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1.
Small ; 20(23): e2310946, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38229536

RESUMO

Owing to their extraordinary photophysical properties, organometal halide perovskites are emerging as a new material class for X-ray detection. However, the existence of toxic lead makes their commercialization questionable and should readily be replaced. Accordingly, several lead alternatives have been introduced into the framework of conventional perovskites, resulting in various new perovskite dimensionalities. Among these, Pb-free lower dimensional perovskites (LPVKs) not only show promising X-ray detecting properties due to their higher ionic migration energy, wider and tunable energy bandgap, smaller dark currents, and structural versatility but also exhibit extended environmental stability. Herein, first, the structural organization of the PVKs (including LPVKs) is summarized. In the context of X-ray detectors (XDs), the outstanding properties of the LPVKs and active layer synthesis routes are elaborated afterward. Subsequently, their applications in direct XDs are extensively discussed and the device performance, in terms of the synthesis method, device architecture, active layer size, figure of merits, and device stability are tabulated. Finally, the review is concluded with an in-depth outlook, thoroughly exploring the present challenges to LPVKs XDs, proposing innovative solutions, and future directions. This review provides valuable insights into optimizing non-toxic Pb-free perovskite XDs, paving the way for future advancements in the field.

2.
J Exp Zool B Mol Dev Evol ; 342(2): 85-100, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38369890

RESUMO

TRPS1 serves as the causative gene for tricho-rhino phalangeal syndrome, known for its craniofacial and skeletal abnormalities. The Trps1 gene encodes a protein that represses Wnt signaling through strong interactions with Wnt signaling inhibitors. The identification of genomic cis-acting regulatory sequences governing Trps1 expression is crucial for understanding its role in embryogenesis. Nevertheless, to date, no investigations have been conducted concerning these aspects of Trps1. To identify deeply conserved noncoding elements (CNEs) within the Trps1 locus, we employed a comparative genomics approach, utilizing slowly evolving fish such as coelacanth and spotted gar. These analyses resulted in the identification of eight CNEs in the intronic region of the Trps1 gene. Functional characterization of these CNEs in zebrafish revealed their regulatory potential in various tissues, including pectoral fins, heart, and pharyngeal arches. RNA in-situ hybridization experiments revealed concordance between the reporter expression pattern induced by the identified set of CNEs and the spatial expression pattern of the trps1 gene in zebrafish. Comparative in vivo data from zebrafish and mice for CNE7/hs919 revealed conserved functions of these enhancers. Each of these eight CNEs was further investigated in cell line-based reporter assays, revealing their repressive potential. Taken together, in vivo and in vitro assays suggest a context-dependent dual functionality for the identified set of Trps1-associated CNE enhancers. This functionally characterized set of CNE-enhancers will contribute to a more comprehensive understanding of the developmental roles of Trps1 and can aid in the identification of noncoding DNA variants associated with human diseases.


Assuntos
Dedos/anormalidades , Doenças do Cabelo , Síndrome de Langer-Giedion , Nariz/anormalidades , Sequências Reguladoras de Ácido Nucleico , Peixe-Zebra , Animais , Camundongos , Humanos , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Genoma , Sequência de Bases , Expressão Gênica , Mamíferos/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
3.
Mol Ecol ; 33(21): e17356, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38634782

RESUMO

DNA methylation has been proposed to be an important mechanism that allows plants to respond to their environments sometimes entirely uncoupled from genetic variation. To understand the genetic basis, biological functions and climatic relationships of DNA methylation at a population scale in Arabidopsis thaliana, we performed a genome-wide association analysis with high-quality single nucleotide polymorphisms (SNPs), and found that ~56% on average, especially in the CHH sequence context (71%), of the differentially methylated regions (DMRs) are not tagged by SNPs. Among them, a total of 3235 DMRs are significantly associated with gene expressions and potentially heritable. 655 of the 3235 DMRs are associated with climatic variables, and we experimentally verified one of them, HEI10 (HUMAN ENHANCER OF CELL INVASION NO.10). Such epigenetic loci could be subjected to natural selection thereby affecting plant adaptation, and would be expected to be an indicator of accessions at risk. We therefore incorporated these climate-related DMRs into a gradient forest model, and found that the natural A. thaliana accessions in Southern Europe that may be most at risk under future climate change. Our findings highlight the importance of integrating DNA methylation that is independent of genetic variations, and climatic data to predict plants' vulnerability to future climate change.


Assuntos
Arabidopsis , Mudança Climática , Metilação de DNA , Epigênese Genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Arabidopsis/genética , Polimorfismo de Nucleotídeo Único/genética , Adaptação Fisiológica/genética , Clima , Seleção Genética , Europa (Continente)
4.
Dev Growth Differ ; 66(1): 75-88, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37925606

RESUMO

Abnormal expression of the transcriptional regulator and hedgehog (Hh) signaling pathway effector Gli3 is known to trigger congenital disease, most frequently affecting the central nervous system (CNS) and the limbs. Accurate delineation of the genomic cis-regulatory landscape controlling Gli3 transcription during embryonic development is critical for the interpretation of noncoding variants associated with congenital defects. Here, we employed a comparative genomic analysis on fish species with a slow rate of molecular evolution to identify seven previously unknown conserved noncoding elements (CNEs) in Gli3 intronic intervals (CNE15-21). Transgenic assays in zebrafish revealed that most of these elements drive activities in Gli3 expressing tissues, predominantly the fins, CNS, and the heart. Intersection of these CNEs with human disease associated SNPs identified CNE15 as a putative mammalian craniofacial enhancer, with conserved activity in vertebrates and potentially affected by mutation associated with human craniofacial morphology. Finally, comparative functional dissection of an appendage-specific CNE conserved in slowly evolving fish (elephant shark), but not in teleost (CNE14/hs1586) indicates co-option of limb specificity from other tissues prior to the divergence of amniotes and lobe-finned fish. These results uncover a novel subset of intronic Gli3 enhancers that arose in the common ancestor of gnathostomes and whose sequence components were likely gradually modified in other species during the process of evolutionary diversification.


Assuntos
Elementos Facilitadores Genéticos , Peixe-Zebra , Animais , Humanos , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Elementos Facilitadores Genéticos/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Animais Geneticamente Modificados , Mamíferos , Evolução Molecular , Sequência Conservada/genética
5.
Chem Rec ; 24(1): e202300233, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37695078

RESUMO

The ever-increasing threat of climate change and the depletion of fossil fuel resources necessitate the use of solar- and wind-based renewable energy sources. Large-scale energy storage technologies, such as redox flow batteries (RFBs), offer a continuous supply of energy. Depending on the nature of the electrolytes used, RFBs are broadly categorized into aqueous redox flow batteries (ARFBs) and non-aqueous redox flow batteries (NARFBs). ARFBs suffer from various problems, including low conductivity of electrolytes, inferior charge/discharge current densities, high-capacity fading, and lower energy densities. NARFBs offer a wider potential window and range of operating temperatures, faster electron transfer kinetics, and higher energy densities. In this review article, a critical analysis is provided on the design of organic electroactive molecules, their physiochemical/electrochemical properties, and various organic solvents used in NARFBs. Furthermore, various redox-active organic materials, such as metal-based coordination complexes, quinones, radicals, polymers, and miscellaneous electroactive species, explored for NARFBs during 2012-2023 are discussed. Finally, the current challenges and prospects of NARFBs are summarized.

6.
Chem Rec ; 24(1): e202300247, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37933973

RESUMO

The high-temperature solid oxide fuel cells (SOFCs) are the most efficient and green conversion technology for electricity generation from hydrogen-based fuel as compared to conventional thermal power plants. Many efforts have been made to reduce the high operating temperature (>800 °C) to intermediate/low operating temperature (400 °C

7.
Chem Rec ; 24(1): e202300171, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37606899

RESUMO

The global rapid transition from fossil fuels to renewable energy resources necessitates the implementation of long-duration energy storage technologies owing to the intermittent nature of renewable energy sources. Therefore, the deployment of grid-scale energy storage systems is inevitable. Sulfur-based batteries can be exploited as excellent energy storage devices owing to their intrinsic safety, low cost of raw materials, low risk of environmental hazards, and highest theoretical capacities (gravimetric: 2600 Wh/kg and volumetric: 2800 Wh/L). However, sulfur-based batteries exhibit certain scientific limitations, such as polysulfide crossover, which causes rapid capacity decay and low Coulombic efficiency, thereby hindering their implementation at a commercial scale. In this review article, we focus on the latest research developments between 2012-2023 to improve the separators/membranes and overcome the shuttle effect associated with them. Various categories of ion exchange membranes (IEMs) used in redox batteries, particularly polysulfide redox flow batteries and lithium-sulfur batteries, are discussed in detail. Furthermore, advances in IEM constituents are summarized to gain insights into different fundamental strategies for attaining targeted characteristics, and a critical analysis is proposed to highlight their efficiency in mitigating sulfur cross-shuttling issues. Finally, future prospects and recommendations are suggested for future research toward the fabrication of more effective membranes with desired properties.

8.
Chem Rec ; 24(1): e202300284, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38010347

RESUMO

In recent years, aqueous organic redox flow batteries (AORFBs) have attracted considerable attention due to advancements in grid-level energy storage capacity research. These batteries offer remarkable benefits, including outstanding capacity retention, excellent cell performance, high energy density, and cost-effectiveness. The organic electrolytes in AORFBs exhibit adjustable redox potentials and tunable solubilities in water. Previously, various types of organic electrolytes, such as quinones, organometallic complexes, viologens, redox-active polymers, and organic salts, were extensively investigated for their electrochemical performance and stability. This study presents an overview of recently published novel organic electrolytes for AORFBs in acidic, alkaline, and neutral environments. Furthermore, it delves into the current status, challenges, and prospects of AORFBs, highlighting different strategies to overcome these challenges, with special emphasis placed on their design, composition, functionalities, and cost. A brief techno-economic analysis of various aqueous RFBs is also outlined, considering their potential scalability and integration with renewable energy systems.

9.
Pak J Med Sci ; 40(3Part-II): 526-533, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356832

RESUMO

Objectives: To review published clinical trials which assessed the effects of deep transverse friction massage on pain and range of motion in patients with adhesive capsulitis. Methods: A systematic review was conducted according to PRISMA guidelines. Literature search was performed in MEDLINE, AMED, EMBASE, HMIC, CINAHL, PEDRO, and SPORTDiscus. Two independent reviewers performed screening of the articles retrieved from different databases. Clinical trials published in English language from the earliest record to March 2022 that reported effects of deep transverse friction massage/Cyriax's friction massage on pain and/or range of motion in patients with diagnosis of adhesive capsulitis were included. The Critical Appraisal Skills Programme was used for quality assessment of the included studies. Results: A total of six studies reporting on 226 adhesive capsulitis patients were included in the systematic review. All the six studies were randomized controlled clinical trials. On the Critical Appraisal Skills Programme tool, four of the six studies had a score of 8/11, while the other two studies received a score of 7/11 and 6/11. Out of these six trials, four reported that pain was significantly (P<0.05) improved in the deep transverse friction massage group as compared to the control group. Regarding range of motion outcome, five studies showed that range of motion was significantly (P<0.05) improved in the deep transverse friction massage group while only one study showed non-significant results. Conclusion: It can be concluded that deep transverse friction massage significantly relieves pain and improves the range of motion in individuals with adhesive capsulitis.

10.
Plant Mol Biol ; 113(6): 415-430, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37566350

RESUMO

Cadmium (Cd) is a non-essential heavy metal, assimilated in plant tissue with other nutrients, disturbing the ions' homeostasis in plants. The plant develops different mechanisms to tolerate the hazardous environmental effects of Cd. Recently studies found different miRNAs that are involved in Cd stress. In the current study, miR397 mutant lines were constructed to explore the molecular mechanisms of miR397 underlying Cd tolerance. Compared with the genetically modified line of overexpressed miR397 (artificial miR397, amiR397), the lines of downregulated miR397 (Short Tandem Target Mimic miR397, STTM miR397) showed more substantial Cd tolerance with higher chlorophyll a & b, carotenoid and lignin content. ICP-OES revealed higher cell wall Cd and low total Cd levels in STTM miR397 than in the wild-type and amiR397 plants.Further, the STTM plants produced fewer reactive oxygen species (ROS) and lower activity of antioxidants enzymes (e.g., catalase [CAT], malondialdehyde [MDA]) compared with amiR397 and wild-type plants after stress, indicating that silencing the expression of miR397 can reduce oxidative damage. In addition, the different family transporters' gene expression was much higher in the amiR397 plants than in the wild type and STTM miRNA397. Our results suggest that miR397 plays a role in Cd tolerance in Arabidopsis thaliana. Overexpression of miR397 could decrease Cd tolerance in plants by regulating the expression of LAC 2/4/17, changing the lignin content, which may play an important role in inducing different stress-tolerant mechanisms and protecting the cell from a hazardous condition. This study provides a basis to elucidate the functions of miR397 and the Cd stress tolerance mechanism in Arabidopsis thaliana.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Cádmio/metabolismo , Lignina/metabolismo , Clorofila A/metabolismo , Antioxidantes/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Regulação da Expressão Gênica de Plantas
11.
Ann Pharmacother ; 57(2): 141-147, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35658717

RESUMO

BACKGROUND: Vasoplegic shock occurs in up to 37% of cardiac surgery patients. We investigated the use of angiotensin II for treating vasoplegic shock in these patients. OBJECTIVES: We assessed clinical outcomes and mortality in patients undergoing cardiac surgery at our center between March 1, 2018 and October 31, 2020 who developed vasoplegic shock, comparing those who received angiotensin II with those who did not. METHODS: This was a retrospective chart review. Response to angiotensin II was defined as increase in or maintenance of mean arterial pressure (MAP) and decrease in background vasopressor dosage. RESULTS: Angiotensin II was administered to 7 patients (postoperatively in 4 patients [57.1%]) with vasoplegic shock and baseline norepinephrine equivalent (NEE) of 0.49 ± 0.08 µg/kg/min; 12 patients with vasoplegic shock did not receive angiotensin II. Within 3 hours of angiotensin II administration, NEE decreased by 38.0 ± 33.1%. Angiotensin patients were more likely to newly require renal replacement therapy (66.7% vs 9.1%, P = 0.03) and had a longer, although not statistically significant, postoperative stay (23.1 vs 14.0 days, P = 0.16). Despite higher NEE requirements at baseline (0.49 vs 0.30, P = 0.03) and over the next 48 hours in the angiotensin group, no between-group differences in 7-day mortality (14.3% vs 0.0%, P = 0.37) or 30-day mortality (28.6% vs 8.3%, P = 0.52) were noted. CONCLUSION AND RELEVANCE: In patients who developed vasoplegic shock after cardiac surgery, angiotensin II administration allowed immediate dosage reductions of other vasopressors while maintaining MAP. Despite its small sample size, this study adds to the paucity of data in these patients and highlights future research needs.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Choque , Veteranos , Humanos , Angiotensina II , Estudos Retrospectivos , Choque/tratamento farmacológico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Vasoconstritores/uso terapêutico , Norepinefrina/uso terapêutico
12.
Chem Rec ; 22(7): e202100327, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35253977

RESUMO

Environmental emissions of mercury from industrial waste and natural sources, even in trace amounts, are toxic to organisms and ecosystems. However, industrial-scale mercury detection is limited by the high cost, low sensitivity/specificity, and poor selectivity of the available analytical tools. This review summarizes the key sensors for mercury detection in aqueous environments: colorimetric-, electrochemical-, fluorescence-, and surface-enhanced Raman spectroscopy-based sensors reported between 2014-2021. It then compares the performances of these sensors in the determination of inorganic mercury (Hg2+ ) and methyl mercury (CH3 Hg+ ) species in aqueous samples. Mercury sensors for aquatic applications still face serious challenges in terms of difficult deployment in remote areas and low robustness, reliability, and selectivity in harsh environments. We provide future perspectives on the selective detection of organomercury species, which are especially toxic and reactive in aquatic environments. This review is intended as a valuable resource for scientists in the field of mercury sensing.


Assuntos
Mercúrio , Poluentes Químicos da Água , Ecossistema , Reprodutibilidade dos Testes , Água , Poluentes Químicos da Água/análise
13.
Chem Rec ; 22(7): e202200059, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35581148

RESUMO

Among several anions, iodide (I- ) ions play a crucial role in human biological activities. In it's molecular form (I2 ), iodine is utilized for several industrial applications such as syntheses of medicines, fabric dyes, food additives, solar cell electrolytes, catalysts, and agrochemicals. The excess or deficiency of I- ions in the human body and environmental samples have certain consequences. Therefore, the selective and sensitive detection of I- ions in the human body and environment is vital for monitoring their overall profile. Amongst various analytical techniques for the estimation of I- ions, optical-chemical sensing possesses the merits of high sensitivity, selectivity, and utilizing the least amount of sensing materials. The distinctive aims of this manuscript are (i) To comprehensively review the development of optical chemical sensors (fluorescent & colorimetric) reported between 2001-2021 using organic fluorescent molecules, supramolecular materials, conjugated polymers, and metal-organic frameworks (MOFs). (ii) To illustrate the design and synthetic strategies to create specific binding and high affinity of I- ions which could help minimize negative consequences associated with its large size and high polarizability. (iii) The challenges associated with sensitivity and selectivity of I- ions in aqueous and real samples. The probable future aspects concerning the optical chemical detection of I- ions have also been discussed in detail.


Assuntos
Iodetos , Estruturas Metalorgânicas , Humanos , Íons , Estruturas Metalorgânicas/química , Polímeros , Água
14.
Chem Rec ; 22(7): e202100336, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35257485

RESUMO

The future challenges associated with the shortage of fossil fuels and their current environmental impacts intrigued the researchers to look for alternative ways of generating green energy. Solar-driven water splitting into oxygen and hydrogen is one of those advanced strategies. Researchers have studied various semiconductor materials to achieve potential results. However, it encountered multiple challenges such as high cost, low photostability and efficiency, and required multistep modifications. The conjugated polymers (CPs) have emerged as promising alternatives for conventional inorganic semiconductors. The CPs offer low cost, sufficient light absorption efficiency, excellent photo and chemical stability, and molecular optoelectronic tunable characteristics. Furthermore, organic CPs also present higher flexibility to tune the basic framework of the backbone of the polymers, amendments in the sidechain to incorporate desired functionalities, and much-needed porosity to serve better for photocatalytic applications. This review article summarizes the recent advancements made in visible-light-driven water splitting covering the aspects of synthetic strategies and experimental parameters employed for water splitting reactions with special emphasis on conjugated polymers such as linear CPs, planarized CPs, graphitic carbon nitride (g-C3 N4 ), conjugated microporous polymers (CMPs), covalent organic frameworks (COFs), and conjugated polymer-based nanocomposites (CPNCs). The current challenges and future prospects have also been described briefly.

15.
Int J Mol Sci ; 23(24)2022 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-36555815

RESUMO

Abscisic acid (ABA) is an important plant hormone that regulates numerous functions in plant growth, development, and stress responses. Several proteins regulate the ABA signal transduction mechanism in response to environmental stress. Among them, the PYR1/PYL/RCAR family act as ABA receptors. This study used the CRISPR/Cas9 gene-editing system with a single gRNA to knock out three soybean PYL genes: GmPYL17, GmPYL18, and GmPYL19. The gRNA may efficiently cause varying degrees of deletion of GmPYL17, GmPYL18, and GmPYL19 gene target sequences, according to the genotyping results of T0 plants. A subset of induced alleles was successfully transferred to progeny. In the T2 generation, we obtained double and triple mutant genotypes. At the seed germination stage, CRISPR/Cas9-created GmPYL gene knockout mutants, particularly gmpyl17/19 double mutants, are less susceptible to ABA than the wild type. RNA-Seq was used to investigate the differentially expressed genes related to the ABA response from germinated seedlings under diverse treatments using three biological replicates. The gmpyl17/19-1 double mutant was less susceptible to ABA during seed germination, and mutant plant height and branch number were higher than the wild type. Under ABA stress, the GO enrichment analysis showed that certain positive germination regulators were activated, which reduced ABA sensitivity and enhanced seed germination. This research gives a theoretical basis for a better understanding of the ABA signaling pathway and the participation of the key component at their molecular level, which helps enhance soybean abiotic stress tolerance. Furthermore, this research will aid breeders in regulating and improving soybean production and quality under various stress conditions.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Germinação , Proteínas de Arabidopsis/genética , Glycine max/genética , Glycine max/metabolismo , Arabidopsis/genética , Sistemas CRISPR-Cas , Sementes/genética , Sementes/metabolismo , Regulação da Expressão Gênica de Plantas
16.
Int J Mol Sci ; 23(8)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35457038

RESUMO

The use of peptides as drugs has progressed over time and continues to evolve as treatment paradigms change and new drugs are developed. Myostatin (MSTN) inhibition therapy has shown great promise for the treatment of muscle wasting diseases. Here, we report the MSTN-derived novel peptides MIF1 (10-mer) and MIF2 (10-mer) not only enhance myogenesis by inhibiting MSTN and inducing myogenic-related markers but also reduce adipogenic proliferation and differentiation by suppressing the expression of adipogenic markers. MIF1 and MIF2 were designed based on in silico interaction studies between MSTN and its receptor, activin type IIB receptor (ACVRIIB), and fibromodulin (FMOD). Of the different modifications of MIF1 and MIF2 examined, Ac-MIF1 and Ac-MIF2-NH2 significantly enhanced cell proliferation and differentiation as compared with non-modified peptides. Mice pretreated with Ac-MIF1 or Ac-MIF2-NH2 prior to cardiotoxin-induced muscle injury showed more muscle regeneration than non-pretreated controls, which was attributed to the induction of myogenic genes and reduced MSTN expression. These findings imply that Ac-MIF1 and Ac-MIF2-NH2 might be valuable therapeutic agents for the treatment of muscle-related diseases.


Assuntos
Doenças Musculares , Miostatina , Animais , Fibromodulina/metabolismo , Camundongos , Desenvolvimento Muscular , Músculo Esquelético/metabolismo , Músculos/metabolismo , Atrofia Muscular/metabolismo , Doenças Musculares/metabolismo , Miostatina/genética , Miostatina/metabolismo , Peptídeos/metabolismo
17.
Molecules ; 27(13)2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35807547

RESUMO

Myostatin (MSTN), a negative regulator of muscle mass, is reported to be increased in conditions linked with muscle atrophy, sarcopenia, and other muscle-related diseases. Most pharmacologic approaches that treat muscle disorders are ineffective, emphasizing the emergence of MSTN inhibition. In this study, we used computational screening to uncover natural small bioactive inhibitors from the Traditional Chinese Medicine database (~38,000 compounds) for the MSTN protein. Potential ligands were screened, based on binding affinity (150), physicochemical (53) and ADMET properties (17). We found two hits (ZINC85592908 and ZINC85511481) with high binding affinity and specificity, and their binding patterns with MSTN protein. In addition, molecular dynamic simulations were run on each complex to better understand the interaction mechanism of MSTN with the control (curcumin) and the hit compounds (ZINC85592908 and ZINC85511481). We determined that the hits bind to the active pocket site (Helix region) and trigger conformational changes in the MSTN protein. Since the stability of the ZINC85592908 compound was greater than the MSTN control, we believe that ZINC85592908 has therapeutic potential against the MSTN protein and may hinder downstream singling by inhibiting the MSTN protein and increasing myogenesis in the skeletal muscle tissues.


Assuntos
Medicina Tradicional Chinesa , Doenças Musculares/tratamento farmacológico , Miostatina/antagonistas & inibidores , Simulação por Computador , Avaliação Pré-Clínica de Medicamentos , Simulação de Dinâmica Molecular , Desenvolvimento Muscular/efeitos dos fármacos , Doenças Musculares/fisiopatologia , Ligação Proteica
18.
Dev Dyn ; 250(5): 669-683, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33381902

RESUMO

BACKGROUND: The zinc finger-containing transcription factor Gli2, is a key mediator of Hedgehog (Hh) signaling and participates in embryonic patterning of various organs including the central nervous system (CNS) and limbs. Abnormal expression of Gli2 can impede the transcription of Hh target genes through disruption of proper balance between Gli2 and Gli3 functions. Therefore, delineation of enhancers that are required for complementary roles of Glis would allow the interrogation of those pathogenic variants that cause gene dysregulation, and a corresponding abnormal phenotype. Previously, we reported tissue-specific enhancers for Gli family including Gli2 through direct tetrapod-teleost comparisons. RESULTS: Here, we employed the sequence alignments of slowly evolving spotted gar and elephant shark and have identified six novel conserved noncoding elements in human GLI2 containing locus. Zebrafish-based transgenic assays revealed that combined action of these autonomous CNEs reflects many aspects of Gli2 specific endogenous transcriptional activity, including CNS and pectoral fins. CONCLUSION: Taken together with our previous findings, this study suggests that Hh-signaling controlled deployment of Gli2 activity in embryonic patterning arose in the common ancestor of gnathostomes. These GLI2 specific cis-regulatory modules will help to identify DNA variants that probably reside outside of coding intervals and are associated with congenital anomalies.


Assuntos
Evolução Biológica , Peixes/crescimento & desenvolvimento , Peixes/genética , Proteína Gli2 com Dedos de Zinco/genética , Animais , Humanos
19.
J Obstet Gynaecol ; 42(6): 1931-1936, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35603674

RESUMO

This study aimed at determining the association between serum neuregulin 4 (NRG4) and insulin in gestational diabetes mellitus (GDM) and their correlation with other metabolic parameters. A cross-sectional study was conducted from June 2018 to February 2019 at Ziauddin University, Karachi. Pregnant women (n = 80), at 24-28 weeks of gestation, were recruited. Demographic data, anthropometric measurements and antenatal history were recorded. The fasting blood was drawn for testing fasting blood sugar (FBS), NRG4, insulin and lipid profile. The subjects were evaluated for glucose challenge test after 50 g glucose ingestion. NRG4 levels (1.00 ± 0.15) were found significantly high (p < .04) in healthy group compared to GDM (0.95 ± 0.11). In GDM females, high levels for FBS (p < .02) and cholesterol (p < .03) were observed. Homeostatic model assessment of insulin resistance (HOMA-IR) had direct weak association with NRG4, inverse relationship with cholesterol and LDL but significant association (p < .05) with insulin. Significantly high NRG4 in healthy females suggests its potential role in regulating insulin sensitivity. Impact StatementWhat is already known on this subject? Neuregulin 4 (NGR4) is a batokine which plays a potential role in regulating insulin sensitivity, maintaining energy and metabolic homeostasis. Due to its role in lipid and glucose homeostasis, some studies report its role in gestational diabetes mellitus (GDM) but the results were controversial.What do the results of this study add? The study showed that NGR4 levels were significantly low in GDM subjects. Other metabolic factors especially insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were found associated significantly (p < .05) with NGR4.What are the implications of these findings for clinical practice and/or further research? NGR4 can be a potential biomarker for gestational diabetes. Nevertheless, in order to confirm these findings, further studies, with bigger sample size are required to further ascertain the prospects of NRG4 as a potential biomarker for gestational diabetes.


Assuntos
Diabetes Gestacional , Resistência à Insulina , Neurregulinas/metabolismo , Biomarcadores , Glicemia/metabolismo , Colesterol , Estudos Transversais , Feminino , Humanos , Insulina , Gravidez
20.
BMC Genomics ; 22(1): 772, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711171

RESUMO

BACKGROUND: Histone methylation occurs primarily on lysine residues and requires a set of enzymes capable of reading, writing, and erasing to control its establishment and deletion, which is essential for maintaining chromatin structure and gene expression. Histone methylation and demethylation are contributed to plant growth and development, and are involved in adapting to environmental stresses. The JmjC domain-containing proteins are extensively studied for their function in histone lysine demethylation in plants, and play a critical role in sustaining histone methylation homeostasis. RESULTS: In this study, a total of 21 JmjC domain-containing histone demethylase proteins (JHDMs) in birch were identified and classified into five subfamilies based on structural characteristics and phylogenetic relationships among Arabidopsis, rice, maize, and birch. Although the BpJMJ genes displayed significant schematic variation, their distribution on the chromosomes is relatively uniform. Additionally, the BpJMJ genes in birch have never experienced a tandem-duplication event proved by WGD analysis and were remaining underwent purifying selection (Ka/Ks < < 1). A typical JmjC domain was found in all BpJMJ genes, some of which have other essential domains for their functions. In the promoter regions of BpJMJ genes, cis-acting elements associated with hormone and abiotic stress responses were overrepresented. Under abiotic stresses, the transcriptome profile reveals two contrasting expression patterns within 21 BpJMJ genes. Furthermore, it was established that most BpJMJ genes had higher expression in young tissues under normal conditions, with BpJMJ06/16 having the highest expression in germinating seeds and participating in the regulation of BpGA3ox1/2 gene expression. Eventually, BpJMJ genes were found to directly interact with genes involved in the "intracellular membrane" in respond to cold stress. CONCLUSIONS: The present study will provide a foundation for future experiments on histone demethylases in birch and a theoretical basis for epigenetic research on growth and development in response to abiotic stresses.


Assuntos
Betula , Histona Desmetilases , Histona Desmetilases com o Domínio Jumonji/genética , Filogenia , Proteínas de Plantas/genética
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