BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/aut...BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in animals.METHODS Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the HCC-group.The opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P<0.05).Carm1 was lower in HCC compared to RIF(P<0.05).Hepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(P<0.05).Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P<0.05).miR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(P<0.05).There was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.展开更多
Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic ...Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.展开更多
BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA ...BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.METHODS Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were collected.Following fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™system.RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides distasonis.The functional prediction provided two different metabolic profiles between MASLD and LOLA.The 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis.The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.展开更多
Several therapies have shown obvious effects on structural conservation contributing to motor functional recovery after spinal cord injury(SCI).Nevertheless, neither strategy has achieved a convincing effect.We purpos...Several therapies have shown obvious effects on structural conservation contributing to motor functional recovery after spinal cord injury(SCI).Nevertheless, neither strategy has achieved a convincing effect.We purposed a combined therapy of immunomodulatory peptides that individually have shown significant effects on motor functional recovery in rats with SCI.The objective of this study was to investigate the effects of the combined therapy of monocyte locomotion inhibitor factor(MLIF), A91 peptide, and glutathione monoethyl ester(GSH-MEE) on chronic-stage spinal cord injury.Female Sprague-Dawley rats underwent a laminectomy of the T9 vertebra and a moderate contusion.Six groups were included: sham, PBS, MLIF + A91, MLIF + GSH-MEE, A91 + GSH-MEE, and MLIF + A91 + GSH-MEE.Two months after injury, motor functional recovery was evaluated using the open field test.Parenchyma and white matter preservation was evaluated using hematoxylin & eosin staining and Luxol Fast Blue staining, respectively.The number of motoneurons in the ventral horn and the number of axonal fibers were determined using hematoxylin & eosin staining and immunohistochemistry, respectively.Collagen deposition was evaluated using Masson's trichrome staining.The combined therapy of MLIF, A91, and GSH-MEE greatly contributed to motor functional recovery and preservation of the medullary parenchyma, white matter, motoneurons, and axonal fibres, and reduced the deposition of collagen in the lesioned area.The combined therapy of MLIF, A91, and GSH-MEE preserved spinal cord tissue integrity and promoted motor functional recovery of rats after SCI.This study was approved by the National Commission for Scientific Research on Bioethics and Biosafety of the Instituto Mexicano del Seguro Social under registration number R-2015-785-116(approval date November 30, 2015) and R-2017-3603-33(approval date June 5, 2017).展开更多
Glial cell activation and neuroinflammation in multiple sclerosis(MS):MS is an irreversible and progressive central nervous system(CNS)disease which originates in the autoimmune attack of lymphocytes against CNS myeli...Glial cell activation and neuroinflammation in multiple sclerosis(MS):MS is an irreversible and progressive central nervous system(CNS)disease which originates in the autoimmune attack of lymphocytes against CNS myelin.This specialized membrane,synthesized by oligodendrocytes(OL)in the CNS,provides metabolic support to axons and allows for saltatory conduction in neurons.The lack of myelin(i.e.,demyelination)leads to axonal degeneration,neuronal death,and the consequent neurological disabilities(Franklin and Ffrench-Constant,2017).展开更多
This study delves into the life and significant contributions of René Théophile Hyacinthe Laennec,a prominent French physician of the 19^(th) century,and thoroughly examines his revolutionary creation,the st...This study delves into the life and significant contributions of René Théophile Hyacinthe Laennec,a prominent French physician of the 19^(th) century,and thoroughly examines his revolutionary creation,the stethoscope.Laennec’s innovative spirit not only revolutionized medical diagnosis during his time but also left a lasting imprint on the broader field of medicine,influencing healthcare for generations.This extensive inquiry covers various aspects,including his historical context,the development of the stethoscope,its profound implications for medical diagnosis,and its enduring impact on the history of medicine.展开更多
Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied i...Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied in clinical practice. In this study, we analyzed the combination of different strategies as a potential therapy for spinal cord injury. Immunization with neural derived peptides(INDP), inhibition of glial scar formation(dipyridyl: DPY), as well as the use of biocompatible matrix(fibrin glue: FG) impregnated with bone marrow mesenchymal stem cells(MSCs) were combined and then its beneficial effects were evaluated in the induction of neuroprotection and neuroregeneration after acute SCI. Sprague-Dawley female rats were subjected to a moderate spinal cord injury and then randomly allocated into five groups: 1) phosphate buffered saline; 2) DPY; 3) INDP + DPY; 4) DPY+ FG; 5) INDP + DPY + FG + MSCs. In all rats, intervention was performed 72 hours after spinal cord injury. Locomotor and sensibility recovery was assessed in all rats. At 60 days after treatment, histological examinations of the spinal cord(hematoxylin-eosin and Bielschowsky staining) were performed. Our results showed that the combination therapy(DPY+ INDP + FG+ MSCs) was the best strategy to promote motor and sensibility recovery. In addition, significant increases in tissue preservation and axonal density were observed in the combination therapy group. Findings from this study suggest that the combination theapy(DPY+ INDP + FG + MSCs) exhibits potential effects on the protection and regeneration of neural tissue after acute spinal cord injury. All procedures were approved by the Animal Bioethics and Welfare Committee(approval No. 178544; CSNBTBIBAJ 090812960)on August 15, 2016.展开更多
A differential pulse voltammetry (DPV) method for amantadine (AT) determination is developed. To this end, all the chemical and instrumental variables affecting the determination of amantadine are optimized. These stu...A differential pulse voltammetry (DPV) method for amantadine (AT) determination is developed. To this end, all the chemical and instrumental variables affecting the determination of amantadine are optimized. These studies have used three types of glassy-carbon electrode, first electrode which has not undergone surface modification or coating, to then modify the working electrode surface with two kinds of suspensions: graphene and graphene-cucurbit[7]uril (CB[7]). From studies of the mechanisms governing the electrochemical response of amantadine, it was concluded that it is an electrochemically system with a diffusive reduction phenomenon. Under optimal conditions and with the appropriate electrode modification, we proceed to study the relation between the peak intensity with the analyte concentration. Thus, we find that when the electrode surface is covered with graphene-CB[7], two linear sections are obtained, the first one in the concentration range of between 0.05 μg·mL﹣1 and 0.75 μg·mL﹣1;and the second one between 1.00 μg·mL﹣1 and 6.00 μg·mL﹣1, with Er (%) = 87 and R.S.D. = 0.94% (n = 10 at 0.5 μg·mL﹣1 level). The minimum detectable amount was 15 ng·mL﹣1 while a concentration of 44 ng·mL﹣1 was calculated as determination limit. The optimized method was applied to the determination of amantadine in biological fluids.展开更多
Spinal cord injury (SCI) is a degenerative disease that causes an important neurological impairment, it is a medically complex and life-disrupting condition. SCI has a devastating impact on international health syst...Spinal cord injury (SCI) is a degenerative disease that causes an important neurological impairment, it is a medically complex and life-disrupting condition. SCI has a devastating impact on international health systems due to its irreversible consequences and lack of efficient treatment, affecting mostly young population within their productive years. Global SCI incidence in high-income countries is 40 to 80 new cases per million per year,展开更多
The general objective of this article was to construct and describe the psychometric properties of a scale of selfcare behaviors against COVID-19.It was a descriptive,cross-sectional,psychometric validation study of a...The general objective of this article was to construct and describe the psychometric properties of a scale of selfcare behaviors against COVID-19.It was a descriptive,cross-sectional,psychometric validation study of a scale created to measure self-care behaviors in relation to COVID-19 in a total sample of 333 probabilistically selected.Qualitative validity was evaluated by a review of 10 experts and quantitative validity by means of exploratory factor analysis using the principal components method.Internal consistency was measured with Cronbach’s alpha twice and the test-retest was evaluated by calculating the intraclass coefficient.The final scale consisted of 29 items.The Kaiser-Meyer-Olkin test of adequacy yielded a value of 0.926,and the Bartlett’s test of sphericity X^(2)=4611 with a p-value<0.001.The variance explained by the three retained factors with a total of 29 items was 50.03%.The Cronbach’s alpha internal consistency evaluation yielded an initial value of 0.923 and,in a second evaluation,showed a value of 0.936.In addition,the intraclass coefficient in the test-retest yielded a value of 0.929.The instrument created and validated possessed the necessary conditions as a useful and reliable tool for measuring self-care behaviors in relation to COVID-19 in a population of university students and it is important that it can be applied in other regions of the world.展开更多
Objective: To evaluate the role of regulatory T cells (Tregs) at late stages of stroke. Methods:Anti-CD25 antibody (or PBS as a control) was injected to reduce the pool of Tregs in Wistar rats;then, ischemia was induc...Objective: To evaluate the role of regulatory T cells (Tregs) at late stages of stroke. Methods:Anti-CD25 antibody (or PBS as a control) was injected to reduce the pool of Tregs in Wistar rats;then, ischemia was induced transiently by middle cerebral artery occlusion during 60 min and reperfusion was allowed for 7 d. Then, Treg frequency was analyzed in peripheral blood, spleen and lymph nodes. Neurological score (0-6) and infarct volume were also determined. Results: Nine days after injection, the CD4+CD25+ T cells were reduced by 70.4%, 44.8% and 57.9% in peripheral blood, spleen and lymph nodes, respectively compared to PBS-treated rats. In contrast, the reduction of CD4+FOXP3+ T cells was lower in the same compartments (38.6%, 12.5%, and 29.5%, respectively). The strongest reduction of CD25+CD4+ T cells was observed in those FOXP3-negative cells in blood, spleen and lymph nodes (77.8%, 52.8%, and 60.7%, respectively), most likely corresponding to activated T cells. Anti-CD25-treated transient middle cerebral artery occlusion rats had a lower neurological deficit and did not develop tissue damage compared with PBS-treated animals. Conclusions: These findings suggest that treatment with anti-CD25 in our model preferentially reduce the T cell population with an activated phenotype, rather than the Treg population, leading to neuroprotection by suppressing the pathogenic response of effector T cells.展开更多
Depressive disorders are recognized as one of the most common mental health conditions across different age groups.However,the risk factors associated with depression among older people from low-and middle-income coun...Depressive disorders are recognized as one of the most common mental health conditions across different age groups.However,the risk factors associated with depression among older people from low-and middle-income countries remains unclear.This study aims to identify socio-demographic,health and psychosocial-related factors associated with depression in Chilean older adults.A cross-sectional study was carried out in a representative sample of 1,765 adults aged≥60 years participants from the Chilean National Health Survey 2016–2017.Depres-sion was assessed with the Composite International Diagnostic Interview(CIDI-SF).Associations between the exposure variables and depression were investigated using Poisson regression analyses.The mainfindings indi-cated that women showed higher likelihood of depression than men(Prevalence Ratio(PR)=2.6[95%CI:1.40;4.89]).An increased likelihood of depression was found in older adults with chronic pain,multimorbidity(≥2 diseases),previous diagnose of depression,high perception of stress,financial stress,and difficulties for social par-ticipation.In women,higher likelihood of depression was found for those with the frailty phenotype(PR:8.53[95%CI:1.68;43.32]),rheumatoid arthritis(PR:2.41[95%CI:1.34;4.34]),insomnia(PR:2.99[95%CI:1.74;5.12])and low self-rated well-being(PR:4.94[95%CI:2.26;10.79]).Men who were divorced(PR:7.10[95%CI:1.44;34.90])or widowed(PR:10.83[95%CI:3.71;31.58]),obese(PR:5.08[95%CI:1.48;17.42])and who had asthma(PR:7.60[95%CI:2.31;24.99])were associated with higher odds of depression.The currentfindings may have clinical implications for the early identification of older adults more susceptible to depression and also suggest the need to implement cultural and age-sensitive strategies to promote mental health in late life.展开更多
AIM: To analyze the attitude of Spanish medical students toward living liver donation (LLD) and to establish which factors have an influence on this attitude.METHODS: Study type: A sociological, interdisciplinary, mul...AIM: To analyze the attitude of Spanish medical students toward living liver donation (LLD) and to establish which factors have an influence on this attitude.METHODS: Study type: A sociological, interdisciplinary, multicenter and observational study. Study population: Medical students enrolled in Spain (n = 34000) in the university academic year 2010-2011. Sample size: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire (PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. Statistical analysis: Student´s t test, χ<sup>2</sup> test and logistic regression analysis.RESULTS: The completion rate was 95.7% (n = 9275). 89% (n = 8258) were in favor of related LLD, and 32% (n = 2937) supported unrelated LLD. The following variables were associated with having a more favorable attitude: (1) age (P = 0.008); (2) sex (P < 0.001); (3) academic year (P < 0.001); (4) geographical area (P = 0.013); (5) believing in the possibility of needing a transplant oneself in the future (P < 0.001); (6) attitude toward deceased donation (P < 0.001); (7) attitude toward living kidney donation (P < 0.001); (8) acceptance of a donated liver segment from a family member if one were needed (P < 0.001); (9) having discussed the subject with one’s family (P < 0.001) and friends (P < 0.001); (10) a partner’s opinion about the subject (P < 0.001); (11) carrying out activities of an altruistic nature; and (12) fear of the possible mutilation of the body after donation (P < 0.001).CONCLUSION: Spanish medical students have a favorable attitude toward LLD.展开更多
Efficient technologies for gene silencing would be important to carry out functional analysis with P. brasiliensis genes, as well as for a better understanding of the biology and pathogenesis of this pathogenic fungus...Efficient technologies for gene silencing would be important to carry out functional analysis with P. brasiliensis genes, as well as for a better understanding of the biology and pathogenesis of this pathogenic fungus. Due to the fact that homologous recombination is unusual in P. brasiliensis, the development of knockout isolates is currently non-feasible. The goal of this work was to assess RNA interference (RNAi) technology as an alternative tool for gene silencing previously employed successfully in H. capsulatum. For this purpose, we built different inverted repeat transgenic hairpin constructs to down-regulate the PbGP43 and PbP27 genes known to codify for two fungal immunogenic proteins that elicit a strong immune response during experimental paracoccidioidomycosis. Using the RNAi strategy, a reduction in the mRNA levels of the PbGP43 and PbP27 genes was observed during the first 20 days after selection;however, in the transformed yeast cells, the gene silencing status proved non-stable through the assay. We demonstrated that electrotransformation was suitable to transform P. brasiliensis yeast cells and integrate the hairpin constructions;nonetheless, gene silencing was not stable along the experimental time. A detailed analysis of the underlying molecular RNAi machinery may provide further insights into the intracellular mechanism that governs this reverse genetic tool.展开更多
Background The positive influence of most types of exercise has been reported repeatedly,but what the most effective exercise approaches are for improving health-related quality of life(HRQoL)in people with cancer rem...Background The positive influence of most types of exercise has been reported repeatedly,but what the most effective exercise approaches are for improving health-related quality of life(HRQoL)in people with cancer remains unknown.The aim of this systematic review and network meta-analysis was to synthesize the evidence from intervention studies to assess the effects of different types of exercise on HRQoL during and after cancer treatment.Methods MEDLINE,SPORTDiscus,the Cochrane Library,Web of Science,and Scopus were searched for randomized controlled trials aimed at testing the effects of exercise interventions meant to improve HRQoL in people with cancer.Separate analyses were conducted for HRQoL as measured by general and cancer-specific questionnaires.We also evaluated whether the effects of exercise were different during and after cancer treatment in both the physical and mental HRQoL domains.Results In total,93 studies involving 7435 people with cancer were included.Network effect size estimates comparing exercise intervention vs.usual care were significant for combined exercise(0.35,95%confidence interval(95%CI):0.14–0.56)for HRQoL as measured by general questionnaires,and for combined(0.31,95%CI:0.13–0.48),mind–body exercise(0.54,95%CI:0.18–0.89),and walking(0.39,95%CI:0.04–0.74)for HRQoL as measured by cancer-specific questionnaires.Conclusion Exercise programs combining aerobic and resistance training can be recommended to improve HRQoL during and after cancer treatment.The scarcity and heterogeneity of these studies prevents us from making recommendations about other exercise modalities due to insufficient evidence.展开更多
Brucellosis is an infectious disease of worldwide distribution, which has a great economic impact due to the productive and reproductive losses that it causes, in addition to the serious public health problem. The aim...Brucellosis is an infectious disease of worldwide distribution, which has a great economic impact due to the productive and reproductive losses that it causes, in addition to the serious public health problem. The aim of this study is to estimate the economic losses, through financial analysis, caused by bovine brucellosis in the province of Carchi, over a one-year period. A random sampling was used to determine the prevalence in the study area, where 2976 animals were considered, and the Rose Bengal (RB) test was used as a screening test and the Fluorescence Polarized Assay (FPA) as a confirmatory test, obtaining a prevalence of 8.2% (244/2976). In addition, parameters associated to the losses caused by brucellosis in cattle were determined by literature review. To estimate costs, field information was collected through a survey of a total of 100 randomly selected farmers. The loss estimated due to calves lost as a result of abortions and neonatal death was USD. 79170.00. The loss due to death of 4 cows as a result of metritis was estimated at USD. 5000.00. The cost of examination and treatment of aborted cows was USD. 20100.00. The losses due to reduction in milk production from aborted and non-aborted seropositive cows were estimated at USD. 158114.21. The financial losses due to brucellosis in province of Carchi were estimated at USD. 262384.21.展开更多
BACKGROUND: Proliferation of hepatic stellate cells (HSCs) plays a pivotal role in the progression of liver fibrosis conse- quent to chronic liver injury. Silibinin, a flavonoid compound, has been shown to possess ...BACKGROUND: Proliferation of hepatic stellate cells (HSCs) plays a pivotal role in the progression of liver fibrosis conse- quent to chronic liver injury. Silibinin, a flavonoid compound, has been shown to possess anti-fibrogenic effects in animal models of liver fibrosis. This was attributed to an inhibition of cell proliferation of activated HSCs. The present study was to gain insight into the molecular pathways involved in silibinin anti-fibrogenic effect. METHODS: The study was conducted on LX-2 human stellate cells treated with three concentrations of silibinin (10, 50 and 100 μmol/L) for 24 and 96 hours. At the end of the treatment cell viability and proliferation were evaluated. Protein expression of p27, p21, p53, Akt and phosphorylated-Akt was evaluated by Western blotting analysis and Ki-67 protein expression was by immunocytochemistry. Sirtuin activity was evaluated by chemiluminescence based assay. RESULTS: Silibinin inhibits LX-2 cell proliferation in doseand time-dependent manner; we showed that silibinin upregulated the protein expressions of p27 and p53. Such regulation was correlated to an inhibition of both downstream Akt and phosphorylated-Akt protein signaling and Ki-67 protein expression. Sirtuin activity also was correlated to silibinin- inhibited proliferation of LX-2 cells. CONCLUSION: The anti-proliferative effect of silibinin on LX-2 human steUate cells is via the inhibition of the expres- sions of various cell cycle targets including p27, Akt and sir- tuin signaling.展开更多
BACKGROUND The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate...BACKGROUND The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16 S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease(IBD) is abnormal and characterized by reduced diversity. Micro RNAs(miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn's disease(CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut microbiota.AIM To investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut microbiota.METHODS Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of newonset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16 S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MGRAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative PCR.RESULTS Microbial community was characterized using 16 S rRNA gene sequencing in 29 samples(n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group(5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showed that a lower metabolism of carbohydrates(P = 0.000) was found in CD group, while the metabolism of lipids was increased. In CD patients, three miRNAs were induced in affected mucosa: mir-144(6.2 ± 1.3 fold), mir-519(21.8 ± 3.1) and mir-211(2.3 ± 0.4). CONCLUSION Changes in microbial function in active non-treated CD subjects and three miRNAs in affected vs non-affected mucosa have been found. miRNAs profile may serve as a biomarker.展开更多
Objective: To evaluate the susceptibility of Pseudomonas aeruginosa(P. aeruginosa)in vitro to the ethanolic extracts obtained from five different Peruvian medicinal plants.Methods: The plants were chopped and soaked i...Objective: To evaluate the susceptibility of Pseudomonas aeruginosa(P. aeruginosa)in vitro to the ethanolic extracts obtained from five different Peruvian medicinal plants.Methods: The plants were chopped and soaked in absolute ethanol(1:2, w/v). The antibacterial activity of compounds against P. aeruginosa was evaluated using the cupplate agar diffusion method.Results: The extracts from Maytenus macrocarpa("Chuchuhuasi"), Dracontium loretense Krause("Jergon Sacha"), Tabebuia impetiginosa("Tahuari"), Eucalyptus camaldulensis Dehn(eucalyptus), Uncaria tomentosa("U?a de gato") exhibited favorable antibacterial activity against P. aeruginosa. The inhibitory effect of the extracts on the strains of P. aeruginosa tested demonstrated that Tabebuia impetiginosa and Maytenus macrocarpa possess higher antibacterial activity.Conclusions: The results of the present study scientifically validate the inhibitory capacity of the five medicinal plants attributed by their common use in folk medicine and contribute towards the development of new treatment options based on natural products.展开更多
基金Supported by the following Brazilian funding agencies:Financiamento e IncentivoàPesquisa from Hospital de Clínicas de Porto Alegre(FIPE/HCPA),No.2021-0105(toÁlvares-da-Silva MR)Coordination for the Improvement of Higher Education Personnel,CAPES/PNPDand this study was financed in part by the Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)(toÁlvares-da-Silva MR).
文摘BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in animals.METHODS Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the HCC-group.The opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P<0.05).Carm1 was lower in HCC compared to RIF(P<0.05).Hepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(P<0.05).Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P<0.05).miR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(P<0.05).There was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.
基金supported by Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT)#1200836,#1210644,and#1240888,and Agencia Nacional de Investigación y Desarrollo(ANID)-FONDAP#15130011(to LL)FONDECYT#3230227(to MFG).
文摘Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.
基金Financiamento e IncentivoàPesquisa from Hospital de Clínicas de Porto Alegre(FIPE/HCPA),No.2020-0037Coordination for the Improvement of Higher Education Personnel,CAPES/PNPDand the Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq).
文摘BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.METHODS Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were collected.Following fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™system.RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides distasonis.The functional prediction provided two different metabolic profiles between MASLD and LOLA.The 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis.The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.
基金supported by Fondo de Investigación en Salud of the Instituto Mexicano del Seguro Social (IMSS), under the support No.FIS/IMSS/PROT/ G17/1676 and FIS/IMSS/PROT/G18/1825the scholarship granted to the students of Master’s degree by Consejo Nacional de Ciencia y Tecnología (CONACYT) and IMSS。
文摘Several therapies have shown obvious effects on structural conservation contributing to motor functional recovery after spinal cord injury(SCI).Nevertheless, neither strategy has achieved a convincing effect.We purposed a combined therapy of immunomodulatory peptides that individually have shown significant effects on motor functional recovery in rats with SCI.The objective of this study was to investigate the effects of the combined therapy of monocyte locomotion inhibitor factor(MLIF), A91 peptide, and glutathione monoethyl ester(GSH-MEE) on chronic-stage spinal cord injury.Female Sprague-Dawley rats underwent a laminectomy of the T9 vertebra and a moderate contusion.Six groups were included: sham, PBS, MLIF + A91, MLIF + GSH-MEE, A91 + GSH-MEE, and MLIF + A91 + GSH-MEE.Two months after injury, motor functional recovery was evaluated using the open field test.Parenchyma and white matter preservation was evaluated using hematoxylin & eosin staining and Luxol Fast Blue staining, respectively.The number of motoneurons in the ventral horn and the number of axonal fibers were determined using hematoxylin & eosin staining and immunohistochemistry, respectively.Collagen deposition was evaluated using Masson's trichrome staining.The combined therapy of MLIF, A91, and GSH-MEE greatly contributed to motor functional recovery and preservation of the medullary parenchyma, white matter, motoneurons, and axonal fibres, and reduced the deposition of collagen in the lesioned area.The combined therapy of MLIF, A91, and GSH-MEE preserved spinal cord tissue integrity and promoted motor functional recovery of rats after SCI.This study was approved by the National Commission for Scientific Research on Bioethics and Biosafety of the Instituto Mexicano del Seguro Social under registration number R-2015-785-116(approval date November 30, 2015) and R-2017-3603-33(approval date June 5, 2017).
基金supported by the VRIP-UA Ph D fellowshipsupported by Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT)11160616 and DIUA166-2019(VRIP-UA)to FCO。
文摘Glial cell activation and neuroinflammation in multiple sclerosis(MS):MS is an irreversible and progressive central nervous system(CNS)disease which originates in the autoimmune attack of lymphocytes against CNS myelin.This specialized membrane,synthesized by oligodendrocytes(OL)in the CNS,provides metabolic support to axons and allows for saltatory conduction in neurons.The lack of myelin(i.e.,demyelination)leads to axonal degeneration,neuronal death,and the consequent neurological disabilities(Franklin and Ffrench-Constant,2017).
文摘This study delves into the life and significant contributions of René Théophile Hyacinthe Laennec,a prominent French physician of the 19^(th) century,and thoroughly examines his revolutionary creation,the stethoscope.Laennec’s innovative spirit not only revolutionized medical diagnosis during his time but also left a lasting imprint on the broader field of medicine,influencing healthcare for generations.This extensive inquiry covers various aspects,including his historical context,the development of the stethoscope,its profound implications for medical diagnosis,and its enduring impact on the history of medicine.
基金supported by the National Council of Science and Technology of Mexico(CONACYT),No.178544(to AI)
文摘Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied in clinical practice. In this study, we analyzed the combination of different strategies as a potential therapy for spinal cord injury. Immunization with neural derived peptides(INDP), inhibition of glial scar formation(dipyridyl: DPY), as well as the use of biocompatible matrix(fibrin glue: FG) impregnated with bone marrow mesenchymal stem cells(MSCs) were combined and then its beneficial effects were evaluated in the induction of neuroprotection and neuroregeneration after acute SCI. Sprague-Dawley female rats were subjected to a moderate spinal cord injury and then randomly allocated into five groups: 1) phosphate buffered saline; 2) DPY; 3) INDP + DPY; 4) DPY+ FG; 5) INDP + DPY + FG + MSCs. In all rats, intervention was performed 72 hours after spinal cord injury. Locomotor and sensibility recovery was assessed in all rats. At 60 days after treatment, histological examinations of the spinal cord(hematoxylin-eosin and Bielschowsky staining) were performed. Our results showed that the combination therapy(DPY+ INDP + FG+ MSCs) was the best strategy to promote motor and sensibility recovery. In addition, significant increases in tissue preservation and axonal density were observed in the combination therapy group. Findings from this study suggest that the combination theapy(DPY+ INDP + FG + MSCs) exhibits potential effects on the protection and regeneration of neural tissue after acute spinal cord injury. All procedures were approved by the Animal Bioethics and Welfare Committee(approval No. 178544; CSNBTBIBAJ 090812960)on August 15, 2016.
文摘A differential pulse voltammetry (DPV) method for amantadine (AT) determination is developed. To this end, all the chemical and instrumental variables affecting the determination of amantadine are optimized. These studies have used three types of glassy-carbon electrode, first electrode which has not undergone surface modification or coating, to then modify the working electrode surface with two kinds of suspensions: graphene and graphene-cucurbit[7]uril (CB[7]). From studies of the mechanisms governing the electrochemical response of amantadine, it was concluded that it is an electrochemically system with a diffusive reduction phenomenon. Under optimal conditions and with the appropriate electrode modification, we proceed to study the relation between the peak intensity with the analyte concentration. Thus, we find that when the electrode surface is covered with graphene-CB[7], two linear sections are obtained, the first one in the concentration range of between 0.05 μg·mL﹣1 and 0.75 μg·mL﹣1;and the second one between 1.00 μg·mL﹣1 and 6.00 μg·mL﹣1, with Er (%) = 87 and R.S.D. = 0.94% (n = 10 at 0.5 μg·mL﹣1 level). The minimum detectable amount was 15 ng·mL﹣1 while a concentration of 44 ng·mL﹣1 was calculated as determination limit. The optimized method was applied to the determination of amantadine in biological fluids.
文摘Spinal cord injury (SCI) is a degenerative disease that causes an important neurological impairment, it is a medically complex and life-disrupting condition. SCI has a devastating impact on international health systems due to its irreversible consequences and lack of efficient treatment, affecting mostly young population within their productive years. Global SCI incidence in high-income countries is 40 to 80 new cases per million per year,
文摘The general objective of this article was to construct and describe the psychometric properties of a scale of selfcare behaviors against COVID-19.It was a descriptive,cross-sectional,psychometric validation study of a scale created to measure self-care behaviors in relation to COVID-19 in a total sample of 333 probabilistically selected.Qualitative validity was evaluated by a review of 10 experts and quantitative validity by means of exploratory factor analysis using the principal components method.Internal consistency was measured with Cronbach’s alpha twice and the test-retest was evaluated by calculating the intraclass coefficient.The final scale consisted of 29 items.The Kaiser-Meyer-Olkin test of adequacy yielded a value of 0.926,and the Bartlett’s test of sphericity X^(2)=4611 with a p-value<0.001.The variance explained by the three retained factors with a total of 29 items was 50.03%.The Cronbach’s alpha internal consistency evaluation yielded an initial value of 0.923 and,in a second evaluation,showed a value of 0.936.In addition,the intraclass coefficient in the test-retest yielded a value of 0.929.The instrument created and validated possessed the necessary conditions as a useful and reliable tool for measuring self-care behaviors in relation to COVID-19 in a population of university students and it is important that it can be applied in other regions of the world.
文摘Objective: To evaluate the role of regulatory T cells (Tregs) at late stages of stroke. Methods:Anti-CD25 antibody (or PBS as a control) was injected to reduce the pool of Tregs in Wistar rats;then, ischemia was induced transiently by middle cerebral artery occlusion during 60 min and reperfusion was allowed for 7 d. Then, Treg frequency was analyzed in peripheral blood, spleen and lymph nodes. Neurological score (0-6) and infarct volume were also determined. Results: Nine days after injection, the CD4+CD25+ T cells were reduced by 70.4%, 44.8% and 57.9% in peripheral blood, spleen and lymph nodes, respectively compared to PBS-treated rats. In contrast, the reduction of CD4+FOXP3+ T cells was lower in the same compartments (38.6%, 12.5%, and 29.5%, respectively). The strongest reduction of CD25+CD4+ T cells was observed in those FOXP3-negative cells in blood, spleen and lymph nodes (77.8%, 52.8%, and 60.7%, respectively), most likely corresponding to activated T cells. Anti-CD25-treated transient middle cerebral artery occlusion rats had a lower neurological deficit and did not develop tissue damage compared with PBS-treated animals. Conclusions: These findings suggest that treatment with anti-CD25 in our model preferentially reduce the T cell population with an activated phenotype, rather than the Treg population, leading to neuroprotection by suppressing the pathogenic response of effector T cells.
文摘Depressive disorders are recognized as one of the most common mental health conditions across different age groups.However,the risk factors associated with depression among older people from low-and middle-income countries remains unclear.This study aims to identify socio-demographic,health and psychosocial-related factors associated with depression in Chilean older adults.A cross-sectional study was carried out in a representative sample of 1,765 adults aged≥60 years participants from the Chilean National Health Survey 2016–2017.Depres-sion was assessed with the Composite International Diagnostic Interview(CIDI-SF).Associations between the exposure variables and depression were investigated using Poisson regression analyses.The mainfindings indi-cated that women showed higher likelihood of depression than men(Prevalence Ratio(PR)=2.6[95%CI:1.40;4.89]).An increased likelihood of depression was found in older adults with chronic pain,multimorbidity(≥2 diseases),previous diagnose of depression,high perception of stress,financial stress,and difficulties for social par-ticipation.In women,higher likelihood of depression was found for those with the frailty phenotype(PR:8.53[95%CI:1.68;43.32]),rheumatoid arthritis(PR:2.41[95%CI:1.34;4.34]),insomnia(PR:2.99[95%CI:1.74;5.12])and low self-rated well-being(PR:4.94[95%CI:2.26;10.79]).Men who were divorced(PR:7.10[95%CI:1.44;34.90])or widowed(PR:10.83[95%CI:3.71;31.58]),obese(PR:5.08[95%CI:1.48;17.42])and who had asthma(PR:7.60[95%CI:2.31;24.99])were associated with higher odds of depression.The currentfindings may have clinical implications for the early identification of older adults more susceptible to depression and also suggest the need to implement cultural and age-sensitive strategies to promote mental health in late life.
文摘AIM: To analyze the attitude of Spanish medical students toward living liver donation (LLD) and to establish which factors have an influence on this attitude.METHODS: Study type: A sociological, interdisciplinary, multicenter and observational study. Study population: Medical students enrolled in Spain (n = 34000) in the university academic year 2010-2011. Sample size: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire (PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. Statistical analysis: Student´s t test, χ<sup>2</sup> test and logistic regression analysis.RESULTS: The completion rate was 95.7% (n = 9275). 89% (n = 8258) were in favor of related LLD, and 32% (n = 2937) supported unrelated LLD. The following variables were associated with having a more favorable attitude: (1) age (P = 0.008); (2) sex (P < 0.001); (3) academic year (P < 0.001); (4) geographical area (P = 0.013); (5) believing in the possibility of needing a transplant oneself in the future (P < 0.001); (6) attitude toward deceased donation (P < 0.001); (7) attitude toward living kidney donation (P < 0.001); (8) acceptance of a donated liver segment from a family member if one were needed (P < 0.001); (9) having discussed the subject with one’s family (P < 0.001) and friends (P < 0.001); (10) a partner’s opinion about the subject (P < 0.001); (11) carrying out activities of an altruistic nature; and (12) fear of the possible mutilation of the body after donation (P < 0.001).CONCLUSION: Spanish medical students have a favorable attitude toward LLD.
基金supported by Colciencias project No 221340820447the Corporacion para Investigaciones Biologicas(CIB)and the Universidad of Antioquia through the fund“Sostenibilidad 2010-2011”COLCIENCIAS National Doctoral Program supported Isaura Torres.
文摘Efficient technologies for gene silencing would be important to carry out functional analysis with P. brasiliensis genes, as well as for a better understanding of the biology and pathogenesis of this pathogenic fungus. Due to the fact that homologous recombination is unusual in P. brasiliensis, the development of knockout isolates is currently non-feasible. The goal of this work was to assess RNA interference (RNAi) technology as an alternative tool for gene silencing previously employed successfully in H. capsulatum. For this purpose, we built different inverted repeat transgenic hairpin constructs to down-regulate the PbGP43 and PbP27 genes known to codify for two fungal immunogenic proteins that elicit a strong immune response during experimental paracoccidioidomycosis. Using the RNAi strategy, a reduction in the mRNA levels of the PbGP43 and PbP27 genes was observed during the first 20 days after selection;however, in the transformed yeast cells, the gene silencing status proved non-stable through the assay. We demonstrated that electrotransformation was suitable to transform P. brasiliensis yeast cells and integrate the hairpin constructions;nonetheless, gene silencing was not stable along the experimental time. A detailed analysis of the underlying molecular RNAi machinery may provide further insights into the intracellular mechanism that governs this reverse genetic tool.
基金supported by the European Regional Development Fund.Supported by Consejería de Educacion,Culturay Deportes-JCCMFondo Europeo de Desarrollo Regional funds (grant no.SBPLY/17/180501/000533)+1 种基金supported by a grant from the University of Castilla-La Mancha (2020-PREDUCLM-15596)supported by a grant from the Universidad de Castilla-La Mancha co-financed by the European Social Fund (2020-PREDUCLM-16746).
文摘Background The positive influence of most types of exercise has been reported repeatedly,but what the most effective exercise approaches are for improving health-related quality of life(HRQoL)in people with cancer remains unknown.The aim of this systematic review and network meta-analysis was to synthesize the evidence from intervention studies to assess the effects of different types of exercise on HRQoL during and after cancer treatment.Methods MEDLINE,SPORTDiscus,the Cochrane Library,Web of Science,and Scopus were searched for randomized controlled trials aimed at testing the effects of exercise interventions meant to improve HRQoL in people with cancer.Separate analyses were conducted for HRQoL as measured by general and cancer-specific questionnaires.We also evaluated whether the effects of exercise were different during and after cancer treatment in both the physical and mental HRQoL domains.Results In total,93 studies involving 7435 people with cancer were included.Network effect size estimates comparing exercise intervention vs.usual care were significant for combined exercise(0.35,95%confidence interval(95%CI):0.14–0.56)for HRQoL as measured by general questionnaires,and for combined(0.31,95%CI:0.13–0.48),mind–body exercise(0.54,95%CI:0.18–0.89),and walking(0.39,95%CI:0.04–0.74)for HRQoL as measured by cancer-specific questionnaires.Conclusion Exercise programs combining aerobic and resistance training can be recommended to improve HRQoL during and after cancer treatment.The scarcity and heterogeneity of these studies prevents us from making recommendations about other exercise modalities due to insufficient evidence.
文摘Brucellosis is an infectious disease of worldwide distribution, which has a great economic impact due to the productive and reproductive losses that it causes, in addition to the serious public health problem. The aim of this study is to estimate the economic losses, through financial analysis, caused by bovine brucellosis in the province of Carchi, over a one-year period. A random sampling was used to determine the prevalence in the study area, where 2976 animals were considered, and the Rose Bengal (RB) test was used as a screening test and the Fluorescence Polarized Assay (FPA) as a confirmatory test, obtaining a prevalence of 8.2% (244/2976). In addition, parameters associated to the losses caused by brucellosis in cattle were determined by literature review. To estimate costs, field information was collected through a survey of a total of 100 randomly selected farmers. The loss estimated due to calves lost as a result of abortions and neonatal death was USD. 79170.00. The loss due to death of 4 cows as a result of metritis was estimated at USD. 5000.00. The cost of examination and treatment of aborted cows was USD. 20100.00. The losses due to reduction in milk production from aborted and non-aborted seropositive cows were estimated at USD. 158114.21. The financial losses due to brucellosis in province of Carchi were estimated at USD. 262384.21.
文摘BACKGROUND: Proliferation of hepatic stellate cells (HSCs) plays a pivotal role in the progression of liver fibrosis conse- quent to chronic liver injury. Silibinin, a flavonoid compound, has been shown to possess anti-fibrogenic effects in animal models of liver fibrosis. This was attributed to an inhibition of cell proliferation of activated HSCs. The present study was to gain insight into the molecular pathways involved in silibinin anti-fibrogenic effect. METHODS: The study was conducted on LX-2 human stellate cells treated with three concentrations of silibinin (10, 50 and 100 μmol/L) for 24 and 96 hours. At the end of the treatment cell viability and proliferation were evaluated. Protein expression of p27, p21, p53, Akt and phosphorylated-Akt was evaluated by Western blotting analysis and Ki-67 protein expression was by immunocytochemistry. Sirtuin activity was evaluated by chemiluminescence based assay. RESULTS: Silibinin inhibits LX-2 cell proliferation in doseand time-dependent manner; we showed that silibinin upregulated the protein expressions of p27 and p53. Such regulation was correlated to an inhibition of both downstream Akt and phosphorylated-Akt protein signaling and Ki-67 protein expression. Sirtuin activity also was correlated to silibinin- inhibited proliferation of LX-2 cells. CONCLUSION: The anti-proliferative effect of silibinin on LX-2 human steUate cells is via the inhibition of the expres- sions of various cell cycle targets including p27, Akt and sir- tuin signaling.
基金Supported by Instituto de Salud CarlosⅢ,and Consejería de Salud Junta de Andalucía PI14/01349
文摘BACKGROUND The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16 S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease(IBD) is abnormal and characterized by reduced diversity. Micro RNAs(miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn's disease(CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut microbiota.AIM To investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut microbiota.METHODS Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of newonset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16 S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MGRAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative PCR.RESULTS Microbial community was characterized using 16 S rRNA gene sequencing in 29 samples(n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group(5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showed that a lower metabolism of carbohydrates(P = 0.000) was found in CD group, while the metabolism of lipids was increased. In CD patients, three miRNAs were induced in affected mucosa: mir-144(6.2 ± 1.3 fold), mir-519(21.8 ± 3.1) and mir-211(2.3 ± 0.4). CONCLUSION Changes in microbial function in active non-treated CD subjects and three miRNAs in affected vs non-affected mucosa have been found. miRNAs profile may serve as a biomarker.
基金partially supported by Universidad Peruana de Ciencias Aplicadas and Nutrition Research Institute,Lima,Peru
文摘Objective: To evaluate the susceptibility of Pseudomonas aeruginosa(P. aeruginosa)in vitro to the ethanolic extracts obtained from five different Peruvian medicinal plants.Methods: The plants were chopped and soaked in absolute ethanol(1:2, w/v). The antibacterial activity of compounds against P. aeruginosa was evaluated using the cupplate agar diffusion method.Results: The extracts from Maytenus macrocarpa("Chuchuhuasi"), Dracontium loretense Krause("Jergon Sacha"), Tabebuia impetiginosa("Tahuari"), Eucalyptus camaldulensis Dehn(eucalyptus), Uncaria tomentosa("U?a de gato") exhibited favorable antibacterial activity against P. aeruginosa. The inhibitory effect of the extracts on the strains of P. aeruginosa tested demonstrated that Tabebuia impetiginosa and Maytenus macrocarpa possess higher antibacterial activity.Conclusions: The results of the present study scientifically validate the inhibitory capacity of the five medicinal plants attributed by their common use in folk medicine and contribute towards the development of new treatment options based on natural products.