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1.
Microorganisms ; 12(5)2024 May 13.
Article in English | MEDLINE | ID: mdl-38792809

ABSTRACT

Despite great advances in the treatment of oncological diseases, the development of medical technologies to prevent or reduce complications of therapy, in particular, those associated with surgery and the introduction of antibiotics, remains relevant. The aim of this study is to evaluate the effectiveness of the use of autoprobiotics based on indigenous non-pathogenic strains of Enterococcus faecium and Enterococcus hirae as a personalized functional food product (PFFP) in the complex therapy of colorectal cancer (CRC) in the early postoperative period. A total of 36 patients diagnosed with CRC were enrolled in the study. Study group A comprised 24 CRC patients who received autoprobiotic therapy in the early postoperative period, while the control group C included 12 CRC patients without autoprobiotic therapy. Prior to surgery and between days 14 and 16 post-surgery, comprehensive evaluations were conducted on all patients, encompassing the following: stool and gastroenterological complaints analysis, examination of the gut microbiota (bacteriological study, quantitative polymerase chain reaction, metagenome analysis), and analysis of interleukins in the serum. Results: The use of autoprobiotics led to a decrease in dyspeptic complaints after surgery. It was also associated with the absence of postoperative complications, did not cause any side effects, and led to a decrease in the level of pro-inflammatory cytokines (IL-6 and IL-18) in the blood serum. The use of autoprobiotics led to positive changes in the structure of escherichia and enterococci populations, the elimination of Parvomonas micra and Fusobacterium nucleatum, and a decrease in the quantitative content of Clostridium perfringens and Akkermansia muciniphila. Metagenomic analysis (16S rRNA) revealed an increase in alpha diversity. Conclusion: The introduction of autoprobiotics in the postoperative period is a highly effective and safe approach in the complex treatment of CRC. Future studies will allow the discovery of additional fine mechanisms of autoprobiotic therapy and its impact on the digestive, immune, endocrine, and neural systems.

2.
World J Clin Cases ; 11(20): 4740-4751, 2023 Jul 16.
Article in English | MEDLINE | ID: mdl-37583996

ABSTRACT

The article discusses various approaches for probiotic treatment of Helicobacter pylori (H. pylori) infection: Probiotics as an adjuvant treatment in the standard eradication therapy; probiotic strains as a monotherapy; and autoprobiotics as a monotherapy. Autoprobiotics refer to indigenous bifidobacteria, lactobacilli, or enterococci isolated from a specific individual, intended to restore his/her microbiota and improve his/her health. The potential mechanisms of probiotic action against H. pylori include correction of the gut microbiota, immunological effects (enhancement of humoral and cellular immunity, and reduction of oxidative stress), direct antagonistic effects against H. pylori (such as colonization resistance and bacteriocin synthesis), and stimulation of local immunological protection (strengthening of the mucous protective barrier and reduction of gastric mucosa inflammation). The incorporation of probiotics into comprehensive eradication therapy shows promise in optimizing the treatment of H. pylori infection. Probiotics can enhance the eradication rates of H. pylori, reduce the occurrence and severity of side effects, and improve patient compliance. Probiotic or autoprobiotic monotherapy can be considered as an alternative treatment approach in cases of allergic reactions and insufficient effectiveness of antibiotics. We recommend including probiotics as adjunctive medications in anti-H. pylori regimens. However, further randomized multicenter studies are necessary to investigate the effects of probiotics and autoprobiotics against H. pylori, in order to gain a better understanding of their mechanisms of action.

3.
J Steroid Biochem Mol Biol ; 231: 106309, 2023 07.
Article in English | MEDLINE | ID: mdl-37037385

ABSTRACT

Heterocyclic derivatives of steroid hormones are potent anticancer agents, which are used in the chemotherapy of breast and prostate cancers. Here, we describe a novel series of androstenes, D-modified with imidazole-annulated pendants, with significant anticancer activity. Novel C17-linked imidazole-annulated heterocyclic derivatives of dehydropregnenolone acetate were synthesized by the cyclocondensation with amidines using 3ß-acetoxy-21-bromopregna-5,16-dien-20-one as the substrate. The antiproliferative potency of all the synthesized compounds was evaluated against human prostate (22Rv1) and human breast (MCF7) cancer cell lines and cytochromes P450. The lead compound, imidazo[1,2-a]pyridine derivative 3h, was revealed to be a promising candidate for future anticancer drug design, particularly against ERα-positive breast cancer. Lead compound 3h was found to be selective against MCF7 cells with IC50 of 0.1 µM and to act as both a potent selective agent blocking estrogen receptor α, which is involved in the stimulation of breast cancer growth, and an effective apoptosis inducer. The potential ability of compound 3h to bind to ERα was studded using molecular docking and molecular dynamics simulation. The selectivity analysis showed that lead steroid 3h produces no effects on cytochromes P450 CYP17A1, CYP7A1, and CYP21A2.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Male , Humans , Estrogen Receptor alpha , Estrogen Receptor Modulators/pharmacology , Molecular Docking Simulation , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Steroids/pharmacology , Steroids/chemistry , Imidazoles/pharmacology , Estrogen Antagonists/pharmacology , Breast Neoplasms/drug therapy , Cytochromes/pharmacology , Cell Proliferation , Structure-Activity Relationship , Drug Screening Assays, Antitumor , Cell Line, Tumor , Molecular Structure
4.
Pharmacol Rev ; 73(4): 1-32, 2021 10.
Article in English | MEDLINE | ID: mdl-34663683

ABSTRACT

Brain cancer is a formidable challenge for drug development, and drugs derived from many cutting-edge technologies are being tested in clinical trials. We manually characterized 981 clinical trials on brain tumors that were registered in ClinicalTrials.gov from 2010 to 2020. We identified 582 unique therapeutic entities targeting 581 unique drug targets and 557 unique treatment combinations involving drugs. We performed the classification of both the drugs and drug targets based on pharmacological and structural classifications. Our analysis demonstrates a large diversity of agents and targets. Currently, we identified 32 different pharmacological directions for therapies that are based on 42 structural classes of agents. Our analysis shows that kinase inhibitors, chemotherapeutic agents, and cancer vaccines are the three most common classes of agents identified in trials. Agents in clinical trials demonstrated uneven distribution in combination approaches; chemotherapy agents, proteasome inhibitors, and immune modulators frequently appeared in combinations, whereas kinase inhibitors, modified immune effector cells did not as was shown by combination networks and descriptive statistics. This analysis provides an extensive overview of the drug discovery field in brain cancer, shifts that have been happening in recent years, and challenges that are likely to come. SIGNIFICANCE STATEMENT: This review provides comprehensive quantitative analysis and discussion of the brain cancer drug discovery field, including classification of drug, targets, and therapies.


Subject(s)
Antineoplastic Agents , Brain Neoplasms , Pharmaceutical Preparations , Brain Neoplasms/drug therapy , Drug Discovery , Humans , Proteasome Inhibitors
5.
Org Biomol Chem ; 18(29): 5571-5576, 2020 08 07.
Article in English | MEDLINE | ID: mdl-32662797

ABSTRACT

An efficient and practical method has been developed for the synthesis of steroidal imidazoheterocycles via cost-effective and environmentally benign FeCl3-catalyzed oxidative amination. A library of steroidal imidazo[1,2-a]pyridines was directly synthesized from readily available 2-aminopyridines and steroidal ketones in aerobic conditions. The synthesized compounds were screened for activity on human microsomal cytochrome P450s CYP7, CYP17 and CYP21. Antiproliferative activity of two lead compounds 3ia and 3la was additionally evaluated against the human MCF-7 (breast cancer), SKOV3 (ovarian cancer), and 22Rv1 (prostate cancer) cell lines. Steroidal imidazo[1,2-a]pyridine 3la which is a substrate molecule for CYP17A1 with IC50 = 1.7 µM (MCF-7), 3.0 (SKOV3), and 6.0 µM (22Rv1) has proved to be more active than reference drug cisplatin.


Subject(s)
Antineoplastic Agents/pharmacology , Ferric Compounds/chemistry , Heterocyclic Compounds/pharmacology , Imidazoles/pharmacology , Steroids/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Catalysis , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Humans , Imidazoles/chemical synthesis , Imidazoles/chemistry , Molecular Conformation , Stereoisomerism , Steroids/chemical synthesis , Steroids/chemistry
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