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1.
Development ; 151(1)2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38063853

ABSTRACT

High-sugar diets (HSDs) often lead to obesity and type 2 diabetes, both metabolic syndromes associated with stem cell dysfunction. However, it is unclear whether excess dietary sugar affects stem cells. Here, we report that HSD impairs stem cell function in the intestine and ovaries of female Drosophila prior to the onset of insulin resistance, a hallmark of type 2 diabetes. Although 1 week of HSD leads to obesity, impaired oogenesis and altered lipid metabolism, insulin resistance does not occur. HSD increases glucose uptake by germline stem cells (GSCs) and triggers reactive oxygen species-induced JNK signaling, which reduces GSC proliferation. Removal of excess sugar from the diet reverses these HSD-induced phenomena. A similar phenomenon is found in intestinal stem cells (ISCs), except that HSD disrupts ISC maintenance and differentiation. Interestingly, tumor-like GSCs and ISCs are less responsive to HSD, which may be because of their dependence on glycolytic metabolism and high energy demand, respectively. This study suggests that excess dietary sugar induces oxidative stress and damages stem cells before insulin resistance develops, a mechanism that may also occur in higher organisms.


Subject(s)
Adult Stem Cells , Diabetes Mellitus, Type 2 , Drosophila Proteins , Insulin Resistance , Animals , Female , Drosophila/metabolism , Drosophila Proteins/metabolism , Reactive Oxygen Species/metabolism , Dietary Sugars/metabolism , Adult Stem Cells/metabolism , Neoplastic Stem Cells/metabolism , Obesity
2.
Article in English | MEDLINE | ID: mdl-38494093

ABSTRACT

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory condition affecting the nasal and paranasal sinus mucosa, often accompanied by olfactory dysfunction. Eosinophilic CRS with nasal polyps (ECRSwNP) is a subtype of CRS characterized by eosinophilic infiltration. Animal models for ECRSwNP with olfactory dysfunction are necessary for exploring potential therapeutic strategies. OBJECTIVE: The aim of this study was to establish a mouse model of ECRSwNP combined with olfactory dysfunction in a shorter time frame using intranasal ovalbumin and Aspergillus protease (AP) administration. The efficacy of the model was validated by evaluating sinonasal inflammation, cytokine levels, olfactory function, and neuroinflammation in the olfactory bulb. METHODS: Male BALB/c mice were intranasally administered ovalbumin and AP for 6 and 12 weeks to induce ECRSwNP. The resultant ECRSwNP mouse model underwent histologic assessment, cytokine analysis of nasal lavage fluid, olfactory behavioral tests, and gene expression profiling to identify neuroinflammatory markers within the olfactory bulb. RESULTS: The developed mouse model exhibited substantial eosinophil infiltration, increased levels of inflammatory cytokines in nasal lavage fluid, and confirmed olfactory dysfunction through behavioral assays. Furthermore, olfactory bulb inflammation and reduced mature olfactory sensory neurons were observed in the model. CONCLUSION: This study successfully established a validated mouse model of ECRSwNP with olfactory dysfunction within a remarkably short span of 6 weeks, providing a valuable tool for investigating the pathogenesis and potential therapies for this condition. The model offers an efficient approach for future research in CRS with nasal polyps and olfactory dysfunction.

3.
Opt Express ; 31(3): 4281-4290, 2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36785400

ABSTRACT

A tapered bus-waveguide is demonstrated to enhance the waveguide-to-cavity coupling by mass-productive, cost-effective i-line UV lithography. Through enlarging the overlap between the evanescent wave and waveguide resonator, we experimentally show that the coupling strength of silicon nitride waveguides can be 7 times stronger than the conventional coupling of a uniform, straight bus-waveguide. For the first time, strong over-coupling is identified at a 400 nm gap and quality factor ≈ 105 without elongating the coupling length. This design relieves the fabrication limits and provides the flexibility for coupling control, especially in the strongly over-coupled regime with i-line UV lithography.

4.
Environ Res ; 224: 115520, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36842698

ABSTRACT

This study discussed the adsorption of mixed heavy metal ions (Cu2+, Co2+, Pb2+) and phosphate ions by ten pristine biochars and those with precipitated Mg/Al layered double hydroxide (LDH). The pristine biochars have adsorption capacities of 6.9-13.4 mg/g for Cu2+, 1.1-9.7 mg/g for Co2+, 7.8-20.7 mg/g for Pb2+, and 0.8-4.9 mg/g for PO43-. The LDH-biochars have markedly increased adsorption capacities of 20.4-25.8 mg/g for Cu2+, 8.6-15.0 mg/g for Co2+, 26.5-40.4 mg/g for Pb2+ with mixed metal ions, and 13.0-21.8 mg/g for PO43-. Part of the Mg ions but Al ions are released from the LDH-biochars during adsorption, counting less than 7.2% of the adsorbed ions. The pristine biochars have specific adsorption sites for Cu2+ and Co2+, separate Pb2+ sites related to ether groups on biochar, and areal-dependent sites for PO43-. There is no universal adsorption mechanism corresponding to mixed metal ion adsorption for individual pristine biochar involving different contributions of C-O-C, C-O-H, and CO groups and graphitic-N, pyrrolic-N, and pyridine-N groups. The LDH complexes with hydroxyl and carbonyl groups of biochar, and the LDH interacts with biochar's ether groups, which contributes to metal adsorption, against the conception that the biochar is merely a carrier of LDH as adsorbents.


Subject(s)
Metals, Heavy , Phosphates , Water , Lead , Hydroxides , Adsorption
5.
Molecules ; 28(14)2023 Jul 24.
Article in English | MEDLINE | ID: mdl-37513470

ABSTRACT

MSN8C, an analog of mansonone E, has been identified as a novel catalytic inhibitor of human DNA topoisomerase II that induces tumor regression and differs from VP-16(etoposide). Treatment with MSN8C showed significant antiproliferative activity against eleven human tumor cell lines in vitro. It was particularly effective against the HL-60/MX2 cell line, which is resistant to Topo II poisons. The resistance factor (RF) of MSN8C for Topo II in HL-60/MX2 versus HL-60 was 1.7, much lower than that of traditional Topo II poisons. Furthermore, in light of its potent antitumor efficacy and low toxicity, as demonstrated in the A549 tumor xenograft model, MSN8C has been identified as a promising candidate for antitumor applications.


Subject(s)
Antineoplastic Agents , DNA Topoisomerases, Type II , Humans , DNA Topoisomerases, Type II/metabolism , Topoisomerase II Inhibitors/pharmacology , Etoposide/pharmacology , Cell Line, Tumor , HL-60 Cells , Antineoplastic Agents/pharmacology
6.
Eur Arch Otorhinolaryngol ; 279(11): 5381-5387, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35731292

ABSTRACT

PURPOSE: Previous cancers can be observed in patients with nasopharyngeal carcinoma (NPC). However, whether prior cancer diagnosis affects survival outcomes remains unknown. This study aimed to explore the impact of prior cancer on the survival of patients with NPC. METHODS: We retrospectively collected data from 666 NPC patients between 2006 and 2018. The patients in this study were divided into those without prior cancer, with prior head and neck cancer, and prior non-head and neck cancer. The demographic data and survival of these groups were then analyzed. The independent prognostic factors for NPC were determined using multivariate Cox regression analysis. RESULTS: We identified 25 NPC patients with prior cancer in our case series, most of whom had a history of colorectal cancer. Patients with a history of cancer were older than those without a history of cancer (p = 0.001). In the subgroup analysis stratified by the timing of prior cancer, NPC patients with prior non-head and neck cancer within 24, 36, 60, and 120 months showed worse survival than patients without prior cancer (all p < 0.05). When stratified by cancer stage, stage III NPC patients with prior non-head and neck cancer showed worse survival than patients without prior cancer (p < 0.001). Prior cancer and diabetes can predict worse survival in patients with stage III NPC. CONCLUSION: This study demonstrated that prior cancer and diabetes are independent prognostic factors in patients with stage III NPC.


Subject(s)
Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Neoplasm Staging , Prognosis , Retrospective Studies
7.
Eur Arch Otorhinolaryngol ; 279(9): 4389-4395, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35076743

ABSTRACT

PURPOSE: There is no report in the literature targeting the role of Pantoea dispersa in rhinosinusitis and P. dispersa has not been identified as a commensal bacterium in the sinonasal cavity. We aimed to investigate the role of P. dispersa in rhinosinusitis. METHODS: We retrospectively reviewed the data of patients diagnosed with rhinosinusitis at a medical center in Taiwan. RESULTS: A total of 274 rhinosinusitis patients underwent sinus culture between July 2017 and July 2019. All 23 patients with acute P. dispersa rhinosinusitis experienced purulent rhinorrhea; three (13%) had nasal obstruction, but none had olfactory dysfunction, facial pressure/pain and nasal polyp. The patients with P. dispersa received a significantly shorter duration of antibiotic treatment (19.9 ± 2.6 vs. 28.9 ± 2.5 days, P = 0.015) and had lower surgery rate (0% vs. 16.7%, P = 0.043) than other patients. Patients with olfactory dysfunction were more likely to receive surgical treatment (P = 0.018). CONCLUSION: Acute rhinosinusitis caused by P. dispersa resulted in less surgical interventions and shorter treatment durations. Olfactory dysfunction may imply longer course and possibility for surgical intervention in chronic rhinosinusitis. The present study revealed that P. dispersa had the potential to colonize in human sinonasal cavities and cause rhinosinusitis.


Subject(s)
Nasal Polyps , Olfaction Disorders , Rhinitis , Sinusitis , Acute Disease , Chronic Disease , Humans , Nasal Polyps/surgery , Olfaction Disorders/etiology , Pantoea , Retrospective Studies , Rhinitis/surgery , Sinusitis/surgery
8.
Molecules ; 27(17)2022 Aug 29.
Article in English | MEDLINE | ID: mdl-36080326

ABSTRACT

Topo II and Hsp90 are promising targets. In this study, we first verified the structural similarities between Topo IIα ATPase and Hsp90α N-ATPase. Subsequently, 720 compounds from the Food and Drug Administration (FDA) drug library and kinase library were screened using the malachite green phosphate combination with the Topo II-mediated DNA relaxation and MTT assays. Subsequently, the antimalarial drug quinacrine was found to be a potential dual-target inhibitor of Topo II and Hsp90. Mechanistic studies showed that quinacrine could specifically bind to the Topo IIα ATPase domain and inhibit the activity of Topo IIα ATPase without impacting DNA cleavage. Furthermore, our study revealed that quinacrine could bind Hsp90 N-ATPase and inhibit Hsp90 activity. Significantly, quinacrine has broad antiproliferation activity and remains sensitive to the multidrug-resistant cell line MCF-7/ADR and the atypical drug-resistant tumor cell line HL-60/MX2. Our study identified quinacrine as a potential dual-target inhibitor of Topo II and Hsp90, depending on the ATP-binding domain, positioning it as a hit compound for further structural modification.


Subject(s)
Antineoplastic Agents , Neoplasms , Adenosine Triphosphatases/metabolism , Antigens, Neoplasm/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , DNA Topoisomerases, Type II/metabolism , Drug Repositioning , HSP90 Heat-Shock Proteins , Quinacrine/pharmacology
10.
Am J Rhinol Allergy ; 37(3): 298-306, 2023 May.
Article in English | MEDLINE | ID: mdl-36426571

ABSTRACT

BACKGROUND: Olfactory dysfunction is a common disease and it may be caused by sinonasal inflammation, toxin inhalation, or neurological disorders. After sinonasal inflammation, if both olfactory neuroinflammation and olfactory dysfunction occur still under investigation. OBJECTIVE: This study aimed to investigate whether neuroinflammation and olfactory dysfunction occur after lipopolysaccharide (LPS)-initiated rhinosinusitis. METHODS: Adult C57BL/6 mice were intranasally administered with LPS for 3 weeks. The olfactory function was evaluated with a buried food test. The inflammatory status of sinonasal cavity and olfactory bulb was evaluated with histology and biochemistry. RESULTS: After 3-week LPS treatment, mice developed olfactory dysfunction, sinonasal cavity, and olfactory bulb inflammation. LPS-treated mice had greater sinonasal mucosal thickness. Besides, pro-inflammatory interleukin-6, the number of goblet cells and neutrophils in the sinonasal cavity was increased after LPS administration. The olfactory sensory neurons in the olfactory epithelium and the olfactory bulb were decreased, and the olfactory function was impaired by LPS administration. Inflammatory cytokines such as interferon-γ and tumor necrosis factor-α were increased in the olfactory bulb. CONCLUSION: This study showed that LPS-initiated rhinosinusitis caused olfactory neuroinflammation and olfactory dysfunction in mice.


Subject(s)
Olfaction Disorders , Sinusitis , Mice , Animals , Lipopolysaccharides , Neuroinflammatory Diseases , Mice, Inbred C57BL , Sinusitis/pathology , Inflammation/pathology , Olfactory Bulb/pathology , Olfaction Disorders/chemically induced , Olfaction Disorders/pathology
11.
Bioresour Technol ; 367: 128303, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36368488

ABSTRACT

Biochar is an eco-friendly, low-cost, and carbon-rich material. This study synthesized the biochars from three agricultural wastes, pinecone, white popinac, and sugarcane bagasse, and then modified them by manganese ferrite (MnFe2O4) co-precipitation. These biochars were applied as adsorbents for the removal of Cu(II) ions from water. All three different MnFe2O4-biochars have similar adsorption performances: rapid adsorption kinetics with equilibrium being reached within 5 hr of contact and significantly enhanced adsorption capacities of Cu(II) ions from water. The principal adsorption mechanisms were identified as complexation reactions, contributed by the carboxyl and hydroxyl groups by pristine biochars and by the Mn-O and Fe-O groups for all three MnFe2O4-biochars. The MnFe2O4-biochars can be reused for three cycles, with the maximum adsorption capacities of Cu(II) of the regenerated biochars declining with the loss of precipitated MnFe2O4.


Subject(s)
Saccharum , Water Pollutants, Chemical , Adsorption , Copper , Cellulose , Charcoal , Ions , Kinetics , Water
12.
Sci Rep ; 13(1): 13211, 2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37580361

ABSTRACT

We demonstrate the engineering of waveguide dispersion by lithographically patterning the polymer cladding on silicon nitride waveguide resonators. Both normal and anomalous dispersion, ranging from - 462 to 409 ps/nm/km, can be achieved for the same waveguide dimension within an integrated photonic chip. In the meantime, this simple process shows no impact on the waveguide loss and the quality factor of the waveguide resonators, offering flexibility in tailoring designable dispersion for a universal photonic platform. In addition, by adjusting the coverage ratio of cladding, relatively low dispersion (≈ - 130 ps/nm/km) is also demonstrated in the same waveguide resonator, yielding the potentials for zero-dispersive waveguide resonators by a proper coverage ratio of the polymer cladding.

13.
Nanomaterials (Basel) ; 12(16)2022 Aug 13.
Article in English | MEDLINE | ID: mdl-36014639

ABSTRACT

Thermo-osmotic energy conversion using waste heat is one of the approaches to harvesting sustainable energy and reducing associated environmental impacts simultaneously. In principle, ions transport through a charged nanopore membrane under the effect of a thermal gradient, inducing a different voltage between two sides of the membrane. Recent publications mainly reported novel materials for enhancing the thermoelectric voltage in response to temperature difference, the so-called Seebeck coefficient. However, the effect of the surface charge distribution along nanopores on thermo-osmotic conversion has not been discussed yet. In this paper, a numerical simulation based on the Nernst-Planck-Poisson equations, Navier-Stokes equations, and heat transfer equations is carried out to consider the effect of surface charge-regulation density and pH of KCl solutions on the Seebeck coefficient. The results show that the highest ionic Seebeck coefficient of -0.64 mV/K is obtained at 10-4 M KCl solution and pH 9. The pH level and pore structure also reveal a strong effect on the thermo-osmotic performance. Moreover, the pH level at one reservoir is varied from 5 to 9, while the pH of 5 is fixed at the other reservoir to investigate the pH effect on the thermos-osmosis ion transport. The results confirm the feasibility that using the pH can enhance the thermo-osmotic conversion for harvesting osmotic power from low-grade heat energy.

14.
In Vivo ; 36(6): 2965-2972, 2022.
Article in English | MEDLINE | ID: mdl-36309350

ABSTRACT

BACKGROUND/AIM: Sinonasal rhabdomyosarcoma (RMS) is a rare soft tissue malignancy. Due to the limited cases, the clinicopathological features and prognostic factors are still not well understood. PATIENTS AND METHODS: This retrospective review included eight patients with sinonasal RMS at our institution between 2004 and 2020. Patient demographics, tumor features, Intergroup Rhabdomyosarcoma Study Group (IRSG) stage and clinical group, treatment strategy, and survival rates were evaluated. Kaplan-Meier analysis and log-rank tests were performed to analyze the possible prognostic factors. RESULTS: We observed a predominance of male sex and alveolar-type tumor in sinonasal RMS. Nasal obstructions and neck masses were the most common symptoms. Patients with pretreatment lactate dehydrogenase (LDH) levels >400 U/l and negative immunohistochemical staining for desmin or MyoD1 had lower survival rates. CONCLUSION: In patients with sinonasal RMS, pretreatment LDH levels >400 U/l and negative immunohistochemical staining for desmin or MyoD1 may suggest a poor prognosis. These factors can not only contribute to the prediction of prognosis in patients with sinonasal RMS but also facilitate the design of more appropriate treatment strategies.


Subject(s)
Paranasal Sinus Neoplasms , Rhabdomyosarcoma , Sarcoma , Humans , Male , Female , Prognosis , Desmin , Rhabdomyosarcoma/diagnosis , Rhabdomyosarcoma/therapy , Rhabdomyosarcoma/pathology , Paranasal Sinus Neoplasms/diagnosis , Paranasal Sinus Neoplasms/therapy , Sarcoma/pathology
15.
Bioresour Technol ; 360: 127529, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35764277

ABSTRACT

This study synthesized nine biochars from different feedstocks and chemically modified their surfaces using MnFe2O4 precipitation at pH 11 (MnFe2O4-biochars). The maximum adsorption quantities (qmax) of Cu(II) at pH 6 and 25 °C for pristine biochars based on Langmuir model ranged 10.4-23.6 mg/g and for MnFe2O4-biochars, 32.7-43.1 mg/g, with enhancement from 65.6% (bamboo biochar) to 246% (white popinac biochar). Type-wide comparison shows no correlation between surface area of pristine or MnFe2O4-biochars on the adsorption performance. Conversely, the carboxyl groups on the nine biochar surfaces have contributed to Cu(II) adsorption. The type-dependence for qmax of different MnFe2O4-biochars becomes insignificant, confirming the role of biochars being principally an oxide carrier instead of an adsorbent.


Subject(s)
Charcoal , Sasa , Adsorption , Copper , Ferric Compounds , Manganese Compounds
16.
Bioresour Technol ; 319: 124100, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32950819

ABSTRACT

Biochars are the solid product of biomass under pyrolysis or gasification treatment, whose wholesale prices are lower than commercial activated carbons and other fine materials now in use. The employment of biochars as a renewable resource for field applications, if feasible, would gain apparent economic niche. Modification using physical or chemical protocol to revise the surface properties of biochar for reaching enhanced performances of target application has attracted great research interests. This article provided an overview of biochar application, particularly with the respect to the use of modified biochar as preferred soil amendment, adsorbent, electrochemical material, anaerobic digestion promotor, and catalyst. Based on literature works the current research trends and the prospects and research needs were outlined.


Subject(s)
Charcoal , Soil , Adsorption , Biomass , Pyrolysis
17.
Micromachines (Basel) ; 12(11)2021 Oct 21.
Article in English | MEDLINE | ID: mdl-34832695

ABSTRACT

Heavy metal contaminants have serious consequences for the environment and human health. Consequently, effective methods for detecting their presence, particularly in water and food, are urgently required. Accordingly, the present study proposes a sensor capable of detecting mercury Hg(II) and lead Pb(II) ions simultaneously, using graphene oxide (GO) as a quenching agent and an aptamer solution as a reagent. In the proposed device, the aptamer sequences are labeled by FAM and HEX fluorescent dyes, respectively, and are mixed well with 500 ppm GO solution before injection into one inlet of the microchannel, and the heavy metal sample solution is injected into another inlet. The presence of Hg(II) and Pb(II) ions is then detected by measuring the change in the fluorescence intensity of the GO/aptamer suspension as the aptamer molecules undergo fluorescence resonance energy transfer (FRET). The selectivity of these two ions is also shown to be clear among other mixed heavy metal ions. The experimental results show that the aptamer sensors have a linear range of 10~250 nM (i.e., 2.0~50 ppb) for Hg(II) ions and 10~100 nM (i.e., 2.1~20.7 ppb) for Pb(II) ions. Furthermore, the limit of detection is around 0.70 ppb and 0.53 ppb for Hg(II) and Pb(II), respectively, which is lower than the maximum limits of 6 ppb and 10 ppb prescribed by the World Health Organization (WHO) for Hg(II) and Pb(II) in drinking water, respectively.

18.
Micromachines (Basel) ; 12(6)2021 Jun 09.
Article in English | MEDLINE | ID: mdl-34207796

ABSTRACT

Since the first demonstration of (Al, In, Ga)N-based blue vertical-cavity surface-emitting lasers (VCSELs) in 2008, the maximum output power (Pmax) and threshold current density (Jth) has been improved significantly after a decade of technology advancements. This article reviewed the key challenges for the realization of VCSELs with III-nitride materials, such as inherent polarization effects, difficulties in distributed Bragg's reflectors (DBR) fabrication for a resonant cavity, and the anti-guiding effect due to the deposited dielectrics current aperture. The significant tensile strain between AlN and GaN hampered the intuitive cavity design with two epitaxial DBRs from arsenide-based VCSELs. Therefore, many alternative cavity structures and processing technologies were developed; for example, lattice-matched AlInN/GaN DBR, nano-porous DBR, or double dielectric DBRs via various overgrowth or film transfer processing strategies. The anti-guiding effect was overcome by integrating a fully planar or slightly convex DBR as one of the reflectors. Special designs to limit the emission polarization in a circular aperture were also summarized. Growing VCSELs on low-symmetry non-polar and semipolar planes discriminates the optical gain along different crystal orientations. A deliberately designed high-contrast grating could differentiate the reflectivity between the transverse-electric field and transverse-magnetic field, which restricts the lasing mode to be the one with the higher reflectivity. In the future, the III-nitride based VCSEL shall keep advancing in total power, applicable spectral region, and ultra-low threshold pumping density with the novel device structure design and processing technologies.

19.
Sci Rep ; 10(1): 3093, 2020 Feb 20.
Article in English | MEDLINE | ID: mdl-32080312

ABSTRACT

Quantum teleportation enables networking participants to move an unknown quantum state between the nodes of a quantum network, and hence constitutes an essential element in constructing large-sale quantum processors with a quantum modular architecture. Herein, we propose two protocols for teleporting qubits through an N-node quantum network in a highly-entangled box-cluster state or chain-type cluster state. The proposed protocols are systematically scalable to an arbitrary finite number N and applicable to arbitrary size of modules. The protocol based on a box-cluster state is implemented on a 14-qubit IBM quantum computer for N up to 12. To identify faithful networking teleportation, namely that the elements on real devices required for the networking teleportation process are all qualified for achieving teleportation task, we quantify quantum-mechanical processes using a generic classical-process model through which any classical strategies of mimicry of teleportation can be ruled out. From the viewpoint of achieving a genuinely quantum-mechanical process, the present work provides a novel toolbox consisting of the networking teleportation protocols and the criteria for identifying faithful teleportation for universal quantum computers with modular architectures and facilitates further improvements in the reliability of quantum-information processing.

20.
Toxins (Basel) ; 11(5)2019 05 08.
Article in English | MEDLINE | ID: mdl-31072027

ABSTRACT

Aflatoxins are carcinogenic secondary metabolites of fungi that contaminate many staple crops and foods. Aflatoxin contamination is a worldwide problem, especially in developing countries, posing health hazards, e.g., causing aflatoxicosis and hepatocellular carcinoma, and even death. Biological solutions for aflatoxin detoxification are environmentally friendly and a cheaper alternative than chemical methods. The aims of the current study were to investigate: (1) the ability of MSMEG_5998, an aflatoxin-degrading F420H2-dependent reductase from Mycobacterium smegmatis, to degrade aflatoxin B1 (AFB1) and reduce AFB1-caused damage in HepG2 cell culture model; and (2) whether a thioredoxin (Trx) linkage of MSMEG_5998 enhanced the enzyme activity. We show that Trx-linked MSMEG_5998 degraded 63% AFB1 and native MSMEG_5998 degraded 31% after 4 h at 22 °C, indicating that the Trx-linked enzyme had a better AFB1-degrading ability. In a HepG2 cell culture model, Trx-linked MSMEG_5998 reduced DNA damage and p53-mediated apoptosis caused by AFB1 to a greater extent than the native enzyme. These findings suggest that Trx-linked MSMEG_5998 could potentially be developed to protect the liver from AFB1 damage, or as a candidate protein to reduce AFB1-related toxicity in animals.


Subject(s)
Aflatoxins/toxicity , Mycobacterium smegmatis/enzymology , Oxidoreductases/pharmacology , Protective Agents/pharmacology , Apoptosis/drug effects , DNA Damage , Enzyme Stability , Hep G2 Cells , Humans , Recombinant Proteins/pharmacology
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