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1.
Artículo en Inglés | MEDLINE | ID: mdl-38743898

RESUMEN

Objective: To explore and analyze the effect of targeted nursing combined with psychological intervention on chemotherapy for gastric carcinoma and its influence on patient compliance. Methods: The study subjects were 88 patients diagnosed with gastric cancer and treated with chemotherapy from December 2019 to May 2021. Results: The Self-Rating Anxiety Scale and Hamilton Depression Cale scores of the study group were significantly lower than those of the control group (33.45±6.11 vs. 44.17±5.76; 35.14±5.44 vs. 46.87±5.23, respectively; P < .05); In the Morisky scale, patients in the study group scored higher than those in the control group in terms of weight control, medication compliance, appropriate exercise, and diet control; the study group had more cases of Grade 0 nausea and vomiting and significantly fewer cases of Grades I, II, III, and IV nausea and vomiting than the control group compliance (P < .05); patients in the study group gave higher scores than those in the control group on the nursing care quality, from the aspects of the quality of nursing staff. These findings highlight the significant improvements in psychological well-being, adherence to health-related behaviors, reduced nausea and vomiting, and overall satisfaction with nursing care in patients receiving targeted nursing and psychological intervention. Conclusion: The utilization of targeted nursing in tandem with psychological counseling has demonstrated a notably positive impact on chemotherapy outcomes for stomach malignancy. The amalgamation of targeted nursing and psychological intervention not only enhances patient compliance during gastric carcinoma chemotherapy but also leads to a reduction in negative emotions, decreased instances of nausea and vomiting, and higher scores for nursing quality. These findings have significant implications for clinical practice, suggesting that the integration of targeted nursing and psychological support could be a valuable approach in optimizing patient care for gastric carcinoma. The observed improvements underscore the potential for widespread adoption of this combined intervention strategy in clinical settings, potentially leading to enhanced treatment outcomes and overall patient well-being.

2.
Anal Methods ; 16(19): 3020-3029, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38690766

RESUMEN

A concise and rapid detection method for Mycoplasma pneumoniae is urgently required due to its severe impact on human health. To meet such a need, this study proposed and constructed an innovative point-of-care testing (POCT) platform that consists of a hydrogen ion-selective loop-mediated isothermal amplification (H+-LAMP) sensor and an electrochemical detection device. The H+-LAMP sensor successfully integrated the working and reference electrodes and converted the H+ generated during the LAMP process into an electrochemical signal. High sensitivity and stability for pathogen detection were also achieved by treating the working electrode with an electrodeposited polyaniline solid contact layer and by using an ion-selective membrane. As a result, the sensor shows a sensitivity of 68.26 mV per pH, a response time of less than 2 s, and a potential drift of less than 5 mV within one hour, which well meets the urgent need. The results also demonstrated that the detection limit for Mycoplasma pneumoniae was lowered to 1 copy per µL, the nucleic acid extraction and detection process could be completed in 30 minutes, and the impact of interfering ions on the sensor was negligible. Validation with 20 clinical samples yielded satisfactory results. More importantly, the storage lifespan of such an electrochemical sensor is over seven days, which is a great advantage for on-site pathogen detection. Therefore, the hydrogen ion-selective sensor constructed in this investigation is particularly suitable as a core component for instant pathogen detection platforms.


Asunto(s)
Técnicas Electroquímicas , Límite de Detección , Mycoplasma pneumoniae , Técnicas de Amplificación de Ácido Nucleico , Mycoplasma pneumoniae/aislamiento & purificación , Mycoplasma pneumoniae/genética , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Técnicas de Amplificación de Ácido Nucleico/métodos , Humanos , Hidrógeno/química , Neumonía por Mycoplasma/diagnóstico , Neumonía por Mycoplasma/microbiología , Técnicas Biosensibles/métodos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/instrumentación , Electrodos
3.
Anal Chim Acta ; 1309: 342693, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38772660

RESUMEN

BACKGROUND: CRISPR-Cas12a based one-step assays are widely used for nucleic acid detection, particularly for pathogen detection. However, the detection capability of the one-step assay is reduced because the Cas12a protein competes with the isothermal amplification enzymes for the target DNA and cleaves it. Therefore, the key to improving the sensitivity of the one-step assay is to address the imbalance between isothermal amplification and CRISPR detection. In previous study, we developed a Cas12a one-step assay using single-stranded DNA (ssDNA)-modified crRNA (mD-crRNA) and applied this method for the detection of pathogenic DNA. RESULTS: Here, we utilized mD-crRNA to establish a sensitive one-step assay that enables the visual detection of SARS-CoV-2 under ultraviolet light, achieving a detection limit of 5 aM without cross-reactivity. The sensitivity of mD-crRNA in the one-step assay was 100-fold higher than that of wild-type crRNA. Mechanistic studies revealed that the addition of ssDNA at the 3' end of mD-crRNA attenuates the binding affinity between the Cas12a-mD-crRNA complex and the target DNA. Consequently, this reduction in binding affinity decreases the cis-cleavage activity of Cas12a, mitigating its cleavage of the target DNA in the one-step assay. As a result, there is an augmentation in the amplification and accumulation of target DNA, thereby enhancing detection sensitivity. In the clinical testing of 40 SARS-CoV-2 RNA samples, the concordance between the results of the one-step assay and known qPCR results was 97.5 %. SIGNIFICANCE: The one-step assay using mD-crRNA proves to be highly sensitive and specificity and visually effective for the detection of SARS-CoV-2. Our study delves into the application of the mD-crRNA-mediated one-step assay in nucleic acid detection and its associated reaction mechanism. This holds great significance in addressing the inherent incompatibility issues between isothermal amplification and CRISPR detection.


Asunto(s)
COVID-19 , ADN de Cadena Simple , Técnicas de Amplificación de Ácido Nucleico , ARN Viral , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , ADN de Cadena Simple/química , ADN de Cadena Simple/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Humanos , ARN Viral/análisis , ARN Viral/genética , COVID-19/diagnóstico , COVID-19/virología , Límite de Detección , Sistemas CRISPR-Cas/genética , Endodesoxirribonucleasas/química , Endodesoxirribonucleasas/metabolismo , Endodesoxirribonucleasas/genética , Proteínas Asociadas a CRISPR/metabolismo , Proteínas Asociadas a CRISPR/genética , Proteínas Bacterianas
4.
J Coll Physicians Surg Pak ; 34(5): 527-532, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38720211

RESUMEN

OBJECTIVE: To develop an intervention based on Notch-1 signalling pathway blockade by investigating the potential application of the neurogenic locus notch homologue protein 1(Notch-1) signalling pathway as a key regulator of chronic inflammation and adipogenesis in the treatment of hepatic insulin resistance (HIR). STUDY DESIGN: Experimental study. Place and Duration of the Study: Animal Laboratory of the Fourth Hospital of Hebei Medical University, Shijiazhuang, China, from April 2021 to June 2022. METHODOLOGY: HIR models were established in Notch-1WT and Notch-1MAC-KO mice by high fat diet (HFD) for 16 weeks. Haematoxylin and eosin (HE) staining and oil red O (ORO) staining were used to detect inflammatory infiltration and lipid accumulation in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of TNF-α and IL-6. Free fatty acid (FFA) and total cholesterol (TC) were measured with relevant kits. Moreover, real-time quantitative polymerase chain reaction (PCR) was performed to detect the relative expressions of F4/80, Mcp1, and CD11b in hepatic tissues. Mass spectrometry was used to analyse the levels of triglyceride (TG), diacylglycerol (DAG) and conformite europeenne (CE) in liver tissue. Western blotting was used to detect the expression of related proteins. RESULTS: Specific knockdown of Notch-1 in macrophages decreases the relative fluorescence intensity of CD68 and attenuates inflammatory infiltration and lipid degeneration. There was no difference in plasma levels of FFA and TG. Specific knockdown of Notch-1 in macrophages decreases the expression of F4/80, Mcp1, and CD11b, as well as the levels of TG, DAG, CE, IL-6, and TNF-α. CONCLUSION: Specific knockout of Notch-1 in macrophages may reduce HIR by inhibiting the IRE1α-XBP1 signalling pathway. KEY WORDS: Hepatic insulin resistance, Macrophages, Notch-1, IRE1α, XBP1.


Asunto(s)
Dieta Alta en Grasa , Resistencia a la Insulina , Macrófagos , Ratones Noqueados , Proteínas Serina-Treonina Quinasas , Receptor Notch1 , Transducción de Señal , Animales , Ratones , Modelos Animales de Enfermedad , Endorribonucleasas/metabolismo , Endorribonucleasas/genética , Resistencia a la Insulina/fisiología , Hígado/metabolismo , Macrófagos/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor Notch1/metabolismo , Receptor Notch1/genética , Proteína 1 de Unión a la X-Box/metabolismo , Proteína 1 de Unión a la X-Box/genética
5.
iScience ; 27(5): 109807, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38766355

RESUMEN

Type I interferon (IFN) production is crucial in tuberculosis pathogenesis, yet the bacterial factors initiating this process are incompletely understood. CpsA, protein of Mycobacterium marinum and Mycobacterium tuberculosis, plays a key role in maintaining bacterial virulence and inhibiting host cell LC3-associated phagocytosis. By utilizing CpsA full deletion mutant studies, we re-verified its essential role in infection-induced pathology and revealed its new role in type I IFN expression. CpsA deficiency hindered IFN production in infected macrophages in vitro as well as zebrafish and mice in vivo. This effect was linked to the cGAS-TBK1-IRF3 pathway, as evidenced by decreased TBK1 and IRF3 phosphorylation in CpsA-deficient bacterial strain-infected macrophages. Moreover, we further show that CpsA deficiency cause decreased cytosolic DNA levels, correlating with impaired phagosomal membrane rupture. Our findings reveal a new function of mycobacterial CpsA in type I IFN production and offer insight into the molecular mechanisms underlying mycobacterial infection pathology.

6.
Nat Food ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773276

RESUMEN

Combatting climate change depends on demand-side mitigation strategies related to food, which is in turn contingent on explicit estimation and management of dish-level emissions. Here, on the basis of a bottom-up integrated emissions framework, we first estimate the greenhouse gas emissions of 540 dishes from 36 cuisines using data from over 800,488 restaurants in China's provincial capital cities. By mining residents' dietary preferences, we then design various dietary change strategies to explicitly link food emissions to the Paris Agreement pledges. The results show that China's food system greenhouse gas emissions were approximately 4.64 GtCO2eq in 2020, accounting for 37% of total emissions, with average per-dish emissions of 8.44 kgCO2eq. Current emission patterns of food consumption in China may not be consistent with the attainment of the 1.5 °C and 2 °C climate targets, but transitioning towards low-emission cuisines and dishes could change that by reducing emissions by 38-69%.

7.
Cell Biol Toxicol ; 40(1): 36, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771396

RESUMEN

Purinergic receptor P2Y11, a G protein-coupled receptor that is stimulated by extracellular ATP, has been demonstrated to be related to the chemotaxis of granulocytes, apoptosis of neutrophils, and secretion of cytokines in vitro. P2Y11 mutations were associated with narcolepsy. However, little is known about the roles of P2RY11 in the occurrence of narcolepsy and inflammatory response in vivo. In this study, we generated a zebrafish P2Y11 mutant using CRISPR/Cas9 genome editing and demonstrated that the P2Y11 mutant replicated the narcolepsy-like features including reduced HCRT expression and excessive daytime sleepiness, suggesting that P2Y11 is essential for HCRT expression. Furthermore, we accessed the cytokine expression in the mutant and revealed that the P2RY11 mutation disrupted the systemic inflammatory balance by reducing il4, il10 and tgfb, and increasing il6, tnfa, and il1b. In addition, the P2RY11-deficient larvae with caudal fin injuries exhibited significantly slower migration and less recruitment of neutrophils and macrophages at damaged site, and lower expression of anti-inflammatory cytokines during tissue damage. All these findings highlight the vital roles of P2RY11 in maintaining HCRT production and secreting anti-inflammatory cytokines in the native environment, and suggested that P2RY11-deficient zebrafish can serve as a reliable and unique model to further explore narcolepsy and inflammatory-related diseases with impaired neutrophil and macrophage responses.


Asunto(s)
Citocinas , Inflamación , Macrófagos , Neutrófilos , Proteínas de Pez Cebra , Pez Cebra , Animales , Neutrófilos/metabolismo , Neutrófilos/inmunología , Macrófagos/metabolismo , Inflamación/metabolismo , Inflamación/patología , Inflamación/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Citocinas/metabolismo , Mutación/genética , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2/deficiencia
8.
Org Lett ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38757610

RESUMEN

gem-Difluoroalkenes and monofluorinated cycloalkenes have emerged as basic structural units in a variety of bioactive molecules and natural products. Thus, developing straightforward and efficient methods for synthesizing fluorinated alkene compounds is of considerable significance. Herein, we disclose a visible-light-induced defluorination of 2-trifluoromethyl-1-alkene via a 1,5-HAT process using N-alkoxyphtalimides as both radical precursor and potential nucleophile. The mild and stepwise reaction leads to a variety of structurally diverse gem-difluoroalkenes and monofluorinated cyclooctenes with high efficiency, respectively.

9.
Eur J Med Res ; 29(1): 268, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702744

RESUMEN

RATIONALE AND OBJECTIVES: Bleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but with very weak evidence, which should be confirmed. This study aimed to conduct whether pre-placing a bronchial balloon in TBLC for diagnosing interstitial lung disease (ILD) is more safety. MATERIALS AND METHODS: In this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed balloon and none-pre-placed balloon groups. The primary outcome was incidence of moderate bleeding in each group. The secondary endpoints were the incidence of severe bleeding, pneumothorax, and other procedural complications. RESULTS: Exactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the none-pre-placed balloon group and pre-placed balloon group (1.6% vs. 0.8%; adjusted p = 0.520), while more moderate bleeding occurred in the none-pre-placed balloon group (26.4% vs. 6.4%, adjusted p = 0.001), as well as more use of hemostatic drug (28.0% vs. 6.4%, adjusted p = 0.001). Three patients in the none-pre-placed balloon group used the bronchial balloon. More samples could be acquired in the pre-placed balloon group than in the none-pre-placed balloon group (3.8 ± 0.9 vs. 3.1 ± 0.9, p < 0.001). There were no significant differences in multidisciplinary discussion (MDD) between the two groups (89.6% vs. 91.2%, adjusted p = 0.182). CONCLUSION: A pre-placed bronchial balloon can reduce the incidence of moderate bleeding and increase the confidence of the bronchoscopists. However, it had no effect on increasing the diagnostic rate of MDD and reducing severe bleeding. REGISTRATION NUMBER: NCT04047667 ( www. CLINICALTRIALS: gov identifier).


Asunto(s)
Broncoscopía , Criocirugía , Enfermedades Pulmonares Intersticiales , Humanos , Masculino , Femenino , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/patología , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Broncoscopía/métodos , Broncoscopía/efectos adversos , Criocirugía/métodos , Criocirugía/efectos adversos , Biopsia/métodos , Biopsia/efectos adversos , Hemorragia/etiología , Hemorragia/diagnóstico , Hemorragia/prevención & control , Pulmón/patología , Bronquios/patología
10.
Front Nutr ; 11: 1389417, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38746938

RESUMEN

Objective: This study aims to evaluate the origin of the neonatal gut microbiota on the 14th day and probiotic intervention in the third trimester. Methods: Samples were obtained from a total of 30 pregnant individuals and their offspring, divided into a control group with no intervention and a probiotic group with live combined Bifidobacterium and Lactobacillus tablets, analyzing by 16S rRNA amplicon sequencing of the V4 region to evaluate the composition of them. Non-metric multidimensional scaling and SourceTracker were used to evaluate the origin of neonatal gut microbiota. Results: We found that the microbiota in the neonatal gut at different times correlated with that in the maternal microbiota. The placenta had more influence on meconium microbiota. Maternal gut had more influence on neonatal gut microbiota on the 3rd day and 14th day. We also found that the maternal gut, vaginal, and placenta microbiota at full term in the probiotic group did not have a significantly different abundance of Bifidobacterium, Lactobacillus, or Streptococcus. However, some other bacteria changed in the maternal gut and their neonatal gut in the probiotic group.

11.
BMC Pregnancy Childbirth ; 24(1): 245, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38582906

RESUMEN

BACKGROUND AND AIMS: To investigate the impact of intrahepatic cholestasis of pregnancy (ICP) with hepatitis B virus (HBV) infection on pregnancy outcomes. METHODS: We selected 512 pregnant women, collected the data including maternal demographics, main adverse pregnancy outcomes and maternal HBV infected markers HBeAg and HBV-DNA loads status, then have a comparative analysis. RESULTS: There were 319 solitary ICP patients without HBV infection (Group I) and 193 ICP patients with HBV infection. Of the latter, there were 118 cases with abnormal liver function(Group II) and 80 cases with normal liver function(Group III). All HBV-infected pregnant women with ICP were divided into hepatitis Be antigen (HBeAg)-positive group (102 cases) and HBeAg-negative group (91 cases), according to the level of the serum HBeAg status; and into high viral load group (92 cases), moderate viral load group (46 cases) and low viral load group (55 cases) according to the maternal HBV-DNA level. Group II had a higher level of serum total bile acids, transaminase, bilirubin as well as a higher percentage of premature delivery, neonatal intensive care unit (NICU) admission and meconium-stained amniotic fluid (MSAF) compared with the other two groups(P < 0.05), but there were no significant differences in the above indicators between the Group I and Group III. Among the HBV-infected patients with ICP, HBeAg-positive group had a higher level of serum transaminase, bilirubin and bile acid as well as earlier gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission than HBeAg-negative group (P < 0.05). Those with a high viral load (HBV-DNA > 106 IU/ml) had a higher level of transaminase, bilirubin, and bile acid as well as shorter gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission compared with those with a low or moderate viral load (P < 0.05). CONCLUSION: HBV-infected pregnant women with ICP combined with abnormal liver function have more severe liver damage, a higher percentage of preterm birth and NICU admission. HBeAg-positive status and a high HBV-DNA load will increase the severity of conditions in HBV-infected pregnant women with ICP. HBV-infected patients with ICP who have abnormal liver function, HBeAg-positive or a high viral load should be treated more actively.


Asunto(s)
Colestasis Intrahepática , Hepatitis B , Complicaciones Infecciosas del Embarazo , Complicaciones del Embarazo , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Virus de la Hepatitis B , Estudios Retrospectivos , Antígenos e de la Hepatitis B , Peso al Nacer , ADN Viral , Antígenos de Superficie de la Hepatitis B , Nacimiento Prematuro/epidemiología , Hepatitis B/complicaciones , Resultado del Embarazo/epidemiología , Transaminasas , Ácidos y Sales Biliares , Bilirrubina
12.
Heliyon ; 10(7): e28620, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38590887

RESUMEN

Objectives: This study aimed to assess the diagnostic, risk stratification, and prognostic capabilities of apelin-13 and APJ in comparison to procalcitonin (PCT) for septic patients presenting to the emergency department (ED). Methods: Two hundred and thirty-eight patients meeting the Third International Consensus Definition (Sepsis-3) criteria were enrolled from Beijing Chaoyang Hospital's ED, along with a control group of forty healthy individuals. Patients were categorized into two groups based on disease severity: those with sepsis or septic shock. Plasma levels of apelin-13, CD4+ Th cells, and PCT were measured. The expression levels of plasma APJ mRNA were quantified using real-time fluorescence quantitative PCR (RT-qPCR) methodology. The Sequential Organ Failure Assessment (SOFA) score was determined at the time of enrollment. The prognostic values of apelin-13 and APJ was evaluated in comparison to that of PCT and the SOFA score. All patients were followed up for a duration of 28 days. Results: The plasma concentrations of apelin-13 and APJ exhibited a positive correlation with the severity of sepsis, while the number of CD4+ T cells decreased in septic patients. The areas under the receiver operating characteristic (AUC) curves for apelin-13 and APJ in the diagnosis and prediction of 28-day mortality were greater than that of PCT. In non-survivors at the 28-day follow-up, the plasma levels of apelin-13 and APJ were significantly higher compared to survivors. Furthermore, apelin-13 levels were notably higher in cases of sepsis-induced cardiomyopathy (SICM) than in those without SICM. Apelin-13 and APJ emerged as independent predictors of 28-day mortality among septic patients. Conclusions: Apelin-13 and APJ demonstrate value in the assessment of risk stratification, early diagnosis, and prognosis of sepsis in the ED. Apelin-13 also proves to be an effective biomarker for assessing the prognosis of SICM in the ED. Sepsis may lead to immune function suppression.

14.
Plant Sci ; 343: 112081, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38579979

RESUMEN

Chlorophyll biosynthesis and breakdown, important cellular processes for photosynthesis, occur in the chloroplast. As a semi-autonomous organelle, chloroplast development is mainly regulated by nuclear-encoded chloroplast proteins and proteins encoded by itself. However, the knowledge of chloroplast development regulated by other organelles is limited. Here, we report that the nuclear-localized XAP5 CIRCADIAN TIMEKEEPER (XCT) is essential for chloroplast development in Arabidopsis. In this study, significantly decreased chlorophyll content phenotypes of cotyledons and subsequently emerging organs from shoot apical meristem were observed in xct-2. XCT is constitutively expressed in various tissues and localized in the nuclear with speckle patterns. RNA-seq analysis identified 207 differently spliced genes and 1511 differently expressed genes, in which chloroplast development-, chlorophyll metabolism- and photosynthesis-related genes were enriched. Further biochemical assays suggested that XCT was co-purified with the well-known splicing factors and transcription machinery, suggesting dual functions of XCT in gene transcription and splicing. Interestingly, we also found that the chlorophyll contents in xct-2 significantly decreased under high temperature and high light condition, indicating XCT integrates temperature and light signals to fine-tune the chlorophyll metabolism in Arabidopsis. Therefore, our results provide new insights into chloroplast development regulation by XCT, a nuclear-localized protein, at the transcriptional and post-transcriptional level.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Cloroplastos/metabolismo , Fotosíntesis , Proteínas Nucleares/metabolismo , Clorofila/metabolismo , Regulación de la Expresión Génica de las Plantas
15.
Nat Commun ; 15(1): 3088, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600064

RESUMEN

Transcriptional regulation is a critical adaptive mechanism that allows bacteria to respond to changing environments, yet the concept of transcriptional plasticity (TP) - the variability of gene expression in response to environmental changes - remains largely unexplored. In this study, we investigate the genome-wide TP profiles of Mycobacterium tuberculosis (Mtb) genes by analyzing 894 RNA sequencing samples derived from 73 different environmental conditions. Our data reveal that Mtb genes exhibit significant TP variation that correlates with gene function and gene essentiality. We also find that critical genetic features, such as gene length, GC content, and operon size independently impose constraints on TP, beyond trans-regulation. By extending our analysis to include two other Mycobacterium species -- M. smegmatis and M. abscessus -- we demonstrate a striking conservation of the TP landscape. This study provides a comprehensive understanding of the TP exhibited by mycobacteria genes, shedding light on this significant, yet understudied, genetic feature encoded in bacterial genomes.


Asunto(s)
Mycobacterium tuberculosis , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Genoma Bacteriano/genética , Operón/genética , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Regulación Bacteriana de la Expresión Génica
16.
J Immunol ; 212(11): 1670-1679, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38668725

RESUMEN

Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease, predominantly affecting women. Although the pathogenesis of HT is incompletely understood, some studies have found that macrophage polarization plays a role. Puerarin is a soy isoflavone compound that has anti-inflammatory and immunomodulatory effects and regulates macrophage immune activity. This study aimed to verify the therapeutic effect of puerarin on HT and explored its regulatory effect on macrophage polarization imbalance in HT. Through bioinformatics analysis and molecular biology methods, it was found that macrophages increased significantly in HT patients and model mice. Immunological staining showed that puerarin intervention could reduce tissue inflammatory cell infiltration. Molecular biological examination displayed that puerarin could inhibit local and systemic inflammation levels, and the expression of marker thyroglobulin and thyroid peroxidase Abs. In vivo experimental results indicated that puerarin regulated macrophage polarity and reduced inflammatory damage, possibly by inhibiting the pyroptosis signaling pathway. In vivo macrophage clearance experiments demonstrated that puerarin relied on macrophages to exert its mechanism of action in treating HT. The results of this study indicate that macrophages are important mediators in the development of HT, and puerarin can regulate macrophage polarity and inflammatory status to provide thyroid tissue protection, which provides a new idea for the treatment of HT.


Asunto(s)
Isoflavonas , Macrófagos , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Animales , Ratones , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Humanos , Femenino , Modelos Animales de Enfermedad , Tiroiditis Autoinmune/tratamiento farmacológico , Tiroiditis Autoinmune/inmunología , Enfermedad de Hashimoto/tratamiento farmacológico , Enfermedad de Hashimoto/inmunología , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Piroptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
17.
BMC Pediatr ; 24(1): 275, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671415

RESUMEN

BACKGROUND: To investigate serum irisin levels in girls at different developmental status and explore the significance of irisin for the diagnosis of central precocious puberty (CPP) in girls. METHODS: In this cross-sectional study 111 girls were enrolled, including 43 cases of CPP, 44 cases of peripheral precocious puberty (PPP) and 24 cases of girls with normal sexual development as controls. The data on age, weight and height, measured blood levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and irisin were collected. Pelvic Doppler ultrasound was performed to evaluate uterine length, transverse diameter, anteroposterior diameter. The girls were divided into non-CPP group and CPP group according to gonadotropin-releasing hormone (GnRH) stimulation test. RESULTS: Serum irisin levels were significantly higher in CPP group than in PPP group and normal control group. Serum irisin level was positively correlated with basal LH level, basal FSH level, peak LH level, peak LH /FSH ratio, uterine volume, bone age, and bone age index. The area under the curve, cut-off value, sensitivity and specificity of serum irisin were 0.958, 219.255 pg/ml, 100% and 80.6%. The combined diagnosis of CPP in girls by serum irisin and serum basal LH combined with uterine volume had an AUC, sensitivity, and specificity of 0.994, 97.6%, and 100%, superior to that of the single index. CONCLUSIONS: Serum irisin level in girls with CPP is significantly increased. An irisin combined index could help the diagnosis of CPP in girls.


Asunto(s)
Fibronectinas , Hormona Folículo Estimulante , Hormona Luteinizante , Pubertad Precoz , Humanos , Pubertad Precoz/sangre , Pubertad Precoz/diagnóstico , Femenino , Estudios Transversales , Fibronectinas/sangre , Niño , Hormona Luteinizante/sangre , Hormona Folículo Estimulante/sangre , Estudios de Casos y Controles , Biomarcadores/sangre , Sensibilidad y Especificidad , Estradiol/sangre , Útero/diagnóstico por imagen
18.
Front Psychiatry ; 15: 1355708, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38628263

RESUMEN

Introduction: Cognitive Impairment (CI) in the elderly, encompassing conditions ranging from Mild Cognitive Impairment (MCI) to dementia, represents a growing public health concern globally. This study aims to investigate the prevalence and correlates of CI among individuals aged 80 and above. Methods: The study conducts 13,027 elderly individual's door-to-door surveys, followed by the cross-tabulation of analysis data, logistic regression analysis, and health condition assessments to examine various determinants of CI. Results: The current study's key findings demonstrate sub-statical correlations between CI and various factors, including educational attainment, marital status, and gender. Pronounced differences are evident between urban and rural demographics. Furthermore, aspects of social engagement, notably communication proficiency and sensory capabilities, exhibit a strong association with CI. Logistic regression analysis highlights that residing in rural areas (Odds Ratio [OR] = 0.637) and being female (OR = 0.71) are linked to a decreased risk of CI. In contrast, behavioral and health-related variables present a complex picture. Specifically, aggressive behavior (Adjusted OR = 1.881) and symptoms of depression (Adjusted OR = 0.549) contrast with conditions such as asthma (OR= 2.857) and cerebral infarction (OR=1.348), which elevate the risk of CI. Intriguingly, hyperlipidemia (OR= 0.671) appears to confer a protective effect against CI. Conclusion: The study highlights the complexity of factors affecting CI in the elderly, advocating for a comprehensive approach to understanding and managing cognitive health.

19.
Heliyon ; 10(8): e29637, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38655354

RESUMEN

Background: As common abnormal conditions in clinical practice, hypoxemia and respiratory failure are mainly caused by various respiratory diseases. However, other causes are easily overlooked but deserve more attention from doctors. Case presentation: A 44-year-old man presented with dyspnea for 10 years. In the early stage, his dyspnea was mild without hypoxemia, and he was misdiagnosed with polycythemia vera due to elevated hemoglobin level. He later developed to respiratory failure but he did not have weakness in his extremities. The positional difference in pulmonary function tests and arterial blood gas analysis led us to identify the respiratory muscle dysfunction. Fatty infiltration of the thigh muscle found by magnetic resonance imaging and muscle biopsies gave us more clues to the causes of diaphragmatic dysfunction. Finally, in combination with his family history and the results of whole exome sequencing, he was diagnosed with hereditary myopathy with early respiratory failure (HMERF, OMIM 603689) caused by a variant in the titin gene (TTN). Conclusions: We have identified a Chinese family with HMERF due to genetic variants in TTN NM_001256850.1: c.90272C > T, p. Pro30091Leu, located at g.179410829A > G on chromosome 2 (GRCh37), which may be specifically associated with the diagrammatic dysfunction. And hyperhemoglobinemia could serve as a potential sign for the early identification of HMERF.

20.
Adv Sci (Weinh) ; : e2309292, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38666459

RESUMEN

Neurological diseases are expected to become the leading cause of death in the next decade. Although little is known about it, the interaction between oxidative stress and inflammation is harmful to the nervous system. To find an advanced tool for neural genetics, mouse haploid neural stem cells (haNSCs) from the somite of chimeric mouse embryos at E8.5 is established. The haNSCs present a haploid neural progenitor identity for long-term culture, promising to robustly differentiate into neural subtypes and being able to form cerebral organoids efficiently. Thereafter, haNSC mutants via a high-throughput approach and screened targets of oxidative stress is generated using the specific mutant library. Deletion of Nfkbia (the top hit among the insertion mutants) reduces damage from reactive oxygen species (ROS) in NSCs exposed to H2O2. Transcriptome analysis revealed that Atp2b4 is upregulated significantly in Nfkbia-null NSCs and is probably responsible for the observed resistance. Additionally, overexpression of Atp2b4 itself can increase the survival of NSCs in the presence of H2O2, suggesting that Atp2b4 is closely involved in this resistance. Herein, a powerful haploid system is presented to study functional genetics in neural lineages, shedding light on the screening of critical genes and drugs for neurological diseases.

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