From Nonfunctioning Adrenocortical Cancer to Biochemically Silent Paraganglioma Associated with SDHB Mutation: An Uncommon Presentation of a Patient with a Retroperitoneal Mass.

The combination of clinical characteristics and diagnostic exams including imaging, laboratory, and molecular tests help in the differential diagnosis of retroperitoneal lesions. We report a 41-year-old male with a metastatic retroperitoneal lesion with atypical characteristics, displaying pathological findings consistent with both nonsecretory pheochromocytomas/paragangliomas and adrenal cortex carcinoma. The patient was examined for abdominal pain, weight loss, and hypertension. Abdominal computed tomography showed a 21 × 8 × 10-cm right retroperitoneal mass. He was initially diagnosed as pheochromocytoma/paraganglioma (PHEO/PGL). However, the diagnosis was later changed to adrenocortical carcinoma based on histopathological features of the metastatic lesions and the findings of normal urinary levels of catecholamines/metanephrines. Systemic chemotherapy and abdominal radiotherapy were performed, in addition to multiple surgical resections, with no satisfactory response. The indolent course of the disease and minimal impact on the patient's performance status led to a genetic evaluation which resulted in the identification of a germline mutation in the succinate dehydrogenase complex subunit B (SDHB). An immunohistology review of previous slides was consistent with the hypothesis of a neuroendocrine tumor. Forty percent of the patients with PHEO/PGL have an underlying germline mutation. SDHB mutation is frequently associated with metastatic disease and dominant secretion of noradrenaline and/or dopamine. In addition to the metastatic disease, few cases with the mutations can be a biochemically silent PHEO/PGL. We concluded that the patient presented a metastatic abdominal paraganglioma associated with an SDHB mutation and we reinforced the need to perform genetic screening for all adrenal/extra-adrenal lesions characteristic of PHEO/PGL.

Utilization of ripe coconut water in the development of probiotic gelatin.

Background: Desserts with vegetable ingredients are a constantly expanding global market due to the search for alternatives to cow's milk. Fermentation of these matrices by lactic acid bacteria can add greater functionality to the product, improving its nutritional, sensory, and food safety characteristics, as well as creating bioactive components with beneficial effects on health. Concern for health and well-being has aroused interest in byproducts of the industry that have functional properties for the body, such as mature coconut water, a normally discarded residue that is rich in nutrients. This study aimed to develop a probiotic gelatin based on pulp and water from mature coconuts and evaluate the physicochemical characteristics, viability of the Lacticaseibacillus rhamnosus LR32 strain in the medium, as well as the texture properties of the product. Methods: After collection and cleaning, the physicochemical characterization, mineral analysis, analysis of the total phenolic content and antioxidant activity of mature coconut water were carried out, as well as the centesimal composition of its pulp. Afterwards, the gelling was developed with the addition of modified corn starch, gelatin, sucrose, and probiotic culture, being subjected to acidity analysis, texture profile and cell count, on the first day and every 7 days during 21 days of storage, under refrigeration at 5 °C. An analysis of the centesimal composition was also carried out. Results: The main minerals in coconut water were potassium (1,932.57 mg L-1), sodium (19.57 mg L-1), magnesium (85.13 mg L-1) calcium (279.93 mg L-1) and phosphorus (11.17 mg L- 1), while the pulp had potassium (35.96 g kg-1), sodium (0.97 g kg-1), magnesium (2.18 g kg-1), 37 calcium (1.64 g kg-1), and phosphorus (3.32 g kg-1). The phenolic content of the water and pulp was 5.72 and 9.77 mg gallic acid equivalent (GAE) 100 g-1, respectively, and the antioxidant capacity was 1.67 and 0.98 39 g of 2, 2-diphenyl-1-picrylhydrazyl (DPPH) mg-1, respectively. The coconut pulp had 2.81 g 100 g-1of protein, 1.11 g 100 g-1 of 40 ash, 53% moisture, and 5.81 g 100 g-1 of carbohydrates. The gelatin produced during the storage period presented firmness parameters ranging from 145.82 to 206.81 grams-force (gf), adhesiveness from 692.85 to 1,028.63 gf sec, cohesiveness from 0.604 to 0.473, elasticity from 0.901 to 0.881, gumminess from 86.27 to 97.87 gf, and chewiness from 77.72 to 91.98 gf. Regarding the viability of the probiotic microorganism, the dessert had 7.49 log CFU g-1 that remained viable during the 21-day storage, reaching 8.51 CFU g-1. Acidity ranged from 0.15 to 0.64 g of lactic acid 100 g-1. The centesimal composition of the product showed 4.88 g 100 g-1 of protein, 0.54 g 100 g-1 of ash, 85.21% moisture, and 5.37g 100 g-1 of carbohydrates. The development of the gelatin made it possible to obtain a differentiated product, contributing to diversification in the food sector, providing a viable alternative for maintaining consumer health and reducing costs compared to desserts already available on the market.

Psychopathological characteristics in patients with arginine vasopressin deficiency (central diabetes insipidus) and primary polydipsia compared to healthy controls.

OBJECTIVE: Distinguishing arginine vasopressin deficiency (AVP-D; central diabetes insipidus) from primary polydipsia (PP), commonly referred to as psychogenic polydipsia, is challenging. Psychopathologic findings, commonly used for PP diagnosis in clinical practice, are rarely evaluated in AVP-D patients, and no comparative data between the two conditions currently exist. DESIGN: Data from two studies involving 82 participants [39 AVP-D, 28 PP, and 15 healthy controls (HC)]. METHODS: Psychological evaluations were conducted using standardized questionnaires measuring anxiety [State-Trait Anxiety Inventory (STAI)], alexithymia [Toronto Alexithymia Scale (TAS-20)], depressive symptoms (Beck's Depression Inventory-II (BDI-II), and overall mental health [Short Form-36 Health Survey (SF-36)]. Higher STAI, TAS-20, and BDI-II scores suggest elevated anxiety, alexithymia, and depression, while higher SF-36 scores signify better overall mental health. RESULTS: Compared to HC, patients with AVP-D and PP showed higher levels of anxiety (HC 28 points [24-31] vs AVP-D 36 points [31-45]; vs PP 38 points [33-46], P < .01), alexithymia (HC 30 points [29-37] vs AVP-D 43 points [35-54]; vs PP 46 points [37-55], P < .01), and depression (HC 1 point [0-2] vs AVP-D 7 points [4-14]; vs PP 7 points [3-13], P < .01). Levels of anxiety, alexithymia, and depression showed no difference between both patient groups (P = .58, P = .90, P = .50, respectively). Compared to HC, patients with AVP-D and PP reported similarly reduced self-reported overall mental health scores (HC 84 [68-88] vs AVP-D 60 [52-80], P = .05; vs PP 60 [47-74], P < .01). CONCLUSION: This study reveals heightened anxiety, alexithymia, depression, and diminished overall mental health in patients with AVP-D and PP. The results emphasize the need for careful interpretation of psychopathological characteristics to differentiate between AVP-D and PP.

Biological Activity and Chemical Composition of Propolis Extracts with Potential Use in Vulvovaginal Candidiasis Management.

Environmental sustainability is an increasing challenge in the pharmaceutical field, leading to the search for eco-friendly active ingredients. Among natural ingredients, propolis arises as an excellent alternative, being a complex substance with pharmacological properties. This work aims to explore the potential of propolis as a new pharmaceutical ingredient for the replacement of conventional vulvovaginal antifungals. Propolis extracts were obtained by Ultrasound-Assisted Extraction using different solvents (water, water/ethanol (50:50, v/v), and ethanol). Afterwards, the extracts were characterized regarding total phenolic content (TPC), antioxidant/antiradical activities, radical scavenging capacity, antifungal activity against strains of Candida species, and viability effect on two female genital cell lines. The aqueous extract achieved the best TPC result as well as the highest antioxidant/antiradical activities and ability to capture reactive oxygen species. A total of 38 phenolic compounds were identified and quantified by HPLC, among which ferulic acid, phloridzin and myricetin predominated. Regarding the anti-Candida spp. activity, the aqueous and the hydroalcoholic extracts achieved the best outcomes (with MIC values ranging between 128 and 512 µg/mL). The cell viability assays confirmed that the aqueous extract presented mild selectivity, while the hydroalcoholic and alcoholic extracts showed higher toxicities. These results attest that propolis has a deep potential for vulvovaginal candidiasis management, supporting its economic valorization.

Patients' prognosis with congenital heart disease followed by ten years: survival and associated factors.

OBJECTIVE: To evaluate the prognosis and influence of associated factors in patients with congenital heart disease admitted for the first time to the Intensive Care Unit of the Hospital da Criança Santo Antônio/Irmandade da Santa Casa de Misericórdia de Porto Alegre, especially those factors associated with death. METHODS: Patients were prospectively and consecutively allocated over a period of one year (August 2005 to July 2006). Now, 15 years after the initial selection, we collected data from these patients in the database of the Cytogenetics Laboratory of the Universidade Federal de Ciências da Saúde de Porto Alegre and in the medical records of the hospital. RESULTS: Of the 96 patients, 11 died and 85 were alive until 20 years old. Four patients died in the Intensive Care Unit. The survival probability up to 365 days of life was 95.8%. The survival assessment identified that the deaths occurred mainly before the patients completed one thousand days of life. We found that complex heart disease was independently associated with an odds ratio of 5.19 (95% confidence interval - CI:1.09-24.71; p=0.038) for death. CONCLUSIONS: Knowledge about the factors that interfere with the prognosis can be crucial in care practice planning, especially considering that congenital heart disease is an important cause of mortality in the first year of life.

Patients' prognosis with congenital heart disease followed by ten years: survival and associated factors / Prognóstico de pacientes com cardiopatia congênita seguidos por dez anos: sobrevida e fatores associados

ABSTRACT Objective: To evaluate the prognosis and influence of associated factors in patients with congenital heart disease admitted for the first time to the Intensive Care Unit of the Hospital da Criança Santo Antônio/Irmandade da Santa Casa de Misericórdia de Porto Alegre, especially those factors associated with death. Methods: Patients were prospectively and consecutively allocated over a period of one year (August 2005 to July 2006). Now, 15 years after the initial selection, we collected data from these patients in the database of the Cytogenetics Laboratory of the Universidade Federal de Ciências da Saúde de Porto Alegre and in the medical records of the hospital. Results: Of the 96 patients, 11 died and 85 were alive until 20 years old. Four patients died in the Intensive Care Unit. The survival probability up to 365 days of life was 95.8%. The survival assessment identified that the deaths occurred mainly before the patients completed one thousand days of life. We found that complex heart disease was independently associated with an odds ratio of 5.19 (95% confidence interval — CI:1.09-24.71; p=0.038) for death. Conclusions: Knowledge about the factors that interfere with the prognosis can be crucial in care practice planning, especially considering that congenital heart disease is an important cause of mortality in the first year of life.

RESUMO Objetivo: Avaliar o prognóstico e a influência de fatores associados em pacientes com cardiopatia congênita internados pela primeira vez na Unidade de Terapia Intensiva do Hospital da Criança Santo Antônio/Irmandade da Santa Casa de Misericórdia de Porto Alegre, principalmente aqueles fatores associados ao óbito. Métodos: Os pacientes foram alocados prospectiva e consecutivamente por um período de um ano (agosto de 2005 a julho de 2006). Agora, 15 anos após a seleção inicial, coletamos dados desses pacientes no banco de dados do Laboratório de Citogenética da Universidade Federal de Ciências da Saúde de Porto Alegre e nos prontuários do hospital. Resultados: Dos 96 pacientes, 11 faleceram e 85 permaneceram vivos até completar 20 anos. Quatro pacientes morreram na Unidade de Terapia Intensiva. A probabilidade de sobrevida até 365 dias de vida foi de 95,8%. A avaliação da sobrevida identificou que os óbitos ocorreram principalmente antes de os pacientes completarem mil dias de vida. Verificamos que a doença cardíaca complexa foi independentemente associada a um odds ratio de 5,19 (intervalo de confiança — IC95% 1,09-24,71; p=0,038) para morte. Conclusões: O conhecimento dos fatores que interferem no prognóstico pode ser fundamental no planejamento da prática assistencial, principalmente considerando-se que as cardiopatias congênitas são importante causa de mortalidade no primeiro ano de vida.

Study of the Antioxidant, Antimicrobial, and Wound Healing Properties of Raw Hydrolyzed Extract from Nile Tilapia Skin (Oreochromis niloticus).

Oreochromis niloticus (Nile tilapia) skin is a by-product of Brazilian fish farming, rich in collagen. The present study aims to evaluate the wound healing, antioxidant, and antimicrobial potential of the raw hydrolyzed extract of Nile tilapia skin, as well as the identification of the main compounds. The in vitro activity was performed using antioxidant, antimicrobial and scratch wound healing assays. An in vivo experiment was performed to evaluate the wound healing potential. On days 1, 7, 14 and 21, the lesions were photographed to assess wound retraction and on the 7th , 14th and 21st  days the skins were removed for histological evaluation and the blood of the animals was collected for glutamic oxaloacetic transaminase and glutamic pyruvic transaminase determination. The chemical study was carried out through liquid chromatography-tandem mass spectrometry and de novo sequencing of peptides. The in vitro assays showed a reduction of the gap area in 24 h, dose-dependent antimicrobial activity for both bacteria, and antioxidant activity. The chemical analysis highlighted the presence of active biopeptides. The histological evaluation showed that the raw hydrolyzed extract of Nile tilapia skin has a healing potential, and does not present toxicological effects; therefore, is promising for the treatment of wounds.

Tissue-resident glial cells associate with tumoral vasculature and promote cancer progression.

Cancer cells are embedded within the tissue and interact dynamically with its components during cancer progression. Understanding the contribution of cellular components within the tumor microenvironment is crucial for the success of therapeutic applications. Here, we reveal the presence of perivascular GFAP+/Plp1+ cells within the tumor microenvironment. Using in vivo inducible Cre/loxP mediated systems, we demonstrated that these cells derive from tissue-resident Schwann cells. Genetic ablation of endogenous Schwann cells slowed down tumor growth and angiogenesis. Schwann cell-specific depletion also induced a boost in the immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes, while reducing immune-suppressor cells. In humans, a retrospective in silico analysis of tumor biopsies revealed that increased expression of Schwann cell-related genes within melanoma was associated with improved survival. Collectively, our study suggests that Schwann cells regulate tumor progression, indicating that manipulation of Schwann cells may provide a valuable tool to improve cancer patients' outcomes.

Schistosomiasis mansoni and hydrographical conditions in São Carlos, São Paulo, Brazil.

BACKGROUND: In Brazil, schistosomiasis mansoni cases still occur, even in non-endemic areas. This study aimed to evaluate schistosomiasis mansoni cases and to delimit water collections investigated for infested planorbidae in São Carlos, São Paulo, Brazil. METHODS: A cross-sectional descriptive study and spatial analysis of schistosomiasis mansoni cases notified in the city from January 2005 to December 2017 was conducted. The study used geographical information system software to map residential and leisure exposures to water courses and bodies and related them to planorbidae surveys of São Paulo state. RESULTS: During the study period, 32 cases were notified. The main forms were intestinal and hepatosplenic. Twenty-eight cases were allochthonous, two autochthonous and two indeterminate. Eleven patients (33.3%) had contact with water collections in São Carlos, mainly the 29 and Broa reservoirs. Three of them had contact only with water collections in the region. A third of cases lived in the Água Fria and Água Quente microbasins, highly impacted by the presence of domestic sewage, and the whole region seems to be colonized by Biomphalaria tenagophila. CONCLUSIONS: The resolution of anthropogenic contamination of water bodies is crucial for controlling schistosomiasis mansoni autochthony in São Carlos.

Fatores relacionados à percepção do risco de adoecer por COVID-19 em adultos da Região Sudeste / Factors related to the perception of the risk of getting sick from COVID-19 in adults in the Southeast Region

O objetivo do presente estudo foi identificar fatores relacionados à percepção do risco de adoecer por COVID-19 em adultos da Região Sudeste. Estudo transversal, websurvey, realizado com amostra de 2.477 residentes da Região Sudeste. Foi empregada a análise de correspondência múltipla para ilustrar graficamente as relações entre os padrões de respostas; e o teste t de student para comparação entre médias. Homens, com ensino médio e 40 anos ou mais de idade demonstraram percepção de risco baixo de adoecer pela COVID-19. A média mais elevada (2,08) da percepção de risco de adoecer foi a dos participantes que tiveram contato próximo com caso suspeito de COVID-19 (p<0,001). Conclui-se que as diferentes técnicas de análise utilizando medidas quantitativas permitiram evidenciar que a percepção de risco elevado de adoecer por COVID-19 relacionou-se com a experiência de contato próximo com caso suspeito da doença.

The objective of this study was to identify factors related to the perception of risk of getting sick from COVID-19 in adults in the Southeast Region. This is a cross-sectional, websurvey study, conducted with a sample of 2,477 residents of the Southeast Region. Multiple correspondence analyses were employed to graphically illustrate relationships among response patterns; and Student's t test for comparison of means. It was observed that, men, with high school education, and 40 years of age or older showed low risk perception of getting sick by COVID-19. The highest mean (2.08) perceived risk of becoming ill was among participants who had close contact with a suspected case of COVID-19 (p<0.001). It is concluded that the different techniques of analysis using quantitative measures allowed evidence that the perception of high risk of becoming ill with COVID-19 was related to the experience of close contact with a suspected case of the disease.

Sympathetic nerve-adipocyte interactions in response to acute stress.

Psychological stress predisposes our body to several disorders. Understanding the cellular and molecular mechanisms involved in the physiological responses to psychological stress is essential for the success of therapeutic applications. New studies show, by using in vivo inducible Cre/loxP-mediated approaches in combination with pharmacological blockage, that sympathetic nerves, activated by psychological stress, induce brown adipocytes to produce IL-6. Strikingly, this cytokine promotes gluconeogenesis in hepatocytes, that results in the decline of tolerance to inflammatory organ damage. The comprehension arising from this research will be crucial for the handling of many inflammatory diseases. Here, we review recent advances in our comprehension of the sympathetic nerve-adipocyte axis in the tissue microenvironment.

Comparison of Neutralizing Dengue Virus B Cell Epitopes and Protective T Cell Epitopes With Those in Three Main Dengue Virus Vaccines.

The four serotypes of Dengue virus (DENV1-4) are arboviruses (arthropod-borne viruses) that belong to the Flavivirus genus, Flaviviridae family. They are the causative agents of an infectious disease called dengue, an important global public health problem with significant social-economic impact. Thus, the development of safe and effective dengue vaccines is a priority according to the World Health Organization. Only one anti-dengue vaccine has already been licensed in endemic countries and two formulations are under phase III clinical trials. In this study, we aimed to compare the main anti-dengue virus vaccines, DENGVAXIA®, LAV-TDV, and TAK-003, regarding their antigens and potential to protect. We studied the conservation of both, B and T cell epitopes involved in immunological control of DENV infection along with vaccine viruses and viral isolates. In addition, we assessed the population coverage of epitope sets contained in each vaccine formulation with regard to different human populations. As main results, we found that all three vaccines contain the main B cell epitopes involved in viral neutralization. Similarly, LAV-TDV and TAK-003 contain most of T cell epitopes involved in immunological protection, a finding not observed in DENGVAXIA®, which explains main limitations of the only licensed dengue vaccine. In summary, the levels of presence and absence of epitopes that are target for protective immune response in the three main anti-dengue virus vaccines are shown in this study. Our results suggest that investing in vaccines that contain the majority of epitopes involved in protective immunity (cellular and humoral arms) is an important issue to be considered.

Fomites and the environment did not have an important role in COVID-19 transmission in a Brazilian mid-sized city.

It is not clear if COVID-19 can be indirectly transmitted. It is not possible to conclude the role of the environment in transmission of SARS-CoV-2 without studying areas in which people transit in great numbers. In this work we aimed to better understand the role of environment in the spread of COVID-19. We investigated the presence of SARS-CoV-2 in fomites as well as in the air and in the sewage using RT-qPCR. We studied both, a reference market area and a COVID-19 reference hospital at Barreiras city, Brazil. We collected and analyzed a total of 418 samples from mask fronts, cell phones, paper money, card machines, sewage, air and bedding during the ascendant phase of the epidemiological curve of COVID-19 in Barreiras. As a result, we detected the human RNAse P gene in most of samples, which indicates the presence of human cells or their fragments in specimens. However, we did not detect any trace of SARS-CoV-2 in all samples analyzed. We conclude that, so far, the environment and inanimate materials did not have an important role in COVID-19 transmission in Barreiras city. Therefore, similar results can probably be found in other cities, mainly those with COVID-19 epidemiological scenarios similar to that of Barreiras city. Our study is a small piece indicating the possibility that fomites and the environment do not have an important role in COVID-19 transmission. However, further studies are necessary to better understand the world scenario.

Pericytes cross-talks within the tumor microenvironment.

Cancer cells are embedded within the tumor microenvironment and interact dynamically with its components during tumor progression. Understanding the molecular mechanisms by which the tumor microenvironment components communicate is crucial for the success of therapeutic applications. Recent studies show, by using state-of-the-art technologies, including sophisticated in vivo inducible Cre/loxP mediated systems and CRISPR-Cas9 gene editing, that pericytes communicate with cancer cells. The arising knowledge on cross-talks within the tumor microenvironment will be essential for the development of new therapies against cancer. Here, we review recent progress in our understanding of pericytes roles within tumors.

N-acylhydrazone Derivative-Loaded Cellulose Acetate Films: Thermoanalytical, Spectroscopic, Mechanical and Morphological Characterization.

Cellulose acetate (ACT) is one of the most important cellulose derivatives due to its biodegradability and low toxicity, presenting itself as one of the main substitutes for synthetic materials in the development of wound dressing films. The incorporation of a N-acylhydrazonic derivative (JR19), with its promising anti-inflammatory activity, may represent an alternative for the treatment of skin wounds. This work aims to develop and to physicochemically and mechanically characterize ACT films containing JR19. The films were prepared using the 'casting' method and further characterized by thermoanalytical and spectroscopic techniques. In addition, mechanical tests and morphological analysis were performed. Thermogravimetry (TG) and differential scanning calorimetry (DSC) analyses showed that the thermal events attributed to excipients and films were similar, indicating the absence of physical incompatibilities between ACT and JR19. Infrared spectroscopy showed that JR19 was incorporated into ACT films. The characteristic band attributed to C≡N (2279 to 2264 cm-1) was observed in the spectra of JR19, in that of the physical mixture of JR19/ACT, and, to a lesser extent, in the spectra of JR19 incorporated into the ACT film, suggesting some interaction between JR19 and ACT. X-ray diffraction (XRD) evidenced the suppression of the crystallinity of JR19 (diffraction peaks at 8.54°, 12.80°, 14.09°, 16.08°, 18.19°, 22.65°, 23.59°, 24.53°, 25.70°, 28.16° and 30.27°2θ) after incorporation into ACT films. The mechanical tests indicated the adequate integrity of the films and their resistance to bending. The morphological characterization showed JR19 crystals along with a homogeneously distributed porous structure throughout the surface of the films with an average diameter of 21.34 µm and 22.65 µm of the films alone and of those incorporating JR19F, respectively. This study was able to characterize the ACT films incorporating JR19, showing their potential to be further developed as wound healing dressings.

A General Approach on Surfactants Use and Properties in Drug Delivery Systems.

Surfactants are amphiphilic molecules of great interest in the pharmaceutical field which are used in combination with other adjuvants to solubilize poorly soluble drugs, improve their dissolution profile, promote permeation, improve drug delivery, enhance stabilization, among other characteristics. Literature shows that surfactants are included in several pharmaceutical compositions: tablets, solid dispersions, emulsions, microemulsions, nanoemulsions, liposomes and niosomes. This review aims to elucidate the different classes of surfactants based on their charges (cationic, anionic, nonionic, zwitterionic, and dimeric), the micelles formation process, and how surfactant molecules geometry can affect this phenomenon. Moreover, current studies regarding the benefits of surfactants in the development of formulations are presented. Finally, a discussion on how charges and chain length of surfactants can affect the stratum corneum epithelial cells leading to increased permeation or skin irritability is reported.

Hematopoietic stem cell stretches and moves in its bone marrow niche.

Hematopoietic stem cells are the most illustrious inhabitants of the bone marrow. Direct visualization of endogenous hematopoietic stem cells in this niche is essential to study their functions. Until recently this was not possible in live animals. Recent studies, using state-of-the-art technologies, including sophisticated in vivo inducible genetic approaches in combination with two-photon laser scanning microscopy, allow the follow-up of endogenous hematopoietic stem cells' behavior in their habitat. Strikingly, the new findings reveal that quiescent hematopoietic stem cells are more mobile than previously thought, and link their retained steady state within the niche to a mobile behavior. The arising knowledge from this research will be critical for the therapy of several hematological diseases. Here, we review recent progress in our understanding of hematopoietic stem cell biology in their niches.

C(3)1-TAg in C57BL/6 J background as a model to study mammary tumor development.

Diagnosis and prognosis of breast cancer is based on disease staging identified through histopathological and molecular biology techniques. Animal models are used to gain mechanistic insights into the development of breast cancer. C(3)1-TAg is a genetically engineered mouse model that develops mammary cancer. However, carcinogenesis caused by this transgene was characterized in the Friend Virus B (FVB) background. As most genetic studies are done in mice with C57BL/6 J background, we aimed to define the histological alterations in C3(1)-TAg C57BL/6 J animals. Our results showed that C3(1)-TAg animals with C57BL/6 J background develop solid-basaloid adenoid cystic carcinomas with increased fibrosis, decreased area of adipocytes, and a high proliferative index, which are triple-negative for progesterone, estrogen, and human epidermal growth factor receptor 2 (HER2) receptors. Our results also revealed that tumor development is slower in the C57BL/6 J background when compared with the FVB strain, providing a better model to study the different stages in breast cancer progression.

Circulating Nestin-GFP+ Cells Participate in the Pathogenesis of Paracoccidioides brasiliensis in the Lungs.

Multiple infectious diseases lead to impaired lung function. Revealing the cellular mechanisms involved in this impairment is crucial for the understanding of how the lungs shift from a physiologic to a pathologic state in each specific condition. In this context, we explored the pathogenesis of Paracoccidioidomycosis, which affects pulmonary functioning. The presence of cells expressing Nestin-GFP has been reported in different tissues, and their roles as tissue-specific progenitors have been stablished in particular organs. Here, we explored how Nestin-GFP+ cells are affected after lung infection by Paracoccidioides brasiliensis, a model of lung granulomatous inflammation with fibrotic outcome. We used Nestin-GFP transgenic mice, parabiosis surgery, confocal microscopy and flow cytometry to investigate the participation of Nestin-GFP+ cells in Paracoccidioides brasiliensis pathogenesis. We revealed that these cells increase in the lungs post-Paracoccidioides brasiliensis infection, accumulating around granulomas. This increase was due mainly to Nestin-GPF+ cells derived from the blood circulation, not associated to blood vessels, that co-express markers suggestive of hematopoietic cells (Sca-1, CD45 and CXCR4). Therefore, our findings suggest that circulating Nestin-GFP+ cells participate in the Paracoccidioides brasiliensis pathogenesis in the lungs.

Targeted phospholipidomic analysis of synovial fluid as a tool for osteoarthritis deep phenotyping.

Objective: The aim of this study was to carry out a targeted phospholipidomic analysis on synovial fluid (SF) from patients with different grades of osteoarthritis (OA) and controls, in order to search for specific phospholipid profiles that may be useful for the deep phenotyping of this disease. Design: Multiple reaction monitoring-mass spectrometry (MRM/MS) was applied to explore the potential phospholipidomic differences in the SF of knee OA patients (n â€‹= â€‹15) (subclassified into early- and late-stage OA) and non-OA controls (n â€‹= â€‹4). Multivariate statistical analyses conducted by partial least squares discriminant analysis (PLS-DA) and hierarchical clustering analysis (HCA) were performed to identify significantly altered phospholipids in OA, characterize phospholipidomic profiles associated with the radiographic stage of the disease and describe potential endotypes at early stages. Results: Significant discrimination of phospholipid profiles between non-OA controls and the early- and late-stage OA groups were found by PLS-DA and HCA. Compared to SF from non-OA controls, OA patients showed higher levels of most quantified phospholipid species, including phosphatidylcholines (PC), phosphatidylserines and phosphatidylinositols. Furthermore, several PC species showed significant differences in abundance between the two OA subgroups and were negatively correlated with cartilage damage. Finally, two distinct endotypes of early-stage OA were identified based on the phospholipidomic profile of SF. Conclusions: Our data provides a novel insight into the phospholipid profiles of OA synovial fluid, revealing specific alterations associated with the radiographic stage of the disease. This targeted phospholipidomic profiling also facilitated the characterization of two different OA endotypes at early stages of the disease.