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1.
Roberto Zenteno-Cuevas Francisco X Silva-Hernández Fabiola Mendoza-Damián Maria Dolores Ramírez-Hernández Karen Vázquez-Medina Lorena Widrobo-García Aremy Cuellar-Sanchez Raquel Mu?íz-Salazar Leonor Enciso-Moreno Lucia Monserrat Pérez-Navarro José Antonio Enciso-Moreno 《Memórias do Instituto Oswaldo Cruz》2013,108(6):718-723
Tuberculosis (TB) is an infectocontagious respiratory disease caused by members
of the Mycobacterium tuberculosis complex. A 7 base pair (bp)
deletion in the locus polyketide synthase
(pks)15/1 is described as polymorphic among members of the
M. tuberculosis complex, enabling the identification of
Euro-American, Indo-Oceanic and Asian lineages. The aim of this study was to
characterise this locus in TB isolates from Mexico. One hundred
twenty clinical isolates were recovered from the states of Veracruz and Estado
de Mexico. We determined the nucleotide sequence of a ± 400 bp fragment of the
locus pks15/1, while genotypic characterisation was
performed by spoligotyping. One hundred and fifty isolates contained the 7 bp
deletion, while five had the wild type locus. Lineages X (22%),
LAM (18%) and T (17%) were the most frequent; only three (2%) of the isolates
were identified as Beijing and two (1%) EAI-Manila. The wild type
pks15/1 locus was observed in all Asian lineage isolates
tested. Our results confirm the utility of locus pks15/1 as a
molecular marker for identifying Asian lineages of the M.
tuberculosis complex. This marker could be of great value in the
epidemiological surveillance of TB, especially in countries like Mexico, where
the prevalence of such lineages is unknown. 相似文献
2.
3.
Nanees F El-Malkey Amira E Alsemeh Wesam MR Ashour Nancy H Hassan Husam M Edrees 《Experimental biology and medicine (Maywood, N.J.)》2021,246(11):1307
Intestinal tissue is highly susceptible to ischemia/reperfusion injury in many hazardous health conditions. The anti-inflammatory and antioxidant glycoprotein fetuin-A showed efficacy in cerebral ischemic injury; however, its protective role against intestinal ischemia/reperfusion remains elusive. Therefore, this study investigated the protective role of fetuin-A supplementation against intestinal structural changes and dysfunction in a rat model of intestinal ischemia/reperfusion. We equally divided 72 male rats into control, sham, ischemia/reperfusion, and fetuin-A-pretreated ischemia/reperfusion (100 mg/kg/day fetuin-A intraperitoneally for three days prior to surgery and a third dose 1 h prior to the experiment) groups. After 2 h of reperfusion, the jejunum was dissected and examined for spontaneous contractility. A jejunal homogenate was used to assess inflammatory and oxidative stress enzymes. Staining of histological sections was carried out with hematoxylin, eosin and Masson’s trichrome stain for evaluation. Immunohistochemistry was performed to detect autophagy proteins beclin-1, LC3, and p62. This study found that fetuin-A significantly improved ischemia/reperfusion-induced mucosal injury by reducing the percentage of areas of collagen deposition, increasing the amplitude of spontaneous contraction, decreasing inflammation and oxidative stress, and upregulating p62 expression, which was accompanied by beclin-1 and LC3 downregulation. Our findings suggest that fetuin-A treatment can prevent ischemia/reperfusion-induced jejunal structural and functional changes by increasing antioxidant activity and regulating autophagy disturbances observed in the ischemia/reperfusion rat model. Furthermore, fetuin-A may provide a protective influence against intestinal ischemia/reperfusion complications. 相似文献
4.
Plant viruses are known to infect most economically important crops and pose a major threat to global food security. Currently, few resistant host phenotypes have been delineated, and while chemicals are used for crop protection against insect pests and bacterial or fungal diseases, these are inefficient against viral diseases. Genetic engineering emerged as a way of modifying the plant genome by introducing functional genes in plants to improve crop productivity under adverse environmental conditions. Recently, new breeding technologies, and in particular the exciting CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR‐associated proteins) technology, was shown to be a powerful alternative to engineer resistance against plant viruses, thus has great potential for reducing crop losses and improving plant productivity to directly contribute to food security. Indeed, it could circumvent the “Genetic modification” issues because it allows for genome editing without the integration of foreign DNA or RNA into the genome of the host plant, and it is simpler and more versatile than other new breeding technologies. In this review, we describe the predominant features of the major CRISPR/Cas systems and outline strategies for the delivery of CRISPR/Cas reagents to plant cells. We also provide an overview of recent advances that have engineered CRISPR/Cas‐based resistance against DNA and RNA viruses in plants through the targeted manipulation of either the viral genome or susceptibility factors of the host plant genome. Finally, we provide insight into the limitations and challenges that CRISPR/Cas technology currently faces and discuss a few alternative applications of the technology in virus research. 相似文献
5.
6.
Martin A. Baraibar Barry B. Muhoberac Holly J. Garringer Thomas D. Hurley Ruben Vidal 《The Journal of biological chemistry》2010,285(3):1950-1956
Mutations in the coding sequence of the ferritin light chain (FTL) gene cause a
neurodegenerative disease known as neuroferritinopathy or hereditary
ferritinopathy, which is characterized by the presence of intracellular
inclusion bodies containing the mutant FTL polypeptide and by abnormal
accumulation of iron in the brain. Here, we describe the x-ray crystallographic
structure and report functional studies of ferritin homopolymers formed from the
mutant FTL polypeptide p.Phe167SerfsX26, which has a C terminus that is altered
in amino acid sequence and length. The structure was determined and refined to
2.85 Å resolution and was very similar to the wild type between
residues Ile-5 and Arg-154. However, instead of the E-helices normally present
in wild type ferritin, the C-terminal sequences of all 24 mutant subunits showed
substantial amounts of disorder, leading to multiple C-terminal polypeptide
conformations and a large disruption of the normally tiny 4-fold axis pores.
Functional studies underscored the importance of the mutant C-terminal sequence
in iron-induced precipitation and revealed iron mishandling by soluble mutant
FTL homopolymers in that only wild type incorporated iron when in direct
competition in solution with mutant ferritin. Even without competition, the
amount of iron incorporation over the first few minutes differed severalfold.
Our data suggest that disruption at the 4-fold pores may lead to direct iron
mishandling through attenuated iron incorporation by the soluble form of mutant
ferritin and that the disordered C-terminal polypeptides may play a major role
in iron-induced precipitation and formation of ferritin inclusion bodies in
hereditary ferritinopathy. 相似文献
7.
8.
Claire Giroud Magali Moreau Tony A. Mattioli Véronique Balland Jean-Luc Boucher Yun Xu-Li Dennis J. Stuehr Jér?me Santolini 《The Journal of biological chemistry》2010,285(10):7233-7245
Nitric-oxide synthases (NOS) are highly regulated heme-thiolate enzymes that
catalyze two oxidation reactions that sequentially convert the substrate
l-Arg first to
Nω-hydroxyl-l-arginine and then
to l-citrulline and nitric oxide. Despite numerous investigations, the
detailed molecular mechanism of NOS remains elusive and debatable. Much of the
dispute in the various proposed mechanisms resides in the uncertainty concerning
the number and sources of proton transfers. Although specific protonation events
are key features in determining the specificity and efficiency of the two
catalytic steps, little is known about the role and properties of protons from
the substrate, cofactors, and H-bond network in the vicinity of the heme active
site. In this study, we have investigated the role of the acidic proton from the
l-Arg guanidinium moiety on the stability and reactivity of the
ferrous heme-oxy complex intermediate by exploiting a series of l-Arg
analogues exhibiting a wide range of guanidinium pKa
values. Using electrochemical and vibrational spectroscopic techniques, we have
analyzed the effects of the analogues on the heme, including characteristics of
its proximal ligand, heme conformation, redox potential, and electrostatic
properties of its distal environment. Our results indicate that the substrate
guanidinium pKa value significantly affects the
H-bond network near the heme distal pocket. Our results lead us to propose a new
structural model where the properties of the guanidinium moiety finely control
the proton transfer events in NOS and tune its oxidative chemistry. This model
may account for the discrepancies found in previously proposed mechanisms of NOS
oxidation processes. 相似文献
9.
10.
Christopher P. Gayer Lakshmi S. Chaturvedi Shouye Wang David H. Craig Thomas Flanigan Marc D. Basson 《The Journal of biological chemistry》2009,284(4):2001-2011
The intestinal epithelium is repetitively deformed by shear, peristalsis,
and villous motility. Such repetitive deformation stimulates the proliferation
of intestinal epithelial cells on collagen or laminin substrates via ERK, but
the upstream mediators of this effect are poorly understood. We hypothesized
that the phosphatidylinositol 3-kinase (PI3K)/AKT cascade mediates this
mitogenic effect. PI3K, AKT, and glycogen synthase kinase-3β
(GSK-3β) were phosphorylated by 10 cycles/min strain at an average 10%
deformation, and pharmacologic blockade of these molecules or reduction by
small interfering RNA (siRNA) prevented the mitogenic effect of strain in
Caco-2 or IEC-6 intestinal epithelial cells. Strain MAPK activation required
PI3K but not AKT. AKT isoform-specific siRNA transfection demonstrated that
AKT2 but not AKT1 is required for GSK-3β phosphorylation and the strain
mitogenic effect. Furthermore, overexpression of AKT1 or an AKT chimera
including the PH domain and hinge region of AKT2 and the catalytic domain and
C-tail of AKT1 prevented strain activation of GSK-3β, but overexpression
of AKT2 or a chimera including the PH domain and hinge region of AKT1 and the
catalytic domain and C-tail of AKT2 did not. These data delineate a role for
PI3K, AKT2, and GSK-3β in the mitogenic effect of strain. PI3K is
required for both ERK and AKT2 activation, whereas AKT2 is sequentially
required for GSK-3β. Furthermore, AKT2 specificity requires its catalytic
domain and tail region. Manipulating this pathway may prevent mucosal atrophy
and maintain the mucosal barrier in conditions such as ileus, sepsis, and
prolonged fasting when peristalsis and villous motility are decreased and the
mucosal barrier fails.Mechanical forces are part of the normal intestinal epithelial environment.
Numerous different forces deform these cells including shear stress from
endoluminal chyme, bowel peristalsis, and villous motility
(1,
2). During normal bowel
function the mucosa is subjected to injury that must be repaired to maintain
the mucosal barrier (3,
4). Deformation patterns of the
bowel are altered in conditions such as prolonged fasting, post-surgical
ileus, and sepsis states, resulting in profoundly reduced mucosal deformation.
When such states are prolonged, proliferation slows, the mucosa becomes
atrophic, and bacterial translocation may ensue as the mucosal barrier of the
gut breaks down
(5–7).In vitro, repetitive deformation is trophic for intestinal
epithelial cells (8) cultured
on type I or type IV collagen or laminin. Human Caco-2 intestinal epithelial
cells (9), non-transformed rat
IEC-6 intestinal epithelial cells
(10), and primary human
intestinal epithelial cells isolated from surgical specimens
(11) proliferate more rapidly
in response to cyclic strain
(12) unless substantial
quantities of fibronectin are added to the media or matrix
(11) to mimic the acute phase
reaction of acute or chronic inflammation and injury. Cyclic strain also
stimulates proliferation in HCT 116 colon cancer cells
(13) and differentiation of
Caco-2 cells cultured on a collagen substrate
(9). This phenomenon has also
been observed in vivo
(14). Thus, repetitive
deformation may help to maintain the normal homeostasis of the gut mucosa
under non-inflammatory conditions. Previous work in our laboratory has
implicated Src, focal adhesion kinase, and the mitogen-activated protein
kinase (MAPK)2
extracellular signal-related kinase (ERK) in the mitogenic effect of strain
(10). Although p38 is also
activated in Caco-2 cells subjected to cyclic strain on a collagen matrix, its
activity is not required for the mitogenic effect of strain
(12).Although often the PI3K/AKT pathway is thought of as a parallel pathway to
the MAPK, this is not always the case. Protein kinase C isoenzymes
differentially modulate thrombin effect on MAPK-dependent retinal pigment
epithelial cell (RPE) proliferation, and it has been shown that PI3K or AKT
inhibition prevented thrombin-induced ERK activation and RPE proliferation
(15).PI3K, AKT, and glycogen synthase kinase (GSK), a downstream target of AKT
(16), have been implemented in
intestinal epithelial cell proliferation in numerous cell systems not
involving strain
(17–19)
including uncontrolled proliferation in gastrointestinal cancers
(20–22).
Mechanical forces activate this pathway as well. PI3K and AKT are required for
increased extracellular pressure to stimulate colon cancer cell adhesion
(23), although the pathway by
which pressure stimulates colon cancer cells in suspension differs from the
response of adherent intestinal epithelial cells to repetitive deformation
(24), and GSK is not involved
in this effect.3
Repetitive strain also stimulates vascular endothelial cell proliferation via
PI3K and AKT (25,
26), whereas respiratory
strain stimulates angiogenic responses via PI3K
(27). We, therefore,
hypothesized that the PI3K/AKT/GSK axis would be involved in the mitogenic
effects of repetitive deformation on a collagen matrix.To test this hypothesis, we used the Flexcell apparatus to rhythmically
deform Caco-2 intestinal epithelial cells. IEC-6 cells were used to confirm
key results. A frequency of 10 cycles per min was used, which is similar in
order of magnitude to the frequency that the intestinal mucosa might be
deformed by peristalsis or villous motility in vivo
(28,
29). Mechanical forces such as
repetitive deformation are likely cell-type and frequency-specific, as
different cell types respond to different frequencies. Vascular endothelial
cells respond to frequencies of 60–80 cycles/min
(25), whereas intestinal
epithelial cells may actually decrease proliferation in response to
frequencies of 5 cycles/min
(30). We characterized PI3K,
AKT, and GSK phosphorylation with strain, blocked these molecules
pharmacologically or by siRNA, and delineated the specificity of the AKT
effect using isozyme-specific siRNA and transfection of AKT1/2 chimeras. We
also characterized the interaction of this pathway with the activation of ERK
by strain, which has previously been implicated in the mitogenic response
(12). 相似文献
11.
C57BL/6N inbred mice are used as the genetic background for producing knockout mice in
large-scale projects worldwide; however, the genetic divergence among C57BL/6N-derived
substrains has not been verified. Here, we identified novel single nucleotide
polymorphisms (SNPs) specific to the C57BL/6NJ strain and selected useful SNPs for the
genetic monitoring of C57BL/6N-derived substrains. Informative SNPs were selected from the
public SNP database at the Wellcome Trust Sanger Institute by comparing sequence data from
C57BL/6NJ and C57BL/6J mice. A total of 1,361 candidate SNPs from the SNP database could
distinguish the C57BL/6NJ strain from 12 other inbred strains. We confirmed 277
C57BL/6NJ-specific SNPs including 10 nonsynonymous SNPs by direct sequencing, and selected
100 useful SNPs that cover all of the chromosomes except Y. Genotyping of 11
C57BL/6N-derived substrains at these 100 SNP loci demonstrated genetic differences among
the substrains. This information will be useful for accurate genetic monitoring of mouse
strains with a C57BL/6N-derived background. 相似文献
12.
Fernando Gómez-Herreros Olga Rodríguez-Galán Macarena Morillo-Huesca Douglas Maya María Arista-Romero Jesús de la Cruz Sebastián Chávez Mari Cruz Mu?oz-Centeno 《The Journal of biological chemistry》2013,288(44):31689-31700
Cell cycle regulation is a very accurate process that ensures cell viability and the genomic integrity of daughter cells. A fundamental part of this regulation consists in the arrest of the cycle at particular points to ensure the completion of a previous event, to repair cellular damage, or to avoid progression in potentially risky situations. In this work, we demonstrate that a reduction in nucleotide levels or the depletion of RNA polymerase I or III subunits generates a cell cycle delay at the G1/S transition in Saccharomyces cerevisiae. This delay is concomitant with an imbalance between ribosomal RNAs and proteins which, among others, provokes an accumulation of free ribosomal protein L5. Consistently with a direct impact of free L5 on the G1/S transition, rrs1 mutants, which weaken the assembly of L5 and L11 on pre-60S ribosomal particles, enhance both the G1/S delay and the accumulation of free ribosomal protein L5. We propose the existence of a surveillance mechanism that couples the balanced production of yeast ribosomal components and cell cycle progression through the accumulation of free ribosomal proteins. This regulatory pathway resembles the p53-dependent nucleolar-stress checkpoint response described in human cells, which indicates that this is a general control strategy extended throughout eukaryotes. 相似文献
13.
Ryosuke Kaneko Toshie Kakinuma Sachiko Sato Atsushi Jinno-Oue Hidekazu Hata 《Experimental Animals》2014,63(4):375-381
In mice, a minimum number of healthy embryos is required to trigger and maintain
pregnancy. Therefore, when recovering mouse embryos from a limited litter, one useful
technique is to transfer carrier ICR embryos along with the embryos of interest, a
technique referred to as cotransfer. In this study, we examined suitable mouse strains for
cotransfer with C57BL/6J (B6) embryos in regards to the maintenance of pregnancy, number
of pups born, intrauterine growth, and postnatal growth. Because the coat color of B6 is
black, we compared two white coat-colored strains, SJL/J and ICR. Cotransfer of SJL/J and
ICR embryos had similar effects on maintenance of pregnancy, number of pups born, and
intrauterine growth. However, the postnatal growth of B6 mouse pups cotransferred and
grown with SJL/J pups was better than for B6 mouse pups cotransferred and grown with ICR
pups, suggesting competition among littermates. These results demonstrate that cotransfer
of SJL/J embryos will be useful not only as carrier embryos with B6-background embryos but
also as a model system to examine littermate competition. 相似文献
14.
Arata Honda Michiko Hirose Tadashi Sankai Lubna Yasmin Kazuaki Yuzawa Kimiko Honsho Haruna Izu Atsushi Iguchi Masahito Ikawa Atsuo Ogura 《Experimental Animals》2015,64(1):31-37
Targeted genome editing of nonrodent mammalian species has provided the potential for
highly accurate interventions into gene function in humans and the generation of useful
animal models of human diseases. Here we show successful clustered regularly interspaced
short palindromic repeat (CRISPR) and CRISPR-associated (Cas)-mediated gene targeting via
circular plasmid injection in rabbits. The rabbit tyrosinase gene (TYR)
was effectively disrupted, and we confirmed germline transmission by pronuclear injection
of a circular plasmid expressing humanized Cas9 (hCas9) and single-guide RNA. Direct
injection into pronuclear stage zygotes was possible following an in
vitro validation assay. Neither off-target mutagenesis nor hCas9 transgenesis
was detected in any of the genetically targeted pups and embryos examined. Gene targeting
with this rapid and simplified strategy will help accelerate the development of
translational research using other nonrodent mammalian species. 相似文献
15.
Estimating the Excess Investment in
Ribulose-1,5-Bisphosphate
Carboxylase/Oxygenase in
Leaves of Spring Wheat Grown under Elevated
CO2 下载免费PDF全文
Julian C. Theobald Rowan A.C. Mitchell Martin A.J. Parry David W. Lawlor 《Plant physiology》1998,118(3):945-955
Wheat (Triticum aestivum L.) was grown under CO2 partial pressures of 36 and 70 Pa with two N-application regimes. Responses of photosynthesis to varying CO2 partial pressure were fitted to estimate the maximal carboxylation rate and the nonphotorespiratory respiration rate in flag and preceding leaves. The maximal carboxylation rate was proportional to ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) content, and the light-saturated photosynthetic rate at 70 Pa CO2 was proportional to the thylakoid ATP-synthase content. Potential photosynthetic rates at 70 Pa CO2 were calculated and compared with the observed values to estimate excess investment in Rubisco. The excess was greater in leaves grown with high N application than in those grown with low N application and declined as the leaves senesced. The fraction of Rubisco that was estimated to be in excess was strongly dependent on leaf N content, increasing from approximately 5% in leaves with 1 g N m−2 to approximately 40% in leaves with 2 g N m−2. Growth at elevated CO2 usually decreased the excess somewhat but only as a consequence of a general reduction in leaf N, since relationships between the amount of components and N content were unaffected by CO2. We conclude that there is scope for improving the N-use efficiency of C3 crop species under elevated CO2 conditions. 相似文献
16.
17.
Dennis Y. Chuang Jiankun Cui Agnes Simonyi Victoria A. Engel Shanyan Chen Kevin L. Fritsche Andrew L. Thomas Wendy L. Applequist William R. Folk Dennis B. Lubahn Albert Y. Sun Grace Y. Sun Zezong Gu 《ASN neuro》2014,6(6)
Sutherlandia (Sutherlandia frutescens) and elderberry
(Sambucus spp.) are used to promote health and for treatment of a
number of ailments. Although studies with cultured cells have demonstrated antioxidative
and anti-inflammatory properties of these botanicals, little is known about their ability
to mitigate brain injury. In this study, C57BL/6 J male mice were fed AIN93G diets without
or with Sutherlandia or American elderberry for 2 months prior to a 30-min global cerebral
ischemia induced by occlusion of the bilateral common carotid arteries (BCCAs), followed
by reperfusion for 3 days. Accelerating rotarod assessment at 24 h after BCCA occlusion
showed amelioration of sensorimotor impairment in the mice fed the supplemented diets as
compared with the ischemic mice fed the control diet. Quantitative digital pathology
assessment of brain slides stained with cresyl violet at 3 days after ischemia/reperfusion
(I/R) revealed significant reduction in neuronal cell death in both dietary groups.
Immunohistochemical staining for ionized calcium-binding adapter molecule-1 demonstrated
pronounced activation of microglia in the hippocampus and striatum in the ischemic brains
3 days after I/R, and microglial activation was significantly reduced in animals fed
supplemented diets. Mitigation of microglial activation by the supplements was further
supported by the decrease in expression of p47phox, a cytosolic subunit of NADPH oxidase,
and phospho-ERK1/2, a mitogen-activated protein kinase known to mediate a number of
cytoplasmic processes including oxidative stress and neuroinflammatory responses. These
results demonstrate neuroprotective effect of Sutherlandia and American elderberry
botanicals against oxidative and inflammatory responses to cerebral I/R. 相似文献
18.
Makoto ASAHINA Fumi SHIMIZU Masayuki OHTA Michiyasu TAKEYAMA Ryuichi TOZAWA 《Experimental Animals》2015,64(3):313-321
Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is
a cluster of metabolic diseases including obesity, diabetes, hypertension, and
dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the
progression of kidney dysfunction. To establish a new nephropathy model with metabolic
syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.)
SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia
is exacerbated more than in an established metabolic syndrome model,
SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed
obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited
exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased
oxidative and inflammatory markers. Histological analyses revealed the characteristic
features of human apoB Tg. SHR-cp/cp rats including prominent
glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg.
SHR-cp/cp rat could be a useful model for the nephropathy in metabolic
syndrome and for understanding the interaction between dyslipidemia and renal dysfunction
in metabolic syndrome. 相似文献
19.
Xiangting Liu Zheng Hu Jiayao Qu Jia Li Ke Gong Li Wang Jing Jiang Xiangning Li Rongzhang He Lili Duan Weihao Luo Chenglai Xia Dixian Luo 《International journal of biological sciences》2021,17(3):756
Nasopharyngeal carcinoma (NPC) is one kind of human head and neck cancers with high incidence in Southern China, Southeast Asia and North Africa. In spite of great innovations in radiation and chemotherapy treatments, the 5-year survival rate is not satisfactory. One of the main reasons is resistance to radiotherapy which leads to therapy failure and recurrence of NPC. The mechanism underlying remains to be fully elucidated. Aldo-keto reductase B10 (AKR1B10) plays a role in the formation and development of carcinomas. However, its role in resistance to radiotherapy of NPC is not clear. In this research, the relationships between AKR1B10 expression and the treatment effect of NPC patients, NPC cell survival, cell apoptosis, and DNA damage repair, as well as the effect and mechanism of AKR1B10 expression on NPC radioresistance were explored. A total of 58 paraffin tissues of NPC patients received radiotherapy were collected including 30 patients with radiosensitivity and 28 patients with radioresistance. The relationships between AKR1B10 expression and the treatment effect as well as clinical characteristics were analyzed by immuno-histochemical experiments, and the roles of AKR1B10 in cell survival, apoptosis and DNA damage repair were detected using the AKR1B10 overexpressed cell models. Furthermore the mechanism of AKR1B10 in NPC radioresistance was explored. Finally, the radioresistance effect of AKR1B10 expression was evaluated by the tumor xenograft model of nude mice and the method of radiotherapy. The results showed AKR1B10 expression level was correlated with radiotherapy resistance, and AKR1B10 overexpression promoted proliferation of NPC cells, reduced apoptosis and decreased cellular DNA damage after radiotherapy. The probable molecular mechanism is that AKR1B10 expression activated FFA/TLR4/NF-κB axis in NPC cells. This was validated by using the TLR4 inhibitor TAK242 to treat NPC cells with AKR1B10 expression, which reduced the phosphorylation of NF-κB. This study suggests that AKR1B10 can induce radiotherapy resistance and promote cell survival via FFA/TLR4/NF-κB axis in NPC, which may provide a novel target to fight against radiotherapy resistance of NPC. 相似文献