[Analysis of curative effect of orbital apex syndrome caused by sinus disease].

Objective:To compare the efficacy of endoscopic sinus surgery and conservative treatment for orbital apex syndrome caused by sinus lesions. Methods:The clinical data of 56 patients with orbital apex syndrome caused by sinus lesions who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to August 2023 were retrospectively analyzed and divided into a surgical group of 21 cases and a conservative group of 35 cases. The clinical features and prognosis of the two groups were compared. Results:Among the sinus lesions in the surgical group, 61.9% were fungal sinusitis, 28.6% were bacterial sinusitis, and 9.5% were sphenoid sinus tumors. In the conservative group, non-fungal sinusitis accounted for 65.7% and fungal sinusitis accounted for 34.3%. In addition to sinus lesions, patients had underlying diseases. In the surgical group, 71.4% had hypertension and 80.9% had diabetes; in the conservative group, 28.6% had hypertension and 42.9% had diabetes. After a follow-up of 1 month to 5 years, the symptom improvement rate in the surgical group was 85.7%, with 1 case of recurrence. No recurrence was found after reoperation, while the symptom improvement rate in the conservative group was 22.9%, and 6 cases recurred after symptom improvement, and were transferred to rhinology department. No recurrence was seen after surgery. Conclusion:Most of the sinus lesions in this study were fungal sinusitis. In addition, patients with underlying diseases such as diabetes, hypertension, nephrotic syndrome, etc. have reduced nasal immunity, which significantly increases the risk of disease. Since early nasal symptoms are not obvious, multidisciplinary cooperation in diagnosis and treatment is very necessary. Once imaging examination suggests orbital apex syndrome caused by sinus lesions, endoscopic sinus opening should be performed as soon as possible.

Endocrine disrupting chemicals in children's and their parents' urine: Is the exposure related to the Chinese and Western lifestyle?

Children are known to be more vulnerable to exposure to endocrine-disrupting chemicals (EDCs) compared to adults, but evaluating the exposure pathways can be challenging. This research employed target and non-target analysis (NTA) to examine the exposure characteristics of EDCs in spot urine samples collected from 46 children's (aged 3-12 years) and their parents in Hong Kong (Chinese/Western lifestyle) and Guangzhou (mainly Chinese lifestyle). The results revealed that the geometric mean concentrations of phthalate esters metabolites (mPAEs) and bisphenols (BPs) in children's urine were 127.3 µg/gcrea and 2.5 µg/gcrea in Guangzhou, and 93.7 µg/gcrea and 2.9 µg/gcrea in Hong Kong, respectively, which were consistent with global levels. NTA identified a total of 1069 compounds, including 106 EDCs, commonly detected in food, cosmetics, and drugs. Notable regional differences were observed between Guangzhou and Hong Kong with potential sources of EDCs including dietary and cosmetic additives, toys, flooring and dust, as well as differences in lifestyles, diet, and living environment. However, age was found to significantly impact EDC exposure. The quantified EDCs (mPAEs and BPs) posed possible health risks to 60% of the children. Moreover, the presence of caffeine in children's urine, which exhibited higher detection rates in children from Hong Kong (95.6%) and Guangzhou (44.4%), warrants further attention. The sources of EDCs exposure in these regions need to be fully confirmed.

A prospective single-arm study on the relationship between dose-volume parameters of pelvic functional bone marrow and acute hematological toxicities during intensity-modulated radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer.

BACKGROUND: FLT-PET/CT can accurately identify and locate functional bone marrow (FBM) with hematopoietic capability, the FBM were divided into two levels as FBM1 (strongest hemopoietic ability region)and FBM2 (moderate hemopoietic ability region) via FLT-PET/CT. The purpose of this study was to explore the relationship between dose-volume parameters of pelvic FBM and hematologic toxicity (HT) during radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer. METHODS: From December 2016 to September 2021, ninety-seven uterine cervical/endometrial cancer patients received intensity-modulated radiation therapy were prospectively recruited in this single-arm, prospective, phase II trial. Blood counts were reviewed weekly during radiotherapy. Single- and multifactor regression methods were used to analyze the relationships between dose-volume parameters of FBM1/2 and grade ≥ 2 HT. ROC curves were used to determine the cutoff values for the dose-volume parameters of FBM1/2. RESULTS: The incidence of grade ≥ 2 leukopenia, neutropenia, thrombocytopenia and anemia in patients during radiotherapy was 63.9%, 45.4%, 19.6% and 38.8% respectively, and the median occurrence time was the 29th, 42th, 35th and 31th day, respectively. Multivariate regression analysis showed that the Dmax of FBM1 was significantly related to grade ≥ 2 leukopenia (OR = 1.277 95% CI 1.067-1.528, P = 0.008), Dmean of FBM2 was significantly related to grade ≥ 2 thrombocytopenia (OR = 1.262 95% CI 1.066-1.494, P = 0.007), and V10 of FBM1 was significantly related to grade ≥ 2 anemia (OR = 1.198 95% CI 1.003-1.431, P = 0.046). The incidence of grade ≥ 2 leukopenia for patients with FBM1 Dmax < 53 Gy was lower than that for patients with FBM1 Dmax ≥ 53 Gy (53.4% vs. 95.8%, P < 0.001). The incidence of grade ≥ 2 thrombocytopenia in patients with FBM2 Dmean < 33 Gy was lower than that in patients with FBM2 Dmean ≥ 33 Gy (0 vs. 28.4%, P < 0.001). The incidence of grade ≥ 2 anemia for patients with FBM1 V10 < 95% was lower than that in patients with FBM1 V10 ≥ 95% (24.4% vs. 57.1%, P = 0.003). CONCLUSIONS: Grade ≥ 2 HT usually occurs in the 4th week of radiotherapy for patients with uterine cervical/endometrial cancer. The Dmax and V10 of FBM1 and the Dmean of FBM2 were significantly associated with the occurrence of grade ≥ 2 HT. The recommended optimal dose constraints were FBM1 Dmax < 53 Gy, V10 < 95%, and FBM2 Dmean <33 Gy.

Occurrence, spatiotemporal distribution patterns,partitioning and risk assessments of multiple pesticide residues in typical estuarine water environments in eastern China.

The low terrain and the prosperous agriculture in the east of China, have caused the accumulation of pesticide residues in the estuaries. Therefore, this study analyzed the spatiotemporal distribution and partition tendency of 106 pesticides based on their abundance, frequencies, and concentrations in the aquatic environment of 16 river estuaries in 7 major basins in the eastern China by using solid-phase extraction (SPE) with high-performance liquid chromatography tandem mass spectrometry (HPLC‒MS/MS) and gas chromatography tandem mass spectrometry (GC‒MS/MS). In addition, potential risk of multiple pesticides was also evaluated. The results showed that herbicides were the dominant pesticide type, while triazines were the predominate substance group of pesticide. In addition, triadimenol, vinclozolin, diethylatrazine, prometryn, thiamethoxam, atrazine, and metalachlor were the major pesticides in the water, while prometryn, metalachlor, and atrazine were the main pesticides in the sediment. The average total concentration of pesticide was 751.15 ng/L in the dry season, 651.17 ng/L in the wet season, and 617.37 ng/L in the normal season, respectively. The estuaries of the Huai River Basin, the Yangtze River Basin, the Hai River Basin, and the Yellow River Basin have been affected by the low pollution treatment efficiency, weak infrastructure, and agricultural/non-agricultural activities in eastern China, resulting in relatively serious pesticide pollution. The estuaries of Huaihe River, Yangtze River, Xiaoqing River, and Luanhe River had large pesticide abundance and comparatively severe pesticide pollution, while the estuaries of Tuhai River and Haihe River had heavy pesticide contamination in the sediment, which might be induced by historical sedimentary factors. The log KOC values showed that except for thioketone, other pesticides were relatively stable due to the adsorption by sediment. The ecological risk assessment results indicated that insecticides had a high risk. Teenagers were the most severely affected by the noncarcinogenic risk of pesticides, while adults were mostly affected by the carcinogenic risk of pesticides. Therefore, pesticide hazards in the water environment of estuaries in eastern China needs to be further close supervision.

SCF/c-Kit-activated signaling and angiogenesis require Gαi1 and Gαi3.

The stem cell factor (SCF) binds to c-Kit in endothelial cells, thus activating downstream signaling and angiogenesis. Herein, we examined the role of G protein subunit alpha inhibitory (Gαi) proteins in this process. In MEFs and HUVECs, Gαi1/3 was associated with SCF-activated c-Kit, promoting c-Kit endocytosis, and binding of key adaptor proteins, subsequently transducing downstream signaling. SCF-induced Akt-mTOR and Erk activation was robustly attenuated by Gαi1/3 silencing or knockout (KO), or due to dominant negative mutations but was strengthened substantially following ectopic overexpression of Gαi1/3. SCF-induced HUVEC proliferation, migration, and capillary tube formation were suppressed after Gαi1/3 silencing or KO, or due to dominant negative mutations. In vivo, endothelial knockdown of Gαi1/3 by intravitreous injection of endothelial-specific shRNA adeno-associated virus (AAV) potently reduced SCF-induced signaling and retinal angiogenesis in mice. Moreover, mRNA and protein expressions of SCF increased significantly in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. SCF silencing, through intravitreous injection of SCF shRNA AAV, inhibited pathological retinal angiogenesis and degeneration of retinal ganglion cells in DR mice. Finally, the expression of SCF and c-Kit increased in proliferative retinal tissues of human patients with proliferative DR. Taken together, Gαi1/3 mediate SCF/c-Kit-activated signaling and angiogenesis.

Spleen-selective co-delivery of mRNA and TLR4 agonist-loaded LNPs for synergistic immunostimulation and Th1 immune responses.

Spleen is an ideal site for initiating and amplifying antigen-specific immune response. However, spleen-selective antigen delivery has limited tumor therapeutic efficacy owing to an inadequate cytotoxic T-cell immune response. In this study, we designed a spleen-selective mRNA vaccine that delivered unmodified mRNA and Toll-like Receptor (TLR) agonists to the spleen after systemic administration, resulting in a sufficient and persistent antitumor cellular immune response with potent tumor immunotherapeutic efficacy. To establish potent tumor vaccines (sLNPs-OVA/MPLA), we co-loaded stearic acid doped lipid nanoparticles with ovalbumin (OVA)-coding mRNA and TLR4 agonists (MPLA). We found that sLNPs-OVA/MPLA facilitated tissue-specific mRNA expression in the spleen after intravenous injection and elicited enhanced adjuvant activity with Th1 immune responses by activating multiple TLRs. In a prophylactic mouse model, sLNPs-OVA/MPLA induced a potent antigen-specific cytotoxic T cell immune response and ultimately prevented the growth of EG.7-OVA tumors with persistent immune memory protection. In addition, sLNPs-OVA/MPLA effectively delayed the tumor growth of EG.7-OVA subcutaneously transplanted lymphoma and lung metastasis formation of B16F10-OVA intravenously injected melanoma. This study showed that the co-delivery of mRNA antigens and appropriate TLR agonists could significantly improve the antitumor immunotherapeutic efficacy of spleen-targeted mRNA vaccines via synergistic immunostimulation and Th1 immune responses.

Platelet-to-lymphocyte ratio predicts short-term mortality in patients with moderate to severe traumatic brain injury.

An easily accessible biomarker with good diagnostic power for patients with traumatic brain injury (TBI) was needed to predict the short-term mortality. Studies have shown that platelet-to-lymphocyte ratio (PLR) is a biomarker for patients with tumor. This study aimed to identify the relationship between PLR and short-term mortality in patients with moderate to severe TBI. This is a retrospective cohort study. We selected patients with moderate to severe TBI who were admitted to the emergency department of The First Affiliated Hospital of Zhengzhou University. Biomarkers were collected within 24 h after admission. To investigate their relationship with short-term mortality, Cox proportional hazards regression and ROC curve analysis were performed. A total number of 170 patients was included. 47 (27.6%) patients had died and 123 (72.4%) patients were survived by the end of the study. Patients with different Rotterdam CT score (HR = 1.571, 95%CI 1.232-2.002, p < 0.001) or PLR levels (HR = 1.523, 95%CI 1.110-2.090, p = 0.009) had significant different mortality rates. The AUC curve analysis showed that the AUC of Rotterdam CT score and PLR groups were 0.729 (95%CI 0.638-0.821, p < 0.001) and 0.711 (95%CI 0.618-0.803 p < 0.001), respectively. PLR level is an independent biomarker with great diagnostic power for short-term mortality in patients with moderate to severe brain injury.

Silencing lncRNA Snhg6 mitigates bleomycin-induced pulmonary fibrosis in mice via miR-26a-5p/TGF-ß1-smads axis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial pulmonary disease with slow onset and high mortality. Epithelial-mesenchymal transition (EMT) is a significant condition for tissue fibrosis, and lncRNA-Snhg6 (small nucleolar RNA host gene 6) is related to EMT in some cancer cells, but its role in pulmonary fibrosis remains obscure. Here, we found that TGF-ß1 and Snhg6 were up-regulated in lung tissues of BLM-induced lung fibrosis mouse, and Snhg6 expression was significantly increased in primary lung fibroblasts after BLM treatment. Snhg6 knockdown notably alleviated the pulmonary dysfunction, and the increase of fibrosis area and collagen deposition induced by BLM. MiR-26a-5p was downregulated in BLM-induced fibrotic lung tissues, and it was negatively regulated by Snhg6. Silencing Snhg6 markedly alleviated the TGF-ß1-induced increase in fibrotic marker expression, cell proliferation, migration and differentiation, as well as the nuclear transport of p-Smad2/3 by modulating miR-26a-5p expression in mouse lung fibroblasts. Moreover, overexpressing Snhg6-induced collagen accumulation and fibroblast activation in fibroblasts, which was reversed by treatment with miR-26a-5p mimic or oxymatrine (an inhibitor of TGF-ß1-Smads pathway). Interestingly, silencing Snhg6 in vivo mitigated BLM-driven pulmonary fibrosis by regulating the miR-26a-5p/TGF-ß1-Smads axis. Our data revealed that Snhg6 contributed to the process of BLM-driven lung fibrosis in mouse by modulating the miR-26a-5p/TGF-ß1-Smads axis, suggesting that Snhg6 might be a therapeutic target for lung fibrosis.

Enhancing Drug Utilization Efficiency via Dish-Structured Triboelectric Nanogenerator.

Due to the finding of severe side effects and low therapeutic efficacy with cancer chemotherapy, there still remains a great challenge to benefit patients with curative effect. In this work, we designed a self-powered drug delivery system comprising a current source derived from the disk TENG (D-TENG) and a pair of Au electrodes. Thus, cells seeded within the electrode gap could be stimulated by the current followed by D-TENG`s work. Under the rotation frequency of about 7.4 Hz, the peak output current and voltage of the D-TENG reached 3.7 µA and 135 V and achieved an average of 2.8 µA of output current. Furthermore, the D-TENG also showed its good stability to output steady current in a long-term condition. When applying the electric stimulation by this self-powered drug delivery system, a chemotherapy drug, doxorubicin (DOX), had significant uptake by cancer cells. Therefore, utilizing a novel TENG device as a part of chemotherapy would provide a new opportunity in future disease treatment.

Effect of Trimethine Cyanine Dye- and Folate-Conjugation on the In Vitro Biological Activity of Proapoptotic Peptides.

Despite continuous advances, anticancer therapy still faces several technical hurdles, such as selectivity on cellular and subcellular targets of therapeutics. Toward addressing these limitations, we have combined the use of proapoptotic peptides, trimethine cyanine dye, and folate to target the mitochondria of tumor cells. A series of proapoptotic peptides and their conjugates with a cyanine dye and/or folate were synthesized in the solid phase, and their toxicity in different human cell lines was assessed. Cyanine-bearing conjugates were found to be up to 100-fold more cytotoxic than the parent peptides and to localize in mitochondria. However, the addition of a folate motif did not enhance the potency or selectivity of the resulting conjugates toward tumor cells that overexpress folate receptor α. Furthermore, while dual-labeled constructs were also found to localize within the target organelle, they were not generally selective towards folate receptor α-positive cell lines in vitro.

Effect of Squid Cartilage Chitosan Molecular Structure on the Properties of Its Monofilament as an Absorbable Surgical Suture.

Suture is an important part of surgery, and wounds closing after surgery remains a challenge for postoperative care. Currently, silk, linen fiber, and cotton are available in the market as non-absorbable suture biomaterials. So, there is an urgent need to develop a novel suture with advantageous characteristics compared to the ones available on the market. In present study, a series of ultra-high molecular weight chitosan with different DD and MV were prepared from squid cartilage by alkaline treatment and ultrasonic degradation. The corresponding chitosan monofilaments were prepared by a wet spinning process and were characterized as sutures. The effects of the DD and MV of chitosan on the properties of its monofilament were studied, including surface morphology, mechanical property, swelling ratio, ash content, in vitro enzymatic degradation, and in vitro cytotoxicity. According to the results, AS-85 was chosen to be the best suitable as an absorbable surgical suture, which was spun from squid cartilage chitosan with DD~85% and MV~1.2 × 106. The outcome of the present study might derive tremendous possibilities for the utilization of squid cartilage ß-chitin for biomedical applications.

Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice.

OBJECTIVES: In this study, we investigated the possible analgesic effects of Botulinum toxin type A (BoNT/A) on trigeminal neuralgia (TN). A modified TN mouse model was established by chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) in mice, and the possible roles of microglia toll-like receptor 2 (TLR2) and neuroinflammation was investigated. METHODS: Male C57BL/6 mice were divided into 3 groups, including sham group, vehicle-treated TN group and BoNT/A-treated TN group. Bilateral mechanical pain hypersensitivity, anxiety-like and depressive-like behaviors were evaluated by using von Frey test, open field, elevated plus-maze testing, and forced swimming test in mice, respectively. The mRNA or protein expression levels of toll-like receptors (TLRs), glia activation markers and proinflammatory factors in the trigeminal nucleus caudalis (TNC) were tested by RT-qPCR, immunofluorescence and Western blotting. We also tested the pain behaviors of TN in Tlr2-/- mice. RESULTS: We found that unilateral subcutaneous injection of BoNT/A into the whisker pad on the ipsilateral side of dIoN-CCI mice significantly attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors induced by dIoN-CCI surgery in mice. The dIoN-CCI surgery significantly up-regulated the expression of TLR2, MyD88, CD11b (a microglia marker), IL-1ß, TNF-α and IL-6 in the ipsilateral TNC in mice, and BoNT/A injection significantly inhibited the expression of these factors. Immunostaining results confirmed that BoNT/A injection significantly inhibited the microglia activation in the ipsilateral TNC in dIoN-CCI mice. TLR2 deficiency also alleviated bilateral mechanical pain hypersensitivity and the up-regulation of MyD88 expression in the TNC of dIoN-CCI mice. CONCLUSION: These results indicate that unilateral injection of BoNT/A attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors in dIoN-CCI mice, and the analgesic effects of BoNT/A may be associated with the inhibition of TLR2-mediated neuroinflammation in the TNC.

Discovery of a Series of 1,2,3-Triazole-Containing Erlotinib Derivatives With Potent Anti-Tumor Activities Against Non-Small Cell Lung Cancer.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are emerging at the vanguard of therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, the increasing therapeutic resistance caused by novel mutations or activated bypass pathways has impaired their performance. In this study, we link one of the commercial EGFR-TKIs, Erlotinib, to different azide compounds to synthesize a novel class of 1,2,3-triazole ring-containing Erlotinib derivatives. We discovered that several new compounds show robust antiproliferation activity against diverse NSCLC cells in vitro including PC-9, H460, H1975 and A549. Two of the most potent compounds, e4 and e12 have been found to be more efficient than Erlotinib in all NSCLC cell lines except PC-9. They significantly induce apoptosis and cell cycle arrest in PC-9 and H460 cells. The antitumor efficacy of compound e4 in vivo is close to that of Erlotinib in a PC-9 xenograft mouse model. Most Erlotinib-1,2,3-triazole compounds exhibit moderate to good inhibitory activities toward wild-type EGFR as indicated by enzyme-linked immunosorbent assay (ELISA), and the EGFR phosphorylation was inhibited in H460 and PC-9 cells exposed to e4 or e12. These data suggest that these Erlotinib-1,2,3-triazole compounds are suitable candidates for use against NSCLC and more unknown mechanisms merit further investigation.

Association of lipid profiles with severity and outcome of acute ischemic stroke in patients with and without chronic kidney disease.

BACKGROUND: Contribution of lipid profiles to stroke severity and outcome was inconclusive, whether chronic kidney disease (CKD) (estimated glomerular filtration rate < 60 mL/min/1.73 m2) affects the association has not been investigated. We aim to evaluate this relationship. METHODS: A retrospective study of consecutive acute ischemic stroke patients was performed. We assessed the risk of severe stroke with the National Institutes of Health Stroke Scale (NIHSS) ≥ 5 at admission and poor outcome with the modified Rankin Scale (mRS) ≥ 3 at discharge. Multivariate stepwise logistic regression models were adopted to study interaction and independent association of lipid components with stroke severity and outcome according to lipid level quartiles by CKD stratification. RESULTS: Among the 875 included patients (mean age 64.9 years, 67.8% males), 213 (24.3%) presented with CKD. Elevated low-density lipoprotein cholesterol (LDL-C) was independently associated with severe stroke in patients with CKD (P for trend = 0.033) than in those without CKD (P for trend = 0.121). The association between the level of LDL-C and stroke severity was appreciably modified by CKD (Pinteraction = 0.013). Compared with without CKD patients in the lowest LDL-C quartile, the multivariable-adjusted risk of severe stroke increased significantly by 2.9-fold (95% CI 1.48-5.74) in patients with CKD in the highest LDL-C quartile. No significant association was observed between lipid components and early outcome in patients with and without CKD. CONCLUSION: LDL-C levels are positively associated with stroke severity in only patients with CKD, with an interactive impact of LDL-C and CKD on ischemic stroke in the acute phase.

Pesticides in human milk collected from Jinhua, China: Levels, influencing factors and health risk assessment.

In China, many studies have been carried out on pesticide residues in human milk, yet all of them are on organochlorine pesticides (OCPs) and mostly focused on large, economically developed cities. In this study, 27 pesticides including OCPs, pyrethroid pesticides (PYRs) and organophosphate pesticides (OPPs) in human milk were investigated in Jinhua, an inland and medium sized city in China. Method based on QuEChERS extraction and gas chromatography-mass spectrometer (GC-MS) determination was adopted to analyze the above pesticide residues. The influencing factors as well as the health risks were also evaluated. Results show that PYRs and OPPs in human milk samples were both undetectable. Regarding OCPs, the detection rate of hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH) and p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE) were 83.6%, 36.4% and 58.2%, respectively, and their mean value were 29.4, 32.0 and 85.2 ng/g lipid, respectively. p,p'-DDE levels in human milk was significantly (p < 0.05) related to maternal age, but no association was detected between OCPs residues and other factors (living environment, dietary habit, living style, etc.), suggesting that OCPs in human milk in Jinhua were originated from nonspecific source. All estimated daily intake of pesticides (EDIpesticides) by infants were under the guideline suggested by Food and Agriculture Organization (FAO) and China Ministry of Health (CMH). Yet 9% of EDIsHCB and 16% of EDIsHCHs exceeded the guideline recommended by Health Canada. The associations between DDE residues and the delivery way as well as HCBs residues and the birth weight were seemly significant, yet the significance disappeared when consider age or gestational age as a cofounder, indicating that OCPs residue in mother's body in Jinhua has no obvious influence on fetus development and the delivery way.

MicroRNA-130a regulates neurological deficit and angiogenesis in rats with ischaemic stroke by targeting XIAP.

MicroRNAs (miRNAs) have already been proposed to be implicated in the development of ischaemic stroke. We aim to investigate the role of miR-130a in the neurological deficit and angiogenesis in rats with ischaemic stroke by regulating X-linked inhibitor of apoptosis protein (XIAP). Middle cerebral artery occlusion (MCAO) models were established by suture-occluded method, and MCAO rats were then treated with miR-130a mimics/inhibitors or/and altered XIAP for detection of changes of rats' neurological function, nerve damage and angiogenesis in MCAO rats. The oxygen-glucose deprivation (OGD) cellular models were established and respectively treated to determine the roles of miR-130a and XIAP in neuronal viability and apoptosis. The expression levels of miR-130a and XIAP in brain tissues of MCAO rats and OGD-treated neurons were detected. The binding site between miR-130a and XIAP was verified by luciferase activity assay. MiR-130a was overexpressed while XIAP was down-regulated in MCAO rats and OGD-treated neurons. In animal models, suppressed miR-130a improved neurological function, alleviated nerve damage and increased new vessels in brain tissues of rats with MCAO. In cellular models, miR-130a inhibition promoted neuronal viability and suppressed apoptosis. Inhibited XIAP reversed the effect of inhibited miR-130a in both MCAO rats and OGD-treated neurons. XIAP was identified as a target of miR-130a. Our study reveals that miR-130a regulates neurological deficit and angiogenesis in rats with MCAO by targeting XIAP.

Cobalt Oxyhydroxide-prompted Synthesis of Fluorescent Polydopamine Nanoparticles for Glutathione Detection.

Glutathione (GSH) plays an important role in cells, which is an essential endogenous antioxidant. Here, we have developed a new detection platform to analyze GSH levels. In our system, fluorescent polydopamine (PDA) nanoparticles, as signal indicators, were obtained by oxidation through cobalt oxyhydroxide (CoOOH) nanosheets. When CoOOH was present, CoOOH could quickly oxidize dopamine to fluorescent PDA nanoparticles. However, once GSH existed, CoOOH nanosheets were decomposed into Co2+, and oxidation between CoOOH and dopamine was prevented with weaker fluorescence occurring. Thus, we could realize detection of the GSH concentration according to the decreased fluorescence value of the fluorescent polydopamine. This method provides a fast, simple, high sensitivity and desirable selectivity platform for GSH monitoring.

Role of XIAP gene overexpressed bone marrow mesenchymal stem cells in the treatment of cerebral injury in rats with cerebral palsy.

BACKGROUND: This study is performed to investigate the effects of adenovirus-mediated X-linked inhibitor of apoptosis protein (XIAP) overexpressed bone marrow mesenchymal stem cells (BMSCs) on brain injury in rats with cerebral palsy (CP). METHODS: Rat's BMSCs were cultured and identified. The XIAP gene of BMSCs was modified by adenovirus expression vector Ad-XIAP-GFP. The rat model of CP with ischemia and anoxia was established by ligating the left common carotid artery and anoxia for 2 h, and BMSCs were intracerebroventricularly injected to the modeled rats. The mRNA and protein expression of XIAP in brain tissue of rats in each group was detected by RT-qPCR and western blot analysis. The neurobehavioral situation, content of acetylcholine (Ach), activity of acetylcholinesterase (AchE), brain pathological injury, apoptosis of brain nerve cells and the activation of astrocytes in CP rats were determined via a series of assays. RESULTS: Rats with CP exhibited obvious abnormalities, increased Ach content, decreased AchE activity, obvious pathological damage, increased brain nerve cell apoptosis, as well as elevated activation of astrocyte. XIAP overexpressed BMSCs improved the neurobehavioral situation, decreased Ach content and increased AchE activity, attenuated brain pathological injury, inhibited apoptosis of brain nerve cells and the activation of astrocytes in CP rats. CONCLUSION: Our study demonstrates that XIAP overexpressed BMSCs can inhibit the apoptosis of brain nerve cells and the activation of astrocytes, increase AchE activity, and inhibit Ach content, so as to lower the CP caused by cerebral ischemia and hypoxia in rats.

Interleukin-17 receptor C gene polymorphism reduces treatment effect and promotes poor prognosis of ischemic stroke.

OBJECTIVE: To study the relationship between Interleukin-17 receptor C (IL-17RC) gene polymorphism and ischemic stroke (IS). METHODS: Three hundred cases of IS patients and 300 cases of the healthy controls were selected. Serum of IS patients and the controls was collected. The relative mRNA levels of IL-17, IL-17RC, IL-6, IL-8, G-CSF and granulocyte-macrophage colony stimulating factor (GM-CSF) by qRT-PCR. The protein expression of IL-17 and IL-17RC was determined by Western blotting. IL-17RC genotype was identified by PCR amplification. The proportion of IL-17RC, SNP and re37511 in IS and control group was determined. The treatment effect on IS and prognosis of patients with IL-17RC, SNP and re37511 was compared. RESULTS: The relative mRNA levels of IL-17, IL-17RC, IL-6, IL-8, G-CSF and GM-CSF in IS group were significantly higher than the control group. The protein expression of IL-17 and IL-17RC in IS group was also markedly higher than the control group. The proportion of IL-17RC re37511 in IS group was much larger than control group and proportion of IL-17RC much less. The percent of poor treatment effect in re37511 was much larger than IL-17RC. The percent of death and recrudescence in patients with IL-17RC re37511 was the highest. CONCLUSION: IS up-regulates the expression of IL-17 and IL-17RC. IL-17RC re37511 indicates the patients have a poorer treatment effect and prognosis.

Quantitative proteomic analysis of mitochondrial proteins differentially expressed between small cell lung cancer cells and normal human bronchial epithelial cells.

BACKGROUND: Small cell lung cancer (SCLC) is highly aggressive and is associated with a dismal prognosis. However, there are no clinically recognized biomarkers for early diagnosis. In this study, we used quantitative proteomics to build differential mitochondrial protein profiles that may be used for early diagnosis and investigated the pathogenesis of lung cancer. METHODS: We cultured SCLC cells (NCI-H446) and normal human bronchial epithelial cells (16-HBE); mitochondria were extracted and purified using differential and Percoll density gradient centrifugation. Subsequently, we used Western blot analysis to validate mitochondrial purity and labeled proteins/peptides from NCI-H446 and 16-HBE cells using relative and absolute quantification of ectopic tags. We then analyzed mixed samples and identified proteins using two-dimensional liquid chromatography-tandem mass spectrometry. Additionally, we performed subsequent bioinformatic proteome analyses using the programs ExPASy, GOA, and STRING. Finally, the relationship between ornithine aminotransferase expression and clinicopathological features in lung cancer patients was evaluated using immunohistochemistry. RESULTS: One hundred and fifty-three mitochondrial proteins were differentially expressed between 16-HBE and NCI-H446 cells. The expression of 30 proteins between 16-HBE and NCI-H446 cells increased more than 1.3-fold. The upregulation of ornithine aminotransferase was associated with pathological grade and clinical tumor node metastasis stage. CONCLUSION: Our experiment represented a promising method for building differential mitochondrial protein profiles between NCI-H446 and 16-HBE cells. Such analysis may also help to identify novel biomarkers of lung cancer.