Abstract
Neuro-immune interactions are essential for our body’s defense and homeostasis. Anatomical and physiological analyses have shown that the nervous system comprises multiple pathways that ...regulate the dynamics and functions of immune cells, which are mainly mediated by the autonomic nervous system and adrenal signals. These are disturbed when the neurons and circuits are damaged by diseases of the central nervous system (CNS). Injuries caused by stroke or trauma often cause immune dysfunction by abrogation of the immune-regulating neural pathways, which leads to an increased risk of infections. Here, I review the structures and functions of the neural pathways connecting the brain and the immune system, and the neurogenic mechanisms of immune dysfunction that emerge after CNS injuries. Recent technological advances in manipulating specific neural circuits have added mechanistic aspects of neuro-immune interactions and their dysfunctions. Understanding the neural bases of immune control and their pathological processes will deepen our knowledge of homeostasis and lead to the development of strategies to cure immune deficiencies observed in various CNS disorders.
Neuro-immune circuitry in CNS injuries.
The blood-brain barrier (BBB) impedes the influx of intravascular compounds from the blood to the brain. The elements composing the BBB are endothelial cells, pericytes and the end-feet of ...astrocytes. Among them, the endothelial cell barrier line is the most critical for preventing toxic substances from entering the brain. In this review, we focus on the ultrastructural distribution of important components in the intracellular junction and cytoplasm of brain endothelial cells. The ultrastructural distribution of tight junction-specific integral membrane proteins such as occludin, junctional adhesion molecules, claudin, peripheral zonula occludens protein-1 (ZO-1), adherens junction-specific transmembrane protein cadherin, and adherens junction-associated peripheral proteins alpha-catenin, beta-catenin, and p120 catenin is reviewed. P-glycoprotein and some other transporters recently discovered in endothelial cells prevent several compounds from entering the brain parenchyma. It is likely that the transient inhibition of P-glycoprotein by antidepressants enables other medicines to enter the brain. Vesicular transport with clathrin-mediated or adsorptive endocytosis through endothelial cells is also critical for transportation of blood-born substances from the bloodstream to the brain. How medicines pass the BBB to reach the brain parenchyma is discussed.
Background
Esophageal cancer is the eighth most common cause of cancer mortality in Japan. More than 11,000 people had died from esophageal cancer in 2018. The Japan Esophageal Society has collected ...the data on patients' characteristics, performed treatment, and outcomes annually.
Methods
We analyzed the data of patients who had first visited the participating hospitals in 2013. In 2019, the data collection method was changed from an electronic submission to a web-based data collection using the National Clinical Database (NCD). Japanese Classification of Esophageal Cancer 10th by the Japan Esophageal Society (JES) and UICC TNM Classification 7th were used for cancer staging
Results
A total of 8019 cases were registered from 334 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.8% and 6.3%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, or esophagectomy were 88.3%, 32.4%, 24.4%, and 59.3%, respectively. Esophagectomy was performed in 4910 cases. The operative and the hospital mortality rates were 0.77% and 1.98%, respectively. The survival curves showed a good discriminatory ability both in the clinical and pathologic stages by the JES system. The 5-year survival rate of patients with pStage IV in the UICC classification that included patients with supraclavicular node metastasis was better than that of patients with pStage IVb in JES classification.
Conclusion
We hope this report contributes to improving all aspects of the diagnosis and treatment of esophageal cancer in Japan.
Inflammatory mechanisms may play an important role in the pathogenesis of cisplatin-induced nephrotoxicity. Curcumin is an orange-yellow polyphenol present in curry spice and has anti-inflammatory ...and antioxidant effects. The purpose of this study was to determine the protective effects of curcumin on cisplatin-induced nephrotoxicity. Mice were randomly divided into four groups: control, cisplatin, cisplatin + curcumin and curcumin. Mice were given cisplatin (20 mg/kg body weight, intraperitoneally) with or without curcumin treatment (100 mg/kg body weight, intraperitoneally, immediately after cisplatin injection). Serum and renal tumor necrosis factor (TNF)-alpha and renal monocyte chemoattractant protein (MCP)-1 concentrations, intercellular adhesion molecule-1 (ICAM-1) mRNA expression in kidney, renal function and histological changes were determined 72 h after cisplatin injection. Serum TNF-alpha concentration in the cisplatin + curcumin group significantly decreased compared with that in the cisplatin group. Renal TNF-alpha and MCP-1 concentrations and ICAM-1 mRNA expression in kidney in the cisplatin + curcumin group also significantly decreased compared with those in the cisplatin group. Consequently, cisplatin-induced renal dysfunction and renal tubular necrosis scores were attenuated by curcumin treatment. These results indicate that curcumin acts to reduce cisplatin-induced nephrotoxicity through its anti-inflammatory effects. Thus, curcumin may become a new therapeutic candidate for the treatment of cisplatin-induced nephrotoxicity.
Background
Recurrent esophageal cancer after radical therapy usually is thought to be incurable and treated with palliative-intent systemic therapy. However, it is empirically known that surgical ...resection may be effective for selected patients, although no consensus exists on the efficacy of surgery for recurrent esophageal cancer. This study sought to identify a group of patients for whom surgical resection is considered effective.
Methods
The study enrolled 206 patients at a single center who had recurrence after radical therapy for esophageal cancer. Prognostic factors after recurrence were identified, and efficacy of surgery was analyzed according to whether the recurrent lesions were oligometastases (i.e., ≤ 5 lesions in a single domain) or not.
Results
In the multivariate analysis, oligometastatic presentation was the only factor associated with survival after recurrence (hazard ratio 6.29; 95% confidence interval, 4.10–9.71). The actuarial survival rates for the patients with oligometastases were 59.5% at 3 years and 51.7% at 5 years. The survival rates at 3 and 5 years were significantly higher for the patients who underwent resection (64.3% and 55.6%, respectively) than for those who did not (both 100%) and for the patients with multiple metastases (9.8% and 0%, respectively). The survival rates for the patients who had oligometastases without resection were comparably lower than for the patients with multiple metastases.
Conclusion
Oligometastatic presentation at recurrence was associated with better survival outcomes for the patients who experienced recurrence after radical treatment for esophageal cancer, and surgical resection could be a choice of treatment for this group of patients.
Highlights • Microglia play bidirectional roles in neurogenesis. • Microglia control the survival and death of developing neurons. • Microglia engage in maintenance of axons and synapses. • Possible ...therapeutic strategy using microglia.
Brain injury causes serious motor, sensory, and cognitive disabilities. Accumulating evidence has demonstrated that histone deacetylase (HDAC) inhibitors exert neuroprotective effects against various ...insults to the central nervous system (CNS). In this study, we investigated the effects of the HDAC inhibition on the expression of brain-derived neurotrophic factor (BDNF) and functional recovery after traumatic brain injury (TBI) in mice. Administration of class I HDAC inhibitor increased the number of synaptic boutons in rewiring corticospinal fibers and improved the recovery of motor functions after TBI. Immunohistochemistry results showed that HDAC2 is mainly expressed in the neurons of the mouse spinal cord under normal conditions. After TBI, HDAC2 expression was increased in the spinal cord after 35 days, whereas BDNF expression was decreased after 42 days. Administration of CI-994 increased BDNF expression after TBI. Knockdown of HDAC2 elevated H4K5ac enrichment at the BDNF promoter, which was decreased following TBI. Together, our findings suggest that HDAC inhibition increases expression of neurotrophic factors, and promote neuronal rewiring and functional recovery following TBI.
Background
Age‐related events, such as cardiopulmonary complications, delirium, transfer to a rehabilitation facility, and dependency are a major problem after hepatic resection in the elderly. This ...prospective multicenter study aimed to preoperatively evaluate frailty in the elderly according to a phenotypic frail index, named the “Kihon Checklist (KCL),” to predict “age‐related events” after hepatic resection.
Methods
Between May 2016 and September 2017, 217 independently living patients who consented among all patients aged ≥65 years who planned to undergo hepatic resection were included in the study. Preoperative frailty was defined as a total KCL score ≥8. We analyzed clinical characteristics and outcomes, including age‐related events (major respiratory and cardiac complications, delirium medication needed, transfer to rehabilitation facility, and dependency) between patients with and without frailty.
Results
Of the 217 patients, 63 and 154 were classified into the frail and non‐frail groups, respectively. The incidences of age‐related events (31.7% vs. 7.8%, P < 0.001) were higher in the frail group. Multivariate analysis indicated that frailty (P < 0.001, hazard ratio 5.16) and resection of ≥2 sectors (P = 0.014, hazard ratio 2.98) were independent risk factors for age‐related events.
Conclusions
Frailty evaluated by KCL in the elderly can predict postoperative age‐related events after hepatic resection.
Highlight
In elderly patients scheduled to undergo hepatic resection, preoperative assessment of age‐related events, including respiratory complications, cardiac events, delirium, transfer to a rehabilitation facility and dependency, is essential. This prospective multicenter study by Tanaka and colleagues found that frailty evaluated by a phenotypic frailty index predicted age‐related events after hepatic resection.
Background
The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes annually.
Methods
We analyzed ...the data of patients who had visited the participating hospitals in 2014. We collected the data with a web-based data collection system using the National Clinical Database. We used the Japanese Classification of Esophageal Cancer 10th edition by JES and the TNM classification 7th edition by the Union of International Cancer Control (UICC) for cancer staging.
Results
A total of 9026 cases were registered from 344 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.9% and 7.1%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.1%, 33.7%, 25.3%, and 59.3%, respectively. Esophagectomy was performed in 5204 cases. Concerning the approach used for esophagectomy, 48.1% of the cases were treated thoracoscopically. The operative mortality (within 30 days after surgery) was 0.75%, and the hospital mortality was 2.0%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system, because pStage IV included the patients with supraclavicular lymph-node metastasis (M1 LYM).
Conclusion
We hope that this report contributes to improving all aspects of diagnosing and treating esophageal cancer in Japan.
Abstract
Type I IFNs (IFN-α and IFN-β), immunomodulatory cytokines secreted from activated plasmacytoid dendritic cells (pDCs), contribute to the innate defense against pathogenic infections and the ...pathogenesis of the autoimmune disease psoriasis vulgaris. A previous study has shown that an E26 transformation-specific (Ets) family transcription factor Spi-B can transactivate the type I IFN promoter in synergy with IFN regulatory factor (IRF)-7 and is required for type I IFN production in pDCs. However, the mechanism of negative regulation of type I IFNs by pDCs remains unknown. In this study, we report that a basic leucine zipper (bZip) transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB) suppresses the induction of type I IFNs in pDCs. The elevated expression of MafB inhibited the transactivation of type I IFN genes in a dose-dependent manner. At the molecular level, MafB interacted with the Ets domain of Spi-B and interfered with IRF-7–Spi-B complexation. Decreased MafB mRNA expression and degradation of MafB protein in the early phase of immune responses led to the enhancement of type I IFNs in pDCs. In vivo studies indicated that MafB is involved in resistance against imiquimod-induced psoriasis-like skin inflammation. Overall, these findings demonstrate that MafB acts as a negative regulator of type I IFN induction in pDCs and plays an important role in maintaining immune homeostasis.
MafB levels regulate type I IFN production in pDCs
Graphical Abstract
Graphical Abstract
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