International Journal of Experimental Pathology最新文献

Deltamethrin (DTM) is a synthetic pyrethroid widely used in the cultivation and management of several crops due to its insecticidal action. Application to crops of pyrethroids such as DTM can result in the exposure of water and fruit consumed by fruit bats having a high pyrethroid content which may be harmful. Therefore the objective of this study was to evaluate the effects of short-term oral exposure of the fruit-eating bats (Artibeus lituratus) to two concentrations of DTM (0.02 and 0.04 mg/kg of papaya) on histopathology of the intestine, liver and kidney. The intestine of the animals exposed to both concentrations showed inflammatory infiltrate, degeneration, necrosis and goblet cell hyperplasia as the most frequent pathologies. Besides, the acid mucins showed an increase in the frequency of non-viable cells. The liver showed hepatocyte vacuolizatio and nuclear enlargement, as well as inflammatory infiltrate and steatosis. The kidneys of the exposed animals showed and inflammatory infiltrate, benign nephrosclerosis, vacuolization and necrosis. Also, DTM reduced nitric oxide synthesis, decreased glomerular diameter and increased glycogen percentage in the proximal tubules. Our results suggest that acute exposure to DTM at low concentrations has the potential to induce pronounced histopathological changes in vital organs, such as intestine, liver and kidney of fruit-eating bats.

The aim of this study was to investigate the potential application of computer-aided analysis in the quantitative assessment of changes in skeletal muscle injury in the rabbit contusion model. Forty healthy rabbits were randomly divided into control (n = 5) and contusion (n = 35) groups. Rabbits in the contusion group were used to construct a muscle contusion model induced by a hammer hitting the right gastrocnemius, while the muscles of rabbits in the control group were non-injured. Two-dimensional ultrasound (2D US) and contrast-enhanced ultrasonography (CEUS) were performed on the rabbits that had received skeletal muscle contusion injury at 1 h, and 1, 3, 7, 14, 21 and 28 days after injury. Afterwards, a multiscale blob feature (MBF) method was used to extract the textural features from the 2D US, and the muscle injuries were quantitatively evaluated. The eight textural parameters of skeletal muscle analysed by MBF at 1 h, and 1, 3 and 7 days post-injury were found to be significantly higher in the contusion group than in the control group (p < .05). On Day 14, the textural parameters (e.g., greyscale mean [Mean], greyscale standard deviation [SDev], number of blobs, average size of blobs, homogeneity of distribution, periodicity of distribution [POD] and irregularity) were also evidently higher in the contusion group than in the control group (p < .05). On Day 28, Mean, SDev and POD in the contusion group were markedly higher (p < .05). After that, the microcirculation in the injured areas increased from Day 7 to Day 21 after injury, but decreased on Day 28 after injury. Thus the quantitative assessment of changes in skeletal muscle injury (SMI) using computer-aided analysis allowed us to describe the geometric features of injured muscle fibres and the microperfusion changes estimated by the modified semi-quantitative scoring system. This provides a scientific basis for the development of a novel approach for the evaluation of SMI and rehabilitation process.

Type 2 diabetes mellitus (T2D) during pregnancy is characterized by high levels of reactive oxygen species and pro-inflammatory factors in the placenta. Once these reactive species reach the foetus, they trigger physiological adaptations that allow the foetus to survive, but programme the organism to develop metabolic disorders in adulthood. The male reproductive system is highly susceptible to foetal programming. This study aimed to investigate the effects of intrauterine exposure to T2D on testicular histomorphometry and redox homeostasis of adult rats and evaluate the effects of maternal treatment with metformin and pentoxifylline. Female rats were induced to T2D, then treated with metformin and pentoxifylline, or co-treated with both drugs. The females were mated, the male offspring were sacrificed on postnatal day 90, and the testicles were collected for analysis. Metformin protected the tubular compartment, with the maintenance of the Sertoli cell population and daily sperm production. Pentoxifylline attenuated the effects of diabetes on Leydig cells, in addition to stimulating testosterone production and lowering lipid peroxidation. Intrauterine exposure to T2D results in important testicular alterations that compromise gonadal function, and the co-treatment with metformin and pentoxifylline may represent a promising therapy that attenuates these effects by combining the positive influences in both the tubular and interstitial compartments of the testicular parenchyma.

Macrophage polarization is an important effector process in acute lung injury (ALI) induced by sepsis. MicroRNAs (miRNAs) have emerged as important players in regulating ALI process. Here, we showed that elevated microRNA-23a-3p (miR-23a-3p) promoted LPS-induced macrophage polarization and ALI in mice, while inhibition of miR-23a-3p led to reduced macrophage response and ameliorated ALI inflammation. Mechanically, miR-23a-3p regulated macrophage M1 polarization through targeting polo-like kinase 1 (PLK1). PLK1 was downregulated in LPS-treated macrophages and ALI mouse lung tissues. Knockdown of PLK1 increased macrophage M1 polarization through promoting STAT1/STAT3 activation, while overexpression of PLK1 reduced macrophage immune response. Collectively, our results reveal a key miRNA regulon that regulates macrophage polarization for LPS-induced immune response.

The creation of multigene panels for prognostic and predictive purposes allows a more accurate indication of adjuvant chemotherapy for patients with breast cancer. In a previous study, we reproduced a multigene panel of 21 genes based on the commercial Oncotype-DX method. We submitted 183 embedded specimens obtained from breast surgery on patients with locoregional disease (stages I to III) between 2005 and 2010 performed at the Hospitals of the Medical School of the ABC Foundation. When we analysed the correlations between the score of the multigene panel and the progression-free interval (PFI) in all patients, we did not find a statistically significant association. However, when we selected only the 71 samples that had amplification of at least eight non-housekeeping genes, we observed that those with scores above the 75th percentile had a significantly lower PFI (p = .0054). Samples processed with nonbuffered formaldehyde were associated with a worse quality of extracted RNA (p = .004) and a significantly higher multigene panel score (p = .021). We conclude that variations in the pre-analytical processing of specimens destined for multigene panel amplification can significantly affect the results, with a potential impact on clinical management.

The purpose of the present study was to investigate the expression of α-SMA and SM22α in airway smooth muscle (ASM) of bronchioles from children younger than 14 years who died of acute interstitial pneumonia (AIP). This is based upon the hypothesis that as contractile marker proteins α-SMA and SM22α can serve as an index of the overcontractile phenotype of ASM that is seen in AIP. Lung tissue samples of children were obtained from autopsies and divided into the AIP group (55.9% male and 44.1% female, between 0.4 and 132 months old, n = 34) and the control group (60% male and 40% female, between 2 and 156 months old, n = 10). We recorded the post-mortem interval (PMI), height, clinical symptoms and abdominal fat thickness (AFT) of each case. Haematoxylin-and-eosin-stained sections were used to examine the luminal area and observe the morphological changes in the bronchioles. Immunohistochemistry and Masson's trichrome staining were used to detect the expression of contractile marker proteins and the degree of pulmonary fibrosis respectively. Compared with the control group, the luminal areas of bronchioles in the AIP group were smaller (p < .001). The expression differences in α-SMA and SM22α between the two groups were statistically significant (p = .01 and p = .02 respectively). Also, there was no significant correlation of the contractile marker proteins expression with PMI, height, clinical symptoms and AFT. The collagen deposition difference in lung between the two groups was not statistically significant (p = .224). These findings suggest that enhancement of ASM contractile function appears to be involved in the death mechanism of children with AIP, which affords more insights into the understanding of AIP.

Wound healing is a dynamic process initiated in response to injury. There are many factors that have detrimental effects on the wound healing process. Numerous studies have been conducted for improving wound healing processes. Dexpanthenol is widely used to accelerate wound healing. Sucralfate is used for the treatment of peptic ulcers. We aimed to compare the efficacy of topical Dexpanthenol and Sucralfate in an experimental wound model in rats via histopathological examinations and immune histochemical determinations, as well, to evaluate their effects on EGF levels. Three different groups were formed: the Control Group, the Dexpanthenol Group and the Sucralfate Group. Full-thickness skin wounds were created on the back of each rat and isotonic saline was applied to the wounds of the rats in the control group, Bepanthol^® cream was applied in Dexpanthenol Group and 10% Sucralfate cream was applied in Sucralfate Group, once a day. On the 7th, 14th and 21st days the wounds were measured and seven rats from each group were sacrificed and the wounds were excised for histopathological examination. Sucralfate increased wound healing rates by increasing neovascularization, fibroblast activation, reepithelialization and collagen density, as well as dexpanthenol. Our study revealed that the dexpanthenol and sucralfate groups were better than the control group in terms of their effects on wound healing, however there was no statistically significant difference among these two groups. Sucralfate improves EGF expression in skin wounds and has positive results on skin wound healing comparable to dexpanthenol.

Wilms' tumour is a solid tumour that frequently occurs in children. Genetic changes in WT1 and epigenetic aberrations that affect imprinted control region 1 in WT2 loci are implicated in its aetiology. Moreover, tumour suppressor genes are frequently silenced by methylation in this tumour. In the present study, we analysed the methylation statuses of promoter regions of 24 tumour suppressor genes using a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA)-based approach in 6 Wilms' tumours. Methylation of RASSF1 was specific to all 6 Wilms' tumours and was not observed in normal tissues. Moreover, methylated HIC1 was identified in stromal-type Wilms' tumours and methylated BRCA1 was identified in epithelial-type Wilms' tumours. Unmethylated CASP8, RARB, MLH1_167, APC and CDKN2A were found only in blastemal predominant-type Wilms' tumour. Our results indicated that methylation of RASSF1 may be a vital event in the tumorigenesis of Wilms' tumour, which informs its clinical and therapeutic management. In addition, mixed-type Wilms' tumours may be classified according to epithelial, stromal and blastemal components via MS-MLPA-based approach.

Emerging evidences have shown that long noncoding RNA (lncRNA) plays an important role in the immune escape of cancer cells. Our previous study has demonstrated that lncRNA MIAT is associated with the immune infiltration of hepatocellular carcinoma (HCC). However, the underlying mechanism of MIAT regulating the PD-L1-mediated immune escape of HCC is poorly understood. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of MIAT and PD-L1 mRNA in HCC. The relationship between MIAT, miR-411-5p, STAT3 and PD-L1 was explored by dual-luciferase reporter assay, cytotoxicity assay, Western blot and RNA immunoprecipitation (RIP). In addition, the xenograft model was established to determine the effect of MIAT on PD-L1 expression in vivo. We found that MIAT and PD-L1 were significantly upregulated in HCC tissues and the expression of PD-L1 was regulated by MIAT. The knockdown of MIAT enhanced the cytotoxicity of T cells on HCC cells. MIAT negatively regulated miR-411-5p expression, upregulated STAT3 and ultimately increased PD-L1 expression from the transcription level. The inhibition of miR-411-5p reversed STAT3 and PD-L1 expression inhibited by MIAT knockdown in HCC cells. This study suggests a novel lncRNA-mediated mechanism for HCC cells to evade the immune response; MIAT/miR-411-5p/STAT3/PD-L1 may be a novel therapeutic target for HCC.