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BACKGROUND & AIMS: Autoimmune gastritis (AIG), distinct from Helicobacter pylori-associated atrophic gastritis (HpAG), is underdiagnosed due to limited awareness. This multicenter study aims to develop a novel endoscopic artificial intelligence (AI) system assisting in AIG diagnosis. METHODS: Patients diagnosed with AIG, as well as HpAG and non-atrophic gastritis (NAG), were retrospectively enrolled from six centers. Endoscopic images with relevant demographic and medical data, were collected for the development of AI-assisted system, SEER-SCOPE AI, based on multi-site feature fusion model. The diagnostic performance of SEER-SCOPE AI was evaluated in the internal and external datasets. Endoscopists' performance with and without AI support was tested and compared using Mann-Whitney U test. Heatmap analysis was performed to interpret SEER-SCOPE AI. RESULTS: 1 070 patients (294 AIG, 386 HpAG, 390 NAG) with 18 828 endoscopy images were collected. SEER-SCOPE AI achieved strong performance for identifying AIG, with 96.9% sensitivity, 92.2% specificity and an AUROC of 0.990 internally, and 90.3% sensitivity, 93.1% specificity and an AUROC of 0.973 externally. The performance of SEER-SCOPE AI (sensitivity 91.3%) was comparable to experts (87.3%) and significantly outperformed non-experts (70.0%). With AI support, the overall performance of endoscopists was improved (sensitivity: 90.3% [95% CI 86.0%-93.2%] vs. 78.7% [95% CI 73.6%-83.2%], p=0.008). Heatmap analysis revealed consistent focus of SEER-SCOPE AI on regions corresponding to atrophic areas. CONCLUSIONS: SEER-SCOPE AI demonstrated expert-level performance in identifying AIG, and enhanced the diagnostic ability of endoscopists. Its application holds promise as a potent endoscopy-assisted tool for guiding biopsy sampling and early detection of AIG.
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Growth differentiation factor 15 (GDF15) is a cell stress-response cytokine within the transforming growth factor-ß (TGFß) superfamily. It is known to exert diverse effects on many metabolic pathways through its receptor GFRAL, which is expressed in the hindbrain, and transduces signals through the downstream receptor tyrosine kinase Ret. Since the liver is the core organ of metabolism, summarizing the functions of GDF15 is highly important. In this review, we assessed the relevant literature regarding the main metabolic, inflammatory, fibrogenic, tumorigenic and other effects of GDF15 on different liver diseases, including Metabolic dysfunction-associated steatotic liver disease(MASLD), alcohol and drug-induced liver injury, as well as autoimmune and viral hepatitis, with a particular focus on the pathogenesis of MASLD progression from hepatic steatosis to MASH, liver fibrosis and even hepatocellular carcinoma (HCC). Finally, we discuss the prospects of the clinical application potential of GDF15 along with its research and development progress. With better knowledge of GDF15, increasing in-depth research will lead to a new era in the field of liver diseases.
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Factor 15 de Diferenciación de Crecimiento , Hepatopatías , Factor 15 de Diferenciación de Crecimiento/metabolismo , Humanos , Hepatopatías/metabolismo , Animales , Cirrosis Hepática/metabolismo , Carcinoma Hepatocelular/metabolismo , Hígado Graso/metabolismo , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Transducción de SeñalRESUMEN
Zearalenone (ZEN), a nonsteroidal estrogenic mycotoxin, causes enormous economic losses in the food and feed industries. Simple, rapid, low-cost, and quantitative analysis of ZEN is particularly urgent in the fields of food safety and animal husbandry. Using the bioluminescent bacterium Photobacterium phosphoreum T3, we propose a bioluminescence inhibition assay to evaluate ZEN levels quickly. The limit of detection (LOD), limit of quantification (LOQ), and quantitative working range of this bioluminescence inhibition assay were 0.1 µg/mL, 5 µg/mL, and 5-100 µg/mL, respectively. The concentration-response curve of the bioluminescence inhibition rate and ZEN concentration was plotted within the range 5 to 100 µg/mL, as follows: y = 0.0069x2 - 0.0190x + 7.9907 (R2 = 0.9943, y is luminescence inhibition rate, x is ZEN concentration). First, we used the bioluminescence inhibition assay to detect the remaining ZEN in samples treated with purified lactonohydrolase ZHD101. The bioluminescence inhibition assay results showed a strong correlation with the HPLC analysis. Furthermore, we successfully evaluated the overall toxicity of samples treated with purified peroxidase Prx and H2O2 using the P. phosphoreum T3 bioluminescence inhibition assay. The results indicate that the degradation products of ZEN created by purified peroxidase Prx and H2O2 showed little toxicity to P. phosphoreum T3. In this study, a simple, rapid, and low-cost assay method of zearalenone by bioluminescent P. phosphoreum T3 was developed. The bioluminescence inhibition assay could be used to estimate the efficiency of enzymatic degradation of ZEN.
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Photobacterium , Zearalenona , Zearalenona/análisis , Zearalenona/metabolismo , Photobacterium/efectos de los fármacos , Mediciones Luminiscentes , Luminiscencia , Contaminación de Alimentos/análisisRESUMEN
A convenient, efficient, and green dispersive liquid-liquid microextraction based on the in situ formation of solidified supramolecular solvents combined with high performance liquid chromatography was developed for the determination of four phenylurea herbicides in liquid samples, including monuron, monolinuron, isoproturon, and chlortoluron. Herein, a novel supramolecular solvent was prepared by the in situ reaction of [P4448]Br and NH4PF6, which had the advantages of low melting point, high density, and good dispersibility. In addition, the microscopic morphology and physical properties of supramolecular solvent were characterized, and the extraction conditions were optimized. The results showed that the analytes had good linearity (R2 > 0.9998) within the linear range. The limits of detection and quantification for the four phenylurea herbicides were in the range of 0.13-0.19 µg L-1 and 0.45-0.65 µg L-1, respectively. The prepared supramolecular solvent is suitable for the efficient extraction of phenylurea herbicides in water, fruit juice, and milk.
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Jugos de Frutas y Vegetales , Herbicidas , Microextracción en Fase Líquida , Leche , Compuestos de Fenilurea , Solventes , Microextracción en Fase Líquida/métodos , Herbicidas/química , Herbicidas/aislamiento & purificación , Herbicidas/análisis , Leche/química , Compuestos de Fenilurea/aislamiento & purificación , Compuestos de Fenilurea/química , Compuestos de Fenilurea/análisis , Jugos de Frutas y Vegetales/análisis , Solventes/química , Animales , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Contaminación de Alimentos/análisisRESUMEN
A simple, fast, and efficient ultrasonic-assisted supramolecular solvent microextraction combined with high performance liquid chromatography method was developed for the determination of coumarins in Cortex fraxini, including esculin, esculetin and fraxetin. In this study, a novel supramolecular solvent was prepared with 1-octanol, tetrahydrofuran and water for the first time, and its composition, viscosity, density, structure, and micromorphology were characterized. The prepared supramolecular solvent exhibited vesicular structures and had the characteristics of low viscosity. Through single-factor experiments, response surface methodology and artificial neural network-genetic algorithm, the optimal extraction conditions were obtained as follows: NaCl concentration of 1 mol mL-1, pH value of 10, solid-liquid ratio of 10:1, vortex time of 30 s, ultrasonic power of 100 W, ultrasonic temperature of 60 °C, ultrasonic time of 15 min, centrifugation speed of 5000 rpm, and centrifugation time of 1 min. The results demonstrated that the artificial neural network model exhibited maximum R-values of 0.98703, 0.97440, 0.99836, and 0.95447 for training, testing, validation, and all dataset, respectively. The minimum mean square errors were 0.75, 10.15, 1.99, and 2.63, respectively. This indicated that the predicted values were almost consistent with the actual values. Under the optimal conditions, the total extraction yields of target analytes reached 2.80 %. The calibration curves for each analyte exhibited excellent linearity within the linear range (r > 0.9993). The limits of detection and quantification ranged from 4.87 to 6.55 ng mL-1 and 16.24 to 21.84 ng mL-1, respectively. The recoveries ranged from 98.71 % to 111.01 % with relative standard deviations of less than 3.6 %. The present method had the advantages of short extraction time (15 min) and less solvent consumption (0.5 mL). The prepared supramolecular solvent was proved to have great potential in extracting coumarins from medicinal plants.
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Medicamentos Herbarios Chinos , Microextracción en Fase Líquida , Solventes/química , Ultrasonido , Microextracción en Fase Líquida/métodos , Cumarinas , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión/métodos , Algoritmos , Límite de DetecciónRESUMEN
BACKGROUND: Acquired immune deficiency syndrome (AIDS) associated with eosinophilic gastroenteritis is rare. We report a case of duodenal "stone" inducing acute pancreatitis with eosinophilic gastroduodenitis in an AIDS patient. CASE SUMMARY: A 73-year-old female AIDS patient came to the hospital with recurrent abdominal pain for 20 days. Computed tomography (CT) showed pancreatitis with exudation and a high-density shadow under the gastric antrum. Gastroscopy showed that the descending part of the duodenum was blocked by a "stone". The mucosa of the duodenum was rough, and a red polyp was found on the gastric body. The pathology result was chronic inflammation with eosinophilic granulocytes in the duodenal mucosa and gastric body polyp. CONCLUSION: When AIDS patients suffer acute pancreatitis, the possibility of eosinophilic gastroenteritis needs to be considered to enable the patient to accept timely treatment.
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Idiopathic mesenteric phlebosclerotic colitis(IMP) is a rare disease. At present, the etiology and pathogenesis are not clear, but the main patients are Asian people, and most of them have a history of taking Chinese herbal medicines. The disease has characteristic endoscopic and imaging manifestations. This paper shares a case of IMP, The patient came to our hospital for one year because of intermittent abdominal pain and diarrhea. It conforms to the typical manifestations of IMP. For patients who take Chinese herbal medicine for a long time, if they have clinical manifestations of gastrointestinal tract, it is necessary to consider the possibility of the disease to avoid serious consequences due to missed diagnosis.
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Colitis , Medicamentos Herbarios Chinos , Humanos , Medicamentos Herbarios Chinos/efectos adversos , Tomografía Computarizada por Rayos X , Venas Mesentéricas/diagnóstico por imagen , Colitis/inducido químicamente , Colitis/diagnóstico por imagen , Colitis/tratamiento farmacológicoRESUMEN
BACKGROUND: Betel nut chewing is very common in Southeast Asia and other tropical countries. Much clinical evidence suggests that chewing betel nut has pro-inflammatory and carcinogenic effects, but there are few clinical reports of acute toxicity caused by it, especially involving esophageal damage. CASE PRESENTATION: We presented a case of a 72-year-old female who was admitted to our hospital for chest pain and hematemesis within several minutes after chewing betel nut. Gastroscopy showed two longitudinal ridge-like mucosal eminences in the esophagus located 20 cm from the incisors down to the gastric cardia, which was similar to varices. At last, a CT scan showed concentric-circle thickening of the esophagus wall, suggesting hematomas. Our treatment included fasting, inhibiting gastric acid and maintaining blood volume. After one week of medical treatment, rechecked gastroscopy showed that esophageal hematomas were gradually absorbed, with the formation of multiple shallow ulcers. CONCLUSIONS: The acute toxicity of chewing betel nut can be easily overlooked. Patients who experience chest pain or hematemesis after chewing betel nut products,especially those who take aspirin at the same time, need to be alert to esophageal hematoma.
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Background: Meckel's diverticulum is a blind-end true diverticulum that contains all of the layers, which is normally found in the ileum. Prevalence of Meckel's diverticulum is around 2% in the general population, and even rare among adults. Gastrointestinal (GI) bleeding is a common complication of Meckel's diverticulum in children and in most cases, caused by peptic ulceration, due to ectopic gastric mucosa, while in minority cases, pancreatic tissue would also appear consisting around 6% of all Meckel's diverticulum patients. Case Description: Herein, we reported a 45-year-old man presented with recurrent hematochezia for over one-month without other remarkable symptoms or past medical history or signs on physical examination. Laboratory examinations showed hemoglobin of 114 g/L and ++++ in stool occult blood test without red blood cell. Contrasted abdominopelvic computerized tomography (CT) were normal and Meckel's electroconvulsive therapy (ECT) for identification was also negative. Considering gastroscopy and colonoscopy were both unremarkable in local hospital, double balloon enteroscopy was adopted and revealed double duct sign at about 100 cm proximal to the ileocecal valve and thus indicated existence of diverticulum. Further, ulceration was found at the far-end bottom of the blind-ending tube. The patient then underwent laparoscopic resection of Meckel's diverticulum and pathology study showed heterotopic pancreas in Meckel's diverticulum. The patient started feeding two days after surgery and was discharged on regular out-patient follow-up two weeks later. Till now, no reappear of hematochezia episode was observed. Conclusions: Heterotopic pancreas in Meckel's diverticulum is relative rare clinical condition in adult which can cause recurrent lower GI bleeding. Thus, special attention should be paid in cases with unexplained lower GI bleeding in adult.
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Four new alkaloids, hippobrines A-D (1-4), along with three new polyacetylenes, hippobrenes A-C (5-7), were isolated from Hippobroma longiflora. Compounds 1-3 possess an unprecedented carbon skeleton. All of the new structures were determined by analyzing their mass and NMR spectroscopic data. The absolute configurations of 1 and 2 were confirmed by single-crystal X-ray analyses, and the absolute configurations of 3 and 7 were deduced using their ECD spectra. Plausible biogenetic pathways of 1 and 4 were proposed. In regard to bioactivities, all compounds (1-7) exhibited weak antiangiogenic activity against human endothelial progenitor cells, with IC50 values ranging from 21.1 ± 1.1 to 44.0 ± 2.3 µg/mL.
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Alcaloides , Humanos , Estructura Molecular , Polímero Poliacetilénico , Alcaloides/farmacología , Alcaloides/químicaRESUMEN
BACKGROUND: Transcatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC), however, the complications of TACE have gradually become a concern of clinicians. Injury to the bile duct has been the focus of many scholars. CASE PRESENTATION: HCC was diagnosed in a 51-year-old female patient, and the first TACE was performed on April 10, 2020. The second TACE was performed on October 18, 2021. After the second TACE, The patient suffered from nausea, jaundice, and body itching. Computed tomography (CT) of the abdomen showed that the lower common bile duct was obviously blocked by the solidified lipiodol accompanied by dilatation of intrahepatic and extrahepatic bile ducts on October 27, 2021. Endoscopic retrograde cholangiopancretography (ERCP) and endoscopic nasobiliary drainage (ENBD) were performed on October 29, 2021. The deposition of lipiodol in the common bile duct was significantly reduced. CONCLUSION: After the transcatheter arterial chemoembolization for hepatocellular carcinoma, we should be on alert for damage to the bile duct, and pay attention to the deposition of lipiodol in the common bile duct.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Femenino , Humanos , Persona de Mediana Edad , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Aceite Etiodizado , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Quimioembolización Terapéutica/métodos , Conducto Colédoco/patologíaRESUMEN
Three new alkaloids, hipporidine A (1: ), hipporidine B (2: ), and (-)-lobeline N-oxide (3: ), were discovered from the whole plant of Hippobroma longiflora together with five known compounds (4: -8: ). Their 2,6-disubstituted piperidine structures were established based on the HRESIMS, NMR (COSY, HMBC, HSQC, NOESY), and UV spectroscopic data. Hipporidines A (1: ) and B (2: ) possess a rare 1,3-oxazinane moiety. Compound 3: is the N-oxide derivative of (-)-lobeline (6: ). Moreover, the absolute configuration of norlobeline (5: ) was established by single-crystal X-ray diffraction analysis. Three major secondary metabolites (6: -8: ) were evaluated for their neuroprotective effect against paclitaxel-induced neurotoxicity. Consequently, pretreatment with compound 8: at a concentration of 1.0 µM displayed significant attenuation on paclitaxel-damaged neurite outgrowth of dorsal root ganglion neurons without interfering with the cytotoxicity of paclitaxel on cervical cancer SiHa cells.
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Alcaloides , Lobelina , Estructura Molecular , Alcaloides/farmacología , Alcaloides/química , Piperidinas/farmacología , Paclitaxel , ÓxidosRESUMEN
A phytochemical investigation of the leaves and twigs of Glycosmis pentaphylla (Rutaceae), collected in Vietnam, yielded three new compounds named glyfuran (1), glyphyllamide (2), and glyphyllazole (3), along with twenty-five known compounds (4-28). The structures of isolates were determined by IR, MS, NMR, and UV data analyses. In the anti-diabetic activity screening, (+)-isoaltholacton (4), glycoborinine (17), 2',4'-dihydroxy-4,6'-dimethoxychalcone (24), and flavokawain A (25) simultaneously exhibited inhibition of dipeptidyl peptidase-4 (DPP4) and stimulation of the glucagon-like peptide-1 (GLP-1) secretion on the murine intestinal secretin tumor cell line (STC-1).
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The purpose of this study aimed to assess the antiproliferation effects of methanol extract of T. swinhoei (METS) and explore the detailed responses of oral cancer cells compared to normal cells. METS effectively inhibits the cell proliferation of oral cancer cells but does not affect normal cell viability, exhibiting preferential antiproliferation function. METS exerted more subG1 accumulation, apoptosis induction, cellular and mitochondrial oxidative stress, and DNA damage than normal cells, reverted by oxidative stress inhibitor N-acetylcysteine. This METS-caused oxidative stress was validated to attribute to the downregulation of glutathione. METS activated both extrinsic and intrinsic caspases. DNA double-strand breaks (γH2AX) and oxidative DNA damage (8-hydroxy-2-deoxyguanosine) were stimulated by METS. Therefore, for the first time, this investigation shed light on exploring the functions and responses of preferential antiproliferation of METS in oral cancer cells.
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Piperazine-derived diazabicycles are privileged structures found in natural products and synthetic chemical entities, including therapeutic agents. Herein, we deciphered the biosynthesis of two unique classes of diazabicyclic alkaloids, fischerazines A-C. Notably, we characterized a multifunctional P450 monooxygenase NfiC that installs ortho-dihydroxyl groups on the dibenzyl-piperazines, in turn triggering a range of NfiC-catalyzed and spontaneous cyclization events.
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Alcaloides , Péptido Sintasas , Sistema Enzimático del Citocromo P-450/química , Péptido Sintasas/química , PiperazinaRESUMEN
The anticancer effect of pomegranate polyphenolic extract POMx in oral cancer cells has rarely been explored, especially where its impact on mitochondrial functioning is concerned. Here, we attempt to evaluate the proliferation modulating function and mechanism of POMx against human oral cancer (Ca9-22, HSC-3, and OC-2) cells. POMx induced ATP depletion, subG1 accumulation, and annexin V/Western blotting-detected apoptosis in these three oral cancer cell lines but showed no toxicity to normal oral cell lines (HGF-1). POMx triggered mitochondrial membrane potential (MitoMP) disruption and mitochondrial superoxide (MitoSOX) generation associated with the differential downregulation of several antioxidant gene mRNA/protein expressions in oral cancer cells. POMx downregulated mitochondrial mass, mitochondrial DNA copy number, and mitochondrial biogenesis gene mRNA/protein expression in oral cancer cells. Moreover, POMx induced both PCR-based mitochondrial DNA damage and γH2AX-detected nuclear DNA damage in oral cancer cells. In conclusion, POMx provides antiproliferation and apoptosis of oral cancer cells through mechanisms of mitochondrial impairment.
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Zearalenone (ZEN), one of the most dangerous mycotoxins, causes enormous economic losses in the food and feed industries. To solve the problem of ZEN pollution, ZEN detoxifying enzymes are in emergent need. In this study, a zearalenone lactonohydrolase from Trichoderma aggressivum, denoted as ZHD-P, was heterologously expressed and characterized. The intracellular ZHD-P from E. coli BL21(DE3) exhibited high activity for ZEN degradation (191.94 U/mg), with the optimal temperature and pH of 45 °C and 7.5-9.0, respectively. With excellent temperature stability, the intracellular ZHD-P retained 100% activity when it was incubated at 25-40 °C for 1 h. Furthermore, we firstly constructed an E. coli cell surface display system for ZHD-P. The surface-displayed ZHD-P exhibited high activity against ZEN and showed optimal activity at 40 °C and pH 9.0. With superior pH stability, the surface-displayed ZHD-P retained 80% activity when it was incubated at pH 5.0-11.0 for 12 h. Interestingly, the metal ions tolerance of the surface-displayed ZHD-P was better than the intracellular form. Additionally, the surface-displayed ZHD-P could be reused four times with the residual enzyme activity of more than 50%. The biotoxicity assessment using P. phosphoreum T3 indicated that ZEN could be degraded into hypotoxic products by the intracellular or surface-displayed ZHD-P. ZHD-P could be feasible for ZEN detoxification.
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Hidrolasas/genética , Proteínas Recombinantes/genética , Zearalenona/metabolismo , Secuencia de Aminoácidos , Escherichia coli , Regulación de la Expresión Génica , Concentración de Iones de Hidrógeno , Hidrolasas/metabolismo , Hypocreales , Unión Proteica , Proteínas Recombinantes/metabolismo , Propiedades de Superficie , Zearalenona/químicaRESUMEN
Application of LC-MS/MS-based molecular networking indicated the ethanol extract of octocoral Asterospicularia laurae is a potential source for the discovery of new xenicane derivatives. A natural product investigation of this soft coral resulted in the isolation of four new xenicane diterpenoids, asterolaurins OâR (1â4), together with six known compounds, xeniolide-A (5), isoxeniolide-A (6), xeniolide-B (7), 7,8-epoxyxeniolide-B (8), 7,8-oxido-isoxeniolide-A (9), and 9-hydroxyxeniolide-F (10). The structures of isolated compounds were characterized by employing spectroscopic analyses, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) and high-resolution electrospray ionization mass spectrometry (HRESIMS). Asterolaurin O is the first case of brominated tricarbocyclic type floridicin in the family Xeniidae. Concerning bioactivity, the cytotoxic activity of those isolates was evaluated. As a result, compounds 1 and 2 demonstrated a selective cytotoxic effect against the MCF-7 cell line at IC50 of 14.7 and 25.1 µM, respectively.
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Antozoos/química , Antineoplásicos/aislamiento & purificación , Diterpenos/aislamiento & purificación , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Cromatografía Liquida , Diterpenos/química , Diterpenos/farmacología , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Taiwán , Espectrometría de Masas en TándemRESUMEN
A chemical investigation of the zoantharian Zoanthus vietnamensis, collected off Taiwan, yielded eleven new alkaloids, 7α-hydroxykuroshine J (1), 18ß-hydroxykuroshine J (2), 5α-hydroxyzoanthenamine (3), 5ß-hydroxyzoanthenamine (4), 14α-hydroxyzoanthenamine (5), 30-hydroxyzoanthenamine (6), 11-dehydroxy-18-epi-kuroshine A (7), 5α-hydroxykuroshine A (8), 7ß-hydroxykuroshine A (9), 11-keto-oxyzoanthamine (10), and 30-hydroxyzoanthamine (11), along with eight known compounds (12-19). The structures of these compounds were identified by detailed spectroscopic data, including HRESIMS, IR, NMR, and UV spectra. All secondary metabolites isolated from Z. vietnamensis were investigated for the anti-angiogenic effect in human endothelial progenitor cells (EPCs). Compounds 6, 7, 11, and 13 exhibited mild anti-angiogenic effect by blocking cell growth and tube formation of EPCs. The neuroprotective potential of four major compounds 12, 14, 15, and 19 against paclitaxel-induced neurotoxicity was evaluated. Pretreatment of 14 and 15 protected paclitaxel-damaged neurite outgrowth of dorsal root ganglion (DRG) neurons, without interfering the cytotoxic activity of paclitaxel on cervical cancer SiHa cells.