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1.
EPMA J ; 15(3): 453-469, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39239105

RESUMEN

Background: Suboptimal Health Status (SHS) is the physical state between health and disease. This study aimed to fill in the knowledge gap by investigating the prevalence of SHS and psychological symptoms among unpaid carers and to identify SHS-risk factors from the perspective of predictive, preventive and personalised medicine (PPPM). Methods: A cross-sectional study was conducted among 368 participants who were enrolled from Australia, including 203 unpaid carers as cases and 165 individuals from the general population as controls. SHS scores were measured using SHSQ-25 (Suboptimal Health Status Questionnaire-25), whilst psychological symptoms were measured by DASS-21 (Depression, Anxiety and Stress Scale-21). Chi-square was used to measure SHS and psychological symptom prevalence. Spearman correlation analysis was utilised to identify the relationship between SHSQ-25 and DASS-21 scores. Logistic regression analysis was used for multivariate analysis. Results: The prevalence of SHS in carers was 43.0% (98/203), significantly higher than the prevalence 12.7% (21/165) in the general population (p < 0.001). In addition, suboptimal health prevalence was higher in female carers (50.3%; 95/189) than females in the general population (12.4%; 18/145). Logistic regression showed that the caregiving role influenced SHS, with carers 6.4 times more likely to suffer from SHS than their non-caring counterparts (aOR = 6.400, 95% CI = 3.751-10.919). Conclusions: Unpaid carers in Australia have a significantly higher prevalence of SHS than that in the general population and experience poorer health. The SHSQ-25 is a powerful tool that can be utilised to screen at-risk individuals to predict their risk of chronic disease development, an essential pillar for shifting the paradigm change from reactive medicine to that of predictive, preventive and personalised medicine (PPPM). Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00370-8.

2.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(9): 954-960, 2024.
Artículo en Chino | MEDLINE | ID: mdl-39267511

RESUMEN

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis. Upon admission, gastroscopy revealed esophageal and gastric varices. Abdominal CT scan, MRI, and color Doppler ultrasound suggested cirrhosis, intrahepatic bile duct dilation, and bilateral kidney enlargement. Genetic testing identified compound heterozygous mutations in the PKHD1 gene: c.2264C>T (p.Pro755Leu) and c.1886T>C (p.Val629Ala). The c.2264C>T (p.Pro755Leu) mutation is a known pathogenic variant with previous reports, while c.1886T>C (p.Val629Ala) is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2. The child was diagnosed with autosomal recessive polycystic kidney disease. In children presenting with gastrointestinal bleeding without obvious causes, particularly those with liver or kidney disease, consideration should be given to the possibility of autosomal recessive polycystic kidney disease, and genetic testing should be conducted for definitive diagnosis when necessary.


Asunto(s)
Riñón Poliquístico Autosómico Recesivo , Humanos , Femenino , Riñón Poliquístico Autosómico Recesivo/genética , Riñón Poliquístico Autosómico Recesivo/complicaciones , Preescolar , Mutación , Receptores de Superficie Celular/genética
3.
ACS Synth Biol ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292964

RESUMEN

Phosphatidylinositol (PI) and its phosphorylated derivatives are of paramount importance in cellular functions and diseases. Understanding their diverse roles is, however, challenged by difficulties in synthesis and labeling techniques. In this proof-of-concept study, we demonstrate that PI can be straightforwardly de novo-synthesized and deuterium (2H)-labeled in Escherichia coli by genomic insertion of PI synthase from Trypanosoma brucei under constitutive synthetic promoter proD. Insertion into loci atpi-gidB and ybb revealed PI accumulation of 41% and 34% (mol/mol), respectively, when cultivated with glycerol as the sole carbon source. Growth of the atpi-gidB-PIS strain in deuterium-labeled (2H) substrates D2O, D8-glycerol, and D6-myo-inositol achieved PI deuteration of 90%, PE deuteration of 95%, and total fatty acids|fatty acid (FA) deuteration of 97%. This study offers an alternative convenient route to chemical and enzymatic labeling synthesis of PI; more excitingly, this work also, in principle, opens a door for tailoring the FA profile of deuterated PI/PE for task-specific application by repurposing FA biosynthesis pathways.

4.
Inorg Chem ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39295540

RESUMEN

In the food industry, 2,3-butanedione is a significant volatile organic compound valued for its unique aroma and flavor. Real-time detection of its concentration during food preparation is crucial for ensuring optimal taste and food safety. However, accurately detecting low concentrations of 2,3-butanedione requires highly sensitive sensing materials. Herein, we present a novel synthesis of branched WO3 nanofibers decorated with ultrafine Pt nanoparticles (Pt NPs-WO3 NFs), templated by polyoxometalate (POM) clusters, through a combination of electrospinning and thermal oxidation strategies for advanced gas sensing applications. This Pt NPs-WO3 NFs-based sensor exhibits impressive sensitivity (Ra/Rg = 2.25 vs 500 ppb), a low detection limit of 10 ppb, high selectivity, excellent repeatability, and stable performance over a period of 25 days. Using POM clusters as templates offers significant advantages over the traditional WCl6 salt in synthesizing WO3 NFs with smooth surfaces. Specifically, the POM clusters guide the dynamic nucleation and hierarchical growth of branched NFs, enhancing the concentration of oxygen vacancies and increasing the number of active adsorption sites. Furthermore, the uniform dispersion of ultrafine Pt NPs (≈ 4 nm) within the WO3 NFs further enhances the catalytic activation of 2,3-butanedione, significantly improving the gas sensing performance. This study introduces an efficient method to synthesize Pt NPs-WO3 NFs with potential for manufacturing advanced nanostructured sensing materials using POM clusters as templates, paving the way for high-performance gas sensing technologies.

5.
Angew Chem Int Ed Engl ; : e202411461, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39295564

RESUMEN

Designing sequences for specific protein backbones is a key step in creating new functional proteins. Here, we introduce GeoSeqBuilder, a deep learning framework that integrates protein sequence generation with side chain conformation prediction to produce the complete all-atom structures for designed sequences. GeoSeqBuilder uses spatial geometric features from protein backbones and explicitly includes three-body interactions of neighboring residues. GeoSeqBuilder achieves native residue type recovery rate of 51.6%, comparable to ProteinMPNN and  other leading methods, while accurately predicting side chain conformations. We first used GeoSeqBuilder to design sequences for thioredoxin and a hallucinated three-helical bundle protein. All the 15 tested sequences expressed as soluble monomeric proteins with high thermal stability, and the 2 high-resolution crystal structures solved closely match the designed models. The generated protein sequences exhibit low similarity (minimum 23%) to the original sequences, with significantly altered hydrophobic cores. We further redesigned the hydrophobic core of glutathione peroxidase 4, and 3 of the 5 designs showed improved enzyme activity. Although further testing is needed, the high experimental success rate in our testing demonstrates that GeoSeqBuilder is a powerful tool for designing novel sequences for predefined protein structures with atomic details. GeoSeqBuilder is available at https://github.com/PKUliujl/GeoSeqBuilder.

6.
Curr Biol ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39146941

RESUMEN

Chlorosis dormancy resulting from nitrogen starvation and its resuscitation upon available nitrogen contributes greatly to the fitness of cyanobacterial population under nitrogen-fluctuating environments. The reinstallation of the photosynthetic machinery is a key process for resuscitation from a chlorotic dormant state; however, the underlying regulatory mechanism is still elusive. Here, we reported that red light is essential for re-greening chlorotic Synechocystis sp. PCC 6803 (a non-diazotrophic cyanobacterium) after nitrogen supplement under weak light conditions. The expression of dark-operative protochlorophyllide reductase (DPOR) governed by the transcriptional factor RpaB was strikingly induced by red light in chlorotic cells, and its deficient mutant lost the capability of resuscitation from a dormant state, indicating DPOR catalyzing chlorophyll synthesis is a key step in the photosynthetic recovery of dormant cyanobacteria. Although light-dependent protochlorophyllide reductase is widely considered as a master switch in photomorphogenesis, this study unravels the primitive DPOR as a spark to activate the photosynthetic recovery of chlorotic dormant cyanobacteria. These findings provide new insight into the biological significance of DPOR in cyanobacteria and even some plants thriving in extreme environments.

7.
Heliyon ; 10(15): e35571, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170375

RESUMEN

Background: The significant rebound of influenza A (H1N1) virus activity, particularly among children, with rapidly growing number of hospitalized cases is of major concern in the post-COVID-19 era. The present study was performed to establish a prediction model of severe case in pediatric patients hospitalized with H1N1 infection during the post-COVID-19 era. Methods: This is a multicenter retrospective study across nine public tertiary hospitals in Yunnan, China, recruiting pediatric H1N1 inpatients hospitalized at five of these centers between February 1 and July 1, 2023, into the development dataset. Screening of 40 variables including demographic information, clinical features, and laboratory parameters were performed utilizing Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression to determine independent risk factors of severe H1N1 infection, thus constructing a prediction nomogram. Receiver operating characteristic (ROC) curve, calibration curve, as well as decision curve analysis (DCA) were employed to evaluate the model's performance. Data from four independent cohorts comprised of pediatric H1N1 inpatients from another four hospitals between July 25 and October 31, 2023, were utilized to externally validate this nomogram. Results: The development dataset included 527 subjects, 122 (23.1 %) of whom developed severe H1N1 infection. The external validation dataset included 352 subjects, 72 (20.5 %) of whom were eventually confirmed as severe H1N1 infection. The LASSO regression identified 19 candidate predictors, with logistic regression further narrowing down to 11 independent risk factors, including underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, neutrophil-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). By integrating these 11 factors, a predictive nomogram was established. In terms of prediction of severe H1N1 infection, excellent discriminative capacity, favorable accuracy, and satisfactory clinical usefulness of this model were internally and externally validated via ROC curve, calibration curve, and DCA, respectively. Conclusion: Our study successfully established and validated a novel nomogram model integrating underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, NLR, ESR, LDH, IL-10, and TNF-α. This nomogram can effectively predict the occurrence of serious case in pediatric H1N1 inpatients during the post-COVID-19 era, facilitating the early recognition and more efficient clinical management of such patients.

9.
Zhonghua Nan Ke Xue ; 30(6): 547-563, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39212365

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of male immune infertility (MII) by meta-analysis. METHODS: We retrieved randomized controlled trial (RCT) on the treatment of male immune infertility with traditional Chinese medicine from the databases of WanFang, Chinese Biomedical Literature, Cochrane Library, Weipu, PubMed and CNKI, and performed methodological quality assessment of the RCTs identified and statistical analysis and evaluation of the publication bias using the RevMan5.4 software. RESULTS: Totally, 25 RCTs (2 563 cases) were included in this study. Compared with Western medicine alone in the treatment of MII, TCM achieved a significantly higher total effectiveness rate (OR = 6.35, 95% CI: 4.96-8.13, P<0.000 01), negative conversion rate of seminal plasma anti-sperm antibodies (OR = 4.52, 95% CI: 2.72 - 7.51, P<0.000 01), negative rate of serum anti-sperm antibodies (OR = 2.98, 95% CI: 2.23-3.96, P<0.000 01), sperm concentration (MD = 15.56, 95% CI: 11.32-19.79, P<0.000 01), grade a sperm motility (MD = 3.85, 95% CI: 1.91-5.79, P=0.000 01), grade a+b sperm motility (MD = 13.77, 95% CI: 7.06-20.48, P<0.000 1), sperm viability (MD = 10.32, 95% CI: 6.78-13.86, P<0.000 01) and pregnancy rate (OR = 3.53, 95% CI: 2.68-4.63, P<0.000 01), but a lower rate of adverse reactions (OR = 0.06, 95% CI: 0.01-0.23, P<0.000 01). There was no statistically significant difference in the percentage of morphologically abnormal sperm between TCM and Western medicine alone in the treatment of MII (MD = -7.53, 95% CI: -15.50-0.44, P = 0.06). CONCLUSION: TCM has a definite effectiveness and high safe in the treatment of male immune infertility.


Asunto(s)
Medicamentos Herbarios Chinos , Infertilidad Masculina , Humanos , Masculino , Medicamentos Herbarios Chinos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Medicina Tradicional China/métodos , Fitoterapia
10.
Precis Clin Med ; 7(3): pbae015, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39139990

RESUMEN

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the pivotal role of the immune response in determining the progression and severity of viral infections. In this paper, we review the most recent studies on the complicated dynamics between SARS-CoV-2 and the host immune system, highlight the importance of understanding these dynamics in developing effective treatments and formulate potent management strategies for COVID-19. We describe the activation of the host's innate immunity and the subsequent adaptive immune response following infection with SARS-CoV-2. In addition, the review emphasizes the immune evasion strategies of the SARS-CoV-2, including inhibition of interferon production and induction of cytokine storms, along with the resulting clinical outcomes. Finally, we assess the efficacy of current treatment strategies, including antiviral drugs, monoclonal antibodies, and anti-inflammatory treatments, and discuss their role in providing immunity and preventing severe disease.

11.
Nat Commun ; 15(1): 5686, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971830

RESUMEN

The assembly and disassembly of biomolecular condensates are crucial for the subcellular compartmentalization of biomolecules in the control of cellular reactions. Recently, a correlation has been discovered between the phase transition of condensates and their maturation (aggregation) process in diseases. Therefore, modulating the phase of condensates to unravel the roles of condensation has become a matter of interest. Here, we create a peptide-based phase modulator, JSF1, which forms droplets in the dark and transforms into amyloid-like fibrils upon photoinitiation, as evidenced by their distinctive nanomechanical and dynamic properties. JSF1 is found to effectively enhance the condensation of purified fused in sarcoma (FUS) protein and, upon light exposure, induce its fibrilization. We also use JSF1 to modulate the biophysical states of FUS condensates in live cells and elucidate the relationship between FUS phase transition and FUS proteinopathy, thereby shedding light on the effect of protein phase transition on cellular function and malfunction.


Asunto(s)
Péptidos , Transición de Fase , Proteína FUS de Unión a ARN , Proteína FUS de Unión a ARN/metabolismo , Proteína FUS de Unión a ARN/química , Proteína FUS de Unión a ARN/genética , Humanos , Péptidos/química , Péptidos/metabolismo , Amiloide/metabolismo , Amiloide/química , Condensados Biomoleculares/metabolismo , Condensados Biomoleculares/química , Luz
12.
Foods ; 13(14)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39063309

RESUMEN

Increased food production and consumption patterns have resulted in higher urban food phosphorus footprints, leading to a series of resource and environmental problems worldwide. We quantified the food phosphorus footprint of the African city of Kisumu using substance flow analysis. Our aim was to develop Kisumu's sustainable phosphorus management framework so that the city would reduce phosphorus losses into the food system. Our results show that in the year 2023, the import and export of food phosphorus in the Kisumu food system was 2730.26 ± 2.7% t P yr-1 and 3297.05 ± 2.4% t P yr-1, respectively. There was -566.79 ± -18% t P yr-1 food phosphorus deficit in the Kisumu food system. Crop planting subsystem runoff/leaching/erosion loss, household consumption subsystem waste loss, and pit latrine subsystem blackwater loss are the major pathways of phosphorus losses into the environment and the main contributors to the food phosphorus footprint in the city. The 2030 scenario analysis shows that implementing a comprehensive scenario scheme throughout the entire lifecycle process from phosphorus input to waste disposal is the best choice for reducing phosphorus losses and suppressing the growth of food phosphorus footprint in the future. Our study shows that the food phosphorus footprint in the Kisumu food system was 0.67 kg P cap-1yr-1 in 2023, which is still at a low level but may enter a continuous upward trend with the improvement of socio-economic development of the city. In our framework, we have proposed a few essential measures that include urine separation, installation of septic tank, adjustment of dietary structure, flexible layout of sanitary disposal facilities, and separation of organic waste streams to reduce food phosphorus footprints in Kisumu. Given the similarity of cities along the shores of Lake Victoria, our calculation methods and management strategies can be applied to other cities in the region.

13.
Food Funct ; 15(15): 7951-7960, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-38980698

RESUMEN

Dietary short- and medium-chain fatty acids have been shown to elevate circulating ketone bodies and confer metabolic health benefits. Cow milk fat contains these lipids in a balanced mix but in relatively low concentrations. Enriching them could amplify health benefits of dairy products. Here, we used a volatility-based workflow to produce milk fat with a 2-fold enrichment of medium- and short-chain fatty acids (referred to as MSFAT). Our proof-of-concept studies in mice demonstrated that intake of MSFAT increased circulating ketone bodies, reduced blood glucose levels, and suppressed food intake. In humans, ingestion of MSFAT resulted in increased circulating ketone bodies, trended to attenuate (p = 0.07) postprandial glucose excursion, and acutely elevated energy expenditure. Our findings show that milk products enriched with MSFAT may hold significant metabolic advantages.


Asunto(s)
Leche , Animales , Leche/química , Humanos , Ratones , Masculino , Femenino , Ácidos Grasos/metabolismo , Bovinos , Adulto , Ratones Endogámicos C57BL , Glucemia/metabolismo , Metabolismo Energético , Cuerpos Cetónicos/metabolismo , Ácidos Grasos Volátiles/metabolismo
14.
Int Immunopharmacol ; 140: 112829, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39083933

RESUMEN

Streptococcus equi subsp. zooepidemicus (S. zooepidemicus, SEZ) is an essential zoonotic bacterial pathogen that can cause various inflammation, such as meningitis, endocarditis, and pneumonia. UDP-glucose dehydrogenase (hasB) is indispensable in synthesizing SEZ virulence factor hyaluronan capsules. Our study investigated the infection of hasB on mice response to SEZ by employing a constructed capsule-deficient mutant strain designated as the ΔhasB strain. This deficiency was associated with a reduced SEZ bacterial load in the mice's blood and peritoneal lavage fluid (PLF) post-infection. Besides, the ΔhasB SEZ strain exhibited a higher propensity for neutrophil infiltration and release of cell-free DNA (cfDNA) in vivo compared to the wild-type (WT) SEZ strain. In vitro experiments further revealed that ΔhasB SEZ more effectively induced the formation of neutrophil extracellular traps (NETs) containing histone 3 (H3), neutrophil elastase (NE), and DNA, than its WT counterpart. Moreover, the release of NETs was determined to be gasdermin D (GSDMD)-dependent during the infection process. Taken together, these findings underscore that the deficiency of the hasB gene in SEZ leads to enhanced GSDMD-dependent NET release from neutrophils, thereby reducing SEZ's capacity to resist NETs-mediated eradication during infection. Our finding paves the way for the development of innovative therapeutic strategies against SEZ.


Asunto(s)
Trampas Extracelulares , Neutrófilos , Proteínas de Unión a Fosfato , Infecciones Estreptocócicas , Streptococcus equi , Trampas Extracelulares/inmunología , Trampas Extracelulares/metabolismo , Animales , Streptococcus equi/inmunología , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/veterinaria , Infecciones Estreptocócicas/microbiología , Neutrófilos/inmunología , Ratones , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/genética , Humanos , Femenino , Ratones Endogámicos C57BL , Factores de Virulencia/genética , Gasderminas
15.
Biomater Adv ; 163: 213950, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38972278

RESUMEN

Traditional tendon engineering using cell-loaded scaffold has limited application potential due to the need of autologous cells. We hypothesize that potent mechanical loading can efficiently induce in situ Achilles tendon regeneration in a rabbit model by using a cell-free porous composite scaffold. In this study, melt-spinning was used to fabricate PGA (polyglycolic acid) and PLA (polylactic acid) filament fibers as well as non-woven PGA fibers. The PLA/PGA (4:2) filament fibers were further braided into a hybrid yarn,which was knitted into a PLA/PGA tubular mesh with potent mechanical property for sustaining natural tendon strain. The results showed that a complete cross-section of Achilles tendon created a model of full mechanical loading on the bridging scaffold, which could efficiently induce in situ tendon regeneration by promoting host cell infiltration, matrix production and tissue remodeling. Histologically, mechanical loading assisted in forming parallel aligned collagen fibers and tenocytes in a fashion similar to those of native tendon. Transmission electron microscope further demonstrated that mechanical strain induced collagen fibril development by increasing fibril diameter and forming bipolar structure, which resulted in enhanced mechanical properties. Interestingly, the synergistic effect between mechanical loading and hyaluronic acid modification was also observed on the induced tenogenic differentiation of infiltrated host fibroblasts. In conclusion, potent mechanical loading is the key inductive microenvironment for in situ tendon regeneration for this polymer-based composite scaffold with proper matrix modification, which may serve as a universal scaffold product for tendon regeneration.


Asunto(s)
Tendón Calcáneo , Poliésteres , Regeneración , Ingeniería de Tejidos , Andamios del Tejido , Animales , Conejos , Andamios del Tejido/química , Ingeniería de Tejidos/métodos , Poliésteres/química , Tenocitos , Polímeros/química , Materiales Biocompatibles/química , Estrés Mecánico
16.
Front Immunol ; 15: 1304973, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39050854

RESUMEN

Background: Evidence from observational studies and clinical trials has associated gut microbiota with infectious diseases. However, the causal relationship between gut microbiota and infectious diseases remains unclear. Methods: We identified gut microbiota based on phylum, class, order, family, and genus classifications, and obtained infectious disease datasets from the IEU OpenGWAS database. The two-sample Mendelian Randomization (MR) analysis was then performed to determine whether the gut microbiota were causally associated with different infectious diseases. In addition, we performed reverse MR analysis to test for causality. Results: Herein, we characterized causal relationships between genetic predispositions in the gut microbiota and nine infectious diseases. Eight strong associations were found between genetic predisposition in the gut microbiota and infectious diseases. Specifically, the abundance of class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae was found to be positively associated with the risk of lower respiratory tract infections (LRTIs). On the other hand, family Acidaminococcaceae, genus Clostridiumsensustricto1, and class Bacilli were positively associated with the risk of endocarditis, cellulitis, and osteomyelitis, respectively. We also discovered that the abundance of class Lentisphaeria and order Victivallales lowered the risk of sepsis. Conclusion: Through MR analysis, we found that gut microbiota were causally associated with infectious diseases. This finding offers new insights into the microbe-mediated infection mechanisms for further clinical research.


Asunto(s)
Enfermedades Transmisibles , Microbioma Gastrointestinal , Predisposición Genética a la Enfermedad , Análisis de la Aleatorización Mendeliana , Humanos , Microbioma Gastrointestinal/genética , Enfermedades Transmisibles/microbiología
17.
Zhonghua Nan Ke Xue ; 30(1): 51-59, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-39046414

RESUMEN

OBJECTIVE: To analyze the main active components and potential molecular mechanism of Yishen Tongluo Prescription (YTP) in the treatment of male infertility based on network pharmacological technology. METHODS: We searched and sorted the main active components of YTP and their individual potential targets in the databases of Systematic Pharmacology of Traditional Chinese Medicine (TCM) and Bioinformatics Analysis Tool of the Molecular Mechanism of TCM, and screened the targets related to male infertility diseases in the databases of Genecards, DisGeNET and OMIM. We made a Venn diagram by intersecting the predicted targets of YTP and those of male infertility diseases, constructed visualized networks for the association of the intersection targets and protein-protein interaction (PPI) using the Cytoscape software and STRING platform respectively, and conducted gene ontology (GO) and KEGG enrichment analyses using the DAVID database and R language "Cluster Profiler" software package respectively. RESULTS: A total of 99 active components, 250 targets of YTP, 4 397 targets of male infertility and 127 common targets were identified. GO analysis revealed that the biological processes of the common targets mainly included transcriptional regulation of RNA polymerase promoter Ⅱ, regulation of gene expressions, regulation of apoptosis, responses to estrogen, and cell responses to hypoxia. KEGG analysis showed significant enrichment of the common targets in the estrogen signaling pathway, cell apoptosis pathway, AGE-RAGE signaling pathway in diabetic complications, and TNF signaling pathway. CONCLUSION: Through network pharmacology, we identified the main active components of YTP and its multi-target and multi-pathway mechanism in the treatment of male infertility, which has paved the ground for animal and cell experiments in verifying the action mechanism of YTP on male infertility.


Asunto(s)
Medicamentos Herbarios Chinos , Infertilidad Masculina , Farmacología en Red , Masculino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Infertilidad Masculina/tratamiento farmacológico , Humanos , Mapas de Interacción de Proteínas , Medicina Tradicional China/métodos , Biología Computacional , Ontología de Genes , Apoptosis/efectos de los fármacos
18.
Plant Physiol ; 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39028839

RESUMEN

The involvement of nuclear factor Y (NF-Y) in transcriptional reprogramming during arbuscular mycorrhizal symbiosis has been demonstrated in several plant species. However, a comprehensive picture is lacking. We showed that the spatial expression of NF-YC3 was observed in cortical cells containing arbuscules via the cis-regulatory element GCC boxes. Moreover, the NF-YC3 promoter was transactivated by the combination of CYCLOPS and autoactive calcium and calmodulin-dependent kinase (CCaMK) via GCC boxes. Knockdown of NF-YC3 significantly reduced the abundance of all intraradical fungal structures and affected arbuscule size. BCP1, SbtM1, and WRI5a, whose expression associated with NF-YC3 levels, might be downstream of NF-YC3. NF-YC3 interacted with NF-YB3a, NF-YB5c, or NF-YB3b, in yeast (Saccharomyces cerevisiae) and in planta, and interacted with NF-YA3a in yeast. Spatial expression of three NF-YBs was observed in all cell layers of roots under both mock and mycorrhizal conditions. Simultaneous knockdown of three NF-YBs, but not individually, reduced the fungal colonization level, suggesting that there might be functional redundancy of NF-YBs to regulate AM symbiosis. Collectively, our data suggest that NF-YC3 and NF-YBs positively regulate AM symbiosis in tomato, and arbuscule-related NF-YC3 may be an important downstream gene of the common symbiosis signaling pathway.

19.
Food Chem X ; 23: 101568, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39022788

RESUMEN

Pomelo flowers emit a strong fragrance and give aromatic odors. Volatile compounds from pomelo flowers were analyzed at three developmental stages and in the main organs by molecular sensory science. A total of 134 volatiles including 25 odorants, were analyzed by gas chromatography-mass spectrometry/pulsed flame photometric detector (GC-MS/PFPD) and multidimensional GC-MS/olfactory (MDGC-MS/O). The total volatile content varied among pomelo flowers at different developmental stages (stage-III > stage-II > stage-I) and among different organs of pomelo flowers (petal > pistil > stamen). Linalool was an important odorant with a high OAV, and floral/fruity comprised the predominant aroma profile. Four odorants, ethyl 2-methylbutanoate, linalool, ß-myrcene, and 2-butenal, were selected based on variable importance in projection (VIP) values and contributed mainly to the discrimination of pomelo flowers at three different developmental stages. Linalool, ß-myrcene, d-limonene, and ethyl hexanoate were potential markers for evaluating flavor differences in pomelo floral organs.

20.
Int J Chron Obstruct Pulmon Dis ; 19: 1491-1513, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38957709

RESUMEN

Background: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes. Methods: Clinical data and PRGs of COPD patients were sourced from the GEO database. The "ConsensusClusterPlus" package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT - PCR to detect the expression levels of eight genes in COPD patient and normal. Results: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them. Conclusion: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.


Asunto(s)
Bases de Datos Genéticas , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica , Piroptosis , Humanos , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Piroptosis/genética , Perfilación de la Expresión Génica , Pulmón/inmunología , Masculino , Femenino , Persona de Mediana Edad , Marcadores Genéticos , Estudios de Casos y Controles , Transcriptoma , Anciano , Reproducibilidad de los Resultados , Predisposición Genética a la Enfermedad , Pronóstico
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