Objective: To investigate the effect of acupuncture on Parkinson's disease (PD) patients with tremor and its potential neuromechanism by functional magnetic resonance imaging (fMRI). Methods: Forty-one PD patients with tremor were randomly assigned to true acupuncture group (TAG, n=14), sham acupuncture group (SAG, n=14) and waiting group (WG, n=13). All patients received levodopa for 12 weeks. Patients in TAG were acupunctured on DU20, GB20 and the Chorea-Tremor Controlled Zone, and patients in SAG accepted sham acupuncture, while patients in WG received no acupuncture treatment until 12 weeks after the course was ended. The UPDRS Ⅱ and Ⅲ subscales, and fMRI scans of the patients' brains were obtained before and after the treatment course. UPDRS Ⅱ and Ⅲ scores were analyzed by SPSS, while the degree centrality (DC), regional homogeneity (ReHo) and amplitude low-frequency fluctuation (ALFF) were determined by REST. Results: Acupuncture improved the UPDRS Ⅱ and Ⅲ scores in PD patients with tremor without placebo effect, only in tremor score. Acupuncture had specific effects on the cerebrocerebellar pathways as shown by the decreased DC and ReHo and increased ALFF values, and nonspecific effects on the spinocerebellar pathways as shown by the increased ReHo and ALFF values (P<0.05, AlphaSim corrected). Increased ReHo values were observed within the thalamus and motor cortex of the PD patients (P<0.05, AlphaSim corrected). In addition, the default mode network (DMN), visual areas and insula were activated by the acupuncture with increased DC, ReHo and (or) ALFF, while the prefrontal cortex (PFC) presented a significant decrease in ReHo and ALFF values after acupuncture (P<0.05, AlphaSim corrected). Conclusions: The cerebellum, thalamus and motor cortex, which are connected to the cerebello-thalamo-cortical (CTC) circuit, were modulated by the acupuncture stimulation to alleviate the PD tremor. The regulation of neural activity within the cognitive brain regions (the DMN, visual areas, insula and PFC) together with CTC circuit may contributes to enhancing movement and improving patients' daily life activities.
The current immunotherapy strategies for triple negative breast cancer (TNBC) are greatly limited due to the immunosuppressive tumor microenvironment (TME). Immunization with cancer vaccines composed of tumor cell lysates (TCL) can induce an effective antitumor immune response. However, this approach also has the disadvantages of inefficient antigen delivery to the tumor tissues and the limited immune response elicited by single-antigen vaccines. To overcome these limitations, a pH-sensitive nanocalcium carbonate (CaCO3 ) carrier loaded with TCL and immune adjuvant CpG (CpG oligodeoxynucleotide 1826) is herein constructed for TNBC immunotherapy. This tailor-made nanovaccine, termed CaCO3 @TCL/CpG, not only neutralizes the acidic TME through the consumption of lactate by CaCO3 , which increases the proportion of the M1/M2 macrophages and promotes infiltration of effector immune cells but also activates the dendritic cells in the tumor tissues and recruits cytotoxic T cells to further kill the tumor cells. In vivo fluorescence imaging study shows that the pegylated nanovaccine could stay longer in the blood circulation and extravasate preferentially into tumor site. Besides, the nanovaccine exhibits high cytotoxicity in 4T1 cells and significantly inhibits tumor growth of tumor-bearing mice. Overall, this pH-sensitive nanovaccine is a promising nanoplatform for enhanced immunotherapy of TNBC.
Objective To investigate not only the relativity between the expression of HBV-DNA in serum and liver fibrosis in hepatitis B patients,but also the relationship between transaminase and the two former concepts.Methods We investigated the application of nuclear amplificatioin by fluorescence quantitative PCR in detecting HBV-DNA,and the adoption of radioimmunoassay for testing 4 liver fibrosis markers including serum hyaluronic acid(HA),sticky layer protein(LN),Ⅲ procollagen(PⅢNP),Ⅳ collagen(Ⅳ-C) in 362 cases.We also tested the utilization of continuous monitoring method and colorimetric method for measuring serum transaminase in 267 cases.Results In the low HBV viral replication group,with the increase of the serum HBV-DNA on the average,the level of concentration of liver fiber index increased;in the high HBV viral replication group,the four index of liver fibrosis in patients decreased when the amount of viral liver replication increased.There was a significant difference between the results in each group(P0.05).The difference of transaminase including AST,ALT in patients between the HBV-DNA negative control group and positive group was significant(P0.05),but in each of the HBV-DNA positive expression groups,serum HBV-DNA levels from hepatitis B patients had no relationship with the concentration of the two kinds of transaminase(P0.05).Conclusion Correlation exists between HBV replication and the serology index of liver fibrosis,but it is not a linear correlation;the status of HBV-DNA replication in patients is not yet closely linked to the liver transaminase.
The levels of MCF2L were detected by PCR and western blotting assay. The effect of MCF2L on ferroptosis was confirmed by MTT, colony formation assay, Brdu, in vivo animal experiment, and the content of Iron, GSH, ROS, and MDA. The underlying mechanisms were explored by PCR, western blotting, and affinity precipitation assay. Our findings demonstrated that MCF2L is remarkedly upregulated in HCC tissues, and sorafenib can induce the levels of MCF2L, suggesting that MCF2L might function in sorafenib resistance of HCC. Further analysis showed that downregulation of MCF2L enhances HCC cell death induced by sorafenib, and ferroptosis inhibitor can reverse this process. Subsequent experiments showed that downregulation of MCF2L elevates the content of Iron, ROS, and MDA, which are all indicators of ferroptosis. Finally, mechanism analysis showed that MCF2L regulates the PI3K/AKT pathway in a RhoA/Rac1 dependent manner.Our study showed that targeting MCF2L may be a hopeful method to overcome sorafenib-resistance through inducing ferroptosis in HCC.
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers, including liver, ovary, lung, large intestine, gastric, bone marrow, and breast malignancies and is involved in the invasion and metastasis of cancer cells. Therefore, we aimed to determine the biological role and molecular mechanism of IQGAP3 in HCC. We used 120 archived clinical HCC samples, 9 snap-frozen HCC tumor tissues, and 4 normal liver tissues. Expression of IQGAP3 mRNA and protein in HCC cell lines (Hep3B, SMMC-7721, HCCC-9810, HepG2, BEL-7404, HCCLM3, QGY-7701, Huh7, and MHCC97H) and normal liver epithelial cells LO2 was examined by western blot, quantitative polymerase chain reaction, and immunohistochemistry. In addition, wound-healing and transwell matrix penetration assays were used to assess the migratory and invasive abilities of HCC cells, respectively. Expression of the IQGAP3 was robustly upregulated in HCC cells and tissues. High expression of IQGAP3 in HCC correlated with aggressive clinicopathological features and was an independent poor prognostic factor for overall survival. Furthermore, ectopic expression of IQGAP3 markedly enhanced HCC cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in vitro and promoted metastasis of orthotopic hepatic tumors in nude mice. Conversely, silencing endogenous IQGAP3 showed an opposite effect. Mechanistically, IQGAP3 promoted EMT and metastasis by activating TGF-β signaling. IQGAP3 functions as an important regulator of metastasis and EMT by constitutively activating the TGF-β signaling pathway in HCC. Our findings present new evidence of the role of IQGAP3 in EMT and metastasis, indicating its potential as a prognostic biomarker candidate and a therapeutic target against HCC.
Infantile Hemangiomas (IHs) are common benign vascular tumors of infancy that may have serious consequences. The research on diagnostic markers for IHs is scarce.The "limma" R package was applied to identify differentially expressed genes (DEGs) in developing IHs. Plugin ClueGO in Cytoscape software performed functional enrichment of DEGs. The Search Tool for Retrieving Interacting Genes (STRING) database was utilized to construct the PPI network. The least absolute shrinkage and selection operator (LASSO) regression model and support vector machine recursive feature elimination (SVM-RFE) analysis were used to identify diagnostic genes for IHs. The receiver operating characteristic (ROC) curve evaluated diagnostic genes' discriminatory ability. Single-gene based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted by Gene Set Enrichment Analysis (GSEA). The chemicals related to the diagnostic genes were excavated by the Comparative Toxicogenomics Database (CTD). Finally, the online website Network Analyst was used to predict the transcription factors targeting the diagnostic genes.A total of 205 DEGs were singled out from IHs samples of 6-, 12-, and 24-month-old infants. These genes principally participated in vasculogenesis and development-related, endothelial cell-related biological processes. Then we mined 127 interacting proteins and created a network with 127 nodes and 251 edges. Furthermore, LASSO and SVM-RRF algorithms identified five diagnostic genes, namely, TMEM2, GUCY1A2, ISL1, WARS, and STEAP4. ROC curve analysis results indicated that the diagnostic genes had a powerful ability to distinguish IHs samples from normal samples. Next, the results of GSEA for a single gene illustrated that all five diagnostic genes inhibited the "valine, leucine, and isoleucine degradation" pathway in the development of IHs. WARS, TMEM2, and STEAP4 activated the "blood vessel development" and "vasculature development" in IHs. Subsequently, inhibitors targeting TMEM2, GUCY1A2, ISL1, and STEAP4 were mined. Finally, 14 transcription factors regulating GUCY1A2, 14 transcription factors regulating STEAP4, and 26 transcription factors regulating ISL1 were predicted.This study identified five diagnostic markers for IHs and further explored the mechanisms and targeting drugs, providing a basis for diagnosing and treating IHs.
Abstract Background Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as World Federation of Neurosurgical Societies (WFNS) grade IV-V has high rates of disability and mortality. The objective of this research is to prognosticate outcomes of poor-grade aSAH accurately. Methods A total of 147 poor-grade aSAH patients in our center were enrolled. Risk variables identified by multivariate logistic regression were used to devise the scoring model (total score of 0–9 points). The score values were estimated according to β coefficients. A cohort of 68 patients from another institute was used to validate the model. Results Multivariate analysis revealed that modified Fisher grade above II (odds ratio [OR], 2.972; p = 0.034), age ≥ 65 years (OR, 3.534; p = 0.006), conservative treatment (OR, 5.078; p = 0.019), WFNS Grade V (OR, 2.638; p = 0.029), delayed cerebral ischemia (OR, 3.170; p = 0.016), shunt-dependent hydrocephalus (OR, 3.202; p = 0.032) and cerebral herniation (OR, 7.337; p < 0.001) were significant predictors of poor prognosis (modified Rankin Scale [mRS] ≥ 3). By integration of above factors, a scoring system was constructed and divided poor-grade aSAH patients into three categories: low risk (0–1 point), intermediate risk (2–3 points) and high risk (4–9 points), with risk of poor prognosis being 11%, 52% and 87% respectively (P < 0.001). The area under the curve in derivation cohort was 0.844 (p < 0.001; 95% CI, 0.778–0.909). AUC in validation cohort was 0.831 (p < 0.001; 95% CI, 0.732–0.929). Conclusions The new scoring model could improve prognostication of prognosis and help decision-making for subsequent complement treatment.
Insulin resistance is a key factor in diabetes development. This study aimed to investigate the association between baseline triglyceride–glucose (TyG) index, a surrogate marker of insulin resistance, and the onset of hyperglycemia in Chinese individuals with hypertension. Using the Rich Healthcare Group database, this retrospective cohort study included 28,687 hypertensive individuals without preexisting diabetes. A wide range of demographic information and baseline biochemical indicators was collected and rigorously analyzed. This study utilized the Cox proportional hazards model and smooth curve fitting to explore the link between TyG index and the risk of developing hyperglycemia. The robustness of the findings was validated by sensitivity and subgroup analyses. During longitudinal monitoring of hypertensive patients in our retrospective cohort study, we observed that 5.31% (1524/28,687) progressed to diabetes, while 21.66% (4620/21,326) developed prediabetes. After adjusting for confounding variables, a statistically significant positive association was observed between the TyG index and the risk of hyperglycemia. Subgroup and sensitivity analyses further supported these findings, demonstrating consistent outcomes and reinforcing the robustness of our conclusions. The TyG index, which is significantly linked to hyperglycemia in hypertensives, can aid early risk identification and intervention.
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