Background
Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis in the world. Reliable biomarkers are required for the non‐invasive diagnosis and monitoring of ...IgAN. This study aims to investigate the difference in urinary exosomal microRNA (miRNA) expression profiles between patients with IgA nephropathy (IgAN) and healthy controls, which may provide clues to identify novel potential non‐invasive miRNA biomarkers for renal diseases.
Methods
Urine samples were collected from eighteen healthy controls and eighteen patients with IgAN. Differential centrifugation was performed to isolate exosomes from urine samples. High‐throughput sequencing and real‐time quantitative polymerase chain reaction (RT‐qPCR) were sequentially used to screen and further validate miRNA expression profiles in urinary exosomes of patients with IgAN in two independent cohorts.
Results
Urinary exosomes were successfully isolated to obtain exosomal miRNAs. MiR‐215‐5p and miR‐378i were significantly upregulated in urinary exosomes of patients with IgAN compared with healthy controls (P<.01), while miR‐29c and miR‐205‐5p were significantly downregulated (P<.05). MiR‐215‐5p, miR‐378i, miR‐365b‐3p and miR‐135b‐5p were found to have altered expression in patients with IgAN from validation cohorts, which was consistent with the high‐throughput sequencing analysis.
Conclusion
This study suggests that there is a significant difference in urinary exosomal miRNA profiles between patients with IgAN and healthy controls. These exosomal miRNAs, such as miR‐29c, miR‐146a and miR‐205 may potentially serve as novel non‐invasive biomarkers for IgAN.
Schizophrenia (SCZ) is a multifaceted mental disorder marked by a spectrum of symptoms, including hallucinations, delusions, cognitive deficits, and negative symptoms. Its etiology involves intricate ...interactions between genetic and environmental factors, posing significant challenges for effective treatment. We hypothesized that intranasal administration of exosomes derived from nasal olfactory mucosal mesenchymal stem cells (OM-MSCs-exos) could alleviate SCZ-like behaviors in a murine model induced by methylazoxymethanol (MAM).
We conducted a comprehensive investigation to assess the impact of intranasally delivered OM-MSC-exos on SCZ-like behaviors in MAM-induced mice. This study encompassed behavioral assessments, neuroinflammatory markers, glial activation, synaptic protein expression, and neurogenesis within the hippocampus.
Our findings demonstrated that intranasal administration of OM-MSC-exos effectively ameliorated SCZ-like behaviors, specifically addressing social withdrawal and sensory gating deficits in the MAM-induced murine model. Furthermore, OM-MSC-exos intervention yielded a reduction in neuroinflammatory markers and a suppression of microglial activation within the hippocampus. Simultaneously, we observed an upregulation of key synaptic protein expression, including PSD95 and TH, the rate-limiting enzyme for dopamine biosynthesis.
Our study underscores the therapeutic potential of OM-MSC-exos in mitigating SCZ-like behavior. The OM-MSC-exos have the capacity to modulate glial cell activation, diminish neuroinflammation, and promote BDNF-associated synaptic plasticity and neurogenesis, thus ameliorating SCZ-like behaviors. In summary, intranasal administration of OM-MSC-exos offers a multifaceted approach to address SCZ mechanisms, promising innovative treatments for this intricate disorder.
Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements ...are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming.
In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent.
The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility.
This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.
In this work, Ni
0.7−
x
Zn
0.3
Co
x
Fe
2
O
4
(
x
= 0, 0.05, 0.10, 0.15 and 0.20, NZCF) ferrites were successfully fabricated by solid-state reaction method. We have been more focused on the effects ...of cobalt-substituted NiZn ferrite on crystal structure, microstructure and magneto-electric properties. With gradual addition of cobalt content, since the smaller ionic radius and larger atomic weight of the cobalt, which leads to decrease lattice parameter (
a
) and enhance X-ray density (
d
x
), respectively. The grain size (
D
) increases (4.86 ± 1.10 to 6.26 ± 1.67 μm). When
x
= 0.05, the initial permeability (
μ
i
) of NiZnCo ferrites reaches the maximum value. The saturation magnetization (
M
s) is firstly decreased slightly from 78.96 to 77.96 emu/g when
x
≤ 0.10, then increased to 83.14 emu/g (
x
= 0.15), ultimately decreased to 81.54 emu/g. Meanwhile, the coercivity (
H
c) is dropped from 19.95 to 13.25 Oe when
x
≤ 0.05, and stabilized at about 13.40 Oe when
x
> 0.05. From the dielectric spectrum, the real dielectric constant (ε′) exhibits typical relaxation-dispersion behavior with increasing frequency. The resistivity temperature spectrum also shows good performance: both dc resistivity (
ρ
) and activation energy (
E
ρ
) increase with the Co substitution. Here, we have developed a NiZnCo ferrite when Co-substituted
x
= 0.05 with the highest permeability (
μ
i
, 123@10 kHz), higher saturation magnetization (
M
s, 78.25 emu/g) and lowest coercivity (
H
c, 13.25Oe), which is expected to be used in high-frequency capacitors and inductors.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for hematologic malignancies and non-malignant disorders, such as aplastic anemia, fanconi anemia, and certain ...immune deficiencies. Post-transplantation kidney injury is a common complication and involves a wide spectrum of structural abnormalities, including glomerular (MSPGN, mesangial proliferative glomerulonephritis; FSGS, focal segmental glomerulosclerosis; MPGN, membranoproliferative glomerulonephritis; MCD, minimal change disease), vascular (TMA, thrombotic microangiopathy), and/or tubulointerstitial (TIN, tubulointerstitial nephritis; ATI, acute tubular injury). Renal biopsy is the gold-standard examination for defining multiple etiologies of kidney impairment. Although kidney injury following HSCT has been studied, little is known about the effects of allo-HSCT on renal pathology in pediatric patients.
We retrospectively analyzed renal biopsy specimens from children with kidney injury after allo-HSCT and correlated results with clinical data in the last 10 years.
Among 25 children (18 males and 7 females), three patients had proteinuria indicating nephrotic syndrome (24-hour urinary total protein/weight > 50 mg/kg/d), nine patients had severely reduced estimated glomerular filtration rate (eGFR < 30 ml/min/1.73 m
) and four patients received kidney replacement therapy (KRT). The main pathologies identified from kidney biopsies were MSPGN (n = 12), FSGS (n = 12), MPGN (n = 5), TMA (n = 4), MCD (n = 3), diffuse glomerular fibrosis (DGF, n = 2), ATI and TIN, in isolation or combined with other pathologies. The median follow-up time was 16.5 (0.5 ~ 68.0) months. Three patients died of recurrent malignancy and/or severe infection, one child developed to end-stage renal disease (ESRD), six patients (24%) had elevated serum creatinine (SCr > 100µmol/l) and nine patients (36%) still had proteinuria.
This study evaluates histomorphologic findings from kidney biopsies of pediatric recipients following allo-HSCT. Detailed evaluation of renal biopsy samples is helpful to elucidate the nature of renal insult, and may potentially identify treatable disease processes.
Chronic inflammation is one of the critical causes to promote the initiation and metastasis of solid malignancies including lung cancer (LC). Here, we aimed to investigate the prognostic roles of ...albumin (Alb)‐to‐fibrinogen (Fib) ratio (AFR), Fib and Alb in LC and to establish a novel effective nomogram combined with AFR. Four hundred twelve LC patients diagnosed between February 2005 and December 2014 were recruited in this prospective study. The prognostic roles of AFR, Fib, Alb, neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) and monocyte‐to‐lymphocyte ratio (MLR) were identified by X‐tile software, Kaplan–Meier curve, Cox regression model, and time‐dependent ROC. Pretreatment high circulating Fib, low AFR, and Alb were significantly associated with increased risk of death for LC patients, especially for non‐small cell lung cancer (NSCLC) patients in all stages. The area under curves (AUCs) of AFR, Fib, and NLR were higher than them within Alb and PLR for predicting the survival of NSCLC patients. Moreover, we found that clinical outcome of high AFR patient with chemo‐radiotherapy was superior to low AFR patient; overall survival rate of stage II‐III NSCLC patients undergoing chemo‐radiotherapy was significantly lower than the surgical patients with treatment of adjuvant chemo‐radiotherapy(P = 0.001) in low AFR subgroup. On the contrary, clinical outcome of the patients receiving chemo‐radiotherapy was the same to the patients undergoing surgery and adjuvant chemo‐radiotherapy (P = 0.405) in high AFR subgroup. In addition, c‐index of predicted nomogram including AFR (0.717) for NSCLC patients with treatment of chemo‐radiotherapy was higher than that without AFR (0.707). Our findings demonstrated that circulating pretreatment AFR might be a potential biomarker to predict clinical efficacy of surgical resection and adjuvant chemo‐radiotherapy and be a prognostic biomarker for NSCLC individuals.
Circulating pretreatment albumin to fibrinogen ratio was a promising prognostic biomarker of NSCLC. According to AFR, stage II–III NSCLC patients were received suitable therapeutic method and the predicted efficacy of nomogram was improved for NSCLC receiving chemo‐radiotherapy.
inhabiting pit mud (PM) is one of the important bacterial populations for synthesizing flavor compounds of Chinese strong-flavor baijiu. The long-term cereal fermentation with sorghum as the main raw ...material creates an environment rich in starch, ethanol, and organic acids (mainly lactic acid). However, the genetic factors underpinning
's adaptation to PM remain poorly understood. Here, we performed comparative genomic analysis between 30 pit mud-associated (PMA) and 100 non-pit mud-associated (NPMA)
strains. Comparison analysis of the enrichment of KEGG pathways between PMA and NPMA
strains showed two-component system, flagellar assembly, and bacterial chemotaxis pathways related to environmental adaptation were enriched in PMA strains. The number of genes encoding alcohol dehydrogenase and l-lactate dehydrogenase in PMA
strains was significantly higher than that in NPMA, which is helpful for them to adapt to the ethanol- and lactic acid-rich environment. The analysis of carbohydrate-active enzymes demonstrated that glycoside hydrolases (GHs) was the most abundant family in all
strains, and genes encoding GH4 and GH13, involved in starch and sucrose metabolism, were enriched in PMA
. Horizontal gene transfer analysis revealed that multiple genes encoding the enzymes involved in carbohydrate and amino acid metabolism were transferred from
to
in pit mud. Most of the PMA
strains had good potential for butyric acid synthesis from ethanol, lactic acid, and starch. Collectively, this study furthers our understanding of the habitat adaptation and metabolic potential of PMA
strains.
Pit mud is a typical artificial ecosystem for Chinese liquor production.
inhabiting pit mud plays essential roles in the flavor formation of strong-flavor baijiu. The relative abundance of
increased with pit mud quality, further influencing the quality of baijiu. So far, the ecological adaptation of
to a pit mud-associated lifestyle is largely unknown. Here, comparative genomic analysis of pit mud-associated (PMA) and non-pit mud-associated (NPMA)
strains was performed. We found genes related to the metabolism of starch, ethanol, and lactic acid were enriched in PMA
strains, which facilitated their adaptation to the unique brewing environment. In addition, horizontal gene transfer contributed to the adaptation of
to pit mud. Our findings provide genetic insights on PMA
strains' ecological adaptation and metabolic characteristics.
Objective
In the present study, the chemical components of Qinghao Biejia decoction (QBD) were qualitatively and quantitatively analyzed using UPLC‐Orbitrap Fusion‐MS/MS and UPLC‐QQQ‐MS/MS ...techniques, followed by identification of each component's origin and evaluation of the antibacterial activity of QBD and its components.
Methods
High‐resolution mass spectrometry was used to obtain information on the precise molecular weight, retention time, and fragmentation ion peaks of the compounds used to identify the components of QBD and establish a method for their quantification. In vitro assays including determination of the minimal inhibitory concentration and growth curves were used to assess the antibacterial activity of QBD and its components.
Results
A total of 39 components, including fatty acids, phenolic acids, amino acids, flavonoids, coumarins, terpenoids, and alkaloids, were identified by UPLC‐Orbitrap Fusion‐MS/MS. A high‐performance analytical method was also established to quantify 12 components of QBD. The content of mangiferin was relatively high (estimated to be 814 μg/g). The results of the antibacterial assays indicated that mangiferin exhibits antibacterial effects against two strains causing respiratory tract infections.
Conclusions
The present study suggests that mangiferin may serve as a natural compound which shows high antibacterial activity. The results can aid the discovery and analysis of the active antimicrobial components present in QBD and further provide a reference for quality assessment of multi‐component herbal prescriptions.
39 compounds were identified and characterised from the QBD, followed by quantitative and methodological validation of 12 components, and finally antibacterial assays showed that mangiferin showed the optimalantibacterial activity against two strains of bacteria causing respiratory tract infections.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause joint inflammation and damage. Leonurine (LE) is an alkaloid found in Leonurus heterophyllus. It has anti-inflammatory ...effects.
The molecular mechanisms by which LE acts in RA are unclear and further investigation is required.
Mice with collagen-induced arthritis (CIA), and RA-fibroblast-like synoviocytes (FLSs) isolated from them were used as in vivo and in vitro models of RA, respectively. The therapeutic effects of LE on CIA-induced joint injury were investigated by micro-computed tomography, and staining with hematoxylin and eosin and Safranin-O/Fast Green. Cell Counting Kit-8, a Transwell® chamber, enzyme-linked immunosorbent assays, RT-qPCR, and western blotting were used to investigate the effects of LE on RA-FLS viability, migratory capacity, inflammation, microRNA-21 (miR-21) levels, the Hippo signaling pathway, and the effects and intrinsic mechanisms of related proteins. Dual luciferase was used to investigate the binding of miR-21 to YOD1 deubiquitinase (YOD1) and yes-associated protein (YAP). Immunofluorescence was used to investigate the localization of YAP within the nucleus and cytoplasm.
Treatment with LE significantly inhibited joint swelling, bone damage, synovial inflammation, and proteoglycan loss in the CIA mice. It also reduced the proliferation, cell colonization, migration/invasion, and inflammation levels of RA-FLSs, and promoted miR-21 expression in vitro. The effects of LE on RA-FLSs were enhanced by an miR-21 mimic and reversed by an miR-21 inhibitor. The dual luciferase investigation confirmed that both YOD1 and YAP are direct targets of miR-21. Treatment with LE activated the Hippo signaling pathway, and promoted the downregulation and dephosphorylation of MST1 and LATS1 in RA, while inhibiting the activation of YOD1 and YAP. Regulation of the therapeutic effects of LE by miR-21 was counteracted by YOD1 overexpression, which caused the phosphorylation of YAP and prevented its nuclear ectopic position, thereby reducing LE effect on pro-proliferation-inhibiting apoptosis target genes.
LE regulates the Hippo signaling pathway through the miR-21/YOD1/YAP axis to reduce joint inflammation and bone destruction in CIA mice, thereby inhibiting the growth and inflammation of RA-FLSs. LE has potential for the treatment of RA.
Liver fibrosis is characterized by the abnormal deposition of the extracellular matrix with a severe inflammatory response and/or metabolic disorder. Asiatic acid (AA), a natural compound derived ...from Centella asiatica, exhibited potent anti-fibrosis effects. This investigation first confirmed the anti-fibrosis effects of AA in TGF-β-LX-2 cells and CCl4-induced liver fibrosis mice, and then sought to elucidate a novel mechanism of action by integrating network pharmacology and lipidomics. Network pharmacology was used to find potential targets of AA, while lipidomics was used to identify differential metabolites between fibrosis and recovered cohorts. AA could suppress hepatic stellate cell activation in vitro and improve liver fibrosis in vivo. Network pharmacology unveiled the genes involved in pathways in cancer, peroxisome proliferators-activated receptors signaling pathway, and arachidonic acid metabolism pathway. Furthermore, five key genes were found in the both human and mouse databases, indicating that arachidonic acid metabolism was important. Changes in lyso-phosphocholine (22:5), prostaglandin F2α, and other related lipid metabolites also suggested the involvement of arachidonic acid metabolism the anti-fibrotic effect. In summary, our integrated strategies demonstrated that AA targeted multiple targets and impeded the progression of liver fibrosis by ameliorating arachidonic acid metabolism.
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