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1.
Adv Healthc Mater ; : e1901710, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32142216

RESUMO

Local drug delivery systems have recently been developed for multiple diseases that have the requirements of site-specific actions, prolonged delivery periods, and decreased drug dosage to reduce undesirable side effects. The challenge for such systems is to achieve directional and precise delivery in inaccessible narrow lesions, such as periodontal pockets or root canals in deeper portions of the dentinal tubules. The primary strategy to tackle this challenge is fabricating a smart tracking delivery system. Here, drug-loaded biodegradable micromotors showing self-propelled directional movement along a hydrogen peroxide concentration gradient produced by phorbol esters-stimulated macrophages are reported. The drug-loaded poly(lactic-co-glycolic acid) micromotors with asymmetric coverage of enzyme (patch-like enzyme distribution) are prepared by electrospraying and postfunctionalized with catalase via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide coupling. Doxycycline, a common drug for the treatment of periodontal disease, is selected as a model drug, and the release study by high-performance liquid chromatography is shown that both the postfunctionalization step and the presence of hydrogen peroxide have no negative influence on drug release profiles. The movement behavior in the presence of hydrogen peroxide is confirmed by nanoparticle tracking analysis. An in vitro model is designed and confirmed the response efficiency and directional control of the micromotors toward phorbol esters-stimulated macrophages.

2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(3): 235-242, 2020 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-32128738

RESUMO

Alpha-thalassemia is an autosomal recessive genetic disease as well as a relatively common hemoglobinopathy. Severe alpha-thalassemia (also known as Hb Bart's Hydrops fetalis syndrome) and intermediate alpha-thalassemia (also known as Hb H disease) are among the most common birth defects in southern China. To implement carrier screening and large population prevention program in high incidence areas can significantly reduce the incidence of alpha-thalassemia. This guideline was established by combining the discoveries of basic research, clinical research and guidelines from other countries and the actual data of Chinese population. It has summarized the medical genetics knowledge and key points in the clinical treatment for alpha-thalassemia, and provided suggestions for the clinical diagnosis and standard management of patients.

3.
Sleep Med ; 69: 204-212, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143064

RESUMO

OBJECTIVE: To investigate the potential prognostic value of sleep electroencephalography (EEG) pattern and serum circadian rhythm biomarkers in the recovery of consciousness in patients at the acute stage of coma. METHODS: A prospective observational study which included 75 patients with coma was conducted. Twenty-four-hour continuous polysomnography (PSG) was performed to determine the sleep EEG pattern according to the modified Valente's Grade (mVG) that we proposed. Serum levels of melatonin and orexin-A at four consecutive time points during the PSG were examined. Patients were then followed for one month to determine their level of consciousness. Multivariate logistic regression analysis was performed to examine associations between demographics, aetiology, baseline clinical features (pupillary and corneal reflex, and neuron-specific enolase [NSE]), clinical scores (Glasgow Coma Scale-Motor Response [GCS-M], Full Outline of Unresponsiveness [FOUR] scale, Acute Physiology and Chronic Health Evaluation II [APACHE II] scale), mVG, serum circadian biomarkers, and recovery of consciousness within one month. RESULTS: Within one month of enrolment, 34 patients regained consciousness and 36 patients remained non-conscious. Spearman rank correlation revealed a significant association between mVG and state of consciousness after one month. Significant variation in serum melatonin or orexin-A was not detected in either the conscious or non-conscious groups. Hypoxic aetiology, APACHE II, and mVG were independently associated with recovery of consciousness within one month. CONCLUSION: Sleep EEG structure, hypoxic aetiology, and APACHE II can independently predict recovery of consciousness in patients with acute coma. Taken together, we encourage neurologists to use sleep elements to assess patients with acute coma.

4.
J Food Biochem ; : e13186, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32163603

RESUMO

Black soldier fly larvae protein (BLP) was hydrolyzed using alcalase, neutrase, trypsin, and papain. The BLP hydrolysates (BLPHs) were fractionated by ultrafiltration into three peptide fractions of molecular weight (<3 kDa, 3-10 kDa and >10 kDa). Their antioxidant activities in vitro and the amino acid composition were determined. Results showed that the alcalase was more efficient in hydrolyzing the BLP into oligopeptides. BLPHs-I presented the best scavenging activity to superoxide radicals, hydroxyl radicals, DPPH, and ABTS radicals. The best scavenging activities were found in BLPHs-I containing high levels of aromatic and hydrophobic amino acids. Seventeen novel sequences with typical features of well-known antioxidant proteins were identified by LC-MS/MS. Results demonstrated that BLPHs-I possesses a great capacity as antioxidant peptides applied in functional foods. PRACTICAL APPLICATIONS: Black soldier fly larvae protein (BLP) can also be hydrolyzed to produce antioxidant peptides and their sequences were identified. It can be used in pharmaceutical products and functional foods.

5.
Biotechnol J ; : e1900430, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32170989

RESUMO

Cyclin D1 is a key regulatory factor of the G1 to S transition during cell cycle progression. Aberrant cyclin D gene amplification and abnormal protein expression have been linked to hepatocellular carcinoma (HCC) tumorigenesis, warranting evaluation of cyclin D1 as a therapeutic target. Intrabodies, effective anti-cancer therapies that specifically inhibit target protein function within all intracellular compartments, may block cyclin D1 function. Here, a single-chain variable fragment (scFv) antibody against cyclin D1 (ADκ) selected from a human semi-synthetic phage display scFv library was expressed in Escherichia coli as soluble ADκ. Purified ADκ specifically bound to recombinant and endogenous cyclin D1 with high affinity. To enable blocking of intracellular cyclin D1 activity, an endoplasmic reticulum (ER) retention signal sequence was added to the ADκ sequence to encode anti-cyclin D1 intrabody ER-ADκ. Transfection of HepG2 cells with expression vector encoding ER-ADκ elicited intracellular ER-ADκ expression leading to cyclin D1 binding, significant G1 phase arrest, and apoptosis that were mechanistically tied to decreased intracellular phosphorylated retinoblastoma protein (Rb) levels. Meanwhile, ER-ADκ dramatically inhibited subcutaneous human HCC xenografts growth in nude mice in vivo after injection of tumors with expression vector encoding ER-ADκ. These results demonstrate the potential of intrabody-based cyclin D1 targeting therapy as a promising treatment for HCC. This article is protected by copyright. All rights reserved.

6.
PLoS One ; 15(3): e0230369, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32142539

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0227475.].

7.
Nano Lett ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32186886

RESUMO

We here describe a novel type of long-wavelength radiation detector that measures illumination intensity at room temperature through mechanical transduction. Compared to semiconductor-based bolometers, our nanomechanical detector exhibits low measurement noise and is inherently transparent and flexible. The presented solid-state device is based on a 2D-material film that acts as radiation absorber and detector of mechanical strain at the substrate-absorber interface. Optimization of the 2D material properties and realization of a novel edge-on device geometry combines unprecedented detectivity of 3.34 × 108 cm Hz1/2 W-1 with micrometer-scale spatial resolution. The observed combination of superior performance with the facile and scalable fabrication using only liquid processes shows the potential of the presented detector for future ubiquitous and wearable electronics.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32125207

RESUMO

Purpose: This study aimed to assess clinical efficacy and long-term patient outcomes in individuals with malignant hilar biliary obstruction (MHBO) that had been treated via insertion of a stent with a radioactive seed strand (RSS).Material and methods: A total of 84 MHBO patients were treated via either normal stent insertion (n = 48) or stent with RSS insertion (n = 36) from January 2015 to December 2018.Results: The technical success rates of normal stent insertion and stent with RSS insertion were 93.8% (45/48) and 97.2% (35/36), respectively (p = .632), with clinical success rates of 93.3% (42/45) and 100% (35/35), respectively (p = .252). In these two patient groups, 11 and seven patients, respectively, suffered from stent dysfunction (p = .637). In the normal and RSS groups, median stent patency was 165 and 225 days, respectively (p < .001). All patients in the present study died due to tumor progression, with median survival times of 188 and 250 days in the normal and RSS stent groups, respectively (p < .001).Conclusion: Relative to normal stent insertion, combined stent with RSS insertion can effectively prolong both stent patency and patient survival in patients with MHBO.

9.
Anal Chim Acta ; 1102: 84-90, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32043999

RESUMO

Sensitive imaging of intracellular microRNAs (miRNAs) in cells is of great significance in clinical diagnoses and disease treatments, and it remains a major challenge to achieve this goal. Herein, we report a new in situ rolling circle transcription synchronization machinery (RCTsm) of lighting-up RNA aptamer strategy for highly sensitive imaging and selective differentiation of miRNA expression levels in cells. Such a RCTsm approach utilizes a DNA promoter to recycle the target miRNAs to trigger the initiation of multiple RCT process for the yield of many lighting-up RNA aptamers. The malachite green dye further binds these aptamers to show significantly enhanced fluorescence for completely label-free detection of the target miRNAs with a high sensitivity in vitro with a low femtomolar detection limit. More importantly, sensitive detection of under-expressed miRNAs in cells and distinct differentiation of the miRNA expression variations in different cells can also be realized with this RCTsm approach in a washing-free format, making it a versatile and useful tool for imaging trace miRNAs in single cells with the great potential for early cancer diagnosis as well as biomedical research.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32022611

RESUMO

Purpose: To explore the clinical efficacy and long-term outcomes of accessory hepatic vein (AHV) recanalization as a means of treating hepatic vein (HV)-type Budd-Chiari syndrome (BCS).Methods: Between January 2011 and December 2018, a total of 46 symptomatic HV-type BCS patients were treated by AHV recanalization in our hospital. The technical and clinical success of this treatment, as well as associated long-term patient prognosis was assessed herein.Results: The AHV recanalization approach was technically successful in 100% of patients, without any instances of complications associated with the operation. This procedure was 95.7% (44/46) clinically successful and resultant. AHV re-obstruction occurred in 12 patients. The cumulative primary one-, two-, and five-year patency rates were 77.3%, 71.7%, and 71.7%, respectively. The secondary cumulative one-, two-, and five-year patency rates were 97.7, 87.1, and 87.1%, respectively. The five-year patency rates did not differ significantly between patients treated with balloons and stents (p = .674). Based on Cox-regression analysis, younger age was an independent predictor of re-obstruction (p = .005). The cumulative one-, two-, and five-year survival rates were 97.7, 92.2, and 92.2%, respectively.Conclusions: AHV recanalization is a safe and effective treatment for HV-type BCS.

11.
Chaos ; 30(1): 013132, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32013462

RESUMO

An abrupt climatic transition could be triggered by a single extreme event, and an α-stable non-Gaussian Lévy noise is regarded as a type of noise to generate such extreme events. In contrast with the classic Gaussian noise, a comprehensive approach of the most probable transition path for systems under α-stable Lévy noise is still lacking. We develop here a probabilistic framework, based on the nonlocal Fokker-Planck equation, to investigate the maximum likelihood climate change for an energy balance system under the influence of greenhouse effect and Lévy fluctuations. We find that a period of the cold climate state can be interrupted by a sharp shift to the warmer one due to larger noise jumps with low frequency. Additionally, the climate change for warming 1.5°C under an enhanced greenhouse effect generates a steplike growth process. These results provide important insights into the underlying mechanisms of abrupt climate transitions triggered by a Lévy process.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32013376

RESUMO

The emergence of self-healing devices in recent years has drawn a great amount of attention in both academics and industry. Self-healed devices can autonomically restore a rupture as unexpected destruction occurs, which can efficiently prolong the life span of the devices; hence, they have an enhanced durability and decreased replacement cost. As a result, integration of wearable devices with self-healed electronics has become an indispensable issue in smart wearable devices. In this study, we present the first self-powered, self-healed, and wearable ultraviolet (UV) photodetector based on the integration of agarose/poly(vinyl alcohol) (PVA) double network (DN) hydrogels, which have the advantages of good mechanical strength, self-healing ability, and tolerability of multiple types of damage. With the integration of a DN hydrogel substrate, the photodetector enables 90% of the initial efficiency to be restored after five healing cycles, and each rapid healing time is suppressed to only 10 s. The proposed device has several merits, including having an all spray coating, self-sustainability, biocompatibility, good sensitivity, mechanical flexibility, and an outstanding healing ability, which are all essential to build smart electronic systems. The unprecedented self-healed photodetector expands the future scope of electronic skin design, and it also offers a new platform for the development of next-generation wearable electronics.

13.
Theranostics ; 10(4): 1719-1732, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32042332

RESUMO

The purpose of this study was to determine the effects of Kinesin family member 3A (KIF3A) on primary cilia and myofibroblast differentiation during silicosis by regulating Sonic hedgehog (SHH) signalling. Methods: Changes in primary cilia during silicosis and myofibroblast differentiation were detected in silicotic patients, experimental silicotic rats, and a myofibroblast differentiation model induced by SiO2. We also explored the mechanisms underlying KIF3A regulation of Glioma-associated oncogene homologs (GLIs) involved in myofibroblast differentiation. Results: Primary cilia (marked by ARL13B and Ac-α-Tub) and ciliary-related proteins (IFT 88 and KIF3A) were increased initially and then decreased as silicosis progressed. Loss and shedding of primary cilia were also found during silicosis. Treatment of MRC-5 fibroblasts with silica and then transfection of KIF3A-siRNA blocked activation of SHH signalling, but increased GLI2FL as a transcriptional activator of SRF, and reduced the inhibitory effect of GLI3R on ACTA2. Conclusion: Our findings indicate that primary cilia are markedly altered during silicosis and the loss of KIF3A may promote myofibroblast differentiation induced by SiO2.

14.
Biosens Bioelectron ; 155: 112099, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32090871

RESUMO

Herein, a new phenomenon of enhanced electrochemiluminescence (ECL) emission by restricting intramolecular motion in the 2D ultra-thin Zr12-adb (adb = 9,10-anthracene dibenzoate) metal-organic framework (MOF) nanoplate was discovered for the first time. The coordination immobilization of adb in porous ultra-thin Zr12-adb nanoplate endowed the Zr12-adb excellent ECL performance, including stronger ECL signal and higher ECL efficiency relative to those of H2adb monomers and H2adb aggregates. In the 2D Zr12-adb nanoplate, the bridging ligand adb was stretched and fixed between two Zr12 clusters, which restricted intramolecular rotations and suppressed unnecessary energy loss caused by self-rotation, thereby remarkably improved the ECL intensity and efficiency. More importantly, the porous ultra-thin structure of Zr12-adb MOF nanoplate not only allowed the coreactants to diffuse into the MOF interior, making both internal and external adb be excited, but also shortened the migration distance of electrons, ions, coreactants and coreactant intermediates, which further improved the ECL efficiency of Zr12-adb and overcame the shortcoming of H2adb aggregates in which the internal luminophores were not easily excited. Regarding the excellent ECL properties above, Zr12-adb nanoplate was selected as a new ECL emitter incorporated with the bipedal walking molecular machine together to fabricate a biosensor for sensitive detection of mucin 1. The enhanced ECL by restriction of intramolecular motions in MOFs provided a new pathway to improve ECL intensity and efficiency, which lighted up a lamp for the design and manufacture of high-performance ECL materials based on MOFs, thus offering new opportunities to develop ultrasensitive ECL biosensors.

15.
Bioorg Med Chem Lett ; 30(8): 127025, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32063430

RESUMO

Twenty-six novel pyrazolo[3,4-b]pyridine-bridged analogues of combretastatin A-4 possessing 3,4,5-trimethoxylphenyl groups, were synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Preliminary biological evaluation demonstrated that some of the target compounds displayed significant antiproliferative effectagainst four different cell lines including MCF-7, MDA-MB-231, HeLa and Kyse150. The most active analogue 6n was found to induce HeLa cells arrest in the G2/M phase in a dose-dependent manner. Molecular modeling studies indicated that derivative 6n most likely occupies the colchicine site of tubulin. The initial results suggest that the 3,4,5-trimethoxyphenyl substituted pyrazolo[3,4-b]pyridine could serve as a promising scaffold for development of potent tubulin inhibitors as anticancer agents.

16.
PLoS One ; 15(2): e0227475, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32074102

RESUMO

Conventional transarterial chemoembolization (cTACE), drug-eluting beads (DEB-TACE) and transarterial radioembolization (TARE) are alternative strategies for unresectable hepatocellular carcinoma (HCC). However, which of these strategies is the best is still controversial. This meta-analysis was performed to evaluate the effects of DEB-TACE, TARE and cTACE in terms of overall survival (OS), tumor response and complications. A literature search was conducted using the EMBASE, PubMed, Google Scholar, and Cochrane databases from inception until July 2019 with no language restrictions. The primary outcome was overall survival, and the secondary outcomes included complete response and local recurrence. The comparison of DEB-TACE with cTACE indicated that DEB-TACE has a better OS at 1 year (RR 0.79, 95% CI 0.67-0.93, p = 0.006), 2 years (RR 0.89; 95% CI 0.81-0.99, p = 0.046), and 3 years (RR 0.89; 95% CI 0.81-0.99, p = 0.035). The comparison of TARE with cTACE indicated that TARE has a better OS than cTACE at 2 years (RR 0.87; 95% CI 0.80-0.95, p = 0.003) and 3 years (RR 0.90; 95% CI 0.85-0.96, p = 0.001). The comparison of DEB-TACE with TARE indicated that DEB-TACE has a better OS than TARE at 2 years (RR 0.40; 95% CI 0.19-0.84, p = 0.016). The current meta-analysis suggests that DEB-TACE is superior to both TARE and cTACE in terms of OS. TARE has significantly lower complications than both DEB-TACE and cTACE for patients with HCC. Further multicenter, well-designed randomized controlled trials are needed, especially for evaluating DEB-TACE versus TARE.

17.
Biomed Pharmacother ; 125: 109980, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32028236

RESUMO

OBJECTIVE: The role and molecular mechanism of long non-coding RNA (lncRNA)-related pathways in silicosis have not been elucidated clearly. The aims of this study were to evaluate the expression of lncRNAs during silica-induced pulmonary fibrosis and verify the function and molecular mechanism of LOC103691771 in myofibroblast differentiation induced by transforming growth factor-ß1 (TGF-ß1). METHODS: RNA-sequencing was performed to assess differential expression of lncRNAs in control and silicotic rat lungs. Differential expression of lncRNAs was analyzed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes to identify their biological roles. LOC103691771, LOC102549714, LOC102550137, LOC103693125, and LOC103692016 were selected to verify their expression by real-time PCR of silicotic rat lung tissue and lung fibroblasts stimulated by TGF-ß1. Specific small interfering RNA and an LOC103691771 overexpression plasmid were used to analyze the molecular mechanism in myofibroblast differentiation induced by TGF-ß1. RESULT: A total of 306 lncRNAs were expressed differentially in silicotic rat lungs, including 224 upregulated and 82 downregulated lncRNAs. The expression of LOC103691771, LOC102549714 and LOC102550137 was upregulated, while the expression of LOC103693125 and LOC103692016 was downregulated in silicotic rat lungs and TGF-ß1-induced fibroblast, which was consistent with the results of RNA-sequencing. Furthermore, LOC103691771 gene silencing attenuated myofibroblast differentiation, whereas LOC103691771 overexpression promoted myofibroblast differentiation via regulation of the TGF-ß1-Smad2/3 signaling pathway. CONCLUSION: Our findings revealed that differential expression of lncRNAs was related to the development of silicosis, and LOC103691771 played a major role in myofibroblast differentiation induced by TGF-ß1, which may serve as a potential therapeutic target for silicosis.

18.
Eur J Clin Invest ; : e13210, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32061097

RESUMO

BACKGROUND: Kawasaki disease (KD) is an acute, self-limited vasculitis. Coronary artery aneurysm (CAA) serves as a major contributor to the long-term prognosis of KD. In addition, acute KD usually also leads to several kinds of noncoronary cardiac abnormalities (NCA) involving the pericardium, myocardium and endocardium. MATERIALS AND METHODS: A total of 142 Chinese children with KD were recruited from July 2015 to April 2018. Blood samples were collected at 24 hours pre-intravenous immunoglobulin (IVIG) therapy. Several inflammatory mediators and biomarkers for acute myocardial infarction were detected. Echocardiography and electrocardiography (ECG) were performed. RESULTS: Plasma white blood cell counts (WBC) were significantly increased in patients with IVIG-nonresponsive KD when compared with their IVIG-responsive counterparts. A total of 106 children (74.65%) suffered from NCA, including 8 patients (5.63%) with pericardial effusion, 23 patients (16.20%) with acute myocarditis, 101 patients (71.13%) with valvular regurgitation and 8 patients (5.63%) with abnormal ECG. No significant differences were observed in the distribution of clinical classification and the response to IVIG therapy regardless of NCA exhibited or not. CONCLUSIONS: Noncoronary cardiac abnormalities is almost universal in acute KD and mainly manifests as valvular regurgitation. However, it has no influence on clinical classification and the response to IVIG therapy.

19.
Molecules ; 25(3)2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32033326

RESUMO

The objective of this study was to synthesize the 9-/13-position substituted berberine derivatives and evaluate their cytotoxic and photocytotoxic effects against three human cancer cell lines. Among all the synthesized compounds, 9-O-dodecyl- (5e), 13-dodecyl- (6e), and 13-O-dodecyl-berberine (7e) exhibited stronger growth inhibition against three human cancer cell lines, (HepG2, HT-29 and BFTC905), in comparison with structurally related berberine (1). These three compounds also showed the photocytotoxicity in human cancer cells in a concentration-dependent and light dose-dependent manner. Through flow cytometry analysis, we found out a lipophilic group at the 9-/13-position of berberine may have facilitated its penetration into test cells and hence enhanced its photocytotoxicity on the human liver cancer cell HepG2. Further, in cell cycle analysis, 5e, 6e, and 7e induced HepG2 cells to arrest at the S phase and caused apoptosis upon irradiation. In addition, photodynamic treatment of berberine derivatives 5e, 6e, and 7e again showed a significant photocytotoxic effects on HepG2 cells, induced remarkable cell apoptosis, greatly increased intracellular ROS level, and the loss of mitochondrial membrane potential. These results over and again confirmed that berberine derivatives 5e, 6e, and 7e greatly enhanced photocytotoxicity. Taken together, the test data led us to conclude that berberine derivatives with a dodecyl group at the 9-/13-position could be great candidates for the anti-liver cancer medicines developments.

20.
Cancer Sci ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32061104

RESUMO

Hepatocellular carcinoma (HCC) is a common and particularly fatal form of cancer for which very few drugs are effective. The fibroblast growth factor 19 (FGF19) has been viewed as a driver of HCC development and a potential Ab target for developing novel HCC therapy. However, a previously developed anti-FGF19 Ab disrupted FGF19's normal regulatory function and caused severe bile-acid-related side-effects despite of having potent antitumor effects in preclinical models. Here, we developed novel human Abs (G1A8 and HS29) that specifically target the N-terminus of FGF19. Both Abs inhibited FGF19-induced HCC cell proliferation in vitro and significantly suppressed HCC tumor growth in mouse models. Importantly, no bile-acid-related side effects were observed in preclinical cynomolgus monkeys. Fundamentally, our study demonstrates that it is possible to target FGF19 for anti-HCC therapies without adversely affecting its normal bile acid regulatory function, and highlights the exciting promise of G1A8 or HS29 as potential therapy for HCC.

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