Resumo em Inglês:

Animal models of diseases are invaluable tools of modern medicine. More than forty years have passed since the first successful experiments and the spectrum of available models, as well as the list of methods for creating them, have expanded dramatically. The major step forward in creating specific disease models was the development of gene editing techniques, which allowed for targeted modification of the animal's genome. In this review, we discuss the available tools for creating transgenic animal models, such as transgenesis methods, recombinases, and nucleases, including zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and CRISPR/Cas9 systems. We then focus specifically on the models of atherosclerosis, especially mouse models that greatly contributed to improving our understanding of the disease pathogenesis and we outline their characteristics and limitations.

Resumo em Inglês:

Special attention has emerged towards biomass smoke-induced chronic obstructive pulmonary disease (COPD), providing new knowledge for prevention and therapeutic approach of non-smoker COPD patients. However, the understanding of biomass smoke COPD is still limited and somewhat controversial. The aim of the present study was to compare COPD exclusively caused by tobacco smoking with COPD exclusively caused by environmental or occupational exposures. For this cross-sectional study, COPD patients were recruited from outpatient clinics and formed two groups: non-smoker COPD group (n=16) with exposure to biomass smoke who did not smoke cigarette and tobacco smoker COPD group (n=15) with people who did not report biomass smoke exposure. Subjects underwent pulmonary function tests, thoracic high-resolution computed tomography, 6-min walk test, and sputum induction. The non-smoker COPD group had biomass smoke exposure of 133.3±86 hour-years. The tobacco COPD group smoked 48.5±27.4 pack-years. Women were 62.5 and 66.7%, respectively, of non-smokers and smokers. The non-smoker COPD group showed higher prevalence of dyspnea, lower arterial oxygen tension (PaO2), and lower arterial oxygen saturation (SaO2%) with similar spirometry results, lung volumes, and diffusion capacity. Regarding inflammatory biomarkers, differences were detected in sputum number of lymphomononuclear cells and in sputum concentrations of interleukin (IL)-6 and IL-8 with higher values in the smoker group. Emphysema was more prevalent in the tobacco smoker group, which also showed higher relative bronchial wall thickness and lower lung density by quantitative analysis. Biomass smoke induced more hypoxemia compared to tobacco in COPD patients with similar severity.

Resumo em Inglês:

Carassius auratus is a teleost fish that has been largely used in behavioral studies. However, little is known about potential environmental influences on its performance of learning and memory tasks. Here, we investigated this question in C. auratus, and searched for potential correlation between exercise and visuospatial enrichment with the total number of telencephalic glia and neurons. To that end, males and females were housed for 183 days in either an enriched (EE) or impoverished environment (IE) aquarium. EE contained toys, natural plants, and a 12-hour/day water stream for voluntary exercise, whereas the IE had none of the above. A third plus-maze aquarium was used for spatial and object recognition tests. Different visual clues in 2 of its 4 arms were used to guide fish to reach the criteria to complete the task. The test consisted of 30 sessions and was concluded when each animal performed three consecutive correct choices or seven alternated, each ten trials. Learning rates revealed significant differences between EE and IE fish. The optical fractionator was used to estimate the total number of telencephalic cells that were stained with cresyl violet. On average, the total number of cells in the subjects from EE was higher than those from subjects maintained in IE (P=0.0202). We suggest that environmental enrichment significantly influenced goldfish spatial learning and memory abilities, and this may be associated with an increase in the total number of telencephalic cells.

Resumo em Inglês:

Studies have shown that an injection with the histamine H4 receptor agonist VUF-8430 modulates emotional memory processes. In the present study, the aim was to verify if intraperitoneal (ip) injection of VUF-8430 (500 ng/kg) in mice affects the synthesis of proteins required for memory consolidation processes by activating the phosphorylation of CREB (pCREB) in classical structures linked to emotional memory (prefrontal cortex, amygdala, and hippocampus) and the cerebellar vermis, a structure that has also been recently implicated in emotional memory. The results obtained using western blot analysis demonstrated that VUF-8430 induced a decrease in CREB and pCREB levels in the cerebellar vermis and prefrontal cortex, suggesting that this dose impaired the activation of cell signaling pathways in these structures. There was no change in protein expression in the amygdala and hippocampus. Our results are preliminary, and further investigations are needed to investigate the role of the H4 receptors in the central nervous system.

Resumo em Inglês:

Posterior long-segment spinal fusion may lead to proximal junctional kyphosis (PJK). The present study sought to identify the appropriate fusion levels required in order to prevent PJK using finite element analysis. A finite element model was constructed based on the whole-spine computed tomography findings of a healthy adult. Nine commonly used posterior spinal fusion methods were selected. Stress on the annulus fibrosis fibers, the posterior ligamentous complex, and the vertebrae after various spinal fusions in the upright position were compared. This study was divided into two groups: non-fusion and fusion. In the former, the stress between the T10 and the upper thoracic vertebrae was higher. Comparing thoracic and lumbar segments in the fusion group, the peak stress values of the upper instrumented vertebrae (UIV) were mainly observed in T2 and L2 whilst those of the UIV+1 were observed in T10 and L2. After normalization, the peak stress values of the UIV and UIV+1 were located in T2 and L2. Similarly, the peak stress values of the annulus fibrosus at the upper adjacent level were on T10 and L2 after normalization. However, the peak stress values of the interspinal/supraspinal complex forces were concentrated on T11, T12, and L1 after normalization whilst the peak stress value of the pedicle screw was on T2. Controversy remains over the fusion of T10, and this study simulated testing conditions with gravitational loading only. However, further assessment is needed prior to reaching definitive conclusions.

Resumo em Inglês:

Multiple myeloma (MM) is a malignant neoplasm of plasma, and exhibits several harmful effects including osteolytic injuries, hypercalcemia, and immune dysfunction. Many patients with MM succumb to the underlying malignancy. An S-phase kinase-related protein 2 (Skp2) inhibitor, designated SKPin C1, has been developed and confirmed to have an inhibitory effect on metastatic melanoma cells. This study aimed to determine the effect of SKPin C1 on MM. Normal B lymphocytes, THP-1 cells, and MM U266 and RPMI 8226 cells were exposed to various dosages of SKPin C1 for 48 h. Cell proliferation was determined by MTT, EdU staining, and cell cycle assays. Western blot assays were performed to assess intracellular protein levels of Skp2, p27, and cleaved caspase-3. The amount of ubiquitin attached to p27 was determined using an immunoprecipitation assay. The viability of U266 and RPMI 8226 cells was significantly inhibited by 10 μM SKPin C1 and the inhibitory effect was enhanced with increasing doses of SKPin C1. In contrast, 50 μM SKPin C1 only marginally decreased viability of normal B lymphocytes in 12 h. Skp2 and p27 expression in U266 and RPMI 8226 cells was higher and lower, respectively, than that in the normal B lymphocytes. Treatment with SKPin C1 or Skp2 knockdown increased p27 protein levels in U266 and RPMI 8226 cells by preventing p27 from being ubiquitinated, which slowed the cell cycle, inhibited cell proliferation, and triggered apoptosis. Therefore, this study suggested SKPin C1 as a potent inhibitor against aberrant proliferation and immortalization of MM.

Resumo em Inglês:

The aim of this study was to evaluate the influence of artesunate on Th1 differentiation and its anti-tumor effect on ovarian cancer. A Murine ovarian cancer model was established by ID8 cells transplantation. The expression of miR-142 and Sirt1 proteins in peripheral CD4+ T cells were quantified with qRT-PCR and western blot, respectively. Peripheral CD4+ T cells were induced for Th1 differentiation. The percentages of apoptosis of Th1/CD4+ T cells and ovarian cancer cells were analyzed by flow cytometry. The IFN-γ level was examined through enzyme-linked immunosorbent assay. Artesunate promoted miR-142 expression in peripheral CD4+ T cells and Th1 differentiation from CD4+ T cells. Artesunate promoted cell apoptosis of ovarian cancer cells by inducing Th1 differentiation. By up-regulating miR-142, artesunate suppressed Sirt1 level and promoted Th1 differentiation. Artesunate enhanced the pro-apoptotic effects of Th1 cells on ovarian cancer via the miR-142/Sirt1 pathway. Artesunate promoted Th1 differentiation from CD4+ T cells by down-regulating Sirt1 through miR-142, thereby enhancing cell apoptosis in ovarian cancer.

Resumo em Inglês:

This study aimed to explore the structural and functional characteristics of the neural network of resting-state brain activities in patients with amnestic mild cognitive impairment (aMCI) by functional magnetic resonance imaging (fMRI) technology. Resting state fMRI scanning was performed on 10 clinically diagnosed aMCI patients and 10 healthy volunteers, and the difference in the resting-state brain activities between aMCI patients and healthy volunteers was compared using the brain function network regional homogeneity (ReHo) analysis method. Results of the ReHo analysis of aMCI patients and healthy volunteers revealed that the ReHo value significantly increased in the posterior cingulate gyrus region, medial frontal lobe, medial cortex of the prefrontal lobe, and part of the parietal lobe. Compared with the normal elderlies, ReHo decreased in aMCI patients in the left temporal lobe (middle temporal gyrus and inferior temporal gyrus), left parahippocampal gyrus, occipital lobe, lingual gyrus, precuneus, and other regions while ReHo increased in regions of the right frontal lobe (inferior frontal gyrus), left superior temporal gyrus, precentral gyrus (frontal lobe), right thalamus, left fusiform gyrus, and other regions. In the resting state, there may be regional abnormalities in brain functional areas in aMCI patients, which may be associated with cognitive impairment.

Resumo em Inglês:

Two new coordination polymers [Zn (bdc)(bpybzimH2)](DMF)0.5 (1, H2bdc=1,4-dicarboxybenzene, bpybzimH2=6,6′-bis-(1H-benzoimidazol-2-yl)-2,2′-bipyridine, DMF=N,N-dimethylformamide) and [Co (bpybzimH2)(sbc)]H2O (2, H2sbc=4-mercaptobenzoic acid) have been successfully prepared under solvothermal conditions using the multi-N chelating organic ligand bpybzimH2 as the foundational building block. In addition, the Cell Counting Kit-8 assay was conducted to evaluate the anti-proliferation activity of compounds 1 and 2 against human spinal tumor cells OPM-2. The cell viability curves showed that the two compounds have anti-proliferation activity on spinal tumor cells, and the activity of compound 1 is higher than compound 2. The annexin V-FITC/PI assay and western blot were used to detect the apoptotic percentage of OPM-2 cells incubated with compounds 1 and 2. The YAP protein expression and its role in cell apoptosis were further studied with qRT-PCR, immunoblotting, and flow cytometer.

Resumo em Inglês:

We determined the effects of enhanced recovery after surgery (ERAS) in patients undergoing radical surgery for gastric carcinoma. Sixty patients undergoing radical gastrectomy for gastric carcinoma in Lishui Hospital between March and October 2016 were randomized to receive either ERAS (30 patients) or conventional care (30 patients, controls). Clinical, economic, and laboratory indices were analyzed. ERAS patients showed faster recovery and shorter postoperative hospital stays than the controls (P<0.05). Some clinical indices (i.e., time to first flatus and defecation, time to removal of drainage tubes, time to resumption of oral feeding, time to postoperative mobilization, and postoperative complications) were significantly better in ERAS patients than in controls. Duration of postoperative infusion was lower in ERAS patients than in controls (P<0.05). In ERAS patients, serum albumin and prealbumin were higher on postoperative day 7, C-reactive protein was lower on postoperative days 3 and 7, and neutrophil count was lower on postoperative day 3 compared to the values in controls (P<0.05 for all). IgM levels were higher in ERAS patients on postoperative days 3 and 7 (P<0.05), while IgG levels were higher on postoperative day 3 (P<0.05). Total T lymphocytes were higher in ERAS patients on postoperative day 3, while helper T cells and CD4+/CD8+ ratio were higher on postoperative days 3 and 7 (P<0.05 for all). In gastric carcinoma patients, ERAS may reduce perioperative inflammation, improve immunity and postoperative nutrition, shorten hospitalization, and enhance rehabilitation.

Resumo em Inglês:

Circumferential mixed hemorrhoids are very difficult to treat non-surgically. Therefore, it is important to explore the surgical methods for its complete resolution as well as maintenance of normal anal anatomy and function. The present study was designed to evaluate the effect of segmented and plastic hemorrhoidectomy (SPH) on patients with circumferential mixed hemorrhoids. A total of 300 patients with circumferential mixed hemorrhoids were divided into experimental group (n=150) undergoing SPH and control group (n=150) undergoing Milligan-Morgan hemorrhoidectomy. There were no differences in cure and effectiveness rates between two groups. Compared with the control group, patients in the experimental group had shorter healing time (15.7±1.3 vs 12.5±0.7 days) and recovery to normal activity (18.5±2.7 vs 14.7±1.2 days). In addition, anal function of all patients in the experimental group was normal during short- and long-term follow-up. However, more cases in the control group showed anal dampness and itching, and poor control of intestinal liquid. Compared with the control group, patients in the experimental group had better outcomes in overall anal function and smoothness at 6, 12, and 18 months after operation as well as patient satisfaction. Furthermore, the rating in the visual analogue scale for defecation pain and edema in the experimental group was less than that in the control group. SPH was more effective, had fewer complications, better protection of anal function, and a better cosmetic result.

Resumo em Inglês:

Gastric cancer (GC) is the third most lethal type of cancer worldwide. Single nucleotide polymorphisms (SNPs) in regulatory sites or coding regions can modify the expression of genes involved in gastric carcinogenesis, as ERBB2, which encodes for the tyrosine-kinase receptor HER-2. The aim of this work was to analyze the association of the polymorphisms: rs2643194, rs2517951, rs2643195, rs2934971, and rs1058808 with GC, as they have not yet been analyzed in GC patients, as well as to report their frequency in the general Mexican population (GMP). We studied genomic DNA from subjects with GC (n=74), gastric inflammatory diseases (GID, n=76 control subjects), and GMP (n=102). Genotypes were obtained by means of real-time PCR and DNA-sequencing. The risks for GC were estimated through odds ratio (OR) using the Cochran-Armitage trend test and multinomial logistic regression. Increased risk for GC was observed under the dominant inheritance model for the rs2643194 TT or CT genotypes with an OR of 2.75 (95%CI 1.12−6.75, P=0.023); the rs2934971 TT or GT genotypes with an OR of 2.41 (95%CI 1.01−5.76, P=0.043), and the rs1058808 GG or CG genotypes with an OR of 2.21 (95%CI 1.00−4.87, P=0.046). The SNPs rs2643194, rs2934971, and rs1058808 of the ERBB2 gene were associated with increased risk for GC.

Resumo em Inglês:

Himatanthus drasticus (Mart.) Plumel belongs to the Apocynaceae family and the latex from its trunk bark (Hd) is known as “janaguba milk”. This latex is widely used in Northeast Brazil, mainly in the Cariri region, for its gastroprotective, anti-inflammatory, and antitumor properties. The objective of this study was to investigate a triterpene-rich fraction (FJNB) from H. drasticus latex on acute models of nociception and inflammation and to clarify its mechanisms of action. Wistar rats or Swiss mice were subjected to the carrageenan-induced paw edema test or the formalin test, respectively, after the acute oral treatment with FJNB. The inflamed paws from the carrageenan-induced paw edema and formalin tests were processed for histological and immunohistochemical assays, respectively. The results were analyzed by ANOVA and considered significant at P<0.05. FJNB (10 mg/kg) decreased the paw edema by 25% at the 3rd h after the carrageenan injection. Indomethacin, used as reference, inhibited the paw edema by 59% at the same time-point. In the formalin test, FJNB inhibited the 1st phase by 27, 49, and 52% and the 2nd phase by 37, 50, and 67%, at the doses of 1, 5, and 10 mg/kg, respectively. In addition, FJNB significantly inhibited the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and the inflammatory cytokine tumor necrosis factor (TNF)-alpha. The histone deacetylase (HDAC) expression and the transcription factor nuclear factor kappa (NF-kB) were also inhibited at the same doses. In conclusion, the FJNB inhibitory actions on iNOS, COX-2, TNF-α, HDAC, and NF-kB could be involved with the drug anti-inflammatory activity.