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1.
Environ Res ; 253: 119142, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750997

RESUMEN

Agricultural water resource utilization efficiency in China is facing significant challenges due to the dual constraints of carbon emissions and water pollution. The inefficiency in water usage in agriculture not only impacts the sustainability of water resources but also contributes to environmental degradation through increased carbon emissions and water pollution. Agricultural water resource utilization efficiency under the constraint of carbon emission and water pollution has been a critical issue in China from 2005 to 2022. This study employs the Quantile Autoregressive Distributed Lag (QARDL) method to comprehensively assess and analyze the complex relationship that exists between agricultural water usage, carbon emissions, and water pollution. By analyzing distinct quantiles of the data distribution, the research investigates how different levels of water resource utilization efficiency relate to carbon emissions and water pollution under various conditions. The findings reveal nuanced insights into the dynamic interactions among these components within the agricultural sector. This research project focuses on the efficiency of water resource utilization in agriculture while considering the constraints of carbon emission and water pollution. Given the dynamic and time-dependent character of these components, the QARDL methodology makes it possible to get a detailed knowledge of how they interact within the framework of agriculture. The study aims to give significant insights and policy suggestions to improve agricultural practices while minimizing environmental concerns linked to carbon emissions and water pollution.


Asunto(s)
Agricultura , Carbono , Recursos Hídricos , China , Carbono/análisis , Contaminación del Agua/análisis
2.
J Environ Manage ; 365: 121578, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38944956

RESUMEN

Recent decades have witnessed an unprecedented transformation in the global energy landscape, driven by environmental concerns and the quest for sustainable economic growth. As the world grapples with the urgent need for decarbonization, the utilization of renewable energy technologies with the instrumental role of rare earth elements (REEs) has come to the forefront. However, empirical investigations into their synergistic pathways for product and economic complexities concerning achieving a low-carbon future remain scarce. Therefore, we forecast synergistic pathways between the REE supply, renewable energy, economic and product complexities, and GDP growth using a panel dataset of 11 REE-producing countries from 1990 to 2023. We used Common Correlated Effects and Temporal Causal Models as primary methods to estimate panel long-run elasticities and subsequently forecast mutual causal synergies between the variables. The results indicated that REE supply led to renewable energy and economic growth that further elevated the countries' product and economic complexities rankings. GDP growth increased REE production, economic complexity, and renewable energy directly, and consequently, product complexity and REE production through them. This underscores the positive role of REE production coupled with renewable energy technologies in achieving a low-carbon future based on economic diversification, enhanced industrial capabilities, and technological sophistication.

3.
Molecules ; 29(3)2024 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-38338462

RESUMEN

Tuberculosis is one of the most common infectious diseases in the world, caused by Mycobacterium tuberculosis. The outbreak of multiple drug-resistant tuberculosis has become a major challenge to prevent this disease worldwide. ClpC1 is a Clp ATPase protein of Mycobacterium tuberculosis, functioning as a chaperon when combined with the Clp complex. ClpC1 has emerged as a new target to discover anti-tuberculosis drugs. This study aimed to explore the ClpC1 inhibitors from actinomycetes, which have been known to provide abundant sources of antibiotics. Two cyclic peptides, including nocardamin (1), halolitoralin A (3), and a lactone pleurone (2), were isolated from the culture of Streptomyces aureus (VTCC43181). The structures of these compounds were determined based on the detailed analysis of their spectral data and comparison with references. This is the first time these compounds have been isolated from S. aureus. Compounds 1-3 were evaluated for their affection of ATPase activity of the recombinant ClpC1 protein. Of these compounds, halolitoralin A (1), a macrocyclic peptide, was effective for the ATPase hydrolysis of the ClpC1 protein.


Asunto(s)
Mycobacterium tuberculosis , Streptomyces , Staphylococcus aureus/metabolismo , Antituberculosos/farmacología , Antituberculosos/metabolismo , Proteínas Bacterianas/química , Adenosina Trifosfatasas/metabolismo
4.
J Anim Physiol Anim Nutr (Berl) ; 108(2): 439-450, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37975278

RESUMEN

Chlorogenic acid (CGA), also known as 3-caffeioylquinic acid or coffee tannin, is a water-soluble polyphenol phenylacrylate compound produced through the shikimate pathway by plants during aerobic respiration. CGA widely exists in higher dicotyledons, ferns and many Chinese medicinal materials, and enjoys the reputation of 'plant gold'. Here, we summarized the source, chemical structure, biological activity functions of CGA and its research progress in pigs, aiming to provide a more comprehensive understanding and theoretical basis for the prospect of CGA replacing antibiotics as a pig feed additive.


Asunto(s)
Ácido Clorogénico , Café , Animales , Porcinos , Ácido Clorogénico/química , Café/química , Antioxidantes
5.
BMC Genomics ; 24(1): 477, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37612620

RESUMEN

BACKGROUND: Numerous circular RNAs (circRNAs) have been recently identified in porcine tissues and cell types. Nevertheless, their significance in porcine spleen development is yet unelucidated. Herein, we reported an extensive overlook of circRNA expression profile during spleen development in Meishan pigs. RESULTS: Overall, 39,641 circRNAs were identified from 6,914 host genes. Among them, many circRNAs are up- or down-regulated at different time points of pig spleen development. Using WGCNA analysis, we revealed two essential modules for protein-coding genes and circRNAs. Subsequent correlation analysis revealed 67 circRNAs/co-expressed genes that participated in immnue-associated networks. Furthermore, a competing endogenous RNA (ceRNA) network analysis of circRNAs revealed that 12 circRNAs modulated CD226, MBD2, SAMD3, SIT1, SRP14, SYTL3 gene expressions via acting as miRNA sponges. Moreover, the circRNA_21767/miR-202-3p axis regulated SIT1 expression in a ceRNA manner, which is critical for the immune-based regulation of spleen development in Meishan pigs. CONCLUSIONS: Overall, our results demonstrated that the circRNAs were differentially expressed during different stages of porcine spleen development, meanwhile the circRNAs interacted with immune-related genes in a ceRNA-based fashion. Moreover, we presented biomedical researchers with RNAseqTools, a user-friendly and powerful software for the visualization of transcriptome profile data.


Asunto(s)
MicroARNs , ARN Circular , Bazo , Porcinos , Animales , Proteínas de Unión al ADN , MicroARNs/genética , ARN Circular/genética , Bazo/crecimiento & desarrollo , Bazo/fisiología , Porcinos/genética , Estudio de Asociación del Genoma Completo , China
6.
J Med Virol ; 94(2): 549-556, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34730256

RESUMEN

To investigate the molecular characteristics of human respiratory syncytial virus (HRSV) detected in Gyeonggi Province from 2015/16 to 2017/18, 2331 specimens from patients with sporadic acute respiratory illness and 85 specimens from four HRSV outbreaks in the postpartum care center were analyzed by real-time reverse transcription PCR. HRSVs were detected in 97 of the 2416 (4.0%) specimens, and among the positive specimens, 38 (39.2%) were identified as HRSV-A and 59 (60.8%) as HRSV-B. During the study periods, HRSV-B predominated in all seasons, except in 2016/17 during which HRSV-A predominated. Depending on the age groups, HRSV prevalence was the highest in 0- to 2-year-old patients. Comparison of noninfected subjects with HRSV-infected subjects revealed that HRSV infection more frequently resulted in fever, nasal obstruction, and wheezing, although the frequency of sore throat was low; however, comparison of the symptoms between HRSV-A- and HRSV-B-infected patients revealed no significant differences in symptoms. Phylogenetic analysis showed that all HRSV-A patients had an ON1 genotype, and all HRSV-B patients had an BA9 genotype. These results provide a valuable reference regarding the circulating pattern and molecular characterization of HRSV. Continuous monitoring will be essential to detect newly emerging HRSV genotypes.


Asunto(s)
Evolución Molecular , Proteínas de Unión al GTP/genética , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Brotes de Enfermedades , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Filogenia , Reacción en Cadena en Tiempo Real de la Polimerasa , República de Corea/epidemiología , Virus Sincitial Respiratorio Humano/clasificación , Estaciones del Año , Adulto Joven
7.
Int J Mol Sci ; 23(21)2022 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-36362221

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease with a rapidly increasing number of cases worldwide. This study aimed to evaluate the effects of Lactobacillus sakei MJM60958 (MJM60958) on NAFLD in vitro and in vivo. In in vitro tests, MJM60958 significantly inhibited lipid accumulation by 46.79% in HepG2 cells stimulated with oleic acid and cholesterol (OA-C). Moreover, MJM60958 showed safe and probiotic characteristics in vitro. In the animal study, MJM60958 administration in a high-fat diet-induced NAFLD mouse model significantly reduced body weight and liver weight, and controlled aspartate aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), urea nitrogen (BUN), and uric acid (UA) levels in the blood, which are features of NAFLD. Further, treatment with MJM60958 also reduced steatosis scores in liver tissues, serum leptin and interleukin, and increased serum adiponectin content. Moreover, administration of MJM60958 resulted in a significantly decreased expression of some genes and proteins which are related to lipid accumulation, such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein 1 (SREBP-1), and also upregulated genes and protein expression of lipid oxidation such as peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1a (CPT1A). Administration of MJM60958 increased the relative abundance of specific microbial taxa such as Verrucomicrobia, which are abundant in non-NAFLD mice, and reduced Firmicutes, which are a major group in NAFLD mice. MJM60958 affected the modulation of gut microbiota and altered the strain profile of short-chain fatty acids (SCFAs) production in the cecum by reduced lactic acid and enhanced acetic acid production. Overall, MJM60958 showed potential as a probiotic that can prevent and treat NAFLD.


Asunto(s)
Microbioma Gastrointestinal , Latilactobacillus sakei , Enfermedad del Hígado Graso no Alcohólico , Probióticos , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Dieta Alta en Grasa/efectos adversos , Metabolismo de los Lípidos , Hígado/metabolismo , Inflamación/metabolismo , Triglicéridos/metabolismo , Probióticos/farmacología , Probióticos/uso terapéutico , Ratones Endogámicos C57BL
8.
Int J Mol Sci ; 24(1)2022 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-36613723

RESUMEN

Gut microbiota are known to play an important role in obesity. Enterobacter cloacae, a Gram-negative bacterium, has been considered a pathogenic bacterium related to obesity in the gut. In this study, we established an obesity model of C. elegans by feeding E. cloacae combined with a high glucose diet (HGD), which significantly induced lipid accumulation. An anti-lipid mechanism study revealed that the fatty acid composition and the expression level of fat metabolism-related genes were altered by feeding E. cloacae to C. elegans under HGD conditions. Lactic acid bacteria that showed antagonistic activity against E. cloacae were used to screen anti-obesity candidates in this model. Among them, L. pentosus MJM60383 (MJM60383) showed good antagonistic activity. C. eleans fed with MJM60383 significantly reduced lipid accumulation and triglyceride content. The ratio of C18:1Δ9/C18:0 was also changed in C. elegans by feeding MJM60383. In addition, the expression level of genes related to fatty acid synthesis was significantly decreased and the genes related to fatty acid ß-oxidation were up-regulated by feeding MJM60383. Moreover, MJM60383 also exhibited a high adhesive ability to Caco-2 cells and colonized the gut of C. elegans. Thus, L. pentosus MJM60383 can be a promising candidate for anti-obesity probiotics. To the best of our knowledge, this is the first report that uses E. cloacae combined with a high-glucose diet to study the interactions between individual pathogens and probiotics in C. elegans.


Asunto(s)
Lactobacillus pentosus , Probióticos , Animales , Humanos , Caenorhabditis elegans/metabolismo , Glucosa/metabolismo , Enterobacter cloacae , Células CACO-2 , Obesidad/metabolismo , Ácidos Grasos/metabolismo , Probióticos/farmacología
9.
Int J Mol Sci ; 23(3)2022 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-35163797

RESUMEN

H1N1 and H3N2 are the two most common subtypes of swine influenza virus (SIV). They not only endanger the pig industry, but are also a huge risk of zoonotic diseases. However, the molecular mechanism and regulatory network of pigs (hosts) against influenza virus infection are still unclear. In this study, porcine alveolar macrophage cell (3D4/21) models infected by swine influenza virus (H1N1 and H3N2) were constructed. The expression profiles of miRNAs, mRNAs, lncRNAs and circRNAs after H1N1 and H3N2 infected 3D4/21 cells were revealed in this study. Then, two ceRNAs (TCONS_00166432-miR10391-MAN2A1 and novel_circ_0004733-miR10391-MAN2A1) that regulated H1N1 and H3N2 infection in 3D4/21 cells were verified by the methods of bioinformatics analysis, gene overexpression, gene interference, real-time quantitative PCR (qPCR), dual luciferase activity assay and RNA immunoprecipitation (RIP). In addition, the important candidate molecules (miR-10391, TCONS_00166432, and novel_circ_0004733) were identified by qPCR and enzyme linked immunosorbent assay (ELISA). Finally, the regulatory effect and possible molecular mechanism of the target gene MAN2A1 were identified by the methods of gene interference, qPCR, Western blot and ELISA. The results of this study suggested that TCONS_00166432 and novel_circ_0004733 could competitively bind miR-10391 to target the MAN2A1 gene to regulate swine influenza virus infecting 3D4/21 cells. This study reported for the first time the ceRNA networks involved in the regulation of the swine influenza virus infecting 3D4/21 cells, which provided a new insight into the molecular mechanism of 3D4/21 cells against swine influenza virus infection.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Subtipo H3N2 del Virus de la Influenza A/patogenicidad , Macrófagos Alveolares/virología , MicroARNs/genética , ARN Circular/genética , alfa-Manosidasa/genética , Animales , Línea Celular , Biología Computacional , Perros , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Macrófagos Alveolares/química , Macrófagos Alveolares/citología , Células de Riñón Canino Madin Darby , Modelos Biológicos , Porcinos
10.
J Nat Prod ; 84(10): 2644-2663, 2021 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-34628863

RESUMEN

Rufomycin and ilamycin are synonymous for the same class of cyclopeptides, currently encompassing 33 structurally characterized isolates and 9 semisynthetic derivatives. Elucidation of new structures prioritized the consolidation of the names and established the structures of four diastereoisomeric rufomycins with a 2-piperidinone, named rufomycins 4-7, including full 1H/13C NMR assignments. The characteristic HSQC cross-peak for the CH-5, the hemiaminal carbon in amino acid #5, allows assignment of the stereocenters C-4 and C-5 within this ring. Semisynthetic derivatives (rufomycinSS 1, 2, and 3) were prepared from a rufomycins 4 and 6 mixture to validate the structural assignments. Based on the X-ray crystal structures of rufomycins 2 and 4, considering the NMR differences of rufomycins 7 vs 4-6 compared to rufomycinSS 1 vs 2 and 3, and taking into account that two major conformers, A and B, occur in both rufomycinSS 2 and 3, structural modeling was pursued. Collectively, this paper discusses the NMR spectroscopic differences of the stereoisomers and their possible 3D conformers and correlates these with the anti-Mycobacterium tuberculosis activity. In addition, a look at the history prioritizes names and numbering schemes for this group of antibiotics and leads to consolidated nomenclature for all currently known members, natural and semisynthetic derivatives, and serves to accommodate future discoveries.


Asunto(s)
Oligopéptidos/química , Péptidos Cíclicos/química , Antituberculosos/química , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Terminología como Asunto
11.
BMC Plant Biol ; 20(1): 62, 2020 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-32028890

RESUMEN

BACKGROUND: Cold stress is one of the primary environmental factors that affect plant growth and productivity, especially for crops like Brassica napus that live through cold seasons. Till recently, although a number of genes and pathways involved in B. napus cold response have been revealed by independent studies, a genome-wide identification of the key regulators and the regulatory networks is still lack. In this study, we investigated the transcriptomes of cold stressed semi-winter and winter type rapeseeds in short day condition, mainly with the purpose to systematically identify the functional conserved transcription factors (TFs) in cold response of B. napus. RESULTS: Global modulation of gene expression was observed in both the semi-winter type line (158A) and the winter type line (SGDH284) rapeseeds, in response to a seven-day chilling stress in short-day condition. Function analysis of differentially expressed genes (DEGs) revealed enhanced stresses response mechanisms and inhibited photosynthesis in both lines, as well as a more extensive inhibition of some primary biological processes in the semi-winter type line. Over 400 TFs were differentially expressed in response to cold stress, including 56 of them showed high similarity to the known cold response TFs and were consistently regulated in 158A and SGDH284, as well as 25 TFs which targets were over-represented in the total DEGs. A further investigation based on their interactions indicated the critical roles of several TFs in cold response of B. napus. CONCLUSION: In summary, our results revealed the alteration of gene expression in cold stressed semi-winter and winter ecotype B. napus lines and provided a valuable collection of candidate key regulators involved in B. napus response to cold stress, which could expand our understanding of plant stress response and benefit the future improvement of the breed of rapeseeds.


Asunto(s)
Brassica napus/genética , Respuesta al Choque por Frío/genética , Genoma de Planta , Proteínas de Plantas/genética , Factores de Transcripción/genética , Transcriptoma , Proteínas de Plantas/metabolismo , Factores de Transcripción/metabolismo
12.
J Nat Prod ; 83(3): 657-667, 2020 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-32031795

RESUMEN

This study represents a systematic chemical and biological study of the rufomycin (RUF) class of cyclic heptapeptides, which our anti-TB drug discovery efforts have identified as potentially promising anti-TB agents that newly target the caseinolytic protein C1, ClpC1. Eight new RUF analogues, rufomycins NBZ1-NBZ8 (1-8), as well as five known peptides (9-13) were isolated and characterized from the Streptomyces atratus strain MJM3502. Advanced Marfey's and X-ray crystallographic analysis led to the assignment of the absolute configuration of the RUFs. Several isolates exhibited potent activity against both pathogens M. tuberculosis H37Rv and M. abscessus, paired with favorable selectivity (selectivity index >60), which collectively underscores the promise of the rufomycins as potential anti-TB drug leads.


Asunto(s)
Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Oligopéptidos/farmacología , Streptomyces/química , Cristalografía por Rayos X , Pruebas de Sensibilidad Microbiana , Estructura Molecular
13.
Proc Natl Acad Sci U S A ; 114(52): E11131-E11140, 2017 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-29229819

RESUMEN

Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.


Asunto(s)
Actinobacteria , Proteínas Bacterianas , Genes Bacterianos/fisiología , Lactamas/metabolismo , Macrólidos/metabolismo , Familia de Multigenes/fisiología , Filogenia , Tiazoles/metabolismo , Tionas/metabolismo , Actinobacteria/enzimología , Actinobacteria/genética , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/genética , Biología Computacional
14.
Artículo en Inglés | MEDLINE | ID: mdl-30602512

RESUMEN

ClpC1 is an emerging new target for the treatment of Mycobacterium tuberculosis infections, and several cyclic peptides (ecumicin, cyclomarin A, and lassomycin) are known to act on this target. This study identified another group of peptides, the rufomycins (RUFs), as bactericidal to M. tuberculosis through the inhibition of ClpC1 and subsequent modulation of protein degradation of intracellular proteins. Rufomycin I (RUFI) was found to be a potent and selective lead compound for both M. tuberculosis (MIC, 0.02 µM) and Mycobacterium abscessus (MIC, 0.4 µM). Spontaneously generated mutants resistant to RUFI involved seven unique single nucleotide polymorphism (SNP) mutations at three distinct codons within the N-terminal domain of clpC1 (V13, H77, and F80). RUFI also significantly decreased the proteolytic capabilities of the ClpC1/P1/P2 complex to degrade casein, while having no significant effect on the ATPase activity of ClpC1. This represents a marked difference from ecumicin, which inhibits ClpC1 proteolysis but stimulates the ATPase activity, thereby providing evidence that although these peptides share ClpC1 as a macromolecular target, their downstream effects are distinct, likely due to differences in binding.


Asunto(s)
Proteasas ATP-Dependientes/antagonistas & inhibidores , Antituberculosos/farmacología , Mycobacterium abscessus/efectos de los fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Oligopéptidos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología
15.
J Org Chem ; 83(12): 6664-6672, 2018 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-29792329

RESUMEN

Residual complexity (RC) involves the impact of subtle but critical structural and biological features on drug lead validation, including unexplained effects related to unidentified impurities. RC commonly plagues drug discovery efforts due to the inherent imperfections of chromatographic separation methods. The new diketopiperazine, rufomyazine (6), and the previously known antibiotic, rufomycin (7), represent a prototypical case of RC that (almost) resulted in the misassignment of biological activity. The case exemplifies that impurities well below the natural abundance of 13C (1.1%) can be highly relevant and calls for advanced analytical characterization of drug leads with extended molar dynamic ranges of >1:1,000 using qNMR and LC-MS. Isolated from an actinomycete strain, 6 was originally found to be active against Mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) of 2 µg/mL and high selectivity. As a part of lead validation, the dipeptide was synthesized and surprisingly found to be inactive. The initially observed activity was eventually attributed to a very minor contamination (0.24% [m/m]) with a highly active cyclic peptide (MIC ∼ 0.02 µM), subsequently identified as an analogue of 7. This study illustrates the serious implications RC can exert on organic chemistry and drug discovery, and what efforts are vital to improve lead validation and efficiency, especially in NP-related drug discovery programs.


Asunto(s)
Antituberculosos/química , Antituberculosos/farmacología , Descubrimiento de Drogas , Mycobacterium tuberculosis/efectos de los fármacos , Oligopéptidos/química , Oligopéptidos/farmacología , Espectroscopía de Resonancia Magnética con Carbono-13 , Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , Pruebas de Sensibilidad Microbiana , Espectroscopía de Protones por Resonancia Magnética
16.
Antimicrob Agents Chemother ; 58(10): 5687-95, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25022591

RESUMEN

Discovering new antibiotics is a major scientific challenge, made increasingly urgent by the continued development of resistance in bacterial pathogens. A fundamental understanding of the mechanisms of bacterial antibiotic resistance will be vital for the future discovery or design of new, more effective antibiotics. We have exploited our intimate knowledge of the molecular mechanism of glycopeptide antibiotic resistance in the harmless bacterium Streptomyces coelicolor to develop a new two-step cell wall bioactivity screen, which efficiently identified a new actinomycete strain containing a previously uncharacterized glycopeptide biosynthetic gene cluster. The screen first identifies natural product extracts capable of triggering a generalized cell wall stress response and then specifically selects for glycopeptide antibacterials by assaying for the induction of glycopeptide resistance genes. In this study, we established a diverse natural product extract library from actinomycete strains isolated from locations with widely varying climates and ecologies, and we screened them using the novel two-step bioassay system. The bioassay ultimately identified a single strain harboring the previously unidentified biosynthetic gene cluster for the glycopeptide ristocetin, providing a proof of principle for the effectiveness of the screen. This is the first report of the ristocetin biosynthetic gene cluster, which is predicted to include some interesting and previously uncharacterized enzymes. By focusing on screening libraries of microbial extracts, this strategy provides the certainty that identified producer strains are competent for growth and biosynthesis of the detected glycopeptide under laboratory conditions.


Asunto(s)
Actinomycetales/metabolismo , Ristocetina/metabolismo , Actinomycetales/efectos de los fármacos , Antibacterianos/farmacología , Pared Celular/efectos de los fármacos , Pared Celular/metabolismo , Farmacorresistencia Bacteriana/genética , Familia de Multigenes/genética , Streptomyces/efectos de los fármacos , Streptomyces/metabolismo
17.
Phytomedicine ; 128: 155456, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38537446

RESUMEN

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous metabolic and endocrine disorder that causes anovulatory infertility and abnormal folliculogenesis in women of reproductive age. Several studies have revealed inflammation in PCOS follicles, and recent evidence suggests that Berberine (BBR) effectively reduces inflammatory responses in PCOS, however, the underlying mechanisms remain unclear. PURPOSE: To determine the underlying mechanisms by which BBR alleviates inflammation in PCOS. STUDY DESIGN: Primary human GCs from healthy women and women with PCOS, and KGN cells were used for in vitro studies. ICR mice were used for in vivo studies. METHODS: Gene expression was measured using RT-qPCR. HAS2, inflammatory cytokines, and serum hormones were assayed by ELISA. Protein expression profiles were assayed by Western blot. Chronic low-grade inflammatory mouse models were developed by intraperitoneal injection with LPS, and PCOS mouse models were established by subcutaneous intraperitoneal injection of DHEA. BBR and 4-MU were administered by gavage. Ovarian morphologic changes were evaluated using H&E staining. HAS2 expression in the ovary was assayed using Western blot and immunohistochemistry. RESULTS: Our results confirmed that HAS2 expression and hyaluronan (HA) accumulation are closely associated with inflammatory responses in PCOS. Data obtained from in vitro studies showed that HAS2 and inflammatory genes (e.g., MCP-1, IL-1ß, and IL-6) are significantly upregulated in PCOS samples and LPS-induced KGN cells compared to their control groups. In addition, these effects were reversed by blocking HAS2 expression or HA synthesis using BBR or 4-MU, respectively. Furthermore, HAS2 overexpression induces the expression of inflammatory genes in PCOS. These results were further confirmed in LPS- and DHEA-induced mouse models, where inflammatory genes were reduced by BBR or 4-MU, and ovarian morphology was restored. CONCLUSIONS: Our results define previously unknown links between HAS2 and chronic low-grade inflammation in the follicles of women with PCOS. BBR exerts its anti-inflammatory effects by down-regulating HAS2. This study provides a novel therapeutic target for alleviating ovarian inflammation in women with PCOS.


Asunto(s)
Berberina , Modelos Animales de Enfermedad , Hialuronano Sintasas , Inflamación , Ratones Endogámicos ICR , Síndrome del Ovario Poliquístico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Berberina/farmacología , Femenino , Animales , Humanos , Hialuronano Sintasas/metabolismo , Inflamación/tratamiento farmacológico , Ratones , Ácido Hialurónico , Adulto , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Deshidroepiandrosterona/farmacología , Ovario/efectos de los fármacos , Lipopolisacáridos , Citocinas/metabolismo
18.
Environ Sci Pollut Res Int ; 30(45): 101599-101615, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37651009

RESUMEN

To ensure China's energy security, the mining industry faces increasing emissions reduction and energy conservation pressures. This study combined index and production-theoretical decomposition analyses to decompose the energy-related CO2 emissions in mining industry (ERCEMI) influencing factors into seven major effects and adopted a gravity model to dynamically visualize the transfer path and gravity distribution from 2000 to 2015. As investment effects were introduced into the decomposition analysis, the results fully considered the regional heterogeneity and spatiotemporal dynamics. The main findings were as follows: (i) a typical heavy emissions trend along the Heihe-Tengchong line, with a concentration of large ERCEMI values; (ii) the gravity center of ERCEMI had shifted to the southwest, and the migration trends were divided into three stages; (iii) the ERCEMI had strong regional heterogeneity, with a diffusion trend from north to south and shrinking from east to west; (iv) the potential energy intensity and investment efficiency effects had significantly inhibited the ERCEMI, while the investment scale had boosted it. Implications for regional layouts, energy intensity reductions, and investment optimization are discussed. This research provides a comprehensive regional analysis for ERCEMI reductions and the sustainable development of the mining industry and provides a reference for local industrial development planning.


Asunto(s)
Dióxido de Carbono , Industrias , Dióxido de Carbono/análisis , Desarrollo Industrial , Desarrollo Económico , China , Carbono/análisis
19.
J Oral Microbiol ; 15(1): 2161179, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36605406

RESUMEN

Streptococcus mutans is known as a contributor to dental caries. In this work, Lactobacillus pentosus MJM60383 was selected for its strong antagonistic activity against S. mutans and was characterized by good oral probiotic properties including lysozyme tolerance, adhesive ability to oral cells, good aggregation (auto-aggregation, co-aggregation) ability, hydrogen peroxide production and inhibition of biofilm formation of S. mutans. L. pentosus MJM60383 also exhibited safety as a probiotic characterized by no hemolytic activity, no D-lactate production, no biogenic amine production, and susceptibility to antibiotics. Furthermore, the biofilm formation of S. mutans was also significantly inhibited by the supernatant of L. pentosus MJM60383. An anti-biofilm mechanism study revealed that sucrose decomposition and the production of water-insoluble exopolysaccharides by S. mutans were inhibited by the treatment with L. pentosus MJM60383 supernatant. Real-time PCR analysis indicated that the supernatant of L. pentosus MJM60383 significantly inhibited the mRNA expression of S. mutans glycosyltransferases, which synthesize glucan to construct biofilm architecture and mediate bacterial adherence. Our study demonstrated L. pentosus MJM60383 as a potential oral probiotic and revealed its anti-biofilm mechanism.

20.
Gene ; 851: 147016, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36374642

RESUMEN

Porcine α-1,3-fucosyltransferase (FUT3), as a member of the fucosyltransferase family, plays an important role in the resistance of the piglet intestine to pathogenic microbial infection. To further investigate the tissue/developmental expression of FUT3 and its regulatory mechanism, we analyzed changes in the expression of FUT3 in the duodenal tissues of Meishan pigs at different ages and found that the expression of FUT3 showed a decreasing trend with increasing age. In addition, bisulfite sequencing identified nine methylated CpG sites in the FUT3 core promoter (-500 âˆ¼ -206) region. Therein, the methylation level at the mC-9 site located in FUT3 showed a significantly negative association with mRNA expression (P < 0.05). A further dual-luciferase assay demonstrated that methylation at the mC-9 site of the FUT3 promoter inhibited its transcriptional activity. Then, we confirmed the binding of Sp1 to the FUT3 promoter using RNA knockdown and a ChIP-qPCR assay. Our findings indicate that DNA methylation at the mC-9 site may inhibit the binding of the transcription factor Sp1, thus regulating the developmental expression of the FUT3 gene in the duodenum, providing some theoretical basis for the FUT3 gene as an important candidate marker of disease resistance in Meishan pigs.


Asunto(s)
Metilación de ADN , Fucosiltransferasas , Animales , Porcinos/genética , Fucosiltransferasas/genética , Regiones Promotoras Genéticas , Inmunoprecipitación de Cromatina , Análisis de Secuencia de ADN
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