RESUMEN
Luteolin, a flavonoid, is mainly found in various vegetables and fruits, including carrots, cabbages, onions, parsley, apples, broccoli, and peppers. Extensive research in vivo and in vitro has been performed to explore its role in disease prevention and treatment. Moreover, this compound possesses the ability to combat cancer by modulating cell-signaling pathways across various types of cancer. The studies have confirmed that luteolin can inhibit cancer-cell survival and proliferation, angiogenesis, invasion, metastasis, mTOR/PI3K/Akt, STAT3, Wnt/ß-catenin, and cell-cycle arrest, and induce apoptosis. Further, scientific evidence describes that this compound plays a vital role in the up/down-regulation of microRNAs (miRNAs) in cancer therapy. This review aims to outline the anti-cancer mechanisms of this compound and its molecular targets. However, a knowledge gap remains regarding the studies on its safety and efficacy and clinical trials. Therefore, it is essential to conduct more research based on safety, efficacy, and clinical trials to explore the beneficial role of this compound in disease management, including cancer.
Asunto(s)
Luteolina , Neoplasias , Humanos , Luteolina/farmacología , Flavonoides/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Neoplasias/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Apoptosis , Proliferación Celular , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Cancer is one of the main causes of death in all developed and developing countries. Various factors are involved in cancer development and progression, including inflammation and alterations in cellular processes and signaling transduction pathways. Natural compounds have shown health-promoting effects through their antioxidant and anti-inflammatory potential, having an important role in the inhibition of cancer growth. In this regard, formononetin, a type of isoflavone, plays a significant role in disease management through the modulation of inflammation, angiogenesis, cell cycle, and apoptosis. Furthermore, its role in cancer management has been proven through the regulation of different signal transduction pathways, such as the signal transducer and activator of transcription 3 (STAT 3), Phosphatidyl inositol 3 kinase/protein kinase B (PI3K/Akt), and mitogen activating protein kinase (MAPK) signaling pathways. The anticancer potential of formononetin has been reported against various cancer types, such as breast, cervical, head and neck, colon, and ovarian cancers. This review focuses on the role of formononetin in different cancer types through the modulation of various cell signaling pathways. Moreover, synergistic effect with anticancer drugs and methods to improve bioavailability are explained. Thus, detailed studies based on clinical trials are required to explore the potential role of formononetin in cancer prevention and treatment.
Asunto(s)
Antineoplásicos , Isoflavonas , Neoplasias , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Neoplasias/tratamiento farmacológicoRESUMEN
Cancer is a major public health concern worldwide and main burden of the healthcare system. Regrettably, most of the currently used cancer treatment approaches such as targeted therapy, chemotherapy, radiotherapy and surgery usually cause adverse complications including hair loss, bone density loss, vomiting, anemia and other complications. However, to overcome these limitations, there is an urgent need to search for the alternative anticancer drugs with better efficacy as well as less adverse complications. Based on the scientific evidences, it is proven that naturally occurring antioxidants present in medicinal plants or their bioactive compounds might constitute a good therapeutic approach in diseases management including cancer. In this regard, myricetin, a polyhydroxy flavonol found in a several types of plants and its role in diseases management as anti-oxidant, anti-inflammatory and hepato-protective has been documented. Moreover, its role in cancer prevention has been noticed through modulation of angiogenesis, inflammation, cell cycle arrest and induction of apoptosis. Furthermore, myricetin plays a significant role in cancer prevention through the inhibition of inflammatory markers such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2). Moreover, myricetin increases the chemotherapeutic potential of other anticancer drugs through modulation of cell signaling molecules activity. This review elaborates the information of myricetin role in cancer management through modulating of various cell-signaling molecules based on in vivo and in vitro studies. In addition, synergistic effect with currently used anticancer drugs and approaches to improve bioavailability are described. The evidences collected in this review will help different researchers to comprehend the information about its safety aspects, effective dose for different cancers and implication in clinical trials. Moreover, different challenges need to be focused on engineering different nanoformulations of myricetin to overcome the poor bioavailability, loading capacity, targeted delivery and premature release of this compound. Furthermore, some more derivatives of myricetin need to be synthesized to check their anticancer potential.
Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Transducción de Señal , Inflamación/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Neoplasias/tratamiento farmacológico , ApoptosisRESUMEN
Cancer is the principal cause of death and its incidence is increasing continuously worldwide. Various treatment approaches are in practice to treat cancer, but these treatment strategies may be associated with severe side effects and also produce drug resistance. However, natural compounds have established their role in cancer management with minimal side effects. In this vista, kaempferol, a natural polyphenol, mainly found in vegetables and fruits, has been revealed to have many health-promoting effects. Besides its health-promoting potential, its anti-cancer potential has also been described in in vivo as well as in in vitro studies. The anti-cancer potential of kaempferol has been proven through modulation of cell signaling pathways in addition to the induction of apoptosis and cell cycle arrest in cancer cells. It leads to the activation of tumor suppressor genes, inhibition of angiogenesis, PI3K/AKT pathways, STAT3, transcription factor AP-1, Nrf2 and other cell signaling molecules. Poor bioavailability of this compound is one of the major limitations for its proper and effective disease management actions. Recently, some novel nanoparticle-based formulations have been used to overcome these limitations. The aim of this review is to provide a clear picture regarding the mechanism of action of kaempferol in different cancers through the modulation of cell signaling molecules. Besides this, strategies to improve the efficacy and synergistic effects of this compound have also been described. However, more studies are needed based on clinical trials to fully explore the therapeutic role of this compound, especially in cancer treatment.
Asunto(s)
Neoplasias , Fosfatidilinositol 3-Quinasas , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Quempferoles/farmacología , Quempferoles/uso terapéutico , Quempferoles/metabolismo , Neoplasias/tratamiento farmacológico , Transducción de Señal , Inflamación , ApoptosisRESUMEN
The innovative advances in transforming clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) into different variants have taken the art of genome-editing specificity to new heights. Allosteric modulation of Cas9-targeting specificity by sgRNA sequence alterations and protospacer adjacent motif (PAM) modifications have been a good lesson to learn about specificity and activity scores in different Cas9 variants. Some of the high-fidelity Cas9 variants have been ranked as Sniper-Cas9, eSpCas9 (1.1), SpCas9-HF1, HypaCas9, xCas9, and evoCas9. However, the selection of an ideal Cas9 variant for a given target sequence remains a challenging task. A safe and efficient delivery system for the CRISPR/Cas9 complex at tumor target sites faces considerable challenges, and nanotechnology-based stimuli-responsive delivery approaches have significantly contributed to cancer management. Recent innovations in nanoformulation design, such as pH, glutathione (GSH), photo, thermal, and magnetic responsive systems, have modernized the art of CRISPR/Cas9 delivery approaches. These nanoformulations possess enhanced cellular internalization, endosomal membrane disruption/bypass, and controlled release. In this review, we aim to elaborate on different CRISPR/Cas9 variants and advances in stimuli-responsive nanoformulations for the specific delivery of this endonuclease system. Furthermore, the critical constraints of this endonuclease system on clinical translations towards the management of cancer and prospects are described.
Asunto(s)
Sistemas CRISPR-Cas , Neoplasias , Humanos , Sistemas CRISPR-Cas/genética , Proteína 9 Asociada a CRISPR/metabolismo , Edición Génica , Neoplasias/genética , Neoplasias/terapia , TecnologíaRESUMEN
Pro-inflammatory macrophage polarization is crucial in acute inflammatory diseases like Acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Prostaglandin E2 (PGE2) is believed to promote inflammation in such cases. Therefore, our study aimed to deliver anti-prostaglandin E synthase 2 small interfering RNA antibodies (anti-PGE2-siRNA) through lipid nanoparticles (LNPs) in RAW264.7 (The murine macrophage cell line) to find a possible cure to the acute inflammatory diseases. LNPs were synthesized by using thin layer evaporation method and were characterized by dynamic light scattering (DLS), Zeta potential, SEM and TEM analysis. The obtained NPs were spherical with an average size of 73 nm and zeta potential +29mV. MTT assay revealed that these NPs were non-toxic in nature. Gel retardation assay displayed 5:2 ratio of siRNA and NPs as the best siRNA:LNPs ratio for the delivery of siRNA into cells. After siRNA delivery by using LNPs, real time gene expression analysis revealed significant decrease in the expression of PGE2. Western blot results confirmed that silencing of PGE2 gene influence inducible nitric oxide synthase (iNOS) and interlukin-1ß (1L-1ß), markers involved in pro-inflammatory macrophage polarization. Our study revealed that LNPs synthesized in present study can be one of the effective methods to deliver anti-PGE2-siRNA to control pro-inflammatory macrophage polarization for the treatment of acute inflammatory response.
RESUMEN
The roles of medicinal plants or their purified bioactive compounds have attracted attention in the field of health sciences due to their low toxicity and minimal side effects. Baicalein is an active polyphenolic compound, isolated from Scutellaria baicalensis, and plays a significant role in the management of different diseases. Epidemiologic studies have proven that there is an inverse association between baicalein consumption and disease severity. Baicalein is known to display anticancer activity through the inhibition of inflammation and cell proliferation. Additionally, the anticancer potential of baicalein is chiefly mediated through the modulation of various cell-signaling pathways, such as the induction of apoptosis, autophagy, cell cycle arrest, inhibition of angiogenesis, signal transducer and activator of transcription 3, and PI3K/Akt pathways, as well as the regulation of other molecular targets. Therefore, the current review aimed to explore the role of baicalein in different types of cancer along with mechanisms of action. Besides this, the synergistic effects with other anti-cancerous drugs and the nano-formulation based delivery of baicalein have also been discussed.
Asunto(s)
Flavanonas , Neoplasias , Fosfatidilinositol 3-Quinasas , Flavanonas/farmacología , Flavanonas/uso terapéutico , Neoplasias/tratamiento farmacológico , Scutellaria baicalensisRESUMEN
Cancer is a main culprit and the second-leading cause of death worldwide. The current mode of treatment strategies including surgery with chemotherapy and radiation therapy may be effective, but cancer is still considered a major cause of death. Plant-derived products or their purified bioactive compounds have confirmed health-promoting effects as well as cancer-preventive effects. Among these products, flavonoids belong to polyphenols, chiefly found in fruits, vegetables and in various seeds/flowers. It has been considered to be an effective antioxidant, anti-inflammatory and to play a vital role in diseases management. Besides these activities, flavonoids have been revealed to possess anticancer potential through the modulation of various cell signaling molecules. In this regard, fisetin, a naturally occurring flavonoid, has a confirmed role in disease management through antioxidant, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential. As well, its cancer-preventive effects have been confirmed via modulating various cell signaling pathways including inflammation, apoptosis, angiogenesis, growth factor, transcription factor and other cell signaling pathways. This review presents an overview of the anti-cancer potential of fisetin in different types of cancer through the modulation of cell signaling pathways based on in vivo and in vitro studies. A synergistic effect with anticancer drugs and strategies to improve the bioavailability are described. More clinical trials need to be performed to explore the anti-cancer potential and mechanism-of-action of fisetin and its optimum therapeutic dose.
Asunto(s)
Flavonoides , Neoplasias , Humanos , Flavonoides/farmacología , Flavonoides/uso terapéutico , Antioxidantes/farmacología , Flavonoles/farmacología , Flavonoles/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , ApoptosisRESUMEN
Cancer is the leading cause of death worldwide. In spite of advances in the treatment of cancer, currently used treatment modules including chemotherapy, hormone therapy, radiation therapy and targeted therapy causes adverse effects and kills the normal cells. Therefore, the goal of more effective and less side effects-based cancer treatment approaches is still at the primary position of present research. Medicinal plants or their bioactive ingredients act as dynamic sources of drugs due to their having less side effects and also shows the role in reduction of resistance against cancer therapy. Apigenin is an edible plant-derived flavonoid that has received significant scientific consideration for its health-promoting potential through modulation of inflammation, oxidative stress and various other biological activities. Moreover, the anti-cancer potential of apigenin is confirmed through its ability to modulate various cell signalling pathways, including tumor suppressor genes, angiogenesis, apoptosis, cell cycle, inflammation, apoptosis, PI3K/AKT, NF-κB, MAPK/ERK and STAT3 pathways. The current review mainly emphases the potential role of apigenin in different types of cancer through the modulation of various cell signaling pathways. Further studies based on clinical trials are needed to explore the role of apigenin in cancer management and explain the possible potential mechanisms of action in this vista.
Asunto(s)
Apigenina , Neoplasias , Apigenina/farmacología , Apigenina/uso terapéutico , Apoptosis , Hormonas/farmacología , Humanos , Inflamación/tratamiento farmacológico , FN-kappa B/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Cancer is among the most prominent causes of mortality worldwide. Different cancer therapy modes employed, including chemotherapy and radiotherapy, have been reported to be significant in cancer management, but the side effects associated with these treatment strategies are still a health problem. Therefore, alternative anticancer drugs based on medicinal plants or their active compounds have been generating attention because of their less serious side effects. Medicinal plants are an excellent source of phytochemicals that have been recognized to have health-prompting effects through modulating cell signaling pathways. Resveratrol is a well-known polyphenolic molecule with antioxidant, anti-inflammatory, and health-prompting effects among which its anticancer role has been best defined. Additionally, this polyphenol has confirmed its role in cancer management because it activates tumor suppressor genes, suppresses cell proliferation, induces apoptosis, inhibits angiogenesis, and modulates several other cell signaling molecules. The anticancer potential of resveratrol is recognized in numerous in vivo and in vitro studies. Previous experimental data suggested that resveratrol may be valuable in cancer management or improve the efficacy of drugs when given with anticancer drugs. This review emphasizes the potential role of resveratrol as an anticancer drug by modulating numerous cells signaling pathways in different types of cancer.
Asunto(s)
Antineoplásicos , Neoplasias , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Polifenoles/farmacología , Polifenoles/uso terapéutico , Resveratrol/farmacología , Resveratrol/uso terapéuticoRESUMEN
Advanced glycation end products (AGEs) are naturally occurring biomolecules formed by interaction of reducing sugars with biomolecules such as protein and lipids etc., Long term high blood sugar level and glycation accelerate the formation of AGEs. Unchecked continuous formation and accumulation of AGEs are potential risks for pathogenesis of various chronic diseases. Current mode of antidiabetic therapy is based on synthetic drugs that are often linked with severe adverse effects. Polyphenolic compounds derived from plants are supposed to inhibit glycation and formation of AGEs at multiple levels. Some polyphenolic compounds regulate the blood glucose metabolism by amplification of cell insulin resistance and activation of insulin like growth factor binding protein signaling pathway. Their antioxidant nature and metal chelating activity, ability to trap intermediate dicarbonyl compounds could be possible mechanisms against glycation and AGEs formation and hence, against AGEs induced health complications. Although, few species of polyphenolic compounds are being used in in vitro trials and their in vivo study is still in progress, increasing the area of research in this field may produce a fruitful approach in management of overall diabetic complications.
Asunto(s)
Antioxidantes/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Hipoglucemiantes/uso terapéutico , Obesidad/tratamiento farmacológico , Fitoquímicos/uso terapéutico , Polifenoles/uso terapéutico , Glucemia/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Regulación de la Expresión Génica , Productos Finales de Glicación Avanzada/genética , Productos Finales de Glicación Avanzada/metabolismo , Glicosilación , Humanos , Resistencia a la Insulina , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Obesidad/genética , Obesidad/metabolismo , Obesidad/patología , Transducción de SeñalRESUMEN
Diethylnitrosamine (DEN) is a well-known hepatocarcinogen, and its oral administration causes severe liver damage including cancer. DEN induces the pathogenesis of the liver through reactive oxygen species mediated inflammation and modulation of various biological activities. 6-Gingerol, a major component of ginger, is reported to prevent liver diseases by reducing the oxidative stress and proinflammatory mediators. The present study investigated the hepatoprotective effects of 6-gingerol through the measurement of oxidative stress, anti-inflammatory markers, liver function enzyme parameter, and histopathological analysis. The rats were randomly divided into four groups as the control, DEN treated (50 mg/kg b.w.), DEN+6-gingerol (each 50 mg/kg b.w.), and 6-gingerol only. To evaluate the hepatoprotective effects, liver function enzymes (ALT, AST, and ALP), oxidative stress markers (SOD, GSH, GST, and TAC), lipid peroxidation, inflammatory markers (CRP, TNF-α, IL-6, and ICAM1), haematoxylin and eosin staining, Sirius red staining, immunohistochemistry, and electron microscopy were performed. The results showed a significant increase in liver function enzymes, oxidative stress, and inflammatory markers in the DEN-treated group as compared to the control group. Besides this, altered architecture of hepatocytes (infiltration of inflammatory cells, congestion, blood vessel dilation, and edema), abundant collagen fiber and organelle structures like distorted shaped and swollen mitochondria, and broken endoplasmic reticulum were noticed. The administration of 6-gingerol significantly ameliorated the biochemical and histopathological changes. The increased expression of TNF-α protein was noticed in the DEN-treated group whereas the administration of 6-gingerol significantly decreased the expression of this protein. Based on these findings, it can be suggested that 6-gingerol may be an alternative therapy for the prevention and treatment of liver diseases.
Asunto(s)
Antiinflamatorios/farmacología , Catecoles/farmacología , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Dietilnitrosamina , Alcoholes Grasos/farmacología , Estrés Oxidativo/efectos de los fármacos , Zingiber officinale/metabolismo , Albúminas/química , Animales , Compuestos de Bifenilo , Depuradores de Radicales Libres , Radicales Libres , Glutatión/metabolismo , Peróxido de Hidrógeno , Técnicas In Vitro , Inflamación/tratamiento farmacológico , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Mitocondrias/metabolismo , Picratos , RatasRESUMEN
Benzopyrene [B(a)P] is a well-recognized environmental carcinogen, which promotes oxidative stress, inflammation, and other metabolic complications. In the current study, the therapeutic effects of thymoquinone (TQ) against B(a)P-induced lung injury in experimental rats were examined. B(a)P used at 50 mg/kg b.w. induced lung injury that was investigated via the evaluation of lipid profile, inflammatory markers, nitric oxide (NO), and malondialdehyde (MDA) levels. B(a)P also led to a decrease in superoxide dismutase (SOD) (34.3 vs. 58.5 U/mg protein), glutathione peroxidase (GPx) (42.4 vs. 72.8 U/mg protein), catalase (CAT) (21.2 vs. 30.5 U/mg protein), and total antioxidant capacity compared to normal animals. Treatment with TQ, used at 50 mg/kg b.w., led to a significant reduction in triglycerides (TG) (196.2 vs. 233.7 mg/dL), total cholesterol (TC) (107.2 vs. 129.3 mg/dL), and inflammatory markers and increased the antioxidant enzyme level in comparison with the group that was administered B(a)P only (p < 0.05). B(a)P administration led to the thickening of lung epithelium, increased inflammatory cell infiltration, damaged lung tissue architecture, and led to accumulation of collagen fibres as studied through haematoxylin and eosin (H&E), Sirius red, and Masson's trichrome staining. Moreover, the recognition of apoptotic nuclei and expression pattern of NF-κB were evaluated through the TUNEL assay and immunohistochemistry, respectively. The histopathological changes were found to be considerably low in the TQ-treated animal group. The TUNEL-positive cells increased significantly in the B(a)P-induced group, whereas the TQ-treated group showed a decreased apoptosis rate. Significantly high cytoplasmic expression of NF-κB in the B(a)P-induced group was seen, and this expression was prominently reduced in the TQ-treated group. Our results suggest that TQ can be used in the protection against benzopyrene-caused lung injury.
Asunto(s)
Benzo(a)pireno/química , Benzoquinonas/análisis , Benzoquinonas/farmacología , Inflamación , Lípidos/química , Lesión Pulmonar/inducido químicamente , Pulmón/efectos de los fármacos , Nigella sativa/metabolismo , Óxido Nítrico/química , Estrés Oxidativo , Fibrosis Pulmonar/inducido químicamente , Animales , Antioxidantes/química , Colesterol/química , Fragmentación del ADN , Molécula 1 de Adhesión Intercelular/biosíntesis , Interleucina-1beta/biosíntesis , Interleucina-6/biosíntesis , Pulmón/patología , Masculino , Fibrosis Pulmonar/fisiopatología , Ratas , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Polyphenolic flavonoids are considered natural, non-toxic chemopreventers, which are most commonly derived from plants, fruits, and vegetables. Most of these polyphenolics exhibit remarkable antioxidant, anti-inflammatory, and anticancer properties. Quercetin (Qu) is a chief representative of these polyphenolic compounds, which exhibits excellent antioxidant and anticancer potential, and has attracted the attention of researchers working in the area of cancer biology. Qu can regulate numerous tumor-related activities, such as oxidative stress, angiogenesis, cell cycle, tumor necrosis factor, proliferation, apoptosis, and metastasis. The anticancer properties of Qu mainly occur through the modulation of vascular endothelial growth factor (VEGF), apoptosis, phosphatidyl inositol-3-kinase (P13K)/Akt (proteinase-kinase B)/mTOR (mammalian target of rapamycin), MAPK (mitogen activated protein kinase)/ERK1/2 (extracellular signal-regulated kinase 1/2), and Wnt/ß-catenin signaling pathways. The anticancer potential of Qu is documented in numerous in vivo and in vitro studies, involving several animal models and cell lines. Remarkably, this phytochemical possesses toxic activities against cancerous cells only, with limited toxic effects on normal cells. In this review, we present extensive research investigations aimed to discuss the therapeutic potential of Qu in the management of different types of cancers. The anticancer potential of Qu is specifically discussed by focusing its ability to target specific molecular signaling, such as p53, epidermal growth factor receptor (EGFR), VEGF, signal transducer and activator of transcription (STAT), PI3K/Akt, and nuclear factor kappa B (NF-κB) pathways. The anticancer potential of Qu has gained remarkable interest, but the exact mechanism of its action remains unclear. However, this natural compound has great pharmacological potential; it is now believed to be a complementary-or alternative-medicine for the prevention and treatment of different cancers.
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Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Humanos , Neoplasias/metabolismo , Neoplasias/patologíaRESUMEN
A proper execution of basic cellular functions requires well-controlled homeostasis including correct protein folding. Endoplasmic reticulum (ER) implements such functions by protein reshaping and post-translational modifications. Different insults imposed on cells could lead to ER stress-mediated signaling pathways, collectively called the unfolded protein response (UPR). ER stress is also closely linked with oxidative stress, which is a common feature of diseases such as stroke, neurodegeneration, inflammation, metabolic diseases, and cancer. The level of ER stress is higher in cancer cells, indicating that such cells are already struggling to survive. Prolonged ER stress in cancer cells is like an Achilles' heel, if aggravated by different agents including nanoparticles (NPs) may be exhausted off the pro-survival features and can be easily subjected to proapoptotic mode. Different types of NPs including silver, gold, silica, graphene, etc. have been used to augment the cytotoxicity by promoting ER stress-mediated cell death. The diverse physico-chemical properties of NPs play a great role in their biomedical applications. Some special NPs have been effectively used to address different types of cancers as these particles can be used as both toxicological or therapeutic agents. Several types of NPs, and anticancer drug nano-formulations have been engineered to target tumor cells to enhance their ER stress to promote their death. Therefore, mitigating ER stress in cancer cells in favor of cell death by ER-specific NPs is extremely important in future therapeutics and understanding the underlying mechanism of how cancer cells can respond to NP induced ER stress is a good choice for the development of novel therapeutics. Thus, in depth focus on NP-mediated ER stress will be helpful to boost up developing novel pro-drug candidates for triggering pro-death pathways in different cancers.
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Estrés del Retículo Endoplásmico , Nanopartículas/toxicidad , Neoplasias/patología , Animales , Enfermedad , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Nanotubos de Carbono/toxicidadRESUMEN
Epigallocatechin-3-gallate (EGCG), an active compound of green tea and its role in diseases cure and prevention has been proven. Its role in diseases management can be attributed to its antioxidant and anti-inflammatory properties. The anti-cancer role of this green tea compound has been confirmed in various types of cancer and is still being under explored. EGCG has been proven to possess a chemopreventive effect through inhibition of carcinogenesis process such as initiation, promotion, and progression. In addition, this catechin has proven its role in cancer management through modulating various cell signaling pathways such as regulating proliferation, apoptosis, angiogenesis and killing of various types of cancer cells. The additive or synergistic effect of epigallocatechin with chemopreventive agents has been verified as it reduces the toxicities and enhances the anti-cancerous effects. Despite its effectiveness and safety, the implications of EGCG in cancer prevention is certainly still discussed due to a poor bioavailability. Several studies have shown the ability to overcome poor bioavailability through nanotechnology-based strategies such as encapsulation, liposome, micelles, nanoparticles and various other formulation. In this review, we encapsulate therapeutic implication of EGCG in cancer management and the mechanisms of action are discussed with an emphasis on human clinical trials.
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Antineoplásicos Fitogénicos/uso terapéutico , Catequina/análogos & derivados , Portadores de Fármacos/uso terapéutico , Nanoestructuras/uso terapéutico , Neoplasias/tratamiento farmacológico , Té/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacocinética , Apoptosis/efectos de los fármacos , Catequina/química , Catequina/farmacocinética , Catequina/uso terapéutico , Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Nanoestructuras/química , Neoplasias/metabolismo , Neoplasias/patología , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Advanced laboratory investigations at reference laboratories play a key role in the diagnosis of the disease, but misuse of this precious and expensive tool may misguide the physician in patient management. This study was carried out as an audit of investigations performed at a reference laboratory, in order to assess their cost effectiveness, to identify various errors, the degree of correlation of requested tests with the clinical diagnosis and benefit to the patients. METHOD: A four phase audit of 337 laboratory investigation prescription was performed from April 2012 to March 2013 in the Medical, Administration in collaboration with Department of Medical Laboratory and various Clinics at the King Salman Armed Forces Hospital in Northwestern Region, - Kingdom of Saudi Arabia. All the information was recorded on a questionnaire pro forma. RESULTS: On data compilation and analysis it was found that 174(51.63%) test results were within normal reference range, while 163 (48.37%) test results were reported as positive. Also 218 (64.69%) investigations results correlated with clinical assessment by the physician, while 119 (35.31%) investigation results did not correlate with the clinical assessment by the physician. The expenses incurred Euro 12868 were spent on non-correlated tests while on correlated tests were Euro 31831. In terms of benefit to the patients 243 (82.09%) patients were reported by clinicians to have benefited from the reference laboratory tests, while 53 (17.91%) cases did not benefit from the reference laboratory tests as assessed by the clinicians and 41 (12.16%) cases in which even clinician did not respond regarding the benefit to the patients. Three categories of errors were identified (26.40%), i.e., at the level of clinicians (12.75%), at the level of hospital lab (5.04%) and at the level of reference lab (8.60%). CONCLUSION: Thorough clinical assessment and judicious utilization of available preliminary laboratory tests are the keys to precise diagnosis and are instrumental in reducing reliance on reference laboratory investigations.
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Auditoría Clínica/métodos , Servicios de Laboratorio Clínico/estadística & datos numéricos , Técnicas y Procedimientos Diagnósticos/estadística & datos numéricos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Arabia Saudita , Encuestas y Cuestionarios , Adulto JovenRESUMEN
We report the case of a child who presented with diencephalic syndrome. During diagnostic work- up, he was found to have a supra-sellar hypothalamic tumour. Histopathological examination of the tumour revealed it to be pilomyxoid astrocytoma, which is a WHO grade-II tumour, previously considered to be part of the spectrum of WHO grade-I pilocytic astrocytomas. However, because of its characteristic histopathology and behaviour, it was later segregated from pilocytic astrocytomas. In this case report, we discuss the cytological and histopathological features of this tumor with the aim of increasing awareness of this tumour amongst general histopathologists, to highlight the importance of its differentiation from pilocytic astrocytomas in view of its different behaviour, treatment and prognosis and that it should be included in the differential diagnosis of diencephalic syndrome.
Asunto(s)
Astrocitoma/complicaciones , Astrocitoma/patología , Neoplasias Hipotalámicas/complicaciones , Neoplasias Hipotalámicas/patología , Astrocitoma/cirugía , Insuficiencia de Crecimiento/etiología , Humanos , Neoplasias Hipotalámicas/cirugía , Lactante , Imagen por Resonancia Magnética , Masculino , Trastornos de la Motilidad Ocular/etiologíaRESUMEN
The antioxidant defense mechanisms play a critical role in mitigating the deleterious effects of reactive oxygen species (ROS). Catalase stands out as a paramount enzymatic antioxidant. It efficiently catalyzes the decomposition of hydrogen peroxide (H2O2) into water and oxygen, a potentially harmful byproduct of cellular metabolism. This reaction detoxifies H2O2 and prevents oxidative damage. Catalase has been extensively studied as a therapeutic antioxidant. Its applications range from direct supplementation in conditions characterized by oxidative stress to gene therapy approaches to enhance endogenous catalase activity. The enzyme's stability, bioavailability, and the specificity of its delivery to target tissues are significant hurdles. Furthermore, studies employing conventional catalase formulations often face issues related to enzyme purity, activity, and longevity in the biological milieu. Addressing these challenges necessitates rigorous scientific inquiry and well-designed clinical trials. Such trials must be underpinned by sound experimental designs, incorporating advanced catalase formulations or novel delivery systems that can overcome existing limitations. Enhancing catalase's stability, specificity, and longevity in vivo could unlock its full therapeutic potential. It is necessary to understand the role of catalase in disease-specific contexts, paving the way for precision antioxidant therapy that could significantly impact the treatment of diseases associated with oxidative stress.
Asunto(s)
Antioxidantes , Catalasa , Estrés Oxidativo , Catalasa/metabolismo , Catalasa/química , Humanos , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Peróxido de Hidrógeno/metabolismo , Terapia Genética/métodosRESUMEN
Apigenin is a powerful flavone compound found in numerous fruits and vegetables, and it offers numerous health-promoting benefits. Many studies have evidenced that this compound has a potential role as an anti-inflammatory and antioxidant compound, making it a promising candidate for reducing the risk of pathogenesis. It has also been found to positively affect various systems in the body, such as the respiratory, digestive, immune, and reproductive systems. Apigenin is effective in treating liver, lung, heart, kidney, neurological diseases, diabetes, and maintaining good oral and skin health. Multiple studies have reported that this compound is capable of suppressing various types of cancer through the induction of apoptosis and cell-cycle arrest, suppressing cell migration and invasion, reduction of inflammation, and inhibiting angiogenesis. When used in combination with other drugs, apigenin increases their efficacy, reduces the risk of side effects, and improves the response to chemotherapy. This review broadly analyzes apigenin's potential in disease management by modulating various biological activities. In addition, this review also described apigenin's interaction with other compounds or drugs and the potential role of nanoformulation in different pathogeneses. Further extensive research is needed to explore the mechanism of action, safety, and efficacy of this compound in disease prevention and treatment.