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1.
Eur J Psychotraumatol ; 15(1): 2351292, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38809665

RESUMO

Background: Preliminary evidence provides support for the proposition that there is a dissociative subtype of Complex posttraumatic stress disorder (CPTSD). Research on this proposition would extend our knowledge on the association between CPTSD and dissociation, guide contemporary thinking regarding placement of dissociation in the nosology of CPTSD, and inform clinically useful assessment and intervention.Objectives: The present study aimed to investigate the co-occurring patterns of CPTSD and dissociative symptoms in a large sample of trauma exposed adolescents from China, and specify clinical features covariates of such patterns including childhood trauma, comorbidities with major depressive disorder (MDD) and generalized anxiety disorder (GAD), and functional impairment.Methods: Participants included 57,984 high school students exposed to the coronavirus disease 2019 (COVID-19) pandemic. CPTSD and dissociative symptoms, childhood traumatic experience, and functional impairment were measured with the Global Psychotrauma Screen for Teenagers (GPS-T). Major depressive disorder (MDD) and generalized anxiety disorder (GAD) symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7), respectively. Latent class analysis (LCA) was employed to test the co-occurring patterns of CPTSD and dissociative symptoms. Analysis of covariance (ANCOVA) and chi-square tests were respectively used to examine between-class differences in continuous and categorical clinical covariates.Results: A 5-class model emerged as the best-fitting model, including resilience, predominantly PTSD symptoms, predominantly disturbances in self-organization (DSO)symptoms, predominantly CPTSD symptoms, and CPTSD dissociative subtype classes. The CPTSD dissociative subtype class showed the lowest level of functioning and the highest rates of MDD, GAD and childhood trauma.Conclusions: Our findings provide initial empirical evidence supporting the existence of a dissociative subtype of CPTSD, and inform for further research and clinical practice on traumatized individuals.


The present study identified a dissociative subtype of ICD-11 CPTSD among trauma exposed youth.The dissociative subtype of ICD-11 CPTSD was associated with poorer mental health outcomes.Findings of this study provide initial empirical evidence supporting the existence of a dissociative subtype of CPTSD.


Assuntos
Transtornos de Ansiedade , COVID-19 , Transtorno Depressivo Maior , Transtornos Dissociativos , Análise de Classes Latentes , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adolescente , China , Masculino , Feminino , Transtornos Dissociativos/psicologia , Transtornos Dissociativos/epidemiologia , COVID-19/psicologia , COVID-19/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , SARS-CoV-2 , Comorbidade , População do Leste Asiático
2.
Animals (Basel) ; 12(2)2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35049773

RESUMO

The division of hard and soft feces is an effective digestion strategy in the order Lagomorpha. Although previous studies have reported that hard and soft feces differ in morphology and component, the discrepancy in the microbiome remains unclear. This study explored the microbiomes of hard and soft feces in plateau pikas by sequencing the V3 and V4 regions of 16S rDNA. We found that hard feces harbored higher Firmicutes, while soft feces harbored higher Akkermansia. Increased rare bacterial taxa were observed in hard feces compared with soft feces. Moreover, hard and soft feces displayed a greater difference in terms of core operational taxonomy units (OTUs) compared to the total OTUs. The soft feces showed enhancements in all predicted Kyoto Encyclopedia of Genes and Genomes (KEGG) functions, indicating an advancing microbial metabolism compared to hard feces. The significantly upregulated pathways in soft feces were mainly enriched in metabolism of energy and carbohydrate, glycan biosynthesis, cofactors and vitamins, and amino acids-all of which are associated with increased contents of microbial proteins, vitamins, and short-chain fatty acids. Our study reports, for the first time, the differential microbiomes between hard and soft feces of pikas and provides direction for the future studies on cecotrophy.

3.
Integr Zool ; 17(3): 379-395, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35051309

RESUMO

Seasonal variations in gut microbiota of small mammals and how they are influenced by environmental variables are relatively poorly understood. We sampled 162 wild plateau pikas (Ochotona curzoniae) in 4 seasons over 2 and a half years and recorded the air temperature, precipitation, and nutrient content in edible vegetation at the sampling site. After conducting 16S rRNA and shotgun metagenomic sequencing, we found that the highest alpha diversity, the relative abundance of Firmicutes, and the simplest co-occurrence network occurred in winter, whereas the highest relative abundance of Proteobacteria and the most complex network structure were observed in spring. The highest relative abundance of Verrucomicrobiota and Spirochaetota was seen in summer and autumn, respectively. Air temperature, precipitation, and the contents of crude protein, crude fiber, and polysaccharide in vegetation had significant effects on the seasonal changes in gut microbiota. Diet contributed more to microbial variation than climatic factors. Metagenomic analysis revealed that the amino acid metabolism pathway and axillary activity enzymes were most abundant in summer, while abundance of carbohydrate-binding modules and carbohydrate esterases was highest in spring. These microbial variations were related to the changes in dietary nutrition, indicating that gut microbiota of plateau pika contribute to the efficient use of food resources. This study provides new evidence of how external environmental factors affect the intestinal environment of small mammals.


Assuntos
Microbioma Gastrointestinal , Lagomorpha , Animais , Carboidratos , Lagomorpha/genética , RNA Ribossômico 16S/genética , Estações do Ano
4.
Front Microbiol ; 12: 688554, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956107

RESUMO

Several studies have shown that dietary fiber can significantly alter the composition and structure of the gut bacterial community in humans and mammals. However, few researches have been conducted on the dynamics of the bacterial community assembly across different graded levels of dietary fiber in different gut regions. To address this, 24 Durco × Bamei crossbred pigs were randomly assigned to four experimental chows comprising graded levels of dietary fiber. Results showed that the α-and ß-diversity of the bacterial community was significantly different between the cecum and the jejunum. Adding fiber to the chow significantly increased the α-diversity of the bacterial community in the jejunum and cecum, while the ß-diversity decreased. The complexity of the bacterial network increased with the increase of dietary fiber in jejunal content samples, while it decreased in cecal content samples. Furthermore, we found that stochastic processes governed the bacterial community assembly of low and medium dietary fiber groups of jejunal content samples, while deterministic processes dominated the high fiber group. In addition, deterministic processes dominated all cecal content samples. Taken together, the variation of gut community composition and structure in response to dietary fiber was distinct in different gut regions, and the dynamics of bacterial community assembly across the graded levels of dietary fiber in different gut regions was also distinct. These findings enhanced our knowledge on the bacterial community assembly processes in gut ecosystems of livestock.

5.
Microorganisms ; 9(9)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34576785

RESUMO

Interactions between species provide the basis for understanding coexisting mechanisms. The plateau pika (Ochotona curzoniae) and the yak (Bos grunniens) are considered competitors because they have shared habitats and consumed similar food on the Qinghai-Tibetan Plateau for more than 1 million years. Interestingly, the population density of plateau pikas increases with yak population expansion and subsequent overgrazing. To reveal the underlying mechanism, we sequenced the fecal microbial 16S rDNA from both sympatric and allopatric pikas and yaks. Our results indicated that sympatry increased both gut microbial diversity and similarity between pikas and yaks. The abundance of Firmicutes, Proteobacteria, Cyanobacteria, and Tenericutes decreased, while that of Verrucomicrobia increased in sympatric pikas. As for sympatric yaks, Firmicutes, Bacteroidetes, and Spirochaetes significantly increased, while Cyanobacteria, Euryarchaeota, and Verrucomicrobia significantly decreased. In sympatry, plateau pikas acquired 2692 OTUs from yaks, and yaks obtained 453 OTUs from pikas. The predominant horizontally transmitted bacteria were Firmicutes, Bacteroidetes, Verrucomicrobia, and Proteobacteria. These bacteria enhanced the enrichment of pathways related to prebiotics and immunity for pikas, such as heparin sulfate, heparin, chitin disaccharide, chondroitin-sulfate-ABC, and chondroitin-AC degradation pathways. In yaks, the horizontally transmitted bacteria enhanced pathways related to hepatoprotection, xenobiotic biodegradation, and detoxification. Our results suggest that horizontal transmission is a process of selection, and pikas and yaks tend to develop reciprocity through the horizontal transmission of gut microbiota.

6.
Appl Microbiol Biotechnol ; 105(16-17): 6419-6433, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34402940

RESUMO

Plants produce various plant secondary compounds (PSCs) to deter the foraging of herbivorous mammals. However, little is known about whether PSCs can reshape gut microbiota and promote gut homeostasis of hosts. Using 16S rDNA sequencing to investigate the effects of PSCs on the gut microbiota of small herbivorous mammals, we studied plateau pikas (Ochotona curzoniae) fed diets containing swainsonine (SW) extracted from Oxytropis ochrocephala. Our results showed that both long- and short-term treatment of a single artificial diet in the laboratory significantly reduced alpha diversity and significantly affected beta diversity, core bacteria abundance, and bacterial functions in pikas. After SW was added to the artificial diet, the alpha diversity significantly increased in the long-term treatment, and core bacteria (e.g., Akkermansiaceae) with altered relative abundances in the two treatments showed no significant difference compared with pikas in the wild. The complexity of the co-occurrence network structure was reduced in the artificial diet, but it increased after SW was added in both treatments. Further, the abundances of bacteria related to altered alanine, aspartate, and glutamate metabolism in the artificial diet were restored in response to SW. SW further decreased the concentration of short-chain fatty acids (SCFAs) in both treatments. Our results suggest that PSCs play a key role in regulating gut microbiota community and intestinal homeostasis, thereby maintaining host health. KEY POINTS: • Swainsonine improves the intestinal bacterial diversity of plateau pikas. • Swainsonine promotes the recovery of core bacterial abundances in the gut of plateau pikas. • Swainsonine promotes the restoration of intestinal bacterial functions of plateau pikas.


Assuntos
Microbioma Gastrointestinal , Lagomorpha , Animais , Bactérias/genética , Fenômenos Fisiológicos Bacterianos , Swainsonina
7.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34282012

RESUMO

The Qinghai-Tibetan Plateau, with low precipitation, low oxygen partial pressure, and temperatures routinely dropping below -30 °C in winter, presents several physiological challenges to its fauna. Yet it is home to many endemic mammalian species, including the plateau pika (Ochotona curzoniae). How these small animals that are incapable of hibernation survive the winter is an enigma. Measurements of daily energy expenditure (DEE) using the doubly labeled water method show that pikas suppress their DEE during winter. At the same body weight, pikas in winter expend 29.7% less than in summer, despite ambient temperatures being approximately 25 °C lower. Combined with resting metabolic rates (RMRs), this gives them an exceptionally low metabolic scope in winter (DEE/RMRt = 1.60 ± 0.30; RMRt is resting metabolic rate at thermoneutrality). Using implanted body temperature loggers and filming in the wild, we show that this is achieved by reducing body temperature and physical activity. Thyroid hormone (T3 and T4) measurements indicate this metabolic suppression is probably mediated via the thyroid axis. Winter activity was lower at sites where domestic yak (Bos grunniens) densities were higher. Pikas supplement their food intake at these sites by eating yak feces, demonstrated by direct observation, identification of yak DNA in pika stomach contents, and greater convergence in the yak/pika microbiotas in winter. This interspecific coprophagy allows pikas to thrive where yak are abundant and partially explains why pika densities are higher where domestic yak, their supposed direct competitors for food, are more abundant.


Assuntos
Aclimatação , Altitude , Metabolismo Basal , Metabolismo Energético , Fezes/química , Lagomorpha/fisiologia , Estações do Ano , Animais , Tibet
8.
Mater Sci Eng C Mater Biol Appl ; 126: 112109, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34082931

RESUMO

OBJECTIVE: This study aimed to construct a tightly binding antibiotic sustained release system on the polyetheretherketone (PEEK) surface and investigate the cellular activity and antibacterial properties of the new oral implant materials. METHODS: Low-temperature argon plasma under certain parameters was used to prepare P-PEEK with nano-topology, and chemical deposition technology was adopted to form a polydopamine (PDA) coating on the PEEK surface to build a biological binding platform, PDA/P-PEEK. Subsequently, vancomycin gelatin nanoparticles (Van-GNPs) were prepared by two-step desolvation method. Finally, Van-GNPs were combined with PEEK implant material surface to form a new composite material, Van-GNPs/PEEK. scanning electron microscope (SEM), atomic force microscope (AFM), energy dispersive spectrometer (EDS), and contact angle tester were used to comprehensively characterize the materials. The in vitro release test of Van was performed by dynamic dialysis with ultraviolet spectrophotometer. The cell cytotoxicity and adhesion tests were studied by mouse embryonic osteoblasts. The antibacterial properties were evaluated by bacterial adhesion test, plate colony counting, and antimicrobial ring test with Staphylococcus aureus and Streptococcus mutans. RESULTS: PEEK was treated with low-temperature argon plasma and attached to PDA to form a biological binding platform. The synthesized Van-GNPs were smooth, round, with uniform particle size distribution, and bound to PEEK to form a new composite material, which can release Van constantly. Cell experiments showed that Van-GNPs/PEEK had no cytotoxicity and had good interaction with osteoblasts. Bacterial experiments showed that surface conjugation with Van-GNPs could significantly improve the antibacterial performance of PEEK against S. aureus and S. mutans. SIGNIFICANCE: This study demonstrated that Van-GNPs/PEEK have good cellular compatibility and autonomous antibacterial properties, which provide a theoretical basis for the wide application of PEEK in the field of stomatology.


Assuntos
Anti-Infecciosos , Staphylococcus aureus , Animais , Antibacterianos/farmacologia , Benzofenonas , Preparações de Ação Retardada/farmacologia , Cetonas/farmacologia , Camundongos , Polietilenoglicóis , Polímeros , Propriedades de Superfície
9.
Front Microbiol ; 12: 594075, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897627

RESUMO

Domestication is a key factor of genetic variation; however, the mechanism by which domestication alters gut microbiota is poorly understood. Here, to explore the variation in the structure, function, rapidly evolved genes (REGs), and enzyme profiles of cellulase and hemicellulose in fecal microbiota, we studied the fecal microbiota in wild, half-blood, and domestic yaks based on 16S rDNA sequencing, shotgun-metagenomic sequencing, and the measurement of short-chain-fatty-acids (SCFAs) concentration. Results indicated that wild and half-blood yaks harbored an increased abundance of the phylum Firmicutes and reduced abundance of the genus Akkermansia, which are both associated with efficient energy harvesting. The gut microbial diversity decreased in domestic yaks. The results of the shotgun-metagenomic sequencing showed that the wild yak harbored an increased abundance of microbial pathways that play crucial roles in digestion and growth of the host, whereas the domestic yak harbored an increased abundance of methane-metabolism-related pathways. Wild yaks had enriched amounts of REGs in energy and carbohydrate metabolism pathways, and possessed a significantly increased abundance of cellulases and endohemicellulases in the glycoside hydrolase family compared to domestic yaks. The concentrations of acetic, propionic, n-butyric, i-butyric, n-valeric, and i-valeric acid were highest in wild yaks. Our study displayed the domestic effect on the phenotype of composition, function in gut microbiota, and SCFAs associated with gut microbiota, which had a closely association with the growth performance of the livestock. These findings may enlighten the researchers to construct more links between economic characteristics and gut microbiota, and develop new commercial strains in livestock based on the biotechnology of gut microbiota.

10.
Microb Biotechnol ; 14(4): 1300-1315, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33369229

RESUMO

The previous studies have reported that the mammalian gut microbiota is a physiological consequence; nonetheless, the factors influencing its composition and function remain unclear. In this study, to evaluate the contributions of the host and environment to the gut microbiota, we conducted a sequencing analysis of 16S rDNA and shotgun metagenomic DNA from plateau pikas and yaks, two sympatric herbivorous mammals, and further compared the sequences in summer and winter. The results revealed that both pikas and yaks harboured considerably more distinct communities between summer and winter. We detected the over-representation of Verrucomicrobia and Proteobacteria in pikas, and Archaea and Bacteroidetes in yaks. Firmicutes and Actinobacteria, associated with energy-efficient acquisition, significantly enriched in winter. The diversity of the microbial community was determined by the interactive effects between the host and season. Metagenomic analysis revealed that methane-metabolism-related pathway of yaks was significantly enriched in summer, while some pathogenic pathways were more abundant in pikas. Both pikas and yaks had a higher capacity for lipid degradation in winter. Pika and yak shared more OTUs when food shortage occurred in winter, and this caused a convergence in gut microbial composition and function. From winter to summer, the network module number increased from one to five in pikas, which was different in yaks. Our study demonstrates that the host is a dominant factor in shaping the microbial communities and that seasonality promotes divergence or convergence based on dietary quality across host species identity.


Assuntos
Microbioma Gastrointestinal , Lagomorpha , Microbiota , Animais , Bactérias/genética , Firmicutes/genética
11.
J Endourol ; 35(4): 436-443, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32935565

RESUMO

Purpose: To investigate the clinical value of contrast-enhanced ultrasound (CEUS) in percutaneous nephrolithotomy (PCNL) for kidney stone patients without hydronephrosis. Methods: Patients with nondilated collecting system kidney stones who underwent PCNL between October 2018 and December 2019 at our hospital were enrolled in this study. Patients who met the inclusion criteria were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided PCNL group. The operation results of the two groups were compared, including the number of attempts for effective puncture, duration to effective puncture, stone clearance rate, blood loss, postoperative complications, and hospital stay. Results: Fifty-six patients with a nondilated collecting system who underwent PCNL for 60 kidneys were included in this study, including 4 patients who underwent bilateral PCNL due to bilateral renal stones. There were 30 kidneys in each group. All patients successfully underwent PCNL. The CEUS-guided PCNL group had more accurate punctures, with a higher effective rate of one puncture and shorter puncture time. There was no statistically significant difference in stone clearance rate between the two groups. Four cases of double channels were established in the conventional US-guided PCNL group, while there was only one case in the CEUS-guided PCNL group. In the CEUS-guided PCNL group, most cases (96.7%, 29/30) had no or only mild complications, which were significantly better than the conventional US-guided PCNL group (76.7%, 23/30). The mean postoperative hemoglobin loss in the CEUS-guided PCNL group was 9.5 (range 1-25) g/L, which was significantly lower than 15.5 (range 5-52) g/L in the conventional US-guided PCNL group. Conclusion: The CEUS technique can improve visibility of the nondilated renal collecting system, facilitate selection of suitable calix, and identify renal calix fornix. It also benefits needle placement in patients with a nondilated collecting system.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Humanos , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Punções , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia
12.
Microorganisms ; 8(9)2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32872148

RESUMO

Animal gut microbiomes can be clustered into "enterotypes" characterized by an abundance of signature genera. The characteristic determinants, stability, and resilience of these community clusters remain poorly understood. We used plateau pika (Ochotona curzoniae) as a model and identified three enterotypes by 16S rDNA sequencing. Among the top 15 genera, 13 showed significantly different levels of abundance between the enterotypes combined with different microbial functions and distinct fecal short-chain fatty acids. We monitored changes in the microbial community associated with the transfer of plateau pikas from field to laboratory and observed that feeding them a single diet reduced microbial diversity, resulting in a single enterotype with an altered composition of the dominant bacteria. However, microbial diversity, an abundance of some changed dominant genera, and enterotypes were partially restored after adding swainsonine (a plant secondary compound found in the natural diet of plateau pikas) to the feed. These results provide strong evidence that gut microbial diversity and enterotypes are directly related to specific diet, thereby indicating that the formation of different enterotypes can help animals adapt to complex food conditions. Additionally, natural plant secondary compounds can maintain dominant bacteria and inter-individual differences of gut microbiota and promote the resilience of enterotypes in small herbivorous mammals.

13.
Front Pediatr ; 8: 138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32363169

RESUMO

The mutations in the ABCA3 (ATP-binding cassette transporter subfamily A member 3) gene could result in lethal respiratory distress syndrome (RDS) in neonates and interstitial lung disease (ILD) in infants and children. Here, we describe a full-term newborn who manifested respiratory distress 20 min after birth and then gradually developed hypoxemic respiratory failure and died on 53 days of life. A homozygous missense mutation (c.746C >T) was identified in exon 8 of ABCA3 gene in the neonate by next-generation sequencing, and the mutations were inherited from parents, respectively. This homozygous mutation is the first reported to date.

14.
Urol Int ; 104(5-6): 402-409, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31910427

RESUMO

BACKGROUND: En bloc transurethral resection (ERBT) is a major topic of discussion as an alternative to conventional transurethral resection (cTURBT) for the treatment of non-muscle-invasive bladder cancer (NMIBC) addressing the limitations of cTURBT. METHODS: We searched through electronic databases including Embase, Cochrane Library, MEDLINE, Web of Science, PubMed, and Google Scholar for articles published up to April 1, 2019; RevMan 5.3 was used to conduct this meta-analysis. Results were expressed as 95% confidence intervals (CI) and risk differences (RD). RESULTS: Nine trials met the inclusion criteria (n = 1,020 patients): 1 study was a randomized controlled trial including a total of 142 participants, 4 studies had a prospective paired design including 605 patients, and 4 studies were retrospective (n = 273 patients). Duration of continuous postoperative bladder irrigation (RD -0.16; 95% CI -3.47 to 0.28; I2 = 97%; p = 0.10) and operation time (RD 0.05; 95% CI -0.23 to 0.32; I2 = 79%; p = 0.74) were not significantly different between ERBT and cTURBT. However, hospitalization time (I2 = 96%; χ2 = 203.16; p = 0.01) and catheterization time (I2 = 95%; χ2 = 163.24; p = 0.02), as well as 24-month recurrence rate (I2 = 0%; χ2 = 0.98; p = 0.008) were significantly better using the ERBT scheme. The incidence of urethral stricture between both schemes (95% CI -0.03 to 0.02; p = 0.50) was not different, but complications such as obturator nerve reflex (95% CI 0.01 to 0.12; p < 0.00001) and bladder perforation (95% CI 0.05 to 0.59; p = 0.50) were less frequent in the ERBT group. CONCLUSION: ERBT is an effective treatment approach with some advantages for NMIBC. Our meta-analysis revealed that hospitalization time, catheterization time, and 24-month recurrence rate is superior in patients treated with ERBT than cTURBT, and ERBT patients also have a lower complication rate. Furthermore, ERBT improves the quality of tumor specimens and decreases the frequency of repeat transurethral bladder cancer resection. Further randomized controlled trials are needed to confirm our results.


Assuntos
Cistectomia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Humanos , Invasividade Neoplásica , Uretra , Neoplasias da Bexiga Urinária/patologia
15.
Food Chem Toxicol ; 97: 150-158, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27587080

RESUMO

Our previous study demonstrated that a combination of alternative medicine berberine and conventional 5-aminosalicylic acid (5-ASA) showed promise to be a novel therapeutic strategy for ulcerative colitis (UC). This present study aims to sketch the pre-clinical toxicity profile of this combination (1:10 dose ratio) on mice. In acute toxicity test, the determined median lethal dose (LD50) was 278.7 mg/kg berberine plus 2787 mg/kg 5-ASA. The results from subacute toxicity test demonstrated that no toxic signs of clinical symptoms, no significant changes in hematological or biochemical parameters were detected in mice treated with 14 + 140, 28 + 280 or 56 + 560 mg/kg of berberine plus 5-ASA treatment. Histological examinations revealed that accompanied with an increase in spleen weight, frequently recorded enlargement and white pulp hyperplasia of spleen were detected in mice when exposed to three doses of combination treatments. Further in vitro assessment suggested that the spleen toxicity was originated from berberine by its inhibition in cell viability and cell proliferation of lymphocytes. The results of this study indicate that the combination of berberine and 5-ASA shows a slight toxic effect on spleen, suggesting that this combination should be used with caution for patients.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Berberina/toxicidade , Eritrócitos/patologia , Linfócitos/patologia , Mesalamina/toxicidade , Testes de Toxicidade/métodos , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Berberina/administração & dosagem , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/efeitos dos fármacos , Feminino , Linfócitos/efeitos dos fármacos , Masculino , Mesalamina/administração & dosagem , Camundongos , Camundongos Endogâmicos ICR
16.
PLoS One ; 10(12): e0144101, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26642326

RESUMO

Ulcerative colitis (UC) is a common chronic remitting disease but without satisfactory treatment. Alternative medicine berberine has received massive attention for its potential in UC treatment. Conventional therapies with the addition of berberine are becoming attractive as novel therapies in UC. In the present study, we investigated the preclinical activity of a conventional oral 5-aminosalicylic acid (5-ASA) therapy plus berberine in experimental colitis. A subclinical dose of 5-ASA (200 mg/kg/day) alone or 5-ASA plus berberine (20 mg/kg/day) was orally administered for 30 days to C57BL/6 mice with colitis induced by three cycles of 2% dextran sulfate sodium (DSS). The disease severity, inflammatory responses, drug accumulation and potential toxicity of colitis mice were examined. The results showed that comparing to 5-ASA alone, 5-ASA plus berberine more potently ameliorated DSS-induced disease severity, colon shortening, and colon histological injury. Further, the up-regulation in mRNA level of colonic TNF-α as well as NFκB and JAK2 phosphorylation caused by DSS were more pronouncedly reversed in animals treated with the combination therapy than those treated with 5-ASA alone. Moreover, the addition of berberine to 5-ASA more significantly inhibited lymphocyte TNF-α secretion of DSS mice than 5-ASA alone. In the meanwhile, no extra drug accumulation or potential toxicity to major organs of colitis mice was observed with this combination treatment. In summary, our studies provide preclinical rationale for the addition of berberine to 5-ASA as a promising therapeutic strategy in clinic by reducing dose of standard therapy.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Berberina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Mesalamina/uso terapêutico , Animais , Berberina/efeitos adversos , Células Cultivadas , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/patologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Quimioterapia Combinada , Janus Quinase 2/metabolismo , Masculino , Mesalamina/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/biossíntese
17.
Sci Rep ; 5: 12095, 2015 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-26160593

RESUMO

A novel neuropeptide spexin was found to be broadly expressed in various endocrine and nervous tissues while little is known about its functions. This study investigated the role of spexin in bowel movement and the underlying mechanisms. In functional constipation (FC) patients, serum spexin levels were significantly decreased. Consistently, in starved mice, the mRNA of spexin was significantly decreased in intestine and colon. Spexin injection increased the velocity of carbon powder propulsion in small intestine and decreased the glass beads expulsion time in distal colon in mice. Further, spexin dose-dependently stimulated the intestinal/colonic smooth muscle contraction. Galanin receptor 2 (GALR2) antagonist M871, but not Galanin receptor 3 (GALR3) antagonist SNAP37899, effectively suppressed the stimulatory effects of spexin on intestinal/colonic smooth muscle contraction, which could be eliminated by extracellular [Ca(2+)] removal and L-type voltage-dependent Ca(2+) channel (VDCC) inhibitor nifedipine. Besides, spexin dramatically increased the [Ca(2+)]i in isolated colonic smooth muscle cells. These data indicate that spexin can act on GALR2 receptor to regulate bowel motility by activating L-type VDCC. Our findings provide evidence for important physiological roles of spexin in GI functions. Selective action on spexin pathway might have therapeutic effects on GI diseases with motility disorders.


Assuntos
Canais de Cálcio Tipo L/metabolismo , Constipação Intestinal/metabolismo , Trânsito Gastrointestinal/fisiologia , Hormônios Peptídicos/metabolismo , Receptor Tipo 2 de Galanina/metabolismo , Animais , Cálcio/metabolismo , Estudos de Casos e Controles , Colo/efeitos dos fármacos , Colo/metabolismo , Constipação Intestinal/tratamento farmacológico , Feminino , Trânsito Gastrointestinal/efeitos dos fármacos , Humanos , Indóis/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Neuropeptídeos/metabolismo , Nifedipino/uso terapêutico , Peptídeos/uso terapêutico , Receptor Tipo 2 de Galanina/antagonistas & inibidores , Receptor Tipo 3 de Galanina/antagonistas & inibidores , Receptor Tipo 3 de Galanina/metabolismo
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