Spinal toll like receptor 3 is involved in chronic pancreatitis-induced mechanical allodynia of rat

<p>Abstract</p> <p>Background</p> <p>Mechanisms underlying pain in chronic pancreatitis (CP) are incompletely understood. Our previous data showed that astrocytes were actively involved. However, it was unclear how astrocytic activation was induced in CP conditions. In the present study, we hypothesized that toll-like receptors (TLRs) were involved in astrocytic activation and pain behavior in CP-induced pain.</p> <p>Results</p> <p>To test our hypothesis, we first investigated the changes of TLR2-4 in the rat CP model induced by intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). Western blot showed that after TNBS infusion, TLR3, but not TLR2 or TLR4, was increased gradually and maintained at a very high level for up to 5 w, which correlated with the changing course of mechanical allodynia. Double immunostaining suggested that TLR3 was highly expressed on astrocytes. Infusion with TLR3 antisense oligodeoxynucleotide (ASO) dose-dependently attenuated CP-induced allodynia. CP-induced astrocytic activation in the spinal cord was also significantly suppressed by TLR3 ASO. Furthermore, real-time PCR showed that IL-1β, TNF-α, IL-6 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in spinal cord of pancreatic rats. In addition, TLR3 ASO significantly attenuated CP-induced up-regulation of IL-1β and MCP-1.</p> <p>Conclusions</p> <p>These results suggest a probable "TLR3-astrocytes-IL-1β/MCP-1" pathway as a positive feedback loop in the spinal dorsal horn in CP conditions. TLR3-mediated neuroimmune interactions could be new targets for treating persistent pain in CP patients.</p

Efficacies of Various Surgical Regimens in the Treatment of Renal Calculi Patients: a Network Meta-Analysis in 25 Enrolled Controlled Clinical Trials

Background/Aims: Renal calculi, or kidney stones, are masses made of crystals that affect people of all geographical, cultural, and racial groups. We conduct this study with the aim of comparing the efficacy of various surgical methods in the treatment of renal calculi. Methods: Controlled clinical trials (CCTs) related to different surgical treatment approaches for renal calculi were included in this study by retrieving them from electronic English databases. The odds ratios (OR), the weighted mean difference (WMD), 95% confidence intervals (95% CI) and surface under the cumulative ranking curves (SUCRA) were evaluated, followed by a cluster analysis. Results: Compared with the extracorporeal shockwave lithotripsy (SWL), minimally invasive percutaneous nephrolithotomy (mini-PCNL), retrograde intrarenal surgery (RIRS), standard percutaneous nephrolithotomy (standard PCNL), ureterorenoscopy (URS) and micro-percutaneous nephrolithotomy (microperc) regimens, the open anatrophic nephrolithotomy (Open AN), URS + RIRS and laparoscopic pyelolithotomy (LP) surgical procedures all presented with a higher stone-free rate in renal calculi. Lower auxiliary procedures were found in the URS + RIRS treatment approach compared with SWL, RIRS, URS and microperc regimens. In addition, the SWL regimen indicated a lower stone-free rate than the mini-PCNL, standard PCNL, Open AN, URS + RIRS and LP regimens. Finally, the RIRS regimen presented with the shortest in-patient stay compared to the mini-PCNL, standard PCNL, Open AN, URS, URS + RIRS and LP regimens. Conclusion: This meta-analysis demonstrated that the URS + RIRS surgical procedure has the best stone-free rate and the lowest number of auxiliary procedures. The RIRS and Microperc both have the shortest hospital stay and operative time

Enhancing androgen ablation response in metastatic hormone-sensitive prostate cancer: the benefits of transurethral resection of the prostate

Presently, there is limited data on the potential survival benefits of transurethral resection of the prostate (TURP) in patients with metastatic hormone-sensitive prostate cancer (mHSPCa). In this study, we aimed to assess the effects of TURP on the survival of mHSPCa patients. Of the 59 patients diagnosed with mHSPCa included, 28 received androgen deprivation therapy (ADT) alone, and the remaining received TURP plus ADT. Their time to biochemical progression (TBCP) and progression-free survival (PFS) were analyzed. Our results showed that for a median follow-up time of 15 (range, 3–40) months and 21 (range, 6–39) months for the ADT group and the TURP group, respectively, the TURP group exhibited significantly longer TBCP than the ADT group (p = 0.020). In addition, patients in the TURP group had numerically longer PFS, although the difference between the two groups was not significantly different (p = 0.110). Cox multivariate analysis indicated that longer TBCP was independently associated with TURP (p = 0.032) and lower Gleason scores (p = 0.001). Altogether this study showed that TURP could prolong TBCP and potentially improve the PFS of mHSPCa patients. However, further studies with a larger sample size are needed to confirm these findings

Synthesis and Bio-Activity Evaluation of Scutellarein as a Potent Agent for the Therapy of Ischemic Cerebrovascular Disease

Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, it is very difficult to obtain scutellarein in nature compared with scutellarin. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. The in vitro antioxidant activities of scutellarein were evaluated by measuring its scavenging capacities toward DPPH, ABTS+•, •OH free radicals and its protective effect on H2O2-induced cytotoxicity in PC12 cells using MTT assay method. The results showed that essential point to the synthesis was the implementation of H2SO4 in 90% ethanol in N2 atmosphere; scutellarein had stronger antioxidant activity than scutellarin. The results have laid the foundation for further research and the development of scutellarein as a promising candidate for ischemic cerebrovascular disease

The dissipative potential induced by QCD at finite temperature and density

In the framework of QCD at finite temperature we have obtained dissipative terms for the effective potential between $q$ and $\bar q$ which would partly explain the $J/\psi$ suppression in the Quark Gluon Plasma (QGP). The derivation of the dissipative potential for QGP is presented and the case for Hadron Matter (HM) is briefly discussed. The suppression effects are estimated based on simple approximations.Comment: 13 page

Cutaneous immunoprofiles of three spotted fever group Rickettsia cases

Spotted fever group rickettsia (SFGR) can cause mild to fatal illness. The early interaction between the host and rickettsia in skin is largely unknown, and the pathogenesis of severe rickettsiosis remains an important topic. A surveillance of SFGR infection by PCR of blood and skin biopsy specimens followed by sequencing and immunohistochemical (IHC) detection was performed on patients with a recent tick bite between 2013 and 2016. Humoral and cutaneous immunoprofiles were evaluated in different SFGR cases by serum cytokine and chemokine detection, skin IHC staining, and transcriptome sequencing (RNA-seq). A total of 111 SFGR cases were identified, including 79 “Candidatus Rickettsia tarasevichiae,” 22 Rickettsia raoultii, 8 Rickettsia sibirica, and 2 Rickettsia heilongjiangensis cases. The sensitivity to detect SFGR in skin biopsy specimens (9/24, 37.5%) was significantly higher than that in blood samples (105/2,671, 3.9%) (P 0.05). As early as 1 day after the tick bite, rickettsiae could be detected in the skin. R. sibirica infection was more severe than “Ca. Rickettsia” and R. raoultii infections. Increased levels of serum interleukin-18 (IL- 18), IP10, and monokine induced by gamma interferon (MIG) and decreased levels of IL-2 were observed in febrile patients infected with R. sibirica compared to those infected with “Ca. Rickettsia.” RNA-seq and IHC staining could not discriminate between SFGR-infected and uninfected tick bite skin lesions. However, the type I interferon (IFN) response was differently expressed between R. sibirica and R. raoultii infections at the cutaneous interface. It is concluded that skin biopsy specimens were more reliable for the detection of SFGR infection in human patients although the immunoprofile may be complicated by immunomodulators induced by the tick bite.The Natural Science Foundation of China (81621005 and 81773492) and the State Key Research Development Program of China (2016YFC 1200301).https://iai.asm.orgam2020Veterinary Tropical Disease

Spinal Astrocytic Activation Is Involved in a Virally-Induced Rat Model of Neuropathic Pain

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and “NO-Astrocyte-Cytokine-NMDAR-Neuron” pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data