Long Noncoding RNA MNX1 antisense RNA 1 Exerts Oncogenic Functions in Bladder Cancer by Regulating miR-218-5p/RAB1A Axis.

LncRNA MNX1 antisense RNA 1 (MNX1-AS1) is significantly overexpressed in patients with bladder cancer, suggesting that it might be associated with bladder cancer. However, the molecular mechanism of MNX1-AS1 in bladder cancer remained indistinct. To illustrate the role of MNX1-AS1 in bladder cancer, the gain- and loss-of-function experiments were conducted in bladder cancer cells. Reduced expression of MNX1-AS1 could suppress cell proliferation, migration, invasion, and epithelial-mesenchymal transition in bladder cancer cells, whereas overexpression of MNX1-AS1 resulted in the opposite effects. Mechanistic analysis demonstrated that miR-218-5p was a direct target of RAB1A. MNX1-AS1 could competitively bind to miR-218-5p to regulate RAB1A expression in bladder cancer cells. Furthermore, in vivo experiments revealed that reduced expression of MNX1-AS1 inhibited tumor growth and metastasis. Taken together, MNX1-AS1 functions as a sponge to miR-218-5p to modulate RAB1A expression in bladder cancer, which suggests that MNX1-AS1 might serve as a novel therapeutic target and a novel biomarker for metastasis and prognosis in bladder cancer. SIGNIFICANCE STATEMENT: Our study demonstrates that long noncoding RNA MNX1-AS1 promotes the initiation and progression of bladder cancer. MNX1-AS1 regulates RAB1A expression to promote proliferation, migration, invasion, and epithelial-mesenchymal transitions of bladder cancer cells via miR-218-5p, which contributes to the tumor growth and metastasis of bladder cancer. Collectively, these results suggest that MNX1-AS1 might serve as a potential biomarker for bladder cancer.

Differential expression of histamine receptors in the bladder wall tissues of patients with bladder pain syndrome/interstitial cystitis - significance in the responsiveness to antihistamine treatment and disease symptoms.

BACKGROUND: Activation of mast cells plays an important role in the pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC). Histamine, a mast cell-derived mediators, induced inflammation and hypersensitivity of the bladder. The present study investigated the expressions of histamine receptors in the bladder wall tissues of patients with BPS/IC, and its association with the effectiveness of antihistamine therapy and disease symptoms. METHODS: Bladder tissues were collected from 69 BPS/IC patients and 10 control female patients. The expression of H3R in BPS/IC was further examined in an independent cohort of 10 female patients with BPS/IC and another 10 age-matched female patients. Immunohistochemistry, Western blotting, and quantitative RT-PCR were performed to quantify the expressions of histamine receptors. Statistical analyses of the correlation of histamine receptor expression with antihistamine therapy outcome and severity of disease symptoms were also performed. RESULTS: The expression of four histamine receptors was significantly elevated in BPS/IC (H1R, P < 0.001; H2R, P = 0.031; H3R, P = 0.008; H4R, P = 0.048). Western blotting revealed that H3R were significantly reduced in the patients, whereas the mRNA levels of H3R were significantly increased. The patients were further divided into antihistamine responders (n = 38) and nonresponders (n = 22). No significant correlation was found in the expression of histamine receptors between responder and nonresponder groups. However, significant correlations between OLS and H1R (P = 0.003) and H3R (P = 0.045) were found. CONCLUSION: The present study showed that expression of all the 4 histamine receptors were elevated in BPS/IC. There were no statistical significant correlations between the expression levels of the four different histamine receptors and the treatment outcome of antihistamine therapy (amtitriptyline or cimetidine).

Effect of Nrf2 on brain injury induced by hydraulic shock via regulation of mitophagy and apoptosis.

The specific protective mechanism of mitophagy and Nrf2 in brain injury has not been fully clarified. This study aimed to reveal the effect of Nrf2 on hydraulic shock brain injury in mice, and explore its possible mechanism. Twenty-four Nrf2 knockout (Nrf2-/-) and wild-type mice (WT) of C57BL/6J were randomly divided into two groups: control group (C) and brain injury group (TBI). Hematoxylin-eosin staining (HE) assay was used for the histomorphological observation. The apoptotic state of brain tissue was detected by TUNEL. Mechanical damage in vitro models of glial cells were prepared. The wild-type (WT) and Nrf2 knockout (KO) mice were constructed to investigate the changes of mitophagy and apoptosis-related indicators by Western blotting. The experimental results showed that 24 h after TBI, the tissue structure was highly porous, the cells were highly edema, the neuronal space increased significantly, the neuron degeneration, and the cell vacuolation was obvious. Meanwhile, the number of apoptotic cells and the apoptosis rate of glial cells increased significantly. After injury, the relative expression of Parkin, Pink, Beclin and LC-3II proteins were significantly decreased in all mice. The protein expressions of Caspase3 and Caspase12 were significantly increased. However, in the TBI group, KO mice were more impaired than WT mice. In conclusion, Nrf2 plays a protective role by promoting mitophagy to inhibit apoptosis in the process of brain injury caused by hydraulic shock in mice, which provides a new idea for the effective treatment of brain injury.

Dendrobium officinale Enzyme Changing the Structure and Behaviors of Chitosan/γ-poly(glutamic acid) Hydrogel for Potential Skin Care.

Hydrogels have been widespreadly used in various fields. But weak toughness has limited their further applications. In this study, Dendrobium officinale enzyme (DOE) was explored to improve chitosan/γ-poly(glutamic acid) (CS/γ-PGA) hydrogel in the structure and properties. The results indicated that DOE with various sizes of ingredients can make multiple noncovalent crosslinks with the skeleton network of CS/γ-PGA, significantly changing the self-assembly of CS/γ-PGA/DOE hydrogel to form regular protuberance nanostructures, which exhibits stronger toughness and better behaviors for skin care. Particularly, 4% DOE enhanced the toughness of CS/γ-PGA/DOE hydrogel, increasing it by 116%. Meanwhile, water absorption, antioxygenation, antibacterial behavior and air permeability were increased by 39%, 97%, 27% and 52%.

Integrative Analysis of the Gut Microbiota and Metabolome in Obese Mice with Electroacupuncture by 16S rRNA Gene Sequencing and HPLC-MS-based Metabolic Profiling.

Acupuncture has been used to treat numerous diseases such as obesity in China for thousands of years. Several mechanisms of acupuncture on obesity have been surveyed based on metabolomics, but the effects of acupuncture on the alterations in the gut flora are still unclear. In this study, an integrated approach based on 16S rRNA gene sequencing combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS) metabolic profiling was conducted to investigate the effects of acupuncture on high-fat-diet-induced obesity through the regulation of the relative abundances of gut microbiota and their relationships with biomarker candidates. A total of 10 significantly altered bacterial genera and 11 metabolites were recognized, which recovered to normal levels after electroacupuncture treatment. The relative abundances of the bacterial families Muribaculaceae,Lachnospiraceae,Desulfovibrionaceae,Helicobacteraceae, Prevotellaceae,Ruminococcaceae,Rikenellaceae,Deferribacteraceae,Bacteroidaceae andTannerellaceaewere remarkedly changed among the three groups. Potential biomarkers, including LysoPC(0:0/16:0) ([Formula: see text]1),PC(0:0/18:0) ([Formula: see text]2),Cholic acid([Formula: see text]3),LysoPC(16:0) ([Formula: see text]4), 3[Formula: see text],6[Formula: see text],7[Formula: see text]-Trihydroxy-5[Formula: see text]-cholanoic acid([Formula: see text]5), 5beta-Cyprinolsulfate([Formula: see text]6),PC(18:0/0:0) ([Formula: see text]7), 1-Nitro-5-hydroxy-6-glutathionyl-5,6-dihydronaphthalene([Formula: see text]8),Glycocholic acid([Formula: see text]9),[Formula: see text]-Arginine([Formula: see text]10) andGulonic acid([Formula: see text]11), were involved in several metabolic pathways, such as the glycerophospholipid metabolism and primary bile acid biosynthesis. Interestingly, there was a strong correlation between the perturbed gut flora in Bilophila and Bifidobacterium and the altered intestinal metabolite of 3[Formula: see text],6[Formula: see text],7[Formula: see text]-Trihydroxy-5[Formula: see text]-cholanoic acid and Cholanoic acid and [Formula: see text]-Arginine. This finding suggested that the effects of electroacupuncture might change the proportions of Bilophila and Bifidobacterium by regulating the constituents of the functional metabolite of 3[Formula: see text],6[Formula: see text],7[Formula: see text]-Trihydroxy-5[Formula: see text]-cholanoic acid and Cholanoic acid and [Formula: see text]-Arginine. These results indicated that the effects of electroacupuncture focused on custom metabolic pathways as well as depend on the changes in the gut microbiota in obesity. These findings suggest that the 16S rRNA gene sequencing and HPLC-MS-based metabolomics approach can be applied to comprehensively assess the effects of traditional Chinese medicines.

Fabrication of a porous chitosan/poly-(γ-glutamic acid) hydrogel with a high absorption capacity by electrostatic contacts.

A porous chitosan (CS)/poly-(γ-glutamic acid) (γ-PGA) hydrogel was prepared by polymerization by electrostatic contacts of CS with γ-PGA without linker. The porosity of the hydrogel remarkably depends on γ-PGA content, pH regulator, and drying way. The optimization of them had given the hydrogel a high swelling capacity of 1398%, 11-fold higher than that of neat CS hydrogel. The hydrogel was applied to recover bovine serum albumin (BSA) from aqueous solution, and its adsorption capacity was influenced by the initial concentration and pH of BSA solution. Based on the studies of kinetics and isotherm, a high equilibrium adsorption capacity (qe = 948 mg/g) and a correlation coefficient of 0.996 were calculated from pseudo-second order kinetic equation, and a high affinitive constant (kF = 472 mL/mg) and a high saturated absorption capacity (qm = 1818.5 mg/g) were observed from Freundlich isotherm equation, indicating the porous hydrogel will be a good absorbent for protein recovery from sewage.

Omega-3 Polyunsaturated Fatty Acids Alleviate Traumatic Brain Injury by Regulating the Glymphatic Pathway in Mice.

Background: The glymphatic pathway has been shown to be impaired in traumatic brain injury (TBI). Omega-3 polysaturated fatty acids (Omega-3, PUFAs) are involved in the clearance of amyloid-ß through the glymphatic system and this effect is Aquaporin-4 (AQP4) dependent. We hypothesize that Omega-3 PUFAs can alleviate neurological impairment in TBI by protecting the glymphatic pathway. Methods: We pretreated mice with Omega-3 PUFAs rich fish oil and introduced TBI in the mice. Neurological functions were assessed through the modified neurological severity score (mNSS) system and Rota-rod test. Aß42 levels and radioisotope clearance were examined to determine the function of glymphatic system. AQP4 protein and mRNA expressions and its polarity were examined in fish oil treated TBI mice or control mice. Finally, the integrity of blood-brain barrier was determined by Evans blue extravasation and measurement of tight junction proteins (ZO-1 and Occludin) levels. Results: TBI surgery induced significant neurological functional impairment, Omega-3 PUFAs attenuated TBI-induced neurological impairment, as evidenced by reduced mNSS, improved performance in the Rota-rod test. Furthermore, Omega-3 PUFAs improved glymphatic clearance after induction of TBI in mice, reduced Aß42 accumulation, partially restored the clearance of both 3H-mannitol and 14C-Inulin. Omega-3 PUFAs also suppressed AQP4 expression and partially prevented loss of AQP4 polarity in mice undergoing TBI. Finally, Omega-3 PUFAs protected mice from TBI induced blood-brain barrier disruption. Conclusion: Omaga-3 PUFAs attenuate neurological function by partially restoring the AQP4 dependent glymphatic system in mice with TBI.

Retracted Article: MicroRNA-135a alleviates lipid accumulation and inflammation of atherosclerosis through targeting lipoprotein lipase.

MicroRNAs (miRNAs) have recently attracted increasing attention for their involvement in atherosclerosis (AS). The purpose of this study was to further explore the function and underlying mechanism of miR-135a in AS progression. The expression levels of miR-135a and lipoprotein lipase (LPL) mRNA were detected by qRT-PCR, and LPL protein expression was measured by western blotting. The levels of blood lipids and inflammatory cytokines, and LPL activity were assessed using corresponding Assay Kits, and an HPLC assay was used to determine the levels of free cholesterol (FC), total cholesterol (TC) and cholesterol ester (CE). A Dil-oxLDL binding assay was performed to evaluate the ability of cholesterol uptake. The direct interaction between miR-135a and LPL was confirmed by a dual-luciferase reporter assay and RNA immunoprecipitation assay. Our data indicated that miR-135a was downregulated in serum samples of AS patients and mice. Upregulation of miR-135a alleviated lipid metabolic disorders and inflammation in AS mice. Moreover, miR-135a negatively regulated lipid accumulation and inflammation in ox-LDL-treated THP-1 macrophages. Mechanistically, miR-135a directly targeted LPL and repressed LPL expression. LPL mediated the regulatory effect of miR-135a on lipid accumulation and inflammation in ox-LDL-treated THP-1 macrophages. In conclusion, our study indicated that miR-135a upregulation ameliorated lipid accumulation and inflammation at least partly by targeting LPL in THP-1 macrophages, highlighting miR-135a as a potential antiatherogenic agent.

Single-plane retroperitoneoscopic adrenalectomy: a new operative procedure for benign adrenal disease.

To evaluate the therapeutic effect of single-plane retroperitoneoscopic adrenalectomy. From February 2014 to March 2017, 251 patients underwent single-plane retroperitoneoscopic adrenalectomy, and their operative outcomes were compared with those of 98 patients who underwent anatomical three-plane retroperitoneoscopic adrenalectomy. Among 35 patients with a body mass index (BMI) of ≥30 kg/m2, their operative outcomes were compared between two operative procedures. The demographic data and perioperative outcomes of the patients were statistically analysed. The single-plane and three-plane groups were comparable in terms of estimated blood loss, time to oral intake, hospital stay, and incidence of complications among patients with similar baseline demographics. The single-plane group had a significantly shorter operation time (46.9 ± 5.8 vs 54.8 ± 7.0 mins, P < 0.0001) and lower analgesia requirement (56/251 vs 33/98, p = 0.03). For obese patients with a BMI of ≥30 kg/m2, single-plane adrenalectomy was also associated with a significantly shorter operation time(48.1 ± 6.2 vs 64.1 ± 5.1 mins, p < 0.0001). Single-plane retroperitoneoscopic adrenalectomy is feasible, safe, and effective in the treatment of adrenal masses <5 cm in size and provides a shorter operation time and better pain control than anatomical retroperitoneal adrenalectomy, especially in obese patients.

Erythropoietin Attenuates the Memory Deficits in Aging Rats by Rescuing the Oxidative Stress and Inflammation and Promoting BDNF Releasing.

Aging is a natural process accompanied with many disorders, including the memory decline. The underlying mechanisms for the age-related memory decline are complicated. Previous work suggested that oxidative stress, inflammatory disturbance, and the neurotropic absence play important roles in the age-related disorders. Thus, to seek a drug to target those abnormalities might be a possible protective approach for aging. Here, we reported that supplements with exogenous erythropoietin (EPO) for 4 weeks could partially rescue the spatial and fear memory impairments in aged rats. The EPO treatment also suppresses the oxidative stress and inflammatory response. Most importantly, EPO supplement restores the mRNA and protein levels of brain-derived neurotrophic factor (BDNF), the critical neurotropic factor for synaptic plasticity and memory. Our study strongly suggests the potential usage of EPO in an anti-aging agent clinically.

Microcatheter looping facilitates access to both the acutely angled parent artery and cerebral aneurysms for effective embolization.

Aneurysms with an acutely angled parent artery are difficult to access for coiling. This study aimed to investigate the safety and effectiveness of microcatheter looping for embolization of cerebral aneurysms with access difficulty. Ten patients (male:female=5:5) with cerebral aneurysms treated with the microcatheter looping technique were analyzed retrospectively. The parent artery formed an acute angle with the major artery in five aneurysms. The microcatheter was looped into a "α" loop for treatment in the anterior temporal artery aneurysm and a "U" loop in the remaining nine aneurysms. All ten aneurysms were successfully treated with the microcatheter looping technique. The microcatheter tip was successfully navigated into the aneurysm sac and remained stable throughout the embolization process. All aneurysms were occluded with total occlusion in five and near-total occlusion in five, and the parent artery remained patent in all cases. No complications occurred peri-procedurally. The Glasgow Outcome Scale was 5 in all patients before discharge. Follow-up angiography six to 12 months later revealed a good occlusion status of the aneurysms. The microcatheter looping technique is effective when the conventional embolization technique fails to treat cerebral aneurysms with difficult access especially when the parent artery forming an acute angle with the major artery exacerbates difficult access to the aneurysms.

The stent-assisted coil-jailing technique facilitates efficient embolization of tiny cerebral aneurysms.

OBJECTIVE: Tiny cerebral aneurysms are difficult to embolize because the aneurysm's sac is too small for a single small coil, and coils within the aneurysm may escape from the confinement of a stent. This study was performed to introduce the stent-assisted coil-jailing technique and to investigate its effect on the coil embolization of tiny intracranial aneurysms. MATERIALS AND METHODS: Sixteen patients with tiny intracranial aneurysms treated with the stent-assisted coil-jailing technique between January 2011 and December 2013 were retrospectively reviewed and followed-up. RESULTS: All aneurysms were successfully treated with the coil-jailing technique, and at the end of embolization, complete occlusion of the aneurysm was achieved in 9 cases (56.3%), incomplete occlusion in 6 (37.5%), and partial occlusion in 1 (6.3%). Intraprocedural complications included acute thrombosis in one case (6.3%) and re-rupture in another (6.3%). Both complications were managed appropriately with no sequela. Follow-up was performed in all patients for 3-24 months (mean, 7.7 months) after embolization. Complete occlusion was sustained in the 9 aneurysms with initial complete occlusion, progressive thrombosis to complete occlusion occurred in the 6 aneurysms with initial near-complete occlusion, and one aneurysm resulted in progressive thrombosis to complete occlusion after initial partial occlusion. No migration of stents or coils occurred at follow-up as compared with their positions immediately after embolization. At follow-up, all patients had recovered with no sequela. CONCLUSION: The stent-assisted coil-jailing technique can be an efficient approach for tiny intracranial aneurysms, even though no definite conclusion regarding its safety can be drawn from the current data.

Increased expression of TNF ligand-related molecule 1A and death receptor 3 in bladder tissues of patients with painful bladder syndrome/interstitial cystitis.

Members of the tumor necrosis factor (TNF) superfamily have been revealed to be associated with painful bladder syndrome/interstitial cystitis (PBS/IC). TNF ligand-related molecule 1A (TL1A) and its receptor, death receptor 3 (DR3), belong to the TNF superfamily and have been implicated in chronic inflammatory diseases. Bladder biopsies from 8 female patients clinically diagnosed with PBS/IC according to the National Institute for Diabetes and Digestive and Kidney Diseases criteria and 8 female bladder carcinoma control patients were investigated to test the protein and mRNA expression levels of TL1A and DR3 using western blotting and real-time RT-PCR. The protein level ratio of TL1A to ß-actin (IC, 0.65±0.03 vs. controls, 0.25±0.02, P<0.001) and of its receptor DR3 to ß-actin (IC, 0.66±0.06 vs. controls, 0.27±0.02, P<0.001) were observed to be significantly higher in the patients with IC. The real-time RT-PCR ΔCts of TL1A minus GAPDH (IC, 7.60±0.52 vs. controls, 10.08±0.32, P<0.001) and the DR3 minus GAPDH (IC, 6.68±0.60 vs. controls, 8.99±0.61, P=0.017) were observed to be significantly lower in the patients with IC, suggesting that the mRNA levels of TL1A and DR3 were higher in the PBS/IC patients. The protein and mRNA expression of TL1A and DR3 are upregulated in the bladder tissues of PBS/IC patients and may be involved in inflammation and apoptosis in PBS/IC.