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1.
J Magn Reson Imaging ; 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35499275

RESUMO

BACKGROUND: The monitoring of immunotherapies is still based on changes in the tumor size in imaging, with a long evaluation period and low sensitivity. PURPOSE: To investigate the effectiveness of diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the therapeutic efficacy of anti-programmed death-1 (PD-1) therapy in a mouse triple negative breast cancer (TNBC) model. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 54 BALB/c mouse subcutaneous 4 T1 transplantation models of TNBC. FIELD STRENGTH/SEQUENCE: A 3.0-T; turbo spin echo (TSE) T2-weighted imaging, DKI with seven b values (0, 500, 1000, 1500, 2000, 2500, and 3000 sec/mm2 ) and T1-twist DCE acquisition series. ASSESSMENT: DKI and DCE-MRI parameters were evaluated by two radiologists independently. Regions of interest (ROIs) were drawn manually on the maximum cross-sectional area of the lesion; care was taken to avoid necrotic areas. The tumor cell density, the CD45 and CD31 levels were analyzed by two pathologists. STATISTICAL TESTS: The two-tailed unpaired t-test, Mann-Whitney U test, Fisher's exact test and Pearson correlation coefficient were performed. A P < 0.05 was considered statistically significant. RESULTS: The apparent diffusion coefficient (ADC), mean diffusivity (MD), Ktrans and Kep values were significantly different between the two groups at each time point after treatment. There were significant differences in the mean kurtosis (MK) and Ve values between the two groups at 5 and 10 days after treatment but no significant differences at 15 days (P = 0.317 and 0.183, respectively). The ADC and MD values were significantly correlated with tumor cell density (ADC, r = -0.833; MD, r = 0.890) and the CD45 level (ADC, r = 0.720; MD, r = 0.718). The Ktrans and Kep values were significantly correlated with the CD31 level (Ktrans , r = 0.820; Kep , r = 0.683). DATA CONCLUSION: DKI and DCE-MRI could reflect the changes in tumor microstructure and tumor tissue vasculature after anti-PD-1 therapy, respectively. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

2.
Front Pharmacol ; 13: 876469, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35517816

RESUMO

Podocytes damage and mesangial cells expansion are two important pathological manifestations of glomerular injury in early diabetes. Telmisartan, as an angiotensin type 1 (AT1) receptor inhibitor, could improve advanced glycation end (AGE) products or angiotensin Ⅱ (Ang Ⅱ)-induced podocytes injury including detachment or apoptosis. In this current paper, we first confirmed the protective effect of telmisartan on early diabetic kidney injury in type 1 diabetic rats. Telmisartan reduced the loss of podocin and inhibited the expression of α-SMA, reflecting its protective effect on podocyte injury and mesangial proliferation, respectively. More interestingly we observed an opposite effect of telmisartan on the cell viability and apoptosis of podocytes and mesangial cells in a high-glucose environment in vitro. The anti-apoptotic effect of telmisartan on podocytes might be related to its inhibition of swiprosin-1 (a protein can mediate high glucose-induced podocyte apoptosis) expression. While telmisartan induced a high expression of PPARγ in mesangial cells, and GW9662 (a PPARγ antagonist) partially inhibited telmisartan-induced apoptosis and reduced viability of mesangial cells. In addition, high glucose-induced PKCß1/TGFß1 expression in mesangial cells could be blocked by telmisartan. These data provide a more precise cellular mechanism for revealing the protective effect of telmisartan in diabetic kidney injury.

3.
Clin Med Insights Oncol ; 16: 11795549221091207, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35496501

RESUMO

Background: Small bowel adenocarcinoma (SBA) is a rare malignancy that accounts for 3% of all gastrointestinal tumors. We evaluated the clinical characteristics, outcomes, and prognostic factors of primary SBAs. Methods: We retrospectively analyzed the clinicopathological features and clinical outcomes of 300 patients with SBA from three institutions in China between January 2003 and July 2020. Overall survival (OS) was analyzed using the Kaplan-Meier method and it was statistically compared using the log-rank test. Single-variable and multivariate analyses were used to identify the significant correlates of OS. Results: The primary tumor was on the duodenal papilla in 156 patients (52%), in the duodenum in 60 patients (20%), and in the jejunum-ileum in 84 patients (28%). The median OS of the entire cohort was 32.5 months (range, 0-213 months), with a 1-year OS rate of 78.0%. For jejunoileal adenocarcinoma, advanced age, advanced T stage, advanced N stage, more positive lymph nodes, distant metastasis, high carcinoembryonic antigen (CEA), and lymphocyte-to-monocyte ratio < 2.32 predicted worse survival on single-variable analysis. Multivariate analysis showed that advanced age, advanced tumor node metastases (TNM) stage, high CEA level, high alpha fetoprotein (AFP) level, and low prealbumin level were independent prognostic factors for non-ampullary SBA. The independent prognostic factors for duodenal papilla adenocarcinoma included TNM Stage III, nerve invasion, low platelet/lymphocyte ratio, and high CA19-9. Conclusion: We found different independent prognostic factors for tumors at different locations. This finding warrants further investigation to ensure more effective management strategies for SBA.

4.
Front Genet ; 13: 894928, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547255

RESUMO

MYB superfamily is one of the most abundant families in plants, and plays critical role in plant growth, development, metabolism regulation, and stress response. Curcuma wenyujin is the main source plant of three traditional Chinese medicines, which are widely used in clinical treatment due to its diverse pharmacological activities. In present study, 88 CwMYBs were identified and analyzed in C. wenyujin, including 43 MYB-related genes, 42 R2R3-MYB genes, two 3R-MYB genes, and one 4R-MYB gene. Forty-three MYB-related proteins were classified into several types based on conserved domains and specific motifs, including CCA1-like type, R-R type, Myb-CC type, GARP-like type, and TBR-like type. The analysis of motifs in MYB DBD and no-MYB regions revealed the relevance of protein structure and function. Comparative phylogeny analysis divided 42 R2R3-MYB proteins into 19 subgroups and provided a reference for understanding the functions of some CwMYBs based on orthologs of previously characterized MYBs. Expression profile analysis of CwMYB genes revealed the differentially expressed genes responding to various abiotic stresses. Four candidate MYB genes were identified by combining the results of phylogeny analysis and expression analysis. CwMYB10, CwMYB18, CwMYB39, and CwMYB41 were significantly induced by cold, NaCl, and MeJA stress treatments. CwMYB18 and CwMYB41 were proved as regulators with activity of transcriptional activation, whereas CwMYB39 and CwMYB10 were not. They may participate in the response to abiotic stresses through different mechanisms in C. wenyujin. This study was the first step toward understanding the CwMYB family and the response to abiotic stresses in C. wenyujin.

5.
Bioinformatics ; 38(10): 2692-2699, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35561178

RESUMO

MOTIVATION: Single-cell RNA sequencing (scRNA-seq) has revolutionized biological research by enabling the measurement of transcriptomic profiles at the single-cell level. With the increasing application of scRNA-seq in larger-scale studies, the problem of appropriately clustering cells emerges when the scRNA-seq data are from multiple subjects. One challenge is the subject-specific variation; systematic heterogeneity from multiple subjects may have a significant impact on clustering accuracy. Existing methods seeking to address such effects suffer from several limitations. RESULTS: We develop a novel statistical method, EDClust, for multi-subject scRNA-seq cell clustering. EDClust models the sequence read counts by a mixture of Dirichlet-multinomial distributions and explicitly accounts for cell-type heterogeneity, subject heterogeneity and clustering uncertainty. An EM-MM hybrid algorithm is derived for maximizing the data likelihood and clustering the cells. We perform a series of simulation studies to evaluate the proposed method and demonstrate the outstanding performance of EDClust. Comprehensive benchmarking on four real scRNA-seq datasets with various tissue types and species demonstrates the substantial accuracy improvement of EDClust compared to existing methods. AVAILABILITY AND IMPLEMENTATION: The R package is freely available at https://github.com/weix21/EDClust. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

6.
Plant Dis ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522955

RESUMO

Soybean (Glycine max L.) seeds showing serious symptoms from rotted pods were collected from fields during the harvesting period (July to August of 2020) in Taihu Farm, Jingzhou City, Hubei Province, China. Fusarium strains were frequently encountered during fungal isolation. According to the morphology and pre-pathogenicity tests, six strains showing variable effects on the seeds were selected for identification based on morphology and multi-locus phylogenetic analysis of the internal transcribed spacer region of the rDNA (ITS), translation elongation factor (EF-1α), calmodulin (CAM), beta-tubulin (TUB), and partial RNA polymerase second largest subunit (RPB2), and to evaluate the pathogenic abilities on seed, root, and pod. The results indicated that the strains contained two species (Fusarium fujikuroi and F. proliferatum) in the Fusarium fujikuroi species complex (FFSC) and two species (F. luffae and F. sulawense) from the Fusarium incarnatum-equiseti species complex (FIESC). The two species of FFSC were more aggressive than those of FIESC on soybean seed, root, and pod. Among the strains, F. proliferatum YZU 201408 exhibited the most pathogenicity on all tests with 72.2-90% disease severity. Keywords: Fusarium, Glycine max L., Morphology, Pathogenicity, Phylogenetic analysis.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 278: 121286, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35526439

RESUMO

Traumatic delayed splenic rupture often follows by a "latent period" without typical symptoms after injury. During this period, though there are no obvious symptoms, the injury is still present and changing. In this study, we constructed an SD rat model of delayed splenic rupture; evaluated the model by HE staining, Perl's staining, Masson trichrome staining and immunohistochemical staining; observed the pathological changes of spleen tissue in delayed splenic rupture at different times after splenic injury; we found that pathological change of injured tissues were different from non-injured, and has phases-change patterns, it can be roughly divided into three phases: 2-7 d, 10-14 d, and 18-28.We then investigated the relationship between the pathological changes and FTIR spectroscopy by chemometric methods. The main distinction of injured and non-injured tissue was the protein secondary structure of amide I, and the main distinctions of different phases of delayed splenic rupture were protein secondary structures and content of amide I and amide II.A classification model developed by SVM-DA was used to infer three phases (2-7 days, 10-12 days and 14-28 days). According to the most probable class, the accuracy of external validation is 96.7%. The results indicate that FTIR spectroscopy combined with various types of pathological staining has a potential for forensic identification and can provide theoretical support and diagnostic reference on clinical persistent injury.

8.
FASEB J ; 36(6): e22341, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35579877

RESUMO

Multiple myeloma (MM), the terminally differentiated B cells malignancy, is widely considered to be incurable since many patients have either developed drug resistance or experienced an eventual relapse. To develop precise and efficient therapeutic strategies, we must understand the pathogenesis of MM. Thus, unveiling the driver events of MM and its further clonal evolution will help us understand this complicated disease. Chromosome 1 instabilities are the most common genomic alterations that participate in MM pathogenesis, and these aberrations of chromosome 1 mainly include copy number variations and structural changes. The chromosome 1q gains/amplifications and 1p deletions are the most frequent structural changes of chromosomes in MM. In this review, we intend to focus on the genes that are affected by chromosome 1 instability: some tumor suppressors were lost or down regulated in 1p deletions, and others that contributed to tumorigenesis were upregulated in 1q gains/amplifications. We have summarized their biological function as well as their roles in the MM pathogenesis, hoping to uncover potential novel therapeutical targets and promote the development of future therapeutic approaches.

9.
Reprod Fertil Dev ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35450570

RESUMO

CONTEXT: Ovarian tissue cryopreservation is effective in preserving fertility in cancer patients who have concerns about fertility loss due to cancer treatment. However, ischemia reduces the lifespan of grafts. Microvascular transplantation of cryopreserved whole ovary may allow immediate revascularisation, but the damage incurred during the cryopreservation procedure may cause follicular depletion; hence, preventing chilling injury would help maintain ovarian function. AIM: This study was designed to investigate the beneficial effects of antifreeze protein III (AFP III) on rabbit ovary cryopreservation. METHODS: Ovaries (n=25) obtained from 5-month-old female rabbits (n=13) were frozen by slow freezing and vitrification. Cryoprotectant media were supplemented with and without 1mg/mL of AFP III. The experiment was divided into five groups: fresh control group (F), slow freezing group (S), slow freezing group with AFP III (AFP III-S), vitrification group (V) and vitrification group with AFP III (AFP III-V). All groups of ovaries were examined by histological characteristics analysis, ultrastructural analysis, apoptosis detection and follicle viability test. KEY RESULTS: With slow freezing, the normal rate of change in follicle morphology, density of stromal cells and the survival rate of follicles in the AFP III supplemented group were significantly higher than those in the non-supplemented group, and a lower oocyte apoptotic rate was shown in the AFP III supplemented group. In the vitrification groups, the normal rate of change in follicle morphology and density of stromal cells in the AFP III supplemented group were significantly higher than those in the non-supplemented group, and a lower oocyte apoptotic rate was found in the AFP III supplemented group. But there was no obvious difference in the survival rate of follicles between the two groups. There was also no significant difference in the normal rate of change in follicle morphology, the survival rate of follicles and the apoptotic rate of oocytes between the vitrification and slow freezing groups (P>0.05), but the density of stromal cells in the vitrification groups was statistically higher than that of the slow freezing group (P<0.05). CONCLUSIONS: The addition of AFP III in slow freezing and vitrification could improve the cryoprotective effect of ovaries, which was more evident in slow freezing. IMPLICATIONS: The findings of this study provide a foundation for further research on the effects of AFP III in human ovarian tissue.

10.
Chemosphere ; 300: 134546, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35405198

RESUMO

Cu(II)-EDTA is a highly stable typical metal-organic complex in a wide pH range (3.0-12.0) and it is difficult to deeply purify Cu(II) by conventional precipitation methods. In this study, Fe(III) replacement/diethyldithiocarbamate (DDTC) precipitation combined process is proposed as a promising strategy to achieve the deep purification of Cu(II) from Cu(II)-EDTA acidic wastewater. The underlying mechanism has also been systematically elucidated by chemical equilibriums, experiments, and density functional theory (DFT) calculations, laying a foundation for the development and application. Chemical equilibriums show that Fe(III) replacement favors the stoichiometric release of Cu(II) from Cu(II)-EDTA and the formation of Fe(III)-EDTA complex under acidic conditions. Experimentally, Cu(II) is removed (over 99.99%) and deeply purified (under 0.008 mg/L) under the optimal conditions, which is lower than the most stringent discharge standards of copper ions in electroplating effluent (<0.5 mg/L, China). DFT calculations reveal that DDTC could further precipitate the released free copper ions via the carbon disulfide (-C(=S)-S) chelating group while exhibiting a slight effect on the Fe(III) in Fe(III)-EDTA. Considering these results, the electronic structures of Cu(II) and Fe(III), as well as their interaction with EDTA and DDTC ligands, are discussed to understand the mechanism of Fe(III)/DDTC process. By introducing a low dosage of Fe(III), the DDTC could efficiently purify Cu(II) from the Cu(II)-EDTA acid wastewater and realize the near-zero discharge of metal pollutants in metal-organic complex wastewater. It is believed that the main findings may benefit the water pollution reduction and comprehensive recycling of metal resources.

11.
Opt Lett ; 47(9): 2210-2213, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35486762

RESUMO

We demonstrate the first nanosecond pulsed single longitudinal mode (SLM) intracavity-pumped diamond Raman laser, to the best of our knowledge. The eye-safe coherent source at 1634 nm, which was converted from the actively Q-switched 1342 nm Nd:YVO4 laser, yielded 4.35 W of multimode average output power with a pulse duration of 6 ns and peak power of 29 kW. By exploiting the spatial hole burning free gain mechanism in the Raman media, stable SLM operation was observed at low output power (0.46 W) for the free-running case. Furthermore, by incorporating an etalon in the fundamental standing-wave cavity, the spectral linewidth of the fundamental field was suppressed substantially below the diamond Raman gain linewidth and slightly less than the free spectral range of the mm-scale Raman resonator. Thereby, a much higher SLM output power of 1.63 W was obtained with a pulse duration of ∼9 ns and a spectral linewidth of ∼77 MHz.

12.
Nat Prod Res ; : 1-4, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428421

RESUMO

Two new phenols, ardisiphenol I (1) and ardisiphenol J (2), along with three known compounds (3-5) were isolated and identified from the roots of Ardisia crenata var. bicolor. Their structures were elucidated by means of spectroscopic techniques. Structurally, new compounds 1 and 2 have rare side chain with seven carbons. All compounds were tested for antibacterial activity, and compound 5 showed moderate antibacterial activity against Enterococcus faecalis. This work provided the isolation and structural identification of all the compounds in detail, and shed a new light on its further research.

13.
Eur Heart J Case Rep ; 6(4): ytac124, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35434511

RESUMO

Background: Patients with malignancy who experience metastasis to cardiac structures may exhibit ST-segment elevations and acute coronary syndrome (ACS) through poorly understood pathophysiologic mechanisms. We present a case in which vasodilator stress cardiovascular magnetic resonance provides unique insight into one such patient who suffered from recurrent episodes resembling ACS. Case summary: A 58-year-old male with metastatic lung adenocarcinoma presented with refractory angina and dynamic inferior electrocardiogram changes. The patient was referred for adenosine stress cardiovascular magnetic resonance, revealing multiple territories of abnormal perfusion during rest with improvement during adenosine infusion. Subsequent computed tomography displayed tumour encasement of the right coronary artery. Taken together, vasodilator-responsive extrinsic compression of multiple epicardial coronary arteries was suspected. Outpatient oncology follow-up for chemoimmunotherapy initiation was arranged with the hope that reducing tumour burden might alleviate coronary compression. However, in the ensuing months, the patient's disease advanced beyond the point of which his symptoms could be controlled medically, and he was ultimately enrolled in hospice care. Discussion: Encasement of coronary arteries can result in anginal symptoms if their position impairs coronary arterial flow. The presented case highlights the unique manner in which these lesions might behave on stress cardiac magnetic resonance imaging. Clinicians who encounter such unusual findings on vasodilator stress imaging should consider metastatic lesions to the cardiac structures on the differential diagnosis.

14.
JACC Cardiovasc Interv ; 15(7): 712-724, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35393104

RESUMO

OBJECTIVES: The aim of this study was to investigate the risk of coronary obstruction during redo-transcatheter aortic valve replacement (TAVR) within a previously implanted self-expanding valve in bicuspid aortic valve (BAV) versus tricuspid aortic valve (TAV) stenosis. BACKGROUND: The prevalence of BAV in TAVR patients is expected to increase as the indication expands; however, no study has investigated the risk of coronary obstruction for future redo-TAVR in these patients. METHODS: Computed tomography (CT) simulation analysis was performed in 86 type 0 BAV, 70 type 1 BAV, and 132 TAV patients who underwent TAVR with 1 VenusA-Valve (Venus Medtech) between January 2014 and December 2019. RESULTS: CT-identified risk of coronary obstruction during redo-TAVR was observed in 36.1% of patients for the left coronary ostium (LCO) and 27.8% of patients for the right coronary ostium (RCO); however, the incidences were significantly lower in the type 0 BAV group than in the type 1 BAV or TAV group (for LCO: OR: 1.00 [reference] vs OR: 2.49; 95% CI: 1.24-5.01 vs OR: 2.60; 95% CI: 1.40-4.81; for RCO: OR: 1.00 [reference] vs OR: 2.14; 95% CI: 1.02-4.48 vs OR: 1.97; 95% CI: 1.02-3.80). The leaflet laceration technique may be unfeasible to improve coronary flow in 61.5% of the threatened LCOs and 58.8% of the threatened RCOs during redo-TAVR. The percentages were significantly or numerically lower in the type 0 BAV group than other groups (for LCO: 26.3% vs 62.1% vs 73.2%; P overall = 0.001; for RCO: 43.8% vs 65.2% vs 61.0%; P overall = 0.374). CONCLUSIONS: Differences in anatomical features may impact the feasibility of future redo-TAVR. Type 0 BAV anatomy was associated with the lower incidence of CT-identified risk of coronary obstruction during redo-TAVR, and the leaflet laceration technique may be more feasible to ensure coronary flow in this population.


Assuntos
Estenose da Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Oclusão Coronária , Lacerações , Substituição da Valva Aórtica Transcateter , Estenose da Valva Tricúspide , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/etiologia , Estenose da Valva Aórtica/cirurgia , Oclusão Coronária/etiologia , Humanos , Lacerações/complicações , Lacerações/cirurgia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento , Estenose da Valva Tricúspide/etiologia
15.
World J Clin Cases ; 10(9): 2710-2720, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35434109

RESUMO

BACKGROUND: Endoscopic removal with forceps/baskets is favored in treating submandibular stones due to its minimal invasiveness. However, recent studies have found that endoscopic removal failure (ERF) is not unusual, and stones in such cases still need to be removed with other surgical methods. If the risk of ERF can be predicted preoperatively, it could be helpful for surgeons when choosing the appropriate therapy. AIM: To develop a predictive nomogram for the risk of ERF when treating submandibular stones based on their preoperative clinical features. METHODS: A total of 180 patients with 211 submandibular stones treated from January 2012 to December 2020 were included in the current study. Based on the preoperative clinical features of the stones, independent risk factors for ERF were identified by logistic regression analysis. The stones were then randomly divided into training and testing sets. A nomogram was constructed to predict the risk of ERF using the training set and then validated using both sets. The predictive performance of the nomogram was assessed by calibration curves and the concordance index (C-index). RESULTS: Three independent predictors, location (P = 0.040), transverse diameter (P < 0.001) and longitudinal diameter (P < 0.001) measured on the cone beam computed tomography (CBCT) images of the submandibular stones, were identified and included in the predictive nomogram. Calibration curves of the nomogram showed good agreement between the predicted and observed probabilities in both sets. The C-index in the training set was 0.917 (95%CI, 0.875-0.959) and that in the testing set was 0.925 (95%CI, 0.862-0.989). CONCLUSION: A nomogram based on the location, transverse and longitudinal diameters on CBCT images of submandibular stones showed satisfactory efficacy in predicting the risk of ERF preoperatively when treating submandibular stones.

16.
Angew Chem Int Ed Engl ; : e202202966, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35396786

RESUMO

Activatable phototheranostics holds promise for precision cancer treatment owing to the "turn-on" signals and therapeutic effects. However, most activatable phototheranostic probes only possess photodynamic therapy (PDT) or photothermal therapy (PTT), which suffer from poor therapeutic efficacy due to deficient cellular oxygen and complex tumor microenvironment. We herein report a dual-locked activatable phototheranostic probe that activates near-infrared fluorescence (NIRF) signals in tumor, triggers PDT in response to a tumor-periphery biomarker, and switches from PDT to PTT upon detecting a tumor-core-hypoxia biomarker. This PDT-PTT auto-regulated probe exhibits complete tumor ablation under the photoirradiation of a single laser source by producing cytotoxic singlet oxygen at the tumor periphery and generating hyperthermia at tumor-core where is too hypoxic for PDT. This dual-locked probe represents a promising molecular design approach toward precise cancer phototheranostics.

17.
Prev Vet Med ; 203: 105620, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35366534

RESUMO

Neosporosis is a worldwide infectious disease caused by the obligate intracellular parasite protozoan Neospora caninum (N. caninum), which has a heteroxenous life cycle and affects a wide range of warm-blooded animals, especially canines and cattle. Here, a meta-analysis was conducted to assess the overall seroprevalence and potential risk factors for N. caninum infection among cattle in China. The VIP Chinese Journal Databases (VIP), PubMed, WanFang, China National Knowledge Infrastructure (CNKI), and ScienceDirect databases were employed for a comprehensive search for relevant studies published from 2011 to 2020. A random-effects model was used to calculate the pooled seroprevalence estimated with 95% confidence intervals. The pooled N. caninum seroprevalence in cattle was estimated to be 12.2%. The highest seroprevalence of N. caninum infection in cattle was in Southern China (20.9%), while the lowest seroprevalence was in Northwest China (9.4%). The seroprevalence of N. caninum in the sub-group 2016 or later (10.2%) was lower than that in 2012-2015 (20.7%) and before 2012 (17.2%). Yaks were the least infected species of cattle (7.3%; Yellow cattle 18.1%; Buffalo 7.8%; Dairy cattle 21.5%). Cattle aged > 5 years had higher seroprevalence (20.7%) than that aged 3-5 years (10.7%) and < 3 years (14.2%). In season subgroups, the lowest N. caninum seroprevalence was found in summer (21.3%). Free ranging cattle had a 27.2% seroprevalence of N. caninum, which was higher than 7.8% in stall-feed cattle. The seroprevalence of N. caninum in female (22.6%) cattle was higher than in males (13.4%). Meanwhile, the prevalence was higher as increased parity and abortion. The results indicated that N. caninum infection in cattle was widely distributed in China. We recommend that more attention should be paid to the management of sanitary conditions for breeding in the areas with rich and warm water sources. In addition, it would appear to be prudent and feasible to selectively cease breeding for N. caninum seropositive animals in herds with low prevalence and farmers should not feed aborted fetuses to dogs on farm.

18.
Microbiol Res ; 260: 127041, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35483312

RESUMO

Aureobasidium melanogenum HN6.2 is a high siderophore-producing yeast-like fungal strain. After blocking siderophore biosynthesis and attenuating the expression of the ornithine carbamoyltransferase gene (the OTC gene), the obtained D-LCFAO-cre strain produced 2.1 ± 0.02 mg of intracellular L-ornithine per mg of the protein. The overexpression of the L-ornithine decarboxylase gene (the SPE1-S gene) from Saccharomyces cerevisiae in the mutant D-LCFAO-cre could make the transformant E-SPE1-S synthesize 3.6 ± 0.1 of intracellular ornithine per mg of protein and produce 10.5 g/L of putrescine. The further overexpression of the ArgB/C gene encoding bifunctional acetylglutamate kinase/N-acetyl-gamma-glutamyl-phosphate reductase in the transformant E-SPE1-S caused the transformant E-SPE1-S-ArgB/C to accumulate L-ornithine (4.2 mg/mg protein) and to produce 21.3 g/L of putrescine. During fed-batch fermentation, the transformant E-SPE1-S-ArgB/C could produce 33.4 g/L of putrescine, the yield was 0.96 g/g of glucose, and the productivity was 0.28 g/L/h. The putrescine titer was much higher than that produced by most engineered strains obtained thus far.

19.
J Control Release ; 345: 661-674, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35364120

RESUMO

SARS-CoV-2 has been the cause of a global pandemic since 2019 and remains a medical urgency. siRNA-based therapies are a promising strategy to fight viral infections. By targeting a specific region of the viral genome, siRNAs can efficiently downregulate viral replication and suppress viral infection. However, to achieve the desired therapeutic activity, siRNA requires a suitable delivery system. The VIPER (virus-inspired polymer for endosomal release) block copolymer has been reported as promising delivery system for both plasmid DNA and siRNA in the past years. It is composed of a hydrophilic block for condensation of nucleic acids as well as a hydrophobic, pH-sensitive block that, at acidic pH, exposes the membrane lytic peptide melittin, which enhances endosomal escape. In this study, we aimed at developing a formulation for pulmonary administration of siRNA to suppress SARS-CoV-2 replication in lung epithelial cells. After characterizing siRNA/VIPER polyplexes, the activity and safety profile were confirmed in a lung epithelial cell line. To further investigate the activity of the polyplexes in a more sophisticated cell culture system, an air-liquid interface (ALI) culture was established. siRNA/VIPER polyplexes reached the cell monolayer and penetrated through the mucus layer secreted by the cells. Additionally, the activity against wild-type SARS-CoV-2 in the ALI model was confirmed by qRT-PCR. To investigate translatability of our findings, the activity against SARS-CoV-2 was tested ex vivo in human lung explants. Here, siRNA/VIPER polyplexes efficiently inhibited SARS-CoV-2 replication. Finally, we verified the delivery of siRNA/VIPER polyplexes to lung epithelial cells in vivo, which represent the main cellular target of viral infection in the lung. In conclusion, siRNA/VIPER polyplexes efficiently delivered siRNA to lung epithelial cells and mediated robust downregulation of viral replication both in vitro and ex vivo without toxic or immunogenic side effects in vivo, demonstrating the potential of local siRNA delivery as a promising antiviral therapy in the lung.

20.
Medicine (Baltimore) ; 101(7): e28878, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35363200

RESUMO

RATIONALE: Aphallia is an extremely rare congenital malformation of unknown cause, with few reports in the literature. It is usually associated with other urogenital and gastrointestinal anomalies and is believed to be a result of either the absence of a genital tubercle or chromosome polymorphism. Herein, we describe an extremely rare case of congenital aphallia with congenital urethrorectal fistula and describe our treatment for this patient. PATIENT CONCERNS: An 8-year-old boy was brought to our hospital by his parents because of congenital absence of the penis. The child was male per karyotype and had excess heterochromatin on chromosome 9 (46 XY with 9 qh+). No urethral orifice was identified, and urine passed rectally since birth; thus, urinary tract outlet obstruction led to urine reflux from the anus to the epididymis for a long time. The boy had to be placed on prophylactic antibiotics because he developed urinary tract infection and epididymitis almost every day. DIAGNOSIS: Congenital aphallia (46 XY normal male karyotype) associated with congenital urethroretal fistula. INTERVENTIONS: We performed urethral exteriorization via perineal urethroplasty and urethrorectal fistula repair. The parents approved for phallic reconstruction when the boy reached puberty. OUTCOME: A new external urethral orifice was created on the lower scrotum. The urinary reflux was corrected, and the epididymitis symptoms disappeared. The urethral fistula was then closed. At 8 months follow up, the patient was no longer on antibiotics and had no symptoms of urinary tract infection or epididymitis. CONCLUSIONS: Compatible treatment should be adopted to address urinary tract drainage and infection. Management requires a stepwise approach to address needs as they arise. Neophalloplasty should be performed by an experienced team in early adolescence.


Assuntos
Doenças do Pênis , Fístula Retal , Doenças Uretrais , Fístula Urinária , Criança , Humanos , Masculino , Fístula Retal/complicações , Fístula Retal/congênito , Fístula Retal/cirurgia , Uretra/anormalidades , Uretra/cirurgia , Doenças Uretrais/complicações , Doenças Uretrais/cirurgia , Fístula Urinária/complicações , Fístula Urinária/cirurgia
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