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Sodium glucose cotransporter 2 inhibitors (SGLT2is) are a newly developed class of anti-diabetics which exert potent hypoglycemic effects in the diabetic milieu. However, the evidence suggests that they also have extra-glycemic effects. The renin-angiotensin-aldosterone system (RAAS) is a hormonal system widely distributed in the body that is important for water and electrolyte homeostasis as well as renal and cardiovascular function. Therefore, modulating RAAS activity is a main goal in patients, notably diabetic patients, which are at higher risk of complications involving these organ systems. Some studies have suggested that SGLT2is have modulatory effects on RAAS activity in addition to their hypoglycemic effects and, thus, these drugs can be considered as promising therapeutic agents for renal and cardiovascular disorders. However, the exact molecular interactions between SGLT2 inhibition and RAAS activity are not clearly understood. Therefore, in the current study we surveyed the literature for possible molecular mechanisms by which SGLT2is modulate RAAS activity.
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Rapid and accurate identification of cardiovascular diseases (CVDs) are crucial for timely medical interventions and improved patient outcomes. Fibrinogen (Fib) has emerged as a valuable biomarker for CVDs, playing a significant role in their early detection. Elevated levels of Fib are associated with an increased risk of developing CVD, highlighting its importance for more precise diagnosis and effective treatment strategies. In recent years, significant advancements have been made in developing biosensor-based approaches for detecting Fib, offering high sensitivity and specificity. This review aims to explore the impact of Fib on cardiovascular conditions, assess the current advancements, and discuss the future potential of biosensors in Fib research for diagnosing cardiovascular disorders. Furthermore, we evaluate various biosensor techniques, including optical, electrochemical, electronic, and gravimetric methods, in terms of their utility for measuring Fib in clinical samples such as serum, plasma, whole blood, and other body fluids. A comparative analysis of these techniques is conducted based on their performance characteristics. By providing a comprehensive overview of the relationship between Fib and cardiovascular ailments, this review aims to clarify the advancements in biosensor technology for Fib detection. The comparison of different biosensor techniques will aid researchers and clinicians in selecting the most suitable approach for their specific diagnostic needs. Ultimately, integrating biosensors into clinical practice has the potential to revolutionize the detection and management of CVDs, leading to improved patient care and outcomes.
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Cancer is a leading cause of death worldwide, and imposes a substantial socioeconomic burden with little impact especially on aggressive types of cancer. Conventional therapies have many serious side effects including generalised systemic toxicity which limits their long-term use. Tumour resistance and recurrence is another main problem associated with conventional therapy. Purified or extracted natural products have been investigated as cost-effective cancer chemoprotective agents with the potential to reverse or delaying carcinogenesis. Curcumin (CUR) as a natural polyphenolic component, exhibits many pharmacological activities such as anti-cancer, anti-inflammatory, anti-microbial, activity against neurodegenerative diseases including Alzheimer, antidiabetic activities (type II diabetes), anticoagulant properties, wound healing effects in both preclinical and clinical studies. Despite these effective protective properties, CUR has several limitations, including poor aqueous solubility, low bioavailability, chemical instability, rapid metabolism and a short half-life time. To overcome the pharmaceutical problems associated with free CUR, novel nanomedicine strategies (including polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs have been developed. These formulations have the potential to improve the therapeutic efficacy of curcuminoids. In this review, we comprehensively summarise and discuss recent in vitro and in vivo studies to explore the pharmaceutical significance and clinical benefits of PLGA-NPs delivery system to improve the efficacy of CUR in the treatment of cancer.
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Conventional systemic cancer therapy often causes numerous adverse events. However, discovering overexpressed folate receptors in solid tumors has paved the way for targeted chemotherapy. Folic acid (FA), a ligand for these receptors, is frequently combined with chemotherapeutic drugs to improve their effectiveness. Carbon nanotubes have emerged as a versatile and promising method for delivering these folate-conjugated nano-systems, ensuring targeted delivery of therapeutic agents to cancerous cells. When FA-conjugated nanotubes dissociate, they release the drug-loaded nanotubes inside the malignant cells, reducing off-target effects. These nanotubes can also be used for combination therapies, producing synergistic effects. This review aims to comprehensively gather and critically evaluate the latest methods for delivering therapeutics using FA-conjugated nanovehicles. Additionally, it seeks to enhance our comprehension of the pertinent chemistry and biochemical pathways involved in this approach.
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Aim: To developed and investigate gallic acid (GA) loaded self-nanoemulsifying drug delivery systems (SNEDDS) for treating onychomycosis via transungual route. Materials & methods: The SNEDDS were prepared by direct dispersion technique and were evaluated for characteristics parameters using Fourier transform infrared, differential scanning calorimetry, confocal microscopy, transmission electron microscopy and zeta sizer. Furthermore, the safety of prepared formulation was evaluated via Hen's egg test-chorioallantoic membrane study and stability was confirmed using different parameters. Also, its effectiveness was evaluated against fungal strain Trichophyton mentagrophytes. Results: The SNEDDS displayed a particle size of 199.8 ± 4.21 nm and a zeta potential; of -22.75 ± 2.09 mV. Drug release study illustrated a sustained release pattern with a release of 70.34 ± 0.20% over a period of 24 h. The penetration across the nail plate was found to be 1.59 ± 0.002 µg/mg and 0.97 ± 0.001 µg/mg for GA loaded SNEDDS and GA solution respectively. An irritation score of 0.52 ± 0.005 and 3.84 ± 0.001 was reported for GA loaded SNEDDS hydrogel and GA solution, indicating a decrease in the drug's irritation potential from slightly irritating to non irritating due to its entrapment within the SNEDDS. Conclusion: GA loaded SNEDDS has potential to address limitations of conventional treatments, enhancing the drug's efficacy and reducing the likelihood of resistance in the treatment of Onychomycosis.
[Box: see text].
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A better understanding of incidences at the cellular level in uterine cancer is necessary for its effective treatment and favourable prognosis. Till date, it lacks appropriate molecular target-based treatment because of unknown molecular mechanisms that proceed to cancer and no drug has shown the required results of treatment with less severe side effects. Uterine Cancer is one of the top five cancer diagnoses and among the ten most common death-causing cancer in the United States of America. There is no FDA-approved drug for it yet. Therefore, it became necessary to identify the molecular targets for molecular targeted therapy of this widely prevalent cancer type. For this study, we used a network-based approach to the list of the deregulated (both up and down-regulated) genes taking adjacent p-Value ≤ 0.05 as significance cut off for the mRNA data of uterine cancer. We constructed the protein-protein interaction (PPI) network and analyzed the degree, closeness, and betweenness centrality-like topological properties of the PPI network. Then we traced the top 30 genes listed from each topological property to find the key regulators involved in the endometrial cancer (ECa) network. We then detected the communities and sub-communities from the PPI network using the Cytoscape network analyzer and Louvain modularity optimization method. A set of 26 (TOP2A, CENPE, RAD51, BUB1, BUB1B, KIF2C, KIF23, KIF11, KIF20A, ASPM, AURKA, AURKB, PLK1, CDC20, CDKN2A, EZH2, CCNA2, CCNB1, CDK1, FGF2, PRKCA, PGR, CAMK2A, HPGDS, and CDCA8) genes were found to be key genes of ECa regulatory network altered in disease state and might be playing the regulatory role in complex ECa network. Our study suggests that among these genes, KIF11 and H PGDS appeared to be novel key genes identified in our research. We also identified these key genes interactions with miRNAs.
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Biomarcadores Tumorais , Mapas de Interação de Proteínas , Neoplasias Uterinas , Humanos , Feminino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Neoplasias Uterinas/metabolismo , Redes Reguladoras de Genes , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica/métodos , CinesinasRESUMO
This comprehensive review elucidates the critical role of antioxidants to mitigate oxidative stress, a common denominator in an array of neurodegenerative disorders. Oxidative stress-induced damage has been linked to the development of diseases such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. This article examines a wide range of scientific literature and methodically delineates the several methods by which antioxidants exercise their neuroprotective benefits. It also explores into the complex relationship between oxidative stress and neuroinflammation, focusing on how antioxidants can alter signaling pathways and transcription factors to slow neurodegenerative processes. Key antioxidants, such as vitamins C and E, glutathione, and polyphenolic compounds, are tested for their ability to combat reactive oxygen and nitrogen species. The dual character of antioxidants, which operate as both direct free radical scavengers and regulators of cellular redox homeostasis, is investigated in terms of therapeutic potential. Furthermore, the study focuses on new antioxidant-based therapy techniques and their mechanisms including Nrf-2, PCG1α, Thioredoxin etc., which range from dietary interventions to targeted antioxidant molecules. Insights into ongoing clinical studies evaluating antioxidant therapies in neurodegenerative illnesses offer an insight into the translational potential of antioxidant research. Finally, this review summarizes our present understanding of antioxidant processes in neurodegenerative illnesses, providing important possibilities for future study and treatment development.
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Nanoparticles (NPs) that target multiple transport mechanisms facilitate targeted delivery of active therapeutic agents to the central nervous system (CNS) and improve therapeutic transport and efficacy across the blood-brain barrier (BBB). CNS nanotherapeutics mostly target neurons and endothelial cells, however, microglial immune cells are the first line of defense against neuronal damage and brain infections. Through triggering release of inflammatory cytokines, chemokines and proteases, microglia can however precipitate neurological damage-a significant factor in neurodegenerative diseases. Thus, microglial inhibitory agents are attracting much attention among those researching and developing novel treatments for neurodegenerative disorders. The most established inhibitors of microglia investigated to date are resveratrol, curcumin, quercetin, and minocycline. Thus, there is great interest in developing novel agents that can bypass or easily cross the BBB. One such approach is the use of modified-nanocarriers as, or for, delivery of, therapeutic agents to the brain and wider CNS. For microglial inhibition, polymeric NPs are the preferred vehicles for choice. Here, we summarize the immunologic and neuroinflammatory role of microglia, established microglia inhibitor agents, challenges of CNS drug delivery, and the nanotherapeutics explored for microglia inhibition to date. We also discuss applications of the currently considered "most useful" polymeric NPs for microglial-inhibitor drug delivery in CNS-related diseases.
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Aggregation-induced emission (AIE) is a unique phenomenon observed in various materials such as organic luminophores, carbon dots (CDs), organic-inorganic nanocomposites, fluorescent dye molecules, and nanoparticles (NPs). These AIE-active materials, or AIEgens, are ideal for balancing multifunctional phototheranostics and energy dissipation. AIE properties can manifest in organic fluorescent probes, rendering them effective for cancer treatment due to their ability to penetrate deeply and provide high therapeutic efficacy. This efficacy is attributed to their high photobleaching thresholds, ability to induce Stokes shifts, and capacity to activate fluorophores. Therefore, the development of innovative AIE-based materials for disease diagnosis and treatment, particularly for cancer, is both important and promising. Recent years have seen successful demonstrations of nanoparticles with AIE properties being used for photodynamic therapy (PDT) and multimodal imaging of tumor cells. These fluorophores have been shown to impact mitochondria and lysosomes, generate reactive oxygen species (ROS), activate the immune system, load and release drugs, and ultimately induce apoptosis in tumor cells. In this review, we examine previous studies on the manufacturing methods and effects of AIEgens on cancer cells, with a theranostic strategy of simultaneous treatment and imaging. We also investigate the factors affecting drug delivery on different cancer cells, including internal stimuli such as pH, ROS, enzymes, and external stimuli like near-infrared (NIR) light and ultrasound waves.
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The prognostic value of microRNA-140-5p (miR-140-5p) expression in cancer patients has been investigated, but with inconsistent results. This meta-analysis aims to determine the prognostic significance of miR-140-5p expression in patients with various malignancies. A comprehensive literature search was conducted using PubMed, Web of Science, ProQuest, Cochrane, and Google Scholar to identify relevant studies published before June 2023. Pooled hazard ratios (HR) and odds ratios (OR) with 95â¯% confidence intervals (CI) were calculated to assess the prognostic importance and clinicopathological features of miR-140-5p in overall survival (OS) and disease-free survival (DFS) of cancer patients, respectively. The CancerMIRNome database and other OS analysis webservers were utilized to explore the prognostic value and expression profile of miR-140-5p. A total of 17 studies were included in the final analysis. The results demonstrated that decreased miR-140-5p expression was significantly associated with inferior OS (pooled HR 0.63; 95â¯% CI, 0.51-0.79; p < 0.001) and DFS (pooled HR 0.40; 95â¯% CI, 0.25-0.64; p < 0.001). Pooled ORs indicated a significant correlation between reduced miR-140-5p expression and positive lymph node metastasis (LNM; OR = 3.42; 95â¯% CI, 2.36-4.94; p < 0.001), advanced tumor stage (OR = 2.80; 95â¯% CI, 2.07-3.78; p < 0.001), and positive distant metastasis (DM; OR = 10.81; 95â¯% CI, 3.31-35.30; p < 0.001). No significant associations were observed between miR-140-5p expression and gender (OR = 0.94; 95â¯% CI, 0.70-1.28; p = 0.70), age (OR = 1.31; 95â¯% CI, 0.99-1.74; p = 0.06), tumor size (OR = 1.55; 95â¯% CI, 0.77-3.10; p = 0.22), and histological grade (OR = 1.20; 95â¯% CI, 0.46-3.10; p = 0.71). Subgroup analyses revealed that decreased miR-140-5p expression was associated with shorter OS in subgroups based on sample size (<100 or >100), tumor origin (GI or non-GI), and cancer type (GC/CRC). Bioinformatic analysis supported the finding that miR-140-5p was downregulated in most tumor tissues, and its reduced expression was linked to poor prognosis in patients with multiple malignancies. The prognostic significance of miR-140-5p in predicting reduced OS and DFS suggests that measuring miR-140-5p expression levels before treatment could serve as a valuable biomarker for identifying cancer patients with an unfavorable prognosis and improving clinical management.
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Biomarcadores Tumorais , Biologia Computacional , MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , Neoplasias/patologia , Neoplasias/genética , Neoplasias/mortalidade , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Regulação Neoplásica da Expressão Gênica , Intervalo Livre de DoençaRESUMO
BACKGROUND: Colon Cancer (CC) incidence has sharply grown in recent years. Long non-coding RNAs (lncRNA) are produced by a group of non-protein-coding genes, and have important functions in controlling gene expression and impacting the biological features of various malignancies including CC. METHODS: Our research focused on examining the function of lncRNAs in the development of colon cancer. To this end, we selected and analyzed a dataset (GSE104836) from the GEO database, which contained information about the expression of mRNAs and lncRNAs in both colon cancer tissues and normal adjacent paired tumor tissues. The DESeq2 R package in Bioconductor was used to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) that showed differences in expression levels. Next, by literature review of previous studies, we chose two lncRNAs (FENDRR and LINC00092) for additional studies. To validate our findings, a series of tests were performed on a total of 31 tumor tissues and normal paired adjacent tumor tissues. The lncRNA expression levels were assessed in tumor tissues as well as in surrounding normal tumor tissues. RESULTS: The data confirmed that just two particular lncRNAs, FENDRR and LINC00092, had considerably decreased expression levels throughout all stages of cancer. In addition, the survival assay was conducted using the GEPIA2 software, revealing that a reduced expression of FENDRR is correlated with a reduced overall survival. Furthermore, our investigation using receiver operating characteristic (ROC) methodology revealed that these two lncRNAs had significant discriminatory ability between colon cancer and normal tissues. To determine the cause of the decrease in the activity of these two long non-coding RNAs (lncRNAs), we used methylation-specific PCR (MSP) to examine the methylation pattern of their promoter regions. Our investigation revealed hypermethylation in the promoter regions of FENDRR and LINC00092 within tumor tissues compared to normal adjacent tumor tissues. CONCLUSION: Taken together, our findings revealed the lncRNAs signatures as potential therapeutic targets and molecular diagnostic biomarkers in colon cancer. Furthermore, the evidence provided substantiates the important role of promoter methylation in regulating the expression levels for both of these lncRNAs.
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Biomarcadores Tumorais , Neoplasias do Colo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Biomarcadores Tumorais/genética , TranscriptomaRESUMO
Cancer is recognized as one of the leading causes of death worldwide. In recent years, advancements in early detection and expanding treatment options have contributed to a decrease in mortality rates. However, the emergence of drug-resistant cancers necessitates the exploration of innovative and more effective drugs. The Akt kinases play a central role in various signaling pathways that regulate crucial cellular processes, including cell growth, proliferation, survival, angiogenesis, and glucose metabolism. Due to frequent disruptions of the Akt signaling pathway in numerous human cancers and its broad biological implications, targeting this pathway has become a key focus in combating tumor aggressiveness and a promising avenue for therapeutic intervention. Curcumin, a compound found in turmeric, has been extensively studied for its potential as an anti-cancer agent. It demonstrates inhibitory effects on cancer initiation, progression, and metastasis by influencing various processes involved in tumor growth and development. These effects are achieved through negative regulation of transcription factors, growth factors, cytokines, protein kinases, and other oncogenic molecules. This review aims to explore curcumin's anticancer activity against different types of cancer mediated via the PI3K/Akt signaling pathway, as well as its practical applications in treatment.
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Curcumina , Neoplasias , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Curcumina/uso terapêutico , Curcumina/farmacologia , Humanos , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , AnimaisRESUMO
Cancer is ranked among the top causes of mortality throughout the world. Conventional therapies are associated with toxicity and undesirable side effects, rendering them unsuitable for prolonged use. Additionally, there is a high occurrence of resistance to anticancer drugs and recurrence in certain circumstances. Hence, it is essential to discover potent anticancer drugs that exhibit specificity and minimal unwanted effects. Curcumin, a polyphenol derivative, is present in the turmeric plant (Curcuma longa L.) and has chemopreventive, anticancer, radio-, and chemo-sensitizing activities. Curcumin exerts its anti-tumor effects on cancer cells by modulating the disrupted cell cycle through p53-dependent, p53-independent, and cyclin-dependent mechanisms. This review provides a summary of the formulations of curcumin based on nanospheres, since there is increasing interest in its medicinal usage for treating malignancies and tumors. Nanospheres are composed of a dense polymeric matrix, and have a size ranging from 10 to 200 nm. Lactic acid polymers, glycolic acid polymers, or mixtures of them, together with poly (methyl methacrylate), are primarily used as matrices in nanospheres. Nanospheres are suitable for local, oral, and systemic delivery due to their minuscule particle size. The majority of nanospheres are created using polymers that are both biocompatible and biodegradable. Previous investigations have shown that the use of a nanosphere delivery method can enhance tumor targeting, therapeutic efficacy, and biocompatibility of different anticancer agents. Moreover, these nanospheres can be easily taken up by mammalian cells. This review discusses the many curcumin nanosphere formulations used in cancer treatment.
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Camptothecin, a natural alkaloid, was first isolated from the bark and stem of the Camptotheca acuminate tree in China. It, along with its analogs, has demonstrated potent anti-cancer activity in preclinical studies, particularly against solid tumors such as lung, breast, ovarian, and colon cancer. Despite its promising anti-cancer activity, the application of camptothecin is limited due to its poor solubility, toxicity, and limited biodistribution. Nanotechnology-based drug delivery systems have been used to overcome limited bioavailability and ensure greater biodistribution after administration. Additionally, various drug delivery systems, particularly polymeric micelles, have been investigated to enhance the solubility, stability, and efficacy of camptothecin. Polymeric micelles offer a promising approach for the delivery of camptothecin. Polymeric micelles possess a core-shell structure, with a typical hydrophobic core, which exhibits a high capacity to incorporate hydrophobic drugs. The structure of polymeric micelles can be engineered to have a high drug loading capacity, thereby enabling them to carry a large amount of hydrophobic drug within their core. The shell portion of polymeric micelles is composed of hydrophilic polymers Furthermore, the hydrophilic segment of polymeric micelles plays an important role in protecting against the reticuloendothelial system (RES). This review provides a discussion on recent research and developments in the delivery of camptothecin using polymeric micelles for the treatment of cancers.
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Antineoplásicos Fitogênicos , Camptotecina , Sistemas de Liberação de Medicamentos , Micelas , Polímeros , Camptotecina/administração & dosagem , Camptotecina/química , Camptotecina/análogos & derivados , Camptotecina/farmacocinética , Camptotecina/farmacologia , Humanos , Polímeros/química , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Portadores de Fármacos/química , Solubilidade , Distribuição Tecidual , Interações Hidrofóbicas e HidrofílicasRESUMO
The application of gold nanoparticles (AuNPs) in cancer therapy, particularly targeted therapy of glioblastoma multiforme (GBM), is an up-and-coming field of research that has gained much interest in recent years. GBM is a life-threatening malignant tumour of the brain that currently has a 95 % death rate with an average of 15 months of survival. AuNPs have proven to have wide clinical implications and compelling therapeutic potential in many researches, specifically in GBM treatment. It was found that the reason why AuNPs were highly desired for GBM treatment was due to their unique properties that diversified the applications of AuNPs further to include imaging, diagnosis, and photothermal therapy. These properties include easy synthesis, biocompatibility, and surface functionalization. Various studies also underscored the ability of AuNPs to cross the blood-brain-barrier and selectively target tumour cells while displaying no major safety concerns which resulted in better therapy results. We attempt to bring together some of these studies in this review and provide a comprehensive overview of safety evaluations and current and potential applications of AuNPs in GBM therapy that may result in AuNP-mediated therapy to be the new gold standard for GBM treatment.
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Neoplasias Encefálicas , Glioblastoma , Ouro , Nanopartículas Metálicas , Glioblastoma/tratamento farmacológico , Glioblastoma/terapia , Ouro/química , Ouro/administração & dosagem , Humanos , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacosRESUMO
Curcumin, as an anti-tumor agent, is not widely used in cancer treatment due to the lack of effective levels of its metabolites in cancerous tissue. Addressing the barriers to the carrier and delivery of drugs to the specific sites of therapeutic action while reducing side effects is a priority. Folate receptor expression is high in malignant and low in normal cells. Folate as a targeted ligand could selectively target cancer cells. Thus, this narrative review aimed to provide an overview of the studies that have investigated the different types of folate-modified curcumin as a carrier and deliverer and their structural properties that enhance therapeutic drug efficacy. A literature search was performed using PubMed, Scopus, Web of Science, and Google Scholar databases. Thirty-eight preclinical studies addressing this topic were identified. The findings of the current review have shown that folate-modified nanoparticles containing curcumin as a promising therapeutic approach can be effective in improving different types of cancers. In vitro studies have shown a higher cellular uptake and cytotoxicity effect, higher cell inhibition, and anti-proliferation with a lower dosage of curcumin. In vivo studies have shown more tumor suppression and smaller tumor volume without toxicity after the administration of folate-modified nanoparticles containing curcumin. Future clinical trials are needed to confirm the beneficial effect of folate-modified curcumin as a new drug delivery platform for cancer treatment.
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Liposomes are nanosized, spherical vesicles consisting of an aqueous core encircled by one or more phospholipid bilayer shells. Liposomes have found extensive use in numerous biomedicine and nanomedicine applications due to their excellent biocompatibility, adaptable chemical composition, ease of preparation, and diverse structural characteristics. These applications include nanocarriers for drug delivery, immunoassays, nutraceuticals, tissue engineering, clinical diagnostics, and theranostics formulations. These applications stimulated significant efforts toward scaling up formation processes in anticipation of appropriate industrial advancement. Despite the advancements in conventional methods and the emergence of new approaches for liposome production, their inherent susceptibility to chemical and mechanical influences contributes to critical challenges, including limited colloidal stability and decreased efficiency in encapsulating cargo molecules. With this context, the current review provides brief insights into liposomes conventional and novel industrial production techniques. With a special focus on the structural parameters, and pivotal elements influencing the synthesis of an appropriate and stable formulation, followed by the various regulatory aspects of industrial production.
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Lipossomos , Humanos , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Química Farmacêutica/métodos , Indústria Farmacêutica/métodos , AnimaisRESUMO
Statins, which are primarily used as lipid-lowering drugs, have been found to exhibit anti-tumor effects through modulating and interfering with various signaling pathways. In observational studies, statin use has been associated with a significant reduction in the progression of various cancers, including colon, lung, prostate, pancreas, and esophagus cancer, as well as melanoma and B and T cell lymphoma. The mevalonate pathway, which is affected by statins, plays a crucial role in activating Rho, Ras, and Rab proteins, thereby impacting the proliferation and apoptosis of tumor cells. Statins block this pathway, leading to the inhibition of isoprenoid units, which are critical for the activation of these key proteins, thereby affecting cancer cell behavior. Additionally, statins affect MAPK and Cdk2, which in turn reduce the expression of p21 and p27 cyclin-dependent kinase inhibitors. Akt signaling plays a crucial role in key cancer cell features like proliferation, invasion, and apoptosis by activating multiple effectors in downstream pathways such as FOXO, PTEN, NF-κB, GSK3ß, and mTOR. The PI3K/Akt signaling is necessary for many events in the metastatic pathway and has been implicated in the resistance to cytostatic drugs. The Akt/PTEN axis is currently attracting great interest for its role in carcinogenesis. Statins have been shown to activate the purinergic receptor P2X7 and affect Akt signaling, which may have important anti-cancer effects. Hence, targeting Akt shows promise as an effective approach to cancer prevention and therapy. This review aims to provide a comprehensive discussion on the specific impact of statins through Akt signaling in different types of cancer.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Humanos , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Neoplasias/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , AnimaisRESUMO
Brain cancers, particularly glioblastoma multiforme (GBM), are challenging health issues with frequent unmet aspects. Today, discovering safe and effective therapeutic modalities for brain tumors is among the top research interests. Immunotherapy is an emerging area of investigation in cancer treatment. Since immune checkpoints play fundamental roles in repressing anti-cancer immunity, diverse immune checkpoint inhibitors (ICIs) have been developed, and some monoclonal antibodies have been approved clinically for particular cancers; nevertheless, there are significant concerns regarding their efficacy and safety in brain tumors. Among the various tools to modify the immune checkpoints, phytochemicals show good effectiveness and excellent safety, making them suitable candidates for developing better ICIs. Phytochemicals regulate multiple immunological checkpoint-related signaling pathways in cancer biology; however, their efficacy for clinical cancer immunotherapy remains to be established. Here, we discussed the involvement of immune checkpoints in cancer pathology and summarized recent advancements in applying phytochemicals in modulating immune checkpoints in brain tumors to highlight the state-of-the-art and give constructive prospects for future research.