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1.
Front Immunol ; 11: 436, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32226431

RESUMO

C-type lectins (CTLs) have received widespread attention in animal immune responses. In the present study, two CTLs (ToCTL1 and ToCTL2) were identified from obscure puffer Takifugu obscurus. The open reading frames of ToCTL1 and ToCTL2 were 687 and 1,380 bp, respectively. The predicted ToCTL1 and ToCTL2 proteins contained a single transmembrane region and one typical carbohydrate recognition domain (CRD). Quantitative real-time polymerase chain reaction detected ToCTL1 and ToCTL2 transcripts in all examined tissues, with high levels in the intestine and kidney, and their expression levels were remarkably altered upon Vibrio harveyi and Aeromonas hydrophila infection. The recombinant proteins ToCTL1-CRD and ToCTL2-CRD agglutinated the Gram-negative and Gram-positive bacteria in a Ca2+-dependent manner. rToCTL1-CRD and rToCTL2-CRD exhibited evident binding activities against seven kinds of bacteria and polysaccharides (lipopolysaccharide and peptidoglycan) in a Ca2+-independent manner. Moreover, rToCTL1-CRD and rToCTL2-CRD could inhibit the growth of four types of bacteria in vitro. These findings collectively demonstrated that ToCTL1 and ToCTL2 could be involved in host defense against bacterial infection in T. obscurus.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32149644

RESUMO

This study investigated the effects of low-intensity transcranial ultrasound stimulation (TUS) on behavior in a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The PD mouse model was induced by consecutive injecting the mice with MPTP for 7 days. When the animal model is completed, we performed behavioral tests including the wire hanging test, open field test and forced swimming test on day 1, 2, 3, 4, 7, 14 during 2 weeks. Simultaneously, the ultrasound was used to stimulate the brain tissue of the mice daily for these 2 weeks. The data were analyzed to examine treatment effects. When the PD+TUS and PD+Sham groups were compared, the behavior of the PD+TUS mice was better on the fourth day after TUS (*p<0.05) and had further improved on the fourteenth day of TUS (**p<0.01). These results demonstrate that TUS can improve behavior in mice with MPTP-induced PD. The treatment effect gradually improved as the TUS duration increased.

3.
Cell Death Differ ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144382

RESUMO

Cancer cells are defective in DNA repair, so they experience increased DNA strand breaks, genome instability, gene mutagenesis, and tumorigenicity; however, multiple classic DNA repair genes and pathways are strongly activated in malignant tumor cells to compensate for the DNA repair deficiency and gain an apoptosis resistance. The mechanisms underlying this phenomenon in cancer are unclear. We speculate that a key DNA repair gene or signaling pathway in cancer has not yet been recognized. Here, we show that the lipogenic liver X receptor (LXR)-sterol response element binding factor-1 (SREBF1) axis controls the transcription of a key DNA repair gene polynucleotide kinase/phosphatase (PNKP), thereby governing cancer cell DNA repair and apoptosis. Notably, the PNKP levels were significantly reduced in 95% of human pancreatic cancer (PC) patients, particularly deep reduction for sixfold in all of the advanced-stage PC cases. PNKP is also deficient in three other types of cancer that we examined. In addition, the expression of LXRs and SREBF1 was significantly reduced in the tumor tissues from human PC patients compared with the adjacent normal tissues. The newly identified LXR-SREBF1-PNKP signaling pathway is deficient in PC, and the defect in the pathway contributes to the DNA repair deficiency in the cancer. Strikingly, further diminution of the vulnerable LXR-SREBF1-PNKP signaling pathway using a small molecule triptonide, a new LXR antagonist identified in this investigation, at a concentration of 8 nM robustly activated tumor-suppressor p53 and readily elevated cancer cell DNA strand breaks over an apoptotic threshold, and selectively induced PC cell apoptosis, resulting in almost complete elimination of tumors in xenograft mice without obvious complications. Our findings provide new insight into DNA repair and apoptosis in cancer, and offer a new platform for developing novel anticancer therapeutics.

4.
Sci Rep ; 10(1): 3889, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127574

RESUMO

A new bacterial strain, designated HM134T, was isolated from a sample of soil collected from a Chinese mangrove Avicennia marina forest. Assessed by a polyphasic approach, the taxonomy of strain HM134T was found to be associated with a range of phylogenetic and chemotaxonomic properties consistent with the genus Micromonospora. Phylogenetic analysis based on the 16s rRNA gene sequence indicated that strain HM134T formed a distinct lineage with the most closely related species, including M. rifamycinica AM105T, M. wenchangensis CCTCC AA 2012002T and M. mangrovi 2803GPT1-18T. The ANI values between strain HM134T and the reference strains ranged from 82.6% to 95.2%, which was below the standard criteria for classifying strains as the same species (96.5%). Strain HM134T and related species shared in silico dDDH similarities values below the recommended 70% cut-off for the delineation of species (range from 25.7-62.6%). The DNA G+C content of strain HM134T was 73.2 mol%. Analysis of phylogenetic, genomic, phenotypic and chemotaxonomic characteristics revealed that strain HM134T is considered to represent a novel species of the genus Micromonospora, for which the name M. zhangzhouensis sp. nov. is proposed. The extract of strain HM134T was demonstrated to exhibit cytotoxic activity against the human cancer cell lines HepG2, HCT-116 and A549. Active substance presented in the fermentation broth of strain HM134T was isolated by bioassay-guided analysis and purified afterwards. A new derivative of diterpenoid was identified through electrospray ionizing mass spectrometry (MS) and nuclear magnetic resonance (NMR). The compound showed different cytotoxic activities against cancer cells, with the highest cytotoxicity against HCT-116, corresponding to IC50 value of 38.4 µg/mL.

6.
Brain Behav Immun ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32173452

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). Among the factors involved in the immunological mechanisms of MS, T helper 1 (Th1) cells and T helper 17 (Th17) cells play a critical role. Compound 21, a novel phloroglucinol derivative, significantly protected myelin from damage in our previous study. However, it remains unclear whether this compound affects MS. In this study, the experimental autoimmune encephalomyelitis (EAE) rat model was established to mimic the pathological process of MS and evaluate the neuroprotective effect of Compound 21. The results illustrated that Compound 21 treatment notably attenuates neurological deficits, immune infiltration, and demyelination in EAE rats. Our mechanistic investigation revealed that Compound 21 treatment reduces the population of Th1/Th17 cells and inhibits their infiltration into the CNS. Furthermore, we found that the inhibition of Th1/Th17 cell infiltration is related to the direct suppression of Th1/Th17 cell differentiation and the inhibition of proinflammatory microglial cells. Collectively, these results confirm that Compound 21 suppresses infiltrated Th1/Th17 cells to alleviate demyelination in EAE rats, suggesting its potential role as a novel candidate for MS treatment.

7.
Nat Commun ; 11(1): 1496, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198415

RESUMO

The ability to grow at moderate acidic conditions (pH 4.0-5.0) is important to Escherichia coli colonization of the host's intestine. Several regulatory systems are known to control acid resistance in E. coli, enabling the bacteria to survive under acidic conditions without growth. Here, we characterize an acid-tolerance response (ATR) system and its regulatory circuit, required for E. coli exponential growth at pH 4.2. A two-component system CpxRA directly senses acidification through protonation of CpxA periplasmic histidine residues, and upregulates the fabA and fabB genes, leading to increased production of unsaturated fatty acids. Changes in lipid composition decrease membrane fluidity, F0F1-ATPase activity, and improve intracellular pH homeostasis. The ATR system is important for E. coli survival in the mouse intestine and for production of higher level of 3-hydroxypropionate during fermentation. Furthermore, this ATR system appears to be conserved in other Gram-negative bacteria.

8.
Curr Microbiol ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123982

RESUMO

A Gram-stain-negative, non-motile and short-rod-shaped bacterium, designated as strain SY7T, was isolated from rhizosphere soil of the mangrove Kandelia obovata of Fugong village, in Zhangzhou, China. The isolate grew at 10-45 °C (optimum 30 °C), pH 6.0-10.0 (optimum pH 7.0) and 0-8% NaCl (optimum 3%, w/v). The 16S rRNA gene sequence and phylogenetic analysis revealed that strain SY7T located within the radiation of genus Nitratireductor and showed the highest sequence similarity of 97.23% to Nitratireductor pacificus MCCC 1A01024T. The DNA G+C content was 64.9%. In silico DNA-DNA hybridization and average nucleotide identity values between strain SY7T with reference strains of N. pacificus MCCC 1A01024T, N. basaltis KCTC 22119T and N. aquibiodomus DSM 15645T were 16.7%, 14.3%, 14.7% and 75.2%, 72.6%, 73.5%, respectively. The major isoprenoid quinone was Q-10. The dominant fatty acids were 11-methyl C18:1ω7c, iso-C17:0, C19:0ω8c cyclo and summed feature 8 (C18:1ω6c/C18:1ω7c), a profile that almost matched the other members of the genus Nitratireductor. The predominant polar lipids were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol. On the basis of the phenotypic, phylogenetic and chemotaxonomic analysis, strain SY7T represents a novel species of the genus Nitratireductor, for which the name Nitratireductor mangrovi sp. nov., is proposed. The type strain is SY7T (= KCTC 72110T = MCCC 1K03723T).

9.
Opt Lett ; 45(3): 702-705, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32004289

RESUMO

We experimentally demonstrate simultaneous turbulence mitigation and channel demultiplexing in a 200 Gbit/s orbital-angular-momentum (OAM) multiplexed link by adaptive wavefront shaping and diffusing (WSD) the light beams. Different realizations of two emulated turbulence strengths (the Fried parameter ${r_0} = 0.4,\,1.0\;{\rm mm}$r0=0.4,1.0mm) are mitigated. The experimental results show the following. (1) Crosstalk between OAM $l = + 1$l=+1 and $l = - 1$l=-1 modes can be reduced by $ {\gt} {10.0}$>10.0 and $ {\gt} {5.8}\;{\rm dB}$>5.8dB, respectively, under the weaker turbulence (${r_0} = 1.0\;{\rm mm}$r0=1.0mm); crosstalk is further improved by $ {\gt} {17.7}$>17.7 and $ {\gt} {19.4}\;{\rm dB}$>19.4dB, respectively, under most realizations in the stronger turbulence (${r_0} = 0.4\;{\rm mm}$r0=0.4mm). (2) The optical signal-to-noise ratio penalties for the bit error rate performance are measured to be ${\sim}{0.7}$∼0.7 and ${\sim}{1.6}\;{\rm dB}$∼1.6dB under weaker turbulence, while measured to be ${\sim}{3.2}$∼3.2 and ${\sim}{1.8}\;{\rm dB}$∼1.8dB under stronger turbulence for OAM $l = + 1$l=+1 and $l = - 1$l=-1 mode, respectively.

10.
J Neurosci ; 40(13): 2680-2694, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32066584

RESUMO

The spinal cord can appropriately generate diverse movements, even without brain input and movement-related sensory feedback, using a combination of multifunctional and behaviorally specialized interneurons. The adult turtle spinal cord can generate motor patterns underlying forward swimming, three forms of scratching, and limb withdrawal (flexion reflex). We previously described turtle spinal interneurons activated during both scratching and swimming (multifunctional interneurons), interneurons activated during scratching but not swimming (scratch-specialized interneurons), and interneurons activated during flexion reflex but not scratching or swimming (flexion reflex-selective interneurons). How multifunctional and behaviorally specialized turtle spinal interneurons affect downstream neurons was unknown. Here, we recorded intracellularly from spinal interneurons activated during these motor patterns in turtles of both sexes in vivo and filled each with dyes. We labeled motoneurons using choline acetyltransferase antibodies or earlier intraperitoneal FluoroGold injection and used immunocytochemistry of interneuron axon terminals to identify their neurotransmitter(s) and putative synaptic contacts with motoneurons. We found that multifunctional interneurons are heterogeneous with respect to neurotransmitter, with some glutamatergic and others GABAergic or glycinergic, and can directly contact motoneurons. Also, scratch-specialized interneurons are heterogeneous with respect to neurotransmitter and some directly contact motoneurons. Thus, scratch-specialized interneurons might directly excite motoneurons that are more strongly activated during scratching than forward swimming, such as hip-flexor motoneurons. Finally, and surprisingly, we found that some motoneurons are behaviorally specialized, for scratching or flexion reflex. Thus, either some limb muscles are only used for a subset of limb behaviors or some limb motoneurons are only recruited during certain limb behaviors.SIGNIFICANCE STATEMENT Both multifunctional and behaviorally specialized spinal cord interneurons have been described in turtles, but their outputs are unknown. We studied responses of multifunctional interneurons (activated during swimming and scratching) and scratch-specialized interneurons, filled each with dyes, and used immunocytochemistry to determine their neurotransmitters and contacts with motoneurons. We found that both multifunctional and scratch-specialized interneurons are heterogeneous with respect to neurotransmitter, with some excitatory and others inhibitory. We found that some multifunctional and some scratch-specialized interneurons directly contact motoneurons. Scratch-specialized interneurons may excite motoneurons that are more strongly activated during scratching than swimming, such as hip-flexor motoneurons, or inhibit their antagonists, hip-extensor motoneurons. Surprisingly, we also found that some motoneurons are behaviorally specialized, for scratching or for flexion reflex.

11.
Curr Microbiol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919672

RESUMO

Emcibacter congregatus ZYLT was isolated from a sediment sample cultured in situ in a coast located in the East China Sea. The genome of E. congregatus ZYLT was sequenced and assembled into one single circular chromosome with the size of 4,189,011 bp and G+C content of 52.6%. Genomic annotation showed that E. congregatus ZYLT had an intact Type II-C CRISPR-Cas system consists of three cas genes (cas 9, cas 1, and cas 2), 34 direct repeat sequences with the length of 36 bp, and 33 spacers. The predicted Cas 9 protein was smaller than most of existing genome editing tools. This structure might have potential in developing new gene editing system and uncovering the regulatory mechanisms of CRISPR-Cas system. Besides, the comparison between E. congregatus ZYLT and its relative species living in neritic environments unraveled some common traits of the defective strategies of these bacteria to face inshore challenges including the motility, multidrug resistance, and universal efflux pumps.

12.
Protein Cell ; 11(4): 251-266, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31919742

RESUMO

Fecal microbiota transplantation (FMT) by manual preparation has been applied to treat diseases for thousands of years. However, this method still endures safety risks and challenges the psychological endurance and acceptance of doctors, patients and donors. Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events. This washing preparation makes delivering a precise dose of the enriched microbiota feasible, instead of using the weight of stool. Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted. The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process. Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing. Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washing-process. In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.

14.
J Mater Chem B ; 8(5): 980-992, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31930242

RESUMO

Localized administration of anti-inflammatory agents benefits patients after myocardial infarction (MI) by repressing/modulating inflammatory response of the MI region and thus accelerating repair of the impaired tissues. Colchicine (Col), an ancient natural drug, has excellent anti-inflammatory effects; however, its utilization is strictly limited due to its severe systemic toxicity and narrow therapeutic window. In this study, we developed an intramyocardial delivery system of Col using an injectable, thermosensitive poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) polymer hydrogel as the vehicle for the treatment of MI while minimizing its systemic toxicity. The aqueous PLGA-PEG-PLGA solution loaded with Col (Col@Gel) underwent a sol-gel transition at 35 °C and maintained a gel state at body temperature. Col was released from the Col@Gel in an initial burst followed by a sustained release manner for over 8 days. The in vitro cell tests showed that the Col@Gel system significantly inhibited macrophage proliferation and migration. In a mouse model of MI, a single intramyocardial administration of the Col@Gel effectively alleviated cardiac inflammation, inhibited myocardial apoptosis and fibrosis, improved cardiac function and structure, and increased mouse survival without inducing severe systemic toxicity, which was observed following intraperitoneal administration of Col solution. These results suggested that the Col@Gel system is a reliable drug delivery system for the sustained local release of Col and has great potential as an anti-inflammatory therapy for the treat of MI.

15.
J Exp Bot ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31989154

RESUMO

Timely degradation of anther tapetal cells is a prerequisite for normal pollen development in flowering plants. Although several genes involved in tapetum development have been identified, the molecular basis of tapetum degeneration regulation remains poorly understood. In this study, we identified and characterized the nucleus-encoded, conserved mitochondrial aldehyde dehydrogenase OsALDH2b as a key regulator of tapetum degeneration in rice (Oryza sativa). OsALDH2b was highly expressed in anthers from meiosis to the early microspore stage. Mutation of OsALDH2b resulted in excess malonaldehyde (MDA) accumulation and earlier programmed cell death (PCD) in the tapetum, leading to premature tapetum degeneration and abnormal microspore development. These results demonstrate that OsALDH2b negatively regulates tapetal PCD and is required for male reproductive development, providing insights into the regulation of tapetum development in plants.

16.
Sci China Life Sci ; 63(1): 92-101, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31709495

RESUMO

Accurate quantitative reverse transcription PCR (qRT-PCR) requires reliable reference genes whose expression does not vary in different tissues and developmental stages. However, few reliable reference genes are available for qRT-PCR in rice (Oryza sativa). Here, we established an effective strategy for identifying novel reference genes (NRGs) for reliable normalization of qRT-PCR data in various rice organs and developmental stages. We selected candidate NRGs using the Information Commons for Rice Database and confirmed their expression in Rice Expression Profile Database (RiceXPro) data. Genes with low variation (<2.5 cycle quantification) across tissues and developmental stages, and little fluctuation in expression in heatmaps from RiceXPro data were considered stable NRGs. To validate this strategy, we selected 11 candidate NRGs and calculated their expression stability in different spatio-temporal conditions using five programs, and compared these genes with five established reference genes (ERGs). Only one of the ERGs (UBQ5) was reliable and 10 of the candidate NRGs were more stable than the four remaining ERGs. Therefore, public transcriptomic databases are useful for identifying NRGs. We selected two NRGs, UFC1 (Homolog of UFM1-Conjugating Enzyme 1) and FhaB (Homolog of Adhesin FhaB) for qRT-PCR analysis in rice; their homologs might be suitable for other monocot plants.

17.
Oral Dis ; 26(1): 182-192, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31696592

RESUMO

This study aims to investigate the levels of SLIT3 in gingival crevicular fluid (GCF) of healthy and periodontal disease subjects, and their correlations to periodontal disease. A total of 45 periodontal patients and 45 periodontally healthy volunteers were enrolled. The clinical parameters, radiographic bone loss and the levels of SLIT3, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in GCF were measured. The prevalences of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia in subgingival plaque were also analyzed. The expression of SLIT3 and RANKL was detected in the periodontium of experimental periodontitis in rats and lipopolysaccharide (LPS)-induced mouse macrophage. The total amounts and concentrations of SLIT3 and RANKL were significantly higher in periodontitis than those in healthy, while the level of OPG was significantly lower (p < .05). Significant positive correlations were observed between the level of GCF SLIT3 and clinical attachment level and radiographic bone loss (p < .05). There existed a significant positive correlation between SLIT3 and RANKL (p < .05). Increased expression of SLIT3 and RANKL was observed in the periodontium of periodontal rats. SLIT3 expression was induced by LPS stimulation in macrophages. These results suggest that SLIT3 may act as a diagnostic indicator of periodontal disease and should be further investigated.


Assuntos
Líquido do Sulco Gengival/química , Proteínas de Membrana/metabolismo , Periodontite/metabolismo , Adulto , Animais , Placa Dentária/microbiologia , Feminino , Humanos , Masculino , Camundongos , Osteoprotegerina/metabolismo , Periodonto/metabolismo , Porphyromonas gingivalis/isolamento & purificação , Ligante RANK/metabolismo , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Tannerella forsythia/isolamento & purificação , Treponema denticola/isolamento & purificação
18.
Leuk Lymphoma ; 61(1): 128-137, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31530212

RESUMO

Myeloid-derived suppressor cells (MDSCs) are considered to be a strong contributor to the immunosuppressive tumor microenvironment. In our study, the counts of MDSCs were correlated with the remission status of CML patients, especially the M-MDSCs. M-MDSCs promoted the proliferation of K562 cells or CD34+ cells from newly diagnosed CML patients, no matter in cells or mice experiments. We also established a TKI discontinuation model using the K562 cell line for examining the effect of microvesicles (MVs) derived from K562 cells before and after TKI discontinuation on MDSCs. We found a mutual promotion of proliferation of tumor cells and MDSCs. Moreover, MVs derived from K562 cells after TKI discontinuation significantly improved the proliferation of MDSCs compared with MVs from before TKI discontinuation. The bidirectional interaction results in a vicious cycle, by providing a protective niche against immune attacks. Therapeutic interventions modulating this interaction might accelerate the success of TFR.

19.
J Hand Surg Am ; 45(1): 64.e1-64.e8, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31076269

RESUMO

PURPOSE: To study the bone resorption pattern of iliac crest grafts after thumb reconstruction with a wrap-around flap from the hallux. METHODS: Patients who underwent thumb reconstruction with a wrap-around flap from the hallux were followed up. We measured the length, proximal, middle, and distal widths, and proximal, middle, and distal thicknesses of the iliac crest grafts on posteroanterior and lateral radiographs and used the length, width, and thickness ratios of the iliac grafts and the first metacarpal bones to calculate the amount of bone resorption. Data from 2 groups reconstructed with or without a terminal tuft were analyzed. RESULTS: Fifteen patients were followed for an average of 20 months (range, 14-72 months). Bone resorption occurred in all 3 measured dimensions in all patients and the degree of resorption increased with time. Resorption amounts of the length dimension in the group with a terminal tuft was significantly decreased compared with those in the group without a terminal tuft at 6 months, 12 months, and the last follow-up. The resorption amount of the width dimension of the distal portion was significantly less in the group with a terminal tuft at the last follow-up. The resorption amount of the thickness dimension of the distal portion was significantly lower in the group with a terminal tuft at 12 months and at the last follow-up. CONCLUSIONS: Bone resorption occurred in all dimensions of the graft after thumb reconstruction using a wrap-around flap from the hallux. Flaps including the terminal tuft had less bone resorption in the distal portion. Wrap-around toe flaps should only be used in cases of thumb amputations at the middle of the proximal phalanx and distal, and the terminal tuft should be preserved in the flap; fixation with a plate should be avoided. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

20.
Toxicol Appl Pharmacol ; 388: 114870, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31866380

RESUMO

Gastric cancer ranks as the third leading cause of cancer-related death worldwide. The uncontrolled tumor growth and robust metastasis are key factors to cause the cancer patient death. Mechanistically, aberrant activation of Notch and NF-κB signaling pathways plays pivotal roles in the initiation and metastasis of gastric cancer. Despite great efforts have been made in recent decades, the effective drug against the advanced and metastatic gastric cancer is still lacking in the clinical setting. In this study, we found that triptonide, a small molecule (MW358) purified from the traditional Chinese medicinal herb Tripterygium wilfordii Hook F, effectively suppressed tumor growth and metastasis in xenograft mice without obvious toxicity at the doses we tested, resulting in potent anti-gastric cancer effect with low toxicity. Triptonide markedly inhibited human metastatic gastric cancer cell migration, invasion, proliferation, and tumorigenicity. Molecular mechanistic studies revealed that triptonide significantly reduced Notch1 protein levels in metastatic gastric cancer cells through degrading the oncogenic protein Notch1 via the ubiquitin-proteasome pathway. Consequently, the levels of Notch1 downstream proteins RBPJ, IKKα, IKKß were significantly diminished, and nuclear factor-kappa B (NF-κB) phosphorylation was significantly reduced. Together, triptonide effectively suppresses gastric cancer growth and metastasis via inhibition of the oncogenic Notch1 and NF-κB signaling pathways. Our findings provide a new strategy and drug candidate for treatment of the advanced and metastatic gastric cancer.

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