Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.556
Filtrar
1.
DNA Cell Biol ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33181035

RESUMO

Glioblastoma multiforme (GBM) is characterized by diffuse infiltration of the brain, active regional recurrence, low cure proportion, and limited chemotherapy efficiency. MutS homolog 6 (MSH6) is a component of the mismatch repair system related to the oncogenesis, tumor evolution, and recurrence of GBM. The impact of MSH6 upregulation on the tumor microenvironment (TME) of GBM and the feasibility of MSH6 as a potential target to improve the prognosis remain unknown. The expression of MSH6 at mRNA level indicated that MSH6 expressed higher in GBM tissues than that in normal ones. The transwell assay and expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) suggested that the capability of invasion and migration in U251-MSH6 was more stubborn. The intracranial tumor model was established with nude mice to further explore in vivo. The time-weight curve, overall survival, tumor volumes, expression levels of MMP-2 and MMP-9 in tissue, and hematoxylin and eosin staining all indicated that MSH6 had a positive effect on metastasis. The expression levels of related proteins suggested that the hypoxia TME induced by MSH6 may promote metastasis via epithelial to mesenchymal transition, stemness, and angiogenesis progress. MSH6 is an overexpressed oncogene in human GBM tissues, which accelerated metastasis by regulating hypoxia inducible factor-1A (HIF1A) to form a hypoxic TME in GBM. The MSH6 was a vital marker of GBM, making it a promising therapeutic target.

2.
BMC Genomics ; 21(1): 786, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176698

RESUMO

BACKGROUND: WRKY transcription factors are a superfamily of regulators involved in diverse biological processes and stress responses in plants. However, there is limited knowledge about the WRKY family in camelina (Camelina sativa), an important Brassicaceae oil crop with strong tolerance for various stresses. Here, a genome-wide characterization of WRKY proteins is performed to examine their gene structures, phylogenetics, expression, conserved motif organizations, and functional annotation to identify candidate WRKYs that mediate stress resistance regulation in camelinas. RESULTS: A total of 242 CsWRKY proteins encoded by 224 gene loci distributed unevenly over the chromosomes were identified, and they were classified into three groups by phylogenetic analysis according to their WRKY domains and zinc finger motifs. The 15 CsWRKY gene loci generated 33 spliced variants. Orthologous WRKY gene pairs were identified, with 173 pairs in the C. sativa and Arabidopsis genomes as well as 282 pairs in the C. sativa and B. napus genomes, respectively. A total of 137 segmental duplication events were observed, but there was no tandem duplication in the camelina genome. Ten major conserved motifs were examined, with WRKYGQK being the most conserved, and several variants were present in many CsWRKYs. Expression analysis revealed that 50% more CsWRKY genes were expressed constitutively, and a set of them displayed tissue-specific expression. Notably, 11 CsWRKY genes exhibited significant expression changes in seedlings under cold, salt, and drought stresses, showing a preferentially inducible expression pattern in response to the stress. CONCLUSIONS: The present article describes a detailed analysis of the CsWRKY gene family and its expression profiles in 12 tissues and under several stress conditions. Segmental duplication is the major force underlying the broad expansion of this gene family, and a strong purifying pressure occurred for CsWRKY proteins during their evolution. CsWRKY proteins play important roles in plant development, with differential functions in different tissues. Exceptionally, eleven CsWRKYs, particularly five alternative spliced isoforms, were found to be the possible key players in mediating plant responses to various stresses. Overall, our results provide a foundation for understanding the roles of CsWRKYs and the precise mechanism through which CsWRKYs regulate high stress resistance as well as the development of stress tolerance cultivars among Cruciferae crops.

3.
Int J Diabetes Dev Ctries ; : 1-9, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33169053

RESUMO

Aim: Some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rapidly develop to critical condition. Here, we investigated the clinical features of critically ill SARS-CoV-2 patients with and without diabetes and identified risk factors for death of these patients. Methods: The medical records including epidemiological, demographic, clinical, and laboratory data from 49 critically ill SARS-CoV-2 patients were collected and analyzed in Huanggang City and Xiaogan City, Hubei Province, outside Wuhan. Results: Sixty-seven percent (33) of patients survived and 33% (16) of patients died in 49 critically ill patients (32 men, 17 women), with a median age of 63 years (IQR 53-73). Univariate analyses indicated that the deceased patients were more often associated with two or more comorbidities, one or more gastrointestinal symptoms, high neutrophil percentage, low lymphocytes and lymphocyte percentage, high C-reactive protein, high procalcitonin, high fasting blood glucose (FBG), and high lactate dehydrogenase (LDH) compared with the survivors; moreover, the patients with T2DM had the higher neutrophil percentage, the lower lymphocyte percentage, and the higher levels of FBG and LDH compared with the patients without T2DM. Multivariable logistic regression analyses indicated that gastrointestinal symptoms (≥ 1 symptoms), decreased lymphocytes (< 1.1 × 109/L), and increased FBG (≥ 7.0 mmol/L) were the independent risk factors for death of critically ill patients. Conclusions: Critically ill COVID patients with T2DM had more severe damages of the lymphocytes, islet cells, and heart function, and gastrointestinal symptoms, lymphopenia, and increased FBG may be early predictors for poor prognosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s13410-020-00888-3.

4.
Phys Chem Chem Phys ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33231227

RESUMO

The heterogeneous oxidation of isoprene (C5H8) by metal-oxide particles, such as the typical mineral aerosols TiO2, plays an important role in the isoprene atmospheric chemistry. However, the underlying mechanism of C5H8 oxidation remains elusive owing to the complexities of aerosol surfaces and reaction channels. Herein, we report the gas-phase reactions of TixOy+ (x = 1-7, y = 1-14) cations with isoprene by using mass spectrometry and density functional theory (DFT) calculations. Five types of reaction channels were observed: association, hydrogen atom transfer (HAT), C-C bond cleavage, combined oxygen atom transfer (OAT) and HAT and combined OAT and C-C bond cleavage. It is noteworthy that formaldehyde is known as the major oxidation product of isoprene/hydroxyl radicals in the atmosphere. In addition, CO has not been observed in the reactions of isoprene with gas-phase ions. Therefore, the reaction mechanisms of CH2O and CO generation observed in Ti2O5+/C5H8 and Ti4O8+/C5H8 systems were further investigated by DFT calculations, and the calculated results are in agreement with the experimental observations. In these two reactions, both Ti and O atoms can be the adsorption sites for C5H8. The reaction channels and mechanistic information gained in these gas-phase model reactions may offer fundamental insights relevant to the corresponding oxidation processes over titanium oxide aerosols in the atmosphere.

5.
J Exp Clin Cancer Res ; 39(1): 224, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109235

RESUMO

Hypoxia is the major influence factor in physiological and pathological courses which are mainly mediated by hypoxia-inducible factors (HIFs) in response to low oxygen tensions within solid tumors. Under normoxia, HIF signaling pathway is inhibited due to HIF-α subunits degradation. However, in hypoxic conditions, HIF-α is activated and stabilized, and HIF target genes are successively activated, resulting in a series of tumour-specific activities. The activation of HIFs, including HIF-1α, HIF-2α and HIF-3α, subsequently induce downstream target genes which leads to series of responses, the resulting abnormal processes or metabolites in turn affect HIFs stability. Given its functions in tumors progression, HIFs have been regarded as therapeutic targets for improved treatment efficacy. Epigenetics refers to alterations in gene expression that are stable between cell divisions, and sometimes between generations, but do not involve changes in the underlying DNA sequence of the organism. And with the development of research, epigenetic regulation has been found to play an important role in the development of tumors, which providing accumulating basic or clinical evidences for tumor treatments. Here, given how little has been reported about the overall association between hypoxic tumors and epigenetics, we made a more systematic review from epigenetic perspective in hope of helping others better understand hypoxia or HIF pathway, and providing more established and potential therapeutic strategies in tumors to facilitate epigenetic studies of tumors.

6.
Plant Mol Biol ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33123851

RESUMO

KEY MESSAGE: Plant CaCA superfamily genes with higher tendency to retain after WGD are more gene expression and function differentiated in ion-response. Plants and animals face different environmental stresses but share conserved Ca2+ signaling pathways, such as Ca2+/Cation transport. The Ca2+/cation antiporters superfamily (CaCAs) is an ancient and widespread family of ion-coupled cation transporters found in all kingdoms of life. We analyzed the molecular evolution progress of the family through comparative genomics and phylogenetics of CaCAs genes from plants and animals, grouping these genes into several families and clades, and identified multiple gene duplication retention events, particularly in the CAX (H+/cation exchanger), CCX (cation/Ca2+ exchanger), and NCL (Na+/Ca2+ exchanger-like) families. The tendency of duplication retention differs between families and gene clades. The gene duplication events were probably the result of whole-genome duplication (WGD) in plants and might have led to functional divergence. Tissue and ion-response expression analyses revealed that CaCAs genes with more highly differentiated expression patterns are more likely to be retained as duplicates than those with more conserved expression profiles. Phenotype of Arabidopsis thaliana mutants showed that loss of genes with a greater tendency to be retained after duplication resulted in more severe growth deficiency. CaCAs genes in salt-tolerant species tended to inherit the expression characteristics of their most recent common ancestral genes, with conservative ion-response expression. This study indicates a possible evolutionary scheme for cation transport and illustrates distinct fates and a mechanism for the evolution of gene duplicates. The increased copy numbers of genes and divergences in expression might have contributed to the divergent functions of CaCAs protein, allowing plants to cope with environmental stresses and adapt to a larger number of ecological niches.

7.
Biomarkers ; : 1-8, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33103496

RESUMO

BACKGROUND: Recent studies reported that serum anion gap could be regarded as a prognostic biomarker for patients admitted to intensive care units. However, the association between AG and mortality in cerebral infarction patients remained largely unknown. METHODS: Relevant clinical data were collected from Medical Information Mart for Intensive Care III. Patients were divided into three groups according to tertiles of AG. Kaplan-Meier curve and Cox proportional hazards models were used to evaluate the association between AG levels and all-cause mortality. Subgroup analyses were performed to verify the predictive role of AG on mortality. RESULTS: Kaplan-Meier analysis showed that patients with higher AG had shorter survival time. Cox regression model indicated high AG as an independent risk factor of 30-day, 60-day and 180-day all-cause mortality (30-day: HR = 2.45, 95% CI = 1.21-4.97, 60-day: HR = 2.04, 95% CI = 1.07-3.89, and 180-day: HR = 1.85, 95% CI = 1.02-3.36). However, no significance was observed between AG and 365-day all-cause mortality (HR = 1.56, 95% CI = 0.87-2.78). CONCLUSIONS: High AG was associated with increased risk of all-cause mortality, and AG could be an independent short-term prognostic factor for cerebral infarction.

8.
Acta Biomater ; 117: 349-360, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33010514

RESUMO

Development of antitumor agents with high efficiency and low toxicity is one of the most important goals for biomedical research. However, most traditional therapeutic strategies were limited due to their non-specificity and abnormal tumor microenvironments, causing a poor therapeutic efficiency and severe side effects. In this paper, a tumor targeted self-synergistic nanoplatform (designated as PAO@PCN@HA) was developed for chemotherapy sensitized photodynamic therapy (PDT) against hypoxic tumors. The efficient drug loading of phenylarsine oxide (PAO) in porphyrinic metal organic framework of PCN-224 as well as the surface modification of hyaluronic acid (HA) improved the targeted drug delivery and reduced the side effects of PAO at the therapeutic dose. Particularly, PAO as an arsenical-based chemotherapeutic agent could not only induce cell apoptosis by generating reactive oxygen species (ROS), but also regulate tumor microenvironments to improve the PDT effect of PCN-224 by mitigating hypoxia and consuming cellular GSH. Both in vitro and in vivo investigations confirmed an effective self-synergy of PAO@PCN@HA in hypoxic tumor therapy with a low systemic toxicity. This integration of microenvironment adjustment with tumor targeted self-synergistic mechanism might provide a new insight for the development of arsenic-based antitumor strategy for clinical applications.

9.
Mol Med Rep ; 22(5): 4031-4040, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000215

RESUMO

Histone deacetylase 4 (HDAC4) plays a vital role in chondrocyte hypertrophy and bone formation. To investigate the function of HDAC4 in postnatal skeletal development, the present study developed lineage­specific HDAC4­knockout mice [collagen type 2α1 (Col2α1)­Cre, HDAC4d/d mice] by crossing transgenic mice expressing Cre recombinase. Thus, a specific ablation of HDAC4 was performed in Col2α1­expressing mice cells. The knee joints of HDAC4fl/fl and Col2α1­Cre, HDAC4d/d mice were analyzed at postnatal day (P)2­P21 using an in vivo bromodeoxyuridine (BrdU) assay, and Safranin O, Von Kossa and whole­body staining were used to evaluate the developmental growth plate, hypertrophic differentiation, mineralization and skeletal mineralization patterns. The trabecular bone was analyzed using microcomputed tomography. The expressions of BrdU, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP)­13, runt­related transcription factor (Runx)­2, osteoprotegerin (OPG), CD34, type X collagen (ColX), osteocalcin and Wnt5a were determined using immunohistochemistry, in situ hybridization (ISH) and reverse transcription­quantitative (RT­q)PCR. The results demonstrated that HDAC4­null mice (HDAC4d/d mice) were severely runted; these mice had a shortened hypertrophic zone (histopathological evaluation), accelerated vascular invasion and articular mineralization (Von Kossa staining), elevated expressions of MMP­13, Runx2, OPG and CD34 (RT­qPCR and immunohistochemistry), downregulated expression of the proliferative marker BrdU and PCNA (immunohistochemistry), increased expression of ColX and decreased expression of Wnt5a (ISH). In conclusion, chondrocyte­derived HDAC4 was responsible for regulating chondrocyte proliferation and differentiation as well as endochondral bone formation.

10.
Mol Ther ; 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-33002417

RESUMO

Ferroptosis is primarily caused by intracellular iron catalytic activity and lipid peroxidation. The potential interplay between ferroptosis and apoptosis remains poorly understood. Here, we show that the expression of a nuclear long non-coding RNA (lncRNA), LINC00618, is reduced in human leukemia and strongly increased by vincristine (VCR) treatment. Furthermore, LINC00618 promotes apoptosis by increasing the levels of BCL2-Associated X (BAX) and cleavage of caspase-3. LINC00618 also accelerates ferroptosis by increasing the levels of lipid reactive oxygen species (ROS) and iron, two surrogate markers of ferroptosis, and decreasing the expression of solute carrier family 7 member 11 (SLC7A11). Interestingly, VCR-induced ferroptosis and apoptosis are promoted by LINC00618, and LINC00618 accelerates ferroptosis in a manner dependent upon apoptosis. LINC00618 attenuates the expression of lymphoid-specific helicase (LSH), and LSH enhances the transcription of SLC7A11 after the recruitment to the promoter regions of SLC7A11, further inhibiting ferroptosis. Knowledge of these mechanisms demonstrates that lncRNAs related to ferroptosis and apoptosis are critical to leukemogenesis and chemotherapy.

11.
J Control Release ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33091528

RESUMO

The combined antiretroviral therapy (cART) can efficiently suppress HIV replication, but the cessation of cART usually results in viral rebound, mostly due to the presence of viral reservoirs. The mesenteric lymphatic system, including mesenteric lymph nodes (MLNs), is an important viral reservoir into which antiretroviral drugs poorly penetrate. In this work, we proposed a novel lipophilic ester prodrug approach, combined with oral lipid-based formulation, to efficiently deliver lopinavir (LPV) to the mesenteric lymph and MLNs. A series of prodrugs was designed using an in-silico model for prediction of affinity to chylomicrons (CMs), and then synthesized. The potential for mesenteric lymphatic targeting and bioconversion to LPV in physiologically relevant media was assessed in vitro and ex vivo. Subsequently, LPV and selected prodrug candidates were evaluated for their in vivo pharmacokinetics and biodistribution in rats. Oral co-administration of lipids alone could not facilitate the delivery of unmodified LPV to the mesenteric lymphatic system and resulted in undetectable levels of LPV in these tissues. However, a combination of the lipophilic prodrug approach with lipid-based formulation resulted in efficient targeting of LPV to HIV reservoirs in mesenteric lymph and MLNs. The maximum levels of LPV in mesenteric lymph were 1.6- and 16.9-fold higher than protein binding-adjusted IC90 (PA-IC90) of LPV for HIV-1 (140 ng/mL) following oral administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Moreover, the concentrations of LPV in MLNs were 1.1- and 7.2-fold higher than PA-IC90 following administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Furthermore, the bioavailability of LPV was also substantially increased following oral administration of activated ester prodrug compared to unmodified LPV. This approach, especially if can be translated to other antiretroviral drugs, has potential for reducing the size of HIV reservoirs within the mesenteric lymphatic system.

12.
Science ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060197

RESUMO

The COVID-19 (Coronavirus disease-2019) pandemic, caused by the SARS-CoV-2 coronavirus, is a significant threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and MERS-CoV. Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analysis for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 Orf9b, an interaction we structurally characterized using cryo-EM. Combining genetically-validated host factors with both COVID-19 patient genetic data and medical billing records identified important molecular mechanisms and potential drug treatments that merit further molecular and clinical study.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33079493

RESUMO

BACKGROUND: To evaluate the failure patterns and prognostic factors in patients with cervical node-negative nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. METHODS: Patients with cervical node-negative NPC treated with IMRT at the Sun Yat-sen University Cancer Center between February 2001 and December 2008 were retrospectively reviewed. The failure patterns, prognostic factors, and efficacy of additional chemotherapy were assessed. RESULTS: The median follow-up time was 78 months for 298 patients. The 5-year local recurrence-free survival (LRFS), nodal recurrence-free survival (NRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and overall survival (OS) were 95.2%, 99.3%, 94.8%, 89.8%, and 92.9%, respectively. The rate of treatment failure remained high in patients with T4 disease (35.4%, 17/48), including eight of local recurrence, two of nodal recurrence, and seven of distant metastasis. Multivariate analyses showed that the primary gross tumor volume (GTVp) was significantly associated with LRFS, DMFS, FFS, and OS. Subgroup analysis revealed that patients with GTVp ≤ 42.5 cc had better 5-year LRFS (98.7% vs 81.4%, P < .001), 5-year DMFS (97.8% vs 82.5%, P < .001), 5-year FFS (96.1% vs 65.4%, P < .001), and 5-year OS (96.6% vs 78.2%, P < .001) than patients with GTVp > 42.5 cc. However, additional chemotherapy showed no significant survival benefit in stratification analysis. CONCLUSIONS: Cervical node-negative NPC has a good prognosis in the IMRT era, and the primary tumor volume is the most important prognostic factor. Further exploration is needed to determine the optimal treatment strategy for patients with a high tumor burden.

14.
Genes (Basel) ; 11(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007888

RESUMO

To investigate the effect of light intensity on flavonoid biosynthesis, grapevine calluses were subjected to high light (HL, 250 µmol m-2 s-1) and dark (0 µmol m-2 s-1) in comparison to 125 µmol m-2 s-1 under controlled conditions (NL). The alteration of flavonoid profiles was determined and was integrated with RNA sequencing (RNA-seq)-based transcriptional changes of the flavonoid pathway genes. Results revealed that dark conditions inhibited flavonoid biosynthesis. Increasing light intensity affected flavonoids differently-the concentrations of flavonols and anthocyanins as well as the expressions of corresponding genes were less affected, whereas flavan-3-ol concentrations were predominantly increased, which caused enhanced trans-flavan-3-ol concentrations. Moreover, genes encoding leucoanthocyanidin reductase (LAR) exhibited different response patterns to light intensity changes-VviLAR1 expression increased with an increased light intensity, whereas VviLAR2 expression was insensitive. We further confirmed that the known transcription factors (TFs) involved in regulating flavan-3-ol biosynthesis utilized VviLAR1 as a target gene in grapevine calluses. In addition, VviLAR1 promoter activity was more sensitive to light intensity changes than that of VviLAR2 as determined using a transgenic Arabidopsis leaf system. These results suggested that light intensity had the most prominent effect on trans-flavan-3-ols in grapevine calluses and demonstrated that the two LAR genes had different response patterns to light intensity changes.

15.
J Hepatol ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039404

RESUMO

BACKGROUND & AIMS: The Nuclear Factor of Activated T-cells (NFAT) plays an important role in immune response by regulating the expression of inflammatory genes. However, it is not known whether it takes part in bile acid (BA)-stimulated expression of proinflammatory cytokines in hepatocytes in cholestatic livers. METHODS: Gene and protein expression and cellular localization were assessed in primary hepatocyte cultures (mouse and human) and cholestatic liver tissues (murine models and patients with PBC and PSC) by Q-PCR, Western blot and immunohistochemistry. Specific NFAT inhibitors were used in vivo and in vitro. Gene reporter assay and ChIP-PCR were used to determine promoter activity. RESULTS: NFAT isoform c1 and c3 were expressed in human and mouse hepatocytes. When treated with cholestatic levels of BA, both human and mouse hepatocytes increased NFATc3 nuclear translocation which was associated with elevated mRNA levels of IL-8, Cxcl2, and Cxcl10 in these cells. Blocking NFAT activation with pathway-specific inhibitors or knocking down Nfatc3 expression significantly decreased BA-induction of these cytokines in mouse hepatocytes. Nuclear expression of NFATc3/Nfatc3 protein was increased in cholestatic livers, both in mouse models (bile duct ligation or Abcb4-/- mice) and in patients with PBC and PSC in association with tissue elevations of Cxcl2 or IL-8, respectively. Gene reporter assays and ChIP-PCR demonstrated that NFAT response element in its promoter played a key role in BA-induced human IL-8 expression. Finally, blocking NFAT activation in vivo in Abcb4-/- mice reduced cholestatic liver injury. CONCLUSIONS: NFAT plays an important role in BA-stimulation of hepatic cytokines in cholestasis. Blocking hepatic NFAT activation may reduce cholestatic liver injury in humans.

16.
J Am Geriatr Soc ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064879

RESUMO

BACKGROUND/OBJECTIVE: Guidelines recommend less intensive glycemic treatment and less frequent glucose monitoring for nursing home (NH) residents. However, little is known about the frequency of fingerstick (FS) glucose monitoring in this population. Our objective was to examine the frequency of FS glucose monitoring in Veterans Affairs (VA) NH residents with diabetes mellitus, type II (T2DM). DESIGN AND SETTING: National retrospective cohort study in 140 VA NHs. PARTICIPANTS: NH residents with T2DM and older than 65 years admitted to VA NHs between 2013 and 2015 following discharge from a VA hospital. MEASUREMENTS: NH residents were classified into five groups based on their highest hypoglycemia risk glucose-lowering medication (GLM) each day: no GLMs; metformin only; sulfonylureas; long-acting insulin; and any short-acting insulin. Our outcome was a daily count of FS measurements. RESULTS: Among 17,474 VA NH residents, mean age was 76 (standard deviation (SD) = 8) years and mean hemoglobin A1c was 7.6% (SD = 1.5%). On day 1 after NH admission, 49% of NH residents were on short-acting insulin, decreasing slightly to 43% at day 90. Overall, NH residents had an average of 1.9 (95% confidence interval (CI) = 1.8-1.9) FS measurements on NH day 1, decreasing to 1.4 (95% CI = 1.3-1.4) by day 90. NH residents on short-acting insulin had the most frequent FS measurements, with 3.0 measurements (95% CI = 2.9-3.0) on day 1, decreasing to 2.6 measurements (95% CI = 2.5-2.7) by day 90. Less frequent FS measurements were seen for NH residents receiving long-acting insulin (2.1 (95% CI = 2.0-2.2) on day 1) and sulfonylureas (1.7 (95% CI = 1.5-1.8) on day 1). Even NH residents on metformin monotherapy had 1.1 (95% CI = 1.1-1.2) measurements on day 1, decreasing to 0.5 (95% CI = 0.4-0.6) measurements on day 90. CONCLUSION: Although guidelines recommend less frequent glucose monitoring for NH residents, we found that many VA NH residents receive frequent FS monitoring. Given the uncertain benefits and potential for substantial patient burdens and harms, our results suggest decreasing FS monitoring may be warranted for many low hypoglycemia risk NH residents.

17.
Luminescence ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068060

RESUMO

In this work, several CaF2 nanoparticles doped with individual ions Nd3+ and Er3+ were synthesized with ligands pentafluorobenzoyl trifluoroacetone (PBTA) and 2-naphthoyltrifluoroacetone (NTA) served as modifiers, respectively. Influence of the modifiers on the luminescent properties of the nanoparticles was investigated. The as-prepared nanoparticles had similar size and dispersion with irregular spherical shape, which reduced the influence of particle size on the luminescence of the nanoparticles. The luminescent spectra of these nanoparticles showed the characteristic luminescence of the central lanthanide ions under the excitation of the maximum excitation wavelength. Compared with nanoparticles modified by NTA ligand, nanoparticles modified by PBTA ligand possessed stronger luminescent intensity of the doping Nd3+ or Er3+ ions.

18.
Toxins (Basel) ; 12(9)2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32906845

RESUMO

Snakebites from Taiwan habus (Protobothrops mucrosquamatus) and green bamboo vipers (Viridovipera stejnegeri) account for two-thirds of all venomous snakebites in Taiwan. While there has been ongoing optimization of antivenin therapy, the proper management of superimposed bacterial wound infections is not well studied. In this Bacteriology of Infections in Taiwanese snake Envenomation (BITE) study, we investigated the prevalence of wound infection, bacteriology, and corresponding antibiotic usage in patients presenting with snakebites from these two snakes. We further developed a BITE score to evaluate the probability of wound infections and guide antibiotic usage in this patient population. All snakebite victims who presented to the emergency departments of seven training and research hospitals and received at least one vial of freeze-dried hemorrhagic antivenin between January 2001 and January 2017 were identified. Patient biodata, laboratory investigation results, and treatment modalities were retrieved. We developed our BITE score via univariate and multiple logistic regression analyses. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive performance of the BITE score. Out of 8,295,497 emergency department visits, 726 patients presented with snakebites from a Taiwan habu or a green bamboo viper. The wound infection rate was 22.45%, with seven positive wound cultures, including six polymicrobial infections. Morganella morganii, Enterococcus spp., Bacteroides fragilis, and Aeromonas hydrophila were most frequently cultured. There were no positive blood cultures. A total of 33.0% (n = 106) of snakebite patients who received prophylactic antibiotics nevertheless developed wound infections, while 44.8% (n = 73) of wound infection patients were satisfactorily treated with one of the following antibiotics: amoxicillin/clavulanic acid, oxacillin, cefazolin, and ampicillin/sulbactam. With the addition of gentamicin, the success of antibiotic therapy increased by up to 66.54%. The prognostic factors for the secondary bacterial infection of snakebites were white blood cell counts, the neutrophil lymphocyte ratio, and the need for hospital admission. The area under the ROC curve for the BITE score was 0.839. At the optimal cut-off point of 5, the BITE score had a 79.58% accuracy, 82.31% sensitivity, and 79.71% specificity when predicting infection in snakebite patients. Our BITE score may help with antibiotic stewardship by guiding appropriate antibiotic use in patients presenting with snakebites. It may also be employed in further studies into antibiotic prophylaxis in snakebite patients for the prevention of superimposed bacterial wound infections.

19.
Andrologia ; : e13781, 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32892424

RESUMO

Long-term consumption of high-fat and high-calorie foods not only causes obesity, but also may cause a decline in sperm quality in men. Rats with abnormal lipid metabolism (high-fat rats) were established by high-fat diet for 24 weeks. HE staining was used to observe the morphological changes of testis in rats, TUNEL and flow cytometer was used to detect the cell apoptosis in rat testis and in vitro. Immunohistochemistry and Western blotting were used to detect the expression of protein. After 24 weeks of high-fat food feeding, the body weight, serum lipids and number of apoptotic spermatogenic cells in the high-fat group rat were significantly higher than those in the control group. In vivo, the expression of HSP60 protein in testis of high-fat rats was positive related to apoptosis of spermatogenic cells, cleaved caspase 3/caspase 3 protein expression and Bax/Bcl2 protein expression in testis of high-fat rats. Proportion of apoptotic spermatogenic cells was increased by up-regulation of HSP60 protein expression in vitro. Long-term consumption of high-fat diets can cause high expression of HSP60 and spermatogenic cells apoptosis in rats, while HSP60 over-expression promotes spermatogenic cell apoptosis and MAPK signal pathway in vitro.

20.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3719-3725, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893564

RESUMO

The aim of this paper was to investigate the effect of Schizonepetae Herba and Saposhnikoviae Radix(wind medicine) on the expression of AQP4 and AQP8 in colonic mucosa in rats with ulcerative colitis(UC). A total of 35 healthy SD male rats were randomly divided into normal group(gavaged with normal saline), DSS model group, as well as low, middle, and high dose wind medicine groups(Schizonepeta and Saposhnikovia 1∶1, gavaged at dosages of 6, 12, and 24 g·kg~(-1)·d~(-1)), with 7 in each group. UC rat model was established by free drinking of 3% dextran sulphate sodium(DSS) solution for 10 days. At the end of the 10 th day after the treatment, mice were put to death to collect colonic mucosa. The length of colon was measured; the colonic mucosal injury index(CMDI) and pathological changes of colon were observed. ELISA method was used for measuring the content of serum IL-1, IL-8, and immunohistochemical method was used to measure AQP4, AQP8 protein expressions in colon mucosa. The expressions of AQP4, AQP8 mRNA were measured by Real-time PCR. As compared with the normal group, the length of colon tissue was significantly reduced(P<0.01), CMDI scores and pathological scores were significantly increased(P<0.01), the levels of serum IL-1 and IL-8 were significantly increased(P<0.05) in model group; the immunohistochemical results showed that the protein expressions of AQP4, AQP8 were lower; the color was light yellow or brown; AQP4, AQP8 mRNA expressions in colon mucosa were significantly decreased in model group(P<0.01). CMDI scores, pathological scores, and the levels of serum IL-1, IL-8 in high, middle, low dose wind medicine groups were obvious lower than those in the model group(P<0.01 or P<0.05); the protein expressions of AQP4, AQP8 were higher; the color was chocolate brown or dark brown; the length of colon tissue, and the expressions of AQP4, AQP8 mRNA were obvious higher in wind medicine groups(P<0.01 or P<0.05). Schizonepetae Herba and Saposhnikoviae Radix could significantly improve the symptoms and histopathology of UC model rats and accelerate the intestinal mucosal healing. The mechanism may be related with up-regulating the expression level of AQP4 and AQP8 in colonic mucosa.


Assuntos
Apiaceae , Colite Ulcerativa , Animais , Aquaporina 4 , Colo , Mucosa Intestinal , Masculino , Camundongos , Raízes de Plantas , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA