The objective of this study was to examine the antimetastatic effects of cordycepin and elucidate its molecular mechanism using MHCC97H cells in vitro and in vivo. Cellular proliferation was detected with MTT assay. The migration and metastatic potential were measured with scratch wound healing as well as transwell migration assays in vitro. Protein expression was detected by Western blotting. Antitumor and antimetastatic effects of cordycepin were evaluated by subcutaneous xenograft and lung metastatic model in vivo. The results demonstrated that cordycepin significantly inhibited MHCC97H cells proliferation and metastasis which was due to the down-regulation of AKT, p-AKT, p-GSK-3β, β-catenin, N-cadherin, MMP-7, MMP-9 and up-regulation the expression of E-cadherin. Furthermore, cordycepin inhibited tumor growth and metastasis in a dose-dependent manner in vivo. Cordycepin(40 and 20 mg·kg^-1)and 5-fluorouracil group significantly inhibited the tumor weights to 0.38 ± 0.04, 0.61 ± 0.08 and 0.65 ± 0.07 g, respectively, comparing with the control group(1.52 ± 0.46 g)(P < 0.01), but not 10 mg·kg^-1 cordycepin group(1.13 ± 0.36 g)(P > 0.05); the lung metastasis nodus numbers showed the same results, which in all group above(48.9 ± 7.2, 67.2 ± 9.4, 73.6 ± 8.6, respectively)were fewer than the control group(123.5 ± 14.5)(P < 0.01), except 10 mg·kg^-1 cordycepin(106.4 ± 11.3)(P > 0.05). Collectively, cordycepin inhibited MHCC97H cell proliferation and metastasis in vivo and in vitro.

【Objective】 To investigate the effects and potential mechanisms of neurodegenerative lesions in male mice caused by ozone exposure. 【Methods】 We divided 23 C57BL/6N male mice aged 8 to 9 months into control group （clean air group， 11） and ozone group （1 mg/m ³， 4h/d， 12）. After 8 weeks of continuous ozone exposure， the Morris water maze experiment was used to detect the mice’s learning and memory ability， HE dyeing to observe pathological changes in hippocampal tissue cells， and immunoprinting tests to detect the expression levels of Tau， p-Tau and α-synuclein proteins in the cerebral cortex tissue. 【Results】 After 8 weeks of ozone exposure， the mice’s spatial learning and memory ability were impaired to a certain extent， the incubation period decreased with time， and the two lines were separated， but the difference was not statistically significant. Ozone exposure caused changes in the morphology of the mice’s hippocampal tissue cells， disorders in the arrangement of hippocampal neuron， and nuclear wrinkles， and significantly increased levels of p-Tau and α-synuclein protein expressions in cerebral cortex tissues （P<0.01）， but there was no statistical significance in the total Tau expression level. 【Conclusion】 Ozone exposure leads to the loss of learning and memory in mice， changes in hippocampal neurocellular pathology， and increased expression levels of neurodegenerative variable-related proteins.

Proteolysis-targeting chimeras (PROTACs) are small-molecule protein degraders based on the ubiquitin-proteasome system. Recently, the development of specific small-molecule ligands for several E3 ligases (CRL4^CRBN, CRL2^VHL and cIAP) have significantly advanced the PROTACs technology. Several PROTACs against various oncogenic proteins including bromodomain-containing protein 4 (BRD4), estrogen receptor (ER) and androgen receptor (AR) have been developed and considered a novel approach for therapy of cancers. There are advantages of the new technology over the traditional small-molecule strategies. This review article provides a summary on the recent progress in the small-molecule-based PROTACs as antitumor drugs, and the challenges of this technology.

BACKGROUND:The gut microbiota in our intestine performs numerous useful functions and has a major impact on the host’s health. Recently some studies have revealed that the gut microbiota cannot only control intestinal activity but also affect bone metabolism by regulating the immune system. OBJECTIVE:To review the new research development in the effects of gut microbiota on bone metabolism. METHODS: We retrieved the PubMed database using “gut microbiota, immune system, bone metabolism, osteoporosis” as keywords. A total of 46 articles were included which were related to gut microbiota, immune system and bone metabolism. For the articles in the same field, those published recently or in authorized journals were selected. RESULTS AND CONCLUSION:Gut microbiota-osteoporosis research wil bridge the gaps between bone physiology, gastroenterology, immunology, and microbiology.In vivo experiments in the germ-free mice and human body have found that the gut microbiota has important effects on bone metabolism, and the intervention of antibiotics, probiotics and prebiotics has further confirmed the effects of gut microbiota on bone mass. The gut microbiota has more obvious effects on bone mass in the adolescent and post-menopause periods.

Angelicae Sinensis Radix， derived from a medicinal and edible plant Angelica sinensis， is one of the traditional bulk Chinese medicines. In addition to gynecological blood stagnation and deficiency， its indications also include dysmenorrhea， deficiency and cold-induced abdominal pain， and rheumatoid arthritis. With the in-depth study of Angelicae Sinensis Radix， its anti-inflammatory and analgesic activities have attracted widespread attention. However， there has been no systemic report. The present study comprehensively reviewed the anti-inflammatory and analgesic activities of Angelicae Sinensis Radix （including its compositions， extracts， and different processed products） and mechanisms published in recent 30 years. The anti-inflammatory effect of Angelicae Sinensis Radix was achieved mainly by blocking the expression of proteins and genes in nuclear factor-κB （NF-κB）， mitogen-activated protein kinases （MAPK）， and Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathways， inhibiting the release of inflammatory mediators including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， nitric oxide （NO）， prostaglandin E₂ （PGE₂） and IL-1β， and maintaining the high sensitivity of immune cells in the host to external stimuli. The mechanism of analgesic effect may be related to the suppression of the production of algesic substances （such as inflammatory factors and chemokines） or blocking of the amplification and transmission of pain perception in cascade reaction. Furthermore， the study also pointed out some problems in modern research and proposed suggestions on its future research to provide references for investigation and clinical applications of Angelicae Sinensis Radix.

OBJECTIVETo investigate the protective effect of progesterone against high intraocular pressure-induced ischemia-reperfusion (IR) injury.

METHODSTwenty-four SD rats were randomly divided into normal control, IR model, dimethyl sulfoxide (DMSO) solvent treatment group, and progesterone treatment group. In the latter 3 groups, retinal IR injury was induced by intraocular injection of saline. In the progesterone group, intraperitoneal injections of 4 mg/kg progesterone were administered 30 min before and 2 h after ischemia, and an equivalent volume of DMSO was used in the DMSO group. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured by spectrophotometer after the treatment, and the pathological changes of the retina were observed by transmission electron microscope and light microscope.

RESULTSSix hours after reperfusion, the content of MDA in the model group was significantly higher than that in the normal control group (P<0.01), but lower than that in progesterone treatment group (P<0.01); reverse changes in SOD activity was observed. In the model group, the inner nuclear layer and nerve fiber layer became thinner with obvious cellular pathologies including nuclear condensation, mitochondria vacuolization and endocytoplasmic reticulum swelling. Progesterone treatment markedly alleviated these pathologies in the inner nuclear layer and nerve fiber layer of the retina.

CONCLUSIONProgesterone offers protection of the retina against IR injury in SD rats by increasing SOD activity and decreasing MDA content in the retina.

Animals ; Dimethyl Sulfoxide ; Female ; Ischemia ; etiology ; pathology ; Male ; Malondialdehyde ; metabolism ; Ocular Hypertension ; complications ; Progesterone ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; etiology ; prevention & control ; Retina ; metabolism ; Retinal Vessels ; physiopathology ; Superoxide Dismutase ; metabolism

Objective: To understand the relationships between college students’ aggression and self-acceptance, family intimacy and adaptability, and to provide reference for college students’ aggression preventing and intervening. Methods: Using general information questionnaire, Aggression Questionnaire, Self-acceptance Questionnaire and FACES II-CV, 984 college students from 3 colleges in Xinxiang, Henan province were surveyed by questionnaire. Results: The total score of physical aggression, verbal aggression, indirect aggression and aggression in male students was higher than that of female students (t=7.17,4.21,2.05,3.63,P<0.05).The score of physical aggression of only children was higher than that of nononly children (t=2.39,P<0.05).The score of indirect attack of disciplined college students was higher than that of undisciplined college students (t=2.60,P<0.01).There were statistically significant differences in the total scores of indirect attack, hostility and attack among college students with different left-behind experiences (F=3.39,4.61, 3.37, P<0.01).There were statistically significant differences in the total scores of physical aggression, anger and aggression among college students by family income(F=5.70,3.94,3.37,P<0.01).Correlation analysis showed that the total score of college students’ aggression was positively correlated with self-acceptance, negatively correlated with actual family intimacy and actual family adaptability (r=0.37，-0.09，-0.07,P<0.01). Regression analysis showed that self-acceptance, gender, disciplinary action, left-behind experience and expected family adaptability showed significant associations with total score of college students’ aggression (P<0.05). Conclusion Self-acceptance and family closeness and adaptability are associated with aggressive behavior in college students. Schools should carry out targeted psychological health education on self-acceptance to ensure that college students maintain a reasonable level of self-acceptance, and family members should develop certain level of intimacy and adaptability, in order to reduce the occurrence of aggressive behavior of college students.

Objective: To investigate the molecular mechanism of circZNF609 targeting miR-153 to regulate the proliferation and apoptosis of diffuse large B-cell lymphoma. Methods: Fifty cases of lymphoma tissue from patients with diffuse large B-cell lymphoma who were diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from July 2018 to December 2019 were collected. Thirty cases of normal lymph node tissues that were confirmed to be reactive hyperplasia by pathological diagnosis during the same period were selected as controls. Real time quantitative polymerase chain reaction (PCR) was used to detect the expression of circZNF609 in diffuse large B-cell lymphoma tissues and control hyperplasia lymph nodes. Diffuse large B-cell lymphoma OCI-LY19 cells were divided into control group (blank control), si-con group (transfected with siRNA control), si-ZNF609 group (transfected with circZNF609 siRNA), and si-ZNF609+ Anti-NC group (co-transfected with circZNF609 siRNA and inhibitor control) and si-ZNF609+ Anti-miR-153 group (co-transfected with circZNF609 siRNA and miR-153 inhibitor). Cell counting kit-8 (CCK-8) was used to detected proliferation, flow cytometry was used to detect cell cycle and apoptosis. Western blot was used to detect the protein expressions of C-caspase-3, cyclin D1, p21. The luciferase reporter system was used to identifie the relationship between circZNF609 and miR-153. Results: The expression level of circZNF609 in diffuse large B-cell lymphoma tissue was (1.44±0.22), higher than (0.37±0.14) in the control tissues (P<0.001). The cell survival rate of the si-ZNF609 group was (51.74±6.39)%, lower than (100.00±10.23)% of the control group and the (99.64±11.67)% of the si-con group (P<0.001). The proportion of cells in the G(0)/G(1) phase was (63.25±4.11)%, higher than (48.62±4.32)% of the control group and (47.12±3.20)% of the si-con group (P<0.001), the apoptosis rate was (13.36±1.42)%, higher than (3.65±0.47)% of the control group and (3.84±0.62)% of the si-con group (P<0.05). The expression levels of C-caspase-3 and p21 protein were (0.85±0.09) and (0.90±0.08), higher than (0.38±0.04) and (0.65±0.07) in the control group and (0.39±0.05) and (0.66±0.05) in the si-con group (P<0.001). The expression level of cyclin D1 protein was (0.40±0.03), lower than (0.52±0.06) of the control group and (0.53±0.04) of the si-con group (all P<0.001). CircZNF609 and miR-153 are mutually targeted. The cell survival rate of the si-ZNF609+ Anti-miR-153 group was (169.92±13.25)%, higher than (100.00±9.68)% of the si-ZNF609+ Anti-NC group (P<0.001), the ratio of cells in G(0)/G(1) phase and apoptosis rate were (52.01±3.62)% and (8.20±0.87)%, respectively, lower than (64.51±5.17)% and (14.03±1.17)% in the si-ZNF609+ Anti-NC group (P<0.001). The protein expression levels of C-caspase-3 and p21 were (0.42±0.06) and (0.52±0.06), lower than (0.80±0.07) and (0.92±0.10) of the si-ZNF609+ Anti-NC group (P<0.001). The protein expression level of cyclin D1 was (0.68±0.07), higher than (0.39±0.04) in the si-ZNF609+ Anti-NC group (P<0.001). Conclusion: Down-regulation of circZNF609 inhibits the proliferation of diffuse large B-cell lymphoma OCI-LY19 cells and induces apoptosis by targeting miR-153.
Apoptosis/genetics* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; MicroRNAs/genetics* ; RNA, Circular/genetics*

OBJECTIVETo investigate the effects of arsenic trioxide (AsO) on K562 cell proliferation by regulating cell cycle protein D1 and cyclin-dependent kinase inhibitor p27kip1.

METHODSMTT was used to detect the effect of AsOon K562 cell proliferation, so as to screen out the appropriate drug concentration. Furthermore, the K562 cell apoptosis was observed by microscopy. The expression of CyclinD1 and p27kip1 in K562 cells treated with AsOwas analyzed by reverse transcription-polymerase chain reaction(RT-PCR), immunohistochemistry and Western blot.

RESULTSAsOcould inhibit the proliferation of K562 cells in a dose- and time- dependent manner (r= 0.967). And the apoptosis cell number in AsOgroup was significantly higher than that in the control group(P<0.05). AsOcould markedly inhibit the expression of CyclinD1 in K562 cells(P<0.05), but the expression of P27kip1 was not significantly changed after AsOtreatment.

CONCLUSIONSAsOcan induce K562 cell apoptosis and inhibit K562 cell proliferation by regulating the expression of CyclinD1.

Objective To compare the effects on blood lipid level by immunosuppressive drugs in renal transplantation recipients. Methods Two hundred and eighty-three renal allograft recipients with tacrolimus(FK506), cyclosporine A(CsA) and rapamycin (SRL) immunosuppressive regimen were reviewed in this study. The variation of whose total cholesterol(TC) and triglyceride(TG) concentration in serum were compared before and after three immunosuppressive regimen. Results There was no significant difference in TC and TG before and after oral FK506 for 93 patients[(4.9± 1. 1) and (1. 4±0. 8)mmol/L vs (4. 9±1.1) and (1.4±1.0)mmol/L, respectively, P>0. 05]. The concentration of TC and TG from 106 patients with CsA[(4. 8±1. 0) and (1. 6±0. 8)mmol/L vs (6. 6±1. 7) and (3. 2±1. 0)mmol/L, respectively] and 29 patients with SRL was higher than those before taking drugs, P<0. 05. The concentration was increased after 12 to 24 weeks generally. The concentration of TC and TG of CsA from FK506 to tacrolimus for 51 patients[(6. 7±1. 1) and (2. 8± 1. 0)mmol/L vs (4. 7±1. 7) and (1. 5±1. l)mmol/L, respectively] were decreased after 12 weeks (P<0. 01). Conclusions Primary factor of dyslipidemia was that CsA and SRL were used for patients post-renal transplantation, which should be regarded. The FK506-based immunosuppressive regimen should be recomended in renal transplantation patients who have a hyperlipidmia.