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BACKGROUND: IgA nephropathy is an important global cause of kidney failure. Dysregulation of IgA production is thought to play a key role in IgA nephropathy pathogenesis, however, little is known about the epigenetic mechanisms such as RNA 5- methylcytosine (5mC) modification in regulating IgA synthesis. METHODS: To decipher the role of RNA 5mC in regulation of IgA class switch, the miR-23b-/- and LCWE induced Kawasaki disease mice were treated with 5-azacytidine. Trdmt1-/- and double Trdmt1-/-/ miR-23b-/- mice, Aid-/- mice or Aid-/-/ miR-23b-/- mice were also employed. RESULTS: We showed that miR-23b down regulated expression of Transfer RNA Aspartic Acid Methyltransferase 1 (Trdmt1) and consequently reduced 5-methylcytosine (m5C) RNA modification and IgA synthesis in B cells. Inhibition of m5C RNA modification normalised serum IgA levels and ameliorated progression of the IgA nephropathy-like kidney disease in miR-23b-/- and Kawasaki disease mice while mesangial IgA and C3 deposition failed to develop in Trdmt1-/-miR-23b-/- mice. By contrast, increased m5C RNA modification resulted in an exaggerated IgA nephropathy phenotype. miR-23b regulation of serum IgA levels and the development of an IgA nephropathy-like kidney disease in miR-23b-/- and Kawasaki disease mice is likely mediated through TRDMT1 driven 5-methylcytosine RNA modification in B cells, resulting in impaired activation-induced cytidine deaminase activity and IgA class switch recombination. CONCLUSIONS: This study revealed TRDMT1 induced RNA 5mC methylation regulate IgA class switch and inhibition of RNA 5mC by 5-Azacytidine could ameliorate progression of IgA nephropathy.
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BACKGROUND: Few primary studies have examined the impact of olfactory and gustatory stimulation on premature infants, and variability exists in reported outcomes. PURPOSE: To explore the effects of olfactory and gustatory stimulation on feeding outcomes in preterm infants. DATA SOURCES: A literature search was conducted in 4 databases (CENTRAL, PubMed, Embase, CINAHL) from the inception of the databases to May 2024. STUDY SELECTION: Randomized controlled trials (RCTs) or quasi-RCTs to explore the effects of olfactory and gustatory stimulation on feeding outcomes in preterm infants were included. DATA EXTRACTION: Two reviewers independently extracted data from the included studies and completed the form designed for data extraction. RESULTS: Eleven RCTs and quasi-RCTs comprising 1009 preterm infants were included. Meta-analysis found that olfactory and gustatory stimulation significantly shortened the time to reach full oral feeds (days) (mean difference [MD]: -2.52, 95% confidence interval [CI]: -3.88 to -1.16, P = .0003), while they had no significant differences in time to achieve full enteral feeds (days), postmenstrual age (PMA) at the removal of the nasogastric tube (weeks), weight at discharge (grams), weight gain (grams), head circumference at discharge (cm), length at discharge (cm), total duration of parenteral nutrition (days), necrotizing enterocolitis, hospitalization duration (days), PMA at discharge (weeks). IMPLICATIONS FOR PRACTICE AND RESEARCH: Large sample, multicenter studies are needed to demonstrate the effectiveness of olfactory and gustatory stimulation on feeding outcomes in preterm infants.
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Cotton has attracted considerable attention due to its functional characteristics. The focus of research on cotton has shifted in recent years towards designing multi-functional and modified media for cotton fibers, which can be firmly combined with textiles, giving them reusability and extending their service life. This study constructed a synergistic antibacterial layer of quaternary ammonium compounds (QACs) and N-halamine (Hals) using an in-situ free radical copolymerization method in water, named QACs/Hals@cotton-Cl. The route significantly increases the number of antibacterial active centers. FTIR, XPS, and SEM were used to systematically analyze the product's chemical structure, surface morphology, and other characteristics. The modified fabric's antibacterial efficiency, wound healing, renewability, and durability were also evaluated. The chlorinated modified cotton fabric could completely eradicate S. aureus and E. coli within 10 min. Compared with pure cotton, it notably promoted the healing rate of infected wounds in mice. The modification method imparted excellent hydrophobicity to the cotton fabric, with a contact angle exceeding 130°, making it easy to remove surface stains. After 30 days of regular storage and 24 h of UV irradiation, the active chlorine concentration (Cl+%) only decreased by 25 % and 39 %, respectively, and the reduced Cl+% was effectively recharged via simple re-chlorination. The hydrophobicity and antimicrobial properties of QACs/Hals@cotton-Cl remained stable even after 20 cycles of friction. This simple synthesis technique provides a convenient approach for the scalable fabrication of multifunctional and rechargeable antibacterial textiles, with potential applications in medical devices and personal hygiene protection.
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Aminas , Antibacterianos , Fibra de Algodão , Escherichia coli , Staphylococcus aureus , Cicatrização , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Aminas/química , Escherichia coli/efeitos dos fármacos , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Têxteis , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Human cytomegalovirus (HCMV) is a herpesvirus that can infect various cell types and modulate host gene expression and immune response. It has been associated with the pathogenesis of various cancers, but its molecular mechanisms remain elusive. METHODS: We comprehensively analyzed the expression of HCMV pathway genes across 26 cancer types using the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases. We also used bioinformatics tools to study immune invasion and tumor microenvironment in pan-cancer. Cox regression and machine learning were used to analyze prognostic genes and their relationship with drug sensitivity. RESULTS: We found that HCMV pathway genes are widely expressed in various cancers. Immune infiltration and the tumor microenvironment revealed that HCMV is involved in complex immune processes. We obtained prognostic genes for 25 cancers and significantly found 23 key genes in the HCMV pathway, which are significantly enriched in cellular chemotaxis and synaptic function and may be involved in disease progression. Notably, CaM family genes were up-regulated and AC family genes were down-regulated in most tumors. These hub genes correlate with sensitivity or resistance to various drugs, suggesting their potential as therapeutic targets. CONCLUSIONS: Our study has revealed the role of the HCMV pathway in various cancers and provided insights into its molecular mechanism and therapeutic significance. It is worth noting that the key genes of the HCMV pathway may open up new doors for cancer prevention and treatment.
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Biologia Computacional , Citomegalovirus , Neoplasias , Microambiente Tumoral , Humanos , Citomegalovirus/genética , Citomegalovirus/patogenicidade , Biologia Computacional/métodos , Neoplasias/genética , Neoplasias/virologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Regulação Neoplásica da Expressão Gênica/genética , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , Prognóstico , Redes Reguladoras de Genes/genética , Perfilação da Expressão Gênica , Bases de Dados GenéticasRESUMO
The misuse of antibiotics has led to increased bacterial resistance, posing a global public health crisis and seriously endangering lives. Currently, antibiotic therapy remains the most common approach for treating bacterial infections, but its effectiveness against multidrug-resistant bacteria is diminishing due to the slow development of new antibiotics and the increase of bacterial drug resistance. Consequently, developing new a\ntimicrobial strategies and improving antibiotic efficacy to combat bacterial infection has become an urgent priority. The emergence of nanotechnology has revolutionized the traditional antibiotic treatment, presenting new opportunities for refractory bacterial infection. Here we comprehensively review the research progress in nanotechnology-based antimicrobial drug delivery and highlight diverse platforms designed to target different bacterial resistance mechanisms. We also outline the use of nanotechnology in combining antibiotic therapy with other therapeutic modalities to enhance the therapeutic effectiveness of drug-resistant bacterial infections. These innovative therapeutic strategies have the potential to enhance bacterial susceptibility and overcome bacterial resistance. Finally, the challenges and prospects for the application of nanomaterial-based antimicrobial strategies in combating bacterial resistance are discussed. This article is categorized under: Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.
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Antibacterianos , Infecções Bacterianas , Nanotecnologia , Humanos , Infecções Bacterianas/tratamento farmacológico , Animais , Farmacorresistência Bacteriana/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , NanomedicinaRESUMO
INTRODUCTION: Various approaches are employed to expedite the passage of meconium in preterm infants within the neonatal intensive care unit (NICU), with glycerine enemas being the most frequently used. Due to the potential risk of high osmolality-induced harm to the intestinal mucosa, diluted glycerine enema solutions are commonly used in clinical practice. The challenge lies in the current lack of knowledge regarding the safest and most effective concentration of glycerine enema. This research aims to ascertain the safety of different concentrations of glycerine enema solution in preterm infants. METHODS AND ANALYSIS: This study protocol is for a single-centre, two-arm, parallel-group, double-blind and non-inferiority randomised controlled trial. Participants will be recruited from a NICU in a teriary class A hospital in China, and eligible infants will be randomly allocated to either the glycerine (mL): saline (mL) group in a 3:7 ratio or the 1:9 ratio group. The enema procedure will adhere to the standardised operational protocols. Primary outcomes encompass necrotising enterocolitis and rectal bleeding, while secondary outcomes encompass feeding parameters, meconium passage outcomes and splanchnic regional oxygen saturation. Analyses will compare the two trial arms based on an intention-to-treat allocation. ETHICS AND DISSEMINATION: This trial is approved by the ethics committee of the Medical Ethics Committee of West China Second University Hospital of Sichuan University. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300079199.
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Enema , Glicerol , Recém-Nascido Prematuro , Mecônio , Feminino , Humanos , Recém-Nascido , Masculino , China , Método Duplo-Cego , Enema/métodos , Enterocolite Necrosante/prevenção & controle , Glicerol/administração & dosagem , Unidades de Terapia Intensiva Neonatal , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.
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Doença das Coronárias , Infecções por HIV , Aprendizado de Máquina , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Medição de Risco/métodos , Adulto , Registros Eletrônicos de Saúde , IdosoRESUMO
Leaf rolling is regarded as an important morphological trait in wheat breeding. Moderate leaf rolling is helpful to keep leaves upright and improve the photosynthesis of plants, leading to increased yield. However, studies on the identification of genomic regions/genes associated with rolling leaf have been reported less frequently in wheat. In this study, a rolling leaf mutant, T73, which has paired spikelets, dwarfism, and delayed heading traits, was obtained from a common wheat landrace through ethyl methanesulfonate mutagenesis. The rlT73 mutation caused an increase in the number of epidermal cells on the abaxial side and the shrinkage of bulliform cells on the adaxial side, leading to an adaxially rolling leaf phenotype. Genetic analysis showed that the rolling leaf phenotype was controlled by a single recessive gene. Further Wheat55K single nucleotide polymorphism array-based bulked segregant analysis and molecular marker mapping delimited rlT73 to a physical interval of 300.29-318.33 Mb on the chromosome arm 1BL in the Chinese Spring genome. We show that a point mutation at the miRNA165/166 binding site of the HD zipper class III transcription factor on 1BL altered its transcriptional level, which may be responsible for the rolling leaf phenotype. Our results suggest the important role of rlT73 in regulating wheat leaf development and the potential of miRNA-based gene regulation for crop trait improvement.
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Melhoramento Vegetal , Triticum , Alelos , Triticum/genética , Mutação , CromossomosRESUMO
Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins, showing a potential threat to humans. Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus, PCoV-GX/P2V, which was isolated from a Malayan pangolin (Manis javanica). PCoV-GX/P2V could grow in human hepatoma, colorectal adenocarcinoma cells, and human primary nasal epithelial cells. It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2 (hACE2) as SARS-CoV-2 did. After intranasal inoculation to the hACE2-transgenic mice, PCoV-GX/P2V not only replicated in nasal turbinate and lungs, but also caused interstitial pneumonia, characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage. Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection. These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.
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Enzima de Conversão de Angiotensina 2 , COVID-19 , Camundongos Transgênicos , Pangolins , SARS-CoV-2 , Animais , Humanos , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , SARS-CoV-2/patogenicidade , SARS-CoV-2/genética , COVID-19/virologia , Pangolins/virologia , Camundongos , Replicação Viral , Pulmão/virologia , Pulmão/patologia , Chlorocebus aethiops , Células VeroRESUMO
Introduction: The initial acquisition and subsequent development of the microbiota in early life is crucial to future health. Cesarean-section (CS) birth is considered to affect early microbial transmission from mother to infant. Methods: In this study, we collected fecal samples from 34 CS infants and their mothers from West China Second Hospital, Sichuan University to assess the microbiota developmental trajectory of mothers and infants. We explored mother-infant gut microbiome transmission via comparison with corresponding Finnish data. Results: Metagenomic analysis of gut microbiota profiles indicated that the communities of mothers and infants were distinct. The composition of the infant gut microbiome was highly variable but also followed predictable patterns in the early stages of life. Maternal communities were stable and mainly dominated by species from Bacteroidacea spp. We used PStrain to analyze and visualize strain transmission in each mother-infant pair. Excluding missing data, we included 32 mother-infant pairs for analysis of strain transmission. Most CS deliveries (65.6%, 21/32) did not demonstrate transmission of strains from mother to infant. To further explore the mother-infant strain transmission, we analyzed metagenomics data from Finnish mother-infant pairs. A total of 32 mother-infant pairs were included in the analysis, including 28 vaginal delivery (VD) infants and four CS infants. Strain transmission was observed in 30 infants, including 28 VD infants and two CS infants. All VD infants received transmitted stains from their mothers. Finally, a total of 193 strain transmission events were observed, comprising 131 strains and 45 species. Discussion: Taken together, our data suggested that delivery mode was an important factor influencing the mother-infant strain transmission.
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BACKGROUND: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD), prompting the exploration of antioxidants as a potential therapeutic avenue for mitigating disease progression. This study aims to investigate the beneficial impact of Tempol on the progression of CKD in a rat model utilizing oxidized albumin as a biomarker. METHODS: After four weeks of treatment, metabolic parameters, including body weight, left ventricle residual weight, kidney weight, urine volume, and water and food intake, were measured. Systolic blood pressure, urinary protein, oxidized albumin level, serum creatinine (Scr), blood urea nitrogen (BUN), 8-OHdG, TGF-ß1, and micro-albumin were also assessed. Renal fibrosis was evaluated through histological and biochemical assays. P65-NF-κB was quantified using an immunofluorescence test, while Smad3, P65-NF-κB, and Collagen I were measured using western blot. TNF-α, IL-6, MCP-1, TGF-ß1, Smad3, and P65-NF-κB were analyzed by RT-qPCR. RESULTS: Rats in the high-salt diet group exhibited impaired renal function, characterized by elevated levels of blood urea nitrogen, serum creatinine, 8-OHdG, urine albumin, and tubulointerstitial damage, along with reduced body weight. However, these effects were significantly ameliorated by Tempol administration. In the high-salt diet group, blood pressure, urinary protein, and oxidized albumin levels were notably higher compared to the normal diet group, but Tempol administration in the treatment group reversed these effects. Rats in the high-salt diet group also displayed increased levels of proinflammatory factors (TNF-α, IL-6, MCP1) and profibrotic factors (NF-κB activation, Collagen I), elevated expression of NADPH oxidation-related subunits (P65), and activation of the TGF-ß1/Smad3 signaling pathway. Tempol treatment inhibited NF-κB-mediated inflammation and TGF-ß1/Smad3-induced renal fibrosis signaling pathway activation. CONCLUSION: These findings suggest that Tempol may hold therapeutic potential for preventing and treating rats undergoing 5/6 nephrectomy. Further research is warranted to elucidate the mechanisms underlying Tempol's protective effects and its potential clinical applications. Besides, there is a discernible positive relationship between oxidized albumin and other biomarkers, such as 8-OHG, urinary protein levels, mALB, Scr, BUN, and TGF-ß1 in a High-salt diet combined with 5/6 nephrectomy rat model. These findings suggest the potential utility of oxidized albumin as a sensitive indicator for oxidative stress assessment.
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Óxidos N-Cíclicos , Insuficiência Renal Crônica , Marcadores de Spin , Fator de Crescimento Transformador beta1 , Animais , Ratos , Albuminas/química , Albuminas/metabolismo , Peso Corporal , Colágeno/metabolismo , Creatinina , Dieta , Fibrose , Inflamação/tratamento farmacológico , Interleucina-6/metabolismo , Nefrectomia , NF-kappa B/metabolismo , Estresse Oxidativo , Insuficiência Renal Crônica/tratamento farmacológico , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Biomarcadores , Sódio na Dieta/efeitos adversosRESUMO
The emergence of drug-resistant bacteria has significantly diminished the efficacy of existing antibiotics in the treatment of bacterial infections. Consequently, the need for finding a strategy capable of effectively combating bacterial infections has become increasingly urgent. Photodynamic therapy (PDT) is considered one of the most promising emerging antibacterial strategies due to its non-invasiveness, low adverse effect, and the fact that it does not lead to the development of drug resistance. However, bacteria at the infection sites often exist in the form of biofilm instead of the planktonic form, resulting in a hypoxic microenvironment. This phenomenon compromises the treatment outcome of oxygen-dependent type-II PDT. Compared to type-II PDT, type-I PDT is not constrained by the oxygen concentration in the infected tissues. Therefore, in the treatment of bacterial infections, type-I PDT exhibits significant advantages over type-II PDT. In this review, we first introduce the fundamental principles of type-I PDT in details, including its physicochemical properties and how it generates reactive oxygen species (ROS). Next, we explore several specific antimicrobial mechanisms utilized by type-I PDT and summarize the recent applications of type-I PDT in antimicrobial treatment. Finally, the limitations and future development directions of type-I photosensitizers are discussed. STATEMENT OF SIGNIFICANCE: The misuse and overuse of antibiotics have accelerated the development of bacterial resistance. To achieve the effective eradication of resistant bacteria, pathfinders have devised various treatment strategies. Among these strategies, type I photodynamic therapy has garnered considerable attention owing to its non-oxygen dependence. The utilization of non-oxygen-dependent photodynamic therapy not only enables the effective elimination of drug-resistant bacteria but also facilitates the successful eradication of hypoxic biofilms, which exhibits promising prospects for treating biofilm-associated infections. Based on the current research status, we anticipate that the novel type I photodynamic therapy agent can surmount the biofilm barrier, enabling efficient treatment of hypoxic biofilm infections.
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Infecções Bacterianas , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Infecções Bacterianas/tratamento farmacológico , OxigênioRESUMO
Helicobacter pylori (H. pylori) infection may alter the host's resistance to tsutsugamushi disease pathogens through the Th1 immune response, leading to potential synergistic pathogenic effects. A total of 117 scrub typhus cases at Beihai People's Hospital and affiliated hospitals of Youjiang University for Nationalities and Medical Sciences were studied from January to December 2022, alongside 130 healthy individuals forming the control group. All participants underwent serum H. pylori antibody testing. The prevalence of H. pylori infection was significantly higher among scrub typhus patients (89.7%) compared to healthy individuals (54.6%) (p < 0.05). Moreover, type I H. pylori infection was notably more prevalent in scrub typhus cases (67.5%) compared to healthy individuals (30%) (p < 0.05). Multifactorial analysis demonstrated type I H. pylori infection as an independent risk factor for scrub typhus (adjusted odds ratio: 2.407, 95% confidence interval: 1.249-4.64, p = 0.009). Among scrub typhus patients with multiple organ damage, the prevalence of type I H. pylori infection was significantly higher (50.6%) than type II H. pylori infection (15.4%) (χ2 = 4.735, p = 0.030). These results highlight a higher incidence of H. pylori infection in scrub typhus patients compared to the healthy population. Additionally, type I H. pylori strain emerged as an independent risk factor for scrub typhus development. Moreover, individuals infected with type I H. pylori are more susceptible to multiple organ damage. These findings suggest a potential role of H. pylori carrying the CagA gene in promoting and exacerbating scrub typhus.
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Dressings seamlessly attached to the open wound bed are necessary for fully unleashing the dressing healing ability, as leaving the voids beneath the dressing poses infection hazards. The present study prepared an instant mucus dressing (IMD) of polyethylene oxide (PEO) reinforced by chitosan (CS) nanofiber scaffold, which formed by immersing PEO/CS nanofiber mat in water. The PEO/CS nanofiber mat were fabricated by the solution blow spinning (SBS) method using PEO and CS mixed solutions. Attenuated total reflection Fourier transform infrared spectroscopy (FTIR-ATR), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and differential scan calorimetry (DSC) analyses indicate that PEO macromolecules formed the most of nanofiber shell due to their lower surface tension while CS macromolecules stayed mainly inside the fiber as the core. When such a PEO/CS nanofiber mat was immersed in water, PEO swelled to form mucus dressing reinforced by CS inside the nanofiber, which was fluidic and able to fully fill the voids on the wound. In vivo rat experiment verified that the dressing significantly accelerated the open wound healing through seamlessly attaching of mucus to the open wound and providing moist environment. The dressings exhibit good platelets and whole blood cells adhesion properties, excellent hemostasis function and no cytotoxicity. This instant mucus dressing provided a new perspective for manufacturing high performance open wound dressings.
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Quitosana , Nanofibras , Ratos , Animais , Quitosana/química , Polietilenoglicóis/química , Nanofibras/química , Cicatrização , Bandagens , Água , Antibacterianos/químicaRESUMO
Human endogenous retroviruses (HERVs) are the remnants of ancient retroviral infections integrated into the human genome. Although most HERVs are silenced or rendered inactive by various regulatory mechanisms, they retain the potential to influence the nearby genes. We analyzed the regulatory map of 91 HERV-Ks on neighboring genes in human breast cancer and investigated the impact of HERV-Ks on the tumor microenvironment (TME) and prognosis of breast cancer. Nine RNA-seq datasets were obtained from GEO and NCBI SRA. Differentially expressed genes and HERV-Ks were analyzed using DESeq2. Validation of high-risk prognostic candidate genes using TCGA data. These included Overall survival (multivariate Cox regression model), immune infiltration analysis (TIMER), tumor mutation burden (maftools), and drug sensitivity analysis (GSCA). A total of 88 candidate genes related to breast cancer prognosis were screened, of which CD48, SLAMF7, SLAMF1, IGLL1, IGHA1, and LRRC8A were key genes. Functionally, these six key genes were significantly enriched in some immune function-related pathways, which may be associated with poor prognosis for breast cancer (p = 0.00016), and the expression levels of these genes were significantly correlated with the sensitivity of breast cancer treatment-related drugs. Mechanistically, they may influence breast cancer development by modulating the infiltration of various immune cells into the TME. We further experimentally validated these genes to confirm the results obtained from bioinformatics analysis. This study represents the first report on the regulatory potential of HERV-K in the neighboring breast cancer genome. We identified three key HERV-Ks and five neighboring genes that hold promise as novel targets for future interventions and treatments for breast cancer.
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Neoplasias da Mama , Retrovirus Endógenos , Humanos , Feminino , Neoplasias da Mama/genética , Retrovirus Endógenos/genética , Genoma Humano , Expressão Gênica , Prognóstico , Microambiente Tumoral/genética , Proteínas de Membrana/genéticaRESUMO
Dexamethasone is commonly used as an adjuvant to prolong peripheral nerve block analgesia, but the optimal timing is unclear. This randomized equivalence trial tested whether preoperative versus postoperative intravenous dexamethasone have equivalent analgesic effects when combined with interscalene brachial plexus block for shoulder surgery. 168 patients were randomized to receive 5 mg dexamethasone either preoperatively or postoperatively. The primary outcome was duration of analgesia, analyzed for equivalence with a 2-h margin. The mean durations were equivalent between groups (11.5 h preoperative versus 10.7 h postoperative). The confidence intervals fell within the equivalence margin. There were no other clinically significant differences in secondary outcomes like time to first analgesia, motor recovery, opioid consumption, blood glucose, or complications. In conclusion, as an adjuvant for nerve block, preoperative and postoperative intravenous dexamethasone provide equivalent analgesic duration, allowing for flexibility in clinical use. This addresses previous uncertainty about timing while demonstrating equivalent efficacy.
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Wound dressings are crucial for wound healing. Ideal wound dressings should possess many functions such as wettability, antibacterial activity and anti-adherent property to promote wound healing. In the present study solution blown spinning (SBS) technology was applied to prepare chitosan/polyethylene oxide (CS/PEO) nanofiber dressings in high efficiency. The obtained nanofiber dressings were treated with anhydrous ethanol to improve the fiber structure and enhance the functionality of the fiber dressings. The results show that the treated nanofibers had higher crystallinities and higher CS contents. The CS/PEO nanofiber dressings fabricated by using no additives and crosslinking had excellent wettability, water stability and antibacterial activity against Escherichia coli and Staphylococcus aureus reached to over 99.99 %. In addition, the CS/PEO nanofiber dressings exhibited high breathability, antioxidant activity and anti-adhesion function. The in vivo animal experiment confirmed that the nanofiber dressings enhanced cell proliferation and significantly accelerated the wound healing within 10 days. The developed CS/PEO nanofiber dressings have great potential in the clinical field of wound healing.
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Quitosana , Nanofibras , Animais , Nanofibras/química , Quitosana/farmacologia , Quitosana/química , Antibacterianos/farmacologia , Antibacterianos/química , Cicatrização , Bandagens , Escherichia coli , Polietilenoglicóis/químicaRESUMO
Analyzing the vast amount of omics data generated comprehensively by high-throughput sequencing technology is of utmost importance for scientists. In this context, we propose HiOmics, a cloud-based platform equipped with nearly 300 plugins designed for the comprehensive analysis and visualization of omics data. HiOmics utilizes the Element Plus framework to craft a user-friendly interface and harnesses Docker container technology to ensure the reliability and reproducibility of data analysis results. Furthermore, HiOmics employs the Workflow Description Language and Cromwell engine to construct workflows, ensuring the portability of data analysis and simplifying the examination of intricate data. Additionally, HiOmics has developed DataCheck, a tool based on Golang, which verifies and converts data formats. Finally, by leveraging the object storage technology and batch computing capabilities of public cloud platforms, HiOmics enables the storage and processing of large-scale data while maintaining resource independence among users.
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Andrographolide (Andro), a labdane diterpene, possesses anti-inflammatory properties and has been used to treat numerous inflammatory diseases. Novel findings revealed that Andro might be vital in regulating pain. However, the contribution of Andro to chronic inflammatory pain has yet to be determined, and its underlying mechanism of action remains unknown. In this study, we observed that Andro attenuated mechanical allodynia in inflammatory pain mice induced by injecting complete Freund's adjuvant (CFA) into the right hind paws. This analgesic effect of Andro is mainly dependent on its inhibition of microglial overactivation and the release of proinflammatory cytokines (TNF and IL-1ß) in lumbar spinal cords of inflammatory pain model mice. More importantly, our data in vivo and in vitro revealed a negative role for Andro in regulating the TLR4/NF-κB signaling pathway, which might contribute to the inhibition of spinal microglial activation and proinflammatory cytokines production, and the improvement of paw withdrawal thresholds in a mouse model of chronic inflammatory pain evoked by CFA. We further found the potential interaction of Andro with TLR4/myeloid differentiation factor 2 heterodimer using molecular modeling, implying that TLR4 might be a potential target for Andro to exert an analgesic effect. Taken together, our findings demonstrated that the modulation of spinal microglial activation by Andro might be substantially conducive to managing chronic pain triggered by neuroinflammation.
Assuntos
Diterpenos , Hiperalgesia , Camundongos , Animais , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Microglia/metabolismo , Inflamação/metabolismo , Receptor 4 Toll-Like/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Diterpenos/metabolismo , Citocinas/metabolismo , Medula Espinal , Analgésicos/farmacologia , Analgésicos/uso terapêuticoRESUMO
KEY MESSAGE: A novel major adult-plant stripe rust resistance QTL derived from cultivated emmer wheat was mapped to a 123.6-kb region on wheat chromosome 2BL. Stripe rust, caused by the fungal pathogen Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating diseases of wheat. Identification of new sources of resistance and their utilization in breeding programs is the effectively control strategy. The objective of this study was to identify and genetically characterize the stripe rust resistance derived from the cultivated emmer accession AS286. A recombinant inbred line population, developed from a cross between the susceptible durum wheat line langdon and AS286, was genotyped using the Wheat55K single nucleotide polymorphism array and evaluated in field conditions with a mixture of the prevalent Chinese Pst races (CYR32, CYR33, CYR34, Zhong4, and HY46) and in growth chamber with race CYR34. Three QTLs conferring resistance were mapped on chromosomes 1BS, 2BL, and 5BL, respectively. The QYrAS286-1BS and QYrAS286-2BL were stable with major effects, explaining 12.91% to 18.82% and 11.31% to 31.43% of phenotypic variation, respectively. QYrAS286-5BL was only detected based on growth chamber seedling data. RILs harboring both QYrAS286-1BS and QYrAS286-2BL showed high levels of stripe rust resistance equal to the parent AS286. The QYrAS286-2BL was only detected at the adult-plant stage, which is different from previously named Yr genes and inherited as a single gene. It was further mapped to a 123.6-kb region using KASP markers derived from SNPs identified by bulked segregant RNA sequencing (BSR-Seq). The identified loci enrich our stripe rust resistance gene pool, and the flanking markers developed here could be useful in marker-assisted selection for incorporating QYrAS286-2BL into wheat cultivars.