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The utilization of nanoformulations derived from natural products for the treatment of many human diseases, including cancer, is a rapidly developing field. Conventional therapies used for cancer treatment have limited efficacy and a greater number of adverse effects. Hence, it is imperative to develop innovative anticancer drugs with superior effectiveness. Among the diverse array of natural anticancer compounds, resveratrol, curcumin, and epigallocatechin gallate (EGCG) have gained considerable attention in recent years. Despite their strong anticancer properties, medicinally significant phytochemicals such as resveratrol, curcumin, and EGCG have certain disadvantages, such as limited solubility in water, stability, and bioavailability problems. Encapsulating these phytochemicals in poly(lactic-co-glycolic acid) (PLGA), a polymer that is nontoxic, biodegradable, and biocompatible, is an effective method for delivering medication to the tumor location. In addition, PLGA nanoparticles can be modified with targeting molecules to specifically target cancer cells, thereby improving the effectiveness of phytochemicals in fighting tumors. Combining plant-based medicine (phytotherapy) with nanotechnology in a clinical environment has the potential to enhance the effectiveness of drugs and improve the overall health outcomes of patients. Therefore, it is crucial to have a comprehensive understanding of the different aspects and recent advancements in using PLGA-based nanocarriers for delivering anticancer phytochemicals. This review addresses the most recent advancements in PLGA-based delivery systems for resveratrol, EGCG, and curcumin, emphasizing the possibility of resolving issues related to the therapeutic efficacy and bioavailability of these compounds.
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Resveratrol, a potent anticancer bioactive compound, has been shown to trigger apoptosis in numerous cancer cells. Although Notch signaling promotes breast cancer apoptosis, it is unclear whether resveratrol induces apoptosis in MCF-7 cells via influencing the Notch pathway. This study aimed to evaluate the effect of resveratrol on modulating Notch signaling targets and provide critical information for employing resveratrol in breast cancer therapy. Thus, in this study, we have deciphered the effect of resveratrol against three potent genes (Notch1, Jagged1, and DLL4) of the notch signaling pathway. For mechanistic studies, in silico, and in vitro analysis was executed to investigate the apoptotic-inducing potential of resveratrol against three selected oncogenes involved in the progression of breast cancer. Docking analysis revealed the inhibitory potential of resveratrol against all three selected targets of the Notch pathway (Notch1: -5.0; Jagged-1: -5.9; DLL4: -5.8). In vitro, findings further displayed a significant reduction in cell viability in resveratrol-treated MCF-7 cancer cells, which were concomitantly related to the downregulation of Notch-1, Jagged-1, and DLL4. Moreover, the antiproliferative efficacy of resveratrol was correlated with apoptosis and modulation in the expression of Bax, Bcl-2, cyclin D1, CDK4, p21, and caspase-3 activation. Taken together, these experimental findings suggested that apoptotic inducing potential of resveratrol was mediated through a novel mechanism involving suppression of the Notch signaling pathway.
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Apoptose , Neoplasias da Mama , Proteína Jagged-1 , Resveratrol , Transdução de Sinais , Humanos , Resveratrol/farmacologia , Apoptose/efeitos dos fármacos , Células MCF-7 , Transdução de Sinais/efeitos dos fármacos , Proteína Jagged-1/metabolismo , Proteína Jagged-1/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Receptor Notch1/metabolismo , Receptor Notch1/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Estilbenos/farmacologia , Receptores Notch/metabolismo , Receptores Notch/genética , Simulação de Acoplamento Molecular , Sobrevivência Celular/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 3/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genéticaRESUMO
Copper is a vital trace element in oxidized and reduced forms. It plays crucial roles in numerous biological events such as redox chemistry, enzymatic reactions, mitochondrial respiration, iron metabolism, autophagy, and immune modulation. Maintaining the balance of copper in the body is essential because its deficiency and excess can be harmful. Abnormal copper metabolism has a two-fold impact on the development of tumors and cancer treatment. Cuproptosis is a form of cell death that occurs when there is excessive copper in the body, leading to proteotoxic stress and the activation of a specific pathway in the mitochondria. Research has been conducted on the advantageous role of copper ionophores and chelators in cancer management. This review presents recent progress in understanding copper metabolism, cuproptosis, and the molecular mechanisms involved in using copper for targeted therapy in cervical cancer. Integrating trace metals and minerals into nanoparticulate systems is a promising approach for controlling invasive tumors. Therefore, we have also included a concise overview of copper nanoformulations targeting cervical cancer cells. This review offers comprehensive insights into the correlation between cuproptosis-related genes and immune infiltration, as well as the prognosis of cervical cancer. These findings can be valuable for developing advanced clinical tools to enhance the detection and treatment of cervical cancer.
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Cobre , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/tratamento farmacológico , Cobre/metabolismo , Feminino , AnimaisRESUMO
Cancer is characterized by persistent cell proliferation driven by aberrant cell cycle regulation and stimulation of cyclin-dependent kinases (CDKs). A very intriguing and potential approach for the development of antitumor medicines is the suppression of CDKs that lead to induction of apoptosis and cell cycle arrest. The shift of the cell cycle from the G0/G1 phase to the S phase, which is characterized by active transcription and synthesis, depends on the development of the cyclin D-CDK4/6 complex. A precise balance between anticancer activity and general toxicity is demonstrated by CDK inhibitors, which can specifically block CDK4/6 and control the cell cycle by reducing the G1 to S phase transition. CDK4/6 inhibitors have recently been reported to exhibit significant cell growth inhibition via modulating the tumour microenvironment in cancerous cells. One significant new understanding is that these inhibitors serve important functions in the interaction among tumour cells and the host immune system in addition to being cytostatic. Herein, we discuss the biological significance of CDK4/6 inhibitors in cancer therapeutics, as well as their biological impact on T cells and other important immune cells. Furthermore, we explore the integration of preclinical findings of these pharmaceuticals' ability to enhance antitumor immunity.
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Neoplasias , Microambiente Tumoral , Humanos , Ciclo Celular/fisiologia , Quinase 2 Dependente de Ciclina , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/imunologia , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Microambiente Tumoral/imunologiaRESUMO
Immune checkpoint inhibitors have ushered in a new era of cancer treatment by increasing the likelihood of long-term survival for patients with metastatic disease and by introducing fresh therapeutic indications in cases where the disease is still in its early stages. Immune checkpoint inhibitors that target the proteins cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) or programmed death-1/programmed death ligand-1 have significantly improved overall survival in patients with certain cancers and are expected to help patients achieve complete long-lasting remissions and cures. Some patients who receive immune checkpoint inhibitors, however, either experience therapeutic failure or eventually develop immunotherapy resistance. Such individuals are common, which necessitates a deeper understanding of how cancer progresses, particularly with regard to nutritional regulation in the tumor microenvironment (TME), which comprises metabolic cross-talk between metabolites and tumor cells as well as intracellular metabolism in immune and cancer cells. Combination of immunotherapy with targeted metabolic regulation might be a focus of future cancer research despite a lack of existing clinical evidence. Here, we reviewed the significance of the tumor microenvironment and discussed the most significant immunological checkpoints that have recently been identified. In addition, metabolic regulation of tumor immunity and immunological checkpoints in the TME, including glycolysis, amino acid metabolism, lipid metabolism, and other metabolic pathways were also incorporated to discuss the possible metabolism-based treatment methods being researched in preclinical and clinical settings. This review will contribute to the identification of a relationship or crosstalk between tumor metabolism and immunotherapy, which will shed significant light on cancer treatment and cancer research.
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Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias/metabolismo , Imunoterapia , Microambiente TumoralRESUMO
Herbal medications or formulations are regularly recommended by clinicians as a potential therapeutic method for a variety of human ailments, including cancer. Although Prosopis juliflora extracts have shown promise in anticancer activity, the effects on prostate cancer and the accompanying molecular mechanisms of action are still unexplored. This research aims at the antioxidant, antiproliferative, and apoptosis-inducing properties of Prosopis juliflora methanolic leaves extract in human prostate cancer LNCaP cells. The antioxidant ability of the extract was assessed using the DPPH (2, 2-diphenyl-2-picrylhydrazyl) and two additional reducing power tests. Antitumor activity was determined using MTT cell viability tests and LDH cytotoxicity assays. The probable mechanism of apoptotic cell death was further investigated utilizing a caspase-3 activation assay and qRT-PCR mRNA expression investigations of apoptotic-related genes. The results revealed that the methanol extract of Prosopis juliflora leaves contains alkaloids, flavonoids, tannins, glycosides, and phenols, all of which have substantial antioxidant activity. In vitro anticancer tests demonstrated that extract therapy resulted in a dose-dependent reduction in cell viability of LNCaP prostate cancer cells, but normal HaCaT cells showed no cytotoxic effects. Furthermore, plant extract therapy increased caspase-3 activation and mRNA expression of apoptotic-related genes, suggesting that this could be a mechanism for cancer cell growth suppression. The significance of Prosopis juliflora as a source of new antioxidant compounds against prostate cancer was emphasized in the current study. However, more study is needed to demonstrate the efficacy of Prosopis juliflora leaves extract in the treatment of prostate cancer.
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Prosopis , Neoplasias da Próstata , Masculino , Humanos , Antioxidantes/química , Prosopis/química , Caspase 3/genética , Caspase 3/análise , Extratos Vegetais/química , Neoplasias da Próstata/tratamento farmacológico , Folhas de Planta/química , RNA MensageiroRESUMO
PKP1 has been crucially involved in enhancing the MYC translation leading to lung carcinogenesis via evading numerous tumour-suppressing checkpoint systems. Plakophilin 1(PKP1) is the part of armadillo and plakophilin gene families and it is a necessary component of desmosomes. Several researches reported PKP1 protein as one of the most overexpressed proteins in human lung cancer. Therefore, we have designed our research towards elucidating better plant-based compounds as drug candidates for the management of lung cancer with minimal adverse effects over other chemotherapeutic drugs such as afatinib. This study comprises forty-six flavonoids for targeting PKP1 using in silico approaches that were not used earlier as an anti-cancerous agent targeting PKP1 in lung cancer treatment. Flavonoids are plant-derived natural compounds that exhibited enormous anti-cancerous potential against several human cancers. NPACT database was used to screen potent flavonoids that have not been used to target the PKP1 protein in lung cancer. Patch Dock and CB Dock were employed to elucidate the PKP1 (1XM9) inhibitory potential of selected flavonoids. Analysis with both the docking tools has revealed that calyxins I showed maximum affinity in comparison to the standard drug, afatinib. Further PASS and BAS analyses were performed using SWISS ADME and molinspiration to investigate the pharmacokinetic profiling of potent flavonoids having significant binding energy. Visualization of complexes was done by using UCSF chimera. However, further detailed in vitro studies are needed to validate the candidature of calyxinsI for being developed as an anticancer drug for the management of lung cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Afatinib , Neoplasias Pulmonares/tratamento farmacológico , Proteínas/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Placofilinas/genética , Placofilinas/metabolismoRESUMO
Cancer remains one of the most crucial human malignancies with a higher mortality rate globally, and is predicted to escalate soon. Dysregulated ion homeostasis in cancerous cells prompted the researchers to investigate further ion homeostasis impeding agents as potent anticancerous agents. Reutilization of FDA-approved non-cancerous drugs has emerged as a practical approach to developing potent, cost-effective drugs for cancer treatment. Across the globe, most nations are incapable of fulfilling the medical demands of cancer patients due to costlier cancerous drugs. Therefore, we have inclined our review towards emphasizing recent advancements in cancer therapies involving ionophores utilization in exploring potent anticancer drugs. Numerous research reports have established the significant anticancerous potential of ionophores in several pre-clinical reports via modulating aberrant cell signaling pathways and enhancing antitumor immunity in immune cells. This review has mainly summarized the most significant ion homeostasis impeding agents, including copper, zinc, calcium, and polyether, that presented remarkable potential in cancer therapeutics via enhanced antitumor immunity and apoptosis induction. Altogether, this study could provide a robust future perspective for developing cost-effective anticancerous drugs rapidly and cost-effectively, thereby combating the limitations of currently available drugs used in cancer treatment.
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Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cobre/metabolismo , Humanos , Ionóforos/farmacologia , Ionóforos/uso terapêutico , Neoplasias/metabolismoRESUMO
Worldwide, since ages and nowadays, traditional medicine is well known, owing to its biodiversity, which immensely contributed to the advancement and development of complementary and alternative medicines. There is a wide range of spices, herbs, and trees known for their medicinal uses. Chilli peppers, a vegetable cum spice crop, are bestowed with natural bioactive compounds, flavonoids, capsaicinoids, phytochemicals, phytonutrients, and pharmacologically active compounds with potential health benefits. Such compounds manifest their functionality over solo-treatment by operating in synergy and consortium. Co-action of these compounds and nutrients make them potentially effective against coagulation, obesity, diabetes, inflammation, dreadful diseases, such as cancer, and microbial diseases, alongside having good anti-oxidants with scavenging ability to free radicals and oxygen. In recent times, capsaicinoids especially capsaicin can ameliorate important viral diseases, such as SARS-CoV-2. In addition, capsaicin provides an ability to chilli peppers to ramify as topical agents in pain-relief and also benefitting man as a potential effective anesthetic agent. Such phytochemicals involved not only make them useful and a much economical substitute to wonder/artificial drugs but can be exploited as obscene drugs for the production of novel stuffs. The responsibility of the TRPV1 receptor in association with capsaicin in mitigating chronic diseases has also been justified in this study. Nonetheless, medicinal studies pertaining to consumption of chilli peppers are limited and demand confirmation of the findings from animal studies. In this artifact, an effort has been made to address in an accessible format the nutritional and biomedical perspectives of chilli pepper, which could precisely upgrade and enrich our pharmaceutical industries towards human well-being.
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Tratamento Farmacológico da COVID-19 , Capsicum , Animais , Antioxidantes/farmacologia , Capsaicina/farmacologia , Capsicum/química , Flavonoides , Humanos , Oxigênio , SARS-CoV-2RESUMO
Modern research propounded that alteration in signaling pathways have shown strong connection with the progression of cervical cancer and modulation of these pathways by natural compounds could be a better treatment approach for the management of cervical cancer. Additionally, inhibitory role of methanolic extract of Moringa oleifera leaves against Jab1 has not been elucidated yet. Therefore, we have elucidated the inhibitory potential of MMLE against Jab1 in cervical cancer by analyzing several In Vitro assays. The MMLE treatment in cervical cancer cells showed decreased cell growth in a dose and time dependent manner. Furthermore, MMLE treated cervical cells have also depicted enhanced nuclear condensation (apoptotic induction potential) confirmed by Hoechst analysis. RT-PCR results clearly illustrated the inhibitory potential of MMLE against Jab1 via down regulating its expression. Conversely, a significant increase in p27 expression was also reported which could explain the cells growth arrest at G0/G1 phase. Additionally, enhanced ROS production and caspase-3 activation explains one of the possible mechanisms behind the inhibitory potential of MMLE against Jab1 in cervical cancer cells (HeLa). Thus our experimental findings may pave a potent phyto compound for targeting a crucial signalosome (Jab1) in cervical cancer.
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Moringa oleifera , Neoplasias do Colo do Útero , Apoptose , Humanos , Metanol/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Neoplasias do Colo do Útero/tratamento farmacológicoRESUMO
AIM OF THE STUDY: Glioblastoma multiforme (GBM) is the most severe forms of brain cancer, eventually becoming the leading cause of brain cancer-related death worldwide. Owing to the bleak surgical interventions and resistance to the different treatment regime, GBM is a parlous disease demanding newer therapeutical perspective for its treatment. Toll-like receptors (TLRs) are well-known members of pathogen recognition receptors (PRRs) and have been extensively explored for their therapeutic and prophylactic potential in an array of disease including cancer. Recent trends in drug delivery research has shown shift towards delivering short DNA sequences (CpG DNA) to endosomal TLR9 within immune cells (macrophages, dendritic cells, etc.) for the activation of desired inflammatory response using non-agonistic ß-glucan particles; a well-known ligand for Dectin-1 receptors. Our study is therefore focused to explore the role of nano-encapsulated CpG ODN as critical players in polarizing M2 scavenging to much desired pro-inflammatory type. MATERIALS AND METHODS: The nanoparticles entrapping CpG ODN 1826 were prepared by using a fungal polymer Schizophyllan (SPG). The constructed nanoparticles were characterized and assessed for their efficacy on rat glioblastoma cells (C6). RESULTS: The constructed Schizophyllan (SPG) nanoparticles entrapping CpG ODN 1826 (95.3%) were of 25.49 nm in diameter and thus capable of crossing blood-brain barrier. The rat glioblastoma (C6) cells evaluated for intracellular oxidative burst and cytokine levels pre- and post-incubation with nanoparticles exhibited marked elevation in the expression of intracellular ROS and IFN-γ as well as IL-1ß post treatment. CONCLUSION: The findings indicate towards potentiality of repolarizing the M2 macrophages to much desired M1 phase by inducing higgh levels of oxidative burst and inflammatory cytokines. Consequently, the apoptosis was induced in glioblastoma cells establishing the suitablity of CpG ODN carrying nanoformulations as emerging therapeutic intervention for GBM.
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Adjuvantes Imunológicos , Neoplasias Encefálicas/tratamento farmacológico , Citocinas/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Lectinas Tipo C , Macrófagos/efeitos dos fármacos , Nanopartículas , Oligodesoxirribonucleotídeos , Sizofirano , Receptor Toll-Like 9/agonistas , Adjuvantes Imunológicos/administração & dosagem , Animais , Linhagem Celular Tumoral , Citocinas/metabolismo , Interferon gama/efeitos dos fármacos , Interferon gama/metabolismo , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sizofirano/administração & dosagemRESUMO
Rutin has been well recognized for possessing numerous pharmacological and biological activities in several human cancer cells. This research has addressed the inhibitory potential of rutin against the Jab1 oncogene in SiHa cancer cells, which is known to inactivate various tumor suppressor proteins including p53 and p27. Further, the inhibitory efficacy of rutin via Jab1 expression modulation in cervical cancer has not been yet elucidated. Hence, we hypothesized that rutin could exhibit strong inhibitory efficacy against Jab1 and, thereby, induce significant growth arrest in SiHa cancer cells in a dose-dependent manner. In our study, the cytotoxic efficacy of rutin on the proliferation of a cervical cancer cell line (SiHa) was exhibited using MTT and LDH assays. The correlation between rutin and Jab1 mRNA expression was assessed by RT-PCR analysis and the associated events (a mechanism) with this downregulation were then explored via performing ROS assay, DAPI analysis, and expression analysis of apoptosis-associated signaling molecules such as Bax, Bcl-2, and Caspase-3 and -9 using qRT-PCR analysis. Results exhibit that rutin produces anticancer effects via inducing modulation in the expression of oncogenes as well as tumor suppressor genes. Further apoptosis induction, caspase activation, and ROS generation in rutin-treated SiHa cancer cells explain the cascade of events associated with Jab1 downregulation in SiHa cancer cells. Additionally, apoptosis induction was further confirmed by the FITC-Annexin V/PI double staining method. Altogether, our research supports the feasibility of developing rutin as one of the potent drug candidates in cervical cancer management via targeting one such crucial oncogene associated with cervical cancer progression.
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Apoptose/efeitos dos fármacos , Complexo do Signalossomo COP9/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeo Hidrolases/metabolismo , Rutina/farmacologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Complexo do Signalossomo COP9/genética , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Peptídeo Hidrolases/genética , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
A natural predominant flavonoid hesperidin rich in citrus fruits exhibits multifunctional medicinal properties. The anticancerous potential of hesperidin has been widely explored; however, the gall bladder carcinoma (GBC) still remains untouched due to the unavailability of efficient experimental model. The aim of our study was to identify the apoptotic and antiproliferative potential of hesperidin in GBC. The promising efficacy of hesperidin was assessed through the generation of reactive oxygen species (ROS), cellular apoptosis, and loss of mitochondrial membrane potential (MMP) in the primary cells generated from surgically removed cancerous gall bladder tissues. Moreover, cell cycle analysis and caspases-3 activity were performed to confirm the apoptosis inducing potential of hesperidin. Results revealed that hesperidin exposure for 24 h at a dose of 200 µM reduced the cell proliferation of GBC cells significantly. In addition, hesperidin treatment further resulted in an increased ROS generation and nuclear condensation at the same dose. Caspase-3 activation and cell cycle arrest at G2/M phase were also accelerated in a dose-dependent manner. Together, these results suggest that hesperidin can be considered as a potential anticancerous compound for the treatment of GBC. Furthermore, evaluation of the pharmacological aspects of hesperidin is desirable for drug development.
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Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/patologia , Hesperidina/farmacologia , Acetilcisteína/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/fisiologia , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Relação Dose-Resposta a Droga , Neoplasias da Vesícula Biliar/metabolismo , Hesperidina/administração & dosagem , Humanos , Macrófagos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas , GencitabinaRESUMO
Background: Vibrio cholerae, the aetiological agent of the deadly diarrhoeal disease cholera, is known to form biofilm. The antibiotic susceptibility status of biofilm of V. cholerae O139, an important epidemic strain in India and other countries, has not previously been studied in detail. Methods: Antibiotic susceptibility status of planktonic and biofilm cultures of V. cholerae O139 was evaluated by determining MIC, MBC and minimum biofilm eradication concentration (MBEC) values of five different classes of antibiotics using established methods. Effects of antibiotic treatment on planktonic and biofilm cultures were analysed by scanning electron microscopy. The virulence of the antibiotic-surviving population (ASP) was evaluated using an infant mouse model. The frequency of spontaneous mutants and inheritability of antibiotic resistance were determined with standard methods. Results: The antibiotic resistance exhibited by biofilm of V. cholerae O139 was found to be significantly higher (Pâ<â0.05) than its planktonic counterpart. The biofilm-associated antibiotic resistance was found to be transient and exclusive to the biofilm culture. The frequency of ASP clones among antibiotic-treated biofilm cultures occurred at a rate of 0.012%-0.95% and these clones were found to retain the virulence and antibiotic resistance of their parent strains. Conclusions: The biofilm of V. cholerae O139 was found to be resistant to different types of antibiotics tested. This unconventional biofilm resistance highlights the hidden danger of antimicrobial escape by V. cholerae, increased risk of cholera transmission and its continued persistence in the environment.
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Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Vibrio cholerae O139/efeitos dos fármacos , Animais , Cólera/microbiologia , Diarreia/microbiologia , Epidemias , Humanos , Índia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Vibrio cholerae O139/fisiologiaRESUMO
Personnel protection is one of the methods for protection from bites of mosquitoes and other arthropod vectors transmitting many dreadful diseases. Insect repellents and other plant products are normally used to ward off mosquitoes. Application of synthetic pyrethroid permethrin on cloth is adopted for repelling arthropod vectors in many countries for military and civil purposes. In the present study, attempt has been made to impregnate permethrin in the army uniform cloth and to evaluate for its knockdown and repellency against unfed female Aedes aegypti mosquitoes in laboratory condition. WHO protocols were adopted for impregnation of permethrin on cloth and evaluation for its knockdown and repellency after different cycles of washing. Results showed that 93.33% of mosquitoes were knocked down within 1 h after the first washing while its efficacy reduced gradually till the fifty-fifth washing. Landing of mosquitoes on the permethrin-treated cloth was found to increase with respect to number of washings as compared to the untreated cloth. Within 24 h, 100% mortality of all the mosquitoes exposed to permethrin-impregnated cloth was observed. SEM-EDX studies on the texture of untreated cloth and permethrin-treated cloth after different cycles of washing also revealed presence of permethrin on treated cloth.
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Aedes/efeitos dos fármacos , Repelentes de Insetos/farmacologia , Lavanderia , Permetrina/farmacologia , Roupa de Proteção , Animais , Feminino , Repelentes de Insetos/administração & dosagem , Controle de Mosquitos , Permetrina/administração & dosagemRESUMO
One important phytochemical is naringenin, which belongs to the flavanone class of polyphenols. It is found in citrus fruits, such as grapefruits, but it can also be found in tomatoes, cherries, and other food-grade medicinal plants. Naringenin has a significant chemotherapeutic promise, as several investigations have conclusively shown. Therefore, the goal of this review is to synthesize the literature that has been done on naringenin as a possible anti-cancer agent and clarify the mechanisms of action that have been described in treatment plans for different kinds of cancer. In a variety of cancer cells, naringenin works by affecting several pathways associated with cell cycle arrest, anti-metastasis, apoptosis, anti-angiogenesis, and DNA repair. It has been shown to alter several molecular targets linked to the development of cancer, such as drug transporters, transcription factors, reactive nitrogen species, reactive oxygen species, cellular kinases, and inflammatory cytokines and regulators of the cell cycle. In summary, this research provides significant insights into the potential of naringenin as a strong and prospective candidate for use in medicines, nutraceuticals, functional foods, and dietary supplements to improve the management of carcinoma.
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Lung cancer remains a formidable challenge in oncology, necessitating the develop-ment of more effective prognostic and diagnostic techniques due to inefficient conventional therapeutic approaches and inadequate methods for early lung cancer diagnosis. Despite im-mense progress in the development of innovative strategies to alleviate the impact of this devas-tating disease, the outcomes, unfortunately, remain unsatisfactory, particularly in targeted drug delivery methods. Consequently, nanotechnology has emerged as a revolutionary force in cancer research to develop more effective targeted drug delivery tools due to its extraordinary capacity at the atomic and molecular levels. It has appeared as a beacon of hope in this area of unmet need, providing innovative ways for the prognosis and diagnosis of lung carcinoma. Therefore, this comprehensive review delves into the evolving field of nano-based therapeutics, shedding light on their potential to transform lung cancer treatment. This study meticulously explores the most promising nano-based strategies that have been extensively linked with the treatment of lung carcinoma and mainly emphasizes targeted drug delivery methods and therapies. Addition-ally, this review encapsulates the favorable results of clinical trials, which support the potential pathways for further development of nanotherapeutics in lung cancer management.
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Cancer has become one of the most multifaceted and widespread illnesses affecting human health, causing substantial mortality at an alarming rate. After cardiovascular problems, the condition has a high occurrence rate and ranks second in terms of mortality. The development of new drugs has been facilitated by increased research and a deeper understanding of the mechanisms behind the emergence and advancement of the disease. Numerous preclinical and clinical studies have repeatedly demonstrated the protective effects of natural terpenoids against a range of malignancies. Numerous potential bioactive terpenoids have been investigated in natural sources for their chemopreventive and chemoprotective properties. In practically all body cells, the signaling molecule referred to as signal transducer and activator of transcription 3 (STAT3) is widely expressed. Numerous studies have demonstrated that STAT3 regulates its downstream target genes, including Bcl-2, Bcl-xL, cyclin D1, c-Myc, and survivin, to promote the growth of cells, differentiation, cell cycle progression, angiogenesis, and immune suppression in addition to chemotherapy resistance. Researchers viewed STAT3 as a primary target for cancer therapy because of its crucial involvement in cancer formation. This therapy primarily focuses on directly and indirectly preventing the expression of STAT3 in tumor cells. By explicitly targeting STAT3 in both in vitro and in vivo settings, it has been possible to explain the protective effect of terpenoids against malignant cells. In this study, we provide a complete overview of STAT3 signal transduction processes, the involvement of STAT3 in carcinogenesis, and mechanisms related to STAT3 persistent activation. The article also thoroughly summarizes the inhibition of STAT3 signaling by certain terpenoid phytochemicals, which have demonstrated strong efficacy in several preclinical cancer models.
Assuntos
Neoplasias , Fator de Transcrição STAT3 , Humanos , Apoptose , Proliferação de Células , Neoplasias/tratamento farmacológico , Extratos Vegetais/farmacologia , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Terpenos/farmacologiaRESUMO
Cancer remains a global health problem that requires constant research for the development of new treatment strategies. Flavonoids, a diverse group of naturally occurring polyphenolic compounds abundant in fruits, vegetables, and other plant sources, have received considerable attention for their potential anticancer properties. This review aimed to provide a comprehensive overview of the current scientific literature on five specific natural flavonoids, namely quercetin, Epigallocatechin Gallate (EGCG), kaempferol, apigenin, and curcumin that have been widely reported in numerous carcinomas and evaluate their effectiveness and mechanisms in fighting different types of cancer. Known for its antioxidant and anti-inflammatory properties, quercetin has shown promise in inhibiting cancer cells and modulating key signaling pathways. EGCG, a prominent catechin found in green tea, has been extensively studied for its ability to induce apoptosis and inhibit angiogenesis, highlighting its potential as an anticancer agent. Kaempferol has antioxidant and anti-inflammatory effects and has shown anticancer potential by modulating cellular processes involved in tumor development. Apigenin, abundant in parsley and chamomile, has been shown to exert anticancer properties by interrupting the cell cycle and inducing apoptosis in cancer cells. Curcumin has shown several anticancer effects, including inhibiting cell proliferation, inducing apoptosis, and modulating inflammatory pathways. Despite these promising findings, it is essential to recognize the complexity of cancer biology and the need for further research to clarify the precise mechanisms of action of these natural flavonoids and optimize their therapeutic applications. Furthermore, understanding flavonoids' potential synergy and interactions with traditional cancer therapies is paramount for developing effective combinatorial strategies. This review thus aimed to summarize the current knowledge on these natural flavonoids and provide insight into their potential role as an adjunctive or stand-alone therapy in the fight against breast, prostate, colon, lung, skin, ovarian, liver, and pancreatic cancer.
RESUMO
Liquid crystalline lipid nanoparticles (LCNPs) represent a type of membrane-based nano-carriers formed through the self-assembly of lyotropic lipids. These lipids, such as unsaturated monoglycerides, phospholipids, and co-lipids, create liquid crystals or vesicles with an aqueous core enclosed by a natural or synthetic phospholipid bilayer upon exposure to an aqueous medium. Liquid crystalline lipid nanoparticles (LCNPs), akin to liposomes, have garnered significant attention as nanocarriers suitable for a diverse range of hydrophobic and hydrophilic molecules. Their notable structural advantage lies in a mono-channel network organization and the presence of multiple compartments, resulting in heightened encapsulation efficiency for various substances. Cubosomes, spongosomes, hexosomes, and multicompartment nanoparticles are examples of lipid nanocarriers with interior liquid crystalline structures that have recently gained a lot of interest as effective drug delivery systems. Additionally, LCNPs facilitate the sustained release of encapsulated compounds, including therapeutic macromolecules. This review delves into the structure of liquid crystalline lipid nanoparticles, explores preparation techniques, and outlines their applications in the context of skin cancer.