An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV) ...epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type) with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism.
The COVID-19 fatality rate is high when compared to the H1N1pdm09 (pandemic Influenza A virus H1N1 subtype) rate, and although both cause an aggravated inflammatory response, the differences in the ...mechanisms of both pandemic pneumonias need clarification. Thus, our goal was to analyze tissue expression of interleukins 4, 13, (IL-4, IL-13), transforming growth factor-beta (TGF-β), and the number of M2 macrophages (Sphingosine-1) in patients who died by COVID-19, comparing with cases of severe pneumopathy caused by H1N1pdm09, and a control group without lung injury. Six lung biopsy samples of patients who died of SARS-CoV-2 (COVID-19 group) were used and compared with ten lung samples of adults who died from a severe infection of H1N1pdm09 (H1N1 group) and eleven samples of patients who died from different causes without lung injury (CONTROL group). The expression of IL-4, IL-13, TGF-β, and M2 macrophages score (Sphingosine-1) were identified through immunohistochemistry (IHC). Significantly higher IL-4 tissue expression and Sphingosine-1 in M2 macrophages were observed in the COVID-19 group compared to both the H1N1 and the CONTROL groups. A different mechanism of diffuse alveolar damage (DAD) in SARS-CoV-2 compared to H1N1pdm09 infections were observed. IL-4 expression and lung remodeling are phenomena observed in both SARS-CoV-2 and H1N1pdm09. However, SARS-CoV-2 seems to promote lung damage through different mechanisms, such as the scarce participation Th1/Th17 response and the higher participation of the Th2. Understanding and managing the aggravated and ineffective immune response elicited by SARS-CoV-2 merits further clarification to improve treatments propose.
Zika virus (ZIKV) infection in humans has been associated with congenital malformations and other neurological disorders, such as Guillain-Barré syndrome. The mechanism(s) of ZIKV intrauterine ...transmission, the cell types involved, the most vulnerable period of pregnancy for severe outcomes from infection and other physiopathological aspects are not completely elucidated. In this study, we analyzed placental samples obtained at the time of delivery from a group of 24 women diagnosed with ZIKV infection during the first, second or third trimesters of pregnancy. Villous immaturity was the main histological finding in the placental tissues, although placentas without alterations were also frequently observed. Significant enhancement of the number of syncytial sprouts was observed in the placentas of women infected during the third trimester, indicating the development of placental abnormalities after ZIKV infection. Hyperplasia of Hofbauer cells (HCs) was also observed in these third-trimester placental tissues, and remarkably, HCs were the only ZIKV-positive fetal cells found in the placentas studied that persisted until birth, as revealed by immunohistochemical (IHC) analysis. Thirty-three percent of women infected during pregnancy delivered infants with congenital abnormalities, although no pattern correlating the gestational stage at infection, the IHC positivity of HCs in placental tissues and the presence of congenital malformations at birth was observed. Placental tissue analysis enabled us to confirm maternal ZIKV infection in cases where serum from the acute infection phase was not available, which reinforces the importance of this technique in identifying possible causal factors of birth defects. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of some aspects of the pathophysiology of ZIKV.
Acute respiratory distress syndrome (ARDS) followed by repair with lung remodeling is observed in COVID-19. These findings can lead to pulmonary terminal fibrosis, a form of irreversible sequelae. ...There is evidence that TGF-β is intimately involved in the fibrogenic process. When activated, TGF-β promotes the differentiation of fibroblasts into myofibroblasts and regulates the remodeling of the extracellular matrix (ECM). In this sense, the present study evaluated the histopathological features and immunohistochemical biomarkers (ACE-2, AKT-1, Caveolin-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-β1 tissue expression) involved in the TGF-β1 signaling pathways and pulmonary fibrosis. The study consisted of 24 paraffin lung samples from patients who died of COVID-19 (COVID-19 group), compared to 10 lung samples from patients who died of H1N1pdm09 (H1N1 group) and 11 lung samples from patients who died of different causes, with no lung injury (CONTROL group). In addition to the presence of alveolar septal fibrosis, diffuse alveolar damage (DAD) was found to be significantly increased in the COVID-19 group, associated with a higher density of Collagen I (mature) and III (immature). There was also a significant increase observed in the immunoexpression of tissue biomarkers ACE-2, AKT-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-β1 in the COVID-19 group. A significantly lower expression of Caveolin-1 was also found in this group. The results suggest the participation of TGF-β pathways in the development process of pulmonary fibrosis. Thus, it would be plausible to consider therapy with TGF-β inhibitors in those patients recovered from COVID-19 to mitigate a possible development of pulmonary fibrosis and its consequences for post-COVID-19 life quality.
Discarded tissues, like human amniotic membranes and adipose tissue, were investigated for the application of Decellularized Human Amniotic Membrane (DAM) as a viable scaffold for transplantation of ...Adipose-derived stromal cells (ASCs) in bone regeneration of non-healing calvarial defects in rats. Amniotic membrane was decellularized to provide a scaffold for male Wistar rats ASCs expansion and transplantation. ASCs osteoinduction in vitro promoted the deposition of a mineralized bone-like matrix by ASCs, as calcified globular accretions associated with the cells on the DAM surface and inside the collagenous matrix. Non-healing calvarial defects on male Wistar rats were randomly divided in control without treatment, treatment with four layers of DAM, or four layers of DAM associated with ASCs. After 12 weeks, tissue blocks were examined by micro-computed tomography and histology. DAM promoted osteoconduction by increasing the collagenous matrix on both DAM treatments. DAM with ASCs stimulated bone deposition, demonstrated by a higher percentage of bone volume and trabecular bone number, compared to control. Besides the osteogenic capacity in vitro, ASCs stimulated the healing of calvarial defects with significant DAM graft incorporation concomitant with higher host bone deposition. The enhanced in vivo bone regeneration by undifferentiated ASCs loaded onto DAM confirmed the potential of an easily collected autologous cell source associated with a broadly available collagenous matrix in tissue engineering.
Zika virus and pregnancy: An overview Carvalho, Newton Sérgio; Carvalho, Beatriz Freitas; Dóris, Bruna ...
American journal of reproductive immunology (1989),
February 2017, 2017-02-00, 20170201, Volume:
77, Issue:
2
Journal Article
Peer reviewed
Open access
In May 2015, the first episodes of Zika virus infection of the Latin America were confirmed in Brazil, where currently 196 976 cases were reported. The main route of transmission occurs by Aedes ...mosquitoes, and the most common symptoms are maculopapular rash, fever, conjunctivitis, polyarthralgia, and periarticular edema. However, the infection is asymptomatic in 80% of the cases. The congenital infection is characterized when the transmission to the fetus occurs during pregnancy, but the mechanisms of how the virus infects the placenta remain unclear. Anatomopathological findings were described in first‐ and third‐trimester human placentas; however, the major affected tissue of the baby is the neural. Several clinical situations were listed in these fetuses, such as neurological, ophthalmological, auditory, and articular alterations. The World Health Organization proposed a new congenital syndrome caused by Zika virus. The virus has an important neurotropism and the main manifestation observed in the syndrome is microcephaly, which is usually severe and associated with other neurological injuries. The appearance of sudden rash in pregnant women determines immediate investigation through RT‐PCR and serological analysis. Moreover, the prevention consists in using repellents and avoiding endemic areas, considering that the vaccine is still under development.
Today there are more than 2 billion alcohol users and about 1.3 billion tobacco users worldwide. The chronic and heavy use of these two substances is at the heart of numerous diseases and may wreak ...havoc on the human oral microbiome. This study delves into the changes that alcohol and tobacco may cause on biofilms of the human oral microbiome. To do so, we used swabs to sample the oral biofilm of 22 subjects; including 9 control-individuals with no or very low consumption of alcohol and no consumption of tobacco, 7 who were chronic and heavy users of both substances and 6 active smokers that reported no significant alcohol consumption. DNA was extracted from swabs and the V1 region of the 16S rRNA gene was PCR amplified and sequenced using the Ion Torrent PGM platform, generating 3.7 million high quality reads. DNA sequences were clustered and OTUs were assigned using the ARB SILVA database and Qiime.
We found no differences in species diversity and evenness among the groups. However, we found a significant decrease in species richness in only smokers and in smokers/drinkers when compared to controls. We found that Neisseria abundance was significantly decreased in both groups when compared to controls. Smokers had significant increases in Prevotella and Capnocytophaga and reductions in Granulicatella, Staphylococcus, Peptostreptococcus and Gemella when compared to the two other groups. Controls showed higher abundance of Aggregibacter, whilst smokers/drinkers had lower abundances of Fusobacteria. Samples from only smokers clustered closer together than to controls and smokers/drinkers, and also had a significant reduction in inter-group dissimilarity distances, indicating a more homogenous group than controls.
Our results indicate that the continued use of tobacco or alcohol plus tobacco significantly reduces bacterial richness, which apparently leads to a reduction in inter-group variability, turning the respective biofilms into a more homogenous microenvironment in terms of bacterial community composition, with possible consequences for human oral diseases.
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is known to present with pulmonary and extra‐pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS‐CoV‐2 ...infection is likely to lead to more severe disease, with multi‐organ effects, including cardiovascular disease. SARS‐CoV‐2 has been associated with acute and long‐term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS‐CoV‐2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS‐CoV‐2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1‐like macrophage infiltration in the cardiac tissues of COVID‐19 patients. The DNA damage present in the SARS‐CoV‐2 patient samples, were further confirmed by γ‐H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon‐stimulated genes, in particular interferon and complement pathways, when compared with COVID‐19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS‐CoV‐2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra‐pulmonary organs, including the cardiovascular system of COVID‐19 patients, to delineate the immunopathobiology of SARS‐CoV‐2 infection, and long term impact on health.
Cardiac tissues collected at rapid autopsy from COVID‐19 and pandemic H1N1 patients were profiled using digital spatial profiling technology. The transcriptional profiles were compared and contrasted in the study to understand the impact of viral infection. Host transcriptomics showed distinct transcriptional profiles, such as DNA damage and repair which were upregulated in COVID‐19. The study highlights the need to understand the pathobiology of severe acute respiratory syndrome coronavirus 2 infection and the multi‐organ effects.
Background: Tracheal grafts have been investigated for over a century, aiming to replace various lesions. However, tracheal reconstruction surgery remains a challenge, primarily due to anatomical ...considerations, intraoperative airway management, the technical complexity of reconstruction, and the potential postoperative morbidity and mortality. Due to research development, the amniotic membrane (AM) and Wharton’s Jelly (WJ) arise as alternatives within the new set of therapeutic alternatives. These structures hold significant therapeutic potential for tracheal defects. This study analyzed the capacity of tracheal tissue regeneration after 60 days of decellularized WJ and AM implantation in rabbits submitted to conventional tracheostomy. Methods: An in vivo experimental study was carried out using thirty rabbits separated into three groups (Control, AM, and WJ) (n = 10). The analyses were performed 60 days after surgery through immunohistochemistry. Results: Different immunomarkers related to scar regeneration, such as aggrecan, TGF-β1, and α-SMA, were analyzed. However, they highlighted no significant difference between the groups. Collagen type I, III, and Aggrecan also showed no significant difference between the groups. Conclusions: Both scaffolds appeared to be excellent frameworks for tissue engineering, presenting biocompatibility and a desirable microenvironment for cell survival; however, they did not display histopathological benefits in trachea tissue regeneration.
Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein-kinin system (KKS), that affect patients inflicted by ...the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on
lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE
MCs, tryptase
MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.
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