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BACKGROUND AND OBJECTIVE: Cyclin-dependent protein kinases (CDKs) have been suggested as prospective therapeutic targets because they control processes vital to the survival and growth of cancer cells. However, research on the varied CDK expression profiles and prognostic factors in osteosarcoma is still lacking. METHODS: The osteosarcoma microRNA (GSE65071) and gene expression profiles were retrieved from the Gene Expression Omnibus (GEO) database (GSE42352). A substantial variation in prognosis was discovered in CDKs using the TARGET database. Cytoscape was used to construct the miRNAs-CDKs network, and functional and pathway enrichment analyses were completed. It was looked at how immune checkpoint genes, m6A-related genes, and CDKs interact. RESULTS: In patients with osteosarcoma compared to normal samples, CDK1-5, CDK18, CDK16, and CDK17 gene expression levels were considerably greater, whereas CDK7-9, CDK11B, CDK16, and CDK20 gene expression levels were significantly lower. Patients with osteosarcoma who had low CDK3 and 18 gene levels or high CDK6, 9 gene levels were predicted to have a favorable prognosis and a long-life expectancy. Immune checkpoint genes, m6A-related gene expression, and CDKs expression all showed some connection. Finally, a network of crucial CDKs and miRNAs was constructed. CONCLUSION: According to our research, CDK3, 6, 9, and 18 have been identified as possible therapeutic targets for osteosarcoma, and CDKs may have a role in controlling m6A mutations in tumor cells as well as immune checkpoint regulation.
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Renal ischemia-reperfusion injury (IRI) is a major cause of delayed graft function (DGF) after transplantation. Currently, a targeted therapy for this important clinical disorder is still lacking. MicroRNA (miRNA) has important roles in the pathogenesis of IRI and may therapeutic approaches to mitigate renal IRI. METHODS: Small RNA sequencing was performed to profile microRNA expression in mouse kidneys after transplantation. Lentivirus incorporating a miR-199a-5p modulator was injected into mouse kidney in situ before unilateral IRI and syngenetic transplantation, to determine the effect of miR-199a-5p in vivo. miR-199a-5p mimic or inhibitor was transfected cultured tubular cells before renal tubular ATP depletion recovery treatment to the examine the role of miR-199a-5p in vitro. RESULTS: Sequencing showed upregulation of miR-199a-5p in post-transplantation mouse kidney following renal IRI was localized to renal tubular epithelial cells. Lentivirus incorporating a miR-199a-5p mimic aggravated renal IRI and opposing effects were obtained with a miR-199a-5p inhibitor. Treatment with the miR-199a-5p inhibitor ameliorated graft function loss, tubular injury and immune response after cold storage transplantation. In vitro experiments demonstrated aggravation of cell death caused by ATP depletion and repletion when the miR-199a-5p mimic was present while the miR-199a-5p inhibitor reduced cell death. miR-199a-5p was shown to target a-kinase anchoring protein 1(AKAP1) by double luciferase assay and miR-199a-5p activation reduced dynamin related protein 1 (Drp1)-s637 phosphorylation and mitochondrial length. Overexpression of AKAP1 preserved Drp1-s637 phosphorylation and reduced mitochondrial fission. CONCLUSION: MiR-199a-5p activation reduced AKAP1 expression, promoted Drp1-s637 dephosphorylation, aggravated the disruption of mitochondrial dynamics and contributed to ischemic kidney injury.
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Adjusting the catalytic activity of nanozymes for enhanced oncotherapy has attracted significant interest. However, it remains challenging to engineer regulatory tactics with a minimal impact on normal tissues. By exploiting the advantages of energy storage, photostimulated, and long afterglow luminescence of persistent nanoparticles (PLNPs), a persistent luminescence-based nanoreservoir was produced to improve its catalytic activity for benign oncotherapy. In the study, PLNPs in a nanoreservoir with the ability to store photons served as a self-illuminant to promote its peroxidase-like activity and therapeutic efficacy by persistently motivating its photothermal effect before and after external irradiation ceased. The photostimulated and persistent luminescence of PLNPs and spatiotemporal controllability of exogenous light jointly alleviated adverse effects induced by prolonged irradiation and elevated the catalytic capability of the nanoreservoir. Ultimately, the system fulfilled benign photothermal-intensive nanozymatic therapy. This work provides new insights into boosting the catalytic activity of nanozymes for secure disease treatment.
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Luminescência , Nanopartículas , Nanopartículas/química , Nanopartículas/uso terapêutico , Humanos , Animais , Camundongos , Terapia Fototérmica , Catálise , Fototerapia , Neoplasias/terapia , Linhagem Celular TumoralRESUMO
BACKGROUND: In total hip arthroplasty (THA), the positioning of components holds critical importance for factors such as joint stability, polyethylene liner wear, and range of motion. This meta-analysis aimed to compare the effects of intraoperative fluoroscopy (IF) versus no use of IF on component positioning and the restoration of patient anatomy during THA. METHODS: We conducted our systematic review following the recommendations outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The literature search was performed from the inception of medical databases up to August 2023. PubMed, Embase, Web of Science, Cochrane Controlled Trials Register, Cochrane Library, Highwire, Wanfang, China National Knowledge Infrastructure (CNKI), China Biology Medicine Disc (CBM), and China Science and Technology Journal (CSTD) databases were systematically searched to identify relevant studies comparing IF versus no IF during primary THA. RESULTS: Thirteen studies involving 2195 patients (2207 hips) were incorporated in the Analysis. No statistically significant differences were observed between the groups in terms of acetabular cup inclination angle (ACIA, Pâ =â .9), ACIA within the safe zone rate (Pâ =â .87), acetabular cup anteversion angle (ACAA, Pâ =â .42), ACAA within the safe zone rate (Pâ =â .35), combined safe zone rate (Pâ =â .30), limb length difference (LLD, Pâ =â .13), dislocation rate (Pâ =â .76), and infection rate (Pâ =â .97). In comparison to the no fluoroscopy group, the IF group exhibited prolonged operation time (Pâ <â .00001) and reduced femoral component offset difference (FCOD, Pâ =â .03). CONCLUSION: IF did not demonstrate improvements in acetabular cup placement, limb length difference, or dislocation occurrence. Nonetheless, IF showed a significant enhancement in restoring femoral offset. It is noteworthy that surgeons operating in facilities with lower patient volumes may observe more pronounced benefits from IF.
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Acetábulo , Artroplastia de Quadril , Humanos , Artroplastia de Quadril/métodos , Fluoroscopia/métodos , Acetábulo/cirurgia , Acetábulo/diagnóstico por imagem , Prótese de QuadrilRESUMO
BACKGROUND: Arterial thrombosis, a condition in which thrombi form in arteries, can lead to various acute cardiovascular diseases and impact the quality of life and survival of patients. Berberine (BBR), a quaternary ammonium alkaloid, has been shown to treat these diseases. However, further exploration is needed to understand underlying mechanisms of BBR. METHODS AND RESULTS: Rats were administered BBR via intramuscular injection. Then, an FeCl3-coated filter paper was applied to a carotid artery to induce thrombosis. The size of the thrombus and the blood flow velocity were evaluated by carotid ultrasound. The shape of the thrombus was observed using staining and microscopy. The expression levels of mRNA and proteins were verified. Additionally, mass spectrometry and single-cell RNA sequencing analysis were conducted. The administration of BBR resulted in a significant reduction in the thrombus area and an extension of the thrombus-clogging time. Furthermore, BBR administration effectively reversed the decreasing tissue-plasminogen activator (t-PA) expression and alterations in fibrinolysis system of model group. Additionally, the expression of PKM2 was suppressed following BBR administration, and the overexpression of PKM2 inhibited t-PA expression. CONCLUSIONS: BBR ameliorates thrombosis by modulating expression of PKM2, subsequently impacting the expression of t-PA within fibrinolytic system. These preliminary findings suggest that BBR could be a potential preventive and therapeutic strategy for arterial thromboembolic diseases.
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Computer haptics (CH) is about integration of tactile sensation and rendering in Metaverse. However, unlike computer vision (CV) where both hardware infrastructure and software programs are well developed, a generic tactile data capturing device that serves the same role as what a camera does for CV, is missing. Bioinspired by electrophysiological processes in human tactile somatosensory nervous system, here we propose a tactile scanner along with a neuromorphically-engineered system, in which a closed-loop tactile acquisition and rendering (re-creation) are preliminarily achieved. Based on the architecture of afferent nerves and intelligent functions of mechano-gating and leaky integrate-and-fire models, such a tactile scanner is designed and developed by using piezoelectric transducers as axon neurons and thin film transistor (TFT)-based neuromorphic circuits to mimic synaptic behaviours and neural functions. As an example, the neuron-like tactile information of surface textures is captured and further used to render the texture friction of a virtual surface for "recreating" a "true" feeling of touch.
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Tato , Humanos , Tato/fisiologia , Percepção do Tato/fisiologia , Neurônios/fisiologia , Axônios/fisiologiaRESUMO
Several studies reported that the widespread use of perfluoroalkyl and polyfluoroalkyl substances (PFASs) causes increased environmental pollution, subsequently impacting aquatic organisms. Perfluoroalkyl substances such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) reportedly cause cardiotoxicity, neurotoxicity, and developmental toxicity in different organisms. However, whether perfluorodecanoic acid (PFDA), a widely used perfluoroalkyl substance, induces animal embryos developmental toxicity remain unknown. Here, we explored the immunotoxicity and associated mechanisms of PFDA in zebrafish embryos via RNA sequencing, morphological assessment and behavioral alteration detection following exposure to 0.5, 1 and 2 mg/L of PFDA. Interestingly, We found that with the increase of PFDA to drug concentration, including neutrophils and macrophages, significantly increased the number of inherent cells, immune related genes expression. Furthermore, oxidative stress increased in the PFDA-treated embryos in a dose-dependent manner and inhibition of oxidative stress levels effectively rescued the number of neutrophils. Changes in embryonic behavior were observed after exposure to PFDA. Overall, our results suggest that PFDA may induce innate immune response by accumulation of oxidative stress in zebrafish at early developmental stages, and concern is needed about its environmental exposure risks for animals embryos development. ENVIRONMENTAL IMPLICATION: Perfluorinated and polyfluorinated alkyl substances (PFASs) are a class of synthetic organic compounds containing fluorine widely used as lubricants, surfactants, insecticides, etc. The PFDA, a typical perfluorinated compound, is often used as a wetting agent and flame retardant in industries. Several studies showed that PFASs can cause serious environmental pollution, leading to developmental toxicity to various animals, including reproductive toxicity, liver toxicity, heart toxicity, neurotoxicity, and immunotoxicity. However, there are still limited studies on the effects and mechanisms of PFDA on aquatic organisms. Therefore, there is a need to evaluate the ecological risks of PFDA in animals.
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Cancer antigen 125 (CA125) is the gold standard biomarker for clinical diagnosis of ovarian cancer, with a threshold value of 35 U/mL in serum. In this paper, a disposable ultrasensitive immunosensor based on Ti3C2Tx-MXene/amino-functionalized carbon nanotube (NH2-CNT) modified screen-printed carbon electrode (SPCE) was constructed for the detection of the ovarian cancer antigen CA125. By optimizing the mass ratio of Ti3C2Tx to NH2-CNT, Ti3C2Tx/NH2-CNT composite with excellent electrochemical properties was prepared, which is beneficial for amplifying the initial electrochemical signal. The positively charged NH2-CNT effectively alleviated the stacking problem of Ti3C2Tx, and its amino group also facilitated the covalent immobilization of the capture antibody. Meanwhile, chitosan (CS) with excellent film-forming ability was also used to successfully enhance the adsorption of electrode material, thus improving the stability of the sensor. In addition, CS could further enhance the current signal. The prepared immunosensor exhibited excellent performance in CA125 detection with a wide linear range from 1 mU/mL to 500 U/mL, and good selectivity, reproducibility and lomg-term stability. Furthermore, the immunosensor showed satisfactory results for the detection of CA125 in clinical serum samples, which is promising for the clinical screening, early diagnosis and prognostic examination of ovarian cancer.
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Background: The effects of the drug-coated balloon (DCB)-only strategy in the treatment of chronic total occlusion (CTO) coronary lesions remain controversial. Patients who underwent an in-stent restenosis (ISR) CTO percutaneous coronary intervention (PCI) had a significantly poorer prognosis than those who underwent a de novo CTO PCI. This retrospective analysis evaluated the efficacy and safety of the DCB-only strategy in the treatment of CTO lesions, and the factors associated with adverse events in the patients. Methods: Patients with CTO lesions who were treated with the DCB-only strategy from 1 January 2016 to 1 May 2021 were retrospectively enrolled in this study. The patients were stratified into the ISR and de novo (primary) groups. All the patients were re-admitted to the hospital and underwent clinical and/or angiographic follow-up. Results: Of the 68 patients with CTO lesions, 38 (55.9%) were categorized as having ISR, and 30 (44.1%) were categorized as having de novo lesions. The outcomes measured included target lesion revascularization (TLR), lumen gain after intervention, and late lumen loss (LLL). After an average follow-up period of 16 months, a total of 15 patients experienced target lesion failure (13 in the ISR group and 2 in the de novo group). The rate of major adverse cardiac events (MACEs) was significantly lower in the de novo group than the ISR group (10% vs. 39%, P=0.004). There was a significant difference in LLL between the two groups, with the de novo group showing a decrease (-0.04±0.83 mm) and the ISR group showing an increase (0.97±1.45 mm) (P=0.03). The univariable Cox proportional hazard analyses revealed that the incidence of TLR was independently associated with the stenosis type (either ISR or de novo lesions) [odds ratio (OR): 7.28; 95% confidence interval (CI): 1.494-35.464; P=0.01]. Male gender (OR: 3.726; 95% CI: 1.014-12.818; P=0.03) and body mass index (BMI) (OR: 1.246; 95% CI: 1.022-1.518, P=0.03) were also associated with the incidence of TLR. However, after adjusting for the variables of age, gender, and BMI, no significant association was found between MACE occurrence and ISR (OR: 4.156, 95% CI: 0.734-23.522; P=0.11). Conclusions: Treatment using the DCB-only strategy was found to be beneficial for patients suffering from CTO coronary lesions, especially those presenting with de novo lesions.
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Background: Prominent epicanthus could not only diminish the eyes' aesthetics but may be deceptive for its typical appearance of pseudo-esotropia. This study aims to apply a deep learning model to characterize the periocular morphology for preliminary identification. Methods: This prospective study consecutively included 300 subjects visiting the ophthalmology department in a tertiary referral hospital. Children aged 7-18 years with simple epicanthus or concomitant esotropia and healthy volunteers who were age- and gender-matched were eligible for inclusion. Multiple metrics were extracted automatically and manually from facial images to characterize the periocular morphology and binocular symmetry. The dice coefficient (Dice), intraclass correlation coefficient (ICC), and Bland-Altman biases were calculated to evaluate their consistency. The receiver operating characteristic (ROC) curve determined the cut-off values of symmetry indexes (SIs) for distinguishing concomitant esotropia subjects from epicanthus ones. Results: The Dice for eyelid and cornea segmentation were 0.949 and 0.944, respectively. The ICCs of the two measurements ranged from 0.898 to 0.983. Biases ranged from 0.16 to 0.74 mm. The periocular morphology of epicanthus eyes was significantly different from the normal ones, including palpebral fissure width (21.41±1.53 vs. 24.45±1.82 mm; P<0.01), and palpebral fissure height (8.91±1.37 vs. 9.60±1.25 mm; P<0.01). The ROC analysis yielded an area under the curve of 0.971 [95% confidence interval (CI): 0.950-0.991] with SI for distinguishing esotropia subjects. Its optimal cut-off value was 1.296 with 0.920 sensitivity and 0.910 specificity. Conclusions: Our study established a standard deep learning system for characterizing the periocular morphology of epicanthus and esotropia eyes with great accuracy. This objective method could be generalized to other periocular morphological assessments for clinical care.
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Human activities have significantly altered the biogeochemical cycles of carbon, nitrogen, and sulfur in aquatic ecosystems, leading to ecological problems.This study utilized 16S rRNA gene high-throughput sequencing and excitation-emission matrix parallel factor analysis (EEM-PARAFAC) to evaluate the bacterial community composition and dissolved organic matter structure in the upstream (less impacted) and downstream (severely impacted) sections of the river, with a focus on the interactions between bacterial diversity and dissolved organic matter (DOM) characteristics.Results indicated significant spatial diversity in bacterial communities, with a higher α-diversity upstream compared to the more polluted downstream sections. Environmental parameters, particularly total phosphorus (TP) and dissolved oxygen (DO), were found to significantly influence the distribution and composition of bacterial phyla through redundancy analysis. The pattern of bacterial community assembly has shifted from predominantly deterministic to predominantly stochastic as a result of human activities. The analysis of DOM through EEM-PARAFAC identified three main fluorescent components, reflecting varied sources and interactions with bacterial communities. Upstream, microbial activities predominantly contributed to autochthonous DOM, while downstream, increased inputs of allochthonous DOM from human activities were evident. Furthermore, the study revealed that through the introduction of various organic pollutants and nutrient loads that shift microbial metabolic functions towards increased degradation and transformation of complex organic compounds downstream. Structural equation modeling (SEM) revealed that upstream human activities primarily affected bacterial communities indirectly by altering DOM properties. In contrast, downstream activities had both direct and indirect effects due to higher pollutant loads and more complex environmental conditions. These interactions underline the profound effect of anthropogenic factors on riverine ecosystems and emphasize the importance of managing human impacts to preserve microbial biodiversity and water quality.
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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that commonly affects children and adolescents with a poor prognosis. The terminal unfolded protein response (UPR) is an emerging anti-cancer approach, although its role in pediatric T-ALL remains unclear. In our pediatric T-ALL cohort from different centers, a lower QRICH1 expression was found associated with a worse prognosis of pediatric T-ALL. Overexpression of QRICH1 significantly inhibited cell proliferation and stimulated apoptosis of T-ALL both in vitro and in vivo. Upregulation of QRICH1 significantly downregulated 78 KDa glucose-regulated protein (GRP78) and upregulated CHOP, thus activating the terminal UPR. Co-overexpression of GRP78 in T-ALL cells overexpressing QRICH1 partially reverted the inhibited proliferation and stimulated apoptosis. QRICH1 bound to the residues Asp212 and Glu155 of the nucleotide-binding domain (NBD) of GRP78, thereby inhibiting its ATP hydrolysis activity. In addition, QRICH1 was associated with endoplasmic reticulum (ER) stress in T-ALL, and overexpression of QRICH1 reversed drug resistance. Overall, low QRICH1 expression is an independent risk factor for a poor prognosis of pediatric T-ALL. By inhibiting GRP78, QRICH1 suppresses pediatric T-ALL.
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Apoptose , Proliferação de Células , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Chaperona BiP do Retículo Endoplasmático/metabolismo , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Criança , Proliferação de Células/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Masculino , Linhagem Celular Tumoral , Feminino , Camundongos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Adolescente , Pré-Escolar , PrognósticoRESUMO
OBJECTIVE: The objective of this article was to investigate how the metabolites produced by the intestinal flora regulate the transformation of ILC2s and intestinal immunity via the receptor Ffar2, which is sensitive to metabolites. MATERIALS AND METHODS: Forty male C57BL/6 mice with wild-type characteristics (6-7 weeks in age) and 20 FFAR2-/- mice were acquired from The Jackson Laboratory. The mice were kept in a controlled environment without any disease-causing agents, with the help of air conditioning and a 12-hour cycle of light and darkness. Throughout the experiment, every mouse was provided with unrestricted availability of both food and water. All protocols were performed following the Regulations of Animal Welfare and the recommendations for Animal Testing. According to the research protocol, the mice were categorized into three groups, each consisting of 20 mice. FFAR2-/- mice in the FFAR2-/- group were reared in conventional environments. Male C57BL/6 mice with wild-type characteristics were reared in conventional conditions in the wild-type group. In the group where wild-type mice were inhibited with Ffar2, a total of 20 mice with the wild-type phenotype were chosen to receive intraperitoneal injection of an FFAR2 antagonist at a dosage of 5 mg/kg per day for a continuous period of 3 weeks. qRT-PCR was used to detect the expression of FFAR2 mRNA in the mucosal tissue of the mouse colon. High-throughput sequencing was used to conduct an examination of metabolites in the intestinal tract of mice. Flow cytometry was used to test the quantity of ILC2s. ELISA was used to measure the levels of IL-5 and IL-13 in cellular mouse intestinal mucosal tissues. Flow cytometry was used to detect the quantity of CD4+ and CD8+ T cells. CCL20 and CCL25 expression was analyzed by Western blotting. The level of FFAR2 mRNA expression was higher in the wild-type group than the FFAR2-/- group (P < 0.05), while it was lower in the wild-type + Ffar2 inhibition group than the wild-type group (P < 0.05). No variations were observed in the composition of metabolites and levels of major SCFAs in the gut microbiota of mice across all groups (P > 0.05). The quantity of CRTH2+ and ST2+ cells in the wild-type category exceeded that in the FFAR2-/- category (P < 0.05), whereas the quantity of CRTH2+ and ST2+ cells in the wild-type + Ffar2 inhibition category was lower than that in the wild-type category (P < 0.05). The concentrations of IL-5 and IL-13 were higher in the wild-type group compared with the FFAR2-/- group (P < 0.05), while the wild-type + Ffar2 inhibition group exhibited lower levels of IL-5 and IL-13 than the wild-type group (P < 0.05). The count of CD4+ T cells and CD8+ T cells in the wild-type group showed an increase in comparison to the FFAR2-/- group (P < 0.05), whereas the count of CD4+ T cells and CD8+ T cells in the wild-type + Ffar2 inhibition group exhibited a decrease in comparison to the wild-type group (P < 0.05). The levels of protein expression for CCL20 and CCL25 were higher in the wild-type group compared with the FFAR2-/- group (P < 0.05), whereas the wild-type + Ffar2 inhibition group exhibited lower protein expression of CCL20 and CCL25 than the wild-type group (P < 0.05). CONCLUSION: Ffar2 has a significant regulatory function in the conversion of ILC2s, consequently impacting the immune response in the intestines. Ffar2, a crucial receptor for metabolites produced by the intestinal flora, plays a vital function in controlling the conversion of ILC2s and the overall immune response in the intestines.
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BACKGROUND: Alleviating the sore throat caused by acute pharyngitis is a primary patient concern. However, antibiotics are not commonly recommended drugs, and abuse can lead to serious consequences such as drug resistance. Therefore, seeking alternative treatments is necessary. PURPOSE: To investigate the efficacy and safety of Kegan Liyan (KGLY) oral liquid for patients with acute pharyngitis. STUDY DESIGN: Randomized, double-blinded, placebo-controlled, multi-center study. METHODS: Participants from 17 hospitals were randomly assigned 1:1 to receive KGLY oral liquid or placebo for five days. Assessments occurred at baseline, day 3, and day 6. The primary outcome was the recovery rate. Secondary outcomes included sore throat and cough visual analogue scale (VAS), the area under the curve (AUC) of sore throat VAS, time to sore throat relief and recovery, proportion of participants with sore throat relief and recovery, traditional Chinese medicine (TCM) syndrome score, single TCM manifestation score and use of acetaminophen. RESULTS: Involving 239 participants (120 in KGLY and 119 in placebo group), the study found a significantly higher recovery rate on day 6 in the KGLY group (between-group difference, 27.20 % [15.00 % to 39.40 %], p < 0.001). On day 3 and 6, the KGLY group showed significantly larger reductions in sore throat (-3.02 vs -2.37, p = 0.001; -4.66 vs -3.64, p < 0.001) and cough VAS scores (-1.55 vs -1.05, p = 0.004; -2.28 vs -1.56, p < 0.001) from baseline. KGLY oral liquid lowered the AUC of sore throat VAS score (-2.33 [-4.10 to -0.56], p = 0.011), shortened time to sore throat recovery (hazard ratio, 0.42 [0.30 to 0.59], p < 0.001), increased sore throat recovery rate at day 6 (75.00 % vs 42.86 %, p < 0.001), decreased the TCM syndrome score (-2.03 [-2.69 to -1.37], p < 0.001), and improved individual TCM symptoms compared to placebo. No significant differences between the groups in acetaminophen usage. KGLY oral liquid was safe and tolerated. CONCLUSION: KGLY oral liquid may be a beneficial and safe alternative treatment for acute pharyngitis, which can alleviate symptoms such as sore throat, swollen throat, cough, and phlegm production.
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Medicamentos de Ervas Chinesas , Faringite , Humanos , Faringite/tratamento farmacológico , Método Duplo-Cego , Masculino , Feminino , Adulto , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Doença Aguda , Adulto Jovem , Administração Oral , Pessoa de Meia-Idade , Medicina Tradicional Chinesa/métodos , Resultado do Tratamento , Tosse/tratamento farmacológicoRESUMO
Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in clinical settings, posing significant treatment challenges. Here, we fabricated a cartilage extracellular matrix mimic hydrogel (GHC, consisting of Gelatin, Hyaluronic acid, and Chondroitin sulfate) to avoid the exacerbation of cartilage deterioration, which is often driven by the accumulation of reactive oxygen species (ROS) and a pro-inflammatory microenvironment. The GHC hydrogel exhibited multifunctional properties, including in situ formation, tissue adhesiveness, anti-ROS capabilities, and the promotion of chondrogenesis. The enhancement of tissue adhesion was achieved by chemically modifying hyaluronic acid and chondroitin sulfate with o-nitrobenzene, enabling a covalent connection to the cartilage surface upon light irradiation. In vitro characterization revealed that GHC hydrogel facilitated chondrocyte adhesion, migration, and differentiation into cartilage. Additionally, GHC hydrogels demonstrated the ability to scavenge ROS in vitro and inhibit the production of inflammatory factors by chondrocytes. In the animal model of superficial cartilage injury, the hydrogel effectively promoted cartilage ECM regeneration and facilitated the interface integration between the host tissue and the material. These findings suggest that the multifunctional GHC hydrogels hold considerable promise as a strategy for cartilage defect repair. STATEMENT OF SIGNIFICANCE: Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in the clinic. Previous cartilage tissue engineering materials are only suitable for full-thickness cartilage defects or osteochondral defects. Here, we developed a multifunctional GHC hydrogel composed of gelatin, hyaluronic acid, and chondroitin sulfate, which are natural cartilage extracellular matrix components. The drug-free and cell-free hydrogel not only avoids immune rejection and drug toxicity, but also shows good mechanical properties and biocompatibility. More importantly, the GHC hydrogel could adhere tightly to the superficial cartilage defects and promote cartilage regeneration while protecting against oxidation. This natural ingredients and multifunctional hydrogel is a potential material for repairing superficial cartilage defects.
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Condrócitos , Hidrogéis , Osteoartrite , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Hidrogéis/química , Hidrogéis/farmacologia , Osteoartrite/patologia , Osteoartrite/tratamento farmacológico , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Materiais Biomiméticos/farmacologia , Materiais Biomiméticos/química , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacologia , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Cartilagem Articular/patologia , Cartilagem Articular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Coelhos , Gelatina/química , Gelatina/farmacologiaRESUMO
BACKGROUND: The genus Hydrocotyle Tourn. ex L. is a key group for further study on the evolution of Apiales, comprising around 170 species globally. Previous studies mainly focused on separate sections and provided much information about this genus, but its infrageneric relationships are still confusing. In addition, the genetic basis of its adaptive evolution remains poorly understood. To investigate the phylogeny and evolution of the genus, we selected ten representative species covering two of three diversity distribution centers and exhibiting rich morphology diversity. Comparative plastome analysis was conducted to clarify the structural character of Hydrocotyle plastomes. Positive selection analyses were implemented to assess the evolution of the genus. Phylogenetic inferences with protein-coding sequences (CDS) of Hydrocotyle and 17 related species were also performed. RESULTS: Plastomes within Hydrocotyle were generally conservative in structure, gene order, and size. A total of 14 regions (rps16-trnK, trnQ-rps16, atpI-atpH, trnC-petN-psbM, ycf3-trnS, accD-psaI-ycf4, petA-psbJ, rps12-rpl20, rpl16 intron, rps3-rpl16 intron, rps9-rpl22, ndhF-rpl32, ndhA intron, and ycf1a) were recognized as hotspot regions within the genus, which suggested to be promising DNA barcodes for global phylogenetic analysis of Hydrocotyle. The ycf15 gene was suggested to be a protein-coding gene for Hydrocotyle species, and it could be used as a DNA barcode to identify Hydrocotyle. In phylogenetic analysis, three monophyletic clades (Clade I, II, III) were identified with evidence of rapid radiation speciation within Clade I. The selective pressure analysis detected that six CDS genes (ycf1b, matK, atpF, accD, rps14, and psbB) of Hydrocotyle species were under positive selection. Within the genus, the last four genes were conservative, suggesting a relation to the unique evolution of the genus in Apiales. Seven genes (atpE, matK, psbH, ycf1a, ycf1b, rpoA, and ycf2) were detected to be under some degree of positive selection in different taxa within the genus Hydrocotyle, indicating their role in the adaptive evolution of species. CONCLUSIONS: Our study offers new insights into the phylogeny and adaptive evolution of Hydrocotyle. The plastome sequences could significantly enhance phylogenetic resolution and provide genomic resources and potential DNA markers useful for future studies of the genus.
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Filogenia , Evolução Molecular , Genomas de Plastídeos , Apiaceae/genéticaRESUMO
Background: Immunoglobulin A nephropathy (IgAN) is the most prevalent form of chronic kidney disease (CKD), marked by diverse pathological patterns and variable prognostic outcomes. Nutritional indexes are crucial for disease assessment and prognosis prediction. This study investigates associations between nutritional indexes and renal function in patients with IgAN. Methods: A cohort of 736 adults diagnosed with IgAN, who underwent renal biopsy at the First Hospital of Jilin University between January 2010 and October 2022, was examined. Clinical and laboratory data were reviewed, and four nutritional indexes were calculated: controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), body mass index (BMI), and prognostic nutritional index (PNI). Cox-proportional hazard analysis evaluated factors associated with end-stage renal disease (ESRD). Results: Patients with ESRD showed significantly lower GNRI (91.84 vs. 98.94, p < 0.001) and median PNI (41.90 vs. 46.30, p < 0.001), with higher median CONUT score (2.00 vs. 1.00, p = 0.001) compared to those without ESRD. PNI, GNRI, and CONUT scores correlated significantly with C2 in MEST-C classification. Kaplan-Meier analysis indicated increased ESRD probability in individuals with specific thresholds of PNI, GNRI, or CONUT scores. Additionally, GNRI emerged as an independent predictor of ESRD (hazard ratio: 0.963, 95% CI: 0.940-0.979, p < 0.001), along with platelet count, serum creatinine, eGFR (CKD-EPI), and triglyceride levels. Conclusion: GNRI, PNI, and CONUT scores hold potential in reflecting IgAN severity and predicting ESRD risk. GNRI especially may serve as a valuable tool for identifying high-risk individuals for ESRD in IgAN.
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A novel rare earth complex, Eu(IAA)2(phen)2 (EuIP), was synthesized by solution-based synthesis method. Then, EuIP and polylactic acid (PLA) were melt-blended at 190 °C to obtain a multifunctional PLA/EuIP composite. The incorporation of EuIP provided PLA/EuIP composites with good light conversion ability. Under UV irradiation, PLA/EuIP composites converted the absorbed UV light into red light. Moreover, the PLA/1.0EuIP composite exhibited excellent light transmittance of 88 % in the visible region and showed strong red emission under UV light. After UV irradiation for 96 h, the molecular weights and mechanical properties of neat PLA decreased dramatically. Interestingly, the molecular weights and mechanical properties of PLA/EuIP composites did not deteriorate after 96 h of UV irradiation. The reason was that EuIP could absorb UV light and utilize the absorbed energy to emit red fluorescence. Furthermore, PLA/EuIP composites showed good antibacterial activities against E. coli and S. aureus. In addition, in vitro cell experiments showed that PLA/EuIP composites was suitable for the growth of murine breast cancer (4 T1) cells. Besides, enzymatic degradation testing also proved that PLA/EuIP composites had good biodegradability. This work provides an ingenious design strategy for the preparation of PLA/EuIP composites possessing light conversion ability, UV resistance, and antibacterial properties.
Assuntos
Antibacterianos , Escherichia coli , Poliésteres , Raios Ultravioleta , Poliésteres/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Animais , Camundongos , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Linhagem Celular TumoralRESUMO
The occurrence of inflammation is closely related to the activation of the NLRP3 inflammasome. IL-1ß produced during the activation of the NLRP3 inflammasome has strong pro-inflammatory activity and can also promote the release of inflammatory factors by other immune cells, exacerbating inflammatory damage to tissues. Utilizing IL-1ß as the detection index to find small-molecule inhibitors targeting NLRP3 from natural products will benefit the search for drugs for inflammation-related diseases. During the exploration of anti-inflammatory active components derived from the flowers of Dolichos lablab L., an ingredient in traditional Chinese medicine with dual applications in both medicinal treatment and dietary consumption, fourteen compounds (1-14), including seven previously unreported ones, named flosdolilabnitrogenousols A-D (1-4) and flosdolilabsaponins A-C (5-7), were found. Their structures were established through extensive NMR spectra determination, HR-ESI-MS analysis, ECD calculations, and chemical reactions. Flosdolilabsaponin A (5) stands out as an exceptionally rare tetracyclic lactone oleane-type saponin. Additionally, the inhibitory activity on IL-1ß release of all compounds, without cytotoxicity, was evaluated using BMDMs stimulated with LPS/Nigericin. An Elisa assay revealed that compounds 1, 8, 9, and 11-14 exhibited significant inhibition of IL-1ß release at a concentration of 30 µM. Structure-activity relationships were also discussed. This study indicates that D. lablab flowers possess anti-inflammatory activity, which might exert its effect by suppressing the activation of the NLRP3 inflammasome.
Assuntos
Anti-Inflamatórios , Flores , Interleucina-1beta , Proteína 3 que Contém Domínio de Pirina da Família NLR , Interleucina-1beta/metabolismo , Interleucina-1beta/antagonistas & inibidores , Flores/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Humanos , Estrutura Molecular , Inflamassomos/metabolismo , Inflamassomos/antagonistas & inibidores , Inflamassomos/efeitos dos fármacosRESUMO
As one of a traditional Chinese medicine with dual applications in both medicinal treatment and dietary consumption, the mature seeds of D. lablab were reported to be rich in saponins and have a good effect on inflammatory related diseases. However, the substance basis for its anti-inflammatory activity remains unclear. Thus, a comprehensive phytochemical investigation on triterpenoid saponins from D. lablab seeds was carried out, resulting in the isolation and identification of twenty-one new triterpenoid saponins including dolilabsaponins A1-A4, B, C, D1-D3, E-M, N1, N2 and O (1-21) along with thirteen known analogs (22-34). Notably, the known saponins, 31, 32, and 34 were obtained from Leguminosae family for the first time. The 1H and 13C NMR data of saponins 24 and 28 were firstly reported here. Additionally, lipopolysaccharide (LPS)-stimulated RAW264.7 cells model was utilized to assess inhibitory activities of compounds 1-34 on nitric oxide (NO) production. The results revealed that compounds 1-3, 9, 10, 13-15, 18, 22, 23 and 28-34 significantly suppressed the elevation of NO levels in LPS-induced RAW264.7 cells at the concentration of 30 µM, exhibiting a concentration-dependent manner at 3, 10, and 30 µM. The results suggested that compounds 1-3, 9, 10, 13-15, 18, 22, 23, and 28-34 possessed potential anti-inflammatory activity. Further western blot assay demonstrated that 1, 9, 10, 13, 14, and 18 suppressed inflammatory response via down-regulated the expression levels of inflammatory factors, tumor necrosis factor-alpha and interleukin-6.