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1.
Open Med (Wars) ; 16(1): 1608-1615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746415

RESUMO

Objectives: The aim of this study is to investigate clinical features of atypical pulmonary tuberculosis (aPTB) mimicking bacterial pneumonia, determine imaging features with the highest degree of correlation, and identify predictors for acid-fast bacilli (AFB) positivity. Methods: The clinical data of 259 patients considered as aPTB were retrospectively analyzed. The correlation of CT patterns was evaluated with Spearman analysis, and the predictors for AFB positivity were assessed with the multivariate analysis. Results: The most common symptom of aPTB was cough (84.6%), followed by fever and anorexia (47.1 and 41.7%, respectively). Infiltrated patchy was the most common radiological pattern (84.9%), followed by nodules (3-10 mm), micronodules (<3 mm), and consolidation (79.2, 78.8, and 66.0%, respectively). Nodules (3-10 mm) and micronodules (r = 0.988, p < 0.001), consolidation and air bronchogram (r = 0.590, p < 0.001), and pulmonary atelectasis and consolidation (r = 0.323, p < 0.001) showed high correlation. In the multivariate analysis, hyperpyrexia (OR, 2.29; 95% CI, 1.22-4.29) and bronchiectasis (OR, 2.06; 95% CI, 1.04-4.06) were the predictors of AFB-smear positivity, while bulla (OR, 0.22; 95% CI, 0.05-0.97) was the predictor of AFB-smear negativity. Conclusion: This study demonstrated the clinical and radiological features of aPTB mimicking pneumonia. Several paired radiological findings may guide us to the diagnosis of aPTB. Hyperpyrexia and bronchiectasis may be helpful for predicting AFB positivity, and bulla may be a predictive sign of AFB negativity.

2.
Ann Palliat Med ; 10(9): 9953-9962, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628919

RESUMO

BACKGROUND: Marfan syndrome (MFS) is a rare autosomal dominant connective tissue disorder. Diagnosing MFS can be challenging as the disease's severity and clinical manifestations differ between pathogenic variants, and because a lack of published information currently exists on phenotype-genotype correlations. This report aims to underline the clinical manifestations associated with fibrillin-1 (FBN1) gene mutations by assessing MFS in 6 families from China. METHODS: We diagnosed 6 patients and their relatives with MFS by combining a clinical examination (based on the 2010 revised Ghent nosology criteria) with a targeted next-generation sequencing analysis. The functional analysis of the causal mutations and clinical details of the affected patients were then assessed. RESULTS: We identified 6 pathogenic mutations in FBN1, including 1 novel frameshift, 1 nonsense, and 4 missense mutations. Most uniquely, mitral valve prolapses (MVP) and ectopia lentis (EL) were found in the cysteine-related mutations. Typically, facial symptoms of MFS are observed in frameshift or nonsense mutants, not in cysteine-related ones. Furthermore, the patients with premature terminal codons had a more serious skin condition than patients with missense mutations, partly indicating the important effect FBN1 has on skin. CONCLUSIONS: This study expands the mutation spectrum of MFS and highlights possible genotype-phenotype correlations, thereby improving the early diagnosis and symptomatic treatment of the disease.


Assuntos
Síndrome de Marfan , Análise Mutacional de DNA , Exoma , Fibrilinas , Genótipo , Humanos , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/genética , Síndrome de Marfan/terapia , Proteínas dos Microfilamentos/genética
3.
Front Public Health ; 9: 691554, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631641

RESUMO

Objective: This paper aimed to systematically review the application methods and components of step counter-based physical activity (PA) promotion programs in patients with chronic obstructive pulmonary disease (COPD). The effects of longer-duration (≥12 weeks) programs on PA, exercise capacity, quality of life, and dyspnea were discussed. Methods: This review was performed in accordance with the preferred reporting items for systematic reviews and meta-analysis. Online data resources PubMed, Web of Science, Embase, and EBSCO were searched. The publication year was limited between January 2000 to August 2020. All randomized controlled trials with ≥12-week duration of step counter-based PA promotion programs of COPD were included. Two researchers independently assessed the quality of the included studies and extracted their characteristics. Results: Nine studies involving 1,450 participants were included. Step counters, counseling, exercise goals, diaries, and tele-communicational approaches were common components of these programs. The PA feedback tools were mostly pedometers (n = 8), whereas accelerometers were often used as assessment tools of PA (n = 5). All studies implemented counseling: five applied behavioral change theories, and three reported motivational interview techniques simultaneously. Six studies reported detailed exercise goals. The usual exercise goal was to reach a total of 8,000-10,000 steps/day. Three research studies used diaries, and five applied tele-communication approaches to deliver interventions. The programs could be implemented alone (n = 4), in combination with exercise training (n = 2), or with pulmonary rehabilitation (n = 2). All studies showed a significant increase in the PA (≥793 steps/day). Three studies observed a significant improvement in exercise capacity (≥13.4 m), and two reported a significant increase in the quality of life (p < 0.05). No study showed significant between-group differences in dyspnea. Conclusion: There are a few studies assessing the impact of long-duration (≥12 weeks) step counter-based interventions in COPD, with different methodologies, although all studies included counseling and exercise goal setting. These interventions seem to have a positive effect on PA. A few studies also showed benefit on exercise capacity and quality of life.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Dispneia , Exercício Físico , Tolerância ao Exercício , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia
4.
World J Clin Cases ; 9(24): 7032-7042, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34540958

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious infection caused by the new coronavirus severe acute respiratory syndrome coronavirus 2. The disease was first identified in December 2019 and has caused significant morbidity and mortality worldwide. AIM: To explore the clinical characteristics and treatments for COVID-19 in the Qinghai-Tibetan Plateau Area in China. METHODS: We retrospectively analyzed the blood cell counts (neutrophils and lymphocytes), blood gas analysis, and thoracic computed tomography changes of patients from Qinghai Province before, during, and after treatment (January 23, 2020 to February 21, 2020). In addition, we summarized and analyzed the information of critical patients. All data were analyzed using SPSS 17.0 (SPSS Inc., Chicago, IL, United States). The quantitative and count variables are represented as the mean ± SD and n (%), respectively. RESULTS: The main symptoms and signs of patients with COVID-19 were fever, dry cough, cough with phlegm, difficulty breathing, and respiratory distress with a respiration rate ≥ 30 times/min, finger oxygen saturation ≤ 93% in the resting state, and oxygenation index less than 200 but greater than 100 (after altitude correction). Eighteen patients with COVID-19, of whom three were critical, and the others were in a mild condition, were included. The main manifestations included fever, dry cough, and fatigue. Three patients developed difficulty breathing and had a fever. They were eventually cured and discharged. Adjuvant examinations showed one case with reduced white cell count (6%) (< 4 × 109/L), six with reduced count of lymphocytes (33%) (< 0.8 × 109/L), and one with abnormal blood glucose level. All 18 patients were discharged, and no death occurred. CONCLUSION: Our findings provide critical insight into assessing the clinical diagnosis and treatment for COVID-19 in the Tibetan plateau area.

5.
Molecules ; 26(15)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34361632

RESUMO

The present study focuses on the biological synthesis, characterization, and antibacterial activities of silver nanoparticles (AgNPs) using extracellular extracts of Aspergillus japonicus PJ01.The optimal conditions of the synthesis process were: 10 mL of extracellular extracts, 1 mL of AgNO3 (0.8 mol/L), 4 mL of NaOH solution (1.5 mol/L), 30 °C, and a reaction time of 1 min. The characterizations of AgNPs were tested by UV-visible spectrophotometry, zeta potential, scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and thermogravimetric (TG) analyses. Fourier transform infrared spectroscopy (FTIR) analysis showed that Ag+ was reduced by the extracellular extracts, which consisted chiefly of soluble proteins and reducing sugars. In this work, AgNO3 concentration played an important role in the physicochemical properties and antibacterial properties of AgNPs. Under the AgNO3 concentration of 0.2 and 0.8 mol/L, the diameters of AgNPs were 3.8 ± 1.1 and 9.1 ± 2.9 nm, respectively. In addition, smaller-sized AgNPs showed higher antimicrobial properties, and the minimum inhibitory concentration (MIC) values against both E. coli and S. aureus were 0.32 mg/mL.


Assuntos
Antibacterianos , Aspergillus/metabolismo , Química Verde/métodos , Nanopartículas Metálicas/química , Prata/química , Antibacterianos/química , Antibacterianos/farmacologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-34424470

RESUMO

The foliar application of selenium (Se) is an effective method for biofortification of Se in crop grains in order to provide sufficient Se for human health. As a staple food in China, the foxtail millet (Setaria italica L.), which had been Se biofortification, would be helpful to overcome Se deficiency in the diet. The Se fertilizer and its application technology are vital for reducing environmental risk while enriching selenium. Hence, the Se-rich nutrient solution developed by ourselves was used, and the effect of its amount and growth stage applied on the accumulation of Se in grains of foxtail millet (Setaria italica L.) was studied in the present study. The results were as follows: (1) the Se concentration in grains increased with the Se application rate increasing, and the highest Se concentration in grains was 1.83 mg kg-1 at the sprayed concentration of 61.5 gSe hm-2; (2) the accumulation of Se sprayed in the grain-filling stage was 1.3-1.6 times higher than that in the joint stage; and (3) the organ damage could be found under low Se/S ratio, which happened in the rice leaves when the Se rate was higher than 76.875 gSe m-2 with the low sulfate application compared with the formulation. This Se-rich nutrient solution could be used to produce the Se-rich millet grains and foliar application in the reproductive stage to produce qualified Se-rich millet.

7.
Medicine (Baltimore) ; 100(33): e26976, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414971

RESUMO

BACKGROUND: We sought to synthesize the evidence about aerobic exercise intervention during pulmonary rehabilitation, and to further explore the difference in rehabilitation effects between water and land-based aerobic exercise. This review's purpose is to provide a basis by which practitioners and therapists can select and create appropriate therapeutic programs. METHODS: Data of randomized and quasi-randomized controlled trials comparing training group (TG, aerobic exercise in water or land) and control group (CG, usual care) in chronic obstructive pulmonary disease (COPD) patients (January 1, 2000-December 28, 2019) were obtained from the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases. Two researchers independently reviewed the literature, extracted the data, and evaluated the quality of the literature. Review Manager software (Rev Man 5.3; Cochrane, London, UK) was used for meta-analysis. The rehabilitation effect of water- or land based aerobic exercise was evaluated by subgroup analysis. The proposed systematic review details were registered in PROSPERO (CRD 42020168331). RESULTS: Eighteen studies (1311 cases of COPD) were included. Meta-analysis results show that compared with the control group, the dyspnea level and functional and endurance exercise capacity in COPD patients were significantly improved after aerobic exercise (P < .05), but there was no significant change in lung function (P > .05). Compared with land-based aerobic exercise, water-based aerobic exercise significantly improved the endurance exercise capacity in COPD patients (mean difference [MD]: 270.18, 95% CI: 74.61-465.75). CONCLUSION: Medium to high-quality evidence shows that aerobic exercise can effectively improve dyspnea and exercise capacity in COPD patients. Compared with land-based aerobic exercise, water-based aerobic exercise had a significant additional effect in improving the endurance exercise capacity of COPD patients.


Assuntos
Dispneia/etiologia , Tolerância ao Exercício , Exercício Físico , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Doença Pulmonar Obstrutiva Crônica/terapia , Dispneia/fisiopatologia , Dispneia/reabilitação , Dispneia/terapia , Exercício Físico/fisiologia , Tolerância ao Exercício/fisiologia , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Água
8.
Food Chem ; 364: 130356, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34147870

RESUMO

The present study illustrated modulation of protein aggregation by affecting disulfide/sulfhydryl exchange reactions by adding different concentrations of free thiol represented by reduced-glutathione (GSH) for modulating myofibrillar protein (MP) gel properties at 75 °C or 95 °C. Gel strength and rheological results showed the effects of GSH were dependent on the concentrations (5, 10, 20, 40, and 80 g/kg) and heating temperatures. SEM results showed that the addition of GSH improved the gel microstructure at 95 °C. AFM and DLS results indicated that protein aggregation was also inhibited. At 75 °C, the addition of GSH influenced both MP aggregation and gel properties. Low concentrations (5, 10 g/kg) of GSH promoted aggregation, whereas high concentrations (20, 40, and 80 g/kg) of GSH inhibited this. By analyzing the protein structure and cross-linking pattern changes of MP and MP/GSH composites, a pathway involving GSH influencing MP gel properties was determined.


Assuntos
Proteínas Musculares , Miofibrilas , Dissulfetos , Géis , Glutationa , Temperatura
9.
Front Physiol ; 12: 684453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163375

RESUMO

Chronic obstructive pulmonary disease (COPD) can cause extrapulmonary injury such as diaphragm dysfunction. Oxidative stress is one of the main factors causing diaphragm dysfunction in COPD. Exercise plays a positive role in the prevention and treatment of diaphragm dysfunction in COPD, and the changes in diaphragm structure and function induced by exercise are closely related to the regulation of oxidative stress. Therefore, on the basis of the review of oxidative stress and the changes in diaphragm structure and function in COPD, this article analyzed the effects of exercise on oxidative stress and diaphragm dysfunction in COPD and explored the possible mechanism by which exercise improves oxidative stress. Studies have found that diaphragm dysfunction in COPD includes the decline of muscle strength, endurance, and activity. Oxidative stress mainly affects the structure and function of the diaphragm in COPD through protein oxidation, protease activation and calcium sensitivity reduction. The effects of exercise on oxidative stress level and diaphragm dysfunction may differ depending on the intensity, duration, and style of exercise. The mechanism of exercise on oxidative stress in the diaphragm of COPD may include improving antioxidant capacity, reducing oxidase activity and improving mitochondrial function.

10.
Bioresour Technol ; 337: 125450, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34192637

RESUMO

A low-cost and high-efficiency waterfall aeration biofilm reactor (WABR) combined with a sequencing batch reactor (SBR) was established to treat wastewater with a C/N ratio of 50. Three WABR-SBR systems with different fillers were used. In the stable operation phase, the removal efficiency of chemical oxygen demand was R1 (approximately 99%), R2 (97-99%), and R3 (96-99%); the effluent concentration of NH4+-N was 0.5 mg/L without nitrite or nitrate accumulation. High-throughput 16S rRNA sequencing revealed that the dominant phyla in the microbial community structure were Proteobacteria, Bacteroidetes, and Planctomycetes. Quantitative PCR was used to quantify the nitrification and denitrification gene expressions (Nitrobacter, nirS, and nirK) to evaluate the simultaneous nitrification and denitrification processes. Both anammox and denitrifying bacteria were abundant. Metagenomic annotation of genes that revealed the metabolic pathways of carbohydrates, amino acids, and the two dominant enzymes (GH and GT) provide valuable information for microbial ecology analysis.


Assuntos
Microbiota , Águas Residuárias , Biofilmes , Reatores Biológicos , Carbono , Desnitrificação , Nitrificação , Nitrogênio , RNA Ribossômico 16S/genética
11.
Meat Sci ; 179: 108527, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33962166

RESUMO

This study investigated the effect of low voltage electrostatic field (LVEF) on the microstructure damage and protein structure changes of prepared beef steak during freezing. The scanning electron microscopy results showed that LVEF-assisted freezing (LVEFF) minimized the gaps in the cross section between muscle fibers induced by freezing and thus improved fiber compactness. Furthermore, LVEFF reduced the length of the enlarged sarcomere, repaired the Z-line fractures, and intensified the dismission of the A band in the air-blast freezing (AF) process. The decreased carbonyl content and increased total sulfhydryl content indicated that LVEFF reduced protein oxidation in the freezing process. In addition, the results of Raman spectroscopy and fluorescence spectroscopy revealed that LVEFF minimized the changes in protein secondary and tertiary structures during freezing. In conclusion, utilization of LVEF in the freezing of prepared beef steak could reduce both the microstructure damage and protein structure changes in the freezing process.


Assuntos
Alimentos Congelados , Produtos da Carne/análise , Eletricidade Estática , Animais , Bovinos , Manipulação de Alimentos/métodos , Congelamento , Masculino , Microscopia Eletrônica de Varredura/veterinária , Fibras Musculares Esqueléticas/ultraestrutura , Sarcômeros
12.
Trends Neurosci ; 44(6): 422-423, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33965214

RESUMO

A recent paper by Zhang et al. shows that REV-ERBα, a negative regulator of the circadian molecular clock, is pro-convulsant through its action on GABA signaling. The findings support the role of the circadian molecular clock in epilepsy and suggest REV-ERBα as a potential therapeutic target for the management of seizures.


Assuntos
Relógios Circadianos , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares , Ritmo Circadiano , Humanos , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Convulsões , Transdução de Sinais
13.
Clin Respir J ; 15(9): 956-966, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33998778

RESUMO

OBJECTIVES: This study was conducted to investigate the effect of water-based Liuzijue exercise on peak exercise capacity, functional exercise capacity, and quality of life in people with COPD. METHODS: The study included 50 participants randomly divided into three groups: a control group (CG = 17), a land-based Liuzijue exercise group (LG = 17), and a water-based Liuzijue exercise group (WG = 16). The LG and WG performed Liuzijue exercise in different environments, and the CG had no exercise intervention. All participants received prescribed medical treatment. Liuzijue exercise was performed according to the description of Health Qigong Liuzijue compiled by Chinese Health Qigong Association for 60 minutes, two times per week, for 12 weeks. RESULTS: After intervention, peak oxygen uptake and peak working rate were significantly improved in WG (P = .02). The results of the 6 minutes walking test (6MWT) and 30 seconds sit-to-stand test were significantly improved in both WG and LG (P < .05), and significant difference was found between WG and CG in 6MWT (P = .03). The St. George's Respiratory Questionnaire (SGRQ) activity score increased significantly in the CG (P = .03), while all domains of SGRQ significantly decreased in both training groups (P < .01). All SGRQ scores showed a significant difference between LG and CG (P < .05) and, except for the activity score, between WG and CG (P < .05). CONCLUSIONS: Water-based Liuzijue exercise can effectively improve peak exercise capacity, functional exercise capacity, and quality of life in people with COPD, especially with respect to increasing peak VO2 and 6MWD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Qigong , Tolerância ao Exercício , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Água
14.
Oxid Med Cell Longev ; 2021: 6654954, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046147

RESUMO

Hypoxic-ischemic encephalopathy (HIE) is recognized as the main cause of neonatal death, and efficient treatment strategies remain limited. Given the prevalence of HIE and the associated fatality, further studies on its pathogenesis are warranted. Oxidative stress and neuroinflammatory injury are two important factors leading to brain tissue injury and nerve cell loss in HIE. Neferine, an alkaloid extracted from lotus seed embryo, exerts considerable effects against several diseases such as cancers and myocardial injury. In this study, we demonstrated the neuroprotective effect of neferine on HIE and hypothesized that it involves the inhibition of neuronal pyroptosis, thereby ameliorating neurological inflammation and oxidative stress. We demonstrated that the mRNA levels of proteins associated with pyroptosis including caspase-1, the caspase adaptor ASC, gasdermin D, interleukin- (IL-) 18, IL-1ß, and some inflammatory factors were significantly increased in neonatal HIBD model rats compared to those in the control group. The increase in these factors was significantly suppressed by treatment with neferine. We stimulated PC12 cells with CoCl2 to induce neuronal HIBD in vitro and investigated the relationship between neferine and pyroptosis by altering the expression of the NLRP3 inflammasome. The overexpression of NLRP3 partially reversed the neuroprotective effect of neferine on HIBD, whereas NLRP3 knockdown further inhibited caspase-1 activation and IL-1ß and IL18 expression. In addition, simultaneous alteration of NLRP3 expression induced changes in intracellular oxidative stress levels after HIBD. These findings indicate that neferine ameliorates neuroinflammation and oxidative stress injury by inhibiting pyroptosis after HIBD. Our study provides valuable information for future studies on neferine with respect to neuroinflammation and pyroptosis.

15.
Onco Targets Ther ; 14: 2575-2578, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33880036

RESUMO

Pulmonary tuberculosis (TB) and lung cancer are both common diseases with poor prognosis and high mortality worldwide. The coexistence of the two diseases has rarely been reported while their relationship has been noted. Here we describe a patient diagnosed with both TB and squamous cell carcinoma in a single lesion. The patient had a cough for four months and polypnea for two months, with a smoking history of over 40 years. Chest computed tomography (CT) showed a lobular mass in the right hilar region, which was diagnosed as TB by transbronchial lung biopsy. The symptoms and CT findings indicated the possibility of lung cancer. So, the patient underwent a further lung biopsy at the periphery of the mass, which was confirmed as squamous cell carcinoma. This case illuminated that when the mass with cancer-like morphologic features and location instead of typical TB, even the initial pathological result shows TB, coexistence of the diseases should be considered.

16.
Food Funct ; 12(9): 4221-4230, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33876796

RESUMO

One polysaccharide, designated as WPEP-A, was isolated from Passiflora edulis Sims peel and its hypoglycemic effects on diabetic db/db mice were evaluated. Physicochemical characterization showed that WPEP-A was composed of galactose, glucose, xylose, rhamnose, galacturonic acid and glucuronic acid with a molecular weight of 9.51 × 104 Da. We observed an inhibition in weight gain and blood glucose levels. Glucose tolerance and insulin tolerance improved after the administration of WPEP-A. In addition, our data showed increased antioxidant enzyme activities. Furthermore, the levels of serum insulin and triglyceride decreased with the recovery of liver damage. Meanwhile, positive changes in short chain fatty acid content were observed, and the mRNA levels of glucagon-like peptide 1 receptor, glucagon and prohormone convertase 3 were up-regulated in the intestinal tract. In summary, our results showed that WPEP-A had hypoglycemic activity and improved intestinal function in diabetic mice, which may contribute to the attenuation of the hypoglycemia effects.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Passiflora/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Glicemia/análise , Carboidratos da Dieta/farmacologia , Ácidos Graxos Voláteis/metabolismo , Glucagon/genética , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Insulina/sangue , Mucosa Intestinal/metabolismo , Camundongos , Polissacarídeos/isolamento & purificação , Pró-Proteína Convertase 1/genética , Triglicerídeos/sangue , Regulação para Cima , Ganho de Peso/efeitos dos fármacos
17.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802660

RESUMO

Proximal tubular (PT) acidosis, which alkalinizes the urinary filtrate, together with Ca2+ supersaturation in PT can induce luminal calcium phosphate (CaP) crystal formation. While such CaP crystals are known to act as a nidus for CaP/calcium oxalate (CaOx) mixed stone formation, the regulation of PT luminal Ca2+ concentration ([Ca2+]) under elevated pH and/or high [Ca2+] conditions are unknown. Since we found that transient receptor potential canonical 3 (TRPC3) knockout (KO; -/-) mice could produce mild hypercalciuria with CaP urine crystals, we alkalinized the tubular pH in TRPC3-/- mice by oral acetazolamide (0.08%) to develop mixed urinary crystals akin to clinical signs of calcium nephrolithiasis (CaNL). Our ratiometric (λ340/380) intracellular [Ca2+] measurements reveal that such alkalization not only upsurges Ca2+ influx into PT cells, but the mode of Ca2+ entry switches from receptor-operated to store-operated pathway. Electrophysiological experiments show enhanced bicarbonate related current activity in treated PT cells which may determine the stone-forming phenotypes (CaP or CaP/CaOx). Moreover, such alkalization promotes reactive oxygen species generation, and upregulation of calcification, inflammation, fibrosis, and apoptosis in PT cells, which were exacerbated in absence of TRPC3. Altogether, the pH-induced alteration of the Ca2+ signaling signature in PT cells from TRPC3 ablated mice exacerbated the pathophysiology of mixed urinary stone formation, which may aid in uncovering the downstream mechanism of CaNL.


Assuntos
Acetazolamida/farmacologia , Cálcio/metabolismo , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Nefrolitíase/metabolismo , Nefrolitíase/patologia , Animais , Transporte Biológico/efeitos dos fármacos , Calcinose/complicações , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fibrose , Concentração de Íons de Hidrogênio , Inflamação/patologia , Túbulos Renais Proximais/efeitos dos fármacos , Camundongos , Nefrolitíase/urina , Estresse Oxidativo/efeitos dos fármacos , Canais de Cátion TRPC/metabolismo , Regulação para Cima/efeitos dos fármacos
18.
Mol Med Rep ; 23(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760172

RESUMO

Sepsis is a life­threatening organ dysfunction caused by a dysregulated host response to infection, and is a leading cause of mortality worldwide. Myocardial dysfunction is associated with poor prognosis in patients with sepsis and contributes to a high risk of mortality. However, the pathophysiological mechanisms underlying sepsis­induced myocardial dysfunction are not completely understood. The aim of the present study was to investigate the role of toll­like receptor 4 (TLR4)/c­Jun N­terminal kinase (JNK) signaling in pro­inflammatory cytokine expression and cardiac dysfunction during lipopolysaccharide (LPS)­induced sepsis in mice. C57BL/6 mice were pretreated with TAK­242 or saline for 1 h and then subjected to LPS (12 mg/kg, intraperitoneal) treatment. Cardiac function was assessed using an echocardiogram. The morphological changes of the myocardium were examined by hematoxylin and eosin staining and transmission electron microscopy. The serum protein levels of cardiac troponin I (cTnI) and tumor necrosis factor­α (TNF­α) were determined by an enzyme­linked immunosorbent assay (ELISA). The TLR4 and JNK mRNA levels were analyzed via reverse transcription­quantitative PCR. TLR4, JNK and phosphorylated­JNK protein levels were measured by western blotting. In response to LPS, the activation of TLR4 and JNK in the myocardium was upregulated. There were significant increases in the serum levels of TNF­α and cTnI, as well as histopathological changes in the myocardium and suppressed cardiac function, following LPS stimulation. Inhibition of TLR4 activation using TAK­242 led to a decrease in the activation of JNK and reduced the protein expression of TNF­α in plasma, and alleviated histological myocardial injury and improved cardiac function during sepsis in mice. The present data suggested that the TLR4/JNK signaling pathway played a critical role in regulating the production of pro­inflammatory cytokines and myocardial dysfunction induced by LPS.


Assuntos
Insuficiência Cardíaca/genética , Sistema de Sinalização das MAP Quinases/genética , Sepse/genética , Receptor 4 Toll-Like/genética , Animais , Apoptose/genética , Citocinas/genética , Modelos Animais de Doenças , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Humanos , Interleucina-6/genética , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Lipopolissacarídeos/toxicidade , Camundongos , Miocárdio/patologia , NF-kappa B/genética , Fosforilação/genética , Sepse/induzido quimicamente , Sepse/complicações , Sepse/patologia , Troponina I/genética , Fator de Necrose Tumoral alfa/genética
19.
Crit Rev Food Sci Nutr ; : 1-14, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33683156

RESUMO

N-nitrosamines, heterocyclic amines, polycyclic aromatic hydrocarbons, biogenic amines, and acrylamide are widely distributed and some of the most toxic substances detected in foods. Hence, reduction of these substances has attracted worldwide attention. Lactic acid bacteria (LAB) inoculation has been found to be an effective way to reduce these toxic substances. In this paper, the reduction of toxic substances by LAB and its underlying mechanisms have been described through the review of recent studies. LAB aids this reduction via different mechanisms. First, it can directly decrease these harmful substances through adsorption or degradation. Peptidoglycans on the cell wall of LAB can bind to heterocyclic amines, acrylamide, and polycyclic aromatic hydrocarbons. Second, LAB can indirectly decrease the content of toxic substances by reducing their precursors. Third, antioxidant properties of LAB also contribute to the reduction in toxic substances. Finally, LAB can suppress the growth of amino acid decarboxylase-positive bacteria, thus reducing the accumulation of biogenic amines and N-nitrosamines. Therefore, LAB can contribute to the decrease in toxic substances in food and improve food safety. Further research on increasing the reduction efficiency of LAB and deciphering the mechanisms at a molecular level needs to be carried out to obtain the complete picture.

20.
Mikrochim Acta ; 188(4): 125, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723966

RESUMO

An electrochemiluminescence (ECL) DNA biosensor based on ExoIII exonuclease assistance and hybridization chain reaction (HCR) amplification technology has been constructed. ExoIII exonuclease and triple-helix DNA molecular switch are used in detecting a target in circulation. By combining HCR with AuNPs@DNA, a novel signal probe is built, which enables multiple signal amplification and the high-sensitive detection of transgenic rice BT63 DNA. The Fe3O4@Au solution is added to a magneto-controlled glassy carbon electrode, and sulfhydryl-modified capture DNA (CP) is immobilized on Fe3O4@Au through the Au-S bond. Mercaptoethanol is added to close sites and prevent the nonspecific adsorption of CP on the magnetron glassy carbon electrode. A target DNA is added to a constructed triple-helix DNA molecular centrifuge tube for reaction. Owing to base complementation and the reversible switching of the triple-helix DNA molecular state, the target DNA turns on the triple-helix DNA molecular switch and hybridizes with a long-strand recognition probe (RP) to form a double-stranded DNA (dsDNA). Exonuclease ExoIII is added to specifically recognize and cut the dsDNA and to release the target DNA. The target DNA strand then circulates back completely to open the multiple triple-helix DNA molecular switch, releasing a large number of signal transduction probes (STP). To hybridize with CP, a large amount of STP is added to the electrode. Finally, a AuNPs@DNA signal probe is added to hybridize with STP. H1 and H2 probes are added for the hybridization chain reaction and the indefinite extension of the primer strand on the probe. Then, tris-(bipyridyl)ruthenium(II) is added for ECL signal detection with PBS-tri-n-propylamine as the base solution. In the concentration range 1.0 × 10-16 to 1.0 × 10-8 mol/L of the target DNA, good linear relationship was achieved with the corresponding ECL signal. The detection limit is 3.6 × 10-17 mol/L. The spiked recovery of the rice samples range from 97.2 to 101.5%. The sensor is highly sensitive and has good selectivity, stability, and reproducibility. A novel electrochemiluminescence biosensor with extremely higher sensitivity was prepared for the determination of ultra-trace amount transgenic rice BT63 DNA. The sensitivity was significantly improved by multiple signal enhancements. Firstly, a large number of signal transduction probes are released when the triple-helix DNA molecular switch unlock after recycles assisted by ExoIII exonuclease under target BT63 DNA; and then the signal transduction probes hybridize with the signal probes of AuNPs@(DNA-HCR) produced through hybridization chain reaction. Finally, the signal probes which were embedded with a large amount of electrochemiluminescence reagent produce high luminescence intensity. The detection limit was 3.6 × 10-17 mol/L, which is almost the most sensitive methods reported.

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