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1.
Cells ; 13(7)2024 Mar 26.
Article En | MEDLINE | ID: mdl-38607019

Previous research indicates that carcinogenesis involves disrupting the functions of numerous genes, including factors involved in the regulation of transcription and cell proliferation. For these reasons, in endometrial carcinogenesis, we decided to investigate the expression of TSG101 (a suppressor of tumor transformation) and LSF (a transcription factor involved in numerous cellular processes, such as cell cycle regulation, cell growth, development, and apoptosis). LSF may be involved in the regulation of TSG101 expression. The research material consisted of endometrial cancer samples from 60 patients. The control group consisted of normal endometrium samples donated by 60 women undergoing surgery for benign diseases of the female reproductive organs. The samples were subjected to immunohistochemical staining with antibodies specific to TSG101 and LSF. Specific antibodies were used to identify TSG101 and LSF in the examined histopathological preparations. An approximately 14-fold lower risk of endometrial cancer development was observed in patients with TSG expression in more than 75% of the assessed cells (4% vs. 36%; OR = 0.07; p = 0.0182). There was a four-fold lower risk of endometrial cancer development in patients with LSF expression in more than 50% of the assessed cells (32% vs. 64%; OR = 0.26; p = 0.0262). A more than three-fold lower risk of endometrial cancer development was observed in patients with LSF expression in more than 75% of the assessed cells (24% vs. 52%; OR = 0.29; p = 0.0454). Endometrial cancer was diagnosed in those with a lower level of TSG101 expression than in those with a cancer-free endometrium. Decreased expression of TSG101 may be a marker of endometrial cancer, and increased expression of LSF when diagnosed with endometrial cancer may indicate greater advancement of the disease. These markers might be used as diagnostic and prognostic markers-however, there is a lack of a correlation between them.


Endometrial Neoplasms , Transcription Factors , Female , Humans , Transcription Factors/metabolism , Cell Transformation, Neoplastic/genetics , Endometrial Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Endometrium/metabolism
2.
Org Lett ; 26(3): 692-696, 2024 01 26.
Article En | MEDLINE | ID: mdl-38227548

New gem-difluoroalkenes were synthesized by the dehydrofluorination of the corresponding 4-CF3-ß-lactams. An unexpected rearrangement mechanism of the ester moiety dependent on a stabilizing negative charge was observed. Hydrogenation to 4-CHF2-ß-lactams was successful from gem-difluoro-ß-lactams.


Anti-Bacterial Agents , beta-Lactams , beta-Lactams/pharmacology , Anti-Bacterial Agents/pharmacology , Hydrogenation , Esters
3.
Chem Commun (Camb) ; 59(33): 4907-4910, 2023 Apr 20.
Article En | MEDLINE | ID: mdl-37009724

In this work, HKUST-1 and Cu-BDC nanoparticles were used as delivery systems for the early anti-COVID-19 drug, hydroxychloroquine. The antiviral MOF/drug combinations significantly reduced the infectivity of SARS-CoV-2, which can be attributed to the nanometric size of the carriers, the presence of copper in the MOF nodes, and the semi-controlled release of the drug.


COVID-19 , Nanoparticles , Humans , SARS-CoV-2 , Antiviral Agents/pharmacology , Hydroxychloroquine/pharmacology
4.
Biomedicines ; 11(3)2023 Mar 08.
Article En | MEDLINE | ID: mdl-36979802

Estrogens enhance cellular mitochondrial activity. The diminution of female hormones during menopause may have an effect on the mitochondrial genome and the expression of mitochondrial proteins. Hence, oxidative stress and the pro-inflammatory state contribute to the formation of systemic illnesses including arterial hypertension (AH). This study aimed to determine the types and frequency of mutations in the mitochondrial DNA (mtDNA) nucleotide sequence in the hypervariable regions 1 and 2 (HV1 and HV2) and the 12S RNA coding sequence of the D-loop in postmenopausal women with hypertension. In our study, 100 women were investigated, 53 of whom were postmenopausal and 47 of whom were premenopausal (53.9 ± 3.7 years vs. 47.7 ± 4.2 years, respectively). Of those studied, 35 premenopausal and 40 postmenopausal women were diagnosed with AH. A medical checkup with 24 h monitoring of blood pressure (RR) and heart rate was undertaken (HR). The polymorphism of the D-loop and 12S rDNA region of mtDNA was examined. Changes in the nucleotide sequence of mtDNA were observed in 23% of the group of 100 women. The changes were identified in 91.3% of HV1 and HV2 regions, 60.9% of HV1 segments, 47.5% of HV2 regions, and 43.5% of 12S rDNA regions. The frequency of nucleotide sequence alterations in mtDNA was substantially higher in postmenopausal women (34%) than in premenopausal women (10.6%), p = 0.016. A higher frequency of changes in HV1 + HV2 sections in postmenopausal women (30.2%) compared to the premenopausal group (10.6%) was detected, p = 0.011. Only postmenopausal women were found to have modifications to the HV2 segment and the 12S rDNA region. After menopause, polymorphism in the mtDNA region was substantially more frequent in women with arterial hypertension than before menopause (p = 0.030; 37.5% vs. 11.5%). Comparable findings were observed in the HV2 and HV1 regions of the AH group (35% vs. 11.5%), p = 0.015, in the HV1 segment (25% vs. 11.5%), p = 0.529, and in the HV2 segment, 12S rDNA (25% vs. 0%). More than 80% of all changes in nucleotide sequence were homoplasmic. The mtDNA polymorphisms of the nucleotide sequence in the HV1 and HV2 regions, the HV2 region alone, and the 12S RNA coding sequence were associated with estrogen deficiency and a more severe course of arterial hypertension, accompanied by symptoms of adrenergic stimulation.

5.
Front Plant Sci ; 13: 979678, 2022.
Article En | MEDLINE | ID: mdl-36388598

Latex-bearing plants have been in the research spotlight for the past couple of decades. Since ancient times their extracts have been used in folk medicine to treat various illnesses. Currently they serve as promising candidates for cancer treatment. Up to date there have been several in vitro and in vivo studies related to the topic of cytotoxicity and anticancer activity of extracts from latex-bearing plants towards various cell types. The number of clinical studies still remains scarce, however, over the years the number is systematically increasing. To the best of our knowledge, the scientific community is still lacking in a recent review summarizing the research on the topic of cytotoxicity and anticancer activity of latex-bearing plant extracts. Therefore, the aim of this paper is to review the current knowledge on in vitro and in vivo studies, which focus on the cytotoxicity and anticancer activities of latex-bearing plants. The vast majority of the studies are in vitro, however, the interest in this topic has resulted in the substantial growth of the number of in vivo studies, leading to a promising number of plant species whose latex can potentially be tested in clinical trials. The paper is divided into sections, each of them focuses on specific latex-bearing plant family representatives and their potential anticancer activity, which in some instances is comparable to that induced by commonly used therapeutics currently available on the market. The cytotoxic effect of the plant's crude latex, its fractions or isolated compounds, is analyzed, along with a study of cell apoptosis, chromatin condensation, DNA damage, changes in gene regulation and morphology changes, which can be observed in cell post plant extract addition. The in vivo studies go beyond the molecular level by showing significant reduction of the tumor growth and volume in animal models. Additionally, we present data regarding plant-mediated biosynthesis of nanoparticles, which is regarded as a new branch in plant latex research. It is solely based on the green-synthesis approach, which presents an interesting alternative to chemical-based nanoparticle synthesis. We have analyzed the cytotoxic effect of these particles on cells. Data regarding the cytotoxicity of such particles raises their potential to be involved in the design of novel cancer therapies, which further underlines the significance of latex-bearing plants in biotechnology. Throughout the course of this review, we concluded that plant latex is a rich source of many compounds, which can be further investigated and applied in the design of anticancer pharmaceuticals. The molecules, to which this cytotoxic effect can be attributed, include alkaloids, flavonoids, tannins, terpenoids, proteases, nucleases and many novel compounds, which still remain to be characterized. They have been studied extensively in both in vitro and in vivo studies, which provide an excellent starting point for their rapid transfer to clinical studies in the near future. The comprehensive study of molecules from latex-bearing plants can result in finding a promising alternative to several pharmaceuticals on the market and help unravel the molecular mode of action of latex-based preparations.

6.
Int J Mol Sci ; 23(16)2022 Aug 17.
Article En | MEDLINE | ID: mdl-36012505

Yellow-orange latex of Chelidonium majus L. has been used in folk medicine as a therapeutic agent against warts and other visible symptoms of human papillomavirus (HPV) infections for centuries. The observed antiviral and antitumor properties of C. majus latex are often attributed to alkaloids contained therein, but recent studies indicate that latex proteins may also play an important role in its pharmacological activities. Therefore, the aim of the study was to investigate the effect of the crude C. majus latex and its protein and alkaloid-rich fractions on different stages of the HPV replication cycle. The results showed that the latex components, such as alkaloids and proteins, decrease HPV infectivity and inhibit the expression of viral oncogenes (E6, E7) on mRNA and protein levels. However, the crude latex and its fractions do not affect the stability of structural proteins in HPV pseudovirions and they do not inhibit the virus from attaching to the cell surface. In addition, the protein fraction causes increased TNFα secretion, which may indicate the induction of an inflammatory response. These findings indicate that the antiviral properties of C. majus latex arise both from alkaloids and proteins contained therein, acting on different stages of the viral replication cycle.


Chelidonium , Latex , Papillomavirus Infections , Alkaloids/pharmacology , Antiviral Agents/pharmacology , Chelidonium/chemistry , Humans , Latex/chemistry , Latex/pharmacology , Papillomavirus Infections/drug therapy , Plant Proteins/pharmacology
7.
Int J Mol Sci ; 23(7)2022 Mar 22.
Article En | MEDLINE | ID: mdl-35408813

Human papillomaviruses (HPVs) are considered to be key etiological agents responsible for the induction and development of cervical cancer. However, it has been suggested that HPV infection alone may not be sufficient to promote cervical carcinogenesis, and other unknown factors might be required to establish the disease. One of the suggested proteins whose deregulation has been linked with oncogenesis is transcription factor Yin Yang 1 (YY1). YY1 is a multifunctional protein that is involved not only in the regulation of gene transcription and protein modification, but can also control important cell signaling pathways, such as cell growth, development, differentiation, and apoptosis. Vital functions of YY1 also indicate that the protein could be involved in tumorigenesis. The overexpression of this protein has been observed in different tumors, and its level has been correlated with poor prognoses of many types of cancers. YY1 can also regulate the transcription of viral genes. It has been documented that YY1 can bind to the HPV long control region and regulate the expression of viral oncogenes E6 and E7; however, its role in the HPV life cycle and cervical cancer development is different. In this review, we explore the role of YY1 in regulating the expression of cellular and viral genes and subsequently investigate how these changes inadvertently contribute toward the development of cervical malignancy.


Papillomavirus Infections , Uterine Cervical Neoplasms , YY1 Transcription Factor , Carcinogenesis/genetics , Carcinogenesis/metabolism , Cell Transformation, Neoplastic , Female , Humans , Oncogene Proteins, Viral/genetics , Papillomaviridae/genetics , Papillomavirus E7 Proteins/genetics , Papillomavirus Infections/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , YY1 Transcription Factor/genetics , YY1 Transcription Factor/metabolism
8.
Int J Mol Sci ; 22(21)2021 Oct 31.
Article En | MEDLINE | ID: mdl-34769268

Chelidonium majus L. is a latex-bearing plant used in traditional folk medicine to treat human papillomavirus (HPV)-caused warts, papillae, and condylomas. Its latex and extracts are rich in many low-molecular compounds and proteins, but there is little or no information on their potential interaction. We describe the isolation and identification of a novel major latex protein (CmMLP1) composed of 147 amino acids and present a model of its structure containing a conserved hydrophobic cavity with high affinity to berberine, 8-hydroxycheleritrine, and dihydroberberine. CmMLP1 and the accompanying three alkaloids were present in the eluted chromatographic fractions of latex. They decreased in vitro viability of human cervical cancer cells (HPV-negative and HPV-positive). We combined, for the first time, research on macromolecular and low-molecular-weight compounds of latex-bearing plants in contrast to other studies that investigated proteins and alkaloids separately. The observed interaction between latex protein and alkaloids may influence our knowledge on plant defense. The proposed toolbox may help in further understanding of plant disease resistance and in pharmacological research.


Alkaloids , Antineoplastic Agents, Phytogenic , Chelidonium/chemistry , Latex/chemistry , Plant Extracts/chemistry , Plant Proteins , Uterine Cervical Neoplasms/drug therapy , Alkaloids/chemistry , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Female , HeLa Cells , Humans , Plant Proteins/chemistry , Plant Proteins/pharmacology , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology
9.
Pharmaceutics ; 13(7)2021 Jun 23.
Article En | MEDLINE | ID: mdl-34201532

Endometriosis is a gynecological disease defined by the presence of endometrial tissue outside the uterus. To date, the effective treatment of this disease is still based on invasive surgery or laparoscopy. Chelidonium majus L. (Papaveraceae) belongs to medicinal, latex-bearing plants. Extracts from the plant are a rich source of pharmacologically active agents. Protoberberine compounds derived from C. majus possess anticancer and antiproliferative activities. In the present study of a rat model of endometriosis, we investigated the influence of the plant protoberberine-rich fraction (BBR) obtained from the medicinal plant C. majus on the development of endometriosis. To understand of BBR therapeutic potential for endometriosis, metabolomics has been applied to study. BBR was prepared from an ethanolic extract of dry plants C. majus. Rats (n = 16) with confirmed endometriosis were treated with BBR administered orally (1 g/kg) for 14 days. Blood serum samples were collected from all of the animals and metabolites were studied using the NMR method. The metabolomic pattern was compared before and after the protoberberine treatment. The performed analysis showed significant changes in the concentrations of metabolites that are involved in energy homeostasis, including glucose, glutamine, and lactate. Histopathological studies showed no recurrence of endometriosis loci after treatment with BBR. The results of the study found that BBR treatment prevents the recurrence of endometriosis in rats. Moreover, metabolomics profiling can be applied to better understand the mechanisms of action of these protoberberine secondary plant metabolites. Our findings provide new insights into the pharmaceutical activity of natural protoberberine plant compounds.

10.
Exp Mol Pathol ; 117: 104530, 2020 12.
Article En | MEDLINE | ID: mdl-32931837

OBJECTIVE: It is well known that mitochondrial dysfunctions are involved in tumorigenesis. A special interest of scientists is mitochondrial ND1 gene (mtND1). Recently detected mutations in the mtND1 can disrupt the normal activity of complex I and affect oxidative phosphorylation, thus leading to increase reactive oxygen species production. This study was undertaken to determine the alternations in the mtND1 and evaluate their association with development of precancerous lesions and cervical cancer. METHODS: In the study 29 cervical cancer, 28 low grade squamous intraepithelial lesion (L-SIL) and 30 high grade squamous intraepithelial lesion (H-SIL) HPV positive fragments tissue were screened for the presence of mtND1 mutations. RESULTS: Our study showed that mutations in the mtND1 gene were detected in patients with precancerous stage, as well as cervical cancer. We have identified 12 point mutations in 116 analyzed precancerous and cancer samples HPV positive. Most detected missense mutations were previously described, except one (p. M156K) with Grantham value 95. The lower expression of mRNA ND1 was detected in cervical cancer cases and in all samples in which mtND1 mutations were identified. Our analyses revealed that level of ROS production was higher in cervical cancer tissues and all cases characterized by mtND1 mutations. CONCLUSIONS: We hypothesize that mutations in MT-ND1 observed in H-SIL and cancer could activate cervical carcinogenesis by increased ROS production.


NADH Dehydrogenase/genetics , Squamous Intraepithelial Lesions/genetics , Uterine Cervical Dysplasia/genetics , Uterine Cervical Neoplasms/genetics , Adult , Carcinogenesis/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Genome, Mitochondrial/genetics , Humans , Middle Aged , Neoplasm Grading , Papillomaviridae/genetics , Papillomaviridae/pathogenicity , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Precancerous Conditions/virology , Squamous Intraepithelial Lesions/pathology , Squamous Intraepithelial Lesions/virology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Young Adult , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/virology
11.
Arch Virol ; 165(9): 1935-1945, 2020 Sep.
Article En | MEDLINE | ID: mdl-32594322

Plants are a rich source of new antiviral, pharmacologically active agents. The naturally occurring plant alkaloid berberine (BBR) is one of the phytochemicals with a broad range of biological activity, including anticancer, anti-inflammatory and antiviral activity. BBR targets different steps in the viral life cycle and is thus a good candidate for use in novel antiviral drugs and therapies. It has been shown that BBR reduces virus replication and targets specific interactions between the virus and its host. BBR intercalates into DNA and inhibits DNA synthesis and reverse transcriptase activity. It inhibits replication of herpes simplex virus (HSV), human cytomegalovirus (HCMV), human papillomavirus (HPV), and human immunodeficiency virus (HIV). This isoquinoline alkaloid has the ability to regulate the MEK-ERK, AMPK/mTOR, and NF-κB signaling pathways, which are necessary for viral replication. Furthermore, it has been reported that BBR supports the host immune response, thus leading to viral clearance. In this short review, we focus on the most recent studies on the antiviral properties of berberine and its derivatives, which might be promising agents to be considered in future studies in the fight against the current pandemic SARS-CoV-2, the virus that causes COVID-19.


Antiviral Agents/pharmacology , Berberine/pharmacology , Viruses/drug effects , Animals , Antiviral Agents/chemistry , Berberine/chemistry , Humans , Plant Extracts/chemistry , Plant Extracts/pharmacology , Virus Diseases/virology , Virus Replication/drug effects , Viruses/genetics , Viruses/growth & development
12.
Postepy Biochem ; 66(4): 356-372, 2020 12 31.
Article Pl | MEDLINE | ID: mdl-33470074

Viruses are intracellular pathogens which utilize a number of host metabolic processes for virus replication in addition to proteins which are encoded for virus itself. Therefore, an effective antiviral drug must interfere with virus encoded proteins without affecting any cellular metabolic processes. Unfortunately, many antiviral drugs that have an inhibitory effect on virus replication, also have an inhibitory effect on molecular processes in infected, as well as uninfected, cells. There is currently no approved remedy for many viruses. Plants represent a large potential source of antiviral agents, such as: alkaloids, flavonoids, phenolic acids, phenylpropanoids, lignins, terpenoids, quinine, tannins, thiophenes, polyacetylenes or proteins. Some of them possess broad spectrum of antiviral activity.


Plants , Viruses , Antiviral Agents/pharmacology , Virus Replication/drug effects
13.
Postepy Biochem ; 66(4): 336-355, 2020 12 31.
Article Pl | MEDLINE | ID: mdl-33470075

Oncogenic viruses (oncoviruses) are implicated in approximately 12% of all human cancers. Currently, the viruses known to cause human cancer are: Hepatitis B and C viruses (HBV and HCV), Human Papillomaviruses (HPV), Merkel Cell Polyomavirus (MCV), Human Herpesvirus-8 (HHV-8), Epstein-Barr Virus (EBV) and Human T-cell lymphotropic virus-1 (HTLV-1). However, oncoviruses are not complete carcinogens, need additional factors andisplay different roles in transformation. Oncoviruses can directly disrupt important regulatory cell genes by inserting virus genom into the DNA of the host cell. They also contain their own genes that damage the regulation of the cell. Some viruses have v-onc that cause disregulation of cellular processes and can lead to cancerous growth.


Neoplasms , Oncogenic Viruses , Hepacivirus , Humans , Retroviridae
14.
Sci Technol Adv Mater ; 20(1): 979-991, 2019.
Article En | MEDLINE | ID: mdl-31692919

Many bacteria become progressively more resistant to antibiotics and it remains a challenging task to control their overall levels. Polymers combined with active biomolecules come to the forefront for the design of antibacterial materials that can address this encounter. In this work, we investigated the photo-crosslinking approach of UV-sensitive benzophenone molecule (BP) with polyvinylpyrrolidone (PVP) polymer within electrospun fibres. The BP and PVP solutions allowed fabricating polymer mats that were subsequently functionalised with antibacterial lysozyme. The physical properties of the crosslinked electrospun fibres were investigated by scanning electron microscopy and atomic force microscopy. The average diameter of the obtained fibres decreased from 290 ± 50 nm to 270 ± 70 nm upon the addition of the crosslinking molecules and then to 240 ± 80 nm and 180 ± 90 nm after subsequent crosslinking reaction at an increasing time: 3 and 5 h, respectively. The peak force quantitative nanomechanical mapping (PF-QNM) indicated the increase of DMT modulus of obtained cross-linked fibres from 4.1 ± 0.8 GPa to 7.2 ± 0.5 GPa. Furthermore, the successful crosslinking reaction of PVP and BP solution into hydrogels was investigated in terms of examining photo-crosslinking mechanism and was confirmed by rheology, Raman, Fourier transform infrared and nuclear magnetic resonance. Finally, lysozyme was successfully encapsulated within cross-linked PVP-BP hydrogels and these were successfully electrospun into mats which were found to be as effective antibacterial agents as pure lysozyme molecules. The dissolution rate of photo cross-linked PVP mats was observed to increase in comparison to pure PVP electrospun mats which opened a potential route for their use as antibacterial, on-demand, dissolvable coatings for various biomedical applications.

15.
Phytomedicine ; 64: 152919, 2019 Nov.
Article En | MEDLINE | ID: mdl-31465980

BACKGROUND: It has been shown that secondary metabolites occur in Chelidonium majus L. (C. majus) crude extract and milky sap (alkaloids such as berberine, coptisine, chelidonine, chelerythrine, sanguinarine, and protopine) are biologically active compounds with a wide spectrum of pharmacological functions. Berberine, an isoquinoline alkaloid extracted from plants, possesses a wide range of biological activities, including inhibition of growth of a variety of cancer cell lines. PURPOSE AND STUDY DESIGN: In the present study, we investigated the potential anticancer effect of a protoberberine alkaloidal fraction (BBR-F) isolated from the medicinal plant C. majus on HeLa and C33A cervical cancer cells after light irradiation (PDT treatment). METHODS: BBR-F was prepared from an ethanolic extract of stems of C. majus. Identification of alkaloidal compounds was performed using high-performance liquid chromatography - mass spectrometry (HPLC/ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy. BBR-F was then biologically evaluated for its anticancer properties. Cytotoxic activity after PDT treatment and without light irradiation (dark cytotoxicity) was determined by colorimetric WST-1 assay. The impact of the protoberberine alkaloidal fraction on the morphology and function of the cells was assessed by fluorescence and confocal microscopy as well as by flow cytometric analysis. To investigate the proinflammatory effect of the extracted natural BBR-F, nitric oxide concentration was determined using the Griess method. RESULTS: An effective reduction in HeLa and C33A cell viability was observed after PDT treatment of BBR-F treated cells. Furthermore, microscopic analysis identified various morphological changes in the studied cells that occurred during apoptosis. Apoptosis of HeLa and C33A cells was also characterized by biochemical changes in cell membrane composition, activation of intracellular caspases, disruption of the mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS) generation. CONCLUSION: Our results strongly suggest that the components of the natural plant protoberberine fraction (BBR-F) extracted from C. majus may represent promising novel photosensitive agents and can be applied in cancer photodynamic therapy as natural photosensitizers.


Alkaloids/pharmacology , Apoptosis/drug effects , Berberine Alkaloids/pharmacology , Chelidonium/chemistry , Photosensitizing Agents/pharmacology , Plant Extracts/pharmacology , Alkaloids/chemistry , Alkaloids/isolation & purification , Berberine Alkaloids/chemistry , Berberine Alkaloids/isolation & purification , Cell Line, Tumor , Humans , Photosensitizing Agents/chemistry , Photosensitizing Agents/isolation & purification , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Stems/chemistry , Plants, Medicinal
16.
J Biomed Mater Res A ; 107(10): 2244-2256, 2019 10.
Article En | MEDLINE | ID: mdl-31136088

It is already known that cells respond strongly to topography and chemistry of 2D surfaces. In this work we study cell-material interactions; in particular, we investigated the attachment and alignment of SH-SY5Y cells of neuronal origin on grooved-patterns made from Silicon (Si) and Gold (Au). The Au-Si groove-pattern stimulated 93% of SH-SY5Y cells to differentiate into neuroblast-like type (N-type) in 2 days and outgrown neurites exhibited strong anisotropy along the grooves with 90% of cells having one or two neurites. In comparison, random distribution of morphology type, neurite number, and alignment were observed on control flat surfaces (Si and Au). We further show that designed Au-Si groove-patterns can be used to form reversed groove patterns on polycarolactone surface via soft lithography approach. Sixty-nine percentage of SH-SY5Y cells aligned along the obtained reversed groove patterns of the same dimensional characteristics to Si-Au grooves. In particular, this work demonstrated that the Au-Si grooves pattern stimulates neurite polarity, elongation, and morphological differentiation of neuroblastoma cells without any exogenous supply of growth factors or stimulants in just 2 days, which can lead to selective procedure of obtaining homologous population of neuron-like cells for future nerve regeneration therapies.


Cell Shape , Gold/pharmacology , Neurons/cytology , Silicon/pharmacology , Cell Differentiation/drug effects , Cell Line, Tumor , Cell Shape/drug effects , Humans , Neural Stem Cells/drug effects , Neural Stem Cells/metabolism , Neurites/drug effects , Neurites/metabolism , Neuroblastoma/pathology , Polyesters/pharmacology , Surface Properties
17.
J Inorg Biochem ; 180: 1-14, 2018 03.
Article En | MEDLINE | ID: mdl-29223825

The present study is focused on the development of liposomes bearing gadolinium chelate (GdLip) providing two functionalities for magnetic resonance imaging (MRI) and photodynamic therapy of cancer. A lipid derivative of gadolinium(III) diethylenetriamine pentaacetic acid salt (GdDTPA1) was inserted in the liposomal membrane and served as MRI contrast agent whereas a zinc phthalocyanine (ZnPc) was used as a model photosensitizer. In addition to conventional liposomes, pegylated lipids were used for the preparation of "stealth" liposomes. The characterization of different GdLip formulations involved evaluation of the liposomes size by nanoparticle tracking analysis, thermal phase behavior by differential scanning calorimetry and ZnPc-mediated singlet oxygen production. Furthermore, relaxivity measurements were performed as well as cytotoxicity and photodynamic activity against cancerous and normal cell lines was studied. Size and thermal behavior were only slightly influenced by GdLip composition, however it distinctly affected singlet oxygen production of ZnPc-loaded GdLip. The quantum yields of singlet oxygen generation by zinc phthalocyanine incorporated in GdLip containing cationic or/and pegylated lipids were smaller than those obtained for non-pegylated carriers with l-α-phosphatidylglycerol. In general, all formulations of GdLip, irrespectively of composition, were characterized by relaxivities higher than those of commercially used contrast agents (e.g. Magnevist®). NMR study has shown that the incorporation of ZnPc into the formulations of GdLip increases the relaxation parameters r1 and r2, compared to the values for the non-loaded vesicles. GdDTPA1 did not influence the photodynamic activity of ZnPc against HeLa cells.


Contrast Media/administration & dosage , Drug Carriers , Gadolinium DTPA/administration & dosage , Indoles/administration & dosage , Magnetic Resonance Imaging/methods , Organometallic Compounds/administration & dosage , Photosensitizing Agents/administration & dosage , Theranostic Nanomedicine , Calorimetry, Differential Scanning , Cells, Cultured , Fibroblasts/cytology , HeLa Cells , Humans , Isoindoles , Liposomes , Microscopy, Confocal , Microscopy, Electron, Transmission , Photochemotherapy , Quantum Theory , Singlet Oxygen/metabolism , Zinc Compounds
18.
Nanotechnology ; 28(5): 055603, 2017 Feb 03.
Article En | MEDLINE | ID: mdl-28029097

Magnetite nanoparticles (NPs) decorated with silver (magnetite/Ag) are intensively investigated due to their application in the biomedical field. We demonstrate that the increase of silver content on the surface of nanoparticles improves the adsorptivity of antibiotic rifampicin as well as antibacterial properties. The use of ginger extract allowed to improve the silver nucleation on the magnetite surface that resulted in an increase of silver content. Physicochemical and functional characterization of magnetite/Ag NPs was performed. Our results show that 5%-10% of silver content in magnetite/Ag NPs is already sufficient for antimicrobial properties against Streptococcus salivarius and Staphylococcus aureus. The rifampicin molecules on the magnetite/Ag NPs surface made the spectrum of antimicrobial activity wider. Cytotoxicity evaluation of the magnetite/Ag/rifampicin NPs showed no harmful action towards normal human fibroblasts, whereas the effect on human embryonic kidney cell viability was time and dose dependent.


Anti-Bacterial Agents/pharmacology , Magnetite Nanoparticles/chemistry , Rifampin/pharmacology , Silver/pharmacology , Zingiber officinale/chemistry , Adsorption/drug effects , Anti-Bacterial Agents/chemistry , Cell Line , Cell Survival/drug effects , Fibroblasts/cytology , Fibroblasts/drug effects , HEK293 Cells , Humans , Magnetite Nanoparticles/ultrastructure , Microbial Sensitivity Tests , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rifampin/chemistry , Silver/chemistry , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Streptococcus salivarius/drug effects , Streptococcus salivarius/growth & development
19.
Mater Sci Eng C Mater Biol Appl ; 55: 343-59, 2015 Oct.
Article En | MEDLINE | ID: mdl-26117765

The article is devoted to preparation and characterization of magnetite/silver/antibiotic nanocomposites for targeted antimicrobial therapy. Magnetite nanopowder was produced by thermochemical technique; silver was deposited on the magnetite nanoparticles in the form of silver clusters. Magnetite/silver nanocomposite was investigated by XRD, SEM, TEM, AFM, XPS, EDX techniques. Adsorptivity of magnetite/silver nanocomposite towards seven antibiotics from five different groups was investigated. It was shown that rifampicin, doxycycline, ceftriaxone, cefotaxime and doxycycline may be attached by physical adsorption to magnetite/silver nanocomposite. Electrostatic surfaces of antibiotics were modeled and possible mechanism of antibiotic attachment is considered in this article. Raman spectra of magnetite, magnetite/silver and magnetite/silver/antibiotic were collected. It was found that it is difficult to detect the bands related to antibiotics in the magnetite/silver/antibiotic nanocomposite spectra due to their overlap by the broad carbon bands of magnetite nanopowder. Magnetic measurements revealed that magnetic saturation of the magnetite/silver/antibiotic nanocomposites decreased on 6-19 % in comparison with initial magnetite nanopowder. Pilot study of antimicrobial properties of the magnetite/silver/antibiotic nanocomposites were performed towards Bacillus pumilus.


Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Nanocomposites/chemistry , Silver/chemistry , Bacillus/drug effects , Cefotaxime/chemistry , Doxycycline/chemistry , Magnetite Nanoparticles/chemistry , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Photoelectron Spectroscopy , Rifampin/chemistry , Silver/pharmacology , Spectrum Analysis, Raman , Static Electricity , X-Ray Diffraction
20.
Acta Biochim Pol ; 62(2): 311-6, 2015.
Article En | MEDLINE | ID: mdl-25980357

Polymeric nanoparticles based on poly-N-isopropylacrylamide (pNiPAM NPs) and their bio-medical applications have been widely investigated in recent years. These tunable nanoparticles are considered to be great candidates for drug delivery systems, biosensors and bioanalytical devices. Thus, the biocompatibility and toxicity of these nanoparticles is clearly a crucial issue. In this work, the cytotoxicity of thermo-responsive pNiPAM nanoparticles was studied, followed by a detailed analysis of the NPs morphology in growing cell cultures and their 3D structure. Cytotoxic examination was conducted for two cell cultures - HeLa (cervical cancer cell line) and HeK293 (human embryonic kidney cell line), employing MTT (3-4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide) assay and viability tests. We used Cryo-SEM (scanning electron microscopy) and fluorescence microscopy (IN Cell Analyzer) in order to investigate the morphological structure of the polymer network. We show that pNiPAM nanoparticles do not exhibit any cytotoxicity effects on the investigated cell lines. Additionally, we report that the pNiPAM nanoparticle based scaffold promotes cell growth.


Acrylamides/chemistry , Biocompatible Materials , Nanoparticles/chemistry , Tissue Scaffolds , Cell Survival , HEK293 Cells/drug effects , HeLa Cells/drug effects , Humans , Materials Testing , Microscopy, Electron, Scanning , Microscopy, Fluorescence , Nanoparticles/toxicity
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