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1.
Nutr Cancer ; : 1-24, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847479

ABSTRACT

Obesity has emerged as an important global health challenge, significantly influencing the incidence and progression of various cancers. This comprehensive review elucidates the complex relationship between obesity and oncogenesis, focusing particularly on the role of dysregulated signaling pathways as central mediators of this association. We delve into the contributions of obesity-induced alterations in key signaling cascades, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and Wnt/ß-catenin to carcinogenesis. These alterations facilitate unchecked cellular proliferation, chronic inflammation and apoptosis resistance. Epidemiological evidence links obesity with increased cancer susceptibility and adverse prognostic outcomes, with pronounced risks for specific cancers such as breast, colorectal, endometrial and hepatic malignancies. This review synthesizes data from both animal and clinical studies to underscore the pivotal role of disrupted signaling pathways in shaping innovative therapeutic strategies. We highlight the critical importance of lifestyle modifications in obesity management and cancer risk mitigation, stressing the benefits of dietary changes, physical activity, and behavioral interventions. Moreover, we examine targeted pharmacological strategies addressing aberrant pathways in obesity-related tumors and discuss the integration of cutting-edge treatments, including immunotherapy and precision medicine, into clinical practice.

2.
Nanomedicine (Lond) ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38661720

ABSTRACT

Aim: To investigate the therapeutic potential of mebendazole (MBZ)-loaded nanostructured lipid carriers (NLCs). Methodology: NLC-MBZ was prepared and characterized to evaluate the in vitro and in vivo anticancer effects and the inhibitory effect on RanGTP and its potential as an antimetastatic treatment in vivo. Results: NLC-MBZ exhibited a size and charge of 155 ± 20 nm and -27 ± 0.5 mV, respectively, with 90.7% encapsulation. Free MBZ and NLC-MBZ had a 50% inhibitory concentration of 610 and 305 nM, respectively, against MDA-MB-231 cell lines. NLC-MBZ decreased tumor size, suppressed tumor lung metastases, and lowered the expression of CDC25A, SKP2, RbX1 and Cullin1 while boosting the Rb proteins. Conclusion: NLC-MBZ displayed antiangiogenic potential and resulted in a reduced rate of lung metastasis in vivo.

3.
Pathol Res Pract ; 257: 155285, 2024 May.
Article in English | MEDLINE | ID: mdl-38653089

ABSTRACT

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


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/pathology , Glioblastoma/therapy , Glioblastoma/genetics , Brain Neoplasms/therapy , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Alkaloids/therapeutic use , Signal Transduction/drug effects , Animals
4.
Expert Opin Drug Deliv ; 21(3): 399-422, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38623735

ABSTRACT

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


Subject(s)
Antibiotics, Antineoplastic , Cardiotoxicity , Doxorubicin , Drug Carriers , Nanoparticles , Doxorubicin/adverse effects , Doxorubicin/administration & dosage , Cardiotoxicity/prevention & control , Cardiotoxicity/etiology , Humans , Animals , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/chemistry , Drug Carriers/chemistry , Nanoparticles/chemistry , Drug Delivery Systems , Polymers/chemistry , Heart Failure/drug therapy , Heart Failure/chemically induced , Lipids/chemistry
5.
Cancer Lett ; 591: 216894, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38626856

ABSTRACT

This comprehensive review delves into the pivotal role of the tumor microenvironment (TME) in cancer metastasis and therapeutic response, offering fresh insights into the intricate interplay between cancer cells and their surrounding milieu. The TME, a dynamic ecosystem comprising diverse cellular and acellular elements, not only fosters tumor progression but also profoundly affects the efficacy of conventional and emerging cancer therapies. Through nuanced exploration, this review illuminates the multifaceted nature of the TME, elucidating its capacity to engender drug resistance via mechanisms such as hypoxia, immune evasion, and the establishment of physical barriers to drug delivery. Moreover, it investigates innovative therapeutic approaches aimed at targeting the TME, including stromal reprogramming, immune microenvironment modulation, extracellular matrix (ECM)-targeting agents, and personalized medicine strategies, highlighting their potential to augment treatment outcomes. Furthermore, this review critically evaluates the challenges posed by the complexity and heterogeneity of the TME, which contribute to variable therapeutic responses and potentially unintended consequences. This underscores the need to identify robust biomarkers and advance predictive models to anticipate treatment outcomes, as well as advocate for combination therapies that address multiple facets of the TME. Finally, the review emphasizes the necessity of an interdisciplinary approach and the integration of cutting-edge technologies to unravel the intricacies of the TME, thereby facilitating the development of more effective, adaptable, and personalized cancer treatments. By providing critical insights into the current state of TME research and its implications for the future of oncology, this review highlights the dynamic and evolving landscape of this field.


Subject(s)
Neoplasm Metastasis , Neoplasms , Tumor Microenvironment , Humans , Neoplasms/pathology , Neoplasms/drug therapy , Neoplasms/immunology , Neoplasms/therapy , Extracellular Matrix/metabolism , Extracellular Matrix/pathology , Drug Resistance, Neoplasm , Animals , Precision Medicine
6.
Bioanalysis ; 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38497721

ABSTRACT

This study was conducted to compare dissolution profiles of four Jordanian registered sildenafil (SDF) products to the originator. Dissolution samples were analyzed utilizing a validated and stability-indicating HPLC method in human plasma. Validation was performed for specificity, linearity, limit of detection, lower limit of quantification, precision, trueness and stability. SDF was extracted from plasma samples using liquid-liquid extraction. The analysis was performed utilizing isocratic elution on C18 column with 1.0 ml/min flow rate. The regression value was ∼0.999 over 3 days with drug recovery between 86.6 to 89.8%with 10 ng/ml lower limit of quantitation. This method displayed a good selectivity of SDF with improved stability under various conditions. The method was used for SDF quantification in dissolution medium. Similarity factors for local products varied according to the used mediums, but all SDF local products passed the dissolution in vitro test since all of them showed a released of >85% after 60 min at the dissolution mediums.

7.
Biopharm Drug Dispos ; 45(2): 71-82, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38400763

ABSTRACT

This research aims to identify regional differences in vildagliptin absorption across the intestinal membrane. Furthermore, it was to investigate the effect of verapamil or metformin on vildagliptin absorptive clearance. The study utilized an in situ rabbit intestinal perfusion technique to determine vildagliptin oral absorption from duodenum, jejunum, ileum, and ascending colon. This was conducted both with and without perfusion of metformin or verapamil. The findings revealed that the vildagliptin absorptive clearance per unit length varied by site and was in the order as follows: ileum < jejunum < duodenum < ascending colon, implying that P-gp is significant in the reduction of vildagliptin absorption. Also, the arrangement cannot reverse intestinal P-gp, but the observations suggest that P-gp is significant in reducing vildagliptin absorption. Verapamil co-perfusion significantly increased the vildagliptin absorptive clearance by 2.4 and 3.2 fold through the jejunum and ileum, respectively. Metformin co-administration showed a non-significant decrease in vildagliptin absorptive clearance through all tested segments. Vildagliptin absorption was site-dependent and may be related to the intestinal P-glycoprotein content. This may aid in understanding the important elements that influence vildagliptin absorption, besides drug-drug interactions that can occur in type 2 diabetic patients taking vildagliptin in conjunction with other drugs that can modify the P-glycoprotein level.


Subject(s)
Metformin , Animals , Humans , Rabbits , Vildagliptin/pharmacology , Metformin/pharmacology , Verapamil/pharmacology , Intestinal Absorption , Intestines , ATP Binding Cassette Transporter, Subfamily B
8.
Pathol Res Pract ; 254: 155161, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38280275

ABSTRACT

Chronic Myeloid Leukemia (CML) is characterized by chromosomal aberrations involving the fusion of the BCR and ABL genes on chromosome 22, resulting from a reciprocal translocation between chromosomes 9 and 22. This fusion gives rise to the oncogenic BCR-ABL, an aberrant tyrosine kinase identified as Abl protein. The Abl protein intricately regulates the cell cycle by phosphorylating protein tyrosine residues through diverse signaling pathways. In CML, the BCR-ABL fusion protein disrupts the first exon of Abl, leading to sustained activation of tyrosine kinase and resistance to deactivation mechanisms. Pharmacological interventions, such as imatinib, effectively target BCR-ABL's tyrosine kinase activity by binding near the active site, disrupting ATP binding, and inhibiting downstream protein phosphorylation. Nevertheless, the emergence of resistance, often attributed to cap structure mutations, poses a challenge to imatinib efficacy. Current research endeavours are directed towards overcoming resistance and investigating innovative therapeutic strategies. This article offers a comprehensive analysis of the structural attributes of BCR-ABL, emphasizing its pivotal role as a biomarker and therapeutic target in CML. It underscores the imperative for ongoing research to refine treatment modalities and enhance overall outcomes in managing CML.


Subject(s)
Genes, abl , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Imatinib Mesylate/therapeutic use , Imatinib Mesylate/pharmacology , Pyrimidines/therapeutic use , Piperazines/therapeutic use , Benzamides/pharmacology , Benzamides/therapeutic use , Drug Resistance, Neoplasm/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Fusion Proteins, bcr-abl/genetics , Fusion Proteins, bcr-abl/metabolism , Fusion Proteins, bcr-abl/pharmacology , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology
9.
Gene ; 905: 148174, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38242374

ABSTRACT

The intersection of mathematical modeling, nanotechnology, and epidemiology marks a paradigm shift in our battle against infectious diseases, aligning with the focus of the journal on the regulation, expression, function, and evolution of genes in diverse biological contexts. This exploration navigates the intricate dance of viral transmission dynamics, highlighting mathematical models as dual tools of insight and precision instruments, a theme relevant to the diverse sections of Gene. In the context of virology, ethical considerations loom large, necessitating robust frameworks to protect individual rights, an aspect essential in infectious disease research. Global collaboration emerges as a critical pillar in our response to emerging infectious diseases, fortified by the predictive prowess of mathematical models enriched by nanotechnology. The synergy of interdisciplinary collaboration, training the next generation to bridge mathematical rigor, biology, and epidemiology, promises accelerated discoveries and robust models that account for real-world complexities, fostering innovation and exploration in the field. In this intricate review, mathematical modeling in viral transmission dynamics and epidemiology serves as a guiding beacon, illuminating the path toward precision interventions, global preparedness, and the collective endeavor to safeguard human health, resonating with the aim of advancing knowledge in gene regulation and expression.


Subject(s)
Communicable Diseases , Humans , Communicable Diseases/epidemiology , Models, Theoretical , Mathematics
10.
Article in English | MEDLINE | ID: mdl-38279763

ABSTRACT

Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.

11.
Expert Opin Drug Deliv ; 21(2): 309-324, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38284386

ABSTRACT

INTRODUCTION: The resistance to chemotherapy is a significant hurdle in breast cancer treatment, prompting the exploration of innovative strategies. This review discusses the potential of dual-loaded liposomal carriers to combat chemoresistance and improve outcomes for breast cancer patients. AREAS COVERED: This review discusses breast cancer chemotherapy resistance and dual-loaded liposomal carriers. Drug efflux pumps, DNA repair pathways, and signaling alterations are discussed as chemoresistance mechanisms. Liposomes can encapsulate several medicines and cargo kinds, according to the review. It examines how these carriers improve medication delivery, cancer cell targeting, and tumor microenvironment regulation. Also examined are dual-loaded liposomal carrier improvement challenges and techniques. EXPERT OPINION: The use of dual-loaded liposomal carriers represents a promising and innovative strategy in the battle against chemotherapy resistance in breast cancer. This article has explored the various mechanisms of chemoresistance in breast cancer, emphasizing the potential of dual-loaded liposomal carriers to overcome these challenges. These carriers offer versatility, enabling the encapsulation and precise targeting of multiple drugs with different modes of action, a crucial advantage when dealing with the complexity of breast cancer treatment.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Humans , Female , Liposomes , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Drug Carriers/therapeutic use , Drug Delivery Systems/methods , Tumor Microenvironment
12.
J Liposome Res ; 34(1): 178-202, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37378553

ABSTRACT

Liposomes are spherical lipidic nanocarriers composed of natural or synthetic phospholipids with a hydrophobic bilayer and aqueous core, which are arranged into a polar head and a long hydrophobic tail, forming an amphipathic nano/micro-particle. Despite numerous liposomal applications, their use encounters many challenges related to the physicochemical properties strongly affected by their constituents, colloidal stability, and interactions with the biological environment. This review aims to provide a perspective and a clear idea about the main factors that regulate the liposomes' colloidal and bilayer stability, emphasising the roles of cholesterol and its possible alternatives. Moreover, this review will analyse strategies that offer possible approaches to provide more stable in vitro and in vivo liposomes with enhanced drug release and encapsulation efficiencies.


Subject(s)
Liposomes , Phospholipids , Liposomes/chemistry , Phospholipids/chemistry , Cholesterol/chemistry , Drug Stability
13.
Int J Pharm ; 650: 123678, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38065344

ABSTRACT

The primary objective of this study was to enhance the effectiveness of the protease inhibitor antiretroviral drug by designing a novel delivery system using carboxylated multiwalled carbon nanotubes (COOH-MWCNTs). To achieve this, Fosamprenavir calcium (FPV), a prodrug of amprenavir known for inhibiting the proteolytic cleavage of immature virions, was selected as the protease inhibitor antiretroviral drug, and loaded onto COOH-MWCNTs using a direct loading method. The structural specificity of the drug-loaded MWCNTs, the percent entrapment efficiency, and in vitro drug release were rigorously evaluated for the developed formulation, referred to as FPV-MWCNT. Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and atomic force microscopy (AFM) techniques were employed to confirm the structural integrity and specificity of the FPV-MWCNT formulation. The results demonstrated a remarkable entrapment efficiency of 79.57 ± 0.4 %, indicating the successful loading of FPV onto COOH-MWCNTs. FE-SEM and AFM analyses further confirmed the well-dispersed and elongated structure of the FPV-MWCNT formulation, without any signs of fracture, ensuring the stability and integrity of the drug delivery system. Moreover, particle size analysis revealed an average size of 290.1 nm, firmly establishing the nanoscale range of the formulation, with a zeta potential of 0.230 mV, signifying the system's colloidal stability. In vitro drug release studies conducted in methanolic phosphate buffer saline (PBS) at pH 7.4 and methanolic acetate buffer at pH 5 demonstrated sustained drug release from the FPV-MWCNT formulation. Over a period of 96 h, the formulation exhibited a cumulative drug release of 91.43 ± 2.3 %, showcasing the controlled and sustained release profile. Furthermore, hemolysis studies indicated a notable reduction in the toxicity of both FPV and MWCNT upon conjugation, although the percent hemolysis increased with higher concentrations, suggesting the need for careful consideration of dosage levels. In conclusion, the findings from this study underscore the potential of the FPV-MWCNT formulation as an effective and promising drug-conjugated system for delivering antiretroviral drugs. The successful encapsulation, sustained drug release, and reduced toxicity make FPV-MWCNT a compelling candidate for enhancing the therapeutic efficacy of protease inhibitor antiretroviral drugs in the treatment of HIV. The developed delivery system holds great promise for future advancements in HIV treatment and paves the way for further research and development in the field of drug delivery utilizing carbon nanotube-based systems.


Subject(s)
Anti-Infective Agents , HIV Infections , Nanotubes, Carbon , Humans , Nanotubes, Carbon/chemistry , Protease Inhibitors , Hemolysis , Drug Delivery Systems , Enzyme Inhibitors , Antiviral Agents
14.
Chem Biodivers ; 21(2): e202301470, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38161147

ABSTRACT

Doxorubicin (DOX) is widely used against solid tumors. Niosomes are self-assembled nanocarriers of non-ionic surfactants. DOX loaded into cationic niosomes (DOX-Nio) was prepared via thin film hydration method. DOX-Nio was then decorated with a hyaluronic acid (DOX-HA-Nio) via electrostatic interaction. DOX-Nio and DOX-HA-Nio displayed a particle size of 120.0±1.02 and 182.9±2.3 nm, and charge of + 35.5±0.15 and -15.6±0.25 mV, respectively, with PDI < 0.3. DOX-HA-Nio showed a good stability regarding size and charge over 4 weeks at 4 °C and maintain their integrity after lyophilization. HPLC results showed a 94.1±4.2 % encapsulation efficiency of DOX with good entrapment and slow, prolonged DOX release even after 48 hrs. Cell viability assay showed an IC50 of 14.26 nM for the DOX-HA-Nio against MCF-7 cell line with micromolar IC50 results against CD-44 negative cell lines (NIH/3T3). DOX-HA-Nio was proven to be an effective, targeted nanocarrier for DOX against MCF-7 cell line.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Liposomes , Hyaluronic Acid , Doxorubicin/pharmacology , MCF-7 Cells
15.
Cell Signal ; 113: 110911, 2024 01.
Article in English | MEDLINE | ID: mdl-37805102

ABSTRACT

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


Subject(s)
Maltose , Neoplasms , Humans , Cell Hypoxia , Maltose/pharmacology , Maltose/therapeutic use , Mannose/pharmacology , Mannose/therapeutic use , Neoplasms/metabolism , Hypoxia , Glucose/pharmacology , Tumor Microenvironment , Drug Resistance
16.
Cell Signal ; 115: 111013, 2024 03.
Article in English | MEDLINE | ID: mdl-38113978

ABSTRACT

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


Subject(s)
Gastrointestinal Microbiome , Gastrointestinal Neoplasms , Microbiota , Infant, Newborn , Humans , Bacteria/genetics
17.
Pharmaceutics ; 15(12)2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38140117

ABSTRACT

Throughout the years, considerable progress has been made in methods for delivering drugs directly to the lungs, which offers enhanced precision in targeting specific lung regions. Currently, for treatment of lung cancer, the prevalent routes for drug administration are oral and parenteral. These methods, while effective, often come with side effects including hair loss, nausea, vomiting, susceptibility to infections, and bleeding. Direct drug delivery to the lungs presents a range of advantages. Notably, it can significantly reduce or even eliminate these side effects and provide more accurate targeting of malignancies. This approach is especially beneficial for treating conditions like lung cancer and various respiratory diseases. However, the journey towards perfecting inhaled drug delivery systems has not been without its challenges, primarily due to the complex structure and functions of the respiratory tract. This comprehensive review will investigate delivery strategies that target lung cancer, specifically focusing on non-small-cell lung cancer (NSCLC)-a predominant variant of lung cancer. Within the scope of this review, active and passive targeting techniques are covered which highlight the roles of advanced tools like nanoparticles and lipid carriers. Furthermore, this review will shed light on the potential synergies of combining inhalation therapy with other treatment approaches, such as chemotherapy and immunotherapy. The goal is to determine how these combinations might amplify therapeutic results, optimizing patient outcomes and overall well-being.

18.
Bioanalysis ; 15(23): 1393-1405, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37847056

ABSTRACT

This study aims to develop and validate an HPLC technique for the determination of fulvestrant and disulfiram in liposomes. Encapsulation of both drugs into liposomes may improve their anticancer potential. Validation was performed following the International Conference on Harmonization guidelines for specificity, linearity, limit of detection, limit of quantification, precision, accuracy and robustness. Method specificity displayed no interference and linearity over 25-200 and 12.5-100 µg/ml for fulvestrant and disulfiram, respectively. Precision and accuracy exhibited a low relative standard deviation (<1.70%) and appropriate recovery. The validated method could be designated as a proper method for the simultaneous determination of fulvestrant and disulfiram in liposomes. The liposomes displayed 148.5 ± 5.1 nm size. The encapsulation efficiencies were 73.52 and 50.50% for fulvestrant and disulfiram, respectively.


Subject(s)
Disulfiram , Liposomes , Limit of Detection , Fulvestrant , Chromatography, High Pressure Liquid/methods
19.
Article in English | MEDLINE | ID: mdl-37668757

ABSTRACT

Silver nanoparticles (AgNPs) possess unmatched chemical, biological, and physical properties that make them unique compounds as antimicrobial, antifungal, antiviral, and anticancer agents. With the increasing drug resistance, AgNPs serve as promising entities for targeted drug therapy against several bacterial, fungal, and viral components. In addition, AgNPs also serve as successful anticancer agents against several cancers, including breast, prostate, and lung cancers. Several works in recent years have been done towards the development of AgNPs by using plant extracts like flowers, leaves, bark, root, stem, and whole plant parts. The green method of AgNP synthesis thus has several advantages over chemical and physical methods, especially the low cost of synthesis, no toxic byproducts, eco-friendly production pathways, can be easily regenerated, and the bio-reducing potential of plant derived nanoparticles. Furthermore, AgNPs are biocompatible and do not harm normally functioning human or host cells. This review provides an exhaustive overview and potential of green synthesized AgNPs that can be used as antimicrobial, antifungal, antiviral, and anticancer agents. After a brief introduction, we discussed the recent studies on the development of AgNPs from different plant extracts, including leaf parts, seeds, flowers, stems, bark, root, and whole plants. In the following section, we highlighted the different therapeutic actions of AgNPs against various bacteria, fungi, viruses, and cancers, including breast, prostate, and lung cancers. We then highlighted the general mechanism of action of AgNPs. The advantages of the green synthesis method over chemical and physical methods were then discussed in the article. Finally, we concluded the review by providing future perspectives on this promising field in nanotechnology.

20.
Environ Res ; 238(Pt 2): 116909, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37673119

ABSTRACT

Xenobiotic pollution in environment is a potential risk to marine life, and human health. Nanobiotechnology is an advanced and emerging solution for the removal of environmental pollutants. Adsorption-based technologies are being used to alleviate the global prevalence of xenobiotics like dyes, due to their high efficacy and cost effectiveness. Current study explored the potential of nanobiochar syntehsized via ultrasonication and centrifugation from rice husk for dye removal from water. It involves the synthesis of nanobiochar from rice husk biochar for removal of Safranin, Malachite green, and a mixture of both from aqueous water. Biochar was synthesized through pyrolysis at 600 °C for 2 h. To convert it into nanobiochar, sonication and centrifugation techniques were applied. The yield obtained was 27.5% for biochar and 0.9% for nanobiochar. Nanobiochar analysis through Fourier-Transform Spectrometer (FTIR), X-ray Power Diffraction (XRD) and scanning electron microscopy (SEM) suggested its crystalline nature having minerals rich in silicon, with a cracked and disintegrated carbon structure due to high temperature and processing treatments. Removal of dyes by nanobiochar was evaluated by changing different physical parameters i.e., nanobiochar dose, pH, and temperature. Pseudo-first order model and pseudo-second order model were applied to studying the adsorption kinetics mechanism. Kinetics for adsorption of dyes followed the pseudo-second order model suggesting the removal of dyes by process of chemical sorption. High adsorption was found at a higher concentration of nanobiochar, high temperature, and neutral pH. Maximum elimination percentages of safranin, malachite green, and a mixture of dyes were obtained as 91.7%, 87.5%, and 85% respectively. We conclude that nanobiochar could be a solution for dye removal from aqueous media.


Subject(s)
Oryza , Water Pollutants, Chemical , Humans , Oryza/chemistry , Water , Coloring Agents/chemistry , Adsorption , Kinetics , Water Pollutants, Chemical/analysis , Hydrogen-Ion Concentration
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