The cytokine genes of Oncorhynchus masou formosanus include a defective interleukin-4/13A gene.

Oncorhynchus masou formosanus (Formosa landlocked salmon) is a critically endangered salmonid fish endemic to Taiwan. To begin to understand how its drastic change in lifestyle from anadromous to exclusively river-dwelling is reflected in its immune genes, we characterized the genes encoding six cytokines (IL-2A, IL-2B, IL-4/13A, IL-4/13B1, IL-4/13B2, and IL-17A/F2a) important for T cell responses as no genomic data is available for this fish. Interestingly, all genes appeared homozygous indicative of a genetic bottleneck. The IL2 and IL17A/F2a genes and their products are highly similar to their characterized homologs in Oncorhynchus mykiss (rainbow trout) and other salmonid fish. Two notable differences were observed in IL4/13 family important for type 2 immune responses. First, O. m. formosanus carries not only one but two genes encoding IL-4/13B1 proteins and expansions of these genes are present in other salmonid fish. Second, the OmfoIL4/13A gene carries a 228 bp deletion that results in a premature stop codon and hence a non-functional IL-4/13A cytokine. This suggests a reduced ability for T cell responses against parasitic infections in this species.

Neuroprotective effect of salidroside on hippocampal neurons in diabetic mice via PI3K/Akt/GSK-3ß signaling pathway.

BACKGROUND: Diabetic encephalopathy is manifested by cognitive dysfunction. Salidroside, a nature compound isolated from Rhodiola rosea L, has the effects of anti-inflammatory and antioxidant, hypoglycemic and lipid-lowering, improving insulin resistance, inhibiting cell apoptosis, and protecting neurons. However, the mechanism by which salidroside alleviates neuronal degeneration and improves learning and memory impairment in diabetic mice remains unclear. OBJECTIVE: To investigate the effects and mechanisms of salidroside on hippocampal neurons in streptozotocin-induced diabetic mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into 4 groups to receive either sham (control group (CON)), diabetes mellitus (diabetes group (DM)), diabetes mellitus + salidroside (salidroside group (DM + SAL)), and diabetes mellitus + salidroside + phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (diabetes mellitus + salidroside + LY294002 group (DM + SAL + LY294002)). After 12 weeks of diabetes onset, the cognitive behaviors were tested using Morris water maze. The number of hippocampal neurons was detected by Nissl staining. The expressions of PI3K, p-PI3K, Akt, p-Akt, GSK-3ß, p-GSK-3ß, cleaved caspase-3, caspase-3, Bax, Bcl-2, MAP2, and SYN in the hippocampus were detected by Western blot. Moreover, the expression of MAP2 and SYN in the hippocampus was further confirmed by immunofluorescence staining. RESULTS: Salidroside increased the time of diabetic mice in the platform quadrant and reduced the escape latency of diabetic mice. Salidroside also increased the expression of p-PI3K, p-Akt, p-GSK-3ß, MAP2, SYN, Bcl-2, while suppressed the expression of cleaved caspase-3, caspase3, and Bax in the DM + SAL group compared with the DM group (P < 0.05). The Nissl staining showed that the number of hippocampus neurons in the DM + SAL group was increased with the intact, compact, and regular arrangement, compared with the DM groups (P < 0.05). Interestingly, the protective effects of salidroside on diabetic cognitive dysfunction, hippocampal morphological alterations, and protein expressions were abolished by inhibition of PI3K with LY294002. CONCLUSIONS: Salidroside exerts neuroprotective properties in diabetic cognitive dysfunction partly via activating the PI3K/Akt/GSK-3ß signaling pathway.

Anemia in patients with Takayasu arteritis: prevalence, clinical features, and treatment.

BACKGROUND: Anemia is a common comorbidity of patients with Takayasu arteritis (TA). This study evaluated the prevalence, clinical characteristics, and treatment in Chinese TA patients with anemia. METHODS: This retrospective study included 533 consecutive patients hospitalized for TA from January 2009 to April 2018. Anemia was diagnosed on the basis of hemoglobin level, according to World Health Organization criteria. RESULTS: A total of 194 patients (36.4%) were diagnosed with anemia. Most had mild anemia (177, 91.2%). Female patients were predominant (92.8% of anemic patients). Normocytic anemia (62.9%) was the most common pattern. Anemic patients were more likely than non-anemic patients to have dizziness (29.4% vs. 21.2%), low body mass index (22.0 ± 3.6 vs. 22.9 ± 3.4 kg/m2), and active disease stage (64.9% vs. 50.1%); pulmonary involvement (12.4% vs. 26.8%), pulmonary hypertension (12.9% vs. 20.1%) and pulmonary hypertensive-target drugs (2.8% vs. 11.6%) were less common among anemic than non-anemic patients (all P < 0.05). Larger left ventricular end-diastolic diameter and lower left ventricular ejection fraction were observed in anemic patients. Over a median follow-up of four months, the increase of hemoglobin in anemic patients was associated with the use of iron supplementation. CONCLUSIONS: Anemia is a very common concurrent condition in TA, especially in young, female patients. Patients with anemia are more likely to be in the active disease stage. Iron supplementation helps increase hemoglobin.

Aortic Aneurysm in Takayasu Arteritis.

BACKGROUND: Aortic aneurysm (AA) is a severe complication of Takayasu arteritis (TA). This study aimed to evaluate the prevalence, clinical and imaging features, management and long-term outcomes of AA in patients with TA. MATERIALS AND METHODS: A retrospective study was performed of TA patients with AA admitted to Fuwai Hospital from 1996-2015. Baseline clinical data and follow-up data of TA patients with AA were collected and analyzed. RESULTS: Thirty-nine (4.2%) of 934 patients with TA were identified with AA that was related to vasculitis. The mean age at disease onset was 31 ± 10 years, with a female-to-male ratio of 1.79:1. The ascending aorta was the most common site of the aneurysmal lesion (18, 33.3%), and the most frequent manifestations associated with AA were chest tightness (12, 30.8%) and shortness of breath (12, 30.8%), which were usually concomitant with aortic valve insufficiency. Involvement of multiple sites in AA was found in 8 patients (20.5%), and multiple AAs were found in 5 patients (12.8%). No significant difference was observed in clinical and imaging findings between sexes. Of 25 patients (64.1%) with a median 72-month follow-up, 1 patient suffered from heart failure owing to perivalvular leakage, and 1 patient died, possibly related to severe complications of the operation. CONCLUSIONS: The prevalence of AA is relatively low in Chinese patients with TA. AA seems to develop more frequently in male patients with TA. Management should consider location and size of AA, complexity of vessel lesions and disease status. Long-term follow-up is indispensable.

Aortic Dissection in Takayasu Arteritis.

BACKGROUND: Aortic dissection (AD) is a rare complication of Takayasu arteritis (TA). The clinical presentation and long-term management outcomes of AD in patients with TA have not been well described. MATERIALS AND METHODS: We conducted a retrospective study of patients with TA along with AD admitted to Fuwai Hospital between January 1985 and March 2016. Clinical data and follow-up data were collected and analyzed. RESULTS: Of the 1,154 patients with TA, we identified 10 patients (0.87%) with AD, which was likely to be associated with vasculitis. All patients were females with a median age at TA onset of 26.5 years (range: 18.3-33.3 years), had type III TA and had a history of hypertension, which was much more common than that in previously reported cases. Stanford type B or DeBakey category III was the dominant anatomic classification of AD. Four patients developed AD after the diagnosis of TA, and 6 developed AD near the time of TA diagnosis. Nine patients underwent conservative treatment, whereas 1 patient underwent endovascular repair due to extensive dissection. At a median 70.5-month follow-up (range: 31.5-138.5), we found that 7 patients had no AD progression, 1 patient had progressed without symptoms, 1 patient was lost and 1 patient died. CONCLUSIONS: Patients with TA along with long-standing and poorly controlled hypertension are liable to develop AD. Those with extensive AD in TA should be carefully treated and intensively followed up.

The association of red blood cell distribution width with anemia and inflammation in patients with Takayasu arteritis.

BACKGROUND: Red blood cell distribution width (RDW) has been shown to be related to both anemia and inflammation in various diseases. However, the role of RDW in patients with Takayasu arteritis (TA) is unknown. Therefore, we investigated the association of RDW with anemia, inflammation, and disease activity in TA. METHODS: RDW was determined in 156 patients with TA and in 156 control subjects. Anemia status and disease activity were defined according to the World Health Organization and National Institutes of Health criteria, respectively. RESULTS: RDW was significantly increased in patients with anemia (14.6±2.2) compared with those without anemia (13.6±1.3, p<0.001) and control subjects (12.7±0.6, p<0.001). Regardless of the presence of anemia, RDW showed correlation with high-sensitivity C-reactive protein (hs-CRP) (both p<0.05). RDW was higher in active TA than inactive TA in patients without anemia (14.1±1.5 vs. 13.3±1.1, p=0.001). Moreover, multiple regression analysis showed that hs-CRP and mean corpuscular volume were independently associated with RDW. CONCLUSIONS: RDW is influenced by both anemia and inflammation, and RDW may be a useful marker to assess disease activity in patients without anemia.

N-terminal Pro-B-type Natriuretic Peptide is Associated with Arterial Stiffness as Measured According to the Brachial-ankle Pulse Wave Velocity in Patients with Takayasu Arteritis.

AIM: Takayasu arteritis (TA) is associated with increased cardiovascular morbidity and mortality, and the degree of arterial stiffness is an independent predictor of cardiovascular mortality in a variety of diseases. In addition, the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of ventricular dysfunction, have been found to be higher in patients with TA than in healthy controls. In this study, we aimed to investigate the relationship between the plasma NT-proBNP levels and arterial stiffness in patients with TA. METHODS: Seventy-two patients with TA were recruited in this study. The participants were analyzed with respect to the NT-proBNP levels, cardiovascular risk factors, TA-related variables and arterial stiffness assessed according to the brachial-ankle pulse wave velocity (baPWV). The patients were divided into two groups based on the mean baPWV, and the association between the NT-proBNP and baPWV values was tested using uni- and multivariate analyses. RESULTS: Twenty-four patients (33.3%) were classified into the high-baPWV group. The body mass index (p=0.035), systolic blood pressure (p＜0.001), diastolic blood pressure (p=0.001), mean blood pressure (p＜0.001), plasma NT-proBNP levels (p=0.036) and total cholesterol levels (p=0.030) were significantly higher in the high-baPWV group than in the low-baPWV group. A stepwise multiple linear regression analysis revealed the mean blood pressure (p＜0.001), age (p=0.002), and NT-proBNP level (p=0.002) to be independent determinants of the ba-PWV after adjusting for other confounding factors. CONCLUSIONS: The plasma NT-proBNP levels are independently associated with the degree of arterial stiffness measured according to the baPWV in patients with TA.

Construction and functional activity of a recombinant vector expressing rat glutamic acid decarboxylase 65.

OBJECTIVE: Glutamic acid decarboxylase 2 (GAD65) is a gamma-aminobutyric acid (GABA) synthetase. This study aimed to construct a recombinant lentivirus-rGAD65 (rLV-rGAD65) vector containing the cDNA of rat GAD65 (rGAD65) and assess its functional activity in vitro and in vivo. METHODS: cDNA of rGAD65 was amplified by RT-PCR and subcloned into the LV vector, forming the rLV-GFP-rGAD65 plasmid. The recombinant lentivirus particles (rLV-rGAD65) were packaged by the LV Helper-Free System and the titer was measured. Primary rat lung fibroblasts were transfected with rLV-rGAD65. The expression of rGAD65 in fibroblasts was detected by immunocytochemistry and western blot and the level of GABA in the medium was assessed by high-performance liquid chromatograph (HPLC). In vivo, rLV-rGAD65 was injected into the subthalamic nucleus (STN) of Sprague-Dawley rats using stereotaxic methods, and rGAD65 protein levels in the STN were assessed by immunohistochemistry and Western blot, while the GABA concentration in the substantia nigra pars reticulata (SNr) was assayed by HPLC. RESULTS: The sequence of rGAD65 cDNA was in accord with that in GenBank. The amino-acid sequence of rGAD65 had no mutations and the titer of rLV-rGAD65 reached 6.8 × 108/mL. The efficiency of infection of fibroblasts was 80%, and the concentration of GABA in the medium was (48.14 +/- 9.35) nmol/L. In vivo, rGAD65 expression was detected in the STN, and the concentration of GABA in the SNr increased from (5.95 +/- 1.09) to (12.44 +/- 3.79) nmol/g tissue. CONCLUSION: The recombinant LV-GFP-rGAD65 vector was successfully constructed. rLV-rGAD65-infected primary fibroblasts in vitro and the expressed rGAD65 catalyzed the formation of GABA from glutamic acid. In vivo, the concentration of GABA in the SNr was increased after rLV-rGAD65 injection into the STN.

[Experimental study on tracheal reconstruction using porous titanium rings and free skin flap].

OBJECTIVE: To investigate the feasibility and efficacy of the cervical tracheal reconstruction using porous titanium rings and free skin flap. METHODS: Twelve adult mongrel dogs were divided randomly into group I and group lI. A segment of cervical trachea (25 mm, 4 rings, about 2/3 circumference) was resected and a rectangular free skin flap was harvested from abdomen. The flap was sutured to the defect part and supported with two porous titanium rings (group I) or without (group II ). X ray and fiberscopic examinations were performed at the end of the first and the sixth months postoperatively. After six months the dogs were sacrificed and the grafts were examined macroscopically and microscopically. RESULTS: In group I, one dog was sacrificed for wound infection and skin flap necrosis with deflexion of titanium rings in the fifth day postoperatively. The other 5 of 6 survived until the end of six months. X-ray examination showed titanium rings were fastened well without displacement or deformity. Through fiberscopy, the trachea luminal patency was maintained well without stricture, shrinkage or necrosis. Histologic examination showed most of the inner surface of the flap was covered with ciliated columnar epithelium. In group II, 3 of 6 dogs died of suffocation within 24 hours postoperatively. The remaining 3 dogs survived from 7 to 16 days with dyspnea and fiberscopic examination showed narrowed trachea lumens. CONCLUSIONS: Porous titanium rings could recreate the framework for cervical tracheal reconstruction using free skin flap and would be one of the options for tracheal reconstruction.

[Clinical results of stent revascularization as treatment for renal artery stenosis during 6 months of follow-up].

OBJECTIVES: To evaluate the safety and midterm efficacy of stent revascularization as treatment for renal artery stenosis. METHODS: Percutaneous transluminal renal angioplasty with stent (PTRA) was performed because of poorly controlled hypertension or preservation of renal function in 150 consecutive patients with severe renal artery stenosis, caused by atheroma (96 patients), arteritis (44 patients) and fibromuscular dysplasia (10 patients). All of them subsequently underwent 6-month clinical follow-up to observe the effect of the procedure on renal function, blood pressure control, number of antihypertensive medications. RESULT: Angiographic success was obtained in 148 (98.7%) of 150 patients after PTRA. At 6 months, both systolic and diastolic blood pressures significantly decreased (from 169.6 to 142.7 mm Hg and from 97.3 to 83.3 mm Hg, respectively; P < 0.001), and less antihypertensive medication was taken (from 2.7 to 1.9). The blood pressure became normal without taking any antihypertensive medications in 48 of 150 patients (32.0%), and the blood pressure control was more facile in 78 patients (52.0%), however, there were no improvement in 22 patients (16.0%). Creatinine level decreased in 34 patients (22.7%), remained stable in 112 patients (74.6%), and increased in 4 (2.7%). There was no statistical significance. No deaths occurred during 6-months follow-up. CONCLUSIONS: Renal artery stent revascularization had a beneficial effect on blood pressure control and a nondeleterious effect on renal function during 6-months follow-up. The long-term efficacy should be investigated. The procedure is safe in usual.