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1.
Artigo em Inglês | MEDLINE | ID: mdl-38653260

RESUMO

Low-dimensional materials with prominent thermoelectric (TE) effect play a pivotal role in realizing state-of-the-art nanoscale TE devices. The fusion of TE effect with the magnetism through seamless integration of thermoelectric and magnetic materials in the 2D limit offers access to control longitudinal as well as transverse TE properties via magnetic proximity effect (MPE). Herein, we design a vdW heterostructure of metallic 1T-MoS2 with promising TE properties and a layer-dependent magnetic CrI3 material. The result highlights exotic electronic and magnetic configurations of the designed ML-CrI3/1T-MoS2 vdW heterostructure, which show magnetically-coupled TE characteristics. The observed remarkable magnetic proximity stems from large magnetic anisotropy energy and spin polarization, which are found to be 2.21 meV/Cr and 12.30%, respectively. To this end, the semiconducting CrI3 layer with intrinsic magnetism leads to efficient control and tunability of the observed spin-correlated anomalous Nernst effect (ANE). Moreover, a large dimensionless Figure of merit of ~ 6 and a power factor of ~ 3.8×10^11/τ_° Wm^(-1) K^(-2) s^(-1) near the Fermi level at 300K endorse the rejuvenated TE effect. The strong relativistic spin-orbit coupling validates the significant correlation of TE properties with intrinsic magnetic configuration. The present study underscores the significance of the magnetic proximity-governed TE effect in vdW heterostructures to engineer low-dimensional thermoelectric (TE) devices. .

2.
ACS Omega ; 9(9): 10748-10768, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38463293

RESUMO

Cerebroside sulfotransferase (CST) is emerging as an important therapeutic target to develop substrate reduction therapy (SRT) for metachromatic leukodystrophy (MLD), a rare neurodegenerative lysosomal storage disorder. MLD develops with progressive impairment and destruction of the myelin sheath as a result of accumulation of sulfatide around the nerve cells in the absence of its recycling mechanism with deficiency of arylsulfatase A (ARSA). Sulfatide is the product of the catalytic action of cerebroside sulfotransferase (CST), which needs to be regulated under pathophysiological conditions by inhibitor development. To carry out in silico-based preliminary drug screening or for designing new drug candidates, a high-quality three-dimensional (3D) structure is needed in the absence of an experimentally derived three-dimensional crystal structure. In this study, a 3D model of the protein was developed using a primary sequence with the SWISS-MODEL server by applying the top four GMEQ score-based templates belonging to the sulfotransferase family as a reference. The 3D model of CST highlights the features of the protein responsible for its catalytic action. The CST model comprises five ß-strands, which are flanked by ten α-helices from both sides as well as form the upside cover of the catalytic pocket of CST. CST has two catalytic regions: PAPS (-sulfo donor) binding and galactosylceramide (-sulfo acceptor) binding. The catalytic action of CST was proposed via molecular docking and molecular dynamic (MD) simulation with PAPS, galactosylceramide (GC), PAPS-galactosylceramide, and PAP. The stability of the model and its catalytic action were confirmed using molecular dynamic simulation-based trajectory analysis. CST response against the inhibition potential of the experimentally reported competitive inhibitor of CST was confirmed via molecular docking and molecular dynamics simulation, which suggested the suitability of the CST model for future drug discovery to strengthen substrate reduction therapy for MLD.

3.
ACS Omega ; 9(7): 7529-7544, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38405466

RESUMO

An assortment of environmental matrices includes arsenic (As) in its different oxidation states, which is often linked to concerns that pose a threat to public health worldwide. The current difficulty lies in addressing toxicological concerns and achieving sustained detoxification of As. Multiple conventional degradation methods are accessible; however, they are indeed labor-intensive, expensive, and reliant on prolonged laboratory evaluations. Molecular interaction and atomic level degradation mechanisms for enzyme-As exploration are, however, underexplored in those approaches. A feasible approach in this case for tackling this accompanying concern of As might be to cope with undertaking multivalent computational methodologies and tools. This work aimed to provide molecular-level insight into the enzyme-aided As degradation mechanism. AutoDock Vina, CABS-flex 2.0, and Desmond high-performance molecular dynamics simulation (MDS) were utilized in the current investigation to simulate multivalent molecular processes on two protein sets: arsenate reductase (ArsC) and laccase (LAC) corresponding arsenate (ART) and arsenite (AST), which served as model ligands to comprehend binding, conformational, and energy attributes. The structural configurations of both proteins exhibited variability in flexibility and structure framework within the range of 3.5-4.5 Å. The LAC-ART complex exhibited the lowest calculated binding affinity, measuring -5.82 ± 0.01 kcal/mol. Meanwhile, active site residues ILE-200 and HIS-206 were demonstrated to engage in H-bonding with the ART ligand. In contrast to ArsC, the ligand binding affinity of this bound complex was considerably greater. Additional validation of docked complexes was carried out by deploying Desmond MDS of 100 ns to capture protein and ligand conformation behavior. The system achieved stability during the 100 ns simulation run, as confirmed by the average P-L RMSD, which was ∼1 Å. As a preliminary test of the enzyme's ability to catalyze As species, corresponding computational insights might be advantageous for bridging gaps and regulatory consideration.

4.
J Cell Physiol ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38327035

RESUMO

A few ubiquitin ligases have been shown to target Runx2, the key osteogenic transcription factor and thereby regulate bone formation. The regulation of Runx2 expression and function are controlled both at the transcriptional and posttranslational levels. Really interesting new gene (RING) finger ubiquitin ligases of which RNF138 is a member are important players in the ubiquitin-proteasome system, contributing to the regulation of protein turnover and cellular processes. Here, we demonstrated that RNF138 negatively correlated with Runx2 protein levels in osteopenic ovariectomized rats which implied its role in bone loss. Accordingly, RNF138 overexpression potently inhibited osteoblast differentiation of mesenchyme-like C3H10T1/2 as well primary rat calvarial osteoblast (RCO) cells in vitro, whereas overexpression of catalytically inactive mutant RNF138Δ18-58 (lacks RING finger domain) had mild to no effect. Contrarily, RNF138 depletion copiously enhanced endogenous Runx2 levels and augmented osteogenic differentiation of C3H10T1/2 as well as RCOs. Mechanistically, RNF138 physically associates within multiple regions of Runx2 and ubiquitinates it leading to its reduced protein stability in a proteasome-dependent manner. Moreover, catalytically active RNF138 destabilized Runx2 which resulted in inhibition of its transactivation potential and physiological function of promoting osteoblast differentiation leading to bone loss. These findings underscore the functional involvement of RNF138 in bone formation which is primarily achieved through its modulation of Runx2 by stimulating ubiquitin-mediated proteasomal degradation. Thus, our findings indicate that RNF138 could be a promising novel target for therapeutic intervention in postmenopausal osteoporosis.

5.
ACG Case Rep J ; 11(2): e01271, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38371471

RESUMO

Hemosuccus pancreaticus is characterized by intermittent bleeding from the ampulla of Vater due to the rupture of a pseudoaneurysm. There are significant diagnostic and therapeutic challenges associated with this rare and potentially life-threatening condition. We present a rare case in an 18-year-old man who presented with recurrent episodes of hematemesis and melena due to hemosuccus pancreaticus as a result of a left gastric artery pseudoaneurysm. Initial radiological angioembolization failed because of median arcuate ligament syndrome, and endoscopic ultrasound-guided glue embolization was successfully performed. This case further reinforces the importance of endoscopic ultrasound-guided therapy in the management of pseudoaneurysm after failed radiological treatment.

7.
Biometals ; 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38206521

RESUMO

Cadmium (Cd+2) renders multifarious environmental stresses and highly toxic to nearly all living organisms including plants. Cd causes toxicity by unnecessary augmentation of ROS that targets essential molecules and fundamental processes in plants. In response, plants outfitted a repertory of mechanisms to offset Cd toxicity. The main elements of these are Cd chelation, sequestration into vacuoles, and adjustment of Cd uptake by transporters and escalation of antioxidative mechanism. Signal molecules like phytohormones and reactive oxygen species (ROS) activate the MAPK cascade, the activation of the antioxidant system andsynergistic crosstalk between different signal molecules in order to regulate plant responses to Cd toxicity. Transcription factors like WRKY, MYB, bHLH, bZIP, ERF, NAC etc., located downstream of MAPK, and are key factors in regulating Cd toxicity responses in plants. Apart from this, MAPK and Ca2+signaling also have a salient involvement in rectifying Cd stress in plants. This review highlighted the mechanism of Cd uptake, translocation, detoxification and the key role of defense system, MAPKs, Ca2+ signals and jasmonic acid in retaliating Cd toxicity via synchronous management of various other regulators and signaling components involved under stress condition.

8.
Nat Prod Res ; 38(6): 1080-1084, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37157823

RESUMO

Semecarpus anacardium L.f. has been commonly used in various traditional medicines from ancient times. The nuts have been described in Ayurveda medication systems to treat numerous clinical ailments. However, isolating phytochemical constituents from nuts remain challenging and exhibits cytotoxic effects on other cells. In this study, we have standardized procedures for isolating phytochemicals from the leaf extract. The ethyl acetate leaf extract selectively affects cancer cells in a dose-dependent manner (IC50: 0.57 µg/ml in MCF-7 cells) in various cancer cell lines and induces apoptosis in cancer cells. However, the non-malignant cells were relatively insensitive to the extract. Next, the incubation of the leaf extract induces cell cycle arrest and suppresses cancer cell migration in the cell culture model. Moreover, oral administration of extract significantly restored tumor growth in mice. Together, these observations suggest the anti-cancer activities of S. anacardium L.f. leaf potential for both in vitro and in vivo models.


Assuntos
Antineoplásicos , Neoplasias , Semecarpus , Camundongos , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Neoplasias/tratamento farmacológico , Nozes
9.
Environ Res ; 241: 117579, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37944691

RESUMO

A wide array of organic compounds have been recognized as pollutants of high concern due to their controlled or uncontrolled presence in environmental matrices. The persistent prevalence of diverse organic pollutants, including pharmaceutical compounds, phenolic compounds, synthetic dyes, and other hazardous substances, necessitates robust measures for their practical and sustainable removal from water bodies. Several bioremediation and biodegradation methods have been invented and deployed, with a wide range of materials well-suited for diverse environments. Enzyme-linked carbon-based materials have been considered efficient biocatalytic platforms for the remediation of complex organic pollutants, mostly showing over 80% removal efficiency of micropollutants. The advantages of enzyme-linked carbon nanotubes (CNTs) in enzyme immobilization and improved catalytic potential may thus be advantageous for environmental research considering the current need for pollutant removal. This review outlines the perspective of current remediation approaches and highlights the advantageous features of enzyme-linked CNTs in the removal of pollutants, emphasizing their reusability and stability aspects. Furthermore, different applications of enzyme-linked CNTs in environmental research with concluding remarks and future outlooks have been highlighted. Enzyme-linked CNTs serve as a robust biocatalytic platform for the sustainability agenda with the aim of keeping the environment clean and safe from a variety of organic pollutants.


Assuntos
Poluentes Ambientais , Nanotubos de Carbono , Poluentes Ambientais/metabolismo , Biodegradação Ambiental , Catálise , Substâncias Perigosas
10.
Phys Chem Chem Phys ; 26(2): 895-902, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38087955

RESUMO

The seamless integration of two-dimensional (2D) ferromagnetic materials with similar or dissimilar materials can widen the scope of low-power spintronics. In this regard, a vertical van der Waals (vdW) heterostructure of 2D ferromagnets with semiconducting transition metal dichalcogenides (TMDCs) forms magnetic junctions with exceptional stability and electrical control. Interestingly, 2D metallic Fe3GeTe2 (FGT) reveals above room temperature Curie temperatures and has large magneto anisotropy due to spin-orbit coupling. In addition, it also possesses topological states and a large Berry curvature. Herein, we designed the FGT/WSe2/FGT vdW heterostructure with a uniform and sharp interface so that FGT could maintain its inherent electronic properties. Also, the uniform thickness of the barrier provides a smooth flow of spins through the junctions as tunneling exponentially decays with an increasing barrier thickness. However, strong energy-dependent spin polarization is crucial for achieving optimum spin valve properties, such as large tunneling magnetoresistance (TMR) along with the manipulation of the magnitude and sign reversal. We have observed a shifting of high-energy localized minority spin states toward low-energy regions, which causes spin polarization fluctuation between -42.5% and 41% over a wide range of bias voltage. This leads to a negative TMR% of ∼-100% at 0.1 V Å-1 and also a large positive TMR% at 0.2 V Å-1 and -0.4 V Å-1. Besides, the system exhibits a highly tunable large anomalous Hall conductivity (AHC) of 626 S cm-1. Interestingly, such unprecedented electronic behaviour with large and switchable spin polarization, anomalous Hall conductivity and TMR can be incorporated into MTJ devices, which provide electrical control and long-range spin transport. Additionally, the system emerges as a standout candidate in low-power spintronic devices (e.g., MRAM and magnetic sensors) owing to its distinctive energy-dependent electronic structure with a wide range of external bias.

11.
Int J Biol Macromol ; 258(Pt 1): 128780, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104688

RESUMO

This review is an effort towards the development of substrate reduction therapy using cerebroside sulfotransferase (CST) as a target protein for the development of inhibitors intended to treat pathophysiological condition resulting from the accumulation of sulfatide, a product from the catalytic action of CST. Accumulation of sulfatides leads to progressive impairment and destruction of the myelin structure, disruption of normal physiological transmission of electrical impulse between nerve cells, axonal loss in the central and peripheral nervous system and cumulatively gives a clinical manifestation of metachromatic leukodystrophy. Thus, there is a need to develop specific and potent CST inhibitors to positively control sulfatide accumulation. Structural similarity and computational studies revealed that LYS85, SER172 and HIS141 are key catalytic residues that determine the catalytic action of CST through the transfer of sulfuryl group from the donor PAPS to the acceptor galactosylceramide. Computational studies revealed catalytic site of CST consists two binding site pocket including PAPS binding pocket and substrate binding pocket. Specific substrate site residues in CST can be targeted to develop specific CST inhibitors. This review also explores the challenges of CST-directed substrate reduction therapy as well as the opportunities available in natural products for inhibitor development.


Assuntos
Leucodistrofia Metacromática , Sulfotransferases , Humanos , Leucodistrofia Metacromática/metabolismo , Sulfoglicoesfingolipídeos , Bainha de Mielina/metabolismo , Neurônios/metabolismo
12.
Chemosphere ; 346: 140681, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37951403

RESUMO

Cadmium (Cd) is absorbed by plant roots from soil along with essential nutrients and affects plant growth and productivity. Methyl jasmonate (Me-JA) play important roles to mitigate Cd toxicity in plants. We have investigated the role of Me-JA to ameliorate Cd toxicity in Pigeon pea (Cajanus cajan). Plant root growth, biomass, cellular antioxidant defense system and expression of key regulatory genes in molecular and signaling process have been analyzed. Two Cajanus cajan varieties AL-882 and PAU-881 were grown at 25 °C, 16/8h light/dark conditions in three biological replicates at 5 mM Cd concentration, three concentration of Me-JA (0, 10 nM, 100 nM) and two concentrations in combination of Me-JA + Cd (10 nM Me-JA +5 mM Cd, 100 nM Me-JA +5 mM Cd). The seedlings were exposed to Cd stress consequently plants showed decrease in primary root growth (60.71%, in AL-882 and 8.33%, in PAU-881), shoot and root biomass and antioxidant enzymes activities. Me-JA treatment resulted in increased primary root growth (63.64%, in AL-882) and overall plant biomass. Oxidative stress generated due to Cd stress was counter balanced by Me-JA treatment. Me-JA reduced H2O2 free radicals formation and enhanced antioxidant enzyme activities and phenolic content in stressed seedlings. Me-JA treatment increased expression of CALM, IP3, CDPK2, MPKs (involved in calcium and kinase signaling pathways) and reduced expression of metal transporters (IRT1 and HMA3) genes. This reduction in metal transporters gene expression is a probable reason for low toxicity effect of Cd in root after Me-JA treatment which has potential implications in reducing the risk of Cd in the food chain.


Assuntos
Antioxidantes , Cajanus , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Cádmio/metabolismo , Cajanus/metabolismo , Fenol/metabolismo , Fenóis/metabolismo , Plântula , Flavonoides
13.
Environ Res ; 239(Pt 1): 117192, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37748672

RESUMO

A wide array of environmental pollutants is often generated and released into the ecosystem from industrial and human activities. Antibiotics, phenolic compounds, hydroquinone, industrial dyes, and Endocrine-Disrupting Chemicals (EDCs) are prevalent pollutants in water matrices. To promote environmental sustainability and minimize the impact of these pollutants, it is essential to eliminate such contaminants. Although there are multiple methods for pollutants removal, many of them are inefficient and environmentally unfriendly. Horseradish peroxidase (HRP) has been widely explored for its ability to oxidize the aforementioned pollutants, both alone and in combination with other peroxidases, and in an immobilized way. Numerous positive attributes make HRP an excellent biocatalyst in the biodegradation of diverse environmentally hazardous pollutants. In the present review, we underlined the major advancements in the HRP for environmental research. Numerous immobilization and combinational studies have been reviewed and summarized to comprehend the degradability, fate, and biotransformation of pollutants. In addition, a possible deployment of emerging computational methodologies for improved catalysis has been highlighted, along with future outlook and concluding remarks.


Assuntos
Ecossistema , Poluentes Ambientais , Humanos , Peroxidase do Rábano Silvestre , Peroxidases , Catálise , Antibacterianos
14.
Nano Lett ; 23(17): 7775-7781, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37603598

RESUMO

Forming atomic-scale contacts with attractive geometries and material compositions is a long-term goal of nanotechnology. Here, we show that a rich family of bimetallic atomic-contacts can be fabricated in break-junction setups. The structure and material composition of these contacts can be controlled by atomically precise electromigration, where the metal types of the electron-injecting and sink electrodes determine the type of atoms added to, or subtracted from, the contact structure. The formed bimetallic structures include, for example, platinum and aluminum electrodes bridged by an atomic chain composed of platinum and aluminum atoms as well as iron-nickel single-atom contacts that act as a spin-valve break junction without the need for sophisticated spin-valve geometries. The versatile nature of atomic contacts in bimetallic junctions and the ability to control their structure by electromigration can be used to expand the structural variety of atomic and molecular junctions and their span of properties.

15.
Gene ; 882: 147644, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37479094

RESUMO

Mycobacterium abscessus is an intrinsically and acquired multidrug resistant (MDR) intracellular pathogen with biofilm formation capability and limited option for treatment. Biofilm is the major characteristic that leads to failure and prolong treatment, intensifies treatment cost and increases mortality/morbidity rate. However, the biofilm formation regulations of M. abscessus remain largely unexplored. In this study, we identify the putative/hypothetical transcriptional regulator (TR) of M. abscessus that are involved in biofilm formation. This study includes fifty TRs belonging to thirteen different families viz., AraC, ArsR, AsnC, CarD, CdaR, GntR, IclR, LysR, MarR, PadR, PrrA, TetR and WhiB, including TRs of unknown family. The promoter of these putative TRs were fused individually with GFP and analyzed their expression using CLSM in planktonic phase and early, mid and mature stages of biofilm formation phase, which overall termed as biofilm formation cycle. Further, qRT-PCR was carried out for selected TRs to analyze their differential expressions. This study found thirteen numbers of TR belonging to TetR family, five TRs belonging to MarR family, four TRs of unannotated TR family, two AraC TRs, two LysR, two GntR, two AsnC, one each of ArsR family, CarD family, IclR family, PadR family, PrrA family and WhiB family selected for this study are involved in biofilm formation cycle. Our study characterized the TRs with respect to their role in biofilm formation for the first time in M. abscessus and also found that their biofilm formation is regulated by diverse TR families.


Assuntos
Mycobacterium abscessus , Humanos , Mycobacterium abscessus/genética , Biofilmes , Antibacterianos
16.
Multimed Tools Appl ; : 1-16, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37362712

RESUMO

The COVID 19 pandemic is highly contagious disease is wreaking havoc on people's health and well-being around the world. Radiological imaging with chest radiography is one among the key screening procedure. This disease contaminates the respiratory system and impacts the alveoli, which are small air sacs in the lungs. Several artificial intelligence (AI)-based method to detect COVID-19 have been introduced. The recognition of disease patients using features and variation in chest radiography images was demonstrated using this model. In proposed paper presents a model, a deep convolutional neural network (CNN) with ResNet50 configuration, that really is freely-available and accessible to the common people for detecting this infection from chest radiography scans. The introduced model is capable of recognizing coronavirus diseases from CT scan images that identifies the real time condition of covid-19 patients. Furthermore, the database is capable of tracking detected patients and maintaining their database for increasing accuracy of the training model. The proposed model gives approximately 97% accuracy in determining the above-mentioned results related to covid-19 disease by employing the combination of adopted-CNN and ResNet50 algorithms.

17.
Acta Radiol ; 64(8): 2431-2438, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37192645

RESUMO

BACKGROUND: Scalp arteriovenous malformations (AVMs), or cirsoid aneurysms of the scalp, usually present with troublesome symptoms and cosmetic disfigurement. Endovascular/percutaneous embolization has evolved as a sole treatment method or adjunct to surgical excision in the management of scalp AVMs with an excellent outcome. PURPOSE: To discuss minimally invasive techniques for treating scalp AVMs as well as to highlight the role of embolization before surgery. MATERIAL AND METHODS: This is a retrospective study of 50 patients with scalp AVM who underwent embolization (percutaneous/endovascular) during 2010-2019 at a tertiary care center. n-butyl cyanoacrylate (n-BCA) was used as an embolizing agent in all the cases and the patients were followed up at three- and six-month intervals with Doppler evaluation. RESULTS: A total of 50 patients were included in the study. The occipital region was the most common location; 82% were Schobinger class II lesions and 18% were class III lesions. Thirteen patients had small-sized AVMs and 37 patients had large-sized AVMs. Post-embolization surgery was performed in 36 patients. Of the patients, 28 underwent percutaneous embolization, 20 underwent endovascular embolization, and two underwent both to achieve complete embolization of the lesion. The number of percutaneous procedures increased in the latter half of the study period as the safety and efficacy of the technique were established. No major complications were seen in this study. CONCLUSION: Embolization of scalp AVMs is a safe and effective technique and can be used in isolation for small lesions and as an adjunct procedure to surgery for large-sized lesions.


Assuntos
Embolização Terapêutica , Malformações Arteriovenosas Intracranianas , Humanos , Malformações Arteriovenosas Intracranianas/cirurgia , Estudos Retrospectivos , Couro Cabeludo/irrigação sanguínea , Resultado do Tratamento , Embolização Terapêutica/métodos , Punções
18.
Int J Biol Macromol ; 242(Pt 3): 124968, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37217044

RESUMO

Lignin modifying enzymes (LMEs) have gained widespread recognition in depolymerization of lignin polymers by oxidative cleavage. LMEs are a robust class of biocatalysts that include lignin peroxidase (LiP), manganese peroxidase (MnP), versatile peroxidase (VP), laccase (LAC), and dye-decolorizing peroxidase (DyP). Members of the LMEs family act on phenolic, non-phenolic substrates and have been widely researched for valorization of lignin, oxidative cleavage of xenobiotics and phenolics. LMEs implementation in the biotechnological and industrial sectors has sparked significant attention, although its potential future applications remain underexploited. To understand the mechanism of LMEs in sustainable pollution mitigation, several studies have been undertaken to assess the feasibility of LMEs in correlating to diverse pollutants for binding and intermolecular interactions at the molecular level. However, further investigation is required to fully comprehend the underlying mechanism. In this review we presented the key structural and functional features of LMEs, including the computational aspects, as well as the advanced applications in biotechnology and industrial research. Furthermore, concluding remarks and a look ahead, the use of LMEs coupled with computational framework, built upon artificial intelligence (AI) and machine learning (ML), has been emphasized as a recent milestone in environmental research.


Assuntos
Inteligência Artificial , Lignina , Lignina/química , Peroxidases/metabolismo , Biotecnologia , Lacase , Fenóis
19.
J Cell Biochem ; 124(7): 961-973, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37204112

RESUMO

Adipogenesis, that is, the formation of terminally differentiated adipocytes is intricately regulated by transcription factors where CCAAT/enhancer binding protein alpha (C/EBPα) plays a key role. In the current study, we demonstrate that E3 ubiquitin ligase AIP4 negatively regulates C/EBPα protein stability leading to reduced adipogenesis. While AIP4 overexpression in 3T3-L1 cells preadipocytes inhibited lipid accumulation when treated with differentiation inducing media (MDI), AIP4 depletion was sufficient to partially promote lipid accumulation even in the absence of MDI. Mechanistically, overexpression of AIP4 inhibited protein levels of both ectopically expressed as well as endogenous C/EBPα while catalytically inactive AIP4 failed. On the contrary, AIP4 depletion profoundly enhanced endogenous C/EBPα protein levels. The observation that AIP4 levels decrease with concomitant increase in C/EBPα levels during adipocyte differentiation further indicated that AIP4 negatively regulates C/EBPα levels. We further show that AIP4 physically interacts with C/EBPα and ubiquitinates it leading to its proteasomal degradation. AIP4 promoted K48-linked ubiquitination of C/EBPα while catalytically inactive AIP4-C830A failed. Taken together, our data demonstrate that AIP4 inhibits adipogenesis by targeting C/EBPα for ubiquitin-mediated proteasome degradation.


Assuntos
Adipogenia , Proteína alfa Estimuladora de Ligação a CCAAT , Ubiquitina-Proteína Ligases , Ubiquitina , Animais , Camundongos , Células 3T3-L1 , Adipócitos/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Diferenciação Celular , Lipídeos , PPAR gama/metabolismo , Ubiquitina/metabolismo , Proteólise , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
20.
Cell Biol Int ; 47(7): 1247-1258, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36950830

RESUMO

Ormeloxifene (ORM) (3,4-trans-2,2-dimethyl-3-phenyl-4-p-(ß-pyrrolidinoethoxy) phenyl-7-methoxychroman), world's first nonsteroidal selective estrogen receptor modulator approved for contraception in India has been shown to have potential anticancer activities. Here, we show that ORM can induce megakaryocyte and myeloid (granulocytic) but not erythroid differentiation in multipotent human myeloid leukemia cell line K562. We show that ORM at an IC50 of 7.5 µM can induce morphological changes similar to megakaryocytes in K562 cells. ORM led to increase in levels of megakaryocytic differentiation markers (CD41 and CD61) as well as key transcription factors GATA1 and AML1. We further show that ORM induces megakaryocytic differentiation in K562 cells through ERK activation and induction of autophagy in a fashion similar to other known inducers of megakaryocytic differentiation such as phorbol esters. In addition, as shown earlier, we yet again observed that ORM led to activation of caspases since their inhibition through pan-caspase inhibitor mitigated megakaryocytic differentiation as they led to significant decrease in CD41 and CD61. Because induction of megakaryocytic differentiation in K562 involves growth arrest and exit from cell cycle, we also observed an increase in levels of p21 and p27 with decrease in c-Myc protein levels in K562 cells treated with 7.5 µM ORM for 24 and 48 h, respectively. Taken together, these findings indicate that ORM can markedly induce megakaryocytic differentiation in K562 cells.


Assuntos
Leucemia , Megacariócitos , Humanos , Megacariócitos/metabolismo , Células K562 , Diferenciação Celular/fisiologia
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