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Objective@#To analyze the status and correlation between screen time, screen behavior type, and anxiety, depression among children and adolescents in Jiangxi Province, so as to provide a basis for effective intervention measures.@*Methods@#Using the method of stratified random sampling, 8 851 primary and secondary school students in 11 districts of Jiangxi Province were investigated by questionnaire during September to December in 2020. Anxiety and depression status were investigated using the State Trait Anxiety Inventory (STAI) and the Center for Epidemiological Studies Depression Scale for Children(CES-DC), respectively. Single factor analysis using χ 2-test, t-test,analysis of variance,and multivariate analysis using generalized linear models.@*Results@#On school days and weekends, 4.7% and 20.4% of primary and secondary school students in Jiangxi Province had a total screen time of over 2 hours per day, respectively. The weighted scores of the total screen time (primary school students: 1.88± 0.68, junior middle school students: 1.96±0.71, high school students: 2.03±0.80) and time spent for playing video games (primary school students: 1.51±0.64, junior middle school students: 1.62±0.69, high school students: 1.68±0.75) daily showed an upward trend with the increase of educational stage ( F =31.48, 42.13), and with significantly higher in boys (1.97±0.74, 1.66± 0.72) than girls (1.93±0.72, 1.53±0.66)( t =2.48, 9.07)( P <0.05). The average scores of state anxiety and trait anxiety were (42.20±9.05) and (40.65±9.85), which showed an upward trend with the increase of educational stage ( F =168.12, 241.98 ), and were higher in girls than boys ( t =6.63, 8.48)( P <0.01). The average score of depression was (11.99±11.00), which was lower in elementary school students than middle school students and high school students ( F =136.42), with significantly higher in girls ( t =6.85)( P <0.01). On school days, with the increase of total screen time and time spent for playing video games daily, the risk of state anxiety, trait anxiety, and depression among primary and secondary school students significantly increased ( OR = 6.70- 818.98, P <0.01). On weekends, among primary and secondary school students, the total screen time of >1-2 hours daily reduced the risk of state anxiety ( OR =0.30). The risk of developing trait anxiety among students playing video games for more than 2 hours daily was 2.50 times higher than those without screen behavior ( OR =2.50). The risk of developing depression with a total screen time of more than 2 hours daily was 3.15 times higher those whithout screen behavior ( OR =3.15). The risk of developing depression among students playing video games >0-1, >1-2, >2 h daily was 2.14, 2.50, 4.90 times that of those without screen behaviors ( OR =2.14, 2.50, 4.90), and showed an upward trend with the increase of educational stage ( P <0.05).@*Conclusions@#Screen behaviors of primary and middle school students in Jiangxi Province are positively associated with the risk of anxiety and depression, but the total daily video time of >1-2 h on weekends was negatively associated with state anxiety. It is necessary to control the screen time as much as possible and reduce the risk of anxiety and depression.
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【Objective】 To investigate the condition of confidential unit exclusion(CUE) in Guangzhou, so as to ensure blood safety. 【Methods】 The number of CUE donors, demographic characteristics of CUE donors, reasons for CUE, and response time of CUE after blood donation in Guangzhou from 2009 to 2022 were statistically analyzed. 【Results】 From 2009 to 2022, the response ratios of CUE was 0.006 2% (260/4 170 984) and the ratios had statistically significant difference between different years(P0.05), but statistically significant differences were found in age, number of blood donations, education background, and marital status (P<0.05). Blood donors aged 18~30 (0.007 3%, P<0.05) and first-time blood donors (0.010 8%, P<0.05) were the main groups of CUE. High risk sexual behavior (28.46%, 74/260) was the primary reason for CUE. The CUE response peak was within 72 hours after blood donation, and the response ratios within 24-72 hours after blood donation was the highest (68.46%, 178/260). 【Conclusion】 CUE is a crucial measure to ensure blood safety. Detailed pre-donation health consultations are suggested for blood donors aged 18-30 and first-time blood donors so as to better excluding high-risk blood donors. Strengthening the publicity of CUE response and process, registering and classifying the reasons for CUE are also important.
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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.
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Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment (TME). In this environment, myeloid cells, such as myeloid-derived suppressor cells (MDSCs), play a pivotal role in suppressing antitumor immunity. Lipometabolism is closely related to the function of myeloid cells. Here, our study reports that acetyl-CoA acetyltransferase 1 (ACAT1), the key enzyme of fatty acid oxidation (FAO) and ketogenesis, is significantly downregulated in the MDSCs infiltrated in GBM patients. To investigate the effects of ACAT1 on myeloid cells, we generated mice with myeloid-specific (LyzM-cre) depletion of ACAT1. The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically. The mechanism behind this effect is elevated secretion of C-X-C motif ligand 1 (CXCL1) of macrophages (Mφ). Overall, our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME.
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[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].
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Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.
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PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells, we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo. Taken together, our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.
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Enormous studies have corroborated that long non-coding RNAs (lncRNAs) extensively participate in crucial physiological processes such as metabolism and immunity, and are closely related to the occurrence and development of tumors, cardiovascular diseases, nervous system disorders, nephropathy, and other diseases. The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases. This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of lncRNAs from the role of disease coding to acting as drug candidates, including the current status and progress in preclinical research. Cutting-edge strategies for lncRNA modulation have been summarized, including the sources of lncRNA-related drugs, such as genetic technology and small-molecule compounds, and related delivery methods. The current progress of clinical trials of lncRNA-targeting drugs is also discussed. This information will form a latest updated reference for research and development of lncRNA-based drugs.
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Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.
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Objective To investigate the morphological changes of the brainstem in patients with Alzheimer's disease (AD) and their relationship with hippocampal morphological changes.Methods Sixty AD patients (AD group) and sixty age-and gender-matched normal elderly (normal control group) were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.The hippocampus and the brainstem of each subject were segmented and their normalized volumes were calculated.According to the hippocampal volume standard value (Z-score),AD patients were divided into two subgroups (hippocampal atrophy group (n=51) and hippocampal spared group (n=9)).A voxel-based morphology (VBM) study was also performed to investigate the morphological differences of the brainstem between the normal control group and the AD group,as well as between the AD subgroups.Results Compared with the normal control group,the brainstem volume in the AD group decreased significantly (16 741.31±1 739.11 vs 15 609.67±1 451.60,t=3.870,P=0.001).In AD subgroups,the volume of the brainstem in the hippocampal atrophy group was significantly smaller than that in the hippocampal spared group (16 556.30 ± 1 514.86 vs 15 442.62 ± 1 389.05,t=2.189,P=0.033).Pearson correlation analysis showed that Mini-Mental State Examination scores were positively correlated with the hippocampal and the brainstem volumes (r=0.590,P<0.01;r=0.234,P<0.05),and there was a positive correlation between the hippocampal and the brainstem volume changes in patients with AD (r=0.315,P=0.014).VBM results showed that both the bilateral midbrain and the bilateral pons in the AD group had significant atrophy compared with the normal control group (P<0.05).In the AD subgroups,the bilateral midbrain and the left pons in the hippocampal atrophy group were significantly atrophied compared with the hippocampal spared group (P<0.05).Conclusion The brainstem showed morphological changes in patients with AD,and the morphological changes of the brainstem in AD patients with different degrees of hippocampal atrophy were different,indicating the morphological changes of the hippocampus and the brainstem may have an interrelated relationship.
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Objective To OxplorO thO opOrating mOthods and clinical OffOcts of arthroscopic anatomical antO-rior cruciatO ligamOnt(ACL) rOconstruction with dirOct insOrtion tOchniquO vOrsus traditional mOthod.Methods From January 2017 to DOcOmbOr 2017,totally 52 patiOnts who accOptOd ACL rOconstruction and mOt thO inclusion and Oxclu-sion critOria in BOijing FriOndship Hospital of Capital MOdical UnivOrsity wOrO OnrollOd in this rOtrospOctivO study. ThOy wOrO dividOd into two groups by random sOquOncO softwarO and patiOnts′sOlOction rOsults. ThO obsOrvation group (27 casOs) rOcOivOd dirOct insOrtion tOchniquO,and thO control group(25 casOs) rOcOivOd traditional mOthod. At post-opOrativO 1 month, 3 months, 6 months, 1 yOar, thO clinical OffOct was OvaluatOd by imaging indOx, subjOctivO and objOctivO indicators.Results All 52 patiOnts wOrO availablO for follow up with an avOragO of 11.5 months. No postop-OrativO complications such as infOction, joint instability and soft lOgs, with a satisfiOd rOcovOry of rangO of motion, pain rOliOvOd significantly. ThO Lysholm scorO of thO obsOrvation group was (94.80 ± 4.18)points, which was signifi-cantly highOr than (91.02 ± 1.96)points of thO control group (t=2.674,P<0.05).Lachman tOst and KT-1000 wOrO improvOd significantly comparOd with thosO bOforO opOration ( all P <0.01), whilO thOrO was no statistically significant diffOrOncO bOtwOOn thO two groups(all P>0.05),but thO pivot-tOst of thO obsOrvation group was bOttOr than that of thO control group, thO diffOrOncO was statistically significant ( P < 0. 05 ). ThO ACL anglO of thO obsOrvation group was (51.52 ± 5.18)°, which was significantly lowOr than (55.86 ± 2.45)° of thO control group ( P<0.05). According to modifiOd Lysholm scorOs classification, in thO obsOrvation group, 24 casOs wOrO OxcOllOnt, 2 casOs wOrO good,1 casO was fair, and thO OxcOllOnt and good ratO was 96.3%. In control group,18 casOs wOrO OxcOllOnt,5 casOs wOrO good,2 casOs wOrO fair, and thO OxcOllOnt and good ratO was 92.0%. ThO diffOrOncO in thO OxcOllOnt and good ratO bOtwOOn thO two groups was statistically significant(P<0.05).Conclusion DirOct insOrtion anatomical rOconstruction is a safO and OffOctivO tOchniquO for rOconstruction of ACL. It can rOstorO thO stability of ACL and rotation of knOO joint.
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To report a case of imported furuncular cutaneous myiasis,and to analyze the sequence of the mitochondrial cytochrome C oxidase subunit Ⅰ (CO Ⅰ) gene of the pathogenic Cordylobia anthropophaga.A 33-year-old female patient had a travel history to Ghana and Cameroon in Africa 1 month prior to the presentation.No anti-mosquito measures were taken during her stay,and she hung up the laundries outside to dry for several times.Skin examination showed furuncular protuberances with diameters of 1-2 cm on the inner side of the left upper arm as well as on the outer side of the left chest,which were bright red and hard on palpation with irregular borders and a small hole on their central surface.Morphological identification revealed that the larva squeezed from the lesion was suspected as myiasis.After PCR amplification of the CO Ⅰ gene of the larva,an about 650-bp PCR product was acquired.Sequencing and BLAST analysis showed that this product was most closely related to the CO Ⅰ gene (GenBank accession number:FR719158.1) of Cordylobia anthropophaga isolated in Cameroon in 2010 with the sequence similarity being 99.84%,and they were grouped together on the phylogenetic tree.According to the clinical features and travel history of the patient and the sequencing results of the pathogenic Cordylobia anthropophaga,this case was confirmed as imported furuncular cutaneous myiasis caused by Cordylobia anthropophaga.
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Objective To study the MR images of patients with Alzheimer's disease (AD) for analysis of the volume changes ofbrainstem and deep brain nuclei,hoping to provide evidence for early clinical diagnosis.Methods Selected for this study were MRI images from the ADNI database from July 2006 to November 2010 of 31 AD patients (AD group),34 patients with mild cognitive impairment (MCI group),and 34 normal aged people (NC group).The follow-up MRI data of all the above subjects 2 years later were also collected.Software Freesufer was used to calculate and compare the volume changes ofbrainstem and deep brain nuclei in all the subjects.Results An identical trend was found concerning the MRI-based volumes of brainstem,hippocampus and deep brain nuclei (caudal nucleus and putamen) before and after follow-up between the 3 groups:AD group<MCI group<NC group,with statistically significant differences between groups (P<0.05).Follow-ups revealed significant decreases in all the indicators in AD and MCI groups (P<0.05),but no such differences in NC group (P>0.05).Pearson relative analysis showed a positive correlation between the brainstem volume and the volume of deep brain nuclei (caudal nucleus and putamen) in AD patients (r=0.653,P=0.021;r=0.596,P=0.014).Conclusions As AD progresses,the brainstem and deep brain nuclei in AD patients continue to shrink in volume and there may be a positive correlation between them.Therefore,detection of the volume changes of the brainstem and deep brain nuclei contributes to the early diagnosis of AD.
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Objective To explore the sample type and drug resistance characteristics of Streptococcus pneu-monia(Spn)isolated from pediatric patients in Guangzhou district,and their age distribution to offer instruc-tions for prevention and clinical treatment.Methods Spn isolates were cultured and identified according to the national standard procedure for clinical laboratory operation,followed by analysis of sample type and age dis-tribution of pediatric patients with positive isolates of Spn in Guangzhou Women and Children′s Medical Cen-ter from 2013 Jan 1st to 2015 Dec 31st,drug resistance status was determined by MIC test.Results Totally, 1 243 strains of Spn were isolated,which were mainly from pediatric patients under 1 year old(42.80%).Spn isolates were mainly isolated from respiratory tract(72.81%),ear secretions(15.37%),blood(5.63%),cere-brospinal fluid(3.06%)and hydrothorax(2.01%).For all Spn isolates,the resistance rate to erythromycin, tetracycline and sulfamethoxazole was especially high as 94.93%,85.76%,73.53% respectively,with relative high resistance to penicillin G(24.70%),amoxicillin(39.59%),ceftriaxone(24.05%),meropenem(22.85%) and cefotaxime(19.89%),low resistance to quinolone antibiotics(<10.00%),and no resistance to vancomycin and linezolid.Conclusion The major age group of children with Spn infection is infants under one year old in Guangzhou,clinicians should be serious about the high resistant rate of Spn to erythromycin,tetracycline and sulfamethoxazole,the significantly increased resistant rate to penicillin,amoxicillin and ceftriaxone.Clinicians should choose antibiotics rationally according to the characteristics of drug sensitivity for better treatment.
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Objective To establish the high-throughput screening fluorescence polarization assay for HSP90 inhibitor.Methods E.coli strain BL21 ( DE3) competent cells were transformed with pET24α( +)-HSP90αplasmid.The cell lysate supernatant was induced to product the soluble protein and purified with Ni-NTA agarose.Western blot analysis was used to identify whether the purified protein is HSP90α.The fluorescence polarization assay for screening HSP90 inhibitors was established and optimized using varying concentrations of recombinant HSP90 protein and molecular probe VER00051001.Meanwhile, the binding activity of GA and NVP-AUY922 for HSP90αwas measured by fluorescence polarization assay.Results HSP90αwas induced expression and purified successfully.The fluorescence polarization assay was performed using 80 nM probe VER00051001 and 2.01μg/mL HSP90α, with the Z factor of 0.83.GA and NVP-AUY922 competed with the probes VER00051001 for binding sites of HSP90, with IC50 of 55 nM and 13 nM, respectively.Conclusion A reliable model was established using fluorescence polarization assay for screening HSP90 inhibitors.
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Objective To establish a malignant pleural effusion model of Lewis lung cancer in C57BL/6 mice based on Micro Echo technology. Methods Single tumor cell suspension of Lewis lung cancer was injected into thoracic cavity.The pleural effusion was detected by Micro Echo technology.The volumes of effusion were quantified and the tumor cells were counted.Results After implanted of tumor cell, malignant pleural effusion can be detected by Micro Echo technology and observed after autopsy.Chemotherapy drugs such as Cyclophosphamide and Cisplatin can decrease the effusion volumes.Conclusion Pleural effusion model of Lewis lung cancer based on Micro Echo technology can be used to evaluate the efficacy of antitumor drugs.
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Objective To investigate the effect of different stimulants on the LAG3 expression and function of spleen lymphocytes in mice. Methods The spleen lymphocytes from mice were isolated by density centrifugation.The LAG3 expressions in T cell subsets after exposure to conA, PMA, PHA or anti-CD3/28 antibodies for 24 h or 72 h were analyzed by Flow cytometry.The IFN-γsecretions of conditional medium were detected by ELISA kit.The proliferation of lymphocytes was examined by MTT analysis.Results Treatment with conA for 24 h or 72 h dose-dependently increased LAG3 +CD3 +and LAG3 +CD4 +CD3 +T cell percentages.Similarly, an exposure of anti-CD3/28 antibodies for 72 h significantly increased LAG3 +CD3 +and LAG3 +CD4 +CD3 + T cell percentages.Meanwhile, conA and anti-CD3/28 antibodies increased the IFN-γsecretion of lymphocytes in a time-dependent manner.Furthermore, Treatment with conA, PMA, PHA or anti-CD3/28 antibodies for 72 h could enhance the proliferation of lymphocyte. Conclusion conA and anti-CD3/28 antibodies are effective activators of T cells, and both of them could promote the expression of LAG3 and IFN-γsecretion of lymphocytes.
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Objective To observe the thyroid hormone (TH) changes in patients with acute cerebral infarction in acute phase and convalescence,and to explore its clinical value.Methods Fifty cases of acute cerebral infarction patients from March 2015 to May 2016 in Heilongjiang Provincial Hospital were selected as observation group,at the same time 30 cases of healthy check-up people as control group.Serum levels of triiodothyronine (T3),thyroxine (T4),free triiodothyronine (FT3),free thyroxine (FT4) and thyroid stimulating hormone (TSH) were measured in 50 cases of acute cerebral infarction patients on the 2nd day (acute phase) and the 14th day (recovery) after onset of the disease,by using chemiluminescence method,and 30 cases of people underwent healthy physical check-up were treated the same way.Neurological injury and recovery of patients with cerebral infarction were evaluated using NIHSS.According to the recovery level of FT3,patients with cerebral infarction were divided into low FT3 group (FT3 < 3.10 pmol/L) and normal FT3 group (FT3 ≥ 3.10 pmol/L).Prognosis of the patients was judged according to the NIHSS scores 90 days after discharged from the hospital,and NIHSS score improving acuity of 2 was judged as good prognosis.Results The T3 and FT3 levels in patients with acute cerebral infarction were significantly lower than those of people underwent healthy physical examination,the differences were statistically significant [(0.68 ± 0.22) vs(1.82 ± 0.31) nmol/L,(2.08 ± 0.31) vs (4.19 ± 0.75) pmol/L,all P < 0.05].The T4,FT4 and TSH levels in patients with acute cerebral infarction were increased significantly,the differences were statistically significant [(142.56 ± 20.78) vs (109.89 ± 12.37) nmol/L,(12.88 ± 1.15) vs (9.77 ± 0.96) pmol/L,(5.15 ± 1.16) vs (2.95 ± 1.31) mU/L,all P < 0.05].Compared with the acute phase,convalescence of cerebral infarction patients' serum T3 and FT3 levels [(1.75 ± 0.19) nmol/L,(3.97 ± 0.61) pmol/L] increased significantly,the differences were statistically significant (all P < 0.05),and T4,FT4 and TSH [(115.64 ± 14.38) nmol/L,(10.05 ± 1.02) pmol/L,(3.16 ± 0.98) mU/L] obviously decreased,the differences were statistically significant (all P < 0.05).Compared with control group,convalescence of cerebral infarction patients' serum T3,T4,FT3,FT4 and TSH were not statistically different (all P > 0.05).There was a negative correlation between FT3 levels and NIHSS scores on admission (r =-0.586,P < 0.05).Ninety days after discharge,7 cases (38.89%) of the patients had a good prognosis in low FT3 group,and normal FT3 group had 22 cases (68.75%) of patients with good prognosis,and the difference was statistically significant (x2 =7.186,P < 0.05).Conclusions The thyroid hormone has a protective stress reaction in patients with acute cerebral infarction.The thyroid hormone level has changed significantly in the acute phase,and returned to normal level with improvement of the patients.As a biochemical indicator thyroid hormone detection can be used to estimate the prognosis of patients with acute cerebral infarction.
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Theinnate immunity system of human body has more and more attention for its antibacterial, antiviral, maintainingimmunehemostasis and promoting tissue damage and repair and other physiological functions.As members of NOD-like receptors(NLRs), NOD1 and NOD2 receptors are identified as intracellular pattern recognition receptors(PRRs), can be identified with molecular damage endogenous(damage-associated molecular patterns, DAMPs)and exogenous injury-molecular pathogen associated molecular(pathogen-associated molecular patterns, PAMPs), and initiation of innate and specific immune response, maintain the steady balance of body.Recently, a bunch of evidence have demonstrated that the importance of NOD1 receptor and NOD2 receptor is not limited in field of anti-infection, and the insulin resistance, kidney and liver damage recovery, cardiovascular disease and tumorigenesis are also closely related with these two receptors.So the aim of this article is to interpret the NOD1 and NOD2 general structure and function, and summarize the link between these two PRRs and tumorigenesis and finally make a clue for cancer immunotherapy.
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Objective: Today, esophageal cancer [EC] has become one of the most common cancer types in China. Therefore, new drug and therapeutic strategies are urgently needed to improve postoperative survival rate of patients with EC. As a food additive, several lines of evidence have shown that citric acid can be served as glycolysis suppressor to inhibit growth of some tumor cells. However, little is known about the effect of this organic acid on the growth of human esophageal carcinoma cell line, EC109
Materials and Methods: In this experimental study, cell proliferation rate was determined using MTT assay. Apoptotic morphological changes were evaluated by fluorescent microscopy using Hoechst 33258 staining. Cell apoptosis rate and mitochondrial membrane potential [MMP] were detected using flow-cytometry. Effect of citric acid on cellular membrane permeability was assessed by measuring lactate dehydrogenase [LDH] activity, using LDH assay kit
Results: Compared to the control group, there was a marked decrease in cells proliferation when the cells were treated with higher citric acid concentrations [800, 1600 micro g/ml]. Typical apoptotic morphology of EC109 cells was observed upon treatment with citric acid, such as chromatin condensation and appearance of apoptotic body. Cell apoptotic indexes were significantly increased [P<0.01] after treatment with citric acid at the concentration of 400-1600 micro g/ml. Extracellular LDH activity and loss of MMP in all of the treated groups were significantly higher than control [P<0.05], in a dose-dependent manner
Conclusion: These results suggest that citric acid prevents EC109 cell growth by inhibiting cell proliferation and inducing apoptosis, which perhaps offers some theoretical guidance for its application in EC treatment