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1.
Pharmaceutics ; 15(6)2023 May 26.
Article in English | MEDLINE | ID: mdl-37376050

ABSTRACT

Metal-organic frameworks (MOFs) are porous materials composed of metal ions and organic ligands. Due to their large surface area, easy modification, and good biocompatibility, MOFs are often used in bio-related fields. Fe-based metal-organic frameworks (Fe-MOFs), as important types of MOF, are favored by biomedical researchers for their advantages, such as low toxicity, good stability, high drug-loading capacity, and flexible structure. Fe-MOFs are diverse and widely used. Many new Fe-MOFs have appeared in recent years, with new modification methods and innovative design ideas, leading to the transformation of Fe-MOFs from single-mode therapy to multi-mode therapy. In this paper, the therapeutic principles, classification, characteristics, preparation methods, surface modification, and applications of Fe-MOFs in recent years are reviewed to understand the development trends and existing problems in Fe-MOFs, with the view to provide new ideas and directions for future research.

2.
J Colloid Interface Sci ; 646: 370-380, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37207419

ABSTRACT

In recent years, small interfering RNA (siRNA) has been widely used in the treatment of human diseases, especially tumors, and has shown great appeal. However, the clinical application of siRNA faces several challenges. Insufficient efficacy, poor bioavailability, poor stability, and lack of responsiveness to a single therapy are the main problems affecting tumor therapy. Here, we designed a cell-penetrating peptide (CPP)-modified metal organic framework nanoplatform (named PEG-CPP33@ORI@survivin siRNA@ZIF-90, PEG-CPP33@NPs) for targeted co-delivery of oridonin (ORI), a natural anti-tumor active ingredient) and survivin siRNA in vivo. This can improve the stability and bioavailability of siRNA and the efficacy of siRNA monotherapy. The high drug-loading capacity and pH-sensitive properties of zeolite imidazolides endowed the PEG-CPP33@NPs with lysosomal escape abilities. The Polyethylene glycol (PEG)-conjugated CPP (PEG-CPP33) coating significantly improved the uptake in the PEG-CPP33@NPs in vitro and in vivo. The results showed that the co-delivery of ORI and survivin siRNA greatly enhanced the anti-tumor effect of PEG-CPP33@NPs, demonstrating the synergistic effect between ORI and survivin siRNA. In summary, the novel targeted nanobiological platform loaded with ORI and survivin siRNA presented herein showed great advantages in cancer therapy, and provides an attractive strategy for the synergistic application of chemotherapy and gene therapy.


Subject(s)
Cell-Penetrating Peptides , Metal-Organic Frameworks , Nanoparticles , Neoplasms , Humans , Survivin/genetics , RNA, Small Interfering/genetics , Lysosomes , Nanoparticles/chemistry , Cell Line, Tumor
3.
Mol Pharm ; 20(2): 875-885, 2023 02 06.
Article in English | MEDLINE | ID: mdl-36689197

ABSTRACT

Chlorin e6 (Ce6) has been extensively researched and developed as an antitumor therapy. Ce6 is a highly effective photosensitizer and sonosensitizer with promising future applications in photodynamic therapy, dynamic acoustic therapy, and combined acoustic and light therapy for tumors. Ce6 is also being studied for other applications in fluorescence navigation, antibacterials, and plant growth regulation. Here we review the role and research status of Ce6 in tumor therapy and the problems and challenges of its clinical application. Other biomedical effects of Ce6 are also briefly discussed. Despite the difficulties in clinical application, Ce6 has significant advantages in photodynamic therapy (PDT)/sonodynamic therapy (SDT) against cancer and offers several possibilities in clinical utility.


Subject(s)
Chlorophyllides , Neoplasms , Photochemotherapy , Porphyrins , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Neoplasms/drug therapy , Porphyrins/pharmacology , Porphyrins/therapeutic use , Cell Line, Tumor
4.
Molecules ; 26(10)2021 May 11.
Article in English | MEDLINE | ID: mdl-34064812

ABSTRACT

A novel approach for synthesizing the key dolutegravir intermediate is described via MgBr2-promoted intramolecular cyclization. Condensation of commercially available methyl oxalyl chloride and ethyl 3-(N,N-dimethylamino)acrylate afforded the vinylogous amide in an excellent yield. Subsequent substitution by aminoacetaldehyde dimethyl acetal and methyl bromoacetate gave rise to the expected precursor for cyclization, which was promoted by MgBr2 to highly selectively convert into pyridinone diester. The key dolutegravir intermediate was finally prepared by the selective hydrolysis of the corresponding diester via LiOH.


Subject(s)
Bromides/chemistry , Heterocyclic Compounds, 3-Ring/chemistry , Magnesium Compounds/chemistry , Oxazines/chemistry , Piperazines/chemistry , Pyridones/chemistry , Cyclization , Heterocyclic Compounds, 3-Ring/chemical synthesis , Hydrolysis , Oxazines/chemical synthesis , Piperazines/chemical synthesis , Pyridones/chemical synthesis , Temperature
5.
Gene ; 741: 144548, 2020 May 30.
Article in English | MEDLINE | ID: mdl-32165292

ABSTRACT

The Integrator complex (INT) contains several subunits that participate in RNAPII transcription and the 3' end process of non-coding RNAs. INTS11 is the catalytic subunit that interacts with the C-terminal domain of RNAPII, recently found to play a role in embryo development in different experimental models. However, the involvement of INTS11 is still ignorant in crustaceans, particularly in post-diapause embryonic development of Artemia sinica. In the present research, the full-length cDNA of As-Ints11 gene (1964 bp) was cloned from A. sinica by the RACE technique. The deduced 597 amino acids sequence contains the most identifiable domains of the INTs and is highly conserved. Immunofluorescence assay showed that the INTS11 was present at diverse developmental status in A. sinica: the As-INTS11 can be found in both cytoplasm and nucleus of the embryos, and the location showed no specificity in tissue or organ of the nauplius. The expression patterns of As-Ints11 were analyzed by qPCR and Western blotting, which show similar trends that peaked at the 15 h stage of embryo development. Moreover, the expressions of interacting proteins As-INTS9 and As-RNAPII were also detected, results display a synergetic effect with the As-INTS11 at both mRNA and protein levels. We also explored the amount of As-INTS11, As-INTS9 and As-RNAPII under different stresses, and the results indicate that the As-INTS11 is a stress-related protein though the mechanism needs further research. Knocking down of the As-INTS11 resulted in a delay of post-diapaused embryonic development in A. sinica.


Subject(s)
Artemia/genetics , Diapause/genetics , Embryonic Development/genetics , Endoribonucleases/genetics , Amino Acid Sequence/genetics , Animals , Artemia/growth & development , Cloning, Molecular , Embryo, Nonmammalian , Gene Expression Regulation, Developmental , RNA, Messenger/genetics
6.
Int J Ophthalmol ; 12(6): 936-942, 2019.
Article in English | MEDLINE | ID: mdl-31236349

ABSTRACT

AIM: To investigate the occurrence of chronic photodamage in the cone-based retina, following long-term exposure to a 650-nm semiconductor laser (power: 2 mW). METHODS: Chickens fed for 1mo under natural light after hatching were irradiated with 650-nm laser light at different times each day. Fifteen animals were included in each group. Group A was a control group, irradiated with natural light during the entire study. Group B was irradiated with laser for 3 min/d. Group C was irradiated with laser for 6 min/d. Group D was irradiated with laser for 30 min/d. The duration of the light experiment was 6mo. We obtained data at 1, 3, and 6mo, including measuring the retinal thickness in vivo using optical coherence tomography, hematoxylin and eosin staining, TUNEL assay, apoptosis staining, malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and Western blotting to detect changes in L/M opsins and rhodopsin. RESULTS: At 1mo, the MDA content in Group D was higher than that observed in Group A (P=0.019). At 3mo the MDA content in Groups C and D was higher than that reported in Group A (P=0.026, 0.003). At 6mo, the MDA content in Groups B, C, and D was higher than that observed in Group A (P=0.038, 0.032, 0.000, respectively). There was no difference in SOD activity, and L/M opsin and rhodopsin content between the groups at 1 and 3mo. The SOD activity in group D was significantly decreased at 6mo (P=0.000), as was the content of rhodopsin. There was no significant reduction observed in retinal thickness, abnormal cell arrangement, and positive staining of TUNEL in the groups during the 6-month study period. CONCLUSION: Irradiation using a 650 nm semiconductor laser (power: 2 mW) for 6min per day over 6mo do not cause photodamage. Similarly, a 3-month exposure of 30min per day do not cause damage. However, irradiation for 6mo resulted in a significant increase in the content of free radicals and a decrease in the content of rhodopsin in the retina, suggesting the presence of photodamage.

7.
Org Lett ; 20(7): 1941-1944, 2018 04 06.
Article in English | MEDLINE | ID: mdl-29522349

ABSTRACT

Oxidation of neo-N-confused phlorin 1 with excessive FeCl3 leads to regioselective ring opening, generating three linear tetrapyrroles, i.e., (10 Z,15 Z)-biladienone 2, (10 Z,15 E)-biladienone 3, and 19-methoxy (10 Z,15 E)-biladiene 4 with an overall yield of 88%. The coordination of these compounds with Zn(II) is affected by the inverted terminal pyrrolic unit, and the presence of the electron-withdrawing keto moiety. The structural identities were also clearly elucidated by the crystal structures of 3 and 4-Zn and were rationalized by DFT calculations.

8.
Molecules ; 22(9)2017 Aug 23.
Article in English | MEDLINE | ID: mdl-28832543

ABSTRACT

Novel meso-meso directly linked porphyrin hybrids were successfully targeted and synthesized, with porphyrin units linked with dipyrrin, bidipyrrin or thiacorrole, expanding the ranges of dipyrrin derivatives and showing diverse metal coordinations and further influencing the chemical shift of pyrrole units. The porphyrinyl dipyrrin nickel complex 3 was successfully obtained in a high yield by the oxidation of porphyrinyl dipyrromethane 2 and subsequent coordination. Further oxidative coupling reactions of 3 afforded por-bidipyrrin-por hybrid 4. Interestingly, an unexpected methoxy por-bidipyrrin-por hybrid 6 was generated by treating 4 with FeCl3 in CH2Cl2/MeOH and subsequent coordination. In addition to open chain hybrids, an aromatic scaffold hybrid por-thiacorrole-por 8 was synthesized by treating porphyrinyl dibromo-dipyrrin nickel complex 7 with Na2S·9H2O. A series of porphyrin hybrids offers a new approach for π-conjugated molecules.


Subject(s)
Porphyrins/chemistry , Pyrroles/chemistry , Crystallography, X-Ray , Dimerization , Molecular Structure , Proton Magnetic Resonance Spectroscopy
9.
Sci Rep ; 7(1): 408, 2017 03 24.
Article in English | MEDLINE | ID: mdl-28341839

ABSTRACT

The aim of this study was to evaluate the effects of intravitreal injection of neural stem cells (NSCs) originating from human umbilical cord-derived mesenchymal stem cells (UC-MSCs) on neurodegeneration of diabetic retinopathy (DR) in rats. UC-MSCs were isolated and passaged, followed by induction to NSCs in neural differentiation medium. Four weeks following NSC transplantation, treatment attenuated retinal vascular dysfunction compared with non-treated rats, and BDNF and Thy-1 expression was significantly higher in the treated group than in the control group. Treatment of diabetic rats with NSCs prevented the decrease in BDNF levels caused by diabetes. The average leakage of Evans Blue (EB) dye in the treated group was significantly less than that in the control group. These morphological improvements were accompanied by a restoration of vision, as documented by F-ERG. NSCs originating from MSCs demonstrated a neuroprotective effect by increasing the number of surviving RGCs and significantly reducing the progression of DR. Thus, transplantation of NSCs could be a novel strategy for the treatment of neurodegeneration in DR.


Subject(s)
Cord Blood Stem Cell Transplantation/methods , Diabetic Retinopathy/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/physiology , Neural Stem Cells/physiology , Animals , Blood-Retinal Barrier/physiopathology , Brain-Derived Neurotrophic Factor/metabolism , Cells, Cultured , Diabetic Retinopathy/physiopathology , Intravitreal Injections , Male , Mesenchymal Stem Cells/metabolism , Neural Stem Cells/metabolism , Rats, Sprague-Dawley , Umbilical Cord/cytology
10.
Org Lett ; 19(3): 650-653, 2017 02 03.
Article in English | MEDLINE | ID: mdl-28112522

ABSTRACT

By the acid-catalyzed [2 + 2] condensation, an unprecedented neo-N-confused phlorin (neo-NCphlorin 1) was successfully synthesized. By treating 1 with N-chlorosuccinimide, the corresponding chloro-substituted neo-NCphlorin (1-Cl) was obtained. The oxidization of 1 with FeCl3 afforded the neo-N-confused phlorinone (neo-NCphlorinone 2), which bears a relatively coplanar conformation, different from the highly distorted ones observed for 1 and 1-Cl. Notably, 2 shows striking long-wavelength absorption beyond 1300 nm upon addition of TBAF.

11.
Org Lett ; 18(19): 5046-5049, 2016 10 07.
Article in English | MEDLINE | ID: mdl-27676364

ABSTRACT

By oxidation of an alternately N-confused bilane in CH2Cl2, a C-N fused tetrapyrrin was synthesized that bears a 5.5.5-tricyclic ring generated from an intramolecular C-N linkage. When CH3CN was used as the reaction medium, a multiply C-N-fused octapyrrolic dimer was also obtained that contained two 5.5.5.7.5-pentacyclic moieties and a bipyrrole unit generated from the intramolecular C-N linkage and intermolecular C-C linkage, respectively. This could be coordinated with Ni(acac)2 to afford a mixed-ligand complex.

12.
Int J Ophthalmol ; 9(1): 41-7, 2016.
Article in English | MEDLINE | ID: mdl-26949608

ABSTRACT

AIM: To investigate whether umbilical cord human mesenchymal stem cell (UC-MSC) was able to differentiate into neural stem cell and neuron in vitro. METHODS: The umbilical cords were obtained from pregnant women with their written consent and the approval of the Clinic Ethnics Committee. UC-MSC were isolated by adherent culture in the medium contains 20% fetal bovine serum (FBS), then they were maintained in the medium contain 10% FBS and induced to neural cells in neural differentiation medium. We investigated whether UC-MSC was able to differentiate into neural stem cell and neuron in vitro by using flow cytometry, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence (IF) analyzes. RESULTS: A substantial number of UC-MSC was harvested using the tissue explants adherent method at about 2wk. Flow cytometric study revealed that these cells expressed common markers of MSCs, such as CD105 (SH2), CD73 (SH3) and CD90. After induction of differentiation of neural stem cells, the cells began to form clusters; RT-PCR and IF showed that the neuron specific enolase (NSE) and neurogenic differentiation 1-positive cells reached 87.3%±14.7% and 72.6%±11.8%, respectively. Cells showed neuronal cell differentiation after induced, including neuron-like protrusions, plump cell body, obviously and stronger refraction. RT-PCR and IF analysis showed that microtubule-associated protein 2 (MAP2) and nuclear factor-M-positive cells reached 43.1%±10.3% and 69.4%±19.5%, respectively. CONCLUSION: Human umbilical cord derived MSCs can be cultured and proliferated in vitro and differentiate into neural stem cells, which may be a valuable source for cell therapy of neurodegenerative eye diseases.

13.
PLoS One ; 10(12): e0144406, 2015.
Article in English | MEDLINE | ID: mdl-26636823

ABSTRACT

OBJECTIVES: To date, the relationship between C-reactive protein (CRP) level and diabetic retinopathy (DR) remains controversial. Therefore, a systematic review and meta-analysis was used to reveal the potential relationship between CRP level and DR. METHODS: A systematic search of PubMed, Embase.com, and Web of Science was performed to identify all comparative studies that compared the CRP level of two groups (case group and control group). We defined that diabetic patients without retinopathy and/or matched healthy persons constituted the control group, and patients with DR were the case group. RESULTS: Two cross sectional studies and twenty case control studies including a total of 3679 participants were identified. After pooling the data from all 22 studies, obvious heterogeneity existed between the studies, so a subgroup analysis and sensitivity analysis were performed. Removing the sensitivity studies, the blood CRP levels in the case group were observed to be higher than those in the control group [SMD = 0.22, 95% confidence interval (CI), 0.11-0.34], and the blood CRP levels in the proliferative diabetic retinopathy (PDR) group were also higher than those in the non-proliferative diabetic retinopathy (NPDR) group [SMD = 0.50, 95% CI, 0.30-0.70]. CONCLUSIONS: The results from this current meta-analysis indicate that the CRP level might be used as a biomarker to determine the severity of DR.


Subject(s)
C-Reactive Protein/metabolism , Diabetic Retinopathy/blood , Severity of Illness Index , Biomarkers/blood , Humans
14.
Int J Ophthalmol ; 8(4): 764-9, 2015.
Article in English | MEDLINE | ID: mdl-26309877

ABSTRACT

AIM: To investigate the visual function and the relationship with vision-related quality of life (VRQOL) after macular hole repair surgery. METHODS: Prospective case series. Thirty-six consecutive eyes in 36 patients who underwent pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peeling were included. The 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was answered by the participants before and 3 and 12mo after operation. Follow-up visits examinations included best-corrected visual acuity (BCVA), clinical examination, and central macular thickness (CMT) measured by optical coherence tomography (OCT). RESULTS: Macular-hole closure was achieved in 35 of 36 eyes (97.2%). At baseline and months 3 and 12, the logMAR BCVAs (mean±SD) were 1.15±0.47, 0.68±0.53 (P<0.0001 versus baseline), and 0.55±0.49 (P<0.001 versus baseline, P =0.273 versus month 3), respectively; the CMTs (µm) were 330±81, 244±62 (P<0.001 versus baseline), and 225±58 (P<0.001 versus baseline, P=0.222 versus month 3), respectively; the median preoperative VFQ-25 composite score of 73.50 (63.92-81.13) increased postoperatively to 85.50 (80.04-89.63) at 3mo (P<0.001) and 86.73(82.50-89.63) at 12mo (P<0.001) respectively. The improved BCVA was correlated with improvements in five subscales (r=-0.605 to -0.336, P<0.001 to P=0.046) at 12mo. CONCLUSION: PPV with ILM peeling improved anatomic outcome, visual function, and VRQOL. The improved BCVA was an important factor related to the improved VRQOL.

15.
Int J Ophthalmol ; 8(2): 257-62, 2015.
Article in English | MEDLINE | ID: mdl-25938037

ABSTRACT

AIM: To observe the effects of intravitreal injections of different concentrations of human umbilical mesenchymal stem cells on retinopathy in rats with diabetes mellitus. METHODS: Healthy and adult male Sprague-Dawley (SD) rats were randomly assigned to a normal control group (group A), a diabetic retinopathy (DR) blank control group (group B), a high-concentration transplantation group (group C), a low-concentration transplantation group (group D) and a placebo transplantation group (group E). The expression of nerve growth factor (NGF) protein in the retinal layers was detected by immunohistochemical staining at 2, 4, 6 and 8wk. RESULTS: The expression of NGF was positive in group A and most positive in the retinal ganglion cell layer. In groups B and E, the expression of NGF was positive 2wk after transplantation and showed an increase in all layers. However, the level of expression had decreased in all layers at 4wk and was significantly reduced at 8wk. In groups C and D, the expression of NGF had increased at 2wk and continued to increase up to 8wk. The level of expression in group C was much higher than that in group D. CONCLUSION: DR can be improved by intravitreal injection of human umbilical mesenchymal stem cells. High concentrations of human umbilical mesenchymal stem cells confer a better protective effect on DR than low concentrations.

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