Tunable temperature-responsive photonic ionogels with dual signals output.

Photonic ionogels with dual electrical and optical output have been intensively studied. However, tunable temperature-responsive photonic ionogel assembled by thermosensitive nanogels has not been studied yet. Herein, an innovative approach to fabricate photonic ionogels has been developed for smart wearable devices with tunable temperature sensitivity and structural color. Firstly, poly(isopropylacrylamide-r-phenylmaleanilic acid) P(NIPAm-r-NPMA) nanogels self-assemble into photonic crystals in 2-hydroxyethyl acrylate (HEA), water, and the ionic liquid of 1-ethyl-3-methylimidazolium trifluoromethanesulfonate. And then robust photonic ionogels are developed through a polymerization of 2-hydroxyethyl acrylate crosslinked by poly(ethylene glycol) diacrylate (PEGDA). The incorporation of the ionic liquid, 1-ethyl-3-methylimidazolium trifluoromethanesulfonate, enhances the mechanical strength of photonic ionogels and tunes the temperature-sensitivity of the ionogels, making them adaptable to various environmental conditions. The findings demonstrate that these ionogels can serve dual functions in smart wearable devices, combining electrical and optical signal outputs due to the conductivity of the ionic liquid and structural color from the nanogel assembly. The resultant photonic ionogels exhibit exceptional substrate adhesion, mechanical stability, and fast resilience. More significantly, the nanogels within these ionogels serve as the building blocks of photonic crystals (PCs) endow with angle-independent coloration and enhance stretchability beyond 200 %, while the stretchability of the ionogles without the nanogels is only about 100 %. Our photonic ionogels with tunable temperature-sensitivity and dual outputs will open an avenue to the development of the innovative smart wearable devices.

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery.

BACKGROUND: Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer (LC). This is achieved using either a thoracic paravertebral block (TPVB) or sufentanil (SUF)-based multimodal analgesia. However, the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction (POCD) remain unclear. AIM: To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes. METHODS: This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023. Patients receiving SUF-based multimodal analgesia (n = 50) and patients receiving TPVB + SUF-based multimodal analgesia (n = 57) were assigned to the control group and TPVB group, respectively. We compared the Ramsay Sedation Scale and visual analog scale (VAS) scores at rest and with cough between the two groups at 2, 12, and 24 h after surgery. Serum levels of epinephrine (E), angio-tensin II (Ang II), norepinephrine (NE), superoxide dismutase (SOD), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), and S-100 calcium-binding protein ß (S-100ß) were measured before and 24 h after surgery. The Mini-Mental State Examination (MMSE) was administered 1 day before surgery and at 3 and 5 days after surgery, and the occurrence of POCD was monitored for 5 days after surgery. Adverse reactions were also recorded. RESULTS: There were no significant time point, between-group, and interaction effects in Ramsay sedation scores between the two groups (P > 0.05). Significantly, there were notable time point effects, between-group differences, and interaction effects observed in VAS scores both at rest and with cough (P < 0.05). The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased (P < 0.05). The TPVB group had lower VAS scores than the control group at 2, 12, and 24 h after surgery (P < 0.05). The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group (P < 0.05). The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery (P < 0.05). Both groups had elevated serum E, Ang II, and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels, with better indices in the TPVB group (P < 0.05). Marked elevations in serum levels of VEGF, TGF-ß1, TNF-α, and S-100ß were observed in both groups at 24 h after surgery, with lower levels in the TPVB group than in the control group (P < 0.05). CONCLUSION: TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC, enhances analgesic effects, reduces postoperative stress response, and inhibits postoperative increases in serum VEGF, TGF-ß1, TNF-α, and S-100ß levels. This scheme also reduced POCD and had a high safety profile.

S100A8/A9hi neutrophils induce mitochondrial dysfunction and PANoptosis in endothelial cells via mitochondrial complex I deficiency during sepsis.

S100a8/a9, largely released by polymorphonuclear neutrophils (PMNs), belongs to the S100 family of calcium-binding proteins and plays a role in a variety of inflammatory diseases. Although S100a8/a9 has been reported to trigger endothelial cell apoptosis, the mechanisms of S100a8/a9-induced endothelial dysfunction during sepsis require in-depth research. We demonstrate that high expression levels of S100a8/a9 suppress Ndufa3 expression in mitochondrial complex I via downregulation of Nrf1 expression. Mitochondrial complex I deficiency contributes to NAD+-dependent Sirt1 suppression, which induces mitochondrial disorders, including excessive fission and blocked mitophagy, and mtDNA released from damaged mitochondria ultimately activates ZBP1-mediated PANoptosis in endothelial cells. Moreover, based on comprehensive scRNA-seq and bulk RNA-seq analyses, S100A8/A9hi neutrophils are closely associated with the circulating endothelial cell count (a useful marker of endothelial damage), and S100A8 is an independent risk factor for poor prognosis in sepsis patients.

Synthesis and thermally-induced gelation of interpenetrating nanogels.

Thermally-induced in-situ gelation of polymers and nanogels is of significant importance for injectable non-invasive tissue engineering and delivery systems of drug delivery system. In this study, we for the first time demonstrated that the interpenetrating (IPN) nanogel with two networks of poly (N-isopropylacrylamide) (PNIPAM) and poly (N-Acryloyl-l-phenylalanine) (PAphe) underwent a reversible temperature-triggered sol-gel transition and formed a structural color gel above the phase transition temperature (Tp). Dynamic light scattering (DLS) studies confirmed that the Tp of IPN nanogels are the same as that of PNIPAM, independent of Aphe content of the IPN nanogels at pH of 6.5 âˆ¼ 7.4. The rheological and optical properties of IPN nanogels during sol-gel transition were studied by rheometer and optical fiber spectroscopy. The results showed that the gelation time of the hydrogel photonic crystals assembled by IPN nanogel was affected by temperature, PAphe composition, concentration, and sequence of interpenetration. As the temperature rose above the Tp, the Bragg reflection peak of IPN nanogels exhibited blue shift due to the shrinkage of IPN nanogels. In addition, these colored IPN nanogels demonstrated good injectability and had no obvious cytotoxicity. These IPN nanogels will open an avenue to the preparation and thermally-induced in-situ gelation of novel NIPAM-based nanogel system.

Preparation and properties of hydrogel photonic crystals assembled by biodegradable nanogels.

Thermally induced physical hydrogels formed through the sol-gel transition of nanogels usually lose structural color above phase transition temperature (Tp). Herein, temperature/pH/redox-responsive nanogels that undergo sol-gel transition still keep structural colors above the Tp have been synthesized and studied. N-isopropylacrylamide (NIPAm) was copolymerized with N-tert-butylacrylamide (TBA) and N-acrylamido-l-phenylalanine (Aphe) to form P(NIPAm/TBA/Aphe) nanogel crosslinked with N,N'-bis(acryloyl)cystine (BISS) (referred to as PNTA-BISS). PNTA-BISS nanogel with a broad range of biodegradable crosslinker BISS content can achieve a reversible sol-gel transition above the Tp, surprisingly, while PNTA nanogels with a comparable content of biodegradable N,N'-Bis(acryloyl)cystam (BAC) crosslinker (referred to as PNTA-BAC) didn't form sol-gel transition. Although BISS and BAC possess same disulfide bonds with redox properties, BISS, unlike BAC, is water-soluble and features two carboxyl groups. The mechanism by which PNTA-BISS nanogels form hydrogel photonic crystals has been deeply explored with temperature-variable NMR. The results showed the introduction of Aphe with both steric hindrance and carboxyl groups greatly slowed down the shrinkage of PNTA-BISS nanogels. Therefore, PNTA-BISS nanogels can form sol-gel transition and further structural color of hydrogel photonic crystals due to carboxyl groups above the Tp. Furthermore, the properties of biodegradable hydrogel photonic crystals above the Tp were investigated for the first time, attributed to the presence of the strong reducing agent 1,4-dithiothreitol (DTT). When loaded with doxorubicin (DOX), PNTA-BISS exhibited favorable degradation properties under the influence of DTT. In summary, the PNTA-BISS nanogel, in addition to its in-situ gelation capabilities, demonstrated degradability, potentially providing a novel nanoplatform for applications in drug delivery, biotechnology, and related fields.

Remarkable sol-gel transition of PNIPAm-based nanogels via large steric hindrance of side-chains.

While the block/graft/branched structures are widely studied to favor the reversible physical gelation, there are no reports regarding the steric hindrance-induced sol-gel transition of PNIPAm-based nanogels above their phase transition temperature (Tp). Generally, the introduction of hydrophobic components into poly (N-isopropylacrylamide) (PNIPAm)-based nanogels only led to collapse and lower viscosity instead of the sol-gel transition upon heating above the Tp. Herein, the results of temperature-variable 1HNMR and FTIR confirm that the introduction of hydrophobic N-tert-butylacrylamide (TBA) with the large steric hindrance of side groups of N-tert-butyl to form NIPAm/TBA copolymer nanogels can dramatically slow down the dehydration of all the hydrophobic alkyl groups, thus resulting in the formation of thermally induced sol-gel transition above the Tp. Furthermore, the N-acrylamido-L-phenylalanine (APhe) monomer composed of a strongly water absorbing carboxyl group and a phenyl group with larger steric hindrance is studied to form P(NIPAm/TBA/APhe) terpolymer nanogels which can self-assemble into colorful colloidal crystals. Surprisingly, owing to the synergistic effect between the water absorbing carboxyl group and the steric hindrance group on the same side group, these colloidal crystals can achieve sol-gel transition above Tp, forming a physically crosslinked colorful hydrogel. This work is expected to greatly advance the design, synthesis, and application of the sol-gel transition of PNIPAm-based nanogel systems.

Identification of a novel 5-methylcytosine-related signature for prognostic prediction of kidney renal papillary cell carcinoma and a Putative target for drug repurposing.

BACKGROUND: Many studies have demonstrated the crucial roles of 5-methylcytosine (m5C) RNA methylation in cancer pathogenesis. METHODS: Two datasets, including TCGA-KIRP and ICGC, and related clinical information were downloaded, where the expression of 13 m5C regulators was examined. We applied LASSO regression to construct a multi-m5C-regulator-based signature in the TCGA cohort, which was further validated using the ICGC cohort. Univariate and multivariate Cox regressions were applied to evaluate the independent prognostic value of our model. The differences in biological functions and immune characterizations between high and low-risk groups divided based on the risk scores were also investigated via multiple approaches, such as enrichment analyses, mutation mining, and immune scoring. Finally, the sensitivities of commonly used targeted drugs were tested, and the connectivity MAP (cMAP) was utilized to screen potentially effective molecules for patients in the high-risk group. Experimental validation was done following qPCR tests in Caki-2 and HK-2 cell lines. RESULTS: 3 m5C regulators, including ALYREF, DNMT3B and YBX1, were involved in our model. Survival analysis revealed a worse prognosis for patients in the high-risk group. Cox regression results indicated our model's superior predictive performance compared to single-factor prognostic evaluation. Functional enrichment analyses indicated a higher mutation frequency and poorer tumor microenvironment of patients in the high-risk group. qPCR-based results revealed that ALYREF, DNMT3B, and YBX1 were significantly up-regulated in Caki-2 cell lines compared with HK-2 cell lines. Molecules like BRD-K72451865, Levosimendan, and BRD-K03515135 were advised by cMAP for patients in the high-risk group. CONCLUSION: Our study presented a novel predictive model for KIRP prognosis. Furthermore, the results of our analysis provide new insights for investigating m5C events in KIRP pathogenesis.

TNFα Enhances Calcium Influx by Interacting with AMPA Receptors in the Spinal Dorsal Horn Neurons.

Tumor necrosis factor alpha (TNFα) is a proinflammatory cytokine and has been implicated in pain regulation. Neuronal activity in the spinal dorsal horn contributes to nociceptive transmission. However, it is not fully understood how TNFα affects the activity of spinal dorsal horn neurons. In the present study, we used calcium imaging to characterize the mechanism by which TNFα regulates calcium influx in the cultured spinal dorsal horn neurons. We observed that TNFα incubation caused an increase in fluorescent intensity of Fura-2, a specific intracellular calcium indicator, in the cultured spinal dorsal horn neurons, and such effect was significantly inhibited by co-incubation with R7050, a selective TNFα receptor antagonist, which suggests that TNFα can enhance calcium influx and increase neuronal activity via activating TNFα receptors in the spinal dorsal horn. Using double immunofluorescence staining, we showed that TNFα receptors were co-expressed with a-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor subunit GluA1 in the spinal dorsal horn neurons. We further observed that treatment with 1-naphthyl acetyl spermine (NASPM), a specific calcium-permeable AMPA receptor blocker, completely blocked the effect of TNFα incubation on calcium influx in the cultured neurons. Moreover, lipopolysaccharide (LPS)-induced calcium influx was inhibited by co-incubation with R7050. Together, our results suggest that TNFα in the spinal dorsal horn can increase calcium-indicated neuronal activity through the interaction between its receptor and calcium-permeable AMPA receptors.

Investigation of the Effects of Opioids on Microglial Nitrite and Nitric Oxide Synthase (iNOS) Production and Phagocytosis during Inflammation.

AIM: This study aimed to investigate how opioids affect phagocytosis and microglial nitrite and nitric oxide synthase (iNOS) production during inflammation. BACKGROUND: Opioids are a group of chemicals that are naturally found in the opium poppy plant and exert a variety of effects on the brain, including pain alleviation in some cases. They are commonly used in surgery and perioperative analgesia. However, research on the impact of opioids on microglial inflammatory factor production and phagocytosis is limited. OBJECTIVES: This study was designed to investigate the effects of opioids on inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) generation. Moreover, the influence of opioids on the engulfment of C8-B4 microglial cells after stimulation with LPS was also examined. METHODS: C8-B4 mouse microglial cells were exposed to various concentrations of opioids after stimulation with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Nitrite production was assayed. The iNOS and Cox-2 were determined by Western blotting, and fluorescent immunostaining was performed to assess the percentage of microglia that engulfed fluorescent microspheres in total microglia cultivating with opioids after being activated by LPS. RESULTS: After LPS and IFN-γ stimulation, microglia produced lower amounts of nitric oxide (NO) production with buprenorphine, salvinorin A, and naloxone (P<0.05). When combined with naloxone, no significant differences were found than buprenorphine. It was observed that buprenorphine and salvinorin A could suppress iNOS expression activated by LPS and IFN-γ. Phagocytosis was greatly increased after LPS stimulation, and a significant increase was observed after adding salvinorin A. CONCLUSION: Buprenorphine and salvinorin A were found to reduce NO production and iNOS induction in microglial cells activated by LPS and IFN-γ. Salvinorin A promoted the phagocytosis of microglia cells treated by LPS.

Anemia tolerance versus blood transfusion on long-term outcomes after colorectal cancer surgery: A retrospective propensity-score-matched analysis.

Background: Perioperative anemia and transfusion are intertwined with each other, and both have adverse impacts on the survival of colorectal cancer (CRC) patients. But the treatment of anemia still relies on transfusion in several countries, which leads us to question the effects of anemia tolerance and transfusion on the long-term outcomes of CRC patients. We investigated the combined effect of preoperative anemia and postoperative anemia and of preoperative anemia and blood transfusion, which imposes a greater risk to survival, to compare the effects of anemia tolerance and transfusion on overall survival (OS) and disease-free survival (DFS) in patients undergoing CRC surgery. Methods: A retrospective propensity-score-matched analysis included patients with CRC undergoing elective surgery between January 1, 2008, and December 31, 2014. After propensity-score matching, Kaplan-Meier survival analysis and univariable and multivariable Cox proportional hazards models were used to study the prognostic factors for survivals. In univariate and multivariate Cox regression analysis, two novel models were built. Results: Of the 8,121 patients with CRC, 1,975 (24.3%) and 6,146 (75.7%) patients presented with and without preoperative anemia, respectively. After matching, 1,690 patients remained in each group. In the preoperative anemia and postoperative anemia model, preoperative anemia and postoperative anemia was independent risk factor for OS (HR, 1.202; 95% CI, 1.043-1.385; P=0.011) and DFS (HR, 1.210; 95% CI, 1.050-1.395; P=0.008). In the preoperative anemia and transfusion model, preoperative anemia and transfused was the most dangerous independent prognostic factor for OS (HR, 1.791; 95% CI, 1.339-2.397; P<0.001) and DFS (HR, 1.857; 95% CI, 1.389-2.483; P<0.001). In patients with preoperative anemia, the OS and DFS of patients with transfusion were worse than those of patients without transfusion (P=0.026 in OS; P=0.037 in DFS). Conclusions: Preoperative anemia and blood transfusion imposed a greater risk to OS and DFS in patients undergoing CRC surgery, indicating that the harm associated with blood transfusion was greater than that associated with postoperative anemia. These findings should encourage clinicians to be vigilant for the timely prevention and treatment of anemia, by appropriately promoting toleration of anemia and restricting the use of blood transfusion in patients with CRC.

Neutrophil extracellular traps-triggered impaired autophagic flux via METTL3 underlies sepsis-associated acute lung injury.

Neutrophil extracellular traps (NETs) assist pathogen clearance, while excessive NETs formation is associated with exacerbated inflammatory responses and tissue injury in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Autophagy is generally considered to be a protective process, but autophagy dysfunction is harmful. Whether and how NETs affect autophagic flux during sepsis-induced ALI are currently unknown. Here, we confirmed that the level of NETs was increased in ARDS patients and mice models, which led to impairment of autophagic flux and deterioration of the disease. Mechanistically, NETs activated METTL3 mediated m6A methylation of Sirt1 mRNA in alveolar epithelial cells, resulting in abnormal autophagy. These findings provide new insights into how NETs contribute to the development of sepsis-associated ALI/ARDS.

Differential Effects of Sevoflurane Exposure on Long-Term Fear Memory in Neonatal and Adult Rats.

It remains unclear whether exposure to sevoflurane produces different effects on long-term cognitive function in developing and mature brains. In the present study, Sprague-Dawley neonatal rats at postnatal day (PND) 7 and adult rats (PND 56) were used in all experiments. We performed fear conditioning testing to examine long-term fear memory following 4-h sevoflurane exposure. We assessed hippocampal synapse ultrastructure with a transmission electron microscope. Moreover, we investigated the effect of sevoflurane exposure on the expression of postsynaptic protein 95 (PSD-95) and its binding protein kalirin-7 in the hippocampus. We observed that early exposure to sevoflurane in neonatal rats impairs hippocampus-dependent fear memory, reduces hippocampal synapse density, and dramatically decreases the expressions of PSD-95 and kalirin-7 in the hippocampus of the developing brain. However, sevoflurane exposure in adult rats has no effects on hippocampus-dependent fear memory and hippocampal synapse density, and the expressions of PSD-95 and kalirin-7 in the adult hippocampus are not significantly altered following sevoflurane treatment. Our results indicate that sevoflurane exposure produces differential effects on long-term fear memory in neonatal and adult rats and that PSD-95 signaling may be involved in the molecular mechanism for early sevoflurane exposure-caused long-term fear memory impairment.

In situ formed thermogelable hydrogel photonic crystals assembled by thermosensitive IPNs.

In this paper, soft thermosensitive photonic crystals are immobilized via a reversible temperature-triggered in situ sol-gel transition above their phase transition temperature (Tp), which may be a significant advance in the field. Specifically, a library of thermosensitive poly(N-isopropylacrylamide)/poly(acrylic acid) (PNIPAm/PAA) interpenetrating nanogels (IPNs) is synthesized, which can achieve a reversible temperature-induced sol-gel transition at a low concentration (1.1 wt%). More interestingly, as the temperature is increased above Tp, the photonic crystals assembled by these IPNs do not disappear but are "immobilized" in the in situ formed hydrogel matrix. Moreover, these colorful IPN dispersions exhibit outstanding syringe-injectability, immediately turning from an aqueous solution into an insoluble hydrogel as they are injected into PBS at 37 °C. Plus, a protein-release study showed that these injectable hydrogels show extended release times and slower release rates in comparison with dilute nanogel dispersions. In brief, these in situ formed hydrogels with brilliant structural colors have potential in optical applications, e.g., color displays, crystal immobilization, and biological applications, e.g., 3D cell culture and drug delivery.

Effect of Blood Transfusion on Short- and Long-Term Outcomes in Oral Squamous Cell Carcinoma Patients Undergoing Free Flap Reconstruction.

Purpose: To analyze the short- and long-term effect of perioperative blood transfusion (PBT) in patients undergoing surgical treatment for oral squamous cell carcinoma (SCC). Methods: Patients undergoing free flap reconstruction were retrospectively enrolled and divided into two groups based on the implementation of PBT. Flap revision, surgical site infection (SSI), flap failure, overall survival (OS), and disease-specific survival (DSS) were compared between the two groups. Results: In 170 patients with PBT, 10 (5.9%) flaps required exploration revision, SSI occurred in 18 (10.6%) patients, and flap necrosis was noted in 6 (3.5%) patients. These rates were comparable to those in patients without PBT. The two groups had similar DSS rates, but the 5-year OS rates were 49 and 59% in patients with PBT and without PBT, respectively. This difference was significant. Patients with 4 units of PBT had OS rates comparable to those of patients with >4 units of PBT. A Cox model confirmed the fact that the decrease in OS was independent of PBT. Conclusion: In patients with free flap reconstruction for oral SCC, PBT did not increase the short-term complication rate or cancer-linked mortality. However, it was related to an elevated overall risk of death.

Emulsions stabilized by highly hydrophilic TiO2 nanoparticles via van der Waals attraction.

HYPOTHESIS: Highly hydrophilic nanoparticles are generally considered not suitable for stabilizing Pickering emulsions, since they could not be effectively wetted by the oil phase at the water-oil interface. However, highly hydrophilic nanoparticles with good dispersity are possibly absorbed and packed onto the surface of the oil droplets in water via the van der Waals attraction between the nanoparticles and the oil droplets. Hence, a novel "van der Waals emulsion" should be possible to be stabilized by highly hydrophilic nanoparticles. EXPERIMENTS: Oil-in-water emulsions solely stabilized by pristine TiO2 nanoparticles (i.e., TiO2 without any modification or additives) were prepared. The emulsification behavior under varying pH value, oil fraction, particle content and temperature of the emulsion were explored. Composite wax-based beads which encapsulated chemical sunscreen and was coated by TiO2 nanoparticles, was also fabricated using the obtained emulsion as the templates. FINDINGS: The emulsions displayed the highest stability near the isoelectric points of the TiO2 nanoparticles, which was attributed to the van der Waals attraction between TiO2 nanoparticles and oil droplets. Such mechanism was supported by a theoretical analysis based on calculation of the Hamaker constants and experimental evidences. Therefore, this work presents a simple, general and green method for preparing particle-stabilized emulsions.

Identification of microRNA-451a as a Novel Circulating Biomarker for Colorectal Cancer Diagnosis.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Successful treatment of CRC relies on accurate early diagnosis, which is currently a challenge due to its complexity and personalized pathologies. Thus, novel molecular biomarkers are needed for early CRC detection. METHODS: Gene and microRNA microarray profiling of CRC tissues and miRNA-seq data were analyzed. Candidate microRNA biomarkers were predicted using both CRC-specific network and miRNA-BD tool. Validation analyses were carried out to interrogate the identified candidate CRC biomarkers. RESULTS: We identified miR-451a as a potential early CRC biomarker circulating in patient's serum. The dysregulation of miR-451a was revealed both in primary tumors and in patients' sera. Downstream analysis validated the tumor suppressor role of miR-451a and high sensitivity of miR-451a in CRC patients, further confirming its potential role as CRC circulation biomarker. CONCLUSION: The miR-451a is a potential circulating biomarker for early CRC diagnosis.

Propofol suppresses hypoxia-induced esophageal cancer cell migration, invasion, and EMT through regulating lncRNA TMPO-AS1/miR-498 axis.

BACKGROUND: Propofol has been reported to be related to the migration, invasion, and epithelial-mesenchymal transition (EMT) of esophageal cancer (EC) cells. However, the detailed mechanism has not yet been fully reported. The purpose of this research was to elucidate the function of long non-coding RNA TMPO antisense RNA 1 (lncRNA TMPO-AS1) and microRNA-498 (miR-498) in propofol-regulated EC. METHODS: Transwell assay was performed to assess cell migratory and invasive abilities. Western blot assay was employed to determine the levels of EMT markers and hypoxia inducible factor-1 (HIF-1α). Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to detect the levels of TMPO-AS1 and miR-498. Moreover, the interaction between TMPO-AS1 and miR-498 was predicted by starBase, and then confirmed by the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: Propofol suppressed hypoxia-induced EC cell migration, invasion, and EMT. Both TMPO-AS1 overexpression and miR-498 knockdown weakened the effect of propofol on hypoxia-induced EC cell progression. Interestingly, TMPO-AS1 targeted miR-498 and suppressed miR-498 expression. TMPO-AS1 regulated EC cell progression via downregulating miR-498 expression. CONCLUSIONS: Collectively, our findings demonstrated that propofol inhibited hypoxia-induced EC cell mobility through modulation of the TMPO-AS1/miR-498 axis, providing a theoretical basis for the treatment of EC.

Propofol facilitates cisplatin sensitivity via lncRNA MALAT1/miR-30e/ATG5 axis through suppressing autophagy in gastric cancer.

AIMS: Recently, chemoresistance has been recognized as an obstacle in the treatment of gastric cancer (GC). The aim of this study was to investigate the biological functions and underlying mechanisms of propofol in GC chemoresistance. MAIN METHODS: CCK-8 assay, flow cytometry and immunofluorescent staining were performed to assess the IC50 concentration, cell apoptosis and autophagy activity of cisplatin in both GC chemosensitive cells (SGC7901) and chemoresistant cells (SGC7901/CDDP). The expression pattern of MALAT1 in GC cells was detected by qRT-PCR. The shRNAs and overexpressing plasmids were employed for the loss or gain-of-function. Dual-luciferase reporter assay was subjected to verify the binding relationship between MALAT1 and miR-30e. Besides, ATG5 mRNA and protein levels were determined using qRT-PCR and western blot analysis. Furthermore, GC xenograft mice model was established to validate the in vitro findings. KEY FINDINGS: Chemoresistant GC cells presented higher IC50 of cisplatin, increased autophagy activity and stronger expression of MALAT1. The application of propofol promoted cell apoptosis and reduced the activity of autophagy through downregulating MALAT1. Silencing of MALAT1 inhibited chemo-induced autophagy, whereas MALAT1 overexpression promoted autophagy in GC cells. Mechanistic researches demonstrated that MALAT1 could bind with miR-30e to regulate ATG5 expression, thus causing the suppression of autophagy. In vivo GC xenograft model treated with both propofol and cisplatin also showed significantly decreased tumor size and weight, which was enhanced by knockdown of MALAT1. SIGNIFICANCE: Altogether, our study revealed a novel mechanism of propofol of lncRNA MALAT1/miR-30e/ATG5 mediated autophagy-related chemoresistance in GC, casting new lights on the understanding of propofol.

Effects of propofol on colon cancer metastasis through STAT3/HOTAIR axis by activating WIF-1 and suppressing Wnt pathway.

BACKGROUND: In the present study, we aim to investigate the potential role of propofol in the tumor progression of colon cancer. METHODS: Human colon cancer cell lines were cultured and exposed with 8 µg/mL propofol. RNA interference was performed to silence the expression of HOTAIR or STAT3 to explore their biological functions in colon cancer. Cell apoptosis and invasion were assessed using flow cytometry and transwell assays, respectively. Quantitative real-time PCR, western blot, and immunohistochemistry were subjected to measure the expression patterns of HOTAIR, STAT3, Wnt signaling factors, and epithelial-mesenchymal transition-related markers, respectively. Besides, nude mice were transplanted with colon cancer cells for further exploration. Tumor formation, volume, and weight were evaluated to validate the in vitro findings. RESULTS: Propofol treatment promoted cell apoptosis and inhibited cell invasion in colon cancer cells, while the effects were reversed by HOTAIR overexpression. Additionally, STAT3 positively regulated HOTAIR expression, which was also negatively modulated by propofol. Moreover, STAT3 and HOTAIR were shown to independently regulate colon cancer cell apoptosis and invasion. Furthermore, HOTAIR could stimulate Wnt signaling pathway via inhibiting WIF-1 expression and upregulating ß-catenin expression, which was also demonstrated by in vivo study. CONCLUSION: Taken together, the current study demonstrated that propofol exerts the inhibition on cell invasion and promotion on cell apoptosis through regulating STAT3/HOTAIR by activating WIF-1 and suppressing Wnt pathway, indicating that propofol might serve as a therapeutic role for colon cancer patients in the future.

Role of estradiol in mediation of etomidate-caused seizure-like activity in neonatal rats.

BACKGROUND: The goal of this study was to investigate the effect of estradiol in mediation of electroencephalogram (EEG) abnormality induced by etomidate in neonatal rats. METHODS: Sprague-Dawley rats were anesthetized using intraperitoneal etomidate for 2 h on postnatal days (P) 4, 5, or 6 and recorded electroencephalogram in two ways. First, pups were recorded EEG two and a half hours under etomidate anesthesia, in subgroups, estradiol receptor antagonist ICI182780 and estradiol synthase inhibitor formestane were given subcutaneously in male rats 15 min prior to etomidate. Second, pups were anesthetized with etomidate for 2 h on P4,5 or 6 and then recovered from anesthesia, EEG were recorded for one hour in two postnatal periods of P9-P11 and P14-P16. Subgroup rats that received bumetanide, NKCC1 inhibitor, to test the NKCC1-GABAAR signaling effect on neonatal brain development, negative control groups and maternally separated for 2 h on P4, 5, or 6 were studied in 16 groups. Each group's n was = 8. RESULTS: Male pups showed more severe seizure-like activities than female pups in P4-P6 under etomidate anesthesia. Pups pretreated with ICI182780 and formestane showed a less abnormalities of EEG in male rats. Etomidate caused seizure-like activity in P4-P6 could extend to P9-P11, but not seen in P14-P16, Pretreated with bumetanide only alleviated abnormalities in male pups other than female in P9-P11. CONCLUSIONS: Estradiol involves in the NKCC1-GABAAR mediated seizure-like activity caused by etomidte in neonatal rats and these the abnormality lasts near two weeks.