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1.
FEBS J ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110129

RESUMEN

CCAAT/enhancer-binding protein α (C/EBPα), a key myeloid transcription factor, drives myeloid differentiation from blast cells by regulating the expression of granulocyte colony stimulating factor receptor and C/EBPε as required for promoting granulocyte differentiation. Here, we show that serine/threonine-protein kinase NLK, also known as Nemo-like kinase, physically associates with C/EBPα and phosphorylates it at multiple sites, including Ser21, Thr226, Thr230 and S234, leading to its ubiquitin-mediated degradation. Individual phospho-point mutants of C/EBPα could be phosphorylated by NLK, but a mutant with all phosphorylatable residues replaced by alanine resisted phosphorylation and degradation by NLK, as did the single point mutants. Furthermore, although ectopic expression of NLK enhanced phosphorylation of C/EBPα levels, it markedly inhibited total C/EBPα protein levels. Conversely, NLK depletion inhibited endogenous C/EBPα phosphorylation but enhanced its total protein levels in several acute myeloid leukemia (AML) cell lines and in peripheral blood mononuclear cells isolated from number of AML patient samples. Importantly, NLK depletion in peripheral blood mononuclear cells from primary AML patients not only restored C/EBPα protein levels, but also induced myeloid differentiation, suggesting that NLK could be therapeutically targeted to restore C/EBPα to resolve differentiation arrest in AML.

2.
J Cell Physiol ; : e31388, 2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39034451

RESUMEN

Runt-related transcription factor 2 (Runx2) is a key regulator of osteoblast differentiation and bone formation. In Runx2-deficient embryos, skeletal development ceases at the cartilage anlage stage. These embryos die of respiratory failure upon birth and display a complete absence of bone and cartilage mineralization. Here, we identified Hakai, a type of E3 ubiquitin ligase as a potential Runx2 interacting partner through affinity pulldown-based proteomic approach. Subsequently, we observed that similar to Runx2, Hakai was downregulated in osteopenic ovariectomized rats, suggesting its involvement in bone formation. Consistent with this observation, Hakai overexpression significantly enhanced osteoblast differentiation in mesenchyme-like C3H10T1/2 as well as primary rat calvaria osteoblast (RCO) cells in vitro. Conversely, overexpression of a catalytically inactive Hakai mutant (C109A) exhibited minimal to no effect, whereas Hakai depletion markedly reduced endogenous Runx2 levels and impaired osteogenic differentiation in both C3H10T1/2 and RCOs. Mechanistically, Hakai physically interacts with Runx2 and enhances its protein turnover by rescuing it from Smad ubiquitination regulatory factor 2 (Smurf2)-mediated proteasome degradation. Wild-type Hakai but not Hakai-C109A inhibited Smurf2 protein levels through proteasome-mediated degradation. These findings underscore Hakai's functional role in bone formation, primarily through its positive modulation of Runx2 protein turnover by protecting it from Smurf2-mediated ubiquitin-proteasomal degradation. Collectively, our results demonstrate Hakai as a promising novel therapeutic target for osteoporosis.

3.
Curr Top Med Chem ; 24(21): 1829-1855, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919089

RESUMEN

Tuberculosis (TB) is one of the leading causes of death world-wide after AIDS. It infects around one-third of global population and approximately two million people die annually from this disease because it is a very contagious disease spread by Mycobacterium tuberculosis. The increasing number of drug-resistant strains and the failure of conventional treatments against this strain are the challenges of the coming decades. New therapeutic techniques aim to confirm cure without deterioration, to reduce deaths, contagions and the formation of drug-resistant strains. A plethora of new diagnostic tests are available to diagnose the active tuberculosis, screen latent M. tuberculosis infection, and to identify drug-resistant strains of M. tuberculosis. When effective prevention strategies do not prevail, high rates of early case detection and successive cures to control TB emergence would not be possible. In this review, we discussed the structural features of M. tuberculosis, Multi drug resistance tuberculosis (MDR-TB), extremely drug-resistant tuberculosis (XDR-TB), the mechanism of M. tuberculosis infection, the mode of action of first and second-line antitubercular drugs, the mechanism of resistance to the existing drugs, compounds in preclinical and clinical trial and drugs presently available for the treatment of tuberculosis. Moreover, the new diagnostic techniques to detect M. tuberculosis are also discussed in this review.


Asunto(s)
Antituberculosos , Mycobacterium tuberculosis , Antituberculosos/farmacología , Antituberculosos/química , Humanos , Mycobacterium tuberculosis/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/diagnóstico
4.
Chemosphere ; 362: 142678, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38908452

RESUMEN

The excessive usage of agrochemicals, including pesticides, along with various reckless human actions, has ensued discriminating prevalence of pesticides and heavy metals (HMs) in crop plants and the environment. The enhanced exposure to these chemicals is a menace to living organisms. The pesticides may get bioaccumulated in the food chain, thereby leading to several deteriorative changes in the ecosystem health and a rise in the cases of some serious human ailments including cancer. Further, both HMs and pesticides cause some major metabolic disturbances in plants, which include oxidative burst, osmotic alterations and reduced levels of photosynthesis, leading to a decline in plant productivity. Moreover, the synergistic interaction between pesticides and HMs has a more serious impact on human and ecosystem health. Various attempts have been made to explore eco-friendly and environmentally sustainable methods of improving plant health under HMs and/or pesticide stress. Among these methods, the employment of PGPR can be a suitable and effective strategy for managing these contaminants and providing a long-term remedy. Although, the application of PGPR alone can alleviate HM-induced phytotoxicities; however, several recent reports advocate using PGPR with other micro- and macro-organisms, biochar, chelating agents, organic acids, plant growth regulators, etc., to further improve their stress ameliorative potential. Further, some PGPR are also capable of assisting in the degradation of pesticides or their sequestration, reducing their harmful effects on plants and the environment. This present review attempts to present the current status of our understanding of PGPR's potential in the remediation of pesticides and HMs-contaminated soil for the researchers working in the area.


Asunto(s)
Biodegradación Ambiental , Metales Pesados , Plaguicidas , Contaminantes del Suelo , Metales Pesados/metabolismo , Metales Pesados/análisis , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/análisis , Plaguicidas/metabolismo , Plaguicidas/análisis , Microbiología del Suelo , Suelo/química , Plantas/metabolismo , Plantas/efectos de los fármacos
5.
J Microbiol ; 62(7): 511-523, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38904697

RESUMEN

Alcaligenes faecalis is one of the most important and clinically significant environmental pathogens, increasing in importance due to its isolation from soil and nosocomial environments. The Gram-negative soil bacterium is associated with skin endocarditis, bacteremia, dysentery, meningitis, endophthalmitis, urinary tract infections, and pneumonia in patients. With emerging antibiotic resistance in A. faecalis, it has become crucial to understand the origin of such resistance genes within this clinically significant environmental and gut bacterium. In this research, we studied the impact of antibiotic overuse in poultry and its effect on developing resistance in A. faecalis. We sampled soil and faecal materials from five poultry farms, performed whole genome sequencing & analysis and identified four strains of A. faecalis. Furthermore, we characterized the genes in the genomic islands of A. faecalis isolates. We found four multidrug-resistant A. faecalis strains that showed resistance against vancomycin (MIC >1000 µg/ml), ceftazidime (50 µg/ml), colistin (50 µg/ml) and ciprofloxacin (50 µg/ml). From whole genome comparative analysis, we found more than 180 resistance genes compared to the reference sequence. Parts of our assembled contigs were found to be similar to different bacteria which included pbp1A and pbp2 imparting resistance to amoxicillin originally a part of Helicobacter and Bordetella pertussis. We also found the Mycobacterial insertion element IS6110 in the genomic islands of all four genomes. This prominent insertion element can be transferred and induce resistance to other bacterial genomes. The results thus are crucial in understanding the transfer of resistance genes in the environment and can help in developing regimes for antibiotic use in the food and poultry industry.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Granjas , Aves de Corral , Microbiología del Suelo , Animales , Farmacorresistencia Bacteriana Múltiple/genética , Aves de Corral/microbiología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Variación Genética , Secuenciación Completa del Genoma , Islas Genómicas , Alcaligenes faecalis/genética , Alcaligenes faecalis/aislamiento & purificación , Alcaligenes faecalis/efectos de los fármacos , Genoma Bacteriano , Heces/microbiología , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/veterinaria
6.
ACS Appl Mater Interfaces ; 16(27): 35438-35446, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38937139

RESUMEN

Moiré superlattices with a robust twist proximity effect in the low-dimensional regime can facilitate nanoscale thermoelectric devices. In pristine systems, the low efficiency and lack of proficient control of thermoelectric properties impede desirable advancements in the field of energy conversion. In the present study, we demonstrate remarkable macroscopic thermoelectric response as a consequence of microscopic band structure modulation via the twist proximity in an engineered CrI3/1T-MoS2 moiré superlattice. The local twist effect, which leads to the microscopic phenomena of electron localization, results in a comprehensive electronic structure modulation. Consequently, these local effects convolute the macroscopic thermoelectric effect. Additionally, flat bands and angle-dependent metallic to semiconducting transitions are observed at 10.89, 23.41, and 30° twist angles. We correlate the observed phenomenon with the augmented spin-charge transport and interconversion via the twist proximity effect in its semiconducting phase. The estimated ultralow electronic and lattice thermal conductivities further corroborate with the observed large figure of merit and Seebeck coefficient. The maximum values of the Seebeck coefficient and figure of merit are estimated to be ∼413 µV/K and ∼4.3 at 200 K for 30° under the constant time relaxation approach. The twist-endowed outstanding thermoelectric effect in moiré superlattices with band modulation unveils a distinctive approach to establish efficient thermoelectric devices.

7.
Australas J Dermatol ; 65(5): 437-443, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38762801

RESUMEN

BACKGROUND: Female-pattern hair loss (FPHL) is characterized by decreased scalp hair density, thinning of hair shafts, and progressive miniaturization of hair follicles. OBJECTIVE: To compare the safety and efficacy of spironolactone versus bicalutamide in female pattern hair loss [FPHL]. METHODS: The study design was retrospective, and all eligible females aged between 18 years and 50 years with FPHL were included. We identified 120 patients from our database who fulfilled the inclusion and exclusion criteria, and patients were then categorized into two groups, Group A comprising patients who were taking 100 mg of spironolactone once daily and Group B comprising patients who were taking 50 mg of bicalutamide once daily along with topical minoxidil 2% in both groups. Patient were analysed at approximately at 24 weeks from the commencement of the treatment. RESULTS: Mean reduction in hair loss severity score on Sinclair scale was 19.51% in spironolactone group compared to 28.20% in bicalutamide group at 24 weeks, which was statistically significant. On global photographic assessment, marked improvement was seen in bicalutamide group compared to spironolactone group (p = 0.139). CONCLUSIONS: Our study, though limited by its retrospective design and small sample size, showed that bicalutamide has greater efficacy and better safety profile in comparison to spironolactone in the treatment of FPHL.


Asunto(s)
Alopecia , Anilidas , Nitrilos , Espironolactona , Compuestos de Tosilo , Humanos , Femenino , Espironolactona/uso terapéutico , Espironolactona/efectos adversos , Anilidas/efectos adversos , Anilidas/uso terapéutico , Estudios Retrospectivos , Alopecia/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Compuestos de Tosilo/efectos adversos , Compuestos de Tosilo/uso terapéutico , Nitrilos/efectos adversos , Nitrilos/uso terapéutico , Nitrilos/administración & dosificación , Adulto Joven , Minoxidil/uso terapéutico , Minoxidil/efectos adversos , Resultado del Tratamiento , Adolescente , Índice de Severidad de la Enfermedad
8.
J Phys Condens Matter ; 36(30)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38653260

RESUMEN

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 TE and magnetic materials in the 2D limit offers access to control longitudinal as well as transverse TE properties via magnetic proximity effect. Herein, we design a van der Waals (vdW) heterostructure of metallic 1T-MoS2with promising TE properties and a layer-dependent magnetic CrI3material. The result highlights exotic electronic and magnetic configurations of the designed monolayer-CrI3/1T-MoS2vdW 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-1and 12.30%, respectively. To this end, the semiconducting CrI3layer with intrinsic magnetism leads to efficient control and tunability of the observed spin-correlated anomalous Nernst effect. Moreover, a large dimensionless figure of merit of ∼6 and a power factor of∼3.8×1011/τ∘ Wm-1K-2s-1near the Fermi level at 300 K 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 TE devices.

9.
Biochem J ; 481(10): 653-666, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38666590

RESUMEN

E3 ubiquitin ligase, ring finger protein 138 (RNF138) is involved in several biological processes; however, its role in myeloid differentiation or tumorigenesis remains unclear. RNAseq data from TNMplot showed that RNF138 mRNA levels are highly elevated in acute myeloid leukemia (AML) bone marrow samples as compared with bone marrow of normal volunteers. Here, we show that RNF138 serves as an E3 ligase for the tumor suppressor CCAAT/enhancer binding protein (C/EBPα) and promotes its degradation leading to myeloid differentiation arrest in AML. Wild-type RNF138 physically interacts with C/EBPα and promotes its ubiquitin-dependent proteasome degradation while a mutant RNF-138 deficient in ligase activity though interacts with C/EBPα, fails to down-regulate it. We show that RNF138 depletion enhances endogenous C/EBPα levels in peripheral blood mononuclear cells (PBMCs) isolated from healthy volunteers. Our data further shows that RNF138-mediated degradation of C/EBPα negatively affects its transactivation potential on its target genes. Furthermore, RNF138 overexpression inhibits all-trans-retinoic acid-induced differentiation of HL-60 cells whereas RNF138 RNAi enhances. In line with RNF138 inhibiting C/EBPα protein turnover, we also observed that RNF138 overexpression inhibited ß-estradiol (E2)-induced C/EBPα driven granulocytic differentiation in C/EBPα inducible K562-p42C/EBPα-estrogen receptor cells. Furthermore, we also recapitulated these findings in PBMCs isolated from AML patients where depletion of RNF138 increased the expression of myeloid differentiation marker CD11b. These results suggest that RNF138 inhibits myeloid differentiation by targeting C/EBPα for proteasomal degradation and may provide a plausible mechanism for loss of C/EBPα expression often observed in myeloid leukemia. Also, targeting RNF138 may resolve differentiation arrest by restoring C/EBPα expression in AML.


Asunto(s)
Proteína alfa Potenciadora de Unión a CCAAT , Diferenciación Celular , Leucemia Mieloide Aguda , Ubiquitina-Proteína Ligasas , Humanos , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Proteína alfa Potenciadora de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT , Diferenciación Celular/genética , Células HEK293 , Células HL-60 , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Proteolisis , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
10.
ACS Omega ; 9(9): 10748-10768, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38463293

RESUMEN

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.

11.
J Cell Physiol ; 239(5): e31217, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38327035

RESUMEN

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.


Asunto(s)
Diferenciación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Osteoblastos , Osteogénesis , Ubiquitina-Proteína Ligasas , Ubiquitinación , Animales , Femenino , Humanos , Ratones , Ratas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Células HEK293 , Osteoblastos/metabolismo , Ovariectomía , Complejo de la Endopetidasa Proteasomal/metabolismo , Estabilidad Proteica , Ratas Sprague-Dawley , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética
13.
ACS Omega ; 9(7): 7529-7544, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38405466

RESUMEN

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.

14.
ACG Case Rep J ; 11(2): e01271, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38371471

RESUMEN

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.

15.
Biometals ; 37(4): 755-772, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38206521

RESUMEN

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.


Asunto(s)
Cadmio , Ciclopentanos , Oxilipinas , Plantas , Transducción de Señal , Cadmio/toxicidad , Cadmio/metabolismo , Plantas/metabolismo , Plantas/efectos de los fármacos , Oxilipinas/metabolismo , Transducción de Señal/efectos de los fármacos , Ciclopentanos/metabolismo , Especies Reactivas de Oxígeno/metabolismo
16.
Phys Chem Chem Phys ; 26(2): 895-902, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38087955

RESUMEN

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.

17.
Environ Res ; 241: 117579, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-37944691

RESUMEN

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.


Asunto(s)
Contaminantes Ambientales , Nanotubos de Carbono , Contaminantes Ambientales/metabolismo , Biodegradación Ambiental , Catálisis , Sustancias Peligrosas
18.
Nat Prod Res ; 38(6): 1080-1084, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37157823

RESUMEN

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.


Asunto(s)
Antineoplásicos , Neoplasias , Semecarpus , Ratones , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Neoplasias/tratamiento farmacológico , Nueces
19.
Chemosphere ; 346: 140681, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37951403

RESUMEN

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.


Asunto(s)
Antioxidantes , Cajanus , Antioxidantes/farmacología , Antioxidantes/metabolismo , Cadmio/metabolismo , Cajanus/metabolismo , Fenol/metabolismo , Fenoles/metabolismo , Plantones , Flavonoides
20.
Int J Biol Macromol ; 258(Pt 1): 128780, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38104688

RESUMEN

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.


Asunto(s)
Leucodistrofia Metacromática , Sulfotransferasas , Humanos , Leucodistrofia Metacromática/metabolismo , Sulfoglicoesfingolípidos , Vaina de Mielina/metabolismo , Neuronas/metabolismo
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