[Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population].

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

[Concordant systemic and local eosinophilia relates to poorer disease control in patients with nasal polyps].

Objective: To explore whether blood and polyp tissue eosinophil numbers are independent risk factors for poor disease control in patients with nasal polyp. Methods: By using the electronic medical records database and manual evaluation, 183 nasal polyp patients who had undergone endoscopic sinus surgery at least one year prior to the study with complete data of tissue specimens, baseline blood routine test, nasal endoscopy and sinus computed tomography, were identified and recruited to assess disease control based on the criteria of a European Position Paper on Rhinosinusitis and Nasal Polyps 2012 (EPOS 2012). Multiple logistic regression model was used to determine the association between blood and tissue eosinophil numbers and risk of poor disease control by adjusting for demographics and comorbidities. Results: We broke down the cohort into 4 groups according to blood (0.3×109/L) and tissue (10%) eosinophils. The patients without eosinophilic inflammation represented the largest group (41.5%). The group with concordant blood and tissue eosinophilia represented the second largest (31.2%), and the patients with isolated tissue (15.3%) or blood (12.0%) eosinophilia were relatively rare. Multiple logistic regression models found blood eosinophil count and tissue eosinophil percentage were independently associated with increased risk for poor disease control after adjustments for covariates related to poor treatment outcome. Furthermore, subjects with concordant blood and tissue eosinophilia had a higher risk for poor disease control than those with isolated blood or tissue eosinophilia. Conclusion: Concordant blood and tissue eosinophilia relates to a higher likelihood of poor disease control than isolated blood or tissue eosinophilia after adjustment of potential confounders in nasal polyp patients.

A Hemodynamic Mechanism Correlating with the Initiation of MCA Bifurcation Aneurysms.

BACKGROUND AND PURPOSE: Previous studies have reported that MCA bifurcation aneurysms usually emerge on inclined bifurcations; however, the reason is unclear. We designed this study to explore hemodynamic mechanisms that correlate with the initiation of MCA bifurcation aneurysms. MATERIALS AND METHODS: Fifty-four patients with unilateral MCA bifurcation aneurysms and 54 control patients were enrolled in this study after propensity score matching, and their clinical and CTA data were collected. We extracted the morphologic features of aneurysmal MCA bifurcations to build a simplified MCA bifurcation model and performed a computational fluid dynamics analysis. RESULTS: The presence of MCA aneurysms correlated with smaller parent-daughter angles of MCA bifurcations (P < .001). Aneurysmal MCA bifurcations usually presented with inclined shapes. The computational fluid dynamics analysis demonstrated that when arterial bifurcations became inclined, the high-pressure regions and low wall shear stress regions shifted from the apexes of the arterial bifurcations to the inclined daughter arteries, while the initial sites of MCA bifurcation aneurysms often overlapped with the shifted high-pressure regions and low wall shear stress regions. CONCLUSIONS: Our results suggest that the initiation of MCA bifurcation aneurysms may correlate with shifts of high-pressure regions and low wall shear stress regions that occur on inclined MCA bifurcations.

[Investigation of temporal and spatial characteristics of allergic rhinitis epidemics by Baidu Index in China].

Objective: To explore the temporal and spatial characteristics of search volume (SV) of allergic rhinitis (AR) and related search terms on Baidu Index, as well as the correlation between SV from Baidu Index and epidemiology of AR. Methods: SV of AR and related search terms in mainland area of China from January 2012 to December 2016 were extracted from Baidu Index. Firstly, we investigated the temporal and spatial characteristics of SV of AR and related search terms ("pollen allergy" and" dust mite allergy", etc.), and explored the correlation between SV of AR and SV of related search terms. Secondly, the SV of specific search terms in Beijing and Guangzhou were compared with the actual pollen count in Beijing from April to September in 2016 and the monthly outpatient volume of AR patients in the Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University from 2014 to 2016 respectively to analyze the consistency between SV from Baidu Index and the real-world data. Spearman correlation analysis was used to explore the correlation between different search terms according to the normality and homogeneity of variance of the data. P<0.05 was considered statistically significant. Results: SV of AR showed repetitively seasonal pattern, with the first peak in May and the second peak from August to September. SV of AR in northeast China, north China and northwest China were correlated with both SV of "pollen allergy" and "dust mite allergy" (r value was 0.533, 0.638, 0.609, 0.791, 0.517, 0.682, respectively, all P<0.05). In east China, central China, south China and southwest China, SV of AR showed significant correlation only with SV of "dust mite allergy" (r value was 0.897, 0.884, 0.799, 0.937, respectively, all P<0.05), but not with SV of "pollen allergy" (r value was 0.110, 0.171, 0.020, 0.265, respectively, all P>0.05). The correlation between pollen count and the SV of AR on the day and SV of "pollen allergy" on the next day was the highest (r value was 0.692 and 0.713, respectively, all P<0.05). The SV of AR was correlated with the monthly outpatient volume of AR patients one month and two months later (r value was 0.523 and 0.503, respectively, all P<0.05). Conclusion: The SV of AR and related search terms show different trends in different times and regions which are consistent with the AR epidemiological survey, and significantly correlate with pollen count and AR outpatient volume.

[Research on feasibility and effectiveness of the bone-implant contact evaluation in dogs by micro-CT].

Objective: To discuss the feasibility and effectiveness of using micro-CT in bone-implant contact (BIC) evaluation in dogs, and to provide reference for clinical and scientific research. Methods: Bilateral mandibular second premolar and first molar of six male Beagle dogs were extracted. After 3 months' healing, eight implants were placed in bilateral mandible of each dog, four on each side. Dogs were sacrificed at 2 weeks, 4 weeks and 8 weeks after implant placement, two on each time point. Samples were scanned with micro-CT and digitally reconstructed. Bone-implant interface was analyzed at different analysis regions (25, 50 and 100 µm from implants' surface), different detection range models were obtained (each time point consists 48 models), and BIC was evaluated, and the results were counted as micro-CT(25), micro-CT(50), and micro-CT(100) groups. Then undecalcified slides were made (three slides for each sample) and stained with toluidine blue for observation and analysis of BIC using an optical microscope, and the results were counted as optical microscope groups. The advantages and disadvantages, evaluation efficiency and BIC of different methods were analyzed. Results: To evaluate BIC of single sample, it took about 90 minutes by micro-CT, which was much lower than the time of 14 days by optical microscope. The success rates of modeling of micro-CT(25), micro-CT(50), and micro-CT(100) groups all were 100.0% (48/48), and total success rate of micro-CT group was 100.0% (144/144). For optical microscope groups, the success rates of making slides 2, 4, 8 weeks were 89.6% (43/48), 93.8% (45/48) and 93.8% (45/48), respectively, and total success rates of optical microscope group was 92.4% (133/144). At 2, 4,8 weeks after implantation, BIC in micro-CT(25) group was significantly smaller than that in optical microscope group at the same time point (P<0.05). However, at 2, 4,8 weeks after implantation, BIC of the micro-CT(50) and micro-CT(100) groups showed no significant difference with optical microscope groups at the same time point (P>0.05). A significant correlation (P<0.001, each) was seen between slides and micro-CT (25, 50, 100 µm groups) concerning BIC (r=0.680, r=0.892, r=0.713), and error bias was -19.4%, -0.9%, 3.0%, respectively. The probability within the 95% limits of agreement were 97.9%. Conclusions: Micro-CT is a faster, simpler and more efficient way to analyze BIC at the implant-bone interface than optical microscope observation. BIC analysis by selecting 50 µm from implants' surface as analysis region using micro-CT is in consistent with that using the optical microscope.

[Clinical features, diagnosis and treatment of silent sinus syndrome].

Objective: To explore the clinical features, diagnostic methods and therapeutic strategy of silent sinus syndrome (SSS). Methods: A retrospective study was made on eight SSS patients treated during 2013-2016 in Longgang ENT Hospital and Otorhinolaryngology Hospital of the First Affiliated Hospital of SUN Yat-sen University. The following clinical data, including demographic data, symptoms, history of trauma and surgery, signs, imaging examination, endoscopic surgery and postoperative outcomes, were analyzed to summarize the diagnosis and treatment experiences. Results: Eight SSS patients showed the following clinical features: the proportions of both sexes and sinus sides were 4 to 4; seven cases (7/8) were adult, with an average of (48.1±11.8)y; seven cases (7/8) had long history of trauma or surgery, with an average of (17.9±10.5)y; seven cases (7/8) cannot recall the exact course of SSS; six cases (6/8) had no nasal symptoms; eight cases (8/8) had unilateral ocular discomforts; eight cases (8/8) had signs of unilateral enophthalmos (2-5 mm), accompanied with hypoglobus; and by CT and MRI scanning, eight cases (8/8) showed the unilateral maxillary sinus outlet obstruction, sinus full opacification, sinus wall bony rarefaction, sinus wall contraction, sinus volume loss, and the ipsilateral orbital floor bowing descent and orbital volume increase. After treated by endoscopic sinus surgery and followed-up for one year, four cases were cured, and the other four improved; no intra- or post-operative complications occurred; and no individual need a two-stage orbital plastic reconstruction. Conclusions: SSS often develops in the unilateral maxillary sinus of adult patient with long history of trauma or surgery, but the nasal symptoms and signs are silent. Diagnostic for SSS depends on characteristic ocular sign and sinus CT imaging. Endoscopic sinus surgery helps to improve ocular and nasal signs and promote orbital self-reconstruction.

Local IL-25 contributes to Th2-biased inflammatory profiles in nasal polyps.

BACKGROUND: IL-25 has been proposed to play a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to evaluate the association of IL-25 with the Th2-biased inflammatory profiles in CRSwNP. METHODS: Nasal polyp (NP) tissues and control uncinate process tissues were collected from 92 patients with CRSwNP, 20 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 16 normal control subjects. IL-25 expression was examined using immunohistochemistry and immunofluorescence staining, flow cytometry, RT-qPCR, and ELISA. The inflammatory profiles and clinical characteristics of 2 NP subtypes (IL-25high and IL-25low ) were evaluated, and the effects of IL-25 on Th2 cytokine production in cultured dispersed polyp cells were examined in vitro. RESULTS: The mRNA and protein levels of IL-25 were significantly increased in the polyp tissues compared with the control uncinate process tissues. The IL-25high subtype showed greater computed tomography scores, endoscopic scores, and Th2 response. Exposure to IL-25 activated type 2 innate lymphoid cells and Th2 cells in NP simultaneously which further increased Th2 cytokine production in vitro. CONCLUSIONS: Local IL-25 plays a crucial role in promoting Th2-biased inflammatory profiles in NP and may serve as a promising therapeutic target in CRSwNP patients.

[The whole genome-wide screening of the longevity-related gene of Uyghur population in Hotan, Xinjiang].

Objective: To discuss the whole genome-wide screening of the longevity-related gene of Uyghur population in Hotan, Xinjiang. Methods: The whole gene scanning using genome-wide association study (GWAS) based on the pooling DNA and the SNP-Map strategy in the longevity group (≥90 years old) and control group (persons who died before 70 years old) was carried out. Then, through detecting varieties of SNP locus, the frequencies of genotype and allele were calculated by sequencing and PCR- restriction fragment length polymorphism (RFLP) method. Results: There was no significant difference of rs6450874, rs6800573 and rs6741735 genotypes and alleles frequency distributions between the two groups, however, there were statistical differences of rs1718307, rs4449651, rs11217987 and rs2907092 genotypes and alleles frequency distributions between the two groups. The TT genotype of rs11217987 (OR=1.462, P=0.034) and the GG genotype of rs2907092 (OR=3.000, P=0.018) were positively correlated to the longevity. And the T allele of rs11217987 (OR=1.382, 95%CI: 1.075-1.776) and the G allele of rs2907092 (OR=1.672, 95%CI: 1.267-2.205) had strong potential function to prolong life. The TT genotype of rs4449651 (OR=6.892, P=0.009) and rs1718307 (OR=4.036, P<0.001) were positively correlated to the longevity. Moreover, the T allele of both SNPs (OR=1.793, 95%CI: 1.298-2.477; OR=1.830, 95%CI: 1.391-2.407) had strong potential function to prolong life. Conclusions: The GWAS test can effectively and extensively analyze human longevity-related genes. And rs1718307, rs4449651, rs11217987 and rs2907092 are related to the longevity of Uyghur population in Hotan, Xinjiang.

[Endoscopic salvage treatment for optic neuropathy caused by sinonasal fibro-osseous lesions].

Objective: To summarize the surgical techniques, benefits and limitations of transnasal endoscopic resection and optic nerve decompression for patients with optic neuropathy caused by fibro-osseous lesions. Methods: Eight patients with optic neuropathy caused by fibro-osseous lesions who accepted endoscopic surgery of either resection of the lesion or decompression of optic nerve in Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University from 2007 to 2016 were retrospectively reviewed and followed until April, 2017. Analyses were performed on the pathology type, disease extent and disease duration, especially on the visual acuity and visual field changes before and after surgery. Results: Eight patients (5 male and 3 female) were included in this study, with a median age of 12 years old (8-19 years old). The median disease duration was 12 months (1-72 months). The visual acuity (VA) of five patients (40 cm/FC, 0.2, 0.1, 0.2, 10 cm/FC, respectively) improved after surgery (0.1, 0.3, 1.2, 0.1, 0.6, respectively), and one patient had no change of VA after the surgery. Two patients (0.02, hand movement, before surgery) became deprived of light perception (VA=0) immediately after surgery. One patient complicated with intra orbital hemorrhage because of anterior artery injury. No complications of cerebral spinal fluid leak, intra-ocular muscle injury, intra-cranial hemorrhage or brain tissue injury occurred. Conclusion: For the treatment of optic neuropathy caused by fibro-osseous lesions, transnasal endoscopic surgery might have a good outcome.

Impaired learning and memory in rats induced by a high-fat diet: Involvement with the imbalance of nesfatin-1 abundance and copine 6 expression.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, resulting not only in liver dysfunction, glucose and lipid metabolism disorder, but also in neuropsychiatric damage. In the present study, a NAFLD rat model was established via feeding of a high-fat diet, and behaviour was observed via the open field test (OFT), the sucrose preference test (SPT), the elevated plus maze (EPM), the forced swimming test (FST) and the Morris water maze (MWM). The plasma concentrations of alanine aminotransferase (ALT), glucose, free fatty acid (FFA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were detected using chemiluminescence technique. The plasma levels of nesfatin-1, leptin and insulin were measured via enzyme-linked immunosorbent assay, and the protein expressions of p-glycogen synthase kinase-3ß (GSK-3ß), GSK-3ß, p-ß-catenin, ß-catenin, cyclinD and copine 6 in the hippocampus and prefrontal cortex (PFC) were detected using western blotting. After 4 consecutive weeks of feeding with a high-fat diet, the rats showed obesity; increased plasma concentrations of ALT, glucose, FFA, TC, TG, HDL-C and LDL-C; decreased plasma levels of leptin and insulin; and inflammation and mild hepatocyte steatosis in the liver. Although there was no significant difference between groups with regard to performance in the OFT, EPM or FST, the NAFLD rats showed a decreased sucrose preference index in the SPT and impaired learning and memory in the MWM task. Moreover, the present study provides the first evidence of an increased plasma nesfatin-1 concentration in NAFLD rats, which was significantly correlated with plasma lipid concentrations and behavioural performance. Furthermore, copine 6 and p-ß-catenin protein expression decreased and p-GSK-3ß increased in the hippocampus and PFC of NAFLD rats. These results suggest that consuming of a high-fat diet for 4 consecutive weeks could successfully induce a NAFLD rat model. More importantly, these results provide the first evidence that impaired learning and memory in NAFLD rats was, at least partly, associated with increased plasma nesfatin-1 concentration and decreased copine 6 expression in the hippocampus and PFC.

YM155 inhibits tumor growth and enhances chemosensitivity to cisplatin in osteosarcoma.

OBJECTIVE: Chemoresistance is the principal reason for poor survival and disease recurrence in osteosarcoma patients. Survivin, a family member of the inhibitor of apoptosis proteins, plays an important role in inhibition of apoptosis. Survivin is expressed in a vast majority of human cancers, which is often correlated with poor prognosis in a wide variety of cancer patients. Furthermore, survivin expression is often related with chemoresistance in cancer cells, including osteosarcoma (OS). Here, we evaluated the therapeutic potential of YM155, a selective survivin suppressant alone and in combination with cisplatin using human OS models. MATERIALS AND METHODS: U-2 OS, SW1353, MG-63 cells were treated with YM155, and/or cisplatin, and cell viability, apoptosis, survivin protein expression levels were then evaluated. Furthermore, the efficacy of YM155 combined with cisplatin was further examined in established xenograft models. RESULTS: YM155 was sufficient to induce spontaneous apoptosis of OS cells. Combination with YM155 significantly augmented the cytotoxicity of cisplatin in OS cells. Combination treatment of YM155 and cisplatin showed antiproliferative effects and induced a greater rate of apoptosis than the sum of the single-treatment rates and promoted tumor regression in established OS xenograft models. CONCLUSIONS: Our findings provide evidence that YM155 could act as a survivin inhibitor on OS cells. Chemotherapeutic approaches using YM155 might enhance the benefit of the cisplatin in the treatment of OS cells. YM155 could be further developed as a potential therapeutic agent for the treatment of OS.

Control of the metal-insulator transition in VO2 epitaxial film by modifying carrier density.

External controlling the phase transition behavior of vanadium dioxide is important to realize its practical applications as energy-efficient electronic devices. Because of its relatively high phase transition temperature of 68 °C, the central challenge for VO2-based electronics, lies in finding an energy efficient way, to modulate the phase transition in a reversible and reproducible manner. In this work, we report an experimental realization of p-n heterojunctions by growing VO2 film on p-type GaN substrate. By adding the bias voltage on the p-n junction, the metal-insulator transition behavior of VO2 film can be changed continuously. It is demonstrated that the phase transition of VO2 film is closely associated with the carrier distribution within the space charge region, which can be directly controlled by the bias voltage. Our findings offer novel opportunities for modulating the phase transition of VO2 film in a reversible way as well as extending the concept of electric-field modulation on other phase transition materials.

Agriculture facilitated permanent human occupation of the Tibetan Plateau after 3600 B.P.

Our understanding of when and how humans adapted to living on the Tibetan Plateau at altitudes above 2000 to 3000 meters has been constrained by a paucity of archaeological data. Here we report data sets from the northeastern Tibetan Plateau indicating that the first villages were established only by 5200 calendar years before the present (cal yr B.P.). Using these data, we tested the hypothesis that a novel agropastoral economy facilitated year-round living at higher altitudes since 3600 cal yr B.P. This successful subsistence strategy facilitated the adaptation of farmers-herders to the challenges of global temperature decline during the late Holocene.

Expression and regulation of osteopontin in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Osteopontin (OPN) has been proposed to be associated with airway inflammation including asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). This study sought to evaluate the expression and regulation of the OPN in CRSwNP patients. METHODS: Nasal polyp (NP) tissues and normal tissues were collected from 30 CRSwNP patients and 16 control subjects. The expression and regulation of OPN, as well eosinophil (EOS) accumulation and activation, were examined in nasal tissues using DNA microarray, immunohistochemical (IHC), immunofluorescent (IF) staining and qPCR analysis. Moreover, the regulation of OPN in nasal epithelial cells and its effects on migration and activation of EOS were evaluated in vitro using flow cytometry, ELISA, qPCR and Western blot, etc. RESULTS: DNA microarray analysis identified OPN as one of the 19 upregulated genes in polyp tissues. The mean number of OPN(+) cells in polyp tissues was found to be significantly increased compared with the normal controls (P < 0.01), and OPN(+) cells in polyp tissues significantly correlated with tissue eosinophilia [major basic protein (MBP)(+) cells; r = 0.51, P < 0.01]. Accordingly, the mRNA and protein levels of OPN in NP tissues were significantly higher than those in normal controls (P < 0.01). Poly I:C, flagellin and TLR-9 agonist CpG ODN, as well as TNF-α, IFN-γ, IL-6, IL-17A and TGF-ß, significantly increased OPN mRNA expression in cultured PECs and NECs (P < 0.05). Recombinant human OPN significantly promoted the migration of EOS, as well as enhanced EOS cationic protein (ECP) production, in an in vitro dispersed NP cells (DNPCs) culture system (P < 0.05). CONCLUSIONS: OPN promotes eosinophilic nasal inflammation in CRSwNP patients, which may represent a promising therapeutic target.

Significance of SODD expression in childhood acute lymphoblastic leukemia and its influence on chemotherapy.

This study explored the clinical significance of silencer of death domain (SODD) expression in childhood acute lymphoblastic leukemia (ALL) and its influence on chemotherapy as well as the effect of SODD expression on apoptosis of leukemic cells. The expression of SODD proteins in different ALL groups was determined by immunocytochemistry. The SODD RNAi-interfering plasmid was constructed and transferred to Jurkat cells, and the effects of SODD expression on cell proliferation and apoptosis were analyzed using the MTT and FCM methods. The expressions of SODD, Phospho-NF-κB-P65, Bcl-2, and Caspase 3 were detected by Western blot analysis. The expression of SODD proteins was significantly higher in the ALL groups than in the control group (P < 0.05). The positive expression rate of SODD was significantly higher in refractory/relapsed and clinical high-risk groups than in standard-risk, initial treatment, and complete remission groups (P < 0.05). Microtubule-targeting drugs such as vincristine and taxol can notably down-regulate SODD expression during apoptosis, whereas DNR, and Ara-c cannot. The sensitivity of Jurkat cells to chemotherapeutic drugs increased with down-regulated SODD expression induced by SODD-interfering plasmid transfection. The sensitivity of the cells transfected with SODD-cloning genes decreased. SODD expression was high in the ALL children. These findings indicated that SODD over-expression might be correlated with the clinical classification, curative effect, and prognosis of ALL cells. Microtubule-targeting drugs can specifically down-regulate SODD expression in leukemic cells, thereby increasing the sensitivity of leukemic cells to SODD-targeting chemotherapeutics. In contrast, increased SODD expression tends to reduce sensitivity.

HIF-1α is critical for hypoxia-mediated maintenance of glioblastoma stem cells by activating Notch signaling pathway.

Hypoxia induces the expansion of glioblastoma stem cells (GSCs), but the mechanism underlying it is still unclear. Here, we supply evidence that hypoxia-inducible factor-1α (HIF-1α) induced activation of Notch pathway is essential for hypoxia-mediated maintenance of GSC. Either depletion of HIF-1α or inactivation of Notch signaling partly inhibits the hypoxia-mediated maintenance of GSC. Further data suggest a role for HIF-1α in the interaction and stabilization of intracellular domain of Notch (NICD), and activation of Notch signaling. The mRNA level of HIF-1α and Notch target gene FABP7 was elevated in GSC. And the STAT3 pathway responsible for the HIF-1α gene transcription, the phosphatidylinositol 3-kinase-Akt and ERK1/2, both of which are contributed to HIF-1α protein translation, are also preferentially activated in GSC. Inhibition of these pathways partly reduces the hypoxia-induced activation of the Notch pathway and subsequent GSC maintenance. Taken together, our findings suggest that HIF-1α requires Notch pathway to drive the maintenance of GSC. The activated regulation of HIF-1α makes GSC more sensitive to hypoxia-mediated maintenance. These findings enhance our understanding of mechanism of hypoxia-mediated GSC expansion and provide HIF-1α as an attractive target for glioblastoma therapy.

Synthesis and biological activity of chiral dihydropyrazole: potential lead for drug design.

Dihydropyrazole, a small bioactive molecule, is a prominent structural motif found in numerous pharmaceutically active compounds. The chiral dihydropyrazole structure has been demonstrated to bear important biological activities such as anticancer, antimicrobial, antimalarial, antinociceptive, antiviral, antitubercular, antiinflammatory, anticonvulsant and steroidal, and can also act as MAO inhibitors, CB1 receptor antagonists and nitric oxide synthase inhibitors. The review describes the latest advances in the synthesis of dihydropyrazole derivatives incorporating physiologically active substances. It is the first attempt at a general and systematic account of the extensive literature data on this subject.