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2.
Biomed Pharmacother ; 174: 116376, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38508080

RESUMO

Alzheimer's disease (AD) is a very common neurodegenerative disorder associated with memory loss and a progressive decline in cognitive activity. The two major pathophysiological factors responsible for AD are amyloid plaques (comprising amyloid-beta aggregates) and neurofibrillary tangles (consisting of hyperphosphorylated tau protein). Polyphenols, a class of naturally occurring compounds, are immensely beneficial for the treatment or management of various disorders and illnesses. Naturally occurring sources of polyphenols include plants and plant-based foods, such as fruits, herbs, tea, vegetables, coffee, red wine, and dark chocolate. Polyphenols have unique properties, such as being the major source of anti-oxidants and possessing anti-aging and anti-cancerous properties. Currently, dietary polyphenols have become a potential therapeutic approach for the management of AD, depending on various research findings. Dietary polyphenols can be an effective strategy to tackle multifactorial events that occur with AD. For instance, naturally occurring polyphenols have been reported to exhibit neuroprotection by modulating the Aß biogenesis pathway in AD. Many nanoformulations have been established to enhance the bioavailability of polyphenols, with nanonization being the most promising. This review comprehensively provides mechanistic insights into the neuroprotective potential of dietary polyphenols in treating AD. It also reviews the usability of dietary polyphenol as nanoformulation for AD treatment.


Assuntos
Doença de Alzheimer , Polifenóis , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/dietoterapia , Doença de Alzheimer/metabolismo , Polifenóis/farmacologia , Humanos , Animais , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Nanopartículas/química , Dieta , Peptídeos beta-Amiloides/metabolismo , Disponibilidade Biológica
3.
ACS Appl Bio Mater ; 7(3): 1656-1670, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38364267

RESUMO

Triple-negative breast cancer (TNBC) is considered to be one of the most difficult subtypes of breast cancer (BC) to treat. The sheer absence of certain receptors makes it very tough to target, leaving high-dose chemotherapy as probably the sole therapeutic option at the cost of nonspecific toxic effects. Carnosic acid (CA) has been established as a potential chemotherapeutic agent against a range of cancer cells. However, its in vivo chemotherapeutic potential is significantly challenged due to its poor pharmacokinetic attributes. In this study, poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were formulated to circumvent the biopharmaceutical limitations of CA. CA-loaded polymeric NPs (CA-PLGA NPs) have been evaluated as a potential therapeutic option in the treatment of TNBC. Different in vitro studies exhibited that CA-PLGA NPs significantly provoked oxidative-stress-mediated apoptotic death in MDA-MB-231 cells. The improved anticancer potential of CA-PLGA NPs over CA was found to be associated with improved cellular uptake of the nanoformulation by TNBC cells. In vivo studies also established the improvement in the chemotherapeutic efficacy of CA-nanoformulation over that of free CA without showing any sign of systemic toxicity. Thus, CA-PLGA NPs emerge as a promising candidate to fix two bugs with a single code, resolving biopharmaceutical attributes of CA as well as introducing a treatment option for TNBC.


Assuntos
Abietanos , Produtos Biológicos , Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Disponibilidade Biológica , Polímeros , Produtos Biológicos/uso terapêutico
4.
Artigo em Inglês | MEDLINE | ID: mdl-38421395

RESUMO

The current research focused on the green synthesis of silver nanoparticles (AgNPs) using Duabanga grandiflora leaf extract. The green synthesis of AgNPs was confirmed by the surface plasmon resonance band at 453 nm in a UV-Visible analysis. The formulated AgNPs had a diameter of around 99.72 nm with a spherical shape. Fourier transform infrared (FTIR) spectrum revealed the bio-reducing potential of phytochemicals present in D. grandiflora, which fundamentally influenced the synthesis of AgNPs. Zeta potential, dynamic light scattering (DLS), scanning electron microscopic (SEM), energy-dispersive X-ray spectroscopic (EDX), X-ray diffraction (XRD), and transmission electron microscopic (TEM) analyses were executed to reveal the physicochemical attributes of the AgNPs. The AgNPs were further investigated for their antioxidant, antidiabetic, anticancer, and antibacterial potential. The DPPH free radical assay revealed the potential radical scavenging capacity (IC50 = 76.73 µg/ml) of green synthesized AgNPs. α-Amylase inhibitory assay displayed significant inhibitory potential (IC50 = 162.11 µg/ml) of this starch-breaking enzyme by AgNPs, revealing the antidiabetic potential of AgNPs. AgNPs exhibited potential cytotoxic activity (IC50 = 244.57 µg/ml) against malignant human kidney cells. In addition, AgNPs showed outstanding antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacterial strains. Interestingly, AgNPs showed cytotoxic and antimicrobial activities at much higher concentrations than radical scavenging and α-amylase inhibitory concentrations. Thus, our finding elaborated the scope of green synthesized AgNPs for diverse therapeutic applications (dose-dependent) for further clinical translation.

5.
Mol Cancer ; 23(1): 18, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243280

RESUMO

The production and release of tumor-derived small extracellular vesicles (TDSEVs) from cancerous cells play a pivotal role in the propagation of cancer, through genetic and biological communication with healthy cells. TDSEVs are known to orchestrate the invasion-metastasis cascade via diverse pathways. Regulation of early metastasis processes, pre-metastatic niche formation, immune system regulation, angiogenesis initiation, extracellular matrix (ECM) remodeling, immune modulation, and epithelial-mesenchymal transition (EMT) are among the pathways regulated by TDSEVs. MicroRNAs (miRs) carried within TDSEVs play a pivotal role as a double-edged sword and can either promote metastasis or inhibit cancer progression. TDSEVs can serve as excellent markers for early detection of tumors, and tumor metastases. From a therapeutic point of view, the risk of cancer metastasis may be reduced by limiting the production of TDSEVs from tumor cells. On the other hand, TDSEVs represent a promising approach for in vivo delivery of therapeutic cargo to tumor cells. The present review article discusses the recent developments and the current views of TDSEVs in the field of cancer research and clinical applications.


Assuntos
Vesículas Extracelulares , MicroRNAs , Neoplasias , Humanos , Relevância Clínica , Neoplasias/patologia , MicroRNAs/genética , Comunicação Celular , Transição Epitelial-Mesenquimal , Microambiente Tumoral , Metástase Neoplásica/patologia
6.
ACS Appl Bio Mater ; 6(11): 4814-4827, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37886889

RESUMO

Bacterial infections and persistent inflammation can impede the intrinsic healing process of wounds. To combat this issue, researchers have delved into the potential use of carbon dots (CDs) in the regulation of inflammation and counteract infections. These CDs were synthesized using a microwave-assisted hydrothermal process and have demonstrated outstanding antibacterial and antibiofilm properties against Gram-positive and Gram-negative bacteria. Additionally, CDs displayed biocompatibility at therapeutic concentrations and the ability to specifically target mitochondria. CD treatment effectively nullified lipopolysaccharide-triggered reactive oxygen species production by macrophages, while simultaneously promoting macrophage polarization toward an anti-inflammatory phenotype (M2), leading to a reduction in inflammation and an acceleration in wound healing. In vitro scratch assays also revealed that CDs facilitated the tissue-repairing process by stimulating epithelial cell migration during reepithelialization. In vivo studies using CDs topically applied to lipopolysaccharide (LPS)-stimulated wounds in C57/BL6 mice demonstrated significant improvements in wound healing due to enhanced fibroblast proliferation, angiogenesis, and collagen deposition. Crucially, histological investigations showed no indications of systemic toxicity in vital organs. Collectively, the application of CDs has shown immense potential in speeding up the wound-healing process by regulating inflammation, preventing bacterial infections, and promoting tissue repair. These results suggest that further clinical translation of CDs should be considered.


Assuntos
Antibacterianos , Infecções Bacterianas , Camundongos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Lipopolissacarídeos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Cicatrização , Macrófagos , Inflamação
7.
Genes Dis ; 10(3): 960-989, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37396553

RESUMO

Continuous revision of the histologic and stage-wise classification of lung cancer by the World Health Organization (WHO) provides the foundation for therapeutic advances by promoting molecular targeted and immunotherapies and ensuring accurate diagnosis. Cancer epidemiologic data provide helpful information for cancer prevention, diagnosis, and management, supporting health-care interventions. Global cancer mortality projections from 2016 to 2060 show that cancer will overtake ischemic heart diseases (IHD) as the leading cause of death (18.9 million) immediately after 2030, surpassing non-small cell lung cancer (NSCLC), which accounts for 85 percent of lung cancers. The clinical stage at the diagnosis is the main prognostic factor in NSCLC therapies. Advanced early diagnostic methods are essential as the initial stages of cancer show reduced mortality compared to the advanced stages. Sophisticated approaches to proper histological classification and NSCLC management have improved clinical efficiency. Although immune checkpoint inhibitors (ICIs) and targeted molecular therapies have refined the therapeutic management of late-stage NSCLC, the specificity and sensitivity of cancer biomarkers should be improved by focusing on prospective studies, followed by their use as therapeutic tools. The liquid biopsy candidates such as circulating tumor cells (CTCs), circulating cell-free tumor DNA (cfDNA), tumor educated platelets (TEP), and extracellular vesicles (EVs) possess cancer-derived biomolecules and aid in tracing: driver mutations leading to cancer, acquired resistance caused by various generations of therapeutic agents, refractory disease, prognosis, and surveillance.

8.
Genes Dis ; 10(4): 1367-1401, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37397557

RESUMO

Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that causes millions of deaths every year. With the new understanding of the molecular mechanism(s) of disease progression, our knowledge about the disease is snowballing, leading to the evolution of many new therapeutic regimes and their successive trials. In the past few decades, various combinations of therapies have been proposed and are presently employed in the treatment of diverse cancers. Targeted drug therapy, immunotherapy, and personalized medicines are now largely being employed, which were not common a few years back. The field of cancer discoveries and therapeutics are evolving fast as cancer type-specific biomarkers are progressively being identified and several types of cancers are nowadays undergoing systematic therapies, extending patients' disease-free survival thereafter. Although growing evidence shows that a systematic and targeted approach could be the future of cancer medicine, chemotherapy remains a largely opted therapeutic option despite its known side effects on the patient's physical and psychological health. Chemotherapeutic agents/pharmaceuticals served a great purpose over the past few decades and have remained the frontline choice for advanced-stage malignancies where surgery and/or radiation therapy cannot be prescribed due to specific reasons. The present report succinctly reviews the existing and contemporary advancements in chemotherapy and assesses the status of the enrolled drugs/pharmaceuticals; it also comprehensively discusses the emerging role of specific/targeted therapeutic strategies that are presently being employed to achieve better clinical success/survival rate in cancer patients.

9.
Mol Cancer ; 22(1): 105, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-37415164

RESUMO

Breast cancer is the second leading cause of death for women worldwide. The heterogeneity of this disease presents a big challenge in its therapeutic management. However, recent advances in molecular biology and immunology enable to develop highly targeted therapies for many forms of breast cancer. The primary objective of targeted therapy is to inhibit a specific target/molecule that supports tumor progression. Ak strain transforming, cyclin-dependent kinases, poly (ADP-ribose) polymerase, and different growth factors have emerged as potential therapeutic targets for specific breast cancer subtypes. Many targeted drugs are currently undergoing clinical trials, and some have already received the FDA approval as monotherapy or in combination with other drugs for the treatment of different forms of breast cancer. However, the targeted drugs have yet to achieve therapeutic promise against triple-negative breast cancer (TNBC). In this aspect, immune therapy has come up as a promising therapeutic approach specifically for TNBC patients. Different immunotherapeutic modalities including immune-checkpoint blockade, vaccination, and adoptive cell transfer have been extensively studied in the clinical setting of breast cancer, especially in TNBC patients. The FDA has already approved some immune-checkpoint blockers in combination with chemotherapeutic drugs to treat TNBC and several trials are ongoing. This review provides an overview of clinical developments and recent advancements in targeted therapies and immunotherapies for breast cancer treatment. The successes, challenges, and prospects were critically discussed to portray their profound prospects.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Imunoterapia/métodos , Terapia Combinada , Terapia de Alvo Molecular/métodos
10.
Mar Drugs ; 21(4)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37103352

RESUMO

Chitin is the second most abundant biopolymer consisting of N-acetylglucosamine units and is primarily derived from the shells of marine crustaceans and the cell walls of organisms (such as bacteria, fungi, and algae). Being a biopolymer, its materialistic properties, such as biodegradability, and biocompatibility, make it a suitable choice for biomedical applications. Similarly, its deacetylated derivative, chitosan, exhibits similar biocompatibility and biodegradability properties, making it a suitable support material for biomedical applications. Furthermore, it has intrinsic material properties such as antioxidant, antibacterial, and antitumor. Population studies have projected nearly 12 million cancer patients across the globe, where most will be suffering from solid tumors. One of the shortcomings of potent anticancer drugs is finding a suitable cellular delivery material or system. Therefore, identifying new drug carriers to achieve effective anticancer therapy is becoming essential. This paper focuses on the strategies implemented using chitin and chitosan biopolymers in drug delivery for cancer treatment.


Assuntos
Antineoplásicos , Quitosana , Nanopartículas , Neoplasias , Humanos , Quitosana/uso terapêutico , Quitina , Sistemas de Liberação de Medicamentos , Biopolímeros , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
11.
Appl Microbiol Biotechnol ; 107(7-8): 2155-2167, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36922438

RESUMO

Genus Crinum L. is a member of the Amaryllidaceae family having beautiful, huge, ornamental plants with umbels of lily-like blooms that are found in tropical and subtropical climates all over the world. For thousands of years, Crinum has been used as a traditional medicine to treat illnesses and disorders. Numerous distinct alkaloids of the Amaryllidaceae group, whose most well-known properties include analgesic, anticholinergic, antitumor, and antiviral, have recently been discovered by phytochemical analyses. However, because of decades of overexploitation for their economically significant bioactive ingredients and poor seed viability and germination rates, these plants are now threatened in their native environments. Because of these factors, researchers are investigating micropropagation techniques to optimize phytochemicals in vitro. This review's objective is to offer details on the distribution, phytochemistry, micropropagation, in vitro galanthamine synthesis, and pharmacology which will help to design biotechnological techniques for the preservation, widespread multiplication, and required secondary metabolite production from Crinum spp. KEY POINTS: • Botanical description and phytochemical profile of Crinum spp. • In vitro micropropagation method of Crinum sp. • Bioactive compound galanthamine isolation techniques and its pharmacological properties.


Assuntos
Alcaloides , Crinum , Crinum/química , Extratos Vegetais/farmacologia , Galantamina , Alcaloides/química , Compostos Fitoquímicos
12.
Mol Cancer ; 22(1): 22, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721153

RESUMO

Malignant brain tumors rank among the most challenging type of malignancies to manage. The current treatment protocol commonly entails surgery followed by radiotherapy and/or chemotherapy, however, the median patient survival rate is poor. Recent developments in immunotherapy for a variety of tumor types spark optimism that immunological strategies may help patients with brain cancer. Chimeric antigen receptor (CAR) T cells exploit the tumor-targeting specificity of antibodies or receptor ligands to direct the cytolytic capacity of T cells. Several molecules have been discovered as potential targets for immunotherapy-based targeting, including but not limited to EGFRvIII, IL13Rα2, and HER2. The outstanding clinical responses to CAR T cell-based treatments in patients with hematological malignancies have generated interest in using this approach to treat solid tumors. Research results to date support the astounding clinical response rates of CD19-targeted CAR T cells, early clinical experiences in brain tumors demonstrating safety and evidence for disease-modifying activity, and the promise for further advances to ultimately assist patients clinically. However, several variable factors seem to slow down the progress rate regarding treating brain cancers utilizing CAR T cells. The current study offers a thorough analysis of CAR T cells' promise in treating brain cancer, including design and delivery considerations, current strides in clinical and preclinical research, issues encountered, and potential solutions.


Assuntos
Neoplasias Encefálicas , Imunoterapia Adotiva , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Anticorpos , Antígenos CD19 , Neoplasias Encefálicas/terapia , Morte Celular , Receptores de Antígenos Quiméricos , Linfócitos T
13.
Life Sci ; 317: 121467, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36736764

RESUMO

AIMS: This research aims to compare the therapeutic potential of target-specific phosphorothioate backbone-modified aptamer L5 (TLS9a)-functionalized paclitaxel (PTX)-loaded nanocarrier (PTX-NPL5) that we formulated with that of non-targeted commercial formulation, protein albumin-bound nanoparticles of PTX, Abraxane® (CF) against hepatocellular carcinoma (HCC) through a myriad of preclinical investigations. MAIN METHODS: A variety of in vitro and in vivo assays have been executed to compare the therapeutic effects of the formulations under investigation, including the investigation of the degree of apoptosis induction and its mechanism, cell cycle analysis, the level of ROS production, and redox status, the morphological and histological characteristics of malignant livers, and in vivo imaging. The formulations were also compared concerning pharmacokinetic behaviors. Finally, in silico molecular docking has been performed to predict the possible interactions between aptamer and target(s). KEY FINDINGS: PTX-NPL5 exhibited therapeutic superiority over CF in terms of inducing apoptosis, cell cycle arrest, endorsing oxidative stress to neoplastic cells, and reducing hepatic cancerous lesions. Unlike CF, PTX-NPL5 did not exhibit any significant toxicity in healthy hepatocytes, proving enough impetus regarding the distinctive superiority of PTX-NPL5 over CF. The pharmacokinetic analysis further supported superior penetration and retention of PTX-NPL5 in neoplastic hepatocytes compared to CF. A molecular modeling study proposed possible interaction between aptamer L5 and heat shock protein 70 (HSP70). SIGNIFICANCE: The target-specificity of PTX-NPL5 towards neoplastic hepatocytes, probably achieved through HSP70 recognition, enhanced its therapeutic efficacy over CF, which may facilitate its real clinical deployment against HCC in the near future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Simulação de Acoplamento Molecular , Neoplasias Hepáticas/tratamento farmacológico , Paclitaxel/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Linhagem Celular Tumoral
14.
Drug Discov Today ; 28(1): 103409, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36265733

RESUMO

Flavonoids are an interesting class of biomolecules, which exhibit cancer-inhibitory effects through both chemopreventive and chemotherapeutic activities. However, their therapeutic efficacy is affected by poor pharmacokinetics (PK) and biopharmaceutical attributes. One of the most promising approaches to resolve these issues is to formulate flavonoids in nanosystems. Different flavonoid nanoformulations have shown therapeutic superiority over free flavonoids. Functionalization of nanoparticles (NPs) further improves their therapeutic efficacy by facilitating site-specific delivery and reducing nonspecific toxicities. In this review, we highlight recent developments in the field of flavonoid-based NPs to gain translational insights into the potential applications of flavonoid-based nanocarriers in cancer management.


Assuntos
Nanopartículas , Neoplasias , Humanos , Portadores de Fármacos , Flavonoides/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico
15.
Food Chem Toxicol ; 171: 113511, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36450305

RESUMO

The devastating complications of coronavirus disease 2019 (COVID-19) result from an individual's dysfunctional immune response following the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS-CoV-2 exploits the dysfunctional immune system to trigger a chain of events ultimately leading to COVID-19. The current study identifies eighty immune system dysfunction-enabling toxic stressors and behaviors (hereafter called modifiable contributing factors (CFs)) that also link directly to COVID-19. Each CF is assigned to one of the five categories in the CF taxonomy shown in Section 3.3.: Lifestyle (e.g., diet, substance abuse); Iatrogenic (e.g., drugs, surgery); Biotoxins (e.g., micro-organisms, mycotoxins); Occupational/Environmental (e.g., heavy metals, pesticides); Psychosocial/Socioeconomic (e.g., chronic stress, lower education). The current study shows how each modifiable factor contributes to decreased immune system capability, increased inflammation and coagulation, and increased neural damage and neurodegeneration. It is unclear how real progress can be made in combatting COVID-19 and other similar diseases caused by viral variants without addressing and eliminating these modifiable CFs.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Inflamação , Sistema Imunitário
16.
Viruses ; 14(12)2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36560690

RESUMO

The Japanese encephalitis virus (JEV) is the most common cause of neurodegenerative disease in Southeast Asia and the Western Pacific region; approximately 1.15 billion people are at risk, and thousands suffer from permanent neurological disorders across Asian countries, with 10-15 thousand people dying each year. JEV crosses the blood-brain barrier (BBB) and forms a complex with receptors on the surface of neurons. GRP78, Src, TLR7, caveolin-1, and dopamine receptor D2 are involved in JEV binding and entry into the neurons, and these receptors also play a role in carcinogenic activity in cells. JEV binds to GRP78, a member of the HSP70 overexpressed on malignant cells to enter neurons, indicating a higher chance of JEV infection in cancer patients. However, JEV enters human brain microvascular endothelial cells via an endocytic pathway mediated by caveolae and the ezrin protein and also targets dopamine-rich areas for infection of the midbrain via altering dopamine levels. In addition, JEV complexed with CLEC5A receptor of macrophage cells is involved in the breakdown of the BBB and central nervous system (CNS) inflammation. CLEC5A-mediated infection is also responsible for the influx of cytokines into the CNS. In this review, we discuss the neuronal and macrophage surface receptors involved in neuronal death.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Vírus da Encefalite Japonesa (Subgrupo) , Encefalite Japonesa , Doenças Neurodegenerativas , Humanos , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Células Endoteliais/metabolismo , Chaperona BiP do Retículo Endoplasmático , Dopamina , Doenças Neurodegenerativas/patologia , Sistema Nervoso Central , Vírus da Encefalite Japonesa (Subgrupo)/metabolismo , Receptores de Superfície Celular , Lectinas Tipo C/metabolismo
18.
Mol Cancer ; 21(1): 204, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307808

RESUMO

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progression by creating an energy crisis for preneoplastic cells, resulting in antiproliferative effects. These effects are referred to as chemopreventive effects mediated by an antioxidant mechanism. In addition, antioxidants minimize chemotherapy-induced nonspecific organ toxicity and prolong survival. Antioxidants also support the prooxidant chemistry that demonstrate chemotherapeutic potential, particularly at high or pharmacological doses and trigger OS by promoting free radical production, which is essential for activating cell death pathways. A growing body of evidence also revealed the roles of exogenous antioxidants as adjuvants and their ability to reverse chemoresistance. In this review, we explain the influences of different exogenous and endogenous antioxidants on brain cancers with reference to their chemopreventive and chemotherapeutic roles. The role of antioxidants on metabolic reprogramming and their influence on downstream signaling events induced by tumor suppressor gene mutations are critically discussed. Finally, the review hypothesized that both pro- and antioxidant roles are involved in the anticancer mechanisms of the antioxidant molecules by killing neoplastic cells and inhibiting tumor recurrence followed by conventional cancer treatments. The requirements of pro- and antioxidant effects of exogenous antioxidants in brain tumor treatment under different conditions are critically discussed along with the reasons behind the conflicting outcomes in different reports. Finally, we also mention the influencing factors that regulate the pharmacology of the exogenous antioxidants in brain cancer treatment. In conclusion, to achieve consistent clinical outcomes with antioxidant treatments in brain cancers, rigorous mechanistic studies are required with respect to the types, forms, and stages of brain tumors. The concomitant treatment regimens also need adequate consideration.


Assuntos
Antioxidantes , Neoplasias Encefálicas , Humanos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Carcinogênese , Microambiente Tumoral
19.
J Food Biochem ; 46(12): e14385, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36069251

RESUMO

This study examined the antidiabetic efficacy of popular fermented soybean foods (FSF) of Northeast (NE) India. Results showed that among different FSF, aqueous extract of Hawaijar (AEH), a traditional FSF of Manipur, NE India, significantly augmented glucose utilization in cultured myotubes treated with high glucose (HG, 25 mM). Furthermore, AEH also upregulated glucose uptake, glucose-6-phosphate level, and phopho-PI3K/phospho-AKT/phospho-AMPK/GLUT4 protein expression in HG-treated myotubes. In vivo studies demonstrated that AEH supplementation (50, 100, or 200 mg/kg body weight/day, oral gavaging, 16 weeks) reduced body weight, fasting blood glucose, glycated hemoglobin, insulin resistance, and glucose intolerance in rats fed with high-fat diet (HFD). AEH supplementation stimulated phopho-PI3K/phospho-AKT/phospho-AMPK/GLUT4 signaling cascades involved in glucose metabolism of muscle tissues in diabetic rats. Chemical profiling of AEH (SDS-PAGE, immunoblotting, and HRMS) suggests the possible role of bioactive proteins/peptides and isoflavones underlying the antihyperglycemic potential AEH. Results from this study will be helpful for developing food-based prophylactics/therapeutics in managing hyperglycemia. PRACTICAL APPLICATIONS: Fermented soybean foods are gaining acceptance due to multiple health benefits. This study for the first time reports the antidiabetic potential of Hawaijar, an indigenous fermented soybean food of North-East India. Higher abundance of bioactive compounds (isoflavones and proteins/peptides) in Hawaijar may be responsible for the alleviation of impaired glucose metabolism associated with diabetes. The findings may be helpful for the development of a novel therapeutic to achieve better control of hyperglycemia and improve the lives of the patient population with diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hiperglicemia , Isoflavonas , Ratos , Humanos , Animais , Hipoglicemiantes/farmacologia , Glucose/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Glycine max/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Índia , Transdução de Sinais , Músculos/metabolismo , Hiperglicemia/tratamento farmacológico
20.
J Control Release ; 350: 698-715, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36057397

RESUMO

Quantum dots (QDs) are semiconductor nanocrystals possessing unique optoelectrical properties in that they can emit light energy of specific tunable wavelengths when excited by photons. They are gaining attention nowadays owing to their all-around ability to allow high-quality bio-imaging along with targeted drug delivery. The most lethal central nervous system (CNS) disorders are brain cancers or malignant brain tumors. CNS is guarded by the blood-brain barrier which poses a selective blockade toward drug delivery into the brain. QDs have displayed strong potential to deliver therapeutic agents into the brain successfully. Their bio-imaging capability due to photoluminescence and specific targeting ability through the attachment of ligand biomolecules make them preferable clinical tools for coming times. Biocompatible QDs are emerging as nanotheranostic tools to identify/diagnose and selectively kill cancer cells. The current review focuses on QDs and associated nanoformulations as potential futuristic clinical aids in the continuous battle against brain cancer.


Assuntos
Neoplasias Encefálicas , Pontos Quânticos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Humanos , Ligantes , Pontos Quânticos/química , Nanomedicina Teranóstica
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