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BACKGROUND: Surgical standardization for transverse colon cancers (TCC) has not been established, and the oncologic benefit of central vessel ligation (CVL) are still unclear. This study aimed to evaluate the oncologic safety of TCC surgery without CVL of the middle colic artery (MCA). METHODS: This is a single-center, retrospective, observational, comparative study. The clinical, surgical, and pathological characteristics of the patients who underwent radical surgery for non-metastatic TCC between January 2012 and December 2020 were investigated, and the characteristic and oncologic outcomes of No CVL and CVL groups were compared. RESULTS: The number of No CVL and CVL groups was 47 (44.3%) and 59 (55.7%), respectively. There was no statistically significant difference between the two groups in surgical complications, stage, mean number of retrieved lymph nodes (LN) (24.12 vs. 22.36 p = 0.464), mean number of metastatic LN (1.53 vs. 0.74, p = 0.163), mean proximal margin (19.2 cm vs. 16.7 cm, p = 0.139), mean distal margin (9.6 cm vs. 9.9 cm, p = 0.753), adjuvant chemotherapy, total recurrence rate (6.4 vs. 11.9%, p = 0.507), lymphatic recurrence rate (0.0% vs. 5.1%, p = 0.253), and local recurrence rate (2.1 vs. 1.7%, p = 0.984). Furthermore, there was no statistically significant difference of 5-year disease-free survival (DFS) and overall survival (OS) in stage II (DFS: 94.4 vs. 91.3%, p = 0.685, OS: 94.1 vs. 95.5%, p = 0.838) and stage III (DFS: 88.5 vs. 68.4%, p = 0.253, OS: 100.0% vs. 79.7, p = 0.328). CONCLUSION: TCC surgery without CVL of the MCA showed comparable surgical and oncologic outcomes compared to surgery with CVL. Therefore, preservation of a branch of the MCA may be considered a safe option, when combined with adequate lymph node dissection, if necessary. A large, prospective, and controlled study will be necessary to provide solid evidence of the oncologic safety of this procedure.
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AIM: The aim of this study was to compare the clinicopathological and oncological characteristics of sporadic colorectal cancer (CRC) between young and elderly patients without any genetic mutations that cause hereditary CRC. METHOD: In this cross-sectional, retrospective study conducted at three tertiary referral hospitals, we enrolled 1599 patients with CRC who underwent surgery between January 2010 and December 2017, including 157 young patients (age ≤ 40 years; yCRC) and 1442 elderly patients (age ≥ 70 years; eCRC). The clinicopathological and oncological outcomes were compared between the two groups. RESULTS: The median age at diagnosis was 37 years in the yCRC group (range 33.0-39.2 years) and 76 years in the eCRC group (range 72.0-79.0 years). The yCRC group did not present with advanced stages at diagnosis compared with the eCRC group, and the distribution of tumour stages was similar between the two groups. Microsatellite instability (MSI) testing revealed no difference in the frequency of tumours with high MSI (7.8% in yCRC, 5.8% in eCRC), and the frequency of mutations in the KRAS, NRAS and BRAF genes was also similar. The 3-year overall survival was better in the yCRC group than in the eCRC group (97.4% vs. 83.5%, p < 0.001); however, no such difference was observed in cancer-specific survival. CONCLUSION: Genetically proven sporadic CRCs did not differ significantly between young and elderly patients in terms of tumour stage, tumour location and various molecular features. CLINICAL TRIAL REGISTRATION NUMBER: The study was retrospectively registered with Clinical Trials.gov (no. NCT05601609).
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Neoplasias Colorrectales , Inestabilidad de Microsatélites , Mutación , Proteínas Proto-Oncogénicas B-raf , Adulto , Anciano , Femenino , Humanos , Masculino , Factores de Edad , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Estudios Transversales , GTP Fosfohidrolasas/genética , Proteínas de la Membrana/genética , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios RetrospectivosRESUMEN
BACKGROUND: Although organs are preserved and quality of life is improved, insufficient evidence is available for the oncologic safety of partial cystectomy in patients with colorectal cancer with suspected bladder invasion. Therefore, we aimed to compare partial and total cystectomy outcomes in patients with pathologically confirmed or clinically suspected bladder invasion. METHODS: Patients with colorectal cancer with suspected bladder invasion who underwent R0 resection from 2000 to 2020 were evaluated. Long-term outcomes were determined in patients with histologically confirmed bladder invasion. RESULTS: Of the 151 consecutive patients, 96 (64.6%) had histologically confirmed bladder involvement, and 105 (69.5%) underwent partial cystectomy. Operative time, estimated blood loss, and reoperation rate in ≤30 days were significantly worse in the total cystectomy group than in the partial cystectomy group. The overall recurrence rate was significantly higher in the total cystectomy group than in the partial cystectomy group (39.1% vs 21.9%; P = .046). Five-year overall survival (75.8% vs 53.2%; P = .006) rates were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival (60.8% vs 41.6%; P = .088) rates were similar in patients with suspected bladder invasion. In patients with histologically confirmed bladder invasion, 5-year overall survival rates (78.1% vs 52.1%; P = .017) were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival rates (53.4% vs 41.2%; P = .220) did not differ significantly. CONCLUSION: R0 resection is associated with favorable long-term outcomes in patients with locally advanced colorectal cancer. If R0 resection is possible, partial cystectomy is considered safe.
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Neoplasias Colorrectales , Cistectomía , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Humanos , Cistectomía/métodos , Masculino , Femenino , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Persona de Mediana Edad , Anciano , Invasividad Neoplásica/patología , Estudios Retrospectivos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Vejiga Urinaria/patología , Vejiga Urinaria/cirugía , Resultado del Tratamiento , Supervivencia sin Enfermedad , Anciano de 80 o más Años , AdultoRESUMEN
Papaya contains high amounts of vitamins A, C, riboflavin, thiamine, niacin, ascorbic acid, potassium, and carotenoids. It is confirmed by several studies that all food waste parts such as the fruit peels, seeds, and leaves of papaya are potential sources of phenolic compounds, particularly in the peel. Considering the presence of numerous bioactive compounds in papaya fruit peels, the current study reports a rapid, cheap, and environmentally friendly method for the production of gold nanoparticles (AuNPs) employing food biowaste (vegetable papaya peel extract (VPPE)) and investigated its antioxidant, antidiabetic, tyrosinase inhibition, anti-inflammatory, antibacterial, and photocatalytic degradation potentials. The phytochemical analysis gave positive results for tannins, saponins, steroids, cardiac steroidal glycoside, protein, and carbohydrates. The manufactured VPPE-AuNPs were studied by UV-Vis scan (with surface plasmon resonance of 552 nm), X-ray diffraction analysis (XRD) (with average crystallite size of 44.41 nm as per the Scherrer equation), scanning electron microscopy-energy-dispersive X-ray (SEM-EDS), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), particle size, zeta potential, etc. The mean dimension of the manufactured VPPE-AuNPs is 112.2 d.nm (PDI-0.149) with a -26.1 mV zeta potential. The VPPE-AuNPs displayed a significant antioxidant effect (93.24% DPPH scavenging and 74.23% SOD inhibition at 100 µg/mL); moderate tyrosinase effect (with 30.76%); and substantial α-glucosidase (95.63%) and α-amylase effect (50.66%) at 100 µg/mL. Additionally, it was found to be very proficient in the removal of harmful methyl orange and methylene blue dyes with degradation of 34.70% at 3 h and 24.39% at 5 h, respectively. Taken altogether, the VPPE-AuNPs have been proven to possess multiple biopotential activities, which can be explored by the food, cosmetics, and biomedical industries.
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Background: Citrus reticulata Blanco essential oil (CBEO) has attracted increasing attention as a potential treatment for depression and anxiety in recent years. However, there is limited evidence regarding the active compounds responsible for its therapeutic effects. In addition, substantial amounts of CBEO and prolonged therapy are often required. This study aims to investigate the rapid acting antidepressant and anxiolytic effects of CBEO, identify the underlying composition as well as optimize its dosage and duration. Methods: CBEO composition was determined using gas chromatography-mass spectrometry (GC-MS), and the corresponding targets were obtained from the SwissTargetPrediction database. Depression-related targets were collected from DisGeNET, GeneCards, Therapeutic Target Database, and Online Mendelian Inheritance in Man. Subsequently, the overlap between CBEO and depression targets was utilized to build a network diagram depicting the relationship between the active ingredients and targets using Cytoscape software. The STRING database facilitated the construction of a protein-protein interaction network, and the Ma'ayan Laboratory Enrichment tool was employed for Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Wiki pathway analyses. Molecular docking was conducted using AutoDock Vina and Discovery Studio Visualizer. Topological analysis predicted the main antidepressant active ingredients in CBEO. A mixture of these compounds was prepared based on their relative GC-MS ratios. Tail suspension test, elevated plus maze, corticosterone-induced PC12 cells, and lipopolysaccharide (LPS)-induced BV2 cells were used to validate the antidepressant and anxiolytic potential of CBEO and CBEO's main bioactive constituents. Results: CBEO contains 18 components that target 121 proteins. We identified 595 targets associated with depression; among them, 29 targets were located between essential oils and depression. Topological results revealed that linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol were the major active compounds of CBEO in the management of depression. GO analysis identified G protein-coupled opioid receptor activity, phospholipase C-activating G protein-coupled receptor, and neuron projections that were mostly related to molecular functions, cellular components, and biological processes. Neuroactive ligand-receptor interactions, chemical carcinogenesis, and calcium signaling pathways were the major pathways identified in KEGG analysis. Molecular docking showed that the main bioactive ingredients of CBEO had favorable binding affinities for Protein-Protein Interaction's hub proteins, including OPRM1, PTGS2, ESR1, SLC6A4, DRD2, and NR3C1. These five compounds were then mixed at 0.8:5:0.6:2:1 (w/w) ratio to form a CBEO antidepressant active compound mixture. An acute intranasal treatment of CBEO (25 mg/kg) only demonstrated an antidepressant effect, whereas the main bioactive compounds combination (12.5 mg/kg) illustrated both antidepressant and anxiolytic effects in mice. Linalool, p-cymene, and terpinene-4-ol exhibited neuroprotective and anti-neuroinflammation in the in vitro study, while these effects were not observed for α-terpinene and α-terpineol. Conclusion: Linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol cymene might be mainly contributing to CBEO's antidepressant effect by regulating neuroactive ligand-receptor interaction, neuron projection, and receptor signaling pathway. A mixture of these compounds showed rapid antidepressant potential via intranasal administration, which was comparable to that of CBEO. The mixture also exhibited an anxiolytic effect while not seen in CBEO.
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BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Colon , Adulto , Anciano , Humanos , Persona de Mediana Edad , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Ensayos Clínicos Fase II como Asunto , Neoplasias del Colon/patología , Supervivencia sin Enfermedad , Estudios Multicéntricos como Asunto , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Fluorouracilo/uso terapéuticoRESUMEN
BACKGROUND: Intranasal administration has been adopted in traditional medicine to facilitate access to the bloodstream and central nervous system (CNS). In modern medicine, nasal drug delivery systems are valuable for disease treatment because of their noninvasiveness, good absorption, and fast-acting effects. OBJECTIVE: This study aimed to systematically organize preclinical and clinical studies on intranasal herbal medicines to highlight their potential in drug development. METHODS: A comprehensive search for literature until February 2023 was conducted on PubMed and the Web of Science. From the selected publications, we extracted key information, including the types of herbal materials, target diseases, intranasal conditions, methods of toxicity evaluation, main outcomes, and mechanisms of action, and performed quality assessments for each study. RESULTS: Of the 45 studies, 13 were clinical and 32 were preclinical; 28 studies used herbal extracts, 9 used prescriptions, and 8 used natural compounds. The target diseases were rhinosinusitis, influenza, fever, stroke, migraine, insomnia, depression, memory disorders, and lung cancer. The common intranasal volumes were 8-50 µl in mice, 20-100 µl in rats, and 100-500 µl in rabbits. Peppermint oil, Ribes nigrum folium, Melia azedarach L., Elaeocarpus sylvestris, Radix Bupleuri, Da Chuan Xiong Fang, Xingnaojing microemulsion, and Ginsenoside Rb1 emerged as potential candidates for rapid intranasal therapy. The in vivo toxicity assessments were based on mortality, body weight, behavioral changes, mucociliary activity, histopathology, and blood tests. Most intranasal treatments were safe, except for Cyclamen europaeum, Jasminum sambac, Punica granatum L., and violet oil, which caused mild adverse effects. At lower doses, intranasal herbal treatments often show greater effects than oral administration. The actions of intranasal herbal medicine mainly involve regulating inflammation and neurotransmission, with the olfactory bulb and anterior cingulate cortex to be relevant brain regions. CONCLUSION: Intranasal delivery of herbal materials holds promise for enhancing drug delivery efficacy and reducing treatment duration, offering a potential future perspective for developing intranasal therapies for various diseases.
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Administración Intranasal , Extractos Vegetales , Animales , Encéfalo , Fiebre/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , HumanosRESUMEN
BACKGROUND: Pterocarpus santalinus L. essential oil (PSEO) is traditionally employed for treating fever and mental aberrations. We aim to explore the antidepressant potential of intranasal PSEO in social defeat stress (SDS)-expose mice and identify its mechanisms and components. METHODS: PSEO components were analyzed using gas chromatography-mass spectrometry (GC-MS). C57BL/6 mice underwent a 10-day SDS with intranasal PSEO (10, 20 mg/kg) for 21 days. Efficacy was evaluated through changes in behaviors and serum corticosterone (CORT), hippocampal neurotransmitter, and inflammatory cytokine levels. In vitro effects were examined using primary hippocampal neurons, PC12 and BV2 cells. RESULTS: GC-MS identified 22 volatile compounds in PSEO, and (+)-ledene (16.7%), cedrol (13.5%), and isoaromadendrene epoxide (7.0%) as major components. PSEO (20 mg/kg) significantly reversed SDS-induced social withdrawal, increased open-area explorations in the open field test (OFT) and elevated plus maze (EPM) test, and reduced immobility time in the tail suspension test (TST) and forced swimming test (FST). PSEO downregulated serum CORT and hippocampal interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α levels, while increasing hippocampal gamma-aminobutyric acid (GABA), norepinephrine (NE), and serotonin (5-HT) levels. PSEO (0.1, 1, 10 µg/mL) reduced neurotoxicity and neuroinflammation in PC12 and BV2 cells, respectively. PSEO (10 µg/mL) enhanced glutamic acid decarboxylase 6 (GAD6)- and GABA B receptor 1 (GABABR1)-positive puncta in the hippocampal neurons and FM1-43 fluorescence intensity. CONCLUSION: Intranasal PSEO exhibited antidepressant-like effects on SDS-exposed mice, potentially through modulating stress hormone, neurotransmission, and neuroinflammation. Further investigation into the pharmacokinetics, bioavailability, and mechanisms of (+)-ledene, cedrol, and isoaromadendrene epoxide is needed.
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Depresión , Aceites Volátiles , Sesquiterpenos Policíclicos , Pterocarpus , Ratones , Animales , Depresión/inducido químicamente , Aceites Volátiles/farmacología , Enfermedades Neuroinflamatorias , Derrota Social , Ratones Endogámicos C57BL , Antidepresivos/farmacología , Hipocampo , Corticosterona , Factor de Necrosis Tumoral alfa/metabolismo , Conducta Animal , Transmisión Sináptica , Compuestos Epoxi/farmacología , Modelos Animales de EnfermedadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Perillae Folium, the leaves and twigs of Perilla frutescens (L.) Britton, has been included in many traditional Chinese medicine herbal formulas to treat depression. However, the precise antidepressant mechanism of the essential oil from Perillae Folium (PFEO) has not been fully investigated. AIM OF THE STUDY: To assess the effects and potential mechanisms of PFEO on depression using animal models and network pharmacology analysis. MATERIALS AND METHODS: PFEO was intranasally administered to a mouse model of social defeat stress (SDS). The antidepressant effects of PFEO on SDS-induced mice were evaluated using behavioral tests. Enzyme-linked immunosorbent assay (ELISA) and western blot were performed to measure the levels of depression-related biomarkers in the hippocampus and serum of the mice. The chemical compounds of PFEO were determined using gas chromatography-mass spectrometry (GC-MS). Network pharmacology and molecular docking analyses were conducted to investigate the potential bioactive components of PFEO and the mechanisms underlying the antidepressant effects. To validate the mechanisms of the bioactive compounds, in vitro models using PC12 and BV2 cells were established and the blood-brain barrier (BBB) permeability was evaluated. RESULTS: The intranasal administration of PFEO suppressed SDS-induced depression in mice by increasing the time spent in the social zone and the social interactions in the social interaction test and by decreasing the immobility time in the tail suspension and forced swimming tests. Moreover, the PFEO treatment reduced the SDS-induced anxiety-like behavior, as inferred from the increased activity in the central zone observed in the open field test and in the open arms observed in the elevated plus maze test. PFEO administration recovered the SDS-induced decrease in the levels of 5-HT, NE, gamma-aminobutyric acid (GABA), and p-ERK in the hippocampus of mice. Furthermore, the increased serum corticosterone level was also attenuated by the PFEO treatment. A total of 21 volatile compounds were detected in PFEO using GC-MS, among which elemicin (15.52%), apiol (15.16%), and perillaldehyde (12.79%) were the most abundant ones. The PFEO compounds targeted 32 depression-associated genes, which were mainly related to neural cells and neurotransmission pathways. Molecular docking indicated good binding affinities between the bioactive components of PFEO (apiol, ß-caryophyllene, elemicin, and myristicin) and the key targets, including ACHE, IL1B, IL6, MAOB, SLC6A2, SLC6A3, SLC6A4, and tumor necrosis factor. Among the four compounds, ß-caryophyllene, elemicin, and myristicin were more effective in reducing neurotoxicity and neuroinflammation. Elemicin showed the highest BBB permeability rate. CONCLUSIONS: This study shows the antidepressant activities of PFEO in an SDS-induced mouse model and suggests its potential mechanisms of action: regulation of the corticosterone levels, hippocampal neurotransmitters, and ERK signaling. Apiol, ß-caryophyllene, elemicin, and myristicin may be the main contributors to the observed effects induced by PFEO. Further studies are needed to fully elucidate the underlying mechanisms and the main PFEO bioactive components.
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Derivados de Alilbenceno , Depresión , Dioxolanos , Aceites Volátiles , Sesquiterpenos Policíclicos , Pirogalol/análogos & derivados , Animales , Ratones , Depresión/tratamiento farmacológico , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Corticosterona , Administración Intranasal , Simulación del Acoplamiento Molecular , Derrota Social , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Conducta Animal , Hipocampo , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: A combination of oral antibiotics and mechanical bowel preparation is recommended for patients scheduled to undergo elective colorectal surgery on the basis of recent large trials that have reported the superiority of this approach in preventing surgical site infections (SSIs). However, there are no standard recommendations for this approach. Therefore, in this study, we evaluated the efficacy of rifaximin and metronidazole and mechanical bowel preparation for preventing SSIs in cases of minimally invasive surgery for colorectal cancer. METHODS: This single-arm prospective observational study included 256 individuals. The primary end point was the rate of SSI. Rifaximin 400 mg and metronidazole 500 mg were administered twice daily (10 am and 10 pm), and mechanical bowel preparation was administered the day before the operation. RESULTS: After excluding 15 patients, 241 were enrolled. No adverse event occurred following the administration of oral antibiotics and mechanical bowel preparation; there was 100% compliance. The total SSI rate was 2.9%; the rates of incisional and organ/space SSIs were 1.2% and 1.7%, respectively. All patients were treated conservatively. Univariate analyses revealed preoperative anemia, hypoalbuminemia, and transfusion and postoperative transfusion were significantly associated with SSIs. DISCUSSION: A 1 day rifaximin and metronidazole regimen with mechanical bowel preparation for elective minimally invasive surgery for colorectal cancer was associated with a favorable SSI rate of 2.9%, safety, and high compliance. This approach is appropriate for inclusion in the current guidelines for perioperative management of patients scheduled to undergo minimally invasive surgery for colorectal cancer.
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Neoplasias Colorrectales , Metronidazol , Humanos , Metronidazol/uso terapéutico , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , Rifaximina , Antibacterianos/uso terapéutico , Procedimientos Quirúrgicos Mínimamente Invasivos , Neoplasias Colorrectales/cirugíaRESUMEN
Halide solid electrolytes (SEs) have been highlighted for their high-voltage stability. Among the halide SEs, the ionic conductivity has been improved by aliovalent metal substitutions or choosing a ccp-like anion-arranged monoclinic structure (C2/m) over hcp- or bcc-like anion-arranged structures. Here, we present a new approach, hard-base substitution, and its underlying mechanism to increase the ionic conductivity of halide SEs. The oxygen substitution to Li2ZrCl6 (trigonal, hcp) increased the ionic conductivity from 0.33 to 1.3 mS cm-1 at Li3.1ZrCl4.9O1.1 (monoclinic, ccp), while the sulfur and fluorine substitutions were not effective. A systematic comparison study revealed that the energetic stabilization of interstitial sites for Li migration plays a key role in improving the ionic conductivity, and the ccp-like anion sublattice is not sufficient to achieve high ionic conductivity. We further examined the feasibility of the oxyhalide SE for practical and all-solid-state battery applications.
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BACKGROUND: Approximately 40% of colorectal cancer (CRC) cases are linked to Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. KRAS mutations are associated with poor CRC prognosis, especially KRAS codon 12 mutation, which is associated with metastasis and poorer survival. However, the clinicopathological characteristics and prognosis of KRAS codon 13 mutation in CRC remain unclear. AIM: To evaluate the clinicopathological characteristics and prognostic value of codon-specific KRAS mutations, especially in codon 13. METHODS: This retrospective, single-center, observational cohort study included patients who underwent surgery for stage I-III CRC between January 2009 and December 2019. Patients with KRAS mutation status confirmed by molecular pathology reports were included. The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed. Survival data were analyzed to identify codon-specific KRAS mutations as recurrence-related factors using the Cox proportional hazards regression model. RESULTS: Among the 2203 patients, the incidence of KRAS codons 12, 13, and 61 mutations was 27.7%, 9.1%, and 1.3%, respectively. Both KARS codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics, but only codon 12 was associated with pathological features, such as stage of primary tumor (T stage), lymph node involvement (N stage), vascular invasion, perineural invasion, tumor size, and microsatellite instability. KRAS codon 13 mutation showed no associations (77.2% vs 85.3%, P = 0.159), whereas codon 12 was associated with a lower 5-year recurrence-free survival rate (78.9% vs 75.5%, P = 0.025). In multivariable analysis, along with T and N stages and vascular and perineural invasion, only codon 12 (hazard ratio: 1.399; 95% confidence interval: 1.034-1.894; P = 0.030) among KRAS mutations was an independent risk factor for recurrence. CONCLUSION: This study provides evidence that KRAS codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for CRC in a large-scale cohort.
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Neoplasias Colorrectales , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos , Mutación , Codón , Neoplasias Colorrectales/genéticaRESUMEN
Depression is a serious psychiatric disorder with high prevalence, and the delayed onset of antidepressant effects remains a limitation in the treatment of depression. This study aimed to screen essential oils that have the potential for rapid-acting antidepressant development. PC12 and BV2 cells were used to identify essential oils with neuroprotective effects at doses of 0.1 and 1 µg/mL. The resulting candidates were treated intranasally (25 mg/kg) to ICR mice, followed by a tail suspension test (TST) and an elevated plus maze (EPM) after 30 min. In each effective essential oil, five main compounds were computationally analyzed, targeting glutamate receptor subunits. As a result, 19 essential oils significantly abolished corticosterone (CORT)-induced cell death and lactate dehydrogenase (LDH) leakage, and 13 reduced lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). From in vivo experiments, six essential oils decreased the immobility time of mice in the TST, in which Chrysanthemum morifolium Ramat. and Myristica fragrans Houtt. also increased time and entries into the open arms of the EPM. Four compounds including atractylon, α-curcumene, α-farnesene, and selina-4(14),7(11)-dien-8-one had an affinity toward GluN1, GluN2B, and Glu2A receptor subunits surpassed that of the reference compound ketamine. Overall, Atractylodes lancea (Thunb.) DC and Chrysanthemum morifolium Ramat essential oils are worthy of further research for fast-acting antidepressants through interactions with glutamate receptors, and their main compounds (atractylon, α-curcumene, α-farnesene, and selina-4(14),7(11)-dien-8-one) are predicted to underlie the fast-acting effect.
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Appetite dysregulation is one of the factors contributing to anorexia, bulimia nervosa, obesity, and diabetes. Essential oils or fragrant compounds have been proven to regulate food intake and energy expenditure; hence, this study aimed to summarize their effects on appetite and the underlying mechanisms. The PubMed and Web of Science databases were searched until July 2022. Only two of the 41 studies were performed clinically, and the remaining 39 used animal models. Oral administration was the most common route, and a dosage range of 100-2000 mg/kg for mice or 2-32 mg/kg for rats was applied, with a duration of 12 days to 4 weeks, followed by inhalation (10-6-10-3 mg/cage or 10-9-10-2 mg/cm3 within 1 h). Approximately 11 essential oil samples and 22 fragrant compounds were found to increase appetite, while 12 essential oils and seven compounds decreased appetite. These fragrant components can exert appetite-regulating effects via leptin resistance, the activity of sympathetic/parasympathetic nerves, or the mRNA expression of neuropeptide Y (NPY)/agouti-related protein (AgRP), cocaine- and amphetamine-regulated transcript (CART)/proopiomelanocortin (POMC) in the hypothalamus. Fragrance memory and cognitive processes may also play roles in appetite regulation. The findings of this study accentuate the potential of essential oils and fragrant compounds to regulate appetite and eating disorders.
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Apetito , Aceites Volátiles , Ratas , Ratones , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuropéptido Y/metabolismo , Hipotálamo/metabolismo , Leptina/metabolismo , Regulación del Apetito , Proteína Relacionada con Agouti/genética , Ingestión de AlimentosRESUMEN
The current investigation aimed at bimetallic gold-silver nanoparticles (Au/Ag NPs), here called BM-GS NPs, synthesis using sericin protein as the reducing agent in an easy, cost-effective, and sustainable way. The obtained BM-GS NPs were characterized by UV-Visible spectroscopy, Transmission electron microscopy (TEM), energy dispersive X-ray analysis (EDS), atomic force microscopy (AFM), Dynamic light scattering (DLS) and Zeta potential, X-ray Powder Diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and Thermogravimetric analysis followed by evaluation of its multitherapeutic and photocatalytic degradation potentials. The TEM analysis revealed its spherical nature and the EDS result displayed the presence of both Ag and Au elements, confirming the synthesis of BM-GS NPs. The XRD pattern verified the crystalline nature of the nanoparticles (NPs). The DLS analysis showed an average size of 86.08 d nm and the zeta potential showed a highly negative value (-26.3 mV) which specifies that the generated bimetallic NPs are stable. The BM-GS NPs exhibited positive wound healing potential (with 63.38% of wound closure rate at 25 µg/ml, as compared to 54.42% by the untreated control) with very negligible toxicity effect on the cell viability of the normal keratinocyte cells. It also demonstrated promising antioxidant properties with 65.00%, 69.23%, and 63.03% activity at 100 µg/ml concentration for ABTS (2, 2-azinobis) (3-ethylbenzothiazoline-6-sulfonic acid)), DPPH (1, 1 diphenyl-2-picrylhydrazyl) and SOD (superoxide dismutase enzyme) assays respectively, antidiabetic potential (with a significantly high α-glucosidase inhibition potential of 99.69% at 10µg/ml concentration and 62.11% of α-amylase enzyme inhibition at 100 µg/ml concentration) and moderate tyrosinase inhibitory potential (with 17.09% at 100 µg/ml concentration). Besides, it displayed reasonable antibacterial potential with the diameter of zone of inhibition ranging between 10.89 and 12.39 mm. Further, its antibacterial mode of action reveals that its effects could be due to being very smaller, the NPs could have penetrated inside the cellular membrane thereby causing rupture and damage to the interior materials leading to cellular lysis. The photocatalytic evaluation showed that synthesized BM-GS NPs have the efficiency of degrading methylene blue dye by 34.70% within 3 h of treatment. The above findings revealed the multi-therapeutic efficacy of the sericin globular protein-mediated BM-GS NPs and its potential future applications in the cosmetics and food sector and environmental contamination management industries.
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Nanopartículas del Metal , Sericinas , Espectroscopía Infrarroja por Transformada de Fourier , Plata/química , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Oro/química , Antibacterianos/farmacología , Antibacterianos/químicaRESUMEN
Introduction: A number of biological wastes and factory waste materials have been tested recently for the eco-friendly biosynthesis of nanoparticles. Sericin protein (SSP) is usually removed from the silk cocoon during the degumming process in the process of making the silk, and this sericin protein is normally thrown away by the sericulture industries as waste materials. It is found that this sericin protein possesses a number of biological properties. Methods: Considering this, in the present study, an effort has been made to biosynthesize gold nanoparticles (SSP-AuNPs) using the waste sericin solution as the reducing and capping agent and investigate its biopotential in terms of its wound healing, antioxidant and antibacterial activities. Results: The synthesis of SSP-AuNPs was perceived by the visual color change and confirmed by UV-Vis spectroscopy with absorption maxima at 522 nm. Further characterization of SSP-AuNPs was done by TEM, EDS, XRD, FTIR, DLS, zeta potential, TGA, AFM, etc. The size of SSP-AuNPs was found out to be 54.82 nm as per the particle size analyzer and the zeta potential is -19.8 mV. The SSP-AuNPs displayed promising wound healing potential of 70.96 and 69.76% wound closure rate at 5 and 10 µg/mL respectively as compared to 74.91% by the Centella asiatica taken as a positive control. It also exhibited promising antioxidant potential in terms of the DPPH, ABTS free radical scavenging, reducing power potential, and total antioxidant capacity. Besides, the SSP-AuNPs also displayed significant antibacterial activities against the tested pathogenic bacterial with the diameter of inhibition zones ranging between 12.10 and 14.96 mm as compared to the positive control cephalexin that displayed inhibition zones ranging between 12.08 and 13.24 mm. Discussion: Taken together, SSP-AuNPs could serve as an interesting candidate for food, cosmetics, and biomedical fields in the applications of wound healing, cosmetics, antibacterial bandages, and ointments, etc.
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Bombyx , Nanopartículas del Metal , Sericinas , Animales , Seda/química , Antioxidantes/farmacología , Antioxidantes/química , Sericinas/química , Sericinas/farmacología , Bombyx/química , Oro/química , Nanopartículas del Metal/química , Antibacterianos/farmacología , Antibacterianos/química , Cicatrización de HeridasRESUMEN
BACKGROUND: Self-expanding metallic stenting (SEMS) is usual for the temporary resolution of obstructive left-sided colorectal cancer (CRC) as a bridge to elective surgery. However, there is no consensus regarding adequate time intervals from stenting to radical surgery. The aim of this study was to identify the optimal time interval that results in favorable short- and long-term outcomes. METHODS: Data on patients with obstructive left-sided CRC who underwent elective radical surgery after clinically successful SEMS deployment in five tertiary referral hospitals from 2004 to 2016 were analyzed, retrospectively. An inverse probability treatment-weighted propensity score analysis was used to minimize bias. Postoperative short- and long-term outcomes were compared between two groups: an early surgery (within 8 days) group and delayed surgery (after 8 days) group. RESULTS: Of 311 patients, 148 (47.6%) underwent early and 163 (52.4%) underwent delayed surgery. The median surgery interval was 9.0 days. After adjustment, the groups had similar patient and tumor characteristics. In terms of short-term outcomes, there was no difference in hospitalization length or postoperative complications. No deaths were observed. With a median follow-up of 71.0 months, no significant difference was observed between the groups in 5-year overall survival (early vs. delayed surgery: 79.6% vs. 71.3%, P = 0.370) and 5-year disease-free survival (early vs. delayed surgery: 59.1% vs. 60.4%, P = 0.970). CONCLUSIONS: In obstructive left-sided CRC, the time interval between SEMS and radical surgery did not significantly influence short- and long-term outcomes. Therefore, early surgery after SEMS could be suggested if there is no reason to postpone surgery for preoperative medical optimization.
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Neoplasias Colorrectales , Obstrucción Intestinal , Stents Metálicos Autoexpandibles , Humanos , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Stents/efectos adversos , Stents Metálicos Autoexpandibles/efectos adversosRESUMEN
AIM: This study investigated the association between preoperative and postoperative changes in skeletal muscle mass and long-term oncological outcomes in patients with non-metastatic colorectal cancer. METHOD: Patients who underwent surgery for Stages I-III colorectal cancer from January 2014 to December 2015 were included. Skeletal muscle mass was evaluated through preoperative and postoperative abdominopelvic CT scans. A multivariable analysis was conducted to determine the factors affecting disease-free survival rates. RESULTS: A total of 238 patients were analysed. Forty-nine (25.9%) patients had preoperative sarcopenia. Patients with preoperative sarcopenia showed lower 3-year disease-free survival (58.5% vs. 78.4%, P = 0.001). Patients with postoperative sarcopenia also showed significantly lower 3-year disease-free survival compared to postoperative patients without sarcopenia at 6, 12 and 18 months, respectively (53.9% vs. 77.8%; 69.7% vs. 81.8%; 69.1% vs. 87.7%, P = 0.004). In a subgroup analysis, patients with both preoperative and postoperative sarcopenia showed the lowest 3-year disease-free survival rates (50.9%). The incidence of tumour recurrence was higher among the patients who had lost more skeletal muscle mass at 12, 18 and 24 months (-14.3 cm2 /m2 vs. -1.5 cm2 /m2 , P < 0.001; -24.5 cm2 /m2 vs. -1.1 cm2 /m2 , P < 0.001; and -31.6 cm2 /m2 vs. -1.4 cm2 /m2 , P < 0.001, respectively). A multivariable analysis demonstrated that the factors associated with disease-free survival included tumour stage, venous invasion, adjuvant chemotherapy, and preoperative or postoperative sarcopenia. CONCLUSION: Not only preoperative but also postoperative sarcopenic changes adversely affect oncological outcomes following curative resection of colorectal cancer. Careful attention should be given to correcting sarcopenic status from the preoperative to the postoperative period.
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Neoplasias Colorrectales , Sarcopenia , Humanos , Sarcopenia/complicaciones , Factores de Riesgo , Recurrencia Local de Neoplasia/patología , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Periodo Posoperatorio , Estudios Retrospectivos , Pronóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Músculo Esquelético/diagnóstico por imagenRESUMEN
Psoriasis is a chronic, immune-mediated inflammatory skin disorder. Rheum palmatum L. is a common traditional medicinal herb with anti-inflammatory and immunomodulatory activities. This study aimed to investigate the anti-psoriatic effects of the ethanolic extract from R. palmatum L. (RPE) and its chemical constituents, as well as the mechanisms underlying their therapeutic significance. An imiquimod (IMQ)-induced psoriasis-like mouse model was used to examine the anti-psoriatic effect of RPE in vivo. Network pharmacological analysis was performed to investigate the potential targets and related pathways of the RPE components, including rhein, emodin, chrysophanol, aloe-emodin, and physcion. The anti-inflammatory effects and underlying mechanisms of these components were examined using in vitro models. Topical application of RPE alleviated psoriasis-like symptoms and reduced levels of inflammatory cytokines and proliferation markers in the skin. Network pharmacological analysis revealed that RPE components target 20 genes that are linked to psoriasis-related pathways, such as IL-17, MAPK, and TNF signaling pathways. Among the five components of RPE, rhein and emodin showed inhibitory effects on TNF-α and IL-17 production in EL-4 cells, attenuated the production of CXCL8, CXCL10, CCL20, and MMP9, and reduced proliferation in HaCaT cells. Chrysophanol, aloe-emodin, and physcion were less effective than rhein and emodin in suppressing inflammatory responses and keratinocyte proliferation. The effects of these compounds might occur through the inhibition of the ERK, STAT3, and NF-κB signaling pathways. This study suggested the anti-psoriatic effect of RPE, with rhein and emodin as the main contributors that regulate multiple signaling pathways.