The tandem cyclization of acrylamide with diselenides facilitated by electrochemical oxidation was successfully developed. This strategy provided an environmentally friendly method for the ...construction of C−Se bond. A series of seleno oxindoles with pharmacological activity were obtained by using this well‐designed tandem cyclization strategy. The in vitro antitumor activity of the compounds was also screened through MTT assay. Results showed that the seleno oxindoles exhibited better antitumor activity than other oxindole derivatives.
We developed an electrochemically enabled dehydrogenative annulation reaction of amides and alkynes for the synthesis of antitumor polycyclic isoquinolinones through a double C–H activation route. No ...external oxidant is required in this reaction, and electricity is used for Ru catalyst circulation. The most remarkable feature of this reaction is the effective improvement of product regioselectivity under mild electrolytic conditions in comparison with previously set strong oxidant conditions.
MicroRNAs (miRNAs) are abnormally expressed in various ocular diseases, including age-related cataract. However, the role of miR-182-5p in the progression of age-related cataract remains unclear.
The ...expression of miR-182-5p in HLE-B3 cells was detected by qRT-PCR. HLE-B3 cells were transfected with miR-182-5p mimics. CCK-8, EdU, flow cytometry, 2',7'-dichlorodihydrofluorescein diacetate, JC-1 kit, and western blot were used to assess the cell viability, proliferation, apoptosis, reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), and protein expression, respectively, in vitro. The relationship between miR-182-5p and NOX4 was confirmed using the dual-luciferase reporter gene analysis.
We found that miR-182-5p expression was significantly decreased by the H
O
exposure. Overexpression of miR-182-5p promoted cell proliferation and inhibited ROS production and apoptosis in H
O
-induced HLE-B3 cells. Moreover, p-p-38, p-ERK, and p-JNK were up-regulated in H
O
-treated HLE-B3 cells, and overexpression of miR-182-5p reversed the effects of H
O
on HLE-B3 cells. In addition, dual-luciferase reporter assay substantiated that NOX4 was a direct target and downregulated by miR-182-5p.
We concluded that miR-182-5p inhibited lens epithelial cells apoptosis through regulating NOX4 and p38 MAPK signaling, providing a novel biomarker for treatment of age-related cataract.
CD147, also known as EMMPRIN or basigin, is a transmembrane glycoprotein receptor that activates matrix metalloproteinases and promotes inflammation. CD147 function is regulated by posttranslational ...modifications of which glycosylation has attracted the most attention. In this study, we demonstrated that glycosylated CD147 was the dominant form in heart tissue, and its levels were markedly elevated in response to transverse aortic constriction (TAC). Adeno-associated virus 9-mediated, cardiac-specific overexpression of wild-type CD147 in mice significantly promoted pressure overload-induced pathological cardiac remodeling accompanied by augmented oxidative stress and ferroptosis. By contrast, mutations of CD147 glycosylation sites notably weakened these detrimental effects of CD147. Mechanistically, CD147 exacerbated TAC-induced pathological cardiac remodeling via direct binding with the adaptor molecule TRAF2 and subsequent activation of TAK1 signalling, which was dependent on glycosylation of CD147. Collectively, our findings provide the first evidence that CD147 promoted pathological cardiac remodeling and dysfunction in a glycosylation-dependent manner through binding the adaptor protein TRAF2 and activating the downstream TRAF2-TAK1 signalling pathway. Thus, glycosylation of CD147 may be a potent interventional target for heart failure treatment.
Purpose. To investigate the effects of lncRNA RHPN1-AS1 on retinoblastoma (RB) and further explore its underlying molecular mechanisms. Methods. The expression of RHPN1-AS1, miR-3133, (JAK2), and ...signal transducer and activator of transcription 3 (STAT3) was detected by qRT-PCR. CCK-8, EDU, and flow cytometry assays were conducted to assess the proliferation activity and apoptosis of RB cells. Double fluorescein and RNA immunoprecipitation assays were performed to detect the interaction between RHPN1-AS1 and miR-3133 or miR-3133 and JAK2. Western blotting was performed to detect the expression of apoptosis-related proteins. Results. In RB cells, RHPN1-AS1 was upregulated. Silencing RHPN1-AS1 inhibited the activity of RB cells and promoted apoptosis. The expressions of proapoptotic factors (Bax and p53) were increased, while antiapoptotic factors (Bcl-2 and Survivin) were suppressed in siRHPN1-AS1 groups. Furthermore, we predicted and verified that RHPN1-AS1 regulated RB progression by targeting miR-3133/JAK2. In addition, siRHPN1-AS1 also inhibited oncogene STAT3 protein expression. Conclusion. lncRNA RHPN1-AS1 served as a sponge for miR-3133 to counteract miR-3133-mediated JAK2/STAT3 suppression, indicating that the lncRNA RHPN1-AS1 may be a potential therapeutic target for the treatment of RB.
To investigate the effects of fluoride on Fas expression, caspase-3 and caspase-8 activity and apoptosis in rat incisor cells.
Forty male SD rats were divided into 4 groups randomly and provided with ...distilled water containing NaF at the doses of 0, 10, 50 and 100 mg/L respectively. Each group had 10 animals. Five animals were sacrificed at 60 and 90 days respectively. Fas expression was measured with immunohistochemistry, and colorimetric assay was used to examine caspase-3 and caspase-8 activity with enzyme-labelled meter. The apoptosis was detected by flow cytometry in mandibular incisor cells.
NaF at the doses of 10, 50 and 100 mg/L for 60 d and 90 d caused Fas overexpression, promoted activity of caspase-3 and caspase-8, increased apoptosis rate in mandibular incisor cells. At 60 days, the value of Fas expression was 0.1819 ± 0.0025 for control, 0.2120 ± 0.0084 for 10 mg/L NaF group, 0.2283 ± 0.0183 for 50 mg/L NaF group, 0.2818 ± 0.0233 for 100 mg/L NaF group. At 90 days, the value of Fas expression was
AIM: To investigate anti-angiogenic effects of polysulfated heparin endostatin(PSH-ES) on alkali burn induced corneal neovascularization(NV) in rabbits.METHODS: An alkali burn was made on rabbit ...corneas to induce corneal NV in the right eye of 24 rabbits. One day after burn creation, a 0.2 m L subconjunctival injection of 50 μg/m L PSH-ES, 50 μg/m L recombinant endostatin(ES), or normal saline was administered every other day for a total of 14d(7 injections). Histology and immunohistochemisty were used to examine corneas.Corneal NV growth was evaluated as microvessel quantity and corneal vascular endothelial growth factor(VEGF)expression was measured by immunohistochemical assay.RESULTS: Subconjunctival injection of ES and PSHES resulted in significant corneal NV suppression, but PSH-ES had a more powerful anti-angiogenic effect than ES. Mean VEGF concentration in PSH-ES treated corneas was significantly lower than in ES treated and saline treated corneas. Histological examination showed that corneas treated with either PSH-ES or ES had significantly fewer microvessels than eyes treated with saline. Additionally corneas treated with PSH-ES had significantly fewer microvessels than corneas treated with ES.CONCLUSION: Both PSH-ES and recombinant ES effectively inhibit corneal NV induced by alkali burn.However, PSH-ES is a more powerful anti-angiogenic agent than ES. This research has the potential to provide a new treatment option for preventing and treating corneal NV.
Endostatin (ES) is an endogenous angiogenesis inhibitor that has the ability to inhibit tumor growth and metastasis. However, its clinical application is limited by a number of disadvantages, such as ...poor stability, short half-life and the requirement of high doses to maintain its efficacy. The chemical modification on ES may offer a solution to these disadvantages. The aim of the present study was to evaluate the effects of ES, polysulfated heparin-endostatin (PSH-ES) and polyethylene glycol-endostatin (PEG-ES) on the endothelial cell proliferation and angiogenesis associated with corneal neovascularization (CNV) and to determine their mechanisms of action. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) was used to study the effects of ES and its derivatives on endothelial cell proliferation in vitro, and rabbits were used to evaluate the effects of ES and its derivatives on CNV in vivo. In the evaluation of CNV, the expression of vascular endothelial growth factor in the cornea was measured via immunohistochemistry and microvessels were counted. ES and its derivatives significantly inhibited endothelial cell proliferation in vitro (P<0.05) and suppressed CNV in vivo. Among the compounds examined, ES most effectively inhibited endothelial cell proliferation in vitro (P<0.05); however, PSH-ES and PEG-ES most effectively inhibited CNV in vivo (P<0.05). These results indicate that PSH-ES and PEG-ES are candidate anti-angiogenesis drugs.
AIM: To investigate the molecular mechanisms of miRNA in advanced gastric cancers(AGCs) before and after cytoreductive surgery(CRS) + hyperthermic intraperitoneal chemotherapy(HIPEC). METHODS: A ...miRNA microarray containing human mature and precursor miRNA sequences was used to compare expression profiles in serum samples of 5 patientswith AGC before and after CRS + HIPEC. The upregulation of miR-218 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in SGC7901 gastric cancer cells. RESULTS: miRNA microarray chip analysis found that the level of miR-218 expression was upregulated more than 8 fold after CRS + HIPEC. Furthermore, miR-218 increased gastric cancer cell chemosensitivity to cisplatin in vitro and inhibited gastric cell tumor growth in nude mice in vivo(0.5 vs 0.78, P < 0.05).CONCLUSION: Our results indicated that targeting miR-218 may provide a strategy for blocking the development of gastric cancer and reverse the multi-drug resistance of gastric cell lines.
PDF
