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AIM: This study aims to compare and evaluate the changes in color caused by four different biomaterials utilized as intracanal coronal barriers in the regenerative endodontic procedure at varying intervals of time. METHODS: A total of 100 extracted mandibular single-rooted premolars were taken. Samples were standardized, and access cavity preparation was done. All the canals were instrumented and irrigated thoroughly. They were divided into five groups: A, B, C, D, and E (n=20), i.e., the control group, gray mineral trioxide aggregate (MTA), white MTA, Biodentine, and calcium hydroxide. Each group was further subdivided into two subgroups (n=10), where one subgroup was prepared with normal saline and the other was prepared with platelet-rich fibrin (PRF). Digital photographs were taken at baseline, immediately after the placement of biomaterials, after 72 hours, seven days, and six months, using a DSLR camera. The color evaluation was done using the Adobe Photoshop 2021 software using the CIE L*a*b color system. The data obtained were recorded and statistically analyzed using IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York). Continuous variables were analyzed using a one-way ANOVA test and post-hoc analysis. The P-value was set to be significant at <0.05. RESULTS: Statistically significant variation was obtained in all four experimental groups regarding change in color (ΔE) over periods of 72 hours, seven days, and six months. At six months, all the experimental groups presented with a perceptible color variation (ΔE>3.3). CONCLUSION: The color change was significant after six months in all groups. Biodentine produced the least color alteration, whereas gray MTA produced the highest.
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Global wheat production amounted to >780 MMT during 2022-2023 whose market size are valued at >$128 billion. Wheat is highly susceptible to high-temperature stress (HTS) throughout the life cycle and its yield declines 5-7% with the rise in each degree of temperature. Previously, we reported an array of HTS-response markers from a resilient wheat cv. Unnat Halna and described their putative role in heat acclimation. To complement our previous results and identify the key determinants of thermotolerance, here we examined the cytoplasmic proteome of a sensitive cv. PBW343. The HTS-triggered metabolite reprograming highlighted how proteostasis defects influence the formation of an integrated stress-adaptive response. The proteomic analysis identified several promising HTS-responsive proteins, including a NACα18 protein, designated TaNACα18, whose role in thermotolerance remains unknown. Dual localization of TaNACα18 suggests its crucial functions in the cytoplasm and nucleus. The homodimerization of TaNACα18 anticipated its function as a transcriptional coactivator. The complementation of TaNACα18 in yeast and overexpression in wheat demonstrated its role in thermotolerance across the kingdom. Altogether, our results suggest that TaNACα18 imparts tolerance through tight regulation of gene expression, cell wall remodeling and activation of cell defense responses.
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Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Termotolerancia , Triticum , Triticum/genética , Triticum/fisiología , Triticum/metabolismo , Triticum/inmunología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Termotolerancia/genética , Termotolerancia/fisiología , Calor , Citoplasma/metabolismo , Proteómica , Respuesta al Choque Térmico/fisiología , Aclimatación/genéticaRESUMEN
Receptors are proteinous macromolecules which remain in the apo form under normal/unliganded conditions. As the ligand approaches, there are specific stereo-chemical changes in the apo form of the receptor as per the stereochemistry of a ligand. Accordingly, a series of substituted dimethyl-chroman-based stereochemically flexible and constrained Tamoxifen analogs were synthesized as anti-breast cancer agents. The synthesized compounds 19a-e, 20a-e, 21, and 22a-e, showed significant antiproliferative activity against estrogen receptor-positive (ER+, MCF-7) and negative (ER-, MDA MB-231) cells within IC50 value 8.5-25.0 µM. Amongst all, four potential molecules viz 19b, 19e, 22a, and 22c, were evaluated for their effect on the cell division cycle and apoptosis of ER+ and ER- cancer cells (MCF-7 & MDA MB-231cells), which showed that these compounds possessed antiproliferative activity through triggering apoptosis. In-silico docking experiments elucidated the possible affinity of compounds with estrogen receptors-α and -ß.
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Antineoplásicos , Apoptosis , Neoplasias de la Mama , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Estereoisomerismo , Relación Estructura-Actividad , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Cromanos/farmacología , Cromanos/síntesis química , Cromanos/química , Simulación del Acoplamiento Molecular , Receptor alfa de Estrógeno/metabolismo , Receptor alfa de Estrógeno/antagonistas & inhibidores , Femenino , Estructura Molecular , Células MCF-7 , Relación Dosis-Respuesta a Droga , Tamoxifeno/farmacología , Tamoxifeno/síntesis química , Tamoxifeno/químicaRESUMEN
The phytochemical investigation of Psidium guajava leaves led to the isolation of total nineteen compounds which belongs to meroterpenoids, flavonoid, phenolics, and triterpenoids. The compounds were isolated using extensive chromatography techniques and identified as psiguanol (4), as new compound along with guajadial (1), psidial A (2), ß-caryophyllene (3), quercetin (5), avicularin (6), guaijaverin (7), hyperin (8), rutin (9), ursolic acid (10), corosolic acid (11), asiatic acid (12), ß-sitosterol (13), ß-sitosterol-D-glucoside (14), ellagic acid (15), 3,3',4'-trimethylellagic acid 4-O-glucoside (16), protocatechuic acid (17), gallic acid (18), and tricosanoic acid (19) as known molecules. The compound 16 was isolated for the first time from this plant. The isolated compounds were evaluated for vasorelaxation activity in rat aorta cells and it was observed that compound 4 exhibited the most potent vasorelaxation response in the ex-vivo model in isolated rat aorta cells. Mechanistically, the vasorelaxation activity of 4 was mediated through cGMP-dependent BKCa channel opening.
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The global impact of the COVID-19 pandemic caused by SARS-CoV-2 necessitates innovative strategies for the rapid development of effective treatments. Computational methodologies, such as molecular modelling, molecular dynamics simulations, and artificial intelligence, have emerged as indispensable tools in the drug discovery process. This review aimed to provide a comprehensive overview of these computational approaches and their application in the design of antiviral agents for COVID-19. Starting with an examination of ligand-based and structure-based drug discovery, the review has delved into the intricate ways through which molecular modelling can accelerate the identification of potential therapies. Additionally, the investigation extends to phytochemicals sourced from nature, which have shown promise as potential antiviral agents. Noteworthy compounds, including gallic acid, naringin, hesperidin, Tinospora cordifolia, curcumin, nimbin, azadironic acid, nimbionone, nimbionol, and nimocinol, have exhibited high affinity for COVID-19 Mpro and favourable binding energy profiles compared to current drugs. Although these compounds hold potential, their further validation through in vitro and in vivo experimentation is imperative. Throughout this exploration, the review has emphasized the pivotal role of computational biologists, bioinformaticians, and biotechnologists in driving rapid advancements in clinical research and therapeutic development. By combining state-of-the-art computational techniques with insights from structural and molecular biology, the search for potent antiviral agents has been accelerated. The collaboration between these disciplines holds immense promise in addressing the transmissibility and virulence of SARS-CoV-2.
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COVID-19 , Humanos , SARS-CoV-2 , Inteligencia Artificial , Pandemias , Simulación de Dinámica Molecular , Antivirales/farmacología , Antivirales/uso terapéutico , Simulación del Acoplamiento Molecular , Inhibidores de ProteasasRESUMEN
BACKGROUND/AIMS: All body functions are activated, synchronized and controlled by a substantial, complex network, the nervous system. Upon injury, pathophysiology of the nerve injury proceeds through different paths. The axon may undergo a degenerative retraction from the site of injury for a short distance unless the injury is near to the cell body, in which case it continues to the soma and undergoes retrograde neuronal degeneration. Otherwise, the distal section suffers from Wallerian degeneration, which is marked by axonal swelling, spheroids, and cytoskeleton degeneration. The objective of the study was to evaluate the potential of mesenchymal stem cell laden neural scaffold and insulin-like growth factor I (IGF-I) in nerve regeneration following sciatic nerve injury in a rat model. METHODS: The animals were anaesthetized and a cranio-lateral incision over left thigh was made. Sciatic nerve was exposed and crush injury was introduced for 90 seconds using haemostat at second locking position. The muscle and skin were sutured in routine fashion and thus the rat model of sciatic crush injury was prepared. The animal models were equally distributed into 5 different groups namely A, B, C, D and E and treated with phosphate buffer saline (PBS), carbon nanotubes based neural scaffold only, scaffold with IGF-I, stem cell laden scaffold and stem cell laden scaffold with IGF-I respectively. In vitro scaffold testing was performed. The nerve regeneration was assessed based on physico-neuronal, biochemical, histopathological examination, and relative expression of NRP-1, NRP-2 and GAP-43 and scanning electron microscopy. RESULTS: Sciatic nerve injury model with crush injury produced for 90 seconds was standardized and successfully used in this study. All the biochemical parameters were in normal range in all the groups indicating no scaffold related changes. Physico-neuronal, histopathological, relative gene expression and scanning electron microscopy observations revealed appreciable nerve regeneration in groups E and D, followed by C and B. Restricted to no regeneration was observed in group A. CONCLUSION: Carbon nanotubes based scaffold provided electro-conductivity for proper neuronal regeneration while rat bone marrow-derived mesenchymal stem cells were found to induce axonal sprouting, cellular transformation; whereas IGF-I induced stem cell differentiation, myelin synthesis, angiogenesis and muscle differentiation.
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Lesiones por Aplastamiento , Células Madre Mesenquimatosas , Nanotubos de Carbono , Neuropatía Ciática , Ratas , Animales , Ratas Wistar , Factor I del Crecimiento Similar a la Insulina/farmacología , Factor I del Crecimiento Similar a la Insulina/uso terapéutico , Neuropatía Ciática/tratamiento farmacológico , Neuropatía Ciática/patología , Nervio Ciático/lesiones , Regeneración Nerviosa/fisiología , Lesiones por Aplastamiento/tratamiento farmacológico , Lesiones por Aplastamiento/patología , Células Madre Mesenquimatosas/patología , ColágenoRESUMEN
BACKGROUND: Breast cancer is one of the most common types of cancer among women worldwide, and its metastasis is a significant cause of mortality. Therefore, identifying potential inhibitors of proteins involved in breast cancer metastasis is crucial for developing effective therapies. BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is a key regulator of mitotic checkpoint control, which ensures the proper segregation of chromosomes during cell division. Dysregulation of BUB1B has been linked to a variety of human diseases, including breast cancer. Overexpression of BUB1B has been observed in various cancer types, and its inhibition has been shown to induce cancer cell death. Additionally, BUB1B inhibition has been suggested as a potential strategy for overcoming resistance to chemotherapy and radiation therapy. Given the importance of BUB1B in regulating cell division and its potential as a therapeutic target, the development of BUB1B inhibitors has been the focus of intense research efforts. Despite these efforts, few small molecule inhibitors of BUB1B have been identified, highlighting the need for further research in this area. In this study, the authors aimed to identify potential inhibitors of BUB1B from mushroom bioactive compounds using computational methods, which could ultimately lead to the development of new treatments for breast cancer metastasis. METHODS: This study has incorporated 70 bioactive compounds (handpicked through literature mining) of distinct mushrooms that were considered and explored to identify a suitable drug candidate. Their absorption, distribution, metabolism and excretion (ADME) properties were obtained to predict the drug-likeness of these 70 mushroom compounds based on Lipinski's rule of 5 (RO5). Screening these bioactive compounds and subsequent molecular docking against BUB1B provided compounds with the best conformation-based binding affinity. The best two complexes, i.e., BUB1B-lepitaprocerin D and BUB1B-peptidoglycan, were subjected to molecular dynamic simulations. Both complexes were assessed for their affinity, stability, and flexibility in protein-ligand complex systems. RESULTS: The molecular dynamic (MD) simulation studies revealed that lepitaprocerin D has an energetically favorable binding affinity with BUB1B. Results showed that the formation of a hydrogen bond between residues ASN123 and SER157, and lepitaprocerin D had strengthened the affinity of lepitaprocerin D with BUB1B. CONCLUSIONS: This study identified lepitaprocerin D as a potential and novel inhibitor for BUB1B that could be a plausible drug candidate for identifying and controlling the spread of breast cancer metastasis.
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In the past two decades, there has been significant progress in the design and development of synthetic receptors for molecular recognition as they find application in the field of chemical, biological, medical, and environmental sciences. Synthetic receptors based on calix systems appended with fluorogenic and chromogenic groups have gained considerable attention for sensing and recognition of ions and molecules. Copper (Cu2+) is an essential element required in trace amounts in all living organisms to carry out various biological processes. The aim of this review is to summarize advancement in π-conjugated fluorogenic and chromogenic groups appended to calix[4]arene motifs for detection and quantitation of Cu2+ ion. The focus is to present a comprehensive account of extended calix[4]arene systems with different linkers and highlight the unique design and binding characteristics for the recognition and sensing of Cu2+ ions.
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ETHNOBOTANICAL RELEVANCE: Rosa damascena Mill. (Rosaceae), commonly known as damask rose, is an ancient medicinal and perfumery plant used in Traditional Unani Medicine due to various therapeutic effects, including cardiovascular benefits. AIM OF THE STUDY: This study aimed to evaluate the vasorelaxant effect of the 2-phenyl ethyl alcohol (PEA) isolated from the spent flowers of R. damascena which remain after the extraction of essential oil. MATERIALS AND METHODS: The freshly collected flowers of R. damascena were hydro-distilled in a Clevenger's type apparatus to extract the rose essential oil (REO). After removing the REO, the spent-flower hydro-distillate was collected and extracted with organic solvents to yield a spent-flower hydro-distillate extract (SFHE), which was further purified by column chromatography. The SFHE and its isolate were characterized by gas chromatography (GC-FID), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) techniques. The PEA, isolated from SFHE, was evaluated for vasorelaxation response in conduit blood vessels like rat aorta and resistant vessels like mesenteric artery. The preliminary screening of PEA was done in aortic preparation pre-constricted with phenylephrine/U46619. Further, a concentration-dependent relaxation response to PEA has been elicited in both endothelium-intact and endothelium-denuded arterial rings, and the mode of action was explored. RESULTS: The SFHE revealed the presence of PEA as the main constituent (89.36%), which was further purified by column chromatography to a purity of 95.0%. The PEA exhibited potent vasorelaxation response both in conduit vessels like the rat aorta and resistance vessels like the mesenteric artery. The relaxation response is mediated without any involvement of vascular endothelium. Further, TEA sensitive BKCa channel was found to be the major target for PEA-induced relaxation response in these blood vessels. CONCLUSIONS: The spent flowers of R. damascena, which remain after the extraction of REO, could be used to extract PEA. The PEA possessed marked vasorelaxation properties in both aorta and mesenteric artery and showed promise for development into an herbal product against hypertension.
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Aceites Volátiles , Alcohol Feniletílico , Rosa , Ratas , Animales , Vasodilatadores/farmacología , Rosa/química , Cromatografía de Gases y Espectrometría de Masas , Aceites Volátiles/farmacología , Aceites Volátiles/químicaRESUMEN
Everyone likes to add color to their life, and plants use them too. However, unlike humans, plants contain natural pigments to add color to fruits, leaves, and vegetables. Plants produce a variety of phytopigments, such as flavonoids, carotenoids, and anthocyanins, which play essential roles in plant stress tolerance. Leveraging natural phytopigments to develop stress-resilient crops will require an in-depth understanding of pigment formation and function. In this context, Zhang et al. (2023) studied the role of MYB6 and bHLH111 in enhancing anthocyanin biosynthesis in petals during drought.
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Antocianinas , Flores , Humanos , Plantas , Flavonoides , Hojas de la Planta , Regulación de la Expresión Génica de las PlantasRESUMEN
The production of nanoparticles (NPs) from chemical and physical synthesis has ended due to the involvement of toxic byproducts and harsh analytical conditions. Innovation and research in nanoparticle synthesis are derived from biomaterials that have gained attention due to their novel features, such as ease of synthesis, low-cost, eco-friendly approach, and high water solubility. Nanoparticles obtained through macrofungi involve several mushroom species, i.e., Pleurotus spp., Ganoderma spp., Lentinus spp., and Agaricus bisporus. It is well-known that macrofungi possess high nutritional, antimicrobial, anti-cancerous, and immune-modulatory properties. Nanoparticle synthesis via medicinal and edible mushrooms is a striking research field, as macrofungi act as an eco-friendly biofilm that secretes essential enzymes to reduce metal ions. The mushroom-isolated nanoparticles exhibit longer shelf life, higher stability, and increased biological activities. The synthesis mechanisms are still unknown; evidence suggests that fungal flavones and reductases have a significant role. Several macrofungi have been utilized for metal synthesis (such as Ag, Au, Pt, Fe) and non-metal nanoparticles (Cd, Se, etc.). These nanoparticles have found significant applications in advancing industrial and bio-medical ventures. A complete understanding of the synthesis mechanism will help optimize the synthesis protocols and control the shape and size of nanoparticles. This review highlights various aspects of NP production via mushrooms, including its synthesis from mycelium and the fruiting body of macrofungi. Also, we discuss the applications of different technologies in NP high-scale production via mushrooms.
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Agaricales , Antiinfecciosos , Nanopartículas , HumanosRESUMEN
Cancer is one of the deadliest diseases developed through tumorigenesis and could be fatal if it reaches the metastatic phase. The novelty of the present investigation is to explore the prognostic biomarkers in hepatocellular carcinoma (HCC) that could develop glioblastoma multiforme (GBM) due to metastasis. The analysis was conducted using RNA-seq datasets for both HCC (PRJNA494560 and PRJNA347513) and GBM (PRJNA494560 and PRJNA414787) from Gene Expression Omnibus (GEO). This study identified 13 hub genes found to be overexpressed in both GBM and HCC. A promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability, leading to improper chromosome segregation, causing aneuploidy. A 13-gene predictive model was obtained and validated using a KM plot. These hub genes could be prognostic biomarkers and potential therapeutic targets, inhibition of which could suppress tumorigenesis and metastasis.
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Herein, we designed two fluorescent tetrasubstituted benzene sulfonyl appended Thiacalix[4]arene receptors named L1 and L2, which sensitively and selectively detect Sulfosulfuron among other herbicides and pesticides. The detection limit (LOD) was found to be 0.21 ppm and 0.35 ppm, and the enhancement constant (Ks) was determined to be 7.07 X 104 M-1 and 5.55 X 104 M-1 for L1 and L2, respectively. Using the non-linear regression method, the association constant was obtained as 2.1 X 104 M-1 and 2.23 X 104 M-1 whereas, the binding ratio was found to be 1:1 for both L1 and L2, respectively. Additionally, the interference studies show the selective nature of receptors for Sulfosulfuron among its sulfonylurea family. To further confirm the interaction mechanism, 1H-NMR spectroscopy, and a computational investigation were carried out, which validates the 1:1 binding ratio. The receptors were found to be recyclable in nature with simple acid-base treatment. This new approach of using supramolecules as fluorescent probes for sensitive and selective detection of herbicides is rare in the literature.
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Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of death in women. Researchers have discovered an increasing number of molecular targets for BC prognosis and therapy. However, it is still urgent to identify new biomarkers. Therefore, we evaluated biomarkers that may contribute to the diagnosis and treatment of BC. We searched TCGA datasets and identified differentially expressed genes (DEGs) by comparing tumor (100 samples) and non-tumor (100 samples) tissues using the Deseq2 package. Pathway and functional enrichment analysis of the DEGs was performed using the DAVID (Database for Annotation, Visualization, and Integrated Discovery) database. The protein-protein interaction (PPI) network was identified using the STRING database and visualized through Cytoscape software. Hub gene analysis of the PPI network was completed using cytohubba plugins. The associations between the identified genes and overall survival (OS) were analyzed using a Kaplan-Meier plot. Finally, we have identified hub genes at the transcriptome level. A total of 824 DEGs were identified, which were mostly enriched in cell proliferation, signal transduction, and cell division. The PPI network comprised 822 nodes and 12,145 edges. Elevated expression of the five hub genes AURKA, BUB1B, CCNA2, CCNB2, and PBK are related to poor OS in breast cancer patients. A promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability, leading to improper chromosome segregation causing aneuploidy. The enriched functions and pathways included the cell cycle, oocyte meiosis, and the p53 signaling pathway. The identified five hub genes in breast cancer have the potential to become useful targets for the diagnosis and treatment of breast cancer.