Switching the proton-coupled electron transfer mechanism for non-canonical tyrosine residues in a de novo protein.

The proton-coupled electron transfer (PCET) reactions of tyrosine (Y) are instrumental to many redox reactions in nature. This study investigates how the local environment and the thermodynamic properties of Y influence its PCET characteristics. Herein, 2- and 4-mercaptophenol (MP) are placed in the well-folded α3C protein (forming 2MP-α3C and 4MP-α3C) and oxidized by external light-generated [Ru(L)3]3+ complexes. The resulting neutral radicals are long-lived (>100 s) with distinct optical and EPR spectra. Calculated spin-density distributions are similar to canonical Y˙ and display very little spin on the S-S bridge that ligates the MPs to C32 inside the protein. With 2MP-α3C and 4MP-α3C we probe how proton transfer (PT) affects the PCET rate constants and mechanisms by varying the degree of solvent exposure or the potential to form an internal hydrogen bond. Solution NMR ensemble structures confirmed our intended design by displaying a major difference in the phenol OH solvent accessible surface area (≤∼2% for 2MP and 30-40% for 4MP). Additionally, 2MP-C32 is within hydrogen bonding distance to a nearby glutamate (average O-O distance is 3.2 ± 0.5 Å), which is suggested also by quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations. Neither increased exposure of the phenol OH to solvent (buffered water), nor the internal hydrogen bond, was found to significantly affect the PCET rates. However, the lower phenol pKa values associated with the MP-α3C proteins compared to α3Y provided a sufficient change in PT driving force to alter the PCET mechanism. The PCET mechanism for 2MP-α3C and 4MP-α3C with moderately strong oxidants was predominantly step-wise PTET for pH values, but changed to concerted PCET at neutral pH values and below when a stronger oxidant was used, as found previously for α3Y. This shows how the balance of ET and PT driving forces is critical for controlling PCET mechanisms. The presented results improve our general understanding of amino-acid based PCET in enzymes.

Anti-tumor effects of cryptotanshinone (C19H20O3) in human osteosarcoma cell lines.

Osteosarcoma is the most prevalent malignant bone tumor and occurs most commonly in the adolescent and young adult population. Despite the recent advances in surgeries and chemotherapy, the overall survival in patients with resectable metastases is around 20%. This challenge in osteosarcoma is often attributed to the drastic differences in the tumorigenic profiles and mutations among patients. With diverse mutations and multiple oncogenes, it is necessary to identify the therapies that can attack various mutations and simultaneously have minor side-effects. In this paper, we constructed the osteosarcoma pathway from literature and modeled it using ordinary differential equations. We then simulated this network for every possible gene mutation and their combinations and ranked different drug combinations based on their efficacy to drive a mutated osteosarcoma network towards cell death. Our theoretical results predict that drug combinations with Cryptotanshinone (C19H20O3), a traditional Chinese herb derivative, have the best overall performance. Specifically, Cryptotanshinone in combination with Temsirolimus inhibit the JAK/STAT, MAPK/ERK, and PI3K/Akt/mTOR pathways and induce cell death in tumor cells. We corroborated our theoretical predictions using wet-lab experiments on SaOS2, 143B, G292, and HU03N1 human osteosarcoma cell lines, thereby demonstrating the potency of Cryptotanshinone in fighting osteosarcoma.

In Silico Modeling of the Induction of Apoptosis by Cryptotanshinone in Osteosarcoma Cell Lines.

Osteosarcoma (OS) is the most common primary malignant bone tumor of both children and pet canines. Its characteristic genomic instability and complexity coupled with the dearth of knowledge about its etiology has made improvement in the current treatment difficult. We use the existing literature about the biological pathways active in OS and combine it with the current research involving natural compounds to identify new targets and design more effective drug therapies. The key components of these pathways are modeled as a Boolean network with multiple inputs and multiple outputs. The combinatorial circuit is employed to theoretically predict the efficacies of various drugs in combination with Cryptotanshinone. We show that the action of the herbal drug, Cryptotanshinone on OS cell lines induces apoptosis by increasing sensitivity to TNF-related apoptosis-inducing ligand (TRAIL) through its multi-pronged action on STAT3, DRP1 and DR5. The Boolean framework is used to detect additional drug intervention points in the pathway that could amplify the action of Cryptotanshinone.

Long COVID outpatient rehabilitation: a call for action / Reabilitação ambulatorial da COVID longa: uma chamada à ação

COVID-19 has motor, cognitive, psychological and nutritional consequences that require rehabilitation. Objetive: To describe the outpatient rehabilitation program developed at the Instituto de Medicina Física e Reabilitação do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Method: We collected sociodemographic and clinical data of 12 adults with laboratory-confirmed COVID-19, severe and critical, who needed hospitalization in the acute phase. Functional assessments included Functional Independence Scale (FIM), EQ-5D-5L, World Health Organization Disability Assessment Schedule (WHODAS 2.0), Post-COVID-19 Functional Status scale (PCFS), Medical Research Council (MRC) dyspnea scale, visual analog scale (VAS) for pain, Douleur Neuropathique 4 (DN-4), Epworth sleepiness scale, Insomnia Severity Index, Montreal Ontario Cognitive Assessment (MoCA), Depression, anxiety and stress scale (DASS-21), nutritional assessment, Timed Up and Go test, 10-meter walking test (10 MWT), handgrip strength, MRC sum score, musculoskeletal ultrasound of the thigh.The outpatient rehabilitation program included electrical and musculoskeletal inductive magnetic stimulation, extracorporeal shockwave treatment, isokinetic exercises, emotional approach, cognitive stimulation, occupational performance stimulation, nutritional guidance, and educational program by COMVC mobile application. Individualized program was delivered twice a week until pre-stablished discharge criteria was achieved. Results: VAS and TUG presented statistically significant improvements (p <0.001). PCFS, FIM, handgrip strength, 10 MWT and DASS-21 anxiety presented slopes in the direction of improvement. Conclusion: The optimized, intensive, interdisciplinary and short-term outpatient rehabilitation program improves pain, mobility and anxiety in long COVID patients.

A COVID-19 tem consequências sensório motoras, cognitivas, psíquicas e nutricionais que necessitam de reabilitação. Objetivo: Descrever o programa de reabilitação ambulatorial desenvolvido no Instituto de Medicina Física e Reabilitação do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, otimizado, intensivo e de curta duração. Método: Obtivemos informações sociodemográficas e clínicas de 12 adultos com diagnóstico laboratorial de COVID-19, grave e crítica, que necessitaram de hospitalização na fase aguda. Avaliações funcionais: Escala de Medida de Independência Funcional (MIF), EQ- 5D-5L, World Health Organization Disability Assessment Schedule (WHODAS 2.0), Post- COVID-19 Functional Status scale, Medical Research Council (MRC) dyspnea scale, escala visual analógica (EVA) para dor, DN-4 (Douleur Neuropathique 4), escala de sonolência de Epworth, Índice de Gravidade da Insônia, Montreal Ontario Cognitive Assessment (MoCA), escala de Depressão, ansiedade e estresse (DASS-21), avaliação nutricional, Timed Up and Go, teste de caminhada de 10 metros, teste de preensão palmar, MRC sum score, ultrassonografia musculoesquelética da coxa antes, durante e após programa de reabilitação ambulatorial. Este incluiu estimulação magnética indutiva e elétrica musculoesquelética, tratamento por ondas de choque extracorpóreas, exercícios isocinéticos, abordagem emocional, estimulação cognitiva, estimulação do desempenho ocupacional, orientação nutricional e programa educacional por aplicativo COMVC. O tratamento foi realizado duas vezes por semana até atingir os critérios de alta pré-estabelecidos. Resultados: VAS e TUG proporcionaram melhora estatisticamente significante (p <0,001). PCFS, MIF, Handgrip, 10 MWT e DASS-21 domínio ansiedade apresentam tendências de melhora. Conclusão: O programa melhora a dor, mobilidade e ansiedade em pacientes com COVID longa.

Comprehensive live-cell imaging analysis of cryptotanshinone and synergistic drug-screening effects in various human and canine cancer cell lines.

BACKGROUND: Several studies have highlighted both the extreme anticancer effects of Cryptotanshinone (CT), a Stat3 crippling component from Salvia miltiorrhiza, as well as other STAT3 inhibitors to fight cancer. METHODS: Data presented in this experiment incorporates 2 years of in vitro studies applying a comprehensive live-cell drug-screening analysis of human and canine cancer cells exposed to CT at 20 µM concentration, as well as to other drug combinations. As previously observed in other studies, dogs are natural cancer models, given to their similarity in cancer genetics, epidemiology and disease progression compared to humans. RESULTS: Results obtained from several types of human and canine cancer cells exposed to CT and varied drug combinations, verified CT efficacy at combating cancer by achieving an extremely high percentage of apoptosis within 24 hours of drug exposure. CONCLUSIONS: CT anticancer efficacy in various human and canine cancer cell lines denotes its ability to interact across different biological processes and cancer regulatory cell networks, driving inhibition of cancer cell survival.

Targeting oncogenic mutations in colorectal cancer using cryptotanshinone.

Colorectal cancer (CRC) is one of the most prevalent types of cancer in the world and ranks second in cancer deaths in the US. Despite the recent improvements in screening and treatment, the number of deaths associated with CRC is still very significant. The complexities involved in CRC therapy stem from multiple oncogenic mutations and crosstalk between abnormal pathways. This calls for using advanced molecular genetics to understand the underlying pathway interactions responsible for this cancer. In this paper, we construct the CRC pathway from the literature and using an existing public dataset on healthy vs tumor colon cells, we identify the genes and pathways that are mutated and are possibly responsible for the disease progression. We then introduce drugs in the CRC pathway, and using a boolean modeling technique, we deduce the drug combinations that produce maximum cell death. Our theoretical simulations demonstrate the effectiveness of Cryptotanshinone, a traditional Chinese herb derivative, achieved by targeting critical oncogenic mutations and enhancing cell death. Finally, we validate our theoretical results using wet lab experiments on HT29 and HCT116 human colorectal carcinoma cell lines.

Assessment of folate and cobalamin concentrations in relation to their dependent intracellular metabolites in serum of pigs between 6 and 26 weeks of age.

Folate (vitamin B9) and cobalamin (vitamin B12) play an important role in amino acid metabolism, nucleic acid synthesis, and methyl group transfer. Two intracellular enzymes, methionine synthase and methylmalonyl-CoA mutase, are folate and/or cobalamin-dependent, respectively. At the cellular level, a lack of folate and cobalamin leads to accumulation of serum homocysteine (HCY) and a lack of cobalamin leads to increased methylmalonic acid (MMA) concentrations. Altered serum HCY and MMA concentrations can influence amino acid metabolism and nucleic acid synthesis in pigs. Therefore, we aimed to evaluate serum folate, cobalamin, HCY, and MMA concentrations in postweaning pigs between 6 and 26 weeks of age. Serum samples from 12 pigs collected at week 6, 7, 8, 9, 10, 14, 18, 22, and 26 as part of an unrelated study were analyzed. Serum folate (p < .0001), cobalamin (p = .0001), HCY (p < .0001), and MMA (p < .0001) concentrations differed significantly during the postweaning period between 6 and 26 weeks of age; with significantly higher serum HCY (at weeks 6 and 7 compared to weeks 9, 14, 18, 22, and 26) and MMA concentrations (at weeks 6, 7, and 8 compared to weeks 14, 18, 22, and 26) and an overall decrease of serum MMA concentrations from week 6 to week 14 in the pigs studied. This study suggests age-dependent changes in intracellular folate- and cobalamin-dependent metabolites (i.e., HCY and MMA) in pigs between 6 and 26 weeks of age, possibly reflecting decreased availability of intracellular folate and/or cobalamin for amino acid metabolism, nucleic acid synthesis, and methyl group transfer.

In Silico Design and Experimental Validation of Combination Therapy for Pancreatic Cancer.

The number of deaths associated with Pancreatic Cancer has been on the rise in the United States making it an especially dreaded disease. The overall prognosis for pancreatic cancer patients continues to be grim because of the complexity of the disease at the molecular level involving the potential activation/inactivation of several diverse signaling pathways. In this paper, we first model the aberrant signaling in pancreatic cancer using a multi-fault Boolean Network. Thereafter, we theoretically evaluate the efficacy of different drug combinations by simulating this boolean network with drugs at the relevant intervention points and arrive at the most effective drug(s) to achieve cell death. The simulation results indicate that drug combinations containing Cryptotanshinone, a traditional Chinese herb derivative, result in considerably enhanced cell death. These in silico results are validated using wet lab experiments we carried out on Human Pancreatic Cancer (HPAC) cell lines.

A Gaussian Mixture-Model Exploiting Pathway Knowledge for Dissecting Cancer Heterogeneity.

In this work, we develop a systematic approach for applying pathway knowledge to a multivariate Gaussian mixture model for dissecting a heterogeneous cancer tissue. The downstream transcription factors are selected as observables from available partial pathway knowledge in such a way that the subpopulations produce some differential behavior in response to the drugs selected in the upstream. For each subpopulation, each unique (drug, observable) pair is considered as a unique dimension of a multivariate Gaussian distribution. Expectation-maximization (EM) algorithm with hill-climbing is then used to rank the most probable estimates of the mixture composition based on the log-likelihood value. A major contribution of this work is to examine the efficacy of the EM based approach in estimating the composition of experimental mixture sets from cell-by-cell measurements collected on a dynamic cell imaging platform. Towards this end, we apply the algorithm on hourly data collected for two different mixture compositions of A2058, HCT116, and SW480 cell lines for three scenarios: untreated, Lapatinib-treated, and Temsirolimus-treated. Additionally, we show how this methodology can provide a basis for comparing the killing rate of different drugs for a heterogeneous cancer tissue. This obviously has important implications for designing efficient drugs for treating heterogeneous malignant tumors.

Cryptotanshinone Induces Cell Death in Lung Cancer by Targeting Aberrant Feedback Loops.

Signaling pathways oversee highly efficient cellular mechanisms such as growth, division, and death. These processes are controlled by robust negative feedback loops that inhibit receptor-mediated growth factor pathways. Specifically, the ERK, the AKT, and the S6K feedback loops attenuate signaling via growth factor receptors and other kinase receptors to regulate cell growth. Irregularity in any of these supervised processes can lead to uncontrolled cell proliferation and possibly Cancer. These irregularities primarily occur as mutated genes, and an exhaustive search of the perfect drug combination by performing experiments can be both costly and complex. Hence, in this paper, we model the Lung Cancer pathway as a Modified Boolean Network that incorporates feedback. By simulating this network, we theoretically predict the drug combinations that achieve the desired goal for the majority of mutations. Our theoretical analysis identifies Cryptotanshinone, a traditional Chinese herb derivative, as a potent drug component in the fight against cancer. We validated these theoretical results using multiple wet lab experiments carried out on H2073 and SW900 lung cancer cell lines.

Avaliação da porcentagem de gordura corporal em um indivíduo com amputação transfemoral bilateral por diferentes métodos: estudo de caso / Evaluation of body fat percentage in individual with bilateral transfemoral amputation by different methods: case study

A amputação predispõe a um risco de alterações na composição corporal, condição que interfere no equilíbrio no uso da prótese, aumenta o cansaço físico e tem como consequência menor rendimento nas terapias físicas. Nesse sentido, é fundamental eleger o método mais apropriado para avaliar a composição corporal. Objetivo: Avaliar a porcentagem de gordura corporal em um indivíduo com amputação transfemoral por diferentes métodos. Método: Trata-se de um estudo de caso de caráter clínico retrospectivo com um participante do sexo masculino, idade 67 anos com amputação transfemoral bilateral por insuficiência vascular, atendido pelo Serviço de Nutrição do Instituto de Medicina Física e Reabilitação do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - IMREA HCFMUSP. Utilizou-se o somatório das dobras cutâneas, absorciometria de raio-X de dupla energia (DXA) e análise de impedância bioelétrica (IB). Resultados: Os dados antropométricos apontaram porcentagem de gordura corporal de 34,3%, a IB 33% e o DXA revelou 37%. Conclusão: Para este caso, sugere-se que na inviabilidade de avaliar a porcentagem de gordura corporal em indivíduos com amputação com o DXA, o somatório das dobras é o método elegível. Estudos futuros são imprescindíveis a fim de estabelecer o método adequado para avaliação da composição corporal de pessoas com amputações bilaterais de membros inferiores, tendo em vista que este resultado contribui para o melhor desfecho clínico de pacientes em processo de reabilitação.

Amputations increase the risk of changes in body composition, a condition that interferes with balance when wearing prosthetics limbs, increases physical tiredness and results in lower performance in physical therapy. As such, it is essential to choose the most appropriate method for assessing body composition. Objective: To evaluate a percentage of body fat of an individual with amputation by different methods and compare the results. Method: This is a retrospective case study of a male amputee, aged 67 years, with bilateral transfemoral amputations due to vascular conditions, who attended treatment at the Nutrition Services of the Physical and Rehabilitation Medicine Institute of the University of São Paulo Medical School General Hospital, Brazil. The study used the sum of skinfold thickness, dual energy X-ray absorptiometry (DXA), and bioelectrical impedance analysis (BIA). Results: Anthropometric data showed a percentage of body fat of 34, 3%, BIA indicated 33%, and DXA revealed 37%. Conclusion: In this case, we suggest that, if it is unfeasible to use DXA to assess the body composition of amputees, skinfold thickness is the most recommended method. Future studies are essential in order to establish the appropriate method for assessing body composition of people with bilateral lower limb amputations, as it contributes to better clinical outcomes of amputee patients undergoing rehabilitation treatment.

Bayesian Inference Identifies Combination Therapeutic Targets in Breast Cancer.

OBJECTIVE: Breast cancer is the second leading cause of cancer death among US women; hence, identifying potential drug targets is an ever increasing need. In this paper, we integrate existing biological information with graphical models to deduce the significant nodes in the breast cancer signaling pathway. METHODS: We make use of biological information from the literature to develop a Bayesian network. Using the relevant gene expression data we estimate the parameters of this network. Then, using a message passing algorithm, we infer the network. The inferred network is used to quantitatively rank different interventions for achieving a desired phenotypic outcome. The particular phenotype considered here is the induction of apoptosis. RESULTS: Theoretical analysis pinpoints to the role of Cryptotanshinone, a compound found in traditional Chinese herbs, as a potent modulator for bringing about cell death in the treatment of cancer. CONCLUSION: Using a mathematical framework, we showed that the combination therapy of mTOR and STAT3 genes yields the best apoptosis in breast cancer. SIGNIFICANCE: The computational results we arrived at are consistent with the experimental results that we obtained using Cryptotanshinone on MCF-7 breast cancer cell lines and also by the past results of others from the literature, thereby demonstrating the effectiveness of our model.

An in-silico study examining the induction of apoptosis by Cryptotanshinone in metastatic melanoma cell lines.

BACKGROUND: Metastatic melanoma is an aggressive form of skin cancer that evades various anti-cancer treatments including surgery, radio-,immuno- and chemo-therapy. TRAIL-induced apoptosis is a desirable method to treat melanoma since, unlike other treatments, it does not harm non-cancerous cells. The pro-inflammatory response to melanoma by nF κB and STAT3 pathways makes the cancer cells resist TRAIL-induced apoptosis. We show that due to to its dual action on DR5, a death receptor for TRAIL and on STAT3, Cryptotanshinone can be used to increase sensitivity to TRAIL. METHODS: The development of chemoresistance and invasive properties in melanoma cells involves several biological pathways. The key components of these pathways are represented as a Boolean network with multiple inputs and multiple outputs. RESULTS: The possible mutations in genes that can lead to cancer are captured by faults in the combinatorial circuit and the model is used to theoretically predict the effectiveness of Cryptotanshinone for inducing apoptosis in melanoma cell lines. This prediction is experimentally validated by showing that Cryptotanshinone can cause enhanced cell death in A375 melanoma cells. CONCLUSION: The results presented in this paper facilitate a better understanding of melanoma drug resistance. Furthermore, this framework can be used to detect additional drug intervention points in the pathway that could amplify the action of Cryptotanshinone.

A Bayesian approach to determine the composition of heterogeneous cancer tissue.

BACKGROUND: Cancer Tissue Heterogeneity is an important consideration in cancer research as it can give insights into the causes and progression of cancer. It is known to play a significant role in cancer cell survival, growth and metastasis. Determining the compositional breakup of a heterogeneous cancer tissue can also help address the therapeutic challenges posed by heterogeneity. This necessitates a low cost, scalable algorithm to address the challenge of accurate estimation of the composition of a heterogeneous cancer tissue. METHODS: In this paper, we propose an algorithm to tackle this problem by utilizing the data of accurate, but high cost, single cell line cell-by-cell observation methods in low cost aggregate observation method for heterogeneous cancer cell mixtures to obtain their composition in a Bayesian framework. RESULTS: The algorithm is analyzed and validated using synthetic data and experimental data. The experimental data is obtained from mixtures of three separate human cancer cell lines, HCT116 (Colorectal carcinoma), A2058 (Melanoma) and SW480 (Colorectal carcinoma). CONCLUSION: The algorithm provides a low cost framework to determine the composition of heterogeneous cancer tissue which is a crucial aspect in cancer research.

Comparative Therapeutic Effects of Minocycline Treatment and Bone Marrow Mononuclear Cell Transplantation following Striatal Stroke.

We explored the comparative effects of minocycline treatment and intrastriatal BMMC transplantation after experimental striatal stroke in adult rats. Male Wistar adult rats were divided as follows: saline-treated (N = 5), minocycline-treated (N = 5), and BMMC-transplanted (N = 5) animals. Animals received intrastriatal microinjections of 80 pmol of endothelin-1 (ET-1). Behavioral tests were performed at 1, 3, and 7 days postischemia. Animals were treated with minocycline (50 mg/kg, i.p.) or intrastriatal transplants of 106 BMMCs at 24 h postischemia. Animals were perfused at 7 days after ischemic induction. Coronal sections were stained with cresyl violet for gross histopathological analysis and immunolabeled for the identification of neuronal bodies (NeuN), activated microglia/macrophages (ED1), and apoptotic cells (active caspase-3). BMMC transplantation and minocycline reduced the number of ED1+ cells (p < 0.05, ANOVA-Tukey), but BMMC afforded better results. Both treatments afforded comparable levels of neuronal preservation compared to control (p > 0.05). BMMC transplantation induced a higher decrease in the number of apoptotic cells compared to control and minocycline treatment. Both therapeutic approaches improved functional recovery in ischemic animals. The results suggest that BMMC transplantation is more effective in modulating microglial activation and reducing apoptotic cell death than minocycline, although both treatments are equally efficacious on improving neuronal preservation.

Cytotoxicity and anti-Leishmania amazonensis activity of Citrus sinensis leaf extracts.

CONTEXT: Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease characterized by lesional polymorphism and the commitment of skin surface. Previous reports demonstrated that the Citrus genus possess antimicrobial activity. OBJECTIVE: This study evaluated the anti-L. amazonensis activity of Citrus sinensis (L.) Osbeck (Rutaceae) extracts. MATERIALS AND METHODS: Citrus sinensis dried leaves were subjected to maceration with hexane (CH), ethyl acetate (CEA), dichloromethane/ethanol (CD/Et - 1:1) or ethanol/water (CEt/W - 7:3). Leishmania amazonensis promastigotes were treated with C. sinensis extracts (1-525 µg/mL) for 120 h at 27 °C. Ultrastructure alterations of treated parasites were evaluated by transmission electron microscopy. Cytotoxicity of the extracts was assessed on RAW 264.7 and J774.G8 macrophages after 48-h treatment at 37 °C using the tetrazolium assay. In addition, Leishmania-infected macrophages were treated with CH and CD/Et (10-80 µg/mL). RESULTS: CH, CD/Et and CEA displayed antileishmanial activity with 50% inhibitory activity (IC50) of 25.91 ± 4.87, 54.23 ± 3.78 and 62.74 ± 5.04 µg/mL, respectively. Parasites treated with CD/Et (131.2 µg/mL) presented severe alterations including mitochondrial swelling, lipid body formation and intense cytoplasmic vacuolization. CH and CD/Et demonstrated cytotoxic effects similar to that of amphotericin B in the anti-amastigote assays (SI of 2.16, 1.98 and 1.35, respectively). Triterpene amyrins were the main substances in CH and CD/Et extracts. In addition, 80 µg/mL of CD/Et reduced the number of intracellular amastigotes and the percentage of infected macrophages in 63% and 36%, respectively. CONCLUSION: The results presented here highlight C. sinensis as a promising source of antileishmanial agents.

Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia.

Neuroblasts from the subventricular zone (SVZ) migrate to striatum following stroke, but most of them die in the ischaemic milieu and this can be related to exacerbated microglial activation. Here, we explored the effects of the non-steroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and neuroblast migration following experimental striatal stroke in adult rats. Animals were submitted to endothelin-1 (ET-1)-induced focal striatal ischaemia and were treated with indomethacin or sterile saline (i.p.) for 7 days, being perfused after 8 or 14 days. Immunohistochemistry was performed to assess neuronal loss (anti-NeuN), microglial activation (anti-Iba1, ED1) and migrating neuroblasts (anti-DCX) by counting NeuN, ED1 and DCX-positive cells in the ischaemic striatum or SVZ. Indomethacin treatment reduced microglia activation and the number of ED1+ cells in both 8 and 14 days post injury as compared with controls. There was an increase in the number of DCX+ cells in both SVZ and striatum at the same survival times. Moreover, there was a decrease in the number of NeuN+ cells in indomethacin-treated animals as compared with the control group at 8 days but not after 14 days post injury. Our results suggest that indomethacin treatment modulates microglia activation, contributing to increased neuroblast proliferation in the SVZ and migration to the ischaemic striatum following stroke.

Rubiaceae in Brazilian Atlantic Forest remnants: floristic similarity and implications for conservation / Rubiaceae en remanentes de Bosque Atlántico de Brasil: similitud florística e implicaciones para la conservación

AbstractBrazil holds most of the Atlantic Forest Domain and is also one of the Rubiaceae diversity centers in the Neotropics. Despite the urban expansion in the state of Rio de Janeiro, large areas of continuous vegetation with high connectivity degree can still be found. Recently, new Rubiaceae species have been described in the Rio de Janeiro flora, which present small populations and very particular distribution. The current paper analyzed the similarity in the floristic composition of the Rubiaceae in eight Atlantic Forest remnants of Rio de Janeiro state protected by Conservation Units. We also surveyed and set guidelines for conservation of microendemic species. The similarity analysis were based on previously published studies in Área de Proteção Ambiental de Grumari, Área de Proteção Ambiental Palmares, Parque Estadual da Serra da Tiririca, Parque Nacional do Itatiaia, Parque Nacional de Jurubatiba, Reserva Biológica de Poço das Antas, Reserva Biológica do Tinguá and Reserva Ecológica de Macaé de Cima - using the PAST software (“Paleontological Statistics”) with Sørensen coefficient. The floristic similarity analysis revealed two groups with distinct physiographic characteristics and different vegetation types. Group A consisted in two Restinga areas, Área de Proteção Ambiental de Grumari and Parque Nacional de Jurubatiba, which showed strong bootstrap support (98 %). Group B included forest remnants with distinct phytophisiognomies or altitudes, but with moderate bootstrap support. Low similarity levels among the eight areas were found due to the habitats’ heterogeneity. The current study pointed out 19 microendemic species from the Atlantic Forest, they present a single-site distribution or a distribution restricted to Mountain and Metropolitan regions of Rio de Janeiro state. Concerning the conservation status of microendemic species, discrepancies between the Catalogue of Flora of Rio de Janeiro and the Red Book of Brazilian Flora (two of the main reference catalogs of Brazilian flora) have been identified. We have also highlighted the need for recollecting microendemic species from the Atlantic Forest, and for properly assessing the degree of threat faced by these taxons early. Rev. Biol. Trop. 64 (2): 655-665. Epub 2016 June 01.

ResumenBrasil tiene la mayor parte de bosque del Atlántico y también es uno de los centros de diversidad de Rubiaceas del Neotrópico. A pesar de la expansión urbana en el estado de Río de Janeiro, todavía se pueden encontrar grandes áreas de vegetación con alto grado de conectividad. Recientemente, nuevas especies de Rubiaceae se han descrito en la flora de Río de Janeiro, las cuales presentan poblaciones pequeñas y distribuciones particulares. El presente documento analiza la similitud en la composición florística de Rubiaceae en ocho remanentes del bosque Atlántico del estado de Río de Janeiro, protegidos por las Unidades de Conservación. También se inspeccionaron y establecieron directrices para la conservación de especies microendémicas. El análisis de similitud se basó en estudios publicados anteriormente en el área de Protección Ambiental de Grumari, área de Protección Ambiental Palmares, Parque Estatal de Serra da Tiririca, Parque Nacional de Itatiaia, Parque Nacional de Jurubatiba, Reserva Biológica de Poço das Antas, Reserva Biológica de Tinguá y Reserva Ecológica de Macaé de Cima, utilizando el software PAST (“Paleontological Statistics”) con coeficiente de Sørensen. El análisis de similitud florística reveló dos grupos con características fisiográficas distintas y diferentes tipos de vegetación. El Grupo A consistió en dos áreas, Área de Protección Ambiental de Grumari y el Parque Nacional de Jurubatiba, que mostraron un fuerte bootstrap support (98 %). El Grupo B incluye remanentes de bosque con fitofisionomía o altitudes distintas, pero con moderado bootstrap support. Los bajos niveles de similitud entre las ocho áreas fueron encontrados debido a la heterogeneidad de los hábitats. El estudio señaló que 19 especies microendémicas del Atlántico presentan una distribución de un solo sitio o una distribución restringida a las regiones de montaña y regiones metropolitanas del estado de Río de Janeiro. En cuanto al estado de conservación de especies microendémicas, se han identificado discrepancias entre el Catálogo de la Flora de Río de Janeiro y el Libro Rojo de la Flora de Brasil (dos de los principales catálogos de referencias de la flora brasileña). También se puso de relieve la necesidad de recolectar especies microendémicas del bosque Atlántico para evaluar temprano y adecuadamente el grado de amenaza que enfrentan estos taxones.

Serviço de nutrição em reabilitação física: perfil epidemiológico de pacientes em atendimento ambulatorial / Nutrition service in physical rehabilitation: epidemiological profile of patients in outpatient care

Estima-se que uma pessoa em cada dez possua algum tipo de deficiência, ou seja, 10% da população mundial. Na deficiência física as causas mais comuns são: amputação, acidente vascular encefálico, traumatismo crânio encefálico, lesão medular, fibromialgia, doenças neurodegenerativas e entre outras. Objetivo: Descrever o perfil dos pacientes atendidos pelo serviço de nutrição do Instituto de Medicina Física e Reabilitação (IMREA) - unidade Vila Mariana, São Paulo, no período de fevereiro de 2012 a setembro de 2015. Métodos: Trata-se de um estudo descritivo, os dados foram obtidos de prontuários de atendimentos onde foram coletados os dados: sexo, idade, equipe de atendimento, doenças associadas, índice de massa corporal inicial e final, hábito intestinal inicial e final. Resultados: A população estudada teve predomínio das seguintes características gênero feminino; adulto jovem; principal etiologia lesão encefálica; o diagnóstico de hipertensão associada a maioria dos casos; maior parte está acima do peso. Conclusão: Observou-se melhora importante do hábito intestinal pós programa de educação nutricional

It is estimated that one person in ten has a deficiency, which is 10% of the world's population. The most common causes of physical disability are amputation, stroke, head trauma, spinal cord injury, fibromyalgia, and neurodegenerative diseases. Objective: This study sought to describe the profile of patients served by the nutrition service at the Instituto de Medicina Física e Reabilitação (IMREA) - Vila Mariana Unit, São Paulo, between February 2012 and September 2015. Method: This is a descriptive study whose data were obtained from medical records of visits where the following data were collected: gender, age, service personnel, associated diseases, initial and final body mass index, and initial and final bowel habits. Results: The studied population was predominantly female; young adult; main etiology of brain damage; diagnosed hypertension associated in most cases; and mostly overweight. Conclusion: Observed significant improvement in bowel habits after nutrition education program

Rubiaceae in Brazilian Atlantic Forest remnants: floristic similarity and implications for conservation.

Brazil holds most of the Atlantic Forest Domain and is also one of the Rubiaceae diversity centers in the Neotropics. Despite the urban expansion in the state of Rio de Janeiro, large areas of continuous vegetation with high connectivity degree can still be found. Recently, new Rubiaceae species have been described in the Rio de Janeiro flora, which present small populations and very particular distribution. The current paper analyzed the similarity in the floristic composition of the Rubiaceae in eight Atlantic Forest remnants of Rio de Janeiro state protected by Conservation Units. We also surveyed and set guidelines for conservation of microendemic species. The similarity analysis were based on previously published studies in Área de Proteção Ambiental de Grumari, Área de Proteção Ambiental Palmares, Parque Estadual da Serra da Tiririca, Parque Nacional do Itatiaia, Parque Nacional de Jurubatiba, Reserva Biológica de Poço das Antas, Reserva Biológica do Tinguá and Reserva Ecológica de Macaé de Cima - using the PAST software ("Paleontological Statistics") with Sørensen coefficient. The floristic similarity analysis revealed two groups with distinct physiographic characteristics and different vegetation types. Group A consisted in two Restinga areas, Área de Proteção Ambiental de Grumari and Parque Nacional de Jurubatiba, which showed strong bootstrap support (98 %). Group B included forest remnants with distinct phytophisiognomies or altitudes, but with moderate bootstrap support. Low similarity levels among the eight areas were found due to the habitats' heterogeneity. The current study pointed out 19 microendemic species from the Atlantic Forest, they present a single-site distribution or a distribution restricted to Mountain and Metropolitan regions of Rio de Janeiro state. Concerning the conservation status of microendemic species, discrepancies between the Catalogue of Flora of Rio de Janeiro and the Red Book of Brazilian Flora (two of the main reference catalogs of Brazilian flora) have been identified. We have also highlighted the need for recollecting microendemic species from the Atlantic Forest, and for properly assessing the degree of threat faced by these taxons early.