Local anesthetic bupivacaine inhibits proliferation and metastasis of hepatocellular carcinoma cells via suppressing PI3K/Akt and MAPK signaling.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Retrospective studies suggest that using local/regional anesthetic (LA/RA) is associated with better outcomes in primary HCC patients. In this study, we evaluated the effects of LA/RA bupivacaine in HCC cells and the underlying molecular mechanisms. The biological functions of bupivacaine in HCC cells were evaluated by transcriptome RNA sequencing, cell viability assay, bromodeoxyuridine incorporation assay, colony formation assay, flow cytometry, western blot, wound healing assay, transwell cell migration assay, tumor xenograft formation, and lung metastasis assay. Bupivacaine suppressed proliferation and induced apoptosis of HepG2 and SNU-449 cells in a time- and dose-dependent manner. Bupivacaine treatment also decreased colony formation, migration, and invasion of HepG2 and SNU-449 cells. In mouse models, bupivacaine repressed tumor xenograft growth and lung metastasis of HepG2 cells. Transcriptome sequencing of HepG2 cells suggested that PI3K/Akt and MAPK signaling pathways were suppressed by bupivacaine treatment. In western blot analysis, bupivacaine reduced the expression of total and phosphorylated Akt, mTOR, and MAPK. Furthermore, reactivated PI3K/Akt and MAPK signaling by EGF or NRG1 partially reversed the effects of bupivacaine on cell growth, colony formation, and invasion of HCC cells. Local anesthetic bupivacaine suppressed proliferation, migration and invasion, and induced apoptosis of HCC cells. Our results provided novel insights into the local anesthetic bupivacaine in the therapy of HCC patients.

Rhein Inhibits the Migration of Ovarian Cancer Cells through Down-Regulation of Matrix Metalloproteinases.

The root of Rheum officinale BAILL as a traditional Chinese medicine, which main function is removing heat from the blood, promoting blood circulation and clearing toxins away. Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is one of the most important active components in the root of Rheum officinale BAILL, which could inhibit the proliferation of tumor cells. However, the study on the mechanism of anti-cell migration capacity of Rhein on ovarian cancer is not yet clear. Here, we demonstrated that Rhein had dose-dependent effects of ovarian tumors on drugs and could inhibit the proliferations and migration of two typical ovarian cancer cell lines, A2780 and OV2008. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that the survival rate of ovarian cancer cells was significantly decreased when treated with Rhein. Rhein inhibited the proliferation of ovarian cancer cells in dose-dependent manner. Moreover, the wound healing assay and transwell assay indicated that the cell migratory potential and expression of matrix metalloproteinases were markedly inhibited by Rhein. Our findings suggested that Rhein could be a potential candidate to be developed as a drug for the prevention of ovarian cancer cell migration.

[Discovery of topiramate's new functions based on medicinal property combinations and study on its mechanism].

OBJECTIVE: To study topiramate's new functions according to the medicinal property combinations, in order to apply the traditional Chinese medicinal theory in discovering new purposes of old drugs. METHOD: According to New Traditional Chinese Medicinal Families--Chemical Traditional Chinese Medicines, the authors found out topiramate's property. Then based on the therapeutic principle of diabetes, hypertension, epilepsy and lung cancer, as well as the relations of efficacies and medicinal property combinations, they summarized the corresponding medicinal property combination modes, compared topiramate's medicinal property combination mode with corresponding medicinal property combination modes of these diseases, and predict topiramate's new functions. RESULT: According to the comparison, the corresponding medicinal property combinations were consistent with topiramate's medicinal property combinations as evidenced by corresponding literatures, whereas other medicinal property combinations were not. CONCLUSION: Based on medicinal property combination modes, the authors screened topiramate's new functions according to e of TCM clinical experience, discovered topiramate's therapeutic effects on diabetes, hypertension and lung cancer in addition to epilepsy, and explore new drug function according to medicinal property combination modes, which could help greatly shorten the new drug R&D period.

[Design of traditional Chinese medicines with antihypertensive components based on medicinal property combination modes].

Multi-component traditional Chinese medicines are an innovative research mode for traditional Chinese medicines. Currently, there are many design methods for developing multi-component traditional Chinese medicines, but their common feature is the lack of effective connection of the traditional Chinese medicine theory. In this paper, the authors discussed the multi-component traditional Chinese medicine design methods based on medicinal property combination modes, provided the combination methods with the characteristics of traditional Chinese medicine for the prescription combinations, and proved its feasibly with hypertension cases.

High-Compressive, Elastic, and Wearable Cellulose Nanofiber-Based Carbon Aerogels for Efficient Electromagnetic Interference Shielding.

Developing excellent electromagnetic interference (EMI) shielding materials with robust EMI shielding efficiency (SE), high mechanical performance, and multifunctionality is imperative. Carbon materials are well recognized as promising alternatives for high-performance EMI shielding, but their high brittleness greatly hampers their applications. In this work, a cellulose nanofiber/reduced graphene oxide-glucose carbon aerogel (C-CNFs/rGO-glu) with high compression, elasticity, and excellent EMI shielding performance was fabricated by directional freeze-drying followed by carbonization. Specifically, the height and stress retention are 88% and 90.9%, respectively, after 100 cycles of compression release at a high strain of 70%. The electromagnetic shielding effectiveness of the aerogels reached 67.5 dB and presented an absorption-dominant shielding mechanism with a 97.5% absorption loss ratio. Further, the carbon aerogel could capture subtle electrical signals to monitor different human behaviors and showed excellent heat insulation and infrared stealth performance.

Wood aerogels decorated amino-functionalized MIL-101(Cr) as efficient filter for multistage purification of wastewater.

Exploring novel water purifier to efficiently remove heavy metal ions from the wastewater is of vital importance. Inspired by the hierarchical structure of natural wood and the chelation of amino group, a high-efficiency water purifier with ethylenediamine functionalized MIL-101(Cr) octahedrons anchored on the wood aerogel (MIL-101(Cr)-ED/WA) was constructed. Benefiting from the two-pronged approach with the hierarchical structure of the wood aerogel frame for multistage filtration and the -NH2 that capable of chelation with metal ions, the fabricated MIL-101(Cr)-ED/WA exhibits excellent water purification performances, and its adsorption capacity of toxic Pb2+ ions could reach up to 6.46 mmol g-1. Furthermore, it demonstrates superior recyclability without secondary pollution and is also suitable for simultaneous treatment of multiple metal species. In general, this work will broaden the utilization of wood-based structural engineering materials in the treatment of heavy metal wastewater.

A Study on the Material Removal Characteristics and Damage Mechanism of Lapping for Pressureless Sintered Silicon Carbide (SSiC) Microlens Cavity.

Microlens arrays have been widely employed to control the reflection, refraction, and diffraction characteristics of light due to its distinctive surface properties. Precision glass molding (PGM) is the primary method for the mass production of microlens arrays, of which pressureless sintered silicon carbide (SSiC) is a typical mold material due to its excellent wear resistance, high thermal conductivity, high-temperature resistance, and low thermal expansion. However, the high hardness of SSiC makes it hard to be machined, especially for optical mold material that requires good surface quality. The lapping efficiency of SSiC molds is quite low. and the underlying mechanism remains insufficiently explored. In this study, an experimental study has been performed on SSiC. A spherical lapping tool and diamond abrasive slurry have been utilized and various parameters have been carried out to achieve fast material removal. The material removal characteristics and damage mechanism have been illustrated in detail. The findings reveal that the material removal mechanism involves a combination of ploughing, shearing, micro-cutting, and micro-fracturing, which aligns well with the results obtained from finite element method (FEM) simulations. This study serves as preliminary reference for the optimization of the precision machining of SSiC PGM molds with high efficiency and good surface quality.

Tramadol suppresses growth of orthotopic liver tumors via promoting M1 macrophage polarization in the tumor microenvironment.

Tumor-associated macrophages (TAMs) are major infiltrating immune cells in liver cancer. They are polarized to anti-tumor M1 type or tumor-supporting M2 type in a dynamic changing state. Tramadol, a synthetic opioid, exhibits tumor-suppressing effect in several cancers, but whether it plays a role in TAMs polarization is uncertain. In the present study, the potential influence of tramadol on TAMs polarization was explored in liver cancer. An orthotopic murine Hepa 1-6 liver cancer model was constructed. The potential function of tramadol was evaluated by cell viability assay, EdU incorporation assay, flow cytometry, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) assay, T cell proliferation and suppression assays and western blot. We found that tramadol suppressed proliferation and tumor formation of murine Hepa 1-6 cells in vitro and in vivo. Tramadol reprogramed the immune microenvironment to favor M1 macrophage polarization in orthotopic Hepa 1-6 tumors. Moreover, tramadol facilitated M1 macrophage polarization and inhibited M2 macrophage polarization of bone marrow-derived macrophages (BMDMs) and human THP-1 macrophages in vitro. Furthermore, tramadol-treated BMDMs promoted proliferation and activation of splenic CD4+ and CD8+ T cells. Tramadol induced cellular ROS production and mitochondrial dysfunction of BMDMs. Finally, tramadol activated NF-κB signaling in BMDMs and THP-1 macrophages, while inhibition of NF-κB signaling by JSH-23 attenuated the influence of tramadol on macrophage polarization. In conclusion, these data elucidated a novel anti-tumor mechanism of tramadol in liver cancer. Tramadol might be a promising treatment strategy for liver cancer patients.

Bed separation backfill to reduce surface cracking due to mining under thick and hard conglomerate: a case study.

After coal mining, the surface above a goaf may experience the discontinuous deformation under some special geological and mining conditions, such as surface cracking, surface step subsidence and collapse pits. Discontinuous deformation seriously threatens the safety of surface buildings and infrastructures. In this paper, the mechanism of discontinuous surface deformation and surface cracking due to coal mining under thick and hard conglomerate in the Huafeng coal mine was studied using a simulation test on similar materials. Bed separation backfill was then proposed to control surface cracking and to protect the Luli bridge. Because of lithological differences between the conglomerate and relatively weak red strata (beneath the conglomerate), the bed separation occurred between them with the advancement of the working face. When the bed separation span exceeded its breaking span, the conglomerate fractured, causing surface cracking of the downhill area and seriously damaging the stability of the Luli bridge. Three drilling holes were arranged along the strikes of the 1412 and 1613 working faces and nearly 387 000 m3 of backfill materials (water, fly ash and gangue powder) were injected into the bed separation space to reduce or prevent fracturing of the conglomerate. The compacted backfill body supported the conglomerate and reduced the subsidence of the basin and surface 'rebound' deformation at the edge of the subsidence basin. Clay in the red strata expanded upon contact with water, and this further backfilled the bed separation zone and supported the conglomerate. The upper and lower structures and foundation of the bridge were reinforced using various methods. It was shown that bed separation backfill effectively controlled conglomerate movement and protected the bridge with a maximum subsidence of 251 mm. No obvious surface cracks were observed near the Luli bridge.

Preliminary report on Sichuan golden snub-nosed monkeys (Rhinopithecus roxellana roxellana) at Laohegou Nature Reserve, Sichuan, China.

Comparative studies of subspecies under different ecological environments offer insights into intraspecies evolutionary adaptive mechanisms. Golden snub-nosed monkeys (Rhinopithecus roxellana) include three subspecies in China classified mainly by their morphological variations: R. r. roxellana (Sichuan and Gansu province), R. r. qinlingensis (Shaanxi province) and R. r. hubeiensis (Hubei province). These three subspecies live in three isolated area with different environments. Past works focused on the last two subspecies, but little information of habitat and behaviors of the nominated subspecies (R. r. roxellana) is available to date. We conducted a two-year study on the diet, activity budget, home range and social organization of 4 herds of R. r. roxellana, based on a total of 106 days' observation in Laohegou (LHG) Nature Reserve, Sichuan province. By using scan sampling method, our results suggest that the R. r roxellana feeds predominantly on leaves (77.5%), and spends more time feeding (40.0%) and resting (27.0%) while compared to the other two subspecies. Kernel Density Estimation Method based on GPS technology confirms that R. r roxellana has relatively larger home ranges (49.1 km2). The unit size (8.3 ± 3.5 individuals) of R. r roxellana is also smaller. Therefore, it is possible that differences in food availability in relation to habitats have important impacts on the feeding strategy and social system of the golden snub-nosed monkey. These results provide data to further explore intraspecific adaptations of living primates.

Clinical application of modified double tracks anastomosis in proximal gastrectomy.

We compared the outcome of two surgical alimentary canal reconstruction methods after proximal gastrectomy. Three hundred ninety-six patients who underwent a radical proximal gastrectomy were randomized into two groups. Group A was treated with modified double tracks anastomosis, and Group B was treated with esophagus-remnant stomach direct anastomosis. Outcome measures were hematological indices, prognostic nutritional index (PNI), plasma hormone concentrations, and Visick index. The operative times in Groups A and B were 210 ± 53 and 150 ± 75 minutes and the hemorrhage volume was 173 ± 67 and 150 ± 75 mL, respectively. Six months after operation, values of hemoglobin concentration, body weights, and PNI indices were significantly increased in Group A compared with Group B. Levels of gastrin and somatostatin were obviously less than preoperative values and levels of cholecystokinin and motilin were significantly higher than preoperative values in both groups. All patients of Group A were classified into Visick index Grades I and II, whereas only 70.37 per cent of Group B belonged to Visick index Grades I and II postoperatively. The overall 3-year survival rate was not significantly different in both groups. Modified double tracks anastomosis as an alimentary canal reconstructive method for radical proximal gastrectomy showed better outcomes than esophagus-remnant stomach direct anastomosis.

A cerebroprotective dose of intravenous citrate/sorbitol-stabilized dehydroascorbic acid is correlated with increased cerebral ascorbic acid and inhibited lipid peroxidation after murine reperfused stroke.

OBJECTIVE: Oxidative damage has been implicated in the pathogenesis of cerebral ischemia. We previously demonstrated that exogenously supplied dehydroascorbic acid (DHA), an oxidized, blood-brain barrier transportable form of the antioxidant ascorbic acid (AA), improves outcome after experimental stroke. METHODS: To investigate the neuroprotective effect of DHA therapy, we measured cerebral AA levels using a novel assay, quantified markers of lipid peroxidation, and evaluated infarct volume after reperfused stroke in a murine model. All experiments were performed using a new citrate/sorbitol-stabilized DHA formulation to improve the stability of the compound. RESULTS: Intraparenchymal AA levels declined after cerebral ischemia/reperfusion and were repleted in a dose-dependent fashion by postischemic administration of intravenous DHA (P < 0.01). Repletion of these levels was associated with reductions in cerebral malondialdehyde levels (P < 0.05), which were also elevated after reperfused stroke. DHA repletion of interstitial AA levels and reduction in cerebral lipid peroxidation was associated with dose-dependent reductions in infarct volume (P < 0.05). CONCLUSION: Together, these results indicate that an intravenous cerebroprotective dose of citrate/sorbitol-stabilized DHA is correlated with increased brain ascorbate levels and a suppression of excessive oxidative metabolism.