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1.
Cell Mol Life Sci ; 81(1): 214, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733529

RESUMO

The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially cancer. The circRNAs have a unique closed loop structure and due to their stability, they are potential diagnostic and prognostic factors in cancer. The increasing evidences have highlighted the role of circRNAs in the modulation of proliferation and metastasis of cancer cells. On the other hand, metastasis has been responsible for up to 90% of cancer-related deaths in patients, requiring more investigation regarding the underlying mechanisms modulating this mechanism. EMT enhances metastasis and invasion of tumor cells, and can trigger resistance to therapy. The cells demonstrate dynamic changes during EMT including transformation from epithelial phenotype into mesenchymal phenotype and increase in N-cadherin and vimentin levels. The process of EMT is reversible and its reprogramming can disrupt the progression of tumor cells. The aim of current review is to understanding the interaction of circRNAs and EMT in human cancers and such interaction is beyond the regulation of cancer metastasis and can affect the response of tumor cells to chemotherapy and radiotherapy. The onco-suppressor circRNAs inhibit EMT, while the tumor-promoting circRNAs mediate EMT for acceleration of carcinogenesis. Moreover, the EMT-inducing transcription factors can be controlled by circRNAs in different human tumors.


Assuntos
Carcinogênese , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Metástase Neoplásica , Neoplasias , RNA Circular , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Transição Epitelial-Mesenquimal/genética , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , Carcinogênese/genética , Carcinogênese/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Plasticidade Celular/genética , Animais , Regulação Neoplásica da Expressão Gênica
2.
Int J Psychiatry Med ; : 912174241255420, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771967

RESUMO

OBJECTIVE: This study investigated the prevalence and correlates of fibromyalgia and insomnia in a sample of Women with Multiple Sclerosis (WMS). METHODS: The study was cross-sectional in design and recruited a sample of 163 women with Relapsing-Remitting Multiple Sclerosis (RRMS). Fibromyalgia was assessed using the Patient Self-Report Survey (PSRS), following criteria outlined by the American College of Rheumatology. Insomnia was measured using the Arabic version of the Insomnia Severity Index (ISI-A). RESULTS: The prevalence of fibromyalgia and insomnia was 28.2% (n = 46) and 46.3% (n = 76), respectively. Multivariate analyses were used to determine significant independent correlates. Fibromyalgia was associated with age above 40 years (OR = 2.29, 95% CI = 1.01-5.18, P = .04), high school education (OR = 3.69, 95% CI = 1.62-8.37, P = .002), and non-use of analgesics (OR = .02, 95% CI = .004-.21, P = .001). Insomnia symptoms were significantly associated only with age above 40 years (OR = 2.16, 95% CI = 1.16-4.04, P = .01). CONCLUSION: These findings highlight the need for increased attention by primary care physicians towards diagnosing and treating fibromyalgia and insomnia among women with RRMS in Jordan, particularly among older women.

3.
Expert Opin Drug Deliv ; 21(3): 399-422, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38623735

RESUMO

INTRODUCTION: Doxorubicin (DOX) emerges as a cornerstone in the arsenal of potent chemotherapeutic agents. Yet, the clinical deployment of DOX is tarnished by its proclivity to induce severe cardiotoxic effects, culminating in heart failure and other consequential morbidities. In response, a panoply of strategies has undergone rigorous exploration over recent decades, all aimed at attenuating DOX's cardiotoxic impact. The advent of encapsulating DOX within lipidic or polymeric nanocarriers has yielded a dual triumph, augmenting DOX's therapeutic efficacy while mitigating its deleterious side effects. AREAS COVERED: Recent strides have spotlighted the emergence of DOX conjugates as particularly auspicious avenues for ameliorating DOX-induced cardiotoxicity. These conjugates entail the fusion of DOX through physical or chemical bonds with diminutive natural or synthetic moieties, polymers, biomolecules, and nanoparticles. This spectrum encompasses interventions that impinge upon DOX's cardiotoxic mechanism, modulate cellular uptake and localization, confer antioxidative properties, or refine cellular targeting. EXPERT OPINION: The endorsement of DOX conjugates as a compelling stratagem to mitigate DOX-induced cardiotoxicity resounds from this exegesis, amplifying safety margins and the therapeutic profile of this venerated chemotherapeutic agent. Within this ambit, DOX conjugates stand as a beacon of promise in the perpetual pursuit of refining chemotherapy-induced cardiac compromise.


Assuntos
Antibióticos Antineoplásicos , Cardiotoxicidade , Doxorrubicina , Portadores de Fármacos , Nanopartículas , Doxorrubicina/efeitos adversos , Doxorrubicina/administração & dosagem , Cardiotoxicidade/prevenção & controle , Cardiotoxicidade/etiologia , Humanos , Animais , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Portadores de Fármacos/química , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Polímeros/química , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/induzido quimicamente , Lipídeos/química
4.
Pathol Res Pract ; 257: 155285, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38653089

RESUMO

Glioblastoma, a highly lethal form of brain cancer, is characterized by its aggressive growth and resistance to conventional treatments, often resulting in limited survival. The response to therapy is notably influenced by various patient-specific genetic factors, underscoring the disease's complexity. Despite the utilization of diverse treatment modalities such as surgery, radiation, and chemotherapy, many patients experience local relapse, emphasizing the critical need for improved therapeutic strategies to effectively target these formidable tumors. Recent years have witnessed a surge in interest in natural products derived from plants, particularly alkaloids, for their potential anticancer effects. Alkaloids have shown promise in cancer chemotherapy by selectively targeting crucial signaling pathways implicated in tumor progression and survival. Specifically, they modulate the NF-κB and MAPK pathways, resulting in reduced tumor growth and altered gene expression across various cancer types. Additionally, alkaloids exhibit the capacity to induce cell cycle arrest, further impeding tumor proliferation in several malignancies. This review aims to delineate recent advances in understanding the pathology of glioblastoma multiforme (GBM) and to explore the potential therapeutic implications of alkaloids in managing this deadly disease. By segregating discussions on GBM pathology from those on alkaloid-based therapies, we provide a structured overview of the current challenges in GBM treatment and the promising opportunities presented by alkaloid-based interventions. Furthermore, we briefly discuss potential future directions in GBM research and therapy beyond alkaloids, including emerging treatment modalities or areas of investigation that hold promise for improving patient outcomes. In conclusion, our efforts offer hope for enhanced outcomes and improved quality of life for GBM patients through alkaloid-based therapies. By integrating insights from pathology and therapeutic perspectives, we underscore the significance of a comprehensive approach in addressing this devastating disease.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/patologia , Glioblastoma/terapia , Glioblastoma/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Alcaloides/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais
5.
Rheumatol Int ; 44(4): 715-723, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38285107

RESUMO

Suboptimal fibromyalgia management with over-the-counter analgesics leads to deteriorated outcomes for pain and mental health symptoms especially in low-income countries hosting refugees. To examine the association between the over-the-counter analgesics and the severity of fibromyalgia, depression, anxiety and PTSD symptoms in a cohort of Syrian refugees. This is a cross-sectional study. Fibromyalgia was assessed using the patient self-report survey for the assessment of fibromyalgia. Depression was measured using the Patient Health Questionnaire-9, insomnia severity was measured using the insomnia severity index (ISI-A), and PTSD was assessed using the Davidson trauma scale (DTS)-DSM-IV. Data were analyzed from 291. Among them, 221 (75.9%) reported using acetaminophen, 79 (27.1%) reported using non-steroidal anti-inflammatory drugs (NSAIDs), and 56 (19.2%) reported receiving a prescription for centrally acting medications (CAMs). Fibromyalgia screening was significantly associated with using NSAIDs (OR 3.03, 95% CI 1.58-5.80, p = 0.001). Severe depression was significantly associated with using NSAIDs (OR 2.07, 95% CI 2.18-3.81, p = 0.02) and CAMs (OR 2.74, 95% CI 1.30-5.76, p = 0.008). Severe insomnia was significantly associated with the use of CAMs (OR 3.90, 95% CI 2.04-5.61, p < 0.001). PTSD symptoms were associated with the use of CAMs (ß = 8.99, p = 0.001) and NSAIDs (ß = 10.39, p < 0.001). Improper analgesics are associated with poor fibromyalgia and mental health outcomes, prompt awareness efforts are required to address this challenge for the refugees and health care providers.


Assuntos
Fibromialgia , Refugiados , Distúrbios do Início e da Manutenção do Sono , Transtornos de Estresse Pós-Traumáticos , Humanos , Feminino , Saúde Mental , Estudos Transversais , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Fibromialgia/diagnóstico , Fibromialgia/tratamento farmacológico , Síria , Depressão/tratamento farmacológico , Analgésicos/efeitos adversos , Anti-Inflamatórios não Esteroides , Internet
6.
Biofactors ; 50(2): 232-249, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37702264

RESUMO

Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.


Assuntos
Doenças não Transmissíveis , Estilbenos , Humanos , Resveratrol/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Estilbenos/farmacologia , Estilbenos/uso terapêutico , Estilbenos/química
7.
Cell Signal ; 113: 110911, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37805102

RESUMO

The rewiring of cellular metabolism is a defining characteristic of cancer, as tumor cells adapt to acquire essential nutrients from a nutrient-poor environment to sustain their viability and biomass. While hypoxia has been identified as a major factor depriving cancer cells of nutrients, recent studies have revealed that cancer cells distant from supporting blood vessels also face nutrient limitations. To overcome this challenge, hypoxic cancer cells, which heavily rely on glucose as an energy source, employ alternative pathways such as glycogen metabolism and reductive carboxylation of glutamine to meet their energy requirements for survival. Our preliminary studies, alongside others in the field, have shown that under glucose-deficient conditions, hypoxic cells can utilize mannose and maltose as alternative energy sources. This review aims to comprehensively examine the hypoxic cancer microenvironment, its association with drug resistance, and potential therapeutic strategies for targeting this unique niche. Furthermore, we will critically evaluate the current literature on hypoxic cancer microenvironments and explore state-of-the-art techniques used to analyze alternate carbohydrates, specifically mannose and maltose, in complex biological fluids. We will also propose the most effective analytical methods for quantifying mannose and maltose in such biological samples. By gaining a deeper understanding of the hypoxic cancer cell microenvironment and its role in drug resistance, novel therapeutic approaches can be developed to exploit this knowledge.


Assuntos
Maltose , Neoplasias , Humanos , Hipóxia Celular , Maltose/farmacologia , Maltose/uso terapêutico , Manose/farmacologia , Manose/uso terapêutico , Neoplasias/metabolismo , Hipóxia , Glucose/farmacologia , Microambiente Tumoral , Resistência a Medicamentos
8.
Cell Signal ; 115: 111013, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38113978

RESUMO

The gut microbiota present in the human digestive system is incredibly varied and is home to trillions of microorganisms. The gut microbiome is shaped at birth, while numerous genetic, dietary, and environmental variables primarily influence the microbiome composition. The importance of gut microbiota on host health is becoming more widely acknowledged. Digestion, intestinal permeability, and immunological and metabolism responses can all be affected by changes in the composition and function of the gut microbiota. There is mounting evidence that the microbial population's complex traits are important biomarkers and indicators of patient outcomes in cancer and its therapies. Numerous studies have demonstrated that changed commensal gut microorganisms contribute to the development and spread of cancer through various routes. Despite the ongoing controversy surrounding the gut microbiome and gastrointestinal cancer, accumulating evidence points to a potentially far more intricate connection than a simple cause-and-effect relationship. SIMPLE SUMMARY: Due to their high frequency and fatality rate, gastrointestinal cancers are regarded as a severe public health issue with complex medical and economic burdens. The gut microbiota may directly or indirectly interact with existing therapies like immunotherapy and chemotherapy, affecting how well a treatment works. The gut microbiome influences the immune response's activity, function, and development. Generally, certain gut bacteria impact the antitumor actions during cancer by creating particular metabolites or triggering T-cell responses. Yet, certain bacterial species have been found to promote cellular proliferation and metastasis in cancer, and comprehending these interactions in the context of cancer may help identify possible treatment targets. Notwithstanding the improvements in the field, additional research is still required to comprehend the underlying processes, examine the effects on existing therapies, and pinpoint certain bacteria and immune cells that can cause this interaction.


Assuntos
Microbioma Gastrointestinal , Neoplasias Gastrointestinais , Microbiota , Recém-Nascido , Humanos , Bactérias/genética
9.
Med Oncol ; 40(8): 225, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37405480

RESUMO

Pancreatic cancer, one of the most aggressive tumors, has a dismal prognosis because of the low rates of early identification, fast progression, difficulties following surgery, and the ineffectiveness of current oncologic therapies. There are no imaging techniques or biomarkers that can accurately identify, categorize, or predict the biological behavior of this tumor. Exosomes are extracellular vesicles that play a crucial rule in the progression, metastasis, and chemoresistance of pancreatic cancer. They have been verified to be potential biomarkers for pancreatic cancer management. Studying the role of exosomes in pancreatic cancer is substantial. Exosomes are secreted by most eukaryotic cells and participated in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long non-coding RNA, circular RNA, etc., play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, in this concise review, we intend to summarize exosomes components and isolation, exosome secretion, function, importance of exosomes in the progression of pancreatic cancer and exosomal miRNAs as possible pancreatic cancer biomarkers. Finally, the application potential of exosomes in the treatment of pancreatic cancer, which provides theoretical supports for using exosomes to serve precise tumor treatment in the clinic, will be discussed.


Assuntos
Exossomos , MicroRNAs , Neoplasias Pancreáticas , Humanos , Exossomos/genética , Neoplasias Pancreáticas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Pancreáticas
10.
Biomedicines ; 11(5)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37239140

RESUMO

COVID-19 vaccines have been widely used to reduce the incidence and disease severity of COVID-19. Questions have lately been raised about the possibility of an association between COVID-19 vaccines and myocarditis, an inflammatory condition affecting the myocardium, or the middle layer of the heart. Myocarditis can be caused by infections, immune reactions, or toxic exposure. The incidence rate of myocarditis and pericarditis was calculated to be 5.98 instances per million COVID-19 vaccine doses delivered, which is less than half of the incidences after SARS-CoV-2 infection. Myocarditis rates in people aged 12 to 39 years are around 12.6 cases per million doses following the second dose of mRNA vaccination. Adolescent men are more likely than women to develop myocarditis after receiving mRNA vaccines. The objectives of this systematic review and meta-analysis are to find out how often myocarditis occurs after receiving the COVID-19 vaccine, as well as the risk factors and clinical repercussions of this condition. Nevertheless, the causal relationship between vaccination and myocarditis has been difficult to establish, and further research is required. It is also essential to distinguish between suggested cases of myocarditis and those confirmed by endomyocardial biopsy.

11.
Int J Mol Sci ; 24(4)2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36834476

RESUMO

Ran is a member of the Ras superfamily of proteins, which primarily regulates nucleocytoplasmic trafficking and mediates mitosis by regulating spindle formation and nuclear envelope (NE) reassembly. Therefore, Ran is an integral cell fate determinant. It has been demonstrated that aberrant Ran expression in cancer is a result of upstream dysregulation of the expression of various factors, such as osteopontin (OPN), and aberrant activation of various signaling pathways, including the extracellular-regulated kinase/mitogen-activated protein kinase (ERK/MEK) and phosphatidylinositol 3-kinase/Protein kinase B (PI3K/Akt) pathways. In vitro, Ran overexpression has severe effects on the cell phenotype, altering proliferation, adhesion, colony density, and invasion. Therefore, Ran overexpression has been identified in numerous types of cancer and has been shown to correlate with tumor grade and the degree of metastasis present in various cancers. The increased malignancy and invasiveness have been attributed to multiple mechanisms. Increased dependence on Ran for spindle formation and mitosis is a consequence of the upregulation of these pathways and the ensuing overexpression of Ran, which increases cellular dependence on Ran for survival. This increases the sensitivity of cells to changes in Ran concentration, with ablation being associated with aneuploidy, cell cycle arrest, and ultimately, cell death. It has also been demonstrated that Ran dysregulation influences nucleocytoplasmic transport, leading to transcription factor misallocation. Consequently, patients with tumors that overexpress Ran have been shown to have a higher malignancy rate and a shorter survival time compared to their counterparts.


Assuntos
GTP Fosfo-Hidrolases , Neoplasias , Humanos , GTP Fosfo-Hidrolases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteína ran de Ligação ao GTP/genética , Neoplasias/patologia , Fenótipo
12.
J Gastrointest Cancer ; 54(2): 368-390, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35285010

RESUMO

PURPOSE: Among all forms of cancers, hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. There are several treatment options for HCC ranging from loco-regional therapy to surgical treatment. Yet, there is high morbidity and mortality. Recent research focus has shifted towards more effective and less toxic cancer treatment options. Curcumin, the active ingredient in the Curcuma longa plant, has gained widespread attention in recent years because of its multifunctional properties as an antioxidant, anti-inflammatory, antimicrobial, and anticancer agent. METHODS: A systematic search of PubMed, Embase and Google Scholar was performed for studies reporting incidence of HCC, risk factors associated with cirrhosis and experimental use of curcumin as an anti-cancer agent. RESULTS: This review exclusively encompasses the anti-cancer properties of curcumin in HCC globally and it's postulated molecular targets of curcumin when used against liver cancers. CONCLUSIONS: This review is concluded by presenting the current challenges and future perspectives of novel plant extracts derived from C. longa and the treatment options against cancers.


Assuntos
Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Curcumina/farmacologia , Curcumina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Curcuma , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
13.
Inflammation ; 46(1): 297-312, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36215001

RESUMO

Hyper-transmissibility with decreased disease severity is a typical characteristic of the SARS-CoV-2 Omicron variant. To understand this phenomenon, we used various bioinformatics approaches to analyze randomly selected genome sequences (one each) of the Gamma, Delta, and Omicron variants submitted to NCBI from December 15 to 31, 2021. We report that the pathogenicity of SARS-CoV-2 variants decreases in the order of Wuhan > Gamma > Delta > Omicron; however, the antigenic property follows the order of Omicron > Gamma > Wuhan > Delta. The Omicron spike RBD shows lower pathogenicity but higher antigenicity than other variants. The reported decreased disease severity by the Omicron variant may be due to its decreased pro-inflammatory and IL-6 stimulation and increased IFN-γ and IL-4 induction efficacy. The mutations in the N protein are probably associated with this decreased IL-6 induction and human DDX21-mediated increased IL-4 production for Omicron. Due to the mutations, the stability of S, M, N, and E proteins decreases in the order of Omicron > Gamma > Delta > Wuhan. Although a stronger spike RBD-hACE2 binding of Omicron increases its transmissibility, the lowest stability of its spike protein makes spike RBD-hACE2 interaction weak for systemic infection and for causing severe disease. Finally, the highest instability of the Omicron E protein may also be associated with decreased viral maturation and low viral load, leading to less severe disease and faster recovery. Our findings will contribute to the understanding of the dynamics of SARS-CoV-2 variants and the management of emerging variants. This minimal genome-based method may be used for other similar viruses avoiding robust analysis.


Assuntos
COVID-19 , Citocinas , Humanos , SARS-CoV-2/genética , Interleucina-4 , Interleucina-6 , Virulência , Fatores de Transcrição , Anti-Inflamatórios , RNA Helicases DEAD-box
14.
Drug Discov Today ; 28(2): 103458, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36427779

RESUMO

Given their superior efficacy, rapid engineering, low-cost manufacturing, and safe delivery prospects, mRNA vaccines offer an intriguing alternative to conventional vaccination technologies. Several mRNA vaccine platforms targeting infectious diseases and various types of cancer have exhibited beneficial results both in vivo and in vitro. Issues related to mRNA stability and immunogenicity have been addressed. Current mRNA vaccines can generate robust immune responses, without being constrained by the major histocompatibility complex (MHC) haplotype of the recipient. Given that mRNA vaccinations are the only transient genetic information carriers, they are also safe. In this review, we provide an update and overview on mRNA vaccines, including their current state, and the problems that have prevented them from being used in more general therapeutic ways.


Assuntos
Vacinas Sintéticas , Vacinas de mRNA , RNA Mensageiro/genética , Desenvolvimento de Vacinas
15.
Cell Signal ; 100: 110488, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36208706

RESUMO

Osteoporosis is a silent disease of skeletal morphology that induces fragility and fracture risk in aged persons irrespective of gender. Juvenile secondary osteoporosis is rare and is influenced by familial genetic abnormalities. Despite the currently available therapeutic options, more-acute treatments are in need. Women suffer from osteoporosis after menopause, which is characterized by a decline in the secretion of sex hormones in the later phase of life. Several studies in the past two decades emphasized hormone-related pathways to combat osteoporosis. Some studies partially examined energy-related pathways, but achieving a more vivid picture of metabolism and bone remodeling in terms of the Warburg phenomenon is still warranted. Each cell requires sufficient energy for cellular propagation and growth; in particular, osteoporosis is an energy-dependent mechanism affected by a decreased cellular mass of the bone morphology. Energy utilization is the actual propagation of such diseases, and narrowing down these criteria will hopefully provide clues to formulate better therapeutic strategies. Oxidative glycolysis is a particular type of energy metabolic pathway in cancer cells that influences cellular proliferation. Therefore, the prospect of utilizing collective glucose metabolism by inducing the Warburg effect may improve cell propagation. The benefits of utilizing the energy from the Warburg effect may be a difficult task. However, it seems to improve their effectiveness in the osteoblast phenotype by connecting the selected pathways such as WNT, Notch, AKT, and Insulin signaling by targeting osteocalcin resulting in phenotypic alteration. Osteocalcin directs ATP utilization through the sclerostin SOST gene in the bone microenvironment. Thus, selective activation of ATP production involved in osteoblast maturation remains a prime strategy to fight osteoporosis.

16.
Life Sci ; 310: 121046, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36209829

RESUMO

RAS-related nuclear protein(RAN) is a nuclear shuttle and normally regulates events in the cell cycle. When overexpressed in cultured cells, it causes increases in cell migration/invasion in vitro and its overexpression is associated with early breast cancer patient deaths in vivo. However, the underlying mechanism is unknown. The effect of RAN overexpression on potential targets MMP2, ATF3, CXCR3 was investigated by Real-Time PCR/Western blots in the triple receptor negative breast cancer(TRNBC) cell line MDA-MB231 and consequent biological effects were measured by cell adhesion, cell migration and cell invasion assays. Results showed that knockdown of RAN lead to a reduction of MMP2 and its potential regulators ATF3 and CXCR3. Moreover, knockdown of ATF3 or CXCR3 downregulated MMP2 without affecting RAN, indicating that RAN regulates MMP2 through ATF3 and CXCR3. Knockdown of RAN and MMP2 reduced cell adhesion, cell migration and cell growth in agar, whilst overexpression of MMP2 reversed the knockdown of RAN. Furthermore, immunohistochemical staining for RAN and MMP2 are positively associated with each other in the same tumour and separately with patient survival times in breast cancer specimens, suggesting that a high level of RAN may be a pre-requisite for MMP2 overexpression and metastasis. Moreover, positive immunohistochemical staining for both RAN and MMP-2 reduces further patient survival times over that for either protein separately. Our results suggest that MMP2 expression can stratify progression of breast cancers with a high and low incidence of RAN, both RAN and MMP2 in combination can be used for a more accurate patient prognosis. SIMPLE SUMMARY: Ran is an important regulator of normal cell growth and behaviour. We have established in cell line models of breast cancer (BC) a molecular pathway between RAN and its protein-degrading effector MMP-2 and properties related to metastasis in culture. Using immunohistochemistry (IHC) staining of primary BCs, we have shown that RAN and MMP-2 are on their own significantly associated with patient demise from metastatic BC. Moreover, when staining for MMP-2 is added to that for RAN in the primary tumours, there is a significant decrease in patient survival time over that for either protein alone. Thus a combination of staining for RAN and MMP2 is an excellent marker for poor prognosis in breast cancer.


Assuntos
Neoplasias da Mama , Metaloproteinase 2 da Matriz , Neoplasias de Mama Triplo Negativas , Proteína ran de Ligação ao GTP , Feminino , Humanos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Guanosina Trifosfato , Metaloproteinase 2 da Matriz/metabolismo , Invasividade Neoplásica , Proteína ran de Ligação ao GTP/genética , Proteína ran de Ligação ao GTP/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
17.
Biomed Pharmacother ; 155: 113649, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36108389

RESUMO

Prostate cancer is one of the most common health hazards for men worldwide, specifically in Western countries. Rapid prostate cancer screening by analyzing the prostate-specific antigen present in male serum has brought about a sharp decline in the mortality index of this disease. Immunoassay technology quantifies the target analyte in the sample using the antigen-antibody reaction. Immunoassays are now pivotal in disease diagnostics, drug monitoring, and pharmacokinetics. Recently, immunosensors have gained momentum in delivering better results with high specificity and lower limit of detection (LOD). Nanomaterials like gold, silver, and copper exhibit numerous exceptional features and their use in developing immunosensors have garnered excellent results in the diagnostic field. This review highlights the recent and different immunoassay techniques used to detect prostate-specific antigens and discusses the advances in nanomaterial-based immunosensors to detect prostate cancer efficiently. The review also explores the importance of specific biomarkers and nanomaterials-based biosensors with good selectivity and sensitivity to prostate cancer.


Assuntos
Técnicas Biossensoriais , Nanoestruturas , Neoplasias da Próstata , Masculino , Humanos , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Técnicas Eletroquímicas/métodos , Antígeno Prostático Específico , Detecção Precoce de Câncer , Prata , Cobre , Neoplasias da Próstata/diagnóstico , Ouro , Biomarcadores
18.
Biomed Pharmacother ; 153: 113413, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076482

RESUMO

Phytotherapy, based on medicinal plants, have excellent potential in managing several diseases. A vital part of the healthcare system is herbal medicines, consisting of therapeutic agents with high safety profile and no or least adverse effects. Herbs or medicinal plants show anticancer, antioxidant, and gene-protective activity, which is useful for pharmaceutical industries. In vitro, the extract of antioxidant compounds prevents the growth of colon and liver cancer cells, followed by a dose-dependent method. The screening of extracts is done by using in vitro models. Reactive oxygen species (ROS) and free radicals lead to diseases based on age which promotes oxidative stress. Different types of ROSs available have central roles in the normal physiology and functioning of processes. Herbal or traditional plant medicines have rich antioxidant activity. Despite the limited literature on the health effect of herbal extract or spices. There are many studies examining the encouraging health effects of single phytochemicals instigating from the medicinal plant. This review provides a detailed overview on herbal antioxidants and how application of nanotechnology can improve its biological activity in managing several major diseases, and having no reported side effects.


Assuntos
Antioxidantes , Plantas Medicinais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Nanotecnologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química
19.
Heliyon ; 8(9): e10358, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36060470

RESUMO

Background: This study aims to address the effects of gold nanoparticles (AuNPs) on diabetic myopathy in streptozotocin (STZ)-induced diabetic rats. Materials and methods: Adult male rats were separated into three groups (n = 15): non-diabetic control (ND), diabetic (D), and diabetic treated with AuNPs (2.5 mg/kg, D + AuNPs) intraperitoneally for 4 weeks. A single injection of 50 mg/kg STZ was used to induce diabetes. Results: Treatment with AuNPs lowered blood glucose levels. Skeletal muscle mRNA expression of two muscle-specific E3 ubiquitin-ligases enzymes, F-box-only protein 32 (FBXO32) and muscle RING-finger protein-1 (MuRF1) were upregulated in the D group. Diabetic rats showed significant increases in the skeletal muscle expression levels of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), and a decrease in glucose transporter 4 (GLUT4) expression. Superoxide dismutase (SOD) activity decreased and malondialdehyde (MDA) level increased in skeletal muscles of D group. Compared to the D group, expression levels of FBXO32, MuRF1, PAI-1 TNF-α, and TGF-ß1 were decreased in the D + AuNPs group, and mRNA of GLUT4 increased. Furthermore, in D + AuNPs group, skeletal muscle MDA levels decreased while SOD activity increased. Conclusion: In experimental models, AuNPs can ameliorate muscle atrophy by reducing hyperglycemia, inflammation, and oxidative stress, and by suppressing the ubiquitin-proteasome proteolytic process.

20.
Integr Cancer Ther ; 21: 15347354221096766, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35796303

RESUMO

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment.


Assuntos
Canabinoides , Cannabis , Neoplasias , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Endocanabinoides , Humanos , Neoplasias/tratamento farmacológico , Receptores de Canabinoides , Microambiente Tumoral
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