Publications by authors named "Lucia de Noronha"

109 Publications

Antitumoral activity of liraglutide, a new DNMT inhibitor in breast cancer cells in vitro and in vivo.

Chem Biol Interact 2021 Sep 14;349:109641. Epub 2021 Sep 14.

Department of Basic Pathology, Laboratory of Epigenetics, Federal University of Paraná, Curitiba, PR, Brazil. Electronic address:

Breast cancer (BC) is the most frequently diagnosed female cancer and second leading cause of death. Despite the discovery of many antineoplastic drugs for BC, the current therapy is not totally efficient. In this study, we investigated the potential of repurposing the well-known diabetes type II drug liraglutide to modulate epigenetic modifications in BC cells lines in vitro and in vivo via Ehrlich mice tumors models. The in vitro results revealed a significant reduction on cell viability, migration, DNMT activity and displayed lower levels of global DNA methylation in BC cell lines after liraglutide treatment. The interaction between liraglutide and the DNMT enzymes resulted in a decrease profile of DNA methylation for the CDH1, ESR1 and ADAM33 gene promoter regions and, consequently, increased their gene and protein expression levels. To elucidate the possible interaction between liraglutide and the DNMT1 protein, we performed an in silico study that indicates liraglutide binding in the catalytic cleft via hydrogen bonds and salt bridges with the interdomain contacts and disturbs the overall enzyme conformation. The in vivo study was also able to reveal that liraglutide and the combined treatment of liraglutide and paclitaxel or methotrexate were effective in reducing tumor growth. Moreover, the modulation of CDH1 and ADAM33 mouse gene expression by DNA demethylation suggests a role for liraglutide in DNMT activity in vivo. Altogether, these results indicate that liraglutide may be further analysed as a new adjuvant treatment for BC.
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http://dx.doi.org/10.1016/j.cbi.2021.109641DOI Listing
September 2021

Placental Morphologic Similarities Between ZIKV-Positive and HIV-Positive Pregnant Women.

Front Immunol 2021 9;12:684194. Epub 2021 Jun 9.

Laboratory of Experimental Pathology, Postgraduate Program of Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

Zika virus (ZIKV) caused global concern due to Brazil's unexpected epidemic, and it was associated with congenital microcephaly and other gestational intercurrences. The study aimed to analyze the placenta morphometric changes of ZIKV-infected pregnant women (ZIKV group; n = 23) compared to placentas of HIV-infected (HIV group; n = 24) and healthy pregnant women (N-control group; n = 22). It also analyzed the relationship between the morphometric results and pathological alterations on conventional microscopy, gestational trimester of infection, and presence of the congenital Zika syndrome (CZS). There was a significant increase in area ( = 0.0172), as well as a higher number of knots ( = 0.0027), sprouts ( < 0.0001), and CD163 +Hofbauer cells (HCs) ( < 0.0001) in the ZIKV group compared to the N-control group, suggesting that villous dysmaturity and HCs hyperplasia could be associated with ZIKV infections. The HIV group had a higher area ( < 0.0001), perimeter ( = 0.0001), sprouts ( < 0.0001), and CD163 + HCs ( < 0.0001) compared to the N-control group, demonstrating that the morphometric abnormalities found in the ZIKV and HIV group are probably similar. However, when ZIKV and HIV groups are compared, it was observed a higher number of sprouts ( = 0.0066) and CD163+ HCs ( < 0.0001) in the first one, suggesting that placental ZIKV congenital changes could be more pronounced.
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http://dx.doi.org/10.3389/fimmu.2021.684194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219962PMC
June 2021

Effects of oral probiotics administration on the expression of transforming growth factor β and the proinflammatory cytokines interleukin 6, interleukin 17, and tumor necrosis factor α in skin wounds in rats.

JPEN J Parenter Enteral Nutr 2021 Jun 26. Epub 2021 Jun 26.

Department of Surgery, Federal University of Paraná, Curitiba, Brasil.

Background: Cytokines and growth factors play key roles during the tissue repair process. We aim to evaluate the effect of perioperative oral of probiotics, on the healing process in skin wound in rats, by histological aspects, and by the expression of TGF-β, and the pro-inflammatory cytokines IL6, IL7, and TNF-α.

Methods: 72 adult male Wistar rats were split into two groups control (n = 36) and probiotic group (n = 36). Each group was subdivided into three subgroups with 12 animals each according to euthanasia day: 3rd, 7th, and 10th postoperative(PO) day.

Results: Wound contraction was faster with the use of probiotics (p = .013). Also fibrosis was significantly higher in the Probiotic group in the 7th PO day (p = .028). In the probiotic group, there was a reduction of TNF-α at 3th PO day (p = .023); and a reduction of IL6 in 7th PO day (p = .030). There was also a reduction of the expression of IL-17 in 3rd PO day (p = .039) and 7rd PO day (P = .024). In contrast, TGF-β was lower in the 10th PO day (p = .031) in the probiotic group as compared to controls, indicating that the increase of the fibrosis caused negative feedback with the TGF-β.

Conclusion: Probiotics are associated with a shorter inflammatory phase by attenuating the expression of cytokines IL-6 and TNF-α and accelerating the reduction of IL-17 and TGF-β, leading to faster and improved cutaneous healing in rats.
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http://dx.doi.org/10.1002/jpen.2216DOI Listing
June 2021

Histological evaluation of capsules formed by texturized silicone implants with and without polyester mesh coverage (Parietex®). A study on female rats.

Acta Cir Bras 2021 14;36(5):e360505. Epub 2021 Jun 14.

PhD. School of Medicine - Pontifícia Universidade Católica do Paraná - Curitiba (PR), Brazil.

Purpose: To evaluate capsules formed by microtextured silicone implants with and without Parietex® mesh coverage histologically.

Methods: Sixty Wistar rats were divided in two groups (meshed and unmeshed). Each group was, then, divided into two subgroups for evaluation at 30 and 90 days. Capsules were analyzed based on hematoxylin and eosin (HE) and picrosirius staining.

Results: The number of fibroblasts, neutrophils and macrophages was similar among all subgroups. There was a higher lymphocyte reaction in the 30-day meshed group (p = 0.003). Giant cell reaction, granulation tissue and neoangiogenesis were similar among the subgroups. Synovial metaplasia was milder at 90-day in the unmeshed (p = 0.002) and meshed group (p < 0.001). Capsular thickness was significantly greater in the meshed samples (30-day p < 0.001 and 90-day p < 0.001). There was a similar amount of collagen types I and III in both groups.

Conclusions: The mesh-covered implants produced capsules similar to the microtextured ones when analyzing inflammatory variables. Synovial metaplasia was milder at 90 than at 30 days, and the capsular thickness was significantly greater in the meshed group. A similar amount of collagen types I and III was observed. Due to these characteristics, the mesh coverage did not seem to significantly affect the local inflammatory activity.
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http://dx.doi.org/10.1590/ACB360505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205442PMC
June 2021

Expression of Parkin, APC, APE1, and Bcl-xL in Colorectal Polyps.

J Histochem Cytochem 2021 Jul 15;69(7):437-449. Epub 2021 Jun 15.

Universidade Estadual de Ponta Grossa, Ponta Grossa, Brazil.

Colorectal cancer can develop through molecular, chromosomal, and epigenetic cumulative changes that transform the normal intestinal epithelium into the colorectal polyps, called conventional adenomas (CAs) or serrated polyps (SPs), recognized as precursors of invasive colorectal neoplasia. These benign lesions need to explore the morphology, histological diagnosis, and biomarkers profile to accurately characterize lesions with potential for evolution to cancer. This study aimed to correlate the immunohistochemical expression of Parkin and Adenomatous Polyposis Coli (APC; tumor suppressors), Human Apurinic/Apyrimidinic endonuclease 1 (APE1), and B-cell lymphoma-extra-large (Bcl-xL; oncogenic proteins) in sporadic colorectal polyps with clinical, endoscopic, and diagnostic data. Immunohistochemical analysis was performed on tissue microarray samples of 306 polyps. Based on the Allred score, the expressions were graduated in the cytoplasm and nucleus of superficial and cryptic cells. There was higher Parkin nuclear expression (=0.006 and 0.010) and APC cytoplasmic expression in cryptic cells (<0.001) in SPs. CAs, APE1 (<0.001) and Bcl-xL (<0.001) were more expressed in the nuclei and cytoplasms, respectively. These results are related to the biological role proposed for these proteins in cellular functions. They can contribute to the diagnosis criteria for polyps and improve the knowledge of biomarkers that could predict cancer development.
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http://dx.doi.org/10.1369/00221554211026296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246528PMC
July 2021

Association Between COVID-19 Pregnant Women Symptoms Severity and Placental Morphologic Features.

Front Immunol 2021 26;12:685919. Epub 2021 May 26.

Postgraduate Program of Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná-PUCPR, Curitiba, Brazil.

Since the beginning of the pandemic, few papers describe the placenta's morphological and morphometrical features in SARS-CoV-2-positive pregnant women. Alterations, such as low placental weight, accelerated villous maturation, decidual vasculopathy, infarcts, thrombosis of fetal placental vessels, and chronic histiocytic intervillositis (CHI), have been described.

Objective: To analyze clinical data and the placental morphological and morphometric changes of pregnant women infected with SARS-CoV-2 (COVID-19 group) in comparison with the placentas of non-infected pregnant women, matched for maternal age and comorbidities, besides gestational age of delivery (Control group).

Method: The patients in the COVID-19 and the Control group were matched for maternal age, gestational age, and comorbidities. The morphological analysis of placentas was performed using Amsterdam Placental Workshop Group Consensus Statement. The quantitative morphometric evaluation included perimeter diameter and number of tertiary villi, number of sprouts and knots, evaluation of deposition of villous fibrin, and deposition of intra-villous collagen I and III by Sirius Red. Additionally, Hofbauer cells (HC) were counted within villi by immunohistochemistry with CD68 marker.

Results: Compared to controls, symptomatic women in the COVID-19 group were more likely to have at least one comorbidity, to evolve to preterm labor and infant death, and to have positive SARS-CoV-2 RNA testing in their concepts. Compared to controls, placentas in the COVID-19 group were more likely to show features of maternal and fetal vascular malperfusion. In the COVID-19 group, placentas of symptomatic women were more likely to show CHI. No significant results were found after morphometric analysis.

Conclusion: Pregnant women with symptomatic SARS-CoV-2 infection, particularly with the severe course, are more likely to exhibit an adverse fetal outcome, with slightly more frequent histopathologic findings of maternal and fetal vascular malperfusion, and CHI. The morphometric changes found in the placentas of the COVID-19 group do not seem to be different from those observed in the Control group, as far as maternal age, gestational age, and comorbidities are paired. Only the deposition of villous fibrin could be more accentuated in the COVID-19 group (p = 0.08 borderline). The number of HC/villous evaluated with CD68 immunohistochemistry did not show a difference between both groups.
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http://dx.doi.org/10.3389/fimmu.2021.685919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187864PMC
July 2021

Lung Neutrophilic Recruitment and IL-8/IL-17A Tissue Expression in COVID-19.

Front Immunol 2021 30;12:656350. Epub 2021 Mar 30.

Laboratory of Experimental Pathology, Postgraduate Program of Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

The new SARS-CoV-2 virus differs from the pandemic Influenza A virus H1N1 subtype (H1N1pmd09) how it induces a pro-inflammatory response in infected patients. This study aims to evaluate the involvement of SNPs and tissue expression of IL-17A and the neutrophils recruitment in lung samples from patients who died of severe forms of COVID-19 comparing to those who died by H1N1pdm09. Twenty lung samples from patients SARS-CoV-2 infected (COVID-19 group) and 10 lung samples from adults who died from a severe respiratory H1N1pdm09 infection (H1N1 group) were tested. The tissue expression of IL-8/IL-17A was identified by immunohistochemistry, and hematoxylin and eosin (H&E) stain slides were used for neutrophil scoring. DNA was extracted from paraffin blocks, and genotyping was done in real time-PCR for two target polymorphisms. Tissue expression increasing of IL-8/IL-17A and a higher number of neutrophils were identified in samples from the H1N1 group compared to the COVID-19 group. The distribution of genotype frequencies in the gene was not statistically significant between groups. However, the G allele (GG and GA) of rs3819025 was correlated with higher tissue expression of IL-17A in the COVID-19 group. SARS-CoV-2 virus evokes an exacerbated response of the host's immune system but differs from that observed in the H1N1pdm09 infection since the IL-8/IL-17A tissue expression, and lung neutrophilic recruitment may be decreased. In SNP rs3819025 (G/A), the G allele may be considered a risk allele in the patients who died for COVID-19.
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http://dx.doi.org/10.3389/fimmu.2021.656350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044579PMC
May 2021

Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients.

Am J Physiol Lung Cell Mol Physiol 2020 Dec 2. Epub 2020 Dec 2.

Research Institute Pelé Pequeno Príncipe.

MicroRNAs (miRNAs) are critical modulators of endothelial homeostasis, which highlights their involvement in vascular diseases, including the ones caused by virus infections. Our main objective was to identify miRNAs involved in the endothelial function and determine their expression in post-mortem lung biopsies of COVID-19 patients with severe respiratory injuries and thrombotic events. Based on functional enrichment analysis, miR-26a-5p, miR-29b-3p, and miR-34a-5p were identified as regulators of mRNA targets involved in endothelial, and inflammatory signaling pathways as well as in viral diseases. A miRNA/mRNA network, constructed based on protein-protein interactions of the miRNA targets and the inflammatory biomarkers characterized in the patients, revealed a close interconnection of these miRNAs with relevance to the endothelial activation/dysfunction. Reduced expression levels of selected miRNAs were observed in the lung biopsies of COVID-19 patients (n=9) compared to the Controls (n=10)(P<0.01-0.0001). MiR-26a-5p and miR-29b-3p presented the best power to discriminate these groups (AUC=0.8286, and AUC=0.8125, respectively). The correlation analysis of the miRNAs with inflammatory biomarkers in the COVID-19 patients was significant for miR-26a-5p [IL-6 (r=0.5414), and ICAM-1(r=0.5624)], and miR-29b-3p [IL-4 (r=0.8332), and IL-8 (r=0.2654)]. Altogether, these findings demonstrate the relevance and the non-random involvement of miR-26a-5p, miR-29b-3p, and miR-34a-5p in endothelial dysfunction and inflammatory response in patients with SARS-CoV-2 infection and the occurrence of severe lung injury and immunothrombosis.
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http://dx.doi.org/10.1152/ajplung.00457.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938642PMC
December 2020

Association of estrogen receptor alpha 1 and TMJ dysfunction: A pilot study.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Apr 28;131(4):e89-e94. Epub 2020 Nov 28.

Full Professor, School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba-PR, Brazil. Electronic address:

Objective: Temporomandibular disorder (TMD) is a multifactorial condition and the most common cause of orofacial pain, affecting mostly women, which points to a female hormone predilection. Therefore, the aim of this study was to analyze the association between TMD and estrogen receptor alpha 1 expression in disks of patients with TMD and condyle fracture (CFx).

Study Design: Forty specimens (from 27 patients) included n = 8 CFx, n = 21 anterior disk displacement with reduction (ADDwR), and n = 11 anterior disk displacement without reduction (ADDwoR). Age, area, and intensity of immunostaining were statistically compared between CFx, ADDwR, and ADDwoR groups using analysis of variance and Kruskal-Wallis analysis (P < .05).

Results: No significant difference between CFx, ADDwR, and ADDwoR groups with respect to age and expression of estrogen receptor alpha 1 was observed on immunohistochemical examination.

Conclusion: No association of estrogen receptor alpha 1 expression and age was found in the CFx, ADDwR, and ADDwoR groups.
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http://dx.doi.org/10.1016/j.oooo.2020.11.010DOI Listing
April 2021

Neuroinflammatory Regulation of Gold Nanoparticles Conjugated to Ethylene Dicysteine Diethyl Ester in Experimental Autoimmune Encephalomyelitis.

ACS Biomater Sci Eng 2021 03 15;7(3):1242-1251. Epub 2021 Feb 15.

Laboratory of Exercise Biochemistry in Health, Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, Paraná, Brazil.

Multiple sclerosis (MS) is a demyelinating chronic autoimmune inflammatory disease of the central nervous system (CNS). A large amount of proinflammatory cytokines is released in the CNS from the self-reactive T cells infiltrate, leading to the destruction of the myelin sheath and contributing to the development of MS. Several drugs have emerged in recent years to treat MS, and studies have shown that gold nanoparticles (GNPs) have anti-inflammatory properties in autoimmune diseases. Thus, the effects of GNP conjugation to ethylene dicysteine diethyl ester (ECD) were evaluated in C57BL/6 female mice exposed to experimental MS. Animals were exposed to experimental autoimmune encephalitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG35-55) in complete Freund's adjuvant supplemented with . The clinical and cerebral effects of the different doses of ECD-GNPs (0.3, 0.6, and 1.0 mg/kg) were first studied, and the results showed that the group treated with 0.6 mg/kg ECD-GNPs improved clinical symptoms, inflammatory infiltrate, and myelin integrity. In the following step, GNPs and ECD-GNPs (0.6 mg/kg) showed improvements in the clinical signs of the disease. Moreover, there was a reduction in the levels of proinflammatory cytokines in both groups compared to EAE, and only the isolated use of GNPs increased IL-4 expression. Both NF-κB and TGFβ immunoexpression were significantly reduced following EAE + GNPs and EAE + ECD-GNPs treatment. In conclusion, GNPs and ECD-GNPs at 0.6 mg/kg attenuate the neurological signs of EAE likely due to inhibition of neuroinflammation induced by EAE.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01592DOI Listing
March 2021

Combined Biomaterials: Amniotic Membrane and Adipose Tissue to Restore Injured Bone as Promoter of Calcification in Bone Regeneration: Preclinical Model.

Calcif Tissue Int 2021 05 9;108(5):667-679. Epub 2021 Jan 9.

Cell Therapy and Biotechnology in Regenerative Medicine Department, The Pelé Pequeno Príncipe Institute, Child and Adolescent Health Research & Pequeno Príncipe Faculties, Ave. Silva Jardim, no. 1632, Box 80240-020, Curitiba, Paraná, Brazil.

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.
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http://dx.doi.org/10.1007/s00223-020-00793-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064990PMC
May 2021

Physical Exercise-Mediated Changes in Redox Profile Contribute to Muscle Remodeling After Passive Hand-Rolled Cornhusk Cigarette Smoke Exposure.

Front Physiol 2020 17;11:590962. Epub 2020 Nov 17.

Laboratory of Exercise Biochemistry in Health, Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

Consumption of non-traditional cigarettes has increased considerably worldwide, and they can induce skeletal muscle dysfunction. Physical exercise has been demonstrated to be important for prevention and treatment of smoking-related diseases. Therfore, the aim of this study was to investigate the effects of combined physical exercise (aerobic plus resistance exercise) on muscle histoarchitecture and oxidative stress in the animals exposed chronically to smoke from hand-rolled cornhusk cigarette (HRCC). Male Swiss mice were exposed to ambient air or passively to the smoke of 12 cigarettes over three daily sessions (four cigarettes per session) for 30 consecutive days with or without combined physical training. 48 h after the last training session, total leukocyte count was measured in bronchoalveolar lavage fluid (BALF), and the quadriceps were removed for histological/immunohistochemical analysis and measurement of oxidative stress parameters. The effects of HRCC on the number of leukocytes in BALF, muscle fiber diameter, central nuclei, and nuclear factor kappa B (NF-κB) were reverted after combined physical training. In addition, increased myogenic factor 5, tumor necrosis factor alpha (TNFα), reduced transforming growth factor beta (TGF-β), and nitrate levels were observed after physical training. However, the reduction in superoxide dismutase and glutathione/glutathione oxidized ratio induced by HRCC was not affected by the training program. These results suggest the important changes in the skeletal muscle brought about by HRCC-induced alteration in the muscle redox profile. In addition, combined physical exercise contributes to remodeling without disrupting muscle morphology.
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http://dx.doi.org/10.3389/fphys.2020.590962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705113PMC
November 2020

Reduced Remodeling Biomarkers Tissue Expression in Nanotextured Compared With Polyurethane Implants Capsules: A Study in Rats.

Aesthet Surg J 2021 05;41(6):NP664-NP683

Postgraduate Program in Physiopathology and Surgical Sciences, State University of Rio de Janeiro (UERJ).

Background: In the biological response to biomaterials, the implant shell plays a key role in immune and inflammatory reactions. We hypothesized that the capsules formed around nanotextured implants exhibit an immunohistochemical behavior different to those formed around polyurethane implants.

Objectives: The aim of this study was to evaluate through immunohistochemistry markers the capsules formed around nanotextured and polyurethane implants.

Methods: Sixty albino female Wistar rats were divided into 2 groups (nanotextured and polyurethane), with 30 animals in each group. A mini silicone implant was inserted on the back of the animals. After a predetermined period, the animals were killed, and the capsules formed around the implants were studied. The capsules in the 30-, 60-, and 90-day subgroups were analyzed via immunohistochemistry to detect markers for fibroblast α smooth muscle actin (α-SMA), transforming growth factor β (TGF-β), cluster of differentiation 34 (CD34), and CD68, via picrosirius staining to determine the density of type I and III collagen fibers and via hematoxylin and eosin staining to assess capsule thickness. A Wilcoxon-Mann-Whitney test was used to compare the groups, and a Kruskal-Wallis test was used to compare the subgroups.

Results: Lower α-SMA, TGF-β, CD34 and CD68 immunoexpression was observed in the nanotextured 30- and 60-day subgroups than in the corresponding polyurethane subgroups. In the 90-day subgroup, more pronounced α-SMA and CD34 immunoexpression was observed in the nanotextured group; however, TGF-β and CD68 immunoexpression remained lower. The nanotextured implants showed reduced capsular thickness and greater formation of type I collagen in all the analyzed subgroups.

Conclusions: Nanotextured implants led to reduced immune and inflammatory reactions compared with polyurethane implants according to all analyzed variables.
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http://dx.doi.org/10.1093/asj/sjaa315DOI Listing
May 2021

The role of the lectin pathway of the complement system in SARS-CoV-2 lung injury.

Transl Res 2021 05 20;231:55-63. Epub 2020 Nov 20.

Laboratory of Experimental Pathology, School of Medicine, Pontifícia Universidade Católica do Paraná - PUCPR, Curitiba, PR, Brazil.

Although some evidence showed the activation of complement systems in COVID-19 patients, proinflammatory status and lectin pathway remain unclear. Thus, the present study aimed to demonstrate the role of MBL and ficolin-3 in the complement system activation and compared to pandemic Influenza A virus H1N1 subtype infection (H1N1pdm09) and control patients. A total of 27 lungs formalin-fixed paraffin-embedded samples (10 from H1N1 group, 6 from the COVID-19 group, and 11 from the control group) were analyzed by immunohistochemistry using anti-IL-6, TNF-alfa, CD163, MBL e FCN3 antibodies. Genotyping of target polymorphisms in the MBL2 gene was performed by real-time PCR. Proinflammatory cytokines such as IL-6 and TNF-alpha presented higher tissue expression in the COVID-19 group compared to H1N1 and control groups. The same results were observed for ICAM-1 tissue expression. Increased expression of the FCN3 was observed in the COVID-19 group and H1N1 group compared to the control group. The MBL tissue expression was higher in the COVID-19 group compared to H1N1 and control groups. The genotypes AA for rs180040 (G/A), GG for rs1800451 (G/A) and CC for rs5030737 (T/C) showed a higher prevalence in the COVID-19 group. The intense activation of the lectin pathway, with particular emphasis on the MBL pathway, together with endothelial dysfunction and a massive proinflammatory cytokines production, possibly lead to a worse outcome in patients infected with SARS-Cov-2. Moreover, 3 SNPs of our study presented genotypes that might be correlated with high MBL tissue expression in the COVID-19 pulmonary samples.
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http://dx.doi.org/10.1016/j.trsl.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677075PMC
May 2021

Covid-19 cytokine storm in pulmonary tissue: Anatomopathological and immunohistochemical findings.

Respir Med Case Rep 2020 12;31:101292. Epub 2020 Nov 12.

Laboratory of Experimental Pathology - School of Medicine, Pontifícia Universidade Católica Do Paraná - PUCPR, R. Imaculada Conceição, 1155, Prado Velho, Curitiba, PR, Brazil.

The COVID-19 pandemic is a worldwide threat, and information on physiopathological aspects of the disease is limited. Despite efforts in searching treatment options, a better understanding of the SARS-CoV-2 pathways can contribute to managing severe cases. In this study, we aim to describe pathological and immunopathogenic findings of two different cases, both in the high-risk group. Post-mortem lung biopsies were analyzed by traditional and immunohistochemical methods. Tissue expression of innate and adaptive immune response biomarkers was tested. We observed a higher innate response in case 1 with an abundance of mast cells, scarce CD8 lymphocytes, high expression of TNF-alpha, and almost absent adaptative immune response. In case 2, the adaptative immune response was present, with numerous CD8 lymphocytes and higher levels of IL-4 and TGF-beta. Both cases converged to a prothrombotic state expressing high IL-6, followed by ICAM-1 expression and endotheliites leading to systemic inflammatory response syndrome. In conclusion, differences in age and comorbidities and immune response described here may be related to the SARS-CoV-2 delay in the adaptative immune response, evolution stage of diffuse alveolar damage, and progression for systemic inflammatory response syndrome.
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http://dx.doi.org/10.1016/j.rmcr.2020.101292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658564PMC
November 2020

Intrauterine Transmission of SARS-CoV-2.

Emerg Infect Dis 2021 Feb 13;27(2):638-641. Epub 2020 Nov 13.

We documented fetal death associated with intrauterine transmission of severe acute respiratory syndrome coronavirus 2. We found chronic histiocytic intervillositis, maternal and fetal vascular malperfusion, microglial hyperplasia, and lymphocytic infiltrate in muscle in the placenta and fetal tissue. Placenta and umbilical cord blood tested positive for the virus by PCR, confirming transplacental transmission.
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http://dx.doi.org/10.3201/eid2702.203824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853547PMC
February 2021

IL-4/IL-13 remodeling pathway of COVID-19 lung injury.

Sci Rep 2020 10 29;10(1):18689. Epub 2020 Oct 29.

Laboratory of Experimental Pathology, School of Medicine, Pontifícia Universidade Católica do Paraná-PUCPR, R. Imaculada Conceição, 1155 - Prado Velho, Curitiba, PR, Brazil.

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.
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http://dx.doi.org/10.1038/s41598-020-75659-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596721PMC
October 2020

From adrenarche to aging of adrenal zona reticularis: precocious female adrenopause onset.

Endocr Connect 2020 Dec;9(12):1212-1220

Pelé Pequeno Príncipe Research Institute, Água Verde, Curitiba, Parana, Brazil.

Objective: Adaptive changes in DHEA and sulfated-DHEA (DHEAS) production from adrenal zona reticularis (ZR) have been observed in normal and pathological conditions. Here we used three different cohorts to assess timing differences in DHEAS blood level changes and characterize the relationship between early blood DHEAS reduction and cell number changes in women ZR.

Materials And Methods: DHEAS plasma samples (n = 463) were analyzed in 166 healthy prepubertal girls before pubarche (<9 years) and 324 serum samples from 268 adult females (31.9-83.8 years) without conditions affecting steroidogenesis. Guided by DHEAS blood levels reduction rate, we selected the age range for ZR cell counting using DHEA/DHEAS and phosphatase and tensin homolog (PTEN), tumor suppressor and cell stress marker, immunostaining, and hematoxylin stained nuclei of 14 post-mortem adrenal glands.

Results: We confirmed that overweight girls exhibited higher and earlier DHEAS levels and no difference was found compared with the average European and South American girls with a similar body mass index (BMI). Adrenopause onset threshold (AOT) defined as DHEAS blood levels <2040 nmol/L was identified in >35% of the females >40 years old and associated with significantly reduced ZR cell number (based on PTEN and hematoxylin signals). ZR cell loss may in part account for lower DHEA/DHEAS expression, but most cells remain alive with lower DHEA/DHEAS biosynthesis.

Conclusion: The timely relation between significant reduction of blood DHEAS levels and decreased ZR cell number at the beginning of the 40s suggests that adrenopause is an additional burden for a significant number of middle-aged women, and may become an emergent problem associated with further sex steroids reduction during the menopausal transition.
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http://dx.doi.org/10.1530/EC-20-0416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774755PMC
December 2020

Mast Cells in Alveolar Septa of COVID-19 Patients: A Pathogenic Pathway That May Link Interstitial Edema to Immunothrombosis.

Front Immunol 2020 18;11:574862. Epub 2020 Sep 18.

School of Medicine, Pontifícia Universidade Católica do Paraná PUCPR, Curitiba, Brazil.

It is currently believed that innate immunity is unable to prevent the spread of SARS-CoV-2 from the upper airways to the alveoli of high-risk groups of patients. SARS-CoV-2 replication in ACE-2-expressing pneumocytes can drive the diffuse alveolar injury through the cytokine storm and immunothrombosis by upregulating the transcription of chemokine/cytokines, unlike several other respiratory viruses. Here we report histopathology data obtained in post-mortem lung biopsies of COVID-19, showing the increased density of perivascular and septal mast cells (MCs) and IL-4-expressing cells ( = 6), in contrast to the numbers found in pandemic H1N1-induced pneumonia ( = 10) or Control specimens ( = 10). Noteworthy, COVID-19 lung biopsies showed a higher density of CD117 cells, suggesting that c-kit positive MCs progenitors were recruited earlier to the alveolar septa. These findings suggest that MC proliferation/differentiation in the alveolar septa might be harnessed by the shift toward IL-4 expression in the inflamed alveolar septa. Future studies may clarify whether the fibrin-dependent generation of the hyaline membrane, processes that require the diffusion of procoagulative plasma factors into the alveolar lumen and the endothelial dysfunction, are preceded by MC-driven formation of interstitial edema in the alveolar septa.
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http://dx.doi.org/10.3389/fimmu.2020.574862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530169PMC
October 2020

Plexiform Lesions in an Experimental Model of Monocrotalin-Induced Pulmonary Arterial Hypertension.

Arq Bras Cardiol 2020 09;115(3):480-490

Hospital Universitário Evangélico Mackenzie (HUEM), Curitiba, PR - Brasil.

Background: The monocrotaline (MCT)-induced pulmonary arterial hypertension model is one of the most reproduced today, presenting as a limitation the absence of plexiform lesions, typical manifestations of the severe disease in humans.

Objective: To evaluate the severity of MCT-induced pulmonary arteriopathy by pathological findings of lung and heart tissue samples, clinical course and 37-day survival.

Methods: Fifty male Wistar rats were divided into one of the four groups - control (CG) (n = 10) and three intervention (MCT) groups. The MCT groups received intraperitoneal injection (60 mg/kg) of MCT and remained exposed to the substance for 15 days (G15, n = 10), 30 days (G30, n = 10) and 37 days (G37, n = 20). At the end of each period, the animals were sacrificed, and pulmonary and cardiac tissues were collected for anatomopathological and morphometric analysis. The Kruskal-Wallis test was used, considering a level of significance of 5%.

Results: In the lungs of MCT animals, lesions related to pulmonary arteriopathy were found, including muscularization of the arterioles, hypertrophy of the middle layer and concentric neointimal lesions. Complex lesions were observed in MCT groups, described as plexiform and plexiform-like lesions. Right ventricular hypertrophy was evidenced by increased thickness and diameter of the cardiomyocytes and a significant increase in the right ventricular wall thickness (p <0.0000).

Conclusion: The MCT model was able to generate moderate-severe pulmonary arteriopathy associated with secondary right ventricular hypertrophy. The 37-day survival rate was 50%. To our knowledge, this study was the first to note the presence of complex vascular lesions, similar to those observed in patients with severe pulmonary arterial hypertension, in an isolated MCT model. (Arq Bras Cardiol. 2020; 115(3):480-490).
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http://dx.doi.org/10.36660/abc.20190306DOI Listing
September 2020

Invasive aspergillosis complication in yellow fever vaccine induced viscerotropic disease.

Med Mycol Case Rep 2020 Dec 17;30:12-14. Epub 2020 Sep 17.

Complexo Hospital de Clínicas, Universidade Federal Do Paraná, 180 General Carneiro Street, Curitiba, 80060-900, Brazil.

Invasive aspergillosis (IA) usually occurs in immunocompromised hosts, but in the last decade IA has emerged in critically ill non-neutropenic patients, as those with severe Influenza and Chronic Obstructive Pulmonary Disease (COPD). We report an unusual fatal case of disseminated IA in a non-immunocompromised patient following yellow fever vaccine-associated viscerotropic disease.
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http://dx.doi.org/10.1016/j.mmcr.2020.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522283PMC
December 2020

Downregulation of IGF2 expression in third trimester placental tissues from Zika virus infected women in Brazil.

J Infect 2020 11 26;81(5):766-775. Epub 2020 Sep 26.

Laboratório de Virologia Molecular, Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba, PR, Brazil. Electronic address:

Objectives: Screening for genes differentially expressed in placental tissues, aiming to identify transcriptional signatures that may be involved in ZIKV congenital pathogenesis.

Methods: Transcriptome data from placental tissues of pregnant women naturally infected with Zika virus during the third trimester were compared to those from women who tested negative for Zika infection. The findings were validated using both a cell culture model and an immunohistochemistry/morphological analysis of naturally infected placental tissues.

Results: Transcriptome analysis revealed that Zika virus infection induces downregulation of insulin-like growth factor II (IGF2) gene, an essential factor for fetal development. The Caco-2 cell culture model that constitutively expresses IGF2 was used for the transcriptome validation. Asiatic and African Zika virus strains infection caused downregulated IGF2 gene expression in Caco-2 cells, whereas other flaviviruses, such as dengue serotype 1, West Nile and wild-type yellow fever viruses, had no effect on this gene expression. Immunohistochemical assays on decidual tissues corroborated our transcriptome analysis, showing that IGF2 is reduced in the decidua of Zika virus-infected women.

Conclusions: Our results draw attention to IGF2 modulation in uterine tissues, and this finding is expected to support future studies on strategies to ameliorate the harmful effects of Zika virus infection during pregnancy.
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http://dx.doi.org/10.1016/j.jinf.2020.09.028DOI Listing
November 2020

IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection.

Virus Res 2020 11 23;289:198171. Epub 2020 Sep 23.

Laboratory of Emerging Infectious Diseases, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil. Electronic address:

Background: Innate and adaptive immune responses have been evaluated in infected patients with COVID-19. The severity of the disease has been supposed to be associated with some profile not reported with other bacterial and viral pneumonia. We proposed a study in patients with moderate to severe COVID-19 infection to evaluate the interleukin patterns and its role as prognosis factors.

Methods: A prospective cohort with moderate and severe cases of COVID-19 infection from June to July 2020. Blood samples from patients were collected regularly to evaluate IFN-γ, TNF-α, IL-4, IL-6, and IL-10. Clinical, laboratory, radiological data, and outcomes were recorded. The outcome variable was in-hospital death, survival, mechanical ventilation, and admission at the intensive care unit. Data are presented in median and interquartile range [IQR].

Results: We evaluated the Th1 and Th2 responses according to evolution, distinguishing possible predictive markers. The IFN-γ median of 323 pg/mL [IQR 166-570] was found in patients who died and 208 pg/mL [IQR 155-392] in the survival group (p = 0.017). IFN-γ was also higher in the early stages of the disease (394 pg/mL [IQR 229-575] against 162 pg/mL [IQR 117-259], p < 0.001). IL-4 that was increased in late-stage (182 pg/mL [IQR 162-199] against 131 pg/mL [IQR 124-152], p < 0.001) but not associated with mortality. Also, death was also related to male gender (relative risk = 1.5 [95 % confidence interval = 1.1-2.0]).

Conclusion: Our results suggest that the activation of the host immune response between Th1 or Th2 in COVID-19 infection may be related to the final result between discharge or death. This implies an attempt to control cytokines, such as IFN-γ, with combined therapies for clinical treatment.
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http://dx.doi.org/10.1016/j.virusres.2020.198171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510544PMC
November 2020

Endothelial Dysfunction and Thrombosis in Patients With COVID-19-Brief Report.

Arterioscler Thromb Vasc Biol 2020 10 7;40(10):2404-2407. Epub 2020 Aug 7.

Laboratory of Experimental Pathology (L.d.N.), School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.

Objective: Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. Approach and Results: Postmortem lung samples (COVID-19 group =6 cases; H1N1 group =10 cases, and control group =11 cases) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-IL (interleukin)-6, anti-TNF (tumor necrosis factor)-α, anti-ICAM-1 (intercellular adhesion molecule 1), and anticaspase-1. From the result, IL-6, TNF-α, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups.

Conclusions: Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples. These conditions might lead to systemic thrombotic events that could impair the clinical staff's efforts to avoid fatal outcomes. One of the health professionals' goals should be to identify the high risk of thrombosis patients early to block endotheliopathy and its consequences.
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http://dx.doi.org/10.1161/ATVBAHA.120.314860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505138PMC
October 2020

The role of IL-17A/IL-17RA and lung injuries in children with lethal non-pandemic acute viral pneumonia.

Immunobiology 2020 07 6;225(4):151981. Epub 2020 Jul 6.

Laboratory of Experimental Pathology, School of Medicine, Pontifical Catholic University of Parana - PUCPR, R. Imaculada Conceição, 1155 - Prado Velho, Curitiba, PR, Brazil; Department of Medical Pathology, Federal University of Parana - UFPR, R. Padre Camargo, 280 - Alto da Glória, Curitiba, PR, Brazil. Electronic address:

This study aimed to evaluate IL-17A (interleukin 17A) and IL-17RA (IL-17A receptor) in a pediatric population that died with non-pandemic acute viral pneumonia compared to the non-viral pneumonia group. Necropsy lung samples (n = 193) from children that died after severe acute infection pneumonia were selected and processed for viral antigen detection by immunohistochemistry. After this, they were separated into two groups: virus-positive (n = 68) and virus-negative lung samples (n = 125). Immunohistochemistry was performed to assess the presence of IL-17A and IL-17RA in the lung tissue. The virus-positive group showed stronger immunolabeling for IL-17A and IL-17RA (p = 0.020 and p < 0.001, respectively). The result of this study may suggest that IL-17A and IL-17RA plays an essential role in the maintenance of viral infection and lung injuries. These aspects may increase the severity of the inflammatory response leading to lethal lung injuries in these patients. Children with community-acquired non-pandemic pneumonia that requiring hospitalization could benefit from using IL-17RA/IL-17A monoclonal antibodies to block their injurious effects.
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http://dx.doi.org/10.1016/j.imbio.2020.151981DOI Listing
July 2020

EFFECTS OF PROBIOTICS SUPPLEMENTATION ON SKIN WOUND HEALING IN DIABETIC RATS.

Arq Bras Cir Dig 2020 Jul;33(1):e1498

Postgraduate Program in Surgical Clinic, Federal University of Paraná, Curitiba PR, Brazil.

Background: Example of wound contraction area at: A) day of surgery in the control group; B) 7PO in the control group; C) day of surgery in the probiotic group; D) 7PO in probiotic group. Chronic wounds in patients with Diabetes Mellitus often become incurable due to prolonged and excessive production of inflammatory cytokines. The use of probiotics modifies the intestinal microbiota and modulates inflammatory reactions.

Aim: To evaluate the influence of perioperative supplementation with probiotics in the cutaneous healing process in diabetic rats.

Methods: Forty-six rats were divided into four groups (C3, P3, C10, P10) according to the treatment (P=probiotic or C=control, both orally administered) and day of euthanasia, 3rd or 10th postoperative days. All rats were induced to Diabetes Mellitus 72 h before starting the experiment with alloxan. Supplementation was initiated five days before the incision and maintained until euthanasia. Scalpel incision was guided by a 2x2 cm mold and the wounds were left to heal per second-intention. The wounds were digitally measured. Collagen densitometry was done with Picrosirius Red staining. Histological parameters were analyzed by staining by H&E.

Results: The contraction of the wound was faster in the P10 group which resulted in a smaller scar area (p=0.011). There was an increase in type I collagen deposition from the 3rd to the 10th postoperative day in the probiotic groups (p=0.016), which did not occur in the control group (p=0.487). The histological analysis showed a better degree of healing in the P10 group (p=0.005), with fewer polymorphonuclear (p<0.001) and more neovessels (p=0.001).

Conclusions: Perioperative supplementation of probiotics stimulates skin wound healing in diabetic rats, possibly due to attenuation of the inflammatory response and increased neovascularization and type I collagen deposition.
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http://dx.doi.org/10.1590/0102-672020190001e1498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357555PMC
July 2020

Analysis of interleukins 6, 8, 10 and 17 in the lungs of premature neonates with bronchopulmonary dysplasia.

Cytokine 2020 07 11;131:155118. Epub 2020 May 11.

Laboratory of Experimental Pathology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil. Electronic address:

Bronchopulmonary dysplasia (BPD) is an abnormality that occurs in premature neonate lung development. The pathophysiology is uncertain, but the inflammatory response to lung injury may be the responsible pathway. The objective of this study is to evaluate the role of interleukins 6, 8, 10, and 17 through the anatomopathological and immunohistochemical study of the lungs of premature neonates with BPD. Thirty-two cases of neonatal autopsies from the Pathology Department of the Clinics Hospital of the Universidade Federal do Paraná, who presented between 1991 and 2005 were selected. The sample included neonates less than 34 weeks of gestational age who underwent oxygen therapy and had pulmonary formalin-fixed paraffin-embedded (FFPE) samples. Pulmonary specimens were later classified into three groups according to histopathological and morphometric changes (classic BPD, new BPD, and without BPD) and subjected to immunohistochemical analysis. The antibodies selected for the study were anti-IL-6, anti-IL-8, anti-IL-10, and anti-IL-17A monoclonal antibodies. IL-6, IL-8, and IL-10 showed no significant differences in tissue expression among the groups. IL-17A had higher tissue immunoreactivity in the group without BPD compared with the classic BPD group (1686 vs. 866 μm, p = 0.029). This study showed that the involvement of interleukins 6, 8, and 10 might not be significantly different between the two types of BPD. We speculated that IL-17A could be a protective factor in this disease.
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http://dx.doi.org/10.1016/j.cyto.2020.155118DOI Listing
July 2020

Conservation of both hematocrit and liver regeneration in hepatectomies: a vascular occlusion approach in rats.

Arq Bras Cir Dig 2020 30;33(1):e1484. Epub 2020 Mar 30.

Department of Surgery, Health Sciences Sector.

Background: Hepatectomies promote considerable amount of blood loss and the need to administrate blood products, which are directly linked to higher morbimortality rates. The blood-conserving hepatectomy (BCH) is a modification of the selective vascular occlusion technique. It could be a surgical maneuver in order to avoid or to reduce the blood products utilization in the perioperative period.

Aim: To evaluate in rats the BCH effects on the hematocrit (HT) variation, hemoglobin serum concentration (HB), and on liver regeneration.

Methods: Twelve Wistar rats were divided into two groups: control (n=6) and intervention (n=6). The ones in the control group had their livers partially removed according to the Higgins and Anderson technique, while the rats in the treatment group were submitted to BCH technique. HT and HB levels were measured at day D0, D1 and D7. The rate between the liver and rat weights was calculated in D0 and D7. Liver regeneration was quantitatively and qualitatively evaluated.

Results: The HT and HB levels were lower in the control group as of D1 onwards, reaching an 18% gap at D7 (p=0.01 and p=0.008, respectively); BCH resulted in the preservation of HT and HB levels to the intervention group rats. BCH did not alter liver regeneration in rats.

Conclusion: The BCH led to beneficial effects over the postoperative HT and serum HB levels with no setbacks to liver regeneration. These data are the necessary proof of evidence for translational research into the surgical practice. A) Unresected liver; B) liver appearance after the partial hepatectomy (1=vena cava; 2=portal vein; 3=hepatic vein; 4=biliary drainage; 5=hepatic artery).
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http://dx.doi.org/10.1590/0102-672020190001e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099868PMC
April 2020

EFFECT OF PROBIOTIC ORAL ADMINISTRATION ON SKIN WOUND HEALING IN RATS.

Arq Bras Cir Dig 2019 9;32(3):e1457. Epub 2019 Dec 9.

Pathology Laboratory, Pontifical Catholic University of Paraná, Curitiba, PR, Brazil.

Background: Manipulating intestinal microbiota with probiotics might stimulate skin response. Understanding all stages of the healing process, as well as the gut-skin-healing response can improve the skin healing process.

Aim: To evaluate the effect of perioperative oral administration of probiotics on the healing of skin wounds in rats.

Methods: Seventy-two Wistar male adult rats were weighed and divided into two groups with 36 each, one control group (supplemented with oral maltodextrin 250 mg/day) and one probiotic group (supplemented with Lactobacillus paracasei LPC-37, Bifidobacterium lactis HN0019, Lactobacillus rhamnosus HN001, Lactobacillus acidophilus NCFM® at a dose of 250 mg/day), both given orally daily for 15 days. The two groups were subsequently divided into three subgroups according to the moment of euthanasia: in the 3rd, 7th and 10th postoperative days.

Results: There were no significant changes in weight in both groups. Wound contraction was faster in probiotic group when compared to the controls, resulting in smaller wound area in the 7th postoperative day. As for histological aspects, the overall H&E score was lower in the probiotic group. The probiotic group showed increased fibrosis from 3rd to the 7th postoperative day. The type I collagen production was higher in the probiotic group at the 10th postoperative day, and the type III collagen increased in the 7th.

Conclusion: The perioperative use of orally administrated probiotic was associated with a faster reduction of the wound area in rats probably by reducing the inflammatory phase, accelerating the fibrosis process and the deposition of collagen.
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http://dx.doi.org/10.1590/0102-672020190001e1457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902899PMC
February 2020
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