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1.
Eur J Cancer Prev ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38837193

RESUMO

OBJECTIVES: This systematic review aims to synthesize the available literature to determine the association between birthweight and the risk of nonneurological childhood cancers. METHODS: We conducted a systematic search of PubMed, Web of Science, and Scopus databases up to May 2023 to identify observational studies. Heterogeneity between studies was evaluated using the I2 statistics. Publication bias was assessed using Begg and Egger tests. We calculated the odds ratio (OR) or risk ratio (RR) with a 95% confidence interval (CI) using a random-effects model. RESULTS: Of 11 034 studies retrieved from the search, 56 studies (including 10 568 091 participants) were eligible. The ORs (95% CI) of low (<2500 g) versus normal birthweight (2500-4000 g) and childhood cancers were as follows: leukemia, 0.92 (0.77-1.11); acute lymphoblastic leukemia, 0.82 (0.72-0.94); acute myeloid leukemia, 0.98 (0.77-1.24); lymphoma, 0.99 (0.47-2.10); Hodgkin, 0.79 (0.61-1.03); non-Hodgkin, 0.85 (0.60-1.20); neuroblastoma, 1.34 (1.14-1.58); retinoblastoma, 0.95 (0.68-1.32); rhabdomyosarcoma, 0.86 (0.61-1.20); embryonal, 0.97 (0.66-1.43); alveolar, 1.92 (0.43-8.51); and Wilms tumor, 1.01 (0.83-1.24). The ORs (95% CI) of high (>4000 g) versus normal birthweight and childhood cancers were as follows: leukemia, 1.30 (1.18-1.42); acute lymphoblastic leukemia, 1.27 (1.16-1.39); acute myeloid leukemia, 1.13 (0.98-1.30); lymphoma, 1.69 (0.72-3.94); Hodgkin, 1.22 (1.02-1.46); non-Hodgkin, 1.22 (0.80-1.86); neuroblastoma, 1.20 (1.02-1.41); retinoblastoma, 1.17 (0.93-1.48); rhabdomyosarcoma, 1.07 (0.90-1.27); embryonal, 1.22 (1.00-1.49); alveolar, 1.02 (0.46-2.27); and Wilms tumor, 1.49 (1.34-1.67). CONCLUSION: This meta-analysis identified high birth weight as a potential risk factor for some childhood cancers, while low birth weight might be protective against a few.

2.
Anticancer Agents Med Chem ; 24(8): 559-570, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38275052

RESUMO

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are widely recognized as effective pain relievers and function by inhibiting the cyclooxygenase enzyme (COXs). Moreover, they have been found to participate in various cellular processes through different signaling pathways, such as WNT, MAPK, NF-κB, and PI3K/AKT/mTOR. This makes them potential candidates for chemoprevention of several malignancies, particularly colorectal cancer (CRC). However, the use of NSAIDs in cancer prevention and treatment is a complex issue due to their adverse effects and gastrointestinal toxicity. Therefore, it is crucial to explore combination therapies that can minimize side effects while maximizing synergistic effects with other agents and to evaluate the success rate of such approaches in both pre-clinical and clinical studies. In this review, we aim to provide an overview of the effects of NSAIDs in the prevention and treatment of CRC. We will focus on elucidating the possible mechanisms of action of these drugs, the signaling pathways involved in CRC, and the potential synergistic effects when combined with other therapeutic agents.


Assuntos
Anti-Inflamatórios não Esteroides , Neoplasias Colorretais , Transdução de Sinais , Humanos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química
3.
Genet Res (Camb) ; 2023: 8283470, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817260

RESUMO

Background: Cytochrome P450 complex plays a key role in drug metabolism. CYP2B6 has an essential part in Cytochrome P450 complex metabolism. This study aims to determine the allelic distribution of CYP2B6∗2 and CYP2B6∗3 in three main Iranian ethnicities: Fars, Turk, and Kurd. Methods: The study was conducted on 174 unrelated healthy volunteers from three main Iranian ethnicities. After DNA extraction from peripheral blood samples, genotyping of CYP2B6∗2 and ∗3 was performed using tetra ARMS and ARMS PCR, respectively. Results: The average age of 174 cases was 40.69 ± 11.87 (mean ± SD) and 39.06 ± 11.63 (mean ± SD) for males and females. In the CYP2B6∗2 variant, the genotyping frequency of wild type (C/C), heterozygous (C/T), and homozygous mutant (T/T) was 8.7%, 86%, and 5.2%, respectively. The CYP2B6∗2 (c.64C > T) allele frequency was 48.2% (95% CI: (37.8-58.6)). In the CYP2B6∗3 variant, the frequency of wild type (C/C), heterozygous (C/T), and homozygous mutant (T/T) was 75.3%, 11%, and 13.6%, respectively. The CYP2B6∗3 (c.777C > A) allelic frequency was 19.1% (95% CI: (17.5-20.7)). Conclusion: Allelic distribution in three main Iranian ethnicities, i.e., Turk, Kurd, and Fars, is remarkably higher than that in other populations, even that in Southern Iran. High frequencies of CYP2B6∗2 and ∗3 in the Iranian population highly affect drug responsiveness. Understanding such variability could help to increase drug efficacy and reduce its toxicity.


Assuntos
Sistema Enzimático do Citocromo P-450 , Polimorfismo de Nucleotídeo Único , Masculino , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Citocromo P-450 CYP2B6/genética , Frequência do Gene , Genótipo , Sistema Enzimático do Citocromo P-450/genética , Alelos
4.
Inform Med Unlocked ; 35: 101134, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406927

RESUMO

Background: SARS-CoV-2 initially originated in Wuhan (China) around December 2019, and spread all over the world. Currently, WHO (Word Health Organization) has licensed several vaccines for this viral infection. However, not everyone can be vaccinated. People with underlying health conditions that weaken their immune systems or those with severe allergies to some vaccine components, may not be able to be vaccinated. Moreover, no vaccination is 100% safe, and the emergence of new SARS-CoV-2 mutations may reduce the efficacy of immunizations. Therefore, it is urgent to develop effective drugs to protect people against this virus. Material and method: We performed structure-based virtual screening (SBVS) of a library that was built from ChemDiv and PubChem databases against four SARS-CoV-2 target proteins: S-protein (spike), main protease (MPro), RNA-dependent RNA polymerase, and PLpro. A virtual screening study was performed using PyRx and AutoDock tools. Results: Our results suggest that twenty-five top-ranked drugs with the highest energy binding as the potential inhibitors against four SARS-CoV-2 targets, relative to the reference molecules. Based on the energy binding, we suggest that these compounds could be used to produce effective anti-viral drugs against SARS-CoV-2. Conclusion: The discovery of novel compounds for COVID-19 using computer-aided drug discovery tools requires knowledge of the structure of coronavirus and various target proteins of the virus. These compounds should be further assessed in experimental assays and clinical trials to validate their actual activity against the disease. These findings may contribute to the drug design studies against COVID-19.

5.
Adv Exp Med Biol ; 1291: 75-101, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34331685

RESUMO

Infectious diseases (IDs) are life-threatening illnesses, which result from the spread of pathogenic microorganisms such as bacteria, viruses, fungi, and parasites. IDs are a major challenge for the healthcare systems around the world, leading to a wide variety of clinical manifestations and complications. Despite the capability of frontline-approved medications to partially prevent or mitigate the invasion and subsequent damage of IDs to host tissues and cells, problems such as drug resistance, insufficient efficacy, unpleasant side effects, and high expenses stand in the way of their beneficial applications. One strategy is to evaluate currently explored and available bioactive compounds as possible anti-microbial agents. The natural polyphenol curcumin has been postulated to possess various properties including anti-microbial activities. Studies have shown that it possess pleiotropic effects against bacterial- and parasitic-associating IDs including drug-resistant strains. Curcumin can also potentiate the efficacy of available anti-bacterial and anti-parasitic drugs in a synergistic fashion. In this review, we summarize the findings of these studies along with reported controversies of native curcumin and its analogues, alone and in combination, toward its application in future studies as a natural anti-bacterial and anti-parasitic agent.


Assuntos
Anti-Infecciosos , Doenças Transmissíveis , Curcumina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Bactérias , Doenças Transmissíveis/tratamento farmacológico , Curcumina/farmacologia , Curcumina/uso terapêutico , Humanos
6.
Anticancer Agents Med Chem ; 21(5): 575-586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32951583

RESUMO

Multiple Myeloma (MM) is the third most common and deadly hematological malignancy, which is characterized by a progressive monoclonal proliferation within the bone marrow. MM is cytogenetically heterogeneous with numerous genetic and epigenetic alterations, which lead to a wide spectrum of signaling pathways and cell cycle checkpoint aberrations. MM symptoms can be attributed to CRAB features (hyperCalcemia, Renal failure, Anemia, and Bone lesion), which profoundly affect both the Health-Related Quality of Life (HRQoL) and the life expectancy of patients. Despite all enhancement and improvement in therapeutic strategies, MM is almost incurable, and patients suffering from this disease eventually relapse. Curcumin is an active and non-toxic phenolic compound, isolated from the rhizome of Curcuma longa L. It has been widely studied and has a confirmed broad range of therapeutic properties, especially anti-cancer activity, and others, including anti-proliferation, anti-angiogenesis, antioxidant and anti-mutation activities. Curcumin induces apoptosis in cancerous cells and prevents Multidrug Resistance (MDR). Growing evidence concerning the therapeutic properties of curcumin caused a pharmacological impact on MM. It is confirmed that curcumin interferes with various signaling pathways and cell cycle checkpoints, and with oncogenes. In this paper, we summarized the anti- MM effects of curcumin.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Curcuma/química , Curcumina/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia
7.
Comb Chem High Throughput Screen ; 24(5): 605-623, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32875976

RESUMO

Cervical malignancy is known as one of the important cancers which is originated from cervix. This malignancy has been observed in women infected with papillomavirus who had regular oral contraceptives, multiple pregnancies, and sexual relations. Early and fast cervical cancer diagnosis is known as two important aspects of cervical cancer therapy. Several investigations indicated that early and fast detection of cervical cancer could be associated with better treatment process and increasing survival rate of patients with this malignancy. Imaging techniques are very important diagnosis tools that could be employed for diagnosis and following responses to therapy in various cervical cancer stages. Multiple lines of evidence indicated that utilization of imaging techniques is related to some limitations (i.e. high cost, and invasive effects). Hence, it seems that along with using imaging techniques, finding and developing new biomarkers could be useful in the diagnosis and treatment of subjects with cervical cancer. Taken together, many studies showed that a variety of biomarkers including, several proteins, mRNAs, microRNAs, exosomes and polymorphisms might be introduced as prognostic, diagnostic and therapeutic biomarkers in cervical cancer therapy. In this review article, we highlighted imaging techniques as well as novel biomarkers for the diagnosis of cervical cancer.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias do Colo do Útero/diagnóstico por imagem , Feminino , Humanos
8.
Curr Mol Med ; 21(5): 355-375, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32888267

RESUMO

Gastric cancer (GC) has been found to be the second leading cause of cancer-associated deaths in the world, and is usually detected in the advanced stages. It has been shown that surgery is the major therapeutic approach in the treatment of subjects with GC. Hence, early and fast diagnosis of this malignancy is very important for good subject outcomes. Non-invasive diagnostic platforms, including evolutionary endoscopy and positron emission tomography (PET), are employed for the diagnosis of subjects with GC. Along with imaging techniques, the utilization of biomarkers has emerged as a new diagnosis option for early and fast detection of GC. Multiple lines of evidence have revealed a variety of biomarkers, including microRNAs, exosomes, circulating tumor cells, circular RNAs, cell free DNAs, and various proteins, which could be used as diagnostic biomarkers in patients with GC. Taken together, these findings suggest that the joint application of imaging techniques and different biomarkers could be introduced as a new detection approach in the treatment and screening response to therapy in the subjects with GC. Herein, we have summarized various imaging techniques and biomarkers as powerful tools in the detection of GC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Diagnóstico por Imagem/métodos , Humanos
9.
Adv Exp Med Biol ; 1328: 21-35, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34981469

RESUMO

INTRODUCTION: Breast cancer is one of the main challenging areas in cancer treatment. Natural compounds such as curcumin and berberine have been approved with anticancer effects and are more favorable to people. Here, we investigated the potential synergistic anticancer effects of these two compounds in combination with the standard cancer drug 5-FU on the growth of MCF-7 breast cancer cells. MATERIALS AND METHODS: This study tested the effects of six different treatments on cancer cell growth: A) control; B) curcumin; C) berberine; D) 5-FU; E) curcumin + berberine; and F) curcumin + berberine + 5-FU. The IC50 concentration of each treatment on cancer cell growth was determined using the MTT assay. Invasiveness of cells grown in 3D culture was analyzed using the transwell chamber technique. Expression levels of genes involved in cancer cell growth and survival (WNT1, APC, AXIN1, CTNNB1, TCF, MTOR, AKT1, MAPK1, PTEN, BIRC5, CCNG1) were evaluated by real-time PCR. RESULTS: There was a reduction in cancer cell growth and invasion, and an increase in cellular decomposition across all treatment groups compared to the control with the strongest effects seen in the combined curcumin/berberine/5-FU group. The expression levels of all tested genes were altered in all treatment groups compared to the control, with that of WNT1, CTNNB1, TCF, MTOR, AKT1, BIRC5, and CCND1 showing the most robust changes in the combined curcumin/berberine/5-FU treatment. CONCLUSIONS: All treatment groups had anti-growth, anti-invasion, and pro-apoptotic effects on MCF-7 breast cancer cells in culture. In addition, all treatment groups showed changes in the expression of the genes involved in cancer cell growth and survival with the strongest effects found for the curcumin/berberine/5-FU combination. Therefore, curcumin and berberine may improve the anticancer effects of chemotherapy and these natural compounds should undergo further testing as potential adjuvants.


Assuntos
Berberina , Neoplasias da Mama , Curcumina , Apoptose , Berberina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proliferação de Células , Curcumina/farmacologia , Sinergismo Farmacológico , Feminino , Fluoruracila/farmacologia , Humanos
10.
Infect Genet Evol ; 85: 104580, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33022425

RESUMO

The non-classical human leukocyte antigens (HLA)-G could be generally considered as a potent tolerogenic molecule, which modulates immune responses. HLA-G due to the immunosuppressive properties may play an important role in the pathogenesis of infections related to the liver. HLA-G may display two distinct activities in the pathological conditions so that it could be protective in the autoimmune and inflammatory diseases or could be suppressive of the immune system in the infections or cancers. HLA-G might be used as a novel therapeutic target for liver diseases in the future. Indeed, new therapeutic agents targeting HLA-G expression or antibodies which block HLA-G activity are being developed and tested. However, further consideration of the HLA-G function in liver disease is required. This review aims to summarize the role of HLA-G in the liver of patients with HBV infection.


Assuntos
Suscetibilidade a Doenças , Antígenos HLA-G/genética , Vírus da Hepatite B , Hepatite B/etiologia , Regulação da Expressão Gênica , Predisposição Genética para Doença , Antígenos HLA-G/imunologia , Vírus da Hepatite B/imunologia , Humanos , Imunomodulação
11.
Cell Commun Signal ; 18(1): 149, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917227

RESUMO

Exosomes are extracellular vesicles characterized by their size, source, release mechanism and contents. MicroRNAs (miRNAs) are single stranded non-coding RNAs transcribed from DNA. Exosomes and miRNAs are widespread in eukaryotic cells, especially in mesenchymal stem cells (MSCs). MSCs are used for tissue regeneration, and also exert paracrine, anti-inflammatory and immunomodulatory effects. However, the use of MSCs is controversial, especially in the presence or after the remission of a tumor, due to their secretion of growth factors and their migration ability. Instead of intact MSCs, MSC-derived compartments or substances could be used as practical tools for diagnosis, follow up, management and monitoring of diseases. Herein, we discuss some aspects of exosomal miRNAs derived from MSCs in the progression, diagnosis and treatment of various diseases. Video Abstract.


Assuntos
Exossomos/genética , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Animais , Comunicação Celular , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo
12.
Iran J Basic Med Sci ; 23(8): 999-1006, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32952945

RESUMO

OBJECTIVES: It has been shown that adipose-derived mesenchymal stem cells (AD-MSC) have protective effects in acute kidney injury (AKI). This study was conducted to assess the therapeutic effects of AD-MSC in rats subjected to acute kidney injury by 45 min of renal ischemia followed by 48 hr of reperfusion (I/R). MATERIALS AND METHODS: 28 male Wistar rats were divided into four groups, including control, 48-hr sham, 48-hr I/R, and 48-hr I/R receiving AD-MSC. After 48 hr of reperfusion, blood samples were taken from rats' hearts, and 24-hr urines were collected using a metabolic cage. Serum creatinine level (Cr), blood urea nitrogen (BUN), creatinine clearance (Ccr), absolute sodium excretion (UNaV°), fractional sodium excretion (FENa), absolute potassium excretion (UKV°), factional potassium excretion (FEK), and urine osmolarity were measured. Malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP) levels were measured in the right kidney, while the left kidney was used for histologic study after Hematoxylin-Eosin staining. RESULTS: Renal I/R significantly increased serum Cr, BUN, UNaV°, FENa, FEK, and tissue MDA, and significantly decreased Ccr and urine osmolarity as compared with the sham group. Moreover, histologic studies showed that I/R increased Bowman capsule area, tubular necrosis, vascular congestion, and caused formation of intratubular casts. Administration of AD-MSC at the time of I/R completely or partially protected kidneys from these I/R induced injuries. CONCLUSION: Our results show that injection of AD-MSC can reduce degree of renal injury caused by 45 min of ischemia followed by 48 hr of reperfusion in rats.

13.
Mol Biol Rep ; 47(7): 5365-5376, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32601923

RESUMO

Emerging of the COVID-19 pandemic has raised interests in the field of biology and pathogenesis of coronaviruses; including interactions between host immune reactions specific, and viral factors. Deep knowledge about the interaction between coronaviruses and the host factors could be useful to provide a better support for the disease sufferers and be advantageous for managing and treatment of the lung infection caused by the virus. At this study, we reviewed the updated information on the pathogenesis of the COVID-19 and the immune responses toward it, with a special focus on structure, genetics, and viral accessory proteins, viral replication, viral receptors, the human immune reactions, cytopathic effects, and host-related factors.


Assuntos
Infecções por Coronavirus/etiologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/etiologia , Pneumonia Viral/imunologia , Animais , Autoimunidade , Betacoronavirus/genética , Betacoronavirus/imunologia , COVID-19 , Infecções por Coronavirus/genética , Infecções por Coronavirus/virologia , Citocinas/imunologia , Humanos , Imunidade Inata , Interferons/imunologia , Pandemias , Pneumonia Viral/genética , Pneumonia Viral/virologia , Receptores de Coronavírus , Receptores Virais , SARS-CoV-2 , Replicação Viral
14.
Cell Oncol (Dordr) ; 43(3): 353-365, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32207043

RESUMO

BACKGROUND: Melanoma is a malignancy that stems from melanocytes and is defined as the most dangerous skin malignancy in terms of metastasis and mortality rates. CXC motif chemokine 10 (CXCL10), also known as interferon gamma-induced protein-10 (IP-10), is a small cytokine-like protein secreted by a wide variety of cell types. CXCL10 is a ligand of the CXC chemokine receptor-3 (CXCR3) and is predominantly expressed by T helper cells (Th cells), cytotoxic T lymphocytes (CTLs), dendritic cells, macrophages, natural killer cells (NKs), as well as some epithelial and cancer cells. Similar to other chemokines, CXCL10 plays a role in immunomodulation, inflammation, hematopoiesis, chemotaxis and leukocyte trafficking. CONCLUSIONS: Recent studies indicate that the CXCL10/CXCR3 axis may act as a double-edged sword in terms of pro- and anti-cancer activities in a variety of tissues and cells, especially in melanoma cells and their microenvironments. Most of these activities arise from the CXCR3 splice variants CXCR3-A, CXCR3-B and CXCR3-Alt. In this review, we discuss the pro- and anti-cancer properties of CXCL10 in various types of tissues and cells, particularly melanoma cells, including its potential as a therapeutic target.


Assuntos
Quimiocina CXCL10/metabolismo , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Antineoplásicos/uso terapêutico , Carcinogênese/metabolismo , Carcinogênese/patologia , Humanos , Modelos Biológicos , Receptores CXCR3/metabolismo
15.
Iran J Pharm Res ; 19(4): 151-159, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33841531

RESUMO

Stem cell therapy is noted for its clinical effect in the treatment of neuropathic pain. This study aimed to investigate the potential anti-apoptotic and anti-inflammatory effects of adipose-derived mesenchymal stem cells (AD-MSCs) and fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells (AD-MSCs FGF1) on chronic constriction injury (CCI) of the rat's sciatic nerve. The rats that underwent CCI were treated with AD-MSCs and AD-MSCs FGF1. Bax, Bcl2, and caspases 3, the major contributors of apoptosis, and inflammatory markers including Iba-1, IL1-ß, and MMP-2 were evaluated in the lumbar portion (L4-L6) of the spinal cord through western bloating at days 3 and 14. The ratio of Bax/Bcl2, cleaved caspases 3, MMP-2, IL-1ß, and Iba1, was elevated in CCI animals compared to sham-operated animals and decreased following treatment with both AD-MSCs and AD-MSCs FGF1. However, the effect of AD-MSCs FGF1 was significantly higher than AD-MSCs. These data suggest that the administration of AD-MSCs FGF1 through modulating apoptosis and neuroinflammation could be considered a promising medicine for treating neuropathic pain.

16.
Fundam Clin Pharmacol ; 34(1): 51-64, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31233627

RESUMO

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. Despite recent advances in the treatment for CRC, resistance to chemotherapy drugs and recurrence of the tumor are among the main problems for treatment in this cancer. The MTT assay was performed to assess the cytotoxic effects of drugs on CRC cell lines (SW742 and SW480) and normal colon cells. Three-dimensional culture (spheroid) was also used to evaluate the effect of drugs on tumor cell masses. The rate of expression of genes was also evaluated using Real-Time PCR. The analysis of the results demonstrated that aspirin and LGK974 have cytotoxic effects on CRC cell lines, and in the IC50 dose, they disintegrate the cancerous cell masses. These drugs reduce the invasion and increase apoptosis in SW742 and SW480 cell lines. A decrease in the expression of WNT, AXIN, TCF and APC genes and an increase in the expression of ß-catenin gene in the WNT signaling pathway were revealed. The genes involved in the MAPK signaling pathway such as ERK, JNK, KRAS and MEK showed a decrease in expression and a increase in expression of RAF gene. In the apoptotic pathway, increased expression of BAX and decreased expression of BCL-2 were reported. Also, decreased expression of P53, cyclin D1 and COX-2 was observed. This study demonstrates that aspirin and LGK974 could be effective in inhibiting the signaling pathways of WNT and MAPK, arresting cell cycle and inducing apoptosis in CRC cell lines.


Assuntos
Aspirina/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Oxaliplatina/administração & dosagem , Pirazinas/administração & dosagem , Piridinas/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Aspirina/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Concentração Inibidora 50 , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Oxaliplatina/farmacologia , Pirazinas/farmacologia , Piridinas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos
17.
Biofactors ; 46(1): 5-20, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31580521

RESUMO

Neurodegenerative diseases (NDs) result from progressive deterioration of selectively susceptible neuron populations in different central nervous system (CNS) regions. NDs are classified in accordance with the primary clinical manifestations (e.g., parkinsonism, dementia, or motor neuron disease), the anatomic basis of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), and fundamental molecular abnormalities (e.g., mutations, mitochondrial dysfunction, and its related molecular alterations). NDs include the Alzheimer disease and Parkinson disease, among others. There is a growing evidence that mitochondrial dysfunction and its related mutations in the form of oxidative/nitrosative stress and neurotoxic compounds play major roles in the pathogenesis of various NDs. Curcumin, a polyphenol and nontoxic compound, obtained from turmeric, has been shown to have a therapeutic beneficial effect in various disorders especially on the CNS cells. It has been shown that curcumin has considerable neuro- and mitochondria-protective properties against broad-spectrum neurotoxic compounds and diseases/injury-associating NDs. In this article, we have reviewed the various effects of curcumin on mitochondrial dysfunction in NDs.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Encéfalo/efeitos dos fármacos , Curcumina/farmacologia , Mitocôndrias/efeitos dos fármacos , Doenças Neurodegenerativas/tratamento farmacológico , Humanos , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
18.
Fundam Clin Pharmacol ; 34(2): 202-212, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31709581

RESUMO

The discovery of stem cells and their potential abilities in self-renewal and differentiation has opened a new horizon in medicine. Scientists have found a small population of stem cells in some types of cancers with the same functions as normal stem cells. There are two models for tumor progression: clonal (stochastic) and cancer stem cell (CSCs) models. According to the first model, all transformed cells in the tumor have carcinogenic potential and are able to proliferate and produce the same cells. The latter model, which has received more attention recently, considers the role of CSCs in drug resistance and tumor metastasis. Following the model, researchers have found that targeting CSCs may be a promising way in cancer therapy. This review describes CSC characteristics in general, while also focusing on CSC properties in the context of pancreatic cancer.


Assuntos
Terapia de Alvo Molecular , Células-Tronco Neoplásicas/citologia , Neoplasias Pancreáticas/tratamento farmacológico , Proliferação de Células/fisiologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Metástase Neoplásica , Neoplasias Pancreáticas/patologia
19.
Biofactors ; 46(3): 309-325, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31846136

RESUMO

Microglia are the primary innate immune system cells in the central nervous system (CNS). They are crucial for the immunity, neurogenesis, synaptogenesis, neurotrophic support, phagocytosis of cellular debris, and maintaining the CNS integrity and homeostasis. Invasion by pathogens as well as in CNS injuries and damages results in activation of microglia known as microgliosis. The activated microglia have the capacity to release proinflammatory mediators leading to neuroinflammation. However, uncontrolled neuroinflammation can give rise to various neurological disorders (NDs), especially the neurodegenerative diseases including Parkinson's disease (PD) and related disorders, Alzheimer's disease (AD) and other dementias, multiple sclerosis (MS), Huntington's disease (HD), spinocerebellar ataxia (SCA), spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and stroke. Statins (HMG-CoA reductase inhibitors) are among the most widely prescribed medications for the management of hypercholesterolemia worldwide. It can be used for primary prevention in healthy individuals who are at higher risk of cardiovascular and coronary heart diseases as well as the secondary prevention in patients with cardiovascular and coronary heart diseases disease. A growing body of evidence has indicated that statins have the potential to attenuate the proinflammatory mediators and subsequent NDs by controlling the microglial activation and consequent reduction in neuroinflammatory mediators. In this review, we have discussed the recent studies on the effects of statins on microglia activation and neuroinflammation.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Microglia/efeitos dos fármacos , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Ratos
20.
Iran J Kidney Dis ; 13(6): 380-388, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31880584

RESUMO

INTRODUCTION: The mortality rate in patients with acute kidney injury (AKI) is high. The aim of this study was to evaluate the efficacy of treatment with adipose-derived mesenchymal stem cells (AD-MSC) in renal ischemia-reperfusion (I/R) model in rats. METHODS: In this study 28 male Wistar rats were divided into four groups of control, sham, I/R24h+PBS, and I/R24h+AD-MSC. Blocking the renal arteries for 45 minutes induced renal I/R and then reperfusion was conducted for 24 hours. Parameters including urine volume, osmolarity, plasma creatinine (Crp), and blood urea nitrogen (BUN) were evaluated and values of creatinine clearance (CCr), absolute sodium excretion (UNaV°), fractional excretion of sodium (FENa), absolute potassium excretion (UKV°) and fractional excretion of potassium (FEK) were calculated. The right kidney was removed to measure the malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP), as well as the left kidney for histological evaluation. RESULTS: I/R caused a significant increase in Crp, BUN, UNaV°, FENa, FEK, MDA, and tissue damages. In addition, the values of CCr, urine osmolarity, and FRAP level decreased significantly (P < .05). Following AD-MSC treatment, values of FENa, Crp, FEK, MDA, and tissue damages decreased significantly, while urine osmolarity increased significantly in the I/R24h + AD-MSC group compared to the I/R24h + PBS group. Furthermore, FRAP values increased significantly (P < .001). CONCLUSION: Treatment with AD-MSC reduced tissue damage and oxidative stress while increasing antioxidant activity. In addition, it improved kidney function after 45 min ischemia and 24 h reperfusion.


Assuntos
Injúria Renal Aguda/terapia , Antioxidantes/metabolismo , Transplante de Células-Tronco Mesenquimais , Traumatismo por Reperfusão/terapia , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Modelos Animais de Doenças , Rim/fisiopatologia , Testes de Função Renal , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Artéria Renal , Fatores de Tempo
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