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1.
Diabetes ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656552

RESUMO

Forkhead box protein O1 (FoxO1) regulates muscle growth, but the metabolic role of FoxO1 in skeletal muscle and its mechanisms remain unclear. To explore the metabolic role of FoxO1 in skeletal muscle, we generated skeletal muscle-specific FoxO1 inducible knockout (mFoxO1 iKO) mice and fed them a high-fat diet to induce obesity. We measured insulin sensitivity, fatty acid oxidation, mitochondrial function, and exercise capacity in obese mFoxO1 iKO mice, and assessed the correlation between FoxO1 and mitochondrial-related protein in the skeletal muscle of diabetic patients. Obese mFoxO1 iKO mice exhibited improved mitochondrial respiratory capacity, which was followed by attenuated insulin resistance, enhanced fatty acid oxidation, and improved skeletal muscle exercise capacity. Transcriptional inhibition of FoxO1 in peroxisome proliferator-activated receptor δ (PPARδ) expression was confirmed in skeletal muscle and deletion of PPARδ abolished the beneficial effects of FoxO1 deficiency. FoxO1 protein levels were higher in the skeletal muscle of diabetic patients and negatively correlated with PPARδ and electron transport chain protein levels. These findings highlight FoxO1 as a new repressor in PPARδ gene expression in skeletal muscle and suggest that FoxO1 links insulin resistance and mitochondrial dysfunction in skeletal muscle via PPARδ.

2.
Int J Biol Macromol ; 267(Pt 2): 131411, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588841

RESUMO

Skeletal muscle (SM) mass and strength maintenance are important requirements for human well-being. SM regeneration to repair minor injuries depends upon the myogenic activities of muscle satellite (stem) cells. However, losses of regenerative properties following volumetric muscle loss or severe trauma or due to congenital muscular abnormalities are not self-restorable, and thus, these conditions have major healthcare implications and pose clinical challenges. In this context, tissue engineering based on different types of biomaterials and scaffolds provides an encouraging means of structural and functional SM reconstruction. In particular, biomimetic (able to transmit biological signals) and several porous scaffolds are rapidly evolving. Several biological macromolecules/biomaterials (collagen, gelatin, alginate, chitosan, and fibrin etc.) are being widely used for SM regeneration. However, available alternatives for SM regeneration must be redesigned to make them more user-friendly and economically feasible with longer shelf lives. This review aimed to explore the biological aspects of SM regeneration and the roles played by several biological macromolecules and scaffolds in SM regeneration in cases of volumetric muscle loss.

3.
Curr Res Food Sci ; 8: 100678, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298827

RESUMO

Cultured meat (CM) is an alternative protein food and is produced by cultivating muscle satellite (stem) cells (MSCs) derived from livestock animals (bovine, chickens, and porcine) through myogenesis leading to generate muscle mass. Myostatin (MSTN) is well well-known negative regulator of myogenesis, and in the present study, in silico screening of natural compounds was performed to identify MSTN inhibitors. Interestingly, quercetin was found to inhibit MSTN (binding energy -7.40 kcal/mol), and this was further validated by a 100 ns molecular dynamics simulation. Quercetin was added to culture media to boost myogenesis, and its potent antioxidant property helped maintain media pH. Furthermore, quercetin increased the myotube thickness and length, increased MSC differentiation, and upregulated the gene and protein expressions of myoblast determination protein 1 (MYOD), Myogenin (MYOG), and Myosin heavy chains (MYH) in vitro. In addition, quercetin inhibited the activities of MSTN, activin receptor type-2B (ACVR2B), and SMAD2 and 3, and thus significantly enhanced MSC differentiation and myotube formation. Overall, this study shows that quercetin might be useful for enhancing large-scale CM production. It is hoped that this study provides a starting point for research in the CM area aimed to enhancing product quality, nutritional values, and the efficacy of large-scale production.

4.
Heliyon ; 10(3): e24942, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38317977

RESUMO

Skeletal muscle (SM) is a highly plastic and dynamic tissue of the body and is largely responsible for body maintenance. SM is primarily responsible for body balance, movement, postural support, thermogenesis, and blood glucose homeostasis. SM regeneration depends on the activation of muscle satellite (stem) cells (MSCs) under the regulation of several muscle regulatory factors that regulate myogenesis. Bibliometric analysis involves the quantitative and qualitative assessments of research and scientific progress that provides researchers access to recent publications, research directions, and thus generates ideas that can be implemented to guide future research. In this analysis, the Web of Science database was searched for articles using the search term "skeletal muscle AND myogenesis AND muscle satellite cell", and 1777 articles (original research/review articles) published from the year 1997 to June 2023 were retrieved. After applying several other exclusion and inclusion criteria, 129 articles were considered for analysis. Types of research, keywords, journals, authors, years, institutions, funding agencies, and average annual citations were analyzed. Muscle regeneration, satellite cell, and myogenesis were often used keywords and exhibited increasing trends in research articles over the decades. Some journals were found to strongly support research publications with high impact factors and citation scores. This study aimed to examine research ideas and growth in the skeletal muscle related field for atrophy and aging improvement.

5.
Phytomedicine ; 125: 155350, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237512

RESUMO

BACKGROUND: Myostatin (MSTN) inhibition has demonstrated promise for the treatment of diseases associated with muscle loss. In a previous study, we discovered that Glycyrrhiza uralensis (G. uralensis) crude water extract (CWE) inhibits MSTN expression while promoting myogenesis. Furthermore, three specific compounds of G. uralensis, namely liquiritigenin, tetrahydroxymethoxychalcone, and Licochalcone B (Lic B), were found to promote myoblast proliferation and differentiation, as well as accelerate the regeneration of injured muscle tissue. PURPOSE: The purpose of this study was to build on our previous findings on G. uralensis and demonstrate the potential of its two components, Licochalcone A (Lic A) and Lic B, in muscle mass regulation (by inhibiting MSTN), aging and muscle formation. METHODS: G. uralensis, Lic A, and Lic B were evaluated thoroughly using in silico, in vitro and in vivo approaches. In silico analyses included molecular docking, and dynamics simulations of these compounds with MSTN. Protein-protein docking was carried out for MSTN, as well as for the docked complex of MSTN-Lic with its receptor, activin type IIB receptor (ACVRIIB). Subsequent in vitro studies used C2C12 cell lines and primary mouse muscle stem cells to acess the cell proliferation and differentiation of normal and aged cells, levels of MSTN, Atrogin 1, and MuRF1, and plasma MSTN concentrations, employing techniques such as western blotting, immunohistochemistry, immunocytochemistry, cell proliferation and differentiation assays, and real-time RT-PCR. Furthermore, in vivo experiments using mouse models focused on measuring muscle fiber diameters. RESULTS: CWE of G. uralensis and two of its components, namely Lic A and B, promote myoblast proliferation and differentiation by inhibiting MSTN and reducing Atrogin1 and MuRF1 expressions and MSTN protein concentration in serum. In silico interaction analysis revealed that Lic A (binding energy -6.9 Kcal/mol) and B (binding energy -5.9 Kcal/mol) bind to MSTN and reduce binding between it and ACVRIIB, thereby inhibiting downstream signaling. The experimental analysis, which involved both in vitro and in vivo studies, demonstrated that the levels of MSTN, Atrogin 1, and MuRF1 were decreased when G. uralensis CWE, Lic A, or Lic B were administered into mice or treated in the mouse primary muscle satellite cells (MSCs) and C2C12 myoblasts. The diameters of muscle fibers increased in orally treated mice, and the differentiation and proliferation of C2C12 cells were enhanced. G. uralensis CWE, Lic A, and Lic B also promoted cell proliferation in aged cells, suggesting that they may have anti-muslce aging properties. They also reduced the expression and phosphorylation of SMAD2 and SMAD3 (MSTN downstream effectors), adding to the evidence that MSTN is inhibited. CONCLUSION: These findings suggest that CWE and its active constituents Lic A and Lic B have anti-mauscle aging potential. They also have the potential to be used as natural inhibitors of MSTN and as therapeutic options for disorders associated with muscle atrophy.


Assuntos
Chalconas , Fibras Musculares Esqueléticas , Miostatina , Camundongos , Animais , Miostatina/metabolismo , Simulação de Acoplamento Molecular , Diferenciação Celular , Fibras Musculares Esqueléticas/metabolismo , Proliferação de Células , Músculo Esquelético/metabolismo
6.
Heliyon ; 10(1): e23512, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38187250

RESUMO

Tetranectin (TN), a serum protein, is closely associated with different types of cancers. TN binds plasminogen and promotes the proteolytic activation of plasminogen into plasmin, which suggests that TN is involved in remodeling the extracellular matrix and cancer tissues during cancer development. TN is also associated with other diseases, such as developmental disorders, cardiovascular diseases, neurological diseases, inflammation, and diabetes. Although the functional mechanism of TN in diseases is not fully elucidated, TN binds different proteins, such as structural protein, a growth factor, and a transcription regulator. Moreover, TN changes and regulates protein functions, indicating that TN-binding proteins mediate the association between TN and diseases. This review summarizes the current knowledge of TN-associated diseases and TN functions with TN-binding proteins in different diseases. In addition, potential TN-targeted disease treatment by inhibiting the interaction between TN and its binding proteins is discussed.

7.
J Ginseng Res ; 48(1): 12-19, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38223826

RESUMO

Skeletal muscle (SM) is the largest organ of the body and is largely responsible for the metabolism required to maintain body functions. Furthermore, the maintenance of SM is dependent on the activation of muscle satellite (stem) cells (MSCs) and the subsequent proliferation and fusion of differentiating myoblasts into mature myofibers (myogenesis). Natural compounds are being used as therapeutic options to promote SM regeneration during aging, muscle atrophy, sarcopenia, cachexia, or obesity. In particular, ginseng-derived compounds have been utilized in these contexts, though ginsenoside Rg1 is mostly used for SM mass management. These compounds primarily function by activating the Akt/mTOR signaling pathway, upregulating myogenin and MyoD to induce muscle hypertrophy, downregulating atrophic factors (atrogin1, muscle ring-finger protein-1, myostatin, and mitochondrial reactive oxygen species production), and suppressing the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cachexia. Ginsenoside compounds are also used for obesity management, and their anti-obesity effects are attributed to peroxisome proliferator activated receptor gamma (PPARγ) inhibition, AMPK activation, glucose transporter type 4 (GLUT4) translocation, and increased phosphorylations of insulin resistance (IR), insulin receptor substrate-1 (IRS-1), and Akt. This review was undertaken to provide an overview of the use of ginseng-related compounds for the management of SM-related disorders.

8.
Acta Pharm Sin B ; 14(1): 273-291, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38261813

RESUMO

Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells (MSC). However, it remains unclear what drives the compromised potency of obese MSC. In this study, we examined the involvement of adiponectin, an adipose tissue-derived hormone, in obesity-induced impaired therapeutic function of MSC. Diet-induced obesity leads to a decrease in serum adiponectin, accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC (ADSC). Interestingly, priming with globular adiponectin (gAcrp) improved the immunomodulatory potential of obese ADSC. Similar effects were also observed in lean ADSC. In addition, gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced colitis. Mechanistically, while obesity inhibited the glycolytic capacity of MSC, gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1α axis. These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.

9.
J Biomol Struct Dyn ; : 1-10, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38100571

RESUMO

The enzyme dipeptidyl peptidase 4 (DPP4) is a potential therapeutic target for type 2 diabetes (T2DM). Many synthetic anti-DPP4 medications are available to treat T2DM. The need for secure and efficient medicines has been unmet due to the adverse side effects of existing DPP4 medications. The present study implemented a combined approach to machine learning and structure-based virtual screening to identify DPP4 inhibitors. Two ML models were trained based on DPP4 IC50 datasets. The ML models random forest (RF) and multilayer perceptron (MLP) neural network showed good accuracy, with the area under the curve being 0.93 and 0.91, respectively. The natural compound library was screened through ML models, and 1% (217) of compounds were selected for further screening. Structure-based virtual screening was performed along with positive control sitagliptin to obtain more specific and selective leads for DPP4. Based on binding affinity, drug-likeness properties, and interaction with DPP4, Z-614 and Z-997 compounds showed high binding affinity and specificity in the catalytic pocket of DPP4. Finally, the stability conformation of the DPP4 enzyme complex was checked by a molecular dynamics (MD) simulation. The MD simulation showed that both compounds bind better in the catalytic pocket, but the Z-614 compound altered the DPP4 native conformation. Therefore, Z-614 showed a high deviation in the backbone. This combined approach (ML and structure-based) study reported that Z-997 binds most stably to DPP4 in their catalytic pocket with a binding free energy of -70.3 kJ/mol, suggesting its therapeutic potential as a treatment option for T2DM disease.Communicated by Ramaswamy H. Sarma.

10.
Int J Mol Sci ; 24(24)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38139116

RESUMO

Ginseng is usually consumed as a daily food supplement to improve health and has been shown to benefit skeletal muscle, improve glucose metabolism, and ameliorate muscle-wasting conditions, cardiovascular diseases, stroke, and the effects of aging and cancers. Ginseng has also been reported to help maintain bone strength and liver (digestion, metabolism, detoxification, and protein synthesis) and kidney functions. In addition, ginseng is often used to treat age-associated neurodegenerative disorders, and ginseng and ginseng-derived natural products are popular natural remedies for diseases such as diabetes, obesity, oxidative stress, and inflammation, as well as fungal, bacterial, and viral infections. Ginseng is a well-known herbal medication, known to alleviate the actions of several cytokines. The article concludes with future directions and significant application of ginseng compounds for researchers in understanding the promising role of ginseng in the treatment of several diseases. Overall, this study was undertaken to highlight the broad-spectrum therapeutic applications of ginseng compounds for health management.


Assuntos
Diabetes Mellitus , Doenças Neurodegenerativas , Panax , Humanos , Obesidade , Inflamação/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico
11.
Food Res Int ; 174(Pt 2): 113660, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37981377

RESUMO

Many researchers and companies around the world are reported to have developed cultured meat, but their specific techniques have rarely been disclosed. Thus, the purpose of this study is to provide an improved procedure for cultured meat. There are four major steps in this cultured meat production: muscle cell isolation, proliferation, differentiation, and validation. The improved isolation enabled the efficient removal of unnecessary cells and tissues compared to previous procedures. In addition, proper use of basal media can improve the proliferation efficiency by about 2-fold. During the differentiation process, improved procedure was performed by using 10 % horse serum-containing media after 3 days of initial differentiation for myotube induction. This method demonstrated significantly enhanced myotube formation, up to 2.6-fold increase in area and up to 1.9-fold increase in fusion index compared to the previous method. This study provides a simple, improved procedure to enable more effective cultured meat production compared to previous procedures and is expected to help produce inexpensive and safe cultured meat.


Assuntos
Células Satélites de Músculo Esquelético , Animais , Bovinos , Células Cultivadas , Fibras Musculares Esqueléticas , Diferenciação Celular
12.
Life (Basel) ; 13(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38004292

RESUMO

Androgenic alopecia (AGA) is a dermatological disease with psychosocial consequences for those who experience hair loss. AGA is linked to an increase in androgen levels caused by an excess of dihydrotestosterone in blood capillaries produced from testosterone by 5α-reductase type II (5αR2), which is expressed in scalp hair follicles; 5αR2 activity and dihydrotestosterone levels are elevated in balding scalps. The diverse health benefits of flavonoids have been widely reported in epidemiological studies, and research interest continues to increase. In this study, a virtual screening approach was used to identify compounds that interact with active site residues of 5αR2 by screening a library containing 241 flavonoid compounds. Here, we report two potent flavonoid compounds, eriocitrin and silymarin, that interacted strongly with 5αR2, with binding energies of -12.1 and -11.7 kcal/mol, respectively, which were more significant than those of the control, finasteride (-11.2 kcal/mol). Molecular dynamic simulations (200 ns) were used to optimize the interactions between compounds and 5αR2 and revealed that the interaction of eriocitrin and silymarin with 5αR2 was stable. The study shows that eriocitrin and silymarin provide developmental bases for novel 5αR2 inhibitors for the management of AGA.

13.
Food Res Int ; 174(Pt 1): 113617, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37986472

RESUMO

Fetal bovine serum (FBS) is an extremely important culture growth supplement, accounting for approximately 60 % of cell-culture-media costs; therefore, lowering FBS-acquisition costs for the industrialization of cultured meat is imperative. This study attempted to produce an FBS substitute using discarded livestock by-products, with particular focus on formulating a product with a composition similar to that of FBS to improve effectiveness. However, to date, no study has precisely analyzed the commercial components of FBS, and this study is the first to compare the chemical composition of FBS and commercially available horse serum purchased from the United States or Europe with that of FBS substitutes developed by our team. This study analyzed the chemical composition of the FBS products purchased by our team over the past 3 years via blood, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and independent composition analyses. While the composition and quality of commercial FBS products are known to vary, the FBS composition of our purchased products was relatively uniform regardless of company, brand, or country of origin. In contrast, FBS substitutes obtained from three major livestock species (cattle, pig, and chicken) clearly exhibited differences in composition, a phenomenon that was also observed upon comparing with FBS as well as among different species. Therefore, to replace commercial FBS entirely, the production of a proportionately effective substitute product comprising an equal or similar composition is required, and the results of this study can be a steppingstone to achieving this. In addition, FBS substitutes manufactured using inexpensive slaughter by-products as raw materials are expected to ultimately reduce the unit cost of cultured meat production.


Assuntos
Soroalbumina Bovina , Bovinos , Animais , Suínos , Meios de Cultura/química , Europa (Continente)
14.
Inflamm Regen ; 43(1): 58, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38008778

RESUMO

The regenerative ability of skeletal muscle (SM) in response to damage, injury, or disease is a highly intricate process that involves the coordinated activities of multiple cell types and biomolecular factors. Of these, extracellular matrix (ECM) is considered a fundamental component of SM regenerative ability. This review briefly discusses SM myogenesis and regeneration, the roles played by muscle satellite cells (MSCs), other cells, and ECM components, and the effects of their dysregulations on these processes. In addition, we review the various types of ECM scaffolds and biomaterials used for SM regeneration, their applications, recent advances in ECM scaffold research, and their impacts on tissue engineering and SM regeneration, especially in the context of severe muscle injury, which frequently results in substantial muscle loss and impaired regenerative capacity. This review was undertaken to provide a comprehensive overview of SM myogenesis and regeneration, the stem cells used for muscle regeneration, the significance of ECM in SM regeneration, and to enhance understanding of the essential role of the ECM scaffold during SM regeneration.

15.
Biomed Pharmacother ; 168: 115642, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37812896

RESUMO

Skeletal muscle (SM) plays a vital role in energy and glucose metabolism by regulating insulin sensitivity, glucose uptake, and blood glucose homeostasis. Impaired SM metabolism is strongly linked to several diseases, particularly type 2 diabetes (T2D). Insulin resistance in SM may result from the impaired activities of insulin receptor tyrosine kinase, insulin receptor substrate 1, phosphoinositide 3-kinase, and AKT pathways. This review briefly discusses SM myogenesis and the critical roles that SM plays in insulin resistance and T2D. The pharmacological targets of T2D which are associated with SM metabolism, such as DPP4, PTB1B, SGLT, PPARγ, and GLP-1R, and their potential modulators/inhibitors, especially natural compounds, are discussed in detail. This review highlights the significance of SM in metabolic disorders and the therapeutic potential of natural compounds in targeting SM-associated T2D targets. It may provide novel insights for the future development of anti-diabetic drug therapies. We believe that scientists working on T2D therapies will benefit from this review by enhancing their knowledge and updating their understanding of the subject.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Músculo Esquelético/metabolismo , Insulina/metabolismo
16.
Pharmacol Rev ; 76(1): 90-141, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37845080

RESUMO

Antimicrobial resistance presents us with a potential global crisis as it undermines the abilities of conventional antibiotics to combat pathogenic microbes. The history of antimicrobial agents is replete with examples of scaffolds containing halogens. In this review, we discuss the impacts of halogen atoms in various antibiotic types and antimicrobial scaffolds and their modes of action, structure-activity relationships, and the contributions of halogen atoms in antimicrobial activity and drug resistance. Other halogenated molecules, including carbohydrates, peptides, lipids, and polymeric complexes, are also reviewed, and the effects of halogenated scaffolds on pharmacokinetics, pharmacodynamics, and factors affecting antimicrobial and antivirulence activities are presented. Furthermore, the potential of halogenation to circumvent antimicrobial resistance and rejuvenate impotent antibiotics is addressed. This review provides an overview of the significance of halogenation, the abilities of halogens to interact in biomolecular settings and enhance pharmacological properties, and their potential therapeutic usages in preventing a postantibiotic era. SIGNIFICANCE STATEMENT: Antimicrobial resistance and the increasing impotence of antibiotics are critical threats to global health. The roles and importance of halogen atoms in antimicrobial drug scaffolds have been established, but comparatively little is known of their pharmacological impacts on drug resistance and antivirulence activities. This review is the first to extensively evaluate the roles of halogen atoms in various antibiotic classes and pharmacological scaffolds and to provide an overview of their ability to overcome antimicrobial resistance.


Assuntos
Antibacterianos , Anti-Infecciosos , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Halogênios/química , Halogenação , Relação Estrutura-Atividade
17.
Opt Express ; 31(12): 19569-19587, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381369

RESUMO

We describe a robust dynamic spectroscopic imaging ellipsometer (DSIE) based on a monolithic Linnik-type polarizing interferometer. The Linnik-type monolithic scheme combined with an additional compensation channel solves the long-term stability problem of previous single-channel DSIE. The importance of a global mapping phase error compensation method is also addressed for accurate 3-D cubic spectroscopic ellipsometric mapping in large-scale applications. To evaluate the effectiveness of the proposed compensation method for enhancing system robustness and reliability, a whole thin film wafer mapping is conducted in a general environment where various external disturbances affect the system.

18.
J Biomol Struct Dyn ; : 1-8, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37338036

RESUMO

Myostatin is a widely recognized inhibitory factor of skeletal muscle growth and significantly influences muscle development and metabolism. In mice, myostatin inhibition improves insulin sensitivity, increases glucose uptake by skeletal muscle, and reduces body fat. Furthermore, Mss51 is downregulated in response to myostatin inhibition, and its deletion appears to improve the metabolic state of skeletal muscle and reduce adipose tissue, which makes Mss51 a potential target for the treatment of obesity and type 2 diabetes. Here, we report a computationally predicted and validated three-dimensional structure of Mss51. Computational screening was used to identify naturally occurring compounds from the Herbal and Specs chemical database that might inhibit Mss51, based on binding affinities and physiochemical and ADMET properties. ZINC00338371, ZINC95099599 and ZINC08214878 were found to bind to Mss51 with high binding affinity and specificity. In addition, 100 ns molecular dynamics simulations were conducted to assess the stabilities of the interactions between the three compounds and Mss51. MD simulation demonstrated that all three compounds bind to the active pocket site of Mss51 stably and cause conformation changes. ZINC00338371 was found to bind most stably with binding free energy -229.022 ± 13.776 kJ/mol to Mss51, suggesting that it has therapeutic potential as a treatment option for obesity and type 2 diabetes.Communicated by Ramaswamy H. Sarma.

19.
Phytochemistry ; 211: 113711, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37150434

RESUMO

During the screening of the cytotoxicity of rare Korean endemic plants, the extract of Thuja koraiensis Nakai displayed potent cytotoxicity against the adenocarcinomic human alveolar basal epithelial A549 cell line. Through a series of separations via column chromatography, three undescribed abietanes, an undescribed labdane along with a labdane, and a biflavonoid were purified from methylene chloride (CH2Cl2) fraction possessing a potent cytotoxic effect. Extensive 1D and 2D NMR spectroscopic data analyses, in combination with quantum chemical calculations were conducted to establish the planar and absolute configurations of thujakoraienes A-C. The chemical structure of thujakoraiene D was elucidated by spectroscopic data analysis and competing enantioselective acylation. Thujakoraienes A and C along with 7,7″-di-O-methylamentoflavone, showed cytotoxic effects on A549 cells, with IC50 values of 64.86, 47.97, and 16.14 µM, respectively. Finally, thujakoraiene C and 7,7″-di-O-methylamentoflavone were identified as potent cytotoxic compounds in A549 cells, followed by an additional cytotoxicity test in the normal human lung fibroblast MRC-5 cell line. This is the first study on the non-volatile chemicals in the extract of T. koraiensis and comparison of chemical profiles of T. orientalis and T. koraiensis.


Assuntos
Antineoplásicos , Diterpenos , Thuja , Humanos , Células A549 , Thuja/química , Estrutura Molecular , Antineoplásicos/farmacologia , Diterpenos/química , Extratos Vegetais/farmacologia , Linhagem Celular Tumoral
20.
Appl Opt ; 62(8): 1943-1951, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-37133079

RESUMO

This paper describes a full Stokes polarimeter employing a monolithic off-axis polarizing interferometric module and a 2D array sensor. The proposed passive polarimeter provides a dynamic full Stokes vector measurement capability of around 30 Hz. As the proposed polarimeter employs no active devices and is operated by employing an imaging sensor, it has significant potential to become a highly compact polarization sensor for smartphone applications. To show the feasibility of the proposed passive dynamic polarimeter scheme, the full Stokes parameters of a quarter-wave plate are extracted and displayed on a Poincare sphere by varying the polarization state of the measured beam.

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