Hydrogels composite optimized for low resistance and loading-unloading hysteresis for flexible biosensors.

With the advancement of wearable and implantable medical devices, hydrogel flexible bioelectronic devices have attracted significant interest due to exhibiting tissue-like mechanical compliance, biocompatibility, and low electrical resistance. In this study, the development and comprehensive performance evaluation of poly(acrylic acid)/ N,N'-bis(acryloyl) cystamine/ 1-butyl-3-ethenylimidazol-1-ium:bromide (PAA/NB/IL) hydrogels designed for flexible sensor applications are introduced. Engineered through a combination of physical and chemical cross-linking strategies, these hydrogels exhibit strong mechanical properties, high biocompatibility, and effective sensing capabilities. At 95 % strain, the compressive modulus of PAA/NB/IL 100 reach up to 3.66 MPa, with the loading-unloading process showing no significant hysteresis loop, indicating strong mechanical stability and elasticity. An increase in the IL content was observed to enlarge the porosity of the hydrogels, thereby influencing their swelling behavior and sensing functionality. Biocompatibility assessments revealed that the hemolysis rate was below 5 %, ensuring their suitability for biomedical applications. Upon implantation in rats, a minimal acute inflammatory response was observed, comparable to that of the biocompatibility control poly(ethylene glycol) diacrylate (PEGDA). These results suggest that PAA/NB/IL hydrogels hold promise as biomaterials for biosensors, offering a balance of mechanical integrity, physiological compatibility, and sensing sensitivity, thereby facilitating advanced healthcare monitoring solutions.

miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR.

Background: Hepatocellular carcinoma (HCC) remains a worldwide burden. However, the mechanisms behind the malignant biological behavior of HCC remain unclear. The homeobox (HOX) family could act as either promoters or suppressors in different kinds of malignancies. Our study discovered the role of HOXB5 in regulating HCC progression. Methods: The HOXB5 expression was assessed by RT-PCR analysis in human HCC samples and cell lines. HOXB5 transcriptional regulation of the EGFR was verified by the luciferase reporter assay and chromatin immunoprecipitation experiment. The oncogenic role of HOXB5 in HCC progression was analyzed by CCK8, colony-forming, and transwell assays. Results: Upregulation of HOXB5 was found in human HCC, and was strongly correlated with HCC tumor size, tumor-nodule metastasis, TNM stage, and relatively unfavorable OS and DFS. Ectopic expression of HOXB5 promoted the capacity of cell growth and clonogenicity, while the inhibition of HOXB5 decreased the proliferation and clonogenicity potential in vitro by CCK8 and colony-forming assays. In addition, HOXB5 also promoted cell migration by transwell experiment. Mechanism studies elucidated that HOXB5 triggers HCC progression via direct transcriptional activation of EGFR. The upregulation of HOXB5 is regulated by miR-200a-3p and miR-181-5p. Transfection of miR-200a-3p and miR-181-5p mimics blocked the cell proliferation and migration regulated by HOXB5, while overexpression of the 3'-UTR mutant HOXB5 abolished the suppressive effect of miR-200a-3p and miR-181-5p, but not the wild-type HOXB5. Conclusion: HOXB5 is a promising prognostic factor in human HCC. Targeting miR-200a-3p and the miR-181-5p/HOXB5/EGFR signaling pathway may provide new options for the treatment strategies of HCC.

Biosafety and differentially expressed genes analysis of melanoma cells treated with cold atmospheric plasma.

Cold atmospheric plasma (CAP) has attracted increasing attention due to its anti-bacterial and anti-tumor effects. Melanoma is an aggressive malignancy with increasing incidence rate and poor prognosis. Evaluating cell viability, apoptosis rate and reactive species injection efficiency of melanoma cells and human keratinocyte cells (HaCaT) treated with CAP to analyze biological safety of CAP. RNA-sequencing (RNA-seq) of A875 cells before and after treatment was performed to further explore the anti-tumor mechanism of CAP. CAP had a more significant biological effect on melanoma cells than HaCaT cells by inhibiting proliferation and promoting apoptosis. RNA-sequencing analysis showed that besides MAPK and p53 apoptotic signaling pathways, necroptosis and autophagy also played important roles in CAP-induced melanoma cells death. CAP can selectively kill melanoma cells and has good biosafety cytologically. Besides apoptosis, CAP can induce cell death via autophagy and necroptosis.

Transgelin-2 interacts with CD44 to regulate Notch1 signaling pathway and participates in colorectal cancer proliferation and migration.

The abnormal expression of transgelin-2 (TAGLN2) is related to tumor occurrence and progression. However, the underlying molecular mechanism of TAGLN2 in human colorectal cancer (CRC) is still poorly understood. Compared with adjacent tissues, TAGLN2 is overexpressed in CRC tissues. Its expression level is negatively correlated with the overall survival rate of patients with CRC. In addition, knockdown of TAGLN2 inhibited the proliferation and invasion of CRC cells. We also showed that TAGLN2 could interact with CD44 to regulate the Notch-1 signaling pathway. Our findings indicate there is increased TAGLN2 expression in CRC and that it may serve as a promising potential therapeutic target for CRC.

HIPK3 Circular RNA Promotes Metastases of HCC Through Sponging miR-338-3p to Induce ZEB2 Expression.

BACKGROUND: Upregulation of circHIPK3 has been observed in several kinds of malignancies. However, the mechanisms of circHIPK3 in HCC metastases remains unclear. We investigated the role and the mechanisms of circHIPK3 in the development of HCC. METHODS: HCC tissues and paired adjacent non-tumor tissues of surgical patients were used to evaluate circHIPK3 expression. A series of biological experiments had been taken to evaluate the pro-metastatic ability of circHIPK3 during HCC development in vitro and in vivo. The potential mechanisms of circHIPK3 in HCC development were identified by RT-qPCR, Western blot, RIP, and luciferase reporter assays. RESULTS: CircHIPK3 expression is significantly upregulated during HCC development. Overexpression of circHIPK3 promotes cell migration, invasion, and metastases in vitro and in vivo. CircHIPK3 promoted HCC metastases by sponging miR-338-3p to regulate EMT-associated proteins E-cadherin, vimentin, and ZEB2 expression. CONCLUSION: CircHIPK3 plays a regulatory role in metastatic HCC by sponging miR-338-3p to induce ZEB2 expression, thus promoting EMT procession.

The long noncoding RNA OTUD6B-AS1 enhances cell proliferation and the invasion of hepatocellular carcinoma cells through modulating GSKIP/Wnt/ß-catenin signalling via the sequestration of miR-664b-3p.

Ovarian tumour domain containing 6B antisense RNA1 (OTUD6B-AS1), a newly identified long noncoding RNA (lncRNA), has been reported as a key cancer-related lncRNA. However, the detailed relevance of OTUD6B-AS1 in hepatocellular carcinoma (HCC) remains undetermined. This study was designed to determine the functional significance and regulatory mechanism of OTUD6B-AS1 in HCC. We found that the expression of OTUD6B-AS1 was up-regulated in HCC tissues, and patients with high levels of OTUD6B-AS1 expression had shorter survival rates than those with low OTUD6B-AS1 expression. Elevated expression of the lncRNA was also found in multiple HCC cell lines and the silencing of OTUD6B-AS1 significantly decreased proliferation, colony formation and invasion. Correspondingly, OTUD6B-AS1 overexpression had the opposite effect on HCC cell invasion, colony formation and proliferation. Notably, OTUD6B-AS1 was identified as a molecular sponge of microRNA-664b-3p (miR-664b-3p). The down-regulation of miR-664b-3p was detected in HCC tissues and cell lines, and the up-regulation of miR-664b-3p repressed proliferation and invasion in HCC cells by targeting the glycogen synthase kinase-3ß interaction protein (GSKIP). Moreover, OTUD6B-AS1 knockdown or miR-664b-3p up-regulation exerted a suppressive effect on Wnt/ß-catenin signalling via the down-regulation of GSKIP. In addition, GSKIP overexpression markedly reversed OTUD6B-AS1 knockdown- or miR-664b-3p overexpression-induced antitumour effects in HCC. Further data confirmed that OTUD6B-AS1 knockdown exerted a tumour-inhibition role in HCC in vivo. Overall, these findings indicate that the lncRNA OTUD6B-AS1 accelerates the proliferation and invasion of HCC cells by enhancing GSKIP/Wnt/ß-catenin signalling via the sequestration of miR-664b-3p. Our study reveals a novel molecular mechanism, mediated by lncRNA OTUD6B-AS1, which may play a key role in regulating the progression of HCC.

Efficacy of transcatheter arterial chemoembolization combined with sorafenib in inhibiting tumor angiogenesis in a rabbit VX2 liver cancer model.

BACKGROUND: The aim of this study was to investigate the effects of transcatheter arterial chemoembolization (TACE) combined with sorafenib on tumor angiogenesis. MATERIALS AND METHODS: Thirty New Zealand rabbit VX2 liver cancer model animals were divided into five groups, which received either normal saline (A), TACE (B), sorafenib (C), sorafenib followed by TACE (D), or TACE followed by sorafenib (E). Serum vascular endothelial growth factor (VEGF) levels were measured before and after TACE via ELISA. Immunohistochemistry for CD34 was performed to evaluate microvessel density (MVD), and ultrasonography was used to access tumor volume. RESULTS: VEGF levels declined in group C but increased significantly on the 3rd post-operative day in groups B, D, and E. Levels decreased after the 7th post-operative day. Peak levels were significantly lower in group D than in groups B and E. On the 14th post-operative day, VEGF levels were the lowest in group C, followed by those in groups D and B. MVD was the lowest in group C followed by that in group D and E, and was the highest in group B. Group D had the smallest tumor volume. HE staining of tumor tissues from group C showed apoptosis in a scattered patchy pattern, whereas in groups B, D, and E, large areas of tumor cell necrosis were visible. CONCLUSION: TACE can up-regulate serum VEGF levels, which in turn accelerates the formation of new blood vessels. Thus, TACE combined with sorafenib inhibits VEGF and angiogenesis, and pre-operative administration of sorafenib has a more superior anti-angiogenic effect than post-operative administration.

ATDC promotes the growth and invasion of hepatocellular carcinoma cells by modulating GSK-3ß/Wnt/ß-catenin signalling.

Accumulating evidence has suggested that the ataxia telangiectasia group D complementing (ATDC) gene is an emerging cancer-related gene in multiple human cancer types. However, little is known about the role of ATDC in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the expression level, biological function and underlying mechanism of ATDC in HCC. The expression of ATDC in HCC cells was detected by quantitative real-time polymerase chain reaction and western blot analysis. Cell growth was determined by cell counting kit-8 assay and colony formation assay. Cell invasion was assessed by Transwell invasion assay. The activation status of Wnt/ß-catenin signalling was evaluated by the luciferase reporter assay. Functional experiments showed that the silencing of ATDC expression significantly suppressed the growth and invasion of HCC cells, whereas the overexpression of ATDC promoted the growth and invasion of HCC cells in vitro. Moreover, we showed that ATDC overexpression promoted the phosphorylation of glycogen synthase kinase (GSK)-3ß and resulted in the activation of Wnt/ß-catenin signalling. Notably, the inhibition of GSK-3ß activity significantly abrogated the tumour suppressive effect of ATDC silencing, while the silencing of ß-catenin partially reversed the oncogenic effect of ATDC overexpression. Taken together, these findings reveal an oncogenic role of ATDC in HCC and show that the suppression of ATDC impedes the growth and invasion of HCC cells associated with the inactivation of Wnt/ß-catenin signalling. Our study suggests that ATDC may serve as a potential therapeutic target for HCC.

[Estrogen protects the dopaminergic neurons in substantia nigra against damage induced by 6-hydroxydopamine].

Substantial evidence strongly implies that sensory gating P50 (also called P50 auditory evoked potential, P50) and dopaminergic neurotransmitters are related. In animal experiment, P50 can be recorded in an awake and quiet state with freedom of movement. Until now there is lack of animal experimental data on the supportive effect of estrogen on function of dopaminergic neurons in substantia nigra (SN) in physiological state. In the present study, female Sprague-Dawley (SD) rats were used as subjects. The animals were divided randomly into four groups: (1) control group (normal animals); (2) Parkinson's disease (PD) model group: the right SN was lesioned with 6-hydroxydopamine (6-OHDA); (3) PD model with bilateral ovariectomized group (OVX-PD): bilateral ovariectomy was performed before administration with 6-OHDA; (4) estrogen + PD model with bilateral ovariectomized group (OVX-E(2)-PD): physiological dose of estrogen was given to the bilateral ovariectomy animals before administration with 6-OHDA. P50 induced by two brief acoustic stimuli were recorded in the right SN and the number of TH(+) dopaminergic neurons in the SN stained by immunohistochemistry was calculated after the determination of P50. The results showed that in the PD model group, the testing/conditioning (T/C) ratio of P50 decreased by 40.60% and the number of TH(+) cells in the right SN decreased by 64.74% as compared with that in the control group (P<0.01); In the OVX-PD group, the T/C ratio of P50 decreased by 45.88% and the number of TH(+) cells was reduced by 57.26% as compared with that in the PD group (P<0.01). Administration with 6-OHDA into the SN pars compacta of ovariectomized rats caused more decrease in the number of TH(+) cells as well as more damage to the function of sensory gating in SN. While in OVX-E(2)-PD group, intramuscular injection with estrogen at physiological dose 3 d before 6-OHDA administration decreased the degree of damage to the SN functionally and morphologically, and its degree of injury corresponded to PD group. These results indicate that the mechanism of protection of dopaminergic neurons in the SN provided by physiological level of estrogen is by promoting the resistibility of the neurons to harmful stimulation. If the gonads are resected resulting in a lack of estrogen, the degree of injury to the function and morphology of dopaminergic neurons in SN induced by 6-OHDA increases. Replacement of estrogen at physiological level on time is necessary. Sensory gating P50 in SN may reflect dynamically the protection of estrogen against dopaminergic neurons depletion in vivo.

[Sexual dimorphisms of dopaminergic neurons in rat substantia nigra].

There are sex differences in some brain areas in mammalians. Parkinson's disease (PD), caused by the mesencephalic substantia nigra (SN) dopaminergic neuronal loss, displays sexual difference, i.e., the incidence is higher and the symptoms are more intense in males than that in females. However, it has not been known whether sexual dimorphisms exist in the SN. Sixty adult Sprague-Dawley rats were randomly divided into 5 groups: (1) Female intact group (F-INT group); (2) Male intact group (M-INT group); (3) Ovariectomized group (OVX group); (4) Castration group (CAST group); (5) Ovariectomized + estrogen-replaced group (OVX-E(2) group): The rats received sequentially physiological dose of estrogen for 3 d from the 7th day after ovariectomization. P50 auditory evoked potential (P50) was recorded for 14 d from electrodes inserted in the rat right SN in quiet and awake state. After recording, the brain tissues were dissected and the tyrosine hydroxylase (TH)-expressing neurons in the compact zone of the SN were counted using immunohistochemical method. The results showed that the number of TH-positive (TH(+)) cells in the SN of normal male animals was less than that in normal female rats (P<0.05), and the T/C ratio of P50 in normal males was significantly less than that in normal females (P<0.01), indicating that there exists sexual difference in function and structure in the SN. No differences in the T/C ratio of P50 or the number of TH(+) cells were found between M-INT and CAST groups. The T/C ratio of P50 and the number of TH(+) cells in the SN in OVX group were reduced significantly compared with those in F-INT group (P<0.01). There was no significant difference in the T/C ratio of P50 and the number of TH(+) cells in the SN between OVX- E(2) and F-INT groups 15-20 d after estrogen replacement, suggesting that estrogen can promote the survival and functional recovery of dopaminergic neurons in the SN. The results suggest that there exist sex-specific differences in the dopaminergic neurons in the SN structurally and functionally. The difference of estrogen level in cerebra between male and female animals may account for the sexual differences. Endogenous estrogen plays an important role in maintaining the integrity and modulating the functional activity of dopamine system in the SN.