Hepatocellular carcinoma (HCC) is a malignant primary liver cancer with poor prognosis. Most previous studies on anti-HCC effects of traditional Chinese medicines (TCM) have focused on the mechanism ...of direct action and few researchers considered that TCM can inhibit tumor progression and improve prognosis of HCC patients through regulating tumor microenvironment (TME). In this study, network pharmacology combined bioinformatics methods were employed to analysis mechanism of Bombyx batryticatus (B. batryticatus, one of the most frequently used traditional Chinese animal medicines, has been used in some Asian countries for centuries as an anticancer agent, anti-inflammatory agent, and antioxidant.) in regulating TME of HCC. The results showed that 24 core targets and 2 compounds were identified from overlapping between differential expression genes related to HCC in the cancer genome atlas (TCGA) database and targets of B. batryticatus in TCMSP database. For further analyzing the role of TME heterogeneity of HCC on anti-HCC mechanism of B. batryticatus, the correlation of core targets related with overall survival of HCC with TME cells in hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (VIR) and non-hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (NVIR) were calculated, respectively. The results showed that AKR1C3, SPP1 were significantly related with macrophages in VIR and other targets including NR1I2, CYP1A2 and CYP3A4 were significantly associated with macrophages in NVIR; the target protein AKR1C3 was significantly negative correlated with macrophages M1 in VIR (cor=–0.35, P-value<0.001) and the correlation between AKR1C3 and macrophages M1 was poor in NVIR group (cor = 0.064, P-value = 0.36). Additionally, survival curve of AKR1C3 showed that poor prognosis in VIR group can be related to high level of AKR1C3 (HR = 2.32, 95 % CI: 1.18–4.56, P-value = 0.012), and no signified gene can be found in NVIR group (P-value>0.05). In conclusion, the molecular mechanism of anti-HCC of B. batryticatus can be related to the tumor microenvironment to some extent. B. batryticatus may exert its anti-cancer effects and improve prognosis of patients by regulating macrophages M1 in VIR and NVIR through acting on different targets.
The vulnerability of microcontroller system against high-altitude electromagnetic pulse (HEMP) is taken as an illustration to demonstrate the assessment methodology based on Bayesian networks (BN). ...The complete procedure is performed by two steps: the qualitative and the quantitative. The first step focuses on the analysis of three classes of properties, the electromagnetic environment, system function/structure, and their interactions. The primary BN model is built at the end of the first step. The second step investigates the BN nodes and branches one by one, which further implemented through two stages, i.e., the data acquisition and data fusion. The susceptibilities of devises are examined with the pulsed current injection. The responses of the transmission lines to HEMP are computed using the field-line coupling model. Comparing the probability density functions of the electromagnetic stresses and strengths produces the failure probabilities of the interface components. Through two-step analysis, the critical elements and coupling paths are identified and highlighted. After neglecting those unimportant factors, many BN nodes and branches are deleted. Thus, the complexity of assessment is reduced. By assigning the probability values to the simplified BN model, the system failure probability is calculated, which characterizes the system vulnerability against HEMP environment. The illustration validates the rationality and flexibility of the BN assessment methodology.
Abstract
Aberrant dynamic switches between internal brain states are believed to underlie motor dysfunction in Parkinson’s disease. Deep brain stimulation of the subthalamic nucleus is a ...well-established treatment for the motor symptoms of Parkinson’s disease, yet it remains poorly understood how subthalamic stimulation modulates the whole-brain intrinsic motor network state dynamics.
To investigate this, we acquired resting-state functional magnetic resonance imaging time-series data from 27 medication-free patients with Parkinson’s disease (mean age: 64.8 years, standard deviation: 7.6) who had deep brain stimulation electrodes implanted in the subthalamic nucleus, in both on and off stimulation states. Sixteen matched healthy individuals were included as a control group. We adopted a powerful data-driven modelling approach, known as a hidden Markov model, to disclose the emergence of recurring activation patterns of interacting motor regions (whole-brain intrinsic motor network states) via the blood oxygen level-dependent signal detected in the resting-state functional magnetic resonance imaging time-series data from all participants. The estimated hidden Markov model disclosed the dynamics of distinct whole-brain motor network states, including frequency of occurrence, state duration, fractional coverage and their transition probabilities.
Notably, the data-driven decoding of whole-brain intrinsic motor network states revealed that subthalamic stimulation reshaped functional network expression and stabilized state transitions. Moreover, subthalamic stimulation improved motor symptoms by modulating key trajectories of state transition within whole-brain intrinsic motor network states. This modulation mechanism of subthalamic stimulation was manifested in three significant effects: recovery, relieving and remodelling effects. Significantly, recovery effects correlated with improvements in tremor and posture symptoms induced by subthalamic stimulation (P < 0.05). Furthermore, subthalamic stimulation was found to restore a relatively low level of fluctuation of functional connectivity in all motor regions to a level closer to that of healthy participants. Also, changes in the fluctuation of functional connectivity between motor regions were associated with improvements in tremor and gait symptoms (P < 0.05).
These findings fill a gap in our knowledge of the role of subthalamic stimulation at the level of neural activity, revealing the regulatory effects of subthalamic stimulation on whole-brain inherent motor network states in Parkinson’s disease. Our results provide mechanistic insight and explanation for how subthalamic stimulation modulates motor symptoms in Parkinson’s disease.
Using an unsupervised model based on functional MRI, Chu et al. identify three specific subthalamic stimulation-induced neural activity patterns in Parkinson’s disease: recovering, relieving and remodelling the dynamics of intrinsic motor network states. The changes are associated with clinical improvement.
Alcoholic liver disease (ALD) is the most common complication of alcohol abuse, while we lack safe and effective treatment for ALD. This study aimed to explore the effects of nicotinamide riboside ...(NR) on lipid metabolism and gut microflora‐bile acid axis in alcohol‐exposed mice. NR significantly improved liver histopathological damage and abnormal liver function. NR as a provider of nicotinamide adenine dinucleotide (NAD+) increased the NAD+/NADH ratio. Meanwhile, NR inhibited the activation of the protein phosphatase 1 signaling pathway, decreased the liver triglyceride and total bile acid levels, and reduced lipid accumulation. According to the results of gut microflora species analysis, NR intervention changed the microbial community structure at the phylum, family and genus levels, and the species abundances returned to a level similar to these of the normal control group. Besides, the results of high‐performance liquid chromatograph‐mass spectrometry showed that NR intervention resulted in fecal bile acid levels tending to be normal with decreased chenodeoxycholic acid level and increased deoxycholic acid and hyocholic acid levels. Spearman's correlation analysis showed a correlation between gut microflora and bile acids. Therefore, NR supplementation has the potential to prevent ALD, and its mechanism may be related to regulating lipid metabolism disorders and the gut microflora‐bile acid axis.
The protective effect of nicotinamide riboside (NR) on liver in alcohol‐exposed mice. NR supplementation could regulate lipid metabolism and the gut flora‐bile acid axis to protect mice from ALD.
A wide range of bacterial pathogens have been identified in ticks, yet the diversity of viruses in ticks is largely unexplored.
Here, we used metagenomic sequencing to characterize the diverse ...viromes in three principal tick species associated with pathogens,
, and
, in North China.
A total of 28 RNA viruses were identified and belonged to more than 12 viral families, including single-stranded positive-sense RNA viruses (
, and
), negative-sense RNA viruses (
, and others) and double-stranded RNA viruses (
and
). Of these, Dermacentor pestivirus-likevirus, Chimay-like rhabdovirus, taiga tick nigecruvirus, and Mukawa virus are presented as novel viral species, while Nuomin virus, Scapularis ixovirus, Sara tick-borne phlebovirus, Tacheng uukuvirus, and Beiji orthonairovirus had been established as human pathogens with undetermined natural circulation and pathogenicity. Other viruses include Norway mononegavirus 1, Jilin partitivirus, tick-borne tetravirus, Pico-like virus, Luteo-like virus 2, Luteo-likevirus 3, Vovk virus, Levivirus, Toti-like virus, and Solemo-like virus as well as others with unknown pathogenicity to humans and wild animals.
In conclusion, extensive virus diversity frequently occurs in
and
among the three tick species. Comparatively,
ticks had been demonstrated as such a kind of host with a significantly higher diversity of viral species than those of
and
ticks. Our analysis supported that ticks are reservoirs for a wide range of viruses and suggested that the discovery and characterization of tick-borne viruses would have implications for viral taxonomy and provide insights into tick-transmitted viral zoonotic diseases.
As people age, their ability to resist injury and repair damage decreases significantly. Platelet-rich plasma (PRP) has demonstrated diverse therapeutic effects on tissue repair. However, the ...inconsistency of patient outcomes poses a challenge to the practical application of PRP in clinical practice. Furthermore, a comprehensive understanding of the specific impact of aging on PRP requires a systematic investigation. We derived PRP from 6 young volunteers and 6 elderly volunteers, respectively. Subsequently, 95% of high-abundance proteins were removed, followed by mass spectrometry analysis. Data are available via ProteomeXchange with the identifier PXD050061. We detected a total of 739 proteins and selected 311 proteins that showed significant differences, including 76 upregulated proteins in the young group and 235 upregulated proteins in the elderly group. Functional annotation and enrichment analysis unveiled upregulation of proteins associated with cell apoptosis, angiogenesis, and complement and coagulation cascades in the elderly. Conversely, IGF1 was found to be upregulated in the young group, potentially serving as the central source of enhanced cell proliferation ability. Our investigation not only provides insights into standardizing PRP preparation but also offers novel strategies for augmenting the functionality of aging cells or tissues.
Alcoholic liver disease is caused as a result of chronic alcohol consumption. In this study, we used an alcoholic liver injury mouse model to investigate the effect of fucoidan on ethanol-induced ...liver injury and steatosis and the underlying mechanisms.
All mice were randomly divided into four groups: 1) control group, 2) model group, 3) diammonium glycyrrhizinate treatment group (200 mg/kg body weight), and 4) fucoidan treatment group (300 mg/kg body weight). Administration of ethanol for 8 weeks induced liver injury and steatosis in mice.
Fucoidan treatment decreased serum alanine aminotransferase activity, serum total cholesterol levels, and hepatic triglyceride levels, and improved the morphology of hepatic cells. Fucoidan treatment upregulated the expression of AMPKα1, SIRT1, and PGC-1α and inhibited the expression of ChREBP and HNF-1α. The levels of hepatic IL-6 and IL-18 were significantly decreased in the fucoidan group. Further, the levels of cytochrome P450-2E1 (CYP2E1), glucose-regulated protein (GRP) 78, and 3-nitrotyrosine (3-NT) in hepatic tissues were reduced in the fucoidan group as compared to the model group. Fucoidan significantly reversed the reduction of ileac Farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) levels induced by alcohol-feeding and reduced CYP7A1 (cholesterol 7α-hydroxylase) expression and total bile acid levels in the liver tissue. In addition, fucoidan regulated the structure of gut flora, with increased abundance of
and decreased abundance of
and
as detected by 16S rDNA high-throughput sequencing.
Fucoidan inhibited alcohol-induced steatosis and disorders of bile acid metabolism in mice through the AMPKα1/SIRT1 pathway and the gut microbiota-bile acid-liver axis and protected against alcohol-induced liver injury in vivo.
OBJECTIVEThis study aimed to explore whether dietary flaxseed oil has effects on acute anterior cruciate ligament (ACL) rupture prognosis after surgical reconstruction. METHODSPatients with primary ...acute ACL rupture diagnosed by magnetic resonance imaging and clinical examination were recruited at Quanzhou First Hospital Affiliated to Fujian Medical University and randomized to either the placebo group or the flaxseed oil group by computer-generated random numbers. Patients in the placebo group took six corn oil capsules daily, while patients in the flaxseed oil group took six flaxseed oil capsules daily. The outcomes were evaluated by specific scales. RESULTSCompared to the placebo group, the flaxseed oil group showed significantly higher International Knee Documentation Committee (IKDC) score (P = 0.007) and total Knee Injury and Osteoarthritis Outcome Score (KOOS) (P = 0.0003) after two-year administration. Patients treated with flaxseed oil exhibited a significantly higher rate of return to sporting level before injury (P = 0.04) and a lower rate of occurrence of giving way (P = 0.04) than those in the placebo group. Patients with flaxseed oil showed significantly less severe adverse events on index knee (P = 0.047). CONCLUSIONThe administration of dietary flaxseed oil enhanced the prognosis of acute ACL rupture.
Existing meta-analysis have shown that the miR-200 family can be taken as a prognostic biomarker for many tumors. However, great heterogeneity was shown in predicting overall survival (OS) and ...progression-free survival (PFS). Emerging studies indicate that the expression levels of members of the miR-200 family are tissue-specific among various tumor tissues, which may be the main reason of the heterogeneity in predicting survival prognosis of tumor patients with the miR-200 family as biomarkers. By further analysis of heterogeneity of the miR-200 family as a biomarker for predicting survival prognosis of patients with different tumors, we expected to provide an accurate basis for the clinical application of the miR-200 family to predict the prognosis of patients with different tumors.
Eligible published studies were identified by searching the databases of PubMed, Embase and Web of Science. The clinical data of patients in the studies were pooled, and pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were used to calculate the strength of this association. The expressions of miRNAs were extracted from The Cancer Genome Atlas (TCGA). We presented the expressions of each member in miR-200 family in 15 types of cancer by boxplot, and analyzed the correlation among the members of miR-200 family by Spearman method. Different subgroup analyses were then performed based on the correlation among the members of miR-200 family, and the publication bias was assessed using the funnel plot of the Egger bias indicator test.
Of 36 articles, including 15 tumor types and 4644 patients were included to perform meta-analysis. It was found that miR-200 family members can be used as independent protective factors in patients with various tumors but the miR-200 family has a higher heterogeneity in predicting prognosis: OS (HR = 0.82, 95% CI: 0.66–1.03, I2 = 85%, P < 0.01) and PFS (HR = 0.81, 95% CI: 0.57–1.16, I2 = 97%, P < 0.01). The data from TCGA database were used to analyze the expression levels of the miR-200 family and the results showed that the expression of miR-429 in different cancers is very different, and there are significant differences in expression levels compared with other miR-200 family members; the expression levels of miR-200a and miR-200b in various tumor tissues were similar to each other, respectively; miR-200c and miR-141 showed similar expression levels in each of most types of cancer tissues except ovarian cancer (OC). The expression levels of members of the miR-200 family in breast cancer (BRCA), cervical cancer (CESC), colon cancer (COAD), esophageal cancer (ESCA), head and neck cancer (HNSC), lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are relatively stable, but great variations can be found in the expression levels of miR-200 family members in ovarian cancer (OC), liver cancer (LIHC), renal clear cell carcinoma (KIRC) and renal papillary cell carcinoma (KIRP). Cluster analysis of expression of target genes of miR-200 family in different cancers yielded similar results to the expression level of the miR-200 family. Subgroup analysis of OC, LIHC, GC and LUAD based on expression levels and clustering results reduced or even eliminated the heterogeneity of miR-200 family members in predicting patient outcomes.
Our results convincingly demonstrated that the miR-200 family could serve as a prognostic biomarker for cancers mentioned above and has potential value in clinical practice. MiR-200 family as prognostic biomarkers needs to be performed according to different tumor tissues and correlation between members in miR-200 family.
•MicroRNA-200 family over expression suggested better prognosis of various cancer types.•Members of microRNA-200 with co-localization or co-expression should priority consider.•Tissue specificity was also important factor for meta-analysis on miRNAs family.
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