Brain entropy changes in classical trigeminal neuralgia

BackgroundClassical trigeminal neuralgia (CTN) is a common and severe chronic neuropathic facial pain disorder. The pathological mechanisms of CTN are not fully understood. Recent studies have shown that resting-state functional magnetic resonance imaging (rs-fMRI) could provide insights into the functional changes of CTN patients and the complexity of neural processes. However, the precise spatial pattern of complexity changes in CTN patients is still unclear. This study is designed to explore the spatial distribution of complexity alterations in CTN patients using brain entropy (BEN).MethodsA total of 85 CTN patients and 79 age- and sex-matched healthy controls (HCs) were enrolled in this study. All participants underwent rs-fMRI and neuropsychological evaluations. BEN changes were analyzed to observe the spatial distribution of CTN patient complexity, as well as the relationship between these changes and clinical variables. Sixteen different machine learning methods were employed to classify the CTN patients from the HCs, and the best-performing method was selected.ResultsCompared with HCs, CTN patients exhibited increased BEN in the thalamus and brainstem, and decreased BEN in the inferior semilunar lobule. Further analyses revealed a low positive correlation between the average BEN values of the thalamus and neuropsychological assessments. Among the 16 machine learning methods, the Conditional Mutual Information Maximization-Random Forest (CMIM-RF) method yielded the highest area under the curve (AUC) of 0.801.ConclusionsOur study demonstrated that BEN changes in the thalamus and pons and inferior semilunar lobule were associated with CTN and machine learning methods could effectively classify CTN patients and HCs based on BEN changes. Our findings may provide new insights into the neuropathological mechanisms of CTN and have implications for the diagnosis and treatment of CTN

AaABF3, an Abscisic Acid–Responsive Transcription Factor, Positively Regulates Artemisinin Biosynthesis in Artemisia annua

Artemisinin is well known for its irreplaceable curative effect on the devastating parasitic disease, Malaria. This sesquiterpenoid is specifically produced in Chinese traditional herbal plant Artemisia annua. Earlier studies have shown that phytohormone abscisic acid (ABA) plays an important role in increasing the artemisinin content, but how ABA regulates artemisinin biosynthesis is still poorly understood. In this study, we identified that AaABF3 encoded an ABRE (ABA-responsive elements) binding factor. qRT-PCR analysis showed that AaABF3 was induced by ABA and expressed much higher in trichomes where artemisinin is synthesized and accumulated. To further investigate the mechanism of AaABF3 regulating the artemisinin biosynthesis, we carried out dual-luciferase analysis, yeast one-hybrid assay and electrophoretic mobility shift assay. The results revealed that AaABF3 could directly bind to the promoter of ALDH1 gene, which is a key gene in artemisinin biosynthesis, and activate the expression of ALDH1. Functional analysis revealed that overexpression of AaABF3 in A. annua enhanced the production of artemisinin, while RNA interference of AaABF3 resulted in decreased artemisinin content. Taken together, our results demonstrated that AaABF3 played an important role in ABA-regulated artemisinin biosynthesis through direct regulation of artemisinin biosynthesis gene, ALDH1

Recent progress of rare earth nanoparticles as magnetic resonance imaging contrast agents

Rare earth ions,owing to their unique 4f electron configurations,exhibit unique optical and magnetic properties.These rare earth nanoparticles are widely used as magnetic resonance imaging contrast agents.This paper reviews the classification,synthesis methods,and applications for magnetic resonance imaging of rare earth nanoparticles and makes some outlook

Chemoradiotherapy and Increased Prescription Dose in Esophageal Squamous Cell Cancer: A Retrospective Study

To analyze the outcomes and adverse events of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiation with modified radiotherapy volume and increased radiation dose. This was a retrospective analysis of patients with ESCC treated with definitive chemoradiotherapy at the Sun Yat-sen University Cancer Center (02/2015 to 02/2017). The dose to the planning gross tumor volume (PGTV) and planning clinical tumor volume (PTV1) was 66-68 Gy (2.0-2.2 Gy/fraction). The dose to the planning regional lymph node drainage area volume (PTV2) was 46 Gy (2.0 Gy/fraction). Treatment response, adverse events, progression-free survival (PFS), overall survival (OS), and locoregional failure-free survival (LRFFS) were analyzed. Twenty-six patients were included. The median follow-up was 31 (range, 4.3-51.3) months. Sixteen (61.5%) patients had a complete response, and four (15.4%) achieved a partial response. The objective response rate was 76.9%, and the disease control rate was 80.8%. The median PFS and OS were not achieved. The 4-year PFS was 63.9%, and the 4-year OS was 71.0%. Grade 1-2 and 3-4 radiation-related esophagitis was observed in 15 (57.7%) and one (4.5%) patients, respectively. Grade 1-2 and 3-4 radiation-related pneumonitis was observed in 12 (46.2%) and one (4.5%) patients, respectively. No patients developed radiation-related heart or skin damage. The modified target volume definition and increased dose of definitive radiotherapy combined with chemotherapy in patients with ESCC had low toxicity and might improve survival, but additional trials are necessary to prove the superiority of this strategy

Dachengqi Decoction Attenuates Inflammatory Response via Inhibiting HMGB1 Mediated NF-κB and P38 MAPK Signaling Pathways in Severe Acute Pancreatitis

Background/Aims: Severe acute pancreatitis (SAP) is a sudden inflammation of the pancreas. The traditional Chinese medicine formula Dachengqi decoction (DCQD) is proven to be beneficial in the comprehensive treatment for pancreatitis patients in clinical practice. However, the molecular mechanism of DCQD on SAP remains unclear. High mobility group box 1(HMGB1) that functions as a damage-associated molecular pattern molecule (DAMP) has attracted much interest. Methods: In this study, we used lipopolysaccharide (LPS) and cerulein to induce severe acute pancreatitis in C57BL/6 mice with subsequent administration with low, medium and high dose (2.3 g/kg, 7 g/kg and 21 g/kg, respectively) of DCQD. Results: DCQD treatment improved the pathological score and decreased serum amylase and lipase in a dose-dependent manner. In addition, it suppressed the immune cell-induced secretion of HMGB1 and its translocation from the nucleus to the cytoplasm, thus repressing the expression of IL-6 and TNF-α. Further, pretreatment with DCQD decreased responses of TLRs, and suppressed the activation of NF-kB and p38 MAPK pathway. Conclusion: Decreasing the secretion of HMGB1 could reduce pro-inflammatory cytokines, which may help cutting down the risks of development from localized pathological changes to a systemic inflammatory response syndrome and even lead to multiple organ failure

Increased Expressions of IL-22 and Th22 cells in the coxsackievirus B3-Induced mice acute viral myocarditis

Abstract Background Recently, a new subset of T helper (Th) cell that predominantly secret cytokine interleukin-22 (IL-22) is identified, termed Th22 cells. The Th22 subset has been demonstrated to be involved in immunity and tissue inflammation. However, the existence of Th22 cells and role of IL-22 in acute viral myocarditis (AVMC) remain unknown. Methods BALB/c mice were intraperitoneally (i.p) infected with CVB3 for establishing AVMC models. Control mice were treated with phosphate-buffered saline (PBS) i.p. On day 14 post injection, frequencies of splenic Th22 cells were determined, productions of IL-22 and expressions of IL-22R (IL-22 receptor) were measured. To further investigate the effects of IL-22, AVMC mice treated with Anti-IL-22 neutralizing antibody were explored. The severity of AVMC were monitored; the frequencies of Th22 cells, the expressions of IL-22 and IL-22R were investigated; in addition to IFN-γ, inflammatory cytokines IL-17, TNF-α, IL-6 as well as IL-1β, were evaluated. Cardiac viral replication were detected. Results Compared with control group, significant elevations of circulating Th22 cells and IL-22, cardiac protein and mRNA of IL-22, and IL-22R1 were demonstrated in AVMC group. Treatment of AVMC mice with Anti-IL-22 Ab exacerbated the severity of viral myocarditis, verified by lower survival rate, higher HW/BW ratios and cardiac pathological scores. Anti-IL-22 Ab decreased the frequencies of Th22 cells and the levels of IL-22, and increased the expressions of cardiac IL-22R1. Up-regulations of IL-17, IL-6 and TNF-α, down-regulations of IFN-γ proteins and gene expressions in the plasma and myocardium, were observed in Anti-IL-22 Ab group. Furthermore, neutralization of IL-22 significantly promoted cardiac viral replication. Conclusions Our data indicate that the increased frequencies of IL-22-producing Th22 cells may play an important role in the pathogenesis of CVB3-induced mice AVMC, IL-22 may act as an myocardium-protective cytokine via the IL-22–IL-22R pathway, and suggest that targeting the Th22 cell and IL-22–IL-22R pathway could provide new therapeutic modalities for the treatment of CVB3-induced AVMC.</p

Genome-wide analysis of the intrinsic apoptotic pathway in the tropical sea cucumber Holothuria leucospilota

To date, studies on apoptosis in echinoderms mainly focus on the caspase-dependent extrinsic apoptotic pathway, while knowledges regarding the intrinsic apoptotic pathway is still limited. In this study, 55 genes belong to 7 families of the intrinsic apoptotic pathway, namely, Bcl-2, caspase, AIF, Cyt c, Apaf-1, Smac, HTRA2 and Endo G, were identified by screening of the genomic database of the tropical sea cucumber Holothuria leucospilota. The Bcl-2 family showed significant gene expansion in H. leucospilota but not in other echinoderms, while the pro-apoptotic factor Endo G is generally lost in echinoderms. Transcriptomic data showed that the genes of the intrinsic apoptotic pathway were ubiquitously expressed in all tissues, and all embryonic and larval developmental stages of H. leucospilota. The gene numbers and functional domains of the caspase family and AIF family were further clarified and showed conserved with their counterparts in vertebrates. In primary coelomocytes, the transcript expression of different caspases showed different responses to pathogenic challenges of vibrio and pathogen-associated molecular patterns, and environmental challenges of heave metal and reactive oxygen species. Overall, this study indicates that the intrinsic apoptotic pathway is conserved between vertebrates and echinoderms by using the sea cucumber H. leucospilota as a model. This study may contribute in increasing the knowledge of development and innate immunity in ancestral deuterostomia species

Overexpression of AaWRKY1 Leads to an Enhanced Content of Artemisinin in Artemisia annua

Artemisinin is an effective component of drugs against malaria. The regulation of artemisinin biosynthesis is at the forefront of artemisinin research. Previous studies showed that AaWRKY1 can regulate the expression of ADS, which is the first key enzyme in artemisinin biosynthetic pathway. In this study, AaWRKY1 was cloned, and it activated ADSpro and CYPpro in tobacco using dual-LUC assay. To further study the function of AaWRKY1, pCAMBIA2300-AaWRKY1 construct under 35S promoter was generated. Transgenic plants containing AaWRKY1 were obtained, and four independent lines with high expression of AaWRKY1 were analyzed. The expression of ADS and CYP, the key enzymes in artemisinin biosynthetic pathway, was dramatically increased in AaWRKY1-overexpressing A. annua plants. Furthermore, the artemisinin yield increased significantly in AaWRKY1-overexpressing A. annua plants. These results showed that AaWRKY1 increased the content of artemisinin by regulating the expression of both ADS and CYP. It provides a new insight into the mechanism of regulation on artemisinin biosynthesis via transcription factors in the future

1‑Phenyl-4-benzoyl‑1<i>H</i>‑1,2,3-triazoles as Orally Bioavailable Transcriptional Function Suppressors of Estrogen-Related Receptor α

Estrogen-related receptor α is a potential candidate target for therapeutic treatment of breast cancer. We describe the discovery and structure–activity relationship study of a series of 1-phenyl-4-benzoyl-1<i>H</i>-1,2,3-triazoles as novel suppressors of ERRα transcriptional functions. The most promising compound, 2-aminophenyl-(1-(3-isopropylphenyl)-1<i>H</i>-1,2,3-triazol-4-yl)­methanone (<b>14n</b>), potently suppressed the transcriptional functions of ERRα with IC₅₀ = 0.021 μM in a cell-based reporter gene assay and also decreased both the mRNA levels and the protein levels of ERRα and the downstream targets. This compound inhibited the proliferation and migration of breast cancer cells with high level of ERRα. Preliminary pharmacokinetic studies suggested that it possessed a good pharmacokinetic profile with an oral bioavailability of 71.8%. The compounds may serve as novel small molecule probes for further validation of ERRα as a molecular target for anticancer drug development