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Alzheimer's disease (AD) is characterized by cognitive decline stemming from the accumulation of beta-amyloid (Aß) plaques and the propagation of tau pathology through synapses. Exosomes, crucial mediators in neuronal development, maintenance, and intercellular communication, have gained attention in AD research. Yet, the molecular mechanisms involving exosomal miRNAs in AD remain elusive. In this study, we treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice, a model for AD, with either vehicle (ADNS) or fasudil (ADF), while C57BL/6 (control) mice received vehicle (WT). Cognitive function was evaluated using the Y-maze test, and AD pathology was confirmed through immunostaining and western blot analysis of Aß plaques and phosphorylated tau. Exosomal RNAs were extracted, sequenced, and analyzed from each mouse group. Our findings revealed that fasudil treatment improved cognitive function in AD mice, as evidenced by increased spontaneous alternation in the Y-maze test and reduced Aß plaque load and phosphorylated tau protein expression in the hippocampus. Analysis of exosomal miRNAs identified three miRNAs (mmu-let-7i-5p, mmu-miR-19a-3p, mmu-miR-451a) common to both ADNS vs ADF and WT vs ADNS groups. Utilizing miRTarBase software, we predicted and analyzed target genes associated with these miRNAs. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of miRNA target genes indicated that mmu-miR-19a-3p and mmu-miR-451a are implicated in signal transduction, immune response, cellular communication, and nervous system pathways. Specifically, mmu-miR-19a-3p targeted genes involved in the sphingolipid signaling pathway, such as Pten and Tnf, while mmu-miR-451a targeted Nsmaf, Gnai3, and Akt3. Moreover, mmu-miR-451a targeted Myc in signaling pathways regulating the pluripotency of stem cells. In conclusion, fasudil treatment enhanced cognitive function by modulating exosomal MicroRNAs, particularly mmu-miR-451a and mmu-miR-19a-3p. These miRNAs hold promise as potential biomarkers and therapeutic targets for novel AD treatments.
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CONTEXT: Diabetic peripheral neuropathy (DPN) results in an enormous burden and reduces the quality of life for patients. Considering there is no specific drug for the management of DPN, traditional Chinese medicine (TCM) has increasingly drawn attention of clinicians and researchers around the world due to its characteristics of multiple targets, active components, and exemplary safety. OBJECTIVE: To summarize the current status of TCM in the treatment of DPN and provide directions for novel drug development, the clinical effects and potential mechanisms of TCM used in treating DPN were comprehensively reviewed. METHODS: Existing evidence on TCM interventions for DPN was screened from databases such as PubMed, the Cochrane Neuromuscular Disease Group Specialized Register (CENTRAL), and the Chinese National Knowledge Infrastructure Database (CNKI). The focus was on summarizing and analyzing representative preclinical and clinical TCM studies published before 2023. RESULTS: This review identified the ameliorative effects of about 22 single herbal extracts, more than 30 herbal compound prescriptions, and four Chinese patent medicines on DPN in preclinical and clinical research. The latest advances in the mechanism highlight that TCM exerts its beneficial effects on DPN by inhibiting inflammation, oxidative stress and apoptosis, endoplasmic reticulum stress and improving mitochondrial function. CONCLUSIONS: TCM has shown the power latent capacity in treating DPN. It is proposed that more large-scale and multi-center randomized controlled clinical trials and fundamental experiments should be conducted to further verify these findings.
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Neuropatías Diabéticas , Medicamentos Herbarios Chinos , Medicina Tradicional China , Humanos , Neuropatías Diabéticas/tratamiento farmacológico , Medicina Tradicional China/métodos , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Animales , Calidad de Vida , Estrés Oxidativo/efectos de los fármacos , Evaluación Preclínica de Medicamentos/métodosRESUMEN
CONTEXT: The global prevalence of type 2 diabetes mellitus (T2DM) has increased significantly in recent decades. Despite numerous studies and systematic reviews, there is a gap in comprehensive and up-to-date evaluations in this rapidly evolving field. OBJECTIVE: This review provides a comprehensive and current overview of the efficacy of Traditional Chinese Medicine (TCM) in treating T2DM. METHODS: A systematic review was conducted using PubMed, Web of Science, Wanfang Data, CNKI, and Medline databases, with a search timeframe extending up to November 2023. The search strategy involved a combination of subject terms and free words in English, including 'Diabetes,' 'Traditional Chinese Medicine,' 'TCM,' 'Hypoglycemic Effect,' 'Clinical Trial,' and 'Randomized Controlled Trial.' The studies were rigorously screened by two investigators, with a third investigator reviewing and approving the final selection based on inclusion and exclusion criteria. RESULTS: A total of 108 relevant papers were systematically reviewed. The findings suggest that TCMs not only demonstrate clinical efficacy comparable to existing Western medications in managing hypoglycemia but also offer fewer adverse effects and a multitarget therapeutic approach. Five main biological mechanisms through which TCM treats diabetes were identified: improving glucose transport and utilization, improving glycogen metabolism, promoting GLP-1 release, protecting pancreatic islets from damage, and improving intestinal flora. CONCLUSIONS: TCM has demonstrated significant protective effects against diabetes and presents a viable option for the prevention and treatment of T2DM. These findings support the further exploration and integration of TCM into broader diabetes management strategies.
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Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Hipoglucemiantes , Medicina Tradicional China , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Medicina Tradicional China/métodos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Resultado del Tratamiento , Animales , Ensayos Clínicos Controlados Aleatorios como Asunto , Glucemia/efectos de los fármacos , Glucemia/metabolismoRESUMEN
Introduction: Diabetes has been recognized as an independent risk factor for periodontitis. Increasing evidences indicate that hyperglycemia aggravates inflammatory response of human periodontal ligament cells (hPDLCs). Carbon monoxide-releasing molecule-3 (CORM-3) is a water-soluble compound that can release carbon monoxide (CO) in a controllable manner. CORM-3 has been shown the anti-inflammatory effect in different cell lineages. Methods: We stimulated periodontal ligament cells with LPS and high glucose. The expression of inflammatory cytokine was detected by ELISA. RT-qPCR, Western blot and immunofluorescence were used to detect the expression of TLR2, TLR4, RAGE and the activation of NF-κB pathway. We performed silencing and overexpression treatment of RAGE targeting the role of RAGE. We performed the immunostaining of paraffin sections of the periodontitis model in diabetes rats. Results: The results showed that CORM-3 significantly inhibited the expression of inflammatory cytokine in hPDLCs stimulated with LPS and high glucose. CORM-3 also inhibited LPS and high glucose-induced expression of RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway. Silence of RAGE resulted in significantly decreased expression of proteins above. Overexpression of RAGE significantly enhanced the expression of these factors. CORM-3 abrogated the effect of RAGE partially. In animal model, CORM-3 suppressed the inflammatory response of periodontal tissues in experimental periodontitis of diabetic rats. Discussion: Our research proved CORM-3 reduced the inflammatory response via RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway in the process of high glucose exacerbated periodontitis. These findings demonstrated the role of RAGE in the process of high glucose exacerbated periodontitis and suggested that CORM3 be a potential therapeutic strategy for the treatment of diabetes patients with periodontitis.
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OBJECTIVE: This study aimed to compare the damage of vocal folds caused by four different surgical instruments: CO2 laser, electrosurgical knife, plasma radiofrequency ablation, and steel knife. STUDY DESIGN: Randomized controlled study. METHODS: The CO2 laser, electrosurgical knife, plasma radiofrequency ablation, steel knife, and other instruments were used to simulate the laryngeal microsurgery on experimental dogs. Both total vocal fold resection and punctate ablation were performed. On the day of surgery and 6 days later, the vocal fold tissue from the surgical site was removed for histological evaluation. The extent of vocal fold damage was assessed using the automatic digital pathological scanning system. RESULTS: We detected varying degrees of damage to the laryngeal tissues. Only the steel knife caused epidermal defects on the vocal fold tissue, while other instruments produced thermal damage of different degrees. Furthermore, the steel knife also showed better and faster healing. The plasma radiofrequency ablation was found to cause more severe thermal burns to vocal folds than other surgical instruments (P < 0.05). Six days postsurgery the inflammatory reaction from the steel knife had basically subsided, with only hyperplasia and tissue repair visible microscopically, showing the best healing degree. On the other hand, the radiofrequency ablation group showed the heaviest inflammatory reaction, indicating relatively poor prognosis (P < 0.05). CONCLUSION: Compared with the CO2 laser, the electrotome and steel knife showed less damage and better healing, while the plasma radiofrequency ablation showed the most obvious thermal burns to laryngeal and vocal tissues during surgery, with relatively poor healing.
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BACKGROUND: Niemann-Pick Disease type C is a fatal autosomal recessive lipid storage disorder caused by NPC1 or NPC2 gene mutations and characterized by progressive, disabling neurological deterioration and hepatosplenomegaly. Herein, we identified a novel compound heterozygous mutations of the NPC1 gene in a Chinese pedigree. CASE PRESENTATION: This paper describes an 11-year-old boy with aggravated walking instability and slurring of speech who presented as Niemann-Pick Disease type C. He had the maternally inherited c.3452 C > T (p. Ala1151Val) mutation and the paternally inherited c.3557G > A (p. Arg1186His) mutation using next-generation sequencing. The c.3452 C > T (p. Ala1151Val) mutation has not previously been reported. CONCLUSIONS: This study predicted that the c.3452 C > T (p. Ala1151Val) mutation is pathogenic. This data enriches the NPC1 gene variation spectrum and provides a basis for familial genetic counseling and prenatal diagnosis.
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Enfermedad de Niemann-Pick Tipo C , Niño , Humanos , Masculino , Proteínas Portadoras/genética , Mutación , Proteína Niemann-Pick C1/genética , Enfermedad de Niemann-Pick Tipo C/diagnóstico , Enfermedad de Niemann-Pick Tipo C/genética , Diagnóstico PrenatalRESUMEN
BACKGROUND: Migraine has a high prevalence in the population and accounts for 12% of primary headaches. Ubrogepant is used for the treatment of acute migraine, and although some clinical trials have demonstrated the safety of Ubrogepant, its long-term safety in a large sample of the population remains to be investigated. METHODS: We collected data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We used reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC) and the empirical Bayes geometric mean (EBGM) to evaluate Ubrogepant-induced adverse events (AEs). RESULTS: We screened out 2,067 reports of Ubrogepant as primary suspected (PS) and 6,190 reports of Ubrogepant-induced AEs as PS. Our results showed that Ubrogepant-induced AEs targeted 4 system organ classes (SOCs), detected 32 Preferred terms (PTs) signals in 9 SOCs, including common Ubrogepant label consistent with Migraine, Nausea, Somnolence, Paraesthesia oral and Dizziness, It also includes the AEs of Hemiparesis, Mental impairment, Dysstasia, Tinnitus, Chest pain, Cold sweat, Neck pain, etc. that have not been demonstrated in previous studies. CONCLUSIONS: Our study identified new AEs that have not been reported, which provides a new guidance to deepen the comprehension of the safety of Ubrogepant.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Trastornos Migrañosos , Estados Unidos/epidemiología , Humanos , Teorema de Bayes , Piridinas/efectos adversos , Pirroles/efectos adversos , Trastornos Migrañosos/tratamiento farmacológico , United States Food and Drug Administration , Sistemas de Registro de Reacción Adversa a Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , FarmacovigilanciaRESUMEN
Metal-organic frameworks (MOFs) have attracted widespread interest due to their unique and unprecedented advantages in microstructures and properties. Besides, surface-enhanced Raman scattering (SERS) technology has also rapidly developed into a powerful fingerprint spectroscopic technique that can provide rapid, non-invasive, non-destructive, and ultra-sensitive detection, even down to single molecular level. Consequently, a considerable amount of researchers combined MOFs with the SERS technique to further improve the sensing performance and broaden the applications of SERS substrates. Herein, representative synthesis strategies of MOFs to fabricate SERS-active substrates are summarized and their applications in ultra-sensitive biomedical trace detection are also reviewed. Besides, relative barriers, advantages, disadvantages, future trends, and prospects are particularly discussed to give guidance to relevant researchers.
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We propose a neuromorphic convolution system using a photonic integrated distributed feedback laser with a saturable absorber (DFB-SA) as a photonic spiking neuron. The experiments reveal that the DFB-SA laser can encode different stimulus intensities at different frequencies, similar to biological neurons. Based on this property, optical inputs are encoded into rectangular pulses of varying intensities and injected into the DFB-SA laser, enabling the convolution results to be represented by the firing rate of the photonic spiking neuron. Both experimental and numerical results show that the binary convolution is successfully achieved based on the rate-encoding properties of a single DFB-SA laser neuron. Furthermore, we numerically predict 4-channel quadratic convolution and accomplish MNIST handwritten digit classification using a spiking DFB-SA laser neuron model with rate coding. This work provides a novel approach for convolution computation, indicating the potential of integrating DFB-SA laser into future photonics spiking neural networks.
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Ganoderma sinense, with more than 2000 years of medicinal history, is a fungus of the basidiomycetes that is rich in polysaccharides and terpenoids. However, the biosynthesis of terpenes, especially sesquiterpenes, has been little studied. The functional identification of sesquiterpene synthases from G. sinense is of great significance to the study of fungal terpenoid biosynthesis and regulation. Our research group has completed the functional characterization of 21 sesquiterpene synthase genes from G. sinense. It was found that gleenol, biosynthesis of which is catalyzed by the sesquiterpene synthase GsSTS26 and GsSTS27, has the functions of killing termites, antihelminth, and plant growth regulation. In the unmodified E. coli Rosetta (DE3) strain, the content of gleenol produced by sesquiterpene synthase from G. sinense is low, which makes it difficult to meet the demand of industrial production and the market. Therefore, it is of great significance to obtain high-yielding strains by means of synthetic biology. In this study, we constructed eight recombinant strains by using tandem gene expression and promoter engineering, and the content of gleenol was increased by up to 23-fold. In this study, we realized the de novo synthesis of gleenol in E. coli and provided a basis for the biosynthesis of terpenoids in basidiomycetes. KEY POINTS: ⢠Eight recombinant expression systems were constructed by using tandem genes and promoter engineering. ⢠The recombinant strain promoted the efficient production of gleenol in E. coli Rosetta (DE3). ⢠The recombinant strain achieved de novo production of gleenol in E. coli.
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Transferasas Alquil y Aril , Sesquiterpenos , Escherichia coli/genética , Escherichia coli/metabolismo , Sesquiterpenos/metabolismo , Terpenos/metabolismo , Transferasas Alquil y Aril/metabolismoRESUMEN
The spread of coronavirus disease 2019 (COVID-19) results in an increasing incidence and mortality. The typical diagnosis technique for severe acute respiratory syndrome coronavirus 2 infection is reverse transcription polymerase chain reaction, which is relatively expensive, time-consuming, professional, and suffered from false-negative results. A reliable, non-invasive diagnosis method is in urgent need for the rapid screening of COVID-19 patients and controlling the epidemic. Here we constructed an intelligent system based on the volatile organic compound (VOC) biomarkers in human breath combined with machine learning models. The VOC profiles of 122 breath samples (65 of COVID-19 infections and 57 of controls) were identified with a portable gas chromatograph-mass spectrometer. Among them, eight VOCs exhibited significant differences (p< 0.001) between the COVID-19 and the control groups. The cross-validation algorithm optimized support vector machine (SVM) model was employed for the prediction of COVID-19 infection. The proposed SVM model performed a powerful capability in discriminating COVID-19 patients from healthy controls, with an accuracy of 97.3%, a sensitivity of 100%, a specificity of 94.1%, and a precision of 95.2%, and anF1 score of 97.6%. The SVM model was also compared with other common machine models, including artificial neural network,k-nearest neighbor, and logistic regression, and demonstrated obvious superiority in the prediction of COVID-19 infection. Furthermore, user-friendly software was developed based on the optimized SVM model. The developed intelligent platform based on breath analysis provides a new strategy for the point-of-care screening of COVID and shows great potential in clinical application.
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COVID-19 , Compuestos Orgánicos Volátiles , Humanos , Pruebas Respiratorias/métodos , Compuestos Orgánicos Volátiles/análisis , Máquina de Vectores de Soporte , Biomarcadores/análisisRESUMEN
Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign, but locally aggressive breast disease. Steroids are widely used as a breast-conserving option, however, the response rate of steroids varies in reported studies, as well as its different reported usage. This prospective observational cohort study aimed to report the outcomes of methylprednisolone for IGM treatment. Methods: From Aug 2019 to Dec 2021, the clinicopathological information of 156 IGM patients who sought treatment at West China Hospital was prospectively collected. A total of 88 patients treated with methylprednisolone were included in the study. The clinical features, treatment response, and follow-up data were analyzed. Results: The median age at diagnosis was 32 years, and 90.9% of patients were multipara. The predominant symptom at presentation was painful breast mass, with a median size of 4.7 cm. For steroid usage, an initial 20 mg methylprednisolone daily was given until disease stable. The median duration of 20 mg methylprednisolone treatment was 45 (range, 14-376) days. The median duration of whole steroid therapy was 105 (range, 28-381) days. A total of 80.7% of patients (71/88) responded well to steroid treatment. In 63 patients, steroid treatment was successfully withdrawn, and treatment was completed. With an average of 283 days follow-up (range, 0-770 days), relapse was observed in 21 (33.33%) patients. Compared with patients with residual disease as shown by physical examination (PE), those with complete clinical remission (CCR) at the end of treatment had longer relapse-free intervals. Conclusions: Steroids are the preferable breast-conserving option for IGM. Treatment with 20 mg methylprednisolone for an average of 1.5 months is usually required, and full steroid treatment might last for 3 months.
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Restoring skin integrity after wound infection remains a tougher health challenge due to the uncontrolled antibiotic-resistant pathogens caused by antibiotic abuse. Herein, an injectable hydrogel with dual antibacterial and anti-inflammatory activities composed of gold nanoclusters (GNCs) and carbomer (CBM) is developed for wound dressing to overcome multidrug-resistant infection. Firstly, both experimental investigations and molecular dynamics simulation validate the protonation state of 6-mercaptohexanoic acid (MHA) ligands play an important role in its antibacterial action of GNCs. The self-organizing GNCs-CBM composite hydrogel is then spontaneously cross-linked by the dimeric hydrogen bonds (H-bonds) between the MHA ligands and the acrylic acid groups of CBM. Benefitting from the dimeric H-bonds, the hydrogel becomes thickening enough as an ideal wound dressing and the GNCs exist in the hydrogel with a high protonation level that contributes to the enhanced bactericidal function. In all, by combining bactericidal and immunomodulatory actions, the GNCs-CBM hydrogel demonstrated excellent synergy in accelerating wound healing in animal infection models. Hence, the dimeric H-bonds strengthening strategy makes the GNCs-CBM hydrogel hold great potential as a safe and effective dressing for treating infected wounds.
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BACKGROUND: Nasopharyngeal carcinoma (NPC) is uncommon in most areas of the world but poses a significant public health burden in endemic regions. OBJECTIVES: We provide an overview of the most recent global epidemiology of nasopharyngeal cancer (NPC). METHODS: We estimated the burden of NPC in 204 countries and territories by age, sex, and Socio-Demographic Index (SDI) from 1990 to 2019. RESULTS: At the GBD regional level, the most severe age-standardized incidence in 2019 occurred in East Asia. From 1990 to 2019, the East Asia and High-income Asia Pacific had the greatest increase in percentage in age-standardized incidence. Central Asia and the Caribbean had the greatest increase in percentage in age-standardized disability-adjusted life-years (DALY) and death rates. At the national level, Cabo Verde, Romania, and the Cyprus reported the largest percentage increases in the age-standardized incidence. Cabo Verde, Romania, and Jamaica reported the largest increases in the age-standardized DALY and death rates. CONCLUSIONS: The global age-standardized incidence of NPC increased globally between 1990 and 2019, especially in the East Asia.
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Carga Global de Enfermedades , Neoplasias Nasofaríngeas , Salud Global , Humanos , Incidencia , Carcinoma Nasofaríngeo/epidemiología , Neoplasias Nasofaríngeas/epidemiología , Años de Vida Ajustados por Calidad de Vida , Factores de RiesgoRESUMEN
Gas sensor-embedded smartphones would offer the opportunity of on-site tracking of gas molecules for various applications, for example, harmful air pollutant alarms or noninvasive assessment of health status. Nevertheless, high power consumption and difficulty in replacing malfunctioned sensors as well as limited space in the smartphone to host the sensor restrain the relevant advancements. In this article, we create a smartphone case-based sensing platform by integrating the functional units into a smartphone case, which performs a low detection limit of 117 ppb to acetone and high specificity. Particularly, dimming glass-regulated light fidelity (Li-Fi) communication is successfully developed, allowing the sensing platform to operate with relatively low power consumption (around 217 mW). Experimental proof on harmful gas sensing and potential clinic application is implemented with the sensing platform, demonstrating satisfactory sensing performance and acceptable health risk pre-warning accuracy (87%). Thus, the developed smartphone case-based sensing platform would be a good candidate for realizing harmful gas alarms and noninvasive assessment of health status.
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Acetona , Teléfono InteligenteRESUMEN
Alzheimer's disease (AD) is the most common cause of progressive dementia. In the present study, we showed hippocampal tissue transcriptome analysis in APPswe/PSEN1dE9 (APP/PS1, AD model) mice treated with fasudil (ADF) and compared with AD mice treated with saline (ADNS) and wild type mice (WT). The competing endogenous RNA (ceRNA) network was constructed and validated the differential expression of mRNA, lncRNA, miRNA, and circRNA. Our study showed differentially expressed mRNAs (DEMs) between WT and ADNS, while enriched in cell growth and death and nervous system pathways. DEMs between ADNS-ADF were enriched in the nervous system, glycosaminoglycan biosynthesis-keratan sulfate (KS) and Quorum sensing pathways. We validated four genes with RT-PCR, whereas enrichment of Acyl-CoA Synthetase Long Chain Family Member 4 (Acsl4, ENSMUST00000112903) in Quorum sensing pathways, and BTG anti-proliferation factor 1 (Btg1, ENSMUST00000038377) in RNA degradation pathways were conducted. Expression of these two genes were higher in ADNS, but were significantly reduced in ADF. Histone H4 transcription factor (Hinfp, ENSMUST00000216508) orchestrate G1/S transition of mitotic cell cycle and co-expressed with mmu-miR-26a-2-3p-mediated ceRNA and mmu-miR-3065-5p-mediated ceRNA; Wnt family member 4 (Wnt4, ENSMUST00000045747) was enriched in mTOR, Hippo and Wnt signaling pathway. Expression of these two genes were significantly lower in ADNS, and fasudil treatment reverse it. The present studies demonstrated four genes: Acsl4, Btg1, Hinfp, Wnt4 could be potential biomarkers of AD and the targets of fasudil treatment. These results will pave a novel direction for future clinic studies for AD and fasudil treatment.
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1-(5-Isoquinolinesulfonil)-2-Metilpiperazina , Enfermedad de Alzheimer , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Animales , Animales Modificados Genéticamente , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Ratones , Ratones Transgénicos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , ARN Largo no Codificante/genética , TranscriptomaRESUMEN
Enzymes boost protein engineering, directed evolution, and the biochemical industry and are also the cornerstone of metabolic engineering. Basidiomycetes are known to produce a large variety of terpenoids with unique structures. However, basidiomycetous terpene synthases remain largely untapped. Therefore, we provide a modeling method to obtain specific terpene synthases. Aided by bioinformatics analysis, three γ-cadinene enzymes from Ganoderma lucidum and Ganoderma sinensis were accurately predicted and identified experimentally. Based on the highly conserved amino motifs of the characterized γ-cadinene enzymes, the enzyme was reassembled as model 1. Using this model as a template, 67 homologous sequences of the γ-cadinene enzyme were screened from the National Center for Biotechnology Information (NCBI). According to the 67 sequences, the same gene structure, and similar conserved motifs to model 1, the γ-cadinene enzyme model was further improved by the same construction method and renamed as model 2. The results of bioinformatics analysis show that the conservative regions of models 1 and 2 are highly similar. In addition, five of these sequences were verified, 100% of which were γ-cadinene enzymes. The accuracy of the prediction ability of the γ-cadinene enzyme model was proven. In the same way, we also reanalyzed the identified Δ6-protoilludene enzymes in fungi and (-)-α-bisabolol enzymes in plants, all of which have their own unique conserved motifs. Our research method is expected to be used to study other terpenoid synthases with a similar or the same function in basidiomycetes, ascomycetes, bacteria, and plants and to provide rich enzyme resources.
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Inflammatory bowel disease (IBD) has been found to be correlated to increased risk of both gastrointestinal and extraintestinal malignancies. It still remains conflicting whether IBD has influence on risk of breast cancer, requesting further investigations. A systematic literature research before June 2020 was conducted in PubMed and Web of Science databases. Observational studies reporting incident breast cancer after IBD diagnosis and providing measures of association were included in the meta-analysis. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to evaluate the associations between IBD and risk of breast cancer. Our analysis included 16 cohort studies and the overall pooled OR in patients with IBD was 0.94 (95% CI, 0.82-1.06). In further subgroup analysis, no significant association with breast cancer risk among patients with Crohn's disease (OR, 0.91; 95% CI, 0.70-1.12) and ulcerative colitis (OR, 0.99; 95% CI, 0.90-1.08). For geographic differences, the summary OR of populations in Asia (OR, 1.01; 95% CI, 0.73-1.30) was only numerically larger than that in European populations (OR, 0.90; 95% CI, 0.75-1.06). Our findings indicated that IBD had no significant influence on breast cancer risk regardless of different IBD types and geographical areas.
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Neoplasias de la Mama , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Enfermedad Crónica , Estudios de Cohortes , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/complicaciones , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Factores de RiesgoRESUMEN
Probing water-soluble organic compounds via Surface-enhanced Raman scattering (SERS) technique could be helpful to prevent harmful impacts of polluted water. A key limitation of restraining SERS technique in probing these pollutants is the difficulty to control the spacing distance of plasmonic nanoparticles within 10 nm so that SERS effect can be efficiently induced. Herein, a strategy of mass-producing Ag-based SERS active material with tunable spacing distance is reported. In brevity, metal-organic framework (MOF) engineered corn-like Ag@Carbon is synthesized by simply thermal treating Ag-MOF. The thermal treatment in-situ turns Ag+ into Ag nanoparticles (NPs), resulting in Ag NPs well-dispersed on the surface of the carbonized MOF and forming ordered SERS hotspots. Due to the spatial distance of Ag+ directly depends on the molecular diameter of MOF organic ligands, spacing distance of Ag NP is fixed at around 7 nm. Theoretical analysis and experimental study confirm that the uniformly distributed Ag NPs lead to desirable SERS activity. Further study evidences the presented corn-like Ag@Carbon could be a good candidate for tacking organic compounds with satisfactory sensitivity, specificity and low detection limit (10-8 M). Conclusively, these impressive results indicate a bright future of adopting the proposed strategy to design future SERS active materials.
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Nanopartículas del Metal , Estructuras Metalorgánicas , Carbono , Plata , Espectrometría Raman , Zea maysRESUMEN
Background: Fasudil, a Rho kinase inhibitor, exerts therapeutic effects in a mouse model of Alzheimer's disease (AD), a chronic neurodegenerative disease with progressive loss of memory. However, the mechanisms remain unclear. In addition, the gut microbiota and its metabolites have been implicated in AD. Methods: We examined the effect of fasudil on learning and memory using the Morris water-maze (MWM) test in APPswe/PSEN1dE9 transgenic (APP/PS1) mice (8 months old) treated (i.p.) with fasudil (25 mg/kg/day; ADF) or saline (ADNS) and in age- and gender-matched wild-type (WT) mice. Fecal metagenomics and metabolites were performed to identify novel biomarkers of AD and elucidate the mechanisms of fasudil induced beneficial effects in AD mice. Results: The MWM test showed significant improvement of spatial memory in APP/PS1 mice treated with fasudil as compared to ADNS. The metagenomic analysis revealed the abundance of the dominant phyla in all the three groups, including Bacteroidetes (23.7-44%) and Firmicutes (6.4-26.6%), and the increased relative abundance ratio of Firmicutes/Bacteroidetes in ADNS (59.1%) compared to WT (31.7%). In contrast, the Firmicutes/Bacteroidetes ratio was decreased to the WT level in ADF (32.8%). Lefse analysis of metagenomics identified s_Prevotella_sp_CAG873 as an ADF potential biomarker, while s_Helicobacter_typhlonius and s_Helicobacter_sp_MIT_03-1616 as ADNS potential biomarkers. Metabolite analysis revealed the increment of various metabolites, including glutamate, hypoxanthine, thymine, hexanoyl-CoA, and leukotriene, which were relative to ADNS or ADF microbiota potential biomarkers and mainly involved in the metabolism of nucleotide, lipids and sugars, and the inflammatory pathway. Conclusions: Memory deficit in APP/PS1 mice was correlated with the gut microbiome and metabolite status. Fasudil reversed the abnormal gut microbiota and subsequently regulated the related metabolisms to normal in the AD mice. It is believed that fasudil can be a novel strategy for the treatment of AD via remodeling of the gut microbiota and metabolites. The novel results also provide valuable references for the use of gut microbiota and metabolites as diagnostic biomarkers and/or therapeutic targets in clinical studies of AD.