Therapeutic effects and mechanisms of isoxanthohumol on DSS-induced colitis: regulating T cell development, restoring gut microbiota, and improving metabolic disorders.

Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60 mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-( +)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC.

Dietary ellagic acid therapy for CNS autoimmunity: Targeting on Alloprevotella rava and propionate metabolism.

BACKGROUND: Mediterranean diet rich in polyphenolic compounds holds great promise to prevent and alleviate multiple sclerosis (MS), a central nervous system autoimmune disease associated with gut microbiome dysbiosis. Health-promoting effects of natural polyphenols with low bioavailability could be attributed to gut microbiota reconstruction. However, its underlying mechanism of action remains elusive, resulting in rare therapies have proposed for polyphenol-targeted modulation of gut microbiota for the treatment of MS. RESULTS: We found that oral ellagic acid (EA), a natural polyphenol rich in the Mediterranean diet, effectively halted the progression of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, via regulating a microbiota-metabolites-immunity axis. EA remodeled the gut microbiome composition and particularly increased the relative abundances of short-chain fatty acids -producing bacteria like Alloprevotella. Propionate (C3) was most significantly up-regulated by EA, and integrative modeling revealed a strong negative correlation between Alloprevotella or C3 and the pathological symptoms of EAE. Gut microbiota depletion negated the alleviating effects of EA on EAE, whereas oral administration of Alloprevotella rava mimicked the beneficial effects of EA on EAE. Moreover, EA directly promoted Alloprevotella rava (DSM 22548) growth and C3 production in vitro. The cell-free supernatants of Alloprevotella rava co-culture with EA suppressed Th17 differentiation by modulating acetylation in cell models. C3 can alleviate EAE development, and the mechanism may be through inhibiting HDAC activity and up-regulating acetylation thereby reducing inflammatory cytokines secreted by pathogenic Th17 cells. CONCLUSIONS: Our study identifies EA as a novel and potentially effective prebiotic for improving MS and other autoimmune diseases via the microbiota-metabolites-immunity axis. Video Abstract.

Peroxisom proliferator-activated receptor-γ coactivator-1α in neurodegenerative disorders: A promising therapeutic target.

Neurodegenerative disorders (NDDs) are characterized by progressive loss of selectively vulnerable neuronal populations and myelin sheath, leading to behavioral and cognitive dysfunction that adversely affect the quality of life. Identifying novel therapies that attenuate the progression of NDDs would be of significance. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a widely expressed transcriptional regulator, modulates the expression of genes engaged in mitochondrial biosynthesis, metabolic regulation, and oxidative stress (OS). Emerging evidences point to the strong connection between PGC-1α and NDDs, suggesting its positive impaction on the progression of NDDs. Therefore, it is urgent to gain a deeper and broader understanding between PGC-1α and NDDs. To this end, this review presents a comprehensive overview of PGC-1α, including its basic characteristics, the post-translational modulations, as well as the interacting transcription factors. Secondly, the pathogenesis of PGC-1α in various NDDs, such as Alzheimer's (AD), Parkinson's (PD), and Huntington's disease (HD) is briefly discussed. Additionally, this study summarizes the underlying mechanisms that PGC-1α is neuroprotective in NDDs via regulating neuroinflammation, OS, and mitochondrial dysfunction. Finally, we briefly outline the shortcomings of current NDDs drug therapy, and summarize the functions and potential applications of currently available PGC-1α modulators (activator or inhibitors). Generally, this review updates our insight of the important role of PGC-1α on the development of NDDs, and provides a promising therapeutic target/ drug for the treatment of NDDs.

Multimodal endovascular treatment for traumatic carotid-cavernous fistula / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To present our experience in treating traumatic carotid-cavernous fistula (TCCF) by multimodal endovascular treatment.</p><p><b>METHODS</b>The management of 28 patients with TCCF between January 2004 and October 2012 in our hospital was retrospectively analyzed. According to imaging charateristics, 24 cases were categorized into Type I, 3 Type II and 1 Type III. Totally 30 endovascular treatments were performed: Type I TCCFs were obliterated via transvenous approach (7/25), or transarterial approach (18/25) including 6 by detachable balloon occlusion, 6 by microcoil embolization, 3 by Hyperglide balloon-assisted coil embolization and 3 by a combination of detachable balloon and coil embolization. Two patients were treated with closure of internal carotid artery (ICA). Type II TCCFs were treated with transvenous embolotherapy (2/3) or carotid artery compression therapy (1/3). The Type III patient underwent detachable balloon embolization.</p><p><b>RESULTS</b>Immediate postoperative angiography showed recovery in 26 cases. One recurrent TCCF was found 2 weeks after detachable balloon embolization, and then re-obliterated by transarterial coils. Reexamination found balloon deflation and fistula recanalization in 1 patient one month after combination of detachable balloons and coil embolization, which was cured by a second treatment via transvenous approach. The immediate angiography revealed residual blood flow in 4 patients. Among them, 2 patients with delayed symptoms at follow-up needed a second treatment, 1 patient recovered after carotid artery compression therapy, and the remaining patient's symptoms disappeared on digital subtraction angiography at five-month follow-up. CT angiography revealed anterior communicating artery aneurysm in the patient who was treated with closure of ICA 4 years later.</p><p><b>CONCLUSION</b>According to results of images, characteristics of the fistula and type of drainage, proper treatment approach and embolic material can maximally heal pathological changes, retain the ipsilateral ICA patency and reduce long-term complications.</p>

Chronic subdural hematoma associated with sylvian arachnoid cyst in juvenile athletes: report of two cases and literature review / 中华创伤杂志(英文版)

The association of chronic subdural hematoma (CSDH) and arachnoid cyst (AC) is uncommon. We reported 2 juvenile athletes with CSDH associated with AC which occurred in their daily sports activities and reviewed the literature. Both of them were treated surgically, with satisfactory outcome. AC is a common predisposing factor in young patients with CSDH. The complication of intracranial bleeding is an indication for surgical management. Though there are still controversies in the treatment of asymptomatic AC, it is the consensus that the patients with AC should avoid violent sports so as to reduce the incidence of intracranial hemorrhage resulted from head injuries.

Posttraumatic hydrocephalus associated with decompressive cranial defect in severe brain-injured patients / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the occurrence of posttraumatic hydrocephalus (PTH) in severe brain- injured patients who underwent decompressive craniectomy (DC) and to discuss the management.</p><p><b>METHODS</b>A total of 389 patients suffering from severe head trauma between January 2004 and May 2010 were enrolled in this study. Clinical data were analyzed retrospectively. Of them, 149 patients who underwent DC were divided into two groups according to the presence of PTH: hydrocephalus group and nonhydrocephalus group. Clinical factors including preoperative Glasgow Coma Score (GCS), bilateral or unilateral decompression, and duraplasty in DC were assessed by single factor analysis to determine its relationship with the occurrence of PTH.</p><p><b>RESULTS</b>Of the 149 patients undergoing DC, 25 (16.8%) developed PTH; while 23 developed PTH (9.6%) among the rest 240 patients without DC. Preoperative GCS, bilateral or unilateral decompression, duraplasty in DC were significantly associated with the development of PTH. Ventriculoperitoneal shunt was performed on 23 of 25 patients with PTH after DC. Frontal horn was preferred for the placement of the catheter. Sixteen of them were operated upon via frontal approach and 7 via occipital approach. After shunt surgery, both radiological and clinical improvements were confirmed in 19 patients. Radiological improvement was found in 2 patients. One patient died eventually of severe pneumonia. Shunt-related infection occurred in 1 patient, which led to the removal of the catheter.</p><p><b>CONCLUSIONS</b>It is demonstrated that the occurrence of PTH is high in patients with large decompressive skull defect. Patients with low GCS and bilateral decompression tend to develop PTH after DC. Duraplasty in DC might facilitate reducing the occurrence of PTH. Patients with PTH concomitant skull defect should be managed deliberately to restore the anatomical and physiological integrity so as to facilitate the neurological resuscitation.</p>