Niosomes as a Promising Therapeutic Approach against Colorectal Cancer: A Focus on the Delivery of Chemotherapeutics and Natural Products.

Nanotechnology has emerged as an effective approach to cancer treatment, including Colorectal Cancer (CRC). While conventional treatments, such as chemotherapeutic agents, are used to manage CRC, their efficacy can be improved using drug delivery systems that enhance their bioavailability and reduce side effects. Niosomes, polymeric nanoparticles, have shown promise as biocompatible vehicles that can transport hydrophilic and lipophilic molecules. This can result in reduced drug dosage and increased efficacy. This review examines the use of niosomal formulations as a delivery platform for treating CRC and provides practical insights into their clinical applications.

Personalized Approaches to Cardiovascular Disease: Insights into FDA-Approved Interventions and Clinical Pharmacogenetics.

Cardiovascular diseases place a considerable burden on global health systems, contributing to high rates of morbidity and mortality. Current approaches to detecting and treating Cardiovascular Diseases (CVD) often focus on symptomatic management and are initiated after the disease has progressed. Personalized medicine, which tailors medical interventions to individual characteristics, has emerged as a promising strategy for improving cardiovascular health outcomes. This article provides an overview of personalized medicine in the context of CVD, with a specific emphasis on FDA-approved interventions. It explores the potential benefits, challenges, and future directions of personalized medicine in cardiovascular disorders. By reviewing the advancements in this field, this article underscores the importance of early detection, intervention, and innovative treatment options in reducing the impact of CVD on individuals and society.

Advancing Novel Strategies against Post-surgical Tendon Adhesion Bands, Exploring New Frontiers.

Current interest in adhesion formation stems from its global impact on the function and quality of life, spanning a spectrum of subtle impairments to significant disabilities, based on the affected area and the extent of adhesion. Yet therapeutic agents are restricted to prophylactic anti-inflammatories, revision surgeries, and biological and physical techniques, none of which grant a decent outcome. Recent advancements in tissue- engineered biomaterials, drug delivery systems, and fabricating technologies such as nanoparticles, hydrogels, and weaving or braiding demonstrate potential for improved outcomes. However, none of the mentioned methods have reliable outcomes, thus this study aims to elucidate the mechanisms involved in the pathophysiology of tendon adhesion and post-surgical adhesion band formation (PSAB), with a closer look at inflammatory pathways stimulating the process. This article consolidates information on diverse therapeutic and prophylactic methods and cutting-edge technologies, aiming to provide a comprehensive update on this topic, and providing researchers an avenue for new and innovative ideas for further investigations.

G-Protein Signaling Modulator 2 as a Potential Biomarker in Colorectal Cancer: Integrative Analysis Using Genetic Profiling and Pan-Cancer Studies.

Colorectal cancer (CRC) imposes a significant healthcare burden globally, prompting the quest for innovative biomarkers to enhance diagnostic and therapeutic strategies. This study investigates the G-protein signaling modulator (GPSM) family across several cancers and presents a comprehensive pan-cancer analysis of the GPSM2 gene across several gastrointestinal (GI) cancers. Leveraging bioinformatics methodologies, we investigated GPSM2 expression patterns, protein interactions, functional enrichments, prognostic implications, genetic alterations, and immune infiltration associations. Furthermore, the expression of the GPSM2 gene was analyzed using real-time analysis. Our findings reveal a consistent upregulation of GPSM2 expression in all GI cancer datasets analyzed, suggesting its potential as a universal biomarker in GI cancers. Functional enrichment analysis underscores the involvement of GPSM2 in vital pathways, indicating its role in tumor progression. The prognostic assessment indicates that elevated GPSM2 expression correlates with adverse overall and disease-free survival outcomes across multiple GI cancer types. Genetic alteration analysis highlights the prevalence of mutations, particularly missense mutations, in GPSM2. Furthermore, significant correlations between GPSM2 expression and immune cell infiltration are observed, suggesting its involvement in tumor immune evasion mechanisms. Collectively, our study underscores the multifaceted role of GPSM2 in GI cancers, particularly in CRC, emphasizing its potential as a promising biomarker for prognosis and therapeutic targeting. Further functional investigations are warranted to elucidate its clinical utility and therapeutic implications in CRC management.

Colorectal Cancer Stem Cell Biomarkers: Biological Traits and Prognostic Insights.

Due to self-renewal, differentiation, and limitless proliferation properties, Cancer Stem Cells (CSCs) increase the probability of tumor development. These cells are identified by using CSC markers, which are highly expressed proteins on the cell surface of CSCs. Recently, the therapeutic application of CSCs as novel biomarkers improved both the prognosis and diagnosis outcome of colorectal Cancer. In the present review, we focused on a specific panel of colorectal CSC markers, including LGR5, ALDH, CD166, CD133, and CD44, which offers a targeted and comprehensive analysis of their functions. The selection criteria for these markersCancer were based on their established significance in Colorectal Cancer (CRC) pathogenesis and clinical outcomes, providing novel insights into the CSC biology of CRC. Through this approach, we aim to elevate understanding and stimulate further research for developing effective diagnostic and therapeutic strategies in CRC.

Wortmannin Inhibits Cell Growth and Induces Apoptosis in Colorectal Cancer Cells by Suppressing the PI3K/AKT Pathway.

BACKGROUND: Colorectal cancer (CRC) remains a significant contributor to mortality, often exacerbated by metastasis and chemoresistance. Novel therapeutic strategies are imperative to enhance current treatments. The dysregulation of the PI3K/Akt signaling pathway is implicated in CRC progression. This study investigates the therapeutic potential of Wortmannin, combined with 5-fluorouracil (5-FU), to target the PI3K/Akt pathway in CRC. METHODS: Anti-migratory and antiproliferative effects were assessed through wound healing and MTT assays. Apoptosis and cell cycle alterations were evaluated using Annexin V/Propidium Iodide Apoptosis Assay. Wortmannin's impact on the oxidant/antioxidant equilibrium was examined via ROS, SOD, CAT, MDA, and T-SH levels. Downstream target genes of the PI3K/AKT pathway were analyzed at mRNA and protein levels using RTPCR and western blot, respectively. RESULTS: Wortmannin demonstrated a significant inhibitory effect on cell proliferation, modulating survivin, cyclinD1, PI3K, and p-Akt. The PI3K inhibitor attenuated migratory activity, inducing E-cadherin expression. Combined Wortmannin with 5-FU induced apoptosis, increasing cells in sub-G1 via elevated ROS levels. CONCLUSION: This study underscores Wortmannin's potential in inhibiting CRC cell growth and migration through PI3K/Akt pathway modulation. It also highlights its candidacy for further investigation as a promising therapeutic option in colorectal cancer treatment.

The Therapeutic Application of Hydrogen in Cancer: The Potential and Challenges.

Hydrogen therapy has emerged as a possible approach for both preventing and treating cancer. Cancers are often associated with oxidative stress and chronic inflammation. Hydrogen, with its unique physiological functions and characteristics, exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties, making it an attractive candidate for cancer treatment. Through its ability to mitigate oxidative damage, modulate inflammatory responses, and sustain cellular viability, hydrogen demonstrates significant potential in preventing cancer recurrence and improving treatment outcomes. Preclinical studies have shown the efficacy of hydrogen therapy in several cancer types, highlighting its ability to enhance the effectiveness of conventional treatments while reducing associated side effects. Furthermore, hydrogen therapy has been found to be safe and well-tolerated in clinical settings. Nonetheless, additional investigations are necessary to improve a comprehensive understanding of the mechanisms underlying hydrogen's therapeutic potential and refine the administration and dosage protocols. However, further clinical trials are still needed to explore its safety profile and capacity. In aggregate, hydrogen therapy represents an innovative and promising treatment for several malignancies.

Repurposing of Angiotensin-converting-enzyme Inhibitor on Prevention of Post-surgical Tendon Adhesion.

BACKGROUND: Formation of adhesion bands is a frequent clinical complication after tendon injury or surgery with limited treatment options. This study investigates the repurposing of Angiotensin-Converting-Enzyme Inhibitor (ACEI) in attenuating post-operative tendon-sheath adhesion bands in an Achilles tendon rat model. METHODS: Structural, mechanical, histological, and biochemical characteristics of the Achilles tendons were compared in the presence and absence of oral ACEI (enalapril) using the Achilles tendon adhesion (TA) model in rats. Inflammation and total fibrosis of tendon tissues were compared between groups using molecular investigations along with macroscopic and histological scoring methods. RESULTS: ACEI significantly alleviated the severity, length, and density of Achilles TAs. Moreover, histopathological changes, recruitment of inflammatory cells, and inflammation were significantly decreased in post-operative tissue samples as quantified with the Moran scoring model. We showed that ACEI treatment elicits a potent anti-fibrotic effect on tendon tissue samples, as illustrated by decreasing the severity and extent of the formed fibrotic tissue and collagen accumulation at the site of surgery when scored either by Tang or Ishiyama grading systems. The H&E staining showed no histopathological changes or damage to the principal organs. CONCLUSION: Our results showed that ACEI is a safe and effective therapeutic candidate with potent immunomodulatory and anti-fibrotic features to alleviate surgery-induced development of fibrotic adhesive tissue. However, its efficacy needs to be further validated in clinical studies.

The Application of Nanotechnological Therapeutic Platforms against Gynecological Cancers.

Gynecological cancers (GCs), ovarian, cervical, and endometrial/uterine cancers, are often associated with poor outcomes. Despite the development of several therapeutic modalities against GCs, the effectiveness of the current therapeutic approaches is limited due to their side effects, low therapeutic index, short halflife, and resistance to therapy. To overcome these limitations, nano delivery-based approaches have been introduced with the potential of targeted delivery, reduced toxicity, controlled release, and improved bioavailability of various cargos. This review summarizes the application of different nanoplatforms, such as lipid-based, metal-based, and polymeric nanoparticles, to improve the chemo/radio treatments of GC. In the following work, the use of nanoformulated agents to fight GCs has been mentioned in various clinical trials. Although nanosystems have their own challenges, the knowledge highlighted in this article could provide deep insight into translations of NPs approaches to overcome GCs.

Therapeutic potency of A1 adenosine receptor antagonists in the treatment of cardiovascular diseases, current status and perspectives.

BACKGROUND: Cardiomyocytes form, transport, and metabolize the omnipresent metabolite adenosine. Depending upon the adenosine concentrations and the pharmacological properties of receptor subtypes, adenosine exerts (patho)physiological responses in the cardiovascular system. The objective of this review is to present different protective mechanisms of A1-adenosine receptor inhibitors in cardiovascular diseases. METHODS AND RESULTS: Literature references were collected and sorted using relevant keywords and key phrases as search terms in scientific databases such as Web of Science, PubMed and Google Scholar. A1 adenosine receptor regulates free fatty acid metabolism, lipolysis, heart rate, blood pressure, and cardiovascular toxicity. The evidence clearly supporting the therapeutic potency of pharmacological A1 adenosine receptors agonists and antagonists in modulating cardiovascular risk factor parameters and treatment of cardiovascular diseases. CONCLUSION: This review summarizes the protective role of pharmacological A1-adenosine receptor regulators in the pathogenesis of cardiovascular diseases for a better management of cardiovascular diseases.

Genetic Determinants of Response to Statins in Cardiovascular Diseases.

Despite extensive efforts to identify patients with cardiovascular disease (CVD) who could most benefit from the treatment approach, patients vary in their benefit from therapy and propensity for adverse drug events. Genetic variability in individual responses to drugs (pharmacogenetics) is considered an essential determinant in responding to a drug. Thus, understanding these pharmacogenomic relationships has led to a substantial focus on mechanisms of disease and drug response. In turn, understanding the genomic and molecular bases of variables that might be involved in drug response is the main step in personalized medicine. There is a growing body of data evaluating drug-gene interactions in recent years, some of which have led to FDA recommendations and detection of markers to predict drug responses (e.g., genetic variant in VKORC1 and CYP2C9 genes for prediction of drug response in warfarin treatment). Also, statins are widely prescribed drugs for the prevention of CVD. Atorvastatin, fluvastatin, rosuvastatin, simvastatin, and lovastatin are the most common statins used to manage dyslipidemia. This review provides an overview of the current knowledge on the pharmacogenetics of statins, which are being used to treat cardiovascular diseases.

Photodynamic Therapy as a Desirable Approach in the Treatment of Colorectal Cancer, with Special Focus on Photodynamic Nanotherapeutics in Immunotherapy.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide; however, there is not a convincing treatment for this disease. Limitations of conventional CRC therapies force scientists to develop novel treatment concepts for both primary care alongside adjuvant therapy. Photodynamic therapy (PDT) has been introduced as a promising therapeutic procedure for CRC mediated through theranostic principle in which special dyes, photosensitizers (PSs), are excited by near-infrared (NIR) and visible light. Recent studies showed that PDT has synergistic effects in combination with chemotherapy or immunotherapy in the treatment of CRC patients. Of note, nanoformulation of PS or immunotherapeutic agents could augment the PDT effectiveness. In this review, we summarize PDT application in CRC management with a special focus on the nanoparticles-based delivery system from the perspective of targeting deeper CRC and increased PDT efficiency, which could provide a desirable approach for clinical translation.

Recent Progress in the Application of Exosome Analysis in Ovarian Cancer Management.

Exosomes are very small (nano-sized) vesicles participating in tumor development by involvement in intercellular communication mediated by transferring biocomponents. Exosomes appear to play vital roles in various cancer development, such as ovarian cancer, a common malignancy in women. Several hallmarks of ovarian cancer are reported to be affected by the exosome-- mediated cellular cross-talk, including modulating peritoneal dissemination and chemoresistance. Since the expression of some biomolecules, such as miRNAs and mRNA, is changed in ovarian cancer, these exo-biomolecules can be applied as prognostic, diagnostic, and therapeutic biomarkers. Also, the selective loading of specific chemotherapeutic agents into exosomes highlights these biocarries as potential delivery devices. Exosomes could be artificially provided and engineered to better target the site of interest in ovarian cancer. In the present review, we summarize the notable achievement of exosome application in ovarian cancer management to gain applicable transitional insight against this cancer.

Microbiome as a biomarker and therapeutic target in pancreatic cancer.

Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC.

Synthesis and evaluation of gene delivery vectors based on PEI-modified metal-organic framework (MOF) nanoparticles.

Objectives: Zirconium-based metal-organic frameworks (MOFs) nanostructures, due to their capability of easy surface modification, are considered interesting structures for delivery. In the present study, the surfaces of UIO-66 and NH2-UIO-66 MOFs were modified by polyethyleneimine (PEI) 10000 Da, and their efficiency for plasmid delivery was evaluated. Materials and Methods: Two different approaches, were employed to prepare surface-modified nanoparticles. The physicochemical characteristics of the resulting nanoparticles, as well as their transfection efficiency and cytotoxicity, were investigated on the A549 cell line. Results: The sizes of DNA/nanocarriers for PEI-modified UIO-66 (PEI-UIO-66) were between 212-291 nm and 267-321 nm for PEI 6-bromohexanoic acid linked UIO-66 (PEI-HEX-UIO-66). The zeta potential of all was positive with the ranges of +16 to +20 mV and +23 to +26 mV for PEI-UIO-66 and PEI-HEX-UIO-66, respectively. Cellular assay results showed that the PEI linking method had a higher rate of gene transfection efficiency with minimal cytotoxicity than the wet impregnation method. The difference between transfection of modified nanoparticles compared to the PEI 10 kDa was not significant but the PEI-HEX-UIO-66 showed less cytotoxicity. Conclusion: The present study suggested that the post-synthetic modification of MOFs with PEI 10000 Da through EDC/NHS+6-bromohexanoic acid reaction can be considered as an effective approach for modifying MOFs' structure in order to obtain nanoparticles with better biological function in the gene delivery process.

The Potential Therapeutic Applications of CRISPR/Cas9 in the Treatment of Gastrointestinal Cancers.

Gastrointestinal (GI) cancer is one the most prevalent types of cancer. Despite current chemotherapy's success, patients with GI cancer continue to have a dismal outcome. The onset and progression of cancer are caused by alterations and the abnormal expression of several families of genes, like tumor-suppressor genes, oncogenes, and chemotherapy-resistant genes. The final purpose of tumor therapy is to inhibit cellular development by modifying mutations and editing the irregular expression of genes It has been reported that CDH1, TP53, KRAS, ARID1A, PTEN, and HLA-B are the commonly mutated genes in GI cancer. Gene editing has become one potential approach for cases with advanced or recurrent CRC, who are nonresponsive to conventional treatments and a variety of driver mutations along with progression cause GI progression. CRISPR/Cas9 technique is a reliable tool to edit the genome and understand the functions of mutations driving GI cancer development. CRISPR/Cas9 can be applied to genome therapy for GI cancers, particularly with reference to molecular-targeted medicines and suppressors. Moreover, it can be used as a therapeutic approach by knocking in/out multiple genes. The use of CRISPR/ Cas9 gene editing method for GI cancer therapy has therefore resulted in some improvements. There are several research works on the role of CRISPR/Cas9 in cancer treatment that are summarized in the following separate sections. Here, the use of CRISPR/Cas9-based genome editing in GI and the use of CRISPR/Cas9 is discussed in terms of Targeting Chemotherapy Resistance-related Genes like; KRAS, TP53, PTEN, and ARID1A.

Pegylated nanoliposomal cisplatin ameliorates chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse effect of cisplatin. The current study aimed to determine whether PEGylated nanoliposomal cisplatin can limit CIPN in an animal model. METHODS: Cisplatin-loaded PEGylated liposome nanoparticles (Cis-PL) were produced as a combination of lecithin, cholesterol, and DSPE-mPEG2000 in a molar ratio of 50:45:5 and were characterized by polydispersity index (PDI), zeta potential, Field emission scanning electron microscopy (FESEM) analysis, as well as encapsulation efficiency (EE). Fifteen male rats were provided and randomly divided into 3 groups including Cis-PL group, cisplatin group, and control group. Behavioural tests (hot-plate test and acetone drop test) were used for evaluating CIPN. Moreover, oxidative stress markers and histopathological analysis were applied. Treatment-related toxicity was assessed by haematological analysis as well as liver and renal function tests. RESULTS: Cis-PL had an average particle size of 125.4, PDI of 0.127, and zeta potential of -40.9 mV. Moreover, the Cis-PL exhibited a high EE as well as low levels of leakage rate at 25 °C. In a hot-plate test, paw withdrawal latency was longer in Cis-PL group in comparison to rats treated with cisplatin. A lower number of withdrawal responses was detected during acetone drop test in Cis-PL group than in cisplatin-treated rats. Assessment of oxidative stress markers showed that Cis-PL could improve oxidative stress. Additionally, histopathological assessment demonstrated that the number of satellite cells was significantly reduced in the dorsal root ganglion (DRG) of Cis-PL-treated rats compared with those treated with cisplatin. The cisplatin group had elevated white blood cells counts, reduced platelet counts, and higher levels of bilirubin, ALT (alanine aminotransferase, and AST (aspartate aminotransferase), and creatinine compared with the control group, which was ameliorated in Cis-PL group. CONCLUSIONS: Data from the current study support the previous hypothesis that Cisplatin-loaded PEGylated liposome could be a promising solution for CIPN in the future by modulating oxidative stress and preventing glial cell activation in DRG, suggesting further clinical studies to investigate the efficacy of this agent and its potential application in clinical practice.

The advancing of polymeric core-shell ZnO nanocomposites containing 5-fluorouracil for improving anticancer activity in colorectal cancer.

The study investigated the use of 5-fluorouracil-loaded ZnO nanocomposites (5-FU/Gd-ZnO NCs) as a potential treatment for cancer. 5-FU is a commonly used drug for cancer treatment but has undesirable side effects. The materials were characterized using various techniques, including PXRD, FTIR, FESEM, TEM, DLS, £-potential, and AFM. The data showed that the nanocomposites had a plate-like agglomeration with particle diameters ranging from 317.6 to 120.1 nm. The IC50 value of 5-FU-ZnO, which inhibits cell growth, was found to be 1.85 ppm. The effects of 5-FU-ZnO on inflammatory markers were also examined. While 5-FU increased the levels of TNF-a and IL-1b, the nanocomposites were able to reduce these levels. Additionally, the 5-FU/Gd-ZnO-NCs group showed an increase in thiol levels and a decrease in catalase and superoxide dismutase levels. Flow cytometry results showed that 5-FU, ZnO-NCs, and 5-FU/Gd-ZnO-NCs did not have any additive or synergistic effects on the suppression or eradication of cancer cells. In vivo, experiments showed that the 5-FU/Gd-ZnO NCs had similar necrotic characteristics and reduced fibrosis and collagen deposition compared to the free medication. The nanocomposites also exhibited higher antioxidative activity and lower inflammatory responses compared to the 5-FU group. It was shown that 5-FU/Gd-ZnO-NCs successfully inhibit cell proliferation. The in vivo results were comparable to those obtained with free 5-FU, suggesting the potential of these nanocomposites as therapeutic agents.

The prognostic, diagnostic, and therapeutic impact of Long noncoding RNAs in gastric cancer.

Gastric cancer (GC), ranking as the third deadliest cancer globally, faces challenges of late diagnosis and limited treatment efficacy. Long non-coding RNAs (lncRNAs) emerge as valuable treasured targets for cancer prognosis, diagnosis, and therapy, given their high specificity, convenient non-invasive detection in body fluids, and crucial roles in diverse physiological and pathological processes. Research indicates the significant involvement of lncRNAs in various aspects of GC pathogenesis, including initiation, metastasis, and recurrence, underscoring their potential as novel diagnostic and prognostic biomarkers, as well as therapeutic targets for GC. Despite existing challenges in the clinical application of lncRNAs in GC, the evolving landscape of lncRNA molecular biology holds promise for advancing the survival and treatment outcomes of gastric cancer patients. This review provides insights into recent studies on lncRNAs in gastric cancer, elucidating their molecular mechanisms and exploring the potential clinical applications in GC.

Therapeutic Potential of Targeting Transforming Growth Factor-beta (TGF-ß) and Programmed Death-ligand 1 (PD-L1) in Pancreatic Cancer.

Pancreatic cancer (PC) is one the most lethal malignancies worldwide affecting around half a million individuals each year. The treatment of PC is relatively difficult due to the difficulty in making an early diagnosis. Transforming growth factor-beta (TGF-ß) is a multifunctional factor acting as both a tumor promoter in early cancer stages and a tumor suppressor in advanced disease. Programmed death-ligand 1 (PD-L1) is a ligand of programmed death-1 (PD-1), an immune checkpoint receptor, allowing tumor cells to avoid elimination by immune cells. Recently, targeting the TGF-ß signaling and PD-L1 pathways has emerged as a strategy for cancer therapy. In this review, we have summarized the current knowledge regarding these pathways and their contribution to tumor development with a focus on PC. Moreover, we have reviewed the role of TGF-ß and PD-L1 blockade in the treatment of various cancer types, including PC, and discussed the clinical trials evaluating TGF-ß and PD-L1 antagonists in PC patients.