Background
This study investigated the activation of mitogen‐activated protein kinases in the spinal dorsal horn to explore the mechanisms underlying morphine‐induced acute and chronic hyperalgesia ...in mice.
Methods
Male adult mice were given a single subcutaneous injection (SC) of morphine (1 μg/kg) or twice‐daily administration of morphine (10 mg/kg/day) for 8 days. Thermal hyperalgesia and mechanical allodynia were assessed using the radiant heat and von Frey filament test. Levels of phospho (p)‐extracellular signal–regulated kinases (p‐ERK), p‐c‐Jun N‐terminal kinase (p‐JNK), p‐p38, p‐PKCγ, N‐methyl‐d‐aspartate receptor (NMDAr), and c‐Fos protein in the spinal dorsal horn were examined by Western blot assays.
Results
A single ultra‐low dose or repeated administration of morphine induced hyperalgesia in mice and caused a significant increase in the levels of p‐ERK and p‐JNK, but not p‐p38, in the spinal dorsal horn. The level of c‐Fos protein was significantly elevated following administration of morphine. The protein levels of p‐PKCγ and NMDAr subunits (NR2B and NR2A) were also altered. Pretreatment with the NMDAr antagonist MK‐801 or the protein kinase C (PKC) inhibitor calphostin C (CC) suppressed the morphine‐induced increase in p‐ERK, p‐JNK, and c‐Fos. Administration of MK‐801 and CC also relieved morphine‐induced hyperalgesia.
Conclusion
These findings suggest that activation of the spinal ERK and JNK signaling pathways contribute to morphine‐induced acute and chronic hyperalgesia in mice.
In this study, we evaluated our findings which suggest the activation of the spinal extracellular signal–regulated kinases, and the c‐Jun N‐terminal kinase signaling pathway contributes to morphine‐induced acute hyperalgesia in mice.
Background
Several studies have shown that scorpion venom peptide BmK AGAP has an analgesic activity. Our previous study also demonstrated that intraplantar injection of BmK AGAP ameliorates ...formalin-induced spontaneous nociceptive behavior. However, the effect of intrathecal injection of BmK AGAP on nociceptive processing is poorly understood.
Methods
We investigated the effects of intrathecal injection of BmK AGAP on spinal nociceptive processing induced by chronic constrictive injury or formalin. Thermal hyperalgesia and mechanical allodynia were measured using radiant heat and the von Frey filaments test. Formalin-induced spontaneous nociceptive behavior was also investigated. C-Fos expression was assessed by immunohistochemistry. Phosphorylated mitogen-activated protein kinase (p-MAPK) expression was monitored by Western blot assay.
Results
Intrathecal injection of BmK AGAP reduced chronic constrictive injury-induced neuropathic pain behavior and pain from formalin-induced inflammation, accompanied by decreased expression of spinal p-MAPKs and c-Fos protein. The results of combining low doses of different MAPK inhibitor (U0126, SP600125, or SB203580; 0.1 µg for each inhibitor) with a low dose of BmK AGAP (0.2 µg) suggested that BmK AGAP could potentiate the effects of MAPK inhibitors on inflammation-associated pain.
Conclusion
Our results demonstrate that intrathecal injection of BmK AGAP produces a sensory-specific analgesic effect via a p-MAPK-dependent mechanism.
Research question
Does artificial oocyte activation (AOA) by a calcium ionophore (ionomycin) improve the previous fertilization failure or poor embryo development of intracytoplasmic sperm injection ...(ICSI) account for male factor infertility or other infertility causes?
Design
This retrospective study involved 114 patients receiving ICSI-AOA in Shanghai First Maternity and Infant Hospital with previous ICSI fertilization failure or poor embryo development. The previous ICSI cycles of the same patients without AOA served as the control group. The fertilization rates, cleavage rates, transferable embryo rates and blastocyst formation rates of the two groups were compared. Additionally, the clinical pregnancy, implantation rate and live birth rates were also compared to assess the efficiency and safety of AOA. Furthermore, two subgroup analyses were performed in this study based on the cause of infertility and the reason for AOA. The fertilization rate, embryonic development potential and clinical outcome were compared among groups.
Results
Among 114 ICSI-AOA cycles, the fertilization rate, top-quality embryo rate, implantation rate, clinical pregnancy per patient and live birth rate per patient were improved significantly compared with previous ICSI cycles (p<0.05 to P< 0.001), and the miscarriage rate in the AOA group was significantly lower than that of the control group (p<0.001). In the AOA subgroups based on the cause of infertility, the fertilization rates of each subgroup were significantly improved compared with previous control cycles except for the mixed factor infertility subgroup (p<0.05 to p<0.001). In the AOA subgroups based on the reason for AOA, the fertilization rates of each subgroup were significantly increased compared with those in their previous ICSI cycle without AOA (p<0.001); however, there was no significant difference in the top-quality embryo rate. No significant improvement was found in the implantation rates and the clinical pregnancy rate in each subgroup except for the poor embryo development subgroup. In the 114 AOA cycles, 35 healthy infants (21 singletons and 7 twins) were delivered without major congenital birth defects or malformations.
Conclusion
This study showed that AOA with the calcium ionophore ionomycin can improve the reproductive outcomes of patients with previous fertilization failure and poor embryo development after ICSI.
Our previous studies have demonstrated that EphBs receptors and ephrinBs ligands were involved in modulation of spinal nociceptive information. However, the downstream mechanisms that control this ...process are not well understood. The aim of this study was to further investigate whether mitogen-activated protein kinases (MAPKs), as the downstream effectors, participate in modulation of spinal nociceptive information related to ephrinBs/EphBs.
Thermal hyperalgesia and mechanical allodynia were measured using radiant heat and von Frey filaments test. Immunofluorescence staining was used to detect the expression of p-MAPKs and of p-MAPKs/neuronal nuclei, or p-MAPKs/glial fibrillary acidic protein double label. C-Fos expression was determined by immunohistochemistry. The expression of p-MAPKs was also determined by Western blot assay.
Intrathecal injection of ephrinB1-Fc produced a dose- and time-dependent thermal and mechanical hyperalgesia, accompanied by the increase of spinal p-MAPKs and c-Fos expression. Immunofluorescence staining revealed that p-MAPKs colocalized with the neuronal marker (neuronal nuclei) and the astrocyte marker (glial fibrillary acidic protein). Inhibition of MAPKs prevented and reversed pain behaviors and the increase of spinal c-Fos expression induced by intrathecal injection of ephrinB1-Fc. Inhibition of EphBs receptors by intrathecal injection of EphB1-Fc reduced formalin-induced inflammation and chronic constrictive injury-induced neuropathic pain behaviors accompanied by decreased expression of spinal p-MAPKs and c-Fos protein. Furthermore, pretreatment with MK-801, an N-methyl-d-aspartate receptor antagonist, prevented behavioral hyperalgesia and activation of spinal MAPKs induced by intrathecal injection of ephrinB1-Fc.
These results demonstrated that activation of MAPKs contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs.
The striped fruit fly, Bactrocera (Zeugodacus) scutellata occurred in East and Southeast Asia and is one of the most serious pest insects in China. Complete mitochondrial genome was sequenced and ...characterized for the fruit fly from Anshun, Guizhou Province in Southwest China. The pest fruit fly has a total length of 15,904 bp, consisting of 13 protein-coding genes (PCGs), 22 tRNA, 2 rRNA genes and a non-coding region (A + T-rich control region). The phylogenetic position of B. scutellata was closely clustered with B. cucurbitae, B. tau, B. caudata and B. diaphora. The all species of the subgenus Zeugodacus formed a sister group which was monophyletic. The complete mitochondrial genome of B. scutellata will provide helpful information for genetics, systematics and phylogeny of tephritid fruit flies, Particularly Bactrocera genus.
EphBs receptors and ephrinBs ligands are present in the adult brain and peripheral tissue and play a critical role in modulating multiple aspects of physiology and pathophysiology. Ours and other ...studies have demonstrated that spinal ephrinBs/EphBs signaling was involved in the modulation of nociceptive information and central sensitization. However, the role of ephrinBs/EphBs signaling in peripheral sensitization is poorly understood. This study shows that intraplantar (i.pl.) injection of ephrinB1-Fc produces a dose- and time-dependent thermal and mechanical hyperalgesia and the increase of spinal Fos protein expression in mice, which can be partially prevented by pre-treatment with EphB1-Fc. EphrinB1-Fc-induced hyperalgesia is accompanied with the NMDA receptor-mediated increase of expression in peripheral and spinal phosphorylated mitogen-activated protein kinases (phospho-MAPKs) including p-p38, pERK and pJNK, and also is prevented or reversed by the inhibition of peripheral and spinal MAPKs. Furthermore, in formalin inflammation pain model, pre-inhibition of EphBs receptors by the injection of EphB1-Fc reduces pain behavior, which is accompanied by the decreased expression of peripheral p-p38, pERK and pJNK. These data provide evidence that ephrinBs may act as a prominent contributor to peripheral sensitization, and demonstrate that activation of peripheral ephrinBs/EphBs system induces hyperalgesia through a MAPKs-mediated mechanism.
The aim of this study is to investigate the effects of enalapril, an angiotensin‐converting enzyme inhibitor, on multiple organ damage after scald injury. Healthy adult rats (half male and half ...female; 8–12 weeks old) were randomly assigned to the following treatments: sham operation, scald injury, and intraperitoneal enalapril (1, 2, and 4 mg/kg body weight) treatment after scalding. At 1, 12, and 24 H postscald, left ventricular and aortic hemodynamics were measured using a multichannel physiological recorder. Functional and pathological changes of the heart, liver, and kidney were examined by biochemical and histological methods. Compared with sham controls, untreated scalded animals showed decreased hemodynamic parameters and increased myocardial angiotensin II, serum creatine kinase heart isoenzyme, and serum cardiac troponin I and histopathological inflammation in the myocardium 12 H postscald. These hemodynamic, functional, and pathological changes were attenuated by 1 mg/kg enalapril. Enalapril reversed scald‐induced elevations in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and blood creatinine 12 H postscald, and ameliorated focal necrosis in the liver and erythrocyte cast formation in renal tubules. However, higher doses of enalapril yielded less or no improvement in organ dysfunction. Enalapril at 1 mg/kg attenuates scald‐induced multiple organ damage in rats.
Abstract The aim of this study was to address the effects of shaking stress (a.k.a. physical agitation) on burn-induced remote organ injury and to evaluate the application of delayed fluid ...resuscitation to treat severe burns under shaking conditions. Healthy adult male rabbits, weighing 2.50 ± 0.40 kg, were randomly assigned to the following groups: control group, burn group, and burn + shaking group. One half of burned animals received a 6-h delayed fluid resuscitation and the other half remained untreated. Cardiovascular hemodynamics and functional and pathological changes of the heart and kidney were examined. Compared to normal controls, untreated burned animals showed decreased hemodynamic parameters, increased serum lactic acid, and severe myocardial inflammation. The burn-induced hemodynamic abnormalities and cardiac injury were aggravated by shaking stress. Burn injury led to reduced urine volume, elevated serum creatinine and blood urea nitrogen, and formation of erythrocyte casts in renal tubules. Shaking stimulation worsened the burn-associated functional and pathological changes of the kidney. Fluid resuscitation markedly mitigated cardiac and renal injury in burned animals, and, to a lesser extent, in the presence of shaking stimulation. Shaking stimulation aggravates burn-induced cardiovascular and renal disturbances. Delayed fluid resuscitation attenuates cardiac and renal damages in burn injury under shaking conditions.
To investigate the influence of Ureaplasma urealyticum (Uu) infection in the male reproductive tract on the outcomes of IVF and the clinical significance of preoperative Uu test by analyzing the ...correlation between the results of Uu culture before IVF-ET and the outcomes of IVF-ET.
Among 1,059 couples undergoing IVF-ET, we selected 973 after excluding genetic factors and divided them into a Uu negative and a Uu positive group according to the results of culture of Uu in the semen of the males. We compared the rates of IVF fertilization, oocyte cleavage, clinical pregnancy and abortion between the two groups, and analyzed the influence of Uu infection on IVF outcomes.
Among the 973 selected subjects, 836 were Uu negative (group A) and 137 Uu positive (group B), and of the latter, 130 were restored to Uu negative after treatment (group B1) and the other 7 remained unchanged (group B2). No significant differences were found between groups A and B in the rates of IVF fertilization (81.6% vs 79.8%, P = 0.13), abno
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