Objective To investitate the efficacy of cannabinoid-2 receptor (CB2R) activation in preventing liver ischemia-reperfusion (I/R) injury in mice.Methods Forty-eight male C57BL/6J mice,weighing 20-30 g,were divided into 4 groups (n =12 each):sham operation group (group S),group I/R,CB2R agonist JWH133 group (group J),and CB2R agonist JWH133 + CB2R antagonist SR144528 group (group JS).Liver I/ R was produced by blocking the hepatic artery and portal vein for 30 min followed by 45 min of reperfusion in anesthetized mice.At 60 min before ischemia,JWH133 20 mg/kg was injected intraperitoneally in group J,and JWH133 20 mg/kg and SR144528 30 mg/kg were injected intraperitoneally in group JS.The liver was removed at 45 min of reperfusion for determination of tumor necrosis factor-α (TNF-α),macrophage inflammatory protein-1α (MIP-1α) and MIP-2 contents (using ELISA),and expression of TNF-α,MIP-1α,MIP-2 and intercellular adhesion molecule-1 (ICAM-1) mRNA (by RT-PCR) in the liver tissues and for microscopic examination of the pathological changes.Results Compared with group S,the contents of TNF-α,MIP-1α and MIP-2 were significantly increased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was up-regulated in J and JS groups.Compared with group I/R,the contents of TNF-α,MIP-1α and MIP-2 were significantly decreased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was down-regulated in J group,and no significant change was found in the parameters mentioned above in JS group.Compared with group J,the contents ofTNF-α,MIP-1α and MIP-2 were significantly increased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was up-regulated in JS group.The pathological changes of liver tissues were significantly attenuated in group J as compared with I/R and JS groups.Conclusion CB2R activation is effective in preventing liver I/R injury in mice and the mechanism is related to inhibitioni of inflammatory responses in liver tissues.

With high selectivity and potency, target protein degradation technology has recently emerged as a strategy for drug discovery and design. Proteolysis-targeting chimeras (PROTAC) function as inducers for the degradation of target proteins and are a research focus in drug development. Current research on PROTAC mainly revolves around the rational design of PROTAC molecules, the discovery of new E3 ubiquitin ligase ligands and improvement in drug targeting. In this review, we focus on the PROTAC linker and its effects on the generation of the E3 enzyme-PROTAC-target protein ternary complex from three standpoints: length, binding site and chemical properties. We discuss the influences of the linker on the efficacy and the selectivity of PROTAC molecules.

Objective To investigate the role of bone marrow mesenchymal stem cells (BM-MSCs) in the invasion and metastasis of gastric cancer cells and to explore its mechanism.Methods SGC7901 and KATO-Ⅲ gastric cancer cells were co-cultured with BM-MSCs respectively,and the invasion ability of SGC7901 and KATO-Ⅲ gastric cancer cells were detected by Transwell assay.Secondly,CD133 + and CD133-cells were sorted from KATO-Ⅲ gastric cancers and co-cultured with BM-MSCs respectively to compare their changes in invasiveness.Meanwhile,the expressions of p-AKT and epithelial-mesenchymal transition (EMT) relative factors in gastric cancer cells were detected by Western-blot.The role of CD133 in BM-MSCs affecting the ability of invasion of gastric cancer cells was further vertified by the overexpression of CD133 in SGC7901 cells.SPSS17.0 software was used for statistical processing,and the stand deviation of the measurement data were expressed as the standard deviation,independent sample t test was conducted.Results The invasiveness of co-cultured SGC7901 and KATO-Ⅲ cells was significantly enhanced.The invasive ability of KATO-Ⅲ CD133+ cells co-cultured with BM-MSCs tended to increase more significantly than that of co-cultured CD133 cells[(259.0 ± 24.0)vs (58.0 ±5.6),P ＜ 0.001].The expressions of p-AKT,Snail and N-cadherin were significantly increased in co-cultured CD133+ cells (P =0.003,P =0.003,P =0.002),while the expression of E-cadherin was reduced (P =0.021).After co-cultured with BM-MSCs,the expression of E-cadherin was also reduced in CD133-cells (P =0.005),but the expressions of p-AKT,Snail and N-cadherin were no significantly changes (P =0.744,P =0.277,P =0.295).SGC7901 co-cultured with BM-MSC after overexpression of CD133 showed higher i nvasiveness than blank control group[(239.3 ± 24.0) vs (103.3 ± 15.5),P ＜ 0.001].The expressions of p-AKT,Snail and N-cadherin were significantly increased when co-cultured with BM-MSCs in the group of CD133 overexpression (P =0.001,P =0.001,P =0.001),while the expression of E-cadherin was significantly decreased(P =0.003).The expressions of Snail and N-cadherin were also significantly increased after co-cultured with BM-MSCs in the blank control group (P =0.001,P =0.004),and the expression of E-cadherin was significantly decreased (P =0.018),while the expression of p-AKT was not significantly changed (P =0.193).Conclusions BM-MSCs can enhance the invasion and metastasis of gastric cancer cells by promoting the EMT of gastric cancer cells.CD133 may be involved in the regulation of EMT in gastric cancer cells through the PI3K/AKT signaling pathway.

AIM: To evaluate the lacrimal gland parameters and their correlation with clinical examination in patients with thyroid-associated ophthalmopathy(TAO)using orbital magnetic resonance imaging(MRI).METHODS: A total of 38 patients(76 eyes)with TAO were selected as case group, and 26 patients(52 eyes)who matched the gender and age with case group and volunteered to accept examination were selected as normal control group. Patients in case group were categorized into active TAO group and inactive TAO group according to the modified clinical activity score(CAS). The exophthalmos was evaluated on T1WI after obtaining the MRI images, the longest lacrimal gland length, width, and the biggest area in axial and coronal images were evaluated on T2WI, and the maximum T2 value and mean T2 value of the lacrimal gland were recorded.RESULTS: There were no significant differences in age, gender and exophthalmos between active TAO and inactive TAO(P>0.05). The area of lacrimal gland was higher in active TAO than that in inactive TAO, and was higher in inactive TAO than that in control group in coronal and axial section(all P<0.01). The length of lacrimal gland in coronal and axial section was higher in the active TAO than that in the inactive TAO and the control group(all P<0.05). The width of lacrimal gland in coronal and axial section was higher in active TAO and inactive TAO than that in the control group(all P<0.05). The maximum T2 value in the active TAO was higher than that in the inactive TAO and control group, and the inactive TAO was higher than that in the control group(all P<0.05). The average T2 value in the active TAO was higher than that in the inactive TAO and control group(all P<0.05). CAS was positively correlated with lacrimal gland area in axial, coronal section and maximum T2 value(all P<0.01).CONCLUSION: The lacrimal gland is significantly enlarged in patients with TAO, especially in active TAO. The lacrimal gland area in axial, coronal section and maximum T2 value could be potentially utilized as valuable radiographic biomarkers for the activity of TAO.

AIM: To explore the key genes and molecular markers involved in the retinoblastoma development through bioinformatics.METHODS: The mRNA microarray datasets from the Gene Expression Omnibus(GEO)database were obtained, and the differentially expressed gene(DEG)between retinoblastoma cell lines and normal retinal pigment epithelial(RPE)cell lines were analyzed through gene ontology(GO)and KEGG enrichment analysis. To screen key genes, establish protein-protein interaction(PPI)network, and use receiver operating characteristic(ROC)curve to assess clinical diagnostic efficacy. The RNA expressions of key genes in retinoblastoma cell lines and normal RPE cell lines were compared by qRT-PCR.RESULTS: A total of 121 DEGs were obtained from the retinoblastoma dataset of GSE97508 and GSE110811. KEGG pathway analysis showed that DEG were enriched in phototransduction, cell cycle, and p53 signaling pathways. A total of 9 key genes, including MCM6, DTL, UBE2T, TOP2A, NUSAP1, CENPK, RRM2, RLBP1, and RHO, were obtained from the intersection of PPI network analysis and the top 30 DEG from each dataset. The differentially expressed 9 key genes were verified in GSE24673. ROC analysis showed that the area under the curve(AUC)for UBE2T, RRM2, and RHO was ≥80%, and there was a statistical significance(P>0.05). The mRNA level of UBE2T and RRM2 in retinoblastoma was significantly higher than APRE-19 cell line, while the mRNA level of RHO was significantly lower than that of ARPE-19 cell line.CONCLUSION: UBE2T, RRM2, and RHO may be served as potential molecular markers and potential therapeutic targets for retinoblastoma.

Objective: To investigate the clinical and pathological features, treatments and prognosis of laryngeal neuroendocrine carcinoma (LNEC). Methods: We conducted the retrospective analysis of the clinical data of 12 patients with LNEC admitted to the Department of Otorhinolaryngology Head and Neck Surgery, Second Hospital of Shanxi Medical University from May 2014 to December 2021, including 9 males and 3 females, aged 50-77 years. There were 4 cases of typical carcinoid tumour (highly differentiated), 5 cases of atypical carcinoid tumour (moderately differentiated) and 3 cases of neuroendocrine small cell carcinoma (hypofractionated). The clinical features, diagnosis, treatment and prognosis of LNEC were analysed. Results: The clinical manifestations of LNEC varied according to the tumour type but did not correlate with the pathological types. The supraglottic type was characterized by sore throat, foreign body sensation in the pharynx, coughing, obstructive sensation when eating and choking on water. The treatments were determined according to the pathological types, lesion location and invasion scope. Of 12 patients 4 underwent horizontal partial laryngectomy plus elective lymphatic dissection plus postoperative radiotherapy/chemotherapy, 4 underwent vertical partial laryngectomy (3 of them with cervical lymphatic dissection), 3 underwent supported laryngoscopic plasma laryngectomy for laryngeal cancer, and 1 abandoned for treatment. With the follow-up of 8 -78 months, 5 patients were alive, 1 died from chemotherapy reactions, 3 died from other diseases, 1 died from lung metastasis, 1 died from lung infection and 1 was lost to follow-up. Conclusion: LNEC is clinically rare, the clinical manifestations are less specificity, diagnosis relies on pathological and immunohistochemical examinations, and treatment modalities and prognoses are closely related to the pathological subtypes of LNEC.
Humans ; Male ; Female ; Laryngeal Neoplasms/pathology* ; Retrospective Studies ; Carcinoma, Neuroendocrine/pathology* ; Laryngectomy ; Carcinoid Tumor/pathology*

Halogenated sesquiterpenes are important derivatives of sesquiterpenes, referring to chemical components of sesquiterpenes that contain halogens such as chlorine, bromine, and iodine. Halogenated sesquiterpenes have attracted attention from researchers in China and abroad because of their diverse structures, unique halogen elements, and extensive pharmacological activities. Studies have shown that halogenated sesquiterpenes exhibit significant antimicrobial, anti-inflammatory, anticancer, insecticidal, hypoglycemic, and enzyme inhibitory activities. In order to better explore the potential pharmaceutical value of halogenated sesquiterpenes, this paper reviewed the structural characteristics and pharmacological activities of halogenated sesquiterpenes in the past two decades, aiming to provide references for further research and development of this class of compounds.
Sesquiterpenes/chemistry* ; Anti-Inflammatory Agents/pharmacology* ; China