Energy and Infrared Radiation Characteristics of the Sandstone Damage Evolution Process.

The mechanical characteristics and mechanisms of rock failure involve complex rock mass mechanics problems involving parameters such as energy concentration, storage, dissipation, and release. Therefore, it is important to select appropriate monitoring technologies to carry out relevant research. Fortunately, infrared thermal imaging monitoring technology has obvious advantages in the experimental study of rock failure processes and energy dissipation and release characteristics under load damage. Therefore, it is necessary to establish the theoretical relationship between the strain energy and infrared radiation information of sandstone and to reveal its fracture energy dissipation and disaster mechanism. In this study, an MTS electro-hydraulic servo press was used to carry out uniaxial loading experiments on sandstone. The characteristics of dissipated energy, elastic energy, and infrared radiation during the damage process of sandstone were studied using infrared thermal imaging technology. The results show that (1) the transition of sandstone loading from one stable state to another occurs in the form of an abrupt change. This sudden change is characterized by the simultaneous occurrence of elastic energy release, dissipative energy surging, and infrared radiation count (IRC) surging, and it has the characteristics of a short duration and large amplitude variation. (2) With the increase in the elastic energy variation, the surge in the IRC of sandstone samples presents three different development stages, namely fluctuation (stage Ⅰ), steady rise (stage Ⅱ), and rapid rise (stage Ⅲ). (3) The more obvious the surge in the IRC, the greater the degree of local damage of the sandstone and the greater the range of the corresponding elastic energy change (or dissipation energy change). (4) A method of sandstone microcrack location and propagation pattern recognition based on infrared thermal imaging technology is proposed. This method can dynamically generate the distribution nephograph of tension-shear microcracks of the bearing rock and accurately evaluate the real-time process of rock damage evolution. Finally, this study can provide a theoretical basis for rock stability, safety monitoring, and early warning.

Ginsenoside Re Attenuates Cisplatin-Induced Intestinal Toxicity via Suppressing GSK-3ß-Dependent Wnt/ß-Catenin Signaling Pathway In Vivo and In Vitro.

Previous reports have confirmed that crude saponins (ginsenosides) in Panax ginseng have a preventive effect on chemotherapy-induced intestinal injury. However, the protective effects and possible mechanisms of ginsenoside Re (G-Re, a maker saponin in ginseng) against chemotherapy-induced intestinal damage have not been thoroughly studied. In this work, a series of experiments in vivo and in vitro on the intestinal toxicity caused by cisplatin have been designed to verify the improvement effect of G-Re, focusing on the levels of Wnt3a and [Formula: see text]-catenin. Mice were intragastric with G-Re for 10 days, and intestinal injury was induced by intraperitoneal administration of cisplatin at a dose of 20 mg/kg. Histopathology, gastrointestinal digestive enzyme activities, inflammatory cytokines, and oxidative status were evaluated to investigate the protective effect. Furthermore, in IEC-6 cells, G-Re statistically reverses cisplatin-induced oxidative damage and cytotoxicity. The TUNEL and Hoechst 33258 staining demonstrated that G-Re possesses protective effects in cisplatin-induced apoptosis. Additionally, pretreatment with G-Re significantly alleviated the apoptosis via inhibition of over-expressions of B-associated X (Bax), as well as the caspase family members, such as caspase 3 and 9, respectively, in vivo and in vitro. Notably, western blotting results showed that G-Re treatment decreased Wnt3a, Glycogen synthase kinase [Formula: see text] (GSK-[Formula: see text]), and [Formula: see text]-catenin expression, suggesting that nuclear accumulation of [Formula: see text]-catenin was attenuated, thereby inhibiting the activation of GSK-[Formula: see text]-dependent Wnt/[Formula: see text]-catenin signaling, which was consistent with our expected results. Therefore, the above evidence suggested that G-Re may be a candidate drug for the treatment of intestinal injury.

20(S)-ginsenoside Rh1 alleviates T2DM induced liver injury via the Akt/FOXO1 pathway.

Diabetes-associated liver injury becomes a dominant hepatopathy, leading to hepatic failure worldwide. The current study was designed to evaluate the ameliorative effects of ginsenoside Rh1 (G-Rh1) on liver injury induced by T2DM. A T2DM model was established using C57BL/6 mice through feeding with HFD followed by injection with streptozotocin at 100 mg·kg-1.. Then the mice were continuously administered with G-Rh1 (5 and 10 mg·kg-1), to explore the protective effects of G-Rh1 against liver injury. Results showed that G-Rh1 exerted significant effects on maintaining the levels of FBG and insulin, and ameliorated the increased levels of TG, TC and LDL-C induced by T2DM. Moreover, apoptosis in liver tissue was relieved by G-Rh1, according to histological analysis. Particularly, in diabetic mice, it was observed that not only the increased secretion of G6Pase and PEPCK in the gluconeogenesis pathway, but also inflammatory factors including NF-κB and NLRP3 were suppressed by G-Rh1 treatment. Furthermore, the underlying mechanisms by which G-Rh1 exhibited ameliorative effects was associated with its capacity to inhibit the activation of the Akt/FoxO1 signaling pathway induced by T2DM. Taken together, our preliminary study demonstrated the potential mechnism of G-Rh1 in protecting the liver against T2DM-induced damage.

Human adipose tissue-derived MSCs improve psoriasis-like skin inflammation in mice by negatively regulating ROS.

BACKGROUND: Psoriasis is chronic incurable skin inflammation. The anti-inflammatory properties of mesenchymal stem cells (MSCs) have been put forward to be involved in several inflammatory diseases. However, little was known about the role of human adipose tissue-derived stem cells (hAD-MSCs) in psoriasis. OBJECTIVE: We sought to explore the feasibility of using hAD-MSCs infusion as a therapeutic approach in psoriatic mice. METHODS: We constructed the psoriasis-like model by IMQ implication, treated with hAD-MSCs by subcutaneous injection. To evaluate the efficacy, we examined the histology, CD45 and ROS positive cells by HE and flow cytometry respectively. We also tested the key cytokines with PCR. Moreover, to achieve a better therapeutic effect, we treated the model by combing with vitamin E application. RESULTS: We found that the classic histological symptoms of psoriasis were relieved after treatment with hAD-MSCs, also, the splenic index, the infiltration of immune cells and several pro-inflammatory cytokines were decreased. Interestingly, we also found that hAD-MSCs could inhibit ROS generation. Moreover, the combination therapy of hAD-MSCs and vitamin E could promote the curative effect with greater ROS inhibition. CONCLUSION: These results suggested that hAD-MSCs could be useful for treating psoriasis by negatively regulating ROS.

Antimicrobial and cytotoxic phenolic bisabolane sesquiterpenoids from the fungus Aspergillus flavipes 297.

Phenolic bisabolane-type sesquiterpenoids (PBS) represent a rare class of natural products with diverse biological activities. In this study, chemical investigations of the fungus Aspergillus flavipes 297 resulted in the isolation and identification of seven PBS, including a pair of new enantiomers (+)-1a and (-)-1b, a new derivative 2, and five previously reported ones 3-7. The chemical structures of the isolated PBS were determined by extensive NMR and HRESIMS spectroscopic analysis. The absolute configurations of the separated enantiomers (+)-1a and (-)-1b were solved by comparison of the experimental ECD spectra with those of the TDDFT-ECD calculated spectra. The new compounds 1 and 2 represent rare cases of PBS bearing a methylsulfinyl group, which was distinct from the commonly-observed PBS structurally. All the isolated compounds 1-7 were evaluated their antimicrobial and cytotoxic activities. As a result, the tested compounds showed selective antimicrobial activity against several pathogenic bacteria and fungi with the MIC (minimum inhibiting concentrations) values ranging from 2 to 64 µg/mL. Moreover, enantiomers (+)-1a and (-)-1b, together with compound 2, exhibited promising cytotoxicity against MKN-45 and HepG2 cell lines, respectively, indicating that the methylsulfinyl substituent enhanced cytotoxicity to a certain degree.

Metformin attenuates diabetic neuropathic pain via AMPK/NF-κB signaling pathway in dorsal root ganglion of diabetic rats.

Neuropathic pain is a common complication of diabetes mellitus with poorly relieved by conventional analgesics. Metformin, a first-line drug for type 2 diabetes, reduces blood glucose by activating adenosine monophosphate protein kinase (AMPK) signalling system. However, the effect of Metformin on diabetic neuropathic pain is still unknown. In the present study, we showed that Metformin was capable of attenuating diabetes induced mechanical allodynia, and the analgesia effect could be blocked by Compound C (an AMPK inhibitor). Importantly, Metformin enhanced the phosphorylation level of AMPK in L4-6 DRGs of diabetic rats but not affect the expression of total AMPK. Intrathecal injection of AICAR (an AMPK agonist) could activate AMPK and alleviate the mechanical allodynia of diabetic rats. Additionally, phosphorylated AMPK and NF-κB was co-localized in small and medium neurons of L4-6 DRGs. Interestingly, the regulation of NF-κB in diabetic rats was obviously reduced when AMPK was activated by AICAR. Notably, Metformin could decrease NF-κB expression in L4-6 DRGs of diabetic rats, but the decrease was blocked by Compound C. In conclusion, Metformin alleviates diabetic mechanical allodynia via activation of AMPK signaling pathway in L4-6 DRGs of diabetic rats, which might be mediated by the downregulation of NF-κB, and this providing certain basis for Metformin to become a potential drug in the clinical treatment of diabetic neuropathic pain.

LncRNA CRNDE promotes the progression and angiogenesis of pancreatic cancer via miR-451a/CDKN2D axis.

BACKGROUND: The lncRNA colorectal neoplasia differentially expressed (lncRNA CRNDE) has been reported to play a pivotal role in various cancers. However, the expression and function of CRNDE in pancreatic cancer remain unclear. The objective of this study was to investigate the effects of CRNDE on pancreatic cancer and the underlying mechanisms. METHODS: The expression of CRNDE in pancreatic cancer tissues and cell lines was determined by RT-qPCR. Proliferation and angiogenesis were detected by MTT, colony formation, transwell and tube formation assays in vitro and in vivo. ELISA assay was used to detect the secretion of VEGFA. IHC was performed to test the expression levels of Ki67 and CD31. The binding sites between CRNDE, CDKN2D and miR-451a were predicted by bioinformatics analysis. Dual luciferase reporter and RNA immunoprecipitation assays were conducted to confirm the interaction with each other. RESULTS: The results showed that CRNDE was significantly up-regulated in pancreatic cancer tissues as well as cell lines. CRNDE overexpression promoted the progression and angiogenesis of pancreatic cancer cells in vitro and in vivo. Moreover, we identified that CRNDE functioned as a sponge for miR-451a and CRNDE overexpression inhibited the expression of miR-451a. Furthermore, we confirmed that miR-451a directly interacted with CDKN2D and negatively regulated CDKN2D expression. In addition, CRNDE was found to positively regulate CDKN2D expression and mediate pancreatic cancer cell proliferation and angiogenesis through miR-451a/CDKN2D axis. CONCLUSION: CRNDE modulates cell proliferation and angiogenesis via miR-451a/CDKN2D axis in pancreatic cancer, which provides a potential therapeutic target for pancreatic cancer treatment.

Therapeutic experience of an 89-year-old high-risk patient with incarcerated cholecystolithiasis: A case report and literature review.

BACKGROUND: The global pandemic of coronavirus disease 2019 pneumonia poses a particular challenge to the emergency surgical treatment of elderly patients with high-risk acute abdominal diseases. Elderly patients are a high-risk group for surgical treatment. If the incarceration of gallstones cannot be relieved, emergency surgery is unavoidable. CASE SUMMARY: We report an 89-year-old male patient with acute gangrenous cholecystitis and septic shock induced by incarcerated cholecystolithiasis. He had several coexisting, high-risk underlying diseases, had a history of radical gastrectomy for gastric cancer, and was taking aspirin before the operation. Nevertheless, he underwent emergency laparoscopic cholecystectomy, with maintenance of postoperative heart and lung function, successfully recovered, and was discharged on day 8 after the operation. CONCLUSION: Emergency surgery for elderly patients with acute abdominal disease is safe and feasible during the coronavirus disease 2019 pandemic, the key is to abide strictly by the hospital's epidemic prevention regulations, fully implement the epidemic prevention procedure for emergency surgery, fully prepare before the operation, accurately perform the operation, and carefully manage the patient postoperatively.

Pseudothrombus deposition accompanied with minimal change nephrotic syndrome and chronic kidney disease in a patient with Waldenström's macroglobulinemia: A case report.

BACKGROUND: Waldenström's macroglobulinemia (WM) is a rare lymphoid neoplasia, which can have renal complications. These rarely occur, and most common renal manifestations are mild proteinuria and microscopic hematuria. Herein we describe a case of WM that presented with pseudothrombi depositing in capillaries associated with minimal change nephrotic syndrome and chronic kidney disease (CKD). CASE SUMMARY: A 52-year-old man presented with features suggesting nephrotic syndrome. Extensive workups were done, and there were elevated serum levels of interleukin-6 and vascular endothelial growth factor (VEGF), capillary pseudothrombus accumulation associated with minimal change nephrotic syndrome, CKD, and WM. Treatment was directed at the patient's WM with bortezomib, thalidomide, and dexamethasone whereby serum immunoglobulin M (IgM) decreased. The damage of IgM on the kidney was corrected; thus, the patient's proteinuria and serum creatinine had improved. The patient is still under clinical follow-up. CONCLUSION: It is essential for clinicians to promptly pay more attention to patients presenting with features of nephrotic syndrome and do extensive workups to come up with a proper therapy strategy.

Down-regulation of CXCL11 inhibits colorectal cancer cell growth and epithelial-mesenchymal transition.

BACKGROUND: The poor prognosis of colorectal cancer (CRC) largely results from local invasion and tumor metastases. Epithelial-mesenchymal transition (EMT) is a key step in the progression of solid tumors and plays a vital role in tumor metastasis. Recent studies demonstrate that C-X-C motif chemokine 11 (CXCL11) is involved in various cancers' progression. However, its biological activity in CRC needs deeper exploration. METHODS: The level of CXCL11 in CRC tissues and cell lines was determined using the quantitative real-time PCR (qRT-PCR) assay. The MTT, colony formation, wound healing and Transwell invasion assays were applied to assess the role of CXCL11 in CRC cell growth, migration and invasion, in vitro, respectively. A xenograft model was constructed to analyze the function of CXCL11 in CRC cell growth in vivo. RESULTS: CXCL11 was over-expressed in CRC tissues and cell lines. Repression of CXCL11 significantly inhibited CRC cell migration, invasion and EMT in vitro. In addition, down-regulation of CXCL11 reduced CRC cell growth and metastasis in vivo. Finally, we revealed that repression of CXCL11 inhibited the metastatic ability of CRC cell in a N-cadherin dependent manner. CONCLUSION: In summary, this study explicates the oncogenic activities of CXCL11 in CRC cell growth and metastasis.

Case report: lipid inclusion in glomerular endothelial and mesangial cells in a patient after contrast medium injection.

BACKGROUND: It is well-recognized that injection of iodinated radiographic contrast media (CM) sometimes causes acute renal injury via multiple mechanisms, such as vasoconstriction, toxicity on glomerular endothelium and tubular epithelium and so forth. CASE PRESENTATION: A 51-year-old man developed acute renal injury with proteinuria after CM administration. To our surprise, in his renal biopsy sample the myelin figure like structure was observed in glomerular endothelium and mesangial cells by transmission electron microscopy. However the patient didn't has any clinic clues of Fabry disease and other lysosomal storage disorders. Moreover in vitro cultured glomerular endothelial and mesangial cells we found CM triggers lipid aggregation along with the increased CD36 and decreased ABCA1 abundance. Thus this patient was administrated statin to correct the aberrant lipid trafficking, 2 months later at his next visit we found his renal function partially recovered with reduced proteinuria. CONCLUSIONS: Besides the well-known underlying mechanisms, CM may cause renal impairment by triggering the dysregulated transportation of lipid. Furthermore statin is suggested to be a very promising medicine to decrease side effects of CM.

POU2F1 promotes growth and metastasis of hepatocellular carcinoma through the FAT1 signaling pathway.

Increasing evidence suggests that POU domain class 2 transcription factor 1 (POU2F1) participates in carcinogenesis and cancer progression via promotion of cell proliferation and metastasis; however, the functional role of POU2F1 in hepatocellular carcinoma (HCC) is largely unknown. In this study, we determined that POU2F1 was significantly up-regulated in HCC tumor tissue and cell lines. We demonstrated that POU2F1 over-expression promoted HCC cell proliferation, colony formation, migration, and invasion, while silencing of POU2F1 inhibited these malignant phenotypes. In vivo experiments indicated that knockdown of POU2F1 inhibited HCC cell metastasis and xenograft growth, whereas ectopic expression of POU2F1 promoted these cellular functions. Microarray analysis suggests that FAT atypical cadherin 1 (FAT1) can function downstream of POU2F1. Functionally, we demonstrated that POU2F1 knockdown induced growth suppression and metastasis inhibition of HCC cells and inactivated the FAT1 pathway, indicating that POU2F1 is a potential novel therapeutic target in HCC.

Up-regulation of CXCR4 expression contributes to persistent abdominal pain in rats with chronic pancreatitis.

Background Pain in patients with chronic pancreatitis is critical hallmark that accompanied inflammation, fibrosis, and destruction of glandular pancreas. Many researchers have demonstrated that stromal cell-derived factor 1 (also named as CXCL12) and its cognate receptor C-X-C chemokine receptor type 4 (CXCR4) involved in mediating neuropathic and bone cancer pain. However, their roles in chronic pancreatic pain remain largely unclear. Methods Chronic pancreatitis was induced by intraductal injection of trinitrobenzene sulfonic acid to the pancreas. Von Frey filament tests were conducted to evaluate pancreas hypersensitivity of rat. Expression of CXCL12, CXCR4, NaV1.8, and pERK in rat dorsal root ganglion was detected by Western blot analyses. Dorsal root ganglion neuronal excitability was assessed by electrophysiological recordings. Results We showed that both CXCL12 and CXCR4 were dramatically up-regulated in the dorsal root ganglion in trinitrobenzene sulfonic acid-induced chronic pancreatitis pain model. Intrathecal application with AMD3100, a potent and selective CXCR4 inhibitor, reversed the hyperexcitability of dorsal root ganglion neurons innervating the pancreas of rats following trinitrobenzene sulfonic acid injection. Furthermore, trinitrobenzene sulfonic acid-induced extracellular signal-regulated kinase activation and Nav1.8 up-regulation in dorsal root ganglias were reversed by intrathecal application with AMD3100 as well as by blockade of extracellular signal-regulated kinase activation by intrathecal U0126. More importantly, the trinitrobenzene sulfonic acid-induced persistent pain was significantly suppressed by CXCR4 and extracellular signal-regulated kinase inhibitors. Conclusions The present results suggest that the activation of CXCL12-CXCR4 signaling might contribute to pancreatic pain and that extracellular signal-regulated kinase-dependent Nav1.8 up-regulation might lead to hyperexcitability of the primary nociceptor neurons in rats with chronic pancreatitis.

Upregulation of cystathionine ß-synthetase in the arcuate nucleus produces pain hypersensitivity via PKC upregulation and GluN2B phosphorylation in rats with chronic pancreatitis.

Hydrogen sulfide (H2S) contributes to visceral hyperalgesia in primary sensory neurons, but its role in central nervous system remains largely unknown. This study was to investigate the roles and underlying mechanisms of H2S and its endogenous synthesis enzymes in the arcuate nucleus (ARC) in rat pancreatic hyperalgesia. Chronic pancreatitis (CP) was induced in male adult Sprague-Dawley rats by intra-pancreatic ductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Western blot analysis was performed to detect protein expression in the ARC. CP markedly upregulated cystathionine ß-synthetase (CBS) expression but did not alter cystathionine-γ-lyase level in the ARC at 4 weeks after TNBS injection. Although the expression of total GluN2B was not altered, CP greatly enhanced the phosphorylation level of GluN2B in the ARC when compared with age- and sex-matched control rats. CP also significantly increased expression of protein kinase Cγ (PKCγ) in the ARC. Arcuate microinjection of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA, an inhibitor of CBS) significantly attenuated abdominal pain in CP rats in a dose-dependent manner and reversed the CP-induced upregulation of p-GluN2B and PKCγ in the ARC. Furthermore, the GluN2B inhibitor or specific PKC inhibitor chelerythrine significantly attenuated abdominal hyperalgesia in CP rats. The p-GluN2B expression was also suppressed by PKC inhibitor. Taken together, our results suggest that the upregulation of CBS in the ARC leads to an activation of GluN2B via PKCγ, which may play an important role in generation of pain hypersensitivity of CP.

Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine ß-synthetase in a rat model of visceral hypersensitivity.

The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood and treatment remains difficult. The present study was designed to investigate roles of adrenergic signaling and the endogenous hydrogen sulfide producing enzyme cystathionine ß-synthetase (CBS) in a previously validated rat model of IBS induced by neonatal colonic inflammation (NCI). Here we showed that NCI-induced visceral hypersensitivity (VH) was significantly attenuated by ß2 subunit inhibitor but not by ß1 or ß3 or α subunit inhibitor. NCI markedly elevated plasma norepinephrine (NE) concentration without alteration in expression of ß2 subunit receptors in dorsal root ganglion (DRGs) innervating the colon. In addition, NCI markedly enhanced TRPV1 and CBS expression in the colon DRGs. CBS inhibitor AOAA reversed the upregulation of TRPV1 in NCI rats. In vitro experiments showed that incubation of DRG cells with NE markedly enhanced expression of TRPV1, which was reversed by application of AOAA. Incubation of DRG cells with the H2S donor NaHS greatly enhanced TRPV1 expression. Collectively, these data suggest that activation of adrenergic signaling by NCI sensitizes TRPV1 channel activity, which is likely mediated by upregulation of CBS expression in peripheral sensory neurons, thus contributing to chronic visceral hypersensitivity.

TLR4 upregulates CBS expression through NF-κB activation in a rat model of irritable bowel syndrome with chronic visceral hypersensitivity.

AIM: To investigate the roles of toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB on cystathionine ß synthetase (CBS) expression and visceral hypersensitivity in rats. METHODS: This study used 1-7-wk-old male Sprague-Dawley rats. Western blot analysis was employed to measure the expression of TLR4, NF-κB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia (DRG) from control and "irritable bowel syndrome" rats induced by neonatal colonic inflammation (NCI). Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques. Immunofluorescence was employed to determine the co-expression of TLR4, NF-κB and CBS in DiI-labeled DRG neurons. RESULTS: NCI significantly upregulated the expression of TLR4 in colon-related DRGs (0.34 ± 0.12 vs 0.72 ± 0.02 for the control and NCI groups, respectively, P < 0.05). Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats. CLI-095 treatment also markedly reversed the hyperexcitability of colon-specific DRG neurons and reduced the expression of CBS (1.7 ± 0.1 vs 1.1 ± 0.04, P < 0.05) and of the NF-κB subunit p65 (0.8 ± 0.1 vs 0.5 ± 0.1, P < 0.05). Furthermore, the NF-κB-selective inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the upregulation of CBS (1.0 ± 0.1 vs 0.6 ± 0.1, P < 0.05) and attenuated visceral hypersensitivity in the NCI rats. In vitro, incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65 (control vs 8 h: 0.9 ± 0.1 vs 1.3 ± 0.1; control vs 12 h: 0.9 ± 0.1 vs 1.3 ± 0.1, P < 0.05; control vs 24 h: 0.9 ± 0.1 vs 1.6 ± 0.1, P < 0.01) and CBS (control vs 12 h: 1.0 ± 0.1 vs 2.2 ± 0.4; control vs 24 h: 1.0 ± 0.1 vs 2.6 ± 0.1, P < 0.05), whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression (1.2 ± 0.1 vs 0.6 ± 0.0, P < 0.01). CONCLUSION: Our results suggest that the activation of TLR4 by NCI upregulates CBS expression, which is mediated by the NF-κB signaling pathway, thus contributing to visceral hypersensitivity.

Adrenergic signaling mediates mechanical hyperalgesia through activation of P2X3 receptors in primary sensory neurons of rats with chronic pancreatitis.

The mechanism of pain in chronic pancreatitis (CP) is poorly understood. The aim of this study was designed to investigate roles of norepinephrine (NE) and P2X receptor (P2XR) signaling pathway in the pathogenesis of hyperalgesia in a rat model of CP. CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Mechanical hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. P2XR-mediated responses of pancreatic dorsal root ganglion (DRG) neurons were measured utilizing calcium imaging and whole cell patch-clamp-recording techniques. Western blot analysis and immunofluorescence were performed to examine protein expression. TNBS injection produced a significant upregulation of P2X3R expression and an increase in ATP-evoked responses of pancreatic DRG neurons. The sensitization of P2X3Rs was reversed by administration of ß-adrenergic receptor antagonist propranolol. Incubation of DRG neurons with NE significantly enhanced ATP-induced intracellular calcium signals, which were abolished by propranolol, and partially blocked by protein kinase A inhibitor H-89. Interestingly, TNBS injection led to a significant elevation of NE concentration in DRGs and the pancreas, an upregulation of ß2-adrenergic receptor expression in DRGs, and amplification of the NE-induced potentiation of ATP responses. Importantly, pancreatic hyperalgesia was markedly attenuated by administration of purinergic receptor antagonist suramin or A317491 or ß2-adrenergic receptor antagonist butoxamine. Sensitization of P2X3Rs, which was likely mediated by adrenergic signaling in primary sensory neurons, contributes to pancreatic pain, thus identifying a potential target for treating pancreatic pain caused by inflammation.

rGO quantum dots/ZnO hybrid nanofibers fabricated using electrospun polymer templates and applications in drug screening involving an intracellular H2O2 sensor.

Throughout the years, reported intracellular H2O2 sensors just focused on unrelated measurements of intracellular H2O2 generated from the stimulus of Cd2+, ascorbic acid (AA) etc., leading to difficulty in data interpretation. Here, a novel reduced graphene oxide quantum dots (rGO QDs)/ZnO hybrid nanofibers-based electrochemical biosensor for the detection of intracellular H2O2 released from cancer and normal cells under the stimuli of the corresponding anticancer drugs permits a quantitative study of the interaction between the target drug compound and the cancer cell, which is suitable for candidate drug screening. Nylon 6/6 nanofibers are used as robust templates for the facile fabrication of novel rGO QDs/ZnO hybrid nanofibers via electrospinning followed by a step hydrothermal growth method. The as-made sensor was applied to determine H2O2 released from a prostate cancer cell (PC-3) versus a noncancerous cell (BPH-1) under the stimuli of the corresponding anticancer drugs (apigenin, antisense CK2αetc.). The amount of H2O2 released from the PC-3 cancer cell is about (320 ± 12) amol per cell and about (210 ± 6) amol per cell for the BPH-1 noncancerous cell under the stimuli of specific therapy drug antisense CK2α. These results demonstrate that the rGO QDs/ZnO hybrid nanofibers-based electrochemical biosensor can efficiently detect the distinct amounts of H2O2 released from cancer and noncancer cells.

[Preparation and characterization of tumor targeted CdTe quantum dots modified with functional polymer].

N-acetyl-L-cysteine (NAC) capped quantum dots (QDs) were synthesized by a hydrothermal method and coated with 2-amino-2-deoxy-D-glucose (DG), polyethylene glycol (PEG), and 9-D-arginine (9R). The optical properties, morphology and structure of 9R/DG-coated CdTe QDs were characterized by ultraviolet-visible spectrometry, fluorescence spectrum, Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), liquid chromatography-mass spectrometer (LC-MS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transmission electron micrographs (TEM). Furthermore, the biocompatibility, tumor targeted ability and transmembrane action of 9R/DG-coated CdTe QDs were studied. Results indicated that 9R/DG-coated CdTe QDs was constructed successfully by ligand exchange. The 9R/DG-coated CdTe QDs with the size of 8-10 nm had good dispersity and the absorbance and fluorescence peaks of CdTe QDs after modification were red shifted from 480 nm to 510 nm and 627 nm to 659 nm, respectively. In addition, the CdTe QDs modified by PEG, DG and 9R displayed good biocompatibility, high targeted ability to the cancer cells with glucose transporter type 1 (GLUT1) receptor high expression and obvious transmembrane ability.