Histology and histopathology Vol.33, nº6 (2018)
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- PublicationOpen AccessRemodelling of collagen fibres in the placentas of women with venous insufficiency during pregnancy(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Ortega, Miguel A.; Asúnsolo, Ángel; Álvarez Rocha, María J.; Romero, Beatriz; De León-Luis, Juan; Álvarez Mon, Melchor; Buján, Julia; García Honduvilla, NatalioHaemodynamic changes produced during pregnancy lead to elevated venous pressure in the legs and an increased resting consumption of oxygen. These events can cause varicose veins, or venous insufficiency (VI), which by creating an environment of hypoxia could affect the structure and function of the placental barrier. This study assesses the remodelling state of the placental villi by examining differences in collagens with a known role in villus structure and in placental barrier permeability between patients with and without VI. Samples of 67 placentas from women with VI (n=24) and without VI (n=43) during their pregnancy were processed for gene and protein expression analysis of COL-I, COL-III, MMP-2 and MMP-9 by RT-qPCR and immunohistochemistry. While no differences in COL-I expression levels were detected in the samples from women with and without VI, significant differences did emerge in both gene and protein expression levels of COL-III. Importantly, COL-I/III ratios were reduced in the VI group compared to controls. MMP-2 activity was similar in the two groups while MMP-9 levels were significantly elevated in VI with greatest expression differences observed at the level of the decidual cells. Mothers who developed VI during pregnancy showed significantly higher COL-III and MMP-9 levels consistent with a state of remodelling of the placental villi.
- PublicationOpen AccessAge-related changes in the morphology and the distribution of IgA and IgG in the palatine tonsils of yaks (Bos grunniens)(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Sun, Juan; Xu, Yuanfang; Cui, Yan; Liu, Penggang; Yu, Sijiu; He, Junfeng; Zhang, Qiang; Huang, Yufeng; Yang, XueThis study aimed to describe the age-related morphological changes and the distribution of IgA and IgG antibody-secreting cells (ASCs) in yaks. The palatine tonsils of twenty clinically healthy yaks, viz. newborn juvenile, adult and aged, were studied using histology, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). The results showed that the palatine tonsils found in two tonsillar sinus were elongated kidney-shaped structures. Some external crypts and internal crypts were present. The palatine tonsils were partially enclosed by a connective tissue capsule and had trabeculae extending into the organ. Within these encapsulated organs, mucous glands were seen very obviously. Each crypt was highly branched and lined with stratified squamous non-keratinized epithelium. Several nonepithelial cells infiltrated between the epithelial cells, forming patches of reticular epithelium or lymphoepithelium. In newborn yaks, the lymphoid follicles were not observed. In other groups, the lymphoid follicles consisted of primary lymphoid follicles and secondary lymphoid follicles. Both IgA and IgG ASCs were distributed in the interfollicular areas, lymphoid follicles, the subepithelial areas of the nonreticular crypt epithelium, and the reticular crypt epithelium, with a few positive cells aggregated around the gland. The density of the two ASCs and the expression of the two proteins gradually increased from newborn to adult and reached a peak at adult age; they then decreased with age. However, the density of the IgG ASCs and the expression of IgG protein was significantly higher than that of IgA in all groups (P<0.01). The results indicated that the palatine tonsils were not only lymphoepithelial structures but also typical secondary lymphoid organs. IgG could be a significant component of mucosal immune responses in the palatine tonsils of yaks.
- PublicationOpen AccessPrognostic role of XTP1/DEPDC1B and SDP35/DEPDC1A in high grade soft-tissue sarcomas(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Pollino, Serena; Benassi, Maria Serena; Pazzaglia, Laura; Conti, Amalia; Bertani, Nicoletta; Righi, Alberto; Piccinni Leopardi, Martina; Picci, Piero; Perris, RobertoBackground. The outcome of patients with metastatic soft tissue sarcoma (STS) remains unfavourable and new therapeutic strategies are needed. The aim of this study was to determine the role of RhoGAP, XTP1/DEPDC1B and SDP35/DEPDC1A, as possible prognostic markers, to be used to identify candidate patients for more effective and personalized therapies. Materials-Methods. SDP35/DEPDC1A and XTP1/ DEPDC1B transcriptional levels were evaluated by Real-Time PCR in 86 primary STS and 22 paired lung metastasis. 17 normal tissues were used as control. Protein expression was evaluated by tissue microarray, including 152 paraffin-embedded STS samples and by western blot in 22 lung metastases and paired primary STS. Non-parametric and parametric analysis were used to establish the differences in gene and protein expression and prognostic factors were tested with Kaplan Meier and Cox’s regression analyses. Results. SDP35/DEPDC1A and XTP1/DEPDC1B gene were down-regulated in adjacent normal tissues while sarcoma specimens presented high mRNA levels, significantly related to metastasis-free survival. Gene expression further increased in paired metastatic lesions. Immunohistochemical staining showed a variable expression in intensity and distribution, with a significantly higher probability of metastatic disease in patients up-regulating SDP35/DEPDC1A. Western blotting assessed high levels of proteins in STS specimens and indicated a stronger expression of SDP35/DEPDC1A in metastases when compared to primary tumours. Multivariate analyses highlighted that SDP35/DEPDC1A abundance, grade III and no history of radiation therapy were significant independent risk factors. Conclusions. Our results demonstrated that increased expression of SDP35/DEPDC1A and XPT1/DEPDC1B correlates with metastatic progression and identified SDP35/DEPDC1A as an independent marker for prediction of poor prognosis.
- PublicationOpen AccessThe matrix synthesis and anti-inflammatory effect of autologous leukocyte-poor platelet rich plasma in human cartilage explants(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Simental Mendía, Mario; Vilchez Cavazos, Félix; García Garza, Rubén; Lara Arias, Jorge; Montes de Oca Luna, Roberto; Said Fernández, Salvador; Martínez Rodríguez, Herminia G.Objective. To determine the effects of autologous leukocyte-poor platelet-rich plasma (LPPRP) on the expression of markers involved in cartilageextracellular matrix production and inflammation in cartilage explants bearing osteoarthritis. Materials and Methods. Cartilage explants and LP-PRP were obtained from 10 patients who underwent total knee arthroplasty. The explants were cultured in spinner flasks for 28 days in the presence of interleukin (IL)-1β and/or LP-PRP. The gene expression of catabolic (MMP13, ADAMTS5, and IL1β) and anabolic factors (COL2A1, ACAN, and SOX9) was quantified. A histological assessment was performed according to a modified Mankin score, and quantification of type II and I collagen deposition. Results. The gene expression of catabolic factors and the Mankin score were lower in LP-PRP- and LP-PRP/IL1β- than in IL-1β-treated explants, suggesting less matrix degradation in explants cultured in the presence of LP-PRP. Higher expression of genes involved in cartilage matrix restoration was observed in LP-PRP and LP-PRP/IL-1β- when compared to IL-1β-treated explants. The explants treated with LP-PRP and LPPRP/IL-1β exhibited a higher deposition of type II collagen as well as a lower deposition of type I collagen and also better surface integrity and a significant increase in the number of chondrocytes. Conclusion. LPPRP treatment favored restoration in early osteoarthritic cartilage and reduced the pro-inflammatory effect of IL1β. LP-PRP is a promising therapy for early osteoarthritis, as it promotes extracellular matrix repair, reduces inflammation, and slows cartilage degeneration.
- PublicationOpen AccessOptimal mesenchymal stem cell delivery routes to enhance neurogenesis for the treatment of Alzheimer's disease(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Park, Sang Eon; Lee, Na Kyung; Na, Duk L.; Chang, Jong WookAlzheimer’s disease (AD) is a common cause of dementia. Alzheimer’s disease (AD) is characterized by progressive loss of memory in addition to cortical atrophy. Despite decades of research and therapeutic trials in AD, an effective treatment is yet to be developed. Mesenchymal stem cells (MSCs) have emerged as promising tools for the treatment of AD, and clinical trials have been completed or are in progress. MSCs secrete various cytotropic factors that may exert beneficial effects in AD. The route of administration is an important factor to enhance MSC based treatment effects for AD. Among various routes, the intracerebroventricular route may possess several advantages such as the activation of neurogenesis, compared to other routes for AD treatments. In this review, we will focus on recent pre-clinical and clinical advances in MSC-based treatment of AD, specifically in relation to enhancement of endogenous neurogenesis.
- PublicationOpen AccessRetrospective analysis of 25 immunohistochemical tissue markers for differentiating multilocular cystic renal neoplasm of low malignant potential and multicystic renal cell carcinoma(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Kim, Sung Han; Park, Boram; Joo, Jungnam; Joung, Jae Young; Seo, Ho Kyung; Lee, Kang Hyun; Park, Weon Seo; Chung, JinsooMultilocular cystic renal neoplasm of low malignant potential (MCRNLMP) and multicystic renal cell carcinoma (MCRCC) are morphologically indistinguishable. MCRNLMP is a tumor composed entirely of numerous cysts, the septa of which contain individual or groups of clear cells without expansile growth. However, unlike MCRCC, neither recurrence nor metastasis has been reported in MCRNLMP. The aim of this study was to identify significant differential pathological characteristics in resected specimens from patients diagnosed with MCRNLMP (n=13) and MCRCC (n=17) using immunohistochemistry of 25 tissue markers. Staining interpretation was performed semi-quantitatively using the H-score (0-300) or intensity score (0-3), and differences between groups were evaluated using the Fisher exact and Wilcoxon rank-sum tests. During a median follow-up of 66.2 months (1-141.9 months), there was only one case of MCRCC recurrence among all 30 patients, including 19 (63.3%) at stage pT1a, 8 (26.7%) at stage pT1b, and 3 (10.0%) patients at stage pT2. Tumor necrosis rate (0% vs. 52.9%) and median tumor size (3.2 cm vs. 4.1 cm) significantly differed between MCRNLMP and MCRCC samples. Among the 25 tissue markers, only HIF1a, PDGFRα, SMA, VEGFR1, VEGFR2, VEGFR3, CD10, CD31, CD34, CK7-tubule, TGAse-2, and Ki-67 showed significantly different expression between the groups. These tissue markers with differential expression between MCRNLMP and MCRCC can provide a clue to understanding their distinct pathophysiology.
- PublicationOpen AccessCotton rats (Sigmodon hispidus) possess pharyngeal pouch remnants originating from different primordia(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Nakamura, Teppei; Ichii, Osamu; Irie, Takao; Mizoguchi, Tatsuya; Shinohara, Akio; Kouguchi, Hirokazu; Sunden, Yuji; Otsuka Kanazawa, Saori; Ali Elewa, Yaser Hosny; Koshimoto, Chihiro; Nagasaki, Ken Ichi; Kon, YasuhiroPharyngeal pouches in mammals develop into specific derivatives. If the differentiation of the pharyngeal pouches is anomalous, their remnants can result in cysts, sinuses, and fistulae in the differentiated organs or around the neck. In the present study, we found several pharyngeal pouch remnants, such as cystic structures in thymus and parathyroid gland and fossulae extended from the piriform fossa, in the inbred cotton rats maintained at Hokkaido Institute of Public Health (HIS/Hiph) and University of Miyazaki (HIS/Mz). In HIS/Hiph, the fossulae extended from the apex of the piriform fossa into the thyroid glands and were lined with stratified squamous and cuboidal epithelium. Calcitonin-positive C-cells were present within their epithelium in HIS/Hiph. In contrast, the fossulae of HIS/Mz ran outside the thyroid glands toward the parathyroid glands; they were lined with columnar ciliated epithelium and a few goblet cells, but had no Ccells, which was consistent with the cystic structures in the thymus and the parathyroid gland. These results indicated that the fossulae were a remnant of the ultimobranchial body in HIS/Hiph and of the thymopharyngeal duct in HIS/Mz. Thus, the fossulae of the piriform fossa resembled the piriform sinus fistula in human. In conclusion, cotton rats frequently possessed pharyngeal pouch remnants, including the piriform sinus fistula, and therefore, might serve as a novel model to elucidate the mechanisms of pharyngeal pouch development.
- PublicationOpen AccessMechanisms of regulation of normal and metaplastic intestinal differentiation(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Rodrigues, Jaime P.; David, Leonor; Almeida, Raquel; Barros, Rita; Freitas, Teresa; Ponte, Ana; Sousa, Mafalda; Silva, João Carlos; Carvalho, JoãoThe gastrointestinal tract is an organized structure originating from the three embryonic germ layers: endoderm, mesoderm and ectoderm. Morphological changes that accompany its formation are relatively well known, although the underlying molecular mechanisms are still poorly defined. Intestinal metaplasia, resulting from an epithelial transdifferentiation process, is considered a precursor lesion of gastric adenocarcinoma, a malignancy with serious consequences in terms of morbidity and mortality worldwide. Similarly to gastrointestinal embryonic development, molecular changes involved in the development of this lesion that recapitulate the intestinal development, out of time and space, are also widely unknown. In this review we present, briefly, the process of formation of the digestive tract, from its embryonic age to adulthood, with emphasis on anterior-posterior patterning and on molecular mechanisms that may play an important role. In addition, we try to establish a parallel and understand what mechanisms can, through their deregulation, originate the metaplastic lesion. Cdx genes appear to be the main regulators of normal intestinal differentiation and also to be largely involved in the metaplastic epithelial transdifferentiation process. However, control of gene expression both during intestinal development and in intestinal metaplasia is complex and seems to depend on several transcription factors. More extensive studies about the mechanisms underlying intestinal metaplasia are needed if we aim to prevent neoplasia development and all its negative consequences in persons at risk.
- PublicationOpen AccessAnimal models for disc degeneration-an update(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Jin, Li; Balian, Gary; Li, Xudong JoshuaIntervertebral disc degeneration is considered a major cause of back pain that places a heavy burden on society, both because of its effect on the physiology of individuals and its consequences on the world economy. During the past few decades, research findings in the pre-clinical setting have led to a significant increase in the understanding of intervertebral disc degeneration, although many aspects of the disease remain unclear. The goal of this review is to summarize existing animal models for disc degeneration studies and the difficulties that are associated with the use of such models. A firm understanding of the cellular and molecular events that ensue as a result of injuries, as well as environmental factors, could be instrumental in the development of targeted therapies for the treatment of intervertebral disc degeneration