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1.
Mini Rev Med Chem ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38639278

RESUMO

Glioblastoma multiforme (GBM), a solid tumor that develops from astrocytes, is one of the most aggressive types of brain cancer. While there have been improvements in the efficacy of treating GBM, many problems remain, especially with traditional therapy methods. Therefore, recent studies have extensively focused on developing novel therapeutic agents for combating glioblastoma. Natural polyphenols have been studied for their potential as chemopreventive and chemotherapeutic agents due to their wide range of positive qualities, including antioxidant, antiinflammatory, cytotoxic, antineoplastic, and immunomodulatory activities. These natural compounds have been suggested to act via modulated various macromolecules within cells, including microRNAs (miRNAs), which play a crucial role in the molecular milieu. In this article, we focus on how polyphenols may inhibit tumor growth by influencing the expression of key miRNAs that regulate oncogenes and tumor suppressor genes.

2.
APMIS ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563150

RESUMO

Multiple sclerosis (MS) is a condition where the central nervous system loses its myelin coating due to autoimmune inflammation. The experimental autoimmune encephalomyelitis (EAE) simulates some aspects of human MS. Boswellic acids are natural compounds derived from frankincense extract, known for their anti-inflammatory properties. The purpose of this research was to investigate therapeutic potential of boswellic acids. Mice were divided into three groups: low-dose (LD), high-dose (HD), and control groups (CTRL). Following EAE induction, the mice received daily doses of boswellic acid for 25 days. Brain tissue damage, clinical symptoms, and levels of TGF-ß, IFN-γ, and IL-17 cytokines in cell cultured supernatant of lymphocytes were assessed. Gene expression of transcription factors in brain was measured using real-time PCR. The levels of brain demyelination were significantly lower in the treatment groups compared to the CTRL group. Boswellic acid reduced the severity and duration of EAE symptoms. Furthermore, boswellic acid decreased the amounts of IFN-γ and IL-17, also the expression of T-bet and ROR-γt in brain. On the contrary, it increased the levels of TGF-ß and the expression FoxP3 and GATA3. Our findings suggest that boswellic acids possess therapeutic potential for EAE by modulating the immune response and reducing inflammation.

3.
Mol Biol Rep ; 51(1): 500, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598005

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) condition comprising Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis involves immune system dysregulation, with increased Th (T helper cell)17 cells and reduced regulatory T cell (Treg) differentiation. Transforming growth factor-ß (TGF-ß) secretion from Tregs helps control inflammation, and its production is regulated by glycoprotein-A repetition predominant (GARP) protein along with non-coding RNAs (ncRNAs) like microRNA(miR)-142-3p and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNAs (LncRNAs). This study analyzed their expression in IBD. METHODS: Blood samples were collected from 44 IBD patients, and 22 healthy controls (HC). RNA extraction and circular DNA (cDNA) synthesis were performed. Real-time polymerase chain reaction (RT-PCR) measured gene expression of GARP, MALAT1, and miR-142-3p. Correlations and group differences were statistically analyzed. RESULTS: Compared to controls, GARP was downregulated while MALAT1 and miR-142-3p were upregulated significantly in IBD group. GARP and MALAT1 expressions positively correlated in controls. MALAT1 and miR-142-3p expressions positively correlated in IBD group. MALAT1 was downregulated in aged HC but upregulated with smoking history across groups. No correlations occurred between gene expression and gender, diet, infections, or disease activity scores. CONCLUSIONS: Dysregulation of GARP, MALAT1, and miR-142-3p likely contributes to inflammation in IBD by reducing TGF-ß. MALAT1 is linked to smoking and age-related changes. These genes have potential as diagnostic markers or therapeutic targets for personalized IBD treatment.


Assuntos
Doenças Inflamatórias Intestinais , MicroRNAs , RNA Longo não Codificante , Humanos , Idoso , RNA Longo não Codificante/genética , Doenças Inflamatórias Intestinais/genética , Inflamação/genética , Glicoproteínas , MicroRNAs/genética , Biomarcadores , Fator de Crescimento Transformador beta/genética
4.
Mol Biol Rep ; 51(1): 256, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302802

RESUMO

Introduction Multiple sclerosis (MS) is an autoimmune condition marked by inflammation and the loss of myelin in the central nervous system (CNS). The aim of this research was to understand how Thymoquinone regulate the molecular and cellular processes involved in controlling experimental autoimmune encephalomyelitis (EAE), which is an animal model often used to study MS. Methods Female C57BL/6 mice were split into different groups receiving different doses (low, medium, and high) of Thymoquinone simultaneously with EAE induction. Clinical scores and other measurements were observed daily throughout the 25-day post immunization. We assessed lymphocyte infiltration and demyelination in the spinal cord through histological staining, analyzed T-cell profiles using ELISA, and quantified the expression levels of transcription factors in the CNS using Real-time PCR. Results Thymoquinone prevented the development of EAE. Histological experiments revealed only a small degree of leukocyte infiltration into the CNS. Thymoquinone resulted in a notable reduction in the generation of IFN-γ, IL-17, and IL-6, while simultaneously increasing the production of IL-4, IL-10, and TGF-ß in Th2 and Treg cells. Results from Real-time PCR suggested Treatment with Thymoquinone decreased the expression of T-bet and ROR-γt while increasing the expression of Foxp3 and GATA3. Conclusion These findings showed that Thymoquinone could decrease both disease incidence and severity.


Assuntos
Benzoquinonas , Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Camundongos , Feminino , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Esclerose Múltipla/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico
5.
Artigo em Inglês | MEDLINE | ID: mdl-38358468

RESUMO

Most animals have large amounts of the special substance melatonin, which is controlled by the light/dark cycle in the suprachiasmatic nucleus. According to what is now understood, the gastrointestinal tract (GIT) and other areas of the body are sites of melatonin production. According to recent studies, the GIT and adjacent organs depend critically on a massive amount of melatonin. Not unexpectedly, melatonin's many biological properties, such as its antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-metastasis, and antiangiogenic properties, have drawn the attention of researchers more and more. Because melatonin is an antioxidant, it produces a lot of secretions in the GIT's mucus and saliva, which shields cells from damage and promotes the development of certain GIT-related disorders. Melatonin's ability to alter cellular behavior in the GIT and other associated organs, such as the liver and pancreas, is another way that it functions. This behavior alters the secretory and metabolic activities of these cells. In this review, we attempted to shed fresh light on the many roles that melatonin plays in the various regions of the gastrointestinal tract by focusing on its activities for the first time.

6.
J Biomol Struct Dyn ; 42(4): 2094-2110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37129119

RESUMO

Monkeypox virus is a member of the Poxviridae family, which causes monkeypox zoonotic disease. Since July 2022, the prevention of monkeypox have become more considerable due to the new outbreak, making it a global concern. Therefore, we used an in silico-based method, including immunoinformatics, bioinformatics, molecular docking, and gene cloning approaches to design a novel multiepitope vaccine against monkeypox. Three immunogenic envelope proteins of monkeypox virus, including G10R, E8L, and A30L, were selected to predict appropriate immune system stimulator epitopes. The A30L is common between smallpox and monkeypox virus, so the proposed vaccine may be effective against smallpox too. There is no evidence of allergenicity and toxicity of the vaccine epitopes. To boost the immunogenicity of the designed vaccine, we used the helper epitope of PADRE and RS01as adjuvants. Furthermore, some linkers are used to link epitopes and adjuvants together. The physicochemical futures of the designed vaccine were assessed. The tertiary structure of the vaccine was modeled and then refined to improve its structure and physicochemical properties. To analyze the vaccine construct and TLR4 complex affinity, they were docked to gather. Besides, the vaccine was cloned into E.coli. pET-21b(+) plasmid to reveal that it can be expressed and stimulate the immune system. Immune stimulation evaluation showed that the candidate vaccine could induce the production of IgM, IgG1, and IgG2 antibodies. Overall, we suggested an effective vaccine candidate against monkeypox. However, Future studies and clinical trials should be done to ensure the efficacy and safety of this vaccine.Communicated by Ramaswamy H. Sarma.


Assuntos
Varíola , Vacinas , Humanos , Receptor 4 Toll-Like , Simulação de Acoplamento Molecular , Biologia Computacional , Epitopos , Escherichia coli , Epitopos de Linfócito T , Epitopos de Linfócito B , Vacinas de Subunidades
7.
Biomed Pharmacother ; 169: 115900, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37981461

RESUMO

Nowadays, lung cancer is the most common cause of cancer-related deaths in both men and women globally. Despite the development of extremely efficient targeted agents, lung cancer progression and drug resistance remain serious clinical issues. Increasing knowledge of the molecular mechanisms underlying progression and drug resistance will enable the development of novel therapeutic methods. It has been revealed that transcription factors (TF) dysregulation, which results in considerable expression modifications of genes, is a generally prevalent phenomenon regarding human malignancies. The forkhead box O1 (FOXO1), a member of the forkhead transcription factor family with crucial roles in cell fate decisions, is suggested to play a pivotal role as a tumor suppressor in a variety of malignancies, especially in lung cancer. FOXO1 is involved in diverse cellular processes and also has clinical significance consisting of cell cycle arrest, apoptosis, DNA repair, oxidative stress, cancer prevention, treatment, and chemo/radioresistance. Based on the critical role of FOXO1, this transcription factor appears to be an appropriate target for future drug discovery in lung cancers. This review focused on the signaling pathways, and molecular mechanisms involved in FOXO1 regulation in lung cancer. We also discuss pharmacological compounds that are currently being administered for lung cancer treatment by affecting FOXO1 and also point out the essential role of FOXO1 in drug resistance. Future preclinical research should assess combination drug strategies to stimulate FOXO1 and its upstream regulators as potential strategies to treat resistant or advanced lung cancers.


Assuntos
Neoplasias Pulmonares , Masculino , Humanos , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Proteína Forkhead Box O1/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição Forkhead/genética , Transdução de Sinais
8.
Mol Biol Rep ; 50(12): 9971-9984, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897611

RESUMO

INTRODUCTION: Clinical and experimental studies highlighted the significant therapeutic role of Mesenchymal stem cells (MSCs) in neurodegenerative diseases. MSCs possess potent immunomodulatory properties by releasing exosomes, which generate a suitable microenvironment. microRNAs (miRNAs), as one of several effective bioactive molecules of exosomes, influence cellular communication and activities in recipient cells. Recent studies revealed that miRNAs could control the progression of multiple sclerosis (MS) via differentiation and function of T helper cells (Th). METHODS: Here, we investigated the therapeutic effects of syngeneic-derived BM-MSC in experimental autoimmune encephalomyelitis (EAE) mouse model of MS by evaluating expression profile of miRNAs, pro- and anti-inflammatory in serum and brain tissues. Three-time scheme groups (6th day, 6th & 12th days, and 12th day, of post-EAE induction) were applied to determine the therapeutic effects of intraperitoneally received 1*106 of BM-MSCs. RESULTS: The expression levels of mature isoforms of miR-193, miR-146a, miR-155, miR-21, and miR-326 showed that BM-MSCs treatment attenuated the EAE clinical score and reduced clinical inflammation as well as demyelination. The improved neurological functional outcome associated with enhanced expression of miR-193 and miR-146a, but decreased expression levels of miR-155, miR-21, and miR-326 were followed by suppressing effects on Th1/Th17 immune responses (reduced levels of IFN-γand IL-17 cytokine expression) and induction of Treg cells, immunoregulatory responses (increase of IL-10, TGF-ß, and IL-4) in treatment groups. CONCLUSION: Our findings suggest that BM-MSCs administration might change expression patterns of miRNAs and downstream interactions followed by immune system modulation. However, there is a need to carry out future human clinical trials and complementary experiments.


Assuntos
Encefalomielite Autoimune Experimental , Células-Tronco Mesenquimais , MicroRNAs , Esclerose Múltipla , Animais , Camundongos , Humanos , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/terapia , MicroRNAs/genética , MicroRNAs/metabolismo , Esclerose Múltipla/genética , Esclerose Múltipla/terapia , Inflamação/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , Células da Medula Óssea
9.
Artigo em Inglês | MEDLINE | ID: mdl-37878043

RESUMO

The control of biological cell death is essential for the body's appropriate growth. The resistance of cells to the apoptotic process presents a new difficulty in the treatment of cancer. To combat cancer cells, researchers are working to find new apoptotic pathways and components to activate. One of the processes of regulated cell death (RCD) is referred to as ferroptosis marked by a decline in the activity of lipid glutathione peroxidase 4 (GPX4) after the buildup of reactive oxygen species (ROS). Since lipid peroxidation is a crucial component of ferroptosis and is required for its start, numerous medicines have been studied, particularly for the treatment of cancer. In this context, autophagy is an additional form of RCD that can govern ferroptosis through shared signaling pathways/factors involved in both mechanisms. In this review, we will explore the molecular mechanisms underlying ferroptosis and its association with autophagy, to gain fresh insights into their interplay in cancer advancement, and the potential of natural products for its treatment.

10.
Cell Biol Int ; 47(11): 1767-1781, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37671447

RESUMO

Breast cancer is a commonly known cancer type and the leading cause of cancer death among females. One of the unresolved problems in cancer treatment is the increased resistance of the tumor to existing treatments, which is a direct result of apoptotic defects. Calculating an alternative to cell death (autophagy) may be the ultimate solution to maximizing cancer cell death. Our aim in this study was to investigate the potential of free nanoparticles (un-drug-loaded) in the induction or inhibition of autophagy and consider this effect on the therapy process. When the studies met the inclusion criteria, the full texts of all relevant articles were carefully examined and classified. Of the 25 articles included in the analysis, carried out on MCF-7, MDA-MB-231, MDA-MB-231-TXSA, MDA-MB-468, SUM1315, and 4T1 cell lines. Twenty in vitro studies and five in vivo/in vitro studies applied five different autophagy tests: Acridine orange, western blot, Cyto-ID Autophagy Detection Kit, confocal microscope, and quantitative polymerase chain reaction. Nanoparticles (NPs) in the basic format, including Ag, Au, Y2 O3 , Se, ZnO, CuO, Al, Fe, vanadium pentoxide, and liposomes, were prepared in the included articles. Three behaviors of NPs related to autophagy were seen: induction, inhibition, and no action. Screened and presented data suggest that most of the involved free NPs (metallic NPs) in this systematic review had reactive oxygen species-mediated pathways with autophagy induction (36%). Also, PI3K/Akt/mTOR and MAPK/ERK signaling pathways were mentioned in just four studies (16%). An impressive percentage of studies (31%) did not examine the NP-related autophagy pathway.

11.
Mol Biol Rep ; 50(11): 8843-8853, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37660318

RESUMO

BACKGROUND: Multiple sclerosis (MS) is an autoimmune central nervous system (CNS) disorder indicated by demyelination, chronic inflammation, and neuronal destruction. Regional demyelination, inflammation responses, scar development, and various axonal damage are pathological characteristics of MS. Curcumin is a hydrophobic polyphenol extracted from the rhizome of the turmeric plant. In addition to anti-inflammatory effects, beneficial therapeutic effects such as antioxidant, anti-cancer and nerve protection have also been seen from this compound. The purpose of the current investigation was to provide light on the potential benefits of Curcumin in treating experimental autoimmune encephalomyelitis (EAE), the animal model of MS. METHODS AND RESULTS: in Female C57BL/6 mice were used to induce EAE through myelin oligodendroglial glycoprotein (MOG). Curcumin doses of 100 and 200 mg/kg were administered orally in the treatment groups starting on the first day of EAE induction. Brains and splenocytes were extracted from euthanized animals on day 25 following EAE induction. Demyelination and leukocyte infiltration, proliferation, cytokine, and gene expression profiles were assessed. Our findings demonstrate that both low and high doses of Curcumin decreased the progression of EAE. Histological analyses revealed low infiltration of leukocytes into the CNS. Curcumin therapy enhanced Th2 and Treg cell secretion of IL-4, IL-10, and TGF-ß although considerably decreasing IFN-γ and TNF-α. Curcumin-induced Th2 and Treg cell cytokine production and transcription factor gene expression (IL-13, GATA3, STAT6 and IL-35, CTLA4, Foxp3) and anti-inflammatory cytokines (IL-27, IL-33). CONCLUSION: Overall, these findings provide additional evidence that Curcumin can slow disease development and alleviate symptoms in EAE through stimulating Treg and Th2 cell polarization. They support Curcumin's potential therapeutic role in MS.


Assuntos
Curcumina , Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Camundongos , Esclerose Múltipla/tratamento farmacológico , Curcumina/farmacologia , Curcumina/uso terapêutico , Especiarias , Camundongos Endogâmicos C57BL , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Imunidade , Anti-Inflamatórios/uso terapêutico , Gravidade do Paciente
12.
Adv Pharm Bull ; 13(3): 423-434, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37646047

RESUMO

Periodontal disease is the most common oral disease. This disease can be considered as an inflammatory disease. The immune response to bacteria accumulated in the gum line plays a key role in the pathogenesis of periodontal disease. In addition to immune cells, periodontal ligament cells and gingival epithelial cells are also involved in the pathogenesis of this disease. miRNAs which are small RNA molecules with around 22 nucleotides have a considerable relationship with the immune system affecting a wide range of immunological events. These small molecules are also in relation with periodontium tissues especially periodontal ligament cells. Extensive studies have been performed in recent years on the role of miRNAs in the pathogenesis of periodontal disease. In this review paper, we have reviewed the results of these studies and discussed the role of miRNAs in the immunopathogenesis of periodontal disease comprehensively. miRNAs play an important role in the pathogenesis of periodontal disease and maybe helpful therapeutic targets for the treatment of periodontal disease.

13.
Chem Biol Drug Des ; 102(5): 1257-1275, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37496299

RESUMO

Noncoding RNAs (ncRNAs) are engaged in key cell biological and pathological events, and their expression alteration is connected to cancer progression both directly and indirectly. A huge number of studies have mentioned the significant role of ncRNAs in cancer prevention and therapy that make them an interesting subject for cancer therapy. However, there are several limitations, including delivery, uptake, and short half-life, in the application of ncRNAs in cancer treatment. Exosomes are introduced as promising options for the delivery of ncRNAs to the target cells. In this review, we will briefly discuss the application and barriers of ncRNAs. After that we will focus on exosome-based ncRNAs delivery and their advantages as well as the latest achievements in drugging ncRNAs with exosomes.

14.
Life Sci ; 329: 121947, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37463653

RESUMO

Cardiovascular disease (CVD) remains the most common cause of death worldwide and has become a public health concern. The proven notable risk factors for CVD are atherosclerosis, hypertension, diabetes, dyslipidemia, inflammation, and some genetic defects. However, research has shown a correlation between metabolic health, gut microbiota, and dietary risk factors. The gut microbiota makes an important contribution to human functional metabolic pathways by contributing enzymes that are not encoded by the human genome, for instance, the breakdown of polysaccharides, polyphenols and vitamins synthesis. TMAO and SCFAs, human gut microbiota compounds, have respective immunomodulatory and pro-inflammatory effects. Choline and l-carnitine are abundant in high-fat diets and are transformed into TMA by gut bacteria. The liver's phase of metabolism then changes TMA into TMAO. In turn, TMAO promotes the activation of macrophages, damages vascular endothelium, and results in CVD-however, dysbiosis decreases SCFAs and bile acids, which raises intestinal permeability. Congestion in the portal vein, a drop in cardiac output, a reduction in intestinal perfusion, and intestinal leakage are all caused by heart failure. These factors induce systemic inflammation by increasing intestinal leakage. By raising CRP and pro-inflammatory reactions, human gut dysbiosis and elevated TMAO levels promote the development of arterial plaque, hasten the beginning of atherosclerosis, and raise the risk of CAD. A healthy symbiosis between the gut microbiota and host is a key factor in shaping the biochemical profile of the diet, therefore which are crucial for maintaining the intestinal epithelial barrier, growing mucosa, reducing inflammation, and controlling blood pressure.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Disbiose , Metilaminas/metabolismo , Aterosclerose/etiologia , Aterosclerose/metabolismo , Inflamação
15.
Bioimpacts ; 13(3): 207-218, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37431478

RESUMO

Introduction: Doxorubicin (DOX) is one of the most common drugs in cancer treatment. However, its partial solubility along with the high incidence of side effects remains a challenge to tackle. To address these issues, we designed a formulation based on graphene oxide (GO) and used it as an anticancer drug delivery system. Methods: The physical and chemical properties of the formulation were studied using FTIR, SEM, EDX, Mapping, and XRD. Release studies in the in vitro condition were used to evaluate the pH sensitivity of drug release from nanocarriers. Other in vitro studies, including uptake assay, MTT, and apoptosis assay were carried out on the osteosarcoma cell line. Results: in vitro release studies confirmed that the synthesized formulation provides a better payload release profile in acidic conditions, which is usually the case in the tumor site. On the OS cell line, the cytotoxicity of the DOX-loaded nanocarrier (IC50=0.293 µg/mL) and early apoptosis rate (33.80 % ) were higher in comparison to free DOX (IC50=0.472 µg/mL, and early apoptosis rate= 8.31 % ) after 48 hours. Conclusion: In summary, our results suggest a DOX-loaded graphene oxide carrier as a potential platform for targeting cancer cells.

16.
Curr Med Chem ; 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37202890

RESUMO

Melanoma accounts for the minority of skin cancer cases. However, it has the highest mortality rate among the subtypes of skin cancer. At the early stages of the disease, patients show a good prognosis after the surgery, but developing metastases leads to a remarkable drop in patients' 5-year survival rate. Despite the advances made in the therapeutic approaches to this disease, melanoma treatment is still facing several obstacles. Systemic toxicity, water insolubility, instability, lack of proper biodistribution, inadequate cellular penetration, and rapid clearance are some of the challenges that should be addressed in the field of melanoma treatment. While various delivery systems have been developed to circumvent these challenges, chitosan-based delivery platforms have indicated significant success. Chitosan that is produced by the deacetylation of chitin can be formulated into different materials (e.g., nanoparticle, film, and hydrogel) due to its characteristics. Both in vitro and in vivo studies have reported that chitosan-based materials can be used in drug delivery systems while offering a solution for the common problems in this area, such as enhancing biodistribution and skin penetration as well as the sustained release of the drugs. Herein, we reviewed the studies concerning the role of chitosan as a drug delivery system in melanoma and discussed how these drug systems are used for delivering chemotherapeutic drugs (e.g., doxorubicin and paclitaxel), genes (e.g., TRAIL), and RNAs (e.g., miRNA199a and STAT3 siRNA) successfully. Furthermore, we take a look into the role of chitosan-based nanoparticles in neutron capture therapy.

17.
Cell Signal ; 107: 110667, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37023996

RESUMO

In recent decades, various investigations have indicated that natural compounds have great potential in the prevention and treatment of different chronic disorders including different types of cancer. As a bioactive flavonoid, Quercetin (Qu) is a dietary ingredient enjoying high pharmacological values and health-promoting effects due to its antioxidant and anti-inflammatory characterization. Conclusive in vitro and in vivo evidence has revealed that Qu has great potential in cancer prevention and development. Qu exerts its anticancer influences by altering various cellular processes such as apoptosis, autophagy, angiogenesis, metastasis, cell cycle, and proliferation. In this way, Qu by targeting numerous signaling pathways as well as non-coding RNAs regulates several cellular mechanisms to suppress cancer occurrence and promotion. This review aimed to summarize the impact of Qu on the molecular pathways and non-coding RNAs in modulating various cancer-associated cellular mechanisms.


Assuntos
Neoplasias , Quercetina , Humanos , Quercetina/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/genética , Transdução de Sinais , Flavonoides/farmacologia , Antioxidantes/farmacologia
18.
Int Immunopharmacol ; 117: 109932, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37012889

RESUMO

Inflammatory bowel disease (IBD) is a widespread autoimmune disease that may even be life-threatening. IBD is divided into two major subtypes: ulcerative colitis and Crohn's disease. Interleukin (IL)-35 and IL-37 are anti-inflammatory cytokines that belong to IL-12 and IL-1 families, respectively. Their recruitment relieves inflammation in various autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, and IBD. Regulatory T cells (Tregs) and regulatory B cells (Bregs) are the primary producers of IL-35/IL-37. IL-35 and IL-37 orchestrate the regulation of the immune system through two main strategies: Blocking nuclear transcription factor kappa-B (NF-kB) and mitogen-activated protein kinase (MAPK) signaling pathways or promoting the proliferation of Tregs and Bregs. Moreover, IL-35 and IL-37 can also inhibit inflammation by adjusting the T helper (Th)17/Treg ratio balance. Among the anti-inflammatory cytokines, IL-35 and IL-37 have significant potential to reduce intestinal inflammation. Therefore, administering IL-35/IL-37-based drugs or blocking their inhibitor microRNAs could be a promising approach to alleviate IBD symptoms. Overall, in this review article, we summarized the therapeutic application of IL-35 and IL-37 in both human and experimental models of IBD. Also, it is hoped that this practical information will reach beyond IBD therapy and shed some light on treating all intestinal inflammations.


Assuntos
Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inflamação/tratamento farmacológico , Citocinas , Anti-Inflamatórios/uso terapêutico , Interleucinas/genética , Interleucinas/uso terapêutico
19.
Med Oncol ; 40(3): 87, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36723692

RESUMO

Chrysin (Chr) has drawn a lot of attention recently due to its possible anticancer properties. However, Chr's short half-life and low bioavailability restricted its utility as a medicinal agent. The purpose of this research is to design, synthesize, and test the cytotoxic effects of nano-niosomes containing chrysin (Chr-Nio) on the SKOV3 ovarian cancer cell line. Chr-Nio has a nanoparticle polydispersity index (PDI) of 0.156 and a zeta potential of - 27.4 mV, with an average diameter of 105 nm. Furthermore, Chr was encapsulated in Nio with an entrapment effectiveness of 85.5%. Chr-Nio cytotoxicity was shown to be more than free Chr in a time- and dose-dependent manner. Furthermore, as compared to free Chr-treated cells, the mRNA expression level of apoptotic genes Bcl-2, Bax, and caspase-3 in Chr-Nio-treated cells was considerably altered. According to the data, Chr may inhibit SKOV3 cell migration in vitro scratch wound experiments in a dose-dependent manner, and cells treated with Chr-Nio had the highest percentage of cell death. The findings of this study suggested that encapsulating Chr in niosome nanoparticles might be an effective medication delivery strategy for increasing Chr anticancer effects in the treatment of ovarian cancer.


Assuntos
Nanopartículas , Neoplasias Ovarianas , Feminino , Humanos , Lipossomos , Sistemas de Liberação de Medicamentos , Neoplasias Ovarianas/tratamento farmacológico , Carcinoma Epitelial do Ovário
20.
Allergy Asthma Clin Immunol ; 19(1): 1, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36593510

RESUMO

BACKGROUND: Asthma is considered to be a chronic inflammatory disorder of the airways. Probiotics are living microorganisms that are found in the human gut and have protective effects against a wide range of diseases such as allergies. The aim of this study was to investigate the improvement of clinical asthma symptoms and changes in the expression pattern of selective microRNAs in patients with asthma and the changes in IL-4 and IFN-γ plasma levels after receiving probiotics. MATERIALS AND METHODS: The present study was a randomized, double-blind, placebo-controlled trial that enrolled 40 asthmatic patients. They were treated with probiotics or placebo: 1 capsule/day for 8 weeks. Pulmonary function tests, IL-4 and IFN-γ levels, and expression of microRNAs were assessed at baseline and after treatment. RESULTS: The results showed that the expression of miR-16, miR146-a and IL-4 levels in patients with asthma after receiving probiotic supplementation was significantly reduced and miR-133b expression was increased. In addition, pulmonary function tests showed a significant improvement in Forced Expiratory Volume in 1 s and Forced Vital Capacity after receiving probiotics. CONCLUSION: In our study, 8-week treatment with probiotic supplementation led to reduced Th2 cells-associated IL-4 and improved Forced Expiratory Volume and Forced Vital Capacity. It appears probiotics can be used in addition to common asthma treatments.

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