1.MRI demonstrates abnormalities of motor nerves and extraocular muscles in congenital fibrosis syndrome due to mutations in KIF21 A
Yong-Hong, JIAO ; Shao-Qin, WU ; Feng-Yuan, MAN ; Hong-Yan, JIA ; Gang, LIU ; Nan, LIN
International Eye Science 2014;(8):1426-1429
AIM:To observe the structural basis of ocular motility abnormalities in patients with congenital fibrosis of the extraocular muscles type Ⅰ ( CFEOM Ⅰ) due to missense mutations in the developmental kinesin KIF21A using high - resolution magnetic resonance imaging ( MRI) .
METHODS: Totally 11 affected individuals reported KIF21A mutations were correlated with MRI studies demonstrating extraocular muscles ( EOMs ) size, location, contractility, and innervation. EOMs and the motor nerve in the orbits were imaged with T1 weighted in a triplanar scan using a dual-phased coils with 2. 0mm thick. Motor nerves were imaged at the brainstem using head coils and 3D-FIESTA with 0. 6-mm thick.
RESULTS: Patients with CFEOM Ⅰ exhibited different degrees of hypoplasia of oculomotor nerve, the abducens nerve and the trochlear nerve were also affected, of which 8 cases of orbital section could see the signal of abnormal nerve dominated by oculomotor nerve to lateral rectus. The both sides of six EOMS in all patients exhibited variable atrophy and abnormal bright internal signal on T1 imaging, particularly severe for the superior rectus and levator muscles.
CONCLUSION: High - resolution MRI can directly demonstrate pathology of motor nerves,affected EOMs, and ‘Pulley' hypoplasia caused by CFEOM Ⅰ due to mutations in KIF21A,and these findings suggest that the neuronal hypoplasia is the etiological factor of CFEOM.
2.Research progress of ionizable lipid nanoparticles for siRNA delivery
Ya-nan ZHAO ; Wei HE ; Quan-lin SHAO ; Hua-yu LIU ; Ming-qi LIU ; Ran MO
Acta Pharmaceutica Sinica 2023;57(8):2292-2299
Small interfering RNA (siRNA) is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA. siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases. However, the naked or unmodified siRNA has poor stability, easy to degrade by nuclease, short half-life, and low intracellular delivery. As an emerging non-viral nucleic acid delivery system, ionizable lipid nanoparticles play an important role in improving the druggability of siRNA. At present, one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease. This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery, focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNA-mediated gene silencing, which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.
3.Prevalence of erectile dysfunction and it's related factors in type 2 diabetic patients
Lin LIU ; Li-Nan PANG ; Chang-Shan LIU ; Jing-Bo SHAO ;
Chinese Journal of General Practitioners 2002;0(01):-
Objective To investigate prevalence of erectile dysfunction(ED)in type 2 diabetic male patients and to analyze its related factors.Methods A total of 904 married male patients with type 2 diabetes were involved in this study and they were interviewed with anonymous questionnaire.An international index of erectile function-5(IIEF-5)was used to determine the severity of ED by self-rating score in age,duration of diabetes,serum level of glycosylated hemoglobin A1c(HbA1c),history of alcohol drinking and smoking,blood pressure and anti-hypertensive medication in diabetic ED patients.Relationship between relevant factors and diabetic ED was analyzed.Results ED was diagnosed in 612 diabetics with prevalence of 67.7 percent(612/904)according to their total scores of IIEF-5.Logistic regression analysis showed that increase in duration of diabetes by five years,age by 10 years,serum level of HbAI c by 2%, systolic blood pressure by 30 mm Hg(1 mm Hg = 0.133 kPa),positive history of smoking and alcohol drinking were all independently associated with prevalence of diabetic ED,with OR of 1.96,1.25,2.32, 1.12,1.67(P
4.Epidemiological characteristics and antimicrobial resistance of 151 cases of melioidosis in Hainan Province
ZENG Zeng ; LUO Xiao-man ; FU Rui-jia ; ZHANG Nan ; CHEN Lin ; CHEN Shao-wen ; LIN Chong ; FU Sheng-miao
China Tropical Medicine 2023;23(6):568-
Abstract: Objective To analyze the epidemiological characteristics of 151 cases of melioidosis and the drug resistance of Burkholderia pseudomallei (BP), in order to provide the basis for diagnosis, treatment and reasonable prevention of melioidosis. Methods A total of 151 inpatients and outpatients from the Second Affiliated Hospital of Hainan Medical University from January 1, 2013 to August 31, 2022 were collected, and clinical specimens were submitted for examination to isolate and identify BP strains. The clinical data of 151cases of melioidosis and the drug resistance characteristics of pathogenic bacteria were retrospectively analyzed, and using SPSS26.0 software for statistical analysis. Results Among 151 cases with BP infection, there were 138 males (91.4%) and 13 females (8.6%); the most patients were aged from 45-<60 years old, accounting for 74 cases (49.0%); melioidosis incidence was concentrated in October (19.2%), November (19.2%), August (9.9%) and July (8.6%), and; the number of confirmed cases showed an increasing trend and the time for confirmation was <10 d; Internal medicine system (31.1%), surgery system (26.5%) and intensive care department (20.5%) were the common departments for treating melioidosis; blood (49.0%), sputum (9.9%) and wound secretion (8.6%) were the main clinical specimens for detecting BP; pulmonary infection (68.2%), sepsis (35.1%) and local suppurative infection (23.8%) were the top clinical manifestations in patients with BP infection; the effective rate of treating melioidosis was 74.8%; abnormal liver function was a risk factor for the curative effect of melioidosis (χ2=5.010, P<0.05); the sensitivity rates of BP strains to sulfamethoxazole-trimethoprim (SXT), doxycycline (DOX), imipenem(IPM), ceftazidime (CAZ), amoxicillin/clavulanate (AMC) and tetracycline (TCY) were generally more than 90%, with sensitivities of 98.7%, 97.2%, 96.7%, 94.0%, 93.2% and 90.7%, respectively. Conclusions It can be concluded that misdiagnosis or missed diagnosis of melioidosis is easy to occur, and the understanding of the epidemiological characteristics and risk factors in this area should be strengthened. The sensitivity of BP to commonly used antibiotics has shown a certain downward trend, clinical use should be standardized, and drug resistance monitoring should be strengthened to improve the efficacy of melioidosis treatment.
5.Effect of microRNA-101 on proliferation and apoptosis of human osteosarcoma cells by targeting mTOR.
Song LIN ; Nan-nan SHAO ; Lei FAN ; Xiu-cai MA ; Fei-fei PU ; Zeng-wu SHAO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2014;34(6):889-895
Studies have proved that microRNA-101 (miR-101) functions as a tumor suppressor and is associated with growth and apoptosis of various human cancers. However, the role of miR-101 in osteosarcoma and the possible mechanism by which miR-101 affects the tumor growth and apoptosis have not been fully elucidated. In this study, we found that the expression of miR-101 was down-regulated in osteosarcoma tissues and Saos-2 cell line as compared with that in adjacent non-neoplastic bone tissues and the osteoblastic cell line. To better characterize the role of miR-101 in osteosarcoma, we used a gain-of-function analysis by transfecting human osteosarcoma cell line Saos-2 with chemically synthesized miR-101 mimics. The results showed that overexpression of miR-101 inhibited the proliferation and promoted the apoptosis of Saos-2 cells. Meanwhile, bioinformatic analysis demonstrated that mTOR gene was a direct target of miR-101. Overexpression of miR-101 significantly decreased the expression of mTOR at both mRNA and protein levels in Saos-2 cells, consequently inhibiting Saos-2 cells proliferation and promoting cells apoptosis in an mTOR-dependent manner. Taken together, these data suggest that miR-101 may act as a tumor suppressor, which is commonly downregulated in both osteosarcoma tissues and cells. mTOR plays an important role in mediating miR-101 dependent biological functions in osteosarcoma. Reintroduction of miR-101 may be a novel therapeutic strategy by down-regulating mTOR expression.
Apoptosis
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Bone Neoplasms
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genetics
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metabolism
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pathology
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Cell Line, Tumor
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Cell Proliferation
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Humans
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MicroRNAs
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genetics
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metabolism
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Neoplasm Proteins
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genetics
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metabolism
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Osteosarcoma
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genetics
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metabolism
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pathology
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RNA, Neoplasm
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genetics
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metabolism
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TOR Serine-Threonine Kinases
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genetics
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metabolism
6.N-methyl-N-nitrosourea-induced apoptosis of photoreceptor cells in Sprague-Dawley rats via nuclear factor-kappaB.
Jin-nan YANG ; Lin LUO ; Shao-chun LIN ; Jin-mao CHEN ; Dai LI ; Shi-xing HU
Chinese Medical Journal 2005;118(13):1081-1086
BACKGROUNDPrevious studies have showed that photooxidative stress can lead to down-modulation of nuclear factor-kappa B (NF-kappaB) activity causing apoptosis of cultured photoreceptor cells. This study aimed at investigating whether NF-kappaB was involved in photoreceptor cells apoptosis induced by N-methyl-N-nitrosourea (MNU) in rats.
METHODSA single intraperitoneal injection of 60 mg/kg MNU was given to 50-day-old female rats. At different intervals after MNU treatment, the animals were sacrificed. Retinal damage was examined by a light microscope. The apoptotic index of the photoreceptor cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL). NF-kappaB was analysed by Western blot and Transcriptin Factor Assay Kits.
RESULTSThe pyknosis of the photoreceptor nuclei and the disorientation of the outer segment of the photoreceptor layer was seen after MNU treatment for 24 hours. The outer nuclear layer and photoreceptor layer were almost completely lost at 7 days. Photoreceptor cells apoptosis reached the peaked value at 24 hours. In apoptotic cascade, the protein levels of NF-kappaB p65 were only detected after MNU treatment for 12 and 24 hours in the nucleus. Conversely, the amounts of IkappaBalpha were markedly increased in the cytoplasm as well as in the nucleus. The activity of NF-kappaB p65 in the nucleus was down-modulated in the end.
CONCLUSIONSMNU-induced photoreceptor cell destruction was attributed to the apoptotic process by down-regulating the activation of NF-kappaB p65.
Animals ; Apoptosis ; drug effects ; Cell Nucleus ; metabolism ; Female ; I-kappa B Proteins ; analysis ; physiology ; Methylnitrosourea ; toxicity ; NF-KappaB Inhibitor alpha ; NF-kappa B ; analysis ; physiology ; Photoreceptor Cells ; chemistry ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley ; Retina ; drug effects ; pathology
7.Changes of NF-kappaB/I kappa B alpha in N-methyl-N-nitrosourea-induced retinal damage in rats.
Jin-nan YANG ; He-qin ZHAN ; Jin-mao CHEN ; Shao-chun LIN ; Dai LI ; Shi-xing HU
Journal of Southern Medical University 2006;26(5):603-605
OBJECTIVETo observe the changes of nuclear factor-kappa B (NF-kappaB) in the course of N-methyl-N-nitrosourea (MNU)-induced apoptosis of rat retinal photoreceptor cells and investigate the mechanism of MNU-induced retinal damage.
METHODSA single intraperitoneal injection of 60 mg/kg MNU was given to 50-day-old female rats, which were sacrificed at different intervals after MNU treatment. The retinal damage was examined with optical microscopy and photoreceptor cell apoptosis detected by TUNEL assay. Western blotting was performed to analyze the changes in NF-kappaB.
RESULTSPyknosis of the photoreceptor cell nuclei and disorientation of the outer segment of the photoreceptor layer was observed 24 h after MNU treatment, and the outer nuclear layer and photoreceptor layer were almost completely lost on day 7. Photoreceptor cell apoptosis peaked at 24 h, and in the apoptotic cascade, NF-kappaB p65 protein was only detected 12 and 24 h after MNU treatment, whereas the amount of I kappa B alpha, in contrast, markedly increased in the cytoplasm as well as in the nuclei.
CONCLUSIONMNU-induced retinal damage might be mediated through the signaling pathway of NF-kappaB/I kappa B alpha.
Animals ; Apoptosis ; drug effects ; Blotting, Western ; Female ; I-kappa B Proteins ; metabolism ; In Situ Nick-End Labeling ; Methylnitrosourea ; toxicity ; NF-kappa B ; metabolism ; Rats ; Rats, Sprague-Dawley ; Retinal Diseases ; chemically induced ; metabolism ; pathology
8.Polymorphisms at HLA-A,-B,-DRB1 loci in Dalian Han population
Lin-Nan SHAO ; Shu-Ting ZHANG ; Ying DUAN ; Xiao-Hua LIANG ; Wei-Jian YU ; Shi-Hang ZHOU
Chinese Journal of Immunology 2018;34(6):919-924,928
Objective:To investigate the polymorphisms at HLA-A,-B,-DRB1 loci in Dalian Han population. Methods: A total of 10 000 unrelated marrow donors who live in Dalian were genotyped by SBT and SSO methods. Haplotype frequencies and linkage dis-equilibrium values were calculated by ARLEQUIN software,and DA genetic distances between populations were calculated by poptree2 software. Results: A total of 18 HLA-A alleles, 32 HLA-B alleles and 13 HLA-DRB1 alleles were found in Dalian Han population. HLA-A?02 (31. 65% ),B?40(14. 84% ) and DRB1?15(15. 82% ) occurred most frequently. A?30-B?13-DRB1?07 (4. 56% ) was determined to be the most common three-locus haplotype and the second predominant haplotype was A?02-B?46-DRB1?09 ( 2. 43% ) . A ?30-B ?13 ( 6. 00% ) and B ?13-DRB1 ?07 ( 59. 89% ) were the most common two-locus haplotypes. Moreover,A?33-B?58 and B?13-DRB1?07 were strongest haplotypes with the linkage disequilibria values 0. 336 6 and 0. 665 1,respectively. In China,the closest genetic distances were found with Heilongjiang (0. 001) followed by Jilin (0. 002) and Shandong (0. 002),the furthest was found with Taiwan (0. 047). Compared with other populations worldwide,the closest genetic distances were found with Thailand (0. 029) and Korea (0. 03),the furthest was found with Italy (0. 183). Conclusion: Dalian Han population had rich polymorphism at HLA-A,-B,-DRB1 loci,and the distribution of HLA-A,-B and-DRB1 was in line with the charac-teristics of the northern population.
9.Protective effect of water soluble CoQ10 on rotenone-induced apoptosis in PC12 cells
Yu-Min JIANG ; Hai-Ning LI ; Shao-Qing LIN ; Yan-Yan CHEN ; Jing AN ; Chun-Huan MA ; Nan-Nan HUAN ; Jiang CHENG
Journal of Xi'an Jiaotong University(Medical Sciences) 2018;39(4):514-518
Objective To investigate the protective effect and the underlying mechanism of water soluble coenzyme Q10 (CoQ10)against rotenone induced injury on PC12 cells model.Methods PC12 cells were cultured with rotenone,water-soluble CoQ1 0 was added to the culture media 3 hours prior to the rotenone incubation.We determined cell viability by CCK8;reactive oxygen species (ROS)was detected by spectrophotometer;and Bcl-2, Bax,active Caspase-3,Caspase-9 and apoptosis-inducing factor (AIF)were measured by Western blotting after 24-hour rotenone incubation.Results After the treatment by rotenone,cell viability decreased significantly (P<0.01)and ROS level increased (P<0.01).CoQ10 could improve PC12 cell viability (P<0.01)and reduce the level of ROS (P<0.01).Western blotting experiments showed that CoQ10 could reduce rotenone-induced Caspase-9 (P<0.05),active Caspase-3 (P<0.05)and Bax (P<0.01)expressions,increase the expression of Bcl-2 (P<0.01),and prevent nuclear translocation of AIF (P<0.05).Conclusion CoQ10 has a protective effect on rotenone-induced apoptosis in PC12 cells,the mechanism of which may be through scavenging ROS in cells;decreasing caspase-9 ,active caspase-3 and Bax expressions;and increasing the expression of Bcl-2 ;and preventing AIF nuclear translocation.
10.Protective effects of ligustrazine against photoreceptor cell injury induced by N-methyl-N-nitrosourea and its mechanism.
Jin-nan YANG ; Jian-gong XU ; Jin-mao CHEN ; Shao-chun LIN ; Lin LUO ; Shi-xing HU
Acta Pharmaceutica Sinica 2005;40(8):690-694
AIMTo study the protective effect of ligustrazine against photoreceptor cell injury induced by N-methyl-N-nitrosourea (MNU) in Sprague-Dawley (SD) rats.
METHODSLigustrazine injections of different doses were injected intraperitoneally into 47-day female SD rats once a day and a single intraperitoneal injection of MNU 60 mg x kg(-1) was given to 50-day rats. At different intervals after MNU treatment,the animals were sacrificed. The apoptotic index of photoreceptor cells was calculated by TUNEL labeling at 24 h following MNU treatment; peripheral retinal damage was evaluated based on retinal thickness at the d 7 after MNU treatment, and the expression of c-jun and c-fos genes was detected by RT-PCR technique.
RESULTSLigustrazine injection could remarkably increase total thickness of peripheral retina and decrease apoptotic index of photoreceptor cells induced by MNU in a dose-dependent manner. Compared with MNU-treated rats, the gene expression of c-jun and c-fos was time-dependently down-regulated in ligustrazine-treated group.
CONCLUSIONLigustrazine injection partially protects against MNU-induced retinal damage by down-modulating the expression of c-jun and c-fos genes to inhibit apoptosis of photoreceptor cells.
Animals ; Apoptosis ; drug effects ; Dose-Response Relationship, Drug ; Female ; Genes, fos ; Genes, jun ; Injections, Intraperitoneal ; Ligusticum ; chemistry ; Methylnitrosourea ; Photoreceptor Cells ; drug effects ; Photoreceptor Cells, Vertebrate ; drug effects ; pathology ; Plants, Medicinal ; chemistry ; Protective Agents ; administration & dosage ; pharmacology ; Pyrazines ; administration & dosage ; isolation & purification ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Retina ; metabolism ; pathology