ICAM5 as a Novel Target for Treating Cognitive Impairment in Fragile X Syndrome.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, resulted from the silencing of the Fmr1 gene and the subsequent loss of fragile X mental retardation protein (FMRP). Spine dysgenesis and cognitive impairment have been extensively characterized in FXS; however, the underlying mechanism remains poorly understood. As an important regulator of spine maturation, intercellular adhesion molecule 5 (ICAM5) mRNA may be one of the targets of FMRP and involved in cognitive impairment in FXS. Here we show that in Fmr1 KO male mice, ICAM5 was excessively expressed during the late developmental stage, and its expression was negatively correlated with the expression of FMRP and positively related with the morphological abnormalities of dendritic spines. While in vitro reduction of ICAM5 normalized dendritic spine abnormalities in Fmr1 KO neurons, and in vivo knockdown of ICAM5 in the dentate gyrus rescued the impaired spatial and fear memory and anxiety-like behaviors in Fmr1 KO mice, through both granule cell and mossy cell with a relative rate of 1.32 ± 0.15. Furthermore, biochemical analyses showed direct binding of FMRP with ICAM5 mRNA, to the coding sequence of ICAM5 mRNA. Together, our study suggests that ICAM5 is one of the targets of FMRP and is implicated in the molecular pathogenesis of FXS. ICAM5 could be a therapeutic target for treating cognitive impairment in FXS.SIGNIFICANCE STATEMENT Fragile X syndrome (FXS) is characterized by dendritic spine dysgenesis and cognitive dysfunctions, while one of the FMRP latent targets, ICAM5, is well established for contributing both spine maturation and learning performance. In this study, we examined the potential link between ICAM5 mRNA and FMRP in FXS, and further investigated the molecular details and pathological consequences of ICAM5 overexpression. Our results indicate a critical role of ICAM5 in spine maturation and cognitive impairment in FXS and suggest that ICAM5 is a potential molecular target for the development of medication against FXS.

Prolonged viral shedding of SARS-CoV-2 and related factors in symptomatic COVID-19 patients: a prospective study.

BACKGROUND: The temporal relationship between SARS-CoV-2 and antibody production and clinical progression remained obscure. The aim of this study was to describe the viral kinetics of symptomatic patients with SARS-CoV-2 infection and identify factors that might contribute to prolonged viral shedding. METHODS: Symptomatic COVID-19 patients were enrolled in two hospitals in Wuhan, China, from whom the respiratory samples were collected and measured for viral loads consecutively by reverse transcriptase quantitative PCR (RT-qPCR) assay. The viral shedding pattern was delineated in relate to the epidemiologic and clinical information. RESULTS: Totally 2726 respiratory samples collected from 703 patients were quantified. The SARS-CoV-2 viral loads were at the highest level during the initial stage after symptom onset, which subsequently declined with time. The median time to SARS-CoV-2 negativity of nasopharyngeal test was 28 days, significantly longer in patients with older age (> 60 years old), female gender and those having longer interval from symptom onset to hospital admission (> 10 days). The multivariate Cox regression model revealed significant effect from older age (HR 0.73, 95% CI 0.55-0.96), female gender (HR 0.72, 95% CI 0.55-0.96) and longer interval from symptom onset to admission (HR 0.44, 95% CI 0.33-0.59) on longer time to SARS-CoV-2 negativity. The IgM antibody titer was significantly higher in the low viral loads group at 41-60 days after symptom onset. At the population level, the average viral loads were higher in early than in late outbreak periods. CONCLUSIONS: The prolonged viral shedding of SARS-CoV-2 was observed in COVID-19 patients, particularly in older, female and those with longer interval from symptom onset to admission.

Synthesis, preliminarily biological evaluation and molecular docking study of new Olaparib analogues as multifunctional PARP-1 and cholinesterase inhibitors.

A series of new Olaparib derivatives was designed and synthesized, and their inhibitory activities against poly (ADP-ribose) polymerases-1 (PARP-1) enzyme and cancer cell line MDA-MB-436 in vitro were evaluated. The results showed that compound 5l exhibited the most potent inhibitory effects on PARP-1 enzyme (16.10 ± 1.25 nM) and MDA-MB-436 cancer cell (11.62 ± 2.15 µM), which was close to that of Olaparib. As a PARP-1 inhibitor had been reported to be viable to neuroprotection, in order to search for new multitarget-directed ligands (MTDLs) for the treatment of Alzheimer's disease (AD), the inhibitory activities of the synthesized compounds against the enzymes AChE (from electric eel) and BChE (from equine serum) were also tested. Compound 5l displayed moderate BChE inhibitory activity (9.16 ± 0.91 µM) which was stronger than neostigmine (12.01 ± 0.45 µM) and exhibited selectivity for BChE over AChE to some degree. Molecular docking studies indicated that 5l could bind simultaneously to the catalytic active of PARP-1, but it could not interact well with huBChE. For pursuit of PARP-1 and BChE dual-targeted inhibitors against AD, small and flexible non-polar groups introduced to the compound seemed to be conducive to improving its inhibitory potency on huBChE, while keeping phthalazine-1-one moiety unchanged which was mainly responsible for PARP-1 inhibitory activity. Our research gave a clue to search for new agents based on AChE and PARP-1 dual-inhibited activities to treat Alzheimer's disease.

TrkB activation by 7, 8-dihydroxyflavone increases synapse AMPA subunits and ameliorates spatial memory deficits in a mouse model of Alzheimer's disease.

We recently demonstrated that activation of tyrosine receptor kinase B (TrkB) by 7, 8-dihydroxyflavone (7, 8-DHF), the selective TrkB agonist, increased surface alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors (AMPARs) AMPA receptor subunit GluR1 (GluA1) subunit expression at the synapses of Fragile X Syndrome mutant mice. This present study investigated the effects of 7, 8-DHF on both memory function and synapse structure in relation to the synapse protein level of AMPARs in the Tg2576 Alzheimer's disease (AD) mouse model. The study found that chronic oral administration of 7, 8-DHF significantly improved spatial memory and minimized dendrite loss in the hippocampus of Tg2576 mice. A key feature of 7, 8-DHF action was the increased expression of both GluA1 and GluA2 at synapses. Interestingly, 7, 8-DHF had no effect on the attenuation of amyloid precursor protein or Aß exhibiting in the Tg2576 AD brains, yet it activated the phosphorylation of TrkB receptors and its downstream signals including CaMKII, Akt, Erk1/2, and cAMP-response element-binding protein. Importantly, cyclotraxin B (a TrkB inhibitor), U0126 (a Ras-ERK pathway inhibitor), Wortmannin (an Akt phosphorylation inhibitor), and KN-93 (a CaMKII inhibitor) counteracted the enhanced expression and phosphorylation of AMPAR subunits induced by 7, 8-DHF. Collectively, our results demonstrated that 7, 8-DHF acted on TrkB and resolved learning and memory impairments in the absence of reduced amyloid in amyloid precursor protein transgenic mice partially through improved synaptic structure and enhanced synaptic AMPARs. The findings suggest that the application of 7, 8-DHF may be a promising new approach to improve cognitive abilities in AD. We provided extensive data demonstrating that 7, 8-dihydroflavone, the TrkB agonist, improved Tg2576 mice spatial memory. This improvement is correlated with a reversion to normal values of GluA1 and GluA2 AMPA receptor subunits and dendritic spines in CA1. This work suggests that 7, 8-DHF is a suitable drug to potentiate in vivo Tropomyosin receptor kinase B (TrkB) signaling in the Alzheimer's disease mice model.

Ophiopogonin D ameliorates non­alcoholic fatty liver disease in high­fat diet­induced obese mice by improving lipid metabolism, oxidative stress and inflammatory response.

Lipid metabolic disorders, oxidative stress and inflammation in the liver are key steps in the progression of non-alcoholic fatty liver disease (NAFLD). Ophiopogonin D (OP-D), the main active ingredient of Ophiopogon japonicus, exhibits several pharmacological activities such as antioxidant and anti-inflammatory activities. Therefore, the current study aimed to explore the role of OP-D in NAFLD in a high-fat diet (HFD)-induced obesity mouse model. To investigate the effect of OP-D on NAFLD in vivo, a NAFLD mouse model was established following feeding mice with HFD, then the mice were randomly treated with HFD or HFD + OP-D for 4 weeks. Subsequently, primary mouse hepatocytes were isolated, and enzyme-linked immunosorbent assay, reverse transcription-quantitative PCR western blotting and immunofluorescence analysis were used for assessment to explore the direct effect of OP-D in vitro. The results of the present study indicated that OP-D could ameliorate NAFLD in HFD-induced obese mice by regulating lipid metabolism and antioxidant and anti-inflammatory responses. Additionally, OP-D treatment decreased lipogenesis and inflammation levels in vitro, suggesting that the NF-κB signaling pathway may be involved in the beneficial effects of OP-D on NAFLD.

[Behavioral response pattern of Aythya baeri under different weather conditions during wintering]. / 不同天气条件下青头潜鸭越冬期行为的响应模式.

We observed behavior response of overwintering Aythya baeri to different weather conditions by using fixed point-based observation and scanning sampling methods, at Henan Minquan National Wetland Park during November to December 2018. The results showed that, on sunny days, the dominant behaviors of A. baeri were resting, flying, and locomotion (65.5%), the second were foraging and maintaining (31.9%). The daily behavioral rhythm was foraging in the morning, resting at noon, and foraging and maintain in the afternoon. The flying usually occurred before the peak of foraging. The locomotion behavior was mostly accompanied by other behaviors, which positively associated with foraging and negatively correlated with resting. A. baeri increased resting and foraging in rainy days compared with that in sunny days. The dominant behaviors were resting, foraging and locomotion (76.5%), and maintaining and flying were the secondary (20.3%). The peaks of foraging and resting postponed to the evening, while the flying and maintaining were significantly decreased. Compared with the sunny days, the resting, foraging, locomotion and maintaining behaviors were increased in mist days, and flying was decreased. The peak of foraging delayed to the noon and afternoon, and that of resting postponed to the afternoon. The dominant behaviors were resting, locomotion and foraging (70.6%), while maintaining and flying behavior were the secondary (27.5%). In summary, there are variations in time allocation of A. baeri behaviors, activity rhythm and dominant behaviors due to the change of weather conditions during wintering. To overcome the bad weather conditions in rainy and mist days, A. baeri would allocate more time on foraging for increasing energy intake, and more resting time for reducing energy consumption.

The Hubei Memory and Aging Cohort Study: Study Design, Baseline Characteristics, and Prevalence of Cognitive Impairments.

BACKGROUND: Despite the improved access to health services in China, inadequate diagnosis and management of dementia are common issues, especially in rural regions. OBJECTIVE: The Hubei Memory & Aging Cohort Study was designed as a prospective study in Central China to determine the prevalence, incidence, and risk factors for dementia and mild cognitive impairment (MCI) among urban and rural older adults. METHODS: From 2018-2020, participants aged ≥65 years were screened, and data regarding their life behaviors, families, socio-economic status, physical and mental health, social and psychological factors, and cognition were collected. Diagnoses of MCI and dementia were made via consensus diagnosis using the Diagnostic and Statistical Manual of Mental Disorders fourth edition criteria. RESULTS: Of 8,221 individuals who completed their baseline clinical evaluation, 4,449 (54.1%) were women and 3,164 (38.4%) were from remote rural areas (average age: 71.96 years; mean education period: 7.58 years). At baseline, 25.98%(95%confidence interval [CI]: 24.99-26.96) and 7.24%(95%CI: 6.68-7.80) of the participants were diagnosed with MCI and dementia, respectively. Prevalence showed a strong relationship with age. The substantial disparities between rural and urban regions in MCI and dementia prevalence and multiple dementia-related risk factors were revealed. Especially for dementia, the prevalence rate in rural areas was 2.65 times higher than that in urban regions. CONCLUSION: Our results suggested that public health interventions are urgently needed to achieve equitable diagnosis and management for people living with dementia in the communities across urban and rural areas.

Population-attributable fractions of risk factors for all-cause dementia in China rural and urban areas: a cross-sectional study.

BACKGROUND: The prevalence of dementia in China, particularly in rural areas, is consistently increasing; however, research on population-attributable fractions (PAFs) of risk factors for dementia is scarce. METHODS: We conducted a cross-sectional survey, namely, the China Multicentre Dementia Survey (CMDS) in selected rural and urban areas from 2018 to 2020. We performed face-to-face interviews and neuropsychological and clinical assessments to reach a consensus on dementia diagnosis. Prevalence and weighted PAFs of eight modifiable risk factors (six classical: less childhood education, hearing impairment, depression, physical inactivity, diabetes, and social isolation, and two novels: olfactory decline and being unmarried) for all-cause dementia were estimated. RESULTS: Overall, CMDS included 17,589 respondents aged ≥ 65 years, 55.6% of whom were rural residents. The age- and sex-adjusted prevalence for all-cause dementia was 9.11% (95% CI 8.96-9.26), 5.19% (5.07-5.31), and 11.98% (11.8-12.15) in the whole, urban, and rural areas of China, respectively. Further, the overall weighted PAFs of the eight potentially modifiable risk factors were 53.72% (95% CI 52.73-54.71), 50.64% (49.4-51.89), and 56.54% (55.62-57.46) in the whole, urban, and rural areas of China, respectively. The eight risk factors' prevalence differed between rural and urban areas. Lower childhood education (PAF: 13.92%) and physical inactivity (16.99%) were primary risk factors in rural and urban areas, respectively. CONCLUSIONS: The substantial urban-rural disparities in the prevalence of dementia and its risk factors exist, suggesting the requirement of resident-specific dementia-prevention strategies.

Urban-Rural Disparities in the Association Between Body Mass Index and Cognitive Impairment in Older Adults: A Cross-Sectional Study in Central China.

BACKGROUND: Some studies have demonstrated an association between low and high body mass index (BMI) and an increased risk of dementia. However, only a few of these studies were performed in rural areas. OBJECTIVE: This cross-sectional study investigated the associations between BMI and cognitive impairment among community-dwelling older adults from rural and urban areas. METHODS: 8,221 older persons enrolled in the Hubei Memory & Ageing Cohort Study (HMACS) were recruited. Sociodemographic and lifestyle data, comorbidities, physical measurements, and clinical diagnoses of cognitive impairment were analyzed. Logistic regression was performed to assess the associations of BMI categories with cognitive impairment. A series of sensitivity analyses were conducted to test whether reverse causality could influence our results. RESULTS: Being underweight in the rural-dwelling participants increased the risk of cognitive impairment. Being overweight was a protective factor in rural-dwelling participants aged 65-69 years and 75-79 years, whereas being underweight was significantly associated with cognitive impairment (OR, 1.37; 95% CI: 1.03-1.83; p < 0.05). Sensitivity analyses support that underweight had an additive effect on the odds of cognitive impairment and was related to risk of dementia. Interaction test revealed that the differences between urban/rural in the relationship between BMI and cognitive impairment are statistically significant. CONCLUSION: Associations between BMI and cognitive impairment differ among urban/rural groups. Older people with low BMI living in rural China are at a higher risk for dementia than those living in urban areas.

Role of gut microbiome in regulating the effectiveness of metformin in reducing colorectal cancer in type 2 diabetes.

The prevalence of colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) is increasing globally. It is rarely noticed that the incidence of CRC is higher in patients with T2DM. What needs to be mentioned is that metformin, a commonly used clinical drug for T2DM, attracts scholars' attention because of its benefits in lowering the risk of developing CRC. Hence, we try to find the common grounds of initiation of T2DM and CRC and the reason why metformin reduces the risk of CRC in patients with T2DM. We noticed consistent changes of gut microbiota, such as elevated Bacteroides, Prevotella and Bifidobacterium and depressed Firmicutes and Lactobacillus. Furthermore, many studies in recent years have proved that the efficacy of metformin, such as improving blood glucose, depends on the gut microbiota. Coincidentally, the progression of CRC is inseparable from the contributions of gut microbiota. Therefore, we first proposed the concept of the metformin-gut microbiota-CRC (in T2DM) axis to explain the effect of metformin in reducing CRC in patients with T2DM. In this review, we elaborated the new concept and its potential clinical application value.

Effect and Safety of Hydroxysafflor Yellow A for Injection in Patients with Acute Ischemic Stroke of Blood Stasis Syndrome: A Phase II, Multicenter, Randomized, Double-Blind, Multiple-Dose, Active-Controlled Clinical Trial.

OBJECTIVE: To assess the effect and safety of Hydroxysafflor Yellow A for Injection (HSYAI) in treating patients with acute ischemic stroke (AIS) and blood stasis syndrome (BSS). METHODS: A multicenter, randomized, double-blind, multiple-dose, active-controlled phase II trial was conducted at 9 centers in China from July 2013 to September 2015. Patients with moderate or severe AIS and BSS were randomly assigned to low-, medium-, high-dose HSYAI groups (25, 50 and 70 mg/d HSYAI by intravenous infusion, respectively), and a control group (Dengzhan Xixin Injection (, DZXXI) 30 mL/d by intravenous infusion), for 14 consecutive days. The primary outcome was the Modified Rankin Scale (mRS) score ⩽1 at days 90 after treatment. The secondary outcomes included the National Institute of Health Stroke Scale (NIHSS) score ⩽1, Barthel Index (BI) score ⩾95, and BSS score reduced ⩾30% from baseline at days 14, 30, 60, and 90 after treatment. The safety outcomes included any adverse events during 90 days after treatment. RESULTS: Of the 266 patients included in the effectiveness analysis, 66, 67, 65 and 68 cases were in the low-, medium-, and high-dose HSYAI and control groups, respectively. The proportions of patients in the medium- and high-dose HSYAI groups with mRS score ⩽1 at days 90 after treatment were significantly larger than the control group (P<0.05). The incidences of favorable outcomes of NIHSS and BI at days 90 after treatment as well as satisfactory improvement of BSS at days 30 and 60 after treatment in the medium- and high-dose HSYAI groups were all significantly higher than the control group (P<0.05). No significant difference was reported among the 4 groups in any specific adverse events (P>0.05). CONCLUSIONS: HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS. The medium (50 mg/d) or high dose (75 mg/d) might be the optimal dose for a phase III trial. (Registration No. ChiCTR-2000029608).

Weighted Extreme Sparse Classifier and Local Derivative Pattern for 3D Face Recognition.

A novel weighted hybrid classifier and a high-order, local normal derivative pattern descriptor is proposed for 3D face recognition. The Local derivative pattern (LDP) captures detailed information, based on the local derivative variation in different directions. The LDP is computed on three normal maps in x, y, and z directions and on different scales. The surface normal captures the orientation of a surface at each point of 3D data. More informative local shape information is extracted using the surface normal, as compared to depth. The nth-order LDP on the surface normal is proposed to encode more detailed features from the (n-1)th-order's local derivative direction variations. An extreme learning machine (ELM) based autoencoder, using a multilayer network structure, is employed to select more discriminant features and provide a faster training speed. A weighted hybrid framework is proposed to handle facial challenges using a combination of the ELM and the sparse representation classifier (SRC). The advantage of speed for the ELM and accuracy for the SRC in a weighted scheme is used to enhance the performance of the recognition system. Experimental results regarding four famous 3D face databases illustrate the generalization and effectiveness of the proposed method in terms of both computational cost and recognition accuracy.

SIRT2 mediated antitumor effects of shikonin on metastatic colorectal cancer.

SIRT2 is involved in the development of a variety of cancers. Shikonin is a natural compound that is known to have antitumor effects. This study aims to assess the effects of shikonin on the development and metastatic progression of colorectal cancer (CRC) through regulation of SIRT2 expression and whether this effect is related to the phosphorylation of extracellular signal-regulated kinases (ERKs). The results demonstrated that SIRT2 is downregulated in CRC biopsy samples (n=31) compared with the adjacent non-cancerous tissues (ANCT, n=26). Furthermore, CRC metastases were positive for SIRT2 despite a lack of expression in the primary tumor. In addition, data from an in vitro assay revealed that overexpression of SIRT2 inhibited the proliferation and metastatic progression of SW480 cells while blocking of SIRT2 expression induced the proliferation and metastatic progression of HT29 cells. Shikonin inhibited the viability, migration and invasion of SW480 cells and it also inhibited the tumor growth in the nude mice model; while AGK2 (a specific inhibitor of SIRT2) reversed these effects. Epidermal growth factor (EGF, an activator of ERK) and ERK-overexpression inhibited the effects of shikonin on SIRT2 expression, proliferation and metastasis in SW480 cells. However, this proliferative effect of EGF was reversed by SIRT2 overexpression. In conclusion, these results suggest that SIRT2 is a new therapeutic target for the treatment of CRC. The antitumor effects of shikonin on CRC seem to be mediated by SIRT2 upregulation via phospho-ERK inhibition.

The lncRNA PDIA3P Interacts with miR-185-5p to Modulate Oral Squamous Cell Carcinoma Progression by Targeting Cyclin D2.

Long noncoding RNAs (lncRNAs) are emerging as important regulators during tumorigenesis by serving as competing endogenous RNAs (ceRNAs). In this study, the qRT-PCR results indicated that the lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) was overexpressed in oral squamous cell carcinoma (OSCC) and decreased the survival rate of OSCC patients. CCK-8 and clonal colony formation assays were used to detect the effects of PDIA3P on proliferation. Results revealed that silencing PDIA3P by small interfering RNA (siRNA) inhibited OSCC cell proliferation and repressed tumor growth and reduced the expression of proliferation antigen Ki-67 in vivo. Furthermore, the interaction between PDIA3P and miRNAs was then analyzed by qRT-PCR and luciferase reporter gene assay. We found that PDIA3P negatively regulated miR-185-5p in OSCC cells. Simultaneously, we found that silencing PDIA3P by siRNA suppressed proliferation via miR-185-5p in OSCC cells. Moreover, silencing PDIA3P by siRNA inhibited CCND2 protein (no influence on mRNA levels) expression via miR-185-5p in OSCC cells, and CCND2 facilitated cell proliferation of SCC4 and SCC15 cells induced by sh-PDIA3P#1. Therefore, our study demonstrated that PDIA3P may be a therapeutic target for the treatment of OSCC.

[Influence of Herbal-cake-separated Moxibustion on Contents of 5-HT, DA and NE in Hypothalamus in Rats with Functional Dyspepsia of Liver Stagnation and Spleen Deficiency Syndrome].

OBJECTIVE: To observe the influence of herbal cake-separated moxibustion on the contents of 5-hydroxy tryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the hypothalamus in rats with functional dyspepsia (FD) of syndrome of liver stagnation and spleen deficiency, so as to explore its mechanism underlying improvement of FD. METHODS: Sixty SD rats were randomly divided into 6 groups: control, model, herbal cake-separated moxibustion, moxa-cone moxibustion, Xiaoyaosan (decoction for relieving liver stagnation) and Domperidon, with 10 rats in each group. The FD model was established by applying chronic restraint stress + excessive fatigue + irregular food + tail clipping+ shaking for 21 consecutive days. Moxibustion (herbal cake-separated or moxa-cone) was applied to bilateral "Ganshu" (BL 18), "Pishu" (BL 20) and "Weishu" (BL 21), or "Zhangmen"(LR 13), "Qimen" (LR 14) and "Zhongwan" (CV 12) for 30 min, once daily for 14 d. For rats of the two medication groups, Xiaoyaosan [1 mL (2 g)/100 g] and Domperidone [1 mL (0.3 g)/100 g] were administrated by gavage, respectively. The contents of 5-HT, DA and NE in the hypothalamus tissue were detected by high performance liquid Phrnm.tnrnh, RESULTS: The gastric empty rate was obviously lower in the model group than in the control group (P<0. 01). After the treatment, the gastric empty rate in the herbal cake-separated moxibustion, moxa-cone moxibustion, Xiaoyaosan and Domperidone groups were significantly increased in comparison with the model group ( P<0. 01) , but there were no significant differences among the four treatment groups (P > 0.05). Compared to the control group, the contents of 5-HT, DA and NE in the hypothalamus were markedly decreased in the model group (P < 0.01), while compared to the model group, the contents of hypothalamic 5- HT, DA and NE contents were significantly up-regulated in both the herbal cake-separated moxibustion and Xiaoyaosan groups (P < 0.01), rather than in the moxa-cone moxibustion and Domperidone groups (P > 0.05). No significant differences were found between the herbal cake-separated moxibustion and Xioayaosan groups in increasing hypothalamic 5-HT, DA and NE levels (P > 0.05). CONCLUSION: Herbal cake-separated moxibustion can promote the gastric empty rate in FD rats, which may be associated with its effects in inhibiting stress induced decrease of hypothalamic 5-HT, DA and NE levels.

Effects of adenovirus-mediated human cyclooxygenase-2 antisense RNA on the growth of hepatocellular carcinoma.

AIM: To investigate the relation between the expression of cyclooxygenase-2 (COX-2) and liver cancer, to construct the recombinant adenovirus encoding human COX-2 antisense RNA, and to explore its effects on liver cancer cell proliferation. METHODS: We studied the expression of COX-2 in 34 cases of hepatocellular carcinoma (HCC) and SMMC7402 and SMMC7721 by immunohistochemical technique. Recombinant adenovirus Ad-AShcox-2 was constructed and transfected into human HCC cell lines SMMC7402 and SMMC7721, and its effects on COX-2 expression, cell apoptosis and cell cycle were analyzed by flow cytometry. Cell proliferation was determined by colony-forming efficiency. RESULTS: We observed COX-2 expression in 82.4% of the HCC and SMMC7402 cells, but no COX-2 expression in SMMC7721 cells. In addition, recombinant adenovirus encoding antisense COX-2 fragment Ad-AShcox-2 was obtained with the titer of 1.06 x 10(12) PFU/mL. Ad-AShcox-2 could reduce the expression of COX-2 and enhance the percentage of cells in G(1)/G(0) phase in SMMC7402 cell line. The difference of apoptotic index between the Ad-AShcox-2 group and control group was statistically significant (t( control group ) = 32.62 and t( Ad-LacZ ) = 10.93, P<0.001) in SMMC7402 but not in SMMC7721. Similarly, colony-forming rates of SMMC7402 and SMMC7721 cell lines, after the transfer of Ad-AShcox-2, were (2.7+/-0.94)% and (33.6+/-4.24)%, respectively. CONCLUSION: Reduction in the expression of COX-2 can inhibit COX-2 expressing HCC cells.

Adenovirus expressing p27kip1 suppresses growth of established esophageal carcinoma xenografts.

AIM: To investigate the growth suppression of adenovirus expressing p27(kip1) on established esophageal tumors in nude mice. METHODS: Esophageal carcinoma xenografts in nude mice were established by tumor tissue mass transplantation. The successfully constructed recombinant adenoviral vectors carrying p27(kip1) gene (Ad-p27(kip1)) were directly injected into the esophageal tumors in nude mice. Compared to control group, the growth curve of tumor was drawn and the growth inhibition rate of tumor was calculated. The histology of tumors was examined by hematoxylin and eosin (H&E) staining. The expression of p27(kip1) and survivin was detected in tumors by immunohistochemical technique. RESULTS: The growth of tumors in gene therapy group with Ad-p27(kip1) was obviously suppressed compared to control group (0.42+/- 0.08 g vs 1.17+/- 0.30 g, t=6.39, P< 0.01), the inhibition rate of tumor growth reached 64.1%. Pathological detection showed that the tumors in nude mice were poorly differentiated esophageal squamous carcinoma. In addition, the expression of p27(kip1) was increased, while the expression of survivin was decreased in tumors after being transfected with Ad-p27(kip1). CONCLUSION: p27(kip1) gene therapy mediated by adenovirus vector has a significant inhibitory effect on esophageal carcinoma in vivo. Up-regulated p27(kip1) expression and down-regulated survivin expression may be its important mechanisms.

[The effects of adenovirus-mediated human COX-2 antisense RNA on the growth of hepatocellular carcinoma].

OBJECTIVE: To investigate the relationship between the expression of COX-2 and liver cancer and construct a recombinant adenovirus encoding human COX-2 antisense RNA, and then to investigate its effects on liver cancer cell proliferation. METHODS: The expression of COX-2 in 34 cases of hepatocellular carcinoma and in SMMC-7402 and SMMC-7721 cell lines was studied by using immunohistochemical techniques. The shuttle plasmid encoding anti-sense COX-2 was constructed by using cloning COX-2 cDNA fragment in the reverse direction into the pHCMVSPIA. Then the plasmid pJM17 and the shuttle plasmid were co-transferred into 293 cells with lipofectamine for homologous recombination to acquire recombinant adenovirus (Ad-AShcox-2), which was confirmed by PCR. Human hepatocellular carcinoma cell lines SMMC-7402 and SMMC-7721 were transduced in vitro. The cell apoptosis and cell cycle were analyzed by flow cytometry. The cell proliferation was determined by colony-forming efficiency. RESULTS: We observed COX-2 expression in 82.4% of the hepatocellular carcinomas and SMMC-7402 cell line, but no COX-2 expression in the SMMC-7721 cell line. In addition, the recombinant adenovirus encoding anti-sense COX-2 fragment Ad-AShcox-2 was obtained with a titer of 1.06 x 10(12) PFU/ml. Ad-AShcox-2 reduced the expression of COX-2 and enhanced the percentage of cells into G1/G0 phase in the SMMC-7402 cell line. The difference of apoptotic index between the Ad-AShcox-2 group and the control group was statistically significant in SMMC-7402 but not in SMMC-7721. Similarly, colony-forming rates of SMMC-7402 and SMMC-7721 cell lines after Ad-AShcox-2 being transferred were (2.7+/-0.94)% and (33.6+/-4.24)%, respectively. CONCLUSION: By reducing the expression of COX-2 in hepatocellular carcinoma cells with the expression of COX-2, the cells could be inhibited.

Utilizing image scales towards totally training free blind image quality assessment.

A new approach to blind image quality assessment (BIQA), requiring no training, is proposed in this paper. The approach is named as blind image quality evaluator based on scales and works by evaluating the global difference of the query image analyzed at different scales with the query image at original resolution. The approach is based on the ability of the natural images to exhibit redundant information over various scales. A distorted image is considered as a deviation from the natural image and bereft of the redundancy present in the original image. The similarity of the original resolution image with its down-scaled version will decrease more when the image is distorted more. Therefore, the dissimilarities of an image with its low-resolution versions are cumulated in the proposed method. We dissolve the query image into its scale-space and measure the global dissimilarity with the co-occurrence histograms of the original and its scaled images. These scaled images are the low pass versions of the original image. The dissimilarity, called low pass error, is calculated by comparing the low pass versions across scales with the original image. The high pass versions of the image in different scales are obtained by Wavelet decomposition and their dissimilarity from the original image is also calculated. This dissimilarity, called high pass error, is computed with the variance and gradient histograms and weighted by the contrast sensitivity function to make it perceptually effective. These two kinds of dissimilarities are combined together to derive the quality score of the query image. This method requires absolutely no training with the distorted image, pristine images, or subjective human scores to predict the perceptual quality but uses the intrinsic global change of the query image across scales. The performance of the proposed method is evaluated across six publicly available databases and found to be competitive with the state-of-the-art techniques.

Inhibition of adenovirus-mediated p27kip1 gene on growth of esophageal carcinoma cell strain.

AIM: To investigate the inhibition of p27kip1 gene on the growth of esophageal carcinoma cell strain (EC9706). METHODS: Recombinant adenovirus Ad-p27kip1 was constructed and transfected into esophageal carcinoma cell EC-9706, and its effect on p27kip1 expression, the growth of esophageal carcinoma cell, DNA replication, protein synthesis, cell multiplication and apoptosis were explored by means of cell growth count, 3H-TdR, 3H-Leucine incorporation, flow cytometry, DNA fragment analysis and TUNEL. RESULTS: Recombinant adenovirus Ad-p27kip1 was successfully constructed with a virus titer of 1.24 X 10(12) pfu/ml. p27kip protein expression increased markedly after EC-9706 transfection, while incorporation quantity of 3H-TdR and 3H-Leucine decreased significantly. The growth of esophageal carcinoma cell was inhibited obviously. Testing of flow cytometry displayed a typical apoptosis peak, and DNA gel electrophoresis showed a typical apoptosis ladder. TUNEL showed the apoptosis rate of Ad-p27kip1 group and control group to be 37.3% and 1.26% (P<0.001) respectively. CONCLUSION: Ad-p27kip1 can inhibit the growth and multiplication of esophageal carcinoma cells and induce apoptosis. Therefore, enhanced p27kip1 expression may be a new way to treat esophageal carcinoma.