Zinc inhibits TRPV1 to alleviate chemotherapy-induced neuropathic pain

Zinc is a transition metal that has a long history of use as an anti-inflammatory agent. It also soothes pain sensations in a number of animal models. However, the effects and mechanisms of zinc on chemotherapy-induced peripheral neuropathy remain unknown. Here we show that locally injected zinc markedly reduces neuropathic pain in male and female mice induced by paclitaxel, a chemotherapy drug, in a TRPV1-dependent manner. Extracellularly applied zinc also inhibits the function of TRPV1 expressed in HEK293 cells and mouse DRG neurons, which requires the presence of zinc-permeable TRPA1 to mediate entry of zinc into the cytoplasm. Moreover, TRPA1 is required for zinc-induced inhibition of TRPV1-mediated acute nociception. Unexpectedly, zinc transporters, but not TRPA1, are required for zinc-induced inhibition of TRPV1-dependent chronic neuropathic pain produced by paclitaxel. Together, our study demonstrates a novel mechanism underlying the analgesic effect of zinc on paclitaxel-induced neuropathic pain that relies on the function of TRPV1

Modeling RedOx-Based Magnetohydrodynamics in Three-Dimensional Microfluidic Channels

RedOx-based magnetohydrodynamic MHD[1] flows in three-dimensional microfluidic channels are investigated theoretically with a coupled mathematical model consisting of the Nernst-Planck equations for the concentrations of ionic species, the local electroneutrality condition for the electric potential, and the Navier-Stokes equations for the flow field. A potential difference is externally applied across two planar electrodes positioned along the opposing walls of a microchannel that is filled with a dilute RedOx electrolyte solution, and a Faradaic current transmitted through the solution results. The entire device is positioned under a magnetic field which can be provided by either a permanent magnet or an electromagnet. The interaction between the current density and the magnetic field induces Lorentz forces, which can be used to pump and/or stir fluids for microfluidic applications. The induced currents and flow rates in three-dimensional 3D[1] planar channels obtained from the full 3D model are compared with the experimental data obtained from the literature and those obtained from our previous two-dimensional mathematical model.Aclosed form approximation for the average velocity flow rate[1] in 3D planar microchannels is derived and validated by comparing its predictions with the results obtained from the full 3D model and the experimental data obtained from the literature. The closed form approximation can be used to optimize the dimensions of the channel and to determine the magnitudes and polarities of the prescribed currents in MHD networks so as to achieve the desired flow patterns and flow rates

Biostratigraphy of the Small Shelly Fossils From the Upper Maidiping Formation (Terreneuvian) at the Fandian Section, Sichuan Province, South China

Small shelly fossils (SSFs) are a useful and critical tool for subdivision and correlation of the Cambrian Terreneuvian stratigraphy. The Maidiping Formation in southern Sichuan is a well-known Terreneuvian lithologic unit with rich SSFs. Here, the upper Maidiping Formation at the Fandian section, an important supplementary section of the classic Maidiping section, is studied for understanding its SSF assemblages and stratigraphic implication. There are 26 genera, 24 species, and 3 undetermined species recovered from the Fandian section, and Watsonella crosbyi was discovered from this section for the first time. Two SSF biozones of the Yangtze Platform, i.e., the possible Paragloborilus subglobosus–Purella squamulosa Assemblage Zone (? Zone II) and the W. crosbyi Assemblage Zone (Zone III), can be recognized. Comparing with the Maidiping section, the Fandian section has a relatively successive SSF biostratigraphy and carbon isotope stratigraphy in the upper Maidiping Formation. The SSF Zone II (?) and Zone III from the Fandian section can be, respectively, correlated to the same zones from the upper Maidiping Formation of the nearby Maidiping section (only Zone III), the upper Zhongyicun and Dahai members of the Zhujiaqing Formation in eastern Yunnan, the top Kuanchuanpu Formation in southern Shaanxi and northern Sichuan, and the beds 4 and 5 (or units 3 and 4) of the Yanjiahe Formation in western Hubei. The almost cosmopolitan distribution and nearly synchronous earliest appearance of W. crosbyi strengthen the applicability of its first appearance data (FAD) to define the base of Cambrian Stage 2 in South China (Xiaotanian) as well as in other continents. The FAD of W. crosbyi just around the onset of the ZHUCE carbon isotope excursion at the Fandian section also further reinforces the utility of the onset of ZHUCE as an auxiliary maker for defining the base of the Xiaotanian in South China

Impact of hypertension and smoking on the rupture of intracranial aneurysms and their joint effect

Background In general population, the prevalence of intracranial aneurysm reaches as high as three percent. The goal of the study was to analyze retrospectively the independent risk factors for the rupture of intracranial aneurysms and their joint effect. Methods The records and angiographies of continuous 519 intracranial aneurysm patients treated at our center between February 2013 and July 2014 were retrospectively analyzed. Ruptured group and unruptured group were included in the study according to their clinical and imaging information. Univariate analysis and multivariate logistic regression analysis was used to identified independent risk factors for the rupture of intracranial aneurysms. We assessed the joint effect of independent risk factors for the rupture of intracranial aneurysms with an additional logistic regression analysis. Results The results of multivariate analysis show that hypertension (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.05–2.18) and smoking (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.06–2.33) were independent risk factors for rupture of intracranial aneurysms. The joint risk of hypertension and smoking was higher (OR, 2.28; 95% CI, 1.29–4.02) than the risks of hypertension (OR, 1.74; 95% CI, 1.11–2.72) and smoking (OR, 1.86; 95% CI, 1.05–3.29) independently. Conclusions Hypertension and smoking increase of the rupture risk of intracranial aneurysms. And the joint risk of hypertension and smoking was higher than the risks of hypertension and smoking independently

Stent-assisted coiling of very small wide-necked intracranial aneurysms: Complications, anatomical results and clinical outcomes

Background and objective Treatment of very small (≤3mm) wide-necked intracranial aneurysms remains controversial, we investigated the efficacy and safety of stent-assisted coiling of such aneurysms. Methods From September 2008 to December 2012, 112 very small wide-necked intracranial aneurysms in 108 patients were embolized with stent-assisted coiling. We assessed the initial neurological conditions, complications and anatomic results. The follow-up results were evaluated with DSA and mRS. Results Stent deployment was successful in 104 of 108 procedures (96.3%). 11 complications (10.2%) occurred during procedures, including 5 events of aneurysm rupture, 3 events of thromboembolism. The rate of complication, rupture and thromboembolism was not statistically different between the ruptured and unruptured patients (P=0.452, P=0.369, P=1.000, respectively). The initial aneurysmal occlusion was Raymond scale (RS) 1 in 34 patients (31.5%), RS2 in 53 patients (49.1%), and RS3 in 21 patients (19.4%). 79 aneurysms were available for anatomic follow-up of 12–47 months, stable occlusion in 45 aneurysms (57.0%), progressive complete occlusion in 34 aneurysms (43.0%). 95 patients(88.0%) were available for a clinical follow-up of 12–52 months, 92 patients (96.8%) had favorable clinical outcomes (mRS ≤2), 3 patients (3.2%) had morbidity (mRS: 3–5). The morbidity was not statistically different between the ruptured and unruptured patients (P=1.000). Conclusions Stent-assisted coiling of very small wide-necked intracranial aneurysms may be effective and safe. Because of low risk of rupture in such aneurysms, the coiling of unruptured such aneurysms must be selective. The long-term efficacy and safety of coiling such aneurysms remains to be determined in larger prospective series

GLP-1 receptor agonist as a modulator of innate immunity

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid hormone secreted by L cells in the distal ileum, colon, and pancreatic α cells, which participates in blood sugar regulation by promoting insulin release, reducing glucagon levels, delaying gastric emptying, increasing satiety, and reducing appetite. GLP-1 specifically binds to the glucagon-like peptide-1 receptor (GLP-1R) in the body, directly stimulating the secretion of insulin by pancreatic β-cells, promoting proliferation and differentiation, and inhibiting cell apoptosis, thereby exerting a glycemic lowering effect. The glycemic regulating effect of GLP-1 and its analogues has been well studied in human and murine models in the circumstance of many diseases. Recent studies found that GLP-1 is able to modulate innate immune response in a number of inflammatory diseases. In the present review, we summarize the research progression of GLP-1 and its analogues in immunomodulation and related signal pathways

Prognostic value of fatty acid metabolism-related genes in colorectal cancer and their potential implications for immunotherapy

IntroductionColorectal cancer is one of the most common gastrointestinal cancers and the second leading cause of cancer-related death. Although colonoscopy screening has greatly improved the early diagnosis of colorectal cancer, its recurrence and metastasis are still significant problems. Tumour cells usually have the hallmark of metabolic reprogramming, while fatty acids play important roles in energy storage, cell membrane synthesis, and signal transduction. Many pathways of fatty acid metabolism (FAM) are involved in the occurrence and development of colon cancer, and the complex molecular interaction network contains a variety of genes encoding key enzymes and related products.MethodsClinical information and RNA sequencing data were collected from TCGA and GEO databases. The prognosis model of colon cancer was constructed by LASSO-Cox regression analysis among the selected fatty acid metabolism genes with differential expression. Nomogram for the prognosis model was also constructed in order to analyze its value in evaluating the survival and clinical stage of the colon cancer patients. The differential expression of the selected genes was verified by qPCR and immunohistochemistry. GSEA and GSVA were used to analyze the enrichment pathways for high- and low-risk groups. CIBERSORT was used to analyze the immune microenvironment of colon cancer and to compare the infiltration of immune cells in the high- and low-risk groups. The “circlize” package was used to explore the correlation between the risk score signature and immunotherapy for colon cancer.ResultsWe analysed the differential expression of 704 FAM-related genes between colon tumour and normal tissue and screened 10 genes with prognostic value. Subsequently, we constructed a prognostic model for colon cancer based on eight optimal FAM genes through LASSO Cox regression analysis in the TCGA-COAD dataset, and its practicality was validated in the GSE39582 dataset. Moreover, the risk score calculated based on the prognostic model was validated as an independent prognostic factor for colon cancer patients. We further constructed a nomogram composed of the risk score signature, age and American Joint Committee on Cancer (AJCC) stage for clinical application. The colon cancer cohort was divided into high- and low-risk groups according to the optimal cut-off value, and different enrichment pathways and immune microenvironments were depicted in the groups.DiscussionSince the risk score signature was significantly correlated with the expression of immune checkpoint molecules, the prognostic model might be able to predict the immunotherapy response of colon cancer patients. In summary, our findings expand the prognostic value of FAM-related genes in colon cancer and provide evidence for their application in guiding immunotherapy

Enhanced hemocompatibility and rapid magnetic anastomosis of electrospun small-diameter artificial vascular grafts

Background: Small-diameter (<6 mm) artificial vascular grafts (AVGs) are urgently required in vessel reconstructive surgery but constrained by suboptimal hemocompatibility and the complexity of anastomotic procedures. This study introduces coaxial electrospinning and magnetic anastomosis techniques to improve graft performance.Methods: Bilayer poly(lactide-co-caprolactone) (PLCL) grafts were fabricated by coaxial electrospinning to encapsulate heparin in the inner layer for anticoagulation. Magnetic rings were embedded at both ends of the nanofiber conduit to construct a magnetic anastomosis small-diameter AVG. Material properties were characterized by micromorphology, fourier transform infrared (FTIR) spectra, mechanical tests, in vitro heparin release and hemocompatibility. In vivo performance was evaluated in a rabbit model of inferior vena cava replacement.Results: Coaxial electrospinning produced PLCL/heparin grafts with sustained heparin release, lower platelet adhesion, prolonged clotting times, higher Young’s modulus and tensile strength versus PLCL grafts. Magnetic anastomosis was significantly faster than suturing (3.65 ± 0.83 vs. 20.32 ± 3.45 min, p < 0.001) and with higher success rate (100% vs. 80%). Furthermore, magnetic AVG had higher short-term patency (2 days: 100% vs. 60%; 7 days: 40% vs. 0%) but similar long-term occlusion as sutured grafts.Conclusion: Coaxial electrospinning improved hemocompatibility and magnetic anastomosis enhanced implantability of small-diameter AVG. Short-term patency was excellent, but further optimization of anticoagulation is needed for long-term patency. This combinatorial approach holds promise for vascular graft engineering