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2.
Aging (Albany NY) ; 16(1): 15-27, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38170244

RESUMEN

OBJECTIVE: The objective of this study was to explore the potential correlation between the composite dietary antioxidant index (CDAI) and biological aging, addressing the insufficient epidemiological evidence in this area. METHODS: Participants meeting eligibility criteria were selected from the National Health and Nutrition Examination Surveys (NHANES) conducted between 2001 and 2018. CDAI was determined based on dietary antioxidants obtained from 24-hour dietary recalls. Biological age was determined using PhenoAge algorithms incorporating various clinical features. Weighted multiple models were employed to investigate and assess the association between CDAI and biological age. RESULTS: Analysis of the CDAI quartile revealed disparities in terms of age, gender, ethnicity, educational level, marital status, poverty, dietary calories intakes, smoking, drinking status, BMI, physical activity, and PhenoAge. After adjusting for potential confounding factors, a significant inverse relationship was found between CDAI and Phenotypic Age, with each standard deviation increase in CDAI score correlating with a 0.18-year decrease in Phenotypic Age. These negative correlations between CDAI and PhenoAge advancement were observed regardless of age, gender, physical activity status, smoking status, and body mass index. CONCLUSIONS: Our findings demonstrate a positive relationship between higher CDAI scores and delayed biological aging. These results have significant implications for public health initiatives aimed at promoting healthy aging through dietary interventions.


Asunto(s)
Envejecimiento , Antioxidantes , Dieta , Humanos , Etnicidad , Encuestas Nutricionales
3.
J Neurogastroenterol Motil ; 30(2): 184-193, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37788825

RESUMEN

Background/Aims: Functional dyspepsia (FD) overlapping with other gastrointestinal disorders are quite common. The characteristics of FD overlap in Chinese population with latest Rome IV criteria were unclear. This large-scale outpatient-based study assessed the characteristics of FD overlap in South China. Methods: Consecutive FD patients visited the Gastroenterology Clinic at 2 tertiary medical centers in Hangzhou, China who fulfilled the Rome IV criteria were enrolled. Complete questionnaires related to the gastrointestinal symptoms (Rome IV criteria), Reflux Disease Questionnaire, anxiety and depression, quality of sleep and life, and demographic information were collected. Results: Among the total of 3281 FD patients, 50.69% overlapped with gastroesophageal reflux disease, 21.46% overlapped with irritable bowel syndrome, 6.03% overlapped with functional constipation. FD overlap had higher proportion of single/divorced/widowed rate, high education level, being employed, drinking, night shift, unhealthy dietary habit than FD only (P < 0.05). They had higher frequency of consultation and economic burden, as well as lower scores in quality of life (P < 0.001). Multivariate logistic regression showed that increasing age, female, low body mass index, history of gastroenteritis, anxiety, depression, and poor sleep quality were independent risk factors for FD overlap. Conclusions: FD overlap was quite common in China with high economic burden and poor quality of life, FD patients with history of gastroenteritis, anxiety, depression, and poor sleep quality were more likely to have overlap disorders. Awareness of the physical and psychosocial stressors in overlapping condition would help optimize the management of FD overlap in clinical practice.

4.
Adv Sci (Weinh) ; 10(36): e2303457, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37983567

RESUMEN

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.


Asunto(s)
Colitis Ulcerosa , Colitis , Humanos , Animales , Ratones , Colitis Ulcerosa/tratamiento farmacológico , Células Th17/metabolismo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Células Epiteliales/metabolismo , Tretinoina/metabolismo , Tretinoina/farmacología , Tretinoina/uso terapéutico
5.
Cell Death Discov ; 9(1): 60, 2023 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-36774350

RESUMEN

Palmitoylation of proteins plays important roles in various physiological processes, such as cell proliferation, inflammation, cell differentiation etc. However, inhibition of protein palmitoylation has led to few new drugs to date. ZDHHC5 serves as a key enzyme to catalyze palmitoylation on SSTR5 (a proven anti-proliferation receptor in pancreatic cells). Herein, we compare single-cell transcriptome data between pancreatic cancer tissues and normal pancreas tissues and identify that ZDHHC5 is a potential target to inhibit proliferation of pancreatic cancer cells. In addition, we report the repositioning of an orphan drug (Lomitapide) as an inhibitor of ZDHHC5, and we speculate that this inhibitor may be able to block palmitylation on SSTR5. Pharmacological blockade of ZDHHC5 with Lomitapide results in attenuated cancer cell growth and proliferation which collectively contributes to antitumor responses in vitro and in vivo. This is the first study, to our knowledge, to demonstrate the utility of a pharmacological inhibitor of ZDHHC5 in pancreatic cancer, representing a new class of palmitoylation targeted therapy and laying a framework for paradigm-shifting therapies targeting cancer cell palmitoylation.

6.
Dig Liver Dis ; 55(8): 1049-1059, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36792433

RESUMEN

BACKGROUND: Aquaporins (AQPs) maintain fluid homeostasis in the colon. The role of colonic AQPs in the pathophysiology of functional constipation (FC) remains largely unknown. AIM: To explore variations in aquaporins and investigate their underlying mechanisms. METHODS: Colonic biopsies were collected from patients with FC and healthy controls. The expression and localization of AQPs were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis, and immunofluorescence assays. Furthermore, osmotic pressure-induced cell model was used in vitro to investigate the potential relationship between AQP8 and osmotic pressure, and to reveal the underlying mechanisms. RESULTS: Upregulation of AQP3 and AQP8, and downregulation of AQP1, AQP7, AQP9, AQP10, and AQP11 were observed in the patients with functional constipation. Furthermore, cellular translocation of AQP8 from the cytoplasm to the plasma membrane was observed in patients with FC. Mechanistically, the increase in osmotic pressure could activate the Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways, and subsequently promote the upregulation and translocation of AQP8. CONCLUSION: Upregulation of AQP8 and AQP3, and translocation of AQP8 were observed in colon biopsies from patients with FC. The p38 and JNK MAPK signaling pathways are involved in the regulation of osmotic pressure-induced AQP8 variation.


Asunto(s)
Acuaporinas , Humanos , Acuaporinas/genética , Acuaporinas/metabolismo , Estreñimiento , Sistema de Señalización de MAP Quinasas , Presión Osmótica , Regulación hacia Arriba , Proteína Quinasa 14 Activada por Mitógenos , Proteína Quinasa 8 Activada por Mitógenos
7.
Oxid Med Cell Longev ; 2023: 3524611, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36798687

RESUMEN

Objectives: The association between dietary antioxidants and soluble Klotho (S-Klotho) levels remains unknown. We investigated to explore whether the composite dietary antioxidant index (CDAI) was associated with serum levels of S-Klotho in the middle-aged population. Methods: Eligible participants were identified from the National Health and Nutrition Examination Surveys (NHANES) from 2007 until 2016. The CDAI was calculated from the intake of six dietary antioxidants. The serum levels of S-Klotho were measured via enzyme-linked immunosorbent assay (ELISA). Generalized linear and nonlinear models were established to analyze the relationship between CDAI and S-Klotho levels. Results: Based on the S-Klotho quartiles, S-Klotho levels were higher in young women, Blacks, higher education, never smokers, lower waistlines, no medication use, and those with higher CDAI. Univariate analysis revealed that age, gender, race, smoking status, body mass index, waistline, and medication use were associated with serum levels of S-Klotho. When potential confounders were controlled, CDAI was significantly associated with S-Klotho levels. Subgroup analysis also revealed that this association remained significant in individuals who had the highest quartiles of CDAI, aged population (>60 years), male, and never smoker. A nonlinear relationship was observed between the CDAI and S-Klotho plasma concentrations. Conclusion: CDAI was positively correlated with plasma levels of S-Klotho after controlling for covariates. Further studies are needed to validate the current findings and explore the fundamental mechanisms.


Asunto(s)
Antioxidantes , Dieta , Proteínas Klotho , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Masa Corporal , Encuestas Nutricionales , Proteínas Klotho/sangre
8.
J Clin Ultrasound ; 51(1): 74-81, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36082876

RESUMEN

OBJECTIVES: This study aimed to evaluate the feasibility of monitoring fetal intracranial volume using three-dimensional ultrasound virtual organ computer-aided analysis (VOCAL) technology and to analyze normal fetal brain growth. METHODS: This multi-center prospective cross-sectional study included 821 pregnant women (18-40 gestational weeks) divided into 23 groups according to gestational week. We used transabdominal three-dimensional ultrasound VOCAL to monitor fetal intracranial volume; explore the correlation between intracranial volume and gestational age, biparietal diameter (BPD), and head circumference (HC); and analyze the proportion of brain weight to body weight. RESULTS: The intracranial volume of normal fetuses conformed to the normal distribution, gradually increased with gestational age, and was highly correlated with gestational age (r = 0.977), BPD (r = 0.975), and HC (r = 0.953; p < 0.001). The median percentage of brain weight (BW) to estimated fetal weight (EFW) was between 13% and 21%, and the BW/EFW ratio showed a significant downward trend in the third trimester. The VOCAL technology monitored the fetal intracranial volume with good repeatability. CONCLUSIONS: VOCAL technology is feasible for monitoring the fetal intracranial volume, and the intracranial volume increases more than 10-times in the second and third trimesters.


Asunto(s)
Pueblos del Este de Asia , Ultrasonografía Prenatal , Embarazo , Femenino , Humanos , Estudios Transversales , Estudios Prospectivos , Ultrasonografía Prenatal/métodos , Desarrollo Fetal , Peso Fetal , Edad Gestacional , Computadores
9.
Gut Microbes ; 14(1): 2145843, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36398889

RESUMEN

Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. Lactobacillus johnsonii (L. johnsonii), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage L. johnsonii could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in Il10-/- mice. We identified this subset of immune cells activated by L. johnsonii as CD206+ macrophagesIL-10. Mechanistically, L. johnsonii supplementation enhanced the mobilization of CD206+ macrophagesIL-10 through the activation of STAT3 in vivo and in vitro. In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of L. johnsonii by macrophages. Clinically, there was positive correlation between the abundance of L. johnsonii and the expression level of MRC1, IL10 and TLR1/2 in UC tissues. L. johnsonii could activate native macrophages into CD206+ macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. L. johnsonii may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.


Asunto(s)
Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Lactobacillus johnsonii , Receptor Toll-Like 1 , Animales , Ratones , Antiinflamatorios , Colitis/genética , Colitis/microbiología , Colitis/terapia , Colitis Ulcerosa/genética , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/terapia , Sulfato de Dextran/toxicidad , Interleucina-10/genética , Macrófagos , ARN Ribosómico 16S , Receptor Toll-Like 1/genética , Receptor Toll-Like 1/metabolismo
10.
Eur J Gastroenterol Hepatol ; 34(12): 1220-1230, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36165068

RESUMEN

OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized with visceral hypersensitivity. Previous studies indicated gut microbiota alteration associated short-chain fatty acids (SCFAs) dysregulation is associated with IBS development. The aim of the study is to explore the potential role of microbiota dysbiosis mediated visceral hypersensitivity in postinfectious-IBS (PI-IBS) mouse model. METHODS: Four-week-old NIH mice were randomly allocated into four groups: control mice, PI-IBS mice, PI-IBS mice co-housing with normal mice, and PI-IBS mice were administrated with a cocktail of antibiotics. Trichinella spiralis infection established PI-IBS mouse model. Microbiota in cecal contents and feces were analyzed by 16S rDNA sequencing. SCFAs were detected by gas chromatography. 5-hydroxytryptamine (5-HT) was evaluated by ELISA, and N-methyl-D-aspartate receptors (NMDARs) were examined by western blot. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distention. RESULTS: Increased SCFAs were observed in cecal contents and feces in PI-IBS mice accompanied with higher 5-HT and NMDAR subunits expressions in ileum and colon. Visceral hypersensitivity was observed in PI-IBS mice compared to control mice. When administrated with antibiotics cocktails and co-housing with normal mice, PI-IBS mice showed decreased SCFAs, 5-HT, NMDAR subunits expressions, and improved visceral hypersensitivity. CONCLUSION: Gut microbiota alteration induced increased SCFAs, 5-HT and NMDAR subunits expressions were associated with visceral hypersensitivity in PI-IBS mice. The critical role of gut microbiota in improving visceral hypersensitivity was further identified by treatment of antibiotics cocktail and co-housing.


Asunto(s)
Microbioma Gastrointestinal , Síndrome del Colon Irritable , Ratones , Humanos , Animales , Serotonina , Disbiosis , Modelos Animales de Enfermedad , Antibacterianos
11.
Pathol Oncol Res ; 28: 1610176, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35665406

RESUMEN

Background: Human papillomavirus type 8 (HPV8) has been implicated in the progress of non-melanoma skin cancers and their precursor lesions. The HPV8 E7 oncoprotein plays a key role in the tumorigenesis of HPV-associated cutaneous tumors. However, the exact role of HPV8 E7 in human epidermal carcinogenesis has not been fully elucidated. Methods: To investigate the potential carcinogenic effects of HPV8 E7 on epithelial cells, we used RNA-sequencing technology to analyze the gene expression profile of HPV8 E7-overexpressed normal human epidermal keratinocytes (NHEKs). Results: RNA-sequencing revealed 831 differentially expressed genes (DEGs) between HPV8 E7-expressing NHEKs and control cells, among which, 631 genes were significantly upregulated, and 200 were downregulated. Gene ontology annotation enrichment analysis showed that HPV8 E7 mainly affected the expression of genes associated with protein heterodimerization activity, DNA binding, nucleosomes, and nucleosome assembly. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that overexpression of HPV8 E7 affected the expression of gene clusters associated with viral carcinogenesis and transcriptional misregulation in cancer and necroptosis signaling pathways that reportedly play crucial roles in HPV infection promotion and cancer progression. We also found the DEGs, such as HKDC1 and TNFAIP3, were associated with epigenetic modifications, immune regulation, and metabolic pathways. Conclusion: Our results demonstrate that the pro-carcinogenic effect of HPV8 expression in epithelial cells may be attributed to the regulatory effect of oncogene E7 on gene expression associated with epigenetic modifications and immune and metabolic status-associated gene expression. Although our data are based on an in vitro experiment, it provides the theoretical evidence that the development of squamous cell carcinoma can be caused by HPV.


Asunto(s)
Alphapapillomavirus , Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Alphapapillomavirus/genética , Alphapapillomavirus/metabolismo , Carcinogénesis/metabolismo , Humanos , Queratinocitos/metabolismo , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , ARN , Transcriptoma/genética
12.
Front Med (Lausanne) ; 9: 869004, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35425770

RESUMEN

Background: Over the past 40 years, endoscopic ultrasound (EUS) has become a safe and effective tool for both diagnostic and therapeutic applications. A growing number of articles have been published annually. We aimed to explore global scientific outputs and hotspots of EUS published by different countries, organizations, and authors. Methods: The global literature regarding EUS during the 1900-2020 period was identified from the Web of Science (WOS) Core database. "Bibliometrix" and software VOSviewer were applied to perform bibliometric analysis. Results: The annual growth rate of publications from 1980 to 2020 was around 16% and the number of EUS-related articles had experienced a sudden increase in the last decade. Bhutani MS was the most productive author over the past years, with 94 publications. Hawes RH had the highest number of citations, with 6,034 citations. The United States and institutions from United States dominated the EUS research. Among the journals, GASTROINTESTINAL ENDOSCOPY published the highest number of articles, followed by ENDOSCOPY. The majority of top 10 frequently cited references were cited more than 200 times. Carcinoma, diagnosis, fine-needle-aspiration, cytology, and pancreatitis were the important keywords in co-occurrence analysis of keywords. Recent studies focused more on tissue acquisition, size of the needle, lumen-apposing metal stent, and fine-needle- biopsy. Conclusion: Research on EUS has significantly increased in the last decade globally and it will continue to increase. Active collaboration among different authors and countries was observed in the EUS field. Tissue acquisition, size of the needle, apposing metal stent, and fine-needle-biopsy might be the latest research frontiers and should receive more attention.

13.
Eur J Gastroenterol Hepatol ; 34(5): 471-477, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35352689

RESUMEN

N-methyl-d-aspartate receptors (NMDARs) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are excitatory neurotransmission receptors of the central nervous system and play vital roles in synaptic plasticity. Although not fully elucidated, visceral hypersensitivity is one of the most well-characterized pathophysiologic abnormalities of functional gastrointestinal diseases and appears to be associated with increased synaptic plasticity. In this study, we review the updated findings on the physiology of NMDARs and AMPARs and their relation to visceral hypersensitivity, which propose directions for future research in this field with evolving importance.


Asunto(s)
N-Metilaspartato , Receptores AMPA , Humanos , Plasticidad Neuronal , Receptores AMPA/fisiología , Receptores de N-Metil-D-Aspartato/fisiología , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico
14.
Biol Pharm Bull ; 45(1): 19-26, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34719576

RESUMEN

With the development of structural biology and data mining, computer-aided drug design (CADD) has been playing an important role in all aspects of new drug development. Reverse docking, a method of virtual screening based on molecular docking in CADD, is widely used in drug repositioning, drug rescue, and traditional Chinese medicine (TCM) research, for it can search for macromolecular targets that can bind to a given ligand molecule. This review revealed the principle of reverse docking, summarized common target protein databases and docking procedures, and enumerated the applications of reverse docking in drug repositioning, adverse drug reactions, traditional Chinese medicine, and coronavirus disease 2019 (COVID-19) treatment. Hope our work can give some inspiration to researchers engaged in drug development.


Asunto(s)
Diseño de Fármacos , Simulación del Acoplamiento Molecular , COVID-19 , Bases de Datos de Proteínas , Reposicionamiento de Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Medicina Tradicional China , SARS-CoV-2/efectos de los fármacos
15.
Artículo en Inglés | MEDLINE | ID: mdl-34484401

RESUMEN

Angiotensin-converting enzyme 2 (ACE2) has been identified as the key receptor of SARS coronavirus that plays a key role in the pathogenesis of SARS. It is known that ACE2 mRNA can be expressed in most organs. However, the protein expression of ACE2 is not clear yet. To explore the role of ACE2 as a precipitating factor in digestive organ damage in COVID-19, this study investigated the expression of ACE2 protein in the human liver, esophagus, stomach, and colon. The result showed that ACE2 can be expressed in the liver, esophagus, stomach, and colon, which suggests SARS-CoV-2 may enter the digestive system through ACE2 and cause liver damage and gastrointestinal damage. It is hoped that the result of the study will provide a new strategy for the prevention and treatment of digestive organ damage under COVID-19.

16.
Am J Clin Nutr ; 113(6): 1531-1545, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33740048

RESUMEN

BACKGROUND: The efficacy and factors associated with patient outcomes for a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (LFD) compared with traditional dietary advice (TDA) based on modified National Institute for Clinical Excellence guidelines for irritable bowel syndrome with diarrhea (IBS-D) in regions consuming a non-Western diet are unclear. OBJECTIVES: We aimed to determine the efficacy of an LFD compared with TDA for the treatment of IBS-D in Chinese patients and to investigate the factors associated with favorable outcomes. METHODS: One hundred and eight Chinese IBS-D patients (Rome III criteria) were randomly assigned to an LFD or TDA. The primary endpoint was a ≥50-point reduction in the IBS Severity Scoring System at 3 wk. Fecal samples collected before and after the dietary intervention were assessed for changes in SCFAs and microbiota profiles. A logistic regression model was used to identify predictors of outcomes. RESULTS: Among the 100 patients who completed the study, the primary endpoint was met in a similar number of LFD (30 of 51, 59%) and TDA (26 of 49, 53%) patients (∆6%; 95% CI: -13%, 24%). Patients in the LFD group achieved earlier symptomatic improvement in stool frequency and excessive wind than those following TDA. LFD reduced carbohydrate-fermenting bacteria such as Bifidobacterium and Bacteroides, and decreased saccharolytic fermentation activity. This was associated with symptomatic improvement in the responders. High saccharolytic fermentation activity at baseline was associated with a higher symptom burden (P = 0.01) and a favorable therapeutic response to the LFD (log OR: 4.9; 95% CI: -0.1, 9.9; P = 0.05). CONCLUSIONS: An LFD and TDA each reduced symptoms in Chinese IBS-D patients; however, the LFD achieved earlier symptomatic improvements in stool frequency and excessive wind. The therapeutic effect of the LFD was associated with changes in the fecal microbiota and the fecal fermentation index. At baseline, the presence of severe symptoms and microbial metabolic dysbiosis characterized by high saccharolytic capability predicted favorable outcomes to LFD intervention.This trial was registered at clinicaltrials.gov as NCT03304041.


Asunto(s)
Diarrea/etiología , Dieta , Azúcares de la Dieta/administración & dosificación , Azúcares de la Dieta/metabolismo , Síndrome del Colon Irritable/dietoterapia , Adulto , Bacterias/clasificación , Ácidos Grasos Volátiles/química , Heces/química , Heces/microbiología , Femenino , Fermentación , Humanos , Síndrome del Colon Irritable/clasificación , Síndrome del Colon Irritable/complicaciones , Masculino , Persona de Mediana Edad
17.
Stroke Vasc Neurol ; 5(4): 381-387, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33376199

RESUMEN

The discovery of targeted drugs heavily relies on three-dimensional (3D) structures of target proteins. When the 3D structure of a protein target is unknown, it is very difficult to design its corresponding targeted drugs. Although the 3D structures of some proteins (the so-called undruggable targets) are known, their targeted drugs are still absent. As increasing crystal/cryogenic electron microscopy structures are deposited in Protein Data Bank, it is much more possible to discover the targeted drugs. Moreover, it is also highly probable to turn previous undruggable targets into druggable ones when we identify their hidden allosteric sites. In this review, we focus on the currently available advanced methods for the discovery of novel compounds targeting proteins without 3D structure and how to turn undruggable targets into druggable ones.


Asunto(s)
Inteligencia Artificial , Macrodatos , Diseño Asistido por Computadora , Minería de Datos , Diseño de Fármacos , Descubrimiento de Drogas , Preparaciones Farmacéuticas/química , Proteínas/química , Animales , Bases de Datos de Proteínas , Humanos , Ligandos , Estructura Molecular , Terapia Molecular Dirigida , Conformación Proteica , Relación Estructura-Actividad
18.
Clin Res Hepatol Gastroenterol ; 43(5): e68-e72, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31196708

RESUMEN

A case of chronic enteropathy associated with SLCO2A1 gene (CEAS) is presented. The female patient was readmitted four times during a three-year follow-up period for intractable dropsy and anemia. Multiple ulcers of small bowel wall were revealed by endoscopic examination. Computed tomography enterography (CTE) and magnetic resonance enterography (MRE) showed the segmental wall thickening of the small bowel. Hepatosplenomegaly and increased bone density of spine and pelvis suggested the diagnosis of myelofibrosis. X-ray films showed the cortical thickening of tibiofibula. The mutations of SLCO2A1 gene were revealed by gene test and the diagnosis of CEAS was confirmed. According to our case report, imaging examinations, including CTE, MRE and X-ray films provide additional valuable information during the diagnostic procedure of CEAS.


Asunto(s)
Enfermedades Intestinales/genética , Mutación , Transportadores de Anión Orgánico/genética , Adulto , Enfermedad Crónica , Femenino , Humanos , Enfermedades Intestinales/diagnóstico por imagen
19.
Stroke Vasc Neurol ; 4(4): 206-213, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32030204

RESUMEN

Different kinds of biological databases publicly available nowadays provide us a goldmine of multidiscipline big data. The Cancer Genome Atlas is a cancer database including detailed information of many patients with cancer. DrugBank is a database including detailed information of approved, investigational and withdrawn drugs, as well as other nutraceutical and metabolite structures. PubChem is a chemical compound database including all commercially available compounds as well as other synthesisable compounds. Protein Data Bank is a crystal structure database including X-ray, cryo-EM and nuclear magnetic resonance protein three-dimensional structures as well as their ligands. On the other hand, artificial intelligence (AI) is playing an important role in the drug discovery progress. The integration of such big data and AI is making a great difference in the discovery of novel targeted drug. In this review, we focus on the currently available advanced methods for the discovery of highly effective lead compounds with great absorption, distribution, metabolism, excretion and toxicity properties.


Asunto(s)
Inteligencia Artificial , Macrodatos , Minería de Datos , Bases de Datos Factuales , Diseño de Fármacos , Descubrimiento de Drogas , Preparaciones Farmacéuticas , Diseño Asistido por Computadora , Humanos , Estructura Molecular , Terapia Molecular Dirigida , Preparaciones Farmacéuticas/química , Preparaciones Farmacéuticas/metabolismo , Farmacocinética , Relación Estructura-Actividad , Toxicología
20.
Clin Exp Med ; 18(4): 569-576, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29876770

RESUMEN

To evaluate potency and safety of 14-day bismuth-furazolidone quadruple regimens and to compare efficacies of five proton pump inhibitors (PPIs) for the initial eradication of Helicobacter pylori (H. pylori), 175 eligible patients were enrolled and randomly assigned to 14-day quadruple regimens consisting of bismuth (400 mg), amoxicillin (1 g), furazolidone (100 mg), and a PPI, twice a day. PPIs used were Group A (pantoprazole capsules, 40 mg), Group B (pantoprazole tablets, 40 mg), Group C (lansoprazole, 30 mg), Group D (esomeprazole, 20 mg), and Group E (rabeprazole, 10 mg). H. pylori status was reassessed by 13C urea breath test on day 56 as the primary outcome. Gastrointestinal symptoms, parenteral side effects, compliance, and stool type were recorded simultaneously. The total eradication rates were 86.9% (152/175 [95% CI 80.9-91.5%]) and 95.6% (152/159 [91.1-98.2%]) by intention-to-treat (ITT) and per-protocol (PP) analysis. The efficacies of Group A, B, C, D, and E by ITT analysis were 91.4% (32/35 [76.9-98.2%]), 85.7% (30/35 [69.7-95.2%]), 88.6% (31/35 [73.3-96.8%]), 85.7% (30/35 [69.7-95.2%]), and 82.9% (29/35 [66.4-93.4%]) (p > 0.05). In the PP analysis, the efficacies were 97.0% (32/33), 93.8% (30/32), 93.9% (31/33), 100% (30/30), and 93.5% (29/31) (p > 0.05). Gastrointestinal symptoms and stool type were improved significantly (p < 0.05). Total side effects rate and poor compliance rate were 15.7% (25/159) and 5.0% (8/159). Fourteen-day bismuth-furazolidone quadruple regimens are of high potency and safety for the initial eradication of H. pylori. Efficacies of different PPIs and different dosages (9-32 mg omeprazole equivalents) showed no significant difference. The appropriate PPI can thus be chosen by clinicians.


Asunto(s)
Amoxicilina/administración & dosificación , Bismuto/administración & dosificación , Furazolidona/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Inhibidores de la Bomba de Protones/administración & dosificación , Adulto , Amoxicilina/farmacología , Bismuto/farmacología , Pruebas Respiratorias , China , Esquema de Medicación , Quimioterapia Combinada , Femenino , Furazolidona/farmacología , Helicobacter pylori/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/administración & dosificación , Omeprazol/farmacología , Estudios Prospectivos , Inhibidores de la Bomba de Protones/farmacología , Resultado del Tratamiento
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