Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation

Objective. The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI). Methods. Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg) were administrated intragastrically at early phase of postoperation (before pain appearance) and later phase of postoperation (after pain appearance), respectively. The concentrations of TNF-α, IL-1β, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment. Results. TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-α and IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1β increase. Conclusion. This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase

Beta-estradiol attenuates hypoxic pulmonary hypertension by stabilizing the expression of p27kip1 in rats

<p>Abstract</p> <p>Background</p> <p>Pulmonary vascular structure remodeling (PVSR) is a hallmark of pulmonary hypertension. P27^kip1, one of critical cyclin-dependent kinase inhibitors, has been shown to mediate anti-proliferation effects on various vascular cells. Beta-estradiol (β-E2) has numerous biological protective effects including attenuation of hypoxic pulmonary hypertension (HPH). In the present study, we employed β-E2 to investigate the roles of p27^kip1and its closely-related kinase (Skp-2) in the progression of PVSR and HPH.</p> <p>Methods</p> <p>Sprague-Dawley rats treated with or without β-E2 were challenged by intermittent chronic hypoxia exposure for 4 weeks to establish hypoxic pulmonary hypertension models, which resemble moderate severity of hypoxia-induced PH in humans. Subsequently, hemodynamic and pulmonary pathomorphology data were gathered. Additionally, pulmonary artery smooth muscle cells (PASMCs) were cultured to determine the anti-proliferation effect of β-E2 under hypoxia exposure. Western blotting or reverse transcriptional polymerase chain reaction (RT-PCR) were adopted to test p27^kip1, Skp-2 and Akt-P changes in rat lung tissue and cultured PASMCs.</p> <p>Results</p> <p>Chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of right ventricle/left ventricle plus septum (RV/LV+S) ratio, medial width of pulmonary arterioles, accompanied with decreased expression of p27^kip1in rats. Whereas, β-E2 treatment repressed the elevation of RVSP, RV/LV+S, attenuated the PVSR of pulmonary arterioles induced by chronic hypoxia, and stabilized the expression of p27^kip1. Study also showed that β-E2 application suppressed the proliferation of PASMCs and elevated the expression of p27^kip1under hypoxia exposure. In addition, experiments both <it>in vivo </it>and <it>in vitro </it>consistently indicated an escalation of Skp-2 and phosphorylated Akt under hypoxia condition. Besides, all these changes were alleviated in the presence of β-E2.</p> <p>Conclusions</p> <p>Our results suggest that β-E2 can effectively attenuate PVSR and HPH. The underlying mechanism may partially be through the increased p27^kip1by inhibiting Skp-2 through Akt signal pathway. Therefore, targeting up-regulation of p27^kip1or down-regulation of Skp-2 might provide new strategies for treatment of HPH.</p

Unraveling the role of NLRP3 inflammasome in allergic inflammation: implications for novel therapies

Allergic diseases like asthma, allergic rhinitis and dermatitis pose a significant global health burden, driving the search for novel therapies. The NLRP3 inflammasome, a key component of the innate immune system, is implicated in various inflammatory diseases. Upon exposure to allergens, NLRP3 undergoes a two-step activation process (priming and assembly) to form active inflammasomes. These inflammasomes trigger caspase-1 activation, leading to the cleavage of pro-inflammatory cytokines (IL-1β and IL-18) and GSDMD. This process induces pyroptosis and amplifies inflammation. Recent studies in humans and mice strongly suggest a link between the NLRP3 inflammasome, IL-1β, and IL-18, and the development of allergic diseases. However, further research is needed to fully understand NLRP3’s specific mechanisms in allergies. This review aims to summarize the latest advances in NLRP3 activation and regulation. We will discuss small molecule drugs and natural products targeting NLRP3 as potential therapeutic strategies for allergic diseases

Genotype V Japanese Encephalitis Virus Is Emerging

Japanese encephalitis (JE) is a global public health issue that has spread widely to more than 20 countries in Asia and has extended its geographic range to the south Pacific region including Australia. JE has become the most important cause of viral encephalitis in the world. Japanese encephalitis viruses (JEV) are divided into five genotypes, based on the nucleotide sequence of the envelope (E) gene. The Muar strain, isolated from patient in Malaya in 1952, is the sole example of genotype V JEV. Here, the XZ0934 strain of JEV was isolated from Culex tritaeniorhynchus, collected in China. The complete nucleotide and amino acid sequence of XZ0934 strain have been determined. The nucleotide divergence ranged from 20.3% to 21.4% and amino acid divergence ranged from 8.4% to 10.0% when compared with the 62 known JEV isolates that belong to genotype I–IV. It reveals low similarity between XZ0934 and genotype I–IV JEVs. Phylogenetic analysis using both complete genome and structural gene nucleotide sequences demonstrates that XZ0934 belongs to genotype V. This, in turn, suggests that genotype V JEV is emerging in JEV endemic areas. Thus, increased surveillance and diagnosis of viral encephalitis caused by genotype V JEV is an issue of great concern to nations in which JEV is endemic

Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation

Objective. The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI). Methods. Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg) were administrated intragastrically at early phase of postoperation (before pain appearance) and later phase of postoperation (after pain appearance), respectively. The concentrations of TNF-α, IL-1β, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment. Results. TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-α and IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1β increase. Conclusion. This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase

Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation

Objective. The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI). Methods. Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg) were administrated intragastrically at early phase of postoperation (before pain appearance) and later phase of postoperation (after pain appearance), respectively. The concentrations of TNF-, IL-1 , and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment. Results. TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-and IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1 increase. Conclusion. This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase

Rubisco Activase Is Also a Multiple Responder to Abiotic Stresses in Rice

<div><p>Ribulose-1,5-bisphosphate carboxylase/oxygenase activase (RCA) is a nuclear gene that encodes a chloroplast protein that plays an important role in photosynthesis. Some reports have indicated that it may play a role in acclimation to different abiotic stresses. In this paper, we analyzed the stress-responsive elements in the 2.0 kb 5’-upstream regions of the RCA gene promoter and the primary, secondary and tertiary structure of the protein. We identified some cis-elements of multiple stress-related components in the RCA promoter. Amino acid and evolution analyses showed that the RCA protein had conserved regions between different species; however, the size and type varied. The secondary structures, binding sites and tertiary structures of the RCA proteins were also different. This might reflect the differences in the transcription and translation levels of the two RCA isoforms during adaptation to different abiotic stresses. Although both the transcription and translation levels of RCA isoforms in the rice leaves increased under various stresses, the large isoform was increased more significantly in the chloroplast stroma and thylakoid. It can be concluded that RCA, especially RCA_L, is also a multiple responder to abiotic stresses in rice, which provides new insights into RCA functions.</p></div

Pairwise amino acid sequence identity of <i>RCA_L</i> and <i>RCA_S</i> among different plants.

<p>Pairwise amino acid sequence identity of <i>RCA_L</i> and <i>RCA_S</i> among different plants.</p

The differences in secondary structure between RCA_L and RCA_S.

<p>(<i>A</i>) The secondary structure and disorder confidence of RCA_S. (<i>B</i>) The secondary structure and disorder confidence of RCA_L. (<i>C</i>) The (<i>B</i>) The quantitative analysis of the secondary structure of RCA.</p