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1.
Phytother Res ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38743584

ABSTRACT

Echinacea purpurea (L.) Moench (EP), a medicinal plant native to North America, is now cultivated in various regions including Europe. With increasing popularity of Echinacea in Korea recently, a human clinical trial was conducted to evaluate immune-enhancing efficacy and safety of EP 60% ethanolic extract (EPE) in Koreans. Eighty volunteers were recruited for this randomized, double-blind, placebo-controlled clinical trial. They were randomly divided into two groups and given either a daily dose of 200 mg of EPE or a placebo. All participants underwent testing for Natural Killer (NK) cell cytotoxic activity, serum cytokine levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, TNF-α), Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), and Multidimensional Fatigue Scale (MFS) during this study to assess changes in outcomes. After 8 weeks of EPE consumption, a significant increase in NK cell cytotoxic activity compared to the placebo was observed. Additionally, serum cytokine levels of IL-2, IFN-γ, and TNF-α also significantly increased following EPE consumption. However, no significant changes were observed in WURSS-21 and MFS before and after EPE consumption. Throughout the 8-week study period, no adverse reactions were reported in relation to EPE consumption, and there were no clinically significant changes in diagnostic laboratory tests or vital signs in the EPE group. These results indicate that consumption of EPE could lead to immune improvement without any adverse effects. This clinical trial was the first to demonstrate beneficial effects of EPE consumption on immunity in Korean adults.

2.
Sci Rep ; 14(1): 12226, 2024 05 28.
Article in English | MEDLINE | ID: mdl-38806600

ABSTRACT

The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.


Subject(s)
Chryseobacterium , Phenylacetates , Vagina , Female , Animals , Phenylacetates/metabolism , Phenylacetates/pharmacology , Vagina/microbiology , Mice , Humans , Chryseobacterium/metabolism , Candida albicans/metabolism , Candida albicans/drug effects , Symbiosis , Hydrogen-Ion Concentration , Gardnerella vaginalis/metabolism , Gardnerella vaginalis/drug effects , Disease Models, Animal , Vaginitis/microbiology , Vaginitis/metabolism , Vaginitis/drug therapy
3.
Biomed Pharmacother ; 173: 116335, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38422661

ABSTRACT

Accumulating evidence indicates that microbial communities in the human body crucially affect health through the production of chemical messengers. However, the relationship between human microbiota and cancer has been underexplored. As a result of a biochemical investigation of the commensal oral microbe, Corynebacterium durum, we identified the non-enzymatic transformation of tryptamine into an anticancer compound, durumamide A (1). The structure of 1 was determined using LC-MS and NMR data analysis as bis(indolyl)glyoxylamide, which was confirmed using one-pot synthesis and X-ray crystallographic analysis, suggesting that 1 is an oxidative dimer of tryptamine. Compound 1 displayed cytotoxic activity against various cancer cell lines with IC50 values ranging from 25 to 35 µM. A drug affinity responsive target stability assay revealed that survivin is the direct target protein responsible for the anticancer effect of 1, which subsequently induces apoptosis-inducing factor (AIF)-mediated apoptosis. Inspired by the chemical structure and bioactivity of 1, a new derivative, durumamide B (2), was synthesized using another indole-based neurotransmitter, serotonin. The anticancer properties of 2 were similar to those of 1; however, it was less active. These findings reinforce the notion of human microbiota-host interplay by showing that 1 is naturally produced from the human microbial metabolite, tryptamine, which protects the host against cancer.


Subject(s)
Antineoplastic Agents , Corynebacterium , Neoplasms , Humans , Survivin , Apoptosis , Apoptosis Inducing Factor , Tryptamines/pharmacology , Tryptamines/therapeutic use , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Oxidative Stress , Cell Line, Tumor , Structure-Activity Relationship , Drug Screening Assays, Antitumor , Molecular Structure , Cell Proliferation
4.
Int J Biol Macromol ; 214: 100-110, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35705125

ABSTRACT

To apply starch nanoparticles (SNP) as host materials for ß-carotene encapsulation, aqueous SNP dispersions (10, 25, 50, and 100 mg/10 mL) and ß-carotene in acetone (10, 50, 100, 150, and 200 µg/mL) were mixed. The acetone in the mixture was evaporated to prepare SNP and ß-carotene composites, which were homogeneously dispersed in aqueous media with over 90 % solubility. When SNP content was higher than 50 mg, over 80 % of ß-carotene was encapsulated in the composite matrix. X-ray diffraction, nuclear magnetic resonance spectroscopy, and transmission electron microscopic analyses confirmed the micellar-shaped composite particles with diameters <120 nm and an amorphous structure. High SNP content in the composites enhanced ß-carotene stability under extremely hot and acidic conditions as well as against ultraviolet rays and oxidation reactions. The encapsulated ß-carotene was not readily released in simulated gastric fluid, but was gradually released in simulated intestinal fluid via SNP digestion in the composites.


Subject(s)
Nanoparticles , beta Carotene , Acetone , Micelles , Nanoparticles/chemistry , Starch/chemistry , beta Carotene/chemistry
5.
Foods ; 11(9)2022 Apr 20.
Article in English | MEDLINE | ID: mdl-35563916

ABSTRACT

Ginseng has been used as a medicinal herb in Asian countries for hundreds of years. It contains many kinds of ginsenosides as major active ingredients and is known to have neuroprotective, anti-inflammatory, antitumor, and antidiabetic properties. In this study, we have developed cream soup with different concentrations (0%, 3%, 5%, 7%, and 10%) of ginseng powder (GP) and determined the quality characteristics (color, viscosity, salinity, etc.) and antioxidant activity, along with sensory parameters. After the addition of GP, significant differences in salinity, L* and a*color value, DPPH, and ABTS were found among different concentrations of GP. Cream soup supplemented with GP 10% exhibited the highest values for DPPH and ABTS (83.5% and 87%, respectively), while the contents of total phenolic and saponin were 0.651 ± 0.02 (mg Gallic acid Equiv./g, DW) and 0.797 ± 0.05 (mg Diosgenin Equiv./g, DW), respectively. Moreover, there were no significant changes for °Brix value, pH, acidity, and total flavonoids content compared to control. The sensory characteristics indicated bitterness with the increase in the concentration of GP. However, a non-significant difference was observed between the control and supplemented samples for color, viscosity, and overall preference. Therefore, the supplementation of GP to cream soup could exhibit health benefits and increase the demand for ginseng to promote public health as functional food material.

6.
IUCrJ ; 8(Pt 5): 823-832, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34584743

ABSTRACT

Transcription factors are the primary regulators of gene expression and recognize specific DNA sequences under diverse physiological conditions. Although they are vital for many important cellular processes, it remains unclear when and how transcription factors and DNA interact. The antitoxin from a toxin-antitoxin system is an example of negative transcriptional autoregulation: during expression of the cognate toxin it is suppressed through binding to a specific DNA sequence. In the present study, the antitoxin HigA2 from Mycobacterium tuberculosis M37Rv was structurally examined. The crystal structure of M. tuberculosis HigA2 comprises three sections: an N-terminal autocleavage region, an α-helix bundle which contains an HTH motif, and a C-terminal ß-lid. The N-terminal region is responsible for toxin binding, but was shown to cleave spontaneously in its absence. The HTH motif performs a key role in DNA binding, with the C-terminal ß-lid influencing the interaction by mediating the distance between the motifs. However, M. tuberculosis HigA2 exhibits a unique coordination of the HTH motif and no DNA-binding activity is detected. Three crystal structures of M. tuberculosis HigA2 show a flexible alignment of the HTH motif, which implies that the motif undergoes structural rearrangement to interact with DNA. This study reveals the molecular mechanisms of how transcription factors interact with partner proteins or DNA.

7.
Article in English | MEDLINE | ID: mdl-34504537

ABSTRACT

Periodontitis is a Gram-negative bacterial infectious disease. Numerous inflammatory cytokines, including interleukin-1ß (IL-1ß), regulate periodontitis pathophysiology and cause periodontal tissue destruction. In human gingival fibroblasts (HGFs), IL-1ß stimulates the production of matrix metalloproteinases (MMPs) and proinflammatory cytokines via various mechanisms. Several transcription factors, such as signal transducer and activator of transcription 3 (STAT-3), activator protein 1 (AP-1), and nuclear factor-κB (NF-κB), regulate gene expression. Mitogen-activated protein kinases (MAPKs) regulate these transcription factors. However, the MAPK/STAT-3 activation signal in HGFs is unknown. We investigated the potential inhibitory effects of the extract of Evodiae fructus (EFE), the dried, ripe fruit of Evodia rutaecarpa, on MMP and proinflammatory cytokine expression in IL-1ß-stimulated HGFs. EFE inhibited the expression of MMP-1, MMP-3, and proinflammatory cytokines (TNF-α, IL-6, and IL-8) in IL-1ß-stimulated HGFs through the inhibition of IL-1ß-induced MAPK/STAT-3 activation. Also, these results suggest that the EFE may be a useful for the bioactive material for oral care.

8.
Food Sci Biotechnol ; 30(2): 287-297, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33732519

ABSTRACT

Rhodiola rosea L. rhizome has been used as a traditional medicine to treat fatigue, depression, and cognitive dysfunction. We aimed to authenticate R. rosea L. rhizome using the DNA barcoding technique and to quantify its main compounds, total phenolics, total flavonoids, and antioxidant capacity, and then to investigate their neuroprotective effects. The sequences of internal transcribed spacer and trnH-psbA of R. rosea L. rhizomes showed a 99% identity with those of NCBI GenBank database according to BLAST searches. Analysis using reversed-phase HPLC revealed five main compounds in R. rosea L. rhizome. Rhodiola rosea L. rhizome and two bioactive compounds, salidroside and tyrosol, showed free radical scavenging activity. Rhodiola rosea L. rhizome and its identified compounds protected neuronal PC-12 cells against oxidative stress and showed moderate acetylcholinesterase inhibition. Taken together, these results suggest that R. rosea L. rhizomes with bioactives can be used as a functional ingredient with potential for neuroprotection. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1007/s10068-020-00868-7) contains supplementary material, which is available to authorized users.

9.
Saudi J Biol Sci ; 27(11): 2968-2971, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33100854

ABSTRACT

BACKGROUND: Amomum villosum Lour., (Zingiberaceae) an herbaceous plant in the ginger family, has been used to treat various diseases. In a single-blind, randomized, crossover study, we assessed the postprandial blood insulin and blood glucose responses in healthy subjects (n = 40) after the Amomum villosum water extract (AVE) (5 g/person) or a placebo (5 g/person) consumption. METHODS: During each treatment course, the healthy subject consumed a regular late afternoon meal, followed by fasting for 12 h, and arrived at the clinical study center the next morning. Blood insulin and blood glucose levels were assessed at 0, 30, 60, 90, and 120 min after AVE consumption. Between each treatment, the subjects accomplished one week of a washout period. RESULTS: The AVE intake demonstrated a significant (67.26%) decline in postprandial blood glucose AUC0-120 min (incremental area under the curve from 0 to 120 min) versus the placebo (P = 0.011). Furthermore, AVE reduced postprandial blood insulin AUC0-120 min by 59.95% compared to the placebo group (P < 0.003), supporting the blood glucose results. CONCLUSION: This study revealed that AVE consumption significantly reduced postprandial insulin and glucose levels in healthy individuals, due in part to inhibition of α-glucosidase, and glucose transport.

10.
Molecules ; 25(19)2020 Oct 07.
Article in English | MEDLINE | ID: mdl-33036491

ABSTRACT

Amomi Fructus is widely used to treat digestive disorders, and Amomum villosum, A. villosum var. xanthioides, and A. longiligulare are permitted medicinally in national pharmacopeias. However, there are a variety of adulterants present in herbal markets owing to their morphological similarities to the genuine Amomum species. Forty-two Amomi Fructus samples from various origins were identified using internal transcribed spacer and chloroplast barcoding analyses, and then their chromatographic profiles were compared using chemometric analysis for chemotaxonomic monitoring. Among the Amomi Fructus samples, A. villosum, A. longiligulare, A. ghaticum, and A. microcarpum were confirmed as single Amomum species, whereas a mixture of either these Amomum species or with another Amomum species was observed in 15 samples. Chemotaxonomic monitoring results demonstrated that two medicinal Amomum samples, A. villosum and A. longiligulare, were not clearly distinguished from each other, but were apparently separated from other non-medicinal Amomum adulterants. A. ghaticum and A. microcarpum samples were also chemically different from other samples and formed their own species groups. Amomum species mixtures showed diverse variations of chemical correlations according to constituent Amomum species. Genetic authentication-based chemotaxonomic monitoring methods are helpful in classifying Amomi Fructus samples by their original species and to distinguish genuine Amomum species from the adulterants.


Subject(s)
Amomum/chemistry , Amomum/classification , Chromatography, High Pressure Liquid/methods , Phylogeny
11.
Article in English | WPRIM (Western Pacific) | ID: wpr-898903

ABSTRACT

A semi-replication-competent retroviral (s-RCR) vector system in which the gag-pol and env (GALV FMG, gibbon ape leukemia virus fusogenic membrane glycoprotein) genes were split into two separate packageable vectors was developed. These vectors are more efficient than replication-defective retroviral (RDR) vectors in gene delivery and have a higher transgene capacity than replication-competent retroviral (RCR) vectors. For thegag-pol vector construction, internal ribosomal entry site-enhanced green fluorescent protein (IRES-EGFP) was introduced downstream of the gag-pol sequence of the previously constructed MoMLV-10A1-EGFP vector to generate MoMLV-gag-pol-IRES-EGFP. For env vector construction, GALV FMG was inserted into the pCLXSN vector to generate pCLXSN-GALV FMG-IRES-EGFP.MoMLV-gag-pol-IRES-EGFP and pCLXSN-GALV FMG-IRES-EGFP were co-transfected into 293T cells to generate s-RCR viruses. These viruses propagated EGFP and induced syncytium formation due to the cytotoxicity of GALV FMG. To improve the cytotoxicity of s-RCR vector system, GALV FMG or the fusogenic envelope G glycoprotein of the vesicular stomatitis virus (VSV-G) was inserted into gag-pol vector. Co-transfection of MoMLV-gag-pol-IRES-GALV FMG + MoMLV-EGFP or MoMLV-VSV-G + pCLXSN-GALV FMG-IRES-EGFP in 293T cells induced stronger syncytium formation than s-RCR vectors (MoMLV-gag-pol-IRES-EGFP + pCLXSN-GALV FMG-IRES-EGFP). In addition, s-RCR stocks collected from transfected 293T cells induced syncytium formation in the human cancer cell lines HT1080 and TE671.Hence, the s-RCR vector systems developed in this study are useful tools for cancer gene therapy.

12.
Article in English | WPRIM (Western Pacific) | ID: wpr-891199

ABSTRACT

A semi-replication-competent retroviral (s-RCR) vector system in which the gag-pol and env (GALV FMG, gibbon ape leukemia virus fusogenic membrane glycoprotein) genes were split into two separate packageable vectors was developed. These vectors are more efficient than replication-defective retroviral (RDR) vectors in gene delivery and have a higher transgene capacity than replication-competent retroviral (RCR) vectors. For thegag-pol vector construction, internal ribosomal entry site-enhanced green fluorescent protein (IRES-EGFP) was introduced downstream of the gag-pol sequence of the previously constructed MoMLV-10A1-EGFP vector to generate MoMLV-gag-pol-IRES-EGFP. For env vector construction, GALV FMG was inserted into the pCLXSN vector to generate pCLXSN-GALV FMG-IRES-EGFP.MoMLV-gag-pol-IRES-EGFP and pCLXSN-GALV FMG-IRES-EGFP were co-transfected into 293T cells to generate s-RCR viruses. These viruses propagated EGFP and induced syncytium formation due to the cytotoxicity of GALV FMG. To improve the cytotoxicity of s-RCR vector system, GALV FMG or the fusogenic envelope G glycoprotein of the vesicular stomatitis virus (VSV-G) was inserted into gag-pol vector. Co-transfection of MoMLV-gag-pol-IRES-GALV FMG + MoMLV-EGFP or MoMLV-VSV-G + pCLXSN-GALV FMG-IRES-EGFP in 293T cells induced stronger syncytium formation than s-RCR vectors (MoMLV-gag-pol-IRES-EGFP + pCLXSN-GALV FMG-IRES-EGFP). In addition, s-RCR stocks collected from transfected 293T cells induced syncytium formation in the human cancer cell lines HT1080 and TE671.Hence, the s-RCR vector systems developed in this study are useful tools for cancer gene therapy.

13.
Arch Oral Biol ; 108: 104530, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31470141

ABSTRACT

OBJECTIVE: Periodontitis is an inflammatory disease of the supporting tissue around teeth commonly caused by gram-negative bacterial infections. Interleukin (IL)-1ß, a cytokine involved in host immune and inflammatory responses, is known to induce the activation of various intracellular signaling pathways. One of these signaling mechanisms involves the regulation of gene expression by activation of transcription factors (AP-1 and NF-κB). These transcription factors are controlled by mitogen-activated protein kinases (MAPKs), which increase cytokine and matrix metalloproteinase (MMP) expression. We examined the preventive effects of reversine, a 2,6-disubstituted purine derivative, on cytokine and MMP-3 expression in human gingival fibroblasts (HGFs) stimulated with IL-lß. STUDY DESIGN: Western blot analyses were performed to verify the activities of MAPK, p65, p50, and c-Jun and the expression of MMPs in IL-1ß-stimulated HGFs. Cytokine and MMP-3 expression in IL-1ß-stimulated HGFs was measured by real-time quantitative polymerase chain reaction. RESULTS: Reversine decreased the IL-1ß-induced expression of proinflammatory cytokines (IL-6 and IL-8) and MMP-3 in HGFs. Furthermore, the mechanism underlying the effects of reversine involved the suppression of IL-1ß-stimulated MAPK activation and AP-1 activation. CONCLUSION: Reversine inhibits IL-1ß-induced MMP and cytokine expression via inhibition of MAPK/AP-1 activation and ROS generation. Therefore, we suggest that reversine may be an effective therapeutic candidate for preventing periodontitis.


Subject(s)
Gingiva/metabolism , Interleukin-6 , Interleukin-8/metabolism , Matrix Metalloproteinase 3/metabolism , Morpholines , Purines , Fibroblasts/metabolism , Humans , Interleukin-1beta , Interleukin-6/metabolism , MAP Kinase Kinase 4/metabolism , Morpholines/pharmacology , NF-kappa B , Periodontitis/drug therapy , Periodontitis/metabolism , Purines/pharmacology , Reactive Oxygen Species , Transcription Factor AP-1
14.
Bioorg Chem ; 91: 103180, 2019 10.
Article in English | MEDLINE | ID: mdl-31416031

ABSTRACT

Novel cage-like indolizine-acenaphthene-pyridinone heterocyclic hybrids were synthesized in good yields through [bmim]Br mediated tandem 1,3-dipolar cycloaddition-annulation sequence. The anti-inflammatory activity of these hybrids was performed using carrageenan-induced hind paw oedema, croton oil-induced ear oedema and cotton pellet-induced granuloma models. Four of these cage-like heterocyclic hybrids viz. 4b, 4d, 4e and 4j showed substantial anti-inflammatory activities against acute and chronic inflammatory models and also showed significant inhibition of PGE2, TNF-α, and nitrite levels in carrageenan-induced hind paw oedema.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Dinoprostone/antagonists & inhibitors , Drug Discovery , Edema/drug therapy , Granuloma/drug therapy , Heterocyclic Compounds/chemistry , Nitrites/antagonists & inhibitors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Anti-Inflammatory Agents/chemistry , Carrageenan/toxicity , Edema/chemically induced , Edema/pathology , Granuloma/chemically induced , Granuloma/pathology , Mice , Rats , Rats, Wistar
15.
Biochem Biophys Res Commun ; 510(3): 409-415, 2019 03 12.
Article in English | MEDLINE | ID: mdl-30711251

ABSTRACT

The lysosomal Ca2+ permeable channel TRPML1 (MCOLN1) plays key roles in lysosomal membrane trafficking, including the fusion of late endosomes to lysosomes and lysosomal exocytosis, both of which are essential for release of exosomes into the extracellular milieu. Multiple lines of evidence indicate that the contents of adipocyte-derived exosomes mediate diverse cellular responses, including adipogenic differentiation. In this study, we aimed to define the potential roles of TRPML1 in lysosomal membrane trafficking during adipogenesis and in exosomal release. In response to adipogenic stimuli, the endogenous TRPML1 expression in OP9 pre-adipocytes was increased in a time-dependent manner, and the acute deletion of TRPML1 reduced lipid synthesis and expression of differentiation-related marker genes. Notably, mature adipocyte-derived exosomes were found to be necessary for adipogenesis and were dependent on TRPML1-mediated lysosomal exocytosis. Taken together, our findings indicate that TRPML1 mediates diverse roles in adipocyte differentiation and exosomal release. Further, we propose that TRPML1 should be considered as a regulator of obesity-related diseases.


Subject(s)
Adipogenesis , Exocytosis , Exosomes/metabolism , Lysosomes/physiology , Transient Receptor Potential Channels/physiology , Animals , Cells, Cultured , Mice , Transient Receptor Potential Channels/antagonists & inhibitors , Transient Receptor Potential Channels/biosynthesis
16.
Eur J Med Chem ; 152: 417-423, 2018 May 25.
Article in English | MEDLINE | ID: mdl-29751235

ABSTRACT

Stereoselective synthesis of a small library of novel spiroheterocyclic hybrids including indolizine, oxindole, and substituted piperidine units has been accomplished in [bmim]Br using a [3 + 2] cycloaddition strategy in good yield and were tested for their anti-inflammatory activities. The effects of compounds (4a-o) against inflammation were studied using carrageenan-induced hind paw oedema, croton oil-induced ear oedema, and cotton pellet-induced granuloma models. Among the heterocyclic hybrids, compounds 4d, 4g, and 4o showed significant anti-inflammatory activities against acute and chronic inflammatory models. These compounds also showed significant inhibition of PGE2, TNF-α, and nitrite levels in carrageenan-induced hind paw oedema. Thus it is evident from our study that these novel spiroheterocyclic hybrids 4d, 4g, and 4o displayed significant anti-inflammatory effects that involve the reduction of PGE2, TNF-α, and nitrite levels.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Edema/drug therapy , Indoles/pharmacology , Indolizines/pharmacology , Nitrites/antagonists & inhibitors , Spiro Compounds/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Carrageenan/administration & dosage , Crystallography, X-Ray , Disease Models, Animal , Dose-Response Relationship, Drug , Edema/chemically induced , Indoles/chemical synthesis , Indoles/chemistry , Indolizines/chemical synthesis , Indolizines/chemistry , Models, Molecular , Molecular Structure , Nitrites/metabolism , Oxindoles , Rats , Spiro Compounds/chemical synthesis , Spiro Compounds/chemistry , Stereoisomerism , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/metabolism
17.
Mol Med Rep ; 17(6): 8397-8402, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29658601

ABSTRACT

Casein kinase 2 (CK2) is a serine/threonine protein kinase that has been considered to represent an important factor in mammary tumorigenesis. Increased expression of matrix metalloproteinase­9 (MMP­9) via nuclear factor­κB (NF­κB) activation has been demonstrated to promote breast cancer cell invasion. In the present study, the involvement of CK2 in protein kinase C (PKC) induced cell invasion in MCF­7 breast cancer cells was investigated as well as the underlying molecular mechanisms. The mRNA and protein levels of MMP­9 in MCF­7 cells were investigated using reverse transcription­quantitative polymerase chain reaction, western blot analyses and a zymography assay. Cell invasiveness was investigated using a Matrigel invasion assay, and it was revealed that small interfering RNA specific for CK2 suppressed PKC induced cell invasion by regulating MMP­9 expression via activation of the p38 kinase/c­Jun N­terminal kinase/NF­κB pathway. In addition, it was demonstrated that CK2 inhibitors [apigenin (20 µM), emodin (20 µM) or 2­dimethylamino­4,5,6,7­tetrabromo­1H­benzimidazole (2 µM)] suppressed PKC induced cell invasion and MMP­9 expression. The results of the present study suggested that CK2 is an important factor involved in the induction of MCF­7 breast cancer cell invasion by PKC. Therefore, CK2 may represent novel candidates for therapy intended to inhibit invasion in breast cancer.


Subject(s)
Casein Kinase II/genetics , Gene Silencing , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Protein Kinase C/metabolism , Cell Movement/drug effects , Cell Movement/genetics , Cell Survival/genetics , Gene Expression , Humans , MCF-7 Cells , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , RNA Interference
18.
Exp Dermatol ; 27(3): 298-301, 2018 03.
Article in English | MEDLINE | ID: mdl-29341262

ABSTRACT

UVB has been shown to stimulate the generation of reactive oxygen species (ROS), which subsequently results in the activation of various intracellular signalling pathways and transcription factors (AP-1, NF-κB). These transcription factors are regulated by MAPKs, which increase cytokine and MMP expression. We examined the preventive effects of reversine on MMP-1 and MMP-3 expressions in NHEKs and NHDFs exposed to UVB irradiation. Also, we confirmed that reversine decreased pro-inflammatory cytokine expression in NHEKs. The mechanism underlying the MMP inhibitory effects of reversine occurred via the suppression of UVB-induced ROS generation and MAPK/AP-1 activation. Therefore, reversine is an effective therapeutic candidate for preventing skin photoageing.


Subject(s)
Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase Inhibitors/pharmacology , Morpholines/pharmacology , Purines/pharmacology , Cytokines/genetics , Fibroblasts , Gene Expression/drug effects , Humans , Keratinocytes , Mitogen-Activated Protein Kinases/metabolism , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Signal Transduction/radiation effects , Transcription Factor AP-1/metabolism , Ultraviolet Rays
19.
ImplantNewsPerio ; 3(1): 77-94, jan.-fev. 2018. ilus
Article in Portuguese | LILACS, BBO - Dentistry | ID: biblio-881654

ABSTRACT

Os implantes imediatos têm sido utilizados com bastante frequência como uma forma de tratamento para a substituição de dentes condenados. Entretanto, quando a área a ser tratada pertence à zona estética, muito cuidado deve ser tomado. Nessa região, quando o objetivo é alcançar um peri-implante com estética satisfatória, o profissional deve utilizar técnicas que, associadas ao implante imediato, evitem a formação de um defeito decorrente da remodelação pós-exodontia, ou ainda, utilizar procedimentos de melhoria tecidual nos casos em que os dentes condenados já apresentem defeitos de tecido ósseo e/ou mole ao seu redor. O objetivo deste trabalho é, através da apresentação de um caso clínico de reposição do elemento 41 condenado, com perda óssea severa e defeito mucogengival, demonstrar e discutir uma modalidade de tratamento que utiliza o implante imediato de carga imediata não funcional associado ao enxerto de tecido conjuntivo e preenchimento com osso mineral bovino particulado.


Immediate implants have been used frequently as a treatment choice for the replacement of compromised teeth. However, when the area to be treated belongs to the aesthetic zone, great care must be exercised. In this region, when the objective is to reach a peri-implant with a satisfactory esthetics, the professional must use techniques that, associated to the immediate implant, prevent the formation of a defect due to the bone remodeling after tooth loss or to use procedures of tissue improvement for cases where the compromised teeth already have defects of bone and/or soft tissue around them. The objective of this study is to present a clinical case of replacement at tooth 41 with severe bone loss and mucogingival defect to demonstrate and discuss a treatment modality that uses the immediate implant with non-functional immediate loading associated with the connective tissue graft and particulate, deproteinized bovine bone filling.


Subject(s)
Humans , Male , Adult , Biocompatible Materials , Connective Tissue/transplantation , Dental Implantation/methods , Free Tissue Flaps/transplantation , Immediate Dental Implant Loading , Tissue Transplantation/methods
20.
Chin J Integr Med ; 24(6): 436-441, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29247342

ABSTRACT

OBJECTIVE: To examinie the synergistic effects of Banxia Xiexin Decoction (, Known as Banhasasim-tang in Korean) extract (BXDE) on cisplatin-induced cytotoxicity in the A549 human lung cancer cell lines. METHODS: A549 cells were treated with varying concentrations (50-200 µg/mL) of cisplatin and BXDE alone or in combination for 96 h. We used 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay and flow cytometry to analyze cell viability and apoptosis, respectively. RESULTS: The exposure of cells to cisplatin and BXDE alone or in combination decreased cell viability dose- and time-dependently (P<0.05), which was found to be mediated by the apoptotic pathway as confirmed by the increase in the annexin V+/propidium iodide- stained cell population and a ladder pattern of discontinuous DNA fragments. Furthermore, the apoptosis was inhibited by the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (z-VAD-FMK). CONCLUSIONS: BXDE significantly potentiated apoptotic effects of cisplatin in A549 cells. Moreover, apoptosis induced by BXDE might be the pivotal mechanism mediating its chemopreventative action against cancer.


Subject(s)
Apoptosis/drug effects , Cisplatin/pharmacology , Plant Extracts/pharmacology , A549 Cells , Apoptosis Regulatory Proteins/metabolism , Caspase Inhibitors/pharmacology , DNA Fragmentation/drug effects , Humans
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