EGR3 Inhibits Tumor Progression by Inducing Schwann Cell-Like Differentiation.

The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer.

Prevalence and risk factors for dementia and mild cognitive impairment among older people in Southeast China: a community-based study.

BACKGROUND: With the aging population, the number of individuals with dementia in China is increasing rapidly. This community-based study aimed to investigate the prevalence and risk factors for dementia and mild cognitive impairment (MCI) among older adults in China. METHODS: In this study, 20,070 individuals aged ≥ 65 were recruited between January 1, 2022, and February 1, 2023, from ten communities in Xiamen City, China. We collected data on age, sex, level of education, and medical history, as well as global cognition and functional status. The prevalence of dementia and MCI was examined, and the risk factors for different groups were assessed. RESULTS: The overall prevalence of dementia and MCI was approximately 5.4% (95% confidence interval [CI], 5.1-5.7) and 7.7% (95% CI, 7.4-8.1), respectively. The results also indicated that dementia and MCI share similar risk factors, including older age, female sex, hypertension, and diabetes mellitus. Compared with individuals with no formal education, those with > 6 years of education had an odds ratio for MCI of 1.83 (95% CI, 1.49-2.25). We also found that only 5.5% of the positive participants chose to be referred to the hospital for further diagnosis and treatment during follow-up visits. CONCLUSIONS: This study estimated the prevalence and risk factors for dementia and MCI among individuals aged ≥ 65 years in Southeast China. These findings are crucial for preventing and managing dementia and MCI in China.

Isolated cerebral mucormycosis that looks like stroke and brain abscess: A case report and review of the literature.

BACKGROUND: Cerebral mucormycosis is an infectious disease of the brain caused by fungi of the order Mucorales. These infections are rarely encountered in clinical practice and are often misdiagnosed as cerebral infarction or brain abscess. Increased mortality due to cerebral mucormycosis is closely related to delayed diagnosis and treatment, both of which present unique challenges for clinicians. CASE SUMMARY: Cerebral mucormycosis is generally secondary to sinus disease or other disseminated disease. However, in this retrospective study, we report and analyze a case of isolated cerebral mucormycosis. CONCLUSION: The constellation of symptoms including headaches, fever, hemiplegia, and changes in mental status taken together with clinical findings of cerebral infarction and brain abscess should raise the possibility of a brain fungal infection. Early diagnosis and prompt initiation of antifungal therapy along with surgery can improve patient survival.

MiR-106a targets Mcl-1 to suppress cisplatin resistance of ovarian cancer A2780 cells.

Resistance to chemotherapy is a major obstacle for the effective treatment of advanced ovarian cancer. The mechanism of chemoresistance is still poorly understood. Recently, more and more evidence showed microRNAs (miRNAs) modulated many key molecules and pathways involved in chemotherapy. microRNA-106a (miR-106a) has been implicated in many cancers, but its role in ovarian cancer and drug resistance still remains unexplored. This study was to investigate whether miR-106a mediated resistance of the ovarian cancer cell line A2780 to the chemotherapeutic agent cisplatin (DDP). The different levels of miR-106a in A2780 cells and their resistant variant A2780/DDP cells were identified by using real-time PCR. MTT assay and flow cytometry were used to analyze the effect of miR-106a on cisplatin resistance of these paired cells. Real-time PCR, Western blotting and luciferase reporter assay were applied to explore whether Mcl-1 was a target of miR-106a. As compared to A2780 cells, the expression of miR-106a was down-regulated in the cisplatin resistant cell line A2780/DDP. Moreover, knockdown of miR-106a dramatically decreased antiproliferative effects and apoptosis induced by cisplatin in A2780 cells, while overexpression of miR-106a significantly increased antiproliferative effects and apoptosis induced by cisplatin in A2780/DDP cells. Furthermore, miR-106a inhibited cell survival and cisplatin resistance through downregulating the expression of Mcl-1. Mcl-1 was a direct target of miR-106a. These results suggest that miR-106a may provide a novel mechanism for understanding cisplatin resistance in ovarian cancer by modulating Mcl-1.

Effect of siRNA targeting MTA1 on metastasis malignant phenotype of ovarian cancer A2780 cells.

Ovarian cancer is the fifth lethal gynecologic malignancy. Metastasis-associated gene 1 (MTA1) is overexpressed in many malignant tumors with high metastatic potential. This study investigated whether down-regulation of MTA1 expression by RNAi in A2780 ovarian cancer cells could affect proliferation, anoikis, migration, invasion and adhesion of the cells and to research the potential for MTA1 gene therapy of ovarian cancer. After transfection with effective Mta1 gene siRNA, the effects on proliferation, anoikis, migration, invasion and adhesion of A2780 cells were tested by MTT assay, flow cytometry, wound-healing assay, Transwell assay and adhesion assay. Expression levels of PTEN, beta 1 integrin, MMP-9, phosphor-AKT (Ser473), and total AKT activity were evaluated in control and transfected cells. The results showed that inhibition of MTA1 mediated by Mta1-siRNA transfection decreased the cell invasion, migration and adhesion, and induced the increased cell anoikis, but no significant difference was found in proliferation of A2780 cancer cells. In addition, beta 1 integrin, MMP-9, and phosphor-AKT protein levels were significantly down-regulated, while PTEN was significantly up-regulated. These results demonstrated that MTA1 played an important role in the cell metastasis in ovarian cancer. MTA1 could serve as another novel potential therapeutic target in ovarian cancer.

[Polypeptide P110 enhances the growth-inhibitory effect of cisplatin on colon cancer HCT-116 cells and xenotransplanted tumors in mice].

OBJECTIVE: To observe the growth-inhibitory effect of polypeptide P110, designed with G3BP protein targets, plus cisplatin on human colon cancer HCT-116 cells and mouse colon cancer C26 xenotransplanted tumors in mice. METHODS: The proliferation inhibition of HCT-116 cells and HUVEC cells in vitro was evaluated by MTT assay. A mouse model of xenotransplanted C26 mouse colon cancer was established. The inhibitory effects of P110 and cisplatin at different concentrations on C26 xenotransplanted tumors were assessed. RESULTS: P110 enhanced the inhibitory effect of cisplatin on proliferation of HCT-116 cells. By treated with 20 µmol/LP110 + 10, 30, 90 µmol/L cisplatin, the proliferation inhibitory rates were (43.3 ± 3.2)%, (46.4 ± 4.6)% and (47.6 ± 5.8)%, respectively, significantly higher than that in the cisplatin group (P < 0.05). 20 µmol/L P110 + 10 µmol/L cisplatin effectively killed HCT-116 cells, whereas with less toxicity to HUVEC cells. The tumor inhibition rates in mice of P110 (25 mg/kg, 50 mg/kg, 100 mg/kg) plus cisplatin (1 mg/kg) were 23.0%, 30.4% and 34.2%, respectively. While, the tumor inhibition rates in mice of the cisplatin group (1 mg/kg) was 22.7%. Compared with cisplatin at the same concentration, the tumor inhibition rates in mice of the P110 plus cisplatin groups were all increased. CONCLUSIONS: P110 can enhance the growth inhibitory effects of cisplatin on HCT-116 cells and C26 xenotransplanted tumors in mice. P110 plus cisplatin can reduce the effective dose of cisplatin and decrease the toxicity of cisplatin.

Solvothermal synthesis of bismuth molybdate hollow microspheres with high photocatalytic activity.

Bi2MoO6 hollow microspheres were successfully synthesized by a simple solvothermal process without using any hard template or surfactant. The effect of solvent and urea on the morphology of the samples was studied systematically. The results indicate that the composition of the mix ethylene glycol/absolute ethanol solvents and the urea content play a key role in the final formation of hollow microspheres. Based on the experimental results, the formation mechanism of the hollow interior by an EG-induced Ostwald ripening process was proposed for the Bi2MoO6 hollow microspheres. The Bi2MoO6 hollow microspheres exhibit higher catalytic activity than the Bi2MoO6 particles for degradation of Rhodamine B under visible-light irradiation (lambda > 420 nm). Further investigation revealed that the surface area, grain size, and hollow structure of the as-prepared Bi2MoO6 microspheres are responsible for the improvement of the photocatalytic activity.

[Effect of antisense KLF4 gene on the expression of vWF and PAI-1 in endothelium cells].

OBJECTIVE: To investigate the effect of antisense KLF4 (Krüppel-like factor 4) gene on the expression of vWF and PAI-1 in endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVEC) were isolated from umbilical vein and cultured in endothelial cell medium. The recombinant adenoviral plasmid carrying the antisense KLF4 gene was constructed by homologous recombination. KLF4, PAI-1 and vWF mRNAs and proteins expression were detected by real time-PCR, Western blot, and confocal laser microscopy. RESULTS: Recombinant adenoviral plasmid carrying the antisense KLF4 gene (Ad-KLF4AS) was constructed successfully. Compared with the control Ad-GFP infection group, Ad-KLF4AS at a 200 MOI can down-regulate the expression of KLF4 gene in HUVEC (from 0.59 ± 0.01 to 0.44 ± 0.06) (P < 0.05), and increase vWF mRNA (from 1.04 ± 0.03 to 1.17 ± 0.05) and protein expression (P < 0.05). PAI-1 mRNA and protein of Ad-KLF4AS infection group was higher than that of Ad-GFP infection group. PAI-1 mRNA between the two groups had no significant difference (P > 0.05). CONCLUSIONS: Down-regulation of KLF4 leads to increase in expression of vWF and PAI-1 in endothelial cells. KLF4 might play an important role in regulation of endothelial coagulant function.

[Construction and identification of recombinant adenoviral vector for antisense klf4 gene].

This study was aimed to construct a recombinant adenovirus vector for antisense klf4 gene through AdEasy system. Human klf4 cDNA was reversely inserted into the multiple cloning sites (MCS)of the pShuttle-CMV by using the backbone plasmid AdEasy-l, the antisense klf4 gene was constructed through homologous recombination in E.coli BJ5183, then the adenoviruses were packaged and amplified in the HEK 293 ce1ls. The adenovirus vector for antisense klf4 gene confirmed by PCR, restriction analysis and DNA sequencing. After being transfected with the adenoviruses at 200 MOI for 48 hours, total RNA and protein were extracted from human umbilical vein endothelial cells (HUVEC). Klf4 mRNA and KLF4 protein expression levels were evaluated by Real-time PCR and Western-blot. The results showed that the recombinant adenovirus vector for antisense klf4 gene was successfully constructed, recombinant adenovirus could suppress the expression of klf4 mRNA and KLF4 protein in HUVECs. It is concluded that the adenovirus vector for antisense klf4 gene has been constructed successfully, which provides the material basis for further studying the biologic function and potential application of klf4.

[Effect of blocking of ROCK-1, an effector of small G protein Rho, on the malignant behavior of ovarian tumor cells in vitro].

OBJECTIVE: To investigate the possible role of ROCK-1 in ovarian cancer invasion and metastasis. METHODS: ROCK-1 ASODN was transfected into SW626 and Caov-3 cell lines mediated by Lipofectamine 2000. The expressions of ROCK-1 mRNA and protein were detected by RT-PCR and Western-blot assay. Boyden chamber was used to assess the effect of ROCK-1 ASODN on the invasion and migration of the cell lines. The changes in the adhesion and proliferation of the transfected cells were detected by MTT assay. RESULTS: The expressions level of ROCK-1 mRNA and protein in the cell lines were decreased significantly after transfection at doses of 10 micromol/L and 20 micromol/L ROCK-1 ASODN. When compared with the control group, the invasion capability of transfected cells was inhibited to an extent of 75.6% +/- 3.8% and 54.7% +/- 2.9%, respectively, for SW626 cell line, and 68.8% +/- 4.7% and 50.0% +/- 4.5% for Caov-3 cell line, respectively. The random migratory activity of these two cell lines was inhibited by 80.0% +/- 1.3%, 63.7% +/- 1.9%, 72.5% +/- 3.4% and 55.9% +/- 2.5%, respectively, and the inhibition of chemotaxis activity of the two cell lines was 83.9% +/- 1.4%, 64.1% +/- 1.3%, 72.5% +/- 3.4% and 54.5% +/- 1.9%, respectively. No significant difference was found in the adhesion and proliferation of the cells transfected with ROCK-1 ASODN and control cells. CONCLUSION: The expression of ROCK-1 was closely related to the invasion capability and migratory activity of ovarian cancer cells. ROCK-1 may play a crucial role in invasion and metastasis of ovarian cancer.

Variation in the coordination mode of arenedisulfonates: syntheses and structural characterization of mononuclear and dinuclear cadmium(II) arenedisulfonate complexes with two- to zero-dimensional architectures.

Seven cadmium(II) arenedisulfonate compounds, namely [Cd(2,2'-bpy)(2)(H(2)O)(peds)].4H(2)O (1), [Cd(2)(2,2'-bpy)(4)(H(2)O)(2)(1,5nds)](1,5nds).4H(2)O (2), [Cd(cyclam)(1,5nds)](2) (3), ([Cd(inia)(2)(H(2)O)(2)(2,6nds)].4H(2)O)(n)(4), ([Cd(inia)(2)(H(2)O)(2)(bpds)].4H(2)O)(n)(5), ([Cd(2)(inia)(4)(H(2)O)(3)(peds)(2)].2H(2)O)(n)(6), and [Cd(1,5nds)(H(2)O)(2)](n) (7), where 2,2'-bpy = 2,2'-bipyridyl, cyclam = 1,4,8,11-tetraazacyclotetradecane, inia = isonicotinamide, nds = naphthalenedisulfonate, bpds = 4,4'-biphenyldisulfonate, and peds = 4,4'-phenyletherdisulfonate, have been obtained from aqueous solution by using similar procedures and structurally characterized by X-ray single-crystal diffraction, IR spectroscopy, and thermal gravimetric analysis. In 1, the peds anion coordinates as a monodentate ligand, leading to a mononuclear unit. In 2 and 3, the 1,5nds anions coordinate as mu(2)-bridging ligands in different modes, producing charged or neutral dinuclear clusters. In 4 and 5, 2,6nds and bpds behave as mu(2)-spacers, resulting in 1-dimensional polymers. While in 6, the peds acts both as terminal and bridging ligands with the SO(3)(-) groups being either monodentate or mu(2)-bridging, creating a knotted 1-dimensional polymer with dinuclear clusters as the repeating units. In 7, 1,5nds acts as a bridging ligand with each SO(3)(-) coordinated as a mu(2)-bridging group to adjacent Cd(II) centers, leading to a 2-dimensional polymer. Together with the reported ([Cu(en)(2)(1,5nds)].2H(2)O)(n) (8), all of the six possible coordination modes adopted by organodisulfonate anions, on the assumption that each SO(3)(-) group could be monodentate or mu(2)-bridging, are realized by introducing nitrogen-containing organic ligands as auxiliaries.

Di-mu-chloro-bis([2-[N,N-bis(2-aminoethyl)amino-kappa3N]ethylaminium]-copper(II)) bis(naphthalene-1,5-disulfonate) pentahydrate.

The title compound, [Cu2(C6H19N4)2Cl2](C10H6O6S2)2*5H2O, is comprised of discrete [Cu2(tren)2Cl2]2+ dimers [tren is 2-[N,N-bis(2-aminoethyl)amino]ethylaminium] and naphthalene-1,5-disulfonate anions. Two Cl- anions bridge two Cu(II) ions, each of which is also coordinated by two of the primary and the tertiary amino N atoms of the tren ligand, giving each metal atom a distorted square-pyramidal coordination geometry. The cation lies about an inversion centre and the asymmetric unit also has two independent anions lying about inversion centres.