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1.
Nat Commun ; 13(1): 6881, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371464

RESUMO

Severe infection commonly results in immunosuppression, which leads to impaired pathogen clearance or increased secondary infection in both humans and animals. However, the exact mechanisms remain poorly understood. Here, we demonstrate that IL-33 results in immunosuppression by inducing thymic involution-associated naive T cell dysfunction with aberrant expression of aging-associated genes and impairs host control of infection in mouse disease models of schistosomiasis or sepsis. Furthermore, we illustrate that IL-33 triggers the excessive generation of medullary thymic epithelial cell (mTEC) IV (thymic tuft cells) in a Pou2f3-dependent manner, as a consequence, disturbs mTEC/cortical TEC (cTEC) compartment and causes thymic involution during severe infection. More importantly, IL-33 deficiency, the anti-IL-33 neutralizing antibody treatment, or IL-33 receptor ST2 deficient thymus transplantation rescues T cell immunity to better control infection in mice. Our findings not only uncover a link between severe infection-induced IL-33 and thymic involution-mediated naive T cell aging, but also suggest that targeting IL-33 or ST2 is a promising strategy to rejuvenate T cell immunity to better control severe infection.


Assuntos
Proteína 1 Semelhante a Receptor de Interleucina-1 , Linfócitos T , Humanos , Camundongos , Animais , Linfócitos T/fisiologia , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Timo , Células Epiteliais/metabolismo , Envelhecimento/fisiologia , Senescência Celular
2.
Food Funct ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36385640

RESUMO

Hyperuricemia (HUA) affects human health and is involved in the pathogenesis of common chronic diseases. Previous studies showed that Ganoderma lucidum extract lowered HUA in animals. However, the active ingredient and pharmacological mechanism of Ganoderma lucidum extract in the improvement of HUA are unknown. The purpose of this study was to determine the anti-HUA efficacy and related mechanism of Ganoderma lucidum polysaccharide peptide (GLPP) using a potassium oxonate (PO)-induced mouse model and an adenosine-induced cell model. The experimental results showed that blood uric acid (UA) was decreased up to 40.6% by GLPP in HUA mice in a dose-dependent manner. Additionally, GLPP significantly reduced UA production by inhibiting the hepatic and blood adenosine deaminase (ADA) activity and increased UA excretion by decreasing the expression of glucose transporter 9 (GLUT9) and increasing the expression of organic anion transporter 1 (OAT1) in kidney. The adenosine-induced cell model showed that the inhibitory effect of GLPP on ADA activity may be the main reason for the alleviation of HUA by GLPP. Furthermore, PO-induced renal histopathological damage was also alleviated by GLPP in a dose-dependent manner. The experimental results in this study indicated that GLPP exerted anti-HUA effects via regulating the UA production and excretion, suggesting that GLPP could be developed into a therapeutic agent for HUA.

3.
Front Nutr ; 9: 1006440, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407509

RESUMO

Ultrasonic washing has been proved to be an abiotic elicitor to induce the accumulation of phenolics in some fruit and vegetables. However, the feasibility of ultrasonic washing on the accumulation of phenolics in fresh-cut red cabbages has not yet been reported. Therefore, the effects of ultrasonic washing on the phenolics and related phenolic metabolism enzymes of fresh-cut red cabbages, as well as quality and microbial safety during cold storage, were investigated. Firstly, the single-factor tests were used to optimize the ultrasonic processing parameters, including frequency mode, frequency amplitude, power density, frequency cycle time, and ultrasonic washing. Then the activities of the enzymes related to phenolic metabolisms after optimal ultrasound treatment were investigated, including phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POD). Additionally, the quality and microbial safety of fresh-cut red cabbages stored at 4°C under the optimal ultrasound treatment were evaluated. The results showed that the content of soluble phenolics (SPs) in fresh-cut red cabbages increased significantly during storage under the optimal conditions (28 ± 2 kHz, 60 W/L, 400 ms, and 20 min) compared with the control (P < 0.05). The PAL activity was activated and the PPO and POD activities were inhibited after ultrasonic washing, which contributed to the increase in the content of SPs. Meanwhile, the storage quality and microbial safety of fresh-cut red cabbages were improved. Ultrasonic washing reduced the weight loss and respiration rate and improved the color and texture characteristics. Additionally, the fresh-cut red cabbages after ultrasonic washing showed more retention of ascorbic acid (AA), total soluble proteins (TSPs), total soluble sugars (TSSs), and total soluble solids (SSs) compared with the control. Finally, ultrasonic washing effectively inhibited the growth of bacteria, molds and yeasts, which is beneficial to the extension of the shelf-life of fresh-cut red cabbages. Therefore, ultrasonic washing can be used as a tool to increase the content of SPs in fresh-cut red cabbages while retaining quality attributes and microbial safety.

4.
Mitochondrial DNA B Resour ; 7(11): 1975-1978, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386019

RESUMO

In this study, the complete mitochondrial genome sequence of the New Guinea tiger fish Datnioides campbelli (Whitley 1938) (Lobotiformes: Datnioididae) was sequenced by next-generation sequencing method. The assembled mitochondrial genome consists of 13 protein-coding genes, 22 transfer RNA genes, and two ribosomal RNA genes, with a length of 16,416 bp. The total base composition of the mitogenome of D. campbelli was 29.31% for A, 29.02% for C, 15.14% for G and 26.54% for T. A phylogenetic tree based on 13 protein-coding genes (PCGs) provides important molecular data for further phylogeographic and evolutionary analysis of Lobotiformes.

5.
Front Pharmacol ; 13: 1037563, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386194

RESUMO

Amygdalus mongolica oil is rich in unsaturated fatty acids such as inoleic acid (47.11%) and oleic acid (23.81%). Our research demonstrates that it exerts a protective effect on rat models of pulmonary fibrosis, however, little is known regarding the underlying mechanism of action. This study aimed to characterize the therapeutic mechanism of action of A. mongolica oil on bleomycin-induced pulmonary fibrosis in rats. A. mongolica oil appears to regulate the levels of potential key serum biomarkers which include tetrahydrobiopterin, L-serine, citrulline and estradiol to participate in folate biosynthesis, glycine, serine and threonine metabolism, arginine biosynthesis and steroid hormone biosynthesis. And it also enriched intestinal microbial abundance, homogeneity and modulated the abundance of Duncaniell, Desulfovibrio, Peptococcaceae_unclassified, Dubosiella, Tyzzerella, Lachnospiraceae_NK4A136_group, Lactobacillus, Clostridiales_unclassified to exert a protective effect against pulmonary fibrosis. A. mongolica oil appears to confer protective effects against pulmonary fibrosis by affecting the level of pulmonary fibrosis metabolites and the abundance of related intestinal flora through multiple targets, as evidenced by our untargeted LC-MS/MS metabonomics evaluation and 16S rDNA sequencing technology.

6.
Yi Chuan ; 44(10): 926-936, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384728

RESUMO

Congenital generalized lipodystrophy (CGL) is an extremely rare genetic disease mainly characterized by absence of whole-body adipose tissue and metabolic dysfunctions such as insulin resistance, diabetes mellitus, hypertriglyceridemia, hepatic steatosis, and acanthosis nigricans. In this study, we reported a novel case of a young woman patient with CGL. The patient came to the hospital for early-onset lipodystrophy and diabetes. She was 19-year-old with a height of 160 cm, a weight of 46 kg, BMI of 17.9 kg/m2, and a serum leptin level of 0.14 µg/L. Genomic DNA was extracted from blood samples of the patient and her family members, including her mother, father and brother. Genetic analysis revealed compound heterozygous mutations of the BSCL2 gene (c.560A>G and c.565G>T) in the patient. Her father carried a heterozygous mutation (c.565G>T), and her mother carried a heterozygous mutation (c.560A>G) in the BSCL2 gene. The mutant p.Y187C plasmid was transfected into HEK293T cells. The protein expression of SEIPIN and its interaction with glycerol-3-phosphate acyltransferase (GPAT3) were observed to be reduced. In addition, based on primary cultured skin fibroblasts from the patient, SEIPIN protein was decreased, and lipid droplets were much smaller when fatty acid was stimulated compared with those observed from healthy subject controls. However, histone deacetylase inhibitors (HDACis) was found capable of rescuing SEIPIN protein in fibroblasts of the patient. In addition, we further summarized and discussed gene mutations of BSCL2 reported in the current literature. Collectively, these findings have expanded the clinical phenotype and pathogenic gene spectrum of CGL, which might help clinicians to achieve better management of lipodystrophy.


Assuntos
Subunidades gama da Proteína de Ligação ao GTP , Lipodistrofia Generalizada Congênita , Lipodistrofia , Feminino , Humanos , Masculino , Subunidades gama da Proteína de Ligação ao GTP/genética , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Células HEK293 , Lipodistrofia/genética , Lipodistrofia/congênito , Lipodistrofia Generalizada Congênita/genética , Lipodistrofia Generalizada Congênita/metabolismo , Mutação
7.
Yi Chuan ; 44(11): 1063-1071, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384998

RESUMO

Glycogen storage disease type V is an autosomal recessive genetic disorder caused by muscle glycogen phosphorylase (PYGM) deficiency, which is characterized by exercise intolerance, second wind phenomena and high level of serum creatine kinase. In this study, we reported a Chinese young man with glycogen storage disease type V, with lower extremity weakness after exercise, increased creatine kinase, and slight fat infiltration in the posterior group of thigh muscle by magnetic resonance imaging (MRI). The proband had complex heterozygous PYGM disease-causing mutations, including c.308T>C (p.L103P) variant transmitted from the mother and c.260_261delCT (p.S87Ffs*23) from the father, of which the former was a novel PYGM mutation. This study enriched the PYGM pathogenic gene mutation spectrum, contributed to improve clinicians' understanding of glycogen storage disease type V and provided a reference for further genetic study of the disease.


Assuntos
Glicogênio Fosforilase Muscular , Doença de Depósito de Glicogênio Tipo V , Humanos , Masculino , Creatina Quinase/genética , Testes Genéticos , Glicogênio Fosforilase Muscular/genética , Doença de Depósito de Glicogênio Tipo V/diagnóstico , Doença de Depósito de Glicogênio Tipo V/genética , Doença de Depósito de Glicogênio Tipo V/patologia , Mutação
8.
World J Clin Cases ; 10(32): 11908-11920, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36405290

RESUMO

BACKGROUND: Multiple rice bodies in the wrist is a rare disorder that requires surgery, and there are still many uncertainties regarding its diagnosis and treatment. CASE SUMMARY: We described a rare case of chronic idiopathic tenosynovitis with rice bodies of the wrist in a 71-year-old man and reviewed similar topics in the literature. A total of 43 articles and 61 cases were included in the literature review. Our case had a usual presentation: it was similar to those in the literature. The affected population was mainly older adults, with an average age of 59.43 (range, 3 to 90) years. The male-to-female ratio was 1.54:1 (37/24).Most of them showed limited swelling and pain, only 23.0% had carpal tunnel symptoms, and the average disease duration was 18.03 (0.5-60) mo. Wrist flexor tendon sheath involvement was the most common (95.1%, 58/61), and only 3 cases had extensor tendon sheath involvement.The main causes were tuberculosis (34.4%, 21/61), non-tuberculous mycobacteria (24.6%, 15/61), idiopathic tenosynovitis (31.1%, 19/61), and others (9.84%, 6/61). There were 10 patients with recurrences; in 6 of them, were due to non-tuberculous mycobacterial infections. CONCLUSION: We reported a case of wrist idiopathic tenosynovitis with rice body formation, and established a clinical management algorithm for wrist tenosynovitis with rice bodies, which can provide some reference for our clinical diagnosis and treatment. The symptoms of rice-body bursitis of the wrist are insidious, nonspecific, and difficult to identify. The aetiology is mainly idiopathic tenosynovitis and mycobacterial (tuberculosis or non-tuberculous) infections; the latter are difficult to treat and require long-duration systemic combination antibiotic therapies. Therefore, before a diagnosis of idiopathic tenosynovitis is made, we must exclude other causes, especially mycobacterial infections.

9.
Front Pharmacol ; 13: 970400, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353502

RESUMO

Bacterial resistance is becoming increasingly serious, the present study aimed to investigate the mechanism of antibacterial sensitization effect of DHA27 combined with tobramycin in tobramycin-resistant Pseudomonas aeruginosa (PA). We found that DHA27 combined with aminoglycosides had an antibacterial sensitization effect on PA. Tobramycin, owing to its lower toxic and side effects, was selected to further study the molecular mechanism of drug combination. A sublethal-dose bacterial challenge/sepsis mouse model was established to study the protective effect of DHA27 plus tobramycin. Scanning electron microscopy was used to investigate whether DHA27 exerts the antibacterial sensitization effect by directly affecting bacterial morphology. The effect of DHA27 on daunorubicin accumulation in bacteria was studied, and quantitative reverse transcription PCR was used to study the effect of DHA27 plus tobramycin on 16S rRNA methyltransferase and aminoglycoside-modifying enzyme mRNA expression. Twenty clinical isolates of PA were found to be tobramycin resistant; DHA27 plus tobramycin had a significant antibacterial sensitization effect on many of these resistant strains. DHA27 plus tobramycin reduced the bacterial load in the spleen and lungs of sepsis model mice and levels of proinflammatory cytokines interleukin-1ß (IL-1ß) and interferon-γ (IFN-γ). DHA27 plus tobramycin significantly inhibited the mRNA expression of aminoglycoside-modifying enzymes in bacteria. DHA27 combined with AGs had an antibacterial sensitization effect on PA; the molecular mechanism underlying this effect is closely related to the inhibition of the mRNA expression of aminoglycoside-modifying enzymes, especially aac(3)-II.

10.
Support Care Cancer ; 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36326908

RESUMO

OBJECTIVE: This overview of systematic reviews aims to critically appraise and consolidate evidence from current systematic reviews (SRs)/meta-analyses on the effects of exercise interventions on cancer-related fatigue (CRF) in breast cancer patients. METHODS: SRs/meta-analyses that explored the effects of exercise interventions on CRF in breast cancer patients compared with the routine methods of treatment and care were retrieved from nine databases. The methodological quality of the included SRs was appraised using A MeaSurement Tool to Assess systematic Reviews II (AMSTAR II). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to calculate the grading of outcomes in the included SRs. The exercise type, frequency, duration, and inclusion/absence of supervision were further evaluated with subgroup analyses. The Stata 16.0 software was utilized for data analysis. RESULTS: Twenty-nine reviews were included. The overall methodological quality and level of evidence of the included reviews were unsatisfactory, with only three reviews rated as high methodological quality and no review identified as high-quality evidence. Moderate certainty evidence indicated that exercise could improve fatigue in breast cancer patients (SMD = - 0.40 [95%CI - 0.58, - 0.22]; P = 0.0001). Subgroup analysis based on the types of exercise showed that yoga (SMD = - 0.30 [95%CI - 0.56, - 0.05]; I2 = 28.7%) and aerobic exercise (SMD = - 0.29 [95%CI - 0.56, - 0.02]; I2 = 16%) had a significantly better effect on CRF in breast cancer patients; exercising for over 6 months (SMD = - 0.88 [95%CI - 1.59, - 0.17]; I2 = 42.7%; P = 0.0001), three times per week (SMD = - 0.77 [95%CI - 1.04, - 0.05]; I2 = 0%; P = 0.0001), and for 30 to 60 min per session (SMD = - 0.81 [95%CI - 1.15, - 0.47]; I2 = 42.3%; P = 0.0001) can contribute to a moderate improvement of CRF. Supervised exercise (SMD = - 0.48 [95%CI - 0.77, - 0.18]; I2 = 87%; P = 0.001) was shown to relieve CRF. CONCLUSION: Exercise played a favorable role in alleviating CRF in breast cancer. Yoga was recommended as a promising exercise modality for CRF management in the majority of the included studies. Exercising for at least three times per week with 30 to 60 min per session could be recommended as a suitable dosage for achieving improvement in CRF. Supervised exercise was found to be more effective in alleviating CRF than unsupervised exercise. More rigorously designed clinical studies are needed to specify the exact exercise type, duration, frequency, and intensity to have an optimal effect on CRF in breast cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: CRD42020219866.

11.
Hemoglobin ; : 1-5, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36317662

RESUMO

Thalassemia is one of southern China's most common inherited disorders. Little is known about the genotypes of thalassemia in children in Jiangxi Province, the People's Republic of China (PRC). Two thousand, nine hundred and fifty-two children with suspected thalassemia were recruited from August 2016 to December 2020 at the Jiangxi Provincial Children's Hospital, Nanchang, PRC. Reverse dot-blot hybridization was used to detect α- and ß-thalassemia (α- and ß-thal) genotypes. A rare mutation was detected using gap-polymerase chain reaction (gap-PCR) and gene sequencing. The overall distribution of thalassemia (1534 cases) was 51.96%, and the detection rate of α-thal (616 cases), ß-thal (888 cases) and concurrent α- and ß-thalassemias (30 cases) was 20.86, 30.08, and 1.02%, respectively. A rare α-thal genotype, -α27.6/- -SEA (Southeast Asian), was identified. Seventy-eight cases of severe ß-thal were detected, accounting for 8.78% of the cases, including 56 double heterozygous cases and 22 cases that were homozygous. Both α- and ß-thalassemias are widely distributed in the children of Jiangxi Province. Thalassemia genetic testing is essential to establish a comprehensive thalassemia prevention program and improve public education.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36361169

RESUMO

Karst water quality is one of the most important environmental issues in karst areas. The study's purpose was to investigate dissolved heavy metal pollution and health risk assessment in karst water basins around mines. River water and groundwater samples were analyzed by principal component analysis, correlation analysis, water quality index, hazard quotient, and hazard index. Median concentrations of dissolved heavy metals in the Sidi River were similar to the world average with a slightly alkaline characteristic. The concentrations of most dissolved heavy metals in river water were higher than those in groundwater. The concentrations of Zn, Pb, and Cd around the mine exceeded the limits of drinking water indicators. The poor water quality samples with high water quality index values were distributed around the mine. Lead (Pb), Zn, As, Cd, and Cr were potentially threatening metals in the study area. The pollution level of dissolved heavy metals in the Sidi River was at a medium level compared with other rivers worldwide. Principal component analysis and correlation analysis showed that Cu, Pb, Zn, Cd, Mn, Fe, As, and Sr mainly came from mine drainage; Ca2+, Mg2+, and Cr mainly came from the contribution of carbonate rocks; Na+ and K+ were related to local human agricultural activities. The concentrations of dissolved heavy metals in groundwater were affected by karst aquifers. The results of this study can provide a data reference for water resources prevention and human health protection in the Sidi River's karst basin and similar karst basins.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Humanos , Monitoramento Ambiental/métodos , Cádmio/análise , Chumbo/análise , Poluentes Químicos da Água/análise , Metais Pesados/análise , Rios , Qualidade da Água , Medição de Risco , China
13.
BMC Public Health ; 22(1): 2068, 2022 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-36369026

RESUMO

BACKGROUND: To evaluate the global burden of cataracts by year, age, region, gender, and socioeconomic status using disability-adjusted life years (DALYs) and prevalence from the Global Burden of Disease (GBD) study 2019. METHODS: Global, regional, or national DALY numbers, crude DALY rates, and age-standardized DALY rates caused by cataracts, by year, age, and gender, were obtained from the Global Burden of Disease Study 2019. Socio-demographic Index (SDI) as a comprehensive indicator of the national or regional development status of GBD countries in 2019 was obtained from the GBD official website. Kruskal-Wallis test, linear regression, and Pearson correlation analysis were performed to explore the associations between the health burden with socioeconomic levels, Wilcoxon Signed-Rank Test was used to investigate the gender disparity. RESULTS: From 1990 to 2019, global DALY numbers caused by cataracts rose by 91.2%, crude rates increased by 32.2%, while age-standardized rates fell by 11.0%. Globally, age-standardized prevalence and DALYs rates of cataracts peaked in 2017 and 2000, with the prevalence rate of 1283.53 [95% uncertainty interval (UI) 1134.46-1442.93] and DALYs rate of 94.52 (95% UI 67.09-127.24) per 100,000 population, respectively. The burden was expected to decrease to 1232.33 (95% UI 942.33-1522.33) and 91.52 (95% UI 87.11-95.94) by 2050. Southeast Asia had the highest blindness rate caused by cataracts in terms of age-standardized DALY rates (99.87, 95% UI: 67.18-144.25) in 2019. Gender disparity has existed since 1990, with the female being more heavily impacted. This pattern remained with aging among different stages of vision impairments and varied through GBD super regions. Gender difference (females minus males) of age-standardized DALYs (equation: Y = -53.2*X + 50.0, P < 0.001) and prevalence rates (equation: Y = - 492.8*X + 521.6, P < 0.001) was negatively correlated with SDI in linear regression. CONCLUSION: The global health of cataracts is improving but the steady growth in crude DALY rates suggested that health progress does not mean fewer demands for cataracts. Globally, older age, females, and lower socioeconomic status are associated with higher cataract burden. The findings of this study highlight the importance to make gender-sensitive health policies to manage global vision loss caused by cataracts, especially in low SDI regions.


Assuntos
Catarata , Carga Global da Doença , Masculino , Humanos , Feminino , Anos de Vida Ajustados por Qualidade de Vida , Saúde Global , Prevalência , Catarata/epidemiologia , Cegueira/epidemiologia , Cegueira/etiologia
14.
Yi Chuan ; 44(10): 967-974, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384732

RESUMO

Glucose metabolism plays a central role in energy supply and metabolism regulation in various tissues and organs. Besides, insulin is the sole hormone lowering blood glucose in the body, and islet function and insulin sensitivity are the key steps modulating glucose metabolism. Since the development of glucose clamp technology, it has been recognized as the gold standard for evaluating insulin metabolism. The main categories include hyperinsulinemia-euglycemia clamp, hyperglycemia clamp, and hyperinsulinemia-hypoglycemia clamp. These can be done on either anesthetized mice or conscious and unrestricted mice. This protocol focuses on the establishment and operation of the mouse glucose clamp technique, including preparation of instrument consumables, surgical operations, clamping procedures, and precautions, serving as reference and guidance.


Assuntos
Hiperinsulinismo , Resistência à Insulina , Camundongos , Animais , Técnica Clamp de Glucose , Insulina/metabolismo , Glicemia/metabolismo
15.
Yi Chuan ; 44(9): 810-818, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384957

RESUMO

Congenital hyperinsulinemia (CHI) is a disease phenotype characterized by persistent or recurrent hypoglycemia due to abnormal secretion of insulin by ß cells of the pancreas. CHI induced by activation mutation of a single allele of glucokinase (GCK) is the rarest type. In this paper, the clinical data of a patient with hypoglycemia of unknown cause were collected without obvious clinical symptoms. And a heterozygous missense mutation (c.295T> C:p.W99R) was detected in exon 3 of the GCK gene. The mutation was found in both the son and daughter of the proband, and the blood glucose level was low, while the others were normal. By summarizing and analyzing the characteristics of this case and the genetic pedigree of the family, the possibility of congenital hyperinsulinemia caused by a single gene mutation should be considered for hypoglycemia whose etiology is difficult to be determined clinically. This case also provides new clinical data for subsequent genetic studies of the disease.


Assuntos
Hiperinsulinismo , Hipoglicemia , Humanos , Glucoquinase/genética , Hipoglicemia/genética , Mutação , Testes Genéticos , Hiperinsulinismo/genética
17.
Small ; : e2206592, 2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36437115

RESUMO

Starvation therapy kills tumor cells via consuming glucose to cut off their energy supply. However, since glucose oxidase (GOx)-mediated glycolysis is oxygen-dependent, the cascade reaction based on GOx faces the challenge of a hypoxic tumor microenvironment. By decomposition of glycolysis production of H2 O2 into O2 , starvation therapy can be enhanced, but chemodynamic therapy is limited. Here, a close-loop strategy for on demand H2 O2 and O2 delivery, release, and recycling is proposed. The nanoreactor (metal-protein-polyphenol capsule) is designed by incorporating two native proteins, GOx and hemoglobin (Hb), in polyphenol networks with zeolitic imidazolate framework as sacrificial templates. Glycolysis occurs in the presence of GOx with O2 consumption and the produced H2 O2 reacts with Hb to produce highly cytotoxic hydroxyl radicals (•OH) and methemoglobin (MHb) (Fenton reaction). Benefiting from the different oxygen carrying capacities of Hb and MHb, oxygen on Hb is rapidly released to supplement its consumption during glycolysis. Glycolysis and Fenton reactions are mutually reinforced by oxygen supply, consuming more glucose and producing more hydroxyl radicals and ultimately enhancing both starvation therapy and chemodynamic therapy. This cascade nanoreactor exhibits high efficiency for tumor suppression and provides an effective strategy for oxygen-mediated synergistic starvation therapy and chemodynamic therapy.

18.
World J Diabetes ; 13(11): 986-1000, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36437866

RESUMO

BACKGROUND: Diabetic retinopathy (DR) is the driving force of blindness in patients with type 2 diabetes mellitus (T2DM). DR has a high prevalence and lacks effective therapeutic strategies, underscoring the need for early prevention and treatment. Yunnan province, located in the southwest plateau of China, has a high pre-valence of DR and an underdeveloped economy. AIM: To build a clinical prediction model that will enable early prevention and treatment of DR. METHODS: In this cross-sectional study, 1654 Han population with T2DM were divided into groups without (n = 826) and with DR (n = 828) based on fundus photography. The DR group was further subdivided into non-proliferative DR (n = 403) and proliferative DR (n = 425) groups. A univariate analysis and logistic regression analysis were conducted and a clinical decision tree model was constructed. RESULTS: Diabetes duration ≥ 10 years, female sex, standing- or supine systolic blood pressure (SBP) ≥ 140 mmHg, and cholesterol ≥ 6.22 mmol/L were risk factors for DR in logistic regression analysis (odds ratio = 2.118, 1.520, 1.417, 1.881, and 1.591, respectively). A greater severity of chronic kidney disease (CKD) or hemoglobin A 1c increased the risk of DR in patients with T2DM. In the decision tree model, diabetes duration was the primary risk factor affecting the occurrence of DR in patients with T2DM, followed by CKD stage, supine SBP, standing SBP, and body mass index (BMI). DR classification outcomes were obtained by evaluating standing SBP or BMI according to the CKD stage for diabetes duration < 10 years and by evaluating CKD stage according to the supine SBP for diabetes duration ≥ 10 years. CONCLUSION: Based on the simple and intuitive decision tree model constructed in this study, DR classification outcomes were easily obtained by evaluating diabetes duration, CKD stage, supine or standing SBP, and BMI.

20.
Transpl Immunol ; 76: 101748, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36423734

RESUMO

BACKGROUND: Genetic polymorphisms and drug interactions are associated with tacrolimus exposure. This study aimed to evaluate the effect of Wuzhi (WZ) preparations on tacrolimus (TAC) concentration and dose requirements in heart transplant recipients with the CYP3A5*1 allele during the early period after transplantation. METHODS: A total of 167 adult heart transplant recipients with the CYP3A5*1 allele were included and divided into the WZ group (n = 115) and the WZ-free group (n = 52). Blood trough concentrations of TAC were detected and the dose-adjusted concentration (C0/D) and dose requirement for achieving the TAC therapeutic range were compared between the two groups. The change in C0/D and dose of TAC were evaluated before and after co-administration with WZ preparations. RESULTS: No significant differences in TAC C0/D and dose requirement were observed between the WZ and WZ-free groups. However, the TAC C0/D in the WZ group was significantly increased an average of 2.10-fold after co-administration of WZ. Moreover, the degree of elevation was related to the dose of the active ingredient (Schisantherin A). Furthermore, ALT, AST, and TB levels were significantly reduced after administration of WZ preparations. CONCLUSION: Co-administration of the WZ/TAC preparation, in heart transplant recipients carrying the CYP3A5*1 allele, considerably increased TAC concentration (C0/D) while decreased high levels of leading indicators in the liver function. More importantly, the effect of the WZ/TAC preparation on C0/D was a dose-dependent event. However, our finding needs to be further confirmed in a larger sample size.

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