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1.
Exp Cell Res ; 442(2): 114236, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39245198

RESUMO

Widespread changes in the expression of microRNAs in cancer result in abnormal gene expression for the miRNAs that control those genes, which in turn causes changes to entire molecular networks and pathways. The frequently altered miR-31, which is found in a wide range of cancers, is one cancer-related miRNA that is particularly intriguing. MiR-31 has a very complicated set of biological functions, and depending on the type of tumor, it may act both as a tumor suppressor and an oncogene. The endogenous expression levels of miR-31 appear to be a key determinant of the phenotype brought on by aberrant expression. Varied expression levels of miR-31 could affect cell growth, metastasis, drug resistance, and other process by several mechanisms like targeting BRCA1-associated protein-1 (BAP1), large tumor suppressor kinase 1 (LATS1) and protein phosphatase 2 (PP2A). This review highlights the current understanding of the genes that miR-31 targets while summarizing the complex expression patterns of miR-31 in human cancers and the diverse phenotypes brought on by altered miR-31 expression.

2.
Cell Biol Int ; 48(3): 280-289, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38225535

RESUMO

Small extracellular (EV) particles known as exosomes are released by a variety of cell types, including immune system cells, stem cells, and tumor cells. They are regarded as a subgroup of EVs and have a diameter that ranges from 30 to 150 nm. Proteins, lipids, nucleic acids (including RNA and DNA), and different bioactive compounds are among the wide range of biomolecules that make up the cargo of exosomes. Exosomes are crucial for intercellular communication because they let cells share information and signaling chemicals. They are involved in various physiological and pathological processes, including immune responses, tissue regeneration, cancer progression, and neurodegenerative diseases. In conclusion, it is essential to continue research into exosome-based cancer medicines to advance understanding, improve treatment plans, create personalized tactics, ensure safety, and speed up clinical translation.


Assuntos
Neoplasias Colorretais , Exossomos , Vesículas Extracelulares , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , MicroRNAs/metabolismo , Exossomos/genética , Exossomos/metabolismo , Transdução de Sinais , Comunicação Celular , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Vesículas Extracelulares/metabolismo
3.
Cell Biochem Funct ; 42(2): e3935, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38379260

RESUMO

50% of cases of infertility are caused by male factor, which acquired or congenital problems may bring on. Male infertility can be caused by oligospermia and asthenozoospermia, which are common. Since the same mutations that cause azoospermia in some people also cause oligozoospermia in others, oligozoospermia may be thought of as a less severe form of azoospermia. Studies have demonstrated telomere length, catalase activity, super oxide dismutase (SOD), and DNA fragmentation can be influential factors for male infertility. The amount of apoptosis, oxidative stress factors, telomere length, and DNA fragmentation were some aspects of healthy sperm that we chose to look into in this study and compare to oligospermia individuals. Oligospermia patients (n = 24) and fertile men (n = 27) semen samples were collected, and the apoptosis rate of sperms in both groups was analyzed (Flow cytometry). Also, gene expression of apoptotic and antiapoptotic markers and telomere length were examined (real-time polymerase chain reaction). The sperm DNA fragmentation kit was used to determine DNA fragmentation and to evaluate catalase and SOD activity; the specific kits and methods were utilized. Higher expression levels of caspase3 (p = .0042), caspase8 (p = .0145), caspase9 (p = .0275), and BAX (p = .0202) mRNA were observed in patients who had oligospermia. In contrast, lower mRNA expression of BCL-2 (p = .0009) was detected in this group. In addition, telomere length was decreased in the oligospermia group (p < .0001) compared to the health group. Moreover, the frequency of apoptosis is induced in patients (p = .0026). The catalase activity is low (p = .0008), but the SOD activity is high (p = .0015) in the patient group. As a result of our findings, we may list the sperm cell apoptosis rate, telomere length, the degree of sperm DNA fragmentation, and lastly, the measurement of significant and efficient oxidative stress markers like SOD and catalase in semen plasma among the principal diagnostic characteristics for oligospermia. Future studies will be better able to treat oligospermia by showing whether these indicators are rising or falling.


Assuntos
Azoospermia , Infertilidade Masculina , Oligospermia , Humanos , Masculino , Oligospermia/genética , Oligospermia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Catalase/genética , Catalase/metabolismo , Azoospermia/metabolismo , Sêmen/metabolismo , Espermatozoides/metabolismo , Infertilidade Masculina/genética , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/metabolismo , Antioxidantes/metabolismo , Fragmentação do DNA , Apoptose , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Telômero/metabolismo , RNA Mensageiro/metabolismo
4.
Cell Biochem Funct ; 42(2): e3957, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38468129

RESUMO

Cerebral ischemic damage is prevalent and the second highest cause of death globally across patient populations; it is as a substantial reason of morbidity and mortality. Mesenchymal stromal cells (MSCs) have garnered significant interest as a potential treatment for cerebral ischemic damage, as shown in ischemic stroke, because of their potent intrinsic features, which include self-regeneration, immunomodulation, and multi-potency. Additionally, MSCs are easily obtained, isolated, and cultured. Despite this, there are a number of obstacles that hinder the effectiveness of MSC-based treatment, such as adverse microenvironmental conditions both in vivo and in vitro. To overcome these obstacles, the naïve MSC has undergone a number of modification processes to enhance its innate therapeutic qualities. Genetic modification and preconditioning modification (with medications, growth factors, and other substances) are the two main categories into which these modification techniques can be separated. This field has advanced significantly and is still attracting attention and innovation. We examine these cutting-edge methods for preserving and even improving the natural biological functions and therapeutic potential of MSCs in relation to adhesion, migration, homing to the target site, survival, and delayed premature senescence. We address the use of genetically altered MSC in stroke-induced damage. Future strategies for improving the therapeutic result and addressing the difficulties associated with MSC modification are also discussed.


Assuntos
Isquemia Encefálica , Precondicionamento Isquêmico , AVC Isquêmico , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/metabolismo , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/metabolismo , Precondicionamento Isquêmico/métodos , Células-Tronco Mesenquimais/metabolismo
5.
Cell Biochem Funct ; 42(2): e3978, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38515237

RESUMO

Ovarian cancer continues to be a difficult medical issue that affects millions of individuals worldwide. Important platforms for cancer immunotherapy include checkpoint inhibitors, chimeric antigen receptor T cells, bispecific antibodies, cancer vaccines, and other cell-based treatments. To avoid numerous infectious illnesses, conventional vaccinations based on synthetic peptides, recombinant subunit vaccines, and live attenuated and inactivated pathogens are frequently utilized. Vaccine manufacturing processes, however, are not entirely safe and carry a significant danger of contaminating living microorganisms. As a result, the creation of substitute vaccinations is required for both viral and noninfectious illnesses, including cancer. Recently, there has been testing of nucleic acid vaccines, or NAVs, as a cancer therapeutic. Tumor antigens (TAs) are genetically encoded by DNA and mRNA vaccines, which the host uses to trigger immune responses against ovarian cancer cells that exhibit the TAs. Despite being straightforward, safe, and easy to produce, NAVs are not currently thought to be an ideal replacement for peptide vaccines. Some obstacles to this strategy include selecting the appropriate therapeutic agents (TAs), inadequate immunogenicity, and the immunosuppressive characteristic of ovarian cancer. We focus on strategies that have been employed to increase NAVs' effectiveness in the fight against ovarian cancer in this review.


Assuntos
Vacinas Anticâncer , Neoplasias Ovarianas , Humanos , Feminino , Vacinas Baseadas em Ácido Nucleico , Neoplasias Ovarianas/tratamento farmacológico , Antígenos de Neoplasias , Vacinas Anticâncer/uso terapêutico
6.
Cell Biochem Funct ; 42(2): e3954, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38403905

RESUMO

The messenger RNA (mRNA) vaccines have progressed from a theoretical concept to a clinical reality over the last few decades. Compared to conventional vaccination methods, these vaccines have a number of benefits, such as substantial potency, rapid growth, inexpensive production, and safe administration. Nevertheless, their usefulness was restricted up to now due to worries about the erratic and ineffective circulation of mRNA in vivo. Thankfully, these worries have largely been allayed by recent technological developments, which have led to the creation of multiple mRNA vaccination platforms for cancer and viral infections. The mRNA vaccines have been demonstrated as a powerful alternative to traditional conventional vaccines because of their high potency, safety and efficacy, capacity for rapid clinical development, and potential for rapid, low-cost manufacturing. The paper will examine the present status of mRNA vaccine technology and suggest future paths for the advancement and application of this exciting vaccine platform as a common therapeutic choice.


Assuntos
Neoplasias , Vacinas , Humanos , RNA Mensageiro/genética , Vacinas/uso terapêutico , Vacinação/métodos , Neoplasias/tratamento farmacológico
7.
Cell Biochem Funct ; 42(1): e3921, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38269511

RESUMO

This comprehensive article explores the complex field of glioma treatment, with a focus on the important roles of non-coding RNAsRNAs (ncRNAs) and exosomes, as well as the potential synergies of immunotherapy. The investigation begins by examining the various functions of ncRNAs and their involvement in glioma pathogenesis, progression, and as potential diagnostic biomarkers. Special attention is given to exosomes as carriers of ncRNAs and their intricate dynamics within the tumor microenvironment. The exploration extends to immunotherapy methods, analyzing their mechanisms and clinical implications in the treatment of glioma. By synthesizing these components, the article aims to provide a comprehensive understanding of how ncRNAs, exosomes, and immunotherapy interact, offering valuable insights into the evolving landscape of glioma research and therapeutic strategies.


Assuntos
Exossomos , Vesículas Extracelulares , Glioma , Humanos , Imunoterapia , Glioma/terapia , Microambiente Tumoral
8.
Clin Exp Nephrol ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935212

RESUMO

BACKGROUND: Renal ischemia-reperfusion injury (RIRI) is a critical phenomenon that compromises renal function and is the most serious health concern related to acute kidney injury (AKI). Pioglitazone (Pio) is a known agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ). PPAR-γ is a nuclear receptor that regulates genes involved in inflammation, metabolism, and cellular differentiation. Activation of PPAR-γ is associated with antiinflammatory and antioxidant effects, which are relevant to the pathophysiology of RIRI. This study aimed to investigate the protective effects of Pio in RIRI, focusing on oxidative stress and inflammation. METHODS: We conducted a comprehensive literature search using electronic databases, including PubMed, ScienceDirect, Web of Science, Scopus, and Google Scholar. RESULTS: The results of this study demonstrated that Pio has antioxidant, anti-inflammatory, and anti-apoptotic activities that counteract the consequences of RIRI. The study also discussed the underlying mechanisms, including the modulation of various pathways such as TNF-α, NF-κB signaling systems, STAT3 pathway, KIM-1 and NGAL pathways, AMPK phosphorylation, and autophagy flux. Additionally, the study presented a summary of various animal studies that support the potential protective effects of Pio in RIRI. CONCLUSION: Our findings suggest that Pio could protect the kidneys from RIRI by improving antioxidant capacity and decreasing inflammation. Therefore, these findings support the potential of Pio as a therapeutic strategy for preventing RIRI in different clinical conditions.

9.
Phytother Res ; 38(8): 4336-4350, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38994919

RESUMO

Lung cancer is the second most prevalent cancer and ranks first in cancer-related death worldwide. Due to the resistance development to conventional cancer therapy strategies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, various natural products and their extracts have been revealed as alternatives. Berberine (BBR), which is present in the stem, root, and bark of various trees, could exert anticancer activities by regulating tumor cell proliferation, apoptosis, autophagy, metastasis, angiogenesis, and immune responses via modulating several signaling pathways within the tumor microenvironment. Due to its poor water solubility, poor pharmacokinetics/bioavailability profile, and extensive p-glycoprotein-dependent efflux, BBR application in (pre) clinical studies is restricted. To overcome these limitations, BBR can be encapsulated in nanoparticle (NP)-based drug delivery systems, as monotherapy or combinational therapy, and improve BBR therapeutic efficacy. Nanoformulations also facilitate the selective delivery of BBR into lung cancer cells. In addition to the anticancer activities of BBR, especially in lung cancer, here we reviewed the BBR nanoformulations, including polymeric NPs, metal-based NPs, carbon nanostructures, and others, in the treatment of lung cancer.


Assuntos
Berberina , Neoplasias Pulmonares , Nanopartículas , Berberina/farmacologia , Berberina/química , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Animais , Antineoplásicos Fitogênicos/farmacologia
10.
Chem Biodivers ; 21(6): e202400344, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38587035

RESUMO

Plant-derived coumarin (PDC) is a naturally occurring heterocyclic backbone that belongs to the benzopyrone family. PDC and its based products are characterized by low toxicity and high distribution in a variety of herbal treatments that have numerous therapeutic potentials. These include anticoagulants, antibacterials, anti-inflammatory agents, anticancer agents, antioxidants, and others. So, it may be appropriate to investigate the qualities and potential bioactivities of PDCs. This article provides an overview of the biomedical potentials, availability, and clinical use possibilities of PDCs, with a focus on their important modes of action, using information on various pharmacological qualities discovered. The data used in this study came from published research between 2015 and 2023. We reviewed a selection of databases, including PubMed, Scopus, Web of Science, and Google Scholar, during that period. In conclusion, because of their abundance in medicinal plants, the clinical biochemistry attributes of PDCs are currently of interest. In a variety of medical specialties, PDCs serve a useful role as therapeutic agents.


Assuntos
Cumarínicos , Cumarínicos/química , Cumarínicos/farmacologia , Humanos , Plantas Medicinais/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Anticoagulantes/química , Anticoagulantes/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Estrutura Molecular
11.
Chem Biodivers ; 21(6): e202400581, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38619505

RESUMO

For the first time, kinetic thermomagnetic extraction is a novel approach presented in this work. It required the application of four distinct variables: rotation speed (50, 75, and 100 rpm), magnetic field (0.8, 1.2, and 1.6 T), time interval (30, 60, and 90 min), and temperature (45, 55, and 65 °C). Numerous phytochemical categories were detected in the 81 crude chloroform extracts of green sweet bell pepper seeds that were collected, according to phytochemical analysis. Nine extracts were discovered to be linked to the coumarin chemical class and to have the same two extraction parameters: a 90-minute extraction duration and a 55 °C extraction temperature. To enable their coumarin contents to be chemically separated and chromatographically purified, two of these extracts containing coumarin were chosen. Four new phytocoumarins have been identified and their molecular structures distinguished using FTIR spectra, 1H-NMR, 13C-NMR, and mass analysis. By using MTT probing, it was discovered that these phytocoumarins exhibited anticancer activities against eight malignant populations and reduced oxidative stress in human SH-SY5Y populations. Similarly, the anti-inflammatory and antidiabetic properties were determined using three and two associated enzymes, respectively. The results demonstrated that the extracted phytocoumarins have exceptional oxidative stress-mitigating characteristics, ranging from 71.51 to 81.48 %, when compared to a positive control. Furthermore, they showed excellent cytotoxicity against the test malignant populations (IC50 values of 46.76-81.45 µg/ml). The isolates need to be taken into account as dual COX-2/5-LOX antagonists because they also showed a fascinating selective anti-inflammatory effect. The phytocoumarins under investigation have selectivity indices that are higher than those of the standards used, suggesting that they may have the ability to selectively block the COX2 enzyme that induces harmful inflammation. Compared to the standards, the phytocoumarins have a higher ability to block the catalytic activity of 5-LOX. This observation suggests that the phytocoumarins are powerful 5-LOX agents. Finally, they had a modest antidiabetic impact when tested against two blood-controlling enzymes. The authors came to the conclusion that the technique adopted is flexible and successful for extraction after modifying its components. Moreover, isolated phytocoumarins in general and natural-B1 in particular provide naturally derived solutions for oxidative stress and its associated diseases.


Assuntos
Antineoplásicos Fitogênicos , Capsicum , Cumarínicos , Extratos Vegetais , Sementes , Humanos , Capsicum/química , Sementes/química , Cumarínicos/isolamento & purificação , Cumarínicos/química , Cumarínicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Relação Estrutura-Atividade
12.
Chem Biodivers ; : e202401309, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011809

RESUMO

Acetaminophen, a centrally-acting old analgesic drug, is a weak inhibitor of cyclooxygenase (COX) isoforms with some selectivity toward COX-2. This compound was used in this work as a precursor to create nine acetaminophen based coumarins (ACFs). To satisfy the aim of this work, which states the synthesis of acetaminophen-based coumarins as selective COX-2 inhibitors, the ACFs were subjected to two types of investigation: in vitro and in silico. Given the former type, the ACFs capacity to block COX-1 and COX-2 was investigated in lab settings. On the other hand, the in silico investigation included docking the chemical structures of ACFs into the active sites of these enzymes, predicting their anticipated toxicities, and determining the ADME characteristics. The results of the in vitro study revealed that the ACFs demonstrated good-to-excellent inhibitory properties against the enzymes under study. Also, these ACFs exhibited a high level of COX-2 selectivity, which improved as the capacity of  aromatic substitute for withdrawing electrons was enhanced. Results of docking were comparable to the in vitro investigation in case of COX-2. On the other hand, the in silico investigations indicated that the synthesized ACFs are safer than their precursor, acetaminophen, with a high potential to consider oral-administrated candidates.

13.
Indian J Clin Biochem ; 39(2): 154-167, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577147

RESUMO

The production of harmful free radicals (H-FRs), especially those with oxygen or nitrogen atoms, depends on both internal and environmental causes. The negative effects of H-FRs are greatly alleviated by antioxidant protection. The harmful impact of oxidative stress, or OS, is brought on by a disparity between the defense mechanisms of the body and the creation of H-FRs. Aging is characterized by a slow decline in tissue and organ competence. Age-mediated pathologies start as an aberrant accumulation of H-FRs, which inhibit cells' capacity to divide, repair, and operate, based on the OS theorem of aging. The natural outcome of this situation is apoptosis. These conditions may include skeletal muscle dysfunction, cancer, cardiovascular, chronic hepatitis, chronic renal, and chronic pulmonary disorders. Given the substantial role that OS plays in the progression of many of these illnesses, antioxidant-based therapy may have a favorable impact on how these diseases progress. To ascertain the true efficacy of this therapy strategy, more research is necessary. The aim of this study is to provide an overview of the literature on this challenging issue that is attracting interest.

14.
Cytokine ; 171: 156379, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37757536

RESUMO

Ovarian cancer poses significant challenges and remains a highly lethal disease with limited treatment options. In the context of ovarian cancer, interleukins (ILs) and interferons (IFNs), important cytokines that play crucial roles in regulating the immune system, have emerged as significant factors influencing its development. This article provides a comprehensive review of the involvement of various ILs, including those from the IL-1 family, IL-2 family, IL-6 family, IL-8 family, IL-10 family, and IL-17 family, in ovarian cancer. The focus is on their impact on tumor growth, metastasis, and their role in evading immune responses within the tumor microenvironment. Additionally, the article conducts an in-depth examination of the oncogenic or antitumor roles of each IL in the context of ovarian cancer pathogenesis and progression. Besides, we elucidated the enhancements in the treatment of ovarian cancer through the utilization of type-I IFN and type-II IFN. Recent research has shed light on the intricate mechanisms through which specific ILs and IFNs contribute to the advancement of the disease. By incorporating recent findings, this review also seeks to inspire further investigations into unexplored mechanisms, fostering ongoing research to develop more effective therapeutic strategies for ovarian cancer. Moreover, through an in-depth analysis of IL- and IFN-associated clinical trials, we have highlighted their promising potential of in the treatment of ovarian cancer. These clinical trials serve to reinforce the significant outlook for utilizing ILs and IFNs as therapeutic agents in combating this disease.

15.
Cytotherapy ; 25(4): 353-361, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36241491

RESUMO

Fractures in bone, a tissue critical in protecting other organs, affect patients' quality of life and have a heavy economic burden on societies. Based on regenerative medicine and bone tissue engineering approaches, stem cells have become a promising and attractive strategy for repairing bone fractures via differentiation into bone-forming cells and production of favorable mediators. Recent evidence suggests that stem cell-derived exosomes could mediate the therapeutic effects of their counterpart cells and provide a cell-free therapeutic strategy in bone repair. Since bone is a highly vascularized tissue, coupling angiogenesis and osteogenesis is critical in bone fracture healing; thus, developing therapeutic strategies to promote angiogenesis will facilitate bone regeneration and healing. To this end, stem cell-derived exosomes with angiogenic potency have been developed to improve fracture healing. This review summarizes the effects of stem cell-derived exosomes on the repair of bone tissue, focusing on the angiogenesis process.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Humanos , Qualidade de Vida , Neovascularização Fisiológica , Células-Tronco , Regeneração Óssea , Osteogênese
16.
Cell Commun Signal ; 21(1): 43, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36829187

RESUMO

Oncolytic viruses (OVs) infect, multiply, and finally remove tumor cells selectively, causing no damage to normal cells in the process. Because of their specific features, such as, the ability to induce immunogenic cell death and to contain curative transgenes in their genomes, OVs have attracted attention as candidates to be utilized in cooperation with immunotherapies for cancer treatment. This treatment takes advantage of most tumor cells' inherent tendency to be infected by certain OVs and both innate and adaptive immune responses are elicited by OV infection and oncolysis. OVs can also modulate tumor microenvironment and boost anti-tumor immune responses. Mesenchymal stem cells (MSC) are gathering interest as promising anti-cancer treatments with the ability to address a wide range of cancers. MSCs exhibit tumor-trophic migration characteristics, allowing them to be used as delivery vehicles for successful, targeted treatment of isolated tumors and metastatic malignancies. Preclinical and clinical research were reviewed in this study to discuss using MSC-released OVs as a novel method for the treatment of cancer. Video Abstract.


Assuntos
Células-Tronco Mesenquimais , Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Vírus Oncolíticos/fisiologia , Terapia Viral Oncolítica/métodos , Neoplasias/patologia , Imunoterapia , Células-Tronco Mesenquimais/patologia , Microambiente Tumoral
17.
Pharmacol Res ; 194: 106775, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37075872

RESUMO

Prostate carcinoma is a malignant situation that arises from genomic alterations in the prostate, leading to changes in tumorigenesis. The NF-κB pathway modulates various biological mechanisms, including inflammation and immune responses. Dysregulation of NF-κB promotes carcinogenesis, including increased proliferation, invasion, and therapy resistance. As an incurable disease globally, prostate cancer is a significant health concern, and research into genetic mutations and NF-κB function has the efficacy to facilitate the introduction of novel therapies. NF-κB upregulation is observed during prostate cancer progression, resulting in increased cell cycle progression and proliferation rates. Additionally, NF-κB endorses resistance to cell death and enhances the capacity for metastasis, particularly bone metastasis. Overexpression of NF-κB triggers chemoresistance and radio-resistance, and inhibition of NF-κB by anti-tumor compounds can reduce cancer progression. Interestingly, non-coding RNA transcripts can regulate NF-κB level and its nuclear transfer, offering a potential avenue for modulating prostate cancer progression.


Assuntos
Neoplasias Ósseas , Neoplasias da Próstata , Masculino , Humanos , NF-kappa B/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias Ósseas/genética , Carcinogênese/genética , Mutação , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral
18.
Mol Biol Rep ; 50(1): 85-95, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36309613

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is an invasive phenotype with undesirable clinical features, poor prognosis, and therapy resistance. Ketoprofen is a Non-steroidal anti-inflammatory drug (NSAID) with anti-tumor properties. AIM: To investigate the effects of Ketoprofen on apoptosis and autophagy in TNBC cell line MDA-MB-231. METHODS: The cytotoxic activity of Ketoprofen was assayed by the MTS method. Flowcytometry was utilized to measure the number of apoptotic MDA-MB-231 cells. The expression levels of apoptosis and autophagy markers, JAK2 and STAT3 were determined using quantitative real time-PCR (qRT-PCR) and western blotting methods. RESULTS: Ketoprofen significantly decreased the proliferation of MDA-MB-231 cells compared to control cells. It also considerably induced apoptosis and apoptotic markers in these cells in comparison to controls. Treating the MADA-MB-231 cell line with Ketoprofen had an inhibitory effect on autophagy markers in this cell line. The use of FasL, as a death ligand, and ZB4, as an antibody that blocks the extrinsic pathway of apoptosis, revealed the involvement of the extrinsic pathway in the apoptosis-stimulating effect of Ketoprofen in the MADA-MB-231 cell line. Ketoprofen also hindered the phosphorylation and activation of JAK2 and STAT molecules leading to the inhibition of the JAK/STAT pathway in this TNBC cell line. CONCLUSION: The outcomes of this study uncovered the anti-TNBC activity of Ketoprofen by inducing apoptosis and inhibiting viability and autophagy in MADA-MB-231 cells. Our data also suggested that Ketoprofen impedes apoptosis in TNBC cells by two different mechanisms including the induction of the extrinsic apoptotic pathway and inhibition of the JAK/STAT signaling.


Assuntos
Cetoprofeno , Neoplasias de Mama Triplo Negativas , Humanos , Cetoprofeno/farmacologia , Cetoprofeno/uso terapêutico , Neoplasias de Mama Triplo Negativas/genética , Transdução de Sinais , Janus Quinases/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição STAT/metabolismo , Apoptose , Proliferação de Células , Autofagia
19.
Mol Biol Rep ; 50(6): 5455-5464, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37155008

RESUMO

Parkinson's disease (PD) as a prevalent neurodegenerative condition impairs motor function and is caused by the progressive deterioration of nigrostriatal dopaminergic (DAergic) neurons. The current therapy solutions for PD are ineffective because they could not inhibit the disease's progression and they even have adverse effects. Natural polyphenols, a group of phytochemicals, have been found to offer various health benefits, including neuroprotection against PD. Among these, resveratrol (RES) has neuroprotective properties owing to its capacity to protect mitochondria and act as an antioxidant. An increase in the formation of reactive oxygen species (ROS) leads to oxidative stress (OS), which is responsible for cellular damage resulting in lipid peroxidation, oxidative protein alteration, and DNA damage. In PD models, it's been discovered that RES pretreatment can diminish oxidative stress by boosting endogenous antioxidant status and directly scavenging ROS. Several studies have examined the involvement of RES in the modulation of the transcriptional factor Nrf2 in PD models because this protein recognizes oxidants and controls the antioxidant defense. In this review, we have examined the molecular mechanisms underlying the RES activity and reviewed its effects in both in vitro and in vivo models of PD. The gathered evidence herein showed that RES treatment provides neuroprotection against PD by reducing OS and upregulation of Nrf2. Moreover, in the present study, scientific proof of the neuroprotective properties of RES against PD and the mechanism supporting clinical development consideration has been described.


Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Transdução de Sinais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
20.
BMC Endocr Disord ; 23(1): 275, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102636

RESUMO

BACKGROUND: Several studies have highlighted the possible positive effects of soluble receptor for advanced glycation end products (sRAGE) against obesity. However, due to their inconsistent results, this systematic review and meta-analysis aimed to quantitatively evaluate and critically review the results of studies evaluating the relationship between sRAGE with obesity among adult population. METHODS: In the systematic search, the eligibility criteria were as follows: studies conducted with a cross-sectional design, included apparently healthy adults, adults with obesity, or obesity-related disorders, aged over 18 years, and evaluated the association between general or central obesity indices with sRAGE. RESULTS: Our systematic search in electronic databases, including PubMed, Scopus, and Embase up to 26 October, 2023 yielded a total of 21,612 articles. After removing duplicates, screening the titles and abstracts, and reading the full texts, 13 manuscripts were included in the final meta-analysis. According to our results, those at the highest category of circulating sRAGE concentration with median values of 934.92 pg/ml of sRAGE, had 1.9 kg/m2 lower body mass index (BMI) (WMD: -1.927; CI: -2.868, -0.986; P < 0.001) compared with those at the lowest category of sRAGE concentration with median values of 481.88 pg/ml. Also, being at the highest sRAGE category with the median values of 1302.3 pg/ml sRAGE, was accompanied with near 6 cm lower waist circumference (WC) (WMD: -5.602; CI: -8.820, -2.383; P < 0.001 with 86.4% heterogeneity of I2) compared with those at the lowest category of sRAGE concentration with median values of 500.525 pg/ml. Individuals with obesity had significantly lower circulating sRAGE concentrations (WMD: -135.105; CI: -256.491, -13.72; P = 0.029; with 79.5% heterogeneity of I2). According to the subgrouping and meta-regression results, country and baseline BMI were possible heterogeneity sources. According to Begg's and Egger's tests and funnel plots results, there was no publication bias. CONCLUSION: According to our results, higher circulating sRAGE concentrations was associated with lower BMI and WC among apparently healthy adults. Further randomized clinical trials are warranted for possible identification of causal associations.


Assuntos
Produtos Finais de Glicação Avançada , Obesidade , Adulto , Humanos , Pessoa de Meia-Idade , Receptor para Produtos Finais de Glicação Avançada , Estudos Transversais , Índice de Massa Corporal , Redução de Peso
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