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1.
Chemosphere ; 359: 142276, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38761830

RESUMEN

The production of solid wastes in the metallurgical industry has significant implications for land resources and environmental pollution. To address this issue, it is crucial to explore the potential of recycling these solid wastes to reduce land occupation while protecting the environment and promoting resource utilization. Steel slag, red mud, copper slag and steel picking waste liquor are examples of solid wastes generated during the metallurgical process that possess high iron content and Fe species, making them excellent catalysts for persulfate-based advanced oxidation processes (PS-AOPs). This review elucidates the catalytic mechanisms and pathways of Fe2+ and Fe0 in the activation PS. Additionally, it underscores the potential of metallurgical iron-containing solid waste (MISW) as a catalyst for PS activation, offering a viable strategy for its high-value utilization. Lastly, the article provides an outlook towards future challenges and prospects for MISW in PS activation for the degradation of organic pollutants.

2.
J Nat Prod ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38785214

RESUMEN

Bioactivity-based molecular networking-guided fractionation enabled the isolation of three new polycyclic tetramic acids bearing cis-decalin, epicolidines A-C (1-3), along with one known compound, PF 1052 (4), from the endophytic fungus Epicoccum sp. 1-042 collected in Tibet, China. Their structures were assigned on the basis of extensive spectroscopic data, partial hydrolysis, advanced Marfey's method, quantum chemistry calculations, and X-ray diffraction analysis. Compounds 2-4 displayed promising activities against Gram-positive bacteria in vitro. Particularly, compound 4 displayed remarkable potential against vancomycin-resistant Enterococcus faecium (VRE) with an MIC value of 0.25 µg/mL, lower than the MIC (0.5 µg/mL) of the antibiotic combination quinupristin/dalfopristin (Q/D). In a further in vivo study, compound 4 increased the survival rate to 100% in the VRE-G. mellonella infection model at a concentration of 10 mg/kg.

3.
Food Chem X ; 22: 101351, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38623513

RESUMEN

Katsuwonus pelamis is a tuna species mostly sold for canned fillets, its livers were lack of utilization. This study thus investigated an oil production method combining microwave (MW) pretreatment and subcritical dimethyl ether (SDME) in aim to reach improved efficiency and oil quality. The heating characteristics from different MW powers (400, 600, and 800 W) were evaluated, and SEM showed MW having hydrolysis effect on matrix lipoprotein, the fortified recovery rate was also found. Under the MW-SDME condition with 600 W power, 1:5 solid-to-liquid ratio, and 100 min, the recovery reached 93.21% in maximal (SDME ∼50%). To further improve quality, MW powers was noticed affecting lipid types, fatty acid composition, and oxidative stability of produced oils. 1286 lipid types (mostly glyceride and phospholipid-type) were identified, while higher MW lowered the emulsifying phospholipids prompting phase separation. Several oxidation indexes consistently increased with the rising MW power, GC-MS suggested 400 W for higher DHA.

4.
Microb Cell Fact ; 23(1): 113, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38622698

RESUMEN

BACKGROUND: Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs. RESULTS: Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield-980.8 mg/L of isatropolone A-achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date. CONCLUSION: In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.


Asunto(s)
Streptomyces , Streptomyces/metabolismo , Vías Biosintéticas/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Regiones Promotoras Genéticas , Familia de Multigenes
6.
Biomolecules ; 14(3)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38540732

RESUMEN

A growing number of studies have indicated that extracellular vesicles (EVs), such as exosomes, are involved in the development of neurodegenerative diseases. Components of EVs with biological effects like proteins, nucleic acids, or other molecules can be delivered to recipient cells to mediate physio-/pathological processes. For instance, some aggregate-prone proteins, such as ß-amyloid and α-synuclein, had been found to propagate through exosomes. Therefore, either an increase of detrimental molecules or a decrease of beneficial molecules enwrapped in EVs may fully or partly indicate disease progression. Numerous studies have demonstrated that dysbiosis of the gut microbiota and neurodegeneration are tightly correlated, well-known as the "gut-brain axis". Accumulating evidence has revealed that the gut bacteria-derived EVs play a pivotal role in mediating microbe-host interactions and affect the function of the "gut-brain axis", which subsequently contributes to the pathogenesis of neurodegenerative diseases. In this review, we first briefly discuss the role of EVs from mammalian cells and microbes in mediating the progression of neurodegenerative diseases, and then propose a novel strategy that employs EVs of plants (plant cell-derived exosome-like nanoparticles) for treating neurodegeneration.


Asunto(s)
Exosomas , Vesículas Extracelulares , Enfermedades Neurodegenerativas , Animales , Enfermedades Neurodegenerativas/metabolismo , Células Vegetales/metabolismo , Vesículas Extracelulares/metabolismo , Exosomas/metabolismo , Bacterias , Mamíferos
7.
Adv Healthc Mater ; : e2303688, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38481054

RESUMEN

Bacterial infections in wounds continue to be a major challenge in clinical settings worldwide and represent a significant threat to human health. This work proposes novel expandable and versatile methods for solidifying sodium alginate (SA) with metal ions (such as Fe3+ , Co2+ , Ni2+ , Cu2+ , and Zn2+ ) to create Metal-Alginate (M-Alg) hydrogel with adjustable morphology, composition, and microstructure. It conforms to the wound site, protects against second infection, reduces inflammation, and promotes the healing of infected wounds. Among these hydrogels, Cu-Alginate (Cu-Alg) shows excellent sterilization effect and good efficacy against both gram-positive and gram-negative bacteria, including multidrug-resistant (MDR) strains such as Methicillin-resistant Staphylococcus aureus (MRSA) and Carbapenem-resistant Klebsiella pneumoniae (CRKP) due to its dual antibacterial mechanisms: contact-killing and reactive oxygen species (ROS) burst. Importantly, it exhibits low cytotoxicity and biodegradability. This simple and cost-effective gel-based system has the potential to introduce an innovative approach to the management of wound infection and offers promising new perspectives for the advancement of wound care practice.

8.
Int J Cardiol ; 403: 131886, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38382850

RESUMEN

BACKGROUND: A novel automated method for measuring left ventricular (LV) global longitudinal strain (GLS) along the endocardium has advantages in terms of its rapid application and excellent reproducibility. However, it remains unclear whether the available normal range for conventional GLS using the manual method is applicable to the automated GLS method. This study aimed to compare automated GLS head-to-head with manual layer-specific GLS, and to identify whether a specialized normal reference range for automated GLS is needed and explore the main determinants. METHODS: In total, 1683 healthy volunteers (men, 43%; age, 18-80 years) were prospectively enrolled from 55 collaborating laboratories. LV GLS was measured using both manual layer-specific and automated methods. RESULTS: Automated GLS was higher than endocardial, mid-myocardial, and epicardial GLS. Women had a higher automated GLS than men. GLS had no significant age dependency in men, but first increased and then decreased with age in women. Accordingly, sex- and age-specific normal ranges for automated GLS were proposed. Moreover, GLS appeared to have different burdens in relation to dominant determinants between the sexes. GLS in men showed no dominant determinants; however, GLS in women correlated with age, body mass index, and heart rate. CONCLUSIONS: Using the novel automated method, was LV GLS higher than when using the manual GLS method. The normal ranges of automated GLS stratified according to sex and age were provided, with dominant determinants showing sex disparities that require full consideration in clinical practice.


Asunto(s)
Ecocardiografía , Tensión Longitudinal Global , Masculino , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Valores de Referencia , Ecocardiografía/métodos , Función Ventricular Izquierda/fisiología , Reproducibilidad de los Resultados
9.
Microorganisms ; 12(1)2024 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-38257948

RESUMEN

Dental caries is a significant oral and public health problem worldwide, especially in low-income populations. The risk of dental caries increases with frequent intake of dietary carbohydrates, including sugars, leading to increased acidity and disruption of the symbiotic diverse and complex microbial community of health. Excess acid production leads to a dysbiotic shift in the bacterial biofilm composition, demineralization of tooth structure, and cavities. Highly acidic and acid-tolerant species associated with caries include Streptococcus mutans, Lactobacillus, Actinomyces, Bifidobacterium, and Scardovia species. The differences in microbiotas depend on tooth site, extent of carious lesions, and rate of disease progression. Metagenomics and metatranscriptomics not only reveal the structure and genetic potential of the caries-associated microbiome, but, more importantly, capture the genetic makeup of the metabolically active microbiome in lesion sites. Due to its multifactorial nature, caries has been difficult to prevent. The use of topical fluoride has had a significant impact on reducing caries in clinical settings, but the approach is costly; the results are less sustainable for high-caries-risk individuals, especially children. Developing treatment regimens that specifically target S. mutans and other acidogenic bacteria, such as using nanoparticles, show promise in altering the cariogenic microbiome, thereby combatting the disease.

10.
Front Oncol ; 13: 1230519, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38074653

RESUMEN

Magnetic resonance-guided adaptive radiotherapy (MRgART) represents the latest frontier in precision radiotherapy. It is distinguished from other modalities by the possibility of acquiring high-contrast soft tissue images, combined with the ability to recalculate and re-optimize the plan on the daily anatomy. The extensive database of available images offers ample scope for using disciplines such as radiomics to try to correlate features and outcomes. This study aimed to correlate the change of radiomics feature along the treatment to pathological complete response (pCR) for locally advanced rectal cancer (LARC) patients. Twenty-eight LARC patients undergoing neoadjuvant chemoradiotherapy (nCRT) with a short course (25 Gy, 5 Gy × 5f) MRgART at 1.5 Tesla MR-Linac were enrolled. The T2-weighted images acquired at each fraction, corresponding target delineation, pCR result of the surgical specimen, and clinical variables were collected. Seven families of features [First Order, Shape, Gray-level Co-occurrence Matrix (GLCM), Gray-level Dependence Matrix (GLDM), Gray-level Run Length Matrix (GLRLM), Gray-level Size Zone Matrix (GLSZM), and Neighborhood Gray Tone Difference Matrix (NGTDM)] were extracted, and delta features were calculated from the ratio of features of each successive fraction to those of the first fraction. Mann-Whitney U test and LASSO were utilized to reduce the dimension of features and select those features that are most significant to pCR. At last, the radiomics signatures were established by linear regression with the final set of features and their coefficients. A total of 581 radiomics features were extracted, and 2,324 delta features were calculated for each patient. Nineteen features and delta features, and one clinical variable (cN) were significant (p< 0.05) to pCR; seven predictive features were further selected and included in the linear regression to construct the radiomics signature significantly discriminating pCR and non-pCR groups (p< 0.05). Delta features based on MRI images acquired during a short course MRgART could potentially be used to predict treatment response in LARC patients undergoing nCRT.

11.
Front Pharmacol ; 14: 1282077, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38044947

RESUMEN

Background: Yuquan Pill (YQW) is a modern concentrated pill preparation of six herbs, namely, Ge Gen (Pueraria lobata Ohwi), Di huang (Rehmannia glutinosa Libosch.), Tian Huafen (Trichosanthes kirilowii Maxim.), Mai Dong (Ophiopogon japonicus (L. f.) Ker Gawl.), Wu Weizi (Schisandra chinensis (Turcz.) Baill.) and Gan Cao (Glycyrrhiza uralensis Fisch.). It is extensively used to treat type 2 diabetes-related glucose and lipid metabolism disorders. But what's the pharmacodynamic substance and how it works in the treatment of Type 2 diabetes mellitus (T2DM) are still unclear. Purpose: The purpose of this study is to determine the likely pharmacological components and molecular mechanism of YQW's intervention on T2DM by combining serum pharmacochemistry, network analysis and transcriptomics. Methods: The efficacy and prototypical components of blood entry were determined after oral administration of YQW aqueous solution to T2DM rats induced by high-fat feed and low-dose streptozotocin (STZ), and the key targets and pathways for these compounds to intervene in T2DM rats were predicted and integrated using network analysis and transcriptomics techniques. Results: In diabetic rats, YQW can lower TG, CHO, NO, and MDA levels (p < 0.05) while increasing HDL-C levels (p < 0.01), and protecting the liver and kidney. 22 prototype components (including puerarin, daidzein, 3'-methoxypuerarin, and liquiritigenin, among others) were found in the serum of rats after oral administration of YQW for 90 min, which might be used as a possible important ingredient for YQW to intervene in T2DM rats. 538 YQW pharmacodynamic components-related targets and 1,667 disease-related targets were projected through the PharmMapper database, with 217 common targets between the two, all of which were engaged in regulating PI3K-Akt, MAPK, Ras and FoxO signal pathway. Finally, the mRNA expression profiles of liver tissues from rats in the control, model, and YQW groups were investigated using high-throughput mRNA sequencing technology. YQW can regulate the abnormal expression of 89 differential genes in a disease state, including 28 genes with abnormally high expression and 61 genes with abnormally low expression. Five common genes (Kit, Ppard, Ppara, Fabp4, and Tymp) and two extensively used regulatory pathways (PI3K-Akt and MAPK signaling pathways) were revealed by the integrated transcriptomics and network analysis study. Conclusion: The mechanism of YQW's intervention in T2DM rats could be linked to 22 important components like puerarin, daidzein, and glycyrrhetinic acid further activating PI3K-Akt and MAPK signaling pathways by regulating key targets Kit, Ppard, Ppara, Fabp4, and Tymp, and thus improving lipid metabolism disorder, oxidative stress, and inflammation levels in T2DM rats. On the topic, more research into the pharmacological ingredient foundation and mechanism of YQW intervention in T2DM rats can be done.

12.
Front Bioeng Biotechnol ; 11: 1278601, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38026887

RESUMEN

Sansanmycins represent a family of uridyl peptide antibiotics with antimicrobial activity specifically against Mycobacterium tuberculosis (including drug-resistant M. tuberculosis) and Pseudomonas aeruginosa. They target translocase I (MraY) to inhibit bacterial cell wall assembly. Given the unique mechanism of action, sansanmycin has emerged as a potential lead compound for developing new anti-tuberculosis drugs, while the 5'-aminouridine moiety plays a crucial role in the pharmacophore of sansanmycin. For expanding the structural diversity of the 5'-aminouridine moiety of sansanmycin through biosynthetic methods, we firstly demonstrated that SsaM and SsaK are responsible for the biosynthesis of the 5'-aminouridine moiety of sansanmycin in vivo. Using the ssaK deletion mutant (SS/KKO), we efficiently obtained a series of new analogues with modified 5'-aminouridine moieties through mutational biosynthesis. Based on molecular networking analysis of MS/MS, twenty-two new analogues (SS-KK-1 to -13 and SS-KK-A to -I) were identified. Among them, four new analogues (SS-KK-1 to -3 and SS-KK-C) were purified and bioassayed. SS-KK-2 showed better antibacterial activity against E. coli ΔtolC than the parent compound sansanmycin A. SS-KK-3 showed the same anti-TB activity as sansanmycin A against M. tuberculosis H37Rv as well as clinically isolated, drug-sensitive and multidrug-resistant M. tuberculosis strains. Furthermore, SS-KK-3 exhibited significantly improved structural stability compared to sansanmycin A. The results suggested that mutasynthesis is an effective and practical strategy for expanding the structural diversity of 5'-aminouridine moiety in sansanmycin.

13.
Front Immunol ; 14: 1259521, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37954611

RESUMEN

Tuft cells are a type of rare epithelial cells that have been recently found to utilize taste signal transduction pathways to detect and respond to various noxious stimuli and pathogens, including allergens, bacteria, protists and parasitic helminths. It is, however, not fully understood how many different types of pathogens they can sense or what exact molecular mechanisms they employ to initiate targeted responses. In this study, we found that an anaerobic pathobiont microbe, Ruminococcus gnavus (R. gnavus), can induce tuft cell proliferation in the proximal colon whereas the microbe's lysate can stimulate these proximal colonic tuft cells to release interleukin-25 (IL-25). Nullification of the Gng13 and Trpm5 genes that encode the G protein subunit Gγ13 and transient receptor potential ion channel Trpm5, respectively, or application of the Tas2r inhibitor allyl isothiocyanate (AITC), G protein Gßγ subunit inhibitor Gallein or the phospholipase Cß2 (PLCß2) inhibitor U73122 reduces R. gnavus-elicited tuft cell proliferation or IL-25 release or both. Furthermore, Gng13 conditional knockout or Trpm5 knockout diminishes the expression of gasdermins C2, C3 and C4, and concomitantly increases the activated forms of caspases 3, 8 and 9 as well as the number of TUNEL-positive apoptotic cells in the proximal colon. Together, our data suggest that taste signal transduction pathways are not only involved in the detection of R. gnavus infection, but also contribute to helping maintain gasdermin expression and prevent apoptotic cell death in the proximal colon, and these findings provide another strategy to combat R. gnavus infection and sheds light on new roles of taste signaling proteins along with gasdermins in protecting the integrity of the proximal colonic epithelium.


Asunto(s)
Gusto , Canales de Potencial de Receptor Transitorio , Ruminococcus , Transducción de Señal , Colon
14.
Zhen Ci Yan Jiu ; 48(11): 1134-1141, 2023 Nov 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-37984911

RESUMEN

OBJECTIVES: To compare the effects of moxibustion and acupuncture of combined "Biao-Ben" acupoints (Biao indicates pathogenic factors of disease, Ben refers to body constitution) on a rat model of irritable bowel syndrome with diarrhea (IBS-D). METHODS: Forty female SD rats were randomly divided into 4 groups:normal group, model group, moxibustion group, and acupuncture group, with 10 rats in each group. The IBS-D rat model was established by administering acute-chronic stress combined with folium sennae gavage for 28 days. Rats in the moxibustion group received moxibustion at bilateral "Zusanli"(ST36), "Guanyuan"(CV4), and "Neiguan"(PC6), while those in the acupuncture group received acupuncture at the same acupoints, both for 15 min every time, once a day. The treatments were administered for 21 days. The loose stool rate was observed. Colonic pain threshold and colonic distension threshold were measured by a self-made balloon catheter. Total distance traveled and grid crossing numbers were observed by open field test. Heart rate variability(HRV) time domain indexes SDANN and PNN50 were acguired by using electrophysiological recorder. Histopathological changes in the colon tissue were observed after HE staining. Contents of interleukin-6(IL-6), IL-8, and tumor necrosis factor-alpha(TNF-α) in serum were detected by ELISA. RESULTS: Compared with the normal group, rats in the model group showed increased loose stool rate(P<0.05), decreased pain threshold and distension threshold(P<0.05), reduced total distance traveled and grid crossing numbers in the open field test(P<0.05), decreased HRV time domain indexes SDANN and PNN50(P<0.01, P<0.05), and elevated levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). Compared with the model group, the moxibustion group and acupuncture group showed decreased loose stool rate(P<0.05), increased total distance traveled and grid crossing numbers in the open field test(P<0.05), increased pain threshold and distension threshold(P<0.05), increased SDANN and PNN50 (P<0.05), and decreased levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). Compared with the acupuncture group, the moxibustion group showed further decreased loose stool rate(P<0.05), increased total distance traveled and grid crossing numbers in the open field test(P<0.05), increased pain threshold and distension threshold(P<0.05), increased SDANN and PNN50(P<0.05), and decreased levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). No significant pathological changes were observed in the colon tissue of rats in each group. CONCLUSIONS: Moxibustion of combined "Biao-Ben" acupoints is more effective in regulating HRV and serum IL-6, IL-8, and TNF-α contents in the IBS-D rat model. Based on the combined "Biao-Ben" acupoints method, moxibustion has better therapeutic effects on IBS-D than acupuncture.


Asunto(s)
Terapia por Acupuntura , Síndrome del Colon Irritable , Moxibustión , Ratas , Femenino , Animales , Síndrome del Colon Irritable/terapia , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genética , Interleucina-8 , Interleucina-6/genética , Puntos de Acupuntura , Diarrea/terapia , Sistema Nervioso Autónomo
15.
Eur Heart J Cardiovasc Imaging ; 24(10): 1384-1393, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37530466

RESUMEN

AIMS: Mitral annular plane systolic excursion (MAPSE) is a simple and reliable index for evaluating left ventricular (LV) systolic function, particularly in patients with poor image quality; however, the lack of reference values limits its widespread use. This study aimed to establish the normal ranges for MAPSE measured using motion-mode (M-mode) and two-dimensional speckle tracking echocardiography (2D-STE) and to explore its principal determinants. METHODS AND RESULTS: This multicentre, prospective, cross-sectional study included 1952 healthy participants [840 men (43%); age range, 18-80 years] from 55 centres. MAPSE was measured using M-mode echocardiography and 2D-STE. The results showed that women had a higher MAPSE than men and MAPSE decreased with age. The age- and sex-specific reference values for MAPSE were established for these two methods. Multiple linear regression analyses revealed that MAPSE on M-mode echocardiography correlated with age and MAPSE on 2D-STE with age, blood pressure (BP), heart rate, and LV volume. Moreover, MAPSE measured by 2D-STE correlated more strongly with global longitudinal strain compared with that measured using M-mode echocardiography. CONCLUSION: Normal MAPSE reference values were established based on age and sex. BP, heart rate, and LV volume are potential factors that influence MAPSE and should be considered in clinical practice. Normal values are useful for evaluating LV longitudinal systolic function, especially in patients with poor image quality, and may further facilitate the use of MAPSE in routine assessments.


Asunto(s)
Ecocardiografía , Válvula Mitral , Masculino , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Valores de Referencia , Estudios Prospectivos , Estudios Transversales , Válvula Mitral/diagnóstico por imagen , Ecocardiografía/métodos , Función Ventricular Izquierda/fisiología
16.
Bioorg Med Chem Lett ; 92: 129405, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37414346

RESUMEN

Structural optimization of a previously reported agonist of µOR, PZM21 is described resulting in the discovery of a novel series of amides with at least 4-folds enhanced CNS penetration in rat. Furthermore, these efforts yielded compounds with varying levels of efficacy on the receptor ranging from high efficacy agonists such as compound 20 to antagonists, such as 24. The correlation between in vitro activation of µOR and relative activity in models of analgesia for these compounds is discussed. The compelling results obtained in these studies demonstrate the potential utility of these newly discovered compounds in the treatment of pain and opioid use disorder.


Asunto(s)
Trastornos Relacionados con Opioides , Dolor , Ratas , Animales , Dolor/tratamiento farmacológico , Amidas , Encéfalo/metabolismo , Receptores Opioides mu/agonistas , Analgésicos Opioides/farmacología , Analgésicos Opioides/uso terapéutico
17.
Toxicol Sci ; 195(2): 184-201, 2023 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-37490477

RESUMEN

During embryonic development, 2 populations of multipotent stem cells, cranial neural crest cells (NCCs) and epibranchial placode cells (PCs), are anatomically adjacent to each other. The coordinated migration of NCCs and PCs plays a major role in the morphogenesis of craniofacial skeletons and cranial nerves. It is known that ethanol-induced dysfunction of NCCs and PCs is a key contributor to the defects of craniofacial skeletons and cranial nerves implicated in fetal alcohol spectrum disorder (FASD). However, how ethanol disrupts the coordinated interaction between NCCs and PCs was not elucidated. To fill in this gap, we established a well-designed cell coculture system to investigate the reciprocal interaction between human NCCs (hNCCs) and human PCs (hPCs), and also monitored the migration behavior of NCCs and PCs in zebrafish embryos. We found that ethanol exposure resulted in a disruption of coordinated hNCCs-hPCs interaction, as well as in zebrafish embryos. Treating hNCCs-hPCs with exosomes derived from ethanol-exposed hNCCs (ExoEtOH) mimicked ethanol-induced impairment of hNCCs-hPCs interaction. We also observed that SDF1, a chemoattractant, was downregulated in ethanol-treated hPCs and zebrafish embryos. Meanwhile, miR-126 level in ExoEtOH was significantly higher than that in control exosomes (ExoCon). We further validated that ExoEtOH-encapsulated miR-126 from hNCCs can be transferred to hPCs to suppress SDF1 expression in hPCs. Knockdown of SDF1 replicated ethanol-induced abnormalities either in vitro or in zebrafish embryos. On the contrary, overexpression of SDF1 or inhibiting miR-126 strongly rescued ethanol-induced impairment of hNCCs-hPCs interaction and developmental defects.


Asunto(s)
Exosomas , MicroARNs , Animales , Femenino , Embarazo , Humanos , Cresta Neural , Pez Cebra , Etanol/toxicidad , Etanol/metabolismo , Exosomas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Comunicación Celular , Movimiento Celular
18.
J Math Biol ; 87(2): 29, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37452969

RESUMEN

As there are no targeted medicines or vaccines for newly emerging infectious diseases, isolation among communities (villages, cities, or countries) is one of the most effective intervention measures. As such, the number of intercommunity edges ([Formula: see text]) becomes one of the most important factor in isolating a place since it is closely related to normal life. Unfortunately, how [Formula: see text] affects epidemic spread is still poorly understood. In this paper, we quantitatively analyzed the impact of [Formula: see text] on infectious disease transmission by establishing a four-dimensional [Formula: see text] edge-based compartmental model with two communities. The basic reproduction number [Formula: see text] is explicitly obtained subject to [Formula: see text] [Formula: see text]. Furthermore, according to [Formula: see text] with zero [Formula: see text], epidemics spread could be classified into two cases. When [Formula: see text] for the case 2, epidemics occur with at least one of the reproduction numbers within communities greater than one, and otherwise when [Formula: see text] for case 1, both reproduction numbers within communities are less than one. Remarkably, in case 1, whether epidemics break out strongly depends on intercommunity edges. Then, the outbreak threshold in regard to [Formula: see text] is also explicitly obtained, below which epidemics vanish, and otherwise break out. The above two cases form a severity-based hierarchical intervention scheme for epidemics. It is then applied to the SARS outbreak in Singapore, verifying the validity of our scheme. In addition, the final size of the system is gained by demonstrating the existence of positive equilibrium in a four-dimensional coupled system. Theoretical results are also validated through numerical simulation in networks with the Poisson and Power law distributions, respectively. Our results provide a new insight into controlling epidemics.


Asunto(s)
Enfermedades Transmisibles , Epidemias , Humanos , Enfermedades Transmisibles/epidemiología , Modelos Biológicos , Redes Comunitarias , Epidemias/prevención & control , Simulación por Computador , Número Básico de Reproducción
19.
Environ Sci Pollut Res Int ; 30(31): 77905-77916, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37266784

RESUMEN

The comprehensive utilization of iron ore tailings (IOTs) not only resolved environmental problems but also brought huge economic benefits. In this study, the synthetic route presented herein provides a novel method for the synthesis of ZSM-5 microspheres from IOTs. The effects of Si/Al molar ratios and the pH of the precursor solution on the formation of zeolite was evaluated by various analytical methods. The catalytic performance of the catalyst prepared by the solid-phase conversion method (denoted as MP-ZSM-5) was evaluated by methanol-to-propylene (MTP) reaction. Compared with the zeolite catalyst that synthesized via the conventional hydrothermal method (denoted as HM-ZSM-5), MP-ZSM-5 not only prolongs catalytic lifetime from 18.7 to 36.0 h but also has higher selectivity for propylene by MP-ZSM-5 (43.7%) than that for HM-ZSM-5 (38.6%). In addition, Kissinger-Akahira-Sunose (KAS) model is applied to the TG result to study the template removal process kinetics. The average activation energy values required for the removal of CTAB and TPABr are 201.11 ± 13.42 and 326.88 ± 16.91 kJ∙mol-1, respectively. Furthermore, this result is well coupled with the model-free kinetic algorithms to determine the conversion and isoconversion of the TPABr and CTAB decomposition in ZSM-5, which serves as important guidelines for the industrial production process.


Asunto(s)
Zeolitas , Zeolitas/química , Cetrimonio , Microesferas , Hierro/química
20.
Org Lett ; 25(26): 4874-4879, 2023 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-37358471

RESUMEN

Two novel cinnamoyl-containing nonribosomal peptides (CCNPs) grisgenomycin A and B were identified in Streptomyces griseus NBRC 13350 (CGMCC 4.5718) and ATCC 12475, through genome mining using conserved adjacent LuxR family regulators as probes and activators. Notably, grisgenomycins represent a new group of bicyclic decapeptides featuring an unprecedented C-C bond between the tryptophan carbocycle and the cinnamoyl group. A plausible biosynthetic pathway for grisgenomycins was deduced by a bioinformatics analysis. Grisgenomycins exhibited activity against human coronaviruses at the micromolar level.


Asunto(s)
Streptomyces griseus , Streptomyces , Humanos , Streptomyces/genética , Streptomyces/metabolismo , Péptidos/química , Genoma Bacteriano , Vías Biosintéticas/genética , Familia de Multigenes
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