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This research investigated a UPLC-QTOF/ESI-MS-based phytochemical profiling of Combretum indicum leaf extract (CILEx), and explored its in vitro antioxidant and in vivo antidiabetic effects in a Long-Evans rat model. After a one-week intervention, the animals' blood glucose, lipid profile, and pancreatic architectures were evaluated. UPLC-QTOF/ESI-MS fragmentation of CILEx and its eight docking-guided compounds were further dissected to evaluate their roles using bioinformatics-based network pharmacological tools. Results showed a very promising antioxidative effect of CILEx. Both doses of CILEx were found to significantly (p < 0.05) reduce blood glucose, low-density lipoprotein (LDL), and total cholesterol (TC), and increase high-density lipoprotein (HDL). Pancreatic tissue architectures were much improved compared to the diabetic control group. A computational approach revealed that schizonepetoside E, melianol, leucodelphinidin, and arbutin were highly suitable for further therapeutic assessment. Arbutin, in a Gene Ontology and PPI network study, evolved as the most prospective constituent for 203 target proteins of 48 KEGG pathways regulating immune modulation and insulin secretion to control diabetes. The fragmentation mechanisms of the compounds are consistent with the obtained effects for CILEx. Results show that the natural compounds from CILEx could exert potential antidiabetic effects through in vivo and computational study.
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Antioxidantes/farmacologia , Combretum/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Arbutina/química , Arbutina/isolamento & purificação , Sítios de Ligação , Glicemia/efeitos dos fármacos , HDL-Colesterol/agonistas , HDL-Colesterol/sangue , LDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/sangue , Biologia Computacional/métodos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Flavonoides/química , Flavonoides/isolamento & purificação , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Insulina/agonistas , Insulina/metabolismo , Masculino , Modelos Moleculares , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Extratos Vegetais/química , Folhas de Planta/química , Ligação Proteica , Conformação Proteica , Ratos , Ratos Long-Evans , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
A corporate feeding antenna array with parasitic patches has been investigated previously for millimeter-wave applications due to its high gain and wide bandwidth. However, the parasitic patch integration in the uniformly powered and spaced patch antenna array led to a high sidelobe level (SLL). In this study, we designed a non-uniformly powered and spaced corporate feeding network to feed a 12-element parasitic patch-integrated microstrip antenna array for SLL reduction at 28 GHz in the millimeter-wave band. In the power divider, we arranged two one-to-six unequally feeding power dividers from the opposite side to feed 12 antenna elements with non-uniform excitation, and effectively controlled the spacing between antenna elements. The two opposite input ports from the power divider were fed 180° out-of-phase for good isolation between the adjacent antenna elements. To verify the SLL reduction effect from the non-uniform spacing in the array, we designed two non-uniformly powered patch antenna arrays with uniform and non-uniform spacing. In the measurement, the non-uniformly powered and spaced patch antenna array demonstrated a nearly 16.56 dBi boresight gain and -17.27 dB SLL, which is nearly 2 dB lower than the uniformly spaced counterpart. Finally, we expect that the non-uniformly powered and spaced high gain patch antenna array with a low SLL will be suitable for millimeter-wave communication applications.
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Decomposition of plant litter is a fundamental process in ecosystem function, carbon and nutrient cycling and, by extension, climate change. This study aimed to investigate the role of temperature on the decomposition of water soluble phenolics (WSP), carbon and soil nutrients in conjunction with the phytotoxicity dynamics of Chrysanthemoides monilifera subsp. monilifera (boneseed) litter. Treatments consisted of three factors including decomposition materials (litter alone, litter with soil and soil alone), decomposition periods and temperatures (5-15, 15-25 and 25-35°C (night/day)). Leachates were collected on 0, 5, 10, 20, 40 and 60th days to analyse physico-chemical parameters and phytotoxicity. Water soluble phenolics and dissolved organic carbon (DOC) increased with increasing temperature while nutrients like SO4(-2) and NO3(-1) decreased. Speed of germination, hypocotyl and radical length and weight of Lactuca sativa exposed to leachates were decreased with increasing decomposition temperature. All treatment components had significant effects on these parameters. There had a strong correlation between DOC and WSP, and WSP content of the leachates with radical length of test species. This study identified complex interactivity among temperature, WSP, DOC and soil nutrient dynamics of litter occupied soil and that these factors work together to influence phytotoxicity.
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Alelopatia , Asteraceae/química , Biodegradação Ambiental , Substâncias Húmicas/análise , Temperatura , Concentração de Íons de Hidrogênio , Lactuca/efeitos dos fármacos , Sementes , Solo/químicaRESUMO
PREMISE OF THE STUDY: Invasive plants are a great threat to the conservation of natural ecosystems and biodiversity. Allelopathy as a mechanism for invasion of plants such as Phragmites australis, one of the most aggressive invaders, has the potential to suppress neighboring plant species. Allelopathic interference, through root exudates of P. australis on native Melaleuca ericifolia, was investigated to find out the underlying invasion mechanisms. METHODS: Germination and growth effects of P. australis on M. ericifolia were studied in the greenhouse using potting mix both with and without activated carbon, and a combination of single and repeated cuttings of P. australis as the management tool. KEY RESULTS: P. AUSTRALIS had significant negative effects on germination and growth of M. ericifolia by inhibiting germination percentage, maximum root length and plant height, biomass, stem diameter, and number of growth points with little effect on leaf physiology. Activated carbon (AC) in turn moderately counteracted these effects. The cutting of P. australis shoots significantly reduced the suppressive effects on M. ericifolia compared to the addition of AC to soil. Furthermore, significant changes in soil such as pH, electrical conductivity, osmotic potential, phenolics, and dehydrogenase activity were identified among cutting treatments with little variation between AC treatments. CONCLUSION: The results demonstrated that allelopathy through root exudates of P. australis had relatively low contribution in suppressing M. ericifolia in comparison to other competitive effects. Management tools combining repeated cutting of P. australis shoots with AC treatments may assist partly in the restoration of native ecosystems invaded by P. australis.
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Melaleuca/efeitos dos fármacos , Feromônios/farmacologia , Exsudatos de Plantas/farmacologia , Poaceae/química , Alelopatia , Biodiversidade , Biomassa , Carbono/metabolismo , Conservação dos Recursos Naturais , Ecossistema , Germinação , Espécies Introduzidas , Melaleuca/crescimento & desenvolvimento , Melaleuca/fisiologia , Raízes de Plantas/química , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/fisiologia , Caules de Planta/efeitos dos fármacos , Caules de Planta/crescimento & desenvolvimento , Caules de Planta/fisiologia , Solo/químicaRESUMO
A circular polarized (CP) pentaband antenna based on the aperture-in-aperture (AIA) concept is presented for CubeSat applications. This AIA consists of five different bands ranging from L-band to Ka-band. Four different antennas, each operating at a specific frequency band, namely 12 GHz, 18.5 GHz, 26 GHz, and 32 GHz, were incorporated into an L-band (viz. 1.5 GHz) antenna. Notably, the five antennas can operate simultaneously for a CubeSat downlink operation with a frequency ratio of 21.3:1. The antenna structure shows a realized gain of 5-10 dBi with good CP bandwidth (< 3 dB) across the overall operational frequency range. That is, the realized gain of L-band (1.5 GHz), X-band (12.5 GHz), K-band1 (18.5 GHz), K-band2 (26 GHz), and Ka-bands (32 GHz) are 5.05 dBi, 8.21 dBi, 7.33 dBi, 7.97 dBi, and 8.56 dBi. A high impedance surface (HIS) is incorporated with the Ka-band antenna to mitigate the ripples in the radiation pattern created by the interference of surface waves. A prototype was fabricated and tested. The measurement data agrees well with the simulation.
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Bladder cancer (BC) is the 10th most common tumour with a high incidence and recurrence rate worldwide; however, the current therapies present limitations as, regularly, not all patients benefit from treatment. Therefore, the search for new, active marine phenolic acids with anti-tumour properties is imperative. In this study, we subjected marine phenolic acids to in silico investigations such as network pharmacology, molecular docking, and molecular dynamics simulation (MD) to identify a plausible pathway and the lead compound that inhibits BC. According to the network pharmacology analysis, eight hub genes (PLAU, MMP2, ITGB3, MAPK1, PTPN11, ESR1, TLR4, MMP9) were found and linked to the enrichment of hsa05205: proteoglycans in cancer, and four hub genes (MMP1, MMP2, MAPK1, MMP9) were involved in the enrichment of hsa05219: BC. Subsequently, molecular docking studies showed that the marine phenolic acids exhibit a strong binding affinity for the target protein, matrix metalloproteinase-9 (MPP9). Among these 14 marine phenolic acids, chicoric acid showed the highest binding affinity of -67.1445â¯kcal/mol and formed hydrogen bonds with the residues of Ala189, Gln227, Leu188, His226, Ala242, Arg249, Ala191, and Gly186 in the active site of the MPP9 protein. Then, molecular dynamics simulation revealed that chicoric acid formed a stable protein-ligand complex with RMSD and RMSF values of 0.72â¯nm and 0.53â¯nm, respectively. Furthermore, the PCA method was employed to understand the dynamical behaviour in the conformational space of MPP9 protein bound to chicoric acid, and the results showed the good conformational space behaviour of MPP9 protein. Moreover, chicoric acid showed a free binding energy value of -32.62â¯kcal/mol, which indicated it could be a BC inhibitor. Overall, chicoric acid demonstrated potential anti-BC activity through MPP9 protein inhibition.
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Low fiber-direction compressive strength is a well-recognized weakness of carbon fiber-reinforced polymer (CFRP) composites. When a CFRP is produced using 3D printing, the compressive strength is further degraded. To solve this issue, in this paper, a novel magnetic compaction force-assisted additive manufacturing (MCFA-AM) method is used to print CFRP laminates reinforced with carbon nanofiber (CNF) z-threads (i.e., ZT-CFRP). MCFA-AM utilizes a magnetic force to simultaneously levitate, deposit, and compact fast-curing CFRP prepregs in free space and quickly solidifies the CFRP laminate part without any mold nor supporting substrate plate; it effectively reduces the voids. The longitudinal compressive test was performed on five different sample types. ZT-CFRP/MCFA-AM samples were printed under two different magnetic compaction rolling pressures, i.e., 0.5 bar and 0.78 bar. Compared with the longitudinal compressive strength of a typical CFRP manufactured by the traditional out-of-autoclave-vacuum-bag-only (OOA-VBO) molding process at the steady-state pressure of 0.82 bar, the ZT-CFRP/MCFA-AM samples showed either comparable results (by -1.00% difference) or enhanced results (+7.42% improvement) by using 0.5 bar or 0.78 bar magnetic rolling pressures, respectively.
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The goal of this work is to use a variety of in-silico techniques to identify anti-diabetic agents against DPP-IV enzyme from five main curcumin analogues. To produce the successful molecules, five main curcumin analogues were docked into the active site of DPP-IV enzyme. In comparison to the control molecule (Saxagliptin, -6.9 kcal/mol), all the compounds have the highest binding affinity (-7.6 to -7.7 kcal/mol) for the DPP-IV enzyme. These compounds underwent further testing for studies on drug-likeness, pharmacokinetics, and acute toxicity to see the efficacy and safety of compounds. To assess the stability of the docking complex and the binding posture identified during the docking experiment, our study got THC as the lead compound, which was then exposed to 200 ns of molecular dynamic simulation and PCA analysis. Additionally, DFT calculations were conducted to determine the thermodynamic, molecular orbital, and electrostatic potential characteristics of lead compound. Overall, the lead chemical has shown strong drug-like properties, is non-toxic, and has a sizable affinity for the DPP-IV enzyme.Communicated by Ramaswamy H. Sarma.
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ETHNOPHARMACOLOGICAL RELEVANCE: Achyranthes ferruginea (A. ferruginea) Roxb. is a common plant used in traditional medicine in Asia and Africa. It has a variety of local names, including "Gulmanci" in Nigeria, "Dangar" in Pakistan, "Thola" in Ethiopia, and "Roktoshirinchi" in Bangladesh. It is edible and has several ethnomedical uses for a wide range of illnesses, including hysteria, dropsy, constipation, piles, boils, asthma, and shigellosis. However, the neuropharmacological and analgesic potential of A. ferruginea remains uninvestigated. AIM OF THE STUDY: To assess the neuropharmacological and analgesic potential of A. ferruginea through a multifaceted approach encompassing both experimental and computational models. MATERIALS AND METHODS: Methanol was used to extract the leaves of A. ferruginea. It was then fractionated with low to high polar solvents (n-hexane, chloroform, ethyl acetate, and water) to get different fractions, including chloroform fraction (CLF). The study selected CLF at different doses and conducted advanced chemical element and proximate analyses, as well as phytochemical profiling using GC-MS. Toxicological studies were done at 300 µg per rat per day for 14 days. Cholinesterase inhibitory potential was checked using an in-vitro colorimetric assay. Acetic acid-induced writhing (AAWT) and formalin-induced licking tests (FILT) were used to assess anti-nociceptive effects. The forced swim test (FST), tail suspension test (TST), elevated plus maze (EPM), hole board test (HBT), and light and dark box test (LDB) were among the behavioral tests used to assess depression and anxiolytic activity. Network pharmacology-based analysis was performed on selected compounds using the search tool for interacting chemicals-5 (STITCH 5), Swiss target prediction tool, and search tool for the retrieval of interacting genes and proteins (STRING) database to link their role with genes involved in neurological disorders through gene ontology and reactome analysis. RESULTS: Qualitative chemical element analysis revealed the presence of 15 elements, including Na, K, Ca, Mg, P, and Zn. The moisture content, ash value, and organic matter were found to be 11.12, 11.03, and 88.97%, respectively. GC-MS data revealed that the CLF possesses 25 phytoconstituents. Toxicological studies suggested the CLF has no effects on normal growth, hematological and biochemical parameters, or cellular organs after 14 days at 300 µg per rat. The CLF markedly reduced the activity of both acetylcholinesterase and butyrylcholinesterase (IC50: 56.22 and 13.22 µg/mL, respectively). Promising dose-dependent analgesic activity (p < 0.05) was observed in chemically-induced pain models. The TST and FST showed a dose-dependent substantial reduction in immobility time due to the CLF. Treatment with CLF notably increased the number of open arm entries and time spent in the EPM test at doses of 200 and 400 mg/kg b.w. The CLF showed significant anxiolytic activity at 200 mg/kg b.w. in the HBT test, whereas a similar activity was observed at 400 mg/kg b.w. in the EPM test. A notable increase in the amount of time spent in the light compartment was observed in the LDB test by mice treated with CLF, suggesting an anxiolytic effect. A network pharmacology study demonstrated the relationship between the phytochemicals and a number of targets, such as PPARA, PPARG, CHRM1, and HTR2, which are connected to the shown bioactivities. CONCLUSIONS: This study demonstrated the safety of A. ferruginea and its efficacy in attenuating cholinesterase inhibitory activity, central and peripheral pain, anxiety, and depression, warranting further exploration of its therapeutic potential.
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Achyranthes , Ansiolíticos , Ratos , Camundongos , Animais , Ansiolíticos/efeitos adversos , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Clorofórmio , Acetilcolinesterase , Butirilcolinesterase , Analgésicos/efeitos adversos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Nigéria , PaquistãoRESUMO
BACKGROUND: Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-induced liver damage-protecting effect of epiphytic Aerides odorata methanol extract (AODE). METHODS: The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand-receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses. RESULTS: AODE significantly (p < 0.05) minimized the dose-dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), ß-actin, paraoxonase-1 (PON1), and phosphofructokinase-1 (PFK-1) were upregulated in AODE-treated paracetamol-intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug-like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (-11.42) with the liver protein human pituitary adenylate cyclase-1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta-1), SRC (proto-oncogene c-Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen-activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity. CONCLUSION: The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound-based animal study.
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BACKGROUND: The deregulated genetic factors are critically associated with idiopathic pulmonary arterial hypertension (IPAH) development and progression. However, the identification of hub-transcription factors (TFs) and miRNA-hub-TFs co-regulatory network-mediated pathogenesis in IPAH remains lacking. METHODS: We used GSE48149, GSE113439, GSE117261, GSE33463, and GSE67597 for identifying key genes and miRNAs in IPAH. We used a series of bioinformatics approaches, including R packages, protein-protein interaction (PPI) network, and gene set enrichment analysis (GSEA) to identify the hub-TFs and miRNA-hub-TFs co-regulatory networks in IPAH. Also, we employed a molecular docking approach to evaluate the potential protein-drug interactions. RESULTS: We found that 14 TFs encoding genes, including ZNF83, STAT1, NFE2L3, and SMARCA2 are upregulated, and 47 TFs encoding genes, including NCOR2, FOXA2, NFE2, and IRF5 are downregulated in IPAH relative to the control. Then, we identified the differentially expressed 22 hub-TFs encoding genes, including four upregulated (STAT1, OPTN, STAT4, and SMARCA2) and 18 downregulated (such as NCOR2, IRF5, IRF2, MAFB, MAFG, and MAF) TFs encoding genes in IPAH. The deregulated hub-TFs regulate the immune system, cellular transcriptional signaling, and cell cycle regulatory pathways. Moreover, the identified differentially expressed miRNAs (DEmiRs) are involved in the co-regulatory network with hub-TFs. The six hub-TFs encoding genes, including STAT1, MAF, CEBPB, MAFB, NCOR2, and MAFG are consistently differentially expressed in the peripheral blood mononuclear cells of IPAH patients, and these hub-TFs showed significant diagnostic efficacy in distinguishing IPAH cases from the healthy individuals. Moreover, we revealed that the co-regulatory hub-TFs encoding genes are correlated with the infiltrations of various immune signatures, including CD4 regulatory T cells, immature B cells, macrophages, MDSCs, monocytes, Tfh cells, and Th1 cells. Finally, we discovered that the protein product of STAT1 and NCOR2 interacts with several drugs with appropriate binding affinity. CONCLUSIONS: The identification of hub-TFs and miRNA-hub-TFs co-regulatory networks may provide a new avenue into the mechanism of IPAH development and pathogenesis.
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MicroRNAs , Humanos , MicroRNAs/genética , Perfilação da Expressão Gênica , Simulação de Acoplamento Molecular , Hipertensão Pulmonar Primária Familiar/genética , Leucócitos Mononucleares/metabolismo , Redes Reguladoras de Genes , Regulação Neoplásica da Expressão Gênica , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Interações Medicamentosas , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismoRESUMO
The present study aimed at (a) determining the concentration of macro-minerals and toxic metals in fish species collected from biofloc and traditional fish farms; (b) assessing the contribution of macro-minerals to our daily diet; and (c) evaluating the health risks of children and adults based on the US Environmental Protection Agency (USEPA) deterministic model. Significantly higher concentrations of macro-minerals and significantly lower levels of toxic metals (at < 0.05 level) were found in most of the biofloc fish species compared to the market fish samples. The values of the target hazard quotient (THQ) were less than 1.0 for all individual trace metals in all species, which indicated that there were no noncarcinogenic health risks. Furthermore, the value of the hazard index (HI) in three samples of Tilapia from the market exceeded the recommended value of 1.0, while all samples from the biofloc fish tank were within the maximum tolerable limit, which suggested that the daily consumption of Tilapia fishes from the market may result in considerable harmful effects. Target cancer risk (TCR) for Pb in all of the studied samples was within the range of 10-6 and 10-4, hence the adults and children would not experience any kinds of carcinogenic effects. The result obtained from this comparative study revealed that the consumption of fish species from both local market and biofloc fish farms was almost safe, but the value of TCR in Pb was higher in traditional fish samples than that of biofloc tanks, hence fish samples from biofloc farms were more suitable for consumption.
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Metais Pesados , Poluentes Químicos da Água , Animais , Metais Pesados/análise , Monitoramento Ambiental , Pesqueiros , Chumbo , Aquicultura , Medição de Risco , Peixes , Receptores de Antígenos de Linfócitos T , Poluentes Químicos da Água/análise , Contaminação de Alimentos/análiseRESUMO
Since the first prevalence of COVID-19 in 2019, it still remains the most devastating pandemic throughout the world. The current research aimed to find potential natural products to inhibit the novel coronavirus and associated infection by MD simulation and network pharmacology approach. Molecular docking was performed for 39 natural products having potent anti-SARS-CoV activity. Five natural products showed high binding interaction with the viral main protease for the SARS-CoV-2 virus, where 3ß,12-diacetoxyabieta-6,8,11,13 tetraene showed stable binding in MD simulation until 100 ns. Both 3ß,12-diacetoxyabieta-6,8,11,13 tetraene and tomentin A targeted 11 common genes that are related to COVID-19 and interact with each other. Gene ontology development analysis further showed that all these 11 genes are attached to various biological processes. The KEGG pathway analysis also showed that the proteins that are targeted by 3ß,12-diacetoxyabieta-6,8,11,13 tetraene and tomentin A are associated with multiple pathways related to COVID-19 infection. Furthermore, the ADMET and MDS studies reveals 3ß,12-diacetoxyabieta-6,8,11,13 as the best-suited compound for oral drug delivery.Communicated by Ramaswamy H. Sarma.
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Produtos Biológicos , COVID-19 , Humanos , SARS-CoV-2 , Simulação de Acoplamento Molecular , Farmacologia em Rede , Produtos Biológicos/farmacologia , Simulação de Dinâmica Molecular , Inibidores de Proteases/farmacologiaRESUMO
BACKGROUND: In the context of zoonosis, Bangladesh's small-scale dairying is yet to frame satisfactory levels due to poor biosecurity practices. OBJECTIVES: This study intended to reveal the degree of knowledge, attitudes and biosecurity practices among Sylhet district, Bangladesh's small-scale dairy farmers. We also focused on the association between biosecurity practices and the incidence of non-specific enteritis in humans. METHODS: A questionnaire-based survey was conducted on the farmers' KAP via personal interviews of 15 farmers from the randomly selected fifteen small-scale dairy farms. The questionnaire was developed with 6 questions for knowledge, 6 questions for attitude and 12 questions for the practice of biosecurity measures. Alongside that, data on the number of non-specific enteritis cases experienced by the farmers or their family members were also recorded. Spearman correlation was used to find out the correlation among KAP variables and between practice scores and non-specific enteritis incidences. RESULTS: We found an insignificant (p > 0.05) influence of demographic characteristics over knowledge, attitude and biosecurity practices. Significant (p < 0.05) and strong correlations were found in knowledge-attitude (r = 0.65), knowledge-practice (r = 0.71) and attitude-practice (r = 0.64). Incidences of non-specific enteritis and biosecurity measures' practice were also strongly correlated (r = -0.9232) and statistically significant (p < 0.05). CONCLUSIONS: Our study suggests that increasing knowledge and developing a good attitude are necessary to increase the adaptation of biosecurity measures as three of these factors are correlated. Moreover, farm biosecurity measures are closely related to human health.
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Doenças dos Bovinos , Fazendeiros , Bovinos , Humanos , Animais , Biosseguridade , Conhecimentos, Atitudes e Prática em Saúde , Bangladesh , Criação de Animais Domésticos , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/epidemiologiaRESUMO
BACKGROUND: The aberrant expression of stromal gene signatures in breast cancer has been widely studied. However, the association of stromal gene signatures with tumor immunity, progression, and clinical outcomes remains lacking. METHODS: Based on eight breast tumor stroma (BTS) transcriptomics datasets, we identified differentially expressed genes (DEGs) between BTS and normal breast stroma. Based on the DEGs, we identified dysregulated pathways and prognostic hub genes, hub oncogenes, hub protein kinases, and other key marker genes associated with breast cancer. Moreover, we compared the enrichment levels of stromal and immune signatures between breast cancer patients with bad and good clinical outcomes. We also investigated the association between tumor stroma-related genes and breast cancer progression. RESULTS: The DEGs included 782 upregulated and 276 downregulated genes in BTS versus normal breast stroma. The pathways significantly associated with the DEGs included cytokine-cytokine receptor interaction, chemokine signaling, T cell receptor signaling, cell adhesion molecules, focal adhesion, and extracellular matrix-receptor interaction. Protein-protein interaction network analysis identified the stromal hub genes with prognostic value in breast cancer, including two oncogenes (COL1A1 and IL21R), two protein kinases encoding genes (PRKACA and CSK), and a growth factor encoding gene (PLAU). Moreover, we observed that the patients with bad clinical outcomes were less enriched in stromal and antitumor immune signatures (CD8 + T cells and tumor-infiltrating lymphocytes) but more enriched in tumor cells and immunosuppressive signatures (MDSCs and CD4 + regulatory T cells) compared with the patients with good clinical outcomes. The ratios of CD8 + /CD4 + regulatory T cells were lower in the patients with bad clinical outcomes. Furthermore, we identified the tumor stroma-related genes, including MCM4, SPECC1, IMPA2, and AGO2, which were gradually upregulated through grade I, II, and III breast cancers. In contrast, COL14A1, ESR1, SLIT2, IGF1, CH25H, PRR5L, ABCA6, CEP126, IGDCC4, LHFP, MFAP3, PCSK5, RAB37, RBMS3, SETBP1, and TSPAN11 were gradually downregulated through grade I, II, and III breast cancers. It suggests that the expression of these stromal genes has an association with the progression of breast cancers. These progression-associated genes also displayed an expression association with recurrence-free survival in breast cancer patients. CONCLUSIONS: This study identified tumor stroma-associated biomarkers correlated with deregulated pathways, tumor immunity, tumor progression, and clinical outcomes in breast cancer. Our findings provide new insights into the pathogenesis of breast cancer.
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Neoplasias da Mama , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Proteínas Quinases/genética , Tetraspaninas/genéticaRESUMO
BACKGROUND: Tumor stroma is a heterogeneous cellular component in the tumor microenvironment of breast cancer. However, very few studies have explored the identification of breast cancer subtypes based on highly heterogeneous tumor stromal signatures. MATERIALS AND METHODS: Using a combined dataset composed of 8 gene expression profiling datasets for breast tumor stroma, we clustered breast cancers based on the expression levels of 100 genes whose expression values were most variable across all samples. Furthermore, we investigated the molecular features of the breast cancer subtypes identified. RESULTS: We identified 2 breast cancer subtypes, termed SBCS-1 and SBCS-2. We found that the contents of stroma and immune cells were lower in SBCS-1 than in SBCS-2, while the proportion of tumor cells was higher in SBCS-1. SBCS-1 was enriched in cancer-associated pathways, including ribosomes, cell cycle, RNA degradation, RNA polymerase, DNA replication, oxidative phosphorylation, proteasome, spliceosome, and glycolysis/gluconeogenesis. SBCS-2 was enriched in pathways of graft versus host disease, type 1 diabetes mellitus, intestinal immune network for IgA production, allograft rejection, and steroid hormone biosynthesis. Moreover, many oncogenic biological processes were highly activated in SBCS-1, including proliferation, stemness, epithelial-to-mesenchymal transition (EMT), and angiogenesis. Gene co-expression network analysis identified prognostic hub genes, transcription factor encoding genes (PFDN5 and EZH2), and protein kinase encoding gene (AURKA) in a gene module highly enriched in SBCS-1. CONCLUSION: Based on the gene expression profiles in breast cancer stroma, breast cancer can be divided into 2 subtypes, which have significantly different molecular, and clinical characteristics. The identification of new subtypes of breast cancer has clinical implications for the management of this disease.
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Neoplasias da Mama , Neoplasias da Mama/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Transcriptoma , Microambiente Tumoral/genéticaRESUMO
Background: Previous studies revealed that colonic cancer-associated fibroblasts (CAFs) are associated with the modulation of the colon tumor microenvironment (TME). However, identification of key transcriptomes and their correlations with the survival prognosis, immunosuppression, tumor progression, and metastasis in colon cancer remains lacking. Methods: We used the GSE46824, GSE70468, GSE17536, GSE35602, and the cancer genome atlas (TCGA) colon adenocarcinoma (COAD) datasets for this study. We identified the differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, hub genes, and survival-associated genes in colon cancer. Finally, we investigated the correlation of key genes with the survival prognosis, immunosuppression, and metastasis. Results: We identified 246 common DEGs between the GSE46824 and GSE70468 datasets of colonic CAFs, which included 72 upregulated and 174 downregulated genes. The upregulated pathways are mainly involved with cancers and cellular signaling, and downregulated pathways are involved with immune regulation and cellular metabolism. The search tool for the retrieval of interacting genes (STRING)-based analysis identified 15 hub genes and 9 significant clusters in colonic CAFs. The upregulation of CTHRC1, PDGFC, PDLIM3, NTM, and SLC16A3 and downregulation of FBN2 are correlated with a shorter survival time in colon cancer. The CTHRC1, PDGFC, PDLIM3, and NTM genes are positively correlated with the infiltration of tumor-associated macrophages (TAM), macrophages, M2 macrophages, the regulatory T cells (Tregs), T cell exhaustion, and myeloid-derived suppressor cells (MDSCs), indicating the immunosuppressive roles of these transcriptomes in colon cancer. Moreover, the CTHRC1, PDGFC, PDLIM3, NTM, and SLC16A3 genes are gradually increased from normal tissue to the tumor and tumor to the metastatic tumor, and FBN2 showed the reverse pattern. Furthermore, the CTHRC1, FBN2, PDGFC, PDLIM3, and NTM genes are positively correlated with the metastatic scores in colon cancer. Then, we revealed that the expression value of CTHRC1, FBN2, PDGFC, PDLIM3, NTM, and SLC16A3 showed the diagnostic efficacy in colonic CAFs. Finally, the expression level of CTHRC1, PDGFC, and NTM genes are consistently altered in colon tumor stroma as well as in the higher CAFs-group of TCGA COAD patients. Conclusion: The identified colonic CAFs-derived key genes are positively correlated with survival prognosis, immunosuppression, tumor progression, and metastasis.
Assuntos
Adenocarcinoma , Fibroblastos Associados a Câncer , Neoplasias do Colo , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Fibroblastos Associados a Câncer/patologia , Neoplasias do Colo/patologia , Proteínas da Matriz Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Terapia de Imunossupressão , Transcriptoma/genética , Microambiente Tumoral/genéticaRESUMO
Medicinally active compounds in the flavonoid class of phytochemicals are being studied for antiviral action against various DNA and RNA viruses. Quercetin is a flavonoid present in a wide range of foods, including fruits and vegetables. It is said to be efficient against a wide range of viruses. This research investigated the usefulness of Quercetin against Hepatitis C virus, Dengue type 2 virus, Ebola virus, and Influenza A using computational models. A molecular docking study using the online tool PockDrug was accomplished to identify the best binding sites between Quercetin and PubChem-based receptors. Network-pharmacological assay to opt to verify function-specific gene-compound interactions using STITCH, STRING, GSEA, Cytoscape plugin cytoHubba. Quercetin explored tremendous binding affinity against NS5A protein for HCV with a docking score of - 6.268 kcal/mol, NS5 for DENV-2 with a docking score of - 5.393 kcal/mol, VP35 protein for EBOV with a docking score of - 4.524 kcal/mol, and NP protein for IAV with a docking score of - 6.954 kcal/mol. In the network-pharmacology study, out of 39 hub genes, 38 genes have been found to interact with Quercetin and the top interconnected nodes in the protein-protein network were (based on the degree of interaction with other nodes) AKT1, EGFR, SRC, MMP9, MMP2, KDR, IGF1R, PTK2, ABCG2, and MET. Negative binding energies were noticed in Quercetin-receptor interaction. Results demonstrate that Quercetin could be a potential antiviral agent against these viral diseases with further study in in-vivo models. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-022-00132-2.
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Background: Previous studies revealed that the gene signatures are associated with the modulation and pathogenesis of pulmonary arterial hypertension (PAH). However, identifying critical transcriptional signatures in the blood of PAH patients remains lacking. Methods: The differentially expressed transcriptional signatures in the blood of PAH patients were identified by a meta-analysis from four microarray datasets. Then we investigated the enrichment of gene ontology and KEGG pathways and identified top hub genes. Besides, we investigated the correlation of crucial hub genes with immune infiltrations, hallmark gene sets, and blood vessel remodeling genes. Furthermore, we investigated the diagnostic efficacy of essential hub genes and their expression validation in an independent cohort of PAH, and we validate the expression level of hub genes in monocrotaline (MCT) induced PAH rats' model. Finally, we have identified the FDA-approved drugs that target the hub genes and their molecular docking. Results: We found 1,216 differentially expressed genes (DEGs), including 521 up-regulated and 695 down-regulated genes, in the blood of the PAH patients. The up-regulated DEGs are significantly associated with the enrichment of KEGG pathways mainly involved with immune regulation, cellular signaling, and metabolisms. We identified 13 master transcriptional regulators targeting the dysregulated genes in PAH. The STRING-based investigation identified the function of hub genes associated with multiple immune-related pathways in PAH. The expression levels of RPS27A, MAPK1, STAT1, RPS6, FBL, RPS3, RPS2, and GART are positively correlated with ssGSEA scores of various immune cells as positively correlated with the hallmark of oxidative stress. Besides, we found that these hub genes also regulate the vascular remodeling in PAH. Furthermore, the expression levels of identified hub genes showed good diagnostic efficacy in the blood of PAH, and we validated most of the hub genes are consistently dysregulated in an independent PAH cohort. Validation of hub genes expression level in the monocrotaline (MCT)-induced lung tissue of rats with PAH revealed that 5 screened hub genes (MAPK1, STAT1, TLR4, TLR2, GART) are significantly highly expressed in PAH rats, and 4 screened hub genes (RPS6, FBL, RPS3, and RPS2) are substantially lowly expressed in rats with PAH. Finally, we analyzed the interaction of hub proteins and FDA-approved drugs and revealed their molecular docking, and the results showed that MAPK1, TLR4, and GART interact with various drugs with appropriate binding affinity. Conclusion: The identified blood-derived key transcriptional signatures significantly correlate with immune infiltrations, hypoxia, glycolysis, and blood vessel remodeling genes. These findings may provide new insight into the diagnosis and treatment of PAH patients.
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Glioblastoma multiforme (GBM) is one of the most common aggressive, resistant, and invasive primary brain tumors that share neurodegenerative actions, resembling many neurodegenerative diseases. Although multiple conventional approaches, including chemoradiation, are more frequent in GBM therapy, these approaches are ineffective in extending the mean survival rate and are associated with various side effects, including neurodegeneration. This review proposes an alternative strategy for managing GBM and neurodegeneration by targeting heat shock protein 90 (Hsp90). Hsp90 is a well-known molecular chaperone that plays essential roles in maintaining and stabilizing protein folding to degradation in protein homeostasis and modulates signaling in cancer and neurodegeneration by regulating many client protein substrates. The therapeutic benefits of Hsp90 inhibition are well-known for several malignancies, and recent evidence highlights that Hsp90 inhibitors potentially inhibit the aggressiveness of GBM, increasing the sensitivity of conventional treatment and providing neuroprotection in various neurodegenerative diseases. Herein, the overview of Hsp90 modulation in GBM and neurodegeneration progress has been discussed with a summary of recent outcomes on Hsp90 inhibition in various GBM models and neurodegeneration. Particular emphasis is also given to natural Hsp90 inhibitors that have been evidenced to show dual protection in both GBM and neurodegeneration.