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1.
BMC Genomics ; 25(1): 207, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395740

RESUMO

BACKGROUND: Darjeeling tea is a globally renowned beverage, which faces numerous obstacles in sexual reproduction, such as self-incompatibility, poor seed germination, and viability, as well as issues with vegetative propagation. Somatic embryogenesis (SE) is a valuable method for rapid clonal propagation of Darjeeling tea. However, the metabolic regulatory mechanisms underlying SE in Darjeeling tea remain largely unknown. To address this, we conducted an integrated metabolomics and transcriptomics analysis of embryogenic callus (EC), globular embryo (GE), and heart-shaped embryo (HE). RESULTS: The integrated analyses showed that various genes and metabolites involved in the phenylpropanoid pathway, auxin biosynthesis pathway, gibberellin, brassinosteroid and amino acids biosynthesis pathways were differentially enriched in EC, GE, and HE. Our results revealed that despite highly up-regulated auxin biosynthesis genes YUC1, TAR1 and AAO1 in EC, endogenous indole-3-acetic acid (IAA) was significantly lower in EC than GE and HE. However, bioactive Gibberellin A4 displayed higher accumulation in EC. We also found higher BABY BOOM (BBM) and Leafy cotyledon1 (LEC1) gene expression in GE along with high accumulation of castasterone, a brassinosteroid. Total flavonoids and phenolics levels were elevated in GE and HE compared to EC, especially the phenolic compound chlorogenic acid was highly accumulated in GE. CONCLUSIONS: Integrated metabolome and transcriptome analysis revealed enriched metabolic pathways, including auxin biosynthesis and signal transduction, brassinosteroid, gibberellin, phenylpropanoid biosynthesis, amino acids metabolism, and transcription factors (TFs) during SE in Darjeeling tea. Notably, EC displayed lower endogenous IAA levels, conducive to maintaining differentiation, while higher IAA concentration in GE and HE was crucial for preserving embryo identity. Additionally, a negative correlation between bioactive gibberellin A4 (GA4) and IAA was observed, impacting callus growth in EC. The high accumulation of chlorogenic acid, a phenolic compound, might contribute to the low success rate in GE and HE formation in Darjeeling tea. TFs such as BBM1, LEC1, FUS3, LEA, WOX3, and WOX11 appeared to regulate gene expression, influencing SE in Darjeeling tea.


Assuntos
Brassinosteroides , Giberelinas , Ácido Clorogênico , Perfilação da Expressão Gênica , Ácidos Indolacéticos/metabolismo , Chá , Desenvolvimento Embrionário , Aminoácidos/metabolismo , Regulação da Expressão Gênica de Plantas
2.
Arch Virol ; 169(7): 145, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864875

RESUMO

Since 2020, African swine fever (ASF) has affected all pig breeds in Northeast India except Doom pigs, a unique indigenous breed from Assam and the closest relatives of Indian wild pigs. ASF outbreaks result in significant economic losses for pig farmers in the region. Based on sequencing and phylogenetic analysis of the B646L (p72) gene, it has been determined that ASFV genotype II is responsible for outbreaks in this region. Recent studies have shown that MYD88, LDHB, and IFIT1, which are important genes of the immune system, are involved in the pathogenesis of ASFV. The differential expression patterns of these genes in surviving ASFV-infected and healthy Doom breed pigs were compared to healthy controls at different stages of infection. The ability of Doom pigs to withstand common pig diseases, along with their genetic resemblance to wild pigs, make them ideal candidates for studying tolerance to ASFV infection. In the present study, we investigated the natural resistance to ASF in Doom pigs from an endemic area in Northeast India. The results of this study provide important molecular insights into the regulation of ASFV tolerance genes.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Surtos de Doenças , Filogenia , Animais , Febre Suína Africana/virologia , Febre Suína Africana/epidemiologia , Febre Suína Africana/imunologia , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/imunologia , Índia/epidemiologia , Suínos , Surtos de Doenças/veterinária , Genótipo , Fator 88 de Diferenciação Mieloide/genética , Resistência à Doença/genética
3.
Arch Virol ; 169(3): 54, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381218

RESUMO

African swine fever (ASF) has emerged as a threat to swine production worldwide. Evasion of host immunity by ASF virus (ASFV) is well understood. However, the role of ASFV in triggering oncogenesis is still unclear. In the present study, ASFV-infected kidney tissue samples were subjected to Illumina-based transcriptome analysis. A total of 2463 upregulated and 825 downregulated genes were differentially expressed (p < 0.05). A literature review revealed that the majority of the differentially expressed host genes were key molecules in signaling pathways involved in oncogenesis. Bioinformatic analysis indicated the activation of certain oncogenic KEGG pathways, including basal cell carcinoma, breast cancer, transcriptional deregulation in cancer, and hepatocellular carcinoma. Analysis of host-virus interactions revealed that the upregulated oncogenic RELA (p65 transcription factor) protein of Sus scrofa can interact with the A238L (hypothetical protein of unknown function) of ASFV. Differential expression of oncogenes was confirmed by qRT-PCR, using the H3 histone family 3A gene (H3F3A) as an internal control to confirm the RNA-Seq data. The levels of gene expression indicated by qRT-PCR matched closely to those determined through RNA-Seq. These findings open up new possibilities for investigation of the mechanisms underlying ASFV infection and offer insights into the dynamic interaction between viral infection and oncogenic processes. However, as these investigations were conducted on pigs that died from natural ASFV infection, the role of ASFV in oncogenesis still needs to be investigated in controlled experimental studies.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Neoplasias Hepáticas , Animais , Suínos , Vírus da Febre Suína Africana/genética , Transcriptoma , Febre Suína Africana/genética , Oncogenes , Transformação Celular Neoplásica , Carcinogênese/genética
4.
Nanotechnology ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025083

RESUMO

Achieving sustainable future energy goals includes enhancing renewable energy production, optimizing daily energy consumption using feedback loops and minimizing/monitoring contributions to atmospheric carbon dioxide (CO2). Developing economic next-generation CO2 sensors enables local monitoring of industrial CO2 emissions, aiding energy management and climate monitoring. This study elucidates the efficacy of CO2 chemiresistor based on indium oxide (In2O3) micro cubes with spilled-over nanoparticles. The investigation primarily focuses on fabricating and optimising In2O3-based CO2 chemiresistors utilizing a hydrothermal technique, creating porous micro cubes essential for enhanced CO2 monitoring. As revealed by various characterization techniques, the minimum crystallite size was found to be 24.92 nm with optimum porosity and a high surface-to-volume ratio comprising spilled-over nanoparticle morphology. The fabricated chemiresistor demonstrated excellent CO2 sensing efficacy with a maximum response of around 4.1% at room temperature with selectivity, repeatability, and reversible sensing behaviour. The sensing mechanism has been revealed, which is supported by theoretical density functional theory evaluations. Notably, the sensing results reveal the capability of In2O3-based sensors to detect CO2 at low concentrations as low as ≤ 10 ppm, which enables the chemiresistor for practical implementation in diverse sectors to achieve sustainability. .

5.
Mol Biol Rep ; 51(1): 195, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270707

RESUMO

BACKGROUND: The angiogenic cytokine vascular endothelial growth factor A (VEGFA) also exerts non-angiogenic effects on endocrine functionality of porcine luteal cells critical for progesterone (P4) production. METHOD AND RESULTS: The expression dynamics of VEGFA-FLT/KDR system were investigated using RT-qPCR during luteal stages and VEGFA gene knock out (KO) porcine luteal cells were generated using CRISPR/Cas9 technology. The downstream effects of VEGFA ablation were studied using RT-qPCR, Annexin V, MTT, ELISA for P4 estimation and scratch wound assay. Bioinformatics analysis of RNA-Seq data of porcine mid-luteal stage was conducted for exploring protein-protein interaction network, KEGG pathways, transcription factors and kinase mapping for VEGFA-FLT/KDR interactomes. The VEGFA-FLT/KDR system expressed throughout the luteal stages with highest expression during mid- luteal stage. Cellular morphology, structure and oil-red-o staining for lipid droplets did not differ significantly between VEGFA KO and wild type cells, however, VEGFA KO significantly decreased (p < 0.05) viability and proliferation efficiency of edited cells on subsequent passages. Expression of apoptotic gene, CASP3 and hypoxia related gene, HIF1A were significantly (p < 0.05) upregulated in KO cells. The relative mRNA expression of VEGFA and steroidogenic genes STAR, CYP11A1 and HSD3B1 decreased significantly (p < 0.05) upon KO, which was further validated by the significant (p < 0.05) decrease in P4 output from KO cells. Bioinformatics analysis mapped VEGFA-FLT/KDR system to signalling pathways associated with steroidogenic cell functionality and survival, which complemented the findings of the study. CONCLUSION: The ablation of VEGFA gene resulted in decreased steroidogenic capability of luteal cells, which suggests that VEGFA exerts additional non-angiogenic regulatory effects in luteal cell functionality.


Assuntos
Sistemas CRISPR-Cas , Células Lúteas , Feminino , Suínos , Animais , Sistemas CRISPR-Cas/genética , Edição de Genes , Fator A de Crescimento do Endotélio Vascular/genética , Anexina A5
6.
Dig Endosc ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695110

RESUMO

Endoscopic ultrasound (EUS) is increasingly used as a therapeutic approach for gastrointestinal diseases, especially with the advent of lumen-apposing metal stents (LAMS). This has led to a rise in of EUS-guided gastrointestinal anastomosis procedures. Due to the reliability of intestinal conduits with LAMS, indications for EUS-guided gastrointestinal anastomosis are becoming more common and trend to potentially be standard care for gastric outlet obstruction, afferent loop syndrome, and EUS-directed transgastric interventions such as EUS-directed endoscopic retrograde cholangiopancreatography. Retrospective and prospective data indicate that the procedure is becoming widely adopted with promising outcomes. This article aims to review the existing literature on EUS-guided gastrointestinal anastomosis and predict its future developments.

7.
Int J Mol Sci ; 25(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38542288

RESUMO

Hypoxia-inducible factor-1α (HIF-1α) is a major transcriptional factor, which plays an important role in cellular reprogramming processes under hypoxic conditions, which facilitate solid tumors' progression. HIF-1α is directly involved in the regulation of the angiogenesis, metabolic reprogramming, and extracellular matrix remodeling of the tumor microenvironment. Therefore, an in-depth study on the role of HIF-1α in solid tumor malignancies is required to develop novel anti-cancer therapeutics. HIF-1α also plays a critical role in regulating growth factors, such as the vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, in a network manner. Additionally, it plays a significant role in tumor progression and chemotherapy resistance by regulating a variety of angiogenic factors, including angiopoietin 1 and angiopoietin 2, matrix metalloproteinase, and erythropoietin, along with energy pathways. Therefore, this review attempts to provide comprehensive insight into the role of HIF-1α in the energy and angiogenesis pathways of solid tumors.


Assuntos
Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição , Fatores de Crescimento do Endotélio Vascular , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neovascularização Patológica/patologia
8.
J Environ Manage ; 355: 120508, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38457896

RESUMO

Crude oil contamination has inflicted severe damage to soil ecosystems, necessitating effective remediation strategies. This study aimed to compare the efficacy of four different techniques (biostimulation, bioaugmentation, bioaugmentation + biostimulation, and natural attenuation) for remediating agricultural soil contaminated with crude oil using soil microcosms. A consortium of previously characterized bacteria Xanthomonas boreopolis, Microbacterium schleiferi, Pseudomonas aeruginosa, and Bacillus velezensis was constructed for bioaugmentation. The microbial count for the constructed consortium was recorded as 2.04 ± 0.11 × 108 CFU/g on 60 d in augmented and stimulated soil samples revealing their potential to thrive in chemically contaminated-stress conditions. The microbial consortium through bioaugmentation + biostimulation approach resulted in 79 ± 0.92% degradation of the total polyaromatic hydrocarbons (2 and 3 rings âˆ¼ 74%, 4 and 5 rings âˆ¼ 83% loss) whereas, 91 ± 0.56% degradation of total aliphatic hydrocarbons (C8-C16 ∼ 90%, C18-C28 ∼ 92%, C30 to C40 ∼ 88% loss) was observed in 60 d. Further, after 60 d of microcosm treatment, the treated soil samples were used for phytotoxicity assessment using wheat (Triticum aestivum), black chickpea (Cicer arietinum), and mustard (Brassica juncea). The germination rates for wheat (90%), black chickpea (100%), and mustard (100%) were observed in 7 d with improved shoot-root length and biomass in both bioaugmentation and biostimulation approaches. This study projects a comprehensive approach integrating bacterial consortium and nutrient augmentation strategies and underscores the vital role of innovative environmental management practices in fostering sustainable remediation of oil-contaminated soil ecosystems. The formulated bacterial consortium with a nutrient augmentation strategy can be utilized to restore agricultural lands towards reduced phytotoxicity and improved plant growth.


Assuntos
Petróleo , Poluentes do Solo , Biodegradação Ambiental , Solo/química , Ecossistema , Poluentes do Solo/análise , Hidrocarbonetos/metabolismo , Microbiologia do Solo
9.
J Vector Borne Dis ; 61(1): 117-122, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38648413

RESUMO

BACKGROUND OBJECTIVES: This study reports observation on circulating serotypes and genotypes of Dengue Virus in North India. METHODS: Serum samples were obtained from suspected cases of dengue referred to the virus diagnostic laboratory during 2014 to 2022. All samples were tested for anti-dengue virus IgM antibodies and NS1Ag by ELISA. NS1Ag positive samples were processed for serotyping and genotyping. RESULTS: Total 41,476 dengue suspected cases were referred to the laboratory of which 12,292 (29.6%) tested positive. Anti-Dengue Virus IgM antibodies, NS1Ag, both IgM and NS1Ag, were positive in 7007 (57.4%); 3200 (26.0%) and 2085 (16.0%) cases respectively. Total 762 strains were serotyped during 9-year period. DENV-1, DENV-2, DENV-3 and DENV-4 serotypes were found in 79 (10.37%), 506 (66.40%), 151 (19.82%) and 26 (3.41%) cases respectively. DENV-1, DENV-2 and DENV-3 were in circulation throughout. Total 105 strains were genotyped. Genotype IV of DENV-1 serotype was circulating till 2014 which was later replaced by genotype V. A distinct seasonality with increase in number of cases in post-monsoon period was seen. INTERPRETATION CONCLUSION: DENV-1, DENV-2 and DENV-3 were found to be in circulation in North India. Predominant serotype/genotype changed at times, but not at regular intervals.


Assuntos
Anticorpos Antivirais , Vírus da Dengue , Dengue , Genótipo , Sorogrupo , Índia/epidemiologia , Vírus da Dengue/genética , Vírus da Dengue/classificação , Vírus da Dengue/isolamento & purificação , Humanos , Dengue/virologia , Dengue/epidemiologia , Dengue/sangue , Anticorpos Antivirais/sangue , Imunoglobulina M/sangue , Feminino , Sorotipagem , Masculino , Adulto , Criança , Ensaio de Imunoadsorção Enzimática , Adolescente , Pessoa de Meia-Idade , Adulto Jovem , Estações do Ano , Pré-Escolar
10.
Molecules ; 29(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38398638

RESUMO

The high concentration of antibiotics in aquatic environments is a serious environmental issue. In response, researchers have explored photocatalytic degradation as a potential solution. Through chemical vapor deposition (CVD), we synthesized copper selenide (ß-Cu2-xSe) and found it an effective catalyst for degrading tetracycline hydrochloride (TC-HCl). The catalyst demonstrated an impressive degradation efficiency of approximately 98% and a reaction rate constant of 3.14 × 10-2 min-1. Its layered structure, which exposes reactive sites, contributes to excellent stability, interfacial charge transfer efficiency, and visible light absorption capacity. Our investigations confirmed that the principal active species produced by the catalyst comprises O2- radicals, which we verified through trapping experiments and electron paramagnetic resonance (EPR). We also verified the TC-HCl degradation mechanism using high-performance liquid chromatography-mass spectrometry (LC-MS). Our results provide valuable insights into developing the ß-Cu2-xSe catalyst using CVD and its potential applications in environmental remediation.

11.
Toxicol Mech Methods ; 34(6): 703-716, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38465425

RESUMO

Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl3) to rats causes dementia and pathophysiological alterations linked to Alzheimer's disease (AD). Taxifolin's neuroprotective effects against AlCl3-induced neurotoxicity in vitro and in vivo studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 µM) was tested against AlCl3 (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin's mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 (hMD-2) was investigated. AlCl3 (25 mg/kg/d, i.p.) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, i.p.) was given along with AlCl3. This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats' brain in addition to histopathology. The docking score for taxifolin with hMD-2 was found to be -4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl3 in both C6 and SH-SY5Y cells. Treatment with 10 µM taxifolin restored AlCl3-induced altered cell morphology. AlCl3 administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl3-induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl3 administration in rats. Thus, taxifolin may protect the brain against AD.


Assuntos
Cloreto de Alumínio , Encéfalo , Fármacos Neuroprotetores , Quercetina , Receptor 4 Toll-Like , Animais , Humanos , Masculino , Ratos , Cloreto de Alumínio/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/metabolismo , Linhagem Celular Tumoral , Demência/induzido quimicamente , Demência/tratamento farmacológico , Demência/prevenção & controle , Demência/patologia , Relação Dose-Resposta a Droga , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Quercetina/análogos & derivados , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos Wistar , Receptor 4 Toll-Like/metabolismo
12.
J Food Sci Technol ; 61(8): 1516-1524, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38966784

RESUMO

Escherichia coli and Staphylococcus aureus are the most important food borne pathogen transmitting from animal meat and meat products. Therefore, it is vital to design an accurate and specific diagnostic tool for identifying those food-borne pathogens in animal meat and meat products. In the current study, E. coli, methicillin-resistant and sensitive S. aureus (MRSA and MSSA) were simultaneously detected using a developed triplex PCR-based technique. To obtain an optimal reaction parameter, the multiplex assay was optimised by changing just one parameter while holding the others constant. Specificity of the assay was assessed using several porcine bacterial template DNA. The plasmid DNA was used to test the multiplex PCR assay's sensitivity and interference in spiked pork samples. E. coli, MRSA, and MSSA each have PCR amplified products with sizes of 335, 533, and 209 bp, respectively. The assay detects a minimum microbial load of 102 CFU/µl for all the three pathogens and can identify bacterial DNA as low as 10-2 ng/µl. The assay was validated employing 210 pork samples obtained from retail meat shops and slaughter houses, with MRSA, E. coli, and MSSA with the occurrence rate of 1.9%, 42.38%, and 18.1%, respectively. The rate of mixed bacterial contamination in pork meat samples examined with the developed method was 6.19%, 1.43%, 1.90%, and 1.43% for MSSA & E. coli, MRSA & E. coli, MSSA & MRSA, and E. coli, MSSA & MRSA, respectively. The developed multiplex PCR assay is quick and efficient, and it can distinguish between different bacterial pathogens in a single reaction tube.

13.
Microb Pathog ; 185: 106452, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37972743

RESUMO

The present investigation focuses on examining the clinical, histopathological, and ultrastructural changes that occurred in pig, during an outbreak of African swine fever (ASF) in 2022 in Assam, India. The disease initially manifested as a per-acute case with high mortality but without any evident clinical signs. Subsequently, some animals exhibited an acute form of the disease characterized by high fever (104-106 °F), anorexia, vomiting, respiratory distress, and bleeding from the anal and nasal orifices. During acute African swine fever virus (ASFV) infections, elevated levels of pro-inflammatory IL-1α, IL-1ß, IL-6, TNF, CCL2, CCL5, and CXCL10 were detected in the palatine tonsil, lymph nodes, spleen, and kidney using qPCR assay. These molecular changes were associated with haemorrhages, edemas, and lymphoid depletion. Postmortem examinations revealed prominent features such as splenomegaly with haemorrhages, haemorrhagic lymphadenitis, severe petechial haemorrhage in the kidney, pneumonia in the lungs, and necrotic palatine tonsil. Histopathological analysis demonstrated lymphocyte depletion in lymphoid organs, multi-organ haemorrhages, and interstitial pneumonia in the lungs. Scanning electron microscopy (SEM) further confirmed lymphocyte depletion in lymphoid organs through lymphocyte apoptosis and kidney damage with distorted tubules due to red blood cell destruction. Transmission electron microscopy reaffirmed lymphocyte apoptosis by observing chromatin condensation and nucleus margination in lymphocytes of lymphoid organs. These findings provide comprehensive insights into the clinical, histopathological, and ultrastructural aspects of ASF outbreak in pigs. Understanding the pathological changes associated with ASF can contribute to improved diagnosis, prevention, and control measures for this highly contagious and economically devastating viral disease.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Suínos , Animais , Febre Suína Africana/epidemiologia , Febre Suína Africana/patologia , Linfócitos , Surtos de Doenças , Hemorragia , Sus scrofa
14.
Plant Cell ; 32(5): 1644-1664, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32193204

RESUMO

Cell polarity is a fundamental feature of all multicellular organisms. PIN auxin transporters are important cell polarity markers that play crucial roles in a plethora of developmental processes in plants. Here, to identify components involved in cell polarity establishment and maintenance in plants, we performed a forward genetic screening of PIN2:PIN1-HA;pin2 Arabidopsis (Arabidopsis thaliana) plants, which ectopically express predominantly basally localized PIN1 in root epidermal cells, leading to agravitropic root growth. We identified the regulator of PIN polarity 12 (repp12) mutation, which restored gravitropic root growth and caused a switch in PIN1-HA polarity from the basal to apical side of root epidermal cells. Next Generation Sequencing and complementation experiments established the causative mutation of repp12 as a single amino acid exchange in Aminophospholipid ATPase3 (ALA3), a phospholipid flippase predicted to function in vesicle formation. repp12 and ala3 T-DNA mutants show defects in many auxin-regulated processes, asymmetric auxin distribution, and PIN trafficking. Analysis of quintuple and sextuple mutants confirmed the crucial roles of ALA proteins in regulating plant development as well as PIN trafficking and polarity. Genetic and physical interaction studies revealed that ALA3 functions together with the ADP ribosylation factor GTPase exchange factors GNOM and BIG3 in regulating PIN polarity, trafficking, and auxin-mediated development.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Ácidos Indolacéticos/metabolismo , Arabidopsis/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Brefeldina A/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Epistasia Genética/efeitos dos fármacos , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Mutação/genética , Proteínas de Transferência de Fosfolipídeos/metabolismo , Ligação Proteica/efeitos dos fármacos , Nicotiana/metabolismo , Rede trans-Golgi/efeitos dos fármacos , Rede trans-Golgi/metabolismo
15.
Ann Hematol ; 102(1): 73-87, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36527458

RESUMO

To gain insights into the idiosyncrasies of CD34 + enriched leukemic stem cells, we investigated the nature and extent of transcriptional heterogeneity by single-cell sequencing in pediatric AML. Whole transcriptome analysis of 28,029 AML single cells was performed using the nanowell cartridge-based barcoding technology. Integrated transcriptional analysis identified unique leukemic stem cell clusters of each patient and intra-patient heterogeneity was revealed by multiple LSC-enriched clusters differing in their cell cycle processes and BCL2 expression. All LSC-enriched clusters exhibited gene expression profile of dormancy and self-renewal. Upregulation of genes involved in non-coding RNA processing and ribonucleoprotein assembly were observed in LSC-enriched clusters relative to HSC. The genes involved in regulation of apoptotic processes, response to cytokine stimulus, and negative regulation of transcription were upregulated in LSC-enriched clusters as compared to the blasts. Validation of top altered genes in LSC-enriched clusters confirmed upregulation of TCF7L2, JUP, ARHGAP25, LPAR6, and PRDX1 genes, and serine/threonine kinases (STK24, STK26). Upregulation of LPAR6 showed trend towards MRD positive status (Odds ratio = 0.126; 95% CI = 0.0144-1.10; p = 0.067) and increased expression of STK26 significantly correlated with higher RFS (HR = 0.231; 95% CI = 0.0506-1.052; p = 0.04). Our findings addressed the inter- and intra-patient diversity within AML LSC and potential signaling and chemoresistance-associated targets that warrant investigation in larger cohort that may guide precision medicine in the near future.


Assuntos
Leucemia Mieloide Aguda , Criança , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Análise da Expressão Gênica de Célula Única , Antígenos CD34/metabolismo , Perfilação da Expressão Gênica , Células-Tronco/metabolismo , Células-Tronco Neoplásicas/metabolismo , Receptores de Ácidos Lisofosfatídicos/genética , Receptores de Ácidos Lisofosfatídicos/metabolismo
16.
Neurochem Res ; 48(7): 2029-2058, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36795184

RESUMO

Neurological disorders pose a great threat to social health and are a major cause for mortality and morbidity. Effective drug development complemented with the improved drug therapy has made considerable progress towards easing symptoms associated with neurological illnesses, yet poor diagnosis and imprecise understanding of these disorders has led to imperfect treatment options. The scenario is complicated by the inability to extrapolate results of cell culture studies and transgenic models to clinical applications which has stagnated the process of improving drug therapy. In this context, the development of biomarkers has been viewed as beneficial to easing various pathological complications. A biomarker is measured and evaluated in order to gauge the physiological process or a pathological progression of a disease and such a marker can also indicate the clinical or pharmacological response to a therapeutic intervention. The development and identification of biomarkers for neurological disorders involves several issues including the complexity of the brain, unresolved discrepant data from experimental and clinical studies, poor clinical diagnostics, lack of functional endpoints, and high cost and complexity of techniques yet research in the area of biomarkers is highly desired. The present work describes existing biomarkers for various neurological disorders, provides support for the idea that biomarker development may ease our understanding underlying pathophysiology of these disorders and help to design and explore therapeutic targets for effective intervention.


Assuntos
Doenças do Sistema Nervoso , Humanos , Doenças do Sistema Nervoso/diagnóstico , Biomarcadores , Encéfalo
17.
Phys Chem Chem Phys ; 25(20): 14374-14386, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37184034

RESUMO

A Cu(II)-salen complex encapsulated in MWW-framework as an efficient chiral organocatalyst was developed for the synthesis of 3,4-dihydropyrimidin-2-(1H)-one (DHPMs) derivatives via an asymmetric pathway. In order to confirm its structural properties, single-crystal X-ray diffraction, powder XRD, BET, XPS, FE-SEM, EDX, UV-Vis, and FTIR spectra were used. Using computer-assisted DFT calculations, the Cu(II)-salen complex has been fine-tuned to fit into the pocket of the porous MWW support while keeping its chirality. This organocatalyst was shown to be a potent catalyst for the formation of the desired DHPMs product under short reaction times. Furthermore, this green protocol allows rapid and simple isolation of active MWW-trapped Cu(II)-salen scaffolds and its reusability in at least five consecutive runs without losing much of its activity.

18.
Environ Res ; 228: 115868, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37040856

RESUMO

Enzymatic (laccase mediated) decolorization of dyes remains inefficient for recalcitrant dyes, which can be better handled by electrocoagulation (EC). However, EC is energy intensive and produce large amount of sludge. In light of the same, present study offers a promising solution for the treatment of textile effluent meeting surface discharge norms, using hybridization of enzymatic and electrocoagulation treatment. The findings revealed best color removal (90%) of undiluted (raw) textile effluent (4592 hazen) is achievable by employing EC using zinc-coated iron electrode at current density 25 mA cm-2 followed by partially purified laccase (LT) treatment, and activated carbon (AC) polishing at ambient conditions. Overall, the decolorization performance of Hybrid EC-LT integrated AC approach was 1.95 times better than only laccase treatment. Also, the sludge generation from Hybrid EC-LT integrated AC (0.7 g L-1) was 3.3 times lesser than EC alone (2.1 g L-1). Therefore, the present study recommends Hybrid EC-LT integrated AC could be potential approach to treat complex textile effluent sustainably with lower energy input and waste sludge generation.


Assuntos
Lacase , Esgotos , Indústria Têxtil , Eletrocoagulação , Corantes , Carvão Vegetal , Resíduos Industriais/análise
19.
Environ Res ; 231(Pt 1): 115862, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37146933

RESUMO

Cancer is a major global public health concern that affects both industrialized and developing nations. Current cancer chemotherapeutic options are limited by side effects, but plant-derived alternatives and their derivatives offer the possibilities of enhanced treatment response and reduced side effects. A plethora of recently published articles have focused on treatments based on cannabinoids and cannabinoid analogs and reported that they positively affect healthy cell growth and reverse cancer-related abnormalities by targeting aberrant tumor microenvironments (TMEs), lowering tumorigenesis, preventing metastasis, and/or boosting the effectiveness of chemotherapy and radiotherapy. Furthermore, TME modulating systems are receiving much interest in the cancer immunotherapy field because it has been shown that TMEs have significant impacts on tumor progression, angiogenesis, invasion, migration, epithelial to mesenchymal transition, metastasis and development of drug resistance. Here, we have reviewed the effective role of cannabinoids, their analogs and cannabinoid nano formulations on the cellular components of TME (endothelial cells, pericytes, fibroblast and immune cells) and how efficiently it retards the progression of carcinogenesis is discussed. The article summarizes the existing research on the molecular mechanisms of cannabinoids regulation of the TME and finally highlights the human studies on cannabinoids' active interventional clinical trials. The conclusion outlines the need for future research involving clinical trials of cannabinoids to demonstrate their efficacy and activity as a treatment/prevention for various types of human malignancies.


Assuntos
Canabinoides , Neoplasias , Humanos , Canabinoides/farmacologia , Células Endoteliais , Transição Epitelial-Mesenquimal , Neoplasias/tratamento farmacológico , Microambiente Tumoral , Ensaios Clínicos como Assunto
20.
Environ Res ; 225: 115592, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36863654

RESUMO

"Save Soil Save Earth" is not just a catchphrase; it is a necessity to protect soil ecosystem from the unwanted and unregulated level of xenobiotic contamination. Numerous challenges such as type, lifespan, nature of pollutants and high cost of treatment has been associated with the treatment or remediation of contaminated soil, whether it be either on-site or off-site. Due to the food chain, the health of non-target soil species as well as human health were impacted by soil contaminants, both organic and inorganic. In this review, the use of microbial omics approaches and artificial intelligence or machine learning has been comprehensively explored with recent advancements in order to identify the sources, characterize, quantify, and mitigate soil pollutants from the environment for increased sustainability. This will generate novel insights into methods for soil remediation that will reduce the time and expense of soil treatment.


Assuntos
Metais Pesados , Poluentes do Solo , Humanos , Ecossistema , Inteligência Artificial , Poluição Ambiental/prevenção & controle , Metais Pesados/análise , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Solo
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