patient had a high probability of having myocarditis. She was then treated with oxygen treatment, vasoconstrictor medicines, inotropic therapy, and cornerstone heart failure medications, and was discharged 2 weeks later after a complete recovery. CONCLUSIONS Myocarditis has been identified as a cause of death in COVID-19, although it is not known how common the ailment is in the general population. Early detection and complete treatment, which should include support for the cardiovascular system, are consequently critical for successful outcomes. Magnetic resonance imaging (MRI) of the cardiovascular system (cardiac MRI) is the most important noninvasive method for diagnosing myocarditis.


Subject(s)
COVID-19 , Myocarditis , Respiratory Insufficiency , Adult , Female , Humans , Myocarditis/diagnosis , Myocarditis/etiology , Pandemics , SARS-CoV-2
16.
J Phys Condens Matter ; 34(31)2022 Jun 10.
Article in English | MEDLINE | ID: mdl-35623336

ABSTRACT

In this work, the magnetic states and thermally induced spin currents in graphene nanoflake sizes with different sizes and shapes have been investigated using Hubbard model combined with non-equilibrium Green's function method. In addition to the antiferromagnetic (AFM) state governed by the sizes, shapes, armchair bond densities, and Coulomb energy, our calculations have also pointed out the emergence of ferromagnetic (FM) and complex magnetic states when the gate voltage is invoked in the graphene nanoflakes. More prominently, by exploiting the geometric symmetry of the nanoflakes without external fields, a pure spin current and zero charge current are generated in spin caloritronic device when the graphene nanoflakes are both in the AFM and FM states. The formation of pure spin currents driven by temperature difference depends on the graphene nanoflakes' size, shape, temperature and gate voltage as well. The study also shows the outstanding advantages of diamond-shaped graphene nanoflakes in both magnetic properties and spin currents. This result paves the way for the possibility of practical applications of graphene materials in spintronics and spin caloritronics.

17.
Biomimetics (Basel) ; 7(2)2022 Apr 08.
Article in English | MEDLINE | ID: mdl-35466259

ABSTRACT

There is an essential need for a change in the way we build our physical environment. To prevent our ecosystems from collapsing, raising awareness of already available bio-based materials is vital. Mycelium, a living fungal organism, has the potential to replace conventional materials, having the ability to act as a binding agent of various natural fibers, such as hemp, flax, or other agricultural waste products. This study aims to showcase mycelium's load-bearing capacities when reinforced with bio-based materials and specifically natural fibers, in an alternative merging design approach. Counteracting the usual fabrication techniques, the proposed design method aims to guide mycelium's growth on a natural rattan framework that serves as a supportive structure for the mycelium substrate and its fiber reinforcement. The rattan skeleton is integrated into the finished composite product, where both components merge, forming a fully biodegradable unit. Using digital form-finding tools, the geometry of a compressive structure is computed. The occurring multi-layer biobased component can support a load beyond 20 times its own weight. An initial physical prototype in furniture scale is realized. Further applications in architectural scale are studied and proposed.

18.
Int J Mol Sci ; 23(6)2022 Mar 10.
Article in English | MEDLINE | ID: mdl-35328400

ABSTRACT

Excessive saturated fatty acids (SFA) uptake is known to be a primary cause of obesity, a widely acknowledged risk factor of insulin resistance and type 2 diabetes. Although specific microRNAs (miRNAs) targeting insulin signaling intermediates are dysregulated by SFA, their effects on insulin signaling and sensitivity are largely unknown. Here, we investigated the role of SFA-induced miR-183-5p in the regulation of proximal insulin signaling molecules and the development of hepatic insulin resistance. HepG2 hepatocytes treated with palmitate and the livers of high-fat diet (HFD)-fed mice exhibited impaired insulin signaling resulting from dramatic reductions in the protein expressions of insulin receptor (INSR) and insulin receptor substrate-1 (IRS-1). Differential expression analysis showed the level of miR-183-5p, which tentatively targets the 3'UTR of IRS-1, was significantly elevated in palmitate-treated HepG2 hepatocytes and the livers of HFD-fed mice. Dual-luciferase analysis showed miR-183-5p bound directly to the 3'UTR of IRS-1 and reduced IRS-1 expression at the post-transcriptional stage. Moreover, transfection of HepG2 hepatocytes with miR-183-5p mimic significantly inhibited IRS-1 expression and hindered insulin signaling, consequently inhibiting insulin-stimulated glycogen synthesis. Collectively, this study reveals a novel mechanism whereby miR-183-5p induction by SFA impairs insulin signaling and suggests miR-183-5p plays a crucial role in the pathogenesis of hepatic insulin resistance in the background of obesity.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , MicroRNAs , 3' Untranslated Regions , Animals , Diabetes Mellitus, Type 2/metabolism , Fatty Acids/metabolism , Hepatocytes/metabolism , Insulin/metabolism , Insulin Receptor Substrate Proteins/genetics , Insulin Receptor Substrate Proteins/metabolism , Insulin Resistance/genetics , Mice , MicroRNAs/metabolism , Obesity/metabolism , Palmitates/metabolism , Palmitates/pharmacology
19.
Biochem Biophys Res Commun ; 599: 17-23, 2022 04 09.
Article in English | MEDLINE | ID: mdl-35168059

ABSTRACT

Actin cytoskeletal dynamics play a critical role in the regulation of myogenesis through mechanotransduction, Hippo signaling modulation, cell proliferation, and morphological changes. Although Twinfilin-1 (TWF1), a highly conserved actin-depolymerizing factor, is known to regulate actin filament assembly by sequestering actin monomer and capping barbed ends, the biological significance of TWF1 during the differentiation of myogenic progenitor cells has not been investigated. In this study, we unveiled the roles played by TWF1 in the proliferation and differentiation of C2C12 myoblasts. TWF1 was the predominant isoform in myoblasts, and its expression was induced during the early stage of differentiation. Knockdown of TWF1 by siRNA (siTWF1) induced the accumulation of actin filaments (F-actin) and promoted the nuclear translocation of Yes-associated protein (YAP) in the Hippo signaling pathway. TWF1 depletion activated transcription of YAP target genes and induced cell cycle and proliferation in myoblasts. Furthermore, TWF1 knockdown markedly reduced the expressions of myogenic regulatory factors, such as MyoD and MyoG, and drastically hindered myoblast differentiation, fusion, and myotube formation. Collectively, this study highlights the essential role of TWF1 in the myogenic differentiation of progenitor cells via modulation of F-actin and YAP, and suggests TWF1 as a potential therapeutic target for muscle wasting and myopathies.


Subject(s)
Microfilament Proteins/metabolism , Myoblasts/cytology , YAP-Signaling Proteins/metabolism , Actins/metabolism , Active Transport, Cell Nucleus/genetics , Animals , Cell Differentiation/genetics , Cell Differentiation/physiology , Cell Line , Cell Proliferation/genetics , Gene Expression Regulation , Gene Knockdown Techniques , Mice , Microfilament Proteins/genetics , Muscle Development/genetics , Muscle Fibers, Skeletal/metabolism , Myoblasts/physiology , YAP-Signaling Proteins/genetics
20.
BMB Rep ; 55(2): 104-109, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35000671

ABSTRACT

Skeletal myogenesis is essential to keep muscle mass and integrity, and impaired myogenesis is closely related to the etiology of muscle wasting. Recently, miR-141-3p has been shown to be induced under various conditions associated with muscle wasting, such as aging, oxidative stress, and mitochondrial dysfunction. However, the functional significance and mechanism of miR-141-3p in myogenic differentiation have not been explored to date. In this study, we investigated the roles of miR-141-3p on CFL2 expression, proliferation, and myogenic differentiation in C2C12 myoblasts. MiR-141-3p appeared to target the 3'UTR of CFL2 directly and suppressed the expression of CFL2, an essential factor for actin filament (F-actin) dynamics. Transfection of miR-141-3p mimic in myoblasts increased F-actin formation and augmented nuclear Yes-associated protein (YAP), a key component of mechanotransduction. Furthermore, miR-141-3p mimic increased myoblast proliferation and promoted cell cycle progression throughout the S and G2/M phases. Consequently, miR-141-3p mimic led to significant suppressions of myogenic factors expression, such as MyoD, MyoG, and MyHC, and hindered the myogenic differentiation of myoblasts. Thus, this study reveals the crucial role of miR-141-3p in myogenic differentiation via CFL2-YAP-mediated mechanotransduction and provides implications of miRNA-mediated myogenic regulation in skeletal muscle homeostasis. [BMB Reports 2022;55(2): 104-109].


Subject(s)
Cell Differentiation , Cofilin 2 , MicroRNAs , Animals , Cell Line , Cell Proliferation/genetics , Cofilin 2/genetics , Cofilin 2/metabolism , Mechanotransduction, Cellular , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Muscle Development/genetics , Myoblasts/metabolism
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