Naturally occurring small molecules with dual effect upon inflammatory signaling pathways and endoplasmic reticulum stress response.

The endoplasmic reticulum (ER) is determinant to maintain cellular proteostasis. Upon unresolved ER stress, this organelle activates the unfolded protein response (UPR). Sustained UPR activates is known to occur in inflammatory processes, deeming the ER a potential molecular target for the treatment of inflammation. This work characterizes the inflammatory/UPR-related molecular machinery modulated by an in-house library of natural products, aiming to pave the way for the development of new selective drugs that act upon the ER to counter inflammation-related chronic diseases. Starting from a library of 134 compounds of natural occurrence, mostly occurring in medicinal plants, nontoxic molecules were screened for their inhibitory capacity against LPS-induced nuclear factor kappa B (NF-κB) activation in a luciferase-based reporter gene assay. Since several natural products inhibited NF-κB expression in THP-1 macrophages, their effect on reactive oxygen species (ROS) production and inflammasome activation was assessed, as well as their transcriptional outcome regarding ER stress. The bioactivities of several natural products are described herein for the first time. We report the anti-inflammatory potential of guaiazulene and describe 5-deoxykaempferol as a novel inhibitor of inflammasome activation. Furthermore, we describe the dual potential of 5-deoxykaempferol, berberine, guaiazulene, luteolin-4'-O-glucoside, myricetin, quercetagetin and sennoside B to modulate inflammatory signaling ER stress. Our results show that natural products are promising molecules for the discovery and pharmaceutical development of chemical entities able to modulate the inflammatory response, as well as proteostasis and the UPR.

Exploring structural determinants of neuroprotection bias on novel glypromate conjugates with bioactive amines.

Neurodegenerative disorders of the central nervous system (CNS) such as Alzheimer's and Parkinson's diseases, afflict millions globally, posing a significant public health challenge. Despite extensive research, a critical hurdle in effectively treating neurodegenerative diseases is the lack of neuroprotective drugs that can halt or reverse the underlying disease processes. In this work, we took advantage of the neuroprotective properties of the neuropeptide glycyl-l-prolyl-l-glutamic acid (Glypromate) for the development of new peptidomimetics using l-pipecolic acid as a proline surrogate and exploring their chemical conjugation with relevant active pharmaceutical ingredients (API) via a peptide bond. Together with prolyl-based Glypromate conjugates, a total of 36 conjugates were toxicologically and biologically evaluated. In this series, the results obtained showed that a constrained ring (l-proline) at the central position of the peptide motif accounts for enhanced toxicological profiles and biological effects using undifferentiated and differentiated human neuroblastoma SH-SY5Y cells. Additionally, it was shown that biased biological responses are API-dependent. Conjugation with (R)-1-aminoindane led to a 38-43% reduction of protein aggregation induced by Aß25-35 (10 µM), denoting a 3.2-3.6-fold improvement in comparison with the parent neuropeptide, with no significative difference between functionalization at α and γ-carboxyl ends. On the other hand, the best-performing neuroprotective conjugate against the toxicity elicited by 6-hydroxydopamine (6-OHDA, 125 µM) was obtained by conjugation with memantine at the α-carboxyl end, resulting in a 2.3-fold improvement of the neuroprotection capacity in comparison with Glypromate neuropeptide. Altogether, the chemical strategy explored in this work shows that the neuroprotective capacity of Glypromate can be modified and fine-tuned, opening a new avenue for the development of biased neurotherapeutics for CNS-related disorders.

Effects of graphene oxide and reduced graphene oxide nanomaterials on porcine endothelial progenitor cells.

Graphene oxide (GO) and reduced graphene oxide (rGO) have been widely used in the field of tissue regeneration and various biomedical applications. In order to use these nanomaterials in organisms, it is imperative to possess an understanding of their impact on different cell types. Due to the potential of these nanomaterials to enter the bloodstream, interact with the endothelium and accumulate within diverse tissues, it is highly relevant to probe them when in contact with the cellular components of the vascular system. Endothelial progenitor cells (EPCs), involved in blood vessel formation, have great potential for tissue engineering and offer great advantages to study the possible angiogenic effects of biomaterials. Vascular endothelial growth factor (VEGF) induces angiogenesis and regulates vascular permeability, mainly activating VEGFR2 on endothelial cells. The effects of GO and two types of reduced GO, obtained after vacuum-assisted thermal treatment for 15 min (rGO15) and 30 min (rGO30), on porcine endothelial progenitor cells (EPCs) functionality were assessed by analyzing the nanomaterial intracellular uptake, reactive oxygen species (ROS) production and VEGFR2 expression by EPCs. The results evidence that short annealing (15 and 30 minutes) at 200 °C of GO resulted in the mitigation of both the increased ROS production and decline in VEGFR2 expression of EPCs upon GO exposure. Interestingly, after 72 hours of exposure to rGO30, VEGFR2 was higher than in the control culture, suggesting an early angiogenic potential of rGO30. The present work reveals that discrete variations in the reduction of GO may significantly affect the response of porcine endothelial progenitor cells.

An electrochemical sensor modified with a molecularly imprinted polymer and carbon black for 17-ß-estradiol detection.

The purpose of this work was to apply an electrochemical sensor modified with a molecularly imprinted polymer (MIP) and carbon black (CB) for 17ß-estradiol (E2) detection in river water samples. The synthesized MIP was characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM).The modification of the electrode with the MIP and CB contributed to increased sensitivity, an increase of over 173% in relation to that of the bare electrode. The experimental parameters, amount of modifiers, pH and possible interfering species were evaluated. The method showed linearity from 0.10 to 23.0 µmol L-1 and detection and quantification limits of 0.03 and 0.10 µmol L-1, respectively. The application of the developed sensor was considered simple, resulting in a fast, low operating cost method, with recovery values between 103 and 105%.

Photodynamic therapy for squamous cell carcinoma of the head and neck: narrative review focusing on photosensitizers.

This narrative review aimed to evaluate the effectiveness of PDT in early or advanced squamous cell carcinoma of the head and neck (SCCHN). Scopus, MEDLINE/PubMed, and Embase were searched electronically following the PRISMA protocol. Quality assessment was performed according to JBI, NIH, and AMSTAR protocols. The main outcomes evaluated were treatment response, recurrence, survival, and adverse effects. A total of 49 articles met the search criteria: 43 case series, two cohort studies, two prospective before-after clinical trials, one systematic review, and one meta-analysis. Data from 2121 SCCHN patients were included. The response to PDT was variable according to the type of photosensitizer, tumor location, and tumor stage. In general, higher complete responses rated were observed in T1/T2 SCCHN, mainly with mTHPC-mediated PDT. With regard to T3/T4 or advanced SCCHN tumors, there is no compelling evidence suggesting the effectiveness of PDT. Any adverse effects reported were well tolerated by patients. The present review suggests that PDT is a promising treatment modality for early-stage SCCHN. Although there are limitations due to the low level of evidence of the included studies, we believe that the present review could help to design robust clinical trials to determine the efficacy of PDT in SCCHN.

Copper in tumors and the use of copper-based compounds in cancer treatment.

Copper homeostasis is strictly regulated by protein transporters and chaperones, to allow its correct distribution and avoid uncontrolled redox reactions. Several studies address copper as involved in cancer development and spreading (epithelial to mesenchymal transition, angiogenesis). However, being endogenous and displaying a tremendous potential to generate free radicals, copper is a perfect candidate, once opportunely complexed, to be used as a drug in cancer therapy with low adverse effects. Copper ions can be modulated by the organic counterpart, after complexed to their metalcore, either in redox potential or geometry and consequently reactivity. During the last four decades, many copper complexes were studied regarding their reactivity toward cancer cells, and many of them could be a drug choice for phase II and III in cancer therapy. Also, there is promising evidence of using 64Cu in nanoparticles as radiopharmaceuticals for both positron emission tomography (PET) imaging and treatment of hypoxic tumors. However, few compounds have gone beyond testing in animal models, and none of them got the status of a drug for cancer chemotherapy. The main challenge is their solubility in physiological buffers and their different and non-predictable mechanism of action. Moreover, it is difficult to rationalize a structure-based activity for drug design and delivery. In this review, we describe the role of copper in cancer, the effects of copper-complexes on tumor cell death mechanisms, and point to the new copper complexes applicable as drugs, suggesting that they may represent at least one component of a multi-action combination in cancer therapy.

A Survey of Naturally Occurring Molecules as New Endoplasmic Reticulum Stress Activators with Selective Anticancer Activity.

The last century has witnessed the establishment of neoplastic disease as the second cause of death in the world. Nonetheless, the road toward desirable success rates of cancer treatments is still long and paved with uncertainty. This work aims to select natural products that act via endoplasmic reticulum (ER) stress, a known vulnerability of malignant cells, and display selective toxicity against cancer cell lines. Among an in-house chemical library, nontoxic molecules towards noncancer cells were assessed for toxicity towards cancer cells, namely the human gastric adenocarcinoma cell line AGS and the lung adenocarcinoma cell line A549. Active molecules towards at least one of these cell lines were studied in a battery of ensuing assays to clarify the involvement of ER stress and unfolded protein response (UPR) in the cytotoxic effect. Several natural products are selectively cytotoxic against malignant cells, and the effect often relies on ER stress induction. Berberine was the most promising molecule, being active against both cell models by disrupting Ca2+ homeostasis, inducing UPR target gene expression and ER-resident caspase-4 activation. Our results indicate that berberine and emodin are potential leads for the development of more potent ER stressors to be used as selective anticancer agents.

Evaluation of the Preventive Effect of Photobiomodulation on Orofacial Discomfort in Dental Procedures: A Randomized-Controlled, Crossover Study and Clinical Trial.

Background: Orofacial pain has been a prevalent symptom in the worldwide population, which may cause restrictions in daily activities and, consequently, have a great impact on the well-being of affected individuals. Photobiomodulation using light sources, such as low-level laser or light emitting diodes, with different wavelengths, has been widely used in the last years, in addition to being a noninvasive, low-cost resource and reducing pain. Objective: This study aimed at evaluating the effect of photobiomodulation as a protocol treatment to prevent facial muscle discomfort after long-term clinical procedures. Methods: The volunteers were randomized and allocated as follows: laser (n = 16) and placebo (n = 16) groups, following a crossover study design. The laser parameters were as following: 786 nm wavelength, 9 J per point, and 100 mW power of 2.393 W/cm2 irradiance. The discomfort was induced by simulating a 50-min dental procedure (with bilateral mouth open), and the pain scale (assessed bilaterally), tiredness, and temperature measurement through thermography were used for analysis. Results: The results showed a significant lower pain and tiredness in the laser group. Also, the results showed a statistically significant valid temperature change between the groups at times: T1, T40, and T50. Conclusions: According to our results, photobiomodulation showed a positive effect on the face musculature in patients submitted to the treatments, reducing pain and improving the subjective perception of exertion.

Effects of photobiomodulation on cellular viability and cancer stem cell phenotype in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy; it has been shown that cancer stem cells (CSC) are present in OSCC and associated with tumor growth, invasion, metastasis, and therapeutic resistance. Photobiomodulation (PBM) is an alternative tool for oncologic treatment adverse effects such as oral mucositis (OM); however, controversy exists regarding the undesirable effects of PBM on tumor or CSC. This study aimed to evaluate in vitro, the effects of PBM, with the same dosimetric parameters as those used in the clinic for OM prevention and treatment, on OSCC cellular viability, as well as PBM's effect on CSC properties and its phenotype. OSCC cell lines were submitted to single or daily PBM with 3 J/cm2 and 6 J/cm2 and then the cellular viability was evaluated by MTT, NRU (neutral red uptake), and CVS (crystal violet staining). The CSC populations were evaluated by clonogenic formation assay, flow cytometry, and RT-qPCR. The single PBM with the 3 J/cm2 group was associated with increased cellular viability. Daily PBM with 3 J/cm2 and 6 J/cm2 was associated with a significant decrease in cellular viability. Additionally, daily PBM was not able to promote CSC self-renewal or the CD44high/ESAlow and CD44high/ESAhigh cellular phenotypes. Moreover, a decrease in the number of spheres and in the expression of the CSC related gene BMI1 was observed after daily PBM with 6 J/cm2. Daily PBM with 3 J/cm2 and 6 J/cm2 showed an inhibitory effect on cellular viability and was not able to promote the CSC self-renewal or phenotype.

Evaluation of photobiomodulation in salivary production of patients with xerostomy induced by anti-hypertensive drugs: Study protocol clinical trial (SPIRIT compliant).

INTRODUCTION: Hypertension (systemic arterial hypertension [SAH]) is a systemic condition that affects about 30% of the world population, according to data from the World Health Organization (WHO). Drugs used to control this disease have the potential to induce xerostomia, an oral condition in which the decrease of the salivary flow is observed and whose presence leads to the increase of the index of caries, periodontal disease, loss of the teeth, dysgeusia, difficulty of mastication, dysphagia, bad breath and oral burning and impairment of prothesis installed in the buccal cavity, including retention of removable and total dentures. METHODS: This is a randomized, placebo-controlled, blind clinical protocol that aims to analyze the impact of phobiomodulation (PBM) on salivary glands of patients with antihypertensive drug induced xerostomia. Patients will be divided into 2 groups: G1: older adults with xerostomia induced by antihypertensive drugs and treatment with PBM (n = 30); G2: placebo PBM (n = 30). The irradiation will be made using a diode laser emitting at 808 nm with 100 mW and 40 seconds of exposure per site at the salivary glands. Twenty sites will be irradiated weekly for 4 weeks. Non-stimulated and stimulated salivary flow will be analyzed before and after the treatment. RESULTS: This protocol will determine the effectiveness of photodynamic therapy regarding the reduction of xerostomia in older adults using antihypertensive drugs. CONCLUSION: This protocol will determine the effectiveness of photodynamic therapy regarding the reduction of xerostomia in older adults using antihypertensive drugs. TRIAL REGISTRATION: Clinicaltrials.gov - NCT03632096.

Effects of photobiomodulation on interleukin-10 and nitrites in individuals with relapsing-remitting multiple sclerosis - Randomized clinical trial.

OBJECTIVE: Investigate the effects of photobiomodulation (PBM) on the expression of IL-10 and nitrites in individuals with Relapsing-Remitting multiple sclerosis (MS), as these biomarkers play a fundamental role in the physiopathology of the disease. The modulation of IL-10 and nitrites through treatment with PBM may be a novel treatment modality for MS. METHODS: A randomized, uncontrolled, clinical trial was conducted involving 14 individuals with a diagnosis of Relapsing-Remitting MS and a score of up to 6.0 on the Expanded Disability Status Scale (EDSS). THE PARTICIPANTS WERE RANDOMIZED TO TWO GROUPS: Group 1 -PBM in the sublingual region; Group 2 -PBM over the radial artery. Irradiation was administered with a wavelength of 808 nm and output power of 100 mW for 360 seconds twice a week, totaling 24 sessions. Peripheral blood was analyzed for the determination of serum levels of IL-10 and nitrites. RESULTS: After treatment with PBM, the expression of IL-10 increased in both the sublingual group (pre-treatment: 2.8 ± 1.4 pg/ml; post-treatment: 8.3 ± 2.4 pg/ml) and the radial artery group (pre-treatment: 2.7 pg/ml ± 1.4; post-treatment: 11.7 ± 3.8 pg/ml). In contrast, nitrite levels were not modulated in the sublingual group (pre-treatment: 65 ± 50 nmol/mg protein; post-treatment: 51 ± 42 nmol/mg protein) or the radial artery group (pre-treatment: 51 ± 16 nmol/mg protein; post-treatment: 42 ± 7 nmol/mg protein). CONCLUSION: Treatment with PBM positively modulated the expression of IL-10 but had no effect on nitrite levels. Further studies should be conducted with a larger sample and a control group, as PBM may be a promising complementary treatment for the management of MS. This trial is registered at ClinicalTrials.gov. Identifier: NCT03360487.

Endoplasmic reticulum stress signaling in cancer and neurodegenerative disorders: Tools and strategies to understand its complexity.

The endoplasmic reticulum (ER) comprises a network of tubules and vesicles that constitutes the largest organelle of the eukaryotic cell. Being the location where most proteins are synthesized and folded, it is crucial for the upkeep of cellular homeostasis. Disturbed ER homeostasis triggers the activation of a conserved molecular machinery, termed the unfolded protein response (UPR), that comprises three major signaling branches, initiated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1) and the activating transcription factor 6 (ATF6). Given the impact of this intricate signaling network upon an extensive list of cellular processes, including protein turnover and autophagy, ER stress is involved in the onset and progression of multiple diseases, including cancer and neurodegenerative disorders. There is, for this reason, an increasing number of publications focused on characterizing and/or modulating ER stress, which have resulted in a wide array of techniques employed to study ER-related molecular events. This review aims to sum up the essentials on the current knowledge of the molecular biology of endoplasmic reticulum stress, while highlighting the available tools used in studies of this nature.

The effects of photodynamic therapy with blue light and papain-based gel associated with Urucum, on collagen and fibroblasts: a spectroscopic and cytotoxicity analysis.

Papacarie Duo™ is clinically used and has proven effectiveness; however, it is necessary to improve its antimicrobial action. The combined treatment of Papacarie Duo™ with Urucum (Bixa Orellana) could create a potential tool for dental caries treatment; its extract obtained from the seeds' pericarp contains a water-soluble primary pigment (cis-bixin) with smaller amounts of other carotenoids. The dicarboxylic acid salts of cis-norbixin and trans-norbixin occur in heated alkaline solutions. To analyze the absorption spectra and cytotoxicity (with human dermal fibroblasts) in different concentrations of Urucum, associated or not with Papacarie Duo™, we performed this in vitro study. The effects of pure Urucum, Papacarie Duo™, and PapaUrucum™ on the microstructure of collagen were also analyzed. The application of papain-based gel with Urucum did not present cytotoxicity, its exhibit UV absorption spectrum peak around 460 ± 20 nm. Also, it showed that the compound used did not alter the chemical structure of collagen. Consequently, this product could be used as a chemomechanical method to remove dentin caries as well as being a potential product for antimicrobial photodynamic therapy (aPDT) application.

Differential expression of inflammatory and anti-inflammatory mediators by M1 and M2 macrophages after photobiomodulation with red or infrared lasers.

In response to stimuli in the microenvironment, macrophages adopt either the M1 or M2 phenotype to coordinate the tissue repair process. Photobiomodulation (PBM) plays an important role in the modulation of acute inflammation, including cellular influx, macrophage polarization, and the release of inflammatory mediators. The aim of the present study was to evaluate the effects of red and infrared PBM on the mRNA expression of cytokines and chemokines in macrophages polarized to the M1 and M2 phenotypes. J774 macrophages activated to induce M1 (lipopolysaccharide + interferon gamma) or M2 (interleukin-4) phenotypes were irradiated with red or infrared PBM (1 J). After 4 and 24 h, gene expression was analyzed by qPCR. PBM at 660 nm decreased the mRNA expression of CCL3, CXCL2, and TNF-α in M1 macrophages and CXCL2 in M2 macrophages 4 h after irradiation. Similarly, PBM at 780 nm decreased mRNA expression levels of CCL3 and IL-6 by M1 macrophages 24 h after irradiation. Moreover, PBM at 780 nm increased the mRNA expression of TGFß1 4 h after irradiation and decreased the expression of this gene after 24 h in M2 macrophages. Although red and infrared PBM were able to modulate and reduce M1/M2a-related markers, infrared laser irradiation promoted a temporal increase in the expression of TGFß1 in M2 macrophages. Thus, depending on the time PBM is used on injured tissue, different parameters can promote optimal results by modulating specific macrophage phenotypes.

Avaliação clínica dos sintomas de pacientes com câncer de cabeça e pescoço / Clinical evaluation of symptoms in patients with cancer of head and neck

Resumo Objetivo: avaliar os sintomas mais frequentes apresentados pelos pacientes com câncer de cabeça e pescoço e fatores associados. Metodologia: trata-se de um estudo transversal realizado com 77 pacientes do serviço de cirurgia de cabeça e pescoço do Instituto Nacional de Câncer (Brasil). Foi utilizado o Memorial Symptom Assessment Scale (MSAS), adaptado ao Brasil. Foi avaliada a prevalência dos sintomas, bem como sua associação com variáveis demográficas e clínicas por meio dos testes de qui- quadrado e de ANOVA. Resultados: os sintomas mais prevalentes foram boca seca (62,5 %), tristeza (60 %), preocupações (53,75 %), nervosismo (48,75 %) e tosse (46,25 %). Quanto à faixa etária, identificou-se diferença nos sintomas físicos de baixa frequência (PHYS-L), com maior queixa entre os jovens (p < 0,01). Na escala global (TMSAS) houve queixa maior dos pacientes ambulatoriais comparados aos internados (p = 0,05). Houve, ainda, queixa maior de sintomas de baixa frequência entre pacientes sem metás-tase (p = 0,05). Conclusão: considerando-se a ocorrência de múltiplos sintomas no paciente oncológico, é necessário ter métodos que sejam capazes de avaliar, de forma mais ampla, os sintomas. Dessa forma, o enfermeiro terá melhor compreensão da complexidade dos grupos de sintomas, permitindo aperfeiçoar as intervenções clínicas no processo de enfermagem.

Resumen Objetivo: evaluar los síntomas más frecuentes presentados por los pacientes con cáncer de cabeza y cuello y factores asociados. Metodología: estudio transversal realizado con 77 pacientes del servicio de cirugía de cabeza y cuello del Instituto Nacional de Cáncer (Brasil). Se utilizó el Memorial Symptom Assessment Scale (MSAS) adaptado a Brasil. Se estimó la prevalencia de los síntomas, así como su asociación con variables demográficas y clínicas, evaluada a través de las pruebas de chi cuadrado y de ANOVA. Resultados: los síntomas más prevalentes fueron boca seca (625 %), tristeza (60 %), preocupaciones (5375 %), nerviosismo (48,75 %) y tos (46,25 %). Para la franja etaria se identificó diferencia en los síntomas físicos de baja frecuencia (PHYS-L), con mayor queja entre los jóvenes (p < 0,01). En la escala global (TMSAS) hubo mayor queja de los pacientes ambulatorios que de los internados (p = 0,05). Se produjo, incluso, mayor queja de síntomas de baja frecuencia entre pacientes sin metástasis (p = 0,05). Conclusión: si se tiene en cuenta la aparición de múltiples síntomas en el paciente oncológico, es necesario tener métodos que sean capaces de evaluar, de forma más amplia, los síntomas. De esa forma, el enfermero tendrá una mejor comprensión de la complejidad de los grupos de síntomas y podrá perfeccionar las intervenciones clínicas en el proceso de enfermería.

Abstract Objective: to evaluate the most frequent symptoms showed by patients with cancer of head and neck, and associated factors. Methodology: cross-sectional study conducted with 77 patients of service of head and neck surgery of the National Institute of Cancer (Brazil). It was used the Memorial Symptom Assessment Scale (MSAS), adapted to Brazil. It was estimated the prevalence of symptoms, as well as its association with demographic and clinical variables, assessed through Chi-squared and ANOVA tests. Results: the most prevalent symptoms were: dry mouth (62.5 %), sadness (60 %), concerns (53.75 %), nervousness (48.75 %) and cough (46.25 %). Difference in the physical symptoms of low frequency (PHYS-L) was identified for the age group, with greater complaint among young people (p < 0.01). On the global scale (TMSAS) there was greater complaint of outpatients than that of hospitalized patients (p = 0.05). There was greater complaint of symptoms of low frequency among patients without metastasis (p = 0.05). Conclusion: if it is taken into account the appearance of multiple symptoms in cancer patients, forms able to assess these in a broader way are necessary, which allow the nurse to get a better understanding of the complexity of the groups of symptoms and improve clinical interventions in the nursing process.

Global and Multidimensional Symptom Assessments in Patients Presenting Abdominal Neoplasms / Evaluación global y multidimensional de síntomas en pacientes con neoplasias abdominales / Avaliação global e miltidimensional de sintomas em pacientes com neoplasias abdominais

ABSTRACT Objective: To evaluate symptoms among patients with abdominal cancer and associated factors. Materials and methods: A cross-sectional study with 100 patients. The prevalence of symptoms was evaluated through the Memorial Symptom Assessment Scale (MSAS) and its association with demographic and clinical variables using chi-square and ANOVA tests. Results: The most prevalent symptoms were weight loss (64.0 %), pain (56.0 %), dry mouth (50.0 %), "I do not look more myself" (48.0 %) and lack of energy (45.0 %). There was a significant difference between sex and high-frequency (PHYS-H) (p = 0.001) and low-frequency (PHYS-L) physical symptoms (p = 0.004), and for general scale (TMSAS) (p = 0.002); (p = 0.001), general range (p = 0.027) and borderline significance for the global scale (GDI) (p = 0.051); high-frequency physical symptoms (p = 0.022), low-frequency physical symptoms (p = 0.034) and the overall scale (p = 0.034). There was one major complaint regarding the severity of high-frequency physical symptoms in patients with liver cancer (p = 0.018). Conclusion: Symptoms of physical and psychological aspects in cancer patients were associated with gender, race, marital status and tumor location. There is a need for tools to assess symptoms and enable health professionals to intervene more effectively.

RESUMEN Objetivo: evaluar los síntomas entre los pacientes con cáncer abdominal y factores asociados. Materiales y método: estudio transversal realizado con 100 pacientes. Se evaluó la prevalencia de los síntomas, a través de la Memorial Symptom Assessment Scale (MSAS), y su asociación con variables demográficas y clínicas, por medio de pruebas de chi cuadrado y ANOVA. Resultados: los síntomas más prevalentes fueron pérdida de peso (64,0 %), dolor (56,0 %), boca seca (50,0 %), "No me siento yo mismo" (48,0 %) y falta de energía (45,0 %). Hay una diferencia significativa entre el sexo y los síntomas físicos de alta frecuencia (PHYS-H) (p = 0,001) y de baja frecuencia (PHYS-L) (p = 0,004), y para escala general (TMSAS) (p = 0,002); entre la raza y los síntomas físicos de alta frecuencia (p = 0,008), la escala general (p = 0,027) y la significancia limítrofe para la escala global (GDI) (p = 0,051); el estado civil y los síntomas físicos de alta frecuencia (p = 0,022), los síntomas físicos de baja frecuencia (p = 0,034) y la escala general (p = 0,034). Hubo una queja mayor en relación a la gravedad de los síntomas físicos de alta frecuencia en pacientes con cáncer de hígado (p = 0,018). Conclusión: síntomas de aspectos físicos y psicológicos en pacientes oncológicos se han asociado al sexo, la raza, el estado civil y la localización del tumor. Existe la necesidad de instrumentos para que los síntomas sean evaluados y permitan que los profesionales de la salud puedan intervenir de manera más eficaz.

RESUMO Objetivo: avaliar sintomas entre pacientes com câncer abdominal e fatores associados. Materiais e método: estudo transversal realizado com 100 pacientes. Foi avaliada a prevalência dos sintomas, através do Memorial Symptom Assessment Scale (MSAS), e sua associação com variáveis demográficas e clínicas, por meio de testes de qui quadrado e ANOVA. Resultados: os sintomas mais prevalentes foram perda de peso (64,0 %), dor (56,0 %), boca seca (50,0 %), "Eu não pareço mais eu mesmo" (48,0 %) e falta de energia (45,0 %). Há diferença significativa entre sexo e sintomas físicos de alta frequência (PHYS-H) (p = 0,001) e de baixa frequência (PHYS-L) (p = 0,004), e para escala geral (TMSAS) (p = 0,002); entre raça e sintomas físicos de alta frequência (p = 0,008), escala geral (p = 0,027) e significância limítrofe para a escala global (GDI) (p = 0,051); estado civil e sintomas físicos de alta frequência (p = 0,022), sintomas físicos de baixa frequência (p = 0,034) e a escala geral (p = 0,034). Houve uma queixa maior em relação à gravidade de sintomas físicos de alta frequência em pacientes com câncer de fígado (p = 0,018). Conclusão: sintomas de aspectos físico e psicológico em pacientes oncológicos foram associados a sexo, raça, estado civil e localização do tumor. Há necessidade de instrumentos para que os sintomas sejam avaliados e permitam que profissionais de saúde possam intervir de maneira mais eficaz.

Protective effects of neocuproine copper chelator against oxidative damage in NSC34 cells.

In this work, we aim to provide evidence for the protective effect of a copper chelator, neocuproine (NeoCu), against the oxidative stress in NSC34 cells, which inhibits biomolecule oxidation and cell death. Results obtained with the comet assay allowed to determine the increase in oxidized purines and pyrimidines by H2O2 exposure, and their changes after the addition of NeoCu. We also observed a higher ATP7b activity in nuclei and a higher Cu concentration inside the cells, proving that the NeoCu acts directly in DNA to promote cell recovery in oxidative stress conditions, also observed in Reactive Oxygen Species (ROS) detection assay by Flow Cytometry. Based on these results, we propose that NeoCu is a promising drug for the protection of motor neuron cells during oxidative stress caused by neurodegenerative diseases in this system.

Mortalidade infantil por malformações congênitas: estudo de série temporal / Infant mortality by congenital malformations: a time series study / Mortalidad infantil por malformaciones congénitas: estudio de serie temporal

As malformações congênitas representam importante causa de mortes infantis e incapacidade ao longo da vida. O objetivo deste estudo foi analisar a série temporal da mortalidade infantil por malformações congênitas de 1999 a 2016 e sua previsão até 2021, no Recife (PE). Trata-se de um estudo de série temporal, realizado a partir de dados do Sistema de Informações sobre Mortalidade e Sistema de informações sobre nascidos vivos. Considerou-se, para a população de estudo, todos os nascidos vivos que tiveram como causa de óbito as malformações congênitas. Calculou-se as proporções, taxas e variações de 1999 a 2008 e 2009 a 2016 relacionadas às características maternas e da criança com auxílio do Epi Info™ 7.1.5.0. O modelo autorregressivo integrado de médias móveis (Arima) foi utilizado para análise de séries temporais da proporção de óbitos (2,1,1) e (2,1,1) e taxa de mortalidade infantil por malformações congênitas. Foram registrados 6.271 óbitos infantis, 1.362 (21,7%) por malformações congênitas. O componente etário neonatal precoce foi o mais frequente no primeiro (n = 317; 45,6%) e segundo período (n = 286; 42,9%). As doenças do sistema circulatório foram responsáveis por 257 (37%) e 210 óbitos (31,5%), respectivamente. Para prever a série temporal da proporção e taxa da mortalidade infantil por malformações congênitas no período de 2017 a 2021 testou-se vários argumentos de ordem do Arima. Observou-se que o mais apropriado para análise da série de proporção de óbitos foi o Sarima (2,1,1) e (2,1,1) que previu tendência ascendente e para a taxa de mortalidade o Sarima (2,1,1) e (2,1,2) que anteviu tendência declinante para os próximos anos. A tendência crescente na proporção desses óbitos demonstra a necessidade de abordagens voltadas à saúde materna e infantil que possibilite a diminuição da mortalidade logo após o nascimento e durante o primeiro ano de vida com acesso às estratégias direcionadas à prevenção de novos casos. Conclui-se que o uso do Arima é uma estratégia bastante útil para o conhecimento e análise das malformações congênitas, pois permite entender como um problema de saúde reage ao longo do tempo. Desse modo, espera-se que este trabalho possa contribuir para a formulação de estratégias e tomada de decisões com o intuito de reduzir as mortes por essa causa.

Congenital malformations are an important cause of childhood deaths and disability throughout life. This study analyzed the time series of infant mortality by congenital malformations from 1999 to 2016 and its prediction until 2021, in Recife (PE). This time series study was based on data from the Mortality Information System and the Live Birth Information System. For the study population, all live births were considered to be the cause of congenital malformations. Proportions, rates, and variations between 1999 and 2008 as well as between 2009 and 2016 related to maternal and child characteristics were calculated using Epi Info™ 7.1.5.0. ARIMA was used to analyze the time series concerning the proportion of deaths (2,1,1) and (2,1,1) and infant mortality rate by congenital malformations. There were 6,271 infant deaths, 1,362 (21.7%) due to congenital malformations. The precocious neonatal age group was the most frequent in the first (n = 317, 45.6%) and second (n = 286, 42.9%) groups. Circulatory system diseases were responsible for 257 (37.0%) and there were 210 deaths (31.5%). In order to predict the time series of the proportion and rate of infant mortality by congenital malformations in the period from 2017 to 2021, a number of ARIMA's arguments were tested. It was observed that SARIMA (2,1,1) and (2,1,1), which predicted an upward trend, were the most appropriate for the analysis of the death rate series. SARIMA (2,1,1) and (2,1,2) predicted a declining trend for the coming years. The increasing trend in the proportion of these deaths demonstrates the need for approaches aimed at maternal and child health that allow for the reduction of mortality soon after birth and during the first year of life with access to strategies for preventing new cases. The use of ARIMA was proven a very useful strategy for the knowledge and analysis of congenital malformations, since it allows to understand how a health problem reacts over time. Thus, this study contributes to the formulation of strategies and decision-making required to reduce deaths from this cause.

Las malformaciones congénitas son una importante causa de muertes infantiles e incapacidad al largo de la vida. El objetivo de este estudio fue analizar la serie temporal de mortalidad infantil por malformaciones congénitas de 1999 a 2016 y su previsión hasta 2021 en Recife (PE). Es un estudio de serie temporal realizado a partir de los datos del Sistema de Información sobre Mortalidad y del Sistema de Información sobre Nacidos Vivos. Se consideró, para la población de estudio, todos los nacidos vivos que tuvieron como causa de muerte las malformaciones congénitas. Se calcularon las proporciones, tasas y variaciones entre períodos de 1999 a 2008 y de 2009 a 2016 relacionadas con las características maternas y del niño con ayuda de Epi Info™ 7.1.5.0. El Modelo Autorregresivo Integrado de Medias Móviles (ARIMA) fue utilizado para análisis de series temporales de la proporción de óbitos (2,1,1) y (2,1,1) la tasa de mortalidad infantil por malformaciones congénitas. Se registraron 6.271 muertes infantiles, 1.362 (21,7%) por malformaciones congénitas. El componente de edad neonatal fue el más frecuente en el primer (n = 317; 45,6%) y segundo período (n = 286; 42,9%). Las enfermedades del sistema circulatorio fueron responsables de 257 (37,0%) y 210 óbitos (31,5%), respectivamente. Para predecir la serie temporal de la proporción y tasa de mortalidad infantil por malformaciones congénitas en el período del 2017 al 2021, se probaron varios argumentos de orden del ARIMA. Se observó que el más apropiado para análisis de la serie de proporción de muertes fue el SARIMA (2,1,1) y (2,1,1), que previó tendencia ascendente; y para la tasa de mortalidad, el SARIMA (2,1, 1) y (2,1,2), que anticipó una tendencia declinante para los próximos años. La tendencia creciente en la proporción de estas muertes demuestra la necesidad de enfoques orientados a la salud materna e infantil para posibilitar la disminución de la mortalidad poco después del nacimiento y durante el primer año de vida con acceso a las estrategias dirigidas a la prevención de nuevos casos. Se concluye que el uso del ARIMA es una estrategia bastante útil para el conocimiento y análisis de las malformaciones congénitas, pues permite entender cómo un problema de salud reacciona a lo largo del tiempo. De este modo, se espera que este trabajo pueda contribuir a la formulación de estrategias y toma de decisiones con el fin de reducir las muertes por esa causa.

Photobiomodulation and different macrophages phenotypes during muscle tissue repair.

Macrophages play a very important role in the conduction of several regenerative processes mainly due to their plasticity and multiple functions. In the muscle repair process, while M1 macrophages regulate the inflammatory and proliferative phases, M2 (anti-inflammatory) macrophages direct the differentiation and remodelling phases, leading to tissue regeneration. The aim of this study was to evaluate the effect of red and near infrared (NIR) photobiomodulation (PBM) on macrophage phenotypes and correlate these findings with the repair process following acute muscle injury. Wistar rats were divided into 4 groups: control; muscle injury; muscle injury + red PBM; and muscle injury + NIR PBM. After 2, 4 and 7 days, the tibialis anterior muscle was processed for analysis. Macrophages phenotypic profile was evaluated by immunohistochemistry and correlated with the different stages of the skeletal muscle repair by the qualitative and quantitative morphological analysis as well as by the evaluation of IL-6, TNF-α and TGF-ß mRNA expression. Photobiomodulation at both wavelengths was able to decrease the number of CD68+ (M1) macrophages 2 days after muscle injury and increase the number of CD163+ (M2) macrophages 7 days after injury. However, only NIR treatment was able to increase the number of CD206+ M2 macrophages (Day 2) and TGF-ß mRNA expression (Day 2, 4 and 7), favouring the repair process more expressivelly. Treatment with PBM was able to modulate the inflammation phase, optimize the transition from the inflammatory to the regeneration phase (mainly with NIR light) and improve the final step of regeneration, enhancing tissue repair.

Effects of formaldehyde exposure on the development of pulmonary fibrosis induced by bleomycin in mice.

Environmental and Occupational pollution has been extensively studied because of its serious implications on the human health. Formaldehyde (FA) is a pollutant widely employed in several industries and also in anatomy, pathology and histology laboratories. Studies have shown the correlation between FA exposure and development or worsening of asthma. However, the effect of FA exposure on the pulmonary fibrosis (PF) is unknown. PF is a progressive and chronic lung disease with high incidence and considerable morbidity and mortality. Few studies have shown a worsening of PF after pollutants exposure such as ozone and nitrogen dioxide. Therefore, our objective was to assess the effects of FA on the PF. Male mice C57BL6 were treated or not with bleomycin (1,5 U/kg) and exposed or not to FA inhalation (0.92 mg/m3, 1 h/day, 5 days/week during 2 weeks). Non-manipulated mice were used as control. Our data showed that FA exposure in fibrotic mice increased the number of granulocytes in the bronchoalveolar lavage followed by elevated levels of interleukin 1 beta and interleukin 17. In addition, FA exposure in fibrotic mice enhanced the gene expression of C-X-C motif chemokine ligand 1 (CXCL1) and tumor necrosis factor alpha (TNF-α) in the lung. We also showed an increase in the collagen production, while lung elastance was reduced. No differences were found in the mucus production, oedema and interstitial thickening in the lung tissue of fibrotic mice after FA exposure. In conclusion our study showed that FA exposure aggravates the lung neutrophils influx and collagen production, but did not alter the lung elastance, mucus production, oedema and interstitial tickening. This work contributes to understand the effects of pollution in the development of PF.