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1.
Article in Portuguese | LILACS | ID: biblio-1368967

ABSTRACT

RESUMO:Introdução: Hipofosfatasia é um distúrbio metabólico que afeta a mineralização óssea e dentária, causada por mutações no gene ALPL, levando à deficiência enzimática da fosfatase alcalina tecido não-específica. A forma adulta caracteriza-se por fraturas atípicas do fêmur, osteomalácia, osteoporose, grave osteoartropatia, condrocalcinose e artralgia. Objetivo: Demonstrar desafios diagnósticos relacionados à hipofosfatasia através do relato de dois casos. Paciente 1: feminino, 59 anos, encaminhada para avaliação clínica devido às fraturas patológicas de difícil consolidação e osteoporose generalizada de causa genética. Relata perda dentária precoce da arcada superior, fraturas na coluna, em ombro esquerdo e no fêmur. Atualmente, queixa-se de dor crônica intensa, com uso de múltiplos medicamentos. Achados clínicos, laboratoriais e radiológicos foram compatíveis com o diagnóstico de hipofosfatasia. Paciente 2: masculino, 31 anos, filho da paciente 1, encaminhado para avaliação clínica por fratura patológica precoce em fêmur esquerdo e osteoporose não esclarecida. Atualmente relata dor e claudicação importante em membro inferior esquerdo, associado à lombalgia crônica. Confirmação do diagnóstico de hipofosfatasia por exames laboratoriais e radiológicos e sequenciamento do gene ALPL, aliados ao diagnóstico da sua genitora. Discussão: Hipofosfatasia é uma doença rara de herança autossômica dominante e recessiva. Pacientes acometidos apresentam fraturas constantes, densidade mineral óssea baixa, cicatrização óssea deficitária. É comum a hipofosfatasia ser diagnosticada erroneamente como osteopenia e/ou osteoporose primária, acarretando prejuízos ao paciente. Ressalta-se a importância da história clínica completa e dos antecedentes familiares a fim de se obter um diagnóstico precoce, garantindo, por sua vez, o adequado acompanhamento e manejo terapêutico. (AU)


ABSTRACT: Introduction: hypophosphatasia is a metabolic disorder affecting bone and tooth mineralization, caused by mutations in the ALPL gene leading to enzymatic deficiency of tissue non-specific alkaline phosphatase. The adult form is characterized by atypical femur fractures, osteomalacia, osteoporosis, severe osteoarthropathy, chondrocalcinosis, and arthralgia. Objective: to demonstrate diagnostic challenges related to hypophosphatasia through the report of two cases. Patient 1: female, 59 years old, referred for clinical evaluation due to pathological fractures of difficult consolidation and generalized osteoporosis of genetic cause. She reports early tooth loss in the upper arch, fractures in the spine, left shoulder and femur. Currently, he complains of severe chronic pain, with use of multiple medications. Clinical, laboratory, and radiological findings were compatible with the diagnosis of hypophosphatasia. Patient 2:male, 31 years old, son of patient 1, referred for clinical evaluation due to an early pathological fracture in the left femur and unclear osteoporosis. He currently reports pain and significant claudication in the left lower limb, associated with chronic low back pain. Confirmation of the diagnosis of hypophasatasia by laboratory and radiological tests and sequencing of the ALPL gene combined with the diagnosis of his mother. Discussion: hypophosphatasia is a rare disease of autosomal dominant and recessive inheritance. Affected patients have constant fractures, low bone mineral density, and impaired bone healing. It is common for hypophosphatasia to be misdiagnosed as osteopenia and/or primary osteoporosis, which can be harmful to the patient. The importance of a complete clinical history and family history is emphasized in order to obtain an early diagnosis, ensuring adequate follow-up and therapeutic management. (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Osteoporosis , Alkaline Phosphatase , Fractures, Spontaneous , Hypophosphatasia/diagnosis
2.
Acta Pharmaceutica Sinica B ; (6): 2300-2314, 2022.
Article in English | WPRIM | ID: wpr-929401

ABSTRACT

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

3.
Acta Pharmaceutica Sinica B ; (6): 907-923, 2022.
Article in English | WPRIM | ID: wpr-929334

ABSTRACT

Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.

4.
Acta Pharmaceutica Sinica B ; (6): 451-466, 2022.
Article in English | WPRIM | ID: wpr-929306

ABSTRACT

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

5.
Asian Journal of Andrology ; (6): 154-160, 2022.
Article in English | WPRIM | ID: wpr-928527

ABSTRACT

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.


Subject(s)
Abiraterone Acetate/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Androstenes , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dexamethasone/therapeutic use , Disease-Free Survival , Humans , Male , Prednisone/therapeutic use , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Treatment Outcome
6.
Article in Chinese | WPRIM | ID: wpr-920560

ABSTRACT

Objective@#To explore the effects of red LEDs on the proliferation and osteogenic differentiation of human stem cells from apical papilla (hSCAPs).@*Methods@#hSCAPs were obtained by isolation, culture and flow cytometry in vitro and irradiated with 1, 3, 5, and 7 J/cm2 red LEDs. The proliferation of hSCAPs was detected using a CCK-8 assay. The osteogenic differentiation of hSCAPs was evaluated using alkaline phosphatase (ALP) staining, ALP activity assay and Alizarin red quantitative detection. The effect of 5 J/cm2 red LEDs on the expression levels of the ALP, Runx2, OCN, OPN and BSP genes and proteins was detected by RT-PCR and western blot, respectively.@*Results@# Red LEDs at 1, 3, 5, and 7 J/cm2 promoted the proliferation of hSCAPs (P < 0.05). The effects of red LEDs with different light energies on the proliferation of hSCAPs were different at different time points (P < 0.05). On the 7th and 14th days after irradiation, red LEDs promoted the osteogenic differentiation of hSCAPs, and the effect of 5 J/cm2 red LEDs was the most obvious under osteogenic induction culture conditions (P<0.05). Red LEDs (5 J/cm2) promoted the expression of the ALP, Runx2, OCN, OPN and BSP genes and proteins (P < 0.05).@*Conclusion @#Red LEDs promoted the proliferation and osteogenic differentiation of hSCAPs.

7.
Article in Chinese | WPRIM | ID: wpr-904798

ABSTRACT

Objective @#To investigate the effect of silencing histone deacetylase 9 (HDAC9) expression on the proliferation and osteogenic differentiation of periodontal ligament stem cells (PDLSCs).@*Methods@# PDLSCs were isolated, cultured and identified in vitro. An siRNA construct specific for HDAC9 was transfected into PDLSCs (siHDAC9 group), and a nontargeting siRNA was used as a control (siNC group). The interference effect was determined by qRT-PCR. The cell cycle progression of PDLSCs was detected using flow cytometry. The proliferation activity of PDLSCs was detected via CCK-8 assay. Western blotting was used to detect the protein expression of proliferating cell nuclear antigen (PCNA). The mRNA expression of runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP) was investigated by qRT-PCR. The protein expression of RUNX2 was detected by western blotting. In addition, the formation of mineralized nodules was assessed by alizarin red staining. @*Results@#Compared with that in the siNC group, the mRNA expression of HDAC9 in the siHDAC9 group was lower (P < 0.01). Moreover, compared with those in the siNC group, the proliferation index (P<0.01), proliferation activity (P<0.05) and protein expression of PCNA (P<0.01) in the siHDAC9 group were all increased. Compared with the siNC group, the siHDAC9 group exhibited higher mRNA expression of RUNX2 and ALP (P < 0.05), and the protein expression of RUNX2 showed the same results (P < 0.01). The results of alizarin red staining showed that compared to the siNC group, the siHDAC9 group formed more mineralized nodules.@* Conclusion@#Silencing HDAC9 expression can promote the proliferation and osteogenic differentiation of PDLSCs.

8.
Braz. dent. sci ; 25(1): 1-6, 2022. tab, ilus
Article in English | LILACS, BBO | ID: biblio-1361486

ABSTRACT

Objetivo: A progressão da cicatrização de um alvéolo após uma extração é geralmente analisada por meio de exame clínico e investigação radiográfica. Embora a cicatrização do tecido mole geralmente seja mantida bem, a progressão da cicatrização do tecido duro é mais difícil de prever e gerenciar, com problemas como alvéolo seco ou má união do osso subjacente. Biomarcadores séricos para progressão da cicatrização óssea, como a Fosfatase Alcalina (FAL), podem ser úteis como ferramenta diagnóstica para intervenção precoce. Material e Métodos:Vinte indivíduos saudáveis de 18-30 anos de idade que deveriam extrair dentes do siso inferiores impactados foram incluídos. Foram coletados 2 ml de sangue, antes do tratamento e 48 horas depois, as amostras seguintes foram coletadas 1 mês, 2 meses e 3 meses após o procedimento. As radiografias intraorais foram realizadas no final dos três meses. Resultados: Houve uma correlação obtida com a cura e os níveis de FAL em intervalos de tempo de 1, 2 e 3 meses (p <0,05), onde 17 pacientes que tiveram um aumento substancial nos níveis de FAL também tiveram cura satisfatória após três meses. Três indivíduos que não apresentaram aumento no nível de FAL não tiveram cura satisfatória. Conclusão: FAL é um biomarcador suplementar útil para a consolidação óssea (AU)


Objective: The progression of a healing socket following an extraction is usually analysed through clinical examination and radiographic investigation. Whilst soft tissue healing is usually maintained well, healing progression of hard tissue is more challenging to predict and manage, with issues such as a dry socket or mal-union of the underlying bone. Serum biomarkers for bone healing progression, such as alkaline phosphatase (ALP), could prove helpful as a diagnostic tool for early intervention. Material and Methods: Twenty healthy 18-30-year-old individuals who were to extract lower impacted wisdom teeth were included. 2ml of blood was collected before treatment, 48 hours after then following samples were collected 1 month, 2 months and 3 months after the procedure. Intra-oral radiographs were taken at the end of the three months. Results: There was a significant correlation elicited with the healing and ALP levels at 1,2 & 3 months' time intervals (p<0.05), where 17 patients who had a substantial increase in the levels of ALP also had satisfactory healing after three months. Three individuals who did not show any increase in ALP level did not have satisfactory healing. Conclusion:ALP is a useful supplementary biomarker for bone healing.(AU)


Subject(s)
Humans , Adult , Surgery, Oral , Tooth Extraction , Wound Healing , Alkaline Phosphatase
9.
Rev. bras. ortop ; 56(6): 796-803, Nov.-Dec. 2021. tab, graf
Article in English | LILACS | ID: biblio-1357140

ABSTRACT

Abstract Objective To evaluate the role of serum alkaline phosphatase (ALP) and ultrasonography (USG) in monitoring the progress of treatment in diaphyseal non-unions. Methods This prospective observational cohort study included adult patients with diaphyseal fractures of major long bones previously treated with internal fixation and eventually resulting in non-union. Following the definitive treatment for non-union, the patients were followed-up periodically for six months, and serial monitoring of the levels of ALP and USG were performed along with radiographs (X-rays) to ascertain the status of the union. Results After an initial rise at seven weeks, ALP levels declined to normal values in fractures which united, whereas they remained high in cases of persistent non-union. Similarly, after an elevation of the vascular resistive index (RI) at around 12 weeks in all the patients, it decreased in cases progressing to union, while it remained persistently high even at 24 weeks in fractures failing to unite. Cases of persistent non-union continued to show hypoechogenic callus at 24 weeks instead of converting into hyperechogenic callus, as observed in cases which progressed to union. Conclusion Significant changes suggestive of union appeared simultaneously on the X-rays, USG and ALP levels during the follow-up. However, a serial examination of the ALP levels and USG during the follow-up gave a hint of the direction of progress in the healing process of fracture non-union. Their role in monitoring the outcome of nonunion is more complimentary than supplementary to the X-rays.


Resumo Objetivo Avaliar o papel da concentração sérica de fosfatase alcalina (FA) e da ultrassonografia no monitoramento do progresso do tratamento da ausência de consolidação em fraturas diafisárias. Métodos Este estudo de coorte observacional prospectivo incluiu pacientes adultos com fraturas diafisárias dos principais ossos longos previamente submetidas a fixação interna sem consolidação. Após o tratamento definitivo, os pacientes foram avaliados periodicamente por seis meses, com realização seriada de ultrassonografia, determinação da concentração de FA e radiografias para verificar a presença de consolidação. Resultados Após um aumento inicial em sete semanas, os níveis de FA voltaram ao valor normal em pacientes com fraturas consolidadas, mas continuaram elevados nos casos de ausência de consolidação. Da mesma forma, após uma elevação do índice de resistência (IR) vascular em cerca de 12 semanas em todos os pacientes, o IR diminuiu nos casos que progrediram para consolidação, mas continuou alto até as 24 semanas em fraturas não consolidadas. Os casos com ausência de consolidação ainda apresentavam calo hipoecogênico às 24 semanas, que não se converteu no calo hiperecogênico observado nos casos que progrediram para consolidação. Conclusão Alterações significativas sugestivas de consolidação foram simultaneamente observadas nas radiografias, na ultrassonografia e na concentração de FA durante o período de acompanhamento. No entanto, a realização seriada de exames da concentração de FA e de ultrassonografia durante o acompanhamento indicou o progresso da consolidação da fratura. Seu papel no monitoramento da ausência de consolidação é mais complementar do que suplementar à radiografia.


Subject(s)
Humans , Male , Female , Bony Callus , Ultrasonography , Outcome Assessment, Health Care , Alkaline Phosphatase , Fractures, Bone/therapy , Fractures, Ununited
10.
Arch. endocrinol. metab. (Online) ; 65(3): 289-294, May-June 2021. tab, graf
Article in English | LILACS | ID: biblio-1285157

ABSTRACT

ABSTRACT Objectives: Alkaline phosphatase (ALP) is the main laboratory marker of hypophosphatasia (HPP), a rare disease unknown to most physicians. The prevalence of HPP has been widely discussed in the literature due to the diverse phenotypes of HPP. The purpose of this study was to search for patients with hypophosphatasemia based on previous biochemistry tests and reevaluate them to confirm the diagnosis of HPP. Subjects and methods: A total of 289,247 biochemical tests for ALP in adults were performed from 2015 to 2019 in two tertiary hospitals in Rio de Janeiro were reviewed (Clementino Fraga Filho University Hospital - HUCFF - and Bonsucesso Federal Hospital - BFH). Results: A total of 1,049 patients were identified with ALP levels below 40 U/L, and 410 patients had hypophosphatasemia confirmed by at least two exams. After the active search of medical reports and/or interviews based on structured questionnaires, 398 subjects were excluded due to secondary causes of reduced ALP. The remaining 12 patients were invited to attend the medical consultation at HUCFF, accompanied by at least one first-degree relative. None of the patients or their relatives had a history or clinical manifestations consistent with HPP. Serum ALP was within reference values in all relatives, but persistently low in further laboratory evaluation in all the 12 patients, in whom secondary causes were ruled out. Thus, we cannot exclude the possibility that they might carry the mutations associated with HPP. Conclusion: Further image evaluations and genetic testing would be appropriate to confirm this asymptomatic adult form of HPP.


Subject(s)
Humans , Adult , Alkaline Phosphatase/blood , Hypophosphatasia/diagnosis , Brazil
11.
Rev. bras. ortop ; 56(3): 351-355, May-June 2021. tab, graf
Article in English | LILACS | ID: biblio-1288681

ABSTRACT

Abstract Objective To compare the serum levels of vitamin D and minerals in children with or without isolated distal radius fractures. Methods The present prospective clinical study included 50 children (aged between 5 and 15 years) with isolated distal radius fractures who were admitted to our emergency unit between February and May 2018 as the study group (group A), and 50 healthy children with no history of fracture as the control group (group B). Peripheral venous blood samples were obtained and analyzed for measurements of 25-hydroxyvitamin D (25(OH)D), calcium (Ca), magnesium (Mg), phosphorus (P), alkaline phosphatase (ALP), and parathyroid hormone (PTH) in both groups. Patient characteristics and peripheral venous blood samples were compared between the groups. Results The mean age, height, weight, body mass index (BMI) and gender distribution were similar in both groups. There were no statistical differences in the blood analyses, including Ca, Mg, P, ALP, and PTH. However, the serum levels of 25(OH)D were statistically lower in group A when compared to group B (p < 0.001), and the number of patients with 25(OH)D insufficiency was statistically higher in group A than in group B (p = 0.012). Conclusion Children with isolated distal radius fracture should be informed about vitamin D deficiency, and, in children with low levels of vitamin D, supplementation may be considered.


Resumo Objetivo Comparar os níveis séricos de vitamina D e minerais de crianças com ou sem fraturas isoladas da extremidade distal do rádio. Métodos Este estudo clínico prospectivo incluiu 50 crianças (com idade entre 5 e 15 anos) com fratura isolada distal do rádio que deram entrada em nossa unidade de emergência entre fevereiro e maio de 2018 como grupo de estudo (grupo A), e 50 crianças saudáveis sem histórico de fratura como grupo controle (grupo B). Foram obtidas e analisadas amostras de sangue venoso periférico para medições de 25-hidroxivitamina D (25(OH)D), Cálcio (Ca), Magnésio (Mg), Fósforo (P), fosfatase alcalina (FA) e hormônio da paratireoide (HPT) em ambos os grupos. As características dos pacientes e as amostras de sangue venoso periférico foram comparadas entre os grupos. Resultados A média de idade, altura, peso, índice de massa corporal (IMC) e distribuição de gênero foram semelhantes em ambos os grupos. Não houve diferenças estatísticas nas análises sanguíneas, incluindo Ca, Mg, P, FA e HPT. No entanto, os níveis séricos de 25(OH)D foram estatisticamente menores no grupo A do que no grupo B (p < 0,001), e o número de pacientes com insuficiência de 25(OH)D foi estatisticamente maior no grupo A do que no grupo B (p = 0,012). Conclusão Crianças com fratura isolada distal do rádio devem ser informadas sobre deficiência de vitamina D, e, em crianças com baixos níveis de vitamina D, a suplementação pode ser considerada.


Subject(s)
Humans , Child , Parathyroid Hormone , Radius Fractures , Vitamin D , Vitamin D Deficiency , Body Weight , Body Mass Index , Calcium , Alkaline Phosphatase
12.
Rev. Assoc. Med. Bras. (1992) ; 67(2): 248-259, Feb. 2021. tab, graf
Article in English | LILACS | ID: biblio-1287808

ABSTRACT

SUMMARY OBJECTIVES: This study aimed to develop artificial intelligence and machine learning-based models to predict alterations in liver enzymes from the exposure of low annual average effective doses in radiology and nuclear medicine personnel of Institute of Nuclear Medicine and Oncology Hospital. METHODS: Ninety workers from the Radiology and Nuclear Medicine departments were included. A high-capacity thermoluminescent was used for annual average effective radiation dose measurements. The liver function tests were conducted for all subjects and controls. Three supervised learning models (multilayer precentron; logistic regression; and random forest) were applied and cross-validated to predict any alteration in liver enzymes. The t-test was applied to see if subjects and controls were significantly different in liver function tests. RESULTS: The annual average effective doses were in the range of 0.07-1.15 mSv. Alanine transaminase was 50% high and aspartate transaminase was 20% high in radiation workers. There existed a significant difference (p=0.0008) in Alanine-aminotransferase between radiation-exposed and radiation-unexposed workers. Random forest model achieved 90-96.6% accuracies in Alanine-aminotransferase and Aspartate-aminotransferase predictions. The second best classifier model was the Multilayer perceptron (65.5-80% accuracies). CONCLUSION: As there is a need of regular monitoring of hepatic function in radiation-exposed people, our artificial intelligence-based predicting model random forest is proved accurate in prediagnosing alterations in liver enzymes.


Subject(s)
Humans , Artificial Intelligence , Occupational Exposure/adverse effects , Radiation Dosage , Algorithms , Liver
13.
Article in Chinese | WPRIM | ID: wpr-912466

ABSTRACT

Objective:To investigate the change and clinical significance of serum alkaline phosphatase (ALP) level in patients with acute spontaneous intracerebral hemorrhage(AICH).Methods:81 patients with AICH admitted to the Neurosurgery Department of Tianjin Third Central Hospital from January 2019 to October 2020 were retrospectively analyzed. 81 patients with non cerebral hemorrhage who came from the health examination center or complained of dizziness and had no hepatobiliary and skeletal diseases were selected as the control group. The clinical data of all the patients were recorded, including gender, age, Glasgow Coma Scale (GCS) score, hemorrhage location, liver function indexes, the history of hypertension, diabetes, heart disease, smoking, drinking, and so on. The differences in clinical data between the two groups were compared. Pearson correlation was used to analyze the correlation between liver function indexes and GCS score. The independent risk factors for AICH were screened by binary logistic regression, and the receiver operating characteristic (ROC) curve was used to evaluate the value of serum ALP in predicting intracerebral hemorrhage.Results:Serum ALP level in AICH group was significantly higher than that in the control group [85.0(70.0, 103.0) U/L vs 65.0(54.5, 71.5)U/L, Z=6.740, P<0.001]. Pearson correlation analysis showed that serum ALP had a negative correlation with GCS score ( r=0.255, P=0.022). Binary logistic regression analysis showed that hypertension ( OR=20.440, 95% CI 8.572-48.737) and ALP ( OR=1.077, 95% CI 1.049-1.105) were risk factors for intracerebral hemorrhage. Serum ALP level was an independent risk factor ( OR=1.069, 95% CI 1.038-1.101) for AICH after adjusting for confounding variables including age, AST, history of hypertension. ROC curve showed that the area under the curve (AUC) of serum ALP in predicting intracerebral hemorrhage was 0.807 (95% CI 0.740-0.873, P<0.001), with sensitivity of 67.9% and specificity of 81.5%. Conclusions:Serum ALP level may be related to the occurrence and severity of AICH. Therefore, serum ALP level can be used as a reference index to evaluate the occurrence, severity of patients with AICH.

14.
Acta Pharmaceutica Sinica B ; (6): 3847-3856, 2021.
Article in English | WPRIM | ID: wpr-922445

ABSTRACT

Bile acids (BAs) are amphipathic molecules important for metabolism of cholesterol, absorption of lipids and lipid soluble vitamins, bile flow, and regulation of gut microbiome. There are over 30 different BA species known to exist in humans and mice, which are endogenous modulators of at least 6 different membrane or nuclear receptors. This diversity of ligands and receptors play important roles in health and disease; however, the full functions of each individual BA

15.
Organ Transplantation ; (6): 103-2021.
Article in Chinese | WPRIM | ID: wpr-862783

ABSTRACT

Objective To explore the value of ultrasound elastography in the non-invasive monitoring of liver elasticity of stable recipients at different stages after liver transplantation. Methods Clinical data of 73 stable recipients after liver transplantation were collected. According to the time after liver transplantation, all patients were divided into the early group (n=25) and medium-to-long group (n=48). In addition, 38 healthy subjects were assigned into the control group. The ultrasound indexes and liver function indexes were statistically compared among each group. The ultrasound elastography indexes of liver and spleen were analyzed, and their correlation with liver function indexes was analyzed. Results Compared with the control group, the ultrasound indexes, alanine aminotransferase (ALT), γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) levels were significantly increased in the early group (all P < 0.05), and the ultrasound indexes in the medium-to-long group were significantly increased, whereas the GGT level was significantly decreased (all P < 0.05). Compared with the early group, the right oblique diameter of liver, ALT, GGT and ALP levels were significantly decreased in the medium-to-long group (all P < 0.05). Compared with the control group, the sound touch elastography (STE) and sound touch quantify (STQ) values of liver and STE value of spleen in the early group and medium-to-long group were significantly increased (all P < 0.05). Compared with the early group, the ultrasound elastography indexes of liver and spleen in the medium-to-long group were remarkably decreased (all P < 0.05). The ultrasound elastography indexes of liver were weakly correlated with the ALT, aspartate aminotransferase (AST) and GGT levels, significantly correlated with ALP level. The STE value of spleen was weakly correlated with the ALP level. The STE value of liver was significantly correlated with the STQ value of liver. The STE and STQ values of liver were weakly correlated with the STE value of spleen. Conclusions The characteristics of liver elasticity in stable recipients after liver transplantation are various among different stages. Persistent monitoring of liver elasticity may provide a novelnon-invasive monitoring method during follow-up after liver transplantation.

16.
Article in Chinese | WPRIM | ID: wpr-873571

ABSTRACT

Objective @#To investigate the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway molecules during the process by which kaempferol (Kae) promotes osteogenic differentiation of mouse bone marrow mesenchymal cells (BMMCs) under cyclic and uniaxial tension.@*Methods @#BMMCs isolated and cultured in vitro were subjected to uniaxial dynamic tension with a 10% shape variable. The appropriate concentration of Kae was selected by cytotoxicity testing. The endogenous mTOR signal was inhibited by pp242. Four hours after traction, alkaline phosphatase (ALP) and osteocalcin (OCN) were detected by chemical colorimetry and ELISA, and the relative concentration of intracellular calcium was detected by flow cytometry. Phosphorylation of mTOR, 4E/BP1, and ribosomal protein S6 kinases (S6K), which are the main molecules of the endogenous mTORC1 signaling pathway, and expression of osteogenic transcription factors (Runx2 and Osterix) were detected by western blotting (WB), and mRNA expression levels of the above factors were detected by qRT-PCR.@*Results @# The cytotoxicity test showed that 10 μmol/L Kae had little inhibitory effect on cell proliferation but had the strongest osteogenic ability. Four hours after stretching, Kae effectively promoted the osteogenic differentiation of BMMCs. The expression of ALP was (153.04 ± 18.72) U/mg, the expression of OCN was (1.64 ± 0.25) U. The mRNA and protein levels of Runx2 and Osterix were upregulated, and the intracellular calcium content was decreased. The mRNA and protein phosphorylation of mTOR and S6K was upregulated, and the opposite effect was observed with 4E/BP1. After pp242 was added to inhibit mTOR signaling, mTOR and S6K mRNA and protein phosphorylation were downregulated, but 4E/BP1 mRNA and protein phosphorylation was upregulated. The osteogenic differentiation of BMMCs was also significantly inhibited, mRNA and protein expression of Runx2 and Osterix were significantly downregulated, ALP and OCN expression were downregulated, and intracellular calcium content was increased. @* Conclusion@#Kae promotes osteogenic differentiation of mouse BMMCs under uniaxial dynamic tension through the mTORC1 signaling pathway.

17.
Palliative Care Research ; : 241-246, 2021.
Article in Japanese | WPRIM | ID: wpr-887232

ABSTRACT

Alkaline phosphatase (ALP) has been measured using a Japan-specific method in Japan. However, the Japan Society of Clinical Chemistry (JSCC) has decided to change to an international standardized method of International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) by the end of fiscal year 2020. The Prognosis in Palliative care Study predictor (PiPS) models were the prognosis predictor methods developed in the UK. The ALP value is included in the test items of PiPS-B of the PiPS models. The international standardization method was not used in previous reports about PiPS in Japan. In this study, we investigated the effect of changing measurement methods of ALP levels on the prognostic value of PiPS using IFCC conversion values. We performed prognostic prediction by PiPS models in 239 consecutive patients admitted to our palliative care unit from March 2019 to March 2021. In 98 PiPS-B calculated patients, the prognosis was recalculated by replacing ALP values with the JSCC recommended conversion values. 5 of 98 patients whose prognosis was “weeks” changed to “months+”. It was suggested that a change in the method of ALP measurement from JSCC to IFCC method may change the “weeks” prognosis prediction by PiPS to a “months+”.

18.
Acta Pharmaceutica Sinica B ; (6): 727-737, 2021.
Article in English | WPRIM | ID: wpr-881165

ABSTRACT

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67

19.
Acta Pharmaceutica Sinica B ; (6): 322-339, 2021.
Article in English | WPRIM | ID: wpr-881139

ABSTRACT

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in

20.
Article in Chinese | WPRIM | ID: wpr-911419

ABSTRACT

The measurement of serum alkaline phosphatase (ALP) levels has been widely used in the clinical setting. However, isolated elevation of serum ALP levels is also commonly seen and needs to be extensiuely evaluated Herein, we present a case of gastric adenocarcinoma with disseminated carcinomatosis of the bone marrow (DCBM). In this case, isolated elevation of serum ALP levels was the only clinical manifestation with no other notable symptom. Additionally, imaging studies including whole body computed tomography (CT) and positron emission tomography-CT (PET-CT) were all negative, which resulted in the misdiagnosis of Paget′s disease of bone initially. This highlights that malignancies involving bones presenting with isolated elevation of serum ALP levels might be misdiagnosed in asymptomatic individuals.

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