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1.
J Stomatol Oral Maxillofac Surg ; : 101908, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38703996

ABSTRACT

OBJECTIVE: To investigate the characteristics and treatment modalities of malignant tumors originating from the sublingual gland, as well as evaluate the therapeutic outcomes following free flap reconstruction. METHODS: A retrospective statistical analysis was conducted on the clinical data of nine patients diagnosed with malignant neoplasms tumor of the sublingual gland. RESULTS: Nine case of malignant tumors originated from the sublingual glandular tissue, encompassing eight adenoid cystic carcinoma (ACC) and a single case of bipartite differentiated carcinoma-a hybrid of epithelial-myoepithelial carcinoma and adenoid cystic carcinoma. Among the nine patients, four anterolateral thigh flaps were used (three of which were thin flaps), and five forearm flaps were also empoyed. The size of flaps varied, with the lengths ranging from 4 cm to 9 cm, and the widths ranging from 2.5 cm to 6 cm. The vessels chosen for anastomosis were the superior thyroid artery in seven cases, the facial artery in one case, and the lingual artery in one case. Among the eight patients who underwent dissection of cervical lymph nodes, metastasis were found in one case. Two patients underwent adjuvant radiotherapy. Upon postoperative follow-up, there was no recurrence in any of the nine patients . CONCLUSION: The anterolateral thigh perforator flap thinning technique can be employed for postoperative reconstruction of malignant sublingual gland tumors.

2.
Bioorg Chem ; 144: 107166, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38308998

ABSTRACT

Twelve phthalideisoquinoline hemiacetal alkaloids including eight new ones (1-8) and one natural alkaloid characterized by an aziridine moiety with unassigned NMR data (9), were isolated and identified from the bulbs of Corydalis decumbens. Their structures were established by comprehensive analyses of HRESIMS, NMR, X-ray crystallography, and ECD analyses. The unambiguously established structures of the phthalideisoquinoline hemiacetal alkaloids indicated that the absolute configurations of C-1, C-9, and C-7' were confusable only relied on coupling constants. A summary of their ECD spectra was concluded and provided an insight for C-1, C-9, and C-7' absolute configuration assignment. These new compounds were evaluated to induce autophagy flux through flow cytometry analysis. Moreover, compounds 2 and 6 could significantly induce autophagy and inhibit Tau pathology by AMPK-ULK1 pathway activation, which provided an avenue for anti-AD lead compounds discovery.


Subject(s)
Alkaloids , Corydalis , Corydalis/chemistry , AMP-Activated Protein Kinases/metabolism , Alkaloids/chemistry , Magnetic Resonance Spectroscopy , Autophagy
3.
Adv Mater ; 36(16): e2308155, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38295870

ABSTRACT

Following the success of the dendritic cell (DC) vaccine, the cell-based tumor vaccine shows its promise as a vaccination strategy. Except for DC cells, targeting other immune cells, especially myeloid cells, is expected to address currently unmet clinical needs (e.g., tumor types, safety issues such as cytokine storms, and therapeutic benefits). Here, it is shown that an in situ injected macroporous myeloid cell adoptive scaffold (MAS) not only actively delivers antigens (Ags) that are triggered by scaffold-infiltrating cell surface thiol groups but also releases granulocyte-macrophage colony-stimulating factor and other adjuvant combos. Consequently, this promotes cell differentiation, activation, and migration from the produced monocyte and DC vaccines (MASVax) to stimulate antitumor T-cell immunity. Neoantigen-based MASVax combined with immune checkpoint blockade induces rejection of established tumors and long-term immune protection. The combined depletion of immunosuppressive myeloid cells further enhances the efficacy of MASVax, indicating the potential of myeloid cell-based therapies for immune enhancement and normalization treatment of cancer.


Subject(s)
Cancer Vaccines , Neoplasms , Humans , Neoplasms/drug therapy , Vaccination , Cell Engineering , Myeloid Cells , Dendritic Cells
4.
Bioorg Chem ; 127: 106004, 2022 10.
Article in English | MEDLINE | ID: mdl-35843015

ABSTRACT

Cardiac glycosides (CGs) show potential broad-spectrum antiviral activity by targeting cellular host proteins. Herein are reported the isolation of five new (1-5) and eight known (7-13) CGs from the roots of Streblus asper Lour. Of these compounds 1 and 7 exhibited inhibitory action against EBV early antigen (EA) expression, with half-maximal effective concentration values (EC50) being less than 60 nM, and they also showed selectivity, with selectivity index (SI) values being 56.80 and 103.17, respectively. Preliminary structure activity relationships indicated that the C-10 substituent, C-5 hydroxy groups, and C-3 sugar unit play essential roles in the mediation of the inhibitory activity of CGs against EBV. Further enzyme experiments demonstrated that these compounds might inhibit ion pump function and thereby change the intracellular signal transduction pathway by binding to Na+/K+-ATPase, as validated by simulated molecular docking. This study is the first report that CGs can effectively limit EBV lytic replication, and the observations made in this study may be of value for lead compound development.


Subject(s)
Cardiac Glycosides , Epstein-Barr Virus Infections , Moraceae , Cardiac Glycosides/chemistry , Epstein-Barr Virus Infections/drug therapy , Herpesvirus 4, Human/metabolism , Molecular Docking Simulation , Moraceae/chemistry
5.
Nano Res ; 15(7): 6328-6339, 2022.
Article in English | MEDLINE | ID: mdl-35464625

ABSTRACT

Immunostimulatory therapies based on pattern recognition receptors (PRRs) have emerged as an effective approach in the fight against cancer, with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment. The agonist cyclic dinucleotides (CDNs) of the stimulator of interferon gene (STING) are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity. However, the tumor immune efficacy of CDNs is limited by several factors, including relatively narrow cytokine production, inefficient delivery to STING, and rapid clearance. In addition, a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect. To address this problem, two or more agonist molecules are often used together to synergistically enhance immune efficacy. In this work, we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8 (TLR7/8) agonist 522 produced a broader cytokine response. Subsequently, we developed multicomponent nanovaccines (MCNVs) consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules. These MCNVs activate bone marrow-derived dendritic cells (BMDCs) to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor T-cell responses. In in vivo experiments, we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes, resulting in significant tumor regression and, notably, a 100% survival rate in mice through 25 days without other partnering therapies. These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency. Electronic Supplementary Material: Supplementary material (synthesis of CDGSF, 522, PC7A and OVA; preparation of MCNVs; representative gating strategies for flow cytometry) is available in the online version of this article at 10.1007/s12274-022-4282-x.

6.
Biomaterials ; 273: 120788, 2021 06.
Article in English | MEDLINE | ID: mdl-33933912

ABSTRACT

Intrinsic immune behaviors of nanomaterials and immune systems promote research on their adjuvanticity and the design of next generation nanovaccine-based immunotherapies. Herein, we report a promising multifunctional nanoadjuvant by exploring the immune-potentiating effects of black phosphorus nanosheets (BPs) in vitro and in vivo. The facile coating of BPs with phenylalanine-lysine-phenylalanine (FKF) tripeptide-modified antigen epitopes (FKF-OVAp@BP) enables the generation of a minimalized nanovaccine by integrating high loading capacity, efficient drug delivery, comprehensive dendritic cell (DC) activation, and biocompatibility for cancer immunotherapy. Systemic immunization elicits potent antitumor cellular immunity and significantly augments checkpoint blockade (CPB) against melanoma in a mouse model. Furthermore, near-infrared (NIR) photothermal effects of BPs create an immune-favorable microenvironment for improved local immunization. This study offers new insight into the integration of immunoactivity and photothermal effects for enhanced cancer immunotherapy by using a nanoadjuvant and thus potentially advances the design and application of multifunctional adjuvant materials for cancer nanotreatment.


Subject(s)
Immunotherapy , Phosphorus , Adjuvants, Immunologic , Animals , Drug Delivery Systems , Immunologic Factors , Mice
7.
Chem Commun (Camb) ; 57(4): 504-507, 2021 Jan 14.
Article in English | MEDLINE | ID: mdl-33331360

ABSTRACT

A novel STING agonist, CDGSF, ipsilaterally modified with phosphorothioate and fluorine, was synthesized. The phosphorothioate in CDGSF might be a site for covalent conjugation. Injection of CDGSF generated an immunogenic ("hot") tumor microenvironment to suppress melanoma, more efficiently than dithio CDG. In particular, immunization with SARS-CoV-2 spike protein using CDGSF as an adjuvant elicited an exceptionally high antibody titer and a robust T cell response, overcoming the drawbacks of aluminum hydroxide. These results highlighted the therapeutic potential of CDGSF for cancer immunotherapy and the adjuvant potential of the STING agonist in the SARS-CoV-2 vaccine for the first time.


Subject(s)
Adjuvants, Immunologic/administration & dosage , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Melanoma, Experimental/drug therapy , Membrane Proteins/agonists , Nucleotides, Cyclic/administration & dosage , Skin Neoplasms/drug therapy , Adjuvants, Immunologic/chemical synthesis , Aluminum Hydroxide/administration & dosage , Aluminum Hydroxide/chemistry , Animals , Antibodies, Viral/biosynthesis , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , B-Lymphocytes/virology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/chemistry , Enzyme-Linked Immunospot Assay , Humans , Immunotherapy/methods , Interferon-gamma/biosynthesis , Melanoma, Experimental/immunology , Melanoma, Experimental/mortality , Melanoma, Experimental/pathology , Membrane Proteins/genetics , Membrane Proteins/immunology , Mice , Nucleotides, Cyclic/chemical synthesis , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Skin Neoplasms/immunology , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Spike Glycoprotein, Coronavirus/administration & dosage , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Survival Analysis , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/virology , Tumor Burden/drug effects , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Vaccination/methods
8.
Phytochemistry ; 181: 112544, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33130375

ABSTRACT

Phytochemical investigation of the roots of Streblus asper Lour. resulted in the isolation of six previously undescribed cardiac glycosides, designated 2'-de-O-methylstrebloside (1), cannogenol-3α-O-ß-D-gluopyranosyl-(1 â†’ 4)-6-deoxy -2,3-dimethoxyl-ß-D-fucopyranoside (2), periplogenin-3-O-α-L-rhamnopyranosyl -(1 â†’ 4)-6-deoxy-ß-D-allopyranoside (3), 5-de-O-hydroxylstrebloside (4), 5ßH-16ß-hydroxylkamaloside (5), and 17S, 21R-21-hydroxylstrebloside (6), and three known analogues (7-9). The structures were elucidated using NMR spectroscopic techniques, mass spectrometry, and comparison of the spectroscopic data with previously reported data. Compound 6 is a novel C-21 hydroxyl cardiac glycoside, its absolute configuration was established from the analysis of computational ECD calculations and NMR spectroscopic data. The effects of the cardiac glycosides on apoptosis and cytotoxicity were examined in human A549 lung cancer cells. All the compounds showed remarkable inhibitory activities, with IC50 values in the range of 0.01-6.08 µM. Furthermore, compound 3 was able to significantly inhibit A549 cell growth proliferation via the induction of apoptosis, due to the activation of caspases-3, -8 and -9 in A549 cells, as revealed by Western blot analysis.


Subject(s)
Cardiac Glycosides , Moraceae , A549 Cells , Apoptosis , Cardiac Glycosides/pharmacology , Glycosides/pharmacology
9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-905994

ABSTRACT

Objective:To re-evaluate the intervention effect of Kuijietong(KJT) on ulcerative colitis(UC). Method:Sixty patients with mild-to-moderate UC in the active stage were enrolled and randomized into a KJT group (<italic>n</italic>=30) and a sulfasalazine (SASP) group (<italic>n</italic>=30). Patients in the KJT group were treated with KJT granules, one bag divided in two daily doses, once in the morning and once in the evening, while those in the SASP group received SASP, 1 g per time, four times per day. Then the clinical efficacy was evaluated. Result:According to the modified Mayo score,the clinical remission rates of the KJT group and SASP group were determined to be 46.7% (14/30)and 40% (12/30),exhibiting no significant difference between the two groups (<italic>P</italic>>0.05). The clinical effective rate of the KJT group was 83.3% (25/30),which was better than 60% (18/30) of the SASP group (<italic>P</italic><0.05). The mucosal healing rate in the KJT group was 36.7% (11/30), not significantly different from 30% (9/30) in the SASP group. In the alleviation of UC symptoms,the score of large intestine dampness heat syndrome in the KJT group was remarkably better than that in the SASP group (<italic>P</italic><0.05),but there was no significant difference in inflammatory bowel disease questionnaire (IBDQ) score between the two groups. In terms of physical and chemical indexes,serum erythrocyte sedimentation rate (ESR) in the KJT group after intervention was lower than that in the SASP group (<italic>P</italic><0.05),whereas the interleukin-10 (IL-10) level was higher(<italic>P</italic><0.05). The comparison between the two groups revealed no significant difference in C-reactive protein (CRP), tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>), CD4<sup>+</sup> T cells and regulatory T (Treg) cells after intervention. During the intervention,no obvious adverse reactions were found in the two groups,indicating good safety. Conclusion:KJT is not inferior to SASP in relieving mild-to-moderate UC in the active stage.

10.
Bioconjug Chem ; 31(11): 2499-2503, 2020 11 18.
Article in English | MEDLINE | ID: mdl-33147965

ABSTRACT

Cyclic dinucleotides (CDNs), agonists of stimulator of interferon genes (STING), are promising agents for immunotherapy. However, the application of CDNs has been limited by their instability and low transmembrane efficiency. Here, we introduced a conjugated adjuvant of STING and TLR1/2, Pam3CSK4-CDGSF. Conjugating CDGSF with Pam3CSK4 increased the stability and intracellular delivery. In addition, by synergistically activating the STING and TLR pathways, Pam3CSK4-CDGSF was able to enhance immune activation. Both humoral and cellular immune responses were triggered by Pam3CSK4-CDGSF plus OVA (V4), and tumor growth was significantly inhibited after V4 administration. More importantly, V4 can also boost the antigen-specific CD8+ T cell response for cancer cell killing. Thus, the conjugated STING and TLR1/2 agonist Pam3CSK4-CDGSF can serve as a potent adjuvant for vaccine construction to augment antitumor immunotherapy.


Subject(s)
Immunotherapy , Lipopeptides/pharmacology , Membrane Proteins/agonists , Neoplasms/therapy , Toll-Like Receptor 2/agonists , Animals , Antibody Formation , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Humans , Immunity, Cellular , Mice , Neoplasms/immunology , Toll-Like Receptor 1/agonists
11.
J Ethnopharmacol ; 257: 112778, 2020 Jul 15.
Article in English | MEDLINE | ID: mdl-32205260

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Sauropus androgynus L. Merr is an underexploited perennial shrub traditionally used as a medicinal plant in South Asia and Southeast Asia. The plant is regarded as not just a green vegetable for diet, but as a traditional herb for certain aliments. For instance, it has traditionally been used to relieve fever, to treat ulcers and diabetes, to promote lactation and eyesight, and to reduce obesity. AIM OF THE STUDY: This paper aims to review the botany, phytochemistry, ethnopharmacology, and pharmacological activities of S. androgynus, and discuss the known chemical constituents at work in S. androgynus-induced bronchiolitis obliterans for providing new ideas to the mechanism of the disease and pharmacology research of the plant. MATERIALS AND METHODS: The data presented in this review were collected from published literatures as well as the electronic databases of PubMed, CNKI, Web of Science, SCI finder, ACS, Science Direct, Wiley, Springer, Taylor, Google Scholar, and a number of unpublished resources, (e.g. books, and Ph.D. and M.Sc. dissertations). RESULTS: The scientific literature indicates that S. androgynus is a valuable and popular herbal medicine whose nutritional value is also higher than that of other commonly used vegetables. Phytochemical analyses identified high content of fatty acids, flavonoids, and polyphenols as the major bioactive components in S. androgynus. Crude extracts and phytochemical compounds isolated from S. androgynus show a wide spectrum of in vitro and in vivo pharmacological activities such as antioxidant, anti-inflammatory, anti-ulcer, skin whitening, anti-diabetic, and immunoregulatory activities. The traditional use, such as increasing lactation, treating ulcers and diabetes, and reducing obesity, have been evaluated and studied with various methods. Numerous reports have revealed the unusual link between the consumption of S. androgynus and the induction of a chronic and irreversible obstructive disease (namely, bronchiolitis obliterans), indicating that the toxicity and side effects of this plant that is presently used in health care and medicine are a major area of concern. CONCLUSION: Though little importance was attached to this green plant, S. androgynus has notable phytochemical constituents and various pharmacological activities including antioxidant, anti-inflammatory, and anti-obesity activities. Studies have firmly established the association between excessive consumption of the uncooked S. androgynus juice over a period of time and the occurrence of bronchiolitis obliterans. It is inadvisable to ingest excessive amounts of S. androgynus before fully understanding the pathogenesis and induction mechanism of this fatal disease. The phytochemistry of S. androgynus, its pharmacology for traditional use, S. androgynus-induced bronchiolitis obliterans still need further investigation.


Subject(s)
Ethnopharmacology , Phytochemicals/pharmacology , Phytochemicals/toxicity , Plant Extracts/pharmacology , Plant Extracts/toxicity , Animals , Asia , Humans , Medicine, Chinese Traditional , Medicine, Traditional , Phytochemicals/chemistry , Phytotherapy , Plant Extracts/chemistry , Plants, Medicinal
12.
Mol Pharm ; 17(2): 417-425, 2020 02 03.
Article in English | MEDLINE | ID: mdl-31841011

ABSTRACT

Constructing an effective therapeutic cancer vaccine is very attractive and promising for cancer immunotherapy. However, the poor immunogenicity of tumor antigens and suppression of the immune system in the tumor microenvironment are two major obstacles for developing effective cancer vaccines. Invariant NKT cells (iNKT cells), which are essential bridges between the innate and adaptive immune systems, can be rapidly activated by their agonists and, consequently, evoke whole immune systems. Herein, we conjugated a potent agonist of the iNKT cell, α-galactosylceramide (α-GalCer), with the tumor-associated MUC1 glycopeptide antigens as novel self-adjuvanting cancer vaccines through click chemistry. Immunological studies revealed that the mouse immune system was potently evoked and that high levels of tumor-specific IgG antibodies were elicited by vaccine conjugates without an external adjuvant. The produced antibodies could specifically recognize and bind to antigen-expressing cancer cells and, subsequently, induce cytotoxicity through complement-dependent cytotoxicity. Thus, the insertion of α-GalCer significantly improved the immunogenicity of the MUC1 glycopeptide and induced strong antigen-specific antitumor responses, indicating that α-GalCer is an effective built-in adjuvant for constructing potent chemical synthetic antitumor vaccines.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Cancer Vaccines/immunology , Galactosylceramides/administration & dosage , Immunization/methods , Immunogenicity, Vaccine , Natural Killer T-Cells/immunology , Vaccines, Synthetic/immunology , Adjuvants, Immunologic/chemistry , Animals , Antigen-Presenting Cells/immunology , Antigens, Neoplasm/chemistry , Antigens, Neoplasm/genetics , Cancer Vaccines/administration & dosage , Click Chemistry/methods , Dendritic Cells/immunology , Female , Galactosylceramides/chemistry , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , MCF-7 Cells , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mucin-1/chemistry , Mucin-1/genetics , Transfection , Vaccines, Synthetic/administration & dosage
13.
J Ethnopharmacol ; 248: 112204, 2020 Feb 10.
Article in English | MEDLINE | ID: mdl-31669442

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Ficus hispida L.f. (Moraceae) has long been used as a traditional medicine in India, China, Sri Lanka, Australia, and Myanmar in the treatment of diarrhea, ulcer, anemia, diabetes, inflammation, and cancer. AIM OF THE REVIEW: This review provides a systematic comment on the botany, traditional uses, and phytochemical and pharmacological studies of F. hispida, with an aim to make critical update of the current knowledge and obtain opportunities for further therapeutic potential. MATERIALS AND METHODS: The information was derived from scientific literature databases including PubMed, Baidu Scholar, Google Scholar, Web of Science, and Science Direct. Additional information was gathered from books, Ph.D. and M.Sc. dissertations, and unpublished materials. RESULTS AND DISCUSSION: F. hispida is used especially in Chinese and Indian traditional medical systems as a remedy for skin disorders, respiratory diseases, and urinary diseases. Wound healing, anti-inflammatory, antinociceptive, sedative, antidiarrheal, antiulcer, antimicrobial, antioxidant, hepatoprotective, antineoplastic, and antidiabetic activities have been reported for crude extracts and isolated metabolites, but the methodologies in these studies often have inadequate design and low technical quality. More than 76 compounds have been isolated from F.hispida, including sesquiterpenoids and triterpenoids, flavonoids, coumarins, phenylpropionic acids, benzoic acid derivatives, alkaloids, steroids, other glycosides, and alkanes, but the method of bioassay-guided fractionation is seldom applied in the isolation from F. hispida. CONCLUSION: F. hispida is used widely in traditional medicines and has multiple pharmacological effects that could support traditional uses. However, pharmacological studies should be viewed with caution because of the inappropriate experimental design. More in vitro and in vivo research is urgently needed to study the molecular mechanisms and assess the effective and safe dose of F. hispida.


Subject(s)
Ficus , Animals , Humans , Medicine, Traditional , Phytochemicals/analysis , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Phytochemicals/toxicity , Plant Preparations/chemistry , Plant Preparations/pharmacology , Plant Preparations/therapeutic use , Plant Preparations/toxicity
14.
Chembiochem ; 21(8): 1150-1154, 2020 04 17.
Article in English | MEDLINE | ID: mdl-31702879

ABSTRACT

The activation of toll-like receptors (TLRs) plays important roles in the immune response. The ability to control the activities of TLRs could be usable as a switch for immune response. Here we have rationally designed and synthesized a photoswitchable Pam3 CSK4 derivative-P10-to control the activation of TLR1/2. The ground-state trans-P10 was able to stimulate and activate antigen-presenting cells (APCs) by promoting TLR1/2 heterodimerization. However, cis-P10, derived from UV irradiation of trans-P10, reduced the activities of APCs by impeding the TLR1/2 heterodimerization. In the absence of UV radiation, the cis-P10 slowly returned to its ground trans state, restoring the activities of the APCs stimulation. Our results indicated that optical control of TLR1/2 heterodimerization mediated by the photoswitchable P10 offers the potential to regulate immune activation and inflammation.


Subject(s)
Antigen-Presenting Cells/immunology , Immunity/immunology , Lipopeptides/pharmacology , Protein Multimerization , Toll-Like Receptor 1/agonists , Toll-Like Receptor 2/agonists , Ultraviolet Rays , Animals , Antigen-Presenting Cells/metabolism , Humans , Mice , RAW 264.7 Cells , Signal Transduction , THP-1 Cells , Toll-Like Receptor 1/chemistry , Toll-Like Receptor 2/chemistry
15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-828624

ABSTRACT

This article reports two children with hereditary hemorrhagic telangiectasia (HHT). Patient 1 was a boy aged 12 years and was admitted due to intermittent cough and wheezing for more than 10 years. This boy and his mother and grandmother had a history of epistaxis. The boy had a history of the rupture of cerebral arteriovenous malformations. Gene detection showed a heterozygous mutation, c.277C>T(p.Arg93*), in the ENG gene. Patient 2 was a girl aged 13 years and was admitted due to cyanosis of lips for more than 1 year. The girl had a history of recurrent epistaxis and the manifestations of severe decline in pulmonary diffuse function, pulmonary hypertension, dilation of blood vessels at the distal end of lungs, and small arteriovenous communications in both lungs. Children with HHT often lack typical respiratory symptoms, which may lead to missed diagnosis and misdiagnosis in the early stage. Pulmonary computed tomography or right cardiac acoustic contrast can help with the diagnosis of HHT, and gene detection can improve the early diagnostic rate of this disease.


Subject(s)
Adolescent , Child , Female , Humans , Male , Lung , Mutation , Telangiectasia, Hereditary Hemorrhagic , Tomography, X-Ray Computed
16.
Front Mol Biosci ; 6: 16, 2019.
Article in English | MEDLINE | ID: mdl-30968030

ABSTRACT

The aggregation of the amyloidogenic protein α-synuclein (α-Syn) into toxic oligomers and mature fibrils is the major pathological hallmark of Parkinson's disease (PD). Small molecules that inhibit α-Syn aggregation thus may be useful therapeutics for PD. Mannitol and naphthoquinone-tryptophan (NQTrp) have been shown in the past to inhibit α-Syn aggregation by different mechanisms. Herein, we tested whether the conjugation of Mannitol and NQTrp may result in enhance efficacy toward α-Syn. The molecules were conjugated either by a click linker or via a PEG linker. The effect of the conjugate molecules on α-Syn aggregation in vitro was monitored using Thioflavin T fluorescence assay, circular dichroism, transmission electron microscopy, and Congo red birefringence assay. One of the conjugate molecules was found to be more effective than the two parent molecules and as effective as a mixture of the two. The conjugate molecules attenuated the disruptive effect of α-Syn on artificial membrane of Large Unilamellar Vesicles as monitored by dye leakage assay. The conjugates were found to be have low cytotoxicity and reduced toxicity of α-Syn toward SH-SY5Y neuroblastoma cells. These novel designed entities can be attractive scaffold for the development of therapeutic agents for PD.

18.
ACS Appl Mater Interfaces ; 10(11): 9310-9314, 2018 Mar 21.
Article in English | MEDLINE | ID: mdl-29484882

ABSTRACT

Immunotherapy is believed to be an ideal method to treat cancer because it can break the immunotolerance of tumor and induce robust immunoresponse. However, constructing a wide antigen-adaptive, easy-handling, and biodegradable system that can recruit and activate antigen-presenting cells (APCs) much effectively is still a challenge. Herein, we show an injectable DNA supramolecular hydrogel vaccine (DSHV) system which could efficiently recruit and activate APCs in vitro and in vivo. The in vitro processes have been visualized by fluorescence microscopy. Through intraperitoneal or subcutaneous injection, the DSHV system can mimic the function of a lymph node where the APCs are recruited and activated by the high local concentration of cytosine-phosphate-guanine. Subsequently, strong immune response and obvious antitumor effects have been obtained. Our findings demonstrated that the DSHV system could serve as a general platform for tumor vaccination and benefit the personalized cancer therapy in the near future.


Subject(s)
DNA/chemistry , Antigen-Presenting Cells , Cancer Vaccines , Hydrogels , Immunotherapy
19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-693727

ABSTRACT

Objective On the basis of previous research, we intended to further explore whether Kuijietong chieving the inhibitory effect on inflammatory action in ulcerative colitis(UC) through inhibiting the phosphorylation of IkappaBalpha/NF-kappaB p65(p-IκBα/NF-κB p65). Methods UC rat model was established by free drinking of dextran sulfate sodium(DSS) water. SD rats were randomly divided into normal group, model group, high-dose Kuijietong group(at intragastric dosage of 15 g·kg-1·d-1), low-dose Kuijietong group(at intragastric dosage of 5 g·kg-1·d-1), SASP group (at intragastric dosage of 0.3 g·kg-1·d-1). After treatment for 2 weeks, the expression levels of p-IκBα/IκBα and p-NF-κB p65/NF-κB p65 in colon tissues were determined by Western blotting method. Results The expression levels of p-IκBα/IκBα and p-NF-κB p65/NF-κB p65 in high-dose Kuijietong group were decreased significantly as compared with those in the model group and western medicine group, the difference being statistically significant(P<0.001). Conclusion Kuijietong has protective effects against inflammation in UC through blocking the activation of NF-κB classic inflammatory pathway, and the effect of high dosage of Kuijietong is the strongest.

20.
Chembiochem ; 18(17): 1721-1729, 2017 09 05.
Article in English | MEDLINE | ID: mdl-28618135

ABSTRACT

Immunotherapy has become one of the most promising therapies for the treatment of diseases. Synthetic immunostimulants and nanomaterial immunostimulant systems are indispensable for the activation of the immune system in cancer immunotherapy. Herein, a strategy for preparing self-assembled nano-immunostimulants (SANIs) for synergistic immune activation is reported. Three immunostimulants self-assemble into nanoparticles through electrostatic interactions. SANIs showed strong synergistic immunostimulation in macrophages. SANIs could also induce a strong antitumor immune response to inhibit tumor growth in mice and act as an efficient adjuvant of antitumor vaccines. Therefore, SANIs may be generally applied in cancer immunotherapy. This novel SANI strategy provides a new way for the development of both immunostimulants and -suppressants.


Subject(s)
Adjuvants, Immunologic/metabolism , Nanoparticles/chemistry , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/therapeutic use , Animals , Cell Line, Tumor , Cell Survival/drug effects , Cytokines/metabolism , Dynamic Light Scattering , Female , Fluoresceins/chemistry , Immunotherapy , Lipopeptides/chemistry , Lipopeptides/immunology , Lipopeptides/pharmacology , Lipopeptides/therapeutic use , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Melanoma, Experimental/therapy , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Microscopy, Fluorescence , RAW 264.7 Cells , Toll-Like Receptor 2/metabolism , Transplantation, Homologous , Vaccines, Synthetic/immunology
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