Studies on photodynamic mechanism of a novel chlorine derivative (TDPC) and its antitumor effect for photodynamic therapy in vitro and in vivo

Photodynamic therapy (PDT) represents a promising method for treatment of cancerous tumors. The chemical and physical properties of used photosensitizer (PS) play key roles in the treatment efficacy. In this study, a novel PS, 5,10,15,20-tetrakis((5-dipropylamino)pentyl)-chlorin (TDPC) which displayed a characteristic long wavelength absorption peak at 650 nm were synthesized. It also shows a singlet oxygen generation rate of 4.257 min-1. Generally, TDPC is localized in mitochondria and nucleus of cell. After light irradiation with 650 nm laser, it can kill many types of cell, in addition, TDPC–PDT can destroy ECA-109 tumor in nude mice and a necrotic scab was formed eventually. The expression levels of many genes which regulated cell growth and apoptosis were determined by RT-PCR following TDPC–PDT. The results showed that it either increased or decreased, among which, the expression level of TNFSF13, a member of tumor necrosis factor superfamily, increased significantly. In general, TDPC is an effective antitumor PS in vitro and in vivo and is worthy of further study as a new drug candidate. TNFSF13 will be an important molecular target for the discovery of new PSs.

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Anti-tumor activities of a novel chlorin derivative for photodynamic therapy in vitro and in vivo

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545815400039 ◽

2015 ◽

Vol 08 (01) ◽

pp. 1540003 ◽

Cited By ~ 6

Author(s):

Li-Jun Zhang ◽

Lai-Xing Wang ◽

Wei-Li Zhang ◽

Yi-Jia Yan ◽

Zhi-Long Chen

Keyword(s):

Photodynamic Therapy ◽

Quantum Yield ◽

Singlet Oxygen ◽

Nude Mice ◽

Absorption Peak ◽

Long Wavelength ◽

Wavelength Absorption ◽

Chlorin Derivative

In this study, a novel photosensitizer meso-tetra (3-pyrrolidinomethyl-4-methoxyphenyl) chlorin (TPMC) was reported. It displays a characteristic long wavelength absorption peak at 656 nm and it shows a singlet oxygen quantum yield of 0.48. After light irradiation with 650 nm laser, it can kill Eca-109 and SMMC-7721 cells in vitro (25 mW/cm2, 1.2 to 3.6 J/cm2) and destroy Eca-109 tumor in nude mice (50 mW/cm2, 90 J/cm2). It has the perspective to be developed as a new anti-tumor drug in photodynamic therapy (PDT) photodiagnosis, and deserves further investigation.

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Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190318120103 ◽

2019 ◽

Vol 20 (4) ◽

pp. 285-292 ◽

Cited By ~ 5

Author(s):

Abdullah M. Alnuqaydan ◽

Bilal Rah

Keyword(s):

Medicinal Plant ◽

Biological Activities ◽

Wide Spectrum ◽

Biological Properties ◽

In Vivo Model ◽

Drug Candidate ◽

Phytochemical Analysis ◽

Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

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In Vitro and In Vivo Investigations into the Carbene Copper Bromide Anticancer Drug Candidate WBC4

Letters in Drug Design & Discovery ◽

10.2174/1570180811666140529004102 ◽

2014 ◽

Vol 11 (7) ◽

pp. 825-832 ◽

Cited By ~ 12

Author(s):

Wolfgang Walther ◽

Iduna Fichtner ◽

Frauke Hackenberg ◽

Wojciech Streciwilk ◽

Matthias Tacke

Keyword(s):

Anticancer Drug ◽

Drug Candidate ◽

Copper Bromide

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Comparative Evaluation of In Vitro and In Vivo Assays for the Detection of Avian Infectious Bronchitis Virus as a Contaminant of Live Poultry Vaccines

Alternatives to Laboratory Animals ◽

10.1177/026119299802600508 ◽

1998 ◽

Vol 26 (5) ◽

pp. 629-634

Author(s):

Emiliana Falcone ◽

Edoardo Vignolo ◽

Livia Di Trani ◽

Simona Puzelli ◽

Maria Tollis

Keyword(s):

Infectious Bronchitis Virus ◽

Serological Response ◽

Avian Infectious Bronchitis Virus ◽

Animal Testing ◽

Rt Pcr ◽

Pcr Assay ◽

In Vivo Test ◽

Infectious Bronchitis

A reverse transcriptase polymerase chain reaction (RT-PCR) assay specific for identifying avian infectious bronchitis virus (IBV) in poultry vaccines, and the serological response to IBV induced by the inoculation of chicks with a Newcastle disease vaccine spiked with the Massachusetts strain of IBV, were compared for their ability to detect IBV as a contaminant of avian vaccines. The sensitivity of the IBV-RT-PCR assay provided results which were at least equivalent to the biological effect produced by the inoculation of chicks, allowing this assay to be considered a valid alternative to animal testing in the quality control of avian immunologicals. This procedure can easily be adapted to detect a number of contaminants for which the in vivo test still represents the only available method of detection.

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Development of Physiologically Based Pharmacokinetic Model for Orally Administered Fexuprazan in Humans

Pharmaceutics ◽

10.3390/pharmaceutics13060813 ◽

2021 ◽

Vol 13 (6) ◽

pp. 813

Author(s):

Yoo-Seong Jeong ◽

Min-Soo Kim ◽

Nora Lee ◽

Areum Lee ◽

Yoon-Jee Chae ◽

...

Keyword(s):

Gastric Acid ◽

Pbpk Model ◽

Pbpk Modeling ◽

Drug Candidate ◽

Metabolite Formation ◽

Pbpk Models ◽

Physiologically Based Pharmacokinetic ◽

Physiologically Based

Fexuprazan is a new drug candidate in the potassium-competitive acid blocker (P-CAB) family. As proton pump inhibitors (PPIs), P-CABs inhibit gastric acid secretion and can be used to treat gastric acid-related disorders such as gastroesophageal reflux disease (GERD). Physiologically based pharmacokinetic (PBPK) models predict drug interactions as pharmacokinetic profiles in biological matrices can be mechanistically simulated. Here, we propose an optimized and validated PBPK model for fexuprazan by integrating in vitro, in vivo, and in silico data. The extent of fexuprazan tissue distribution in humans was predicted using tissue-to-plasma partition coefficients in rats and the allometric relationships of fexuprazan distribution volumes (VSS) among preclinical species. Urinary fexuprazan excretion was minimal (0.29–2.02%), and this drug was eliminated primarily by the liver and metabolite formation. The fraction absorbed (Fa) of 0.761, estimated from the PBPK modeling, was consistent with the physicochemical properties of fexuprazan, including its in vitro solubility and permeability. The predicted oral bioavailability of fexuprazan (38.4–38.6%) was within the range of the preclinical datasets. The Cmax, AUClast, and time-concentration profiles predicted by the PBPK model established by the learning set were accurately predicted for the validation sets.

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Preclinical Studies in Anti-Trypanosomatidae Drug Development

Pharmaceuticals ◽

10.3390/ph14070644 ◽

2021 ◽

Vol 14 (7) ◽

pp. 644

Author(s):

Cintya Perdomo ◽

Elena Aguilera ◽

Ileana Corvo ◽

Paula Faral-Tello ◽

Elva Serna ◽

...

Keyword(s):

Rural Communities ◽

Chagas Disease ◽

Murine Model ◽

Mammalian Cells ◽

Drug Candidate ◽

Murine Macrophages ◽

Causative Agents ◽

Trypanosomatid Parasites

The trypanosomatid parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania are the causative agents of human African trypanosomiasis, Chagas Disease and Leishmaniasis, respectively. These infections primarily affect poor, rural communities in the developing world, and are responsible for trapping sufferers and their families in a disease/poverty cycle. The development of new chemotherapies is a priority given that existing drug treatments are problematic. In our search for novel anti-trypanosomatid agents, we assess the growth-inhibitory properties of >450 compounds from in-house and/or “Pathogen Box” (PBox) libraries against L. infantum, L. amazonensis, L.braziliensis, T. cruzi and T. brucei and evaluate the toxicities of the most promising agents towards murine macrophages. Screens using the in-house series identified 17 structures with activity against and selective toward Leishmania: Compounds displayed 50% inhibitory concentrations between 0.09 and 25 μM and had selectivity index values >10. For the PBox library, ~20% of chemicals exhibited anti-parasitic properties including five structures whose activity against L. infantum had not been reported before. These five compounds displayed no toxicity towards murine macrophages over the range tested with three being active in an in vivo murine model of the cutaneous disease, with 100% survival of infected animals. Additionally, the oral combination of three of them in the in vivo Chagas disease murine model demonstrated full control of the parasitemia. Interestingly, phenotyping revealed that the reference strain responds differently to the five PBox-derived chemicals relative to parasites isolated from a dog. Together, our data identified one drug candidate that displays activity against Leishmania and other Trypanosomatidae in vitro and in vivo, while exhibiting low toxicity to cultured mammalian cells and low in vivo acute toxicity.

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Synthesis and Characterization of Polyvinylpyrrolidone-Modified ZnO Quantum Dots and Their In Vitro Photodynamic Tumor Suppressive Action

International Journal of Molecular Sciences ◽

10.3390/ijms22158106 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8106

Author(s):

Tianming Song ◽

Yawei Qu ◽

Zhe Ren ◽

Shuang Yu ◽

Mingjian Sun ◽

...

Keyword(s):

Quantum Dots ◽

Photodynamic Therapy ◽

Inhibitory Effect ◽

Therapeutic Effects ◽

In Vivo Experiments ◽

Potential Applications ◽

Zno Quantum Dots ◽

Zno Qds

Despite the numerous available treatments for cancer, many patients succumb to side effects and reoccurrence. Zinc oxide (ZnO) quantum dots (QDs) are inexpensive inorganic nanomaterials with potential applications in photodynamic therapy. To verify the photoluminescence of ZnO QDs and determine their inhibitory effect on tumors, we synthesized and characterized ZnO QDs modified with polyvinylpyrrolidone. The photoluminescent properties and reactive oxygen species levels of these ZnO/PVP QDs were also measured. Finally, in vitro and in vivo experiments were performed to test their photodynamic therapeutic effects in SW480 cancer cells and female nude mice. Our results indicate that the ZnO QDs had good photoluminescence and exerted an obvious inhibitory effect on SW480 tumor cells. These findings illustrate the potential applications of ZnO QDs in the fields of photoluminescence and photodynamic therapy.

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Interaction of periodontitis and orthodontic tooth movement—an in vitro and in vivo study

Clinical Oral Investigations ◽

10.1007/s00784-021-03988-4 ◽

2021 ◽

Author(s):

Birgit Rath-Deschner ◽

Andressa V. B. Nogueira ◽

Svenja Beisel-Memmert ◽

Marjan Nokhbehsaim ◽

Sigrun Eick ◽

...

Keyword(s):

Alveolar Bone ◽

Tooth Movement ◽

Mechanical Strain ◽

Orthodontic Tooth Movement ◽

Fusobacterium Nucleatum ◽

In Vivo Study ◽

Rt Pcr ◽

Periodontal Inflammation

Abstract Objectives The aim of this in vitro and in vivo study was to investigate the interaction of periodontitis and orthodontic tooth movement on interleukin (IL)-6 and C-X-C motif chemokine 2 (CXCL2). Materials and methods The effect of periodontitis and/or orthodontic tooth movement (OTM) on alveolar bone and gingival IL-6 and CXCL2 expressions was studied in rats by histology and RT-PCR, respectively. The animals were assigned to four groups (control, periodontitis, OTM, and combination of periodontitis and OTM). The IL-6 and CXCL2 levels were also studied in human gingival biopsies from periodontally healthy and periodontitis subjects by RT-PCR and immunohistochemistry. Additionally, the synthesis of IL-6 and CXCL2 in response to the periodontopathogen Fusobacterium nucleatum and/or mechanical strain was studied in periodontal fibroblasts by RT-PCR and ELISA. Results Periodontitis caused an increase in gingival levels of IL-6 and CXCL2 in the animal model. Moreover, orthodontic tooth movement further enhanced the bacteria-induced periodontal destruction and gingival IL-6 gene expression. Elevated IL-6 and CXCL2 gingival levels were also found in human periodontitis. Furthermore, mechanical strain increased the stimulatory effect of F. nucleatum on IL-6 protein in vitro. Conclusions Our study suggests that orthodontic tooth movement can enhance bacteria-induced periodontal inflammation and thus destruction and that IL-6 may play a pivotal role in this process. Clinical relevance Orthodontic tooth movement should only be performed after periodontal therapy. In case of periodontitis relapse, orthodontic therapy should be suspended until the periodontal inflammation has been successfully treated and thus the periodontal disease is controlled again.

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