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5-Fluorouracil (5-FU) is a first-line treatment for colorectal cancer, but side effects such as severe diarrhea are common in clinical use and have been linked to its induction of normal cell senescence. Chloramphenicol (CAP) is an antibiotic commonly used to treat typhoid or anaerobic infections, but its senescence-related aspects have not been thoroughly investigated. Here, we used 5-FU to induce senescence in human umbilical vein endothelial cells (HUVECs) and investigated the relationship between CAP and cellular senescence at the cellular level. In a model of cellular senescence induced by 5-FU treatment, we discovered that CAP treatment reversed the rise in the percentage of senescence-associated galactosidase (SA-β-gal)-positive cells and decreased the expression of senescence-associated proteins (p16), senescence-associated genes (p21), and senescence-associated secretory phenotypes (SASPs: IL-6, TNF-α). In addition, CAP subsequently restored the autophagic process inhibited by 5-FU and upregulated the levels of autophagy-related proteins. Mechanistically, we found that CAP restored autophagic flux by inhibiting the mTOR pathway, which in turn alleviated FU-induced cellular senescence. Our findings suggest that CAP may help prevent cellular senescence and restore autophagy, opening up new possibilities and approaches for the clinical management of colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Cancer and diabetes mellitus are quite common diseases found together worldwide. A considerable amount of evidence is available for the rapid development and presentation of various types of cancer in the type 2 diabetes mellitus (DM2) population as compared with the population without diabetes. The objective of the study is to formulate and evaluate 5-fluorouracil (5-FU) and metformin (MET) nanoparticles (NPs) and to establish the characteristic features of the biodegradable NPs. 5-FU and MET NPs with chitosan as a biodegradable polymer were formulated by the ionotropic cross-linking method. 0.25 gm of MET and 0.25 gm of 5-FU were dissolved in 100 ml of distilled water, and stock solution was prepared. 5 ml of stock solution was slowly mixed into the chitosan solution to obtain the mixture of drugs and chitosan. The tripolyphosphate reserve liquid was dripped slowly into the chitosan solution with constant stirring until the opaline appearance was noticed in the mixture, then filtered, and dried. The NPs were evaluated for their physical properties and drug release kinetics. Cell proliferation assay was done using human colorectal carcinoma cell line (HCT 116). Results: The formulation composed of 1.5 w/v of chitosan, 0.25 w/v of MET, and 5-FU had an average particle diameter of 198.7 nm. The polydispersity index was 0.757. Thermal and infrared spectroscopy results indicated the drugs and polymers selected for the formulation were unique without any identifiable interaction. The NPs were spherical in appearance, with numerous pours on the surface, which was evident when microscopically examined. Uniformity in drug release was observed, and the formulation demonstrated excellent release kinetics. HTC 116 cell line confirmed that the maximum percentage of cell death and minimum viability of cells were observed while using the combination of MET and 5-FU-NPs as compared to the pure MET or 5-FU alone. Conclusion: MET and 5-FU-loaded chitosan NPs were found to have excellent physiochemical properties, particle size, and drug release from the polymer in a controlled manner. Half-maximal inhibitory concentration value (IC50) of MET and 5-FU-NPs was found to be significantly less as compared to MET and 5-FU alone or the combination. [ABSTRACT FROM AUTHOR]

Berberine (BER) is a naturally occurring alkaloid with a multitude of beneficial effects on human health. Although it is one of the most studied phytochemicals, its curative effect against ovarian damage caused by 5-fluorouracil (5-FU) has not been demonstrated to date. The aim of this study was to investigate the possible protective effect of BER against 5-FU-induced ovotoxicity, focusing on its ability to attenuate oxidative stress, inflammation and apoptosis. The 30 female rats were randomly divided into five groups: Control, BER (2 mg/kg), 5-FU (100 mg/kg), 5-FU+BER (1 mg/kg) and 5-FU+BER (2 mg/kg). The levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), 8-hydroxy-2’-deoxyguanosine (8-OHdG), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and caspase-3 were determined using spectrophotometric methods. In addition, ovarian samples were evaluated histopathologically using hematoxylin&eosin staining method. The MDA, TOS, 8-OHdG, IL-6, TNF-α and caspase-3 levels significantly increased by 5-FU administration. Also, we found that 5-FU significantly decreased TAS, SOD and CAT levels. Treatments with BER significantly attenuated the 5-FU-induced ovarian damage via increasing the antioxidant capacity and reducing the oxidative stress, inflammation and apoptosis in a dose-dependent manner. Moreover, the ovoprotective effect of BER was also confirmed by histopathological evaluation. BER may be evaluated as a potential candidate molecule to reduce 5-FU-induced ovarian toxicity. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMaterials and methodsResultsConclusion5-Fluorouracil (5-FU) is a chemotherapy drug commonly prescribed in cancer management. Unfortunately, intestinal mucositis restricts 5-FU clinical use. Vinpocetine (VNP) is a synthetic alkaloid that is derived from vincamine. Our study was conducted to elucidate the intestinal protective effects of VNP on 5-FU intestinal injury in rats and explore the underlying mechanisms.5-FU was injected i.p. for five days, while VNP was given P.O (5 and 10 mg/kg).VNP effectively mitigates oxidative stress by a significant increase in GSH and SOD and decreasing MDA content mediated by Nrf2, HO-1 upregulation, and significant Keap1 downregulation. VNP mitigated inflammatory perturbations by decreasing MPO, TNF-α, IL-1β, and IL-6 facilitated by downregulating NF-κB and TLR4 and upregulating SOCS3 levels. In addition, the RIPK1, RIPK3, MLKL, and caspase-8 expression levels were significantly decreased, evidenced improvement of intestinal necroptosis by VNP.Hence, VNP potently prevents intestinal injury induced by 5-FU by modulating Keap1/Nrf2/HO-1, NF-κB/TLR4/SOCS3, and RIPK1/RIPK3/MLKL signals. [ABSTRACT FROM AUTHOR]

Co‐delivering FDA‐approved drugs can be less harmful and boost biological activity by targeting different protein mechanism at same time. Gemcitabine and 5‐Fluorouracil (GE5F) adduct work together to destroy cancer cells and increase the efficacy in the fight against breast cancer. The basis set B3LYP/6‐311 G was utilized in this investigation to improve the structure of GE5F adduct. The natural bond analysis exhibited the intermolecular interactions of the GE5F adduct. Electronic transitions were seen to be π → π*, and theoretical calculations were performed for the ultraviolet to visible spectrum. The energy gap between HOMO and LUMO was used to study the GE5F adduct's structural stability and reactivity; the computed energy gap (ΔE) was 3.912 eV. The Mulliken charge population was assessed and the complex structure's electrostatic potential was established. Weak interactions of the GE5F were assessed using RDG analysis, and topological aspects were investigated using LOL and ELF analysis. Investigating the GE5F adduct's adsorption, distribution, metabolism, excretion, and toxicity properties, the results confirmed that GE5F adduct comes under the safety parameters being a drug‐likeness molecule. Molecular docking experiments were conducted using target proteins for breast cancer. The complex molecule had a higher binding affinity as indicated by the docking scores, which validated the better combinatorial interaction between gemcitabine and 5‐Fluorouracil. With − 9.4 kcal/mol, the complex molecule's strongest binding capacity was against PARP protein, and stable confirmation was observed through molecular dynamic simulation for 100 ns with four hydrogen bond interactions. These in silico finding will pave a way for in vitro and in vivo experiments with better enhancement of FDA approved drugs. [ABSTRACT FROM AUTHOR]

A 74-year-old Chinese man underwent extracapsular cataract extraction in his right eye and developed a translucent iris membrane 4 months later. He was treated with two intracameral 5-FU injections and membranectomy at 2 weeks apart. At one year following the second membranectomy, the patient maintained a clear cornea without residual or recurrent membrane, an endothelial cell density of 1072 cell/mm2, a visual acuity of 20/50 and a normal intraocular pressure. Our technique of using dispersive and cohesive viscoelastics in protecting the corneal endothelium from intracameral 5-FU, helped preserve corneal endothelial cells and maintain corneal clarity at one year after surgery. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is a chronic autoimmune skin disorder characterized by depigmented skin regions caused by a loss of melanocytes. Although vitiligo's origin is unknown, environmental, immunological, and genetic factors are involved. In treating vitiligo, microneedling is an effective adjuvant that improves the administration and effectiveness of medications such as trichloroacetic acid, 5-fluorouracil, and latanoprost. There is currently little data regarding the combination that is both safe and effective. This study aimed to compare the efficacy of microneedling delivery of latanoprost versus microneedling delivery of 5-fluorouracil and microneedling delivery of Trichloroacetic acid 35% in induction of skin re-pigmentation in stable vitiligo. Methods: This non-randomized controlled clinical trial was conducted on 54 patients, 18-60 years old, with stable vitiligo. They were divided into; Group (A) patients treated with dermapen followed by 5% 5-fluorouracil, Group (B) patients treated with dermapen followed by latanoprost, and Group (C) patients treated with dermapen followed by Trichloroacetic acid 35%. Results: There was an increase in excellent response among the group compared to B&C but without statistical significance. Also, there was no statistically significant difference between the studied groups in time of starting response. There was an increase in the frequency of very satisfaction among group A compared to B&C but without statistical significance. Conclusion: The combination of microneedling with either 5-Flourouracil or latanoprost or Trichloroacetic acid 35% is safe and effective in treatment of localized stable vitiligo. The degree of improvement was higher with 5-5-fluorouracil than with latanoprost and Trichloroacetic acid 35%. [ABSTRACT FROM AUTHOR]

Purpose: The transmembrane serine protease 4 (TMPRSS4) gene is upregulated in various human cancers. However, its biological functions in pancreatic ductal adenocarcinoma remain unclear. We examined the expression of TMPRSS4 in pancreatic ductal adenocarcinoma tissues and its correlation with clinicopathological parameters in patients with pancreatic ductal adenocarcinoma who underwent surgery. Methods: The TMPRSS4 expression was immunohistochemically examined in 81 PDAC patients with pancreatic ductal adenocarcinoma. We analyzed the association between the TMPRSS4 expression and clinicopathological factors, the recurrence-free survival (RFS), and the overall survival (OS) and examined the effect of TMPRSS4 expression on cell migration and sensitivity to 5-fluorouracil. Results: The expression rate of TMPRSS4 in the samples was 62.9% (51/81). The TMPRSS4 expression was not correlated with any clinicopathological feature. The five-year overall and recurrence-free survival rates were significantly lower in the TMPRSS4-positive group than in the TMPRSS4-negative group. On a multivariate analysis, TMPRSS4 positivity, poorly differentiated histology, and non-adjuvant chemotherapy predicted a poor OS, while TMPRSS4 positivity and poorly differentiated histology predicted a poor RFS. TMPRSS4-silenced pancreatic ductal adenocarcinoma cells showed higher sensitivity to 5- fluorouracil than did the control siRNA-transfected cells. Conclusions: TMPRSS4 can be considered a prognostic factor and therapeutic target for pancreatic ductal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Saccharomyces cerevisiae is an excellent model to study the effect of external cues on cell division and stress response. 5‐Fluorocuracil (5‐FU) has been used to treat solid tumors since several decades. The drug was initially designed to interfere with DNA replication but was later found to exert its antiproliferative effect also via RNA‐dependent processes. Since 5‐FU inhibits the activity of the 3′−5′‐exoribonuclease Rrp6 in yeast and mammals, earlier work has compared the effect of 5‐FU treatment and RRP6 deletion at the transcriptome level in diploid synchronized yeast cells. To facilitate interpreting the expression data we have developed an improved 5‐Fluorouracil RNA (5‐FUR) expression viewer. Users can access information via genome coordinates and systematic or standard names for mRNAs and Xrn1‐dependent‐, stable‐, cryptic‐, and meiotic unannotated transcripts (XUTs, SUTs, CUTs, and MUTs). Normalized log2‐transformed or linear data can be displayed as filled diagrams, line graphs or color‐coded heatmaps. The expression data are useful for researchers interested in processes such as cell cycle regulation, mitotic repression of meiotic genes, the effect of 5‐FU treatment and Rrp6 deficiency on the transcriptome and expression profiles of sense/antisense loci that encode overlapping transcripts. The viewer is accessible at http://5fur.genouest.org. Take away: We present an improved 5‐Fluorouracil RNA (5‐FUR) expression viewerStrand‐specific RNA‐Seq data are available for mRNAs and different classes of lncRNAsNormalized data are displayed as filled diagrams, line graphs or heatmapsThe expression data are pertinent for regulation of mitotic and meiotic genesUsers can interpret the expression profiles of sense/antisense transcripts [ABSTRACT FROM AUTHOR]

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Zinc-phosphate/hydroxyapatite hybrid form (ZP/HP) in core-shell nanostructure was developed and functionalized with both chitosan (CS@ZP/HP) and β-cyclodextrin (CD@ZP/HP) as bio-composite of enhanced physicochemical and biological properties. These structures were assessed as potential deliveries of 5-fluorouracil, exhibiting enhanced loading, release, and anti-cancer behaviors. The functionalization strongly prompted the loading effectiveness to be 301.3 mg/g (CS@ZP/HP) and 342.8 mg/g (CD@ZP/HP) instead of 238.9 mg/g for ZP/HP. The loading activities were assessed based on the hypotheses of traditional kinetic and isotherm models, alongside the computational variables of the monolayer model with a single energetic site as an advanced isotherm model. The functionalized versions exhibit much greater loading efficacy compared to ZP/ HP as a result of the increment in the density of the existing loading sites [Nm(5-Fu) = 78.85 mg/g (ZP/HP), 93.87 mg/g (CS@ZP/HP), and 117.8 mg/g (CD@ZP/HP)]. Furthermore, the loading energies of approximately 40 kJ/mol, together with the loading potential of each receptor (n > 1) and Gaussian energies of approximately 8 kJ/mol, indicate the physical entrapment of 5-Fu molecules according to a vertical orientation. The materials mentioned verify long-term and continuous release characteristics. Following the modification processes, this behavior became faster as both CS@ZP/HP and CD@ZP/HP displayed complete release within 120 h at pH 1.2. The kinetic studies and diffusing exponent (>0.45) indicate that release characteristics are controlled by both diffusion and erosion processes. These carriers also markedly increase the cytotoxicity of 5-Fu against HCT-116 colorectal cancer cell lines: 5-Fu-ZP/HP (3.2% cell viability), 5-Fu-CS@ZP/HP (1.12% cell viability), and 5-Fu-CD@ZP/HP (0.63% cell viability). [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the top 10 most common cancers worldwide and caused approximately 10 million deaths in 2022. CRC mortality has increased by 10% since 2020 and 52.000 deaths will occur in 2024, highlighting the limitations of current treatments due to ineffectiveness, toxicity, or non-adherence. The widely used chemotherapeutic agent, 5-fluorouracil (5-FU), is associated with several adverse effects, including renal, cardiac, and hepatic toxicity; mucositis; and resistance. Taurine (TAU), an essential β-amino acid with potent antioxidant, antimutagenic, and anti-inflammatory properties, has demonstrated protective effects against tissue toxicity from chemotherapeutic agents like doxorubicin and cisplatin. Taurine deficiency is linked to aging and cancers such as breast and colon cancer. This study hypothesized that TAU may mitigate the adverse effects of 5-fluorouracil (5-FU). Carcinogenesis was chemically induced in rats using 1,2-dimethylhydrazine (DMH). Following five months of cancer progression, taurine (100 mg/kg) was administered orally for 8 days, and colon tissues were analyzed. The results showed 80% of adenocarcinoma (AC) in DMH-induced control animals. Notably, the efficacy of 5-FU showed 70% AC and TAU 50% while, in the 5-FU + TAU group, no adenocarcinoma was observed. No differences were observed in the inflammatory infiltrate or the expression of genes such as K-ras, p53, and Ki-67 among the cancer-induced groups whereas APC/β-catenin expression was increased in the 5FU + TAU-treated group. The mitotic index and dysplasia were increased in the induced 5-FU group and when associated with TAU, the levels returned to normal. These data suggest that 5-FU exhibits a synergic anticancer effect when combined with taurine. [ABSTRACT FROM AUTHOR]

Purpose: To report the demographic profile, clinical presentation, and management outcomes of ocular surface squamous neoplasia (OSSN) treated with primary topical chemotherapy in a limited resource secondary eye care facility in rural parts of South India. Methods: Retrospective interventional study of 38 eyes of 37 patients with OSSN treated with topical 1% 5-Fluorouracil (5FU), over a period of two years. Results: The median age at presentation with OSSN was 44 years (mean, 46 years; range 13 to 74 years). Majority (76%) were males. The most common morphological variant was placoid OSSN (18, 47%). Limbus was the most common epicenter (31, 82%). Corneal OSSN was the most initially misdiagnosed variant (n = 3). Of the 38 eyes receiving one week on and 3-weeks off cycles of 5FU regimen, complete tumor resolution was achieved in 36 (95%) eyes. The median number of topical 5FU cycles for tumor resolution was 2 (mean, 2; range, 1 to 4). Over a median follow-up period of 5 months (mean, 6 months; range, 1 to 27 months), tumor recurrence was noted in 3 eyes (8%), of which one case had xeroderma pigmentosum with bilateral multifocal recurrence. Complication rate was 5% (n = 2), which included transient conjunctival hyperemia (n = 1), and bacterial keratitis (n = 1) which resolved with fortified antibiotics. Conclusion: Primary chemotherapy with topical 1% 5FU is a safe and effective management modality for OSSN at limited resource settings in rural India. [ABSTRACT FROM AUTHOR]

Background: L-Leucovorin (l-LV; 5-formyltetrahydrofolate, folinic acid) is a precursor for 5,10-methylenetetrahydrofolate (5,10-CH2-THF), which is important for the potentiation of the antitumor activity of 5-fluorouracil (5FU). LV is also used to rescue antifolate toxicity. LV is commonly administered as a Racemic mixture of its l-LV and d-LV stereoisomers. We compared dl-LV with l-LV and investigated whether d-LV would interfere with the activity of l-LV. Methods: Using radioactive substrates, we characterized the transport properties of l-LV and d-LV, and compared the efficacy of l-LV with d-LV to potentiate 5FU- mediated thymidylate synthase (TS) inhibition. Using proliferation assays, we investigated their potential to protect cancer cells from cytotoxicity of the antifolates methotrexate, pemetrexed (Alimta), raltitrexed (Tomudex) and pralatrexate (Folotyn). Results: l-LV displayed an 8-fold and 3.5-fold higher substrate affinity than d-LV for the reduced folate carrier (RFC/SLC19A1) and proton coupled folate transporter (PCFT/SLC46A1), respectively. In selected colon cancer cell lines, the greatest enhanced efficacy of 5FU was observed for l-LV (2-fold) followed by the racemic mixture, whereas d-LV was ineffective. The cytotoxicity of antifolates in lymphoma and various solid tumor cell lines could be protected very efficiently by l-LV but not by d-LV. This protective effect of l-LV was dependent on cellular RFC expression as corroborated in RFC/PCFT-knockout and RFC/PCFT- transfected cells. Assessment of TS activity in situ showed that TS inhibition by 5FU could be enhanced by l-LV and dl-LV and only partially by d-LV. However, protection from inhibition by various antifolates was solely achieved by l-LV and dl-LV. Conclusion: In general l-LV acts similar to the dl-LV formulations, however disparate effects were observed when d-LV and l-LV were used in combination, conceivably by d-LV affecting (anti)folate transport and intracellular metabolism. [ABSTRACT FROM AUTHOR]

Co-administration of microRNAs and chemotherapy drugs effectively treats several cancers. The current study sought to investigate the function of matrix metalloproteinase 16 (MMP16) and miR-193a-5p in the pathogenesis of gastric cancer (GC). Sixty-five surgical patients, 15 receiving 5-fluorouracil (5-FU), provided GC and adjacent non-cancerous tissue. Following that, qPCR was used to assess the expression levels of MMP16 and miR-193a-5p in GC cells. The impact of miR-193a-5p and 5-FU administration on MMP16 mRNA expression was evaluated using qRT-PCR and Western blotting. MTT and Scratch tests were also conducted to assess their effects on cell viability and migration. Moreover, a rescue experiment using an MTT assay was performed. Using flow cytometry, the apoptotic rate was calculated. Finally, it was evaluated how MMP16 and miR-193a-5p related to the clinicopathological characteristics of the patients. The current study found that while MMP16 expression increased in GC patients (P ​< ​0.0001), miR-193a-5p expression significantly decreased (P ​< ​0.001). MMP16 down-regulation was another effect of miR-193a-5p replacement, particularly when 5-FU was added (P ​< ​0.01). In addition, this study found that miR-193a-5p, by concentrating on MMP16, decreased the migration of GC cells brought on by MMP16. In GC cell lines, miR-193 and 5-FU induce apoptosis, with the 5-FU being more pronounced when combined with mir-193, according to flow cytometry results. A strong correlation was also found between clinicopathological traits associated with MMP16 and miR-193a-5p. These findings suggest that miR-193a-5p, in conjunction with 5-FU, down-regulates MMP16 in GC, where it suppresses tumor growth. [ABSTRACT FROM AUTHOR]

Ecofriendly organically modified bentonite based on curcumin-extracted compounds was applied as a catalytic carrier for green ZnO particulates (Zn@CU/BEN). The composite developed was evaluated as a cost-effective, highly efficient, and versatile photocatalyst for improving the oxidation of 5-fluorouracil (5-FU) residues in water resources. The ZnO@CU/BEN blend, with a dose of 0.5 g/L, exhibits notable catalytic characteristics, leading to the full oxidation of 5-FU at a concentration of 25 mg/L within 80 min. The kinetic assessment reflects the high fitness of the Firs order model with best rate constant value of 0.0156 and quantum yield (ɸ) value of 2.9 × 10–7. Nevertheless, the total reduction in organic carbon (TOC) was identified only after 160 min, indicating the existence of considerable byproducts of intermediates. The secondary compounds that were detected, alongside the establishment of hydroxyl radicals as the crucial oxidizing agent, revealed a degradation path consisting of two steps: hydroxylation and defluorination reactions. The toxicity characteristics of untreated pollutants and their resulting oxidized products were evaluated by measuring the inhibitory effects of the solutions on Vibrio fischeri at various time intervals. The sample that underwent partial oxidation during the first period exhibited a greater degree of toxicity compared to the unprocessed 5-FU. Nevertheless, the sample that underwent treatment for 200 min exhibited noteworthy characteristics of biosafety and non-toxicity. The synergistic effect of bentonite and organo-modified bentonite with curcumin extracts improves both the retention and oxidation activities of green ZnO. [ABSTRACT FROM AUTHOR]

Objective: Little progress has been made in recent years using first-line chemotherapy, including gemcitabine combined with nab- paclitaxel, FOLFIRINOX, and NALIRIFOX, for advanced pancreatic adenocarcinoma (APC). In addition, the optimal second-line chemotherapy regimen has not been determined. This study aimed to compare the effectiveness of different types of second-line chemotherapy for APC. Methods: Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Results: Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil- and gemcitabine-based chemotherapy as first-line treatment, respectively. Demographic and clinical features, except age and liver metastasis, were comparable between the two groups (P < 0.05). The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil- and gemcitabine-based combined regimen for first-line therapy, respectively (HR = 1.244, 95% CI = 1.090–1.419; P < 0.001). The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care, respectively (HR = 0.766, 95% CI = 0.677–0.867; P < 0.001). The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination therapy. Conclusions: A 5-fluorouracil-or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is one of the most common causes of death worldwide. Today, this disease does not have an effective treatment, leading to the exploration of novel pharmacological molecules. In this paper, we design and synthesize with a new synthetic route the lipophilic cation derived from gallic acid (TPP+C10) and gentisic acid (GA-TPP+C10), both able to reach mitochondria and uncouple the electron transport chain. Our results show that combining 5-fluorouracil with GA-TPP+C10 has a synergistic cytotoxic effect on CRC cells. Both compounds show antimigratory effects, decreasing signaling pathways and biomarkers. Our results show that mitochondrial agents could be an alternative to standard CRC drugs against this disease. Colorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC—such as 5-fluorouracil (5FU)—remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP+C10), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP+C10), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP+C10 with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP+C10 and TPP+C10 using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP+C10 and TPP+C10, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP+C10 and GA-TPP+C10 increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity. [ABSTRACT FROM AUTHOR]

Background: Sinonasal tumors represent a rare and heterogeneous group of rhinologic neoplasms. Even with advancements in surgical approaches, mortality rates of patients with sinonasal adenocarcinoma (SNAC) have not significantly improved and persistently high rates of recurrence in certain patients with inverted papilloma (IP) are seen. The use of 5-fluorouracil (5-FU) has been successfully described as an adjuvant treatment of SNAC and in the prevention of IP recurrence. Objective: This review aims to present the current evidence on the management of SNAC and IP with topical 5-FU. Methods: A three-author independent literature review was conducted to identify research involving the use of topical 5-FU for the treatment of SNAC and IP. A total of nine papers on the treatment of SNAC and IP were collected. Results: The earliest study looking at the combination of adjuvant low-dose radiation and topical 5-FU for adenocarcinoma of the ethmoid sinus showed a 5-year survival rate of 100%. A follow-up study evaluating a similar protocol reported adjusted disease-free survival at 2, 5, and 10 years of 96%, 87%, and 74%, respectively. Similar results have been demonstrated for adjuvant 5-FU use following endoscopic resection and have even been described in the novel setting of transcutaneous 5-FU delivery following frontal trephination. Topical 5-FU has also been described in the treatment of aggressive IP. The largest case series described the use of 5-FU for eighteen cases and demonstrated only a single recurrence. Conclusion: The use of topical 5-FU currently represents an underutilized therapeutic modality within the treatment of rhinologic neoplasms. Available literature suggests that neoadjuvant use of topical 5-FU can improve survival and decrease recurrence for SNAC and IP. However, the small sample sizes prevent advocation for routine use in the general population and further research on 5-FU is necessary. [ABSTRACT FROM AUTHOR]

5-Fluorouracil has demonstrated certain efficiency in patients with colorectal cancer. However, significant side effects of use by injection are common. To address this issue defects, a reengineered 5′-deoxy-5-fluorocytidine (DFCR) based drug delivery system (POACa) is developed as a prominent tumor-selective nano-activator. Investigations demonstrate that the constructed nano-activator exhibits good biocompatibility and high therapeutic efficiency in mice with subcutaneous and orthotopic SW-480 colorectal tumors, as its activity is strictly dependent on the tumor-associated acid environment and thymidine phosphorylase. These strategies diminish the off-target toxicity and improve the specificity and sensitivity of human colorectal cancer cells to 5-Fu, obtaining potent efficiency by the combination of H 2 O 2 mediated oxidative stress, calcium overload and 5-Fu-induced chemotherapy (the combination index is 0.11). Overall, the engineered nano-activator exhibits a high therapeutic index in vitro and in vivo. In this study, we designed and prepared a pH-responsive polymer to synchronously deliver DFCR (5′-deoxy-5-fluorocytidine, a prodrug of 5-Fu), Ca2+ and H 2 O 2. The constructed nano-activator was denoted as POACa. (1) To address the problem of premature leakage of cargo by physical embedding, our research modified the inactive prodrug DFCR through chemical bonding. (2) The activation of the prepared nano-activator was strictly dependent on the tumor-associated acid environment and thymidine phosphorylase, providing the drug delivery system with inherent safety. (3) A distinctly low combination index value (0.11) of CaO 2 and DFCR indicated that POACa has a prominent tumor suppression effect by tumor calcium overload sensitized chemotherapy and H 2 O 2 mediated cytotoxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

The increasing use of hyaluronic acid (HA) implants has made adverse effects more apparent. Here, we present a rare case of massive allergic dermatitis due to HA injections. We performed dermoscopy and color ultrasound, which clarified that this was an allergic dermatitis caused by fillers, and analyzed the possible causes of the allergy. Common treatments were compared, and the advantages of 5-FU-based treatment regimens and their associated mechanisms were noted. A low dose of 5-fluorouracil and triamcinolone acetonide was administered to the patient's entire face and neck, and significant efficacy was achieved. We aimed to gather evidence on extensive dermatitis caused by HA injection, provide new perspectives and solutions for subsequent HA injections, and promote further research on the potential mechanisms of extensive skin inflammation and allergies caused by local HA injections. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU) is a clinically established anticancer drug effective in treating various solid tumors, including colorectal, breast, and pancreatic cancers. However, its therapeutic efficacy is often hindered by rapid metabolism and the development of drug resistance. This study investigates a nanocomposite comprising chitosan (CS), agarose (Aga), carbon quantum dots (CQDs), and titanium dioxide (TiO2_CQDs) as a potential nanocarrier (NC) to enhance 5-FU delivery. A CS/Aga hydrogel was synthesized through physical cross-linking to improve biocompatibility. Subsequently, the drug-loaded nanocomposite (CS/Aga/TiO2_CQDs@5-FU) was prepared using a W/O/W double emulsion process. A comprehensive characterization of the NC and 5-FU incorporation was conducted. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) were employed to evaluate the crystalline properties of the nanoparticles (NPs) and confirm 5-FU integration. Dynamic light scattering (DLS) and zeta potential measurements assessed the stability and particle size distribution of the drug-loaded nanocomposites, confirming the formation of stable NPs. Field emission scanning electron microscopy (FE-SEM) verified the uniform dispersion of NPs, characterized by smooth and nearly spherical structures. Drug release kinetics were evaluated under controlled conditions. The encapsulation efficiency (EE) and loading efficiency (LE) were determined to be 86% and 47.25%, respectively, indicating the nanocomposite's high drug-carrying capacity. An MTT assay on U-87 MG and L929 cell lines demonstrated the biocompatibility of the fabricated NC. Notably, the drug-loaded nanocomposite exhibited lower cytotoxicity compared to pure 5-FU. These findings suggest that the nanocomposite holds promise as a drug delivery system, particularly for overcoming challenges associated with brain cancer treatment. [ABSTRACT FROM AUTHOR]

Primary cilia are crucial for neurogenesis, and cilium-related genes are involved in the closure of neural tubes. Inositol polyphosphate-5-phosphatase (Inpp5e) was enriched in primary cilia and closely related to the occurrence of neural tube defects (NTDs). However, the role of Inpp5e in the development of NTDs is not well-known. To investigate whether Inpp5e gene is associated with the neural tube closure, we established a mouse model of NTDs by 5-fluorouracil (5-FU) exposure at gestational day 7.5 (GD7.5). The Inpp5e knockdown (Inpp5e-/-) mouse embryonic stem cells (mESCs) were produced by CRISPR/Cas9 system. The expressions of Inpp5e and other cilium-related genes including intraflagellar transport 80 (Ift80), McKusick-Kaufman syndrome (Mkks), and Kirsten rat sarcoma viral oncogene homolog (Kras) were determined, utilizing quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot, PCR array, and immunofluorescence staining. The result showed that the incidence of NTDs was 37.10% (23 NTDs/62 total embryos) and significantly higher than that in the control group (P < 0.001). The neuroepithelial cells of neural tubes were obviously disarranged in NTD embryos. The mRNA and protein levels of Inpp5e, Ift80, Mkks, and Kras were significantly decreased in NTD embryonic brain tissues, compared to the control (P < 0.05). Knockdown of the Inpp5e (Inpp5e-/-) reduced the expressions of Ift80, Mkks, and Kras in mESCs. Furthermore, the levels of α-tubulin were significantly reduced in NTD embryonic neural tissue and Inpp5e-/- mESCs. These results suggested that maternal 5-FU exposure inhibited the expression of Inpp5e, which resulted in the downregulation of cilium-related genes (Ift80, Mkks, and Kras), leading to the impairment of primary cilium development, and ultimately disrupted the neural tube closure. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU) is widely used in chemotherapy but poses serious risks of cardiotoxicity, which can significantly affect treatment outcomes. Identifying interventions that can prevent these adverse effects without undermining anticancer efficacy is crucial. This study investigates the efficacy of Thymoquinone (TQ) and Hesperidin (HESP) in preventing cardiotoxicity induced by 5-FU in Wistar rats and elucidates the molecular interactions through docking studies. We employed an experimental design involving multiple groups of Wistar rats exposed to 5-FU, with and without the concurrent administration of TQ and HESP. Cardiac function markers, oxidative stress indicators, and inflammatory markers were assessed. Additionally, molecular docking was used to analyze the interaction of TQ and HESP with key inflammatory proteins. Treatment with TQ and HESP not only lowered levels of cardiac enzymes but also improved antioxidant capacity and reduced inflammation in cardiac tissues. Notably, the combination of TQ and HESP provided more significant protective effects than either agent alone. Molecular docking supported these findings, showing effective binding of TQ and HESP to inflammatory targets. TQ and HESP demonstrate potential as protective agents against cardiotoxicity in 5-FU-treated rats, with their combined use offering enhanced protection. These findings suggest a viable strategy for reducing cardiac risks associated with 5-FU chemotherapy. [ABSTRACT FROM AUTHOR]

Colon cancer is the third most common cancer worldwide, with high mortality. Adverse side effects and chemoresistance of the first-line chemotherapy 5-fluorouracil (5-FU) have promoted the widespread use of combination therapies. Thymoquinone (TQ) is a natural compound with potent antioxidant activity. Loading antioxidants into nano delivery systems has been a major advance in enhancing their bioavailability to improve clinical application. Hence, this study aimed to prepare the optimal TQ-loaded calcium carbonate nanoparticles (TQ-CaCO3 NPs) and investigate their therapeutic potential and underlying molecular mechanisms of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Firstly, we developed purely aragonite CaCO3 NPs with a facile mechanical ball-milling method. The pH-sensitive and biocompatible TQ-CaCO3 NPs with sustained release properties were prepared using the optimal synthesized method (a high-speed homogenizer). The in vitro study revealed that the combination of TQ-CaCO3 NPs (15 μM) and 5-FU (7.5 μM) inhibited CT26 cell proliferation and migration, induced cell apoptosis and cell cycle arrest in the G0/G1 phase, and suppressed the CT26 spheroid growth, exhibiting a synergistic effect. Finally, network pharmacology and molecular docking results indicated the potential targets and crucial signaling pathways of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Therefore, TQ-CaCO3 NPs combined with 5-FU could enhance the anti-colon cancer effects of 5-FU with broader therapeutic targets, warranting further application for colon cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Cancer and diabetes mellitus are quite common diseases found together worldwide. A considerable amount of evidence is available for the rapid development and presentation of various types of cancer in the type 2 diabetes mellitus (DM2) population as compared with the population without diabetes. The objective of the study is to formulate and evaluate 5-fluorouracil (5-FU) and metformin (MET) nanoparticles (NPs) and to establish the characteristic features of the biodegradable NPs. 5-FU and MET NPs with chitosan as a biodegradable polymer were formulated by the ionotropic cross-linking method. 0.25 gm of MET and 0.25 gm of 5-FU were dissolved in 100 ml of distilled water, and stock solution was prepared. 5 ml of stock solution was slowly mixed into the chitosan solution to obtain the mixture of drugs and chitosan. The tripolyphosphate reserve liquid was dripped slowly into the chitosan solution with constant stirring until the opaline appearance was noticed in the mixture, then filtered, and dried. The NPs were evaluated for their physical properties and drug release kinetics. Cell proliferation assay was done using human colorectal carcinoma cell line (HCT 116). Results The formulation composed of 1.5 w/v of chitosan, 0.25 w/v of MET, and 5-FU had an average particle diameter of 198.7 nm. The polydispersity index was 0.757. Thermal and infrared spectroscopy results indicated the drugs and polymers selected for the formulation were unique without any identifiable interaction. The NPs were spherical in appearance, with numerous pours on the surface, which was evident when microscopically examined. Uniformity in drug release was observed, and the formulation demonstrated excellent release kinetics. HTC 116 cell line confirmed that the maximum percentage of cell death and minimum viability of cells were observed while using the combination of MET and 5-FU-NPs as compared to the pure MET or 5-FU alone. Conclusion MET and 5-FU-loaded chitosan NPs were found to have excellent physiochemical properties, particle size, and drug release from the polymer in a controlled manner. Half-maximal inhibitory concentration value (IC50) of MET and 5-FU-NPs was found to be significantly less as compared to MET and 5-FU alone or the combination.

Abstract A 74-year-old Chinese man underwent extracapsular cataract extraction in his right eye and developed a translucent iris membrane 4 months later. He was treated with two intracameral 5-FU injections and membranectomy at 2 weeks apart. At one year following the second membranectomy, the patient maintained a clear cornea without residual or recurrent membrane, an endothelial cell density of 1072 cell/mm2, a visual acuity of 20/50 and a normal intraocular pressure. Our technique of using dispersive and cohesive viscoelastics in protecting the corneal endothelium from intracameral 5-FU, helped preserve corneal endothelial cells and maintain corneal clarity at one year after surgery.

Introduction: The use of antineoplastic drugs in cancer treatment, while essential, poses risks due to their non-selective action on both cancerous and healthy cells. Assessing and controlling environmental contamination with these drugs in workplaces is crucial. This study aimed to evaluate the efficacy of various commercial wipes in sampling the antineoplastic drug 5-fluorouracil from surfaces to develop standardized sampling methods. Material and Methods: This study assessed the efficiency of commonly used commercial wipes (Whatman cellulose filter, cotton swab, Millipore™ filter, sterile gauze pad, and alcohol pad) for sampling 5-fluorouracil from different surfaces (stainless steel, vinyl, and ceramic). The sampling area was defined using disposable cardboard frames, and 1000 microliters of a 1 µg/mL 5-fluorouracil solution were applied to each surface. Sampling and extraction were conducted following NIOSH guidelines. The frame dimensions were 10 × 10 cm, limiting the sampling area to 100 square centimeters. Analysis was performed using high-performance liquid chromatography (HPLC), and results were analyzed using Prism GraphPad software, version 8. Results: The sampling efficiency varied across wipes and surfaces, ranging from 11.2% to 86.2%. Alcohol pads showed the highest efficiency on stainless steel surfaces, while the Millipore™ filter had the lowest efficiency across all surfaces. Extraction efficiency ranged from 43.8% to 98.8%, with alcohol pads providing the highest recovery. Sample stability was maintained over 15 days. Conclusion: Alcohol pads were most effective in collecting and extracting 5-fluorouracil, particularly from hard, smooth surfaces such as stainless steel and ceramic. These findings may improve sampling methods, thereby reducing occupational exposure to antineoplastic drugs. Further research on different wipes and extraction parameters could refine drug analysis techniques.

Abstract 5-Fluorouracil (5-FU) is the leading chemotherapeutic drug used to treat hepatocellular carcinoma, one of the major cancer diseases after atherosclerosis. Because of chemo-resistance, the success rate of treatment declines with time due to continuous drug exposure. Though autophagy induction is majorly responsible for acquired resistance, the exact role of this evolutionary conserved mechanism is unknown in cancer cell survival and suppression. The usual practice involves the combinatorial use of chemotherapeutic drugs with autophagy inhibitors like Chloroquine and Bafilomycin A, while neglecting the side effects caused by autophagy impairment in healthy cells. Starvation is a well-known physiological inducer of autophagy. In this study, by caloric modulation, we tried to circumvent the resistance imposed by prolonged drug exposure and investigated the effect of 5-FU in nutrient-sufficient and deficient conditions. Our findings show a substantial correlation between autophagy and increased cancer cell death in the presence of 5-FU, with negligible effects on normal cells. Experimental data revealed that nutritional deprivation augmented cell death in the presence of 5-FU through mitochondrial membrane damage and excessive reactive oxygen species (ROS) production, initiating apoptosis. Lipidation study also unveiled that under such combinatorial treatment cellular metabolism shifts from glucose to lipid biosynthesis. Overall, our experimental findings suggest that nutritional deprivation in combination with chemotherapeutic medication can be a new effective strategy to control hepatocellular carcinoma.

Abstract 5-Fluorouracil (5-FU) is used as a standard first-line drug for colorectal cancer malignancy (CRC), but it brings a series of side effects such as severe diarrhea and intestinal damage. Our previous study found that a large number of senescent cells increased while 5-Fu induced intestinal damage, and anti-senescence drugs can alleviate its side effects of inflammatory damage. Oleanolic acid (OA) is a common pentacyclic triterpenoid mainly derived from food fungi and medicinal plants, and studies have shown that it mainly possesses hepatoprotective, enzyme-lowering, anti-inflammatory, and anti-tumor effects. But its role in senescence is still unclear. In the present study, we demonstrated for the first time that OA ameliorated 5-Fu-induced human umbilical vein endothelial cells (HUVECs) and human normal intestinal epithelial cells (NCM460) in a 5-Fu-induced cellular senescence model by decreasing the activity of SA-β-gal-positive cells, and the expression of senescence-associated proteins (p16), senescence-associated genes (p53 and p21), and senescence-associated secretory phenotypes (SASPs: IL-1β, IL-6, IL-8, IFN-γ and TNF-α). Meanwhile, in this study, in a BALB/c mouse model, we demonstrated that 5-FU induced intestinal inflammatory response and injury, which was also found to be closely related to the increase of senescent cells, and that OA treatment was effective in ameliorating these adverse phenomena. Furthermore, our in vivo and in vitro studies showed that OA could alleviate senescence by inhibiting mTOR. In colon cancer cell models, OA also enhanced the ability of 5-FU to kill HCT116 cells and SW480 cells. Overall, this study demonstrates for the first time the potential role of OA in counteracting the side effects of 5-FU chemotherapy, providing a new option for the treatment of colorectal cancer to progressively achieve the goal of high efficacy and low toxicity of chemotherapy.

Abstract Background Fluoropyrimidines are chemotherapy drugs utilized to treat a variety of solid tumors. These drugs predominantly rely on the enzyme dihydropyrimidine dehydrogenase (DPD), which is encoded by the DPYD gene, for their metabolism. Genetic mutations affecting this gene can cause DPYD deficiency, disrupting pyrimidine metabolism and increasing the risk of toxicity in cancer patients treated with 5-fluorouracil. The severity and type of toxic reactions are influenced by genetic and demographic factors and, in certain instances, can result in patient mortality. Among the more than 50 identified variants of DPYD, only a subset has clinical significance, leading to the production of enzymes that are either non-functional or impaired. The study aims to examine treatment-related mortality in cancer patients undergoing fluoropyrimidine chemotherapy, comparing those with and without DPD deficiency. Methods The meta-analysis selected and evaluated 9685 studies from Pubmed, Cochrane, Embase and Web of Science databases. Only studies examining the main DPYD variants (DPYD*2A, DPYD p.D949V, DPYD*13 and DPYD HapB3) were included. Statistical Analysis was performed using R, version 4.2.3. Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed with I2 statistics. Results There were 36 prospective and retrospective studies included, accounting for 16,005 patients. Most studies assessed colorectal cancer, representing 86.49% of patients. Other gastrointestinal cancers were evaluated by 11 studies, breast cancer by nine studies and head and neck cancers by five studies. Four DPYD variants were identified as predictors of severe fluoropyrimidines toxicity in literature review: DPYD*2A (rs3918290), DPYD p.D949V (rs67376798), DPYD*13 (rs55886062) and DPYD Hap23 (rs56038477). All 36 studies assessed the DPYD*2A variant, while 20 assessed DPYD p.D949V, 7 assessed DPYD*13, and 9 assessed DPYDHap23. Among the 587 patients who tested positive for at least one DPYD variant, 13 died from fluoropyrimidine toxicity. Conversely, in the non-carrier group there were 14 treatment-related deaths. Carriers of DPYD variants was found to be significantly correlated with treatment-related mortality (OR = 34.86, 95% CI 13.96–87.05; p

Abstract Purpose To report the demographic profile, clinical presentation, and management outcomes of ocular surface squamous neoplasia (OSSN) treated with primary topical chemotherapy in a limited resource secondary eye care facility in rural parts of South India. Methods Retrospective interventional study of 38 eyes of 37 patients with OSSN treated with topical 1% 5-Fluorouracil (5FU), over a period of two years. Results The median age at presentation with OSSN was 44 years (mean, 46 years; range 13 to 74 years). Majority (76%) were males. The most common morphological variant was placoid OSSN (18, 47%). Limbus was the most common epicenter (31, 82%). Corneal OSSN was the most initially misdiagnosed variant (n = 3). Of the 38 eyes receiving one week on and 3-weeks off cycles of 5FU regimen, complete tumor resolution was achieved in 36 (95%) eyes. The median number of topical 5FU cycles for tumor resolution was 2 (mean, 2; range, 1 to 4). Over a median follow-up period of 5 months (mean, 6 months; range, 1 to 27 months), tumor recurrence was noted in 3 eyes (8%), of which one case had xeroderma pigmentosum with bilateral multifocal recurrence. Complication rate was 5% (n = 2), which included transient conjunctival hyperemia (n = 1), and bacterial keratitis (n = 1) which resolved with fortified antibiotics. Conclusion Primary chemotherapy with topical 1% 5FU is a safe and effective management modality for OSSN at limited resource settings in rural India.

Background: Drug resistance in colorectal cancer (CRC) is modulated by multiple molecular factors, which can be ascertained through genetic investigation. Single nucleotide polymorphisms (SNPs) within key genes have the potential to impair the efficacy of chemotherapeutic agents such as 5-fluorouracil (5-FU). Therefore, the identification of SNPs linked to drug resistance can significantly contribute to the advancement of tailored therapeutic approaches and the enhancement of treatment outcomes in patients with CRC. Material and Method: To identify dysregulated genes in 5-FU-based chemotherapy responder or non-responder CRC patients, a meta-analysis was performed. Next, the protein–protein interaction (PPI) network of the identified genes was analyzed using the STRING database. The most significant module was chosen for further analysis. In addition, a literature review was conducted to identify drug resistance-related genes. Enrichment analysis was conducted to validate the main module genes and the genes identified from the literature review. The associations between SNPs and drug resistance were investigated, and the consequences of missense variants were assessed using in silico tools. Result: The meta-analysis identified 796 dysregulated genes. Then, to conduct PPI analysis and enrichment analysis, we were able to discover 23 genes that are intricately involved in the cell cycle pathway. Consequently, these 23 genes were chosen for SNP analysis. By using the dbSNP database and ANNOVAR, we successfully detected and labeled SNPs in these specific genes. Additionally, after careful exclusion of SNPs with allele frequencies below 0.01, we evaluated 6 SNPs from the HDAC1, MCM2, CDK1, BUB1B, CDC14B, and CCNE1 genes using 8 bioinformatics tools. Therefore, these SNPs were identified as potentially harmful by multiple computational tools. Specifically, rs199958833 in CDK1 (Val124Gly) was predicted to be damaging by all tools used. Our analysis strongly indicates that this specific SNP could negatively affect the stability and functionality of the CDK1 protein. Conclusion: Based on our current understanding, the evaluation of CDK1 polymorphisms in the context of drug resistance in CRC has yet to be undertaken. In this investigation, we showed that rs199958833 variant in the CDK1 gene may favor resistance to 5-FU-based chemotherapy. However, these findings need validation in an independent cohort of patients. [ABSTRACT FROM AUTHOR]

Fluorouracil (5-Fu, 1) is an antimetabolite cancer drug and the first-line drug of anticancer administration by WHO that has been widely used worldwide for more than 50 years. The development of 5-fluorouracil is an effort to obtain higher activity, decrease side effects, and create a specific target receptor compared to 5-fluorouracil. In this research, a series of novel 5-Fluorouracil (5-Fu) derivatives has been synthesized based on a benzoylation reaction (Schotten-Baumann reaction) of N1-hydroxylated 5-Fu called compound 2, 5-fluoro-1-(hydroxymethyl)-uracil. The benzoyl chloride substituents used in this research, including 3-chlorobenzoyl (4a), 2-chlorobenzoyl (4b), 3-nitrobenzoyl (4c), 4-methoxy benzoyl (4d), 4-trifluoromethylbenzoyl (4e), 3,4-dichlorobenzoyl (4f), and 4-nitrobenzoyl (4g) chloride become (4a-4f)-5Fu. This research meticulously examined the conditions (time and reaction temperature) at the second step of the synthesis reaction (esterification), ensuring the reliability of the results. The best synthesis conditions for 4a, 4b, 4c, 4d, and 4g compounds were found to be reflux at 40°C for 6 hours, whereas 4e and 4f compounds reactions were performed in an ice bath for 11 and 17 hours, respectively. All product syntheses, 4a-4g compound, were purified using column chromatography and eluted using eluent hexane: acetone (6:4), and the yields of 4a-4g compounds were around 61-79%. The pure compounds were characterized using FTIR and 1HNMR spectrometer, further validating the research. Based on these findings, it can be concluded that all 5-Fu derivatives can be synthesized using the Schotten-Baumann reaction method.

Abstract Background Gastric cancer (GC) encompasses many different histological and molecular subtypes. It is a major driver of cancer mortality because of poor survival and limited treatment options. Personalised medicine in the form of patient-derived organoids (PDOs) represents a promising approach for improving therapeutic outcomes. The goal of this study was to overcome the limitations of current models by ameliorating organoid cultivation. Methods Organoids derived from cancer tissue were evaluated by haematoxylin and eosin staining, immunohistochemistry, mRNA, and whole-exome sequencing. Three representative chemotherapy drugs, 5-fluorouracil, docetaxel, and oxaliplatin, were compared for their efficacy against different subtypes of gastric organoids by ATP assay and apoptosis staining. In addition, drug sensitivity screening results from two publicly available databases, the Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopaedia, were pooled and applied to organoid lines. Once key targeting genes were confirmed, chemotherapy was used in combination with poly (ADP ribose) polymerase (PARP)-targeted therapy. Results We successfully constructed GC PDOs surgically resected from GC patient tissue. PDOs closely reflected the histopathological and genomic features of the corresponding primary tumours. Whole-exosome sequencing and mRNA analysis revealed that changes to the original tumour genome were maintained during long-term culture. The drugs caused divergent responses in intestinal, poorly differentiated intestinal, and diffuse gastric cancer organoids, which were confirmed in organoid lines. Poorly differentiated intestinal GC patients benefited from a combination of 5-fluorouracil and veliparib. Conclusion The present study demonstrates that combining chemotherapy with PARP targeting may improve the treatment of chemotherapy-resistant tumours.

Objective: Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme that degrades uracil, thymine, and 5-fluorouracil, which are important for treating gastric, colorectal, and breast cancers. In this study, we aimed to determine the association between chemotherapy-related toxicities and DPD gene variants; evaluate the consequences of these genetic differences; and integrate DPYD genetic screening into conventional cancer treatment regimens. Methods: Sixty-two patient files from 2015 to 2018 were retrospectively reviewed to investigate whether the DPYD gene causes toxicity before or during treatment. A total of 50 patients were enrolled after receiving informed consent and ethical clearance for the comprehensive examinations. The aim of this study was to reveal the genetic causes of adverse effects and better understand treatment responses. Results: Our analysis of 50 patients with cancer revealed that the severity of response to fluoropyrimidine compounds used in chemotherapy varied depending on DPYD gene polymorphisms. These mutations increased susceptibility to severe neutropenia -which can weaken immune systems- among other negative effects. It also found that IVS14 + 1G>A had a significant effect on treatment outcome, indicating that genetic screening should be included in planning therapy as it can prevent major side effects. Conclusion: Dihydropyrimidine connected to dehydrogenase gene polymorphism occurred in patients with gastrointestinal cancer who developed diarrhea, nausea, anemia, thrombostitopenia, and grade 3-4 neutropenia side effects while receiving 5-FU.

Yixin Li,1– 6,&ast; Qi Sun,2,3,7,&ast; Lingjia Hao,1,8 Han Shan,2,3,7 Zixi Jiang,1– 6 Ying Wang,1– 6 Zeyu Chen,2,3,7 Wu Zhu,1– 6 Shuang Zhao1– 6 1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 2Furong Laboratory (Precision Medicine), Changsha, 410008, People’s Republic of China; 3National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 4Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 5Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 6National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 7School of Mechanical and Electrical Engineering, Central South University, Changsha, 410083, People’s Republic of China; 8Xiangya School of Medicine, Central South University, Changsha, 410083, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuang Zhao; Wu Zhu, Department of Dermatology, Xiangya Hospital of Central South University, 87 Xiangya Road, Kaifu District, Changsha, Hunan Province, People’s Republic of China, Email shuangxy@csu.edu.cn; zhuwuxy@csu.edu.cnIntroduction: Pathological scars, such as hypertrophic scars and keloids, are characterized by the proliferation of fibroblasts and the deposition of collagen that often cause pruritus, pain, and disfigurement. Due to their high incidence and deformity, pathological scars have resulted in severe physical and psychological trauma for patients. Intralesional injection of 5-fluorouracil (5-Fu) is a recommended option for treating pathological scars. However, the efficacy of 5-Fu injection was limited and unstable due to limited drug penetration and short retention time.Methods: Liposomes are promising carriers that have advantages, such as high biocompatibility, controlled release property, and enhanced clinical efficacy. Here, we constructed a transdermal 5-Fu-loaded liposome (5-Fu-Lip) to provide a more effective and safer modality to scar treatment.Results: Compared to 5-Fu, 5-Fu-Lip showed superior ability in inhibiting primary keloid fibroblasts proliferation, migration, and collagen deposition, and also significantly inhibited human umbilical vein endothelial cells (HUVECs) proliferation and microvessel construction. In vivo experiments demonstrated that 5-Fu-Lip can significantly reduce the severity of hypertrophic scars in a rabbit ear wounding model.Discussion: 5-Fu-Lip provides a promising strategy to improve drug efficacy, which has great potential in the treatment of pathological scars.Keywords: liposome, pathological scar, 5-fluorouracil, fibroblast

Background: Keloids and hypertrophic scars are a commonly encountered problem in dermatology. There are many treatment modalities available with variable efficacy and recurrences. This study highlights the use of hyaluronidase with triamcinolone acetonide (TAC) and 5-fluorouracil (5-FU). Purpose: To assess the utility of hyaluronidase in combination with TAC and 5-FU in treatment of hypertrophic scars and keloids. Methods: In this study a combination of hyaluronidase along with TAC and 5-FU was given in one part and a combination of TAC and 5-FU was given in another half of same hypertrophic scar/keloid keeping 1cm gap in between the two untreated at 4 weekly interval for 24 weeks. Results were assessed by measuring height, volume of lesion and their percentage decrease. Also, pliability, vascularity, pigmentation of lesion and Vancouver scar assessment scale score were assessed. Side effects like ulceration, surrounding skin atrophy and telangiectasias were noted. Results: There was a reduction in all the parameters in both the treatment segments. Faster improvement in height, volume, pliability, vascularity, pigmentation, and Vancouver scar assessment scale score was noted with combination of hyaluronidase, TAC, and 5-FU compared to TAC and 5-FU alone. Side effect profile of ulceration, surrounding skin atrophy and telangiectasias was comparable in both the segments. Conclusion: Combination of hyaluronidase along with TAC and 5-FU offered a better outcome and faster response when compared to combination of TAC and 5-FU.

Abstract Background and aims The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been identified as a novel predictive marker for the development of cardiovascular illnesses in individuals without pre-existing health conditions. However, it remains unclear whether the levels of SII are linked to cardiotoxicity related to 5-FU. This retrospective study aims to fill this knowledge gap by examining the correlation between SII and cardiotoxicity related to 5-FU in a colorectal cancer cohort. Methods The study comprised colorectal cancer patients who received 5-FU-based chemotherapy at the affiliated cancer hospital of Guizhou Medical University between January 1, 2018 and December 31, 2020. After adjustment for confounders and stratification by tertiles of the interactive factor, linear regression analyses, curve fitting and threshold effect analyses were conducted. Results Of the 754 patients included final analysis, approximately 21% (n = 156) of them ultimately experienced cardiotoxicity related to 5-FU. Monocytes (M) was found as an influential element in the interaction between SII and cardiotoxicity related to 5-FU. In the low tertile of M (T1: M ≤ 0.38 × 109/L), increasing log SII was positively correlated with cardiotoxicity related to 5-FU (Odds Ratio [OR], 8.04; 95% confidence interval [95%CI], 1.68 to 38.56). However, a curvilinear relationship between log SII and cardiotoxicity was observed in the middle tertile of M (T2: 0.38 0.52 × 109/L), there was a tendency towards a negative linear correlation between the log SII and cardiotoxicity was observed (OR, 0.85; 95%CI, 0.37 to 1.98). Conclusion Our findings suggest that SII may serve as a potential biomarker for predicting cardiotoxicity related to 5-FU in colorectal cancer patients. SII is an independent risk factor for cardiotoxicity related to 5-FU with low monocytes levels (T1). Conversely, in the middle monocytes levels (T2), SII is a protective factor for cardiotoxicity related to 5-FU but with a threshold effect.

Abstract Background 5-Fluorouracil (5-FU) is used as an antineoplastic agent in distinct cancer types. Increasing evidence suggests that the gut microbiota might modulate 5-FU efficacy and toxicity, potentially affecting the patient’s prognosis. The current experimental study investigated 5-FU-induced microbiota alterations, as well as the potential of prebiotic fibre mixtures (M1-M4) to counteract these shifts. Methods A pooled microbial consortium was derived from ten healthy donors, inoculated in an in vitro model of the colon, and treated with 5-FU, with or without prebiotic fibre mixtures for 72 h. Four different prebiotic fibre mixtures were tested: M1 containing short-chain galacto-oligosaccharides (sc GOS), long-chain fructo-oligosaccharides (lcFOS), and low viscosity pectin (lvPect), M2 consisting of arabinoxylan, beta-glucan, pectin, and resistant starch, M3 which was a mixture of scGOS and lcFOS, and M4 containing arabinoxylan, beta-glucan, pectin, resistant starch, and inulin. Results We identified 5-FU-induced changes in gut microbiota composition, but not in microbial diversity. Administration of prebiotic fibre mixtures during 5-FU influenced gut microbiota composition and taxa abundance. Amongst others, prebiotic fibre mixtures successfully stimulated potentially beneficial bacteria (Bifidobacterium, Lactobacillus, Anaerostipes, Weissella, Olsenella, Senegalimassilia) and suppressed the growth of potentially pathogenic bacteria (Klebsiella, Enterobacter) in the presence of 5-FU. The short-chain fatty acid (SCFA) acetate increased slightly during 5-FU, but even more during 5-FU with prebiotic fibre mixtures, while propionate was lower due to 5-FU with or without prebiotic fibre mixtures, compared to control. The SCFA butyrate and valerate did not show differences among all conditions. The branched-chain fatty acids (BCFA) iso-butyrate and iso-valerate were higher in 5-FU, but lower in 5-FU + prebiotics, compared to control. Conclusions These data suggest that prebiotic fibre mixtures represent a promising strategy to modulate 5-FU-induced microbial dysbiosis towards a more favourable microbiota, thereby possibly improving 5-FU efficacy and reducing toxicity, which should be evaluated further in clinical studies.

Prostate and bladder cancer treatments have several challenges, including intense side effects and mechanisms of resistance. Thus, it is urgent to find drugs that can fill these gaps. For this purpose, Entecavir (ETV) was tested alone and in combination with 5-Fluorouracil (5-FU). Prior to this, a preliminary computational analysis was conducted to evaluate the combination of these two drugs. After exposing PC-3 and UM-UC-5 cells to the drugs, cell morphology was assessed using a microscope, while cell viability, proliferation, and cytotoxicity were evaluated using the MTT assay, and finally, the statistical analysis was performed. It was concluded that ETV showed significant cytotoxic effects in the PC-3 cells, and 5-FU, although not as effective as in other tumor types, it managed to inhibit the viability of the PC-3 cells. The combination of 5-FU with ETV after 72 h of exposure is an advantageous association, surpassing the results of each drug alone. In the UM-UC-5 cells, ETV alone did not produce the expected effect, neither did the combination. Nevertheless, repurposing ETV has proven to be an effective strategy in PC, especially through its combination with 5-FU.

As a chemotherapy drug, 5‐fluorouracil (5‐FU) has been used for colon cancer for decades. Excessive levels of 5‐FU in the human body can lead to notable adverse effects, including severe diarrhea, infection, mouth sores, skin peeling, skin inflammation, and ulcers, which are important and relatively common digestive side effects. In addition, 5‐FU is an analog of uracil and also has similarities to pyrimidines. Therefore, it is not easy to separate them. This research presented a sensor capable of detecting drugs in minimal amounts. An alginate‐derived carbon dot (CD) was synthesized by unique optical properties that obey an on–off fluorescence mechanism for 5‐FU sensing. Introducing copper (Cu(I)) to CDs results in fluorescence quenching through electron transfer. However, when 5‐FU is added to the system as an oxidizing agent, a redox reaction occurs on the surface of the CDs, which leads to the restoration of fluorescence as Cu(I) is altered to Cu(II). Experimental results showed a strong linear correlation (R2 = 0.99) in the concentration range of 1.00–45.00 nM, with the following linear regression, and revealed the relative standard deviation (RSD%) and detection limit of 2.57%, and 1.00 nM, respectively. These results validated the excellent detection capability of the proposed method even at low concentrations of 5‐FU and in the presence of other drugs and interfering substances. Also, the recovery of 5‐FU (varies from 100.46% to 113.7%, with RSD equal to 1.89–3.63) in serum samples indicates the absence of matrix interference in the determination of 5‐FU. In summary, this novel approach to developing a cost‐effective and sensitive sensor holds great potential for future applications in healthcare and related fields. [ABSTRACT FROM AUTHOR]

Background: Among the three most used anticancer drugs, cyclophosphamide, Adriamycin, and 5-Fluorouracil (CAF), the most significant outcome is chemobrain, caused by increased oxidative stress, inflammatory insult, and mitochondrial dysfunction. Objective: In this study, endogenous antioxidant coenzyme Q10 (CoQ10) was evaluated for its neuroprotective effects in CICI. Materials and methods: The chemobrain was induced in Swiss albino female mice by administering CAF (40 + 4 + 25 mg/kg) intraperitoneal (i.p.) in three cycles (single injection per week) followed by treatment with CoQ10 (40 mg/kg; p.o.) for up to 3 weeks followed by behavioral, biochemical, molecular and histopathological analysis. Results: Treatment with CoQ10 significantly improved cognition by improving exploring time in novel objects recognition test followed by increasing the time spent in the target quadrant in MWM test as compared to CAF-treated animals. Moreover, CoQ10 demonstrated antioxidant properties by reducing the expression of LPO while increasing levels of GSH, SOD, and catalase as compared to CAF-treated animals. While the levels of AChEs were significantly reduced after CoQ10 treatment in CAF-treated animals. In terms of its mechanism, it effectively counteracted the pro-inflammatory substances (TNF-α and IL-1β) triggered by CAF while also enhancing the levels of anti-inflammatory markers (IL-10 and Nrf2). Moreover, CoQ10 showed mitochondrial enhancers and it improved the level of Complex (I, II, and IV). Besides that, mitochondrial morphological analysis was done by TEM, and neuronal morphology along with quantification analysis was performed by H&E staining using Image J software to confirm the neuroprotective effect of CoQ10 over CAF-induced cognitive impairment. Conclusion: This study suggests CoQ10 can protect the mitochondria by imposing antioxidant, and anti-inflammatory properties, which could be a potential therapy for CICI. [ABSTRACT FROM AUTHOR]

Background: Despite advances in the treatment of cancer, pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to the lack of effective therapies. Our previous study showed that Luteolin (Lut), a flavonoid, suppressed pancreatocarcinogenesis and reduced the expression of dihydropyrimidine dehydrogenase (DPYD), an enzyme that degrades pyrimidines such as 5‐fluorouracil (5‐FU), in PDACs. In this study, we investigated the role of DPYD and evaluated the therapeutic potential of combining 5‐FU with Lut in PDACs. Methods and Results: PDAC cells overexpressing DPYD showed increased proliferation, and invasiveness, adding to the resistance to 5‐FU. The xenograft tumors of DPYD‐overexpressing PDAC cells also exhibit enhanced growth and invasion compared to the control xenograft tumors. RNA‐seq analysis of the DPYD‐overexpressing PDAC xenograft tumors revealed an upregulation of genes associated with metallopeptidase activity—MMP9 and MEP1A. Furthermore, the overexpression of MEP1A in PDAC was associated with invasion. Next, we investigated the combined effects of Lut, a DPYD suppressor, and 5‐FU on DPYD‐overexpressing xenograft tumors and PDAC of Pdx1‐Cre; LSL‐KrasG12D/+; Trp53flox/flox(KPPC) mice. Neither single administration of 5‐FU nor Lut showed significant inhibitory effects; however, the combined administration of 5‐FU and Lut exhibited a significant tumor‐suppressive effect in both the xenograft tumors and KPPC models. Conclusion: We have elucidated that DPYD expression contributes to proliferation, invasiveness, and 5‐FU resistance, in PDACs. The combination therapy of Lut and 5‐FU holds the potential for enhanced efficacy against PDACs. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) encompasses many different histological and molecular subtypes. It is a major driver of cancer mortality because of poor survival and limited treatment options. Personalised medicine in the form of patient-derived organoids (PDOs) represents a promising approach for improving therapeutic outcomes. The goal of this study was to overcome the limitations of current models by ameliorating organoid cultivation. Methods: Organoids derived from cancer tissue were evaluated by haematoxylin and eosin staining, immunohistochemistry, mRNA, and whole-exome sequencing. Three representative chemotherapy drugs, 5-fluorouracil, docetaxel, and oxaliplatin, were compared for their efficacy against different subtypes of gastric organoids by ATP assay and apoptosis staining. In addition, drug sensitivity screening results from two publicly available databases, the Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopaedia, were pooled and applied to organoid lines. Once key targeting genes were confirmed, chemotherapy was used in combination with poly (ADP ribose) polymerase (PARP)-targeted therapy. Results: We successfully constructed GC PDOs surgically resected from GC patient tissue. PDOs closely reflected the histopathological and genomic features of the corresponding primary tumours. Whole-exosome sequencing and mRNA analysis revealed that changes to the original tumour genome were maintained during long-term culture. The drugs caused divergent responses in intestinal, poorly differentiated intestinal, and diffuse gastric cancer organoids, which were confirmed in organoid lines. Poorly differentiated intestinal GC patients benefited from a combination of 5-fluorouracil and veliparib. Conclusion: The present study demonstrates that combining chemotherapy with PARP targeting may improve the treatment of chemotherapy-resistant tumours. [ABSTRACT FROM AUTHOR]

Drug resistance is a major challenge in the treatment of advanced cholangiocarcinoma (CCA). Understanding the mechanisms of drug resistance can aid in identifying novel prognostic biomarkers and therapeutic targets to improve treatment efficacy. This study established 5-fluorouracil- (5-FU) and gemcitabine-resistant CCA cell lines, KKU-213FR and KKU-213GR, and utilized comparative proteomics to identify differentially expressed proteins in drug-resistant cells compared to parental cells. Additionally, bioinformatics analyses were conducted to explore the biological and clinical significance of key proteins. The drug-resistant phenotypes of KKU-213FR and KKU-213GR cell lines were confirmed. In addition, these cells demonstrated increased migration and invasion abilities. Proteomics analysis identified 81 differentially expressed proteins in drug-resistant cells, primarily related to binding functions, biological regulation, and metabolic processes. Protein–protein interaction analysis revealed a highly interconnected network involving MET, LAMB1, ITGA3, NOTCH2, CDH2, and NDRG1. siRNA-mediated knockdown of these genes in drug-resistant cell lines attenuated cell migration and cell invasion abilities and increased sensitivity to 5-FU and gemcitabine. The mRNA expression of these genes is upregulated in CCA patient samples and is associated with poor prognosis in gastrointestinal cancers. Furthermore, the functions of these proteins are closely related to the epithelial–mesenchymal transition (EMT) pathway. These findings elucidate the potential molecular mechanisms underlying drug resistance and tumor progression in CCA, providing insights into potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: 5-Fluorouracil (5-FU) has been used as a standard first-line treatment for colorectal cancer (CRC) patients. Although 5-FU-based chemotherapy and immune checkpoint blockade (ICB) have achieved success in treating CRC, drug resistance and low response rates remain substantial limitations. Thus, it is necessary to construct a 5-FU resistance-related signature (5-FRSig) to predict patient prognosis and identify ideal patients for chemotherapy and immunotherapy. Methods: Using bulk and single-cell RNA sequencing data, we established and validated a novel 5-FRSig model using stepwise regression and multiple CRC cohorts and evaluated its associations with the prognosis, clinical features, immune status, immunotherapy, neoadjuvant therapy, and drug sensitivity of CRC patients through various bioinformatics algorithms. Unsupervised consensus clustering was performed to categorize the 5-FU resistance-related molecular subtypes of CRC. The expression levels of 5-FRSig, immune checkpoints, and immunoregulators were determined using quantitative real-time polymerase chain reaction (RT‒qPCR). Potential small-molecule agents were identified via Connectivity Map (CMap) and molecular docking. Results: The 5-FRSig and cluster were confirmed as independent prognostic factors in CRC, as patients in the low-risk group and Cluster 1 had a better prognosis. Notably, 5-FRSig was significantly associated with 5-FU sensitivity, chemotherapy response, immune cell infiltration, immunoreactivity phenotype, immunotherapy efficiency, and drug selection. We predicted 10 potential compounds that bind to the core targets of 5-FRSig with the highest affinity. Conclusion: We developed a valid 5-FRSig to predict the prognosis, chemotherapeutic response, and immune status of CRC patients, thus optimizing the therapeutic benefits of chemotherapy combined with immunotherapy, which can facilitate the development of personalized treatments and novel molecular targeted therapies for patients with CRC. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to compare the clinical outcomes of deep sclerectomy and trabeculectomy surgeries, both utilizing 5-fluorouracil. Methods: In this study, 11 eyes of 10 patients (14.3%) in the deep sclerectomy group and 66 eyes of 61 patients (85.7%) in the trabeculectomy group were retrospectively examined. Success in intraocular pressure (IOP) was defined as being below 21 mmHg without medication, partially successful if achieved below 21 mmHg with a single molecule, considered less successful with two to four molecules for maintaining IOP below 21 mmHg, and deemed unsuccessful if IOP exceeded 21 mmHg. Results: The deep sclerectomy group showed a success rate of 81.8% on post-operative day 1, with 18.2% considered unsuccessful; at post-operative 6 months, the success rate was 12.5%, with 50% partially successful and 37.5% less successful. In the trabeculectomy group, the success rate was 97% on post-operative day 1, with 3% considered unsuccessful; at post-operative 6 months, the success rate was 60.8%, with 15.7% partially successful, 13.7% less successful, and 9.8% unsuccessful. Trabeculectomy patients experienced complications such as choroidal detachment (6.1%), shallow anterior chamber (4.5%), tight suturing (3%), internal ostium occlusion (3%), posterior synechia (3%), bleb failure (1.5%), cyclodialysis/iridodialysis (1.5%), and hyphema (1.5%). In the deep sclerectomy group, tight suturing (36.3%), and dellen (9.09%) were observed, with no other complications reported. Conclusion: Trabeculectomy surgery has been observed to be superior to deep sclerectomy in follow-ups up to 48 months postoperatively. However, it is noted that there is a higher risk of post-operative complications. [ABSTRACT FROM AUTHOR]

Probiotics and prebiotics have gained attention for their potential health benefits. However, their efficacy hinges on probiotic survival through the harsh gastrointestinal environment. Microencapsulation techniques provide a solution, with resistant starch (RS)-based techniques showing promise in maintaining probiotic viability. Specifically, RS-encapsulated probiotics significantly improved probiotic survival in gastric acid, bile salts, and simulated intestinal conditions. This study investigated the effects of a resistant-starch-encapsulated probiotic cocktail (RS-Pro) in the context of 5-fluorouracil (5-FU) chemotherapy, which frequently induces microbiota dysbiosis and intestinal mucositis. Female BALB/c mice were divided into three groups: a 5-FU group, a 5-FU+Pro group receiving free probiotics, and a 5-FU+RS-Pro group receiving RS-encapsulated probiotics. After 28 days of treatment, analyses were conducted on fecal microbiota, intestinal histology, peripheral blood cell counts, and body and organ weights. It was revealed by 16S rRNA MiSeq sequencing that 5-FU treatment disrupted gut microbiota composition, reduced microbial diversity, and caused dysbiosis. RS-Pro treatment restored microbial diversity and increased the population of beneficial bacteria, such as Muribaculaceae, which play roles in carbohydrate and polyphenol metabolism. Furthermore, 5-FU administration induced moderate intestinal mucositis, characterized by reduced cellularity and shortened villi. However, RS-Pro treatment attenuated 5-FU-induced intestinal damage, preserving villus length. Mild leukopenia observed in the 5-FU-treated mice was partially alleviated in 5-FU+Pro and 5-FU+RS-Pro groups. These findings suggest that RS-Pro may serve as an adjunct to chemotherapy, potentially reducing adverse effects and improving therapeutic outcomes in future clinical applications. [ABSTRACT FROM AUTHOR]

Highlights: The goal is to optimize the microsponge drug delivery system's preparation. Scaling up ensures product repeatability. FTIR, DSC, and SEM confirmed the drug-loaded microsponge particles' compatibility and porous shape. The final gel dosage had shear-thinning rheology, suggesting dermal use. Ultimately, it supports and advances the UN's sustainable development goals and G20. In 1987, Won invented the solid-phase porous microsphere (MS), which stores bioactive compounds in many interconnected voids. Spherical particles (5–300 μm), MS, may form clusters of smaller spheres, resulting in many benefits. The current investigation focussed on gel-encased formulation, which can be suitable for dermal usage. First, quasi-emulsion (w/o/w) solvent evaporation was used to prepare 5-fluorouracil (5 FU) MS particles. The final product was characterized (SEM shows porous structure, FTIR and DSC showed drug compatibility with excipients, and gel formulation is shear-thinning) and further scaled up using the 8-fold method. Furthermore, CCD (Central Composite Design) was implemented to obtain the optimized results. After optimizing the conditions, including the polymer (600 mg, ethyl cellulose (EC), eudragit RS 100 (ERS)), stirring speed (1197 rpm), and surfactant concentration (2% w/v), we achieved the following results: optimal yield (63%), mean particle size (152 µm), drug entrapment efficiency (76%), and cumulative drug release (74.24% within 8 h). These findings are promising for industrial applications and align with the objectives outlined in UN Sustainable Development Goals 3, 9, and 17, as well as the goals of the G20 initiative. [ABSTRACT FROM AUTHOR]