Effect of Cellulose Powder on Human Nasal Epithelial Cell Activity and Ciliary Beat Frequency.

BACKGROUND: Cellulose powder (CP) has been reported as a safe and effective complementary treatment for allergic rhinitis (AR). Currently, CP has gained increasing application for clinical management worldwide, particularly in China. However, studies focusing on the effect of CP on normal human nasal epithelial cells (hNECs) and ciliary function are lacking. Here, we aimed to explore the adverse effects of CP on the activity and ciliary function of hNECs. METHODS: We biopsied ethmoid sinus or middle turbinate tissues during surgical resection from control subjects who underwent endoscopic sinus surgery for diseases other than AR. Cells were isolated and passaged, followed by differentiation in an air-liquid interface (ALI). Flow cytometry and cell viability test (cell counting kit-8) were performed to detect the cytotoxicity of CP (effects on cell proliferation) on normal hNECs. By using the ALI culture model, we investigated the effects of CP on ciliary beat frequency (CBF). RESULTS: There was a significant reduction in hNEC count at high concentrations of CP (2.5 mg/mL) at days 3 and 7 (both p < 0.05). As the concentration increased, cell death increased progressively from day 3 to day 7. However, these effects were not evident at low concentrations (0.25 mg/mL, p > 0.05). High-dose CP (2.5 mg) significantly reduced the CBF (p < 0.05). At lower concentrations (0.25-2.5 mg/mL), CP initially increased but subsequently reduced the CBF of hNECs compared with control group. CONCLUSIONS: Cytotoxicity and the suppression of ciliary beat at high concentrations justify more prudent use of CP for the management of AR.

An Integrated Model for Input and Migration of Mercury in Chinese Coastal Sediments.

Coastal sediments are a major sink of the global mercury (Hg) biogeochemical cycle, bridging terrestrial Hg migration to the open ocean. It is thus of substantial interest to quantify the Hg contributors to coastal sediments and the extents to which the Hg sequestered into coastal sediments affects the ocean. Here, we measured concentrations and isotope compositions of Hg in Chinese coastal sediments and found that estuary sediments had distinctly higher δ202Hg and lower Δ199Hg values than marine sediments. Hg isotope compositions of marine sediments followed a latitudinal trend where δ202Hg decreases and Δ199Hg increases from north to south. An integrated model was developed based on a Hg isotope mixing model and urban distance factor (UDF), which revealed a significant difference in Hg source contributions among the estuary and marine sediments and a gradual change of dominant Hg sources from terrestrial inputs (riverine and industrial wastewater discharges) to atmospheric deposition with a decrease in urban impact. A UDF value of 306 ± 217 was established as the critical point where dominant Hg sources started to change from terrestrial inputs to atmospheric deposition. Our study helps explain the input and migration of Hg in Chinese marginal seas and provides critical insights for targeted environmental management.

Mercury isotopic compositions of mosses, conifer needles, and surface soils: Implications for mercury distribution and sources in Shergyla Mountain, Tibetan Plateau.

Understanding the distribution and sources of mercury (Hg) in the Tibetan Plateau is of great value to study the long-range transport of Hg. Herein, the total Hg (THg) concentrations and the isotopic compositions of mosses, conifer needles, and surface soils collected from both slopes of the Shergyla Mountain of Tibetan Plateau were analyzed. The contents of THg in samples (except mosses on the eastern slope) were significantly positively correlated with altitude in both the western and eastern slopes, possibly caused by topographic factors. In contrast, Δ199Hg in samples was significantly negatively correlated with altitude. On the basis of Hg isotopic compositions, atmospheric Hg0 uptake was indicated as the primary accumulation pathway of Hg in mosses (Δ199Hg: -0.12 ±â€¯0.09‰, -0.26 - 0.00‰, 1 SD, n = 10) and conifer needles (Δ199Hg: -0.21 ±â€¯0.08‰, -0.36 - -0.11‰, 1 SD, n = 9). Moreover, the contributing fractions of atmospheric Hg0 to Hg in surface soils (Δ199Hg: -0.20 ±â€¯0.07‰, -0.31 - -0.06‰, 1 SD, n = 17) increased with altitude and accounted for an average of 87 ± 9% in atmospheric sources. Due to the special geographic positions and environmental conditions of the Tibetan Plateau, the results of this study were essential for further understanding the long-range transport and global cycling of Hg.

Tracing aquatic bioavailable Hg in three different regions of China using fish Hg isotopes.

To trace the most concerned bioavailable mercury (Hg) in aquatic environment, fish samples were collected from three typical regions in China, including 3 rivers and 1 lake in the Tibetan Plateau (TP, a high altitude background region with strong solar radiation), the Three Gorges Reservoir (TGR, the largest artificial freshwater reservoir in China), and the Chinese Bohai Sea (CBS, a heavily human-impacted semi-enclosed sea). The Hg isotopic compositions in fish muscles were analyzed. The results showed that anthropogenic emissions were the main sources of Hg in fish from TGR and CBS because of the observed negative δ202Hg and positive Δ199Hg in these two regions (TGR, δ202Hg: - 0.72 to - 0.29‰, Δ199Hg: 0.15 - 0.52‰; CBS, δ202Hg: - 2.09 to - 0.86‰, Δ199Hg: 0.07 - 0.52‰). The relatively higher δ202Hg and Δ199Hg (δ202Hg: - 0.37 - 0.08‰, Δ199Hg: 0.50 - 1.89‰) in fish from TP suggested the insignificant disturbance from local anthropogenic activities. The larger slopes of Δ199Hg/Δ201Hg in fish from TGR (1.29 ± 0.14, 1SD) and TP (1.25 ± 0.06, 1SD) indicated methylmercury (MeHg) was produced and photo-reduced in the water column before incorporation into the fish. In contrast, the photoreduction of Hg2+ was the main process in CBS (slope of Δ199Hg/Δ201Hg: 1.06 ± 0.06, 1SD). According to the fingerprint data of Hg isotopes, the most important source for aquatic bioavailable Hg in TP should be the long-range transported Hg, contrasting to the anthropogenic originated MeHg from surface sediments and runoffs in TGR and inorganic Hg from continental inputs in CBS. Therefore, the isotopic signatures of Hg in fish can provide novel clues in tracing sources and behaviors of bioavailable Hg in aquatic systems, which are critical for further understanding the biogeochemical cycling of Hg.

Mutual detoxification of mercury and selenium in unicellular Tetrahymena.

Selenium (Se) is commonly recognized as a protective element with an antagonistic effect against mercury (Hg) toxicity. However, the mechanisms of this Hg-Se antagonism are complex and remain controversial. To gain insight into the Hg-Se antagonism, a type of unicellular eukaryotic protozoa (Tetrahymena malaccensis, T. malaccensis) was selected and individually or jointly exposed to two Hg and three Se species. We found that Se species showed different toxic effects on the proliferation of T. malaccensis with the toxicity following the order: selenite (Se(IV))>selenomethionine (SeMeth)>selenate (Se(VI)). The Hg-Se antagonism in Tetrahymena was observed because the joint toxicity significantly decreased under co-exposure to highly toxic dosages of Hg and Se versus individual toxicity. Unlike Se(IV) and Se(VI), non-toxic dosage of SeMeth significantly decreased the Hg toxicity, revealing the influence of the Se species and dosages on the Hg-Se antagonism. Unexpectedly, inorganic divalent Hg (Hg2+) and monomethylmercury (MeHg) also displayed detoxification towards extremely highly toxic dosages of Se, although their detoxifying efficiency was discrepant. These results suggested mutual Hg-Se detoxification in T. malaccensis, which was highly dependent on the dosages and species of both elements. As compared to other species, SeMeth and MeHg promoted the Hg-Se joint effects to a higher degree. Additionally, the Hg contents decreased for all the Hg-Se co-exposed groups, revealing a sequestering effect of Se towards Hg in T. malaccensis.

The TH2-polarizing function of atopic interleukin 17 receptor B-positive dendritic cells up-regulated by lipopolysaccharide.

BACKGROUND: Recent studies suggest that epithelial cell (EC)-derived cytokines contribute to allergic airway disease exacerbation. OBJECTIVE: To confirm our hypothesis that atopic dendritic cells (DCs) are activated to up-regulate the receptors of cytokines that mainly derived from ECs and enhance TH2 responses. METHODS: The expressions of interleukin 17 receptor B (IL-17RB) (IL-25 receptor), membrane-bound ST2 (IL-33 receptor), thymic stromal lymphopoietin receptor (TSLPR), granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), and several functional markers on CD1c+ monocyte-derived DCs (mo-DCs) were detected by flow cytometry. Lipopolysaccharide (LPS)-activated mo-DCs were cocultured with autologous CD4+ T cells, and cytokine production by these T cells was determined by intracellular flow cytometry. RESULTS: LPS activated both nonatopic and atopic mo-DCs to express a higher level of GM-CSFR but only activated atopic mo-DCs to express increased IL-17RB, which was subsequently activated by IL-25 involved with signal transducer and activator of transcription 5 phosphorylation. In addition, LPS increased the expression of the OX40 ligand (OX40L) but decreased inducible costimulator ligand on atopic CD86+ mo-DCs. More importantly, IL-25 further up-regulated OX40L on atopic CD86+ mo-DCs. After coculturing with LPS-activated mo-DCs from atopic individuals, CD4+ T cells had enhanced inflammatory responses by increased production of IL-4, IL-5, IL-13, and interferon γ (IFN-γ). In contrast, further addition of IL-25 led CD4+ T cells to produce higher level of IL-4 but lower level of IFN-γ. CONCLUSION: Atopic IL-17RB+ DCs can be up-regulated by LPS and promote a TH2-type response, implying that the IL-25/IL-17RB pathway may represent a potential molecular mechanism underlying the regulation of ECs on DCs in allergic airway disease.

Characterization and speciation of mercury in mosses and lichens from the high-altitude Tibetan Plateau.

The accumulation and species of mercury (Hg) in mosses and lichens collected from high-altitude Tibetan Plateau were studied. The altitudes of the sampling sites spanned from 1983 to 5147 m, and a total of 130 mosses and 52 lichens were analyzed. The total mercury (THg) contents in mosses and lichens were in the ranges of 13.1-273.0 and 20.2-345.9 ng/g, respectively. The average ratios of methylmercury (MeHg) in THg in mosses and lichens were 2.4 % (0.3-11.1 %) and 2.7 % (0.4-9.6 %), respectively, which were higher than those values reported in other regions. The contents of THg in both mosses and lichens were not correlated with the THg in soils (p > 0.05). The lipid contents displayed a significantly positive correlation with concentrations of MeHg in mosses (r = 0.461, p < 0.01, n = 90), but not in lichens. The correlations between Hg contents in mosses and the altitudes, latitudes and longitudes of sampling sites indicated the mountain trapping and spatial deposition of Hg in the Tibetan Plateau.

Tetrabromobisphenol-A/S and Nine Novel Analogs in Biological Samples from the Chinese Bohai Sea: Implications for Trophic Transfer.

Tetrabromobisphenol-A/S (TBBPA/S) analogs have raised substantial concern because of their adverse effects and potential bioaccumulative properties, such as TBBPA bis(allyl ether) (TBBPA-BAE) and TBBPA bis(2,3-dibromopropyl ether) (TBBPA-BDBPE). In this study, a comprehensive method for simultaneous determination of TBBPA/S and nine novel analogs, including TBBPA-BAE, TBBPA-BDBPE, TBBPS-BDBPE, TBBPA mono(allyl ether) (TBBPA-MAE), TBBPA mono(2-bromoallyl ether) (TBBPA-MBAE), TBBPA mono(2,3-dibromopropyl ether) (TBBPA-MDBPE), TBBPS-MAE, TBBPS-MBAE, and TBBPS-MDBPE in biological samples was developed. The distribution patterns and trophic transfer properties of TBBPA/S and analogs in various biological samples collected from the Chinese Bohai Sea were then studied in detail. For the first time, TBBPA-MBAE and TBBPS-BDBPE were detected in biological samples and TBBPA-MBAE was identified as a byproduct. The concentrations of TBBPA and analogs ranged from ND (not detected or below the method detection limit) to 2782.8 ng/g lipid weight (lw), and for TBBPS and analogs ranged from ND to 927.8 ng/g lw. High detection frequencies (>86%) for TBBPA, TBBPS and TBBPA-MAE, TBBPA-MDBPE, TBBPS-MAE, TBBPS-MBAE, and TBBPS-MDBPE were obtained. Meanwhile, TBBPA, TBBPS, and these five analogs displayed trophic dilution tendencies due to significantly negative correlations between trophic levels and lipid-corrected concentrations together with the trophic magnification factors (from 0.31 to 0.55). The results also indicated the novel TBBPA-MAE, TBBPA-MBAE, TBBPA-MDBPE, TBBPS-MAE, TBBPS-MBAE, and TBBPS-MDBPE could be generated not only as byproducts, but also as the probable transformation products of commercial TBBPA/S derivatives.

Metabolic landscape of head and neck squamous cell carcinoma informs a novel kynurenine/Siglec-15 axis in immune escape.

BACKGROUND: Metabolic reprograming and immune escape are two hallmarks of cancer. However, how metabolic disorders drive immune escape in head and neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, the aim of the present study was to investigate the metabolic landscape of HNSCC and its mechanism of driving immune escape. METHODS: Analysis of paired tumor tissues and adjacent normal tissues from 69 HNSCC patients was performed using liquid/gas chromatography-mass spectrometry and RNA-sequencing. The tumor-promoting function of kynurenine (Kyn) was explored in vitro and in vivo. The downstream target of Kyn was investigated in CD8+ T cells. The regulation of CD8+ T cells was investigated after Siglec-15 overexpression in vivo. An engineering nanoparticle was established to deliver Siglec-15 small interfering RNA (siS15), and its association with immunotherapy response were investigated. The association between Siglec-15 and CD8+ programmed cell death 1 (PD-1)+ T cells was analyzed in a HNSCC patient cohort. RESULTS: A total of 178 metabolites showed significant dysregulation in HNSCC, including carbohydrates, lipids and lipid-like molecules, and amino acids. Among these, amino acid metabolism was the most significantly altered, especially Kyn, which promoted tumor proliferation and metastasis. In addition, most immune checkpoint molecules were upregulated in Kyn-high patients based on RNA-sequencing. Furthermore, tumor-derived Kyn was transferred into CD8+ T cells and induced T cell functional exhaustion, and blocking Kyn transporters restored its killing activity. Accroding to the results, mechanistically, Kyn transcriptionally regulated the expression of Siglec-15 via aryl hydrocarbon receptor (AhR), and overexpression of Siglec-15 promoted immune escape by suppressing T cell infiltration and activation. Targeting AhR in vivo reduced Kyn-mediated Siglec-15 expression and promoted intratumoral CD8+ T cell infiltration and killing capacity. Finally, a NH2-modified mesoporous silica nanoparticle was designed to deliver siS15, which restored CD8+ T cell function status and enhanced anti-PD-1 efficacy in tumor-bearing immunocompetent mice. Clinically, Siglec-15 was positively correlated with AhR expression and CD8+PD-1+ T cell infiltration in HNSCC tissues. CONCLUSIONS: The findings describe the metabolic landscape of HNSCC comprehensively and reveal that the Kyn/Siglec-15 axis may be a novel potential immunometabolism mechanism, providing a promising therapeutic strategy for cancers.

Mimecan is involved in aortic hypertrophy induced by sinoaortic denervation in rats.

This study was designed to investigate whether mimecan was involved in aortic hypertrophy induced by sinoaortic denervation in rats. 8 weeks after sinoaortic denervation, when compared to sham-operated rats, sinoaortic denervated rats exhibited aortic hypertrophy and down-regulation of mimecan. Through classic univariate correlation analysis, it was found that mimecan mRNA was negatively related to extent of aortic hypertrophy. Treatment of primary cultured vascular smooth muscle cells with the Ang II (1 µM), which was found locally increased in the aortae of sinoaortic denervated rats, resulted in a reduction of mimecan expression. In vitro, knockdown of mimecan in vascular smooth muscle cells promoted cell proliferation induced by 15% of fetal bovine serum or Ang II (1 µM). We concluded that down-regulation of mimecan was involved in aortic hypertrophy induced by sinoaortic denervation in rats.

[Increasing expression of microglia in the retina after optic nerve transection in rats].

OBJECTIVE: To investigate the expression of microglia after optic nerve transection in rats. METHOD: Thirty healthy adult female SD rats were randomly grouped to experimental and control groups according to the random number table. The experimental group received an optic nerve transection (ONT) on their right eyes. ONT was performed 1.5 mm from the eye ball. The control group received a surgery on day 5. Rats were killed 7 days after the first operation. Retinal ganglion cells (RGC) were retrograde labeled by placing fluorogold dye on the stump of the optic nerve. Microglia was immunohistochemically stained in the retinas of normal and 7-day injury groups using ionized calcium adaptive molecular 1 (Iba-1) as the marker. The protein levels of Iba-1 in the retinas were also examined using Western blotting. The number of RGCs was quantified using flatmount of retinas in the two groups. RESULTS: There were some resting microglia (Iba-1 positive cells) in the nerve fiber layer and inner plexiform layer in the normal control retina. However, microglia showed a moderately activated morphology with increased Iba-1 immunoreactivity in the stroma and processes up to outer plexiform layer. Western blotting showed that the levels of Iba-1 was lower in the normal retina and increased to 2.3-fold 7 days after injury (t = 7.669, P = 0.001). The number of RGCs after injury was (1182 ± 64) per mm(2), decreased to 51% in the normal groups (t = 23.85, P < 0.0001). CONCLUSIONS: The results implicated that microglia was increased and partially activated after the optic nerve transection. This may be a manifestation of the self-protection mechanism of RGCs against the injury insult.

LINGO-1 negatively regulates TrkB phosphorylation after ocular hypertension.

The antagonism of LINGO-1, a CNS-specific negative regulator of neuronal survival, was shown to promote short-term survival of retinal ganglion cell (RGC) in an ocular hypertension model. LINGO-1 antagonists, combined with brain-derived neurotrophic factor (BDNF), can increase the length of neuron survival through an unclear molecular mechanism. To determine the relationship between LINGO-1 and BDNF/TrkB receptor in neuronal protection, we show here that LINGO-1 forms a receptor complex with TrkB and negatively regulates its activation in the retina after ocular hypertension injury. LINGO-1 antagonist antibody 1A7 or soluble LINGO-1 (LINGO-1-Fc) treatment upregulates phospho-TrkB phosphorylation and leads to RGC survival after high intraocular pressure injury. This neuronal protective effect was blocked by anti-BDNF antibody. LINGO-1 antagonism therefore promotes RGC survival by regulating the BDNF and TrkB signaling pathway after ocular hypertension.

Frontal sinus cerebrospinal fluid leaks: repair in 15 patients using an endoscopic surgical approach.

OBJECTIVES: To clarify the utility of a safe and effective endoscopic procedure for closing frontal sinus cerebrospinal fluid (CSF) leaks. METHODS: A retrospective review of all 15 patients seen at our hospital from 2002 to 2008 whose CSF leak originated within the frontal sinus or frontal recess. A transnasal endoscopic or combined transfrontal endoscopic approach was used to repair the CSF leak. RESULTS AND SURGICAL OUTCOMES: Four defects originated in the frontal recess and 11 involved the posterior wall of the frontal sinus. Nine patients were repaired by a direct endoscopic approach and 4 patients were repaired after widening the frontal recess endoscopically. Two patients were repaired using the combined transfrontal and transnasal approach. The leak was stopped in 14 cases (93%) after the first operation. One patient (7%) required a second repair 1 month after initial surgery and has remained well after 27 months. Complications included a frontal lobe abscess and a frontal sinus obstructive mucocele. These 2 patients were successfully treated without further complications. Patient follow-up ranged from 4 to 44 months (mean 30 months). CONCLUSIONS: Most frontal CSF leaks can be successfully closed by an endoscopic surgical approach.

Bcl2 like protine-12 (Bcl2L12) facilitates experimental airway allergic inflammation by inducing autocrine eotaxin in eosinophils.

BACKGROUND: The pathogenesis of airway allergic disorders (AAD) needs to be further investigated. Eosinophils (Eos) are the canonical effector cells in AAD attacks. Bcl2 like protein-12 (Bcl2L12) is an apoptosis inhibitor and an immune regulator. Eos have the defects of apoptosis. This study aims to investigate the role of Bcl2L12 in the AAD pathogenesis by regulating Eo activities. METHODS: Human nasal lavage fluids (NLF) and mouse bronchoalveolar lavage fluids (BALF) was collected. Eos in NLF and BALF were analyzed by flow cytometry. A murine AAD model was developed with ovalbumin as a specific antigen. RESULTS: We found that Eos isolated from NLF or BALF of AAD subjects expressed high levels of Bcl2L12 and showed defects of apoptosis. The Bcl2L12 expression in Eos was positively correlated with the AAD response. High lipopolysaccharide levels were detected in the AAD airways, that promoted the Bcl2L12 expression in Eos. Bcl2L12 mediated the LPS-induced autocrine eotaxin 1 expression in Eos through activating the MAPK p38/STAT6/NF-κB signal pathway. Depletion of Bcl2L12 in Eos suppressed experimental AAD in mice. CONCLUSIONS: AAD Eos express high levels of Bcl2L12, the latter is associated with AAD response by regulating the autocrine eotaxin 1 in Eos. Depletion of Bcl2L12 in Eos attenuates experimental AAD, suggesting that to suppress the Bcl2L12 Eos has the translational potential in the treatment of AAD.

Terrestrial mercury transformation in the Tibetan Plateau: New evidence from stable isotopes in upland buzzards.

Understanding the geochemical cycle of mercury (Hg) in the high-altitude Tibetan Plateau is of great value for studying the long-range transport of Hg. Herein, speciation and isotopic compositions of Hg in the muscle and feathers of upland buzzards (Buteo hemilasius) were studied to trace the terrestrial transformation of Hg in the Tibetan Plateau. Very low Hg content and relatively low δ202Hg values (feather: -0.77 ± 0.50‰, n = 9, muscle: -1.29 ± 0.29‰, n = 13, 1SD) were observed in upland buzzards. In contrast, the Δ199Hg values could be as high as 2.89‰ in collected samples. To our knowledge, this is the highest Δ199Hg value reported in avian tissues. Moreover, upland buzzards showed significantly different Δ199Hg values from fish collected from the same region, suggesting different generation and transformation processes of methylmercury (MeHg) in terrestrial and aquatic ecosystems. We speculated that different percentages of Hg undergoing photochemical reactions and contributions of atmospheric MeHg were possible reasons for observed differences. The results provide new clues for different circulation histories of Hg in terrestrial and aquatic ecosystems, which will be critical for further study of geochemical cycle and ecological risk of Hg in the environment.

Mercury isotope variations within the marine food web of Chinese Bohai Sea: Implications for mercury sources and biogeochemical cycling.

Mercury (Hg) speciation and isotopic compositions in a large-scale food web and seawater from Chinese Bohai Sea were analyzed to investigate methylmercury (MeHg) sources and Hg cycling. The biota showed ∼5‰ variation in mass dependent fractionation (MDF, -4.57 to 0.53‰ in δ202Hg) and mostly positive odd-isotope mass independent fractionation (odd-MIF, -0.01 to 1.21‰ in Δ199Hg). Both MDF and odd-MIF in coastal biota showed significant correlations with their trophic levels and MeHg fractions, likely reflecting a preferential trophic transfer of MeHg with higher δ202Hg and Δ199Hg than inorganic Hg. The MDF and odd-MIF of biota were largely affected by their feeding habits and living territories, and MeHg in pelagic food web was more photodegraded than in coastal food web (21-31% vs. 9-11%). From the Hg isotope signatures of pelagic biota and extrapolated coastal MeHg, we suggest that MeHg in the food webs was likely derived from sediments. Interestingly, we observed complementary even-MIF (mainly negative Δ200Hg of -0.36 to 0.08‰ and positive Δ204Hg of -0.05 to 0.82‰) in the biota and a significant linear slope of -0.5 for Δ200Hg/Δ204Hg. This leads us to speculate that atmospheric Hg0 is an important source to bioaccumulated MeHg, although the exact source-receptor relationships need further investigation.

Proteomics profiling of epithelium-derived exosomes from nasal polyps revealed signaling functions affecting cellular proliferation.

BACKGROUND: Nasal polyps are a significantly associated pathology of chronic rhinosinusitis (CRS) whose mechanisms of pathogenesis are not fully elucidated, especially the interaction of the polyp with its environment that allows its growth on the nasal epithelial lining. Exosomes are nanovesicles that serve important biological functions, including cell-to-cell signaling and communication. OBJECTIVE: Hence, we sought to explore the roles of the epithelial-derived exosomal proteome obtained from the human nasal epithelium in the modulation of CRS with nasal polyp (CRSwNP) pathogenesis. METHODS: We sampled exosomes from nasal lavage fluid and primary human nasal epithelial cells (hNECs) from healthy controls and patients with CRSwNP with and without coexisting asthma. The presence of exosomes was confirmed using a NanoSight assay, transmission electron microscopy and western blotting. The exosomal proteome was profiled with mass spectrometry. The Cell Counting Kit-8 was used to confirm the roles of exosomes in mediating cellular proliferation. RESULTS: The hNEC-derived exosomes from diseased epithelium contained differentially expressed proteins that were mainly involved in epithelial remodeling via pathways such as p53. An in vitro study further demonstrated that epithelial-derived exosomes from patients with CRSwNP (with and without coexisting asthma) significantly reduced the rate of proliferation of control hNECs at an effective concentration of ≥10 µg/ml. CONCLUSIONS: Exosomes secreted by hNECs from patients with CRSwNP, regardless of their coexistence with asthma, are laden with proteins that influence cell proliferation pathways, potentially leading to remodeling of the sinonasal mucosa.

[Transnasal endoscopic optic nerve decompression for traumatic optic neuropathy: analysis of 155 cases].

OBJECTIVE: To explore the outcome of transnasal endoscopic optic nerve decompression (TEOND) for traumatic optic neuropathy (TON). METHODS: The clinical data of 155 consecutive patients with TON treated with TEOND after failure of mega-dose steroid therapy were retrospectively analyzed, their outcomes were summarized after follow-up, and then Logistic regression was used to analyze the prognosis-related information to explore the factors influencing prognosis. RESULTS: Patients were followed up for 3 - 60 months. The total effective rate of the 155 patients was 44.5%. The effective rate of the patients with light perception or better vision was 87.5%, much higher than that of the patients without light perception (29.6%). Eyesight was improved, mostly occurring 1 - 5 days after operation and lasting for 1 - 3 months, in 69 patients. Residual vision degree after trauma (OR = 0.04) and the interval between injury and surgery (OR = 4.62) were significant prognostic factors of the general effect (P < 0.01), and the gradual or immediate visual loss history (OR = 0.22) and the interval between injury and surgery (OR = 6.34) were significant to the outcomes of the patients with no light perception (P < 0.05). Sex, age, duration of coma after trauma, pre- and post-operative duration of steroid treatment, operators, fracture site of optic canal, and nerve sheath incision were not correlated to the outcomes of patients (all P > 0.05). Intraoperative cerebrospinal fluid rhinorrhea and postoperative transient visual loss occurred in one and the other two cases, respectively, but these conditions were resolved successfully. CONCLUSION: TEOND is effective and safe for TON patients, but the visual outcome is poor for the immediate blindness cases. The surgery is indicated for the patients with some residual vision or with a gradual visual loss and is suggested to perform early within seven days after injury.

Obestatin ameliorates water retention in chronic heart failure by downregulating renal aquaporin 2 through GPR39, V2R and PPARG signaling.

AIMS: Obestatin regulates water metabolism by inhibiting arginine vasopressin (AVP) release and upregulated obestatin has been detected in patients with chronic heart failure (CHF). However, the significance of obestatin in CHF, particularly with regard to water retention and aquaporin 2 (AQP2) expression, remains unknown. MAIN METHODS: Using a CHF rat model, the effects of 2-week exogenous obestatin administration were evaluated. Expression of AQP2 was evaluated by immunoblotting, immunohistochemical staining, and quantitative real-time PCR (qPCR) in CHF rat model and mouse inner medullary collecting duct (mIMCD) 3 cell line. Moreover, the influence of obestatin on the genetic transcription profile in mIMCD3 cells was evaluated by microarray, and the potential regulatory mechanisms of obestatin on AQP2 were evaluated by RNA silencing of vasopressin receptor 2 (V2R), peroxisome proliferator-activated receptor gamma (PPARG), and G protein-coupled receptor 39 (GPR39). KEY FINDINGS: Obestatin increased urinary output and improved expression of CHF biomarker without significantly altering cardiac function, plasma electrolyte concentrations, or the plasma AVP concentration. AQP2 expression was significantly reduced. The results of microarray analyses and qPCR indicated that mRNA levels of Aqp2, Pparg, and V2r were significantly decreased. Inhibition of V2r and Pparg mRNA further reduced the expression of AQP2, while the inhibitory efficacy of obestatin on AQP2 was significantly offset after Gpr39 knockdown. SIGNIFICANCE: Long-term treatment with obestatin improves water retention in CHF by increasing urinary output through downregulation of AQP2 expression in renal IMCD cells. These effects may be at least partially mediated by regulation of GPR39, V2R and PPARG signaling.